[Pd(NHC)(μ-Cl)Cl]2: versatile and highly reactive complexes for cross-coupling reactions that avoid formation of inactive Pd(I) off-cycle products

Tongliang Zhou; Siyue Ma; Fady Nahra; Alan M.C. Obled; Albert Poater; Luigi Cavallo; Catherine S.J. Cazin; Steven P. Nolan; Michal Szostak

doi:10.1016/j.isci.2020.101377

[Pd(NHC)(μ-Cl)Cl]₂: versatile and highly reactive complexes for cross-coupling reactions that avoid formation of inactive Pd(I) off-cycle products

Tongliang Zhou, Siyue Ma, Fady Nahra, Alan M.C. Obled, Albert Poater, Luigi Cavallo, Catherine S.J. Cazin, Steven P. Nolan, Michal Szostak

School of Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

The development of more reactive, general, easily accessible, and readily available Pd(II)–NHC precatalysts remains a key challenge in homogeneous catalysis. In this study, we establish air-stable NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]₂, as the most reactive Pd(II)–NHC catalysts developed to date. Most crucially, compared with [Pd(NHC)(allyl)Cl] complexes, replacement of the allyl throw-away ligand with chloride allows for a more facile activation step, while effectively preventing the formation of off-cycle [Pd₂(μ-allyl)(μ-Cl)(NHC)₂] products. The utility is demonstrated via broad compatibility with amide cross-coupling, Suzuki cross-coupling, and the direct, late-stage functionalization of pharmaceuticals. Computational studies provide key insight into the NHC–Pd(II) chloro-dimer activation pathway. A facile synthesis of NHC–Pd(II) chloro-dimers in one-pot from NHC salts is reported. Considering the tremendous utility of Pd-catalyzed cross-coupling reactions and the overwhelming success of [Pd(NHC)(allyl)Cl] precatalysts, we believe that NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]₂, should be considered as go-to precatalysts of choice in cross-coupling processes.

Original language	English
Article number	101377
Journal	iScience
Volume	23
Issue number	8
Early online date	16 Jul 2020
DOIs	https://doi.org/10.1016/j.isci.2020.101377
Publication status	Published - 21 Aug 2020

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Copyright 2020 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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Pd(NHC)(μ-Cl)Cl]2: Versatile and Highly Reactive Complexes for Cross-Coupling Reactions that Avoid Formation of Inactive Pd(I) Off-Cycle Products
Zhou, T. (Creator), Ma, S. (Creator), Nahra, F. (Creator), Obled, A. M. C. (Creator), Poater Teixidor, A. (Creator), Cavallo, L. (Creator), Cazin, C. S. J. (Creator), Nolan, S. P. (Creator) & Szostak, M. (Creator), CORA.Repositori de Dades de Recerca, 2023
DOI: 10.34810/data643
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@article{7513cf3e57fd47d8a961ab68a59628aa,

title = "[Pd(NHC)(μ-Cl)Cl]2: versatile and highly reactive complexes for cross-coupling reactions that avoid formation of inactive Pd(I) off-cycle products",

abstract = "The development of more reactive, general, easily accessible, and readily available Pd(II)–NHC precatalysts remains a key challenge in homogeneous catalysis. In this study, we establish air-stable NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]2, as the most reactive Pd(II)–NHC catalysts developed to date. Most crucially, compared with [Pd(NHC)(allyl)Cl] complexes, replacement of the allyl throw-away ligand with chloride allows for a more facile activation step, while effectively preventing the formation of off-cycle [Pd2(μ-allyl)(μ-Cl)(NHC)2] products. The utility is demonstrated via broad compatibility with amide cross-coupling, Suzuki cross-coupling, and the direct, late-stage functionalization of pharmaceuticals. Computational studies provide key insight into the NHC–Pd(II) chloro-dimer activation pathway. A facile synthesis of NHC–Pd(II) chloro-dimers in one-pot from NHC salts is reported. Considering the tremendous utility of Pd-catalyzed cross-coupling reactions and the overwhelming success of [Pd(NHC)(allyl)Cl] precatalysts, we believe that NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]2, should be considered as go-to precatalysts of choice in cross-coupling processes.",

author = "Tongliang Zhou and Siyue Ma and Fady Nahra and Obled, {Alan M.C.} and Albert Poater and Luigi Cavallo and Cazin, {Catherine S.J.} and Nolan, {Steven P.} and Michal Szostak",

