Chiral amides via copper-catalysed enantioselective conjugate addition

Schoonen, Anne K.; Fernández-Ibáñez, M. Á́ngeles; Fañanás‐Mastral, Martín; Teichert, Johannes F.; Feringa, Bernard

doi:10.1039/c3ob41923a

Cited by 11 publications

(4 citation statements)

References 49 publications

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“…Among α,β-unsaturated carbonyl compounds, amides are significantly less reactive substrates because of their high LUMO energy . Therefore, examples of the asymmetric 1,4-addition of arylboronic acids to unsaturated amides are limited and they usually require high loadings of homogeneous Rh complex catalysts (>3 mol %) .…”

Section: Bifunctional Chiral Diene-modified Rhodium Nanoparticle Systemmentioning

confidence: 99%

Chiral Rhodium Nanoparticle-Catalyzed Asymmetric Arylation Reactions

2020

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Conspectus The development of heterogeneous catalyst systems for enantioselective reactions is an important subject in modern chemistry as they can be easily separated from products and potentially reused; this is particularly favorable in achieving a more sustainable society. Whereas numerous homogeneous chiral small molecule catalysts have been developed to date, there are only limited examples of heterogeneous ones that maintain high activity and have a long lifetime. On the other hand, metal nanoparticle catalysts have attracted much attention in organic chemistry due to their robustness and ease of deposition on solid supports. Given these advantages, metal nanoparticles modified with chiral ligands, defined as “chiral metal nanoparticles”, would work efficiently in asymmetric catalysis. Although asymmetric hydrogenation catalyzed by chiral metal nanoparticles was pioneered in the late twentieth century, the application of chiral metal nanoparticle catalysis for asymmetric C–C bond-forming reactions that give a high level of enantioselectivity with wide substrate scope was very limited. This Account summarizes recent investigations that we have carried out in the field of chiral rhodium (Rh) nanoparticle catalysis for asymmetric arylation reactions. We initially utilized composites of polystyrene-based copolymers with cross-linking moieties and carbon black incarcerated Rh nanoparticle catalysts for the asymmetric 1,4-addition of arylboronic acids to enones. We found that chiral diene-modified heterogeneous Rh nanoparticles were effective in these reactions, with excellent enantioselectivities and without causing metal leaching, and that bimetallic Rh/Ag nanoparticle catalysts enhanced activity. The catalyst could be easily recovered and reused more than ten times, thus demonstrating the robustness of metal nanoparticle catalysts. We then developed a secondary amide-substituted chiral diene modifier designed as a bifunctional ligand that possesses a metal biding site and a NH group to activate a substrate through hydrogen bonding. This chiral diene was very effective for the Rh/Ag nanoparticle-catalyzed asymmetric arylation of various electron-deficient olefins, including enones, unsaturated esters, unsaturated amides and nitroolefins, and imines to afford the corresponding products in excellent yields and with outstanding enantioselectivities. The system was also applicable for the synthesis of intermediates of various useful compounds. Furthermore, the compatibility of chiral Rh nanoparticles with other catalysts was confirmed, enabling the development of tandem reaction systems and cooperative catalyst systems. The nature of the active species was investigated. Several characteristic features of the heterogeneous nanoparticle systems that were completely different from those of the corresponding homogeneous metal complex systems were found.

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Section: Bifunctional Chiral Diene-modified Rhodium Nanoparticle Systemmentioning

confidence: 99%

Chiral Rhodium Nanoparticle-Catalyzed Asymmetric Arylation Reactions

2020

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“…This represents a formal catalytic asymmetric conjugate addition to amides, which is not yet directly achievable due to the lower reactivity of amide substrates. The same strategy was applied to linear α,β-unsaturated esters, and a wide range of chiral amides could be obtained [41]. Chromones [42], isomers of coumarins as well as structurally related pyranones [43] were also subjected to similar reaction conditions to obtain the 1,4-addition products in good yields and enantioselectivities.…”

