1,3-Dipolar Cycloaddition with Diazo Groups: Noncovalent Interactions Overwhelm Strain

Org Lett. 2016 Sep 16;18(18):4466-4469. doi: 10.1021/acs.orglett.6b01938. Epub 2016 Sep 6.

Abstract

Like azides, diazoacetamides undergo 1,3-dipolar cycloadditions with oxanorbornadienes (OND) in a reaction that is accelerated by the relief of strain in the transition state. The cycloaddition of a diazoacetamide with unstrained ethyl 4,4,4-trifluoro-2-butynoate is, however, 35-fold faster than with the analogous OND because of favorable interactions with the fluoro groups. Its rate constant (k = 0.53 M(-1) s(-1) in methanol) is comparable to those of strain-promoted azide-cyclooctyne cycloadditions.

Publication types

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

MeSH terms

  • Acetamides / chemistry
  • Azides / chemistry
  • Butyrates / chemistry
  • Cycloaddition Reaction
  • Kinetics
  • Methanol / chemistry
  • Pyrazoles / chemical synthesis*
  • Quantum Theory
  • Solvents / chemistry

Substances

  • Acetamides
  • Azides
  • Butyrates
  • Pyrazoles
  • Solvents
  • Methanol