Fluorohydration of alkynes via I(I)/I(III) catalysis

Neufeld, Jessica; Daniliuc, Constantin G.; Gilmour, Ryan

doi:10.3762/bjoc.16.135

Cited by 7 publications

(7 citation statements)

References 64 publications

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“…However, slower reaction rates have been observed with electron-rich substrates, probably due to competitive side reactions such as formation of diaryl iodanes. , The main parameter affecting the overall reaction rate was found to be the substitution of the iodoarene (Figure b). The obtained negative ρ value (−1.95) strongly indicates a buildup of positive charge on the iodine atom of the iodoarene (oxidation) as the rate-limiting step.…”

Section: Mechanistic Investigationssupporting

confidence: 91%

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Decarboxylative Ritter-Type Amination by Cooperative Iodine (I/III)─Boron Lewis Acid Catalysis

et al. 2021

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Recent years have witnessed important progress in synthetic strategies exploiting the reactivity of carbocations via photochemical or electrochemical methods. Yet, most of the developed methods are limited in their scope to certain stabilized positions in molecules. Herein, we report a metal-free system based on the iodine (I/III) catalytic manifold, which gives access to carbenium ion intermediates also on electronically disfavored benzylic positions. The unusually high reactivity of the system stems from a complexation of iodine (III) intermediates with BF3. The synthetic utility of our decarboxylative Ritter-type amination protocol has been demonstrated by the functionalization of benzylic as well as aliphatic carboxylic acids, including late-stage modification of different pharmaceutical molecules. Notably, the amination of ketoprofen was performed on a gram scale. Detailed mechanistic investigations by kinetic analysis and control experiments suggest two mechanistic pathways.

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Section: Mechanistic Investigationssupporting

confidence: 91%

“…18,28 The main parameter affecting the overall reaction rate was found to be the substitution of the iodoarene (Figure 1b). The obtained negative ρ value (−1.95) 29 strongly indicates a buildup of positive charge on the iodine atom of the iodoarene (oxidation) as the rate-limiting step.…”

Section: ■ Mechanistic Investigationsmentioning

confidence: 99%

Decarboxylative Ritter-Type Amination by Cooperative Iodine (I/III)─Boron Lewis Acid Catalysis

et al. 2021

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“…The dominant formation of the cis isomer suggests that the ester functionality may play a role in coordinating the iodine(III) species to the same face of the alkene. This coordinating role of the ester is well-established in the I(I)/I(III)-catalyzed fluorohydration of alkynes (the fluoro-Kucherov reaction) and supported by the observation that CO 2 Me → SO 2 Ph exchange erodes stereoselectivity ( 3q ; Scheme ). Fluorination to generate the cyclobutane II would enable a stereospecific ring contraction to liberate the catalyst and generate a cis -configured cyclopropyl carbinyl cation.…”

mentioning

confidence: 72%

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

et al. 2022

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

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“…Very recently, α‐fluoroketones were readily synthesized from terminal and internal alkynes via I(I)/I(III) catalysis utilizing p ‐TolI as an organocatalyst with selectfluor, water, and amine ⋅ HF mixtures . Selectfluor‐mediated oxidation of p ‐TolI in the presence of an amine ⋅ HF source in situ generated p ‐TolIF 2 , which productively engaged with pentynyl benzoates to form the desired α‐fluoroketones.…”

Section: Fluorination Mediated By Hypervalent Iodine Reagentsmentioning

confidence: 99%

“…Preliminary mechanistic studies, including Hammett analyses, identified the importance of the pentynyl linker and the benzoyl ester in the substrates, which were the key determinants for reaction efficiency, suggesting a highly preorganised structure. Although the origin of this specificity requires clarification, this fluorohydration constituted a rare case of substrate specificity in small‐molecule catalysis …”

Section: Fluorination Mediated By Hypervalent Iodine Reagentsmentioning

confidence: 99%

Fluorination and Fluoroalkylation Reactions Mediated by Hypervalent Iodine Reagents

Han

Zhang

2020

Adv Synth Catal

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This review summarizes the progress in the fluorination and fluoroalkylation of electron-rich systems with diverse fluorine (F) and fluoroalkyl (R fn) reagents employing hypervalent iodine compounds as initiators in the last few decades. Because of the strong electrophilicity, high oxidizing properties, low toxicity, air and moisture stability, ready availability, ease of handling, and mild reaction conditions, the hypervalent iodine reagents have been widely utilized in modern organic chemistry. In particular, the use of hypervalent iodine reagents to initiate the CÀ F and CÀ R fn (R fn =CF 2 H, CF 3 , perfluoroalkyl, OCH 2 CF 3 , SCF 3 , SeCF 3 and etc) bond formation has been increasingly developed. In these reactions, hypervalent iodine compounds behave as powerful oxidants or electrophiles and activate the fluorination/fluoroalkylation reagents, the transitionmetal catalysts, or the substrates to in situ form electrophilic or radical intermediates, which subsequently participate in fluorination, difluoromethylation, trifluoromethylation, perfluoroalkylation, trifluoroethoxylation, fluoroalkylthiolation, trifluoromethylselenolation and others under mild conditions. Although great achievements have been made in this area, they are just the initial phase and still require a wide scope for improvement. It is anticipated that this review will draw much attention from the organic chemistry community and inspire more contributions in the development of new hyper-valent-iodine-mediated fluorination and fluoroalkylation reactions.

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Fluorohydration of alkynes via I(I)/I(III) catalysis

Cited by 7 publications

References 64 publications

Decarboxylative Ritter-Type Amination by Cooperative Iodine (I/III)─Boron Lewis Acid Catalysis

Decarboxylative Ritter-Type Amination by Cooperative Iodine (I/III)─Boron Lewis Acid Catalysis

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

Fluorination and Fluoroalkylation Reactions Mediated by Hypervalent Iodine Reagents

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