Palladium‐Catalyzed Decarbonylative Difluoromethylation of Acid Chlorides at Room Temperature

Pan, Fei; Boursalian, Gregory B.; Ritter, Tobias

doi:10.1002/anie.201811139

Cited by 87 publications

(34 citation statements)

References 110 publications

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“…1a), has been less explored. The traditional strategies for the synthesis of difluoromethylated heterocycles include deoxyfluorination of aldehydes 28 , difluorination of benzylic C−H bonds 29,30 , decarbonylation/decarboxylation difluoromethylation 31,32 , cycloaddition reactions 24,33,34 , and conversion of CF 2 R containing heterocycles precursors 35,36 . However, these above-mentioned methods need expensive and toxic fluorinating agents, harsh reaction conditions, and are limited in functional group compatibility.…”

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confidence: 99%

Direct C–H difluoromethylation of heterocycles via organic photoredox catalysis

Zhang

Xiang

Chen³

et al. 2020

Nat Commun

145

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The discovery of modern medicine relies on the sustainable development of synthetic methodologies to meet the needs associated with drug molecular design. Heterocycles containing difluoromethyl groups are an emerging but scarcely investigated class of organofluoro molecules with potential applications in pharmaceutical, agricultural and material science. Herein, we developed an organophotocatalytic direct difluoromethylation of heterocycles using O 2 as a green oxidant. The C-H oxidative difluoromethylation obviates the need for pre-functionalization of the substrates, metals and additives. The operationally straightforward method enriches the efficient synthesis of many difluoromethylated heterocycles in moderate to excellent yields. The direct difluoromethylation of pharmaceutical moleculars demonstrates the practicability of this methodology to late-stage drug development. Moreover, 2′-deoxy-5-difluoromethyluridine (F 2 TDR) exhibits promising activity against some cancer cell lines, indicating that the difluoromethylation methodology might provide assistance for drug discovery.

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confidence: 99%

Direct C–H difluoromethylation of heterocycles via organic photoredox catalysis

Zhang

Xiang

Chen³

et al. 2020

Nat Commun

145

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“…In general, decarbonylation process usually proceeds at high temperature, the yield of desired products is thus decreased at lower reaction temperature because the non‐decarbonylative by‐products were observed. In 2018, Ritter's group demonstrated the decarbonylative difluoromethylation of acyl chlorides by the Pd(dba) 2 and RuPhos catalytic system, which opened the new window for decarbonylative transformations at room temperature (Scheme ) . This phenomenon could be explained by the rapid decarbonylation of the 3‐coordinated (RuPhos)Pd II (C(O)Ar)(CF 2 H) complex, which left an empty coordination site for smooth decarbonylation.…”

Section: Other Decarbonylative Transformations Of Acyl Halidesmentioning

confidence: 99%

“…On the other hand, Ritter found that acyl(chloro)palladium, (RuPhos)Pd II (C(O)Ar)Cl, could not proceed a decarbonylative step at room temperature, whereas a fast decarbonylation of (RuPhos)Pd II (C(O)Ar)(CF 2 H) complex was observed even below room temperature, which indicates that transmetalation can occur prior to decarbonylation in this transformation . Similarly, computational data for decarbonylative trifluoromethylation of acyl fluorides revealed that decarbonylation of complexes formed through transmetalation required lower activation energy barrier than decarbonylation of an acyl(fluoro)palladium(II) complex .…”

Section: Plausible Mechanismsmentioning

confidence: 99%

Nickel or Palladium‐Catalyzed Decarbonylative Transformations of Carboxylic Acid Derivatives

Wang

Nishihara

2020

Chemistry An Asian Journal

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Carboxylic acid derivatives containing acyl halides, anhydrides, esters, amides and acyl nitriles are highly appealing electrophiles in transition-metal-catalyzed carboncarbon bond-forming reactions due to their ready availability and low cost, which can provide divergent transformations of carboxylic acids into other value-added products. In this Minireview, we focus on the recent advances of decarbonylative transformations of carboxylic acid derivatives in carbon-carbon bond formations using Ni or Pd catalysts. A series of reaction types, product classifications and reaction pathways are presented herein, which show the advantageous features of carboxylic acid derivatives as alternative to aryl or alkyl halides in terms of reactivity and compatibility. The well-accepted mechanism of nickel-or palladiumcatalyzed decarbonylative transformations involves initial oxidative addition of carboxylic acid derivatives, followed by decarbonylation or transmetalation (or insertion), and reductive elimination to generate the products, thereby regenerating the catalysts. 2 3 4 5 6 7 8

