ASYMMETRIC-SYNTHESIS OF BETA-AMINO-ALPHA-HYDROXY ACIDS VIA DIASTEREOSELECTIVE HYDROXYLATION OF HOMOCHIRAL BETA-AMINO ENOLATES

The highly diastereoselective conjugate addition of lithium N-benzyl-N-alpha-methylbenzylamide with enoate accepters, and the electrophilic hydroxylation of the resultant beta-amino enolates with (camphorsulfonyl) oxaziridine, is identified as a direct and general strategy for the asymmetric synthesis of homochiral beta-amino-alpha-hydroxy acids and their derivatives. A structurally diverse array of beta-amino enolate substrates can be hydroxylated with generally excellent anti diastereoselectivity (> 90% d.e.) using this protocol; an alternative stepwise hydroxylation procedure, where the beta-amino enolate is prepared by enolisation of the preformed conjugate adduct is also found to lead to formation of the anti diastereoisomer, The diastereofacial selectivity of enolate hydroxylation appears to be under predominantly substrate-controled asymmetric induction, although a measurable degree of chirality recognition with the oxaziridine reagent can be observed. Homochiral beta-amino-alpha-keta esters are also prepared and their stereoselective reductions examined.