Nitrogen atom transfer

Process and apparatus for addition of nitrogen to an organic molecule under electrochemical conditions. Processes include aziridination of olefins and imination of sulfoxides to form sulfoximines. Nitrene generation in the presence of a carboxylate is described

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Description
FIELD OF THE INVENTION

This invention is in the field of electrochemical atom transfer, particularly the introduction of a nitrogen atom into an organic molecule in an electrochemical process.

BACKGROUND OF THE INVENTION

The reactions of organic compounds can be classified into two broad categories: carbon-carbon bond forming processes and reactions in which carbon atoms change their oxidation states (redox processes). The redox reactions in nature are accomplished by the enzyme molecules. These catalysts contain metal centers that carry out the requisite electron and/or atom transfer reactions. Over the years, remarkable progress has been achieved in design and applications of novel metal-based complexes. The metal center of a synthetic catalyst is surrounded by a small molecule ligand that often resembles and emulates the catalytic reaction site of an enzyme. One of the key roles of the ligand is to modulate reactivity at the metal center. This permits the reactivity of the metal ion in a given oxidation state to be adjusted to control the steric and electronic parameters of a given reaction. This strategy has been shown to adequately address the issues of regio-, chemo-, and stereoselectivity of a number of widely used synthetic transformations. The judicious choice of stoichiometric reductant or oxidant is required in order to render a given reaction catalytic in the metal reagent.

Aziridination of olefins is of particular current interest due to the enormous synthetic potential of aziridines.1 These nitrogen-containing heterocycles have 28 kcal/mol of strai2 and are amenable to ring-opening reactions with a wide range of nucleophiles. Such transformations lead to molecules with valuable 1,2-heteroatom relationships, commonly found in natural products and in pharmaceuticals.3 Olefin aziridination reactions are usually accomplished via metal-mediated transfer of a nitrene fragment to the olefin.4 The corresponding processes can produce a variety of by-products that stem from metal additives and from oxidants. To date, there are no examples of catalytic oxidation systems based on readily available oxidants that convert simple amines or amides into active nitrogen transfer species in the presence of olefins and leave no by-products.

A synthetically attractive route is the aziridination of olefins with N-aminophthalimide and lead tetraacetate as oxidant (eq. 1).5 However, its widespread application is hampered by the use of large amounts of Pb(OAc)4, known for its high toxicity.6

SUMMARY OF THE INVENTION

This invention provides an electrochemical process by which a new organic molecule is obtained through the formation of a nitrogen bond. An example is the formation of an aziridine by addition of the nitrogen across a double bond between two carbon atoms, in which two C—N bonds form. Another example is formation of a sulfoxime by addition of the nitrogen to the sulfur atom of a sulfoxide, in which a S═N bond forms. The results of the various addition reactions shown herein can be explained in terms of the formation of a nitrene intermediate formed under the electrochemical conditions of the invention.

In one aspect, the invention is an electrochemical process for the formation of a compound having formula I:
The process includes a step of contacting a compound having formula II and a compound having formula III with each other in an electrolytic cell under conditions of electrolysis sufficient to form the compound of formula I.
“A” shown in these formulae is selected from the group consisting of C, N and O, and

    • (i) when A is a carbon atom, each of R1, R2, R3, and R is hydrogen or an organic group;
    • (ii) when A is a nitrogen atom, each of R1, R2, and R3, is hydrogen or an organic group, and R4 is an electron pair;
    • (iii) when A is an oxygen atom, each of R1 and R2 is hydrogen or an organic group, and each of R3 and R4 is an electron pair; and
    • (iv) R5 is NR6R7 and each of R6 and R7 is an organic group.

A is preferably a carbon atom, but it can be a nitrogen atom, or an oxygen atom.

The group from which each of R1, R2, R3, and R4 may be selected can be the group consisting of alkyl, alkenyl, alkynyl, aryl, phenyl, biphenyl, and substituted alkyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of alkyl, alkenyl, alkynyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane.

In another aspect, the group from which each of R1, R2, R3, and R4 may be selected is the group consisting of alkyl, alkenyl, alkynyl, aryl, and substituted alkyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of alkyl aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.

In a narrower aspect, the group from which each of R1, R2, R3, and R4 may be selected can the group consisting of alkyl and aryl, and substituted alkyl and aryl, wherein the substituents are selected from the group of alkyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.

More particularly, the substituents can be selected from the group of halide, ketone, alcohol and ester.

In another aspect, “A” of starting compound II is a carbon atom, (i) if R3 and R4 are each hydrogen, then each of R1 and R2 is not hydrogen, or the double bond shown in formula II is conjugated with another olefinic double bond, (ii) if a first carbon atom of the double bond shown in formula II is in an α-position with respect to a carbonyl group of R1, then the second carbon atom of the double bond is not in an α-position with respect to a carbonyl group of R3, and (iii) if a first carbon atom of the double bond shown in formula II is in an α-position with respect to a carbonyl group of R2, then the second carbon atom of the double bond is not in an α-position with respect to carbonyl group of R4.

In another aspect of a process of the invention, II is selected from the group consisting of cyclohexene, cyclohex-2-enone, 2-methyl-pent-2-ene, 3-bromo-2-methyl-propene, trans-3-phenyl-acrylic acid methyl ester, cyclooctene, 2-methyl-buta-1,3-diene, trans-1,3-diphenylpropenone, trans-hex-4-en-3-one, trans-but-2-enedioic acid dimethyl ester, trans-3-phenyl-prop-2-en-1-ol, trans-4-phenyl-but-3-enoic acid methyl ester, 2-(acetoxy-phenyl-methyl)-acrylic acid methyl ester, 2-(hydroxy-phenyl-methyl)-acrylic acid methyl ester, trans-1,4-dichlorobutene, cis-1,4 dichlorobutene, 2-(phenylp-toluenesulfonamidomethyl)acrylic acid methyl ester and any derivative thereof obtained by substitution of a hydrogen of a C—H bond with an alkyl, phenyl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane, wherein any such group can itself be substituted with a said group.

In a specific aspect, compound II is selected from the group consisting of cyclohexene, cyclohex-2-enone, 2-methyl-pent-2-ene, 3-bromo-2-methyl-propene, trans-3-phenyl-acrylic acid methyl ester, cyclooctene, 2-methyl-buta-1,3-diene, trans-1,3-diphenylpropenone, trans-hex en-3-one, trans-but-2-enedioic acid dimethyl ester, trans-3-phenyl-prop-2-en-1-ol, trans-4-phenyl-but-3-enoic acid methyl ester, 2-(acetoxy-phenyl-methyl)-acrylic acid methyl ester, 2-(hydroxy-phenyl-methyl)-acrylic acid methyl ester, trans-1,4-dichlorobutene, cis-1,4 dichlorobutene, and 2-(phenyl p-toluenesulfonamidomethyl)acrylic acid methyl ester.

In another aspect, the invention is process for the syn-addition of a nitrogen atom across a double bond.

The R5 group of compound III, can be selected from the specific group:
wherein each of R8, R9, R10, R11, R12 and R13 is an organic group.

Even more specifically, each of R8, R9, R10, R11, R12 and R13 can be selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, phenyl, biphenyl and substituted alkyl, alkenyl, alkynyl, aryl, phenyl and biphenyl wherein the substituents are selected from the group of alkyl, alkenyl, alknyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane.

In a narrower aspect of the invention, each of R8, R9, R10, R11, R12 and R13 can be selected from the group consisting of alkyl, aryl, phenyl and substituted alkyl, aryl and phenyl, wherein the substituents are selected from the group of alkyl, aryl, phenyl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane Each of R8, R9, R10, R11, R12 and R13 preferably includes up to 20 carbon atoms, more preferably up to 18 carbon atoms, more preferably up to 16 carbon atoms, more preferably up to 14 carbon atoms, or up to 12 carbon atoms, or up to 10 carbon atoms, or up to 8 carbon atoms, or up to 6 carbon atoms.

Each of the substituents of the substituted groups from which R8, R9, R10, R1 1, R12 and R13 can be selected is preferably selected from the group consisting of halide, ketone, alcohol and ester, and more preferably from halide, alcohol and ester.

In a specific aspect of the invention, the compound having formula III is N-aminophthalimide. Any of the four C—H bonds of this molecule can be replaced with substituents that would not destroy the primary amino group of this compound to be electrochemically oxidized, i.e., alkyl, aryl, halide, alkyl halide, etc.

In another aspect of the invention, the compound having formula Im has a lower oxidation potential than that of a compound having formula II. It is also preferred that the compound having formula III is oxidized at a faster rate than a compound having formula II under the conditions of electrolysis of the invention.

The solvent the electrolytic cell can be a polar non-protic solvent, and particularly wherein the solvent can be selected from the group consisting of dichloromethane, acetonitrile, N,N-dimethylformamide, tetrahydrofuran, nitromethane, chloroform, propylene carbonate, and mixtures thereof, or other solvent suitable for conducting an electrochemical process of the invention.

In another aspect, the invention is an electrochemical process for the formation of a compound having formula IV,
In this aspect, the process includes contacting a compound having formula V and a compound having formula III with each other in an electrolytic cell under conditions of electrolysis sufficient to form the compound of formula IV.
In the indicated formulae,

    • (i) B is selected from the group consisting of P, S, Se and Te;
    • (ii) each of R14 and R15 is hydrogen or an organic group; and
    • (iii) R5 is NR6R7 and each of R and R7 is an organic group.

The “B” is most preferably a sulfur atom, but it can be a phosphorus atom, a selenium atom, or a tellurium atom.

The group of organic groups from which each of R14, and R15 may be selected can be the group of alkyl, alkenyl, alkynyl, aryl, phenyl, biphenyl, and substituted alkyl, alkenyl, alkynyl, aryl, phenyl and biphenyl wherein the substituents are selected from the group of alkyl, alkenyl, alkynyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane.

More particularly, the group from which each of R14, and R15 may be selected can be the group consisting of alkyl, alkenyl, alkynyl, aryl, and substituted alkyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of alkyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide; nitro, epoxide, aziridine, sulfone, phosphone, and silane.

Even more particularly, the group from which each of R14, and R15 may be selected is the group consisting of alkyl and aryl, and substituted alkyl and aryl, wherein the substituents are selected from the group of alkyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane. More particularly, wherein the substituents are selected from the group of halide, ketone, alcohol and ester, and more particularly, halide, alcohol and ester.

The invention includes a process wherein compound V is selected from the group consisting of compounds VIII to XV:
and any derivative of any of compounds VII to XV obtained by substitution of a hydrogen of a C—H bond with an alkyl, phenyl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane, wherein any said group can itself include such a substituent.

More specifically, compound V can be selected from any of compounds VIII to XV.

R5 can be selected as described above, for reaction of compound V and III.

In a particular embodiment, the compound having formula III has a lower oxidation potential than that of a compound having formula II. Further, the compound having formula III is oxidized at a faster rate than a compound having formula II under the conditions of electrolysis.

