手性双哌啶酰胺的合成及在共轭加成中的应用  

Synthesis of Chiral Amides Emodying the Bispidine Framwork and Their Application in 1,4-Addition Reaction

作　　者：石乃月[1] 高敬园[1] 张月成[1] 赵继全[1] 

机构地区：[1]河北工业大学化工学院,天津300130

出　　处：《有机化学》2011年第4期497-504,共8页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金青年科学基金(No.20806020)资助项目

摘　　要：以N-苄基-4-哌啶酮、异丙胺为初始原料,经双Mannich反应、Wolf-Kishner还原、Pd/C脱苄基一系列反应得到3-异丙基-3,7-二氮杂双环[3.3.1]壬烷(9);化合物9再与4个叔丁氧羰基(Boc)保护的L-氨基酸反应生成相应酰胺,然后脱Boc保护基得到四个新的手性双哌啶α-氨基酰胺化合物12a～12d.它们与Ni(acac)_2结合形成配合物,用作二乙基锌对α,β-不饱和酮的不对称1,4-加成反应的催化剂.考察了手性配体的空间结构、配体与镍源的比例及用量、反应溶剂和反应温度对反应选择性的影响.在优化的反应条件下,即:以乙腈为溶剂,12c(20%)为手性配体,7%的乙酰丙酮镍为催化剂,二乙基锌与查尔酮的物质的量比为1.5:1,二乙基锌(150%)与查尔酮1,4-共轭加成反应产物的收率为87%,对映体过量值(ee)为77%.探讨了产生不对称加成反应的原因.3-Isopropyl-3,7-diazabicyclo[3.3.1]nonane 9 4-piperidinone and isopropyl amine via double Mannich was conveniently synthesized from N-benzylreaction, Wolff-Kishner reduction, debenzylation through Pd/C catalyzed hydrogenation. Subsequently, compound 9 was reacted with four N-tert-butoxycarbonyl-L-amino acids, followed by deprotection of tert-butoxycarbonyl group, to generate four new chiral a-amino amide ligends 12a-12d. They were used in Ni-catalyzed enantioselective 1,4-conjugate addition of diethyl zinc to α,β-unsaturated ketones. The effects of steric properties of chiral ligands, molar ratio of chiral ligand to nickel source, loading amount of ligand, solvent and temperature on 1,4-conjugate addition were investigated. Under the optimized conditions： MeCN as solvent, 12c （20 mol%） as ligand, Ni（acac）2 （7 mol%）, Et2Zn （150%）, a yield of 87% and an enantioselectivity of 77% were obtained, respectively. The possible mechanism for the asymmetric addition reactions was discussed.

关 键 词：N-苄基-4-哌啶酮 双哌啶 氨基酸 二乙基锌 手性酰胺 不对称1  4-共轭加成 

分 类 号：O621.3[理学—有机化学]