Photoredox Generation of Carbon‐Centered Radicals Enables the Construction of 1,1‐Difluoroalkene Carbonyl Mimics

Abstract

We describe a facile, scalable route to access functional group-rich gem-difluoroalkenes. Using visible-light activated catalysts in conjunction with an arsenal of carbon-radical precursors, an array of trifluoromethyl-substituted alkenes undergoes radical defluorinative alkylation. Non-stabilized primary, secondary, and tertiary radicals can be used to install functional groups in a convergent manner that would otherwise be challenging via two-electron pathways. The process readily extends to other perfluoroalkyl-substituted alkenes. In addition, we report the development of an organotrifluoroborate reagent to expedite the synthesis of the requisite trifluoromethyl-substituted alkene starting materials.

Picking One out of Three: Selective Single C−F Activation in Trifluoromethyl Groups

“…In 2017, Molander extended this approach to 1°, 2° and 3° alkyl radicals with a variety of radical precursors having diverse functional groups for the conversion of 1‐CF 3 ‐alkenes 79 (Scheme ) . In these studies the organometallic complex Ru(bpy) 3 (PF 6 ) 2 but also the less expensive organic photocatalyst 4CzIPN were employed and no further additives were required.…”

“…In 2017, Molander extended this approacht o1 8,2 8 and3 8 alkyl radicals with av ariety of radical precursors having diverse functional groups for the conversion of 1-CF 3 -alkenes 79 (Scheme18). [39] In these studies the organometallic complex Ru(bpy) 3 (PF 6 ) 2 but also the lesse xpensive organic photocatalyst 4CzIPN were employed and no further additives were required. a-silylamine precursors 81 afforded the introductiono f cyclic anda cyclic amines into the gem-difluoroalkenes 80, whereas with RBF 3 Kp recursors 82 the process was successful with 18,2 8 and even the difficult 38 radicals.…”

Visible‐Light‐Induced Selective Defluoroborylation of Polyfluoroarenes, gem‐Difluoroalkenes, and Trifluoromethylalkenes

“…gem-Difluoroallylboranes are important synthons for preparation of bioactive fluorinated compounds. [13] We speculated that the HAT-induced nucleophilic NHC-boryl radical [33] could add to an a-trifluoromethyl alkene,and asubsequent single electron reduction [20] would promote an E1cB-type fluoride elimination [34] to access such boranes.I ndeed, after slight modifications of the photo-induced defluoroborylation protocol, this transformation was achieved efficiently under the transition-metal free conditions,w ith 4-CzIPN as the photocatalyst. Thes cope of trifluoromethylalkenes is illustrated in Scheme 4.…”

“…When ap roton is located at the paraposition of an electron-withdrawing group in the polyfluoroarene,protonation of intermediate IV occurs to generate the dearomatized hydroborylation product 4 (Scheme 6b), which may exclude the second possible pathway.D etailed coupling mechanistic investigations to distinguish between these pathways and gain abetter appreciation of the source of selectivity are currently under progress in our laboratory.W ith trifluoromethylalkene substrates,t he in situ formed NHC-boryl radical II will undergo radical addition to the alkene followed by aS ET reduction by the reduced state of 4-CzIPN to generate acarbanion VI. [20] Thefollowing E1cB-type fluoride elimination will provide the gem-difluoroallylborane product 8 (Scheme 6c).…”

“…[19b] TheMolander group achieved afascinating synthesis of gem-difluoroalkene moieties by photoredox-induced carbon radical addition to a-trifluoromethylalkenes. [20] On the other hand, the development of boron-centered radical chemistry has recently gained increasing momentum, and is conceptually appealing because it may offer regio-or stereoselectivities different from those of transition-metalcatalysis. [21] Elegant work from Fensterbank, Lacôte,M alacria, and Curran has shown that N-heterocyclic carbene (NHC)-boryl radicals can be generated by hydrogen atom abstraction from NHCÀBH 3 complexes, [21a, 22] which are powerful intermediates useful in building aw ide range of value-added boron compounds.F or instance,W ang has developed radical borylation/cyclization cascade of 1,6enynes with NHCÀBH 3 , [21c] and Curran and Taniguchi reported the Sato-Myers cyclization triggered by NHC-boryl radicals.…”