title: High yielding synthesis of N-ethyl dehydroamino acids.
abstract: Recently we reported the use of a sequence of alkylation and dehydration methodologies to obtain N-ethyl-α, β-dehydroamino acid derivatives. The application of this N-alkylation procedure to several methyl esters of β,β-dibromo and β-bromo, β-substituted dehydroamino acids protected with standard amine protecting groups was subsequently reported. The corresponding N-ethyl, β-bromo dehydroamino acid derivatives were obtained in fair to high yields and some were used as substrates in Suzuki cross-coupling reactions to give N-ethyl, β,β-disubstituted dehydroalanine derivatives. Herein, we further explore N-ethylation of β-halo dehydroamino acid derivatives using triethyloxonium tetrafluoroborate as alkylating agent, but substituting N,N-diisopropylethylamine for potassium tert-butoxide as auxiliary base. In these conditions, for all β-halo dehydroamino acid derivatives, reactions were complete and the N-ethylated derivative could be isolated in high yield. This method was also applied for N-ethylation of non-halogenated dehydroamino acids. Again, with all compounds the reactions were complete and the N-ethyl dehydroamino acid derivatives could be isolated in high yields. Some of these N-ethyl dehydroamino acid methyl ester derivatives were converted in high yields to their corresponding acids and coupled to an amino acid methyl ester to give N-ethyl dehydrodipeptide derivatives in good yields. Thus, this method constitutes a general procedure for high yielding synthesis of N-ethylated dehydroamino acids, which can be further applied in peptide synthesis.
authors.affiliation: Chemistry Centre, University of Minho, Gualtar, 4710-057, Braga, Portugal. monteiro@quimica.uminho.pt
authors.forename: Luís S
authors.initials: LS
authors.lastname: Monteiro
authors.forename: Ana S
authors.initials: AS
authors.lastname: Suárez
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D000478:Alkylation; D000596:Amino Acids / Q000138:chemical synthesis*; D001881:Borates / Q000737:chemistry*; D000440:Butanols / Q000737:chemistry*; D004151:Dipeptides / Q000138:chemical synthesis*; D004952:Esters; D014867:Water / Q000737:chemistry
chemical_list: D000596:Amino Acids; D001881:Borates; D000440:Butanols; D004151:Dipeptides; D004952:Esters; D014867:Water; C077664:tert-butoxide, potassium; C015102:dehydroalanine; D000409:Alanine; C005142:triethyloxonium tetrafluoroborate