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

Abstract

A systematic search for reaction pathways for the vinylogous Mannich-type reaction was performed by the artificial force induced reaction method. This reaction affords δ-amino-γ-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 Si-O 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.

Artificial Force Induced Reaction (AFIR) Method for Exploring Quantum Chemical Potential Energy Surfaces

“…Applications have already been made to a variety of organo and organometallic catalyses 52–64. Catalysis of metal clusters has also been a target of previous applications 70,71.…”

“…This account will focus on the artificial force induced reaction46–49 (AFIR) method, developed by ourselves and implemented in the GRRM (global reaction route mapping) program 50,51. The AFIR has been applied most extensively to organo and organometallic catalysis, in combination with quantum chemical calculations 52–64. The other applications are: gas‐phase reactions;65–67 enzyme catalysis;68 domino reactions;69 and metal‐cluster catalysis 70,71.…”

Ionic and Neutral Mechanisms for C–H Bond Silylation of Aromatic Heterocycles Catalyzed by Potassium tert-Butoxide

“…It is not surprising that a reaction may have more than one mechanism. [10][11][12] The accompanying paper, communicated together with this manuscript, describes the radical mechanism for this reaction. We present here the ionic mechanism of the KO t Bu catalyzed silylation of heteroaromatic C-H bonds.…”

Exploring transition state structures for intramolecular pathways by the artificial force induced reaction method

“…Fully automated reaction path search in organic reactions had been not very successful until 2010, especially for intermolecular associative reactions of type A + B → X (+Y). Since 2010, the very efficient artificial force induced reaction (AFIR) method has been developed, and it has been applied to a variety of organic reactions such as multicomponent (MC) reaction, organometallic catalysis, metalloenzyme, and photoaddition reaction . It can be applied not only to associative reactions between two or more molecules but also to intramolecular bond rearrangements.…”