Enantioselective Cross-[4 + 2]-Cycloaddition/Decarboxylation of 2-Pyrones by Cooperative Catalysis of the Pd(0)/NHC Complex and Chiral Phosphoric Acid.

ABSTRACT

Here, we describe a cooperative Pd(0)/chiral phosphoric acid catalytic system that allows us to realize the first chemo-, regio-, and enantioselective sequential cross-[4 + 2]-cycloaddition/decarboxylation reaction between 2-pyrones and unactivated acyclic 1,3-dienes. The key to the success of this transformation is the utilization of an achiral N-heterocyclic carbene (NHC) as the ligand and a newly developed chiral phosphoric acid as the cocatalyst. Experimental investigations and computational studies support the idea that the Pd(0)/NHC complex acts as a π-Lewis base to increase the nucleophilicity of 1,3-dienes via η2 coordination, while the chiral phosphoric acid simultaneously increases the electrophilicity of 2-pyrones by hydrogen bonding. By this synergistic catalysis, the sequential cross-[4 + 2]-cycloaddition and decarboxylation reaction proceeds efficiently, enabling the preparation of a wide range of chiral vinyl-substituted 1,3-cyclohexadienes in good yields and enantioselectivities. The synthetic utility of this reaction is demonstrated by synthetic transformations of the product to various valuable chiral six-membered carbocycles.