Latent Carbene in Diaminomethylation of Benzenes: Mechanism and Practical Application

Silylformamidine 1 exists in equilibrium with its carbenic form 1′ due to an easy migration of the silyl group. The reaction of 1 with variously substituted fluorobenzenes proceeds as an insertion of the nucleophilic carbene 1′ into the most acidic C–H bond upon mixing the reagents and does not require any catalyst. According to DFT calculations, the classical interpretation of the insertion reaction proceeding via a three-membered transition state structure requires high activation energy. Instead, low activation barriers are predicted for a transfer of the most acidic proton in the aromatic substrate to the carbene carbon. As the next step, a barrierless rearrangement of the formed ion pair toward the product completes the process. The reactivity of substituted benzenes in the reaction with silylformamidine can be roughly assessed by calculated pKa (DMSO) values for the C–H hydrogens. Benzene derivatives having pKa approx. less than 31 can undergo C–H insertion. The reaction provides aminals as the first products, which can easily be transformed into the corresponding aldehydes via acidic hydrolysis. As silylformamidine 1 is tolerant to many functional groups, the reaction can be applied to numerous benzene derivatives, making it a reliable strategy for application in organic synthesis.