Rhodium-Catalyzed Cyclohydrocarbonylation: Application to the Synthesis of (+)-Prosopinine and (−)-Deoxoprosophylline

Abstract

Efficient convergent total syntheses of (+)-prosopinine (1) and (−)-deoxoprosophylline (4) were accomplished using Rh−BIPHEPHOS complex-catalyzed cyclohydrocarbonylation as the key step. The Rh−BIPHEPHOS complex-catalyzed cyclohydrocarbonylation of I, derived from (R)-serine, at 65 °C and 4 atm of CO and H2 (1:1) in ethanol afforded 6-ethoxypiperidine II, which was transformed to enantiopure (+)-prosopinine (1) in 3 steps. In a similar manner, (−)-deoxoprosophylline was synthesized through cyclohydrocarbonylation of IV derived from (S)-serine, giving 6-ethoxypiperidine V. The key intermediate V was transformed to enantiopure (−)-deoxoprosophylline (4) in 4 steps. These two short total syntheses clearly demonstrate the usefulness of the extremely regioselective cyclohydrocarbonylation process developed in these laboratories for the concise syntheses of piperidine alkaloids and related compounds.