Reaction between Indazole and Pd-Bound Isocyanides-A Theoretical Mechanistic Study

Area of Science:

• Organometallic Chemistry
• Computational Chemistry
• Reaction Mechanism Studies

Background:

• Indazole (Ind) is a bifunctional nucleophile.
• Palladium(II) complexes with isocyanides are relevant in catalysis.
• Understanding reaction pathways is crucial for synthetic control.

Purpose of the Study:

• To elucidate the detailed mechanism of indazole addition to a palladium-bound cyclohexyl isocyanide.
• To investigate the role of indazole tautomerism in the reaction outcome.
• To determine the factors governing the regioselectivity of aminocarbene ligand formation.

Main Methods:

• Density Functional Theory (DFT) calculations were employed.
• Analysis of reaction pathways and transition states.
• Investigation of bonding in key intermediates and products.

Main Results:

• An associative mechanism involving nucleophilic attack by indazole's N atom was identified.
• Two reaction channels corresponding to different indazole tautomers were explored.
• The experimentally observed product arises from a less stable indazole tautomer, indicating thermodynamic control over kinetic preference.

Conclusions:

• The reaction proceeds via nucleophilic attack followed by proton transfer.
• Regioselectivity is dictated by thermodynamic stability rather than kinetic favorability.
• The findings provide insights into the factors controlling ligand formation in palladium chemistry.