Synthesis of Pleuromutilin.

Synthesis of a potent inhibitor of bacterial protein synthesis, pleuromutilin, is described. Assembly of the critical cyclooctane fragment relies on an oxidative ring-expansion, and complete stereochemical relay in the synthetic sequence is enabled by the judicious choice of tactics. The requisite connectivity pattern of the perhydroindanone motif is rapidly established in a sequence of cycloaddition and radical cyclization events. Application of this strategy allows for preparation of the target natural product in 16 steps from commercially available material.

Catalytic Radical-Polar Crossover Reactions of Allylic Alcohols.

Radical-polar crossover hydrofunctionalizations of tertiary allylic alcohols are described. Depending on the structure of the catalyst, corresponding epoxides or semipinacol rearrangement products are selectively obtained in good yields. Experimental evidence points to the participation of alkylcobalt complexes as electrophilic intermediates.

Dual Lewis Acid/Photoredox-Catalyzed Addition of Ketyl Radicals to Vinylogous Carbonates in the Synthesis of 2,6-Dioxabicyclo[3.3.0]octan-3-ones.

A combined Lewis acid/photoredox catalyst system enabled the intramolecular umpolung addition of ketyl radicals to vinylogous carbonates in the synthesis of 2,6-dioxabicyclo[3.3.0]octan-3-ones. This reaction proceeded on a variety of aromatic ketones to provide THF rings in good yield (up to 95%). Although diastereoselectivity was found to be modest (1.4-5:1) for the C-C bond forming reaction, the minor diastereomers were converted to 2,6-dioxabicyclo[3.3.0]octan-3-ones by an efficient Lewis acid-mediated epimerization cascade in up to 90% yield.