Direct N‐Alkylation and Kemp Elimination Reactions of 1‐Sulfonyl‐1H‐Indazoles

Abstract

The reactions of 1-sulfonyl-1H-indazoles under basic conditions are discussed, and the direct N-alkylation and Kemp elimination reactions of these compounds are reported. A series of 2-(p-tosylamino)benzonitriles and N-alkyl indazoles were prepared in good yields. Moreover, the 2-(p-tosylamino)benzonitriles could be transformed into a diverse range of important derivatives in a one-pot reaction. This method was successfully applied to the total syntheses of quindolinone and cryptolepinone; quindolinone was prepared in a one-pot reaction from 1-sulfonyl-1H-indazole.

Origin of Ligand and Acid Effects on the Pd-Catalyzed Regiodivergent Coupling Reaction of Indazoles and Isoprene: A DFT Study

“…10,11 However, due to the competitive nucleophilic sites between the N 1 and N 2 of indazoles, a mixture of N 1 -or N 2 -isomers is delivered normally under basic conditions. 12,13 Despite the fact that significant advances have been achieved in these pioneering works, the discovery of efficient catalysis for the selective N-allylation of indazoles is very limited. 14,15 Therefore, understanding how to obtain the desired product by regulating the competition for nucleophilic sites between the N 1 and N 2 positions of indazole is crucial for its development in this field.…”

“…Indazoles are important building blocks found in various pharmaceuticals and biologically important molecules due to their biological and chemical activities. − Given their importance as privileged scaffolds in medicinal chemistry, diversely substituted indazole derivatives with different functional groups have received significant attention in recent years, and a large number of synthetic methodologies available in the literature for the functionalization of indazoles have been extensively studied. − The alkylation of indazoles represents one of the most efficient methods in terms of atom- and step-economy. , The transition metal catalyst has been designed as an effective tool for controllable selective functionalization in the alkylation of indazoles. Previous findings have shown that both rhodium and palladium could promote the coupling of N-substituted indazole with allenes for the synthesis of medicinally important targets. , However, due to the competitive nucleophilic sites between the N 1 and N 2 of indazoles, a mixture of N 1 - or N 2 -isomers is delivered normally under basic conditions. , Despite the fact that significant advances have been achieved in these pioneering works, the discovery of efficient catalysis for the selective N-allylation of indazoles is very limited. , Therefore, understanding how to obtain the desired product by regulating the competition for nucleophilic sites between the N 1 and N 2 positions of indazole is crucial for its development in this field. ,, …”

TfOH-catalyzed regioselective N2-alkylation of indazoles with diazo compounds

“…[13][14][15] However, one limitation becomes evident due to the competitive nucleophilic sites between the N 1 and N 2 of indazoles in the transformation, resulting in a mixture of N 1 -or N 2 -isomers (Scheme 1). 16,17 Thus, controlled alkylation of indazoles in a regioselective manner is still a highly challenging topic in this arena, specifically for C3-unsubstituted indazoles. Generally, selectivity for alkylation of indazoles is achieved through addition of a strong or weak base, heating the reaction and altering the nature of the electrophile.…”

“…Increasing the temperature to 50 1C proved to be beneficial, increasing the yield of 3a to 79% yield with high selectivity (Table 1, entries 11-16). The loading of TfOH was decreased to 5 mol% with a slightly lower yield, but further increase led to a low yield (Table 1, entries [17][18][19][20]. The amount of the diazo substrates was also examined, providing excellent yields (Table 1, entries [21][22][23].…”

“…13–15 However, one limitation becomes evident due to the competitive nucleophilic sites between the N 1 and N 2 of indazoles in the transformation, resulting in a mixture of N 1 - or N 2 -isomers (Scheme 1). 16,17…”