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 (camphorsulfon yl) oxaziridine, is identified as a direct and general strategy for th e asymmetric synthesis of homochiral beta-amino-alpha-hydroxy acids an d their derivatives. A structurally diverse array of beta-amino enolat e substrates can be hydroxylated with generally excellent anti diaster eoselectivity (> 90% d.e.) using this protocol; an alternative stepwis e hydroxylation procedure, where the beta-amino enolate is prepared by enolisation of the preformed conjugate adduct is also found to lead t o formation of the anti diastereoisomer, The diastereofacial selectivi ty of enolate hydroxylation appears to be under predominantly substrat e-controled asymmetric induction, although a measurable degree of chir ality recognition with the oxaziridine reagent can be observed. Homoch iral beta-amino-alpha-keta esters are also prepared and their stereose lective reductions examined.