A General Enantioselective α-Alkyl Amino Acid Derivatives Synthesis Enabled by Cobalt-Catalyzed Reductive Addition DOI

Chengxi Zhang,

Xianqing Wu, Jingping Qü

et al.

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

Published: Sept. 12, 2024

Enantioenriched unnatural amino acids represent a prevalent motif in organic chemistry, with profound applications biochemistry, medicinal and materials science. Herein, we report cobalt-catalyzed aza-Barbier reaction of dehydroglycines unactivated alkyl halides to afford α-amino esters high enantioselectivity. This catalytic reductive alkylative addition protocol circumvents the use moisture-, air-sensitive organometallic reagents, stoichiometric chiral auxiliaries, enabling conversion variety primary, secondary, even tertiary α-alkyl-amino under mild conditions, thus leading broad functional group tolerance. The expedient access biologically active motifs demonstrates practicality this by reducing number synthetic steps enhancing efficiency.

Language: Английский

Cobalt-Catalyzed Sequential Site- and Stereoselective Hydrosilylation of 1,3- and 1,4-Enynes DOI

Wenxin Lu,

Yongmei Zhao,

Fanke Meng

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(12), P. 5233 - 5240

Published: March 17, 2022

Catalytic sequential hydrosilylation of 1,3-enynes and 1,4-enynes promoted by cobalt complexes derived from bisphosphines are presented. Site- stereoselective Si–H addition primary silanes to followed intramolecular diastereo- enantioselective afforded enantioenriched cyclic alkenylsilanes with simultaneous construction a carbon-stereogenic center silicon-stereogenic center. Reactions proceeded through isomerization the alkene moiety site- hydrosilylation. A wide range were in high efficiency selectivity. Functionalization containing stereogenic at silicon delivered variety chiral building blocks that otherwise difficult access.

Language: Английский

Citations

76
Highly Regio‐ and Enantioselective Hydrosilylation of gem‐Difluoroalkenes by Nickel Catalysis DOI
Dachang Bai, Fen Wu,

Lingna Chang

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(10)

Published: Dec. 27, 2021

The synthesis of small organic molecules with a difluoromethylated stereocenter is particularly attractive in drug discovery. Herein, we have developed an efficient method for the direct generation stereocenters through Ni0 -catalyzed regio- and enantioselective hydrosilylation gem-difluoroalkenes. reaction also represents construction carbon(sp3 )-silicon bonds nickel catalysis, which provides atom- step-economical route high-value optically active α-difluoromethylsilanes. This protocol features readily available starting materials commercial chiral broad substrates spanning range functional groups high yield (up to 99 % yield) excellent enantioselectivity 96 ee). enantioenriched products undergo variety stereospecific transformations. Preliminary mechanistic studies were performed.

Language: Английский

Citations

63
Cobalt‐Catalyzed Regio‐, Diastereo‐ and Enantioselective Intermolecular Hydrosilylation of 1,3‐Dienes with Prochiral Silanes DOI
Lei Wang,

Wenxin Lu,

Jiwu Zhang

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(30)

Published: May 24, 2022

Abstract One of the most straightforward approaches to access chiral silanes is catalytic enantioselective hydrosilylation. Although significant advances have been achieved in construction either a carbon‐stereogenic center or silicon‐stereogenic through hydrosilylation, simultaneous establishment carbon‐ and an acyclic molecule single intermolecular hydrosilylation remained undeveloped. Herein, unprecedented cobalt‐catalyzed regio‐, diastereo‐ 1,3‐dienes presented, enabling transformation. A wide range bearing were generated high efficiency stereoselectivity. Functionalization enantioenriched delivered variety valuable building blocks that are otherwise difficult access.

Language: Английский

Citations

53
Rhodium‐Catalyzed Dynamic Kinetic Asymmetric Hydrosilylation to Access Silicon‐Stereogenic Center DOI
Yan Zeng,

Xiao‐Jun Fang,

Ren‐He Tang

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(51)

Published: Nov. 4, 2022

Abstract Strategies on the construction of enantiomerically pure silicon‐stereogenic silanes generally relies desymmetrization prochiral and symmetric substrates. However, dynamic kinetic asymmetric transformations organosilicon compounds have remained underdeveloped unforeseen owing to a lack an effective method for deracemization static silicon stereocenters. Here we report first Rh‐catalyzed intramolecular hydrosilylation (DyKAH) with “silicon‐centered” racemic hydrosilanes that enables facile preparation benzosiloles in good yields excellent enantioselectivities. The special rhodium catalyst controlled by non‐diastereopure‐type mixed phosphine‐phosphoramidite ligand axial chirality multiple stereocenters can induce enantioselectivity efficiently this novel DyKAH reaction. Density functional theory (DFT) calculations suggest amide moiety chiral plays important role facilitating S N 2 substitution chloride ion realize inversion center.

