Indium-Mediated Reformatsky-Type Reaction of β-Aminovinyl Chlorodifluoro­methyl Ketones with Heteroaryl Aldehydes

Abstract

Indium can efficiently mediate the Reformatsky-type reaction between some b-aminovinyl chlorodifluoromethyl ketones and a series of heteroaryl aldehydes, to afford the corresponding difluoromethylene compounds in good to high yields.

Bidentate and Tetradentate β‐Aminovinyl Trifluoromethylated Ketones and Their Copper(II) Complexes: Synthesis, Characterization and Redox Chemistry

“…These organic substrates can be structurally modified at different sites (R 1 , R 2 , R 3 and R 4 ), by variation of the amine (R 1 ), the substitution on the C=C bond (R 2 and R 3 ) and at the fluoroalkyl moiety (R 4 ). [14][15][16][17][18][19][20] In principle, organic functionalities with specific properties can be attached at the four positions of the enaminone from readily available starting materials using different synthetic strategies. The fluorine atoms are significant as they may induce specific interactions in the solid state such as F···H, F···F, F···O=C, F···N and F···S contacts; these properties have been used with success in materials science and crystal engineering, [30][31] in medicinal chemistry in order to design more active drug candidates and have been exemplified by cocrystallized structures of potent therapeutic agents with target enzymes.…”

Indium-mediated reduction of β-aminovinyl chloro-difluoromethylated ketones in the presence of heteroaryl aldehydes

“…This paper is an extension of our previous report [6], that describes indium as a potential synthetic electron transfer reagent, to promote C-C coupling reactions with some new baminovinyl chloro-difluoromethylated ketones and a series of heteroaryl aldehydes (Scheme 1). The coupling adducts are envisaged as potential building blocks to prepare new fluorinated aromatics and heterocycles.…”

“…Some chloro-difluoromethylated analogs were also prepared in these studies, but the synthetic potential that could be derived from the chemoselective activation of the C-Cl bond, has been rarely investigated [5]. As part of a research program directed to the synthesis of novel fluorinated heterocycles with potential biological applications, we presented the indium activation of some aromatic chloro-difluoromethylated enaminones in the presence of a series of heteroaryl aldehydes [6]. Indium closely resembles zinc in several aspects and its first ionization potential (5.8 eV) is the lowest relative to other metal elements near in the periodic table [7].…”

Vinylic Halogenation in 4‐Alkylidenazetidin‐2‐ones

“…[9] Direct bromination of more complex substrates such as uracils [10] or β-amino-and β-alkoxy α,β-unsaturated compounds, has been accomplished more frequently, [11] as in the cases of the bromination of 2-alkylidenetetrahydrofurans and 2-alkylidenepyrrolidines, [12] β-butoxyvinyl trifluoromethyl ketone [13] and β-aminovinyl chlorodifluoromethyl ketones. [14] To the best of our knowledge, vinylic substitution on β-amido α,β-unsaturated esters has never been reported in the literature.…”