Modular Synthesis of Benzothiophene-Fused Pentalene Reveals Substituent-Dependent Antiaromaticity

Abstract

Antiaromatic π-electron systems provide unique electronic features arising from the cyclic conjugation of 4n π-electrons, yet synthetic access to strongly antiaromatic heteroarene-fused scaffolds remains limited. Here we report a general and scalable synthetic route to benzothiophene-fused pentalenes via the first thiophene analogue of Brand’s bicyclo[3.3.0]octadiene-1,4-dione intermediate. The pre-installation of the bicyclic five-membered-ring core at an early stage of synthesis enables efficient annulation of benzothiophene moieties and late-stage diversification at the 1,4-positions through the 1,2-addition of organometallic nucleophiles, followed by optimized dehydration. This strategy affords a series of benzothiophene-fused pentalenes bearing diverse aryl, heteroaryl, and alkynyl substituents in practical yields, with isolation by simple filtration. The benzothiophene-fused pentalenes thus obtained exhibit strong antiaromatic character that correlates with electronic effects, consistent with the topological charge stabilization rule. This work establishes a versatile platform for probing substituent-dependent antiaromaticity and for designing functional materials based on strongly antiaromatic π-systems.