Investigation Of Multicomcponent Reactions On Ynamides And Tandem Reaction Of Diazo Compounds And Para-Quinone Methides

The multicomponent reactions(MCRs)are important synthetic tools for preparation of small-molecule compounds.Compared to the traditional multi-step approach,MCRs usually involve starting materials in one-step protocol to receive the target compounds.So,it has higher atomic economy and is simple to be operated.Ynamide is a type of amide-substituted alkynes.Compared with ordinary alkynes,due to the electron-donating character of the nitrogen atom makes a strong polarization of the trip bond,they have the dual nucleophilic and electrophilic properties and higher activity.They are similar to the isocyanides.So,based on these analyses,we believe that ynamides can be applied in the MCRs as a C2 synthetic module.The Ugi reaction is a well-known multicomponent reaction.Based on the similarity between the ynamides and the cyanogen,we explored the mimic-Ugi reaction at first.After investigatation of different conditions,we successfully developed a one-pot multicomponent reaction to synthesize β-amino amides with aldehydes,anilines,carboxylic acids and ynamides.Moreover,an isotope labeling reaction was conducted to elucidate a plausible reaction mechanism(Scheme 1).Scheme 1.One-pot multicomponent synthesis of β-amino amidesIn addition,we also developed a nickel-catalyzed acetamidation and lactamization of arylboronic acids via a one-pot reaction with ynamides and N-hydroxyphthalimide.Firstly,ynamides coupled with the the weakly acidic N-hydroxyphthalimide(pKa = 6.1)to form redox-active enamide,then it could be transformed into arylsubstituted acetamide and lactam via a single-electron transfer(SET)process catalyzed by nickel(II).Moreover,a radical-capture reaction was conducted to elucidate a plausible mechanism(Scheme 2).Scheme 2.Nickel-Catalyzed Acetamidation and Lactamization of Arylboronic acidsBesides,we also developed a tandem reaction of diazo compounds and para-quinone methides(p-QMs)to synthesize tetrasubstituted alkenes and quinolinones.Due to the para-quinone methides(p-QMs)have a high electrophilic property,they could be easily attacked by diazo compounds to form tetrasubstituted alkenes and quinolinones via the addition and rearrangement process with the help of Lewis acid.Furthermore,the 13C-labeling experiments were also conducted to elucidate a possible mechanism(Scheme 3).