Synthesis of gem-Difluoroalkenes through Nickel-Promoted Electrochemical Reductive Cross-Coupling DOI Open Access
Zhe Chang, Jiaxin Wang, Xi Lu

et al.

Chinese Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 42(1), P. 147 - 147

Published: Jan. 1, 2022

gem-Difluoroalkenes are important fluorine-containing compounds with structural superiority in organic synthetic chemistry and medicinal chemistry.For instance, the gem-difluoroethylene moiety could be converted to monofluoroalkenyl, difluoroalkyl, trifluoromethyl moiety, many other structures conveniently.The is also an ideal carbonyl group bioisostere has already been widely used drug design.Herein, a nickel-promoted electrochemical reductive cross-coupling access functionalized substituted gem-difluoroalkenes reported.This reaction enables combination of allylic defluorination alkenes decarboxylation redox-active esters or dehalogenation alkyl halides under mild reduction conditions undivided cell, therefore obviates use stoichiometric amount metal powder reductants.Furthermore, this provides efficient biologically interesting molecules containing moiety.Keywords gem-difluoroalkene; alkene; ester; halide; cross-coupling; electrochemistry design. [6]Direct difluoroolefination ketones diazo was strategy deliver gemdifluoroalkenes (Figures 1b,i). [7]Hu, [8] Xiao, [9] Wang, [10] others enjoyed outstanding achievements area.More recently, defluorinative functionalization different nucleophiles developed as powerful tools synthesize 1b,ii). [11]For example, Cao, [12] Shi, [13] Murakami, [14] Hayashi, [15] Zhang, [16] reported carbonation trifluo-有机化学

Language: Английский

Site-Selective Defluorinative sp3 C–H Alkylation of Secondary Amides DOI

Wen‐Jun Yue,

Craig S. Day, Rubén Martı́n

et al.

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(17), P. 6395 - 6400

Published: April 27, 2021

A site-selective defluorinative sp3 C–H alkylation of secondary amides that rapidly and reliably incorporates gem-difluoroalkene motifs into previously unfunctionalized sites is disclosed. This protocol distinguished by its mild conditions, wide scope, exquisite site-selectivity, thus unlocking a new platform to introduce carbonyl isosteres at saturated hydrocarbon sites.

Language: Английский

Citations

160
Cross-Electrophile Coupling: Principles, Methods, and Applications in Synthesis DOI Creative Commons
Lauren E. Ehehalt, Omar M. Beleh, Isabella C. Priest

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Cross-electrophile coupling (XEC), defined by us as the cross-coupling of two different σ-electrophiles that is driven catalyst reduction, has seen rapid progression in recent years. As such, this review aims to summarize field from its beginnings up until mid-2023 and provide comprehensive coverage on synthetic methods current state mechanistic understanding. Chapters are split type bond formed, which include C(sp

Language: Английский

Citations

18
Catalytic asymmetric synthesis of monofluoroalkenes and gem-difluoroalkenes: advances and perspectives DOI
Xiaojuan Zhang, Yamin Cheng, Xiaowei Zhao

et al.

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(10), P. 2315 - 2327

Published: Jan. 1, 2021

The latest achievements in the catalytic asymmetric synthesis of both monofluoro- and gem-difluoroalkenes are discussed.

Language: Английский

Citations

79
Stereoselective gem-Difluorovinylation of gem-Difluorinated Cyclopropanes Enabled by Ni/Pd Cooperative Catalysis DOI
Baojian Xiong, Xuemeng Chen, Jiangjun Liu

et al.

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(19), P. 11960 - 11965

Published: Sept. 13, 2021

A cross-electrophile coupling between gem-difluorinated cyclopropanes and 2,2-difluorovinyl tosylate via dual Ni/Pd cooperative catalysis under mild reaction conditions is presented. Various structurally unique organofluorine compounds bearing both monofluoroalkene gem-difluoroalkene moieties can be effectively afforded in good yields with a high (Z)-selectivity. The synthetic utility of this protocol has been successfully demonstrated by the late-stage modification series complex bioactive molecules.

Language: Английский

Citations

61
Pd/NHC-Controlled Regiodivergent Defluorinative Allylation of gem-Difluorocyclopropanes with Allylboronates DOI
Leiyang Lv, Huijun Qian,

Anna B. Crowell

et al.

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(11), P. 6495 - 6505

Published: May 17, 2022

Controlling the selectivity of synthetically useful reactions has been a longstanding objective organic chemistry. We report regiodivergent synthetic protocol allowing access to diverse fluorinated 1,5-dienes through Pd/NHC-catalyzed ring-opening allylation gem-difluorocyclopropanes. Density functional theory (DFT) calculations on regioselectivity-determining transition states provided critical insight into design NHC ligand for switching regioselectivity. Consistent with DFT predictions, N-heterocyclic carbene (NHC) ligands bulky ortho substituents favored branched allylation, IHept providing > 20:1 branched/linear less hindered such as IMes thermodynamically more stable linear products. were able carry out late-stage modification various complex molecules using this protocol. Our ligand-controlled approach provides efficient regioisomeric from same starting materials and constitutes valuable addition toolbox diversity-oriented synthesis.

