Stereoselective hydrodefluorination of CF₃-substituted alkenes and gem-difluoroalkenes by H⁻

Abstract

Zn-catalyzed stereoselective hydrodefluorination of CF3-substituted alkenes, gem-difluoroalkenes and polyfluoroarenes by hydride ion addition has been realized through controlled C(sp3)–F and/or C(sp2)–F bonds cleavage.

Transition‐Metal‐Free Carbonyl Reduction and Hydrodefluorination of β‐Trifluoromethyl Enones with Hydrosilanes: Synthesis of gem‐Difluorovinyl Alcohols

“…Based on the experimental results and previous reports, [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] we propose two plausible reaction mechanisms for the transition-metal-free hydrodefluorination of β-trifluoromethyl enones with hydrosilanes, as depicted in Scheme 2D. Initially, reduction of the carbonyl group occurs preferentially in the presence of excess hydrosilane, yielding the OH-containing trifluoromethyl alkene A.…”

“…More impressively, in all of these cases, hydrosilylated, [19] defluorosilylated, [20] and excessive hydrodefluorinated byproducts were not obtained. [21] Besides (hetero)aryl enones, aliphatic substrate 1 s derived from 1cyclohexylethan-1-one was also a competent reaction partner. However, when the R 2 pattern was replaced with a Me, H, or CF 3 , only trace amounts or low yields of product 3 t-v were detected.…”

“…The present protocol offers an eco-friendly alternative when compared to the above methods: (i) hydrosilane is able to mediate the carbonyl reduction and defluorination as the hydrogen source and also provides the fluorine acceptor; [18] (ii) the reduced carbonyl moiety on the π-system is vital for the feasibility of the HDF process; (iii) the necessity for additional catalysts, additives, or ligands is eliminated. It should be noted that previously reported competitive hydrosilylation, [19] defluorosilylation, [20] and excessive hydrodefluorination [21] could be easily bypassed.…”

Transition-Metal-Free Hydrodefluoroamination of Trifluoromethyl Enones for the Synthesis of α-Fluoroenamides

“…By leveraging sequential carbonyl reduction, hydrodefluorination, and defluoroamination steps in one pot, the capability of the cascade to exclusively form α-fluoroenamides in moderate to good yields with moderate E -selectivity and good functional group tolerance through two C­(sp 3 )-F bond activations is demonstrated. Impressively, our method efficiently bypassed various previously reported competitive side reactions, including 1,4-addition ( I ), hydrodefluorination ( II ), hydroamination ( III ), hydrosilylation ( III ), defluorodiamination (Scheme B, a), defluoroamination ( IV ), and defluorosilylation ( IV ) (Scheme B, c). The configuration, unsaturated alkenyl motif, and auxiliary function of a carbonyl group in CF 3 -alkenes are all crucial for modulating the inherent reactivity and selectivity.…”

“…In addition, it was observed that Cs 2 CO 3 played a crucial role in the reaction, as other bases such as Na 2 CO 3 , K 2 CO 3 , and Et 3 N almost failed to promote the reaction (entries 11–13). Additionally, we explored various commonly used H-reductants (e.g., PhMe 2 SiH, LiAlH 4 , NaBH 4 ; entry 14), among which no superior result was observed.…”