A Dichotomy in Cross-Coupling Site Selectivity in a Dihalogenated Heteroarene: Influence of Mononuclear Pd, Pd Clusters, and Pd Nanoparticles—the Case for Exploiting Pd Catalyst Speciation

Neil Scott; Mark J. Ford; Neda Jeddi; Anthony  Eyles; Lauriane Simon; Adrian C. Whitwood; Theo Tanner; Charlotte E. Willans; Ian James Stewart Fairlamb

doi:10.1021/jacs.1c05294

A Dichotomy in Cross-Coupling Site Selectivity in a Dihalogenated Heteroarene: Influence of Mononuclear Pd, Pd Clusters, and Pd Nanoparticles—the Case for Exploiting Pd Catalyst Speciation

Neil Scott, Mark J. Ford, Neda Jeddi, Anthony Eyles, Lauriane Simon, Adrian C. Whitwood, Theo Tanner, Charlotte E. Willans, Ian James Stewart Fairlamb

Chemistry

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

Abstract

Site-selective dihalogenated heteroarene cross-coupling with organometallic reagents usually occurs at the halogen proximal to the heteroatom, enabled by intrinsic relative electrophilicity, particularly in strongly polarized systems. An archetypical example is the Suzuki–Miyaura cross-coupling (SMCC) of 2,4-dibromopyridine with organoboron species, which typically exhibit C2-arylation site-selectivity using mononuclear Pd (pre)catalysts. Given that Pd speciation, particularly aggregation, is known to lead to the formation of catalytically competent multinuclear Pdn species, the influence of these species on cross-coupling site-selectivity remains largely unknown. Herein, we disclose that multinuclear Pd species, in the form of Pd3-type clusters and nanoparticles, switch arylation site-selectivity from C2 to C4, in 2,4-dibromopyridine cross-couplings with both organoboronic acids (SMCC reactions) and Grignard reagents (Kumada-type reactions). The Pd/ligand ratio and the presence of suitable stabilizing salts were found to be critically important in switching the site-selectivity. More generally, this study provides experimental evidence that aggregated Pd catalyst species not only are catalytically competent but also alter reaction outcomes through changes in product selectivity.

Original language	English
Pages (from-to)	9682-9693
Number of pages	12
Journal	Journal of the American Chemical Society
Volume	143
Issue number	25
DOIs	https://doi.org/10.1021/jacs.1c05294
Publication status	Published - 21 Jun 2021

Bibliographical note

Keywords

Catalysis
Palladium

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Cite this

Scott, N., Ford, M. J., Jeddi, N., Eyles, A., Simon, L., Whitwood, A. C., Tanner, T., Willans, C. E., & Fairlamb, I. J. S. (2021). A Dichotomy in Cross-Coupling Site Selectivity in a Dihalogenated Heteroarene: Influence of Mononuclear Pd, Pd Clusters, and Pd Nanoparticles—the Case for Exploiting Pd Catalyst Speciation. Journal of the American Chemical Society, 143(25), 9682-9693. https://doi.org/10.1021/jacs.1c05294

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title = "A Dichotomy in Cross-Coupling Site Selectivity in a Dihalogenated Heteroarene: Influence of Mononuclear Pd, Pd Clusters, and Pd Nanoparticles—the Case for Exploiting Pd Catalyst Speciation",

abstract = "Site-selective dihalogenated heteroarene cross-coupling with organometallic reagents usually occurs at the halogen proximal to the heteroatom, enabled by intrinsic relative electrophilicity, particularly in strongly polarized systems. An archetypical example is the Suzuki–Miyaura cross-coupling (SMCC) of 2,4-dibromopyridine with organoboron species, which typically exhibit C2-arylation site-selectivity using mononuclear Pd (pre)catalysts. Given that Pd speciation, particularly aggregation, is known to lead to the formation of catalytically competent multinuclear Pdn species, the influence of these species on cross-coupling site-selectivity remains largely unknown. Herein, we disclose that multinuclear Pd species, in the form of Pd3-type clusters and nanoparticles, switch arylation site-selectivity from C2 to C4, in 2,4-dibromopyridine cross-couplings with both organoboronic acids (SMCC reactions) and Grignard reagents (Kumada-type reactions). The Pd/ligand ratio and the presence of suitable stabilizing salts were found to be critically important in switching the site-selectivity. More generally, this study provides experimental evidence that aggregated Pd catalyst species not only are catalytically competent but also alter reaction outcomes through changes in product selectivity.",

keywords = "Catalysis, Palladium",

author = "Neil Scott and Ford, {Mark J.} and Neda Jeddi and Anthony Eyles and Lauriane Simon and Whitwood, {Adrian C.} and Theo Tanner and Willans, {Charlotte E.} and Fairlamb, {Ian James Stewart}",

