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Keywords:

  • Hydrazones;
  • Amines;
  • Radical reactions;
  • Nucleophilic addition;
  • Asymmetric 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, 69451 Weinheim, Germany, 2005)