Rapid Synthesis of β-Chiral Sulfones by Ni-Organophotocatalyzed Enantioselective Sulfonylalkenylation of Alkenes DOI Creative Commons
Ming‐Shang Liu, Wei Shu

JACS Au, Journal Year: 2023, Volume and Issue: 3(5), P. 1321 - 1327

Published: April 27, 2023

β-Chiral sulfones are substructures widespread in drug molecules and bioactive targets serve as important chiral synthons organic synthesis yet challenging to access. Herein, a three-component strategy enabled by visible-light- Ni-catalyzed sulfonylalkenylation of styrenes for the enantioenriched β-chiral has been developed. This dual-catalysis allows one-step skeletal assembly along with control enantioselectivity presence ligand, providing an efficient straightforward access β-alkenyl from easily available simple starting materials. Mechanistic investigations reveal that reaction undergoes chemoselective radical addition over two alkenes followed Ni-intercepted asymmetric Csp3-Csp2 coupling alkenyl halides.

Language: Английский

Photocatalytic Late-Stage C–H Functionalization DOI
Peter Bellotti, Huan‐Ming Huang,

Teresa Faber

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(8), P. 4237 - 4352

Published: Jan. 24, 2023

The emergence of modern photocatalysis, characterized by mildness and selectivity, has significantly spurred innovative late-stage C–H functionalization approaches that make use low energy photons as a controllable source. Compared to traditional strategies, photocatalysis paves the way toward complementary and/or previously unattainable regio- chemoselectivities. Merging compelling benefits with workflow offers potentially unmatched arsenal tackle drug development campaigns beyond. This Review highlights photocatalytic strategies small-molecule drugs, agrochemicals, natural products, classified according targeted bond newly formed one. Emphasis is devoted identifying, describing, comparing main mechanistic scenarios. draws critical comparison between established ionic chemistry photocatalyzed radical-based manifolds. aims establish current state-of-the-art illustrate key unsolved challenges be addressed in future. authors aim introduce general readership functionalization, specialist practitioners evaluation methodologies, potential for improvement, future uncharted directions.

Language: Английский

Citations

334
Streamlined Alkylation via Nickel-Hydride-Catalyzed Hydrocarbonation of Alkenes DOI
Zhikun Zhang, Srikrishna Bera, Chao Fan

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(16), P. 7015 - 7029

Published: April 12, 2022

Compounds rich in sp3-hybridized carbons are desirable drug discovery. Nickel-catalyzed hydrocarbonation of alkenes is a potentially efficient method to synthesize these compounds. By using abundant, readily available, and stable as pro-nucleophiles, reactions can have broad scope high functional group tolerance. However, this methodology still an early stage development, the first examples were reported only 2016. Herein, we summarize progress emerging field, with emphasis on enantioselective reactions. We highlight major developments, critically discuss wide range possible mechanisms, offer our perspective state challenges field. hope Perspective will stimulate future works area, making widely applicable organic synthesis.

Language: Английский

Citations

130
Radical Carbonyl Umpolung Arylation via Dual Nickel Catalysis DOI
Huan‐Ming Huang, Peter Bellotti, Johannes E. Erchinger

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(4), P. 1899 - 1909

Published: Jan. 18, 2022

The formation of carbon-carbon bonds lies at the heart synthetic organic chemistry and is widely applied to construct complex drugs, polymers, materials. Despite its importance, catalytic carbonyl arylation remains comparatively underdeveloped, due limited scope functional group tolerance. Herein we disclose an umpolung strategy achieve radical via dual catalysis. This redox-neutral approach provides a complementary method Grignard-type products from (hetero)aryl bromides aliphatic aldehydes, without need for pre-functionalization. A sequential activation, hydrogen-atom transfer, halogen atom transfer process could directly convert aldehydes corresponding ketyl-type radicals, which further react with aryl-nickel intermediates in overall polarity-reversal process. tolerates─among others─acidic groups, heteroaryl motifs, sterically hindered substrates has been late-stage modification drugs natural products.

Language: Английский

Citations

71
Direct synthesis of unprotected aryl C-glycosides by photoredox Ni-catalysed cross-coupling DOI
Chen Zhang,

Shiyang Xu,

Hao Zuo

et al.

Nature Synthesis, Journal Year: 2023, Volume and Issue: 2(3), P. 251 - 260

Published: Jan. 16, 2023

Language: Английский

Citations

69
Carbon-centered radical capture at nickel(II) complexes: Spectroscopic evidence, rates, and selectivity DOI Creative Commons
Qiao Lin, Ethan Spielvogel, Tianning Diao

et al.

