Photoredox‐Catalyzed Deoxygenation of Hexafluoroacetone Hydrate Enables Hydroxypolyfluoroalkylation of Alkenes

Abstract

An unprecedented photoredox‐catalyzed phosphine‐mediated deoxygenation of hexafluoroacetone hydrate was established to accomplish the hydroxylpolyfluoroalkylation of electron‐deficient alkenes. A range of bis(trifluoromethyl)carbinols were facilely accessed by using readily available hexafluoroacetone hydrate, instead of toxic gaseous hexafluoroacetone. A range of electron‐deficient alkenes are tolerated, giving the corresponding hydro‐hydroxylpolyfluoroalkylated products in moderate to high yields. Remarkable features of this synthetic strategy include operational simplicity, mild reaction conditions, excellent regioselectivity, and broad functional group tolerance. The success of this strategy relies on the delicate utilization of aldehyde/ketone‐gem‐diol intrinsic equilibrium, which offers an innovated open‐shell pathway for the assembly of synthetically challenging polyfluoroalkylated scaffolds.

Deoxygenation of oximes for the synthesis of pyrrolinesviahydroimination cyclization

“…10 a The resultant phosphine radical cation may react with carboxylic acids or alcohols to form phosphoranyl radicals that fragment to provide synthetically valuable acyl or alkyl radicals, respectively. 10 Analogically, direct deoxygenation of oximes was described by Yang 11 a–c and Yi 11 d groups (Scheme 1C), where the iminyl radicals induced strained ring opening or 5- exo-trig cyclization. Stimulated by our continuous interest in phosphoranyl and iminyl radical-participating reactions, we have now studied the N–O cleavage of non-functionalized oximes.…”

“…The development of radical chemistry has enabled the utilization of trivalent phosphines for direct deoxygenative reactions. 9–11 In 2018, the group of Xie and Zhu demonstrated an elegant photocatalytic approach for the single electron oxidation of PPh 3 under mild reaction conditions (Scheme 1B). 10 a The resultant phosphine radical cation may react with carboxylic acids or alcohols to form phosphoranyl radicals that fragment to provide synthetically valuable acyl or alkyl radicals, respectively.…”

Solvent-free base-controlled addition reaction ofH-phosphonates andH-phosphine oxides to α-CF3styrenes: facile synthesis of β-CF3-substituted phosphonates and phosphine oxides

“…12 However, hydrofunctionalization and difunctionalization of α-(trifluoromethyl)styrenes with retaining of three C–F bonds still remain formidable and unexplored challenges, largely because of the competing ready defluorination of α-(trifluoromethyl)styrenes. 13 For example, in 2019, Huang et al developed a novel base-promoted defluorinative phosphorylation of α-(trifluoromethyl)styrenes, and diverse phosphorus-containing gem -difluoroalkenes were synthesized with high efficiency via the S N 2′-type pathway (Scheme 1c). 14…”

Photochemical Alkene Trifluoromethylimination Enabled by Trifluoromethylsulfonylamide as a Bifunctional Reagent

“…CF 3 and amino groups are privileged moieties engaged in diverse biologically active products . Our continuing interest in alkene difunctionalization prompted us to explore the feasibility of trifluoromethylamination of olefins by trifluoromethylsulfonamide. Notably, Glorius’s group first recognized that installation of diphenylmethanimine into an oxime ester as the EnT acceptor core would favor the homolytic N–O bond cleavage .…”