Aminomethylation of Enals through Carbene and Acid Cooperative Catalysis: Concise Access to β<sup>2</sup>‐Amino Acids

Xu, Jianfeng; Chen, Xingkuan; Wang, Ming; Zheng, Pengcheng; Song, Baoan; Robin, Yonggui

doi:10.1002/anie.201412132

Cited by 107 publications

(41 citation statements)

References 88 publications

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“…NHCs and acids play differentc atalytic roles in the reaction system. [39][40][41][42] These syntheses require the presence, in the reaction mixture, of both an NHCa nd an acid;t his situation is possible only if the Brønsted acid is unable to protonate the NHC quantitatively (in spite of the significant basicity of the NHC).…”

Section: Stability Of Nhc:role Of Acetic Acidmentioning

confidence: 99%

N‐Heterocyclic Carbenes and Parent Cations: Acidity, Nucleophilicity, Stability, and Hydrogen Bonding—Electrochemical Study and Ab Initio Calculations

et al. 2016

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N‐Heterocyclic carbenes (NHCs) are widely used as organocatalysts. Their reactivity (and instability) is related to their basicity and nucleophilicity, which, in turn, are linked to their scaffold. NHCs can be generated by chemical deprotonation or electrochemical reduction of the parent azolium cations, NHCH+s. Cyclic voltammetry enabled the reduction potential of the NHCH+s to be determined; the reduction potential is related to the acidity of the NHCH+s and the oxidation potential of the NHCs, which is related to the nucleophilicity of the NHCs. It was thus possible to order different NHCH+s and NHCs by their acidity and nucleophilicity, respectively. A study on the stability of NHCs was also performed in the absence and in the presence of acetic acid to assess the possibility of the coexistence of NHC and an acid in the same solution, opening the possibility of co‐catalysis. Finally, ab initio calculations confirmed the presence, in DMF, of hydrogen‐bonded NHCH+–NHC adducts, which could influence catalyst activity.

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Section: Stability Of Nhc:role Of Acetic Acidmentioning

confidence: 99%

N‐Heterocyclic Carbenes and Parent Cations: Acidity, Nucleophilicity, Stability, and Hydrogen Bonding—Electrochemical Study and Ab Initio Calculations

et al. 2016

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“…The resulting β-amino carbonyl compounds are versatile synthetic building blocks for a wide variety of natural products and biologically active compounds 9 . Different types of formaldehyde-derived imines or iminium salts, which are generally unstable and have to be in situ generated from formaldehyde with aromatic amines 10,11 , α-aminomethyl ethers [12][13][14][15][16][17] , N,O-acetals [18][19][20] , or 1,3,5-triaryl-1,3,5-triazines [21][22][23][24] , have been successfully applied. Within this context, enantioselective version of this transformation has also been achieved by catalytic asymmetric activation of the nucleophilic carbonyl compounds with either amine catalysts 10,11,14,16 or chiral Lewis acid 23,24 .…”

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confidence: 99%

Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines

et al. 2020

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Enantioselective α-aminomethylation of carbonyl compounds constitutes a powerful protocol for introducing aminomethyl groups to simple organic molecules. However, current strategies rely on nucleophile-based enantioselective activation with inherently activated substrates only, and enantioselective protocol based on the activation of in situ-generated unstable formaldimines remains elusive, probably owing to their unstable nature and the lack of steric environment for efficient stereocontrols. Here, based on a rhodium/chiral phosphoric acid cooperative catalysis, we achieved an enantioselective three-component reaction of α-diazo ketones with alcohols and 1,3,5-triazines. A dual hydrogen bonding between the chiral phosphoric acid catalyst and two distinct active intermediates was proposed to be crucial for the efficient electrophile-based enantiocontrol. A series of chiral β-amino-α-hydroxy ketones including those derived from simple aliphatic alcohols, allylic alcohol, propargyl alcohol, complicated natural alcohols and water could all be prepared in high efficiency and enantioselectivity.

