One‐Pot, Enantioselective Synthesis of 2,3‐Dihydroazulen‐6(1H)‐one: A Concise Access to the Core Structure of Cephalotaxus Norditerpenes

Abstract

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.

Total Synthesis and Cytotoxicity Evaluation of Pareitropone and Analogues

“… Regiochemistry of step #2 leading to 12 was undetermined but inconsequential in this example. A straightforward retrosynthetic analysis of 1 emerged by adaptation of Kende’s powerful method (Scheme ), which received surprisingly little attention despite great potential in developing efficient and scalable syntheses of fused tropones under mild conditions . Phenol-nitroalkane 14 was envisioned as a penultimate intermediate for total synthesis of 1 via the intermediacy of 13 .…”