Enantioselective and diastereoselective mukaiyama-Michael reactions catalyzed by bis(oxazoline) Copper(II) complexes

The scope of highly enantioselective and diastereoselective Michael additio ns of enolsilanes to unsaturated imide derivatives has been developed with use of [Cu((S,S)-t-Bu-box)](SbF6)(2) (1a) as a Lewis acid catalyst. The pro ducts of these additions are useful synthons that contain termini capable o f differentiation under mild conditions. Michael acceptor ct-facial selecti vity is consistent with two-point binding of the imide substrate and can be viewed as an extension of substrate enantioselection in the corresponding Diels-Alder reactions. A model analogous to the one employed to describe th e hetero Diels-Alder reaction is proposed to account for the observed relat ion between enolsilane geometry and product absolute diastereocontrol. Insi ghts into modes of catalyst inactivation are given, including spectroscopic evidence for inhibition of the catalyst by a dihydropyran intermediate tha t evolves during the course of the reaction. A procedure is disclosed in wh ich an alcohol additive is used to hydrolyze the inhibiting dihydropyran an d afford the desilylated Michael adduct in significantly shortened reaction time.