Organic Catalyzed Double Michael Addition Reaction Of Chiral Building Indene Compounds Studied Full Class Of Multi-substituted

Based on the principle of hydrogen-bonding catalytysis, some chiral acid-basebifunctional catalysis hydrogen-bond donors were synthsized by use of cinchonaalkaloid,(1R,2R)-cyclohexane-1,2-diamine (CHDA) and(1R,2R)-1,2-diphenylethane-1,2-diamine(DPEN) as the chiral sourse. Then thedeveloped chiral acid-base bifunctional catalysis were employed for cascadeMichael-Michael reactions of dienone and nitromethane, which were provided thedesired multifunctionalized chiral indane derivatives in good yields (51%–91%) withexcellent diastereoselectivities (>20:1dr) and excellent enantioselectivities(86%–99%ee).In recent years, various chiral organocatalysts have been developed and exploredin asymmetric catalysis. We firstly use Mitsunobu reaction and Staudinger reaction tosynthesize some chiral thioureas derived from cinchona alkaloids. Then,cyclohexane-1,2-diamine (CHDA) and1,2-diphenylethylene diamine (DPEN) wereused to synthesize the corresponding acid-base bifunctional catalysts by throughamino protection, double methylated reaction and deprotection.The indane units constitute core structural elements ubiquitous in large numberof biologically and pharmaceutically active moleculars such as Indatraline, Indinavirand Rasagiline. We have developed a new type of route to build chiral indan motifscompounds. The cascade asymmetric double Michael addition of dienone andnitromethane were carried out by the use of toluene as solvent and4MS asadditives in the presence of chiral thioureas catalyst derived from cinchona alkaloid,which furnished the multifunctionalized chiral indane derivatives with three alternatetrans-stereocenters in moderate to good yields (51%–91%) with excellentdiastereoselectivities (>20:1dr) and excellent enantioselectivities (86%–99%ee).Remarkably, the resulting products are readily converted into optically active1-indanmethylamine and tetrahydroindeno[2,1-b] pyrrole derivatives, and xcellentenantioselective and diastereoselectivity were retained in the process oftransformation.