C(sp³)-H (N-Phenyltetrazole)thiolation as an Enabling Tool for Molecular Diversification

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Broad diversification of C(sp³)-H bonds is crucial for chemical synthesis.
• Developing methods for site-selective C-H functionalization remains a key challenge.

Purpose of the Study:

• To report a site-selective thiolation of aliphatic and (hetero)benzylic C(sp³)-H bonds.
• To provide a versatile method for accessing N-phenyltetrazole thioethers.

Main Methods:

• Utilized a commercially available disulfide for N-phenyltetrazole thiolation.
• Employed a radical-chain pathway involving hydrogen atom transfer.
• Investigated the role of hexafluoroisopropanol in facilitating C(sp³)-H thiolation.

Main Results:

• Achieved site-selective thiolation of various C(sp³)-H bonds.
• Synthesized N-phenyltetrazole thioethers, which serve as versatile intermediates.
• Demonstrated exceptional functional group tolerance for late-stage diversification.

Conclusions:

• The developed method offers a valuable tool for the broad diversification of C(sp³)-H bonds.
• The N-phenyltetrazole thioethers are readily elaborated in diverse fragment couplings.
• The reaction mechanism involves radical-chain processes and is enhanced by specific solvents.