TRANSITION METAL BASE-CATALYZED ALDOL REACTIONS OF ISOCYANOACETIC ACID-DERIVATIVES WITH PROCHIRAL KETONES, A STRAIGHTFORWARD APPROACH TO STEREOCHEMICALLY DEFINED BETA,BETA-DISUBSTITUTED-BETA-HYDROXY-ALPHA-AMINO ACIDS - SCOPE AND LIMITATIONS/

A systematic study of the transition metal/base-catalyzed aldol reacti ons of methyl isocyanoacetate with a wide range of prochiral ketones, giving rise to the -(methoxycarbonyl)-5,5-disubstituted-2-oxazolines, has been made. The diastereoselectivity of these reactions was found t o be influenced by a mix of several factors, including steric characte ristic of the substituents, nature of the catalyst, electrostatic, and electron donor-acceptor type interactions. The former factor, a stere ochemical discrimination between the substituents at the ketone carbon , was shown to be the most pronounced in controlling of the stereochem ical outcome, which could be markedly improved with a proper choice of the catalyst. In particular, for the reactions of methyl isocyanoacet ate with polyhaloalkyl aryl(alkyl) ketones, high diastereoselectivity (80-98% de) was achieved, thus allowing for straightforward and genera lized access to the corresponding )-beta,beta-disubstituted-beta-hydro xy-alpha-amino carboxylic acid.