Deuterium- and Electron-Shuttling Catalysis for Deoxygenative Deuteration of Alcohols DOI

Bin‐Qing He,

Xuesong Wu

Organic Letters, Journal Year: 2023, Volume and Issue: 25(35), P. 6571 - 6576

Published: Aug. 30, 2023

A practical and precise method for visible-light-promoted deoxygenative deuteration of common aliphatic alcohols using D2O as the deuterium source is reported. Upon intermediacy xanthate anions, a variety primary, secondary, tertiary can be facilely transformed into deuterioalkanes with excellent D-incorporation at predicted sites. The deoxygenation sequence catalyzed by in situ formed deuterated 2-mercaptopyridine, which plays dual roles atom transfer catalyst an electron shuttle well.

Language: Английский

Nontraditional Fragment Couplings of Alcohols and Carboxylic Acids: C(sp3)–C(sp3) Cross-Coupling via Radical Sorting DOI
Holt A. Sakai, David W. C. MacMillan

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(14), P. 6185 - 6192

Published: March 30, 2022

Alcohols and carboxylic acids are among the most commercially abundant, synthetically versatile, operationally convenient functional groups in organic chemistry. Under visible light photoredox catalysis, these native synthetic handles readily undergo radical activation, resulting open-shell intermediates can subsequently participate transition metal catalysis. In this report, we describe C(sp3)–C(sp3) cross-coupling of alcohols through dual combination N-heterocyclic carbene (NHC)-mediated deoxygenation hypervalent iodine-mediated decarboxylation. This mild practical Ni-catalyzed radical-coupling protocol was employed to prepare a wide array alkyl–alkyl cross-coupled products, including highly congested quaternary carbon centers from corresponding tertiary or acids. We demonstrate applications methodology alcohol C1-alkylation formal homologation, as well late-stage functionalization drugs, natural biomolecules.

Language: Английский

Citations

147
Photocatalytic C(sp3) radical generationviaC–H, C–C, and C–X bond cleavage DOI Creative Commons
Chia‐Yu Huang, Jianbin Li, Chao‐Jun Li

et al.

Chemical Science, Journal Year: 2022, Volume and Issue: 13(19), P. 5465 - 5504

Published: Jan. 1, 2022

C(sp 3 ) radicals (R˙) are of broad research interest and synthetic utility.

Language: Английский

Citations

75
Practical and General Alcohol Deoxygenation Protocol DOI Creative Commons
Oliver P. Williams, Alyah F. Chmiel, Myriam Mikhael

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(18)

Published: Feb. 25, 2023

Herein, we describe a practical protocol for the removal of alcohol functional groups through reductive cleavage their benzoate ester analogs. This transformation requires strong single electron transfer (SET) reductant and means to accelerate slow fragmentation following substrate reduction. To accomplish this, developed photocatalytic system that generates potent from formate salts alongside Brønsted or Lewis acids promote reduced intermediate. deoxygenation procedure is effective across structurally electronically diverse alcohols enables variety difficult net transformations. no precautions exclude air moisture remains efficient on multigram scale. Finally, can be adapted one-pot benzoylation-deoxygenation sequence enable direct deletion. Mechanistic studies validate role acidic additives key C(sp

Language: Английский

Citations

42
Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions DOI

Adam Cook,

Stephen G. Newman

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(9), P. 6078 - 6144

Published: April 17, 2024

Alcohols are abundant and attractive feedstock molecules for organic synthesis. Many methods their functionalization require them to first be converted into a more activated derivative, while recent years have seen vast increase in the number of complexity-building transformations that directly harness unprotected alcohols. This Review discusses how transition metal catalysis can used toward this goal. These broadly classified three categories. Deoxygenative functionalizations, representing derivatization C–O bond, enable alcohol act as leaving group formation new C–C bonds. Etherifications, characterized by O–H represent classical reactivity has been modernized include mild reaction conditions, diverse partners, high selectivities. Lastly, chain reactions described, wherein acts mediator formal C–H alkyl backbone. Each these classes transformation will discussed context intermolecular arylation, alkylation, related reactions, illustrating alcohols harnessed

Language: Английский

Citations

35
Engaging Alkenes in Metallaphotoredox: A Triple Catalytic, Radical Sorting Approach to Olefin-Alcohol Cross-Coupling DOI
Qinyan Cai, Iona M. McWhinnie, Nathan W. Dow

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(18), P. 12300 - 12309

Published: April 24, 2024

Metallaphotoredox cross-coupling is a well-established strategy for generating clinically privileged aliphatic scaffolds via single-electron reactivity. Correspondingly, expanding metallaphotoredox to encompass new C(

Language: Английский

Citations

19
Visible-Light Photoredox-Catalyzed Carboxylation of Activated C(sp3)─O Bonds with CO2 DOI

Chuan‐Kun Ran,

Ya‐Nan Niu,

Lei Song

et al.

