1078-58-6Relevant articles and documents
Elusive transmetalation intermediate in copper-catalyzed conjugate additions: Direct Nmr detection of an ethyl group attached to a binuclear phosphoramidite copper complex
Von Rekowski, Felicitas,Koch, Carina,Gschwind, Ruth M.
, p. 11389 - 11395 (2014)
Copper-catalyzed asymmetric conjugate addition reactions are a very powerful and widely applied method for enantioselective carbon-carbon bond formation. However, structural and mechanistic insight into these famous reactions has been very limited so far. In this article, the first direct experimental detection of transmetalation intermediates in copper-catalyzed reactions is presented. Special combinations of 1H,31P HMBC spectra allow for the identification of complexes with chemical bonds between the alkyl groups and the copper complexes. For the structural characterization of these transmetalation intermediates, a special approach is applied, in which samples using enantiopure ligands are compared with samples using enantiomeric mixtures of ligands. It is experimentally proven, for the first time, that the dimeric copper complex structure is retained upon transmetalation, providing an intermediate with mixed trigonal/tetrahedral coordination on the copper atoms. In addition, monomeric intermediates with one ligand, but no intermediates with two ligands, are detected. These experimental results, in combination with the well-known optimal ligand-to-copper ratio of 2:1 in synthetic applications, allow us to propose that a binuclear transmetalation intermediate is the reactive species in copper-catalyzed asymmetric conjugate addition reactions. This first direct experimental insight into the structure of the transmetalation intermediate is expected to support the mechanistic and theoretical understanding of this important class of reactions and to enable their further synthetic development. In addition, the special NMR approach presented here for the identification and characterization of intermediates below the detection limit of 1H NMR spectra can be applied also to other classes of catalyses.
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Gilman,Bailie
, p. 84,85,86 (1937)
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Nickel-catalyzed multicomponent coupling of alkyne, buta-1,3-diene, and dimethylzinc under carbon dioxide
Mori, Yasuyuki,Mori, Takamichi,Onodera, Gen,Kimura, Masanari
, p. 2287 - 2292 (2014)
A nickel catalyst promoted the coupling of alkynes with buta-1,3-diene and dimethylzinc under carbon dioxide to provide (5E,8Z)-2-vinyldeca-5,8-dienoic acids with high regio- and stereo selectivity. Georg Thieme Verlag Stuttgart. New York.
Remarkably Selective Formation of Allenyl and Dienyl Alcohols via Ni-Catalyzed Coupling Reaction of Conjugated Enyne, Aldehyde, and Organozinc Reagents
Mori, Yasuyuki,Kawabata, Toshiki,Onodera, Gen,Kimura, Masanari
, p. 2385 - 2395 (2016)
A nickel catalyst promotes the multi-component reactions (MCRs) of conjugated enynes, aldehydes, and organozinc reagents to form unsaturated alcohols. Ligand effects dramatically control the regioselectivity in these Ni-catalyzed MCRs, leading to the selective formation of allenyl alcohols and conjugated dienyl alcohols.
Organozinc-Mediated Direct C?C Bond Formation via C?N Bond Cleavage of Ammonium Salts
Wang, Dong-Yu,Morimoto, Koki,Yang, Ze-Kun,Wang, Chao,Uchiyama, Masanobu
, p. 2554 - 2557 (2017)
We report a direct cross-coupling reaction between diarylzinc (Ar2Zn) and aryltrimethylammonium salts (ArNMe3 +??OTf) in the presence of LiCl, via C?N bond cleavage. The reaction takes place smoothly upon heating in THF without any external catalyst, enabling an efficient and chemoselective formation of biaryl products. Mechanistic studies indicate that the reaction proceeds through a single electron transfer route.
