Beilstein Journal of Organic Chemistry (Oct 2017)

A mechanochemical approach to access the proline–proline diketopiperazine framework

  • Nicolas Pétry,
  • Hafid Benakki,
  • Eric Clot,
  • Pascal Retailleau,
  • Farhate Guenoun,
  • Fatima Asserar,
  • Chakib Sekkat,
  • Thomas-Xavier Métro,
  • Jean Martinez,
  • Frédéric Lamaty

DOI
https://doi.org/10.3762/bjoc.13.217
Journal volume & issue
Vol. 13, no. 1
pp. 2169 – 2178

Abstract

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Ball milling was exploited to prepare a substituted proline building block by mechanochemical nucleophilic substitution. Subsequently, the mechanocoupling of hindered proline amino acid derivatives was developed to provide proline–proline dipeptides under solvent-free conditions. A deprotection–cyclization sequence yielded the corresponding diketopiperazines that were obtained with a high stereoselectivity which could be explained by DFT calculations. Using this method, an enantiopure disubstituted Pro–Pro diketopiperazine was synthesized in 4 steps, making 5 new bonds using a ball mill.

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