Asymmetric α‐Allylation of Glycinate with Switched Chemoselectivity Enabled by Customized Bifunctional Pyridoxal Catalysts

Ma, Jiguo; Gao, Bin; Song, Guanshui; Zhang, Ruixin; Wang, Qingfang; Ye, Zi; Chen, Wenwen; Zhao, Baoguo

doi:10.1002/anie.202200850

Cited by 37 publications

(34 citation statements)

References 128 publications

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“…Inspired by biological processes, carbonyl catalysis [7] utilizes an appropriate aldehyde or ketone to catalyze direct asymmetric α‐C−H functionalization of primary amines without pre‐protection of the NH 2 groups [8] . The strategy has been succesfully applied to asymmetric biomimetic Mannich reaction, [7] aldol reaction, [9a] α‐C Michael addition [9b, 10b] and α‐C allylation [9c, 10c] of glycinates, to afford various chiral amino acid derivatives in good yields with excellent stereoselectivities. Nevertheless, the scope of carbonyl catalysis has been mainly limited to strongly‐activated primary amines, such as α‐amino acid esters [7, 9, 10a–c, 11] (p K a ≈24) and (2‐pyridyl)methylamines [10d,e] .…”

Section: Methodsmentioning

confidence: 99%

Direct Asymmetric α‐C−H Addition of N‐unprotected Propargylic Amines to Trifluoromethyl Ketones by Carbonyl Catalysis

Liu

et al. 2022

Angewandte Chemie

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Direct asymmetric functionalization of the inert α C−H bonds of N‐unprotected propargylic amines is a big challenge in organic chemistry, due to the low acidity (pKa≈42.6) of the α C−H bonds and interruption of the nucleophilic NH2 group. By using a chiral pyridoxal as carbonyl catalyst, we have successfully realized direct asymmetric α‐C−H addition of N‐unprotected propargylic amines to trifluoromethyl ketones, producing a broad range of chiral alkynyl β‐aminoalcohols in 54–84 % yields with excellent stereoselectivities (up to 20 : 1 dr and 99 % ee). The α C−H bonds of propargylic amines are greatly activated by the pyridoxal catalyst via the formation of an imine intermediate, resulting in the increase of acidity by up to 1022 times (from pKa 42.6 to pKa 20.1), which become acidic enough to be deprotonated under mild conditions for the asymmetric addition. This work presented an impressive example for asymmetric functionalization of inert C−H bonds enabled by an organocatalyst.

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Section: Methodsmentioning

confidence: 99%

Direct Asymmetric α‐C−H Addition of N‐unprotected Propargylic Amines to Trifluoromethyl Ketones by Carbonyl Catalysis

Liu

et al. 2022

Angewandte Chemie

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“…Meanwhile, they cluster together in a specific steric orientation to avoid the steric repulsion between the CF 3 group of 22 and the bulky Tf 2 N group, resulting in the high efficiency as well as excellent diastereo-and enantioselectivities. Kinetic isotope effect (KIE) studies indicate that Chiral-aldehyde-catalyzed asymmetric -C-allylation of glycine with MBH acetates was also achieved in 2022 by Zhao and co-workers 26 (Scheme 11). Pyridoxal C3d has proven to be an efficient catalyst for this asymmetric transformation.…”

Section: Short Review Synthesismentioning

confidence: 99%

Recent Advances in Chiral Aldehyde Catalysis for Asymmetric Functionalization of Amines

Wen¹,

Guo²

2022

Synthesis

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Asymmetric functionalization of amines and their derivatives is of great significance in synthetic chemistry and is widely used in the preparation of natural products and pharmaceuticals. In recent years, chiral aldehyde catalysis has emerged as a well-established and recognized tool, providing excellent catalytic activation and stereoselective control in asymmetric reactions of N-unprotected amino acid esters and amino acid ester analogs. In this Minireview, recent advances in enantioselective aldehyde catalysis, including chiral aldehydes as organocatalysts and co-catalysis combined with transition metals, will be summarized. Lastly, continued development of enantioselective aldehyde catalysis is prospected in the future.

