Ni Hui-Qi, Alturaifi Turki M, Rodphon Warabhorn, Scherschel Nicholas F, Yang Shouliang, Wang Fen, McAlpine Indrawan J, Piercey Davin G, Liu Peng, Engle Keary M
Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, United States.
Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States.
J Am Chem Soc. 2024 Sep 4;146(35):24503-24514. doi: 10.1021/jacs.4c07039. Epub 2024 Aug 22.
A facile approach to obtaining densely functionalized cyclopropanes is described. The reaction proceeds under mild conditions via the directed nucleopalladation of nonconjugated alkenes with readily available pronucleophiles and gives excellent yields and good -selectivity using I and TBHP as oxidants. Pronucleophiles bearing a diverse collection of electron-withdrawing groups, including -CN, -COR, -COR, -SOPh, -CONHR, and -NO, are well tolerated. Internal alkenes, which are generally challenging substrates in other cyclopropanation methods, provide excellent yields and good diastereoselectivity in this methodology, allowing for controlled access to cyclopropanes substituted at all three C atoms. DFT calculations and mechanistic experiments reveal that the major mechanistic pathway involves the initial α-iodination of the nucleophile, followed by -carbopalladation and intramolecular C(sp)-I oxidative addition. Strain-release-promoted C(sp)-C(sp) reductive elimination then furnishes the cyclopropanated product.
描述了一种获得密集官能化环丙烷的简便方法。该反应在温和条件下通过非共轭烯烃与易于获得的亲核前体的定向亲核钯化进行，以I和叔丁基过氧化氢（TBHP）作为氧化剂时，产率优异且选择性良好。带有多种吸电子基团（包括-CN、-COR、-COR、-SOPh、-CONHR和-NO）的亲核前体具有良好的耐受性。在其他环丙烷化方法中通常具有挑战性的内烯烃，在此方法中提供了优异的产率和良好的非对映选择性，从而能够可控地获得在所有三个碳原子上均被取代的环丙烷。密度泛函理论（DFT）计算和机理实验表明，主要的机理途径涉及亲核试剂的初始α-碘化，随后是β-碳钯化和分子内C(sp)-I氧化加成。然后，应变释放促进的C(sp)-C(sp)还原消除生成环丙烷化产物。
