One-Pot, Enantioselective Synthesis Of 2,3-Dihydroazulen-6(1H)-One: A Concise Access To The Core Structure Of Cephalotaxus Norditerpenes

A one-pot enantioselective synthesis of cis-substituted 2,3-dihydroazulen-6(1H)-one is described. In this cascade reaction, an organocatalyzed asymmetric Michael reaction furnishes a highly optically pure nitrobutylphenol intermediate, which is converted into an annulated tropone species by sequential oxidative dearomatization, conjugate addition, electrocyclic ring opening and nitrous acid elimination in the same reaction vessel. Both aliphatic and aromatic nitroalkenes are good substrates for the one-pot reaction, and this protocol appears to be general for various phenylpropionaldehydes as well. In the case of asymmetrically substituted phenylpropionaldehydes, the regioselectivity is likely determined by both the steric and electronic properties of the substituents. This methodology is successfully applied to the synthesis of the tricyclic core structure of Cephalotaxus norditerpenes