Recent development of direct asymmetric functionalization of inert C–H bonds

Zheng, Chao; You, Shu‐Li

doi:10.1039/c3ra46996d

Cited by 550 publications

(148 citation statements)

References 529 publications

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“…[4e, 5,6] The functionalization of unactivated methylene CÀH bonds through metal insertion is very rare. These are, however, arguably the most interesting cases because in RÀ CH 2 ÀR' systems the hydrogen atoms are enantiotopic.…”

Section: Introductionmentioning

confidence: 99%

Palladium–N‐Heterocyclic Carbene (NHC)‐Catalyzed Asymmetric Synthesis of Indolines through Regiodivergent C(sp³)H Activation: Scope and DFT Study

Katayev

Larionov

Nakanishi

et al. 2014

Chemistry A European J

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Two bulky, chiral, monodentate N‐heterocyclic carbene ligands were applied to palladium‐catalyzed asymmetric CH arylation to incorporate C(sp3)H bond activation. Racemic mixtures of the carbamate starting materials underwent regiodivergent reactions to afford different trans‐2,3‐substituted indolines. Although this CArCalkyl coupling requires high temperatures (140–160 °C), chiral induction is high. This regiodivergent reaction, when carried out with enantiopure starting materials, can lead to single structurally different enantiopure products, depending on the catalyst chirality. The CH activation at a tertiary center was realized only in the case of a cyclopropyl group. No CH activation takes place alpha to a tertiary center. A detailed DFT study is included and analyses of methyl versus methylene versus methine CH activation is used to rationalize experimentally observed regio‐ and enantioselectivities.

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Section: Introductionmentioning

confidence: 99%

Palladium–N‐Heterocyclic Carbene (NHC)‐Catalyzed Asymmetric Synthesis of Indolines through Regiodivergent C(sp³)H Activation: Scope and DFT Study

Katayev

Larionov

Nakanishi

et al. 2014

Chemistry A European J

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“…Enantioenriched dihydroisoquinolones could hence be accessed from very simple starting materials. Subsequently, the chiral [CpRh]-derived complexes were applied in several others asymmetric C-H activation reactions [155][156][157].…”

Section: New Trends and Perspectivesmentioning

confidence: 99%

Rh(III)- and Ir(III)-Catalyzed C–C Bond Cross Couplings from C–H Bonds

Wencel‐Delord

Patureau

Glorius

2015

Topics in Organometallic Chemistry

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(M¼Ir, Rh) is formed and undergoes further transformations, according to the nature of the coupling partner, to finally afford a myriad of valuable, often complex, and otherwise difficult to access scaffolds like heterocycles and polyunsaturated skeletons. The major advances achieved in this field clearly showcase the potential of these catalysts to functionalize latent C-H bonds under surprisingly mild reaction conditions. The aim of this chapter is to present the latest and most representative contributions in the field of Rh(III)-and Ir(III)-catalyzed C-H activation by focusing on the reactivity of the corresponding metallacyclic intermediates.

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“…[1] Within this context, by taking advantage of a broad selection of transition-metal catalysts, both non-asymmetric and asymmetric functionalizations of C(sp 3 ) À H bonds have been extensively studied over the past several decades.…”

Section: Carbene-induced C à H Functionalization By Transition-mentioning

confidence: 99%

Catalytic Asymmetric Functionalization of Aromatic CH Bonds by Electrophilic Trapping of Metal‐Carbene‐Induced Zwitterionic Intermediates

