Asymmetric Conjugate Additions To Alpha Beta Unsaturated Enones Using Chiral Beta Silyl Amidocuprates

Asymmetric Conjugate Additions to [alpha], [beta]-unsaturated Enones Using Chiral [beta]-silyl Amidocuprates

[Beta]-silyl groups have shown to have a pronounced effect on the organocuprate reagents forming more reactive and thermally stable reagents. Their properties have led to these reagents being used as non-transferable ligands in Michael addition reactions. We have prepared the first chiral [beta]-silyl amidoheterocuprate for 1,4-conjugate additions to enones. A highly reactive organocuprate has been synthesized from (1R,2S)-( - )-norephedrine. Enantiomeric excesses up to 99% (S) with yields as high as 90% have been obtained using chalcone as substrate and diethyl ether as solvent. The effect of different silyl groups on the enantioselectivity of the addition reaction has been discussed. The effect of different solvents and the enantioselectivity obtained with different acyclic and cyclic enones has been presented. Several reactions have been carried out with an attempt to understand the reaction mechanism. The success of the stoichiometric reactions, led us to the copper-catalysed approach towards these reactions and we have observed selectivity with butyllithium and chalcone. A catalytic cycle for the reaction has been proposed and reactions have been carried out to understand the optimum conditions required for the formation of the organocuprate at the catalytic level. The problems associated with the catalytic cycle have been understood and these problems have been overcome in a catalytic batch process in which the organocuprate has been used successfully for several turnovers.

Asymmetric Conjugate Addition of Boronates to N-Acylimines and [beta]-Silyl-[alpha], [beta]-unsaturated Ketones Catalyzed by 3,3'-Disubstituted Binaphthols

Asymmetric Conjugate Additions to Enones Using Chiral Carbon-bound Heterocuprate Reagents

ABSTRACT: Organocopper reagents are useful in 1,4-addition (or conjugate addition) to [alpha], [beta]-unsaturated ketones. These reagents have found great synthetic utility in natural product synthesis because of their generality in additions to enones. Enantioselective versions of the organocuprate reagent are still, however, far from being general. Also vague is the understanding of the non-transferable characteristics of some ligands used in heterocuprates (such as thiophene). These two problems are the focus of the research contained herein.