Multiple Reaction Pathways Operating in the Mechanism of Vinylogous Mannich-Type Reaction Activated by a Water Molecule

A systematic search for reaction pathways for the vinylogous Mannich-type reaction was performed by the artificial force induced reaction method. This reaction affords -amino--butenolide in one pot by mixing 2-trimethylsiloxyfuran, imine, and water under solvent-free conditions. Surprisingly, the search identified as many as five working pathways. Among them, two concertedly produce anti and syn isomers of the product. Another two give an intermediate, which is a regioisomer of the main product. This intermediate can undergo a retro-Mannich reaction to give a pair of intermediates: an imine and 2-furanol. The remaining pathway directly generates this intermediate pair. The imine and 2-furanol easily react with each other to afford the product. Thus, all of these stepwise pathways finally converge to give the main product. The rate-determining step of all five (two concerted and three stepwise) pathways have a common mechanism: concerted SiO bond formation through the nucleophilic attack of a water molecule on the silicon atom followed by proton transfer from the water molecule to the imine. Therefore, these five pathways have comparable barriers and compete with each other.