Synthesis of Benzodithieno[5.5.5.6]Fenestranes: Unexpected Epimerization and Regiochemical Outcomes

Abstract Isomeric [5.5.5.6]fenestranes bearing one benzene and two thiophene rings annulated to all‐ cis ‐ and cis , cis , trans , cis ‐fenestrane cores are presented. The synthesis route previously established for the corresponding tribenzo[5.5.5.6]fenestranes includes twofold cyclodehydration of the stereoisomeric spiro[cyclohexane‐1,2’‐indane]‐1’,3’‐diol intermediates and enables construction of the first heteroaromatic, benzodithieno‐annulated fenestranes. Both the regio‐ and stereoselectivity of the twofold cyclization depend on the choice of 2‐ or 3‐thienyl building blocks and their relative orientation at the spiranediols. Twofold acid‐catalyzed cyclodehydration of the trans ‐ and cis ‐di‐2‐thienylspiranediols is stereoconvergent, yielding the same all‐ cis ‐fenestranes, which implies involvement of a Brønsted acid‐induced epimerization in the case of the cis ‐series. In contrast, similar acid‐catalyzed twofold cyclization of the cis ‐ and trans ‐di‐3‐thienyl isomers are stereospecific, giving the cis , cis , trans , cis ‐ and all‐ cis ‐benzodithieno[5.5.5.6]fenestrane skeletons, respectively. While the former proceeds with high regioselectivity, the latter results in poor regioselectivity with regard to the orientation of the thiophene rings. The solid‐state molecular structures of an all‐ cis ‐benzodithieno[5.5.5.6]fenestrane and a strained cis , cis , trans , cis ‐congener with a significantly flattened geometry at the central carbon atom were determined by X‐ray diffraction. Mechanistic alternatives to rationalize the unprecedented acid‐catalyzed epimerization during the formation of the [5.5.5.6]fenestrane skeleton are discussed.