Copper‐Catalyzed Enantioconvergent Radical C(sp3)−N Cross‐Coupling: Access to α,α‐Disubstituted Amino Acids DOI

Yu‐Feng Zhang,

Jiahuan Wang,

Ning‐Yuan Yang

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(27)

Published: May 8, 2023

Abstract Transition‐metal catalyzed enantioconvergent cross‐coupling of tertiary alkyl halides with ammonia offers a rapid avenue to chiral unnatural α,α‐disubstituted amino acids. However, the construction C−N bonds between tertiary‐carbon electrophiles and nitrogen nucleophiles presented great challenge owing steric congestion. We report copper‐catalyzed radical sulfoximines (as surrogates) under mild conditions by employing anionic N,N,N‐ligand long spreading side arm. An array acid derivatives were obtained good efficiency enantioselectivity. The synthetic utility strategy has been showcased elaboration coupling products into different α‐fully substituted amine building blocks.

Language: Английский

Enantioconvergent Cu-catalysed N-alkylation of aliphatic amines DOI
Ji‐Jun Chen,

Jia‐Heng Fang,

Xuan‐Yi Du

et al.

Nature, Journal Year: 2023, Volume and Issue: 618(7964), P. 294 - 300

Published: March 20, 2023

Language: Английский

Citations

91

Ligand Development for Copper-Catalyzed Enantioconvergent Radical Cross-Coupling of Racemic Alkyl Halides DOI
Xiaoyang Dong, Zhong‐Liang Li, Qiang‐Shuai Gu

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(38), P. 17319 - 17329

Published: Sept. 1, 2022

The enantioconvergent cross-coupling of racemic alkyl halides represents a powerful tool for the synthesis enantioenriched molecules. In this regard, first-row transition metal catalysis provides suitable mechanism stereoconvergence by converting to prochiral radical intermediates owing their good single-electron transfer ability. contrast noble development chiral nickel catalyst, copper-catalyzed is less studied. Besides enantiocontrol issue, major challenge arises from weak reducing capability copper that slows reaction initiation. Recently, significant efforts have been dedicated basic research aimed at developing ligands halides. This perspective will discuss advances in burgeoning area with particular emphasis on strategic anionic ligand design tune initiation under thermal conditions our group.

Language: Английский

Citations

86

Photoinduced, Copper-Catalyzed Enantioconvergent Alkylations of Anilines by Racemic Tertiary Electrophiles: Synthesis and Mechanism DOI Open Access
Hyungdo Cho, Hidehiro Suematsu, Paul H. Oyala

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(10), P. 4550 - 4558

Published: March 7, 2022

Transition-metal catalysis of substitution reactions alkyl electrophiles by nitrogen nucleophiles is beginning to emerge as a powerful strategy for synthesizing higher-order amines, well controlling their stereochemistry. Herein, we report that readily accessible chiral copper catalyst (commercially available components) can achieve the photoinduced, enantioconvergent coupling variety racemic tertiary with aniline generate new C–N bond good ee at fully substituted stereocenter product; whereas this copper-catalyzed proceeds −78 °C, in absence light and catalyst, virtually no formation observed even upon heating 80 °C. The mechanism catalytic process has been interrogated aid wide array tools, including independent synthesis proposed intermediates reactivity studies, spectroscopic investigations featuring photophysical EPR data, DFT calculations. These studies led identification three copper-based cycle, three-coordinate formally copper(II)–anilido (DFT analysis points its formulation copper(I)–anilidyl radical) complex serves persistent radical couples organic desired enantioselectivity.

Language: Английский

Citations

82

Copper-catalysed enantioconvergent alkylation of oxygen nucleophiles DOI
Caiyou Chen, Gregory C. Fu

Nature, Journal Year: 2023, Volume and Issue: 618(7964), P. 301 - 307

Published: March 30, 2023

Language: Английский

Citations

49

Copper‐Catalyzed C(sp3)‐Amination of Ketone‐Derived Dihydroquinazolinones by Aromatization‐Driven C−C Bond Scission DOI Creative Commons
Xin‐Yang Lv, Roman Abrams, Rubén Martı́n

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(8)

Published: Dec. 28, 2022

Herein, we describe the development of a copper-catalyzed C(sp3 )-amination proaromatic dihydroquinazolinones derived from ketones. The reaction is enabled by intermediacy open-shell species arising homolytic C-C bond-cleavage driven aromatization. protocol characterized its operational simplicity and generality, including chemical diversification advanced intermediates.

