Dispersion Interactions in Asymmetric Induction for Constructing Vicinal Stereogenic Centers

Area of Science:

• Organic Chemistry
• Computational Chemistry
• Asymmetric Synthesis

Background:

• Vicinal stereogenic centers are crucial in natural products and bioactive molecules.
• Stereodivergent synthesis using bimetallic catalysis is vital for constructing complex chiral molecules.
• Asymmetric allylic alkylation is a key reaction for creating vicinal stereogenic centers.

Purpose of the Study:

• To computationally investigate stereodivergent asymmetric allylic alkylation.
• To elucidate the molecular mechanism of asymmetric induction in bimetallic catalysis.
• To understand the role of noncovalent interactions in controlling stereoselectivity.

Main Methods:

• Computational investigations of synergistic bimetallic catalysis.
• Analysis of chiral copper-azomethine ylide and rhodium-Josiphos catalyst systems.
• Systematic computational analyses of ligand-substrate interactions (dispersion and sterics).

Main Results:

• Dispersion attraction and steric repulsion dictate face-selective stereoinduction in allylic alkylation.
• Noncovalent interactions and ligand-auxiliary distortions control stereochemistry in rhodium-catalyzed asymmetric hydrogenation.
• Identified similarities in interaction mechanisms between PHOX-type and Josiphos-type ligands.

Conclusions:

• Nonbonded dispersion interactions are foundational for asymmetric induction in constructing vicinal stereogenic centers.
• Computational methodologies provide atomistic insights for rational molecular and reaction design.
• Future computational approaches will focus on interaction-based design for chiral synthesis.