ACS Catalysis, Journal Year: 2021, Volume and Issue: 12(1), P. 18 - 24

Published: Dec. 9, 2021

The photocatalytic carboxylation with CO2 has emerged as an efficient way to afford valuable aliphatic carboxylic acids. However, the difficultly available starting materials, limited substrate scope, and/or use of high loading transition-metal catalysts hamper their wide application. In contrast, alcohols and derivatives, which are environmentally benign readily in nature industry, have rarely been investigated such a process. Herein, we report visible-light photoredox-catalyzed activated C(sp3)─O bonds under mild transition-metal-free conditions. A variety benzyl bearing primary, secondary, more challenging tertiary bonds, undergo CO2, generating aryl acetic acids, ibuprofen, naproxen, fenoprofen, flurbiprofen, broad scope good functional group tolerance. Moreover, this strategy is also applicable other carboxylates α-hydroxyl amides, esters, nitriles, well allyl alcohols, representing practical method for acid synthesis.

Language: Английский

Citations

61
Alcohols as Alkylating Agents: Photoredox‐Catalyzed Conjugate Alkylation via In Situ Deoxygenation DOI
Johnny Wang, Holt A. Sakai, David W. C. MacMillan

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(35)

Published: June 21, 2022

The rapid exploration of sp

Language: Английский

Citations

50
Radical Deoxyfunctionalisation Strategies** DOI Creative Commons
Khadijah Anwar, Kay Merkens, Francisco José Aguilar Troyano

et al.

European Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 2022(26)

Published: May 10, 2022

Abstract Due to their abundance and readily available synthesis, alcohols provide ideal handles for the selective derivatisation of organic molecules. Radical chemistry offers versatile strategies conversion Csp 3 −O bonds into a wide range −C, −H, or −heteroatom bonds. In these reactions, are derivatised with an activator group which can undergo facile mesolysis generate primary, secondary, tertiary open‐shell species that engage in further transformations. These particularly effective at overcoming steric limitations associated nucleophilic substitution pathways. Despite potential, use radical deoxyfunctionalisation reactions as general strategy synthesis useful complex molecules remains underutilised. this Review, we highlight recent advancements exciting field photocatalysis, transition metal catalysis electrochemistry used initiate processes.

Language: Английский

Citations

39
Photoinduced Electron Transfer from Xanthates to Acyl Azoliums: Divergent Ketone Synthesis via N‐Heterocyclic Carbene Catalysis DOI
Chang‐Yin Tan, Minseok Kim, Sungwoo Hong

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(32)

Published: June 12, 2023

Considering the prevalence of alcohols and carboxylic acids, their fragment cross-coupling reactions could hold significant implications in organic synthesis. Herein, we report a versatile method for synthesizing diverse range ketones from acid derivatives via N-heterocyclic carbene (NHC) catalysis. Mechanistic investigations revealed that photoexcited xanthates acyl azoliums undergo single electron transfer (SET) under photocatalyst-free conditions, generating NHC-derived ketyl radicals alkyl radicals. These open-shell intermediates subsequently radical-radical reaction, yielding valuable ketones. Furthermore, this approach can be employed three-component involving alkenes enynes, resulting structurally cross-coupled The unified strategy offers unique opportunity coupling derivatives, accommodating functional groups even complex settings.

Language: Английский

Citations

33
Dehydroxylative radical N-glycosylation of heterocycles with 1-hydroxycarbohydrates enabled by copper metallaphotoredox catalysis DOI Creative Commons
Dapeng Liu,

Xiao-Sen Zhang,

Shuai Liu

et al.

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

Published: April 22, 2024

Abstract N-Glycosylated heterocycles play important roles in biological systems and drug development. The synthesis of these compounds heavily relies on ionic N-glycosylation, which is usually constrained by factors such as labile glycosyl donors, precious metal catalysts, stringent conditions. Herein, we report a dehydroxylative radical method for synthesizing N -glycosides leveraging copper metallaphotoredox catalysis, stable readily available 1-hydroxy carbohydrates are activated direct N-glycosylation. Our employs inexpensive photo- copper- catalysts can tolerate some extent water. reaction exhibits broad substrate scope, encompassing 76 examples, demonstrates high stereoselectivity, favoring 1,2- trans selectivity furanoses α-selectivity pyranoses. It also site-selectivity substrates containing multiple N-atoms. synthetic utility showcased through the late-stage functionalization bioactive pharmaceuticals like Olaparib, Axitinib, Metaxalone. Mechanistic studies prove presence radicals importance catalysis.

Language: Английский

Citations

16