Tunable alkoxy-nucleophilic addition under photochemical condition: Dioxidation of gem‑difluoroalkenes with O2

Synthesis of α-Difluoromethylene Ethers via Photoredox-Induced Hyperconjugative Ring Opening of gem-Difluorocyclopropanes

“…Notably, the classic S N 2 reaction was not feasible for the reaction of alcohols with difluoromethyl halides (i.e., −CF 2 I and −CF 2 Br) (Scheme b). Recently, sporadic examples, involving Cu­(II)- and Co­(II)-catalyzed reaction of gem -difluoroalkenes with phenols to construct RCF 2 –OR’ bond, have been reported . Carbon-fluorine bond (C–F) is the strongest carbonic single bond, the C–F bond activation was considered to be one of the most challenging problems in modern synthetic chemistry .…”

A diselenide additive enables photocatalytic hydroalkoxylation ofgem-difluoroalkenes

“…Specifically, photocatalysts with excited state reduction potentials close to the measured peak potential of the gem-difluoroalkene substrate 6a (E p = +1.0 V, see ESI †) afforded the desired product (entries 2, 6, 7), whereas photocatalysts with reduction potentials significantly lower than that of 6a did not generate product (entries 3-5). This trend suggested that oxidation of the gem-difluoroalkene 28,[33][34][35] might promote the desired transformation. Moreover, the highest yield of 7a was obtained using the photocatalyst possessing the highest excited state reduction potential, PC-I [E 1/2 (PC* + /PC ) = +1.70 V; 36,37 entry 7].…”

“…The excited state photocatalyst PC-I* + [ E 1/2 (PC* + /PC˙) = +1.70 V] 36,37 then oxidizes (BnSe) 2 ( E p = +1.0 V, see ESI†) to generate PC-I˙ and selenyl radical cation 10 , which in turn oxidizes gem -difluoroalkene 6 ( E p = +1.0–1.4 V, see ESI†) to generate radical cation 6 •+ . 28,33–35 The resultant PC-I˙ [ E 1/2 (PC + /PC˙) = –0.97 V] 36,37 reduces selenyl radical 11 to regenerate the ground state PC-I + and form selenolate 12 (p K a calc’d = 6.61 in H 2 O) 45 – direct reduction of (BnSe) 2 is unlikely given its low measured reduction potential ( E p = –1.7 V, see ESI†). Separately, alcohol nucleophile 9 adds to radical cation 6˙ + to form radical oxonium intermediate 13 , an acidic species that can release a proton to form radical intermediate 14 and selenol 15 .…”

“…24 Previous examples of this general reactivity pattern have exploited photoand transition metal catalysis, though these systems exclusively promote difunctionalization, and simple monofunctionalization/hydroalkoxylation reactions remain unreported. [26][27][28] To address this gap, we report a photocatalytic strategy to promote convergent hydroalkoxylation reactions of gem-difluoroalkenes with aliphatic alcohols that significantly expands the scope of accessible a,a-difluorinated ethers (Scheme 1C). Notably, an uncommon diselenide co-catalyst serves a key role in promoting the hydrofunctionalization process, perhaps by facilitating a radical-polar crossover event.…”

“…A combination of physicochemical data and literature precedent for photocatalyzed functionalization reactions of alkenes and gem-difluoroalkenes supports a mechanism involving diselenide-mediated oxidation of the gem-difluoroalkene to form a radical cation (6-6 + ), nucleophilic attack by the alcohol (9) to generate radical oxonium 13, loss of an acidic proton to afford stabilized C-based radical 14 and selenol 15, and subsequent H abstraction to release a,a-difluorinated ether product 7 (Scheme 3). 28,[40][41][42] This net process initiates with blue light irradiation that promotes two separate events: (1) homolytic fragmentation of (BnSe) 2 to form selenyl radical 11, 43,44 and (2) excitation of PC-I + to PC-1* + . The excited state photocatalyst PC-I* + [E 1/2 (PC* + /PC ) = +1.70 V] 36,37 then oxidizes (BnSe) 2 (E p = +1.0 V, see ESI †) to generate PC-I and selenyl radical cation 10, which in turn oxidizes gem-difluoroalkene 6 (E p = +1.0-1.4 V, see ESI †) to generate radical cation 6 + .…”