Developing an Ionic Halide Transfer and Addition Process Driven by Theoretical and Experimental Synergy.

Area of Science:

• Organic Chemistry
• Synthetic Methodology
• Computational Chemistry

Background:

• Atom Transfer Radical Addition (ATRA) is a widely used method for forming C-C bonds.
• Developing novel, efficient, and versatile synthetic methods is crucial for organic chemistry.
• Ionic reaction mechanisms offer alternative pathways to radical-based transformations.

Purpose of the Study:

• To develop a novel ionic reaction as an alternative to the ATRA reaction.
• To establish a base-mediated protocol for concurrent C(sp3)-C(sp3) and C(sp3)-X bond formation.
• To elucidate the mechanism of the novel reaction using theoretical and experimental approaches.

Main Methods:

• Combines theoretical (DFT modeling) and experimental approaches.
• Utilizes a base-mediated protocol termed Halide Transfer and Addition (HTA).
• Employs α-halo carbonyls and electron-deficient alkenes as starting materials.

Main Results:

• Developed a novel ionic alternative to ATRA, named Halide Transfer and Addition (HTA).
• Demonstrated concurrent formation of C(sp3)-C(sp3) and C(sp3)-X bonds.
• DFT modeling revealed the role of 1,4-dioxane and K+ cation in reaction initiation and progression.

Conclusions:

• The HTA reaction provides a new, efficient route for C-C and C-X bond formation.
• The reaction mechanism involves a halogenophilic nucleophilic substitution (SN2X) pathway.
• Synergistic optimization of the reaction model and mechanism was achieved through iterative experimental and theoretical studies.