Study Of Asymmetric Catalytic 1, 4-Conjugate Additions

Huihui Wan (Organic Chemistry) Directed by Prof. Zhuo Zheng and Associate Prof. Xinquan HuTwo new chiral backbones R-(+)- and S-(-)-2-amino-2'-hydroxy-4,4',6,6'-tetra methyl-1,1'-biphenyl were synthesized via nitration, diazotation/iodination, Ulhnann coupling, selective reduction, diazotation/hydrolysis, hydrogenation and resolution from 2,4-dimethyl-aniline in seven steps.Amidation of (S)-(-)-2-amino-2'-hydroxy-6,6'-dimethyl-1, 1'-biphenyl 7a, (S)-(-)-2-amino-2'-hydroxy-4,4',6,6'-tetramethyl-l,r-biphenyl 7b with 2-picolinic acid separately afforded the amides 8a-d in high yields with DMTMM as the condensation reagent. Four phosphite-pyridine (P,N) ligands 9a-d were conveniently prepared in high yield via the phosphite-exchange by refluxing the amides and Feringa's phosphorus-amidite 10 in toluene.In the Cu(I)-catalyzed enantioselective 1,4-conjugate addition of diethylzinc to acyclic enones, the reaction conditions, such as the amount of diethylzinc, solvents, temperature and the reaction time, were investigated in detail with 9a as the standard ligand and chalcone as the typical substrate. The optimum reaction is as follows: substrate / [Cu(CH3CN)4]BF4 / Et2Zn = 1 / 0.01 / 0.025 /1.5 in toluene at -20 0C forUnder the optimized condition the Cu(I)-catalyzed enantioselective 1,4-conjugate additions of diethylzinc to eleven acyclic enones (chalcone, 4-chlorochalcone, 4-methyl-chalcone, 4-methoxy-chalcone, 4'-chlorochalcone, 4'-methyl-chalcone, 4'-methoxy-chalcone, 4-phenyl-3 -buten-2-one, 4-(4-chlorophenyl)-3 -buten-2-one, 4-(4-methyl-phenyl)-3-buten-2-one and 4-(4-methoxy-phenyl)-3-buten-2-one) were studied with [Cu(CH3CN)4]BF4 / 9a-d as the catalysts. The electron-rich and sterically hindered ligand 9d provides the best enantioselectivities (up to 97.8 % ee) for various chalcones as the substrates. However, when trans-4-aryl-3-buten-2-ones were taken as the substrates, the electron-rich but less sterically hindered ligand 9c gives the best results (up to 96.4 % ee) with highly catalytic activity.