Asymmetric synthesis of α-amino carbonyl derivatives using lithium ( R)- N-benzyl- N-α-methylbenzylamide

Abstract

An efficient protocol for the transformation of homochiral α-hydroxy-β-amino esters to their α-amino carbonyl components is presented. Diastereoselective conjugate addition of lithium ( R)- N-benzyl- N-α-methylbenzylamide to a range of α,β-unsaturated esters and subsequent enolate hydroxylation with (1 R)-(−)-(camphorsulfonyl)oxaziridine, followed by LiAlH 4 reduction produces homochiral 3-amino 1,2-diols. Subsequent oxidative cleavage with H 5IO 6 provides N-benzyl- N-α-methylbenzyl protected α-amino aldehydes (96–98% d.e.) and ketones (88% d.e.). Further oxidation of the α-amino aldehydes with sodium chlorite and Pd-catalysed hydrogenation provides α-amino acids in 94–98% e.e.