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Scott, N, Ford, MJ, Jeddi, N, Eyles, A, Simon, L, Whitwood, AC, Tanner, T, Willans, CE & Fairlamb, IJS 2021, 'A Dichotomy in Cross-Coupling Site Selectivity in a Dihalogenated Heteroarene: Influence of Mononuclear Pd, Pd Clusters, and Pd Nanoparticles—the Case for Exploiting Pd Catalyst Speciation', Journal of the American Chemical Society, vol. 143, no. 25, pp. 9682-9693. https://doi.org/10.1021/jacs.1c05294

A Dichotomy in Cross-Coupling Site Selectivity in a Dihalogenated Heteroarene: Influence of Mononuclear Pd, Pd Clusters, and Pd Nanoparticles—the Case for Exploiting Pd Catalyst Speciation. / Scott, Neil; Ford, Mark J.; Jeddi, Neda et al.
In: Journal of the American Chemical Society, Vol. 143, No. 25, 21.06.2021, p. 9682-9693.

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

TY - JOUR

T1 - A Dichotomy in Cross-Coupling Site Selectivity in a Dihalogenated Heteroarene

T2 - Influence of Mononuclear Pd, Pd Clusters, and Pd Nanoparticles—the Case for Exploiting Pd Catalyst Speciation

AU - Scott, Neil

AU - Ford, Mark J.

AU - Jeddi, Neda

AU - Eyles, Anthony

AU - Simon, Lauriane

AU - Whitwood, Adrian C.

AU - Tanner, Theo

AU - Willans, Charlotte E.

AU - Fairlamb, Ian James Stewart

PY - 2021/6/21

Y1 - 2021/6/21

N2 - Site-selective dihalogenated heteroarene cross-coupling with organometallic reagents usually occurs at the halogen proximal to the heteroatom, enabled by intrinsic relative electrophilicity, particularly in strongly polarized systems. An archetypical example is the Suzuki–Miyaura cross-coupling (SMCC) of 2,4-dibromopyridine with organoboron species, which typically exhibit C2-arylation site-selectivity using mononuclear Pd (pre)catalysts. Given that Pd speciation, particularly aggregation, is known to lead to the formation of catalytically competent multinuclear Pdn species, the influence of these species on cross-coupling site-selectivity remains largely unknown. Herein, we disclose that multinuclear Pd species, in the form of Pd3-type clusters and nanoparticles, switch arylation site-selectivity from C2 to C4, in 2,4-dibromopyridine cross-couplings with both organoboronic acids (SMCC reactions) and Grignard reagents (Kumada-type reactions). The Pd/ligand ratio and the presence of suitable stabilizing salts were found to be critically important in switching the site-selectivity. More generally, this study provides experimental evidence that aggregated Pd catalyst species not only are catalytically competent but also alter reaction outcomes through changes in product selectivity.

AB - Site-selective dihalogenated heteroarene cross-coupling with organometallic reagents usually occurs at the halogen proximal to the heteroatom, enabled by intrinsic relative electrophilicity, particularly in strongly polarized systems. An archetypical example is the Suzuki–Miyaura cross-coupling (SMCC) of 2,4-dibromopyridine with organoboron species, which typically exhibit C2-arylation site-selectivity using mononuclear Pd (pre)catalysts. Given that Pd speciation, particularly aggregation, is known to lead to the formation of catalytically competent multinuclear Pdn species, the influence of these species on cross-coupling site-selectivity remains largely unknown. Herein, we disclose that multinuclear Pd species, in the form of Pd3-type clusters and nanoparticles, switch arylation site-selectivity from C2 to C4, in 2,4-dibromopyridine cross-couplings with both organoboronic acids (SMCC reactions) and Grignard reagents (Kumada-type reactions). The Pd/ligand ratio and the presence of suitable stabilizing salts were found to be critically important in switching the site-selectivity. More generally, this study provides experimental evidence that aggregated Pd catalyst species not only are catalytically competent but also alter reaction outcomes through changes in product selectivity.

KW - Catalysis

KW - Palladium

U2 - 10.1021/jacs.1c05294

DO - 10.1021/jacs.1c05294

M3 - Article

SN - 0002-7863

VL - 143

SP - 9682

EP - 9693

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 25

ER -