In another aspect, the invention is an electrochemical process for the formation of a compound having formula VI:
Here, the process involves contacting a compound having formula VII and a compound having formula III with each other in an electrolytic cell under conditions of electrolysis sufficient to form the compound of formula VI.
In this aspect of the invention,

    • (i) when D is a carbon atom, each of R16 and R17 is hydrogen or an organic group; and
    • (ii) when D is a nitrogen atom, R16 is hydrogen or an organic group, and R17 is an electron pair.

In one aspect of this process of the invention, the group from which each of R16, and R17 may be selected can be the group consisting of alkyl, alkenyl, alkynyl, aryl, phenyl, biphenyl, etc., and substituted alkyl, alkenyl, alkynyl, aryl, phenyl, biphenyl wherein the substituents are selected from the group of alkyl, alkenyl, alkynyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane.

The group from which each of R16, and R17 may be selected, in a narrower aspect of the invention, is the group consisting of alkyl, alkenyl, alkynyl, aryl, and substituted alkyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of alkyl, aryl, halide, ketone, aldehyde, alcohol ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.

The group from which each of R16, and R17 may be selected can also be the group consisting of alkyl and aryl, and substituted alkyl and aryl, wherein the substituents are selected from the group of alkyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.

More preferably, the substituents are selected from the group of halide, ketone, alcohol and ester.

Again, wherein R5 of compound III can be selected as previously described.

The compound having formula III preferably has a lower oxidation potential than that of a compound having formula II, and preferably is oxidized at a faster rate than a compound having formula II under the conditions of electrolysis.

In one general aspect, the invention involves including a carboxylate anion in the anodic cell in which the hydrazine compound II is oxidized. Preferably, the cell is substantially free, or even completely free, of a toxic metal catalyst. Toxic metal catalysts that are to avoided include of lead cadmium, cerium, cobalt, chromium, copper, ion, mercury, iridium, manganese, molybdenum, nickel, osmium, palladium, rhenium, rhodium, ruthenium, antimony, thallium, tin and vanadium.

The anodic electrode is preferably a platinum electrode.

In a preferred aspect, the acid form of the carboxylate has a first pKa, and the anolyte solution further includes an acid having a second pKa wherein the second pKa exceeds the first pKa.

Preferably, the carboxylate and the acid having the second p& are solubilized in the solution and the carboxylate is provided in solution in a stoichiometric amount equal to at least half that of the hydrazine derivative, but more preferably to at least 60% that of the hydrazine derivative, or at least 70% that of the hydrazine derivative, or 80% that of the hydrazine derivative, or 90% that of the hydrazine derivative, or the carboxylate can be present in a stoichiometric amount about equal to that of the hydrazine derivative, or it could be said, in an amount at least as great as that of the hydrazine derivative.

Usually, the acid form of the carboxylate has the formula RCO2H wherein R is an organic group. According to a preferred aspect, the acid for of the carboxylate has the formula RCO2H wherein R is an alkyl group or a haloalkyl group.

The first pKa is preferably in the range of about −2 to about +7, more preferably in the range of about −1 to about +6, more preferably in the range of about 0 to about +5. The first pKa can be about 0.3 first pKa, or it can be about 2.8, or the first pKa can be about 4.8. The carboxylate can be one or more of acetate, trifluoroacetate, and monochloroacetate.

The acid is preferably an ammonium acid and the second pKa preferably exceeds the first pKa by at least 2. The ammonium acid typically has the wherein each of R1, R2 and R3 is an organic group or hydrogen. Commonly, each of R1, R2 and R3 of the ammonium acid is an alkyl group (e.g., methyl, ethyl, propyl, butyl and pentyl) or hydrogen. In a specifically disclosed aspect of the invention, the acid having the second pKa is triethylammonium.

In another aspect, the anolyte solution includes a counterion to the carboxylate, the counterion having the formula R1R2R3 R4 N+ wherein each of R1, R2, R3, and R4 is an organic group selected from the group described in connection with R1, R2 and R3 of R1R2R3NH+.

The contacting step is preferably carried out in an anodic half cell divided from and operatively linked to a cathodic half cell. Preferably, the half cells are linked by an ion permselective diaphragm. The diaphragm is preferably made up of a synthetic polymer having anions affixed (usually covalently bonded) thereto. A preferred anion is perfluorosulfonate. A commercially available diaphragm suitable for many aspects of the invention is that sold under the name Nafion.

In one aspect of the invention, compound II, V, or VII, as the case may be, has a more positive potential than the voltage at which the contacting step is conducted.

Compound III preferably has first and second peak potentials, each of which potentials is between about 0 and 3 volts against Ag/AgCl, more preferably between about 1 and 2 volts.

Preferably, the mole ratio of the compound having formula III to the compound having formula II, V, or VII, as the case may be, is from about 1:1 to about 1000:1; more preferably between 500:1 and 1:1; more preferably between about 100: and 1:1; more preferably between about 25:1 and 1:1; more preferably between about 10:1 and 1:1; more preferably between about 5:1 and 1:1, more preferably between about 2:1 and 1:1.

The process can be carried out such that the electric potential applied during the contacting step is applied for a period between about 1 minute and 10 hours.

In another aspect the invention is a process of addition of a nitrogen across a multiple bond of an organic molecule wherein a first atom of the multiple bond is a carbon atom, and the second atom is selected from the group of carbon, oxygen and nitrogen, the improvement comprising electrochemically generating the nitrogen for the addition from a primary hydrazine derivative in the presence of a carboxylate anion. It is preferred here that the nitrogen is generated from a compound having the structure indicated by formula III, as defined above and that the organic molecule has the structure indicated by formula I formula VII.

Another process of the invention is addition of a nitrogen to a heteroatom of an organic molecule wherein the heteroatom forms a double bond with an oxygen atom and is a P, S, Se or Te atom, the improvement comprising electrochemically generating the nitrogen for the addition from a primary hydrazine derivative in the presence of a carboxylate anion. Again, the nitrogen is preferably generated from a compound having the structure indicated by formula III, as defined above and the organic molecule has the structure indicated by formula V.

Another aspect of the invention is a process for electrochemically generating a nitrene. The process includes exposing a hydrazine derivative contained in an anolyte solution of an electroytic cell to the anode of the cell in the presence of a carboxylate ion, wherein one of the nitrogens of the hydrazine group is a primary amino group.

Preferably, the anolyte solution is substantially free of a metal catalyst, particularly a toxic metal catalyst.

Preferably, the anode a platinum electrode.

Preferably, an acid form of the carboxylate has a first pKa, and the anolyte solution further comprises an acid having a second pKa wherein the second pKa exceeds the first pKa, and the carboxylate and acid (or counterion to the carboxylate) are selected as described above.

Preferably, the carboxylate and the acid having the second pKa are solubilized in the solution and the carboxylate is provided in solution in a stoichiometric amount equal to at least half that of the hydrazine derivative, but more preferably to at least 60% that of the hydrazine derivative, or at least 70% that of the hydrazine derivative, or 80% that of the hydrazine derivative, or 90% that of the hydrazine derivative, or the carboxylate can be present in a stoichiometric amount about equal to that of the hydrazine derivative, or it could be said, in an amount at least as great as that of the hydrazine derivative.

In this process for generating a nitrene, the hydrazine derivative can be a molecule having the structure indicated as formula III as described above, and the anolyte solution can be a solvent as described above.

In another aspect, the invention is an apparatus for electrochemical generation of a nitrene. The apparatus includes an anodic half cell operatively linked to a cathodic half cell, and an anolyte solution comprising a carboxylate anion and a primary hydrazine derivative.

Preferably, the half cells are linked by an ion permselective diaphragm. A preferred diaphragm is a synthetic polymer having anions affixed thereto, as by covalent bonding, and the anions can include perfluorosulfonate groups. A commercially available diaphragm suitable for use according to many processes of the invention is a Nafion membrane.

The hydrazine of the apparatus includes any of those having formula III, as described above.

Preferably, the anolyte solution is substantially free of a metal catalyst

Preferably, the anode of the apparatus is a platinum electrode.

Preferably, the an acid form of the carboxylate of the apparatus has a first pKa, and the anolyte solution includes an acid having a second pKa wherein the second pKa exceeds the first pKa. The carboxylate and counterion included in the apparatus can be selected and included in the apparatus as described above.

An apparatus of the invention can be used for nitrene generation, an aziridination, sulfoximation, or other nitrogen addition to a suitable organic substrate.

Another aspect of the invention is a process for screening an olefin for electrochemical aziridination of an olefin with a hydrazine derivative, the process comprising the steps of:

    • providing the olefin;
    • determining the redox potential of the olefin at a predetermined voltage at which the aziridine derivative is oxidized, wherein a said olefin determined to have a less positive potential than the predetermined voltage is eliminated as a candidate for electrochemical aziridination by the hydrazine derivative.

In another aspect, the invention is a process for screening an olefin for electrochemical aziridination of an olefin with a hydrazine derivative, the process comprising the steps of:

    • providing the olefin;
    • determining the redox potential of the olefin at a predetermined voltage at which the aziridine derivative is oxidized, wherein a said olefin determined to have a more positive potential than the predetermined voltage is selected as a candidate for electrochemical aziridination by the hydrazine derivative.

Preferably, the hydrazine derivative has first and second peak potentials, each of which potentials is between about 0 and 3 volts against Ag/AgCl, more preferably between about 1 and 2 volts.

BRIEF DESCRIPTION OF THE DRAWINGS

Reference is made to the attached drawings, in which:

FIG. 1 shows cyclic voltammetry (CV) of N-aminophthalimide (dashed line) and cyclohexene (solid line) in acetonitrile with 0.1 M HEt3NOAc on platinum electrode; y-axis: current, 10−6 A, x-axis: potential vs Ag/AgCl, V;

FIG. 2 shows Scheme 1, electrochemical aziridination of olefins;

FIG. 3 shows five olefins which did not undergo electrochemical aziridination;

FIG. 4 shows cyclic voltammetry of N-aminophthalimide (dashed line) and cyclohexene (solid line) in acetonitrile with 0.1 M HEt3NOAc on glassy carbon electrode; y-axis: current, 10−6 A, x-axis: potential vs Ag/AgCl, V;

FIG. 5 shows cyclic voltammetry of N-aminophthalimide (dashed line) and tetramethylene sulfoxide (solid line) in acetonitrile with 0.1 M HEt3NOAc on platinum electrode; y-axis: current, 10−6 A, x-axis: potential vs Ag/AgCl, V;

FIG. 6 shows cyclic voltammetry of N-aminophthalimide (dashed line) and tetramethylene sulfoxide (solid line) in acetonitrile with 0.1 M HEt3NOAc on glassy carbon electrode; y-axis: current, 10−6 A, x-axis: potential vs Ag/AgCl, V;

FIG. 7 shows Scheme 2, electrochemical sulfoximination;

FIG. 8 shows Scheme 3, a proposed mechanism for Pb(OAc)4-mediated aziridination; and

FIG. 9 shows Scheme 4, a proposed mechanism for electrochemical oxidation of N-aminophthalimide.

