Asymmetric Total Syntheses of Di- and Sesqui-Terpenoids via Catalytic C-C Activation of Cyclopentanones.

To show the synthetic utility of the catalytic C-C activation of less strained substrates, here we describe collective and concise syntheses of natural products (-)-microthecaline A, (-)-leubehanol, (+)-pseudopteroxazole, (+)- seco -pseudopteroxazole, pseudopterosin A-F and G-J aglycones, and (+)-heritonin. The key step in these syntheses involve a Rh-catalyzed C-C/C-H activation cascade of 3-arylcyclopentanones, which provides a rapid and enantioselective route to access the polysubstituted tetrahydronaphthalene cores presented in these natural products. Other important features include (i) the direct C-H amination of the tetralone substrate in the synthesis of (-)-microthecaline A, (ii) the use of phosphoric acids to enhance efficiency and regioselectivity for problematic cyclopentanone substrates in the C-C activation reactions, and (iii) the direct conversion of serrulatane to amphilectane diterpenes via an allylic cyclodehydrogenation coupling.