Advances and Applications in Organocatalytic Asymmetric aza‐Michael Addition

Wang, Jun; Li, Pengfei; Choy, Pui Ying; Chan, Albert S. C.; Kwong, Fuk Yee

doi:10.1002/cctc.201200135

Cited by 157 publications

(27 citation statements)

References 65 publications

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“…The reaction was performed in CCl 4 at room temperature with 10 mol% of each catalyst and 4 Å molecular sieves. Although the electron-deficient arylboronic acid 4a gave no desired product 2a, affording only double-addition adduct 3a in moderate yield, mixtures of 2a and 3a were obtained with other catalyst combinations 4b/5 and c/5, giving only racemic 2a in low yields.…”

Section: Resultsmentioning

confidence: 99%

“…As expected, all integrated catalysts, except sulfonamide 6c, afforded the desired β-benzyloxyamino acid 2a as a single product; in addition, the nature of the hydrogen-bond-donor moiety was observed to substantially affect the yield. Among catalysts 6a-e, thiourea 6e bearing a 3,5-bis(trifluoromethyl) phenyl group gave the best results in terms of yield and enantioselectivity (entries [1][2][3][4][5]. Regarding the achiral N-substituent of the thiourea moiety, catalysts 6g and i bearing phenyl and 4-nitrophenyl groups, respectively, exhibited higher enanti- 15% (0% ee) 6% (c) 4c and 5:…”

Section: Resultsmentioning

confidence: 99%

“…The residue was purified by column chromatography on silica gel (n-hexane-ethyl acetate=10 : 1 to 4 : 1) to afford 9 as a colorless solid (402 mg, 89, 95% α,β-isomer; >99% E-isomer), which was further purified by recrystallization from ethyl acetate/n-hexane at 0°C. mp 36.5-36.8°C (ethyl acetate-n-hexane); 4 (0.25 mL) at room temperature. The reaction mixture was stirred at the room temperature for 24 h. The reaction mixture was directly purified by flash chromatography on silica gel (nhexane-ethyl acetate=4 : 1 to ethyl acetate-methanol=7 : 3) to afford crude adduct (37.9 mg) as a colorless oil.…”

Section: Methyl (S)-3-(n-(benzyloxy)-4-methylbenzamido)octanoate (2e-mentioning

confidence: 99%

“…The catalytic asymmetric aza-Michael addition of α,β-unsaturated carboxylic acid derivatives has been extensively investigated as a powerful protocol for the synthesis of optically active β-amino acids, [1][2][3][4] which are frequently encountered as important structural components in biologically active natural products and pharmaceuticals. 5) However, simple α,β-unsaturated esters and amides have only been used in a limited number of successful studies because of their inherent low reactivity as Michael acceptors.…”

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confidence: 99%

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Chiral Integrated Catalysts Composed of Bifunctional Thiourea and Arylboronic Acid: Asymmetric Aza-Michael Addition of α,β-Unsaturated Carboxylic Acids

