Copper-Catalyzed Enantioselective Difluoromethylation of Amino Acids via Difluorocarbene

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(17), P. 6376 - 6381

Published: April 26, 2021

Difluoromethyl amino acids (DFAA) exhibit intriguing biological properties, making them highly desirable motifs in agrochemical and pharmaceutical science. However, stereochemical control of direct difluoromethyl transformation via the difluorocarbene species has not been demonstrated. Here we describe an efficient copper-catalyzed asymmetric difluoromethylation reaction that systematically delivers chiral DFAA as rationally designed mechanism-based inhibitors PLP-dependent acid decarboxylases. The employs difluoromonochloromethane, abundant raw material, precursor species, enabling unprecedentedly conversion esters into corresponding valuable products good yields with excellent enantioselectivities. This de novo synthesis creates opportunities to integrate catalytic platform for preparation diverse libraries biologically important derivatives will support efforts both drug discovery development.

Language: Английский

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Efficient Asymmetric Biomimetic Aldol Reaction of Glycinates and Trifluoromethyl Ketones by Carbonyl Catalysis

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(37), P. 20166 - 20172

Published: June 17, 2021

Abstract The direct asymmetric aldol reaction of glycinates represents an intriguing and straightforward strategy to make biologically significant chiral β‐hydroxy‐α‐amino‐acid derivatives. But it is not easy realize the transformation due disruption reactive NH 2 group glycinates. Inspired by enzymatic glycine, we successfully developed glycinate 5 trifluoromethyl ketones 4 with 0.1–0.0033 mol % N ‐methyl pyridoxal 7 a as catalyst, producing β‐trifluoromethyl‐β‐hydroxy‐α‐amino‐acid esters 6 in 55–82 yields (for syn ‐diastereomers) up >20:1 dr 99 ee under very mild conditions. proceeds via catalytic cycle similar glycine. Pyridoxal catalyst activates both reactants at same time brings them together specific spatial orientation, accounting for high efficiency well excellent diastereo‐ enantioselectivities.

Language: Английский

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Catalytic Asymmetric Dearomative 1,3-Dipolar Cycloaddition of 2-Nitrobenzothiophenes and Isatin-Derived Azomethine Ylides

Organic Letters, Journal Year: 2021, Volume and Issue: 23(21), P. 8600 - 8605

Published: Oct. 21, 2021

An enantioselective dearomative 1,3-dipolar cycloaddition of 2-nitrobenzothiophenes and isatin-derived azomethine ylides with a bifunctional hydrogen-bonding thiourea catalyst was established, giving polyheterocyclic compounds in excellent results (up to 99% yield, >20:1 dr for all cases up ee). The enantioselectivity could be reversed by the squaramide containing same chiral source as catalyst. DFT calculations revealed origin observed stereochemistry reversal enantioselectivity.

Language: Английский

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

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(17)

Published: Feb. 19, 2022

Abstract Owing to the strong nucleophilicity of NH 2 group, free‐NH glycinates react with MBH acetates usually deliver N‐allylated products even in absence catalysts. Without protection chiral pyridoxal catalysts bearing an amide side chain at C3 position naphthyl ring switched chemoselectivity from intrinsic N‐allylation α‐C allylation. The reaction formed multisubstituted glutamic acid esters as S N 2′–S 2′ good yields excellent stereoselectivity (up 86 % yield, >20 : 1 dr, 97 ee). As compared arm C2 position, pyridoxals this study have a bigger catalytic cavity enable effective activation larger electrophiles, such and related intermediates. is proposed proceed via cooperative bifunctional catalysis pathway, which accounts for high level diastereo‐ enantiocontrol

Language: Английский

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Catalytic asymmetric α C(sp3)–H addition of benzylamines to aldehydes

Nature Catalysis, Journal Year: 2022, Volume and Issue: 5(11), P. 1061 - 1068

Published: Nov. 28, 2022

Language: Английский

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