Synthesis of Cyclotryptamine Alkaloids: New Reagent and Catalyst for Asymmetric Halogenation Reactions
Weiqing Xie
Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, 22 Xinong Road, Yangling 712100, Shaanxi, China
Although halogenation reactions have been well developed and widely employed in total synthesis, catalytic asymmetric halogenation reactions have experienced great progress only in recent years. The employment of bifunctional catalysts, which could activate both substrate and halogenating reagent, is believed to be critical for the success for those reactions. However, unmet challenges still exist in this field, e.g. asymmetric intermolecular asymmetric halo-functionalization of olefins, formation strained three-membered rings via asymmetric halo-cyclization.
Figure. New reagent and ion-pair organocatalyst for asymmetric halogenation reactions.
We have been interesting in asymmetric halogenation reactions, which could be applied in synthesis of natural products and pharmaceutical molecules. Recently, we discovered that highly enantioselective bromocyclization of tryptamine could be achieved by using chiral anionic phase-transfer catalyst. A new bromine reagent, N- benzyl-DABCO/bromine complex B3, was also identified as the best bromine source for this reaction. Relying on this reaction, 3-steps enantioselective synthesis of (-)-chimonanthine was accomplished. More recently, we accomplished asymmetric synthesis of (-)-conolutinine in ten steps, which also took advantage of this reaction. We also work on designing new organocatalyst that enables reactions that is otherwise difficult to be realized by other catalysts. In this context, a novel ion-pair catalyst C1 comprised of chiral phosphate and N-alkyl-DABCO was determined to be unique in catalyzing 3-exo iodo-cycloetherification of allyl alcohol to furnish iodomethyl epoxide in high enantioselectivities. One-pot synthesis chiral cycloketone with quaternary all-carbon center via 3-exo iodo-cycloetherification/Wagner Meerwein rearrangement is also developed.
