Remarkable Enhancement of Enantioselectivity in the Asymmetric Conjugate Addition of Dimethylzinc to (Z)‐Nitroalkenes with a Catalytic [(MeCN)₄Cu]PF₆–Hoveyda Ligand Complex

Abstract

An enantioselective copper-catalyzed asymmetric conjugate addition of Me 2 Zn to (Z)-nitroalkenes led to the formation of all-carbon quaternary stereogenic centers with high stereoselectivity. The key features of the new method are the unprecedented use of [(MeCN) 4 Cu]PF 6 in conjunction with the Hoveyda ligand L1 and the use of (Z)-nitroalkene substrates so that undesired nitroalkene isomerization is minimized and enantioselectivity is enhanced dramatically. We also describe a novel, practical, and highly (Z)-selective nitroalkene synthesis. Scheme 1. A structural motif of medicinal interest. EWG = electron-withdrawing group.

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

“…62 Using the less reactive dimethylzinc, process chemists at Boehringer Ingelheim later adapted this method for conjugate methylations of ( Z )-nitroalkenes, which react with generally higher levels of enantioselectivity (not shown). 63 Fillion established that alkylidene Meldrum’s acid derivatives are excellent electrophiles in enantioselective conjugate additions of organozinc reagents. 64–67 Using a copper catalyst modified by phosphoramidite ligand VII , high yields and enantioselectivities are observed.…”