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

Research Project

Project/Area Number	62550629
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Synthetic chemistry
Research Institution	Kyoto University
Principal Investigator	TSUDA Tetsuo Faculty of Engineering,Kyoto University, Associate Professor, 工学部, 助教授 (10025992)
Project Period (FY)	1987 – 1988
Project Status	Completed (Fiscal Year 1988)
Budget Amount *help	¥2,000,000 (Direct Cost: ¥2,000,000) Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000) Fiscal Year 1987: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywords	Amino acid synthesis / -Allylpalladium complex having two different functional groups / CーNカップリング反応 / 二官能基化π-アリルパラジウム錯体 / C-Nカップリング反応 / 二官能性π-アリルパラジウム錯体の位置選択的反応 / π-アリルパラジウム錯体と窒素求核剤との反応
Research Abstract	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.