Practical asymmetric amine nucleophilic approach for the modular construction of protected α-quaternary amino acids

Chemical Science, Journal Year: 2022, Volume and Issue: 13(23), P. 6806 - 6812

Published: Jan. 1, 2022

We report the first amine nucleophilic approach for modular construction of enantioenriched protected α-quaternary amino acids. The key to success is use an alcohol solvent, which makes a rationally designed COOMe-bonded Cu-allenylidene electrophilic intermediate stable enough couple with nucleophiles before its decomposition. reaction features wide functional group tolerance high enantioselectivity, typically >90% ee, and amenable modification commercially available bioactive molecules. resultant α-amino acids could be readily converted into number precious amines featuring α-hindered tertiary carbon centers, are otherwise synthetically quite challenging, including those aldehyde, peptides or α-vinyl ester >92% ee in excellent yields. This protocol utilized synthesis α-ethylnorvaline 3 steps, significant advancement comparison 11-step sequence reported previously.

Language: Английский

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Synthesis of gem-Difluorinated 2,3-Dihydrobenzofurans Using Freon-22 via [4 + 1] Annulation of Difluorocarbene and Antitumor Activity Evaluation

Organic Letters, Journal Year: 2024, Volume and Issue: 26(6), P. 1212 - 1217

Published: Feb. 1, 2024

As an inexpensive industrial chemical, chlorodifluoromethane (Freon-22), despite its relatively low reactivity, can serve as a practical CF

Language: Английский

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Recent Advances in Transition-Metal Catalyzed C—H Bond Activation for the Synthesis of C(sp³)-Fluoroalkyl Compounds

Chinese Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 45(2), P. 516 - 516

Published: Jan. 1, 2025

Language: Английский

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Visible-Light-Driven Palladium-Catalyzed 1,4-Difluoromethylative Functionalization of Conjugated Dienes Using Freon-22

Published: Feb. 19, 2024

We unveil a novel strategy that leverages cost-effective fluorine-containing sources for rapid synthesis of fluorinated com-pounds through multicomponent reactions. Our study introduces visible light-driven palladium-catalyzed 1,4-difluoromethyl difunctionalization conjugated dienes, capitalizing on the abundant industrial resource chlorodifluoro-methane (ClCF2H, Freon-22). Illuminated by blue LED light, palladium catalyst orchestrates efficient single electron reduction Freon-22's C-Cl bond, yielding CF2H radicals. This versatile protocol accommodates an extensive array amines, sulfinates, and enolates as nucleophiles, delivering regioselective products via SN2' substitution allylic intermediate. Redox-neutral in nature, this transformation finds utility late-stage functionalization drug molecules, while broad compatibility with diverse functional groups dienes underscores its versa-tility. Initial insights suggest involvement difluoromethyl radical intermediate, unveiling direct mild avenue to harness radicals from Freon-22.

Language: Английский

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Asymmetric synthesis of difluorinated α-quaternary amino acids (DFAAs) via Cu-catalyzed difluorobenzylation of aldimine esters

Chinese Chemical Letters, Journal Year: 2024, Volume and Issue: 35(12), P. 109665 - 109665

Published: Feb. 23, 2024

Language: Английский

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Highly Enantioselective Decarboxylative Difluoromethylation

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(43), P. 29297 - 29304

Published: Oct. 15, 2024

Organofluorine molecules that contain difluoromethyl groups (CF2H) at stereogenic centers have gained importance in pharmaceuticals due to the unique ability of CF2H act as lipophilic hydrogen bond donors. Despite their potential, enantioselective installation into readily available starting materials remains a challenging and underdeveloped area. In this study, we report nickel-catalyzed decarboxylative difluoromethylation reaction converts alkyl carboxylic acids difluoromethylated products with exceptional enantioselectivity. This Ni-catalyzed protocol exhibits broad functional group tolerance is applicable for synthesizing fluorinated bioisosteres biologically relevant molecules.

Language: Английский

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Difluoromethylsulfonyl Imidazolium Salt for Difluoromethylation of Alkenes

Organic Letters, Journal Year: 2022, Volume and Issue: 24(41), P. 7611 - 7616

Published: Oct. 6, 2022

Herein, we describe the design and synthesis of a difluoromethylsulfonyl imidazolium salt, which can act as radical difluoromethylation reagent to achieve challenging amino- oxy-difluoromethylation alkenes. Notably, three steps for salt do not require any tedious distillation or column chromatography purification process, paths are simply determined by selection reaction solvents.

Language: Английский

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Cu-Catalyzed Switchable Asymmetric Defluoroalkylation and [3 + 2] Cycloaddition of Trifluoropropene

Organic Letters, Journal Year: 2022, Volume and Issue: 24(42), P. 7828 - 7833

Published: Oct. 20, 2022

Chiral fluorinated amino esters and pyrrolidines are privileged scaffolds in synthetic chemistry exhibit unique biological properties. We report the facile preparation of these compounds through copper-catalyzed switchable defluoroalkylation [3 + 2] cycloaddition trifluoropropene an asymmetric fashion. The choice solvent chiral ligand was crucial for efficient transformation exquisite chemoselectivity pattern from identical starting materials that rapidly reliably incorporate gem-difluoroalkene trifluoromethyl (CF3) motifs to generate a diverse range enantioenriched building blocks good excellent yields with high induction.

Language: Английский

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The Revival of Enantioselective Perfluoroalkylation – Update of New Synthetic Approaches from 2015–2022

The Chemical Record, Journal Year: 2023, Volume and Issue: 23(9)

Published: May 23, 2023

Over the last years, methods devoted to synthesis of asymmetric molecules bearing a perfluoroalkylated chain have been limited in number. Among them, only few can be used on large variety scaffolds. This microreview aims at summarizing these recent advances enantioselective perfluoroalkylation (-CF3 , -CF2 H, -Cn F2n+1 ) and highlights need for new easily synthesize chiral fluorinated which would useful pharmaceutical agrochemical industries. Some perspectives are also mentioned.

Language: Английский

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Direct Asymmetric α-Alkylation of NH₂-Unprotected Amino Acid Esters Enabled by Biomimetic Chiral Pyridoxals

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(13), P. 9150 - 9157

Published: June 26, 2023

Biosynthesis utilizes kinetic strategies to regulate the chemoselectivity for transformations of molecules containing multiple active reaction sites. But it is a grand challenge realize without protecting group manipulations chemosynthesis. α-Amino acid esters contain NH2 and α-C-H, two nucleophilic Direct asymmetric α-C-alkylation NH2-unprotected amino with alkyl halides represents one most straightforward access chiral quaternary α-amino acids, which are widely present in many pharmaceuticals. However, transformation challenging due high reactivity intrinsic N-alkylation. Here, by using pyridoxal 6 having benzene-pyridine biaryl skeleton as carbonyl catalyst, we successfully unlock C–H bonds toward protection group, forming wide range up 99% yield ee. Like biological systems, this protocol featured no atom step efficiencies enabled biomimetic organocatalyst.

Language: Английский

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