Controlling Enantioselectivity and Diastereoselectivity in Radical Cascade Cyclization for Construction of Bicyclic Structures.
Controlling Enantioselectivity and Diastereoselectivity in Radical Cascade Cyclization for Construction of Bicyclic Structures.
复制标题
控制自由基级联环化中的对映选择性和非对映选择性以构建双环结构。
DOI：
10.1021/jacs.1c04719
复制
发表时间：
2021-07-28
影响因子：
15
通讯作者：
Zhang XP
中科院分区：
文献类型：
--
作者：
Zhang C;Wang DS;Lee WC;McKillop AM;Zhang XP
自由基级联环化反应是有机合成中构建多环分子的极具吸引力的合成工具。尽管自由基级联环化已成功地应用于天然产物和其他复杂化合物的非对映选择性合成，但自由基级联环化面临着控制对映体选择性的重大挑战。作为金属催化(MRC)在自由基级联环化反应中控制对映体选择性和非对映选择性的首次应用，本文报道了一种基于Co(II)的催化体系用于1，6-烯炔与重氮化合物的不对称自由基环化反应。通过微调D2对称的手性氨基卟啉作为支撑配体，Co(II)催化的自由基级联过程在温和的条件下一次操作就可以实现多取代环丙烷稠合四氢呋喃的不对称构建，该过程具有三个连续的立体生成中心，包括两个全碳四元中心，高产率和良好的立体选择性。计算和实验相结合的研究揭示了这种新的基于Co(II)的级联自行车反应的潜在的逐步自由基机制，其中包括几个Co支撑的C中心自由基中间体的接力，包括α-，β-，γ-和ε-金属烷基自由基。所得到的富含对映体的环丙烷稠合四氢呋喃在桥头含有三取代乙烯基，如几个立体专一性转化所示，可作为立体选择性有机合成的有用中间体。通过Co(II)-MRC成功地演示了这一新的不对称自由基反应过程，指出了在合成的吸引人的自由基级联反应中控制对映体选择性和非对映选择性的潜在的一般方法。
Radical cascade cyclization reactions are highly attractive synthetic tools for the construction of polycyclic molecules in organic synthesis. While it has been successfully implemented in diastereoselective synthesis of natural products and other complex compounds, radical cascade cyclization faces a major challenge of controlling enantioselectivity. As the first application of metalloradical catalysis (MRC) for controlling enantioselectivity as well as diastereoselectivity in radical cascade cyclization, we herein report the development of a Co(II)-based catalytic system for asymmetric radical bicyclization of 1,6-enynes with diazo compounds. Through the fine-tuning of D2-symmetric chiral amidoporphyrins as the supporting ligands, the Co(II)-catalyzed radical cascade process, which proceeds in a single operation under mild conditions, enables asymmetric construction of multisubstituted cyclopropane-fused tetrahydrofurans bearing three contiguous stereogenic centers, including two all-carbon quaternary centers, in high yields with excellent stereoselectivities. Combined computational and experimental studies have shed light on the underlying stepwise radical mechanism for this new Co(II)-based cascade bicyclization that involves the relay of several Co-supported C-centered radical intermediates, including α-, β-, γ-, and ε-metalloalkyl radicals. The resulting enantioenriched cyclopropane-fused tetrahydrofurans that contain a trisubstituted vinyl group at the bridgehead, as showcased in several stereospecific transformations, may serve as useful intermediates for stereoselective organic synthesis. The successful demonstration of this new asymmetric radical process via Co(II)-MRC points out a potentially general approach for controlling enantioselectivity as well as diastereoselectivity in synthetically attractive radical cascade reactions.
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DOI：
10.1002/anie.201808183
发表时间：
2018-09-24
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Bonilla P;Rey YP;Holden CM;Melchiorre P
通讯作者：
Melchiorre P
影响因子：
8.4
作者：
Cui X;Xu X;Jin LM;Wojtas L;Zhang XP
通讯作者：
Zhang XP
影响因子：
15
作者：
Das, Sandip Kumar;Roy, Satyajit;Chattopadhyay, Buddhadeb
通讯作者：
Chattopadhyay, Buddhadeb
影响因子：
5.4
作者：
Alessandro Perego, Luca;Bonilla, Pablo;Melchiorre, Paolo
通讯作者：
Melchiorre, Paolo
影响因子：
21.8
作者：
Arceo, Elena;Jurberg, Igor D.;Melchiorre, Paolo
通讯作者：
Melchiorre, Paolo