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Preparation of some ferrocene amino and carbamic acids with chiral center

In continuation of our studies on ferrocene amino acids [1, 2] and the derived conjugates with L-alanine [3] we decided to prepare the similar amino acids containing the chiral center incorporated in the aminoaliphatic part of the molecule. The action of NH3(aq) HgCl2/ NH4 Cl on 4-ferrocenyl-3-thiavaleric acid (1) gave 1-(ferrocenyl)ethylamine (2), which was converted into 91% of N-Boc- (3) and 84% of N-Ac- derivate 4. Heteroannular acylation of compound 4 with o, o-Cl2C6H3COCl/ AlCl3 afforded ketone 5 but its cleavage into the desired 1-[1-(acetamido)ethyl]ferrocen-1-carboxylic acid (6) was unsuccessful. By the action of Cl(C=O)SMe/ AlCl3 N-protected derivatives 3 and 4 were converted into thiolesters 7a and 8a in low yields. Hydrolysis of 8a gave 76% of N-Ac-derivative of the amino acid 6. Similarly as in transformation 12, reaction of 4-(1-bromoferrocenyl)-3-thiavaleric acid (9) with NH3(aq)/ HgCl2/ NH4Cl gave 67% of 1-(1-bromoferrocenyl)ethylamine (10), which was converted into 98% of N-(tert-butoxy-carbonyl)-1-(1-bromoferrocenyl)ethylamine (11) and 84% of N-acetyl-1-(1-bromofer-rocenyl)ethylamine (12). Sucessive lithiation and ethoxycarbonylation of compound 10 resulted in formation of N, N-bisethoxycarbonyl-1-(ferrocenyl)ethylamine (13). Similary, bromine derivatives 11 and 12 were converted into the corresponding N-ethoxycarbonylated compounds 14 (77%) and 15 (66%). Lithiation/carboxylation of 3 and 11 afforded compound 16 in 27% and 30% yield, respectively. In a similar manner 4 was converted into 50% of 6.

Ferrocene Amino and Carbamic Acids with Chiral Center

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