A New Paradigm for Carbon−Carbon Bond Formation:  Aerobic, Copper-Templated Cross-Coupling

Villalobos, Janette M.; Šrogl, Jiří; Liebeskind, Lanny S.

doi:10.1021/ja074931n

Cited by 189 publications

(99 citation statements)

References 15 publications

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“…So, we conceived that the simultaneous activation of both the carboxylic acid and the alcohol by using PPh 3 and NBS in the same pot, followed by treatment with reagent 1 could form the corresponding thioester. Accordingly, benzoic acid (2a; 1.0 equiv.)…”

Section: Resultsmentioning

confidence: 99%

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Synthesis of Thioesters by Simultaneous Activation of Carboxylic Acids and Alcohols Using PPh₃/NBS with Benzyltriethylammonium Tetrathiomolybdate as the Sulfur Transfer Reagent

2009

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A new and simple route for the synthesis of thioesters starting from carboxylic acids and alcohols is reported by using tetrathiomolybdate as the key sulfur transfer reagent. Triphenylphosphane and N-bromosuccinimide were used for the activation of the carboxylic acid and alcohol in the same pot followed by the transfer of sulfur from tetrathiomolybdate. Thioesters were obtained in good to moderate yields. Pri-

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Section: Resultsmentioning

confidence: 99%

“…[2] The recent advent of organometallic coupling [3] reactions with thioesters as coupling partners has increased the quest for newer methods of thioester synthesis. Thioesters also serve as important intermediates in the biosynthesis of polyketides and nonribosomal polypeptides from fatty acids and amino acids.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Thioesters by Simultaneous Activation of Carboxylic Acids and Alcohols Using PPh₃/NBS with Benzyltriethylammonium Tetrathiomolybdate as the Sulfur Transfer Reagent

2009

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“…This chemistry is based upon a recently disclosed "second generation desulfitative coupling of thiol esters and boronic acids that takes place through a mechanistically novel Cu-catalyzed , aerobic desulfitative process. [73, 74]…”

mentioning

confidence: 99%

“…As described in the initial manuscript disclosing the "second generation" desulfitative coupling,[73] the reaction is rendered catalytic in Cu under aerobic conditions through "scavenging" of the thiolate residue with a second sacrificial equivalent of the boronic acid. A Cu-centered transmetalation/reductive elimination sequence generates a thioether thus removing thiolate from the reaction system and regenerating Cu I for subsequent reaction with O 2 and continuation of the catalytic cycle.…”

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confidence: 99%

A Copper‐Catalyzed, pH‐Neutral Construction of High‐Enantiopurity Peptidyl Ketones from Peptidic S‐Acylthiosalicylamides in Air at Room Temperature

Liebeskind

Yang

2009

Angew Chem Int Ed

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Described herein is a Cu-catalyzed transformation of peptidic thiol esters and boronic acids into peptidyl ketones that takes place at room temperature in DMF or in DMF/H 2 O open to air and uses only catalytic quantities of a Cu carboxylate to mediate the reaction. This aerobic transformation occurs only at a thiol ester capable of coordinating to Cu through its S-appendage and is hampered neither by racemization of the reactants or products, nor by the presence of disulfides or of unprotected phenols, alcohols, or indoles. KeywordsC-C coupling; Cross-coupling; Synthetic methods; Copper; Peptidomimetics; Protein modifications In recent decades great strides have been made in uncovering novel methods for the metalcatalyzed construction of C-C and C-X bonds from organic halides/sulfonates/ phosphonates [1][2][3][4][5][6][7][8][9][10][11] and through C-H functionalization. [12][13][14][15][16][17][18][19][20][21][22][23][24] The great majority of these metal-catalyzed couplings are now carried out using mild organic transfer agents such as boronic acids, organostannanes, and organosilanes. The synthetic power and breadth of impact of these modern methods for the efficient and selective generation of a variety of bond types in a vast array of target molecules is unquestioned. And, yet, significant unmet challenges remain for the synthetic scientist to address. One holy grail is the highly chemoselective, nonenzymatic formation of a C-C or C-X bond at a specific site on a functionally complex biomolecule under biologically relevant conditions (i.e., minimal or no protecting groups, ambient temperatures, neutral pH reaction conditions, aerobic or anaerobic conditions, compatibility with protic solvents). [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] NIH Public Access In probing the value of Cu-catalyzed, aerobic, desulfitative coupling for the construction of peptidyl ketones, a control experiment using tryptophan-derived thiol esters validated the importance of the nature of the thiol ester S-pendant on the substrate reactivity (Scheme 1): at 50 °C in DMF with 5 mol % Cu I 3-methylsalicylate (CuMeSal) the reaction occurred only with the tryptophan derived thiophenyl ester bearing an ortho CONHt-Bu group and not with the simple thiophenyl ester.This result clearly confirmed that a coordinating moiety on the pendant group of the thiol ester is a requisite condition for this Cu-catalyzed, aerobic reaction. As described in the initial manuscript disclosing the "second generation" desulfitative coupling,[73] the reaction is rendered catalytic in Cu under aerobic conditions through "scavenging" of the thiolate residue with a second sacrificial equivalent of the boronic acid. A Cu-centered transmetalation/ reductive elimination sequence generates a thioether thus removing thiolate from the reaction system and regenerating Cu I for subsequent reaction with O 2 and continuation of the catalytic cycle.A brief study of the influence of the nature of the ortho-positioned amide group on the obs...

