A protecting group free synthesis of (+/-)-neostenine via the [5 + 2] photocycloaddition of maleimides.
Lainchbury MD., Medley MI., Taylor PM., Hirst P., Dohle W., Booker-Milburn KI.
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.