Synthesis of a γ-lactam library via formal cycloaddition of imines and substituted succinic anhydrides

Darlene Q. Tan, Amy L. Atherton, Austin J. Smith, Cristian Soldi, Katherine A. Hurley, James C. Fettinger, Jared T. Shaw

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Formal cycloaddition reactions between imines and cyclic anhydrides serve as starting point for the synthesis of diverse libraries of small molecules. The synthesis of succinic anhydrides substituted with electron-withdrawing groups is facilitated by new mild conditions for alkylation of aryl-substituted acetyl esters with ethyl bromoacetate. These anhydrides are then used in formal cycloaddition reactions with imines to produce γ-lactams. 2-Fluoro-5-nitrophenylsuccinic anhydride reacts efficiently with imines to provide lactams that are further diversified by conversion of the nitro group to either an aniline and an azide for subsequent reactions with acylating agents and alkynes, respectively. The synthesis of cyanosuccinic anhydride is reported for the first time, and the use of this compound in reactions with imines and subsequent functionalization of the resultant lactams is demonstrated.

Original languageEnglish (US)
Pages (from-to)218-223
Number of pages6
JournalACS Combinatorial Science
Volume14
Issue number3
DOIs
StatePublished - Mar 12 2012

Fingerprint

Succinic Anhydrides
Lactams
Imines
Cycloaddition
Anhydrides
Alkynes
Azides
Alkylation
Esters
Molecules
Electrons

Keywords

  • γ-lactams
  • cyanosuccinic anhydrides
  • imine-anhydride formal cycloaddition
  • spirooxindole

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Tan, D. Q., Atherton, A. L., Smith, A. J., Soldi, C., Hurley, K. A., Fettinger, J. C., & Shaw, J. T. (2012). Synthesis of a γ-lactam library via formal cycloaddition of imines and substituted succinic anhydrides. ACS Combinatorial Science, 14(3), 218-223. https://doi.org/10.1021/co2001873

Synthesis of a γ-lactam library via formal cycloaddition of imines and substituted succinic anhydrides. / Tan, Darlene Q.; Atherton, Amy L.; Smith, Austin J.; Soldi, Cristian; Hurley, Katherine A.; Fettinger, James C.; Shaw, Jared T.

In: ACS Combinatorial Science, Vol. 14, No. 3, 12.03.2012, p. 218-223.

Research output: Contribution to journalArticle

Tan, DQ, Atherton, AL, Smith, AJ, Soldi, C, Hurley, KA, Fettinger, JC & Shaw, JT 2012, 'Synthesis of a γ-lactam library via formal cycloaddition of imines and substituted succinic anhydrides', ACS Combinatorial Science, vol. 14, no. 3, pp. 218-223. https://doi.org/10.1021/co2001873
Tan, Darlene Q. ; Atherton, Amy L. ; Smith, Austin J. ; Soldi, Cristian ; Hurley, Katherine A. ; Fettinger, James C. ; Shaw, Jared T. / Synthesis of a γ-lactam library via formal cycloaddition of imines and substituted succinic anhydrides. In: ACS Combinatorial Science. 2012 ; Vol. 14, No. 3. pp. 218-223.
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