Organocatalytic Asymmetric Domino Knoevenagel/Diels-Alder Reactions: A Bioorganic Approach to the Diastereospecific and Enantioselective Construction of Highly Substituted Spiro[5,5]undecane-1,5,9-triones

摘要

One of the ultimate goals in organic chemistry is the catalytic asymmetric assembly of simple and readily available precursor molecules into stereochemically complex products. In this regard, the Diels-Alder reaction is one of the most powerful synthetic methodologies for the construction of cyclic sixmembered rings, and tremendous efforts have been directed to expand the scope of this cycloaddition reaction with various combinations of dienes, dienophiles, catalysts, and reaction conditions. Recently organocatalysis has emerged as a promising synthetic tool for constructing C-C and C-N bonds in aldol, Michael, Mannich, Diels-Alder, and related reactions with high diastereoselectivity and enantioselectivity. Structurally simple and stable chiral organoamines typically facilitate iminium- and enamine-based transformations with carbonyl compounds and may be used as catalysts in operationally simple, and in some cases environmentally friendly, experimental protocols. Previously we extended our studies of organoamine-catalyzed aldol, Michael, Mannich, and related reactions founded on enamine catalysis, and reported the first direct asymmetric Diels-Alder reactions of α,β-unsaturated ketones with nitro olefins.