Enantioselective Total Synthesis of (+)-Colletoic Acid via Catalytic Asymmetric Intramolecular Cyclopropanation of an α-Diazo-β-keto Diphenylphosphine Oxide

The enantioselective total synthesis of (+)-colletoic acid, a potent naturally occurring 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) inhibitor, is described. This total synthesis features a highly enantioselective catalytic asymmetric intramolecular cyclopropanation of an alpha-diazo-beta-keto diphenylphosphine oxide and five highly stereoselective reactions (cyclopropane opening, Diels-Alder reaction, iodolactonization, alkene formation, and reduction of alpha,beta-unsaturated carboxylic acid).