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“…Our group has been devoted to the development of vitamin B 6 -based biomimetic asymmetric catalysis by using chiral pyridoxals/pyridoxamines as the catalysts (Figure ). We are particularly interested in biomimetic transamination ,− and α-C–H transformations of glycinates, − ,− respectively, imitating enzymatic transamination and aldol reaction of glycine promoted by threonine aldolase. With chiral pyridoxals/pyridoxamines 32 – 35 , we have developed the asymmetric biomimetic transamination of α-keto acids and α-keto amides.…”

Section: Introductionmentioning

confidence: 99%

Vitamin B₆-Based Biomimetic Asymmetric Catalysis

Xiao

Zhao

2023

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: One of the fundamental goals of chemists is to develop highly efficient methods for producing optically active compounds, given their wide range of applications in chemistry, pharmaceutical industry, chemical biology, and material science. Biomimetic asymmetric catalysis, which imitates the structures and functions of enzymes, has emerged as an extremely attractive strategy for producing chiral compounds. This field has drawn tremendous research interest and has led to various protocols for constructing complex molecular scaffolds. The Vitamin B 6 family, including pyridoxal, pyridoxamine, pyridoxine, and the corresponding phosphorylated derivatives, serves as the cofactors to catalyze more than 200 enzymatic functions, accounting for ∼4% of all enzyme activities. Although significant progress has been made in simulating the biological roles of vitamin B 6 during the past several decades, its extraordinary catalytic power has not yet been successfully applied into asymmetric synthesis. In recent years, our group has been devoted to developing vitamin B 6 -based biomimetic asymmetric catalysis using chiral pyridoxals/pyridoxamines as catalysts. We are particularly interested in mimicking the processes of enzymatic transamination and biological aldol reaction of glycine, respectively, developing asymmetric biomimetic transamination and carbonyl catalysis enabled α-C−H transformation of primary amines. Using a chiral α,α-diarylprolinol-derived pyridoxal as the catalyst, we reported the first chiral pyridoxal catalyzed asymmetric transamination of α-keto acids in 2015. A significant breakthrough in biomimetic transamination was achieved by using an axially chiral biaryl pyridoxamine catalyst that bears a lateral amine side arm. The amine side arm acts as an intramolecular base, accelerating the transamination and proving highly effective for transamination of α-keto acids and α-keto amides. In addition, we discovered the catalytic power of chiral pyridoxals as carbonyl catalysts for asymmetric biomimetic Mannich/aldol reactions of glycinates. These chiral pyridoxals also enabled more α-C− H conversions of glycinates, such as asymmetric 1,4-addition toward α,β-unsaturated esters and asymmetric α-allylation with Morita−Baylis−Hillman acetates. Moreover, carbonyl catalysis can be further applied to highly challenging primary amines with inert α-C−H bonds, such as propargylamines and benzylamines, which represents a powerful strategy for direct asymmetric α-C−H functionalization of various primary amines without protection of the NH 2 group. These biomimetic/bioinspired transformations provide efficient new protocols for the synthesis of chiral amines. Herein, we summarize our recent efforts on the development of the vitamin B 6 -based biomimetic asymmetric catalysis.

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Asymmetric α‐Allylation of Glycinate with Switched Chemoselectivity Enabled by Customized Bifunctional Pyridoxal Catalysts

Cited by 37 publications

References 128 publications

Direct Asymmetric α‐C−H Addition of N‐unprotected Propargylic Amines to Trifluoromethyl Ketones by Carbonyl Catalysis

Direct Asymmetric α‐C−H Addition of N‐unprotected Propargylic Amines to Trifluoromethyl Ketones by Carbonyl Catalysis

Recent Advances in Chiral Aldehyde Catalysis for Asymmetric Functionalization of Amines

Vitamin B₆-Based Biomimetic Asymmetric Catalysis

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Asymmetric α‐Allylation of Glycinate with Switched Chemoselectivity Enabled by Customized Bifunctional Pyridoxal Catalysts

Cited by 37 publications

References 128 publications

Direct Asymmetric α‐C−H Addition of N‐unprotected Propargylic Amines to Trifluoromethyl Ketones by Carbonyl Catalysis

Direct Asymmetric α‐C−H Addition of N‐unprotected Propargylic Amines to Trifluoromethyl Ketones by Carbonyl Catalysis

Recent Advances in Chiral Aldehyde Catalysis for Asymmetric Functionalization of Amines

Vitamin B6-Based Biomimetic Asymmetric Catalysis

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Product

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Vitamin B₆-Based Biomimetic Asymmetric Catalysis