Palladium-Catalyzed Radical Annulation of α-Iodo-gem-Diborylalkanes with Alkenes: A Facile Approach to Semisaturated Cyclic Scaffolds.

Abstract

Semisaturated cyclic scaffolds are increasingly valued in medicinal chemistry due to their balanced sp2/sp3 character and unique physicochemical properties, yet their synthesis often relies on lengthy de novo sequences. Herein, we report a palladium-catalyzed radical annulation of α-iodo-gem-diborylalkanes with alkenes, enabling a two-phase approach to these architectures from readily accessible precursors. The key transformation proceeds via a tandem Giese addition/homolytic aromatic substitution sequence and accommodates a broad range of (hetero)aromatic systems with diverse electronic properties and substitution patterns. Mechanistic experiments are consistent with the intermediacy of gem-diboryl carbon-centered radicals, and density functional theory (DFT) calculations support the proposed Pd(I)/radical catalytic cycle. The retained gem-diboryl moiety in the products provides opportunities for diverse downstream functionalization and skeletal diversification, including deborylative cyclization to fused and bridged tricyclic frameworks that are otherwise difficult to obtain. This study establishes a boron-enabled platform for semisaturated scaffold construction and highlights the synthetic potential of α-iodo-gem-diboryl reagents.