Formal α-Vinylation of Amino Acids. Use of a New Benzeneselenolate Equivalent

Michelle L. Pedersen, David B Berkowitz

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

A new synthetic approach to the formal α-vinylation of α-amino acids is described, in which the readily available electrophile, ethylene oxide, serves as the vinyl cation equivalent. N-Benzoyl α-amino esters bearing appropriate side-chain protecting groups are deprotonated with lithium diisopropylamide in THF/TMEDA at −78 °C to generate the corresponding dianions. Exposure of these to ethylene oxide results in C-alkylation and lactonization to give the corresponding racemic, α-substituted homoserine lactones 2a-j in 61–85% yield. Next, reduction of diphenyl diselenide with sodium trimethoxyborohydride generates a benzeneselenolate anion equivalent which efficiently cleaves the α-substituted homoserine lactones without competing lactone reduction (69–97% yields for 3a-j following diazomethane workup). The protected α-[2-(phenylseleno)ethyl] amino acids thereby obtained are oxidized to the corresponding selenoxides through the agency of ozone at −78 °C. Pyrolysis of these in refluxing benzene or carbon tetrachloride gives the protected α-vinyl amino acids 4a-c and 4e-j in 95–100% yield. In the case of methyl Nα-benzoyl-2-[2′-(phenylseleno)ethyl]-Nτ-tritylhistidinate (3d), oxidation and pyrolysis (80%) are carried out in one pot by refluxing with tetrabutylammonium periodate in chloroform. Finally, deprotection is achieved by acidic hydrolysis. This methodology has been successfully applied to the synthesis, in racemic form, of the α-vinyl amino acids derived from phenylalanine (5a), DOPA (5b), histidine (5c), lysine (5d), ornithine (5e), valine (5f), alanine (5g), and homoserine (5h). In addition, α-vinylaspartic acid (9) and α-vinylarginine (10) could be obtained from α-vinylhomoserine derivative 4j and α-vinylornithine (5f), respectively.

Original languageEnglish (US)
Pages (from-to)6966-6975
Number of pages10
JournalJournal of Organic Chemistry
Volume58
Issue number25
DOIs
StatePublished - Jan 1 1993

Fingerprint

Amino Acids
Ethylene Oxide
Pyrolysis
Bearings (structural)
Diazomethane
Homoserine
Ornithine
Carbon Tetrachloride
Ozone
Alkylation
Valine
Lactones
Chloroform
Benzene
Phenylalanine
Histidine
Alanine
Lysine
Anions
Cations

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Formal α-Vinylation of Amino Acids. Use of a New Benzeneselenolate Equivalent. / Pedersen, Michelle L.; Berkowitz, David B.

In: Journal of Organic Chemistry, Vol. 58, No. 25, 01.01.1993, p. 6966-6975.

Research output: Contribution to journalArticle

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abstract = "A new synthetic approach to the formal α-vinylation of α-amino acids is described, in which the readily available electrophile, ethylene oxide, serves as the vinyl cation equivalent. N-Benzoyl α-amino esters bearing appropriate side-chain protecting groups are deprotonated with lithium diisopropylamide in THF/TMEDA at −78 °C to generate the corresponding dianions. Exposure of these to ethylene oxide results in C-alkylation and lactonization to give the corresponding racemic, α-substituted homoserine lactones 2a-j in 61–85{\%} yield. Next, reduction of diphenyl diselenide with sodium trimethoxyborohydride generates a benzeneselenolate anion equivalent which efficiently cleaves the α-substituted homoserine lactones without competing lactone reduction (69–97{\%} yields for 3a-j following diazomethane workup). The protected α-[2-(phenylseleno)ethyl] amino acids thereby obtained are oxidized to the corresponding selenoxides through the agency of ozone at −78 °C. Pyrolysis of these in refluxing benzene or carbon tetrachloride gives the protected α-vinyl amino acids 4a-c and 4e-j in 95–100{\%} yield. In the case of methyl Nα-benzoyl-2-[2′-(phenylseleno)ethyl]-Nτ-tritylhistidinate (3d), oxidation and pyrolysis (80{\%}) are carried out in one pot by refluxing with tetrabutylammonium periodate in chloroform. Finally, deprotection is achieved by acidic hydrolysis. This methodology has been successfully applied to the synthesis, in racemic form, of the α-vinyl amino acids derived from phenylalanine (5a), DOPA (5b), histidine (5c), lysine (5d), ornithine (5e), valine (5f), alanine (5g), and homoserine (5h). In addition, α-vinylaspartic acid (9) and α-vinylarginine (10) could be obtained from α-vinylhomoserine derivative 4j and α-vinylornithine (5f), respectively.",
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