Enantiodivergent Cyclization by Inversion of the Reactivity in Ambiphilic Molecules

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Ambiphilic molecules offer unique reactivity.
• Late-stage functionalization is crucial in drug discovery.

Purpose of the Study:

• To develop a new synthetic strategy for late-stage enantiodivergence.
• To demonstrate the synthesis of enantiomeric oxacycles from a common chiral precursor.

Main Methods:

• Cyclization of ambiphilic linear precursors containing propargylic alcohol and epoxide functionalities.
• Modulating precursor structure and reaction conditions to invert functional group reactivity.

Main Results:

• Successful synthesis of substituted five- and six-membered oxacycles.
• Demonstrated control over stereochemistry at three stereogenic centers.
• Achieved enantiodivergence from a single chiral substrate with complete enantiomeric purity transfer.

Conclusions:

• The developed enantiodivergent cyclization is a powerful strategy for accessing both enantiomers of complex molecules.
• This method enables efficient late-stage synthesis of chiral oxacycles.