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

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 fluoridemediated 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 onepot reactions can be extended beyond nucleophilic acyl substitutions to mild reductions of carboxylic acids using NaBH4 (13 examples, 33-80% yields)

Automated summary

Thionyl fluoride (SOF2) is a promising reagent that has not been extensively studied for its synthetic applications. This research expands the scope of thionyl fluoride-mediated nucleophilic acyl substitutions and demonstrates its effectiveness in the synthesis of peptides, amides, esters, and thioesters. In addition, it shows that thionyl fluoride can be used as a mild reducing agent in one-pot reactions.