Transition-Metal Complex-Catalyzed Synthesis of Novel Biologically Active Amino Acids

研究了氮亲核试剂与烯丙基碳原子上均有羟基烷基和羧基官能团的烯丙基钯配合物反应合成-不饱和氨基酸或-不饱和氨基酸衍生物。钯(O)-磷配体配合物催化甲基，-环氧山梨酸酯与氮亲核试剂如邻苯二胺和苯磺酰胺的反应，产生高收率的区域特异性(E)-5-羟基-4-氨基-2-己酸酯，即-不饱和-氨基酸衍生物。磷配体（P(OCH_2)_3CEt、PPh_3、PCy_3、PEt_3、dppf）和溶剂（THF、C_6H_6-THF、DMSO、DMF）对C-N偶联反应的-区域特异性没有影响。羰基官能团从酯基到酰胺基的变化没有改变C-N偶联反应的-区域特异性：钯(O)催化的N，N-二乙基- -环氧脲与邻苯二胺的反应产生相应的-N取代产物。因此，本研究确定了钯(O)催化的-环氧山梨酸衍生物与氮亲核试剂的反应为-不饱和氨基酸衍生物的合成提供了一种方便的方法。

Synthesis of a , -unsaturated -amino acid or , -unsaturated -amino acid derivative by the reaction of a nitrogen nucleophile with a -allylpalladium complex having hydroxyalkyl and carboxyl functional groups at both allylic carbon atoms was investigated. Palladium(O)-phosphorus ligand complexes catalyzed the reaction of methyl , -epoxysorbate with nitrogen nucleophiles such as phthalimide and benzenesulfonamide to afford regiospecifically (E)-5-hydroxy-4-amino-2-hexenoates, i.e., , -unsaturated -amino acid derivatives, in high yields. The -regiospecificity of the C-N coupling reaction was not influenced by the phosphorus ligand (P(OCH_2)_3CEt, PPh_3, PCy_3, PEt_3, dppf) and the solvent used (THF, C_6H_6-THF, DMSO, DMF). Change of the carbonyl functionality from the ester group to the amide group did not alter the -regiospecificity of the C-N coupling reaction: the palladium(O)-catalyzed reaction of N,N-diethyl- , -epoxysorbamide with phthalimide produced the corresponding -N-substituted product. Thus it was established in the present study that the palladium(O)-catalyzed reaction of , -epoxysorbic acid derivatives with nitrogen nucleophiles provides a convenient synthetic method of , -unsaturated -amino acid derivatives.