DESCRIPTION OF PREFERRED EMBODIMENTS

General Information

Cyclohexene, 2-cyclohexen-1-one, 2-methyl-2-pentene, 3-bromo-2-methyl-1-propene, methyl trans-cinnamate, cyclooctene, isoprene, trans-chalcone, 4-hexen-3-one, dimethyl fumarate, dimethyl maleate, cinnamyl alcohol, hydrazine monohydrate, phthalimide, cis- and trans-1,2-dichlorobutene, methyl p-tolyl sulfoxide, phenyl sulfoxide, phenyl vinyl sulfoxide, tetramethylene sulfoxide, benzyl phenyl sulfide, thiophenol, acrylonitrile, tetrabutylammonium hydroxide, 3-chloroperoxybenzoic acid (mCPBA), anisole, sodium benzenesulfinate, thionyl chloride, benzoylchloride, and triethylamine were purchased from Aldrich Chemical Company. DMSO was purchased from BDH Inc., Canada. Anhydrous aluminum chloride was purchased from Anachemia Canada Inc. Column chromatography was carried out using 230-400 mesh silica gel. 1H NMR spectra were referenced to residual CHCl3 (δ 7.26 ppm) and 13C spectra were referenced to CDCl3 (δ 77.2 ppm). Cyclic voltammetry characterization was conducted on a BAS CV-50W Voltammetric Analyzer (Bioanalytical Systems, Inc.) equipped with a BAS C3 three-electrode cell stand. A three-compartment (anodic: 2.0 cm dia.×10 cm; cathodic: 2.0 cm dia.×10 cm; reference: 1.0 cm dia×7 cm) divided cell with glass frit (medium pore size) separators was used for electrochemical aziridination of olefins and imination of sulfoxides. HPLC analysis was performed on a Hewlett Packard Series 1100 HPLC system with a Daicel Chiralcel AS column.

N-aminophthalimide7: Hydrazine monohydrate (4.4 g) in 95% ethanol (80 mL) was treated with powdered phthalimide (12 g) and the mixture was stirred at room temperature for 2 min. The resulting spongy mass was quickly heated and refluxed for 3 min. while ammonia was evolved. Cold water (250 mL) was added at once and N-aminophthalimide crystallized during an hour. Recrystallization from 95% ethanol gave white needles (5.6 g, 43%, Mp 223-224° C.).

Electrochemical Aziridination of Cyclohexene

The anodic compartment was charged with 82 mg (1.0 mmol) cyclohexene, 210 mg (1.3 mmol) N-aminophthalimide, 60 mg (1.0 mmol) acetic acid (glacial), 101 mg (1.0 mmol) triethylamine, and 20 mL acetonitrile. Portions of 0.05 M AcOH in MeCN were added to the cathodic (20 mL) and reference (4 mL) compartments. Platinum foils (2.5×2.5 cm, 99.99%) were used as working and auxiliary electrodes. Silver wire (1.5 mm dia., 99.99%) was used as a pseudo-reference electrode. The electrolysis was performed at +1.80 V (with an AMEL potentiostat, Model 2049) at ambient temperature and was stopped when the cell current dropped to less than 5% of its original value. The contents of anodic compartment were collected and concentrated in vacuo. The residue was washed with water and extracted with dichloromethane (3×5 mL). The organic phases were combined, dried over MgSO4, concentrated, charged onto a silica gel column, and eluted using EtOAc/hexane (1:3) which afforded 7-phthalimido-7-azabicyclo[4.1.0]heptane (1) as a yellow solid (223 mg, 85%).

Electrochemical aziridination of each of the olefin substrates listed in Table 1 was carried out, and products isolated, under similar conditions, except that for the aziridination of isoprene, which was carried out at 0° C. to avoid evaporation of isoprene.

The compounds were characterized as indicated below.

7-Phthalimido-7-azabicyclo[4.1.0]heptane (1): 1H NMR (CDCl3) δ: 7.24-7.75 (m, 4H), 2.72-2.75 (m, 2H), 2.20-2.30 (m, 2H), 1.90-2.10 (m, 2H), 1.20-1.50 (m, 4H). Mp 132-133° C. (lit.8 133-136° C.).

7-Phthalimido-7-aiabicyclo[4.1.0]heptan-2-one (2): 1H NMR (CDCl3) δ: 7.60-7.90 (m, 4H), 3.42-3.46 (m, 1H), 3.07 (d, 1H, J=7.2 Hz), 2.49-2.56 (m, 2H), 1.60-2.15 (m, 4H). 13C NMR (CDCl3) δ: 202.91, 164.31, 134.00, 129.90, 122.98, 48.86, 45.97, 36.77, 21.78, 18.03. HRMS 256.0841 (Calc. 256.0848 for C14H12N2O3). Mp 75-77° C.

1-Phthalimido-2-ethyl-3,3-dimethylaziridine (3): 1H NMR (CDCl3) δ: 7.64-7.76 (m, 4H), 2.74 (t, 2H, J=7.0 Hz), 1.78-1.90 (m, 1H), 1.48-1.61 (m, 1H), 1.39 (s, 3H), 1.27 (s, 3H), 1.14 (t, 1H, J=7.3 Hz). 13C NMR (CDCl3) δ: 166.35, 134.01, 130.90, 122.95, 54.38, 47.92, 22.10, 21.07, 19.22, 11.50. HRMS 244.1209 (Calc. 244.1212 for C14H16N2O2).

1-Phthalimido-2-bromomethyl-2-methylaziridine (4): 1H NMR (CDCl3) δ: 7.65-7.85 (m, 4H), 3.77 (dd, 0.78H, J=10.5, 1.0 Hz), 3.73 (dd, 0.22H, J=10.5, 1.8 Hz), 3.27 (d, 0.78H, J=10.5 Hz), 3.17 (d, 0.22H, J=10.5 Hz), 2.93 (dd, 0.78H, J=1.0, 3.0 Hz), 2.89 (d, 0.22H, J=2.7 Hz), 2.64 (m, 0.22H), 2.61 (d, 0.78H, J=3.0 Hz). 13C NMR (CDCl3) δ: 165.95, 134.45, 134.36, 130.62, 123.39, 123.31, 46.25, 43.20, 39.24, 15.97. HRMS 294.0018 (Calc. 294.0004 for C12H11BrN2O2). Mp 81-82° C.

1-Phthalimido-3-phenyl-2-aziridine carboxylic acid methyl ester (5): 1H NMR (CDCl3) δ: 7.60-7.80 (m, 4H), 7.30-7.50 (m, 5H), 4.37 (d, 1H, J=5.1 Hz), 3.72 (s, 3H), 3.51 (d, 1H, J=5.1 Hz). 13C NMR (CDCl3) δ: 166.73, 164.65, 134.48, 134.08, 130.19, 128.66, 127.25, 123.13, 52.96, 49.66, 45.96. Mp 141-142° C. (lit.9 144° C.).

9-Phthalimido-9-azabicyclo[6.1.0]nonane (6): 1H NMR (CDCl3) δ: 7.65-7.80 (m, 4H), 2.52-2.56 (m, 4H), 1.20-1.80 (m, 10H). 13C NMR (CDCl3) δ: 165.19, 133.96, 130.60, 122.91, 48.05, 26.54, 26.47, 25.45. Mp 88-89° C. (lit.10 89° C.).

1-Phthailmido-2-isopropenylaziridine (7)11: 1H NMR (CDCl3) δ: 7.60-7.80 (m, 4H), 5.13 (m, 1H), 5.05 (quintet, 1H, J=1.5 Hz), 3.04 (t, 1H, J=6.9 Hz), 2.57-2.62 (m, 2H), 1.84 (t, 3H, J=1.5 Hz). 13C NMR (CDCl3) 6:165.01, 140.49, 134.08, 130.35, 123.03, 114.83, 46.72, 37.69, 19.26.

1-Phthalimido-2-benzoyl-3-phenylaziridine (8): 1H NMR (CDCl3) δ: 8.05-8.15 (m, 2H), 7.30-7.80 (m, 12H), 4.69 (d, 1H, J=4.8 Hz), 4.39 (d, 1H, J=4.8 Hz). 13C NMR (CDCl3) δ: 190.39, 164.50, 137.25, 135.15, 133.95, 133.59, 130.19, 128.74, 128.73, 128.66, 128.57, 127.20, 123.10, 50.73, 48.77. Mp 121-123° C. (lit.12 124° C.).

1-Phthalimido-2-methyl-3-propionylaziridine (9): 1H NMR (CDCl3) δ: 7.55-7.80 (m, 4H), 3.38 (quintet, 0.83H, J=5.7 Hz), 3.31 (d, 0.17H, J=5.4 Hz), 3.22 (d, 0.85H, J=5.1 Hz), 2.95-3.12 (m, 1H), 2.63-2.76 (m, 1.17H), 1.50 (d, 0.83H, J=5.7 Hz), 1.42 (d, 0.17H, J=5.4 Hz), 1.13 (t, 0.17H, J=7.2 Hz), 1.04 (t, 0.83H, J=7.2 Hz). 13C NMR (CDCl3) δ: 202.33, 164.91, 134.36, 133.98, 130.35, 123.32, 123.07, 49.88, 45.22, 37.94, 16.81, 7.81. HRMS 258.0994 (Calc. 258.1004 for C14H14N2O3). Mp 102-103.5° C.

trans-1-Phthalimido-2,3-aziridine dicarboxylic acid dimethyl ester (10)13: 1H NMR (CDCl3) δ: 7.65-7.80 (m, 4H), 3.97 (d, 1H, J=4.8 Hz), 3.87 (s, 3H), 3.75 (s, 3H), 3.61 (d, 1H, J=4.8 Hz). 13C NMR (CDCl3) δ: 166.60, 165.34, 164.10, 134.34, 130.05, 123.49, 53.56, 53.41, 44.94, 42.94. Mp 149-150° C. X-ray data for 10 (recrystallized from chloroform/hexane): C14H12N2O6, MW=304.26, pale yellow prismatic crystal, crystal size 0.35×0.34×0.25 mm3, orthorhombic, space group Pbca, a=7.3819(2) A, b=16.9618(7) Å, c=22.3703(8) Å, V=2800.99(17) Å3, Z=8, dcalc=1.443 g/cm3, F(000)=1264, μ=0.115 mm−1, T=150(1) K, 13499 reflections collected, 2447 independent reflections, R=0.0435, Rw=0.1021, GOF on F2=1.020.

