gem-DifluoroVinylcyclopropane (DF-VCP) Rearrangement to Cyclopentenones Catalyzed by Rh: Reaction Development, Mechanism, and Application to the Total Synthesis of (±)-15-nor-Pentalenene

Rh catalyzed gem-difluorovinylcyclopropane (DF-VCP) rearrangement (which can also be named 1,3-sigma migratory ring expansion) has been developed to synthesize 2-cyclopentenones with high efficiency and a wide substrate scope. In this reaction, water as the oxygen source was used to convert the CF2 group of the substrates to a carbonyl group in the final products. Utility of the DF-VCP rearrangement to the total synthesis of (±)-15-nor-pentalenene, an advanced model of branched triquinane natural products, has also been achieved, further demonstrating the practice of the present reaction to build triquinane skeleton from highly substituted DF-VCPs. Of the same importance, the mechanism of this rearrangement has been investigated by conducting experiments and DFT calculations, showing that gem-difluoro ene as a ketene surrogate works here (changing CF2 group to CO group in the catalytic cycle) to realize otherwise difficult reductive elimination of forming a C(sp3)-C(sp3) bond. This strategy could be applied to design further reactions in the future.

铑(Rh)催化的偕二氟乙烯基环丙烷（gem-difluorovinylcyclopropane，DF-VCP）重排反应（又可称为1,3-σ迁移扩环反应）已被成功开发，可高效合成底物适用范围广泛的2-环戊烯酮。本反应以水作为氧源，将底物中的CF₂基团转化为最终产物中的羰基。此外，本DF-VCP重排反应还成功应用于(±)-15-去甲骈五茚（(±)-15-nor-pentalenene）的全合成，该化合物是支链三奎烷（triquinane）类天然产物的高级模型分子，进一步验证了本反应可从高取代DF-VCP构建三奎烷骨架的实用性。同样值得关注的是，研究团队通过实验与密度泛函理论（DFT）计算对该重排反应的机理展开了探究，结果显示：作为烯酮（ketene）替代物的偕二氟烯烃（gem-difluoro ene）在催化循环中可将CF₂基团转化为羰基，从而实现原本难以发生的C(sp³)-C(sp³)键还原消除过程。该策略未来可用于设计开发更多新型反应。