Selective Phenylephrine. Allyl Alcohol Reduction, Isomerization, And Intramolecular Cyclization

This thesis focuses on the redox reaction of allylic alcohols:We have demonstrated M-SiCl₄ promoted deoxygenative coupling of allylic alcohols,which further enriched the application of dysprosium in organic synthesis.We have established iron salt catalyzed disproportionation and cyclization of allylic alcohols.We successfully applied disproportionation to selective deoxygenation of allylic alcohols and allylic derivatives with benzyl alcohol.We have developed a method for the synthesis of dilithio reagent from allylic alcohol.The structure of the dilithio intermediate was verified by X-ray.The whole thesis is divided into four chapters,the details are as follows:Chapter 1:Investigation of the deoxygenative coupling of allylic alcohols promoted by metal-SiCl₄.At first,we observed that Dy-SiCl₄ promoted the deoxygenative coupling of allylic alcohols.The deoxygenative coupling products were obtained in moderate to high yields,when various allylic alcohols were used as substrates. Tetrakis(1,3-diphenylallyl)siloxane and 1,3-diphenylallyl chloride,which could be formed in the process,reacted with Dy-SiCl₄ giving coupling products in 85%and 84%yield respectively.When PhCHCHCH(OD)Ph was used as substrate,the reduction of product included the deuterium atom in the allyl position.On the basis of these results,we proposed the plausible mechanism of Dy-SiCl₄ promoted deoxygenative coupling of allylic alcohols.We found that Fe-SiCl₄ could also efficiently promote the deoxygenative coupling of allylic alcohols without an additive under mild reaction conditions.However,Sm-SiCl₄ and Zn-SiCl₄ exhibited much lower activities in the same conditions.Chapter 2:FeCl₃·6H₂O catalyzed the disproportionation of allylic alcohols and selective allylic reduction of allylic alcohols and their derivatives with benzyl alcohol. We observed that FeCl₃·6H₂O not only catalyzed the disproportionation of allylic alcohol yielding alkene and chalcone,but also catalyzed cross disproportionation of two different alcohols(allylic alcohol and benzyl alcohol) giving alkene and benzaldehyde.The yield of deoxygenation of allylic alcohol depended on the stoichiometric ratio of allylic alcohol and benzyl alcohol,and the best result was achieved in neat benzyl alcohol.Other benzyl alcohols and triethylsilane also worked as reducing agents,but alkyl alcohols(such as:ethanol and 2-propanol) were not effective.We successfully applied this reaction to selective allylic reduction of allylic alcohols,allylic acetates and allylic ethers with benzyl alcohol.On the basis of deuterium isotope-labeling experiments,the plausible mechanism was proposed for the FeCl₃-catalyzed allylic reduction of allylic alcohols with benzyl alcohol.Chapter 3:An efficient procedure for the synthesis of substituted indenes through the FeCl₃·6H₂O catalyzed intramolecular Friedel-Crafts cyclization of aryl-substituted allylic alcohols have been developed.Although it has proved successful for aryl-substituted allylic alcohols to serve as precursors for the synthesis of indenes via the intramolecular Friedel-Crafts reactions,in most cases a strong acidic medium and/or an excess amount of Lewis acid promoter were required.Considering cost and environment factors,we tried to use catalytic amount of FeCl₃·6H₂O to catalyze the cyclization of allylic alcohols.The results showed that the strategy was feasible. Screening of the other iron salts revealed that Fe(acac)₃,Fe(NH₄)(SO₄)₂·12H₂O, FeCl₂·6H₂O and Fe(AcO)₂ were inefficient for the cyclization of allylic alcohols except anhydrous FeCl₃.Subsequently,we studied the scope of the reaction.The results indicated that tertiary allylic alcohols can easily undergo the cyclization to afford indene derivatives through isomerization/cyclization in the catalytic amount of FeCl₂·6H₂O.Secondary allylic alcohols including a substituent at the 2-position of allylic alcohols can also undergo the intramolecular Friedel-Crafts reaction.Chapter 4:Synthesis of dilithio reagents via isomerization of allylic alcohols promoted by BuLi:Structural characterization of the dianion intermediate and its application in organic synthesis.We observed that reaction of allylic alcohols with butyl lithium can form the stable intermediate due to releasing butane in the process. We successfully obtained the crystal of dianion intermediate,which was determined by X-ray diffraction.Subsequently,dilithio reagents successfully were applied in organic synthesis.When deuterium oxide was used as electrophile to react with the dilithio reagents,α,β-dideuterioketones were efficiently obtained.While trimethylsilane chloride was used as electrophile to react with the dilithio reagents, allyloxylsilanes and silyl enol ethers were obtained.These results demonstrated that the dilithio reagent can react with various electrophiles to form various carbon-carbon bonds and carbon-heteroatom bonds.