Palladium-Catalyzed Difluoromethylation of Aryl Chlorides and Bromides with TMSCF₂H

The Journal of Organic Chemistry, Journal Year: 2019, Volume and Issue: 84(6), P. 3735 - 3740

Published: Feb. 21, 2019

A palladium-catalyzed cross-coupling of aryl chlorides/bromides with TMSCF2H is described. Two different catalysts, Pd(dba)2/BrettPhos and Pd(PtBu3)2, are demonstrated provide a variety difluoromethylated arenes in good yields.

Language: Английский

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Decarbonylative Suzuki–Miyaura Cross-Coupling of Aroyl Chlorides

Organic Letters, Journal Year: 2020, Volume and Issue: 22(16), P. 6434 - 6440

Published: Aug. 10, 2020

Herein, we report a catalyst system for Pd-catalyzed decarbonylative Suzuki–Miyaura cross-coupling of aroyl chlorides with boronic acids to furnish biaryls. This strategy is suitable broad range common and acids. The synthetic utility highlighted in the direct late-stage functionalization pharmaceuticals natural products capitalizing on presence carboxylic acid moiety. Extensive mechanistic DFT studies provide key insight into reaction mechanism high selectivity.

Language: Английский

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Copper-catalyzed carbo-difluoromethylation of alkenes via radical relay

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: June 1, 2021

Abstract Organic molecules that contain alkyl-difluoromethyl moieties have received increased attention in medicinal chemistry, but their synthesis a modular and late-stage fashion remains challenging. We report herein an efficient copper-catalyzed radical relay approach for the carbo-difluoromethylation of alkenes. This simultaneously introduces CF 2 H groups along with complex alkyl or aryl into alkenes regioselectivity opposite to traditional addition. demonstrate broad substrate scope wide functional group compatibility. scalable protocol is applied functionalization analogues bioactive molecules. Mechanistic studies density theory calculations suggest unique ligand effect on reactivity Cu-CF species.

Language: Английский

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[Ph₄P]⁺[Cu(CF₂H)₂]⁻: A Powerful Difluoromethylating Reagent Inspired by Mechanistic Investigation

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(42)

Published: Aug. 29, 2022

Abstract The quest of the active species in copper‐mediated difluoromethylation aryl halides led to discovery a powerful difluoromethylating reagent [Ph 4 P] + [Cu(CF 2 H) ] − . Complex was able difluoromethylate variety electrophiles including electron‐deficient and electron‐rich iodides, heteroaryl activated bromides, chloride bromides with directing group, as well other such alkenyl iodide, benzyl allyl alkyl carbonates acid chloride. In addition, presence an oxidant, complex reacted various lithium n butyl arylboronic pinacol esters, alkyne heteroarene. Moreover, could transmetalate difluoromethyl metals [CuCl [(DPPF)PdCl ].

Language: Английский

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Mechanism-Driven Development of Group 10 Metal-Catalyzed Decarbonylative Coupling Reactions

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(23), P. 3430 - 3444

Published: Nov. 16, 2022

ConspectusTransition-metal-catalyzed cross-coupling reactions are widely used in both academia and industry for the construction of carbon–carbon carbon–heteroatom bonds. The vast majority utilize aryl (pseudo)halides as electrophilic coupling partner. Carboxylic acid derivatives (RC(O)X) represent a complementary class electrophiles that can engage decarbonylative couplings to produce analogous products. This approach offers advantage RC(O)X abundant inexpensive. In addition, enables intramolecular (between R X carboxylic derivative) well intermolecular bond-forming (in which an exogeneous nucleophile is coupled with group derived from RC(O)X). these reactions, X-substituent on be tuned facilitate oxidative addition transmetalation, thus eliminating need base. Account details our group's development diverse variety base-free catalyzed by 10 metals. Furthermore, it highlights how catalyst design guided stoichiometric organometallic studies systems.Our early focused transform corresponding R–X extrusion CO. We first identified Pd Ni monodentate phosphine catalysts convert thioesters (ArC(O)SR) thioethers (ArSR). next expanded this reactivity fluoroalkyl thioesters, using readily available acids (RF) source. A Ni-phosphinoferrocene proved optimal, large bite angle bidentate ligand was necessary promote challenging RF–S reductive elimination step.We pursued aroyl halides. Palladium-based bearing dialkylbiaryl ligands (e.g., BrettPhos) were optimal converting chlorides (ArC(O)Cl) (ArCl). These selected based their ability key C–Cl step catalytic cycle. contrast, all attempts fluorides [ArC(O)F)] (ArF) unsuccessful either Pd- or Ni-based catalysts. Organometallic Ni-system show C(O)–F CO deinsertion proceed smoothly, but resulting nickel(II) fluoride intermediate fails undergo C–F elimination.In contrast its inertness elimination, highly reactive toward transmetalation. serves internal base, such no additional base required. leveraged "transmetalation active" achieve Ni-catalyzed between boron reagents access biaryl aryl-boronate ester By tuning electrophile, transmetalating reagent, catalyst, same also applicable fluoroalkylation difluoromethylacetyl arylboronate esters) amination phenol esters silyl amines).Moving forward, goal identify systems enable more bond constructions via manifold. inhibition remains major issue leading requirement high temperatures loadings. Identifying resistant binding and/or approaches remove under mild conditions will critical making practical scalable.

Language: Английский

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