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

The synthesis of 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 microwaves 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. The plausible reaction mechanisms involved were discussed. The effect of the substituent at the alkynyl terminus on the cyclization mode was tentatively rationalized.