Nucleophilic Carbenes Derived from Dichloromethane

Area of Science:

• Organometallic Chemistry
• Catalysis
• Organic Synthesis

Background:

• Cyclopropanation reactions are fundamental in organic synthesis.
• Developing efficient and selective methods for cyclopropane synthesis remains a key challenge.
• Nickel catalysis offers a promising avenue for novel transformations.

Purpose of the Study:

• To develop a novel nickel-catalyzed nucleophilic cyclopropanation reaction.
• To explore the substrate scope and enantioselectivity of the developed method.
• To elucidate the reaction mechanism using mechanistic studies and DFT calculations.

Main Methods:

• Utilized Nickel PyBox catalysts for cyclopropanation.
• Employed dichloromethane as the methylene source and manganese as a reductant.
• Investigated a broad range of electron-deficient alkenes as substrates.
• Developed enantioselective variants using chiral PyBox ligands.
• Conducted mechanistic studies and Density Functional Theory (DFT) modeling.

Main Results:

• Successfully promoted nucleophilic cyclopropanation reactions with broad substrate scope.
• Achieved enantioselective cyclopropanations of α,β-unsaturated esters.
• Identified a (PyBox)Ni=CH2 species as a key intermediate.
• Proposed a stepwise [2+2]-cycloaddition/C-C reductive elimination mechanism.
• DFT models rationalized the carbene's nucleophilic character and enantioinduction.

Conclusions:

• Nickel PyBox catalysts are effective for nucleophilic cyclopropanation.
• The developed method offers a versatile route to functionalized cyclopropanes.
• Mechanistic insights provide a foundation for further catalyst and reaction development.