note = "Authors thank Rutgers University (M.S.), the NSF (CAREER CHE-1650766, M.S.), and the NIH (1R35GM133326, M.S.) for financial support. The Bruker 500 MHz spectrometer used in this study was supported by the NSF-MRI grant (CHE-1229030). For work conducted in Belgium, S.P.N. and C.S.J.C. wish to thank the UGent BOF (starter and senior research grants). Umicore AG is thanked for gifts of materials. A.P. is a Serra H{\'u}nter Fellow and ICREA Academia Prize 2019 holder. A.P. thanks the Spanish MICINN for project PGC2018-097722-B-I00.",

year = "2020",

month = aug,

day = "21",

doi = "10.1016/j.isci.2020.101377",

language = "English",

volume = "23",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier Inc.",

number = "8",

}

TY - JOUR

T1 - [Pd(NHC)(μ-Cl)Cl]2

T2 - versatile and highly reactive complexes for cross-coupling reactions that avoid formation of inactive Pd(I) off-cycle products

AU - Zhou, Tongliang

AU - Ma, Siyue

AU - Nahra, Fady

AU - Obled, Alan M.C.

AU - Poater, Albert

AU - Cavallo, Luigi

AU - Cazin, Catherine S.J.

AU - Nolan, Steven P.

AU - Szostak, Michal

N1 - Authors thank Rutgers University (M.S.), the NSF (CAREER CHE-1650766, M.S.), and the NIH (1R35GM133326, M.S.) for financial support. The Bruker 500 MHz spectrometer used in this study was supported by the NSF-MRI grant (CHE-1229030). For work conducted in Belgium, S.P.N. and C.S.J.C. wish to thank the UGent BOF (starter and senior research grants). Umicore AG is thanked for gifts of materials. A.P. is a Serra Húnter Fellow and ICREA Academia Prize 2019 holder. A.P. thanks the Spanish MICINN for project PGC2018-097722-B-I00.

PY - 2020/8/21

Y1 - 2020/8/21

N2 - The development of more reactive, general, easily accessible, and readily available Pd(II)–NHC precatalysts remains a key challenge in homogeneous catalysis. In this study, we establish air-stable NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]2, as the most reactive Pd(II)–NHC catalysts developed to date. Most crucially, compared with [Pd(NHC)(allyl)Cl] complexes, replacement of the allyl throw-away ligand with chloride allows for a more facile activation step, while effectively preventing the formation of off-cycle [Pd2(μ-allyl)(μ-Cl)(NHC)2] products. The utility is demonstrated via broad compatibility with amide cross-coupling, Suzuki cross-coupling, and the direct, late-stage functionalization of pharmaceuticals. Computational studies provide key insight into the NHC–Pd(II) chloro-dimer activation pathway. A facile synthesis of NHC–Pd(II) chloro-dimers in one-pot from NHC salts is reported. Considering the tremendous utility of Pd-catalyzed cross-coupling reactions and the overwhelming success of [Pd(NHC)(allyl)Cl] precatalysts, we believe that NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]2, should be considered as go-to precatalysts of choice in cross-coupling processes.

AB - The development of more reactive, general, easily accessible, and readily available Pd(II)–NHC precatalysts remains a key challenge in homogeneous catalysis. In this study, we establish air-stable NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]2, as the most reactive Pd(II)–NHC catalysts developed to date. Most crucially, compared with [Pd(NHC)(allyl)Cl] complexes, replacement of the allyl throw-away ligand with chloride allows for a more facile activation step, while effectively preventing the formation of off-cycle [Pd2(μ-allyl)(μ-Cl)(NHC)2] products. The utility is demonstrated via broad compatibility with amide cross-coupling, Suzuki cross-coupling, and the direct, late-stage functionalization of pharmaceuticals. Computational studies provide key insight into the NHC–Pd(II) chloro-dimer activation pathway. A facile synthesis of NHC–Pd(II) chloro-dimers in one-pot from NHC salts is reported. Considering the tremendous utility of Pd-catalyzed cross-coupling reactions and the overwhelming success of [Pd(NHC)(allyl)Cl] precatalysts, we believe that NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]2, should be considered as go-to precatalysts of choice in cross-coupling processes.

U2 - 10.1016/j.isci.2020.101377

DO - 10.1016/j.isci.2020.101377

M3 - Article

SN - 2589-0042

VL - 23

JO - iScience

JF - iScience

IS - 8

M1 - 101377

ER -

[Pd(NHC)(μ-Cl)Cl]2: versatile and highly reactive complexes for cross-coupling reactions that avoid formation of inactive Pd(I) off-cycle products

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Pd(NHC)(μ-Cl)Cl]2: Versatile and Highly Reactive Complexes for Cross-Coupling Reactions that Avoid Formation of Inactive Pd(I) Off-Cycle Products

Cite this

[Pd(NHC)(μ-Cl)Cl]₂: versatile and highly reactive complexes for cross-coupling reactions that avoid formation of inactive Pd(I) off-cycle products