Mild Access to N-Formylation of Primary Amines using Ethers as C1 Synthons under Metal-Free Conditions

A new synthetic protocol has been developed for the synthesis of N-formamide derivatives using ethers as a C1 synthon under metal-free reaction conditions. The reaction is proposed to proceed through C-H functionalization, C-O cleavage, and C-N bond formation. This protocol is applicable to a variety of primary amines resulting in N-formamides in moderate to good yields. 1,4-dioxane was chosen as best C1 synthon after screening with various ethers. Mechanistic studies disclosed that the reaction proceeds through a radical pathway. While using alpha-amino ketones a alpha-alkylation product was formed rather than formylation. By replacing dioxane with Tetramethylethylenediamine (TMEDA) under standard conditions also gave the N-formamide derivatives in moderate yields.