Language: Английский

Citations

46

Decarboxylative sulfoximination of benzoic acids enabled by photoinduced ligand-to-copper charge transfer DOI Creative Commons
Peng Xu, Wanqi Su, Tobias Ritter

et al.

Chemical Science, Journal Year: 2022, Volume and Issue: 13(45), P. 13611 - 13616

Published: Jan. 1, 2022

Sulfoximines are synthetically important scaffolds and serve roles in drug discovery. Currently, there is no solution to decarboxylative sulfoximination of benzoic acids; although thoroughly investigated, limited substrate scope harsh reaction conditions still hold back traditional thermal aromatic functionalization. Herein, we realize the first acids via photo-induced ligand copper charge transfer (copper-LMCT)-enabled carbometalation. The transformation proceeds under mild conditions, has a broad scope, can be applied late-stage functionalization complex small molecules.

Language: Английский

Citations

45

Dynamic kinetic asymmetric arylation and alkenylation of ketones DOI

Lin‐Xin Ruan,

Bo Sun, Jiaming Liu

et al.

Science, Journal Year: 2023, Volume and Issue: 379(6633), P. 662 - 670

Published: Feb. 16, 2023

Despite the importance of enantioenriched alcohols in medicinal chemistry, total synthesis, and materials science, efficient selective construction tertiary bearing two contiguous stereocenters has remained a substantial challenge. We report platform for their preparation through enantioconvergent, nickel-catalyzed addition organoboronates to racemic, nonactivated ketones. prepared several important classes α,β-chiral single step with high levels diastereo- enantioselectivity dynamic kinetic asymmetric aryl alkenyl nucleophiles. applied this protocol modify profen drugs rapidly synthesize biologically relevant molecules. expect nickel-catalyzed, base-free ketone racemization process be widely applicable strategy development processes.

Language: Английский

Citations

42

A general copper-catalysed enantioconvergent radical Michaelis–Becker-type C(sp3)–P cross-coupling DOI
Lilei Wang, Huan Zhou, Yuxi Cao

et al.

Nature Synthesis, Journal Year: 2023, Volume and Issue: 2(5), P. 430 - 438

Published: Feb. 23, 2023

Language: Английский

Citations

41

Metal-Catalyzed Enantioconvergent Transformations DOI Creative Commons
Miguel Yus, Carmén Nájera, Francisco Foubelo

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(20), P. 11817 - 11893

Published: Oct. 4, 2023

Enantioconvergent catalysis has expanded asymmetric synthesis to new methodologies able convert racemic compounds into a single enantiomer. This review covers recent advances in transition-metal-catalyzed transformations, such as radical-based cross-coupling of alkyl electrophiles with nucleophiles or alkylmetals and reductive two mainly under Ni/bis(oxazoline) catalysis. C–H functionalization can be performed an enantioconvergent manner. Hydroalkylation alkenes, allenes, acetylenes is alternative reactions. Hydrogen autotransfer been applied amination alcohols C–C bond forming reactions (Guerbet reaction). Other metal-catalyzed involve addition allylic systems carbonyl compounds, propargylation phenols, 3-bromooxindoles, allenylation allenolates propargyl bromides, hydroxylation 1,3-dicarbonyl compounds.

Language: Английский

Citations

40

A general copper-catalysed enantioconvergent C(sp3)–S cross-coupling via biomimetic radical homolytic substitution DOI
Yu Tian,

Xi-Tao Li,

Ji‐Ren Liu

et al.

Nature Chemistry, Journal Year: 2023, Volume and Issue: 16(3), P. 466 - 475

Published: Dec. 6, 2023

Language: Английский

Citations

29