Copper-catalysed synthesis of chiral alkynyl cyclopropanes using enantioconvergent radical cross-coupling of cyclopropyl halides with terminal alkynes

Gao, Zeng1,2,3; Liu, Lin1,4,5; Liu, Ji-Ren1,2,3; Wang, Wang1,2,3; Yang, Ning-Yuan1,2,3; Tao, Lizhi2,3; Li, Zhong-Liang2,3; Gu, Qiang-Shuai2,3; Liu, Xin-Yuan1,2,3

2024-09-01

10.1038/s44160-024-00654-x

NATURE SYNTHESIS   影响因子和分区

2731-0582

["Transition-metal-catalysed enantioconvergent cross-coupling reactions of highly reactive alkyl radicals often suffer from reduced chemoselectivity, mainly due to side reactions with closed-shell reactants. A strategy to overcome this challenge has yet to be identified, posing substantial limitations on the synthetic utility of this method. Here we report a method for enantioconvergent radical carbon-carbon cross-coupling of highly reactive cyclopropyl radicals with terminal alkynes, using redox state-tuned copper catalysis, under mild conditions. Key to this method is the use of hard chiral N,N,N-ligands in combination with Cu(II) salts of hard ligands/counterions, which results in elevated concentrations of Cu(II) species and thus enhanced cross-coupling reactions. This protocol not only exhibits a broad substrate scope across a wide range of both racemic cyclopropyl halide and terminal alkyne coupling partners but also provides access to useful yet synthetically challenging enantioenriched cyclopropane building blocks.","The synthetic use of highly reactive alkyl radicals typically results in low chemoselectivity due to competing side reactions. Now, a redox-state-tuned copper catalytic method is reported, which enables the enantioconvergent cross-coupling of cyclopropyl radicals and terminal alkynes with high chemo- and stereoselectivity."]

ESCI

英语

第一 ; 通讯

National Natural Science Foundation of China (National Science Foundation of China)["22025103","92256301","22331006","22271133","22201127"] ; National Natural Science Foundation of China["2021YFF0701604","2021YFF0701704"] ; National Key R&D Program of China[2019BT02Y335] ; Guangdong Innovative Program[2023B0303000020] ; New Cornerstone Science Foundation["KQTD20210811090112004","JCYJ20220818100600001"] ; Shenzhen Science and Technology Program[ZDSYS20220328104200001] ; Shenzhen Key Laboratory of Cross-Coupling Reactions[G03050K003] ; High-Level of Special Funds[G030210001]

Chemistry

Chemistry, Multidisciplinary

WOS:001320881100001

SPRINGERNATURE

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Key Lab Cross Coupling React, Shenzhen, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Dept Chem, Shenzhen, Peoples R China
3.Southern Univ Sci & Technol, Guangming Adv Res Inst, Shenzhen, Peoples R China
4.Great Bay Univ, Great Bay Inst Adv Study, Dept Chem, Dongguan, Peoples R China
5.Great Bay Univ, Guangdong Prov Key Lab Math & Neural Dynam Syst, Dongguan, Peoples R China

Gao, Zeng,Liu, Lin,Liu, Ji-Ren,et al. Copper-catalysed synthesis of chiral alkynyl cyclopropanes using enantioconvergent radical cross-coupling of cyclopropyl halides with terminal alkynes[J]. NATURE SYNTHESIS,2024.

Gao, Zeng.,Liu, Lin.,Liu, Ji-Ren.,Wang, Wang.,Yang, Ning-Yuan.,...&Liu, Xin-Yuan.(2024).Copper-catalysed synthesis of chiral alkynyl cyclopropanes using enantioconvergent radical cross-coupling of cyclopropyl halides with terminal alkynes.NATURE SYNTHESIS.

Gao, Zeng,et al."Copper-catalysed synthesis of chiral alkynyl cyclopropanes using enantioconvergent radical cross-coupling of cyclopropyl halides with terminal alkynes".NATURE SYNTHESIS (2024).