Concerted metalation deprotonation information

Concerted metalation-deprotonation (CMD) is a mechanistic pathway through which transition-metal catalyzed C–H activation reactions can take place. In a CMD pathway, the C–H bond of the substrate is cleaved and the new C–Metal bond forms through a single transition state.^[1] This process does not go through a metal species that is bound to the cleaved hydrogen atom. Instead, a carboxylate or carbonate base deprotonates the substrate.^[2] The first proposal of a concerted metalation deprotonation pathway was by S. Winstein and T. G. Traylor in 1955 for the acetolysis of diphenylmercury.^[3] It was found to be the lowest energy transition state in a number of computational studies,^[4] was experimentally confirmed through NMR experiments,^[5]^[6] and has been hypothesized to occur in mechanistic studies.^[7]

While there are a number of different possible mechanisms for C–H activation, a CMD pathway is common for high valent, late transition metals like Pd^II,^[8] Rh^III, Ir^III, and Ru^II.^[9] The C–H bonds that have been found to undergo C–H activation through CMD include those that are aryl,^[1] alkyl,^[10]^[11] and alkenyl.^[2] Investigations into CMD paved the way for the development of many new C–H functionalization reactions, especially in the areas of direct arylation and alkylation by palladium and ruthenium.^[2]

^ ^a ^b Lapointe, David; Fagnou, Keith (2010-09-18). "Overview of the Mechanistic Work on the Concerted Metallation–Deprotonation Pathway". Chemistry Letters. 39 (11): 1118–1126. doi:10.1246/cl.2010.1118. ISSN 0366-7022.
^ ^a ^b ^c Ackermann, Lutz (2011-03-09). "Carboxylate-Assisted Transition-Metal-Catalyzed C−H Bond Functionalizations: Mechanism and Scope". Chemical Reviews. 111 (3): 1315–1345. doi:10.1021/cr100412j. ISSN 0009-2665. PMID 21391562.
^ Winstein, S.; Traylor, T. G. (1955-07-01). "Mechanisms of Reaction of Organomercurials. II. Electrophilic Substitution on Saturated Carbon. Acetolysis of Dialkylmercury Compounds". Journal of the American Chemical Society. 77 (14): 3747–3752. doi:10.1021/ja01619a021. ISSN 0002-7863.
^ Davies, David L.; Macgregor, Stuart A.; McMullin, Claire L. (2017-07-12). "Computational Studies of Carboxylate-Assisted C–H Activation and Functionalization at Group 8–10 Transition Metal Centers". Chemical Reviews. 117 (13): 8649–8709. doi:10.1021/acs.chemrev.6b00839. hdl:2381/40233. ISSN 0009-2665. PMID 28530807.
^ Kapdi, Anant R. (2014-01-29). "Organometallic aspects of transition-metal catalysed regioselective C–H bond functionalisation of arenes and heteroarenes". Dalton Transactions. 43 (8): 3021–3034. doi:10.1039/C3DT52737A. ISSN 1477-9234. PMID 24419051.
^ Olah, George A.; Yu, Simon H.; Parker, David G. (1976-05-01). "Organometallic chemistry. XII. Proton and carbon-13 nuclear magnetic resonance study of arenemercurinium ions, the intermediate complexes of aromatic mercuration". The Journal of Organic Chemistry. 41 (11): 1983–1986. doi:10.1021/jo00873a020. ISSN 0022-3263.
^ Fung, Chung W.; Khorramdel-Vahed, Mehdi; Ranson, Richard J.; Roberts, Roger M. G. (1980-01-01). "Kinetics and mechanism of mercuriation of aromatic compounds by mercury trifluoroacetate in trifluoroacetic acid". Journal of the Chemical Society, Perkin Transactions 2 (2): 267–272. doi:10.1039/P29800000267. ISSN 1364-5471.
^ Gorelsky, Serge I.; Lapointe, David; Fagnou, Keith (2008-07-29). "Analysis of the Concerted Metalation-Deprotonation Mechanism in Palladium-Catalyzed Direct Arylation Across a Broad Range of Aromatic Substrates". Journal of the American Chemical Society. 130 (33): 10848–10849. doi:10.1021/ja802533u. ISSN 0002-7863. PMID 18661978.
^ Gensch, T.; Hopkinson, M. N.; Glorius, F.; Wencel-Delord, J. (2016-05-17). "Mild metal-catalyzed C–H activation: examples and concepts". Chemical Society Reviews. 45 (10): 2900–2936. doi:10.1039/C6CS00075D. ISSN 1460-4744. PMID 27072661.
^ He, Jian; Wasa, Masayuki; Chan, Kelvin S. L.; Shao, Qian; Yu, Jin-Quan (2016-12-02). "Palladium-Catalyzed Transformations of Alkyl C–H Bonds". Chemical Reviews. 117 (13): 8754–8786. doi:10.1021/acs.chemrev.6b00622. ISSN 0009-2665. PMC 5516964. PMID 28697604.
^ Hartwig, John F. (2016-01-13). "Evolution of C–H Bond Functionalization from Methane to Methodology". Journal of the American Chemical Society. 138 (1): 2–24. doi:10.1021/jacs.5b08707. ISSN 0002-7863. PMC 4809212. PMID 26566092.

