Synthesis of Chiral α‐Benzyl‐β2‐hydroxy Carboxylic Acids through Iridium‐Catalyzed Asymmetric Hydrogenation of α‐Oxymethylcinnamic Acids

Li, Zeyu; Song, Song; Zhu, Shou‐Fei; Guo, Na; Wang, Lixin; Zhou, Qi‐Lin

doi:10.1002/cjoc.201400361

Cited by 16 publications

(4 citation statements)

References 30 publications

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“…A comparison of the optical rotations between the synthetic and natural samples also established the absolute configurations for three (i.e., 1 , 2 , and 4 ) of the four natural homoisoflavonoids. Apart from significant additions to the limited literature precedents12k–12m of enantioselective syntheses of these natural products, the present results may serve to define the relationship between the absolute configuration and the sign of the optical rotation when assigning the absolute configurations of closely related homoisoflavonoids (e.g., close analogues of 1 and 2 , with different substituents on the aromatic rings). Any confusion caused by errors in reports of previous NMR spectroscopic data and solvents has also been clarified.…”

Section: Discussionmentioning

confidence: 91%

Enantioselective Synthesis of Four Natural Homoisoflavonoids

Zhu

et al. 2015

Eur J Org Chem

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Four naturally occurring sappanin‐type homoisoflavonoids were synthesized in optically active form with the stereogenic centers of predefined absolute configuration constructed by using Evans' asymmetric aldol reaction. Analysis of the synthesized compounds not only confirmed the previously assigned planar structures but also was used to determine the absolute configurations of the natural products. Errors in previously reported NMR signals/solvents are also revealed.

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Section: Discussionmentioning

confidence: 91%

Enantioselective Synthesis of Four Natural Homoisoflavonoids

Zhu

et al. 2015

Eur J Org Chem

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“…Two years later, Zhou's group employed the same catalyst ( CAT4 ) in the AH of α-methylaryloxy-cinnamic acids 17 (Scheme 7). 64 Under 6 atm of hydrogen pressure, using Et 3 N as a basic additive in MeOH at 45 °C, eight substrates were hydrogenated with excellent yields (>98% for all) and enantioselectivities (98 to >99% ee). To demonstrate the applicability of this methodology, the authors reported the enantioselective synthesis of a natural ( S )-homoisoflavanone 19 based on the chiral carboxylic acid ( S )- 18e (Scheme 8).…”

Section: Asymmetric Hydrogenation (Ah)mentioning

confidence: 99%

Asymmetric hydrogenation and transfer hydrogenation in the enantioselective synthesis of flavonoids

et al. 2022

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“…However, previously reported catalysts for the asymmetric hydrogenation of α-oxymethylcinnamic acids show only low to moderate enantioselectivity or low yield. With catalyst ( S a )- 3f , high activity (TON up to 2000) and excellent enantioselectivity (96–99.5% ee) were achieved in the hydrogenation of α-oxymethylcinnamic acids . Using this efficient hydrogenation as a key step, we accomplished a concise, enantioselective total synthesis of the natural product homoisoflavone, which has significant antibacterial activity.…”

Section: Asymmetric Hydrogenation Of αβ-Unsaturated Carboxylic Acidsmentioning

confidence: 99%

Iridium-Catalyzed Asymmetric Hydrogenation of Unsaturated Carboxylic Acids

2017

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Chiral carboxylic acid moieties are widely found in pharmaceuticals, agrochemicals, flavors, fragrances, and health supplements. Although they can be synthesized straightforwardly by transition-metal-catalyzed enantioselective hydrogenation of unsaturated carboxylic acids, because the existing chiral catalysts have various disadvantages, the development of new chiral catalysts with high activity and enantioselectivity is an important, long-standing challenge. Ruthenium complexes with chiral diphosphine ligands and rhodium complexes with chiral monodentate or bidentate phosphorus ligands have been the predominant catalysts for asymmetric hydrogenation of unsaturated acids. However, the efficiency of these catalysts is highly substrate-dependent, and most of the reported catalysts require a high loading, high hydrogen pressure, or long reaction time for satisfactory results. Our recent studies have revealed that chiral iridium complexes with chiral spiro-phosphine-oxazoline ligands and chiral spiro-phosphine-benzylamine ligands exhibit excellent activity and enantioselectivity in the hydrogenation of α,β-unsaturated carboxylic acids, including α,β-disubstituted acrylic acids, trisubstituted acrylic acids, α-substituted acrylic acids, and heterocyclic α,β-unsaturated acids. On the basis of an understanding of the role of the carboxy group in iridium-catalyzed asymmetric hydrogenation reactions, we developed a carboxy-group-directed strategy for asymmetric hydrogenation of olefins. Using this strategy, we hydrogenated several challenging olefin substrates, such as β,γ-unsaturated carboxylic acids, 1,1-diarylethenes, 1,1-dialkylethenes, and 1-alkyl styrenes in high yield and with excellent enantioselectivity. All these iridium-catalyzed asymmetric hydrogenation reactions feature high turnover numbers (up to 10000) and turnover frequencies (up to 6000 h), excellent enantioselectivities (greater than 95% ee with few exceptions), low hydrogen pressure (<12 atm), and operational simplicity. These features make chiral iridium catalysts superior or comparable to well-established chiral ruthenium and rhodium catalysts for asymmetric hydrogenation of unsaturated carboxylic acids. A number of chiral natural products and pharmaceuticals have been prepared by concise routes involving an iridium-catalyzed asymmetric hydrogenation of an unsaturated carboxylic acid as a key step. As part of a mechanistic study of iridium-catalyzed asymmetric hydrogenation of unsaturated acids, we isolated, for the first time, the migratory insertion intermediate in the iridium-catalyzed asymmetric hydrogenation of olefins, and this result strongly supports the involvement of an Ir(III)/Ir(V) catalytic cycle. The rigid, bulky scaffold of the chiral spiro-P,N-ligands of the catalysts not only prevents them from undergoing deactivating aggregation under the hydrogenation conditions but also is responsible for the efficient chiral induction. The carboxy group of the substrate acts as an anchor to ensure coordination of the substrate to the iridium cent...

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Synthesis of Chiral α‐Benzyl‐β²‐hydroxy Carboxylic Acids through Iridium‐Catalyzed Asymmetric Hydrogenation of α‐Oxymethylcinnamic Acids

Cited by 16 publications

References 30 publications

Enantioselective Synthesis of Four Natural Homoisoflavonoids

Enantioselective Synthesis of Four Natural Homoisoflavonoids

Asymmetric hydrogenation and transfer hydrogenation in the enantioselective synthesis of flavonoids

Iridium-Catalyzed Asymmetric Hydrogenation of Unsaturated Carboxylic Acids

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