et al. 2014

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Asymmetric functionalization of aromatic C À H bonds of N,N-disubstituted anilines with diazo compounds and imines is reported for the efficient construction of a,a-diaryl benzylic quaternary stereocenters in good yields with high diastereoselectivities and excellent enantioselectivities. This Rh II /chiral phosphoric acid cocatalyzed transformation is proposed to proceed through a metal-carbene-induced zwitterionic intermediate which undergoes electrophilic trapping. To the best of our knowledge, this is the first asymmetric example of metal carbene-induced intermolecular functionalization of aryl CÀH bonds.Carbene-induced C À H functionalization by transitionmetal-catalyzed decomposition of diazo compounds is among the most efficient and reliable synthetic tools for the construction of CÀC bonds.[1] Within this context, by taking advantage of a broad selection of transition-metal catalysts, both non-asymmetric and asymmetric functionalizations of C(sp 3 ) À H bonds have been extensively studied over the past several decades.[1b-e] However, while non-asymmetric functionalization of aromatic C(sp 2 )ÀH bonds have also been developed to some extent, [2][3][4][5] the asymmetric version of metal-carbene-induced functionalization of aromatic C(sp 2 )À H bonds remains unexplored except for intramolecular examples [6] or those starting from heteroarenes. [7] Unlike the carbene-induced C(sp 3 ) À H functionalization in which efficient asymmetric control could be achieved by chiral transition-metal catalysts via a concerted nonsynchronous transition state, [1b,d, 8] the functionalization of aromatic CÀH bonds is generally considered to proceed through the formation of a zwitterionic intermediate from electrophilic addition of a metal carbene to the aromatic ring and a subsequent rapid proton transfer (Scheme 1, path a). [1b] This stepwise mechanism makes it very challenging to achieve efficient enantioselective control by means of chiral transition-metal catalysts, [9] probably owing to the difficulty in controlling enantioselectivity during the asymmetric protonation step.[10] As part of our continuous research efforts in exploring new transformations based on asymmetric electrophilic trapping of active intermediates generated from metal carbenes, [11,12] we became interested in developing catalytic asymmetric functionalization of aromatic C À H bonds with a similar strategy. We envisioned that the proposed metalcarbene-induced zwitterionic intermediate could be intercepted by electrophiles such as active imines prior to 1,2-proton transfer to give formal CÀH insertion products (Scheme 1, path b). With such a strategy, asymmetric control could be realized during the trapping process by introducing chiral cocatalyst such as chiral phosphoric acid (PPA; Scheme 1, path b).[13] Herein, we report the successful development of a catalytic asymmetric functionalization of aromatic CÀH bonds from a novel three-component reaction of arenes, diazo compounds, and imines in the presence of a rhodium(II)/chiral PPA cat...

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Recent development of direct asymmetric functionalization of inert C–H bonds

Cited by 550 publications

References 529 publications

Palladium–N‐Heterocyclic Carbene (NHC)‐Catalyzed Asymmetric Synthesis of Indolines through Regiodivergent C(sp³)H Activation: Scope and DFT Study

Palladium–N‐Heterocyclic Carbene (NHC)‐Catalyzed Asymmetric Synthesis of Indolines through Regiodivergent C(sp³)H Activation: Scope and DFT Study

Rh(III)- and Ir(III)-Catalyzed C–C Bond Cross Couplings from C–H Bonds

Catalytic Asymmetric Functionalization of Aromatic CH Bonds by Electrophilic Trapping of Metal‐Carbene‐Induced Zwitterionic Intermediates

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Recent development of direct asymmetric functionalization of inert C–H bonds

Cited by 550 publications

References 529 publications

Palladium–N‐Heterocyclic Carbene (NHC)‐Catalyzed Asymmetric Synthesis of Indolines through Regiodivergent C(sp3)H Activation: Scope and DFT Study

Palladium–N‐Heterocyclic Carbene (NHC)‐Catalyzed Asymmetric Synthesis of Indolines through Regiodivergent C(sp3)H Activation: Scope and DFT Study

Rh(III)- and Ir(III)-Catalyzed C–C Bond Cross Couplings from C–H Bonds

Catalytic Asymmetric Functionalization of Aromatic CH Bonds by Electrophilic Trapping of Metal‐Carbene‐Induced Zwitterionic Intermediates

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Palladium–N‐Heterocyclic Carbene (NHC)‐Catalyzed Asymmetric Synthesis of Indolines through Regiodivergent C(sp³)H Activation: Scope and DFT Study

Palladium–N‐Heterocyclic Carbene (NHC)‐Catalyzed Asymmetric Synthesis of Indolines through Regiodivergent C(sp³)H Activation: Scope and DFT Study