Squaramide-Catalyzed Asymmetric Intramolecular Oxa-Michael Reaction of α,β-Unsaturated Carbonyls Containing Benzyl Alcohol: Construction of Chiral 1-Substituted Phthalans

Organocatalytic enantioselective intramolecular oxa-Michael reactions of benzyl alcohol bearing alpha,beta-unsaturated carbonyls as Michael acceptors are presented herein. Using cinchona squaramide-based organocatalyst, enones as well as alpha,beta-unsaturated esters containing benzyl alcohol provided their corresponding 1,3-dihydroisobenzofuranyl-1-methylene ketones and 1,3-dihydroisobenzofuranyl-1-methylene esters in excellent yields with high enantioselectivities. In addition, enantioenriched 1,3-dihydroisobenzofuranyl-1-methylene ketone could be obtained from the Wittig/oxa-Michael reaction cascade of 1,3-dihydro-2-benzofuran-1-ol.

Automated summary

Organocatalytic enantioselective intramolecular oxa-Michael reactions can efficiently produce 1,3-dihydroisobenzofuranyl-1-methylene ketones and esters with high yields and enantioselectivities.