Although alpha-nitroketones are versatile synthetic intermediates toward more complex molecules, there are few methods to prepare them. Most methods require multiple steps, and asymmetric syntheses where a chiral quaternary carbon is formed are very rare. Since there is an ever-increasing need to develop asymmetric methodologies toward the synthesis of quaternary carbon centers in natural product and pharmaceutical synthesis, this proposal intends to develop planar chiral heterocycles as Lewis base catalysts to generate quaternary carbon centers via asymmetric acylation of silylnitronates. In addition, a """"""""one-pot"""""""" synthesis will be explored where asymmetric acylation occurs after in situ generation of the nitronate. This proposal will investigate the scope of the asymmetric acylation reaction and determine the reaction mechanism and origin of stereochemical control. The products, enantiopure alpha-nitroketones, will be further transformed into alpha-alkyl-alpha-amino acids, which are potent enzymatic inhibitors and are important in investigations on protein structure since they impart conformational constraints.
| Lee, Elaine C; McCauley, Kevin M; Fu, Gregory C (2007) Catalytic asymmetric synthesis of tertiary alkyl chlorides. Angew Chem Int Ed Engl 46:977-9 |
