Recent Progress in Synthetic Applications of Hypervalent Iodine(III) Reagents

Chemical Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Hypervalent iodine(III) compounds have found wide application in modern organic chemistry as environmentally friendly reagents and catalysts. iodine are commonly used synthetically important halogenations, oxidations, aminations, heterocyclizations, various oxidative functionalizations of substrates. Iodonium salts arylating reagents, while iodonium ylides imides excellent carbene nitrene precursors. Various derivatives benziodoxoles, such azidobenziodoxoles, trifluoromethylbenziodoxoles, alkynylbenziodoxoles, alkenylbenziodoxoles group transfer the presence transition metal catalysts, under metal-free conditions, or using photocatalysts photoirradiation conditions. Development hypervalent catalytic systems discovery highly enantioselective reactions chiral represent a particularly recent achievement field chemistry. Chemical transformations promoted by many cases unique cannot be performed any other common, non-iodine-based reagent. This review covers literature published mainly last 7-8 years, between 2016 2024.

Language: Английский

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Expanding organofluorine chemical space: the design of chiral fluorinated isosteres enabled by I(i)/I(iii) catalysis

Chemical Science, Journal Year: 2021, Volume and Issue: 12(32), P. 10686 - 10695

Published: Jan. 1, 2021

Short aliphatic groups are prevalent in bioactive small molecules and play an essential role regulating physicochemistry molecular recognition phenomena.

Language: Английский

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Regio‐ and Enantioselective Intermolecular Aminofluorination of Alkenes via Iodine(I)/Iodine(III) Catalysis**

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(32)

Published: May 18, 2022

The regio- and enantio-selective, intermolecular vicinal fluoroamination of α-trifluoromethyl styrenes has been achieved by enantioselective I

Language: Английский

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Regioselective, catalytic 1,1-difluorination of enynes

Nature Chemistry, Journal Year: 2023, Volume and Issue: 15(11), P. 1515 - 1522

Published: Oct. 16, 2023

Fluorinated small molecules are prevalent across the functional small-molecule spectrum, but scarcity of naturally occurring sources creates an opportunity for creative endeavour in developing routes to access these important materials. Iodine(I)/iodine(III) catalysis has proven be particularly well-suited this task, enabling abundant alkene substrates readily intercepted by situ-generated λ3-iodanes and processed high-value (di)fluorinated products. These organocatalysis paradigms often emulate metal-based processes engaging π bond and, case styrenes, facilitating fluorinative phenonium-ion rearrangements generate difluoromethylene units. Here we demonstrate that enynes competent proxies thereby mitigating recurrent need aryl substituents, highly versatile homopropargylic difluorides generated operationally simple manner. The scope method is disclosed, together with application target synthesis (>30 examples, up >90% yield).

Language: Английский

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Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(3), P. 1030 - 1076

Published: Nov. 18, 2023

Synthetic chemistry plays an indispensable role in drug discovery, contributing to hit compounds identification, lead optimization, candidate drugs preparation, and so on. As Nobel Prize laureate James Black emphasized, "the most fruitful basis for the discovery of a new is start with old drug"

Language: Английский

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Catalytic Hydrodifluoroalkylation of Unactivated Olefins

Organic Letters, Journal Year: 2022, Volume and Issue: 24(28), P. 5109 - 5114

Published: July 10, 2022

Herein, we report a modular catalytic technique that streamlines the preparation of gem-difluoroalkanes from unactivated sp3 precursors. The method is characterized by its simplicity, generality, and site selectivity, including functionalization advanced intermediates olefin feedstocks. Our approach enabled cooperative interplay halogen- hydrogen-atom transfer, thus offering new entry point to difluorinated alkyl bioisosteres interest in drug discovery.

Language: Английский

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Skeletal Ring Contractions via I(I)/I(III) Catalysis: Stereoselective Synthesis of cis-α,α-Difluorocyclopropanes

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(23), P. 14507 - 14516

Published: Nov. 10, 2022

The clinical success of α,α-difluorocyclopropanes, combined with limitations in the existing synthesis portfolio, inspired development an operationally simple, organocatalysis-based strategy to access cis-configured derivatives high levels stereoselectivity (up >20:1 cis:trans). Leveraging I(I)/I(III)-catalysis platform presence inexpensive HF source, it has been possible exploit disubstituted bicyclobutanes (BCBs) as masked cyclobutene equivalents for this purpose. In situ generation strained alkene, enabled by Brønsted acid activation, facilitates unprecedented 4 → 3 fluorinative ring contraction, furnish cis-α,α-difluorinated cyclopropanes a highly stereoselective manner 88% yield). Mechanistic studies are disclosed together conformational analysis (X-ray crystallography and NMR) validate cis-α,α-difluorocyclopropanes isosteres 1,4-dicarbonyl moiety. Given importance unit biology foundational no π* interactions that manifest themselves conformation (e.g., collagen), is envisaged title motif will find application focused molecular design.

Language: Английский

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Integrating I(I)/I(III) catalysis in reaction cascade design enables the synthesis of gem-difluorinated tetralins from cyclobutanols

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 2, 2023

Partially saturated, fluorine-containing rings are ubiquitous across the drug discovery spectrum. This capitalises upon biological significance of native structure and physicochemical advantages conferred by fluorination. Motivated aryl tetralins in bioactive small molecules, a reaction cascade has been validated to generate novel gem-difluorinated isosteres from 1,3-diaryl cyclobutanols single operation. Under Brønsted acidity catalysis conditions, an acid-catalysed unmasking/fluorination sequence generates homoallylic fluoride situ. species serves as substrate for I(I)/I(III) cycle is processed, via phenonium ion rearrangement, (isolable) 1,3,3-trifluoride. A final C(sp3)-F bond activation event, enabled HFIP, forges difluorinated tetralin scaffold. The highly modular, enabling intermediates be intercepted: this provides expansive platform generation structural diversity.

Language: Английский

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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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Regio- and stereochemical behavior of cyclooctane and cyclodecane derivatives containing CF2 moieties

Journal of Fluorine Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 110397 - 110397

Published: Jan. 1, 2025

Language: Английский

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