Diazotization-Enabled Deaminative Late-Stage Functionalization of Primary Sulfonamides

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Late-stage functionalization is crucial for drug discovery.
• Primary sulfonamides are important functional groups in pharmaceuticals.
• Existing methods often require prefunctionalization, limiting scope.

Purpose of the Study:

• To develop a novel, efficient late-stage functionalization strategy for primary sulfonamides.
• To bypass the need for prefunctionalization steps.
• To demonstrate the method's applicability to drug molecules.

Main Methods:

• Diazotization of primary sulfonamides.
• Conversion to sulfonyl chlorides, sulfonates, and complex sulfonamides.
• Application to sulfonamide-containing drug candidates.

Main Results:

• A simple and efficient protocol for late-stage sulfonamide functionalization was established.
• The method successfully generated diverse sulfonamide derivatives.
• Late-stage functionalization of sulfonamide drugs was demonstrated.

Conclusions:

• This diazotization-based strategy offers a versatile approach for modifying primary sulfonamides.
• The protocol simplifies synthetic routes by avoiding prefunctionalization.
• This method holds potential for accelerating drug development and medicinal chemistry efforts.