GOLD(I)-CATALYZED ASYMMETRIC ALDOL REACTION OF N-METHOXY-N-METHYL-ALPHA-ISOCYANOACETAMIDE (ALPHA-ISOCYANO WEINREB AMIDE) - AN EFFICIENT SYNTHESIS OF OPTICALLY-ACTIVE BETA-HYDROXY-ALPHA-AMINO ALDEHYDES AND KETONES

Asymmetric aldol reaction of N-methoxy-N-methyl-alpha-isocyanoacetamide (alpha-isocyano Weinreb amide) with aldehydes [RCHO: R = Ph, Me, i-Pr, (E)-MeCH=CH, (E)-BnOCH(2)CH=CH] in the presence of a gold(I) catalyst prepared in situ from [Au(c-HexNC)(2)]BF4 and chiral ferrocenylphosphine ligand (R)-N-methyl-N-(2-morpholinoethyl)-1-[(S)-1',2-bis(diphenylphosphino)ferrocenyl]ethylamine gave high yields of optically active trans-5-alkyl-2-oxazoline-4-(N-methoxy-N-methylcarboxamides) with high diastereo- and enantioselectivities. The diastereoselectivities (trans:cis) and enantiomeric excesses of the trans-oxazolines for the reaction with 1 mol % of the catalyst are as follows: R = Ph, 97:3, 96% ee; R = Me, 95:5, 97% ee; R = i-Pr, 98:2, 97% ee; R = (E)-MeCH=CH, 97:3; 99% ee; (E)-BnOCH(2)CH=CH, 96:4, 95% ee. These optically active oxazolines were converted to N,O-protected beta-hydroxy-alpha-amino aldehydes and ketone in high yields. An N-protected alpha-amino aldehyde (R = Ph) lacking the beta-hydroxyl group was also obtained through the catalytic hydrogenolysis of the oxazoline.