Palladium-catalyzed chemoselective direct α-arylation of carbonyl compounds with chloroaryl triflates at the C–Cl site

Chen, Zicong; Gu, Changxue; Yuen, On Ying; So, Chau Ming

doi:10.1039/d1sc06701j

Cited by 20 publications

(24 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Pd/ L45 and Pd/ L47 ( t -BuPhSelectPhos) catalytic systems can manipulate the order of reactivity, achieving excellent chemoselectivity toward Ar–Cl bonds, and using a mild base to promote the catalytic system to prevent triflate hydrolysis. 134 L45 and L47 can invert the chemoselectivity (–Cl over –OTf),affording to the desired products, with excellent yields of chloride-substituted products. Furthermore, the authors investigated the substrate scope of this catalytic system.…”

Section: Alkyl-based Phosphine Ligands (Selectphos)mentioning

confidence: 99%

“…The system also exhibits high tolerance to electron-rich/electron-deficient substituents (Scheme 22). 134…”

Section: Alkyl-based Phosphine Ligands (Selectphos)mentioning

confidence: 99%

“…The synthetic utility of the developed catalytic system was demonstrated by flurbiprofen synthesis, a non-steroidal anti-inflammatory drug (NSAID), from 4-chloro-2-fluorophenyl triflates (Scheme 23). 134…”

Section: Alkyl-based Phosphine Ligands (Selectphos)mentioning

confidence: 99%

“…The system also exhibits high tolerance to electron-rich/electron-deficient substituents (Scheme 22). 134 The authors also investigated the effects of dynamic interactions between -PR 2 modules and the C2-alkyl group of alkylindolyl-based phosphines. The -PR 2 moiety with an alkyl group exhibited chemoselectivity toward the Ar-Cl bond, and Pd with the ligand bearing the -PPh 2 group (L46) (PhSelectPhos) can chemoselectively react with the Ar-OTf bond.…”

Section: Alkyl-based Phosphine Ligands (Selectphos)mentioning

confidence: 99%

See 3 more Smart Citations

Recent advances in the application of ligands in palladium-catalyzed chemoselective coupling reactions at C–Br, C–OTf, and C–Cl sites

Pang

Yuen

et al. 2023

Org. Chem. Front.

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Alkyl-based Phosphine Ligands (Selectphos)mentioning

confidence: 99%

“…The system also exhibits high tolerance to electron-rich/electron-deficient substituents (Scheme 22). 134…”

Section: Alkyl-based Phosphine Ligands (Selectphos)mentioning

confidence: 99%

Section: Alkyl-based Phosphine Ligands (Selectphos)mentioning

confidence: 99%

Section: Alkyl-based Phosphine Ligands (Selectphos)mentioning

confidence: 99%

See 2 more Smart Citations

Recent advances in the application of ligands in palladium-catalyzed chemoselective coupling reactions at C–Br, C–OTf, and C–Cl sites

Pang

Yuen

et al. 2023

Org. Chem. Front.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The chemoselective direct α-arylation of carbonyl compounds with chloroaryl triflates using SelectPhos or tBuPhSelectPhos was first reported by So (Scheme 16C). 53 An array of oxindoles and ketones were arylated with chloroaryl triflates with excellent chemoselectivity for the C− Cl bond. This method was also applied to the synthesis of Flurbiprofen, demonstrating the practicality of such transformations.…”

Section: Direct C−h Functionalizationmentioning

confidence: 99%

Facile Assembly of Modular-Type Phosphines for Tackling Modern Arylation Processes

2022

View full text Add to dashboard Cite

Conspectus This Account presents an overview of a promising collection of phosphine ligands simply made from the modular Fischer indolization process and their applications in modern arylation processes. Using one easily accessible 2-arylindole scaffold, three major phosphino-moiety-positioned ligand series can be readily generated. We have attempted to explore challenging electrophilic and nucleophilic partners for the coupling reaction using the modular ligand tool. For the electrophilic partner study, CM-phos-type ligands, where the phosphino group is located at the 2-arene position of 2-arylindole, allow the successful cross-coupling of aryl mesylates. The CM-phos ligand forms a palladacycle before entering the cross-coupling catalytic cycle. For the nucleophilic partner investigation, the indole C3-positioned phosphines show the first accomplishment of Pd-catalyzed organotitanium nucleophile arylation. Indeed, the aryl-titanium nucleophile undergoes cross-coupling more efficiently than does the organoboron coupling partner in particular cases. Moreover, in the indole C3-positioned phosphine series, the −PPh2-containing ligands perform better in the highly sterically hindered cross-coupling of aryl chlorides than do ligands containing the −PCy2 moiety. The catalyst loading can even be reduced to 0.2 mol % Pd for tetra-ortho-substituted biaryl synthesis. This finding offers a new perspective on the next-generation design of phosphine ligands in which the sterically bulky and electron-rich −PR2 group (R = alkyl) may not be necessary for the cross-coupling of aryl chlorides. In general, we hypothesize that a good balance of steric and electronic properties for entertaining the oxidative addition and reductive elimination steps is crucial to the success of the reaction. For the steric factor, the highly sterically congested −PR2 group normally favors the reductive elimination, yet we conjecture that this sterically bulky group would serve as an obstacle for the incoming aryl halides. For the electronic factor, the electron rich −PR2 group is believed to support the oxidative cleavage of the C(Ar)–Cl bond by donating more electron density to the corresponding σ* orbital. Nevertheless, the high electron richness of the −PR2 group may disfavor the reductive elimination electronically. Overall, an appropriate balance of both electron density and steric bulkiness is suggested to allow the sterically hindered cross-coupling to proceed smoothly. We have found that the −PPh2-containing ligand is a good starting point for this investigation. The formation of aromatic carbon–carbon (C–C) and carbon–heteroatom (C–X) bonds from aryl chlorides was successfully realized using our proprietary phosphines. In addition to the indole-core-bearing ligand skeleton, we also explored the relevant imidazolyl and carbazolyl phosphines for their unique applications. Interestingly, the carbazolyl ligand, having more flexible C–N axial chirality, displays particular interchangeable Pd–N and Pd–arene coordination, which facilitates both oxid...

show abstract

Palladium‐Catalyzed Chemoselective Mono‐α‐Arylation of O‐Protected Hydroxyacetone with Ortho‐Substituted (Hetero)aryl Electrophiles

et al. 2023

View full text Add to dashboard Cite

show abstract

Palladium-catalyzed chemoselective direct α-arylation of carbonyl compounds with chloroaryl triflates at the C–Cl site

Abstract: Palladium-catalyzed chemoselective direct α-arylation of carbonyl compounds with chloroaryl triflates in the Ar–Cl bond is reported. The effects of –PR2 and C2-alkyl groups of the ligands are investigated using experimental and computational methods.

Cited by 20 publications

References 67 publications

Recent advances in the application of ligands in palladium-catalyzed chemoselective coupling reactions at C–Br, C–OTf, and C–Cl sites

Recent advances in the application of ligands in palladium-catalyzed chemoselective coupling reactions at C–Br, C–OTf, and C–Cl sites

Facile Assembly of Modular-Type Phosphines for Tackling Modern Arylation Processes

Palladium‐Catalyzed Chemoselective Mono‐α‐Arylation of O‐Protected Hydroxyacetone with Ortho‐Substituted (Hetero)aryl Electrophiles

Contact Info

Product

Resources

About