The ortho‐Difluoroalkylation of Aryliodanes with Enol Silyl Ethers: Rearrangement Enabled by a Fluorine Effect

Abstract

Presented herein is an intriguing effect of fluorine, and it allows difluoroenol silyl ethers to couple with aryliodanes in ar edox-neutral manner to affordo rtho-iodo difluoroalkylated arenes.T he remaining iodide group provides av ersatile platform for converting the products into various valuable difluoroalkylated arenes.T he reaction shows excellent functional-group compatibility and broad substrate scope. AD FT mechanistic study suggests that the fluorine effect facilitates as ubtle nucleophilic attacko ft he oxygen atom of enol silyl ethers onto aryliodanes,t herefore leading to ar earrangement.Scheme 1. Backgrounda nd initial results. TMS = trimethylsilyl.

Synthesis of Versatile Aryliodine Synthons by Aryliodonium Rearrangement Reactions

“…In 2019, Peng and co‐workers reported an intriguing rearrangement of aryliodanes with difluoroenol sily ether, leading to ortho ‐iodo difluoroalkylated arenes [27] . The remaining iodide group in HIRs provides a versatile platform for converting the products into various valuable difluoroalkylated arenes.…”

2,2-difluorovinyl benzoates for diverse synthesis of gem-difluoroenol ethers by Ni-catalyzed cross-coupling reactions

“…Bonnet–Delpon and co-workers already demonstrated that gem -difluoroalkene-derivatized artemisinins exhibit prolonged in vivo antimalarial activity through replacement of the carbonyl group 5 . Moreover, gem -difluoroalkenes can be transformed to various organofluorine motifs 6 , 7 such as trifluoromethyl 8 – 10 , difluoromethyl 11 – 14 , monofluoroalkenyl 15 – 18 , and difluoromethylenyl 19 , 20 groups for late-stage functionalization. Conventionally, Wittig- or Horner-Wadsworth-Emmons-type olefination and S N 2’ reactions of vinyl trifluoromethyl compounds are widely employed to construct the gem -difluoroalkene moiety 7 , 21 , 22 .…”

Promising reagents for difluoroalkylation

“…52 Difluoroacetic acids were also found to be good difluoroalkyl radical precursors for decarboxylative difluoroalkylation. [53][54][55][56][57] In 2019, the Zhu group realized visible-light-induced acyldifluoroalkylation of alkenyl aldehydes with difluoroacetic acids (Scheme 9). 58 PhI(OAc) 2 should be added as the oxidant, which could react with the excited state Ir(III)* and difluoroacetic acids via SET process to give difluoromethyl radical.…”