Electrochemical Vicinal Difluorination of Alkenes: Sustainable, Scalable, and Amenable to Electron-rich Substrates

Fluorinated alkyl groups are important motifs in bioactive compounds, positively influencing pharmacokinetics, potency and F conformation. The oxidative difluorination of alkenes represents an H important strategy for their preparation, yet current methods are limited in their alkene-types and tolerance of electron-rich, readily oxidized functionalities, as well as in their scalability. Herein, we report a method for the difluorination of a number of unactivated alkene-types that is tolerant of electron-rich functionality, giving products that are otherwise unattainable. Key to success is the electrochemical generation of a hypervalent iodine mediator (in the presence of nucleophilic fluoride and HFIP) using an ‘ex-cell’ approach, which avoids the oxidative decomposition of the substrate. The more sustainable conditions give good to excellent yields of product in up to decagram scales<br /

3D print files for electrochemical reactors

.stl files for 3D printing electrochemical reactors designed by the LennoxLa

Structure-reactivity analysis of novel hypervalent iodine reagents in S-vinylation of thiols

The transition-metal free S-vinylation of thiophenols by vinylbenziodoxolones (VBX) constituted an important step forward in hypervalent iodine-mediated vinylations, highlighting the difference to vinyliodonium salts and that the reaction outcome was influenced by the substitution pattern of the benziodoxolone core. In this study, we report several new classes of hypervalent iodine vinylation reagents; vinylbenziodazolones, vinylbenziodoxolonimine and vinyliodoxathiole dioxides. Their synthesis, structural and electronic properties are described and correlated to the S-vinylation outcome, shedding light on some interesting facets of these reagents

DataSheet1_Structure-reactivity analysis of novel hypervalent iodine reagents in S-vinylation of thiols.ZIP

The transition-metal free S-vinylation of thiophenols by vinylbenziodoxolones (VBX) constituted an important step forward in hypervalent iodine-mediated vinylations, highlighting the difference to vinyliodonium salts and that the reaction outcome was influenced by the substitution pattern of the benziodoxolone core. In this study, we report several new classes of hypervalent iodine vinylation reagents; vinylbenziodazolones, vinylbenziodoxolonimine and vinyliodoxathiole dioxides. Their synthesis, structural and electronic properties are described and correlated to the S-vinylation outcome, shedding light on some interesting facets of these reagents.</p

DataSheet2_Structure-reactivity analysis of novel hypervalent iodine reagents in S-vinylation of thiols.PDF

The transition-metal free S-vinylation of thiophenols by vinylbenziodoxolones (VBX) constituted an important step forward in hypervalent iodine-mediated vinylations, highlighting the difference to vinyliodonium salts and that the reaction outcome was influenced by the substitution pattern of the benziodoxolone core. In this study, we report several new classes of hypervalent iodine vinylation reagents; vinylbenziodazolones, vinylbenziodoxolonimine and vinyliodoxathiole dioxides. Their synthesis, structural and electronic properties are described and correlated to the S-vinylation outcome, shedding light on some interesting facets of these reagents.</p

Alkene 1,3-Difluorination via Transient Oxonium Intermediates

The 1,3-difunctionalization of unactivated alkenes is an under-explored transformation that leads to moieties that are otherwise challenging to prepare. Herein, we report a hypervalent iodine-mediated 1,3-difluorination of homoallylic (aryl) ethers to give unreported 1,3-difluoro-4-oxy groups with moderate to excellent diastereoselectivity. The transformation proceeds through a different mode of reactivity for 1,3-difunctionalization, in which a regioselective addition of fluoride opens a transiently formed oxonium intermediate to rearrange an alkyl chain. The optimized protocol is scalable and shown to proceed well with a variety of functional groups and substitution on the alkenyl chain, hence providing ready access to this fluorinated, conformationally controlled moiety