In Situ Enamine Activation in Aqueous Salt Solutions: Highly Efficient Asymmetric Organocatalytic Diels-Alder Reaction of Cyclohexenones with Nitroolefms

摘要

The Diels-Alder reaction is one of the most powerful pericyclic reactions for the construction of six-membered functionalized cyclic frameworks. In the wake of the emergence of organocatalysis, great efforts have been devoted to the development of organocatalytic enantioselective versions of this reaction, as it allows in principle the formation of four contiguous asymmetric centers. MacMillan and co-workers developed the first highly enantioselective amine-catalyzed Diels-Alder reaction of α,β-unsaturated carbonyl compounds as dienophiles via LUMO-lowering iminium formation. Since then, iminum ion catalysis has been established as an effective platform for enantioselective Diels-Alder reactions. Alternatively, Barbas and co-workers discovered the first amine-catalyzed Diels-Alder reaction of α,β-unsaturated carbonyl compounds as dienes involving in situ enamine activation. This strategy has been successfully applied in several hetero-Diels-Alder reactions. Other organocatalytic Diels-Alder reactions have also been reported that use chiral Bronsted acids,N-heterocyclic carbenes, and cinchona alkaloids.