A concise, linear synthesis of the Stemona alkaloid (+/-)-neostenine is reported. Key features include an organocopper-mediated bislactone C2-desymmetrization for the stereoselective construction of the cyclohexane-lactone C,D-rings. The assembly of the fused pyrrolo[1,2-a]azepine core was achieved by application of a [5 + 2] maleimide photocycloaddition. A custom FEP flow reactor was used to successfully overcome the scale limitations imposed by a classical immersion well batch reactor. The synthesis was completed in 14 steps from furan, in 9.5% overall yield, without the use of any protecting groups.
J Org Chem
6497 - 6505
Alkaloids, Azepines, Cyclohexanes, Furans, Lactones, Maleimides, Models, Chemical, Photochemistry, Pyrroles, Stemonaceae, Stereoisomerism