Creation of Fluorinated Amino Acids Library

为了建立含氟氨基酸库，对镁促进的C-F键活化进行了基础研究，并对几种含氟氨基酸进行了立体选择性合成。以下是合成的摘要。1)在三氟乙醇中经Pd(OCOCF3)2对映选择性加氢，合成具有光学活性的β，β-二氟脯氨酸(1)和β，β-二氟葡萄糖酸酯(2α-亚氨基-β溴-β，β-二氟丙酸酯，以87%的ee得到相应的胺，通过顺序化学反应转化为(1)和(2)。2)合成旋光性α-三氟甲基-α-碳氧基叠氮吡啶(3)旋光性α-三氟甲基叠氮吡啶在四氢呋喃中锂化，并与甲酸氯进行碳氧基化，收率为95%，构型保持不变。偶氮吡啶可被亲核试剂开环，导致α-三氟甲基化氨基酸的合成。(3) N、α-C-二硅基-β、β-二氟胺的合成及其在四氢呋喃中的应用(4)。在提供N、α-C-二硅基-β、β-二氟胺的四氢呋喃中，smg以优异的产率促进了三氟乙酸酰氯的C-F键活化，它们是N、α-C和α-C-β- c -dianion的合成等价物。双硅基胺可以被逐步全环化，从而得到多种功能化的氨基酸前体。4)合成具有光学活性的三氟甲基降冠酸（5)用氰化物稳定的碳离子取代羟基，得到具有光学活性的三氟甲基环丙烷，可转化为氨基酸(5)。5）合成三氟甲基异半胱氨酸（6)三氟乙酰氯与s保护的α-硫乙酸酯缩合，然后双立体选择性地还原免疫段并脱保护硫段，得到(6)6）铑用三氟乙酰咪啶酰氯和乙炔羧酸盐在一锅反应中催化喹啉环的形成。少

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(2α-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 … More or fluorinated amino acidsMg-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