Stereospecific Alkenylation of C−H Bonds via Reaction with β-Heteroatom-Functionalized Trisubstituted Vinyl Triflones¹

Abstract

Aryl and alkyl β-heteroatom-trisubstituted vinyl triflones react with THF and cyclohexane to undergo trifluoromethyl radical-mediated C−H functionalization reactions to afford E and Z β-heteroatom-trisubstituted olefins. Most reactions proceed with both high yield and high stereospecificity (retention of configuration). β-Substituents which have been employed in this study are iodine, bromine, fluorine, benzoate, ethylcarbonate, and phthalimide. β-Substituents bearing powerful electron-releasing groups such as alkoxy or amino render the vinyl triflone unreactive.

Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators

“…Only the transoid (formally Z ) quaternary, α-(1′-fluoro-2′tributylstannyl) vinyl-AAs were observed as judged by the consistent vicinal J H–F values observed (71–73 Hz) 58 across all side chains. This is notable because radical sulfide-stannane interchange reactions are known to sometimes lead to scrambling of alkene geometry.…”

“…The condensation is stereoselective as exclusively the transoid (nominally Z ) addition/elimination products are obtained, as inferred from the 29–34 Hz vicinal J H–F coupling constants observed 9a–j . 50b,57 This condensation proceeds efficiently across a diverse array of AA ester enolates including those bearing thioether (Met), silyl ether (Tyr), acetal (Tyr), imine (Lys), amide (Trp) functionality. Moreover, even though a quaternary AA-center is being formed, sterically encumbered AA ester enolates, such as those carrying either α-(Val) or β-alkyl branching (Leu), give some of the highest yields.…”

Copper-Catalyzed Alkenylation of Alcohols with β-Nitrostyrenes via a Radical Addition–Elimination Process

“…In the absence of alcohol, only denitro methylation product was obtained and the self-coupling of β-nitrostyrenes was not observed, which suggested that the styrene radical is not formed in the reaction system (Scheme 4, b). Moreover, an intermolecular kinetic isotope effect (KIE) experiment was carried out for isopropanol, and a significant KIE value of k H /k D = 4.8 was observed (Scheme 4,c). It indicates that the rate-determining step of the sp 3 C-H bond cleavage should be involved in this procedure.…”

Titanium‐Mediated Domino Radical Cyclization/β Elimination of Phosphine Oxides

“…[22] Because sulfinyl radicals are very special b-eliminating moieties, the elimination rate of which is close to the diffusion limit, [23] the observed side reaction led us to speculate that a phosphine oxide might be a viable, kinetically different alternative to a sulfoxide and afford a novel reaction sequence. Intermolecular (but achiral), [24,25] and semi-intermolecular [26] versions involving sulfones and sulfides as leaving groups have also been reported, but none involving phosphine oxides.…”

“…[22] Because sulfinyl radicals are very special b-eliminating moieties, the elimination rate of which is close to the diffusion limit, [23] the observed side reaction led us to speculate that a phosphine oxide might be a viable, kinetically different alternative to a sulfoxide and afford a novel reaction sequence. Intermolecular (but achiral), [24,25] and semi-inter-molecular [26] versions involving sulfones and sulfides as leaving groups have also been reported, but none involving phosphine oxides.In 1988, Nugent and RajanBabu reported that [Cp 2 TiCl] was able to transfer one electron to oxiranes with formation of b-titanoxy radicals, which could be used further in syntheses. [27] This seminal work was made even more useful when Gansäuer et al rendered this reaction catalytic, [28] and soon thereafter asymmetric.…”