Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations.

Herein, we report a pair of regioselective - and alkylations of a versatile indazole, methyl 5-bromo-1-indazole-3-carboxylate () and the use of density functional theory (DFT) to evaluate their mechanisms. Over thirty - and -alkylated products were isolated in over 90% yield regardless of the conditions. DFT calculations suggest a chelation mechanism produces the -substituted products when cesium is present and other non-covalent interactions (NCIs) drive the -product formation. Methyl 1-indazole-7-carboxylate () and 1-indazole-3-carbonitrile () were also subjected to the reaction conditions and their mechanisms were evaluated. The - and -partial charges and Fukui indices were calculated for compounds , , and via natural bond orbital (NBO) analyses which further support the suggested reaction pathways.