A general copper-catalysed enantioconvergent radical Michaelis–Becker-type C(sp 3)–P cross-coupling

Wang，Li Lei1; Zhou，Huan1; Cao，Yu Xi1; Zhang，Chi1; Ren，Yang Qing1; Li，Zhong Liang2; Gu，Qiang Shuai2; Liu，Xin Yuan1

2023-05-01

10.1038/s44160-023-00252-3

Nature Synthesis   Impact Factor & Quartile

2731-0582

The Michaelis–Becker reaction of H-phosphonates with alkyl halides represents an ideal means for synthesizing alkyl phosphorous compounds. However, the enantioconvergent conversion of racemic alkyl halides into α-chiral alkyl phosphorous compounds in this reaction is an insurmountable challenge because of the inherent S2 mechanism. Here we disclose a copper-catalysed enantioconvergent radical Michaelis–Becker-type C(sp )–P cross-coupling. Key to the success of this reaction is the use of multidentate chiral anionic ligands for enhancing the reducing capability of the copper catalyst to favour a stereoablative radical pathway over a stereospecific S2-type process. Moreover, the ligand architecture is also able to assist the robust association of copper species with alkyl radicals over H-phosphonates, therefore exerting remarkable chemo- and enantioselectivity. This protocol covers a range of (hetero)benzyl-, propargyl- and α-aminocarbonyl alkyl bromides and chlorides. When allied with follow-up transformations, this method provides a versatile platform for valuable α-chiral alkyl phosphorous building blocks and drug leads. [Figure not available: see fulltext.]

English

First

2-s2.0-85163709534

Scopus

1.Shenzhen Grubbs Institute and Department of Chemistry,Guangdong Provincial Key Laboratory of Catalysis,Southern University of Science and Technology,Shenzhen,China
2.Academy for Advanced Interdisciplinary Studies and Department of Chemistry,Southern University of Science and Technology,Shenzhen,China

Wang，Li Lei,Zhou，Huan,Cao，Yu Xi,等. A general copper-catalysed enantioconvergent radical Michaelis–Becker-type C(sp 3)–P cross-coupling[J]. Nature Synthesis,2023,2(5):430-438.

Wang，Li Lei.,Zhou，Huan.,Cao，Yu Xi.,Zhang，Chi.,Ren，Yang Qing.,...&Liu，Xin Yuan.(2023).A general copper-catalysed enantioconvergent radical Michaelis–Becker-type C(sp 3)–P cross-coupling.Nature Synthesis,2(5),430-438.

Wang，Li Lei,et al."A general copper-catalysed enantioconvergent radical Michaelis–Becker-type C(sp 3)–P cross-coupling".Nature Synthesis 2.5(2023):430-438.