Regio- and Enantioselective Hydromethylation of 3-Pyrrolines and Glycals Enabled by Cobalt Catalysis DOI Creative Commons

Mengyang Shen,

C. NIU,

Xuchao Wang

et al.

JACS Au, Journal Year: 2024, Volume and Issue: 4(6), P. 2312 - 2322

Published: June 11, 2024

Enantioenriched 3-methylpyrrolidine, with its unique chiral nitrogen-containing core skeleton, exists widely in various functional molecules, including natural products, bioactive compounds, and pharmaceuticals. Traditional methods for synthesizing these valuable methyl-substituted heterocycles often involve enzymatic processes or complex procedures auxiliaries, limiting the substrate scope efficiency. Efficient catalytic methylation, especially an enantioselective manner, has been a long-standing challenge chemical synthesis. Herein, we present novel approach remote stereoselective installation of methyl group onto N-heterocycles, leveraging CoH-catalyzed asymmetric hydromethylation strategy. By effectively combining commercial cobalt precursor modified bisoxazoline (BOX) ligand, variety easily accessible 3-pyrrolines can be converted to enantiopure 3-(isotopic labeling)methylpyrrolidine compounds outstanding enantioselectivity. This efficient protocol streamlines two-step synthesis enantioenriched which previously required up five six steps under harsh conditions expensive starting materials.

Language: Английский

Ligand-Controlled Cobalt-Catalyzed Regio-, Enantio-, and Diastereoselective Oxyheterocyclic Alkene Hydroalkylation DOI
Zhen Li,

Bingxue Liu,

Cheng-Yu Yao

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 3405 - 3415

Published: Jan. 29, 2024

Metal-hydride-catalyzed alkene hydroalkylation has been developed as an efficient method for C(sp

Language: Английский

Citations

20
Nickel-Catalyzed Migratory Cross-Coupling Reactions: New Opportunities for Selective C–H Functionalization DOI
You Wang, Yuli He, Shaolin Zhu

et al.

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(23), P. 3475 - 3491

Published: Nov. 16, 2023

ConspectusMigratory cross-coupling via metal migration is a process of significant academic and industrial interest. It provides an attractive alternative for the selective installation functional group at remote C-H positions from simple precursors, thus enabling direct synthesis challenging structures not accessible with traditional cross-coupling. In particular, merger 1,n-Ni/H shift nickel, Ni-catalyzed migratory functionalization precursors has undergone particularly intense development emerged as valuable field research in past few years. This Account will outline recent progress made this arena terms migration-functionalization modes, diverse functionalizations, strategies regio- stereocontrol. Mechanistic studies synthetic applications are also discussed.In detail, we systematically categorize our work into two parts based on modes. first part, platform created sp3 alkenes or alkyl halides iterative 1,2-Ni/H shift-selective The key reactive Ni(II)H species chain-walking could be generated situ either polarity-reversed fashion relying stoichiometric reductants (X-Ni(II)-H) redox-neutral participation nucleophilic coupling partners (FG-Ni(II)-H). One advantage associated NiH system use relatively stable, abundant, safe olefin surrogates instead sensitive organometallics required reactions. Another that including carbonation more amination thiolation smoothly achieved suitable electrophiles their precursors. Finally, to address multifaceted selectivity reactivity issues asymmetric reactions, have developed feasible ligand relay catalytic strategy. dynamic exchange process, one promotes rapid while other highly stereoselective coupling. innovative strategy overcomes formidable challenge stemming difficulty designing single efficiently promote both steps second new sp2 1,4-Ni/H been reported. Starting readily available aryl vinyl partners, situ-generated aryl- vinylnickel(II) undergo reversible along backbone, subsequent various would allow access 1,4-migratory products. success was discovery appropriate A vinyl-to-aryl successfully enables modular ipso/ortho difunctionalization aryl-to-vinyl functionalized trisubstituted alkenes.We hope inspire broad interest future We strongly believe continued efforts fascinating overcome many remaining challenges, cutting-edge ligand/catalyst design enhance selectivity, conceptually modes additional transformations, in-depth mechanistic rational reaction design.

Language: Английский

Citations

35
Cobalt‐Catalyzed Facial‐Selective Hydroalkylation of Cyclopropenes DOI
Zhilin Zhang, Zhen Li,

Yuantai Xu

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(30)

Published: May 31, 2023

Abstract Cyclopropene hydrofunctionalization has been a promising strategy for accessing multi‐substituted cyclopropanes; however, cyclopropene hydroalkylation remains underdeveloped. Herein, we report low‐valent CoH‐catalyzed facial‐selective to access cyclopropanes. This reaction exhibits broad substrate scope of alkyl halides and cyclopropenes tolerates many functional groups. Moderate‐to‐good facial‐selectivity is obtained without any directing Mechanism studies provide evidence that radicals are generated from irreversible CoH insertion responsible the facial‐selectivity. Our preliminary exploration demonstrates asymmetric can be realized conspicuous auxiliary

Language: Английский

Citations

27
Palladium‐Catalyzed Inward Isomerization Hydroaminocarbonylation of Alkenes DOI

Xian‐Jin Zou,

Zhao‐Xing Jin,

Huiyi Yang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(26)

