Theoretical Investigation on Lewis/Brønsted Acid Catalyzed Modulation of BCB Reactive Site in Synthesis of Spirocyclic and Bicyclic Framework

Abstract

Abstract: Our DFT calculation provided the first theoretical investigation on Lewis/Brønsted acids-catalyzed syntheses of bicyclo[2.1.1]hexane and spirocyclic compound from disubstituted BCB and ester activated quinone. For [2π + 2σ] cycloaddition with Ni(OTf)2 , BCB was activated as nucleophile to attack quinone initially. Then bicyclic product was achieved via cyclization. For (3 + 2) cycloaddition with DTBP, the dehydrogenation of BCB and aromatization of quinone is promoted owing to enhanced acidity of DTBP. The activation of BCB via hydrogen bonding between DTBP forms ion pair through intramolecular bridgehead bond cleavage. The nucleophilic addition of enolized BCB happens followed by deprotonation mediated by DTBP anion and aromatizes to cyclobutene. Another spirocyclic product was yielded via ester exchange along with recovered DTBP and CH4 release. The nucleophilic attack and ester exchange are rate-limiting for Ni(OTf)2-catalyzed [2π + 2σ] and DTBP-catalyzed (3 + 2) cycloaddition.

Keywords: Bicyclo[1.1.0]butane; Lewis/Brønsted acid; (3 + 2) cycloaddition; [2π + 2σ] cycloaddition; Quinone

Citation

Nan Lu. Theoretical Investigation on Lewis/Brønsted Acid Catalyzed Modulation of BCB Reactive Site in Synthesis of Spirocyclic and Bicyclic Framework. WebLog J Mol Cell Biol. wjmcb.2025.i0101. https://doi.org/10.5281/zenodo.17092177