Aromatic Allylation via Diazotization; Application in synthesis of heterocyclic compounds

A new method for allylation of aromatic systems has been developed. A number of arylamines were converted via diazotization to the corresponding allylaromatic compounds using tert-butyl nitrite and an excess of allylic bromides with complete regioselectivity. Electron-withdrawing groups, in the aromatic moiety, were necessary to obtain good yields. The convenient experimental procedure allowed the synthesis of allyl-3,5-dinitrobenzene at a large scale. In addition, a new allylation-bromocyclization reaction was demonstrated. This result initiated the development of a new method to obtain fused heterocycles via iodocyclization. A number of tetrazoles and imidazole derivatives were prepared in good to excellent yields. The cyclization of some of the substrates deviated from Baldwin’s cyclization rules i.e. exo-selectivity. The obtained fused heterocyclic compounds were useful substrates for further derivatization. Furthermore, a method to obtain fused tetrazole derivatives from allylic bromides, generated in the allylation reaction, was developed. This new tandem reaction comprises a cycloaddition between a nitrile and trimethylsilyl azide induced by dibutyltin oxide followed by a intramolecular N-alkylation. These heterocyclic derivatives, incorporating a exomethylene functionality, were used in the parallel synthesis of a small library of amines. The fused tetrazole derivatives have structural similarities with Bengamides, a group of natural products possessing interesting pharmacological properties. This motivated the development of an analogue of Bengamide A, based on a fused tetrazole derivative. Key-intermediates of the analogue have been prepared.