Direct Amination And Olefination Of Alcohols Promoted By Bases

The cascade reactions which are based on self-hydride transferring strategy have received increasing attention in these days.Because they are not only atom economic,effective,but also environmental friendly.Our group keeps interest in the self-hydride transferring reactions and their mechanism investigation.Several years ago our group has already found the phenomenon that N-O bond cleavage,rearrangement and self-hydride transferring would happen to N-methylisoxazolidine under the catalysis of ruthenium.We are interested in the self-hydride transferring reactions and we applied this strategy to other cascade reactions.This paper includes the following several parts:(1)Direct amination of alcohols:alkylation of amine by alcohols was achieved by catalytic amount of potassium hydroxide under metal-free conditions."Hemiaminal－model" was first proposed to explain the mechanism with the support of the control reactions.This method was also applied in gram scale synthesis and it proved that this method was useful.Compared with the method in this paper,transition metal catalyzed reactions had been reported in the literature before.However,excessive base and high temperature were also needed for these methods which usually need complex operation and high cost.(2)Direct Julia olefination of alcohols:E-specific direct Julia olefination of alcohols is achieved with alcohols and sulfone reagents under excessive base,high temperature and metal-free conditions,which is based on the self-hydride transferring strategy and the experience of the first subject.This reaction has easy operation and specific selectivity.The starting materials are cheap and commercial available.Compared with the method in this paper,mutiple steps and complex operation are needed for the classic Julia olefination reactions.Besides,"BuLi and Na/Hg are also used in the reation which are unfriendly to the environment.(3)Direct Wittig olefination of alcohols:We inferred that direct Wittig olefination of alcohols might occur according to the previous research.The further research showed that the predicted reaction could be achieved by using excessive amount of base and air as the oxidant.This method is not only effective under mild condition,but also is friendly to the environment.It has been applied to synthesize bioactive anti-cancer molecules DUM-212 and resveratrol in gram scale.Besides,enantiomeric pure 2-hydroxyhelicene also could be synthesized by this method.Compared with the method in this paper,the two-step Oxidation-Wittig Olefination methods were usually used in the literature.However,not only the amount of oxidants,temperature and reaction time should be strictly controlled,but also the waste material of the oxidants might be harmful to the environment.