1-Phthalimido-2-hydroxymethyl-3-phenylaziridine (11): 1H NMR (CDCl3) δ: 7.15-7.45 (m, 5H), 7.65-7.80 (m, 4H), 4.15-4.35 (m, 1H), 4.02-4.10 (m, 0.36H), 3.80-3.90 (m, 0.64H), 3.40-3.60 (m, 1.36H), 3.18-3.22 (m, 0.64H), 2.57 (t, 0.36H, J=6.0 Hz), 2.69 (bs, 0.64H). 13C NMR (CDCl3) δ: 166.63, 135.82, 134.59, 134.04, 130.49, 129.51, 128.85, 128.67, 128.29, 128.25, 127.30, 123.51, 123.03, 62.31, 59.30, 52.42, 48.96, 46.65, 46.29. HRMS 294.1000 (Calc. 294.1004 for Cl7H14N2O3). Mp 141-142° C.

1-Phthalimido-2-phenyl-3-aziridine acetic acid methyl ester (12): 1H NMR (CDCl3) δ: 7.20-7.80 (m, 9H), 4.34 (dd, 0.47H, J=1.6, 5.6 Hz), 3.89 (d, 0.53H, J=5.6 Hz), 3.76 (s, 1.41H), 3;71 (s, 1.59H), 3.66 (d, 0.47H, J=1.6 Hz), 3.05-3.23 (m, 1.53H), 2.50-2.70 (m, 1H). 13C NMR (CDCl3) δ: 170.85, 170.73, 166.13, 136.35, 135.26, 134.44, 134.03, 130.99, 130.60, 129.71, 128.87, 128.63, 128.27, 128.17, 127.41, 124.58, 123.32, 122.98, 52.32, 52.17, 51.56, 48.40, 45.53, 41.05, 37.49, 33.36. HRMS 336.1097 (Calc. 336.1110 for Cl9H16N2O4). Mp 113-115° C.

1-Phthalimido-2-phenylacetoxymethyl-2-aziridine carboxylic acid methyl ester (13, mixture of two diastereomers): 1H NMR (CDCl3) δ: 7.55-7.75 (m, 4H), 7.20-7.45 (m, 5H), 3.66 (s, 1H), 3.54-3.56 (m, 2.33H), 3.48 (d, 0.67H, J=1.8 Hz), 2.95 (d, 0.67H, J=1.8 Hz), 2.83 (d, 0.33H, J=2.1 Hz), 2.15 (s, 1H), 2.10 (s, 2H). 13C NMR (CDCl3) δ: 169.28, 169.19, 166.44, 166.18, 164.46, 164.31, 136.55, 135.42, 134.15, 134.00, 130.21, 130.09, 128.70, 128.36, 128.25, 128.20, 127.83, 127.65, 123.45, 123.02, 72.83, 70.80, 53.37, 53.16, 48.69, 39.57, 38.68, 21.15. HRMS 394.1151 (Calc. 394.1165 for C21H18N2O6).

1-Phthalimido-2-phenylhydroxymethyl-2-aziridine carboxylic acid methyl ester (14, mixture of two diastereomers): 1H NMR (CDCl3) δ: 7.60-7.80 (m, 4H), 7.20-7.45 (m, 5H), 5.70 (s, 0.82H), 5.16 (s, 0.181H), 3.80 (b, 1H), 3.64 (d, 0.181H, J=2.1 Hz), 3.61 (s, 2.46H), 3.58 (d, 0.82H, J=1.8 Hz), 3.55 (s, 0.541), 2.91 (d, 0.18H, J=2.1 Hz), 2.85 (d, 0.82H, J=1.8 Hz). 13C NMR (CDCl3) 8:167.01, 165.05, 139.24, 134.34, 130.21, 128.55, 128.51, 128.37, 127.94, 127.71, 126.81, 126.73, 123.69, 123.37, 73.37, 70.11, 53.26, 52.06, 50.98, 40.19. HRMS 352.1062 (Calc. 352.1059 for Cl9H16N2O5).

trans-1-Phthalimido-2,3-bis(chloromethyl)aziridine (15a): 1H NMR (CDCl3) δ: 7.60-7.80 (m, 4H), 4.08 (dd, 2H, J=6.0, 11.7 Hz), 3.54 (dd, 2H, J=8.1, 11.7 Hz), 3.20-3.25 (m, 2H). 13CNMR (CDCl3) δ: 164.75, 134.57, 130.22, 123.52, 48.05, 40.14.

cis-1-Phthalimido-2,3-bis(chloromethyl)aziridine (15b): 1H NMR (CDCl3) δ: 7.60-7.80 (m, 4H), 4.00-4.06 (m, 2H), 3.45-3.60 (m, 3H), 2.98 (dt, 1H, J=5.1, 7.5 Hz). 13C NMR (CDCl3) δ: 165.85, 134.62, 130.48, 123.56, 47.03, 46.48, 43.50, 40.67.

1-Phthalimido-2-phenyltosylaminomethyl-2-aziridine carboxylic acid methyl ester (16): 1H NMR (CDCl3) δ: 7.65-7.80 (m, 4H), 7.63 (d, 2H, J=12.5 Hz), 7.38 (d, 1H, J=8.2 Hz), 7.18 (bs, 5H), 7.13 (d, 2H, J=12.5 Hz), 5.49 (d, 1H, J=8.2 Hz), 3.50 (s, 3H), 3.48 (d, 1H, J=3.1 Hz), 2.35 (s, 3H), 2.12 (d, 1H, J=3.1 Hz). 13C NMR (CDCl3) δ: 166.82, 165.43, 142.58, 138.93, 136.34, 134.48, 130.14, 129.21, 128.37, 128.29, 128.11, 127.26, 123.56, 56.56, 53.44, 49.09, 41.91, 21.55. X-ray data for 16 (recrystallized from chloroform/hexane): C26H23N3O6S, MW=505.53, colorless prismatic crystal, crystal size 0.29×0.28×0.28 mm3, triclinic, space group P1, a=7.9575(1) Å, α87.6210(10)°, b=8.8478(1) Å, β=79.6990(10)°, c=17.3936(3) Å, γ=73.6590(10)°, V=1156.16(3) Å3, Z=2, dcalc=1.452 g/cm3, F(000)=528, μ=0.190 mm−1, T=150(1) K, 13257 reflections collected, 5282 independent reflections, R=0.0448, Rw=0.0949, GOF on F2=1.045.

Sulfoxide Syntheses

2-Cyanoethyl phenyl sulfoxide: A modified literature procedure14 was used to make this compound. Thiophenol (1.10 g, 10 mmol) was added dropwise to a mixture of acrylonitrile (1.06 g, 20 mmol) and tetrabutylammonium hydroxide (40 wt % aq. 0.1 mL) dissolved in dichloromethane (50 mL). The reaction mixture was stirred at room temperature for 2 hours and concentrated in vacuo. The residue was charged onto a silica gel column and eluted with EtOAc/hexane to afford 2-cyanoethyl phenyl sulfide (1.50 g, 92%) as a colorless oil. 1H NMR (CDCl3) δ: 2.59 (t, 2H, J=7.2 Hz), 3.13 (t, 2H, J=7.2 Hz), 7.30-7.45 (m, 5H). 13C NMR (CDCl3) δ: 18.59, 30.58, 127.68, 129.32, 131.37, 133.10. The sulfide (815 mg, 5 mmol) was dissolved in 20 mL DCM and mCPBA (57-86%, 2 g) was added. The reaction mixture was stirred at room temperature for 5 hours and concentrated in vacuo. The residue was washed with saturated aqueous NaHCO3 and extracted with DCM (3×10 mL). The organic phases were combined, dried over MgSO4, concentrated, and charged onto a silica gel column, which was eluted with EtOAc/hexane. 2-Cyanoethyl phenyl sulfoxide was obtained as a white solid (770 mg, 86%). 1H NMR (CDCl3) δ: 2.40-2.60 (m, 11), 2.80-3.00 (m, 2H), 3.10-3.30 (m, 1H), 7.40-7.60 (m, 5H). 13CNMR (CDCl3) δ: 9.95, 50.48, 123.89, 129.59, 131.72, 141.22. Mp 61-62° C. (lit.15 64-65° C.).

4-Methoxydiphenyl sulfoxide: A modified literature procedure16 was used to prepare this compound. To a well stirred suspension of sodium benzenesulfinate (5.41 g, 30 mmol, dried at 100° C. for 2 h.) in cold (ice water bath) dry toluene (30 mL) was added dropwise thionyl chloride (2.98 g, 25 mmol). The reaction mixture was allowed to warm up to room temperature and stirred overnight. Toluene was removed by applying high vacuum (0.5 mmHg) and crude bezenesulfinyl chloride was dissolved in dry DCM (20 mL), cooled to 0-5° C., and was added dropwise to a mixture of anisole (3.24 g, 30 mmol) and anhydrous aluminum chloride (4.0 g, 30 mmol) in DCM (20 mL) at 0-5° C. under nitrogen. This mixture was stirred at 0-5° C. for 3 hours. Water was added slowly and organic phase separated, dried over MgSO4, filtered and concentrated in vacuo to give a pale yellow oil. A hexane wash of the crude material afforded the sulfoxide as a white solid (4.76 g, 82%). 1H NMR (CMCl3) δ: 3.81 (s, 3H), 6.95 (d, 2H, J=9.0 Hz), 7.40-7.48 (m, 3H), 7.55 (d, 2H, J=9.0 Hz), 7.56-7.62 (m, 2H). 13C NMR (CDCl3) δ: 55.74, 114.84, 124.58, 127.21, 129.16, 130.69, 136.78, 145.77, 161.88. Mp 85-86° C. (lit.17 86-89° C.).

Preparation of (R)-methyl p-tolyl suffoxide18 and 18: To a solution of (R)-binaphthol (0.10 mmol) in carbon tetrachloride were added Ti(OiPr)4 (0.050 mmol) and H2O (1.0 mmol) under aerial conditions. After the resulting brown solution was stirred at room temperature for 1 h, methyl p-tolyl sulfide (1.0 mmol) was introduced by a syringe, followed by TBHP (2.0 mmol, 5.0-6.0 M in decane), and the mixture was stirred open to air for 7 h. The reaction mixture was directly submitted to column chromatography with silica gel using 1:1 hexane/ethyl acetate as eluent. HPLC analysis on a Daicel Chiralcel AS column (3:7 iPrOH/hexane, 1.0 mL/min.) gave 93% ee of the R-enantiomer. Electrochemical sulfoximination of this sample was carried out under above conditions and HPLC analysis of the product 18 on AS column (3:7 iPrOH/hexane, 0.50 ml/min.) gave the ee value of 97%.

Electrochemical Sulfoximination Procedure

For the sulfoxide substrate corresponding to each sulfoximine listed in Table 2, the following procedure was followed. The anodic compartment was charged with 1.0 mmol sulfoxide, 210 mg (1.3 mmol) N-aminophthalimide, 78 mg (1.3 mmol) acetic acid (glacial), 130 mg (1.3 mmol) triethylamine, and 20 mL acetonitrile. Portions of 0.05 M AcOH in MeCN were added to the cathodic (20 mL) and reference (4 mL) compartments. Platinum foils (2.5×2.5 cm, 99.99%) were used as working and auxiliary electrodes. Silver wire (1.5 mm dia., 99.99%) was used as a pseudo-reference electrode. The electrolysis was performed at +1.80 V at ambient temperature and was stopped when the cell current dropped to less than 5% of its original value. The contents of anodic compartment were collected and concentrated in vacuo. The residue was washed with water and extracted with dichloromethane (3×5 mL). The organic phases were combined, dried over MgSO4, concentrated, charged onto a silica gel column, and eluted using EtOAc/hexane to afford sulfoximine. The isolated products were characterized, as indicated below.

