Chiral N-acylhydrazones: Versatile imino acceptors for asymmetric amine synthesis

Abstract

Addition to C=N bonds with acyclic stereocontrol offers excellent potential for development of new carbon-carbon bond construction approaches to chiral amines. This review features the design and implementation of novel chiral N-acylhydrazones as versatile imino acceptors for addition of radicals and nucleophiles. The initial design was inspired by the goal of asymmetric radical addition to chiral C=N radical acceptors. The chiral N-acylhydrazones are prepared from commercially available materials by amination of 4-alkyl-2-oxazolidinones with NH2+ equivalents to afford N-(amino) oxazolidinones, followed by condensation with aldehydes or ketones. These chiral N-acylhydrazones undergo addition reactions with various partners, including radicals, allylsilanes, allylindiums, silyl enol ethers, and hydride donors. The adducts can be converted to chiral amines by N-N bond cleavage. Reliably high stereoselectivity was observed for addition reactions in the presence of Lewis acids. For the prototype case, N-acylhydrazones derived from (S)-4-benzyl-2-oxazolidinone, two alternative stereocontrol models are consistent with the results. Lewis acids capable of chelate formation activate through two-point binding of the imino nitrogen and the carbonyl oxygen, exposing the si-face for addition. On the other hand, boron trifluoride activates through a monodentate interaction, favoring a rotamer which exposes the re-face. Applications from the author's research program are reviewed together with results from other groups. © Wiley-VCH Verlag GmbH & Co. KGaA, 2005.