Electron-Transfer Photoredox Catalysis: Development of a Tin-Free Reductive Dehalogenation Reaction

Abstract

We report an operationally simple, tin-free reductive dehalogenation system utilizing the well-known visible-light-activated photoredox catalyst Ru(bpy)(3)Cl(2) in combination with (i)Pr(2)NEt and HCO(2)H or Hantzsch ester as the hydrogen atom donor. Activated C-X bonds may be reduced in good yields with excellent functional-group tolerance and chemoselectivity over aryl and vinyl C-X bonds. The proposed mechanism involves visible-light excitation of the catalyst, which is reduced by the tertiary amine to produce the single-electron reducing agent Ru(bpy)(3)(+). A subsequent single-electron transfer generates the alkyl radical, which is quenched by abstraction of a hydrogen atom. Reductions can be accomplished on a preparative scale with as little as 0.05 mol % Ru catalyst.

A highly reducing metal-free photoredox catalyst: design and application in radical dehalogenations

“…19 In this system, PTH acts as a photoreductant in a similar manner to Ir(ppy) 3 with a reduction potential (E 1/2 * = À2.1 V vs. SCE) significantly higher than Ir(ppy) 3 (E 1/2 * = À1.7 V vs. SCE). Based on our interest in metalfree ATRP, we envisioned that the same radical based processes enabled by PTH could also be used to access a variety of carboncentered radical intermediates that could be used for subsequent synthetic transformations, such as the reduction of carbon-halogen bonds.…”

“…[14][15][16] However, despite the notable advantages of photoredox catalysis, 1 a number of major challenges still exist. This includes the use of catalysts based on rare-earth transition metals such as Ru and Ir, which have inherent limitations due to the cost of the catalyst itself (B$1 mg À1 for Ir(ppy) 3 ), 17 as well as the expense associated with the removal of trace metals from the desired products -critical for applications from pharmaceuticals to micro-electronics. In addition, although an assortment of activated carbon-halogen bonds have been accessed using these catalysts, 1 higher energy unactivated halides are a significantly more challenging task, with only unactivated iodides being explored to date.…”

“…After optimization (Tables S1-S3, ESI †), quantitative reduction of iodobenzene (1) to benzene (98% yield) could be achieved in 1 h under 380 nm LED irradiation (Table 1) in the presence of 5 mol% PTH and 5 equivalents each of tributylamine and formic acid. It is worth noting that although we utilize higher catalyst loadings than traditional metal-based photoredox systems such as Ir(ppy) 3 , calculations based on a cost per reaction basis illustrate that 5 mol% PTH is still over an order of magnitude cheaper than using 0.01 mol% of rare-earth derived Ir(ppy) 3 (see ESI †). Significantly, the reaction was compatible with a range of solvents as well as amine sources leading to similar yields and reaction rates.…”

“…In each case, no reaction was observed (Table S2, ESI †). We next sought to compare the performance of PTH with widely used photoredox systems such as Ir(ppy) 3 , as well as the metal-free PDI based system, and in both cases we observed higher reactivity. 20 For example, only 23% yield was obtained after 1 h for the reduction of iodobenzene using Ir(ppy) 3 when compared to the quantitative reduction observed for PTH (Table 1).…”

“…We next sought to compare the performance of PTH with widely used photoredox systems such as Ir(ppy) 3 , as well as the metal-free PDI based system, and in both cases we observed higher reactivity. 20 For example, only 23% yield was obtained after 1 h for the reduction of iodobenzene using Ir(ppy) 3 when compared to the quantitative reduction observed for PTH (Table 1). 21 It is worth noting that the 380 nm LED light source matches the excitation maximum of Ir(ppy) 3 (378 nm), 1 while the absorption spectrum of PTH has only a small shoulder at this wavelength (Fig.…”