Reductive Coupling Reactions of Nitrones and Imines, Modern Versions

INTRODUCTION Pinacol coupling was first described by Fittig in 1859, when he reported the formation of 2,3dimethyl-2,3-butanediol (1) from acetone and sodium metal. Since then, this ketyl radical anion coupling process has undergone significant advancement, including the development of asymmetric variants. 3 Alternatives to use of strong reducing metals are low valent transition metals and lanthanides. A recent development in these reductive couplings has been the extension to carbon-nitrogen double bonds (C=N), long known to be radical acceptors, 6 particularly in radical-mediated cyclizations with alkyl halides. Much progress has also been made on intramolecular versions of these processes, due to their highly organized and stable cyclic transition states and low rates of competing homocoupling reactions (Scheme 1). Intermolecular reductive coupling of C=N substrates represents an atom-efficient construction of an inherently functionalized C-C bond for the synthesis of vicinal diamines, 1,2-amino alcohols, and -amino esters from relatively simple starting materials. This review will cover general substrate considerations, limitations, and asymmetric variants of intermolecular reductive 1,2and 1,4coupling reactions involving nitrone and imine components. O Na HO OH 1