Synthesis of tricyclic fused 3-aminopyridines through intramolecular Co(I)-catalyzed [2+2+2] cycloaddition between ynamides, nitriles, and alkynes

Chemistry. 2009;15(9):2129-39. doi: 10.1002/chem.200802301.

Abstract

Three-ring circus: An expedient route to tricyclic fused 2-trimethylsilyl-3-aminopyridines exhibiting unprecedented skeletons is described. The key step is a very efficient cobalt-catalyzed [2+2+2] cycloaddition of a polyunsaturated compound displaying an ynamide, an alkyne, and a nitrile functionality (see picture). The first [2+2+2] cocyclizations between ynamides, nitriles, and alkynes are reported. They open a new access to unprecedented nitrogen-containing heterocycles of type 2-trimethylsilyl-3-aminopyridines. Such frameworks, which can be found in various compounds of biological interest, are very difficult to prepare by conventional methods. However, using [CpCo(C(2)H(4))(2)] (Cp=cyclopentadienyl) as catalyst, the intramolecular cyclizations could be achieved in up to 100 % yield. The presence of the trimethylsilyl group allowed a rare type of Hiyama cross-coupling: one of the silylated pyridines could be coupled with p-iodoanisole to give a new type of biaryl system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Amides / chemistry*
  • Aminopyridines / chemical synthesis*
  • Aminopyridines / chemistry
  • Catalysis
  • Cobalt / chemistry*
  • Cyclization
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Nitriles / chemistry*
  • Silicon Compounds / chemical synthesis*
  • Silicon Compounds / chemistry

Substances

  • Alkynes
  • Amides
  • Aminopyridines
  • Nitriles
  • Silicon Compounds
  • Cobalt