Direct Cyclopalladation of Fluorinated Benzyl Amines by Pd3(OAc)6: The Coexistence of Multinuclear PdnReaction Pathways Highlights the Importance of Pd Speciation in C-H Bond Activation

Ian J.S. Fairlamb; Jan Lang; Aleš Růžička; Miloš Sedlák; Jiří Váňa

doi:10.1021/acs.organomet.3c00178

Direct Cyclopalladation of Fluorinated Benzyl Amines by Pd₃(OAc)₆: The Coexistence of Multinuclear Pd_nReaction Pathways Highlights the Importance of Pd Speciation in C-H Bond Activation

Ian J.S. Fairlamb, Jan Lang, Aleš Růžička, Miloš Sedlák, Jiří Váňa

Chemistry

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

Abstract

Palladacycles are key intermediates in catalytic C-H bond functionalization reactions and important precatalysts for cross-couplings. It is commonly believed that palladacycle formation occurs through the reaction of a substrate bearing a C-H bond ortho to a suitable metal-directing group for interaction with, typically, mononuclear "Pd(OAc)2"species, with cyclopalladation liberating acetic acid as the side product. In this study, we show that N,N-dimethyl-fluoro-benzyl amines, which can be cyclopalladated either ortho or para to fluorine affording two regioisomeric products, can occur by a direct reaction of Pd3(OAc)6, proceeding via higher-order cyclopalladated intermediates. Regioselectivity is altered subtly depending on the ratio of substrate:Pd3(OAc)6 and the solvent used. Our findings are important when considering mechanisms of Pd-mediated reactions involving the intermediacy of palladacycles, of particular relevance in catalytic C-H bond functionalization chemistry.

Original language	English
Number of pages	9
Journal	Organometallics
Early online date	30 May 2023
DOIs	https://doi.org/10.1021/acs.organomet.3c00178
Publication status	E-pub ahead of print - 30 May 2023

Bibliographical note

Funding Information:
The University of Pardubice, Royal Society (Industry Fellowship to I.J.S.F.) and EPSRC (grant number EP/S009965/1) are acknowledged for financial support. We are very grateful to the University of York for hosting a research visitor position for J.V. (2019; hosted by I.J.S.F.) and to Prof. RN Perutz for initial discussions concerning this research. I.J.S.F. acknowledges the Royal Society for an Industry Fellowship.

Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.

Access to Document

10.1021/acs.organomet.3c00178Licence: CC BY-NC

DirectCyclopalladationof FluorinatedBenzylAminesby Pd3(OAc)6:The Coexistenceof MultinuclearPdnReactionPathwaysHighlightsthe Importanceof Pd Speciationin C−H BondActivation
© 2023 The Authors.
Final published version, 3.53 MBLicence: CC BY-NC

Cite this

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title = "Direct Cyclopalladation of Fluorinated Benzyl Amines by Pd3(OAc)6: The Coexistence of Multinuclear PdnReaction Pathways Highlights the Importance of Pd Speciation in C-H Bond Activation",

abstract = "Palladacycles are key intermediates in catalytic C-H bond functionalization reactions and important precatalysts for cross-couplings. It is commonly believed that palladacycle formation occurs through the reaction of a substrate bearing a C-H bond ortho to a suitable metal-directing group for interaction with, typically, mononuclear {"}Pd(OAc)2{"}species, with cyclopalladation liberating acetic acid as the side product. In this study, we show that N,N-dimethyl-fluoro-benzyl amines, which can be cyclopalladated either ortho or para to fluorine affording two regioisomeric products, can occur by a direct reaction of Pd3(OAc)6, proceeding via higher-order cyclopalladated intermediates. Regioselectivity is altered subtly depending on the ratio of substrate:Pd3(OAc)6 and the solvent used. Our findings are important when considering mechanisms of Pd-mediated reactions involving the intermediacy of palladacycles, of particular relevance in catalytic C-H bond functionalization chemistry.",

author = "Fairlamb, {Ian J.S.} and Jan Lang and Ale{\v s} Rů{\v z}i{\v c}ka and Milo{\v s} Sedl{\'a}k and Ji{\v r}{\'i} V{\'a}{\v n}a",

note = "Funding Information: The University of Pardubice, Royal Society (Industry Fellowship to I.J.S.F.) and EPSRC (grant number EP/S009965/1) are acknowledged for financial support. We are very grateful to the University of York for hosting a research visitor position for J.V. (2019; hosted by I.J.S.F.) and to Prof. RN Perutz for initial discussions concerning this research. I.J.S.F. acknowledges the Royal Society for an Industry Fellowship. Publisher Copyright: {\textcopyright} 2023 The Authors. Published by American Chemical Society.",

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AU - Fairlamb, Ian J.S.

AU - Lang, Jan

AU - Růžička, Aleš

AU - Sedlák, Miloš

AU - Váňa, Jiří

N1 - Funding Information: The University of Pardubice, Royal Society (Industry Fellowship to I.J.S.F.) and EPSRC (grant number EP/S009965/1) are acknowledged for financial support. We are very grateful to the University of York for hosting a research visitor position for J.V. (2019; hosted by I.J.S.F.) and to Prof. RN Perutz for initial discussions concerning this research. I.J.S.F. acknowledges the Royal Society for an Industry Fellowship. Publisher Copyright: © 2023 The Authors. Published by American Chemical Society.

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N2 - Palladacycles are key intermediates in catalytic C-H bond functionalization reactions and important precatalysts for cross-couplings. It is commonly believed that palladacycle formation occurs through the reaction of a substrate bearing a C-H bond ortho to a suitable metal-directing group for interaction with, typically, mononuclear "Pd(OAc)2"species, with cyclopalladation liberating acetic acid as the side product. In this study, we show that N,N-dimethyl-fluoro-benzyl amines, which can be cyclopalladated either ortho or para to fluorine affording two regioisomeric products, can occur by a direct reaction of Pd3(OAc)6, proceeding via higher-order cyclopalladated intermediates. Regioselectivity is altered subtly depending on the ratio of substrate:Pd3(OAc)6 and the solvent used. Our findings are important when considering mechanisms of Pd-mediated reactions involving the intermediacy of palladacycles, of particular relevance in catalytic C-H bond functionalization chemistry.

AB - Palladacycles are key intermediates in catalytic C-H bond functionalization reactions and important precatalysts for cross-couplings. It is commonly believed that palladacycle formation occurs through the reaction of a substrate bearing a C-H bond ortho to a suitable metal-directing group for interaction with, typically, mononuclear "Pd(OAc)2"species, with cyclopalladation liberating acetic acid as the side product. In this study, we show that N,N-dimethyl-fluoro-benzyl amines, which can be cyclopalladated either ortho or para to fluorine affording two regioisomeric products, can occur by a direct reaction of Pd3(OAc)6, proceeding via higher-order cyclopalladated intermediates. Regioselectivity is altered subtly depending on the ratio of substrate:Pd3(OAc)6 and the solvent used. Our findings are important when considering mechanisms of Pd-mediated reactions involving the intermediacy of palladacycles, of particular relevance in catalytic C-H bond functionalization chemistry.

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