Abstract: This invention pertains to the development of methods that accomplish efficient, non-enzymatic, nucleic acid-directed (e.g. RNA-directed) nucleic acid (e.g. RNA) synthesis. In certain embodiments the methods provide conditions that favor oligouridylate synthesis with excellent yield and, at least, up to 30% regioselectivity favoring the RNA linkage. The methods preferably involve contacting, in the presence of lead ions (Pb2+) and/or tin ions (Sn2+) and, optionally, magnesium ions (Mg2+), a template nucleic acid with a nucleotide derivatized with an imidazolide.