Published: April 15, 2024

In contrast to the kinetically favored outward isomerization-hydrocarbonylation of alkenes, disfavored inward alkenes remains an important challenge. Herein, we have developed a novel and effective palladium-catalyzed isomerization-hydroaminocarbonylation unactivated aniline hydrochlorides for formation synthetically valuable α-aryl carboxylic amides in high yields site-selectivities. The efficiency reaction is attributed relay catalysis strategy, which Markovnikov-favored [PdH]-P

Language: Английский

Citations

13
Palladium-Catalyzed Enantioselective Multicomponent Cross-Coupling of Trisubstituted Olefins DOI

Wenyi Huang,

Yang Xi, Deng Pan

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(24), P. 16892 - 16901

Published: June 6, 2024

The development of a catalytic method for stereogenic carbon center formation holds immense significance in organic synthesis. Transition-metal-catalyzed cross-coupling reaction has been regarded as straightforward and efficient tool stereoselectively forging C–C bond. Nevertheless, the creation acyclic all-carbon quaternary-containing vicinal stereocenters remains notoriously challenging within domain chemistry despite their prominence various bioactive small molecules. Herein, we describe palladium-catalyzed asymmetric multicomponent trisubstituted alkene with aryl diazonium salts arylboronic acids to realize tertiary-quaternary centers high regio-, distereo-, enantioselectivity. Specifically, precise manipulation stereoconfiguration alkenes enables divergent stereoselective reaction, thus allowing facile construction all four enantiomers. Harnessing ligand-swap strategy involving chiral bisoxazoline an achiral fumarate individually accelerates enantioselective migratory insertion reductive elimination step process, supported by density functional theory (DFT) calculations, obviating requirement neighboring directing group internal olefin skeleton.

Language: Английский

Citations

10
NiH-Catalyzed Regio- and Enantioselective Hydroalkylation for the Synthesis of β- or γ-Branched Chiral Aromatic N-Heterocycles DOI
Ju‐Song Yang,

Ka Lu,

Chen‐Xiao Li

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(40), P. 22122 - 22134

Published: Sept. 25, 2023

A nickel hydride-catalyzed regio- and enantioselective hydroalkylation reaction was developed to give access a library of chiral β- or γ-branched aromatic N-heterocycles. This intriguing asymmetric transformation features excellent selectivities, step- atom-economies, generating two kinds products through one synthetic strategy. Furthermore, the possible mechanism extensively investigated using numerous control experiments density functional theory calculations.

Language: Английский

Citations

22
Selective Hydrofunctionalization of Alkenyl Fluorides Enabled by Nickel-Catalyzed Hydrogen Atoms and Group Transfer: Reaction Development and Mechanistic Study DOI
Fan Chen, Qianwei Zhang, Yingying Li

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: April 15, 2024

Due to the unique effect of fluorine atoms, efficient construction high-value alkyl fluorides has attracted significant interest in modern drug development. However, enantioselective catalytic strategies for assembly highly functionalized chiral C(sp

Language: Английский

Citations

9
Hydrodeuteroalkylation of Unactivated Olefins Using Thianthrenium Salts DOI
Jie Zhang,

Mengjie Jiao,

Zheng Lu

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(36)

Published: June 13, 2024

Isotopically labeled alkanes play a crucial role in organic and pharmaceutical chemistry. While some deuterated methylating agents are readily available, the limited accessibility of other deuteroalkyl reagents has hindered synthesis corresponding products. In this study, we introduce nickel-catalyzed system that facilitates various deuterium-labeled through hydrodeuteroalkylation d2-labeled alkyl TT salts with unactivated alkenes. Diverging from traditional reagents, thianthrenium (TT) can effectively selectively deuterium at α position chains using D

Language: Английский

Citations

9
Enantioselective alkene hydroalkylation overcoming heteroatom constraints via cobalt catalysis DOI
Yan Li, Deguang Liu, Xiao Hu

et al.

Nature Synthesis, Journal Year: 2024, Volume and Issue: 3(9), P. 1134 - 1144

Published: July 10, 2024

Language: Английский

Citations

8
NiH-catalyzed C–N bond formation: insights and advancements in hydroamination of unsaturated hydrocarbons DOI Creative Commons
Changseok Lee, Hyung‐Joon Kang, Sungwoo Hong

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 15(2), P. 442 - 457

Published: Dec. 6, 2023

The formation of C-N bonds is a fundamental aspect organic synthesis, and hydroamination has emerged as pivotal strategy for the synthesis essential amine derivatives. In recent years, there been surge interest in metal hydride-catalyzed reactions common alkenes alkynes. This method avoids need stoichiometric organometallic reagents overcomes problems associated with specific compounds that may impact functional group compatibility. Notably, developments have brought to forefront olefinic hydroamidation facilitated by nickel hydride (NiH) catalysis. inclusion suitable chiral ligands paved way realization asymmetric realm olefins. review aims provide an in-depth exploration latest achievements bond through intermolecular catalyzed hydrides. Leveraging this innovative approach, diverse range alkene alkyne substrates can be efficiently transformed into value-added enriched bonds. intricacies are succinctly elucidated, offering concise overview underlying reaction mechanisms. It our aspiration comprehensive will stimulate further progress NiH-catalytic techniques, fine-tune systems, drive innovation catalyst design, foster deeper understanding

Language: Английский

Citations

17