Chemoselective catalytic hydrodefluorination of trifluoromethylalkenes towards mono-/gem-di-fluoroalkenes under metal-free conditions

Abstract

Fluorine-containing moieties show significant effects in improving the properties of functional molecules. Consequently, efficient methods for installing them into target compounds are in great demand, especially those enabled by metal-free catalysis. Here we show a diazaphospholene-catalyzed hydrodefluorination of trifluoromethylalkenes to chemoselectively construct gem-difluoroalkenes and terminal monofluoroalkenes by simple adjustment of the reactant stoichiometry. This metal-free hydrodefluorination features mild reaction conditions, good group compatibility, and almost quantitative yields for both product types. Stoichiometric experiments indicated a stepwise mechanism: hydridic addition to fluoroalkenes and subsequent β-F elimination from hydrophosphination intermediates. Density functional theory calculations disclosed the origin of chemoselectivity, regioselectivity and stereoselectivity, suggesting an electron-donating effect of the alkene-terminal fluorine atom.

Metal-free photocatalytic intermolecular trifluoromethylation-gem-difluoroallylation of unactivated alkenes

“…15,16 The reduction of 5f with Red-Al afforded monofluoroalkene 5fd with excellent Z / E selectivity. 17…”

Diazaphospholene‐Catalyzed Radical Reactions from Aryl Halides**

“…These defluorination transformations do not appear to involve radical chemistry. [19,20] PhSiH 3 and HB(pin) are not directly reactive with 3 in acetonitrile, unlike the DAP fluoride. [21] DAP chlorides and bromides are reduced to 1 using LiAlH 4 or Red-Al, [1] but these reductants are incompatible with acetonitrile, require cooling, produce significant phosphine (PH 3 ) byproduct, and give modest yields of 1, making them unsuitable as terminal reductants catalytic reactions at room-temperature.…”

Diazaphospholene‐Catalyzed Radical Reactions from Aryl Halides**

“…These defluorination transformations do not appear to involve radical chemistry. [19,20] PhSiH 3 and HB(pin) are not directly reactive with 3 in acetonitrile, unlike the DAP fluoride. [21] DAP chlorides and bromides are reduced to 1 using LiAlH 4 or Red-Al, [1] but these reductants are incompatible with acetonitrile, require cooling, produce significant phosphine (PH 3 ) byproduct, and give modest yields of 1, making them unsuitable as terminal reductants in catalytic reactions at room-temperature.…”

“…A cinnamyl thioether underwent clean conversion to form 8 f. The cyclization of substrates containing aryl fluorides to form 8 g and 8 h were successful, with no defluorination observed. [20] Two isomeric trifluoromethyl containing cinnamyl ethers also underwent cyclization to form 8 i and 8 j without defluorination. Nitrile containing ethers underwent cyclization to form 8 k and 8 l, and ester groups were similarly tolerated to give 8 m and 8 n. A terminal allyl ether cyclized with high conversion to give 8 o but small amounts of what we suspected were the 6-endo cyclization mode were noted.…”