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 - Funding Information:
We 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.
Funding Information:
We 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. T.Z. S.M. F.N. A.M.C.O. A.P. L.C. and C.S.J.C. performed the experiments. M.S. A.P. and S.P.N. wrote the manuscript and directed the project. All the authors discussed the results and commented on the manuscript. The authors declare no competing interests.
Publisher Copyright:
© 2020 The Author(s)
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.
KW - Catalysis
KW - Chemistry
KW - Inorganic Chemistry
KW - Organic Synthesis
UR - http://www.scopus.com/inward/record.url?scp=85088973933&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088973933&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2020.101377
DO - 10.1016/j.isci.2020.101377
M3 - Article
AN - SCOPUS:85088973933
SN - 2589-0042
VL - 23
JO - iScience
JF - iScience
IS - 8
M1 - 101377
ER -