An Acid Catalyzed Alkynyl‐Prins Cyclization‐Rearrangement Cascade of 2‐(Alkynol)Benzoates: An Approach to 3‐Alkyl‐[n,5]‐Oxaspirophthalides

Abstract

The oxaspiro‐phthalides ([n,5]‐oxaspirobenzalactones) bearing a phthalide spirofused to a cyclic‐ether of various sizes are frameworks found in bioactive natural products. The discovery and development of an alkynyl‐Prins cyclization based, strategy for the construction of structurally interesting, medicinally useful [5,5]‐ [6,5]‐, and [7,5]‐oxaspirophthalides is reported in this manuscript. Our strategy may represent the first report on the construction of oxaspiro‐phthalides using the alkynyl‐Prins cyclization. This approach exhibits broad substrate scope with respect to carbonyl compounds and 2‐(alkynol)benzoates, with yields ranging between 71‐98%. Isolation of intermediate, and further conversion of it to the end‐product supported the proposed mechanistic pathway.