Synthesis of Bicyclo[1.1.0]butanes from Iodo-Bicyclo[1.1.1]pentanes

Abstract

We describe a two-step process for the synthesis of substituted bicyclo[1.1.0]butanes. A photo-Hunsdiecker reaction generates iodo-bicyclo[1.1.1]pentanes under metal-free conditions at room temperature. These intermediates react with nitrogen and sulfur nucleophiles to afford substituted bicyclo[1.1.0]butane products.

Decarboxylative C–N Coupling of 2,2-Difluorobicyclo[1.1.1]pentane (BCP-F2) Building Blocks

“…In the case of 3 , although the desired product 23b was not observed, the rearranged byproduct 25 was isolated in 23% yield with 1:1 regioisomeric ratio (rr, Scheme ) with respect to N -1 versus N -2 alkylation. We speculated that this transformation may occur through an iodo-BCP or iodonium-BCP intermediate based on a recent publication by researchers from BMS …”

Synthesis of Stereodefined Polysubstituted Bicyclo[1.1.0]butanes

“…In recent years, we have witnessed a remarkable renaissance of the field with BCBs serving as an entry to stereodefined cyclobutanes and C­(sp 3 )-rich bioisosteres. − However, the synthesis of stereodefined polysubstituted BCBs has received limited attention. Following the pioneering independent reports by Moore and Skattebo̷l of the synthesis of bridge-substituted BCBs, , several alternative strategies have appeared in the literature for the preparation of BCBs possessing two or more substituents (Scheme a). − As the number of substituents increases, many of these strategies often struggle to achieve precise stereochemical control, especially stereocontrolled quaternary centers. Furthermore, most of them necessitate electron-withdrawing groups (EWGs) on a bridgehead carbon center. − These limitations significantly restrict the diversity of accessible BCBs.…”