Access to gem-Difluoroalkenes via Organic Photoredox-Catalyzed gem-Difluoroallylation of Alkyl Iodides

Abstract

An organic photoredox-catalyzed gem-difluoroallylation of α-trifluoromethyl alkenes with alkyl iodides via C–F bond cleavage for the synthesis of gem-difluoroalkene derivatives is reported. This transition-metal-free transformation utilized a readily available organic dye 4CzIPN as the sole photocatalyst and employed a common chemical N,N,N′,N′-tetramethylethylenediamine as the radical activator of alkyl iodides via halogen-atom transfer. In addition, a variety of iodides, including primary, secondary, and tertiary alkyl iodides, were tolerated and provided good to high yields.

Photocatalytic Hydroalkylation of Aryl-Alkenes

“…Addition of the carbon-centered radical to the aryl-alkene is well precedented, affording a highly stabilized radical Int-3 . 26 , 27 Reduction of radical Int-3 to the anion Int-4 by the reduced Ir(II) complex ( E red [Ir III /Ir II ] = −1.37 V vs SCE) 29 returns the ground state Ir(III) catalyst. Literature reports of single-electron reduction of substituted benzyl radicals ( E red [Bn · /Bn – ] = −1.43 V vs SCE) 44 show this potential to be beyond the reach of the photocatalyst; this result was confirmed experimentally, with no hydroalkylation of styrene observed.…”

“…Halogen atom transfer between the α-amino radical Int-1 and alkyl iodide 2 has been shown to be very fast (10 8 M – 1 s – 1 ), providing key alkyl radical Int-2 . , The formation of this radical is further verified through the detection of its TEMPO adduct 4 (Scheme a). Addition of the carbon-centered radical to the aryl-alkene is well precedented, affording a highly stabilized radical Int-3 . , Reduction of radical Int-3 to the anion Int-4 by the reduced Ir­(II) complex ( E red [Ir III /Ir II ] = −1.37 V vs SCE) returns the ground state Ir­(III) catalyst. Literature reports of single-electron reduction of substituted benzyl radicals ( E red [Bn · /Bn – ] = −1.43 V vs SCE) show this potential to be beyond the reach of the photocatalyst; this result was confirmed experimentally, with no hydroalkylation of styrene observed.…”

“… 24 , 25 Wang et al exploited pendant α-trifluoromethyl groups to afford the difluoroalkenes after elimination of fluoride. 26 , 27 Here, we present the development of a photocatalytic hydroalkylation reaction without the requirement for additional transition metal complexes or strategically placed leaving groups, allowing access to hydroalkylation products catalyzed by visible light. 28 Thus, we became interested in developing a reaction platform allowing for the photocatalytic, radical C–C bond formation between aryl-alkenes and alkyl iodides.…”

“…There are several methods to turnover such radical intermediates to give synthetically useful transformations; the alkylation of aryl-alkenes with alkyl iodides has been achieved using two methods (Scheme b). Leonori et al reported the formal Heck reaction utilizing cobalt (and later copper) complexes to trap the benzylic radical and returning the derivatized alkene through β-hydride elimination. , Wang et al exploited pendant α-trifluoromethyl groups to afford the difluoroalkenes after elimination of fluoride. , Here, we present the development of a photocatalytic hydroalkylation reaction without the requirement for additional transition metal complexes or strategically placed leaving groups, allowing access to hydroalkylation products catalyzed by visible light . Thus, we became interested in developing a reaction platform allowing for the photocatalytic, radical C–C bond formation between aryl-alkenes and alkyl iodides.…”

Defluorinative Alkylation of Trifluoromethyl Alkenes with Soft Carbon Nucleophiles Enabled by a Catalytic Amount of Base

“…Meanwhile, catalytic variants by virtue of transition metals, [6] photoredox, [7] and electrochemical [8] technique were also described to enable the incorporation of diversified functional groups attached to gem ‐difluoroalkenes through β‐F elimination of TAs. In the historical context of synthesizing alkyl substituted gem ‐difluoroalkenes, existing protocols usually relied on the pre‐functionalized alkyl group progenitors as the coupling partners, such as halides, [6c,i,j,7f–i,8a,b] acetals, [6d] oxime ethers, [6e,7e] carboxylates, [6h,7b–d,8c] trifluoroborates, [7a] etc (Figure 1a). Notwithstanding these achievements, the exploration of efficient and operationally mild strategies that avoid the use of organometallic reagents, strong bases, and transition metals, and install a densely functionalized alkyl group to gem ‐difluoroalkenes that permits further elaborations is highly sought‐after.…”