N-Phthalimido-S,S-dimethylsuffoximine (17):19 1H NMR (CDCl3) δ: 3.29 (s, 6H), 7.67-7.71 (m, 2H), 7.79-7.82 (m, 2H). 13C No (CDCl3) δ: 41.39, 123.38, 130.74, 134.15, 167.44. Mp 205-206° C. (lit.20 208-210° C.).

N-Phthalimido-S-methyl-S-Tolyl)sulfoximine (18):21 1H NMR (CDCl3) δ: 2.43 (s, 3H), 3.33 (s, 3H), 7.35 (d, 2H, J=8.4 Hz), 7.63-7.76 (m, 4H), 8.09 (d, 2H, J=8.4 Hz). 13C NMR (CDCl3) δ: 21.90, 42.86, 123.21, 129.61, 130.08, 130.80, 133.33, 133.91, 145.49, 167.06. Mp 167-169° C. X-ray data for (R)-18 (recrystallized from toluene): C16H14N2O3S, MW=314.35, colorless prismatic crystal, crystal size 0.30×0.12×0.10 mm−1, orthorhombic, space group P21/21/21, a=7.9615(2) Å, b=9.9599(2) Å, c=38.3334(10) Å, V=3039.68(13) Å3, Z=8, dcalc=1.374 g/cm3, F(000)=1312, μ=0.227 mm−1, T=150(1) K, 12041 reflections collected, 6335 independent reflections, R=0.0614, Rw=0.0936, GOF on F2=1.022.

N-Phthallmido-S,S-diphenylsulfoximine (19):22 1H NMR (CDCl3) δ: 7.46-7.58 (m, 6H), 7.60-7.62 (m, 2H), 7.72-7.74 (m, 2H), 8.22-8.28 (m, 4H). 13C NMR (CDCl3) δ: 123.17, 129.36, 129.59, 130.83, 133.82, 133.85, 137.45, 166.81. Mp 218-219° C. (lit. 220-221° C.).

N-Phthalimido-S-phenyl-vinylsulfoximine (20):22 1H NMR (CDCl3) δ: 6.19 (dd, 1H, J=0.9, 9.3 Hz), 6.54 (dd, 1H, J=0.9, 16.5 Hz), 6.86 (dd, 1H, J=9.3, 16.5 Hz), 7.50-7.90 (m, 7H), 8.20-8.30 (m, 2H). 13C NMR (CDCl3) 6:123.27, 129.50, 1-29.57, 130.86, 131.99, 133.98, 134.39, 135.24, 135.93, 167.00. Mp 138-140° C. (lit.20 136-137° C.).

N-Phthalimido-S-benzyl-S-phenylsulfoximine (21): 1H NMR (CDCl3) δ: 4.65 (d, 1H, J=20.7), 4.78 (d, 1H, J=20.7), 7.01-7.94 (m, 14H). 13C NMR (CDCl3) S: 61.19, 123.29, 127.19, 128.65, 129.01, 129.18, 130.67, 130.98, 131.32, 133.89, 134.01, 134.29, 167.33. HRMS 376.0885 (Calc. 376.0882 for C21H16N2O3S). Mp 153-155° C.

N-Phthalimido-S-(2-cyanoethyl)S-phenylsulfoximine (22): 1H NMR (CDCl3) 6:3.01 (t, 2H, J=11.1 Hz), 3.64 (dt, 1H, J=21.5, 11.1 Hz), 3.87 (dt, 1H, J=21.5, 11.1 Hz), 7.64-7.78 (m, 7H), 8.22 (d, 2H, J=11.7 Hz). 13C NMR (CDCl3) S: 12.63, 50.01, 115.90, 123.43, 129.95, 130.11, 130.74, 133.90, 134.22, 135.32, 166.98. HRMS 339.0670 (Calc. 339.0678 for C17H13N3O3S).

N-Phthalimido-S-(4-methoxyphenyl)S-phenylsulfoximine (23): 1H NMR (CDCl3) δ: 3.83 (s, 3H), 6.97 (d, 2H, J=9.3 Hz), 7.48-7.74 (m, 7H), 8.17-8.22 (m, 4H). 13C NMR (CDCl3) δ: 55.83, 114.78, 123.22, 127.86, 129.27, 129.35, 130.85, 132.02, 133.62, 133.92, 138.07, 164.13, 167.07. HRMS 392.0817 (Calc. 392.0831 for C21H16N2O4S).

N-Phthalimidotetramethylene sulfoximine (24): 1H NMR (CDCl3) δ: 2.33-2.44 (m, 4H), 3.14-3.28 (m, 21′), 3.64-3.78 (m, 2H), 7.60-7.90 (m, 4H). 13C NMR (CDCl3) δ: 24.09, 52.90, 123.37, 130.92, 134.16, 167.56. Mp 179-180° C. HRMS 264.0567 (Calc. 264.0569 for C12H12N2O3S).

Electrochemical Aziridination of Olefins.

Recently, Compton and coworkers23 showed that an electrochemical redox cycle involving Pb(IV) and Pb(II) can be realized. The cyclic voltammetry (CV) of Pb(OAc)2 in acetonitrile was found to give a value of +1.60 V (vs. Ag/AgCl) for the oxidation potential of Pb(II) to Pb(IV),23 whereas the CV of N-aminophthalimide (0.01 M in acetonitrile) shows two irreversible one-electron oxidation processes with anodic peak potentials at +1.35 V and at +1.68 V (vs. Ag/AgCl). Using 10 mol % Pb(OAc)2, the electrochemical aziridination of cyclohexene with N-aminophthalimide was conducted at a constant potential of +1.60 V, and gave a 75% isolated yield of 1.

Furthermore, the CV of cyclohexene24 (0.01 M in acetonitrile) has been found to produce an anodic current of −1.3 μA at +1.68 V (vs Ag/AgCl), which is only a small fraction of the current recorded for N-aminophthalimide (−152 μA, FIG. 1). This indicates that the background oxidation of olefins on a platinum electrode is kinetically disfavored due to olefin overpotential. It was found that a simple combination of platinum electrodes, triethylamine, and acetic acid leads to a room temperature nitrene transfer from N-aminophthalimide to cyclohexene (Scheme 1 of FIG. 2). The reaction utilized only a small excess of N-aminophthalimide relative to the olefin and can be performed in a divided cell using a silver wire as a pseudo reference electrode.

A variety of olefins were subject of aziridination in this process, as summarized in Table 1. Both electron-rich and electron-poor olefins were converted to aziridines electrochemically. For certain monosubstituted terminal olefins (FIG. 3) the electrochemical aziridination was not found to be successful although the redox behavior of these olefins is similar to that of the others. The cis-olefin dimethyl maleate was also found to be inert towards electrochemical aziridination, while its trans-isomer dimethyl fumarate gave excellent yield of aziridine (Table 1, entry 10). In all cases with inert olefins, N-aminophthalimide was completely converted to phthalimide (precipitated out during the reaction) and the olefins were recovered quantitatively. A possible explanation of this observation is that the nitrene transfer to olefin is either very slow, or it might be reversible. In the first case dimerization of the N-acetoxyamino intermediate (Scheme 2 of FIG. 7) predominates to give phthalimide as product. In the latter case the aziridine product could be produced to then quickly decompose to give back the nitrene intermediate which may also undergo a dimerization process affording the more stable product phthalimide.

The aziridination reaction was found not to take place when a graphite electrode was used. The CV study on carbon electrode revealed that anodic current corresponding to the oxidation cyclohexene (−5.3 μA at +1.68 V) was comparable to that of N-aminophthalimide (−15.6 μA at +1.68 V). Such small difference in the rate of electrochemical oxidation apparently does not secure high selectivity in olefin aziridination.

Electrochemical Imination of Sulfoxides

Imination of sulfoxides, to obtain the corresponding sulfoximines, with N-aminophthalimide is known to be mediated by Pb(OAc)4.25 As mentioned above, the CV of N-aminophthalimide (0.01 M in acetonitrile) on a platinum electrode (FIG. 5) shows two irreversible one-electron oxidation processes with anodic peak potentials at +1.35 V and +1.68 V (vs Ag/AgCl). At +1.68 V, tetramethylene sulfoxide (0.01 M in acetonitrile) produces a considerably smaller anodic current of −7.52 μA than the current observed for N-aminophthalimide (−152 μA), suggesting a relatively kinetically sluggish background oxidation of sulfoxides on a platinum electrode.

The nature of electrode material was found to be important the electrochemical transfer process. The CV (FIG. 6) of tetramethylene sulfoxide (0.01 M in acetonitrile) on a glassy carbon electrode showed two irreversible oxidation processes with peak potentials at +1.64 V and +1.82 V and a much higher anodic current (−272 μA) than that of N-aminophthalimide at +1.68 V (−15.6 μA). Thus, bulk electrolysis of tetramethylene sulfoxide in the presence of N-aminophthalimide on a graphite anode gave tetramethylene sulfone as the major product with no evidence of sulfoximine formation.

On the platinum anode, the electrolysis conditions were similar to those of aziridination (Scheme 2 of FIG. 7). A small excess of N-aminophthalimide relative to the sulfoxide was used. The electrolysis was performed in a divided cell using a silver wire as a pseudo-reference electrode, which was calibrated against the ferrocene/ferricinium couple in the electrolysis medium (Epa=0.47 V, Epc=0.30 V). No special precautions to exclude moisture or air were taken. The reaction was stopped when the cell current dropped to less than 5% of its original value. Imination of a variety of sulfoxide substrates was achieved, as shown in Table 2. For sulfoxide 20 (Table 2, entry 4), no aziridination product was observed, indicating the possibility to achieve chemoselective nitrene transfer to the sulfoxide moiety. There was no evidence for the background formation of sulfone by-product. The oxidative imination of sulfides (resulting in sulfimines) was also performed using the same methodology. However, a mixture of products consisting mainly of sulfoxide and sulfoximine was obtained, presumably, due to the less positive oxidation potential of sulfides compared to N-aminophthalimide.

Furthermore, this electrochemical nitrene transfer process was found to be stereospecific. An enantiomerically enriched (93% ee of the R-enantiomer)18 sample of methyl p-tolyl sulfoxide was electrolyzed under the conditions described above. The ee value measured for the product sulfoximine 18 was the same (97%) within the error of HPLC analysis and the X-ray structure of the product showed retention of configuration, indicating that no racemization occurred during nitrene transfer process.

