Pd-catalyzed Asymmetric Allyation Of Chiral Sulfinimines And Total Synthesis Of Vinylamycin

Amines are present in a large majority of drugs and drug candidates.Consequently,the asymmetric synthesis of amine containing compounds represents an extremely improtant endeavor in the discovery and productiom of new pharmaceutical agents.Over the past decade,an ever increasing collection of methods besed upon the chiral amine reagent tert-butanesulfinamide have become some of the most extensively used synthetic approaches for both the discovery and production of drug candicates.Also,tert-butanesulfinamide are extensively explored to synthese aldimines and ketimines.The combination of the ease of synthesis,hydrolytic stability,electrophilicity and stereocontrol makes N-tert-butanesulfinyl imines attractive intermediates for the synthesis of chiral centre-containing compounds.Stereoselective C-C bond formation has always been an important area of organic synthesis research.Among the methods available,the palladium(0)catalyzed asymmetric allylation reaction provides a powerful method for the formation of C-C bonds from activated methylene compounds,such as 1,3-dicarbonyls.Usually,chiral ligands are used to promate allylation reaction.While these ligands are sensitive to moisture and air that restricts their application.Herein,we try to explore a new method to construct stereoselective C-C bond with high yield and excellent stereoselectivity.Herein,we developed the first highly diastereoselective palladium(0)-catalysed allylation reaction of simple chiral sulfinimines.The reactions were carried out under mild conditions using commercially available Pd2(dba)3 in conjunction with the simple and readily available ligand P(n-Bu)3 and DIPEA as a base.Products bearing an allyl group at the ?-position of chiral sulfinimines are obtained in high chemical yield,with good diastereoselectivity and excellent regiocontrol.The reaction displays good substrate tolerance.More importantly,it can be scaled up easily,uses cheap reagents and mild conditions.The chiral auxiliary can be removed in almost quantitative yield under very mild conditions following hydrolytic cleavage without any racemisation,which makes this method an attractive one for industrial applications.Also,we explored the total synthesis of natural product vinylamycin belonged to a family of cyclic depsipeptides.It was discovered to be a metabolite of Streptomyces sp.by the group of Igarashi in 1999.As its similar structure with Rakicidin A attracted our interest.Herein we completed the synthesis of Vinylamycin and determined its absolute confirguration,also its primary anti-cancer activity was discovered.