Dehydration of Chiral α-Amides to Chiral α-Nitriles Under the Appel Reaction Conditions

Abstract

An efficient synthesis of Nα-protected amino nitriles from Nα-protected amino acid amides employing Ph3P, I2 and NMM was described. Various amino acid amides, protected by Fmoc, Z and Boc were conveniently converted to nitriles in high yields. Side chain protected amino acid amides were well-tolerated and a good yield of products was obtained. The protocol serves as one of the mild, among a few available, methods for the racemization-free conversion of Nα-protected amino acid amides to corresponding nitriles with neither harsh condition nor catalyst.

Graphic Abstract

Nα-protected amino acid amides were efficiently transformed to Nα-protected amino acid nitriles employing I2, PPh3, and NMM under mild reaction conditions. Fmoc, Boc and Cbz-protected amino acid amides were converted into their corresponding nitriles groups. Side chain protected amino acid amides also underwent facile conversion to their corresponding nitriles with good yields.

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Fig. 1
Scheme 1
Scheme 2

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Acknowledgements

Shekharappa is thankful to University Grants Commission for NFSC. Roopesh Kumar L are thankful to DST Nano-mission, Government of India, for financial assistance.

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Correspondence to Vommina V. Sureshbabu.

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Shekharappa, Roopesh Kumar, L., Srinivasulu, C. et al. Dehydration of Chiral α-Amides to Chiral α-Nitriles Under the Appel Reaction Conditions. Int J Pept Res Ther 27, 497–502 (2021). https://doi.org/10.1007/s10989-020-10101-y

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Keywords

  • α-Amide
  • α-Nitrile
  • N-Methylmorpholine
  • Molecular iodine
  • Triphenylphosphine