Enantioselective Nickel-Catalyzed Alkyne-Azide Cycloaddition by Dynamic Kinetic Resolution

En Chih Liu, Joseph J. Topczewski

Research output: Contribution to journalArticlepeer-review

Abstract

The triazole heterocycle has been widely adopted as an isostere for the amide bond. Many native amides are α-chiral, being derived from amino acids. This makes α-N-chiral triazoles attractive building blocks. This report describes the first enantioselective triazole synthesis that proceeds via nickel-catalyzed alkyne-azide cycloaddition (NiAAC). This dynamic kinetic resolution is enabled by a spontaneous [3,3]-sigmatropic rearrangement of the allylic azide. The 1,4,5-trisubstituted triazole products, derived from internal alkynes, are complementary to those commonly obtained by the related CuAAC reaction. Initial mechanistic experiments indicate that the NiAAC reaction proceeds through a monometallic Ni complex, which is distinct from the CuAAC manifold.

Original languageEnglish (US)
Pages (from-to)5308-5313
Number of pages6
JournalJournal of the American Chemical Society
Volume143
Issue number14
DOIs
StatePublished - Apr 14 2021

Bibliographical note

Funding Information:
We thank Victor Young, Jr., and Margaret Clapham for assistance with diffraction analysis of compounds 3a, 3r, and 3w. We thank Juliana Alexander for the preparation of ynamides. E.-C.L acknowledges support from the Wayland Nolan Fellowship and the Doctoral Dissertation Fellowship. This research was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award R35GM124718. We also acknowledge NIH Shared Instrumentation Grant S10OD011952. Funding from the University of Minnesota is acknowledged.

Funding Information:
We thank Victor Young, Jr., and Margaret Clapham for assistance with diffraction analysis of compounds 3a , 3r , and 3w . We thank Juliana Alexander for the preparation of ynamides. E.-C.L acknowledges support from the Wayland Nolan Fellowship and the Doctoral Dissertation Fellowship. This research was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award R35GM124718. We also acknowledge NIH Shared Instrumentation Grant S10OD011952. Funding from the University of Minnesota is acknowledged.

Publisher Copyright:
© 2021 American Chemical Society.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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