Regio- and Chemoselective Synthesis of 3-(Dihydrofuran-3(2H)-ylidene)isobenzofuran-1(3H)-imines via Tandem Alkynyl Prins- and Intramolecular Oxycyclization Reactions.

Abstract

A metal-free Lewis acid-initiated protocol for the synthesis of highly substituted 3-(dihydrofuran-3(2H)-ylidene)isobenzofuran-1(3H)-imines from 2-(4-hydroxybut-1-yn-1-yl)benzamides and aldehydes has been demonstrated. The reaction involves the initial formation of dihydrofuranylidene carbocation via a Prins cyclization reaction using BF3·OEt2, followed by intramolecular cyclization to produce 3-(dihydrofuran-3(2H)-ylidene)isobenzofuran-1(3H)-imines up to E/Z = 6:1 with moderate to good yields. The methodology can also be used for the synthesis of 3-(dihydro-2H-pyran-3(4H)-ylidene)-isobenzofuran-1(3H)-imines. The strategy leads to the formation of two C-O bonds and one C-C bond with two different heterocycles connected by a tetra-substituted double bond. Post synthetic application of the reaction was extended for the synthesis of furanylidene isobenzofuranones in excellent yields.