Mechanistic Consideration in Electrochemical Aziridination Process

The mechanism of the Pb(OAc)4 mediated olefin aziridination with N-aminophthalimide and other N-amino heterocycles has been studied by Atkinson and coworkers.26 It has been suggested that the oxidation of N-aminophthalimide by Pb(OAc)4 generates an N-acetoxyamino intermediate, which can be isolated or is stable enough to be observed by NMR at low temperature (<5° C.). Addition of olefin at higher temperature to this intermediate results in aziridine (Scheme 3 of FIG. 8). In the absence of olefin, the N-acetoxyamino intermediate dimerizes to generate the tetrazene which then decomposes to phthalimide by extrusion of N2. Fuchigami and coworkers27 have shown that the electrochemical oxidation of N-aminophthalimide using Bu4NBF4 or LiClO4 as supporting electrolyte at 0° C. gave tetrazene as major product and 10-20% of phthalimide. The authors proposed an electrochemically generated N-nitrene intermediate which inserts into the N—H σ-bond of the unoxidized N-aminophthalimide to afford the tetrazane intermediate (Scheme 4 of FIG. 9). The tetrazane is further oxidized to give tetrazene.

Here, the results obtained in the oxidation of N-aminophthalimide in the presence of olefin with supporting electrolytes other than triethylammonium acetate are shown in Table 3. In cases of LiClO4, Bu4NBF4, and Et4NOTs, no aziridine was detected while phthalimide was isolated in high yields (80-85%). The apparent need for a carboxylate anion of some sort, particularly acetate, for aziridine generation implies that a similar N-acetoxyamino intermediate may be involved in this process. This is also evidenced by the correlation between the aziridine yields and acetate concentrations.

More mechanistic evidence has been obtained by comparing the electrochemical and chemical (Pb(OAc)4 mediated) aziridination results, especially in stereochemical aspects. Dreiding and coworkers28 showed that the Pb(OAc)4 promoted aziridination is stereospecific, i.e., E-olefins afford only the trans-aziridines and Z-olefins only the cis-aziridines. Here, the NMR analysis and X-ray structure of 10 showed exclusive formation of a trans-aziridine. The corresponding Z-olefin, dimethyl maleate, was found to give aziridination product, however, electrochemical aziridination of the E- and Z-1,2-dichloro-2-butene and the results showed that this process is also stereospecific (Table 4, entries 2, 3). Furthermore, the diastereoselectivity of the electrochemical and chemical approaches were found to be comparable (Table 4, entries 4, 5). An exclusive syn-aziridine (shown by its X-ray structure) was obtained for 16.

The continuum of accessible electrode potentials provided by electrochemistry enables differentiating substrates based on their overpotentials.

All citations referred to in this document are incorporated herein by reference in their entirety, as though the contents of each such reference was reproduced in its entirety in this document.

The scope of protection sought for any invention described herein is defined by the claims which follow. It will be appreciated by those skilled in the art that a variety of possible combinations and subcombinations of the various compounds obtainable through the processes described herein exist, and all of these combinations and subcombinations should be considered to be within the inventor's contemplation though not explicitly enumerated here. This is also true of the variety of aspects of the processes and the combinations and subcombinations of elements thereof.

TABLE 1 Electrochemical Aziridination of Olefins. product entry Substrate (yield, %) 1 2 3 4 5 6 7 8 9 10 11 12 13 14
areaction at 0° C.

b2:1 ratio of diastereomers.

c4.4:1 ratio of diastereomers.

TABLE 2 Electrochemical Synthesis of N-Phthalimido Sulfoximines. N-phthalimido Entry sulfoximine (yield, %) 1 2 3 4 5 6 7 8

TABLE 3 Cation and Anion Effects on Electrochemical Aziridination with 1.0 mmol Cyclohexene, 1.3 mmol N-Aminophthalimide, and x mmol Supporting Electrolyte. amount of supporting X yield of aziridine phthalimide electrolyte (mmol) (%) (mmol) LiClO4 1.0 0 1.06 Bu4NBF4 1.0 0 1.11 Et4NOTs 1.0 0 1.03 1:1 Et3N/CF3CO2H 1.0 90 0.33 1:1 Et3N/ClCH2CO2H 1.0 87 0.33 Me4NOAc 1.0 85 0.39 Et4NOAc 1.0 81 0.37 Bu4NOAc 1.0 83 0.37 1:1 Et3N/HOAc 0.20 55 0.64 ″ 0.50 69 0.51 ″ 2.0 83 0.40 ″ 5.0 89 0.32

TABLE 4 Comparison of Electrochemical and Chemical Aziridination of Olefins. configuration of product entry Substrate Product electrochemical method (yield, %) chemical methoda 1 transb (92) trans 2 trans (76) trans 3 cis (73) cis 4 4.4:1 d.r. (73) 4.2:1 d.r. 3.8:1 d.r.c 5 synb (78) syn
aAll aziridination reactions with Pb(OAc)4 were studied by NMR in CD3CN. The products were not isolated and their configurations were determined by comparing with the products from electrochemical reactions.

bX-ray structure.

cNMR study in CDCl3.

REFERENCES

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Claims

1. An electrochemical process for the formation of a compound having formula I, the process comprising step of:

contacting a compound having formula II and a compound having formula III,
with each other in an electrolytic cell under conditions of electrolysis sufficient to form the compound of formula I, wherein: (A) A is selected from the group consisting of C, N and O, and (i) when A is a carbon atom, each of R1, R2, R3, and R4 is hydrogen or an organic group; (ii) when A is a nitrogen atom, each of R1, R2, and R3, is hydrogen or an organic group, and R4 is an electron pair; (iii) when A is an oxygen atom, each of R1 and R2 is hydrogen or an organic group, and each of R3 and R4 is an electron pair; and (iv) R5 is NR6R7 and each of R6 and R7 is an organic group.

2. The process of claim 1, wherein A is a carbon atom.

3. The process of claim 1, wherein A is a nitrogen atom.

4. The process of claim 1, wherein A is an oxygen atom.

5. The process of claim 2, 3, or 4, wherein the group of organic groups from which each of R1, R2, R3, and R4 may be selected is the group consisting of alkyl, alkenyl, alkynyl, aryl, and substituted alkyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of alkyl, alkenyl, alkynyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane.

6. The process of claim 5, wherein said group from which each of R1, R2, R3, and R4 may be selected is the group consisting of alkyl, alkenyl, alkynyl, aryl, and substituted alkyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of alkyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.

7. The process of claim 6, wherein said group from which each of R1, R2, R3, and R4 may be selected is the group consisting of alkyl and aryl, and substituted alkyl and aryl, wherein the substituents are selected from the group of alkyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane, and preferably wherein each of R1, R2, R3, and R4 includes up to 20 carbon atoms, more preferably up to 18 carbon atoms, more preferably up to 16 carbon atoms, more preferably up to 14 carbon atoms, or up to 12 carbon atoms, or up to 10 carbon atoms, or up to 8 carbon atoms, or up to 6 carbon atoms.

8. The process of claim 5, 6 or 7, wherein the substituents are selected from the group of halide, ketone, alcohol and ester.

9. The process of any of claims 2 to 8 wherein, when A is a carbon atom, (i) if R3 and P4 are each hydrogen, then each of R1 and R2 is not hydrogen, or the double bond shown in formula II is conjugated with another olefinic double bond, (ii) if a first carbon atom of the double bond shown in formula II is in an α-position with respect to a carbonyl group of R1, then the second carbon atom of the double bond is not in an α-position with respect to a carbonyl group of R3, and (iii) if a first carbon atom of the double bond shown in formula II is in an α-position with respect to a carbonyl group of R2, then the second carbon atom of the double bond is not in an α-position with respect to carbonyl group of R4.

10. The process of any of claims 1 to 9, wherein compound II is selected from the group consisting of cyclohexene, cyclohex-2-enone, 2-methyl-pent-2-ene, 3-bromo-2-methyl-propene, trans-3-phenyl-acrylic acid methyl ester, cyclooctene, 2-methyl-buta-1,3-diene, trans-1,3-diphenylpropenone, trans-hex-4-en-3-one, trans-but-2-enedioic acid dimethyl ester, trans-3-phenyl-prop-2-en-1-ol, trans-4-phenyl-but-3-enoic acid methyl ester, 2-(acetoxy-phenyl-methyl)-acrylic acid methyl ester, 2-(hydroxy-phenyl-methyl)-acrylic acid methyl ester, trans-1,4-dichlorobutene, cis-1,4-dichlorobutene, 2-(phenyl p-toluenesulfonamidomethyl)acrylic acid methyl ester and any derivative thereof obtained by substitution of a hydrogen of a C—H bond with an alkyl, phenyl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane, wherein any said group can itself be substituted with a said group.

11. The process of claim 10, wherein compound II is selected from the group consisting of cyclohexene, cyclohex-2-enone, 2-methyl-pent-2-ene, 3-bromo-2-methyl-propene, trans-3-phenyl-acrylic acid methyl ester, cyclooctene, 2-methyl-buta-1,3-diene, trans-1,3-diphenylpropenone, trans-hex-4-en-3-one, trans-but-2-enedioic acid dimethyl ester, trans-3-phenyl-prop-2-en-1-ol, trans-4-phenyl-but-3-enoic acid methyl ester, 2-(acetoxy-phenyl-methyl)-acrylic acid methyl ester, 2-(hydroxy-phenyl-methyl)-acrylic acid methyl ester, trans-1,4-dichlorobutene, cis-1,4-dichlorobutene, and 2-(phenyl p-toluenesulfonamidomethyl)acrylic acid methyl ester.

12. The process of any of claims 1 to 11, wherein R5 is selected from the group consisting of: wherein each of R8, R9, R10, R11, R12 and R13 is an organic group.

13. The process of claim 12, wherein each of R8, R9, R10, R11, R12 and R13 is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, and substituted alkyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of alkyl, alkenyl, alkynyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane.

14. The process of claim 12, wherein each of R8, R9, R10, R11, R12 and R13 is selected from the group consisting of alkyl, aryl, phenyl and substituted alkyl, aryl and phenyl, wherein the substituents are selected from the group of alkyl, aryl, phenyl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.

15. The process of claim 14, wherein each of R8, R9, R10, R11, R12 and R13 includes up to 20 carbon atoms, more preferably up to 18 carbon atoms, more preferably up to 16 carbon atoms, more preferably up to 14 carbon atoms, or up to 12 carbon atoms, or up to 10 carbon atoms, or up to 8 carbon atoms, or up to 6 carbon atoms.

16. The process of claim 13, 14, or 15, wherein each of the substituents of said substituted alkyl and aryl groups from which R8, R9, R10, R11, R12 and R13 can be selected is selected from the group consisting of halide, ketone, alcohol and ester.

17. The process of any of claims 1 to 16, wherein the compound having formula III is N-aminophthalmide.

18. The process of any of claims 1 to 17, wherein the compound having formula III has a lower oxidation potential than that of a compound having formula II.

