Reductant-Controlled Access to Sulfinamides from Aliphatic Primary Amines.

Area of Science:

• Organic Chemistry
• Synthetic Methodology
• Medicinal Chemistry

Background:

• Sulfinamides are valuable functional groups in organic synthesis and medicinal chemistry.
• Current methods for sulfinamide synthesis often lack efficiency or broad applicability.
• Subtle functional group editing, such as sulfoxide insertion, presents a synthetic challenge.

Purpose of the Study:

• To develop a novel method for the synthesis of sulfinamides from primary amines.
• To achieve selective C(sp3)-S bond formation via reductive deaminative sulfinamidation.
• To demonstrate the utility of this method for late-stage functionalization of complex molecules.

Main Methods:

• Reductive deaminative sulfinamidation of N-alkylpyridinium salts with N-sulfinylamine.
• Utilizing reductant-controlled generation of primary or secondary alkyl radicals.
• Employing aliphatic primary amines as common building blocks.

Main Results:

• Successful synthesis of sulfinamides with a C(sp3)-S bond.
• Demonstrated broad functional group compatibility.
• Achieved selective access to distinct sulfinamides based on reductant control.
• Exemplified late-stage functionalization by synthesizing a sulfinamide analogue of mexiletine.

Conclusions:

• A novel, operationally simple, and scalable method for sulfinamide synthesis is presented.
• The method allows for subtle functional group editing through formal sulfoxide insertion.
• This approach is suitable for late-stage functionalization of amine-containing pharmaceuticals.