Asymmetric Synthesis of 3,4-Dihydrocoumarins Bearing an α,α-Disubstituted Amino Acid Moiety

An organocatalytic approach for the stereoselective synthesis of 3,4-dihydrocoumarins with an alpha,alpha-disubstituted amino acid moiety incorporated is presented. The developed methodology is based on the cascade reaction between a-substituted azlactones and 2-hydroxychalcones. It is initiated by a chiral Bronsted base-catalyzed enantio- and diastereoselective Michael reaction followed by the azlactone ring opening to construct a 3,4-dihydrocoumarin framework. Products bearing two adjacent stereogenic centers, one being quaternary, were formed with high enantioselectivities and excellent diastereoselectivities. Furthermore, the complete regioselectivity of the new cascade reactivity is worthy of notice.