Copper-Catalyzed Asymmetric Conjugate Addition of Aryl Aluminum Reagents to Trisubstituted Enones: Construction of Aryl-Substituted Quaternary Centers

摘要

In the field of asymmetric conjugate addition (ACA) to enones. much effort has been directed towards the development of copper- and rhodium-catalyzed reactions of alkylme-tal as well as aryl- and vinylboronic acid reagents. While most reports deal with disubstituted substrates, the construction of enantioenriched all-carbon quaternary stereocenters is still a synthetic challenge. Recently, a number of interesting reports concerning the copper-catalyzed version provided solutions to this problem. However, the use of the classical alkylzinc reagents requires special conditions, such as reactive substrates, for example, nitroalkenes and doubly activated enones. Less-reactive trisubstituted cyclic enones are only accessible with specialized N-heterocyclic carbene (NHC) ligands or more reactive nucleophiles, such as, trialkylalu-minum reagents. In combination with stronger coordinating solvents, their enhanced Lewis acidity has made trialkylalu-minum reagents very successful in the ACA. Grignard reagents are also useful owing to their wide scope of reaction, but the enantioselectivities are generally lower than with Al and Zn reagents.