Ring systems Horner-Wadsworth-Emmons reaction

Pyridylidenehydantoins such as 139, obtained from pyridinecarbaldehydes by Horner-Wadsworth-Emmons reactions, are cyclized under acidic conditions to tricycles of the type 140 (Scheme 39) <2004TL553>. Similar benzannulated ring systems can be prepared by the reaction of 2-benzimidazolylacetonitriles and, for example, 2-chloronicotinic esters or 2-chloronicotinamides under basic conditions (Equation 32) <1996JHC1147, 1997JHC397>. 

A new ring system, which is a combination of a tropone and quinolines, was synthesized as a potential pharmaceutical target (Scheme 67). The approach involves preparation of 2-styrylquinoline-3-carboxylic acids from the Arbuzov reaction of ethyl 2-(bromoethyl)quinoline-3-carboxylate followed a Horner—Wadsworth—Emmons reaction to form the alkene.The ester can then be hydrolyzed to provide the free acid. AU three of these reactions can be carried out in one pot and in good yields, 18 examples, 68-83%. Heteroaryl aldehydes can also be employed in the Horner-Wadsworth-Emmons step, although the yields were lower, 54—61%. While the final Friedel-Crafts step should be catalyzed by a number of acids, only PPA (polyphosphoric... 

Synthetic routes to the benzocyclazines are analogues of those which lead to the cyclazines themselves. Representatives of the benzoh ]cycl[3.2.2]azine (indolizi no [3,4,5- ] isoindole, 365) ring system result from cycloaddition of, for example, DMAD to pyrido[2,l-tf]isoindole-6-carbonitrile 370 <1986H(24)3071> (Scheme 100). An alternative synthesis, which starts from the cyclazine 371 and involves construction of the additional benzenoid ring by a double Horner-Wadsworth-Emmons type of reaction, apparently gives the tetracyclic product 365 in only very low yields (Scheme 101) <1988H(27)2251>. 

Another strategy [115] for the preparation of these carbapenem analogs 221 used an intramolecular Wadsworth-Horner-Emmons reaction to form simultaneously the fused ring system and the endocyclic double-bond (Scheme 65). 

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