Synthesis Of Chiral Amides Embodying The Bispidine Framwork And Their Application In The Asymmetric Addition Of Diethylzinc To α,β-Unsaturated Aldehyde/Ketones

3-Alkyl-3, 7-diazabicyclo[3.3.1]nonanes (3a³b) were conveniently synthesized from N- benzyl- 4- piperidinone and simple primary amines via double Mannich reaction, followed by Wolff-Kishner reduction, and debenzylation through Pd/C catalyzed hydrogenation. Subsequently, compounds 3a³b reacted with six N- tert-butoxycarbonyl–L-amino acids, followed by deprotection of tert-butoxycarbonyl group, to generate six new chiralα-amino amide ligands 6a⁶d/9a⁹b. The structures of the intermediates and the final products were characterized by 1H NMR, 13C NMR, FT-IR and MS. Furthermore, the optical rotation of the target products was measured and the results confirmed that all the products were chiral compounds.Then the compounds 6a⁶d and 9a⁹b combined with Ni(acac)2 were applied to the enantioselective 1, 4-conjugate addition of diethyl zinc to chalcone. The effects of steric properties of chiral ligands, molar ratio of chiral ligand to nickel source, loading amount of ligand, solvent and temperature on the 1, 4-conjugate addition were investigated and the optimized conditions were received with (S)-isopropyl- 7- (2-phenyl-2-amino) acetyl -3,7- diazadicyclo [3.3.1] nonane (6c) as ligand. Under the optimized conditions, which MeCN was used as solvent, the molar ratios of substrate: 6c: Ni(acac)2: Et2Zn were 1: 0.2: 0.07: 1.5, a yield of 87% of the product and an enantioselectivity of 77% were obtained, respectively. In addition, S enantiomer was the predominant component. The possible mechanism for the asymmetric addition reactions was also discussed. The chiral ligands were also applied to the enantioselective addition of dimethylzinc to other 1, 4-unsaturated aldehydes and ketones under the optimized conditions in the case of 6c as substrate. Besides, the ligands were also applied to the CuCl₂ catalyzed asymmetric addition of dimethylzinc to1, 4-unsaturated aldehydes and ketones and the mechanism was also discussed.