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“…[18] Eine überraschende Wendung erfuhr das Thema der Pdkatalysierten und Cu I -vermittelten C-C-Kupplungen durch die jüngste Entdeckung einer formal ähnlichen Ketonsynthese, die aber einem einzigartigen Mechanismus folgt. Villalobos, Srogl und Liebeskind [19] beschrieben eine Cu-katalysierte Thiolester-Boronsäure-Kupplung unter aeroben Bedingungen, die auch ohne Pd-Quelle abläuft (Schema 3). Alle bisher veröffentlichten Kupplungen zwischen Organoschwe- [6] TC = Thiophen-2-carboxylat.…”

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Kupferkatalysierte C‐C‐Kupplung von Thiolestern und Boronsäuren unter aeroben Bedingungen

Prokopcová

Kappe

2008

Angewandte Chemie

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A New Paradigm for Carbon−Carbon Bond Formation: Aerobic, Copper-Templated Cross-Coupling

Cited by 189 publications

References 15 publications

Synthesis of Thioesters by Simultaneous Activation of Carboxylic Acids and Alcohols Using PPh₃/NBS with Benzyltriethylammonium Tetrathiomolybdate as the Sulfur Transfer Reagent

Synthesis of Thioesters by Simultaneous Activation of Carboxylic Acids and Alcohols Using PPh₃/NBS with Benzyltriethylammonium Tetrathiomolybdate as the Sulfur Transfer Reagent

A Copper‐Catalyzed, pH‐Neutral Construction of High‐Enantiopurity Peptidyl Ketones from Peptidic S‐Acylthiosalicylamides in Air at Room Temperature

Kupferkatalysierte C‐C‐Kupplung von Thiolestern und Boronsäuren unter aeroben Bedingungen

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A New Paradigm for Carbon−Carbon Bond Formation: Aerobic, Copper-Templated Cross-Coupling

Cited by 189 publications

References 15 publications

Synthesis of Thioesters by Simultaneous Activation of Carboxylic Acids and Alcohols Using PPh3/NBS with Benzyltriethylammonium Tetrathiomolybdate as the Sulfur Transfer Reagent

Synthesis of Thioesters by Simultaneous Activation of Carboxylic Acids and Alcohols Using PPh3/NBS with Benzyltriethylammonium Tetrathiomolybdate as the Sulfur Transfer Reagent

A Copper‐Catalyzed, pH‐Neutral Construction of High‐Enantiopurity Peptidyl Ketones from Peptidic S‐Acylthiosalicylamides in Air at Room Temperature

Kupferkatalysierte C‐C‐Kupplung von Thiolestern und Boronsäuren unter aeroben Bedingungen

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Synthesis of Thioesters by Simultaneous Activation of Carboxylic Acids and Alcohols Using PPh₃/NBS with Benzyltriethylammonium Tetrathiomolybdate as the Sulfur Transfer Reagent

Synthesis of Thioesters by Simultaneous Activation of Carboxylic Acids and Alcohols Using PPh₃/NBS with Benzyltriethylammonium Tetrathiomolybdate as the Sulfur Transfer Reagent