Rhodium-Catalyzed (1H)-Indazole Regioselective C7-Allylation Reaction

Replace(1H)-indazole ring system is a kind of universal existence in nature all kinds of important nitrogen heterocyclic compounds in natural products,especially(1H)-indazole with a substituent at the C7 position compounds;they have a wide range of biological activities and an irreplaceable role in drug development.However,traditional synthesis methods are not in line with the current concept of green development,which greatly limits its development and application.The C-H-activated functionalization reaction may be the most direct and convenient method in the future,but due to the uneven distribution of the electron cloud density on the(1H)-indazole ring and its inherently poor reactivity means that it is directly carried out at the C7 position of the indazole ring regional selective functionalization remains a huge challenge.According to the previous regioselective C-H activation reaction of biologically active heterocyclic compounds carried out by the research group,in this paper,the reaction of indazole substrate with N,N-diisopropylformyl as the guiding group and allyl methyl carbonate is used as the template reaction,and the effect of a series of different conditions on the reaction is investigated using a single variable methods,and finally got the optimal conditions for the reaction.On this basis,the tolerance of the functional groups of the reaction was investigated.It is satisfactory that the reaction of(1H)-indazole substrates substituted with groups with different electronic effects and allyl methyl carbonate was satisfactory results;especially(1H)-indazole substrates containing a strong electron-withdrawing group-nitro can also be carried out.At the end of the study,the application of the reaction in synthesis was also tried and the ideal results were obtained.This study revealed the first region-specific method for the selective synthesis of C7-H allylated indazole.