Enantioselective aldehyde α-nitroalkylation via oxidative organocatalysis

(Chemical Equation Presented) The first enantioselective organocatalytic α-nitroalkylation of aldehydes has been accomplished. The aforementioned process involves the oxidative coupling of an enamine intermediate, generated transiently via condensation of an amine catalyst with an aldehyde, with a silyl nitronate to produce a β-nitroaldehyde. Two methods, one that furnishes the syn β-nitroaldehyde and a second that provides access to the anti isomer, have been developed. Data are presented to support a hypothesis that explains this phenomenon in terms of a silyl group-controlled change in mechanism. Finally, a three-step procedure for the synthesis of both syn- and anti-α,β-disubstituted β-amino acids is presented.