et al. 2016

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The first intermolecular asymmetric Michael addition of nitrogen-nucleophiles to α,β-unsaturated carboxylic acids was achieved through a new type of arylboronic acid equipped with chiral aminothiourea. The use of BnONH 2 as a nucleophile gives a range of enantioenriched β-(benzyloxy)amino acid derivatives in good yields and with high enantioselectivity (up to 90% yield, 97% enantiomeric excess (ee)). The obtained products are efficiently converted to optically active β-amino acid and 1,2-diamine derivatives.Key words aza-Michael addition; α,β-unsaturated carboxylic acid; integrated catalyst; thiourea; arylboronic acid; O-benzylhydroxylamine Stereoselective functionalization of electron-deficient alkenes continues to play a fundamental role in modern organic synthesis. The catalytic asymmetric aza-Michael addition of α,β-unsaturated carboxylic acid derivatives has been extensively investigated as a powerful protocol for the synthesis of optically active β-amino acids, [1][2][3][4] which are frequently encountered as important structural components in biologically active natural products and pharmaceuticals. 5) However, simple α,β-unsaturated esters and amides have only been used in a limited number of successful studies because of their inherent low reactivity as Michael acceptors.6,7) Instead, a variety of activated ester/amide surrogates possessing greater reactivity and rigidity, which enables them to interact with appropriate catalysts, have been developed for the Michael addition.8) Recently, a range of activated carboxylates-specifically, α,β-unsaturated imides, 9,10) acyl pyrroles, 11) and acyl pyrazoles 12) -have been successfully applied in asymmetric metal-and organocatalyzed Michael additions to furnish the desired products with excellent enantioselectivity (Chart 1). However, this masked ester/amide strategy requires a stoichiometric amount of an activating auxiliary and additional protection and deprotection steps. From the perspective of atom and step economy, achieving a direct Michael reaction of α,β-unsaturated carboxylic acids without the use of any activating templates is highly desirable. Despite strong synthetic utility, the direct Michael addition of α,β-unsaturated carboxylic acids has never been reported, except for an enzyme-catalyzed azaMichael addition 13,14) ; very few strategies have been exploited to catalytically activate the hydroxy group of carboxylic acids via transient covalent bond formation.By contrast, since the discovery by Yamamoto and Ishihara that electron-deficient arylboronic acids are efficient activators of carboxylic acids in direct amidation reactions, [15][16][17][18] 24,25) Hall reported that different types of arylboronic acids could be used for the cycloaddition of α,β-unsaturated carboxylic acids to dienes and 1,3-dipoles. 20,21) Recently, we also revealed that aminoarylboronic acid was the best catalyst for the intramolecular hetero-Michael addition of α,β-unsaturated carboxylic acids bearing sulfonamides or phenols.26) In addition, the asymmetric oxa-Michael ...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methyl (S)-3-(n-(benzyloxy)-4-methylbenzamido)octanoate (2e-mentioning

confidence: 99%

mentioning

confidence: 99%

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Chiral Integrated Catalysts Composed of Bifunctional Thiourea and Arylboronic Acid: Asymmetric Aza-Michael Addition of α,β-Unsaturated Carboxylic Acids

et al. 2016

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“…In particular, the development of organocatalytic asymmetric Michael reactions of carbonyl compounds with nitroalkenes has garnered great interest in recent years. [30][31][32][33][34] However, asymmetric Michael reactions using monoester or acid directly as prenucleophiles have never been reported. The use of pyrazole amides as special Michael donors to react with nitroolefins, reported by Barbas III and co-workers, and the use of quinine derived urea catalysts gave the desired product with high dr and ee value.…”

Section: Introductionmentioning

confidence: 99%

Organocatalytic asymmetric Michael reaction with acylsilane donors

et al. 2013

Org. Biomol. Chem.

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We have developed an organocatalytic asymmetric Michael reaction of acylsilane through the selection of acylsilane substrates and organocatalysts, thus creating a rare example of acylsilane α-alkylation with a chiral guanidine catalyst, which afforded products in good yields and high stereoselectivity. The corresponding adducts described here have also been demonstrated to be useful in the synthesis of unnatural amino acids and biologically active compounds.

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aza‐Michael reaction

Scherg¹

2020

Catalysis From a to Z

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Advances and Applications in Organocatalytic Asymmetric aza‐Michael Addition

Abstract: Scheme 25. Domino reaction between hydrazines 101 to chalcones 102 catalyzed by phase-transfer catalyst 103. Scheme 26. Aza-Michael addition of 107 to nitroalkenes 108 catalyzed by phase-transfer catalyst 106. 924 www.chemcatchem.org

Cited by 157 publications

References 65 publications

Chiral Integrated Catalysts Composed of Bifunctional Thiourea and Arylboronic Acid: Asymmetric Aza-Michael Addition of α,β-Unsaturated Carboxylic Acids

Chiral Integrated Catalysts Composed of Bifunctional Thiourea and Arylboronic Acid: Asymmetric Aza-Michael Addition of α,β-Unsaturated Carboxylic Acids

Organocatalytic asymmetric Michael reaction with acylsilane donors

aza‐Michael reaction

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