Direct C3-functionalization of indoles with alpha-heteroaryl-substituted methyl alcohols via a metal-free hydrogen autotransfer-type reaction

The Cs2CO3/oxone®-mediated C3-alkylation of indoles proceeds in moderate to high yields with a variety of C4–C7 functionalized indoles and is applicable to 2-, 3- and 4-hydroxymethyl pyridines and related electron-deficient heterocycles, permitting novel late-stage drug functionalizations and preparations of dimethyltryptamine analogs. Preliminary mechanistic studies support a chain process starting with an initital oxidation of the alcohol to the corresponding aldehyde, followed by a subsequent condensation onto indole and reduction/ hydride delivery from another equivalent of the primary alcohol.