Thionyl Fluoride-Mediated One-Pot Substitutions and Reductions of Carboxylic Acids

• Published in: Journal of organic chemistry 2022-06, Vol.87 (11), p.7308-7318
• Main Authors: Bolduc, Trevor G., Lee, Cayo, Chappell, William P., Sammis, Glenn M.
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.2c00496

Thionyl fluoride (SOF2) is an underutilized reagent that is yet to be extensively studied for its synthetic applications. We previously reported that it is a powerful reagent for both the rapid syntheses of acyl fluorides and for one-pot peptide couplings, but the full scope of these nucleophilic acyl substitutions had not been explored. Herein, we report one-pot thionyl fluoride-mediated syntheses of peptides and amides (35 examples, 45–99% yields) that were not explored in our previous study. The scope of thionyl fluoride-mediated nucleophilic acyl substitutions was also expanded to encompass esters (24 examples, 64–99% yields) and thioesters (11 examples, 24–96% yields). In addition, we demonstrate that the scope of thionyl fluoride-mediated one-pot reactions can be extended beyond nucleophilic acyl substitutions to mild reductions of carboxylic acids using NaBH4 (13 examples, 33–80% yields).