[:0-1] Lapointe, David; Fagnou, Keith (2010-09-18). "Overview of the Mechanistic Work on the Concerted Metallation–Deprotonation Pathway". Chemistry Letters. 39 (11): 1118–1126. doi:10.1246/cl.2010.1118. ISSN 0366-7022.

[:1-2] Ackermann, Lutz (2011-03-09). "Carboxylate-Assisted Transition-Metal-Catalyzed C−H Bond Functionalizations: Mechanism and Scope". Chemical Reviews. 111 (3): 1315–1345. doi:10.1021/cr100412j. ISSN 0009-2665. PMID 21391562.

[3] Winstein, S.; Traylor, T. G. (1955-07-01). "Mechanisms of Reaction of Organomercurials. II. Electrophilic Substitution on Saturated Carbon. Acetolysis of Dialkylmercury Compounds". Journal of the American Chemical Society. 77 (14): 3747–3752. doi:10.1021/ja01619a021. ISSN 0002-7863.

[:2-4] Davies, David L.; Macgregor, Stuart A.; McMullin, Claire L. (2017-07-12). "Computational Studies of Carboxylate-Assisted C–H Activation and Functionalization at Group 8–10 Transition Metal Centers". Chemical Reviews. 117 (13): 8649–8709. doi:10.1021/acs.chemrev.6b00839. hdl:2381/40233. ISSN 0009-2665. PMID 28530807.

[5] Kapdi, Anant R. (2014-01-29). "Organometallic aspects of transition-metal catalysed regioselective C–H bond functionalisation of arenes and heteroarenes". Dalton Transactions. 43 (8): 3021–3034. doi:10.1039/C3DT52737A. ISSN 1477-9234. PMID 24419051.

[6] Olah, George A.; Yu, Simon H.; Parker, David G. (1976-05-01). "Organometallic chemistry. XII. Proton and carbon-13 nuclear magnetic resonance study of arenemercurinium ions, the intermediate complexes of aromatic mercuration". The Journal of Organic Chemistry. 41 (11): 1983–1986. doi:10.1021/jo00873a020. ISSN 0022-3263.

[7] Fung, Chung W.; Khorramdel-Vahed, Mehdi; Ranson, Richard J.; Roberts, Roger M. G. (1980-01-01). "Kinetics and mechanism of mercuriation of aromatic compounds by mercury trifluoroacetate in trifluoroacetic acid". Journal of the Chemical Society, Perkin Transactions 2 (2): 267–272. doi:10.1039/P29800000267. ISSN 1364-5471.

[8] Gorelsky, Serge I.; Lapointe, David; Fagnou, Keith (2008-07-29). "Analysis of the Concerted Metalation-Deprotonation Mechanism in Palladium-Catalyzed Direct Arylation Across a Broad Range of Aromatic Substrates". Journal of the American Chemical Society. 130 (33): 10848–10849. doi:10.1021/ja802533u. ISSN 0002-7863. PMID 18661978.

[9] Gensch, T.; Hopkinson, M. N.; Glorius, F.; Wencel-Delord, J. (2016-05-17). "Mild metal-catalyzed C–H activation: examples and concepts". Chemical Society Reviews. 45 (10): 2900–2936. doi:10.1039/C6CS00075D. ISSN 1460-4744. PMID 27072661.

[10] He, Jian; Wasa, Masayuki; Chan, Kelvin S. L.; Shao, Qian; Yu, Jin-Quan (2016-12-02). "Palladium-Catalyzed Transformations of Alkyl C–H Bonds". Chemical Reviews. 117 (13): 8754–8786. doi:10.1021/acs.chemrev.6b00622. ISSN 0009-2665. PMC 5516964. PMID 28697604.

[:3-11] Hartwig, John F. (2016-01-13). "Evolution of C–H Bond Functionalization from Methane to Methodology". Journal of the American Chemical Society. 138 (1): 2–24. doi:10.1021/jacs.5b08707. ISSN 0002-7863. PMC 4809212. PMID 26566092.

Concerted metalation deprotonation information

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Concerted metalation deprotonation

CMD

Transition metal carboxylate complex

Aryne

Azomethine ylide

Transition metal indenyl complex

Leaving group

Ketenyl anion

Isocyanide

Cyclopentadienylcobalt dinitrosyl

Glutamine synthetase

Kinetic isotope effect

Proteasome

Catalytic triad

Aspartoacylase