Original scientific paper

Synthesis of the First Heteroannularly Substituted Ferrocene Amino Acid and Isomeric Carbamic Acid Derivatives Containing Chiral Centres

Mojca Čakić Semenčić
Maja Dropučić
Lidija Barišić
Vladimir Rapić

Abstract

Syntheses of N- and C-protected derivatives of 1'-(1-aminoethyl)ferrocene-1-carboxylic acid (Fcca) and isomeric carbamic acid are reported. The first attempt to prepare N-Ac-Fcca (8) by cleavage of 1-[1-(acetamido)ethyl]-1'-(o-chlorobenzoyl)ferrocene (7) with t-BuOK/H2O/GLYME failed. Friedel-Crafts reactions of N-substituted (1-ferrocenylethyl)amines [Boc-Fea (5) and Ac-Fea (6)] with ClCOSMe/AlCl3 gave the corresponding heteroannularly substituted thioesters 9/10, which were hydrolyzed into Boc-Fcca/Ac-Fcca and esterified into Boc-Fcca-OMe (11)/ Ac-Fcca-OMe (12). In a multi-step sequence, bromoferrocene was transformed into 1’- brominated Fea (15), Boc-Fea (16) and Ac-Fea (17). Lithiation/ethoxycarbonylation of these bromine compounds gave the corresponding carbamic esters 18 and 19, instead of the expected Fcca esters. By lithiation/carboxylation and subsequent esterification, 5, 6, 16 and 17 were converted into the desired 11 and 12. 1'-Acetylferrocene-1-carboxylic acid (21) was transformed into oxime 22 and oxime-ester 23. Hydrogenation of this intermediate resulted in formation of Fcca-OMe (24) in very good yield. The structure of the compounds prepared was confirmed by HRMS and spectroscopic analyses.

Keywords

ferrocene chiral amino acid; ferrocene chiral carbamic acid; oxime reduction; lithiation; carboxylation

Hrčak ID:

5806

URI

https://hrcak.srce.hr/5806

Publication date:

13.12.2006.

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