1H-Indazoles via Huisgen [3+2] Cycloaddition of Benzynes with Nitrile Imines

Significance

Reported is a simple and efficient synthesis of 1-substituted-1H-indazoles via [3+2] cycloaddition between in situ generated nitrile im­ines and arynes. Based on previous results from the same laboratory (Chem. Commun. 2010, 46, 1272) and after screening of different fluoride sources, conditions were devised for the simultaneous generation of nitrile imines and benzynes using CsF/18-crown-6, the latter reagent showing significant enhancement in rates of formation of 3 and 4 (B. L. Feringa and co-workers Org. Biomol. Chem. 2008, 6, 3461). The reaction tolerates a range of functionalities, including aryl- and heterocycle-substituted hydrozonyl chlorides. However, it was demonstrated that the electronic effects (EWGs and EDGs) and steric hindrance play a key role in particular in terms of self-dimerization and life-time of the species 3 in solution. The difference in regiocontrol of the Huisgen cycloaddition was attributed to a more pronounced electronic effect exerted by the OMe group as compared to Me.