來源：市場(chǎng)資訊

（來源：康龍化成）

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(反應(yīng)類型), C(sp2)─C(sp3)(成鍵類型), Alkenyl bromides, Alcohols (原料), Multisubstituted alkenes (產(chǎn)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.

美國(guó)普林斯頓大學(xué)MacMillan教授課題組報(bào)道了一例鎳/光氧化還原雙催化的交叉偶聯(lián)反應(yīng)，可使醇直接脫氧與烯基溴或偕二溴烯烴反應(yīng)，構(gòu)建多取代烯烴及立體構(gòu)型確定的烯基溴。該方法官能團(tuán)耐受性優(yōu)異，對(duì)三取代烯烴和烯基溴具有高立體選擇性，并可通過迭代組裝的方式模塊化構(gòu)建復(fù)雜烯烴骨架，為從廉價(jià)原料出發(fā)合成高價(jià)值烯烴結(jié)構(gòu)提供了新路徑。