Deoxygenative dual CO2 conversions: methylenation and switchable N-formylation/N-methylation of tryptamines

Abstract

The unprecedented one-pot synthesis of N-formyl/N-methyltryptolines from tryptamines was achieved via phenylsilane-assisted deoxygenative dual CO₂ conversions. Two CO₂ molecules acted as different synthons and were converted into methylene and N-formyl/N-methyl groups. The CO₂ reduction step was catalyzed by a pentanuclear zinc complex at atmospheric pressure under solvent-free conditions. The N-formyl/N-methyl products could be switched by changing the amount of phenylsilane, and the amounts of in situ generated bis(silyl)acetals and silyl formates were key to the chemoselectivity. Methylenation, N-formylation, and N-methylation proceeded via the Pictet–Spengler reaction, amine–acid condensation, and the Eschweiler–Clarke reaction, respectively. The CO₂ reduction with phenylsilane could also be applied to the one-pot three-step synthesis of spiro[oxindole-pyrrolidine]s.