The Transmetalation Process in Suzuki–Miyaura Reactions: Calculations Indicate Lower Barrier via Boronate Intermediate

Ortuño, Manuel Á.; Lledós, Agustı́; Maseras, Feliu; Ujaque, Gregori

doi:10.1002/cctc.201402326

Cited by 76 publications

(56 citation statements)

References 83 publications

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“…30,31 A forgoing computational study has evaluated monoligated structures similar to ours as intermediates in the Suzuki–Miyaura cross-coupling. 32 In this study, the authors were able to predict the presence of the pretransmetalation intermediate we have experimentally observed, as well as predict the correct operative pathway. This study differed from our own in that the authors examine a triphenylphosphine ligated system, for which they predicted the rate-determining step to be Pd–O bond breakage in the monoligated species rather than transmetalation.…”

Section: Resultsmentioning

confidence: 84%

Elucidating the Role of the Boronic Esters in the Suzuki–Miyaura Reaction: Structural, Kinetic, and Computational Investigations

et al. 2018

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The Suzuki–Miyaura reaction is the most practiced palladium-catalyzed, cross-coupling reaction because of its broad applicability, low toxicity of the metal (B), and the wide variety of commercially available boron substrates. A wide variety of boronic acids and esters, each with different properties, have been developed for this process. Despite the popularity of the Suzuki–Miyaura reaction, the precise manner in which the organic fragment is transferred from boron to palladium has remained elusive for these reagents. Herein, we report the observation and characterization of pretransmetalation intermediates generated from a variety of commonly employed boronic esters. The ability to confirm the intermediacy of pretransmetalation intermediates provided the opportunity to clarify mechanistic aspects of the transfer of the organic moiety from boron to palladium in the key transmetalation step. A series of structural, kinetic, and computational investigations revealed that boronic esters can transmetalate directly without prior hydrolysis. Furthermore, depending on the boronic ester employed, significant rate enhancements for the transfer of the B-aryl groups were observed. Overall, two critical features were identified that enable the transfer of the organic fragment from boron to palladium: (1) the ability to create an empty coordination site on the palladium atom and (2) the nucleophilic character of the ipso carbon bound to boron. Both of these features ultimately relate to the electron density of the oxygen atoms in the boronic ester.

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Section: Resultsmentioning

confidence: 84%

Elucidating the Role of the Boronic Esters in the Suzuki–Miyaura Reaction: Structural, Kinetic, and Computational Investigations

et al. 2018

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“…Progressing from A , the transmetalation step, which is the most characteristic step of the C−C cross‐coupling reaction, with aryl iodide proceeds . This process is expected to show differences, depending on the particular cross‐coupling reactions .…”

Section: Resultsmentioning

confidence: 99%

Mechanistic Insights into Palladium‐Catalyzed Silylation of Aryl Iodides with Hydrosilanes through a DFT Study

Zhang

et al. 2017

Chemistry An Asian Journal

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The catalytic cycles of palladium-catalyzed silylation of aryl iodides, which are initiated by oxidative addition of hydrosilane or aryl iodide through three different mechanisms characterized by intermediates R Si-Pd -H (Cycle A), Ar-Pd -I (Cycle B), and Pd (Cycle C), have been explored in detail by hybrid DFT. Calculations suggest that the chemical selectivity and reactivity of the reaction depend on the ligation state of the catalyst and specific reaction conditions, including feeding order of substrates and the presence of base. For less bulky biligated catalyst, Cycle C is energetically favored over Cycle A, through which the silylation process is slightly favored over the reduction process. Interestingly, for bulky monoligated catalyst, Cycle B is energetically more favored over generally accepted Cycle A, in which the silylation channel is slightly disfavored in comparison to that of the reduction channel. Moreover, the inclusion of base in this channel allows the silylated product become dominant. These findings offer a good explanation for the complex experimental observations. Designing a reaction process that allows the oxidative addition of palladium(0) complex to aryl iodide to occur prior to that with hydrosilane is thus suggested to improve the reactivity and chemoselectivity for the silylated product by encouraging the catalytic cycle to proceed through Cycles B (monoligated Pd catalyst) or C (biligated Pd catalyst), instead of Cycle A.

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“…Trace water not only helps solvate inorganic salts, [9] but is also needed for efficient transmetalation in the absence of a hydroxide base. [10,11] However, because polar solvents were previously reported to favor reaction at triflate using Pd/P t Bu 3 , we were concerned that added water could erode selectivity for reaction at chloride. Gratifyingly, small amounts of H 2 O greatly improved conversion and were not detrimental to selectivity (entries [3][4][5].…”

mentioning

confidence: 99%

Solvent Effects on the Selectivity of Palladium‐Catalyzed Suzuki‐Miyaura Couplings

Reeves

Bauman

Mitchem

et al. 2019

Israel Journal of Chemistry

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The use of polar solvents MeCN or dimethylformamide (DMF) was previously shown to induce a selectivity switch in the Pd/P t Bu 3 -catalyzed Suzuki-Miyaura coupling of chloroaryl triflates. This phenomenon was attributed to the ability of polar solvents to stabilize anionic transition states for oxidative addition. However, we demonstrate that selectivity in this reaction does not trend with solvent dielectic constant. Unlike MeCN and DMF, water, alcohols, and several polar aprotic solvents such as MeNO 2 , acetone, and propylene carbonate provide the same selectivity as nonpolar solvents. These results indicate that the role of solvent on the selectivity of Suzuki-Miyaura couplings may be more complex than previously envisioned. Furthermore, this observation has the potential for synthetic value as it greatly broadens the scope of solvents that can be used for chloride-selective cross coupling of chloroaryl triflates.

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The Transmetalation Process in Suzuki–Miyaura Reactions: Calculations Indicate Lower Barrier via Boronate Intermediate

Cited by 76 publications

References 83 publications

Elucidating the Role of the Boronic Esters in the Suzuki–Miyaura Reaction: Structural, Kinetic, and Computational Investigations

Elucidating the Role of the Boronic Esters in the Suzuki–Miyaura Reaction: Structural, Kinetic, and Computational Investigations

Mechanistic Insights into Palladium‐Catalyzed Silylation of Aryl Iodides with Hydrosilanes through a DFT Study

Solvent Effects on the Selectivity of Palladium‐Catalyzed Suzuki‐Miyaura Couplings

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