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“…In 2018, Schoenebeck and co-workersr eported aP d 0 /Xantphos-catalyzed decarbonylativet rifluoromethylation of acid fluorides. [16] Our group together with Hong and co-workers reported aP d 0 /dppb [1,4-bis(diphenylphosphino)butane]-catalyzed direct borylation of carboxylic acidsb y using in situ pivalic anhydride activation. [15] Ritter and co-workersi ndependently accomplished extraordinary mild, Pd 0 /RuPhos-catalyzed difluoromethylationo fa cid chlorides.…”

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confidence: 99%

“…[16] They reported that that Pd(dba) 2 (dba = dibenzylideneacetone), in combination with the bulky monodentate phosphine RuPhos and [(dmpu) 2 Zn(CF 2 H) 2 ]( dmpu = N,N'-dimethylpropyleneurea) as an ucleophilic difluoromethylating agent,p romotes decarbonylativec ross-coupling within 5min at room temperature. [16] They reported that that Pd(dba) 2 (dba = dibenzylideneacetone), in combination with the bulky monodentate phosphine RuPhos and [(dmpu) 2 Zn(CF 2 H) 2 ]( dmpu = N,N'-dimethylpropyleneurea) as an ucleophilic difluoromethylating agent,p romotes decarbonylativec ross-coupling within 5min at room temperature.…”

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confidence: 99%

Redox‐Neutral Decarbonylative Cross‐Couplings Coming of Age

Zhao

Szostak

2019

ChemSusChem

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Carboxylica cids represent quintessential substrates for organic synthesis. [1] Diverse electrophilic and nucleophilic reactions of carboxylic acids form the foundation of daily research by practicing organic chemists [2] and feature as ap illar of all undergraduate organic chemistry textbooks. [3] The steadily increasing demandf or efficient and sustainable carbon-carbon bondforming protocols has given rise to the exponential growth of transition-metal-catalyzed cross-coupling reactions, as firmly manifestedb yt he 2010 NobelP rize in Chemistry. [4] Following the inspiring breakthrough reported by Gooßen and co-workers in 2006, [5] traditionally,t he cross-couplingo fc arboxylic acids is addressed by decarboxylation. [6] Typically,t his involves generation of arenecarboxylate speciesa nd extrusion of carbon dioxide, which converts carboxylic acids into aryl nucleophiles. [7] This approachh as provene xtremely valuable, as it allows carboxylic acids to serve as ubiquitous, orthogonal, and readily accessible cross-coupling partners in paradigms under decarboxylative regimen. However,d espite the profound impact on chemical synthesis, decarboxylative cross-couplings have been ac hallenge, owing to high energy requirements for the decarboxylation step, [5] which often requires stoichiometric metal additives, substrates that favor decarboxylation, and typically high temperatures. [6] Recently,s ignificant progressh as been made in the developmento fc ross-coupling reactions of carboxylic acids via redox-neutral decarbonylative pathways ( Figure 1).In this approach, the carboxylic acid is first converted into an activated,e asily accessible acyl carboxylic acid derivative, followed by metal insertion, transmetallation/decarbonylation, and reductivee limination, thus mimicking the classical M 0/II (M = metal) cross-coupling mechanism under redox-neutral conditions ( Figure 2). Altogether,this provides ap owerful alternative approach to the decarboxylative cross-couplingo fc arboxylic acids [6] as wella st he traditional cross-coupling of aryl halides. [4] Of course,d ecarbonylative cross-couplingsa re not new. [4] One of the first efficient examples of ad ecarbonylative crosscoupling was reported by de Vries and co-workersi n1 998 and involved the use of symmetrical anhydrides in aP dCl 2 /LiClcocatalyzed decarbonylative Heck cross-coupling. [8,9] Subsequently,t his approachw as refinedb yG ooßen and co-workers who utilized aromatice sters and vinylice sters thus minimizing generation of toxic halide waste. [10] The idea of forming aryl electrophiles from carboxylic acids by decarbonylation laid dormant until 2012w hen Itami and co-workersr eported that relatively unactivated phenolic esters can be induced to undergo selectived ecarbonylation/CÀCc ross-coupling with acidic heterocycles utilizingN i(cod) 2 (cod = 1,5-cycooctadiene) and dcype [1,2-bis(dicyclohexylphosphino)ethane] as ak ey bidentate ligand. [11] In 2015, our group introduced decarbonylative cross-coupling of amides by selectiveN ÀCb ond activati...

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Palladium‐Catalyzed Decarbonylative Difluoromethylation of Acid Chlorides at Room Temperature

Cited by 87 publications

References 110 publications

Direct C–H difluoromethylation of heterocycles via organic photoredox catalysis

Direct C–H difluoromethylation of heterocycles via organic photoredox catalysis

Nickel or Palladium‐Catalyzed Decarbonylative Transformations of Carboxylic Acid Derivatives

Redox‐Neutral Decarbonylative Cross‐Couplings Coming of Age

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