19. The process of any of claims 1 to 17 wherein the compound having formula III is oxidized at a faster rate than a compound having formula II under said conditions of electrolysis.

20. The process of any preceding claim, wherein the solvent of the electrolytic cell is a polar non-protic solvent, and particularly wherein the solvent is selected from the group consisting of dichloromethane, acetonitrile, N,N-dimethylformamide, tetrahydrofuran, nitromethane, chloroform, propylene carbonate, and mixtures thereof.

21. An electrochemical process for the formation of a compound having formula IV, the process comprising step of:

contacting a compound having formula V and a compound having formula III,
with each other in an electrolytic cell under conditions of electrolysis sufficient to form the compound of formula IV, wherein: (i) B is selected from the group consisting of P, S, Se and Te; (ii) each of R14 and R15 is hydrogen or an organic group; and (iii) R5 is NR6R7 and each of R6 and R7 is an organic group.

22. The process of claim 21, wherein B is a phosphorus atom.

23. The process of claim 21, wherein B is a sulfur atom.

24. The process of claim 21, wherein B is an selenium atom.

25. The process of claim 21, wherein B is an tellurium atom.

26. The process of claim 22, 23, 24 or 25 wherein each of R14, and R15 may be selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, and substituted alkyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of alkyl, alkenyl, alkynyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane.

27. The process of claim 26, wherein each of R14, and R15 maybe selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, and substituted alkyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of alkyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane and preferably wherein each of R14 and R15 includes up to 20 carbon atoms, more preferably up to 18 carbon atoms, more preferably up to 16 carbon atoms, more preferably up to 14 carbon atoms, or up to 12 carbon atoms, or up to 10 carbon atoms, or up to 8 carbon atoms, or up to 6 carbon atoms.

28. The process of claim 27, wherein each of R14, and R15 may be selected from the group consisting of alkyl and aryl, and substituted alkyl and aryl, wherein the substituents are selected from the group of alkyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.

29. The process of claim 26, 27 or 28, wherein the substituents are selected from the group of halide, ketone, alcohol and ester.

30. The process of any of claims 21 to 29, wherein compound V is selected from the group consisting of compounds VIII to XV, and any derivative of any of compounds VIII to XV obtained by substitution of a hydrogen of a C—H bond with an alkyl, phenyl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane, wherein any said group can itself include such a substituent.

31. The process of claim 30, wherein compound V is selected from the group consisting of compounds VIII to XV.

32. The process of any of claims 21 to 31, wherein R5 is selected from the group consisting of: wherein each of R8, R9, R10, R11, R12 and R13 is an organic group.

33. The process of claim 32, wherein each of R8, R9, R10, R1, R12 and R13 is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, and substituted alkyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of alkyl, alkenyl, alkynyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane.

34. The process of claim 32, wherein each of R8, R9, R10, R11, R12 and R13 is selected from the group consisting of alkyl, aryl, phenyl and substituted alkyl, aryl and phenyl, wherein the substituents are selected from the group of alkyl, aryl, phenyl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.

35. The process of claim 34, wherein each of R8, R9, R10, R11, R12 and R13 includes up to includes up to 20 carbon atoms, more preferably up to 18 carbon atoms, more preferably up to 16 carbon atoms, more preferably up to 14 carbon atoms, or up to 12 carbon atoms, or up to 10 carbon atoms, or up to 8 carbon atoms, or up to 6 carbon atoms.

36. The process of claim 33, 34, or 35, wherein each of the substituents of said substituted alkyl and aryl groups from which R8, R9, R10, R1, R12 and R13 can be selected is selected from the group consisting of halide, ketone, alcohol and ester.

37. The process of any of claims 21 to 36, wherein the compound having formula III is N-aminophthalimide.

38. The process of any of claims 21 to 37, wherein the compound having formula III has a lower oxidation potential than that of a compound having formula II.

39. The process of any of claims 21 to 37 wherein the compound having formula III is oxidized at a faster rate than a compound having formula II under said conditions, of electrolysis.

40. The process of any of claims 21 to 39, wherein the solvent of the electrolytic cell is a polar non-protic solvent, and particularly wherein the solvent is selected from the group consisting of dichloromethane, acetonitrile, N,N-dimethylformamide, tetrahydrofuran, nitromethane, chloroform, propylene carbonate, and mixtures thereof.

41. An electrochemical process for the formation of a compound having formula VI, the process comprising step of:

contacting a compound having formula VII and a compound having formula III,
with each other in an electrolytic cell under conditions of electrolysis sufficient to form the compound of formula VI, wherein: (i) when D is a carbon atom, each of R16 and R17 is hydrogen or an organic group; and (ii) when D is a nitrogen atom, R16 is hydrogen or an organic group, and R17 is an electron pair.

42. The process of claim 41, wherein D is a carbon atom.

43. The process of claim 41, wherein D is a nitrogen atom.

44. The process of claim 42 or 45 wherein each of R16, and R17 may be selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, and substituted alkyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of alkyl, alkenyl, alkynyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane, and preferably wherein each of R16 and R17 includes up to 20 carbon atoms, more preferably up to 18 carbon atoms, more preferably up to 16 carbon atoms, more preferably up to 14 carbon atoms, or up to 12 carbon atoms, or up to 10 carbon atoms, or up to 8 carbon atoms, or up to 6 carbon atoms.

45. The process of claim 44, wherein each of R16, and R17 maybe selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, and substituted alkyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of alkyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.

46. The process of claim 45, wherein each of R16, and R17 may be selected from the group consisting of alkyl and aryl, and substituted alkyl and aryl, wherein the substituents are selected from the group of alkyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.

47. The process of claim 44, 45 or 46, wherein the substituents are selected from the group of halide, ketone, alcohol and ester.

48. The process of any of claims 41 to 47, wherein R5 is selected from the group consisting of: wherein each of R8, R9, R10, R11, R12 and R13 is an organic group.

49. The process of claim 48, wherein each of R8, R9, R10, R11, R12 and R13 is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, and substituted alkyl, alkenyl, alkynyl, aryl, wherein the substituents are selected from the group of alkyl, alkenyl, alkynyl, aryl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitrile, nitro, epoxide, imine, aziridine, sulfone, phosphone, and silane.

50. The process of claim 48, wherein each of R8, R9, R10, R11, R12 and R13 is selected from the group consisting of alkyl, aryl, phenyl and substituted alkyl, aryl and phenyl, wherein the substituents are selected from the group of alkyl, aryl, phenyl, halide, ketone, aldehyde, alcohol, ether, ester, carboxylic acid, primary amino, secondary amino, tertiary amino, amide, nitro, epoxide, aziridine, sulfone, phosphone, and silane.

51. The process of claim 50, wherein each of R8, R9, R10, R11, R12 and R13 includes up to includes up to 20 carbon atoms, more preferably up to 18 carbon atoms, more preferably up to 16 carbon atoms, more preferably up to 14 carbon atoms, or up to 12 carbon atoms, or up to 10 carbon atoms, or up to 8 carbon atoms, or up to 6 carbon atoms.

52. The process of claim 49, 50, or 51, wherein each of the substituents of said substituted alkyl and aryl groups from which R8, R9, R10, R11, R12 and R13 can be selected is selected from the group consisting of halide, ketone, alcohol and ester.

53. The process of any of claims 41 to 52, wherein the compound having formula II is N-aminophthalimide.

54. The process of any of claims 41 to 53, wherein the compound having formula III has a lower oxidation potential than that of a compound having formula II.

55. The process of any of claims 41 to 53 wherein the compound having formula III is oxidized at a faster rate than a compound having formula II under said conditions of electrolysis.

56. The process of any of claims 41 to 55, wherein the solvent of the electrolytic cell is a polar non-protic solvent, and particularly wherein the solven is selected from the group consisting of dichloromethane, acetonitrile, N,N-dimethylformamide, tetrahydrofuran, nitromethane, chloroform, propylene carbonate, and mixtures thereof.

57. An electrochemical process of any preceding claim wherein said contacting step includes contacting said compounds with each other in an anode compartment of said electrolytic cell in an anolyte which comprises a carboxylate ion.

58. The process of claim 57, wherein the anolyte solution is substantially free of a metal catalyst.

59. The process of claim 58, wherein said metal is selected from the group of lead cadmium, cerium, cobalt, chromium, copper, ion, mercury, iridium, manganese, molybdenum, nickel, osmium, palladium, rhenium, rhodium, ruthenium, antimony, thallium, tin and vanadium.

60. The process of any of claims 57 to 59, wherein said anode a platinum electrode.

61. The process of any of claims 57 to 60, wherein an acid form of said carboxylate has a first pKa, and said anolyte solution further comprises an acid having a second pKa wherein said second pKa exceeds the first pKa.

62. The process of claim 61 wherein the carboxylate and the acid having the second pKa are solubilized in the solution and the carboxylate is provided in solution in a stoichiometric amount equal to at least half that of the hydrazine derivative.

63. The process of claim 62 wherein the acid form of said carboxylate has the formula RCO2H wherein R is an organic group.

64. The process of claim 62 wherein the acid for of said carboxylate has the formula RCO2H wherein R is an alkyl group or a haloalkyl group.

65. The process of any of claims 61 to 64 wherein the first pKa is in the range of about −2 to about +7.

66. The process of claim 65 wherein the first pKa is in the range of about −1 to about +6.

67. The process of claim 66 wherein the first pKa is in the range of about 0 to about +5.

68. The process of claim 67 wherein the first pKa is about 0.3.

69. The process of claim 67 wherein the first pKa is about 2.8.

70. The process of claim 67 wherein the first pKa is about 4.8.

71. The process of any of claims 57 to 65, wherein said carboxylate is selected from the group acetate, trifluoroacetate, and monochloroacetate.

72. The process of any of claims 61 to 71, wherein said acid is an ammonium acid and said second pKa exceeds the first pKa by at least 2.

73. The process of claim 72, wherein said ammonium acid has the formula R1R2R3NH+ wherein each of R1, R2 and R3 is an organic group or hydrogen.

74. The process of claim 73, wherein each of R1, R2 and R3 of the ammonium acid is an alkyl group or hydrogen.

75. The process of any of claims 61 to 63, wherein said acid having the second pKa is triethylammonium.

76. The process of any of claims 57 to 75, wherein the carboxylate is provided in solution in a stoichiometric amount about equal to that of the hydrazine derivative.

77. The process of any of claims 57 to 76, wherein the anolyte solution further comprises a counterion to the carboxylate, the counterion having the formula R1R2R3 R4 N+ wherein each of R1, R2, R3, and R4 is an organic group.

78. The process of claim 77, wherein each said organic group of the counterion is an alkyl group or a haloalkyl group.

79. The process of claim 78, wherein each said organic group of the counterion is an alkyl group.

80. The process of claim 79, wherein each said organic group of the counterion is an alkyl group selected from the group of methyl, ethyl, propyl, butyl and pentyl.

