Lewis Acid Catalyzed Divergent Reaction of Bicyclo[1.1.0]Butanes With Quinones for the Synthesis of Diverse Polycyclic Molecules.

Bicyclo[1.1.0]butanes (BCBs) are highly strained hydrocarbons with unique structural properties and intrinsic reactivity, making them valuable building blocks for constructing complex molecular architectures. Herein, we report the Lewis acid-catalyzed divergent reactions of BCBs with quinones, yielding a diverse array of polycyclic molecules. Using Sc(OTf)₃ as a catalyst, pyrazole-substituted BCBs efficiently undergo formal (3 + 2) cycloaddition reactions with quinones, producing highly substituted bicyclo[2.1.1]hexanes featuring a caged framework. Monosubstituted BCB ketones undergo a sequential cascade involving Alder-ene reaction, 4π electrocyclic ring-opening, and [4 + 2] cycloaddition reaction, yielding fused benzoxepines efficiently. Disubstituted BCB esters, ketones, and amides undergo a tandem isomerization and (3 + 2) cycloaddition process, stereoselectively yielding tetrahydrocyclobuta[b]benzofuran products. Notably, strong Lewis acids such as SnCl₄ and BiBr₃ directly participate in the ring-opening reactions of monosubstituted BCB ketones, generating halogenated cyclobutane derivatives. Additionally, the synthetic potential of these approaches has been further highlighted through scale-up experiments and a range of transformations. This study demonstrates the tunability of reaction pathways based on the diverse substitution patterns of BCBs, providing efficient methods for the synthesis of a range of polycyclic compounds.