Ketone Synthesis by a Nickel-Catalyzed Dehydrogenative Cross-Coupling of Primary Alcohols

Verheyen, T. Vincent; Turnhout, Lars van; Vandavasi, Jaya Kishore; Isbrandt, Eric S.; Borggraeve, Wim M. De; Newman, Stephen G.

doi:10.1021/jacs.9b03280

Cited by 61 publications

(38 citation statements)

References 72 publications

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“…A deuterium-labeled isopropyl bromide (6b-D 6 ) was examined under the standard conditions, the deborylation product (8b) was isolated in 47% yield with 31% Dincorporation ( Fig. 4f) 56,57 . These results suggest that the hydrogen atom of the deborylation product is partly from the alkyl electrophile, which agrees with the proposed catalytic cycle (Fig.…”

Section: Articlementioning

confidence: 99%

Reaction scope and mechanistic insights of nickel-catalyzed migratory Suzuki–Miyaura cross-coupling

et al. 2020

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Cross-coupling reactions have developed into powerful approaches for carbon-carbon bond formation. In this work, a Ni-catalyzed migratory Suzuki-Miyaura cross-coupling featuring high benzylic or allylic selectivity has been developed. With this method, unactivated alkyl electrophiles and aryl or vinyl boronic acids can be efficiently transferred to diarylalkane or allylbenzene derivatives under mild conditions. Importantly, unactivated alkyl chlorides can also be successfully used as the coupling partners. To demonstrate the applicability of this method, we showcase that this strategy can serve as a platform for the synthesis of terminal, partially deuterium-labeled molecules from readily accessible starting materials. Experimental studies suggest that migratory cross-coupling products are generated from Ni(0/II) catalytic cycle. Theoretical calculations indicate that the chain-walking occurs at a neutral nickel complex rather than a cationic one. In addition, the original-site cross-coupling products can be obtained by alternating the ligand, wherein the formation of the products has been rationalized by a radical chain process. 1 1234567890():,; Reductive conditions Redox-neutral conditions Redox-neutral conditions Alkyl reagents Metal migration a Migratory cross-coupling of alkyl electrophiles Ni-catalyzed reductive migratory cross-coupling (Zhu and our group): Pd-catalyzed migratory suzuki-miyaura cross-coupling (Sigman): Ni-catalyzed migratory suzuki-miyaura cross-coupling (this work): b c d Fig. 1 Transition metal-catalyzed migratory cross-coupling. a Migratory cross-coupling of alkyl electrophiles. b Ni-catalyzed reductive migratory crosscoupling. c Pd-catalyzed migratory Suzuki-Miyaura cross-coupling. d The approach developed in this study. ARTICLE NATURE COMMUNICATIONS | https://doi.

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Section: Articlementioning

confidence: 99%

Reaction scope and mechanistic insights of nickel-catalyzed migratory Suzuki–Miyaura cross-coupling

et al. 2020

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“…57 Moreover, unlike tertiary alcohols, secondary alcohols would readily undergo dehydrogenation and further derivatization in the presence of Ni/NHC catalysts. 42,[58][59][60][61][62][63] Furthermore, Nicatalyzed Suzuki-Miyaura couplings of various electrophiles are well-developed, 64 posing further challenges for control of chemoselectivity. Finally, it would be nontrivial to control enantioselectivity for an intermolecular arylation of aldehyde in a η 2 -activation manner.…”

Section: Introductionmentioning

confidence: 99%

Chemo- and Enantioselective Arylation and Alkenylation of Aldehydes Enabled by Nickel/ N -Heterocyclic Carbene Catalysis

et al. 2022

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We herein report the first highly enantioselective Ni-catalyzed arylation and alkenylation of simple aldehydes using readily available and stable organoboronic esters. This protocol provides various chiral secondary alcohols in high yields and enantioselectivities (up to 97% ee) with a broad scope of substrates, functional groups, and heterocycles. The use of a bulky N-heterocyclic carbene (NHC) ligand for nickel catalyst is the key for high enantiocontrol. The competitive Ni-catalyzed transformations, including Tishchenko reaction, dehydrogenation/hydrogenation reaction, Suzuki-Miyaura couplings, are avoided. The excellent chemoselectivity is probably due to the application of mild base CsF and η 2 -coordination of aldehydes with nickel.

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“…Catalytic reactions are sensitive to a wide range of experimental conditions, even in homogeneous systems. [1][2][3][4][5][6][7][8][9] These conditions include variables, such as concentration of reactants and catalyst, [10] stirring rate, [11] reaction time and temperature, [12] which contribute to the outcome of a catalytic system after optimization. This study focuses on the influence of stirring in a small-scale crosscoupling reaction.…”

Section: Introductionmentioning

confidence: 99%

Standardized Stirring for Small Scale Surveys

Omari¹,

Paul²,

McIndoe³

2021

Preprint

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Stirring rates in heterogeneous catalytic reactions have an effect on reaction rates. When conducting small-scale surveys using a single central stir plate, reaction vessels in different positions experience slightly different levels and patterns of agitation. We probed this effect by running the same reaction 40 times, varying the stir rate (fast/slow) and the vial position using two 3D printed vial holders. We found variability of conversion (measured mass spectrometrically) to be approximately two times higher for vials placed at different distances, but the effect was relatively small and could be minimized by using a high stir rate. For those experimenters wishing to completely eliminate differential stirring as a cause for variation in results, the 3D printed circular array we designed is recommended over a conventional rectangular array.

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Ketone Synthesis by a Nickel-Catalyzed Dehydrogenative Cross-Coupling of Primary Alcohols

Cited by 61 publications

References 72 publications

Reaction scope and mechanistic insights of nickel-catalyzed migratory Suzuki–Miyaura cross-coupling

Reaction scope and mechanistic insights of nickel-catalyzed migratory Suzuki–Miyaura cross-coupling

Chemo- and Enantioselective Arylation and Alkenylation of Aldehydes Enabled by Nickel/ N -Heterocyclic Carbene Catalysis

Standardized Stirring for Small Scale Surveys

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