Reactivity of mixed organozinc and mixed organocopper reagents: 5-A kinetic insight to compare the transfer ability of the same group in copper catalyzed alkylation of mixed and homozincates
Erdik, Ender,Serdar, Ebru Zeynep
, p. 1 - 8 (2012)
A detailed kinetic investigation and activation parameters are reported for copper catalyzed coupling reaction of mixed zincate, n-BuPh2ZnMgBr and homozincate, Ph3ZnMgBr with n-pentyl bromide in THF at 25-65 °C. An empirical rate law can be expressed as rate = k[zincate]0 [alkyl bromide]1 [CuI]1. The reaction rate of transferable phenyl group in mixed catalytic cuprate, n-BuPhCuMgBr derived from mixed zincate is higher than the rate of catalytic homocuprate Ph2CuMgBr derived from homozincate. A catalytic cycle and the mechanism which accommodates the kinetic data and activation parameters is given. These results show that the reaction rate of transferable group changes depending on the residual group in the reactions of mixed diorganocuprates and also provide a kinetic support for the commonly accepted hypothesis regarding the dependence of the R 1 group transfer ability on the strength of R2-Cu bond in reactions of R1R2CuMgBr reagents.
Exploring Electrochemical C(sp3)-H Oxidation for the Late-Stage Methylation of Complex Molecules
Ho, Justin S. K.,Lin, Song,Liu, Kaida,Mao, Kaining,Neurock, Matthew,Novaes, Luiz F. T.,Tanwar, Mayank,Terrett, Jack A.,Villemure, Elisia
supporting information, p. 1187 - 1197 (2022/02/05)
The magic methyl effect, a dramatic boost in the potency of biologically active compounds from the incorporation of a single methyl group, provides a simple yet powerful strategy employed by medicinal chemists in the drug discovery process. Despite significant advances, methodologies that enable the selective C(sp3)-H methylation of structurally complex medicinal agents remain very limited. In this work, we disclose a modular, efficient, and selective strategy for the α-methylation of protected amines (i.e., amides, carbamates, and sulfonamides) by means of electrochemical oxidation. Mechanistic analysis guided our development of an improved electrochemical protocol on the basis of the classic Shono oxidation reaction, which features broad reaction scope, high functional group compatibility, and operational simplicity. Importantly, this reaction system is amenable to the late-stage functionalization of complex targets containing basic nitrogen groups that are prevalent in medicinally active agents. When combined with organozinc-mediated C-C bond formation, our protocol enabled the direct methylation of a myriad of amine derivatives including those that have previously been explored for the magic methyl effect. This synthesis strategy thus circumvents multistep de novo synthesis that is currently necessary to access such compounds and has the potential to accelerate drug discovery efforts.
Atom-efficient transition-metal-free arylation ofN,O-acetals using diarylzinc reagents through Zn/Zn cooperativity
Borys, Andryj M.,Gil-Negrete, Jose M.,Hevia, Eva
supporting information, p. 8905 - 8908 (2021/09/10)
Exploiting the cooperative action of Lewis acid Zn(C6F5)2with diarylzinc reagents, the efficient arylation ofN,O-acetals to access diarylmethylamines is reported. Reactions take place under mild reaction conditions without the need for transtion-metal catalysis. Mechanistic investigations have revealed that Zn(C6F5)2not only acts as a Lewis acid activator, but also enables the regeneration of nucleophilic ZnAr2species, allowing a limiting 50 mol% to be employed.
Chiral Lithium Amido Aryl Zincates: Simple and Efficient Chemo- and Enantio-Selective Aryl Transfer Reagents
Chaumont-Olive, Pauline,Rouen, Mathieu,Barozzino-Consiglio, Gabriella,Ben Abdeladhim, Amel,Maddaluno, Jacques,Harrison-Marchand, Anne
supporting information, p. 3193 - 3197 (2019/01/25)
An enantioselective aryl transfer is promoted using chiral tricoordinated lithium amido aryl zincates that are easily accessible reagents and whose chiral appendage is simply recovered for reuse. The arylation reaction is run in good yields (60 % average on twenty substrates) and high enantiomeric excesses (95 % ee average). This occurs whatever the ortho, meta, or para substituent borne by the substrate and a complete chemoselectivity is observed with respect to the aldehyde function. Sensitive groups such as nitriles, esters, ketones, and enolisable substrates resist to the action of the ate reagent, warranting a large scope to this methodology.