Selective Base-Promoted Synthesis of Dihydroisobenzofurans by Domino Addition/Annulation Reactions of ortho-Alkynylbenzaldehydes

Abstract

Synthesis of the dihydroisobenzofuran nucleus was achieved by the base-promoted tandem nucleophilic addition/annulation reaction of ortho-alkynylbenzaldehydes in the presence of methanol. The reactions of aryl-, trimethylsilyl- and diethoxymethyl-substituted alkynylbenzaldehydes occurred with complete regio­selectivity in good to excellent yields under microwave irradiation. The reactions of alkyl-substituted alkynylbenzaldehydes took place with good yields and high regioselectivity only when performed at room temperature and in the presence of a catalytic amount of a gold(III) salt. Plausible reaction mechanisms involved are discussed. The effect of the substituent at the alkynyl terminus on the cyclisation mode was tentatively rationalised.