Base‐Promoted Formylation and N‐Difluoromethylation of Azaindoles with Ethyl Bromodifluoroacetate as a Carbon Source

Abstract

Azaindoles | C1 building blocks | Difluoromethylene | Hydrolysis | Synthetic methodsWe reported for the first time that ethyl bromodifluoroacetate directly reacts with azaindole without transition metal catalysis to produce a difluoromethyl protected 5-aldehyde group product in one step. It is worth mentioning that the reacted aldehyde group is only formed at the 5 position. In addition, this method has good substrate applicability and functional group tolerance. Finally, we also carried out some mechanism auxiliary experiments, which confirmed that the aldehyde-based carbon comes from ethyl bromodifluoroacetate.

Efficient Synthesis of N-(Difluoropropenyl)amides/Amines from Fluorinated Olefins under Base Promotion

“…Based on our research group's previous work on trifluoromethylation and difluoromethylation, we report a concise and efficient method for synthesizing codifluoromethyl olefins. [23][24][25][26][27][28][29][30] Template for SYNLETT Thieme We initially chose the reaction of pmethoxyphenylacrylamide (1a) and 3-bromo-3,3difluoropropene (2) as the difluoromethylation reagents for the model system. The target compound was successfully obtained by using potassium tert-butoxide ( t -BuOK) as a base and acetonitrile (MeCN) as a solvent and reacting at 100 °C for 8 hours with an isolated yield of 55% (Table 1, entry 3).…”

“…[8][9][10][11][12][13][14][15][16][17][18][19][20][21] Although there have been many successful syntheses of ,-difluorinated olefins, a simple and efficient synthesis of high-value-added ,-difluoroolefins, preferably by methods not requiring transition metals, remains our goal. Based on our previous work on trifluoromethylation and difluoromethylation, [22][23][24][25][26][27][28] we report a concise and efficient method for synthesizing ,-difluorinated olefins (Scheme 1d).…”