Gold(I)-Catalyzed Cyclization–3-Aza-Cope–Mannich Cascade and Its Application to the Synthesis of Cephalotaxine
Takeo Sakai, Chise Okumura, Masatoshi Futamura, Naotaka Noda, Akari Nagae, Chiharu Kitamoto, Madoka Kamiya, Yuji Mori
Abstract
The discovery of a new gold(I)-catalyzed cascade reaction involving cyclization onto a vinylammonium, 3-aza-Cope rearrangement, and Mannich cyclization is reported. A variety of fused nitrogen heterocycles were prepared from simple cyclic tertiary amines using 1–5 mol % of a AuCl(PPh3)/Ag[C5(CN)5] cocatalyst system. The developed reaction was used in a study aimed at synthesizing cephalotaxine. A five-step operation from norhydrastinine provided demethylcephalotaxinone in 39.1% overall yield, which was transformed to (−)-cephalotaxine in two steps.
Topics & Concepts
ChemistryCatalysisYield (engineering)Mannich reactionCascadeCombinatorial chemistryOrganic chemistryChromatographyMaterials scienceMetallurgyBiological Activity of Diterpenoids and BiflavonoidsCatalytic Alkyne ReactionsSynthesis of Organic Compounds