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“…In 2015, Chi reported a redox‐neutral catalytic asymmetric aminomethylation of enals (Scheme ) . The key for the success of this transformation was a catalytic system comprising an N‐heterocyclic carbene (NHC) and Et 3 N · HBF 4 , both of which cooperatively promoted the desired reaction.…”

Section: C(α)–c(β) Bond Formationmentioning

confidence: 99%

Recent Advances in the Catalytic Asymmetric Synthesis of β²‐ and β^2,2‐Amino Acids

Noda

Shibasaki

2019

Eur J Org Chem

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The importance of -amino acids for peptidomimetics and their presence in numerous natural products and pharmaceuticals make the development of the corresponding synthetic procedures a task of high practical significance. Herein, we focus on the recent developments in the catalytic asymmetric synthesis of 2 -and 2,2 -amino acids. The examples are arranged according to strategic bond disconnections. Despite the abundance of feasible approaches, only a handful of reaction [a] Dr. 2350 types can effectively furnish 2 -and 2,2 -amino acid derivatives with sufficient enantioselectivity suitable for peptide applications. These include asymmetric hydrogenation or conjugate addition of acrylates, α-functionalization of -amino acid enolate precursors, and aminomethylation of carbonyl compounds. Hence, future research directions are discussed considering these literature precedents.fied so far, -peptides -oligomers of -amino acids -have attracted considerable attention due to their structural similarity to native α-peptides and the conformational rigidity and chemical stability bestowed by the unnatural residues. [2] Contemporary research has further diverged into the use of γ-amino acids and α/ -hybrid peptides. [3] -Amino acids are also found in many natural products and pharmaceutical agents such as -lactams, [4] rendering the development of corresponding synthetic procedures an important task of synthetic organic chemistry.-Amino acids are homologated variants of α-amino acids, which are structurally categorized by their side-chain substitution patterns. The nomenclature for -amino acids is as follows: 3 denotes those with a substituent at the -position, 2 at the α-position, 2,3 at both αand -positions, and so on (Figure 1). Cyclic -amino acids are also classified in a similar fashion. 3 -Amino acids can be synthesized from the corresponding Minireview 2352 Scheme 3. Rh-catalyzed enantioselective hydrogenation of -phthalimide acrylates 5 reported by Zheng. Scheme 4. Rh-catalyzed enantioselective hydrogenation of (α-aminomethyl)acrylates 7 reported by Qiu. Scheme 16. Organocatalytic asymmetric conjugate addition of pyrrolidin-2,3dione 30 for the synthesis of 2,2 -peptidic compounds reported by Palomo.acid derivative 33, followed by the asymmetric protonation of the resulting enolate of the 5-membered ring to afford 4-substituted isoxazolidin-5-ones 35 (Scheme 17). [49] Although the selectivities need further improvement for practical applications, this work is one of the rare examples of the synthesis of 2 -amino acids bearing functionalized side chains (e.g., 35d).Scheme 17. Organocatalytic asymmetric protonation for the synthesis of 4-substituted isoxazolidin-5-ones 35 reported by Brière.

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Aminomethylation of Enals through Carbene and Acid Cooperative Catalysis: Concise Access to β²‐Amino Acids

Cited by 107 publications

References 88 publications

N‐Heterocyclic Carbenes and Parent Cations: Acidity, Nucleophilicity, Stability, and Hydrogen Bonding—Electrochemical Study and Ab Initio Calculations

N‐Heterocyclic Carbenes and Parent Cations: Acidity, Nucleophilicity, Stability, and Hydrogen Bonding—Electrochemical Study and Ab Initio Calculations

Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines

Recent Advances in the Catalytic Asymmetric Synthesis of β²‐ and β^2,2‐Amino Acids

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Aminomethylation of Enals through Carbene and Acid Cooperative Catalysis: Concise Access to β2‐Amino Acids

Cited by 107 publications

References 88 publications

N‐Heterocyclic Carbenes and Parent Cations: Acidity, Nucleophilicity, Stability, and Hydrogen Bonding—Electrochemical Study and Ab Initio Calculations

N‐Heterocyclic Carbenes and Parent Cations: Acidity, Nucleophilicity, Stability, and Hydrogen Bonding—Electrochemical Study and Ab Initio Calculations

Enantioselective three-component aminomethylation of α-diazo ketones with alcohols and 1,3,5-triazines

Recent Advances in the Catalytic Asymmetric Synthesis of β2‐ and β2,2‐Amino Acids

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Aminomethylation of Enals through Carbene and Acid Cooperative Catalysis: Concise Access to β²‐Amino Acids

Recent Advances in the Catalytic Asymmetric Synthesis of β²‐ and β^2,2‐Amino Acids