AUXILIARY CHIRAL KETONES IN THE ASYMMETRI C-SYNTHESIS OF ALPHA-AMINO-ACIDS BY STRECKER REACTION

The asymmetric synthesis of alpha-aminoamides 1 R1CH(CONH2)NH2 [1a : R 1 = Ph-CH2, 1b : R1 = Pr(i), 1c : R1 = Ph] that leads to the correspon ding alpha-amino acids is achieved by a classical Strecker reaction [1 ] [R1CHO, HCN, NH3] using an auxiliary chiral ketone (R2R'2CO) as a ca talyst. In the presence of an aqueous solution of HCN and NH3, the 5R- (methylethenyl)-3R-cyano-2R-methylcyclohexanone 2(-) leads to the heny l)-3R-cyano-2R-methyl-1R-cyano-cyclohexylamine 3 with 80% stereoselect ivity. Following condensation with R1CHO, this alpha-aminonitrile R2R' 2C(CN)NH2 3 yields the corresponding iminonitrile which undergoes a se cond asymmetric addition of HCN yielding an asymmetric alpha-aminodini trile 4 R2R'2C(CN)-NH-CHR1(CN) with stereoselectivity that varies betw een 62% (R1 = Ph) and 79% (R1 = Ph-CH2). The alpha-aminodinitrile obta ined as the major product undergoes regioselective hydration of the se condary aminonitrile moiety followed by the decomposition (''retro-Str ecker'') of the tertiary aminonitrile moiety yielding an optically act ive alpha-aminoamide (eg 78% optical purity for 1a) and the auxiliary chiral ketone 2 and ketonic derivatives.