Stereodivergent Rhodium(III)-Catalyzed cis-Cyclopropanation Enabled by Multivariate Optimization

Area of Science:

• Organic Chemistry
• Catalysis
• Stereoselective Synthesis

Background:

• Stereodivergent transformations offer control over reaction outcomes with minor adjustments.
• Controlling stereochemistry in cyclopropanation reactions is crucial for synthesizing complex molecules.

Purpose of the Study:

• To develop a physical organic approach for stereodivergent cyclopropanation of alkenes.
• To invert the sense of diastereoselective induction in rhodium(III)-catalyzed reactions.

Main Methods:

• Utilized rhodium(III) catalysis for diastereoselective cyclopropanation.
• Employed physical organic methods, including linear-free energy relationships.
• Developed a statistical model correlating catalyst-substrate determinants with stereochemical outcomes.

Main Results:

• Established a robust statistical model for predicting stereochemical outcomes.
• Achieved a diastereodivergent cyclopropanation tool with high accuracy.
• Identified a mechanistic dichotomy responsible for switching between trans- and cis-diastereoselection.

Conclusions:

• The stereochemical outcome is dictated by the flexibility of rhodacyclic intermediates.
• Phthalimide ring size and ligand Sterimol B1 parameter influence selectivity.
• This work provides a general and tunable method for diastereoselective cyclopropanation.