Language: Английский

Citations

44
Nickel‐Catalyzed Defluorinative Asymmetric Cyclization of Fluoroalkyl‐Substituted 1,6‐Enynes for the Synthesis of Seletracetam DOI

Kuai Wang,

Jiachang Chen, Wenfeng Liu

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(46)

Published: Sept. 23, 2022

Abstract The introduction of fluorine‐containing groups into organic molecules can significantly affect their physical and chemical properties has long been used as an effective strategy for drug discovery development. Consequently, the development catalytic asymmetric methods synthesis heterocycles is highly desirable sought after. Herein, we describe a nickel‐catalyzed defluorinative cyclization fluoroalkyl‐substituted 1,6‐enynes, providing expedient access to synthetically attractive 4‐fluorovinyl‐substituted 2‐pyrrolidones in good yields with remarkable high levels chemo‐, regio‐, enantioselectivities (90–99 % ee,>35 examples). This protocol features readily available starting materials excellent functional group compatibility, exhibits complementary regioselectivity. utility this was demonstrated enantioselective antiepileptic Seletracetam.

Language: Английский

Citations

41
Catalytic asymmetric silicon-carbon bond-forming transformations based on Si-H functionalization DOI Open Access
Li Li, Wei‐Sheng Huang, Zheng Xu

et al.

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(6), P. 1654 - 1687

Published: May 4, 2023

Language: Английский

Citations

37
Ni-catalyzed ligand-controlled divergent and selective synthesis DOI
Yang Ke, Wei Li, Wenfeng Liu

et al.

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(11), P. 2951 - 2976

Published: May 5, 2023

Language: Английский

Citations

29
Cobalt-catalyzed enantioselective intramolecular reductive cyclization via electrochemistry DOI Creative Commons

Shiquan Gao,

Chen Wang, Junfeng Yang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 9, 2023

Transition-metal catalyzed asymmetric cyclization of 1,6-enynes has emerged as a powerful method for the construction carbocycles and heterocycles. However, very rare examples worked under electrochemical conditions. We report herein Co-catalyzed enantioselective intramolecular reductive coupling enynes via electrochemistry using H2O hydride source. The products were obtained in good yields with high regio- enantioselectivities. It represents progress on cobalt-catalyzed transformation general substrate scope. DFT studies explored possible reaction pathways revealed that oxidative by LCo(I) is more favorable than addition or other pathways.

Language: Английский

Citations

24
Nickel-catalyzed switchable arylative/endo-cyclization of 1,6-enynes DOI Creative Commons
Wenfeng Liu, Wei Li,

Weipeng Xu

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 4, 2024

Abstract Carbo- and heterocycles are frequently used as crucial scaffolds in natural products, fine chemicals, biologically pharmaceutically active compounds. Transition-metal-catalyzed cyclization of 1,6-enynes has emerged a powerful strategy for constructing functionalized carbo- heterocycles. Despite significant progress, the regioselectivity alkyne functionalization is entirely substrate-dependent. And only exo -cyclization/cross-coupling products can be obtained, while endo -selective cyclization/cross-coupling remains elusive still poses formidable challenge. In this study, we disclose nickel-catalyzed switchable arylation/cyclization which nature ligand dictates arylation, electrophilic trapping reagents determine selectivity mode. Specifically, using commercially available 1,10-phenanthroline facilitates trans -arylation/cyclization to obtain seven-membered ring 2-naphthyl-substituted bisbox promotes cis access six-membered products. Diastereoselective cyclizations have also been developed synthesis enantioenriched piperidines azepanes, core structural elements pharmaceuticals possessing important biological activities. Furthermore, experimental density functional theory studies reveal that arylation process controlled by steric hindrance ligand; reaction mechanism involves -cyclization followed Dowd-Beckwith-type expansion form

Language: Английский

Citations

12
The role of silicon in drug discovery: a review DOI Creative Commons
Jenny‐Lee Panayides, Darren L. Riley, Felix Hasenmaile

et al.

RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 15(10), P. 3286 - 3344

Published: Jan. 1, 2024

This review aims to highlight the role of silicon in drug discovery.

Language: Английский

Citations

10