Synthetic Applications of 2-Cyano-1,2,3,6-tetrahydropyridines. Improved Synthesis of the Fundamental Tetracyclic Framework of Dasycarpidone

Article abstract of DOI:10.1021/jo00133a039

2-Cyano-1,2,3,6-tetrahydropyridines 2b-d, with a functionalized C-4 substituent, were prepared from the corresponding pyridinium salts by sodium borohydride reduction in the presence of sodium cyanide.Reaction of these 2-cyanotetrahydropyridines with indolylmagnesium iodide afforded 3-(1,2,3,6-tetrrahydro-2-pyridyl)indoles 3b-d.Alternatively, 3c and 3d were prepared in excellent yield by condensation of 2-cyanotetrahydropyridines 2c and 2d with indole in acetic acid medium.Deethyldasycarpidone was obtained from 3b in poor or moderate yields by three alternative procedures and from 3c in a three-step sequence.The preparation of deethyldasycarpidone from 2-cyanotetrahydropyridine 2c via the (tetrahydropyridyl)indole 3c constitutes an improved synthesis of this tetracyclic ring system.Similarly, 20-deethyl-4-demethyldasycarpidone was obtained from (tetrahydropyridyl)indole 3d.