Enantioselective Synthesis of β-Aryl-γ-amino Acid Derivatives via Cu-Catalyzed Asymmetric 1,4-Reductions of γ-Phthalimido-Substituted α,β-Unsaturated Carboxylic Acid Esters

Deng, Jun; Hu, Xiang‐Ping; Huang, Jia‐Di; Yu, Sijie; Wang, Daoyong; Duan, Zheng-Chao; Zheng, Zhuo

doi:10.1021/jo800794p

Cited by 38 publications

(17 citation statements)

References 41 publications

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“…Zheng et al reacted ( Z )-3-phthalimido-3-arylbut-2-enoates with PMHS in the presence of Cu(OAc) 2 ·H 2 O, t -BuOH and ( S )-BINAP ( S )-L16 to produce the corresponding butanoate in good yield and with high ee (Scheme ). The protocol was applied to a synthesis of the muscle relaxant ( R )-baclofen 33 from 32 (Scheme ).…”

Section: Asymmetric Reduction Of αβ-Unsaturated Estersmentioning

confidence: 99%

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Organosilanes in Metal-Catalyzed, Enantioselective Reductions

Larson

Liberatore

2021

Org. Process Res. Dev.

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The growth and development of an extensive range of metals complexed with chiral ligands for the purpose of catalyzing a variety of reactions in an enantioselective manner has been impressive for its scope, chemical yields and high ee values. Chief among the classes of synthetic transformations has been that of the asymmetric reduction of prochiral substrates. These include the asymmetric reduction of prochiral ketones, imines, unsaturated aldehydes, ketones, esters, nitriles and olefins, as well as a number of asymmetric coupling reactions. In concert with these efficient catalyst systems, organosilanes have the ability to carry out any number of organic reductions under a variety of conditions. In these reactions, which in reality are hydrosilylations (hydrosilylation and reduction are considered interchangeable herein) in which the initially resulting silylated product is hydrolyzed to the ultimate desired functionality, the ability to sterically and electronically alter the organosilane reductant can contribute to the overall success of the transformation. In this review, we present a thorough compilation of the literature covering the use of organosilanes in metal-catalyzed asymmetric reductions (hydrosilylations) and coupling reactions.

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Section: Asymmetric Reduction Of αβ-Unsaturated Estersmentioning

confidence: 99%

“…The reaction performed considerably better when using MeOH as the promoter rather than the usual t-BuOH. The 115 The protocol was applied to a synthesis of the muscle relaxant (R)-baclofen 33 from 32 (Scheme 116).…”

Section: Asymmetric Reduction Of αβ-Unsaturatedmentioning

confidence: 99%

Organosilanes in Metal-Catalyzed, Enantioselective Reductions

Larson

Liberatore

2021

Org. Process Res. Dev.

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“…Moreover, numerous asymmetric synthetic routes to 15 have been reported in the literature including asymmetric aldol additions, 42 Michael additions, 43−47 nucleophilic substitution, 48−50 conjugate addition, 51−55 and reductions. [56][57][58][59]27 Here we will highlight a simple, enantioselective route to 15 (Scheme 4). Corey and Zhang employed a key enantioselective Michael addition of nitromethane to an α,β-unsaturated enone 18 with a chiral quaternary ammonium salt catalyst 19 to deliver adduct 20 in 89% yield and 80% ee.…”

Section: ■ Chemical Properties and Synthesismentioning

confidence: 99%

Classics in Chemical Neuroscience: Baclofen

Kent

Park

Lindsley

2020

ACS Chem. Neurosci.

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Baclofen, β-(4-chlorophenyl)-γ-aminobutyric acid, holds a unique position in neuroscience, remaining the only U.S. Food and Drug Administration (FDA) approved GABAB agonist. While intended to be a more brain penetrant, i.e, ability to cross the blood-brain barrier (BBB), version of GABA (γ-aminobutyric acid) for the potential treatment of epilepsy, baclofen’s highly efficacious muscle relaxant properties led to its approval, as a racemate, for the treatment of spasticity. Interestingly, baclofen received FDA approval before its receptor, GABAB, was discovered and its exact mechanism of action was known. In recent times, baclofen has a myriad of off-label uses, with the treatment for alcohol abuse and drug addiction garnering a great deal of attention. This Review aims to capture the >60 year legacy of baclofen by walking through the history, pharmacology, synthesis, drug metabolism, routes of administration, and societal impact of this Classic in chemical neuroscience.

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“…In 2008, Zheng and co-workers reported the asymmetric hydrogenation of 65 using Cu(OAc) 2 •H 2 O as the catalyst and (R)-or (S)-BINAP as the ligand (Scheme 23), 43 together with PMHS as the hydride source and t-BuOH as an additive. Using this methodology the desired chiral compound 66 was obtained in 92% yield with 94% ee (98% ee after recrystallization).…”

Section: Short Review Syn Thesismentioning

confidence: 99%

Asymmetric Synthetic Strategies of (R)-(–)-Baclofen: An Antispastic Drug

2017

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Baclofen is an antispastic drug used as a muscle relaxant in the treatment of the paroxysmal pain of trigeminal neuralgia, spasticity of the spinal cord and cerebral origin. Baclofen resides biological activity exclusively in its (R)-(–)-enantiomer. In this review, various asymmetric synthetic strategies for (R)-(–)-baclofen are described.1 Introduction2 Resolution Synthetic Approaches2.1 Chemical Resolution2.2 Biocatalytic Resolution3 Asymmetric Desymmetrization3.1 Catalytic Enantioselective Desymmetrization3.2 Enzymatic Desymmetrization4 Chiral Auxiliary Induced Asymmetric Synthesis4.1 Asymmetric Michael Addition4.2 Asymmetric Aldol Addition4.3 Asymmetric Nucleophilic Substitution5 Asymmetric Reduction5.1 Catalytic Asymmetric Hydrogenation5.2 Bioreduction6 Catalytic Asymmetric Conjugate Addition7 Conclusion

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Enantioselective Synthesis of β-Aryl-γ-amino Acid Derivatives via Cu-Catalyzed Asymmetric 1,4-Reductions of γ-Phthalimido-Substituted α,β-Unsaturated Carboxylic Acid Esters

Cited by 38 publications

References 41 publications

Organosilanes in Metal-Catalyzed, Enantioselective Reductions

Organosilanes in Metal-Catalyzed, Enantioselective Reductions

Classics in Chemical Neuroscience: Baclofen

Asymmetric Synthetic Strategies of (R)-(–)-Baclofen: An Antispastic Drug

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