81. The process of any preceding claim, wherein said contacting step is carried out in an anodic half cell divided from and operatively linked to a cathodic half cell.

82. The process of claim 81, wherein said half cells are linked by an ion permselective diaphragm.

83. The process of claim 82 wherein said diaphragm comprises a synthetic polymer having anions affixed thereto.

84. The process apparatus of claim 83, wherein said anions include perfluorosulfonate groups.

85. The process of claim 84, wherein said diaphragm comprises a Nafion membrane.

86. The process of any preceding claim, wherein compound II, V, or VII, as the case may be, has a more positive potential than the voltage at which the contacting step is conducted.

87. The process of claim 86 wherein compound III has first and second peak potentials, each of which potentials is between about 0 and 3 volts against Ag/AgCl, more preferably between about 1 and 2 volts.

88. The process of any preceding claim wherein the mole ratio of the compound having formula Im to the compound having formula II, V, or VU, as the case may be, is from about 1:1 to about 1000:1; more preferably between 500:1 and 1:1; more preferably between about 100: and 1:1; more preferably between about 25:1 and 1:1; more preferably between about 10:1 and 1:1; more preferably between about 5:1 and 1:1, more preferably between about 2:1 and 1:1.

89. The process of any preceding claim wherein the electric potential applied during the contacting step is applied for a period between about 1 minute and 10 hours.

90. In a process of addition of a nitrogen across a multiple bond of an organic molecule wherein a first atom of the multiple bond is a carbon atom, and the second atom is selected from the group of carbon, oxygen and nitrogen, the improvement comprising electrochemically generating the nitrogen for the addition from a primary hydrazine derivative in the presence of a carboxylate anion.

91. The process of claim 90, wherein the nitrogen is generated from a compound having the structure indicated by formula III, as defined in any of claims 1 and 12 to 17.

92. The process of claim 91, wherein the organic molecule has the structure indicated by formula I as defined in any of claims 1 to 11, or formula VII as defined in any of claims 41 to 47.

93. In a process of addition of a nitrogen to a heteroatom of an organic molecule wherein the heteroatom forms a double bond with an oxygen atom and is a P, S, Se or Te atom, the improvement comprising electrochemically generating the nitrogen for the addition from a primary hydrazine derivative in the presence of a carboxylate anion.

94. The process of claim 93, wherein the nitrogen is generated from a compound having the structure indicated by formula HI, as defined in any of claims 1 and 12 to 17.

95. The process of claim 94, wherein the organic molecule has the structure indicated by formula V as defined in any of claims 21 to 29.

96. A product when obtained by a process defined by any preceding claim.

97. A process for electrochemically generating a nitrene, the process comprising the step of:

exposing a hydrazine derivative contained in an anolyte solution of an electroytic cell to the anode of the cell in the presence of a carboxylate ion, wherein one of the nitrogens of the hydrazine group is a primary amino group.

98. The process of claim 97, wherein the anolyte solution is substantially free of a metal catalyst.

99. The process of claim 98, wherein said metal is selected from the group of lead cadmium, cerium, cobalt, chromium, copper, ion, mercury, iridium, manganese, molybdenum, nickel, osmium, palladium, rhenium, rhodium, ruthenium, antimony, thallium, tin and vanadium.

100. The process of any of claims 97 to 99, wherein said anode a platinum electrode.

101. The process of any of claims 97 to 100, wherein an acid form of said carboxylate has a first pKa, and said anolyte solution further comprises an acid having a second pKa wherein said second pKa exceeds the first pKa.

102. The process of claim 101 wherein the carboxylate and the acid having the second pKa are solubilized in the solution and the carboxylate is provided in solution in a stoichiometric amount equal to at least half that of the hydrazine derivative.

103. The process of claim 102 wherein the acid form of said carboxylate has the formula RCO2H wherein R is an organic group.

104. The process of claim 102 wherein the acid for of said carboxylate has the formula RCO2H wherein R is an alkyl group or a haloalkyl group.

105. The process of any of claims 101 to 104 wherein the first pKa is in the range of about −2 to about +7.

106. The process of claim 105 wherein the first pKa is in the range of about −1 to about +6.

107. The process of claim 106 wherein the first pKa is in the range of about 0 to about +5.

108. The process of claim 107 wherein the first pKa is about 0.3.

109. The process of claim 107 wherein the first pKa is about 2.8.

110. The process of claim 107 wherein the first pKa is about 4.8.

111. The process of any of claims 97 to 105, wherein said carboxylate is selected from the group acetate, trifluoroacetate, and monochloroacetate.

112. The process of any of claims 101 to 111, wherein said acid is an ammonium acid and said second pKa exceeds the first pKa by at least 2.

113. The process of claim 112, wherein said ammonium acid has the formula R1R2R3NH+ wherein each of R1, R2 and R3 is an organic group or hydrogen.

114. The process of claim 113, wherein each of R1, R2 and R3 of the ammonium acid is an alkyl group or hydrogen.

115. The process of any of claims 101 to 103, wherein said acid having the second pKa is triethylammonium.

116. The process of any of claims 97 to 115, wherein the carboxylate is provided in solution in a stoichiometric amount about equal to that of the hydrazine derivative.

117. The process of any of claims 97 to 116, wherein the anolyte solution further comprises a counterion to the carboxylate, the counterion having the formula R1R2R3 R4 N+ wherein each of R1, R2, R3, and R4 is an organic group.

118. The process of claim 117, wherein each said organic group of the counterion is an alkyl group or a haloalkyl group.

119. The process of claim 118, wherein each said organic group of the counterion is an alkyl group.

120. The process of claim 119, wherein each said organic group of the counterion is an alkyl group selected from the group of methyl, ethyl, propyl, butyl and pentyl.

121. The process of any of claims 97 to 120 wherein said hydrazine derivative comprises a molecule having the structure indicated as formula Im as defined in any of claims 1 and 12 to 17.

122. The process of any of claims 97 to 121, wherein the anolyte solution comprises a solvent as defined in claim 20.

123. An apparatus for electrochemical generation of a nitrene, the apparatus comprising:

an anodic half cell operatively linked to a cathodic half cell; and
an anolyte solution comprising a carboxylate anion and a primary hydrazine derivative.

124. The apparatus of claim 123, wherein said half cells are linked by an ion permselective diaphragm.

125. The apparatus of claim 124, wherein said diaphragm comprises a synthetic polymer having anions affixed thereto.

126. The apparatus of claim 125, wherein said anions include perfluorosulfonate groups.

127. The apparatus of claim 126, wherein said diaphragm comprises a Nafion membrane.

128. The apparatus of any of claims 123 to 127, wherein the hydrazine has a formula im as defined in any of claims 1 and 5 to 17.

129. The apparatus of any of claims 123 to 128, wherein the anolyte solution is substantially free of a metal catalyst.

130. The apparatus of claim 129, wherein said metal is selected from the group of lead cadmium, cerium, cobalt, chromium, copper, ion, mercury, iridium, manganese, molybdenum, nickel, osmium, palladium, rhenium, rhodium, ruthenium, antimony, thallium, tin and vanadium.

131. The apparatus of any of claims 123 to 130, wherein said anode a platinum electrode.

132. The apparatus of any of claims 123 to 131, wherein an acid form of said carboxylate has a first pKa, and said anolyte solution further comprises an acid having a second pKa wherein said second pKa exceeds the first pKa.

133. The apparatus of claim 132 wherein the carboxylate and the acid having the second pKa are solubilized in the solution and the carboxylate is provided in solution in a stoichiometric amount equal to at least half that of the hydrazine derivative.

134. The apparatus of claim 133 wherein the acid form of said carboxylate has the formula RCO2H wherein R is an organic group.

135. The apparatus of claim 133 wherein the acid for of said carboxylate has the formula RCO2H wherein R is an alkyl group or a haloalkyl group.

136. The apparatus of any of claims 132 to 135 wherein the first pKa is in the range of about −2 to about +7.

137. The apparatus of claim 136 wherein the first pKa is in the range of about −1 to about +6.

138. The apparatus of claim 137 wherein the first pKa is in the range of about 0 to about +5.

139. The apparatus of claim 138 wherein the first pKa is about 0.3.

140. The apparatus of claim 138 wherein the first pKa is about 2.8.

141. The apparatus of claim 138 wherein the first pKa is about 4.8.

142. The apparatus of any of claims 123 to 136, wherein said carboxylate is selected from the group acetate, trifluoroacetate, and monochloroacetate.

143. The apparatus of any of claims 132 to 142, wherein said acid is an ammonium acid and said second pKa exceeds the first pKa by at least 2.

144. The apparatus of claim 143, wherein said ammonium acid has the formula R1R2R3NH+ wherein each of R1, R2 and R3 is an organic group or hydrogen.

145. The apparatus of claim 144, wherein each of R1, R2 and R3 of the ammonium acid is an alkyl group or hydrogen.

146. The apparatus of any of claims 132 to 134, wherein said acid having the second pKa is triethylammonium.

147. The apparatus of any of claims 123 to 146, wherein the carboxylate is provided in solution in a stoichiometric amount about equal to that of the hydrazine derivative.

148. The apparatus of any of claims 123 to 147, wherein the anolyte solution further comprises a counterion to the carboxylate, the counterion having the formula R1R2R3 R4 N+ wherein each of R1, R2, R3, and R is an organic group.

149. The apparatus of claim 148, wherein each said organic group of the counterion is an alkyl group or a haloalkyl group.

150. The apparatus of claim 149, wherein each said organic group of the counterion is an alkyl group.

151. The apparatus of claim 149, wherein each said organic group of the counterion is an alkyl group selected from the group of methyl, ethyl, propyl, butyl and pentyl.

152. A process for screening an olefin for electrochemical aziridination of an olefin with a hydrazine derivative, the process comprising the steps of:

providing the olefin;
determining the redox potential of the olefin at a predetermined voltage at which the aziridine derivative is oxidized, wherein a said olefin determined to have a less positive potential than the predetermined voltage is eliminated as a candidate for electrochemical aziridination by said hydrazine derivative.

153. A process for screening an olefin for electrochemical aziridination of an olefin with a hydrazine derivative, the process comprising the steps of:

providing the olefin;
determining the redox potential of the olefin at a predetermined voltage at which the aziridine derivative is oxidized, wherein a said olefin determined to have a more positive potential than the predetermined voltage is selected as a candidate for electrochemical aziridination by said hydrazine derivative.

154. The process of claim 152 or 153, wherein said hydrazine derivative has first and second peak potentials, each of which potentials is between about 0 and 3 volts against Ag/AgCl.

155. The process of claim 154, wherein said hydrazine derivative has first and second peak potentials, each of which potentials is between about 0 and 3 volts against Ag/AgCl.

Patent History
Publication number: 20050006246
Type: Application
Filed: Jul 25, 2002
Publication Date: Jan 13, 2005
Inventors: Andrei Yudin (Ontario), Tung Siu (Ontario)
Application Number: 10/484,843
Classifications
Current U.S. Class: 205/423.000