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

研究了用含氮亲核试剂与两个烯丙基碳原子上都含有羟基烷基和羧基的α-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)-磷配体络合物催化环氧山梨酸甲酯与邻苯二甲酰亚胺、苯磺酰胺等氮亲核试剂反应，高产率地合成了区域专一性的(E)-5-羟基-4-氨基-2-己烯酸酯，即-不饱和氨基酸衍生物。磷配体(P(OCH2)3CEt、PPh_3、PCy_3、PET_3、dppf)和所用溶剂(THF、C_6H_6-THF、DMSO、DMF)不影响C-N偶联反应的区域特异性。羧基由酯基变为酰胺基并不改变C-N偶联反应的-区域专一性：钯(O)催化N，N-二乙基-环氧山梨酰胺与邻苯二甲酰亚胺的反应生成相应的-N-取代产物。因此，本研究确定了钯(O)催化的α-环氧山梨酸衍生物与氮亲核试剂的反应为合成α-不饱和氨基酸衍生物提供了一种简便的方法。

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.