Language: Английский

Citations

51
Reductive quenching-initiated catalyst-controlled divergent alkylation of α-CF3-olefins DOI Creative Commons
Yunxiao Zhang, Yizhi Zhang, You-Yuan Guo

et al.

Chem Catalysis, Journal Year: 2022, Volume and Issue: 2(6), P. 1380 - 1393

Published: April 21, 2022

Gem-difluoroalkenes and trifluoromethyl alkanes are pervasive in biologically active molecules. Photo-catalyzed alkylation of α-CF3-olefins provides a straightforward approach to access these scaffolds; however, such strategy is often hampered, gem-difluoroalkenes usually formed instead under reductive quenching-initiated photoredox conditions. It both mechanistically synthetically appealing if simple change the catalyst can chemo-selectively lead either type products. Here, we show visible-light-induced photo-catalyst for preparing from α-CF3-olefins. The chemo-selectivity reactions arises judicious choice rather than modification substrate structures. A wide variety substrates bearing an assortment functional groups (62 examples) compatible with this strategy. use HFIP as additive promotes formation probably via facilitation hydrogen atom transfer step O-H but not α-C-H bond.

Language: Английский

Citations

49
Handling fluorinated gases as solid reagents using metal-organic frameworks DOI
Kaitlyn T. Keasler, Mary E. Zick, Emily Stacy

et al.

Science, Journal Year: 2023, Volume and Issue: 381(6665), P. 1455 - 1461

Published: Sept. 28, 2023

Fluorine is an increasingly common substituent in pharmaceuticals and agrochemicals because it improves the bioavailability metabolic stability of organic molecules. Fluorinated gases represent intuitive building blocks for late-stage installation fluorinated groups, but they are generally overlooked require use specialized equipment. We report a general strategy handling as benchtop-stable solid reagents using metal-organic frameworks (MOFs). Gas-MOF prepared on gram-scale used to facilitate fluorovinylation fluoroalkylation reactions. Encapsulation gas-MOF within wax enables stable storage benchtop controlled release into solution upon sonication, which represents safer alternative gas directly. Furthermore, our approach high-throughput reaction development with these gases.

Language: Английский

Citations

34
Nickel-Catalyzed Reductive Cross-Coupling of Heteroaryl Chlorides and Aryl Chlorides DOI
Bijan Mirabi, Austin D. Marchese, Mark Lautens

et al.

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(20), P. 12785 - 12793

Published: Oct. 6, 2021

We report a nickel-catalyzed cross-electrophile coupling reaction of aryl chlorides and heteroaryl enabled by synergistic combination consisting halide effects the addition magnesium salt. The relies on electronic difference between aromatic heteroaromatic partners to afford cross-coupled biaryl products using single catalyst. A variety heterocycles were amenable reaction, as well wide range chlorides, with electron-deficient performing best in reaction. Preliminary mechanistic evidence demonstrates MgCl2 is essential accelerating reduction Ni(II), that small quantities iodide lead improved yields.

Language: Английский

Citations

47
Defluorinative C–C Bond-Forming Reaction of Trifluoromethyl Alkenes with gem-(Diborylalkyl)lithiums DOI
Haeun Kim,

Yujin Jung,

Seung Hwan Cho

et al.

Organic Letters, Journal Year: 2022, Volume and Issue: 24(14), P. 2705 - 2710

Published: April 5, 2022

We report the transition-metal-free defluorinative C-C bond-forming reaction of trifluoromethyl alkenes with gem-(diborylalkyl)lithiums. This synthetic strategy provides access to a variety 4,4-difluoro homoallylic diboronate esters, which serve as versatile intermediates in efficient preparation valuable gem-difluoroalkene derivatives. Further modifications are conducted demonstrate utility obtained esters.

Language: Английский

Citations

30
Nickel-Catalyzed Cross-Electrophile Ring Opening/gem-Difluoroallylation of Aziridines DOI
Wei Tang, Pei Fan

Organic Letters, Journal Year: 2023, Volume and Issue: 25(31), P. 5756 - 5761

Published: July 28, 2023

Herein we report a nickel-catalyzed regioselective cross-electrophile ring opening reaction of sulfonyl-protected aziridines with trifluoromethyl-substituted alkenes as the gem-difluoroallylating agents, providing new and efficient entry to prepare gem-difluorobishomoallylic sulfonamides. Moreover, scaffold 6-fluoro-1,2,3,4-tetrahydropyridine can be constructed starting from products via NaH-mediated intramolecular defluorinative nucleophilic vinylic substitution.

Language: Английский

Citations

17