Synthesis of Cyclo-2,2':4',4":2",2"':4"',4"":2"",2""':4""',4-sexipyridine

Preparation of the title compound (2) by use of Stille couplings and a Kröhnke pyridine synthesis is described. By application of the Stille coupling reaction, preparation and functionalization of quater- and quinquepyridines 26, 27, and 28 were achieved. Elaboration of quinquepyridine 27 to the pyridinium salt 30 bearing a protected enal allowed for the synthesis of 2 by a one-pot deprotection/Kröhnke reaction in nine steps from 4,4'-bipyridine. Use of the Kröhnke pyridine synthesis has been applied to prepare sexipyridine dibromide 19, but attempts to induce a macrocyclization via metal-mediated (Pd/Ni/Cu) aryl-aryl coupling procedures proved unsuccessful. Acetylene-bridged sexipyridines 3a and 3b incorporating 2,2'-bipyridine units proved to be inaccessible via sp-sp(2) or sp-sp coupling protocols.