Stereoselective synthesis of unnatural α-amino acid derivatives through photoredox catalysis

Shatskiy, Andrey; Axelsson, Anton; Stepanova, Elena V.; Liu, Jian‐Quan; Темердашев, А. З.; Kore, Bhushan P.; Blomkvist, Björn; Gardner, James M.; Dinér, Peter; Kärkäs, Markus D.

doi:10.1039/d1sc00658d

Cited by 50 publications

(36 citation statements)

References 59 publications

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“…The classical approach used to cleave the SA auxiliary involves acidic condition in protic solvents, typically HCl or trifluoroacetic acid in methanol. , Unfortunately, those conditions did not work and a complex reaction mixture was obtained. Finally, the SIA chiral auxiliary was removed by treatment with triflic acid and anisole in CH 2 Cl 2 and the amine was obtained in 90% yield and 95:5 dr (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Accessing Perfluoroaryl Sulfonimidamides and Sulfoximines via Photogenerated Perfluoroaryl Nitrenes: Synthesis and Application as a Chiral Auxiliary

et al. 2021

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Sulfonimidamides (SIAs) and sulfoximines (SOIs) have attracted attention due to their potential in agriculture and in medicinal chemistry as bioisosteres of biologically active compounds, and new synthetic methods are needed to access and explore these compounds. Herein, we present a light-promoted generation of perfluorinated aromatic nitrenes, from perfluorinated azides, that subsequently are allowed to react with sulfinamides and sulfoxides, generating achiral and chiral SIAs and SOIs. One of the enantiopure SIAs was evaluated as a novel chiral auxiliary in Grignard additions to the imines yielding the product in up to 96:4 diastereomeric ratio.

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Section: Resultsmentioning

confidence: 99%

Accessing Perfluoroaryl Sulfonimidamides and Sulfoximines via Photogenerated Perfluoroaryl Nitrenes: Synthesis and Application as a Chiral Auxiliary

et al. 2021

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“…Scheme 4 Photoredox-mediated synthesis of unnatural -amino esters/acids with unactivated carboxylic acids as radical precursors amino acids, our group aimed at realizing this approach with a chiral glyoxylate-derived N-sulfinyl imine as the radical acceptor. 21 Previously, Baran and co-workers demonstrated a highly versatile stereoselective radical-based approach to unnatural α-amino acids with the same radical acceptor. 22 In this catalytic system, the free radical intermediates were generated by one-electron reduction of TCNHPI esters with Zn as the stoichiometric reducing agent (3 equiv.)…”

Section: Synlett Account / Synpactsmentioning

confidence: 99%

Photoredox-Enabled Decarboxylative Synthesis of Unnatural α-Amino Acids

Shatskiy¹,

Kärkäs²

2021

Synlett

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Recently, development of general synthetic routes to unnatural α-amino acids has gained a significant momentum, driven by the high demand for such building blocks in fundamental research within molecular and structural biology, as well as for development of new pharmaceuticals. Herein, we highlight the recent progress in employing photoredox-mediated synthetic methods for accessing unnatural α-amino acids with a focus on various decarboxylative radical-based strategies.

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“…While several elegant reports are outlined in this review, it is clear that the asymmetric introduction of fluorinated side chains as well as the diastereocontrol in preparing -branched and polyfunctionalized amino acids from -imino esters are delicate. To fill this gap, other synthetic strategies are available 29 and innovative tactics such as novel aldol 30 or single-electron strategies 31 are constantly emerging. It goes without saying that the development of novel tactics towards quaternary NPAAs will also impact this field.…”

Section: S P Rochementioning

confidence: 99%

In the Pursuit of (Ald)Imine Surrogates for the Direct Asymmetric Synthesis of Non-Proteinogenic α-Amino Acids

Roche

2021

Synthesis

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Nature remarkably employs posttranslational modifications of the 20 canonical α-amino acids to devise a far larger structural, conformational, and functional diversity found in non-proteinogenic amino acids (NPAAs) which ultimately translates into a plethora of complex biological functions. Synthetic chemists are continuously trying to reproduce and even extrapolate the repertoire of NPAA building blocks to build structural diversity into bioactive molecules and materials. The direct asymmetric functionalization of α-imino esters represents one of the most robust and attractive routes to NPAAs. This review summarizes the most prominent examples of bench-stable (ald)imine surrogates exploited for the synthesis of NPAAs including our most recent results in the nucleophilic substitution of α-haloglycines and other α-haloaminals. A synopsis of kinetic studies, reaction optimizations, and enantioselective catalytic methods is also presented.

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Stereoselective synthesis of unnatural α-amino acid derivatives through photoredox catalysis

Abstract: A protocol for stereoselective C-radical addition to a chiral glyoxylate-derived N-sulfinyl imine was developed through visible light-promoted photoredox catalysis, providing a convenient method for the synthesis of unnatural α-amino acids....

Cited by 50 publications

References 59 publications

Accessing Perfluoroaryl Sulfonimidamides and Sulfoximines via Photogenerated Perfluoroaryl Nitrenes: Synthesis and Application as a Chiral Auxiliary

Accessing Perfluoroaryl Sulfonimidamides and Sulfoximines via Photogenerated Perfluoroaryl Nitrenes: Synthesis and Application as a Chiral Auxiliary

Photoredox-Enabled Decarboxylative Synthesis of Unnatural α-Amino Acids

In the Pursuit of (Ald)Imine Surrogates for the Direct Asymmetric Synthesis of Non-Proteinogenic α-Amino Acids

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