CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis , Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences , 345 Lingling Road , Shanghai 200032 , China.
The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine (IRI) , Shanghai University of Traditional Chinese Medicine , 1200 Cailun Road , Shanghai 201203 , China.
J Am Chem Soc. 2019 Aug 14;141(32):12770-12779. doi: 10.1021/jacs.9b05583. Epub 2019 Aug 2.
Because of the inherent difficulty in differentiating two olefins, the development of metal-catalyzed asymmetric cyclization of 1,6-dienes remains challenging. Herein, we describe the first rhodium(III)-catalyzed asymmetric borylative cyclization of cyclohexadienone-tethered mono-, 1,1-di-, and ()-1,2-disubstituted alkenes (1,6-dienes), affording optically pure -bicyclic skeletons bearing three or four contiguous stereocenters with high yields (25-93%), and excellent diastereoselectivities (>20:1 dr) and enantioselectivities (90-99% ee). This mild catalytic approach is generally compatible with a wide range of functional groups, which allows several facile conversions of the cyclization products. Furthermore, on the basis of our SAESI-MS experiment and computational study, a Rh(I)/(III) catalytic cycle is proposed in this tandem reaction, and the Rh(I) active species catalyzes the overall transformation via sequential oxidative addition of Bpin, olefin insertion, cyclizing conjugate addition, and reductive elimination. The irreversible conjugate addition determines the overall regioselectivity of borylative cyclization, and the ring strain favors the formation of 5,6-bicyclic structure. This highlights the control of ring strain in diene cyclizations, which provides a useful basis for future reaction designs.
由于两种烯烃难以区分，因此金属催化的 1,6-二烯不对称环化反应的发展仍然具有挑战性。在此，我们描述了首例铑(III)催化的环己二烯酮连接的单取代、1,1-二取代和 ()-1,2-二取代烯烃（1,6-二烯）的不对称硼化环化反应，以高收率（25-93%）、优异的非对映选择性（>20:1 dr）和对映选择性（90-99%ee）提供光学纯的 -双环骨架，具有三个或四个连续的立体中心。这种温和的催化方法通常与广泛的官能团兼容，允许对环化产物进行多种简便转化。此外，基于我们的 SAESI-MS 实验和计算研究，提出了该串联反应中的 Rh(I)/(III)催化循环，Rh(I)活性物种通过 Bpin 的顺序氧化加成、烯烃插入、环化共轭加成和还原消除来催化整个转化。不可逆的共轭加成决定了硼化环化的整体区域选择性，而环张力有利于 5,6-双环结构的形成。这突出了在二烯环化中控制环应变的重要性，为未来的反应设计提供了有用的依据。
