The synthesis of C-13 functionalized pleuromutilins via C–H amidation and subsequent novel rearrangement product

Abstract

Multi-gram quantities of C-13 functionalized pleuromutilin intermediates were synthesized under mild conditions via C–H amidation chemistry. The initial work was performed using rhodium catalysis. However, the highest yields were achieved using silver catalysis, resulting in stereoselective oxazolidinone formation. The ring closure was performed in the presence of a C-12 vinyl group, which differentiates it from historical methods involving the saturated pleuromutilin skeleton. A highlight of this vinyl template is a unique tetracyclic rearrangement product that can be generated from its treatment with hydrochloric acid and heat.