Catalytic Deprotonative α-Formylation of Heteroarenes by an Amide Base Generated in Situ from Tetramethylammonium Fluoride and Tris(trimethylsilyl)amine

Abstract

Heteroarene formylations in DMF solution proceed in the presence of an amide base catalyst generated in situ from tetramethylammonium fluoride (TMAF) and tris(trimethylsilyl)amine (N(TMS) 3 ). The reaction proceeds at room temperature and has an operationally simple procedure. Various heteroarenes, including benzothiophene, thiophene, benzothiazole, oxazole, and indole derivatives, can be formylated with high functional group tolerance.

Unsymmetrical Thienopentalenes: Synthesis, Optoelectronic Properties, and (Anti)aromaticity Analysis

“…Synthesis of 3-Bromobenzo[b]thiophene-2-carbaldehyde (2). 61,62 Bromine (1.33 g, 428 μL, 8.32 mmol) in CHCl 3 (2 mL) was added dropwise to a stirred, ice cold solution of benzo[b]thiophene-2-carbaldehyde (1) (1.35 g, 8.32 mmol) in CHCl 3 (10 mL). After the addition, the solution was allowed to warm to rt and was stirred for 10 h. The mixture was diluted with CHCl 3 , washed once with water, twice with 1 M NaOH, and once with brine.…”

A Journey from June 2018 to October 2021 with N,N-Dimethylformamide and N,N-Dimethylacetamide as Reactants

“…The regioselective 2-formylation of 3-bromobenzofuran and 3-bromobenzothiophene was achieved with NaHMDS and DMF at low temperature in THF, while the C5 position was favored at room temperature (Scheme 31a) [87]. Formylation of a variety of fivemembered heteroarenes succeeded at room temperature with in situ generated amide base (Scheme 31b) [88]. The latter reactions proceed via proton abstraction and nucleophilic addition of the resulting carbanion to DMF.…”

“…base (Scheme 31b) [88]. The latter reactions proceed via proton abstraction and nucleophilic addition of the resulting carbanion to DMF.…”

Tetramethylammonium Fluoride Tetrahydrate-Mediated Transition Metal-Free Coupling of Aryl Iodides with Unactivated Arenes in Air

“…Our group has developed transition metal-free reactions involving C-C bond formation by amide bases generated in situ from fluoride and aminosilane. [56][57][58][59][60][61] Very recently, we reported the amide base-mediated biaryl coupling of aryl iodides and arenes. 62) Tetramethylammonium fluoride (TMAF) and hexamethyldisilazane (HMDS) were used to generate the amide base in situ.…”