Copper-catalysed cyanoalkylative cycloetherification of alkenes to 1,3-dihydroisobenzofurans: development and application to the synthesis of citalopram

Abstract

A copper-catalysed cyanoalkylative cycloetherification of alkenes was developed. Heating a solution of substituted (2-vinylphenyl)methanol in MeCN/MeOH (v/v 7/3) in the presence of a catalytic amount of copper(II) tetrafluoroborate hydrate [Cu(BF₄)₂·6H₂O], bathophenanthroline, K₃PO₄, BnOH and (tBuO)₂ afforded 1,3-dihydroisobenzofurans (phthalanes) via formation of one C(sp³)–C(sp³) and one C(sp³)–O bonds. A concise synthesis of citalopram, a marketed anti-depressant drug, was accomplished by applying this novel synthetic transformation.