Zhuang Hong-Feng, Gu Jun, Ye Zhiwen, He Ying
School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China.
Angew Chem Int Ed Engl. 2025 Feb 10;64(7):e202418951. doi: 10.1002/anie.202418951. Epub 2024 Nov 14.
Transition-metal catalyzed asymmetric allylic substitution with alkyl and heteroaryl carbon nucleophiles has been well-established. However, the asymmetric allylic arylation of acyclic internal alkenes with aryl nucleophiles remains challenging and underdeveloped. Herein we report a stereospecific 3-aza-Cope rearrangement interrupted asymmetric allylic substitution-isomerization (Int-AASI) that enables asymmetric allylic arylation. By means of this stepwise strategy, both enantioenriched allylic arylation products and axially chiral alkenes could be readily obtained in high enantioselectivities. Experimental studies support a mechanism involving a cascade of asymmetric allylic amination, stereospecific 3-aza-Cope rearrangement and alkene isomerization. Density functional theory studies detailed the reasons of achieving the high chemoselectivity, regioselectivity, stereoselectivity and stereospecificity, respectively.
过渡金属催化的与烷基和杂芳基碳亲核试剂的不对称烯丙基取代反应已经得到了充分确立。然而，无环内烯烃与芳基亲核试剂的不对称烯丙基芳基化反应仍然具有挑战性且发展不足。在此，我们报道了一种立体专一性的3-氮杂-Cope重排中断的不对称烯丙基取代-异构化反应（Int-AASI），该反应能够实现不对称烯丙基芳基化。通过这种分步策略，可以很容易地以高对映选择性获得对映体富集的烯丙基芳基化产物和轴手性烯烃。实验研究支持了一个涉及不对称烯丙基胺化、立体专一性3-氮杂-Cope重排和烯烃异构化的级联反应机理。密度泛函理论研究分别详细阐述了实现高化学选择性、区域选择性、立体选择性和立体专一性的原因。