Section: L11 Taniaphosmentioning

confidence: 99%

1,2- Versus 1,4-Asymmetric Addition of Grignard Reagents to Carbonyl Compounds

Ortiz

Lanza

Harutyunyan

2016

Progress in Enantioselective Cu(I)-Catalyzed Formation of Stereogenic Centers

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The first copper(I)-catalysed conjugate addition of Grignard reagents to α,β-unsaturated carbonyl compounds was reported in 1941. Impressive developments have been made since then, with catalytic asymmetric additions representing the most remarkable achievement. The recent discovery that copper(I) is able to catalyse the asymmetric 1,2-addition of Grignard reagents to α,β-unsaturated, as well as aromatic ketones, was a true revelation. Recent progress in copper(I)catalysed addition of Grignard reagents is reviewed throughout this chapter, comparing and contrasting the well-established 1,4-selectivity of Cu(I)-ligand complexes with the newly introduced 1,2-selectivity. Mechanistic insights towards the better understanding of the regiodivergence are also discussed.

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“… 5 − 7 Another nondirect method to β-substituted chiral amides is based on 1,4-addition to α,β-unsaturated esters, followed by quenching of the reaction mixture with the corresponding amines. 8 Intriguingly, the only reported direct addition to simple enamides makes use of Grignard reagents, but the limited scope of the resulting chiral β-alkyl substituted amides and the modest enantioselectivities led the authors to switch to a chiral auxiliary strategy. 9 …”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the only reported examples of catalytic ACA to simple enamides are confined to Rh-catalyzed arylations that do not suffer from noncatalyzed additions at high temperatures . The challenge faced in the development of efficient and stereoselective alkylations of simple enamides has led to the development of several alternative approaches, with the most common ones based on specific enamide substrates activated by placing an electron-withdrawing group at the N-atoms (Scheme c) to allow electronic activation and/or bidentate coordination with the chiral catalyst. − Another nondirect method to β-substituted chiral amides is based on 1,4-addition to α,β-unsaturated esters, followed by quenching of the reaction mixture with the corresponding amines . Intriguingly, the only reported direct addition to simple enamides makes use of Grignard reagents, but the limited scope of the resulting chiral β-alkyl substituted amides and the modest enantioselectivities led the authors to switch to a chiral auxiliary strategy …”

Section: Introductionmentioning

confidence: 99%

Lewis Acid Enabled Copper-Catalyzed Asymmetric Synthesis of Chiral β-Substituted Amides

et al. 2017

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Here we report that readily available silyl- and boron-based Lewis acids in combination with chiral copper catalysts are able to overcome the reactivity issues of unactivated enamides, known as the least reactive carboxylic acid derivatives, toward alkylation with organomagnesium reagents. Allowing unequaled chemo-reactivity and stereocontrol in catalytic asymmetric conjugate addition to enamides, the method is distinguished by its unprecedented reaction scope, allowing even the most challenging and synthetically important methylations to be accomplished with good yields and excellent enantioselectivities. This catalytic protocol tolerates a broad temperature range (−78 °C to ambient) and scale up (10 g), while the chiral catalyst can be reused without affecting overall efficiency. Mechanistic studies revealed the fate of the Lewis acid in each elementary step of the copper-catalyzed conjugate addition of Grignard reagents to enamides, allowing us to identify the most likely catalytic cycle of the reaction.

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Chiral amides via copper-catalysed enantioselective conjugate addition

Cited by 11 publications

References 49 publications

Chiral Rhodium Nanoparticle-Catalyzed Asymmetric Arylation Reactions

Chiral Rhodium Nanoparticle-Catalyzed Asymmetric Arylation Reactions

1,2- Versus 1,4-Asymmetric Addition of Grignard Reagents to Carbonyl Compounds

Lewis Acid Enabled Copper-Catalyzed Asymmetric Synthesis of Chiral β-Substituted Amides

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