DMSO activation in Pseudo-Swern reaction

Mechanism + Description

The mechanisms are similar to the Swern and Pfitzner-Moffat as given in previous examples.

General comments

While oxalyl chloride, TFAA, and Pyr-SO3 are common choices for DMSO activation to facilitate alcohol oxidation, other variations are available. Some less referenced but equally beneficial reagents include acetic anhydride, P2O5, and trimethylchlorosilane. Ac2O would be a cheaper and more environmentally friendly alternative to TFAA. Reaction of electrophiles like TFFA and P2O5 with DMSO can be highly exothermic.

Key references

Goodman, S. N.; Dai, Q.; Wang, J.; Clark, W. M., Jr. A Scalable Oxidation for the Final Stage of Synthesis of Cathepsin K Inhibitor SB-462795. Org. Process Res. Dev. 2011, 15 (1), 123–130.

Relevant scale up example

Org. Process Res. Dev. 2004, 8 (5), 777–780.

© 2015 Green Chemistry Institute Pharmaceutical Roundtable. All rights reserved.