Enantioselective Potassium-Catalyzed Wittig Olefinations

Area of Science:

• Organic Chemistry
• Asymmetric Catalysis
• Organometallic Chemistry

Background:

• Wittig olefination is a fundamental reaction for forming carbon-carbon double bonds.
• Achieving high enantioselectivity in Wittig reactions, especially with non-stabilized ylides, remains a significant challenge.
• Axially chiral alkenes are important structural motifs in pharmaceuticals and materials science.

Purpose of the Study:

• To develop a novel asymmetric catalytic system for the enantioselective Wittig olefination of cyclohexanones.
• To synthesize highly enantioenriched axially chiral alkenes.
• To elucidate the catalytic mechanism using kinetic, spectroscopic, and computational methods.

Main Methods:

• Asymmetric Wittig olefination catalyzed by potassium-isothiourea-boronate complexes.
• Use of non-stabilized phosphorus ylides and 4-substituted cyclohexanones.
• Kinetic studies, spectroscopic analysis (NMR, IR), and Density Functional Theory (DFT) calculations.

Main Results:

• High enantioenrichment (>90% ee) of axially chiral alkenes was achieved.
• The optimal catalyst involved a macrocyclic amide-potassium-boronate chelate.
• A Lewis acid mechanism involving a transient oxaphosphetane intermediate formed under cryogenic conditions was proposed.
• Computational studies revealed a stepwise cycloaddition mechanism via a potassium betaine complex.

Conclusions:

• The developed potassium-isothiourea-boronate catalytic system enables highly enantioselective Wittig olefinations.
• The reaction proceeds via a Lewis acid-catalyzed pathway with a distinct mechanistic pathway involving a betaine intermediate.
• This work provides a valuable new method for accessing enantioenriched axially chiral alkenes.