Domino Reaction Based On The Aza-of Mbh Reaction, Small Molecule Organic Phosphine-catalyzed

Morita-Baylis-Hillman reaction:Tertiary phosphine or tertiary amine catalyzed coupling of aldehydes and activated olefins atαposition to give the highly functionlized products.This reaction has become one of the most extensively studied topics in organic chemistry,due to its inherently atom economic and mild reaction conditions.Considerable efforts have been made to expand its scope of application.In this thesis,included are the advanced of Morita-Baylis-Hillman detailedly summarized and our work on the design and syntheses of bifunctional phosphine catalyst,as well as their application to the MBH-based Domino reaction.We have synthesized a LBBA-1 containing the OH,and applied it to the reaction of acrolein and imines.According to our experimental results,if THF was employed as solvent,traditional aza-MBH products could be obtained in high yield in one hour, while with CHCl₃ as solvent,tetrahydropyridine derivative as final products were afforded in moderate yield within 15 min.The investigations of the mechanism revealed that an aza-MBH/Michael/Aodol/Dehydration Domino reaction are involved.This reaction can serve as a concise and effective method for the synthesis of tetrahydropyridine derivatives.Structures of all the products were confirmed by X-ray,NMR and HRMS.Studies of the LBBA-1 suggested that the OH of this catalyst not only accelerated the reaction,but also stabilized the intermediate via intramolecular hydrogen bond.Thus,we have designed and synthesized a more nucleophilic one, LBBA-2,and applied it to the reaction of 2,3-butadienoate and salicyl N-thiophosphinylimines.However neither the[3+2]compound nor the chromenes reported by shi was observed.As a matter of fact,an aza-MBH/umpolung domino reaction had taken placed and given the cis-2,3-dihydrobenzofurans.Compared with the ⁿBu₃P,the OH is critical for the products' configuration.2,3-butadienoate acted as a one carbon synthon in this reaction,which was rarely reported.In the presence of DMAP,chromans and chromenes were obtained,respectively,for the imines with the electron-withdrawing groups and the ones with electron-donating groups.Structures of all the products are confirmed by X-ray,NMR and HRMS.If 2,3-pentadienoate rather than 2,3-pentadienoate was employed,in the presence of LBBA-2 as catalyst,Chromans instead of dihydrobenzofurans were obtained.But the yields of product were unsatisfied.Further investigations shown that PPh₃,which proved to be ineffective catalyst in the formation of dihydrobenzofurans,serves as the most effective one in this reaction.For the imines bearing electron-withdrawing groups on the phenyl ring,cis products were obtained with well selectivity.In contrast,for their counterparts with electron-donating groups,cis and trans mixtures are obtained.This is the first case where theγ-methyl of allene is involved in the cycloation and thus serves as two carbon synthon.LBBA-1 and LBBA-2 are highly effective catalysts for the MBH,aza-MBH reaction.Due to the coexistence of Lewis base and Bronsted acid,they can effectively catalyze the reactions between aldehydes and methyl vinyl ketone(MVK)/acrylate,as well as the aza-MBH reactions between MVK and salicyl N-thiophosphinyl imines.