Catalytic Ring Expanding Difluorination: An Enantioselective Platform to Access β,β‐Difluorinated Carbocycles

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(22)

Published: March 14, 2024

Abstract Cyclic β,β‐difluoro‐carbonyl compounds have a venerable history as drug discovery leads, but limitations in the synthesis arsenal continue to impede chemical space exploration. This challenge is particularly acute arena of fluorinated medium rings where installing difluoromethylene unit subtly alters ring conformation by expanding internal angle (∠C−CF 2 −C>∠C−CH −C): this provides handle modulate physicochemistry (e.g. p K ). To reconcile disparity, highly modular expansion has been devised that leverages simple α,β‐unsaturated esters and amides, processes them one‐carbon homologated with concomitant geminal difluorination (6 10 membered rings, up 95 % yield). process rare example formal an alkene enabled sequential I(III)‐enabled O ‐activation. Validation enantioselective catalysis generation unprecedented scaffolds reported (up 93 : 7 e.r .) together X‐ray structural analyses product derivatization.

Language: Английский

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A decade of lessons in the activation of ArIL₂ species

Chemical Science, Journal Year: 2024, Volume and Issue: 15(11), P. 3784 - 3799

Published: Jan. 1, 2024

Developments in methods to increase the oxidative capacity of ArIL 2 reagents are discussed, with a focus on an understanding these species' behaviour from perspective iodine.

Language: Английский

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Catalytic Ring Expanding Difluorination: An Enantioselective Platform to Access β,β‐Difluorinated Carbocycles

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(22)

Published: March 14, 2024

Abstract Cyclic β,β‐difluoro‐carbonyl compounds have a venerable history as drug discovery leads, but limitations in the synthesis arsenal continue to impede chemical space exploration. This challenge is particularly acute arena of fluorinated medium rings where installing difluoromethylene unit subtly alters ring conformation by expanding internal angle (∠C−CF 2 −C>∠C−CH −C): this provides handle modulate physicochemistry (e.g. p K ). To reconcile disparity, highly modular expansion has been devised that leverages simple α,β‐unsaturated esters and amides, processes them one‐carbon homologated with concomitant geminal difluorination (6 10 membered rings, up 95 % yield). process rare example formal an alkene enabled sequential I(III)‐enabled O ‐activation. Validation enantioselective catalysis generation unprecedented scaffolds reported (up 93 : 7 e.r .) together X‐ray structural analyses product derivatization.

Language: Английский

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Polymorphism in 5-methylsalicylic acid: Insights into relative thermal behavior, luminescent properties, crystal structure, and Hirshfeld surface analysis

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1319, P. 139397 - 139397

Published: July 23, 2024

Language: Английский

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1.4 Recent Developments in Enantioselective Fluorination

Published: Jan. 1, 2024

Abstract This review describes the main advances in enantioselective fluorination over last decade, while also recalling early developments this area. Three strategies have been employed to achieve concomitant introduction of a fluorine atom by C(sp3)—F bond formation with stereocon-trol at same carbon center: (1) use chiral fluorinating agents, (2) diverse organocatalytic approaches, and (3) transition-metal-catalyzed fluorinations. These complementary ap-ply both electrophilic nucleophilic

Language: Английский

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