Rikkyo University

Hydrogen bonds, which are the basic interaction of molecular recognition, are pervasive in living organisms and elsewhere. Although hydrogen bonds are widely used in the activation of reaction substrates, they do not have sufficient functional group selectivity for controlling advanced catalytic chemistry. The advancement of modern fine chemistry requires the introduction of novel activation modes that can achieve specific forms of activation. The halogen bond has attracted attention as a new interaction for creating functional molecules due to hopes it will be able to selectively activate highly soft chemical species (functional groups). It has previously been demonstrated in fields such as crystal engineering, biochemistry, and solution chemistry that halogen bond-donor iodine compounds form bonds with π electron compounds. However, there are no examples of the application of halogen bonds between an iodine compound and a π electron (C-I···π halogen bond) in catalytic chemistry, and the possibilites of application to functional molecule creation remain unexplored. In this study, our objective was to develop activation functions for π electron system compounds using a halogen bond-donor iodine catalyst, and to synthesize useful compounds.

① We discovered that when a halogen bond-donor iodine catalyst was reacted with 2-alkenyl indole, then stirred at room temperature in chloroform, the desired progression of a dimerization reaction was obtained at a high yield (Fig. 2). Further, combining 2-vinylindole and 2-styrylindole promoted a crossover [4+2] cycloaddition reaction, which obtained the desired product at a high yield. Analysis of the reaction mechanism using experimental chemistry and computational chemistry revealed that the cycloaddition reaction was driven by the formation of halogen bonds between iodine compounds and indole π electrons.

② When the Brønsted acid catalyst trifluoroacetic acid is applied to a crossover [4+2] cycloaddition reaction, non-cyclic compound B is generated preferentially over target compound A (Fig. 3). Our results show that a halogen bond-donor iodine catalyst could be used as complementary tool for existing acid catalysts.

③ Transition state analysis using computational chemistry showed that the iodine catalyst joins with a π electron at the indole 3 position via a halogen bond, which contributes to the stabilization of the transition state (Fig. 4). In the transition state conveying the primary diastereomer, the existence of an N-H···π interaction between an indole NH proton and a π electron on the benzene ring was also suggested.