Selective single C–F bond arylation of trifluoromethylalkene derivatives

Abstract

Through an SN2′ amination, N-alkylation and palladium-catalyzed allylic substitution sequence, we realized ipso-C–F bond arylation/alkenylation of trifluoromethylalkene derivatives.

The role of allyl ammonium salts in palladium-catalyzed cascade reactions towards the synthesis of spiro-fused heterocycles

“…To improve the reactivity of the starting material further on, other allylic leaving groups were considered. In this respect, allylic ammonium salts, which have been largely neglected in intermolecular palladium-catalyzed allylic substitutions, attracted our attention 39 , 46 , 47 . This class of compounds are in general highly stable and can be conveniently prepared from a variety of amines.…”

“…Obviously, applying substrate 2d does not allow to distinguish between S N 2-mechanism and S N 2’-mechanism in the first reaction step due to its symmetry. Based on the actual interest in fluorinated building blocks 51 – 53 , the gem -difluorinated allylic ammonium salt 2e 39 was reacted with 2-iodophenol, which gave product 3c in 99% yield and excellent regioselectivity. Again, the following palladium-catalyzed steps took place smoothly and provided 4c in high yield (80%).…”

“…2 ) was investigated. Most of the ammonium salts were conveniently obtained from commercially available phenylboronic acid and vinyl bromides via Suzuki reaction, base-mediated amination, and final N -methylation 39 . With regard to the cascade reaction, both electron-donating groups including alkyl, aryl, alkoxy and aryloxy and electron-withdrawing groups including fluoro and chloro were perfectly compatible with the conditions, and the corresponding products 4f – 4l were obtained in 53 − 86% yield.…”

“…Herein, we describe our recent efforts to establish a palladium-catalyzed allylic substitution/Heck/C–H activation(/alkyne) cascade processes for the synthesis of spiro-fused heterocycles. Key challenges of such processes are obviously the compatibility of the well-matched reactant partners 39 , the required conditions of the individual reactions, the development of a general catalyst system able to promote all three (or four) transformations efficiently, and to achieve the needed high chemo-selectivity, regio-selectivity, and stereoselectivity throughout all elementary steps.…”

Defluoroalkylation of sp3 C−F Bonds of Industrially Relevant Hydrofluoroolefins

“…[13][14][15] In contrast, methods for selective carboncarbon bond formation from vinylic trifluoromethyl groups are far less well advanced, likely due to the difficulty in controlling the reactivity of the adjacent C=C p-system. [16][17][18][19] Ito andc o-workers have reportedt he enantioselective defluoroalkylation of trifluoromethyl-substituted alkenes. [20] The key step in this report was the defluoroborylation of the substrateu sing ac hiral copper(I) catalyst.B oth racemic and enantioselective variants of this reactionh ave been widely studied.…”