Chem, Journal Year: 2023, Volume and Issue: 9(5), P. 1295 - 1308

Published: March 13, 2023

Language: Английский

Citations

68
Dual Nickel/Photoredox-Catalyzed Asymmetric Carbosulfonylation of Alkenes DOI Creative Commons
Xiaoyong Du, Iván Cheng‐Sánchez, Cristina Nevado

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(23), P. 12532 - 12540

Published: May 30, 2023

An asymmetric three-component carbosulfonylation of alkenes is presented here. The reaction, involving the simultaneous formation a C-C and C-S bond across π-system, uses dual nickel/photoredox catalytic system to produce both β-aryl β-alkenyl sulfones in high yields with excellent levels stereocontrol (up 99:1 er). This protocol exhibits broad substrate scope functional group tolerance its synthetic potential has been demonstrated by successful applications toward pharmacologically relevant molecules. A array control experiments supports involvement secondary alkyl radical intermediate generated through addition sulfonyl double bond. Moreover, stoichiometric cross-over further suggest an underlying Ni(0)/Ni(I)/Ni(III) pathway operative these transformations.

Language: Английский

Citations

64
Ligand-controlled stereodivergent alkenylation of alkynes to access functionalized trans- and cis-1,3-dienes DOI Creative Commons
Tianyu Long, Chen Zhu, Ling Li

et al.

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

Published: Jan. 4, 2023

Precise stereocontrol of functionalized alkenes represents a long-standing research topic in organic synthesis. Nevertheless, the development catalytic, easily tunable synthetic approach for stereodivergent synthesis both E-selective and even more challenging Z-selective highly substituted 1,3-dienes from common substrates remains underexploited. Here, we report photoredox nickel dual catalytic strategy sulfonylalkenylation terminal alkynes with vinyl triflates sodium sulfinates under mild conditions. With judicious choice simple catalyst ligand, this method enables efficient divergent access to Z- E-sulfonyl-1,3-dienes same set starting materials. This features broad substrate scope, good functional compatibility, excellent chemo-, regio-, stereoselectivity. Experimental DFT mechanistic studies offer insights into observed stereoselectivity controlled by ligands.

Language: Английский

Citations

51
Nickel-catalysed enantioselective alkene dicarbofunctionalization enabled by photochemical aliphatic C–H bond activation DOI Creative Commons
Xia Hu, Iván Cheng‐Sánchez, Wangqing Kong

et al.

Nature Catalysis, Journal Year: 2024, Volume and Issue: 7(6), P. 655 - 665

Published: April 29, 2024

Abstract The development of novel strategies to rapidly construct complex chiral molecules from readily available feedstocks is a long-term pursuit in the chemistry community. Radical-mediated alkene difunctionalizations represent an excellent platform towards this goal. However, asymmetric versions remain highly challenging, and more importantly, examples featuring simple hydrocarbons as reaction partners are elusive. Here we report three-component dicarbofunctionalization capitalizing on direct activation C( sp 3 )–H bonds through combination photocatalysed hydrogen atom transfer nickel catalysis. This protocol provides efficient for installing two vicinal carbon–carbon across alkenes atom-economic fashion, providing wide array high-value α-aryl/alkenyl carbonyls phosphonates, well 1,1-diarylalkanes ubiquitous alkane, ether alcohol feedstocks. method exhibits operational simplicity, broad substrate scope regioselectivity, chemoselectivity enantioselectivity. compatibility with bioactive motifs expedient synthesis pharmaceutically relevant highlight synthetic potential protocol.

Language: Английский

Citations

43
Iron-catalyzed fluoroalkylative alkylsulfonylation of alkenes via radical-anion relay DOI Creative Commons
Xiaoya Hou, Hongchi Liu, Hanmin Huang

et al.

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

Published: Feb. 17, 2024

Abstract Transition metal-catalyzed reductive difunctionalization of alkenes with alkyl halides is a powerful method for upgrading commodity chemicals into densely functionalized molecules. However, super stoichiometric amounts metal reductant and the requirement installing directing group to suppress inherent β-H elimination bring great limitations this type reaction. We demonstrate herein that two different accessible via radical-anion relay Na 2 S O 4 as both sulfone-source. The together electron-shuttle catalyst crucial divert mechanistic pathway toward formation sulfone anion instead previously reported alkylmetal intermediates. Mechanistic studies allow identification carbon-centered radical sulfur-centered radical, which are in equilibrium capture or extrusion SO could be converted accelerated by iron catalysis, leading observed high chemoselectivity.

Language: Английский

Citations

25
Photoredox/Cr-catalyzed enantioselective radical-polar crossover transformation via C-H functionalization DOI Creative Commons
Siyuan Tang,

Zhan-Jie Wang,

Ao Yu

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 4, 2025

Asymmetric multicomponent reactions that aim to control multiple chiral centers with high selectivity in a single step remain an on-gonging challenge. The realm of enantioselective radical-polar crossover transformation achieved through C-H Functionalization has yet be fully explored. Herein, we present successful description photoredox/Cr-catalyzed three-component (hetero)arylalkylation 1,3-dienes functionalization. A diverse array homoallylic alcohols could obtained good excellent yields, accompanied by outstanding enantioselectivity. asymmetric build two simultaneously and demonstrates broad substrate tolerance, accommodating various drug-derived aldehydes, (hetero)aromatics, 1,3-diene derivatives. Preliminary mechanistic studies indicate the involvement radical intermediate, allylic chromium species reacting aliphatic aromatic aldehydes Zimmerman–Traxler transition states enabled dual photoredox catalysis. ongoing Here, authors photoredox- chromium-catalyzed

Language: Английский

Citations

3