Compatibility Score for Rational Electrophile Selection in Pd/NBE Cooperative Catalysis

Area of Science:

• Organic Chemistry
• Catalysis
• Computational Chemistry

Background:

• Palladium-catalyzed reactions are vital in organic synthesis.
• Achieving selective difunctionalization of aryl halides requires orthogonal reactants.
• Understanding reaction mechanisms is key to controlling selectivity.

Purpose of the Study:

• To develop a method for predicting electrophile compatibility in Pd/NBE cooperative catalysis.
• To identify key intermediates and mechanisms in aryl halide difunctionalization.
• To enable rational selection of reactants for selective transformations.

Main Methods:

• Detailed experimental mechanistic studies.
• Computational modeling of reaction pathways.
• Development and application of the electrophile compatibility score (ECS).

Main Results:

• Identified the catalytically active Pd(II) intermediate.
• Elucidated substrate-dependent reaction mechanisms with various electrophiles.
• Introduced the electrophile compatibility score (ECS) for rational reactant selection.
• Demonstrated successful prediction of electrophile compatibility in diverse coupling reactions.

Conclusions:

• The developed mechanistically guided approach and ECS effectively predict electrophile compatibility.
• This facilitates selective ipso/ortho difunctionalization of aryl halides using Pd/NBE cooperative catalysis.
• The findings enable broader application of this catalytic system in organic synthesis.