来源：市场资讯
（来源：康龙化成）
Piecewise Stereoselective Assembly of Multisubstituted Alkenes
Eli Jones,Robert T. Martin,David W. C. MacMillan*
Merck Center for Catalysis at Princeton University, Princeton, New Jersey 08544, United States
Recommended by Depei Meng _ MC4
KEY WORDS: Ni catalysis, deoxygenation, photo chemistry(反应类型), C(sp2)─C(sp3)(成键类型), Alkenyl bromides, Alcohols (原料), Multisubstituted alkenes (产物)
ABSTRACT: Multisubstituted alkenes are valuable structural motifs that also serve as key intermediates in complexity-building transformations; however, their stereoselective synthesis remains a longstanding challenge. Alkenyl bromides are appealing coupling handles for alkene synthesis, though their application would be greatly enhanced if they could be coupled directly with alkyl radicals derived from feedstock alcohols. Herein, we report a nickel metallaphotoredox-enabled deoxygenative cross-coupling of alkenyl bromides with alcohols, providing a direct, modular approach to multisubstituted alkenes. This transformation exhibits a broad substrate scope across both alcohol and alkenyl bromide partners, delivering over 30 multisubstituted alkenes. Moreover, we developed a complementary stereoselective bromoalkenylation from readily synthesized gem-dibromoolefins to address the limited availability of stereodefined alkenyl bromides. In the presence of a phthalimide additive, selective monofunctionalization enables access to over 40 stereodefined alkenyl bromides, providing a general and stereoselective pathway to these otherwise difficult-to-access intermediates. Direct access to alkenyl bromides enables piecewise stereoselective assembly of multisubstituted alkenes through sequential alcohol coupling or stereoretentive Suzuki–Miyaura reactions. These strategies are illustrated via iterative cross-coupling sequences and the total synthesis of (+)-sponalisolide B.
Strategic approach to stereoselective multisubstituted alkene synthesis
Proposed mechanism
Alkylation of Alkenyl Bromides (selected examples)
Deoxygenative Alkylation of gem-Dibromoolefins (selected examples)
Sequential strategies toward piecewise assembly of multisubstituted alkenes
Summary and Comments
In summary, Prof. MacMillan’s group have reported the direct deoxygenative nickel metallaphotoredox-catalyzed cross-coupling of alcohols with alkenyl bromides and gem-dibromoolefins to generate multisubstituted alkenes and stereodefined alkenyl bromides. These reactions proceed with excellent functional group tolerance and─in the case of trisubstituted alkenes and alkenyl bromides─high stereoselectivity. This platform enables iterative, piecewise assembly of multisubstituted alkenes, providing a new pathway for the synthesis of these highly valued motifs from feedstock building blocks. We anticipate that the modularity and functional group tolerance of this platform will find broad application in the synthesis of complex alkene-containing molecules.
美国普林斯顿大学MacMillan教授课题组报道了一例镍/光氧化还原双催化的交叉偶联反应，可使醇直接脱氧与烯基溴或偕二溴烯烃反应，构建多取代烯烃及立体构型确定的烯基溴。该方法官能团耐受性优异，对三取代烯烃和烯基溴具有高立体选择性，并可通过迭代组装的方式模块化构建复杂烯烃骨架，为从廉价原料出发合成高价值烯烃结构提供了新路径。
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