Regioselective, Asymmetric Formal Hydroamination of Unactivated Internal Alkenes

Xi, Yumeng; Butcher, Trevor W.; Zhang, Jing; Hartwig, John F.

doi:10.1002/anie.201509235

Cited by 129 publications

(78 citation statements)

References 52 publications

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“…36 This process allows for the efficient assembly of a variety of chiral amines from readily available olefin precursors with excellent enantioselectivity. As illustrated in Figure 1b, this catalytic hydroamination begins with the addition of the CuH species ( I ) across the double bond of the olefin ( II ), giving rise to an enantioen-riched alkylcopper intermediate ( III ).…”

Section: Introductionmentioning

confidence: 99%

Ligand–Substrate Dispersion Facilitates the Copper-Catalyzed Hydroamination of Unactivated Olefins

et al. 2017

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Current understanding of ligand effects in transition metal catalysis is mostly based on the analysis of catalyst-substrate through-bond and through-space interactions, with the latter commonly considered to be repulsive in nature. The dispersion interaction between the ligand and the substrate, a ubiquitous type of attractive non-covalent interaction, is seldom accounted for in the context of transition metal-catalyzed transformations. Herein we report a computational model to quantitatively analyze the effects of different types of catalyst-substrate interactions on reactivity. Using this model, we show that in the copper(I) hydride (CuH)-catalyzed hydroamination of unactivated olefins, the substantially enhanced reactivity of copper catalysts based on bulky bidentate phosphine ligands originates from the attractive ligand-substrate dispersion interaction. These computational findings are validated by kinetic studies across a range of hydroamination reactions using structurally diverse phosphine ligands, revealing the critical role of bulky P-aryl groups in facilitating this process.

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Section: Introductionmentioning

confidence: 99%

Ligand–Substrate Dispersion Facilitates the Copper-Catalyzed Hydroamination of Unactivated Olefins

et al. 2017

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“…By employing a class of electrophilic aminating reagents established by Johnson (17) to intercept these organometallic intermediates, our laboratory (18) and Miura and Hirano (19–21) have independently developed a CuH-catalyzed approach for the enantioselective hydroamination of olefins (22). Based on these studies and notable contributions from other groups in the area of copper-catalyzed enantioselective reductive aldol reactions (6,7, 23–26), we envisioned the development of CuH chemistry as a general platform for the use of simple olefins as latent carbon nucleophiles in carbonyl addition (Fig.…”

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confidence: 99%

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

Yang

Perry

Lü

et al. 2016

Science

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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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“…Useful regioisomeric control can also be imparted, either using steric effects of the substrate, or using a directing group that electronically biases the π-bond. 10 …”

Section: Discussionmentioning

confidence: 99%