KATAGIRI Toshimasa Okayama University, Graduate School, Faculty of Natural Science and Technology, Associate Professor, 大学院・自然科学研究科, 助教授 (70202009)
AMII Hideki Okayama University, Graduate School, Faculty of Natural Science and Technology, Research Associate, 大学院・自然科学研究科, 助手 (00284028)
In order to create a library of fluorinated amino acids, a basic study on magnesium-promoted C-F bond activation has been done and then several fluoorinated amino acids have been synthesized stereoselectively. The followings are a summary of the syntheses.
1) Syntheses of optically active β,β-difluoroproline(1) and β,β-difluoroglutamates(2
α-imino-β bromo-β,β-difluoropropanate was enantioselecdvely hydrogenated by Pd(OCOCF3)2 in trifluoroethanol to provide the corresponding amine in 87%ee, which was transformed to (1) and (2) by sequensial chemical reactions.
2) Syntheses of optically active α-trifluoromethyl-α-carboalkoxyaziridine (3)
Optically active α-trifluoromethylaziridine was lithiated in THF and carboalkoxylated with chloro formate in 95% yield with retention of the configuration. The aziridine could be ring-opened by the nucleuophiles leading to the general syntheses of α-trifluoromethylated amino acids.
3) Synthese of N, α-C-disilyl-β,β-difluoroenamines (4) and their utilization f
or fluorinated amino acids
Mg-promoted C-F bond activation of trifluoroacetimidoyl chloride in THF provided of N, α-C-bissilyl-β,β-difluoroenamines in excellent yields, which are synthetic equivalents of N, α-C-and α-C-β-C-dianion. The bissilyl enamines could be allcylated stepwise leading to a vaiety of functionalized amino acid precursors.
4) Syntheses of optically active trifluoromethylnorcoronamc acids (5)
The intramolecular stereospecific substitution of hydroxy group with cyanide-stabilized carbanion provided optically active trifluoromethylcyclopropanes which could be transformed to amino acids (5).
5) Syntheses of trifluoromethylisocysteine(6)
Condensation of trifluoroacetimidoyl chloride with S-protected α-thioacetate followed by disstereoselective reduution of imono moiety and deprotection of thio moiety gave (6).
6) Rhodium catalyzed quinoline ring formation by the reaction of trifluoroacetimidoyl chloride with acetylene carboaylates provided quinoline carboxylates in one-pot reaction. Less