Lewis Base Catalyzed Annulation Reaction Of Allenoates&Isocyanates

Organic phosphine catalyst and organic amine catalyst are two kinds of Lewis base catalysts,which have been widely used in the catalytic reaction of organic chemistry in recent years.Phosphine-catalyzed annulation of allenoates which can be used as C1,C2,C3,C4 and other synthons,have been developed as an important strategy for the construction of functionalized carboncyclic and heterocyclic compounds.Isocyanates are a class of compounds with active alpha hydrogen.It is very easy to be deprotonated by the organic amine catalysts to obtain the intermediate of carbon anion,showing reactive activity with the electron-poor alkenes or imines.Phosphine-catalyzed annulations of allenoates with NTs-chalcones,NBoc-chalcones,barbituric-tropilidene have been developed.In addition,amine-catalyzed[3+2]annulation reaction of sulfamate-derived cyclic imines with isocyanoacetates has been achieved.Finally,we constructed four series of compounds with potential biological activity.(1)A highly diastereoselective phosphine-catalyzed[4+1]annulation of 2-tosylaminochalcones and allenoate has been designed and developed.The reaction works very well under mild conditions to provide biologically important trans-2,3-disubstitued indoline derivatives as major diastereoisomers in moderate to good yields.Using PhCO2H as the additive,the yield was dramatically increased,which can be involved in the proton shift process.The acid may help the proton shift.(2)In the process of expanding the scope of the substrates of NR-chalcones,we found that when the N was protected by Boc substituent,[4+1]annulation did not occur.In this work,chiral phosphine-catalyzed asymmetric[3+2]annulation of chalcones with allenoates gave multi-substituted cyclopentenes in good to excellent yields with excellent regioselectivities,diastereoselectivities and enantioselectivities.Compared with previous works on chiral phosphine-catalyzed[3+2]annulation reactions of chalcones with allenoates,the yields and enantioselectivities have remarkably been improved when NBoc-chalcones were used as the substrates.Boc-amino is a key moiety to help achieve high yield and enantioselectivity.The possible reason might be that the nitrogen atoms interact with the substrates or the phosphine catalysts to form a hydrogen bond interaction,which can control the attack direction of the substrate.(3)Barbiturates are well-known as an important class of potentially active molecules.In this work,we developed phosphine-catalyzed[8+2]annulation of 5-(cyclohepta-2,4,6-trien-1-ylidene)-1,3-dimethylpyrimidine-2,4,6-(1H,3H,5H)-trione with allenoates under mild condition,giving pharmaceutically important spirobarbiturate-cyclopentane derivatives in moderate to high yield.With the use of Kwon's phosphine as the chiral catalyst,the optically active products were obtained in good yield with excellent enantioselectivities.It provides a new method for the synthesis of chiral barbiturates drugs.(4)Lewis base-catalyzed[3+2]annulation reaction of sulfamate-derived cyclic imines with isocyanoacetates has been developed,affording sulfamate-fused 2-imidazolines in moderate to excellent yields with moderate to excellent diastereoselectivities.The reaction provided a convenient method for preparation of pharmaceutically interesting sulfamate-fused 2-imidazolines.