Article pubs.acs.org/Organometallics
Zinc-Catalyzed Dehydrogenative Silylation of Indoles Kyohei Yonekura, Yoshihiko Iketani, Masaru Sekine, Tomohiro Tani, Fumiya Matsui, Daiki Kamakura, and Teruhisa Tsuchimoto* Department of Applied Chemistry, School of Science and Technology, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, 214-8571, Japan S Supporting Information *
ABSTRACT: A unique Lewis acid/base system consisting of zinc triflate and pyridine was found to act as an effective catalyst for making an N(indolyl)−Si bond in a dehydrogenative fashion. Execution in a nitrile medium brings out the best performance of the Zn−pyridine system, which enables participation of flexible pieces of indoles and hydrosilanes, thereby giving diverse N-silylindoles in high to excellent yields. The Zn−pyridine system in the nitrile solvent is also applicable to the corresponding C-silylation in the case that the nitrogen atom of indoles has a substituent. Pyrrole, carbazole, arylamine, and thiophene substrates other than indoles undergo the dehydrogenative N- and/or Csilylation as well. Mechanistic studies showed that the role of the zinc Lewis acid is to activate the hydrosilane. The ratedetermining step of the present reaction was found to be involved in the stage of the indolyl−H bond cleavage, on the basis of kinetic isotope effect experiments. Kinetic studies indicated that the indole-based dehydrogenative N-silylation is first-order in indole, second-order in each of hydrosilane and zinc triflate, and positive and negative fractional orders in pyridine.
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emerged in succession.8−12 However, among the studies released thus far, effectively catalyzing both N- and C-silylation is limited to the ruthenium complex of Tatsumi and Ohki,5,8b,13 the synthesis of which requires three steps.14 We therefore envisioned that a readily available catalytic system applicable to both the N- and C-silylation would be an attractive and powerful synthetic tool when requiring silylindoles. Herein, we report that a zinc salt along with a pyridine base in a nitrile medium, all of which are commercially available, effectively catalyzes both of the dehydrogenative N- and C-silylation of indoles. We also disclose that the trinary zinc−pyridine−nitrile system is applicable to the dehydrogenative silylation of other aromatic molecules including pyrroles and carbazoles as well as arylamines and thiophenes.
INTRODUCTION Silylindoles are one of the important structural motifs in the field of organic synthesis. For example, N- and C-silylindoles have been widely used as synthetic intermediates for constructing valuable organic molecules such as natural products and biologically active compounds1 as well as optoelectronic materials.2 The most common way to synthesize the silylindole includes preparation of indolylmetals with strong metallic bases such as Li−Bu, K−N(SiMe3)3, and Na−H (met−base), followed by adding halosilanes (X−SiR3).3 This strategy, however, results in the coproduction of stoichiometric amounts of wastes including met−X and H−base. Requiring the handling of the moisture-sensitive reagents, met−base and X−SiR3, should be also disadvantageous. Moreover, indoles with base or nucleophile (e.g., Bu−) sensitive functional groups are incompatible with the reaction conditions. In contrast to such traditional strategy, dehydrogenative coupling of the indolyl−H and H−Si bonds coproducing only H2 gas would be an ideal process to introduce the silyl group onto the indole framework. In fact, significant progress has recently been made on the dehydrogenative silylation of indoles. In 2008, Falck disclosed the first dehydrogenative silylation of indoles, where an iridium complex acts as a catalyst to silylate the C2 of indoles.4 The ruthenium-catalyzed C3silylation of indoles has been also reported by Oestreich as well as Tatsumi and Ohki research groups.5 Different from these Csilylation reactions, as a preliminary communication, we reported in 2012 the first practical dehydrogenative synthesis of N-silylindoles, which are produced uniquely with the aid of a zinc Lewis acid catalyst. 6,7 After its publication, the dehydrogenative N- and C-silylation of indoles catalyzed mainly by transition metals such as Fe, Ru, Rh, and Ir have © XXXX American Chemical Society
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RESULTS AND DISCUSSION We first investigated suitable reaction conditions for the dehydrogenative N-silylation of indole (1a) with methyldiphenylsilane (2a) (Table 1). When In(OTf)3 (10 mol %) was used as a catalyst, the treatment of 1a and 2a in EtCN at 80 °C for 15 h provided only a small amount of N-(methyldiphenylsilyl)indole (3aa), along with a significant quantity of indoline (4) (entry 1).15 Other triflate salts of Bi, Cu, Ag, Sc, and Mg metals gave no improvements in the yield of 3aa (Bi, Cu, Sc, and Mg: < 1%, Ag: 5%). In marked contrast, Zn(OTf)2 exhibited a remarkable catalytic activity, and 3aa was thus obtained in an almost quantitative yield. However, 4 was formed again in 1% yield (entry 2). Inspired by this result, other zinc Lewis acid Received: May 23, 2017
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DOI: 10.1021/acs.organomet.7b00382 Organometallics XXXX, XXX, XXX−XXX
Article
Organometallics
reduced further to 1 mol % without significant lowering of the yield (entry 18). A catalytic use of pyridine (50 mol %) is also possible (entry 19). As shown separately in Figure 1, there seems to be an important correlation between the basicity of the organic base
Table 1. Lewis Acid Catalyzed Dehydrogenative N-Silylation of Indole with Methyldiphenylsilanea,b
yield (%)c entry
Lewis acid (mol %)
organic base (pKa value)
3aa
4
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
In(OTf)3 (10) Zn(OTf)2 (10) Zn(ONf)2 (10) Zn(NTf2)2 (10) Zn(OAc)2 (10) ZnF2 (10) ZnCl2 (10) ZnBr2 (10) Zn(OTf)2 (5) Zn(OTf)2 (5) Zn(OTf)2 (5) Zn(OTf)2 (5) Zn(OTf)2 (5) Zn(OTf)2 (5) Zn(OTf)2 (5) Zn(OTf)2 (5) Zn(OTf)2 (5) Zn(OTf)2 (1) Zn(OTf)2 (5)
none none none none none none none none none DBU (12.4) Et3N (10.8) DMAP (9.7) 2,6-Lut (6.7) 4-t-BuPy (6.0) Py (5.3) 3-MeOPy (4.9) 3-ClPy (2.8) Py (5.3) Py (5.3)d
4 99 84 18
