Catalytic Carbonyl Addition through Transfer Hydrogenation: A Departure from Preformed Organometallic Reagents

Bower, John F.; Kim, In Su; Patman, Ryan L.; Krische, Michael J.

doi:10.1002/anie.200802938

Cited by 288 publications

(83 citation statements)

References 194 publications

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“…23-34 Additionally, related methods from Krische developing transfer hydrogenation methods are especially attractive in that the alcohol oxidation state may be directly employed as the source of the electrophilic partner. 25 The specific variant of aldehyde-alkyne reductive couplings that has been most extensively developed and studied in our laboratory involves silane reductants paired with phosphine or N -heterocyclic carbene (NHC) complexes of nickel(0), with NHC’s being the most effective in addressing challenging problems in regiocontrol. 26-28 A brief perspective on the phosphine-promoted intramolecular addition studies from our laboratory will first be described, since this process was the focus of our initial evaluation of kinetics in this reaction class.…”

Section: Mechanisms Of Nickel-catalyzed Aldehyde-alkyne Reductive Coumentioning

confidence: 99%

Mechanistic Basis for Regioselection and Regiodivergence in Nickel-Catalyzed Reductive Couplings

et al. 2015

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CONSPECTUS The control of regiochemistry is a considerable challenge in the development of a wide array of catalytic processes. Simple π-components such as alkenes, alkynes, 1,3-dienes, and allenes are among the many classes of substrates that present complexities in regioselective catalysis. Considering an internal alkyne as a representative example, when steric and electronic differences between the two substituents are minimal, differentiating among the two termini of the alkyne presents a great challenge. In cases where the differences between the alkyne substituents are substantial, overcoming those biases to access the regioisomer opposite that favored by substrate biases often presents an even greater challenge. Nickel-catalyzed reductive couplings of unsymmetrical π-components make up a group of reactions where control of regiochemistry presents a challenging but important objective. In the course of our studies of aldehyde-alkyne reductive couplings, complementary solutions to challenges in regiocontrol have been developed. Through careful selection of the ligand and reductant, as well as the more subtle reaction variables such as temperature and concentration, effective protocols have been established that allow highly selective access to either regiosiomer of the the allylic alcohol products using a wide range of unsymmetrical alkynes. Computational studies and an evaluation of reaction kinetics have provided an understanding of the origin of the regioselectivity control. Throughout the various procedures described, the development of ligand-substrate interactions play a key role, and the overall kinetic descriptions were found to differ between protocols. Rational alteration of the rate-determining step plays a key role in the regiochemistry reversal strategy, and in one instance, the two possible regioisomeric outcomes in a single reaction were found to operate by different kinetic descriptions. With this mechanistic information in hand, the empirical factors that influence regiochemistry can be readily understood, and more importantly, the insights suggest simple and predictable experimental variables to achieving a desired reaction outcome. These studies thus present a detailed picture of the influences that control regioselectivity in a specific catalytic reaction, but they also delineate strategies for regiocontrol that may extend to numerous classes of reactions. The work provides an illustration of how insights into the kinetics and mechanism of a catalytic process can rationalize subtle empirical findings and suggest simple and rational modifications in procedure to access a desirable reaction outcome. Furthermore, these studies present an illustration of how important challenges in organic synthesis can be met by novel reactivity afforded by base metal catalysis. The use of nickel catalysis in this instance not only provides an inexpensive and sustainable method for catalysis, but also enables unique reactivity patterns not accessible to other metals.

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Section: Mechanisms Of Nickel-catalyzed Aldehyde-alkyne Reductive Coumentioning

confidence: 99%

Mechanistic Basis for Regioselection and Regiodivergence in Nickel-Catalyzed Reductive Couplings

et al. 2015

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“…A recently developed complementary alternative to hydroamination for the catalytic synthesis of amines is the catalytic C-C bond-forming reaction, coined "hydroaminoalkylation", resulting from a C-H bond activation on an sp 3 -hybridized carbon center α to N [7]. This approach formally parallels C-C bond formation α to hydroxyl groups using group 8 and 9 catalysts (typically Ru, Ir based) making use of their activity in transfer hydrogenation [8].…”

Section: Introductionmentioning

confidence: 99%

Catalytic synthesis of amines and N-containing heterocycles: Amidate complexes for selective C–N and C–C bond-forming reactions

Eisenberger

Schafer

2010

Pure and Applied Chemistry

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“…In elegant work using Ru-, Rh- and Ir-based noble metal catalysts, Krische has pioneered the development of a range of synthetically versatile stereoselective coupling reactions of olefins and carbonyls under hydrogenation and transfer hydrogenation conditions (8–10). To date, however, the synthesis of sterically demanding tertiary alcohols from simple ketones remains challenging with these processes, in part due to the increased steric hindrance and the attenuated electrophilicity of ketones relative to aldehydes.…”

mentioning

confidence: 99%

Copper-catalyzed asymmetric addition of olefin-derived nucleophiles to ketones

Yang

Perry

Lü

et al. 2016

Science

247

134

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Enantioenriched alcohols found in an array of bioactive natural products and pharmaceutical agents are often synthesized by asymmetric nucleophilic addition to carbonyls. However, this approach generally shows limited functional group compatibility, requiring the use of preformed organometallic reagents in conjunction with a stoichiometric or sub-stoichiometric amount of chiral controller to deliver optically active alcohols. Herein we report a copper-catalyzed strategy for the stereoselective nucleophilic addition of propargylic and other alkyl groups to ketones using easily accessible (poly)unsaturated hydrocarbons as latent carbanion equivalents. Our method features the catalytic generation of highly enantioenriched organocopper intermediates and their subsequent diastereoselective addition to ketones, allowing for the effective construction of highly substituted stereochemical dyads with excellent stereocontrol. Moreover, this process is general, scalable, and occurs at ambient temperature.

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Catalytic Carbonyl Addition through Transfer Hydrogenation: A Departure from Preformed Organometallic Reagents

Cited by 288 publications

References 194 publications

Mechanistic Basis for Regioselection and Regiodivergence in Nickel-Catalyzed Reductive Couplings

Mechanistic Basis for Regioselection and Regiodivergence in Nickel-Catalyzed Reductive Couplings

Catalytic synthesis of amines and N-containing heterocycles: Amidate complexes for selective C–N and C–C bond-forming reactions

Copper-catalyzed asymmetric addition of olefin-derived nucleophiles to ketones

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