Rhodium-Catalyzed Enantioconvergent Isomerization of Homoallylic and Bishomoallylic Secondary Alcohols

We present herein an unprecedented
enantioselective isomerization
of homoallylic and bishomoallylic secondary alcohols, catalyzed by
a commercially available rhodium-complex and a base. This catalytic
redox-neutral process provides an effective access to chiral ketones
in high efficiency and enantioselectivity, without the use of any
stoichiometric reagent or generation of any waste. For the reaction
of homoallylic alcohols, this system achieved not only a stereoconvergent
access to chiral ketones bearing a β-stereocenter (up to 95%,
86% ee) but also a concomitant oxidative kinetic resolution of the
alcohol substrates (S > 20). In the case of bishomoallylic alcohols,
an intriguing ligand-induced divergent reactivity was observed. A
terminal-to-internal alkene isomerization promoted by Rh/L7 followed by redox isomerization using Rh/BINAP system produced chiral
ketones bearing a γ-stereocenter with high yield and enantioselectivity.
Mechanistic studies provided strong support for the redox-isomerization
pathway with chain walking of the key alkyl-Rh intermediate.

本研究报道了一种前所未有的均烯丙基与双高烯丙基二级醇的对映选择性异构化反应，该反应以商业化可得的铑络合物与碱作为催化剂。此催化氧化还原中性过程可高效、高对映选择性地合成手性酮类化合物，且无需使用任何化学计量试剂，亦无副产物生成。针对均烯丙基醇的反应，该体系不仅实现了带有β-手性中心的手性酮类化合物的立体汇聚式合成（最高收率95%，对映选择性86% ee），还可同步实现醇底物的氧化动力学拆分（选择性因子S > 20）。对于双高烯丙基醇，则观察到了有趣的配体诱导反应路径分歧现象：由Rh/L7催化的端烯到内烯烃异构化，再结合Rh/BINAP体系进行氧化还原异构化，可合成带有γ-手性中心的手性酮类化合物，且收率与对映选择性俱佳。机理研究为关键烷基-铑中间体的链行走过程所介导的氧化还原异构化反应路径提供了有力支撑。