Dynamic Kinetic Resolution Allows Control of Remote Stereochemistry in Asymmetric Hydrogen Borrowing Alkylation

Area of Science:

• Organic Chemistry
• Asymmetric Catalysis
• Organometallic Chemistry

Background:

• Hydrogen borrowing alkylation is a powerful strategy for C-C bond formation.
• Asymmetric synthesis of chiral ketones remains a significant challenge in organic chemistry.
• Iridium catalysts have shown promise in various catalytic transformations.

Purpose of the Study:

• To develop a catalytic asymmetric method for synthesizing γ-substituted ketones.
• To utilize hydrogen borrowing alkylation for the enantioselective synthesis of cyclohexanes.
• To investigate the mechanism of enantioinduction using computational modeling.

Main Methods:

• Catalytic asymmetric synthesis employing hydrogen borrowing alkylation.
• Dynamic kinetic resolution of racemic linear precursors and 1,5-diols.
• Density Functional Theory (DFT) modeling to elucidate reaction mechanisms.

Main Results:

• Highly enantioenriched cyclohexanes were synthesized in excellent yields.
• A base-mediated racemization of an intermediate cyclohexenone facilitated dynamic kinetic resolution.
• DFT calculations revealed a stepwise enantioinduction mechanism involving iridium catalyst.

Conclusions:

• The developed method provides an efficient route to chiral γ-substituted ketones.
• The combination of hydrogen borrowing and dynamic kinetic resolution offers a powerful strategy for asymmetric synthesis.
• Understanding the catalytic mechanism aids in the design of more efficient catalysts.