This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
Communication Cite This: J. Am. Chem. Soc. 2019, 141, 9175−9179
pubs.acs.org/JACS
Chalcogen−Chalcogen Bonding Catalysis Enables Assembly of Discrete Molecules Wei Wang, Haofu Zhu, Shuya Liu, Zhiguo Zhao, Liang Zhang, Jingcheng Hao, and Yao Wang* School of Chemistry and Chemical Engineering, Key Laboratory of the Colloid and Interface Chemistry, Ministry of Education, Shandong University, Jinan, Shandong 250099, China
Downloaded via 91.200.81.80 on July 18, 2019 at 03:06:30 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
S Supporting Information *
drug design, and materials science.3,4,6 Analogous to the role in modulating the conformational preferences of drug molecules,4 the elegant studies by the research groups of Birman,7 Romo,8 and Smith9 reveal that the intramolecular chalcogen bonds are of significance in controlling the conformation of reactive intermediates in covalent Lewis-base catalyzed transformations. The origin of chalcogen bonds has been studied by theoretical chemists.6,10−12 Since chalcogen-bonding interactions are very weak, the application of chalcogen bonds to intermolecular, noncovalent catalysis remains a largely elusive problem. Recently, Matile et al. and Huber et al. discovered that the reduction of quinolines and imines with Hantzsch ester13 as well as the abstraction of halides from activated molecules14 could be achieved by chalcogen-bonding activation. Despite these important discoveries, the intrinsically weak noncovalent interactions between the chalcogen catalysts and substrates pose a great challenge, thus restricting their practice to fundamental reactions with high reactivity. The development of new reactions through catalysis with chalcogen bonding remains a virtually unexplored research area. Despite the potential as a streamlined strategy for organic synthesis, there are some unsolved fundamental problems that restrict chalcogen-bonding activation to emerge as a generalized catalysis discipline. For example, it is an obvious obstacle to discover simple, flexible, and modular chalcogen catalysts that are capable of showing comparable/superior efficiency in contrast to traditional catalysts. Inspired by the observation of intermolecular noncovalent S···O interactions in biological systems,4,5 we envisioned that this type of chalcogen−chalcogen interactions might provide a general solution to the intrinsic limitations of chalcogen bonding catalysis (Figure 1). Herein, we report the development and application of a class of extraordinary chalcogen-bonding catalysts. The analysis of the X-ray crystal structure of compound Ch0 reveals the existence of chalcogen−chalcogen bonding interaction (Figure 2).15,16 Strong S···O interaction was observed as the S···O distance (2.81 Å) is markedly shorter than the van der Waals radii sum (3.30 Å). An ideal chalcogenbonding interaction is highly directional with an angle of approximately 180°.6,17 The X-ray crystal structure of Ch0 shows almost linear orientation of N−S···O (177°). This compound was capable of serving as a chalcogen bonding
ABSTRACT: Despite the observation of noncovalent interactions between chalcogen atoms in X-ray crystal structures, catalysis that harnesses the power of such chalcogen−chalcogen bonding interactions to produce advanced molecules remains an unresolved problem. Here, we show that a class of extraordinary chalcogenbonding catalysts enables assembly of discrete small molecules including three β-ketoaldehydes and one indole, leading to the construction of N-heterocycles in a highly efficient manner. The strong activation ability of these rationally designed catalysts provides a general solution to the intrinsic limitations of chalcogen bonding catalysis.
O
rganic molecules containing electron-donating elements of group 16 (chalcogen), such as sulfur, selenium, are widely used as Lewis-base catalysts that activate electrondeficient organic molecules through formation of covalent bonds (Figure 1).1,2 Naturally, it is reasonable to envision that
Figure 1. From covalent Lewis-base catalysis to noncovalent chalcogen−chalcogen bonding catalysis.
a converse catalysis strategy operating through noncovalent chalcogen−chalcogen interactions may not be a favorable approach. However, such weak noncovalent interactions (i.e., S···O) have been observed in many protein structures.3 Moreover, it has been demonstrated that the intermolecular chalcogen−chalcogen bonds play a significant role in the interactions between proteins and small organic molecules.4 For instance, the X-ray crystal structure of a complex between CHK1 and an inhibitor indicates the important role of S···O interaction.5 These chalcogen−chalcogen bonding interactions have been applied in crystal engineering, biological systems, © 2019 American Chemical Society
Received: April 9, 2019 Published: May 24, 2019 9175
DOI: 10.1021/jacs.9b03806 J. Am. Chem. Soc. 2019, 141, 9175−9179
Communication
Journal of the American Chemical Society Table 1. Substrate Scopea
a
Unless otherwise indicated, reactions were carried out with indole derivative (0.20 mmol), β-ketoaldehyde (3.0 mmol), Ch9 (15 mol %, 0.03 mmol), NaBF4 (0.12 mmol, 0.6 equiv), and Na2SO4 (0.50 g) in DCE (2.0 mL) at room temperature. The data are reported as isolated yields. b20 mol % Ch9 was used. cRun in DCM. dRun at 0 °C using NaBArF4 (0.16 mmol, 0.8 equiv). eNaBF4 (0.16 mmol, 0.8 equiv). DCE, 1,2-dichloroethane; DCM, dichloromethane.
A diverse array of substituent groups could be installed in all the possible places (i.e., 3−7 positions of indoles), delivering decorated products in reasonable yields. Meanwhile, indole substrates are allowed to incorporate substituent groups with different electronic properties. Furthermore, heterocyclic aromatic substituent groups could also be tolerated (22 and 23). The employment of several different ketoaldehydes was successful (31−33). To gain insights into the chalcogen−chalcogen bonding interaction, a series of control experiments were carried out (Scheme 1). Recent investigation suggests that the binding ability of chalcogen-halide anion interaction follows the order of Cl− > Br− ≫ I−.18 In agreement with the trend of Se···halide anion-binding property, the addition of tetrabutylammonium chloride (2 equiv, 0.2 M) to the standard reaction system led to a substantial suppression of the cyclization reaction (
