Research group of Professor Song Qiuling of Huaqiao University: Lewis acid mediated [3 + 3] cycloaddition reaction

In January, song Qiuling's research group of lead overseas Chinese University was invited to be our first report object, reporting the new progress of visible light induced functional group reaction of alkenes (click to view) Recently, song Qiuling's research group of new generation material transformation Institute of Huaqiao University has made some new progress in Lewis acid mediated [3 + 3] cycloaddition reaction In this regard, CBG information first paid attention to and reported the latest research results of "old friends" （ DOI: 10.1002/adsc.201701641 ）。 Research results: benzimidazol pyrimidine and pyrimidine indazole compounds are very important fused heterocyclic compounds in Lewis acid mediated [3 + 3] cycloaddition reactions These skeletons exist in many drug molecules with good biological activity These two important condensed ring compounds are mainly obtained by condensation of 2-aminobenzimidazole with 3-aminoindazole and carbonyl compounds However, in the literature, most of the condensation reactions between 2-aminobenzimidazole and 3-aminoindazole and carbonyl compounds are the first-order amino group preferentially attacking the carbonyl group and then cyclizing At present, the study of other nucleophilic nitrogen atoms in 2-aminobenzimidazole and 3-aminoindazole compounds preferentially attacking carbonyl and then generating other cyclization reactions is still lacking Therefore, it is of great significance to design and develop a mild reaction system for the selective condensation of 2-aminobenzimidazole and 3-aminoindazole derivatives with carbonyl compounds to construct more abundant and diverse benzimidazoles and pyrimidinyindazole fused heterocycles Recently, song Qiuling's group has realized the selective condensation of 2-aminobenzimidazole and 3-aminoindazole compounds with 3-ethoxycyclobutanone by using BF 3 · et 2O as Lewis acid, and [3 + 3] cycloaddition reaction under the condition of no transition metal catalysis to construct benzimidazoline and pyrimidinyindazole derivatives , relevant research work was published on adv synth Catalyst Recently (adv synth Catalyst., 2018, DOI: 10.1002/adsc.201701641) Fig 1 Selective condensation of 2-aminobenzimidazole and 3-aminoindazole derivatives with carbonyl compounds (source: adv.synth Catalyst.) the authors determined that the optimal yield could be obtained by [3 + 3] cycloaddition reaction of 2-aminobenzimidazole and 3-aminoindazole derivatives with 3-ethoxycyclobutanone under the action of BF 3 · et 2O through condition screening Under this optimal condition, the reaction substrate was expanded It can be seen from Fig 2 that various substituted 3-aminoindazole and ethoxycyclobutanone reactions can obtain the target compound in a relatively good yield It can also be seen from Fig 3 that the [3 + 3] cycloaddition activity of 2-aminobenzimidazole and 3-ethoxycyclobutanone is lower than that of 3-aminoindazole, but different 2-aminobenzimidazole can also obtain a series of benzimidazole pyrimidine derivatives in this system Figure 2 Substrate development of 3-aminoindazole derivatives (source: adv.synth Catalyst.) Figure 3 Substrate development of 2-aminobenzimidazole derivatives (source: adv.synth Catalyst.) The mechanism study shows that the [3 + 3] cycloaddition reaction mechanism of 2-aminobenzimidazole and 3-aminoindazole derivatives with 3-ethoxycyclobutanone is different from the [3 + 3] cycloaddition reaction of enamine and amidine with 3-ethoxycyclobutanone previously reported by the research group (adv synth Catalyst., 2017, 359, 952-958) In the [3 + 3] cycloaddition reaction of enamine and amidine with 3-ethoxycyclobutanone, the first-order amino group of enamine and amidine preferentially condenses with the carbonyl group of cyclobutanone, and then the subsequent intramolecular nucleophilic cyclization reaction occurs, while the [3 + 3] cycloaddition reaction of 2-aminobenzimidazole and 3-aminoindazole derivatives with 3-ethoxycyclobutanone is not the first-order amino group, but The heterocyclic nitrogen atom is superior to the active intermediate after ring opening of cyclobutanone, and then the subsequent cyclization reaction takes place Figure 4 The [3 + 3] cycloaddition reaction of amines and amidines with 3-ethoxycyclobutanone (source: adv.synth Catalyst.) was strongly supported by the "youth thousand talents" program of the Central Organization Department, the natural science foundation of Fujian Province, the science and technology innovation and Leading Talents Program of Huaqiao University, and the Postgraduate Innovation Fund of Huaqiao University Nowadays, people and scientific research have been paid more and more attention in the economic life China has ushered in the "node of science and technology explosion" Behind the progress of science and technology is the work of countless scientists In the field of chemistry, in the context of the pursuit of innovation driven, international cooperation has been strengthened, the influence of Returned Scholars in the field of R & D has become increasingly prominent, and many excellent research groups have emerged in China For this reason, CBG information adopts the 1 + X reporting mechanism CBG information, chembeango app, chembeango official microblog, CBG wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the domestic representative research group, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.