Reports: AC4
48388-AC4 Reactions of p-Benzynes with Nucleophiles
Recently we discovered a new reaction whereby halide anions add to a p-benzyne derived from an enediyne. We could verify this mechanism through kinetic studies on cyclodeca-1,5-diyn-3-ene. This is quite different from the usual radical chemistry of this biradical. We have proposed to study the generality of the addition of nucleophiles to p-benzynes. Through competition experiments with a series of nucleophiles we will define the selectivity of this reaction. So far we have been unable to add fluoride to a p-benzyne. A large number of experimental conditions were explored, including excess tetrabutylammonium fluoride or bifluoride in acetonitrile, DMSO, or THF, tri-t-butylphenol or 1,8-bis(dimethylamino)naphthalene bifluoride or t-butanol as proton source, and also tetrabutylammonium difluorotriphenylstannate, TBAT, and TASF, as well as microwave assistance. One difficulty is that "anhydrous" tetrabutylammonium fluoride, prepared from tetrabutylammonium cyanide and hexafluorobenzene, seems to react with the enediyne before it cyclizes. This project was very frustratin gofr the undergraduate who carried it out.
We were successful with tetrabutylammonium cyanide, and cyanotetralin was characterized by NMR and mass spectrometry. When the reaction is carried out in CD3CN, the cyanotetralin contains deuterium, showing that the aryl anion is capable of deprotonating even a weak acid.
Progress in extending this study to other nucleophiles has been slow, owing to difficulty in synthesis of the enediyne. In our hands the yield in the final step is far lower than what is reported, even though we take great care to follow the procedure. We have therefore developed three alternatives. One is to add only one equivalent of base to the dibromide and allow a slow cyclization to occur at 0ºC. The resulting monobromocyclodecadiyne can be detected by the characteristic doublet and triplet in its 1H NMR spectrum. Addition of the second equivalent of base then produces a good yield of the enediyne. Another method is to convert the dibromide to the bistriphenylphosphonium salt and then with base to the bis-ylide. Oxidative cyclization, catalyzed by vanadyl(acac)2, then produces a good yield of the enediyne. We are currently optimizing reaction conditions. A third approach is to prepare the known benzocyclodeca-1,5-diyn-3-ene. A complication is that its cyclization, at higher temperature, is reversible, as judged by previous studies on the kinetics of hydrogen-atom abstraction. Therefore in our reactions the rate-limiting step will become the nucleophilic addition. However, this does not matter for our study of competition kinetics.
