Inner-Sphere Oxygen Activation Promoting Outer-Sphere Nucleophilic Attack on Olefins

Area of Science:

• Organometallic Chemistry
• Catalysis
• Organic Synthesis

Background:

• Alkoxylation and hydroxylation are crucial transformations in organic chemistry.
• Developing selective catalytic methods for these reactions remains a significant challenge.
• Metal-catalyzed oxidation of olefins often involves complex mechanistic pathways.

Purpose of the Study:

• To describe the alkoxylation and hydroxylation reactions of 1,5-cyclooctadiene (cod) using iridium complexes.
• To elucidate the mechanism of these reactions, particularly the role of oxygen reduction and hydroperoxide intermediates.
• To investigate the stereochemical outcomes and potential for enantioselective synthesis.

Main Methods:

• Reactions of 1,5-cyclooctadiene (cod) with alcohols and water in the presence of iridium complexes and oxygen.
• Isolation and characterization of key iridium intermediates, including a cationic diolefin iridium(III) complex.
• Density Functional Theory (DFT) studies to investigate reaction mechanisms.
• Application of the protocol to rhodium complexes for enantioselective synthesis.

Main Results:

• The exo configuration of products suggests nucleophilic attack at the olefin's external face.
• A cationic diolefin iridium(III) complex, [Ir(cod)(pic)₂ ]⁺, was isolated and shown to mediate alkoxy group exchange.
• DFT studies revealed a low-energy proton-coupled electron-transfer step involving superoxide and hydroperoxide iridium intermediates.
• Hydroperoxide intermediates dictate the regio- and stereoselectivity of hydroxylation/alkoxylation.
• Enantioselective synthesis of alkyl ethers was achieved using a chiral amino acid with a rhodium complex.

Conclusions:

• Iridium complexes effectively catalyze the alkoxylation and hydroxylation of 1,5-cyclooctadiene (cod) via a mechanism involving hydroperoxide intermediates.
• The reaction pathway provides insights into controlling regio- and stereoselectivity.
• The developed protocol can be adapted for enantioselective synthesis using rhodium catalysts and chiral auxiliaries.