Teruhisa Tsuchimoto

Indium-catalyzed annulation of 2-aryl- and 2-heteroarylindoles with propargyl ethers: concise synthesis and photophysical properties of diverse aryl- and heteroaryl-annulated[a]carbazoles.

Treatment of 2-aryl- and 2-heteroarylindoles with propargyl ethers in the presence of a catalytic amount of indium nonafluorobutanesulfonate [In(ONf)(3)] gave aryl- and heteroaryl-annulated[a]carbazoles in good yields. The synthetically attractive feature is reflected by its applicability to a wide range of 2-aryl- and 2-heteroarylindoles. In the annulation reaction, propargyl ethers act as C3 sources (HC[triple bond]C-CH(2)OR). Among these, two carbon atoms are incorporated into the product as members of a newly constructed aromatic ring and the remaining carbon atom forms a methyl group on the aromatic ring, where the methyl group is always located next to the C3 position of the indole nucleus. The methyl group can be easily removed through SeO(2) oxidation followed by decarbonylation with RhCl(CO)(PPh(3))(2)-Ph(2)P(CH(2))(3)PPh(2) as a catalyst. The new annulation strategy is applicable also to symmetrical dimers such as bithiophene and bifuran derivatives. Mechanistic studies suggest that the first step is addition reaction initiated by regioselective nucleophilic attack of the C3 of 2-aryl- and 2-heteroarylindoles to the internal carbon atom of the C[triple bond]C bond in propargyl ethers. The next stage is ring-closing S(N)2 process kicking out the alkoxy group and then aromatization via a 1,3-hydrogen shift is the final step. The two carbon-carbon bond-forming reactions achieved in one-pot contribute largely to the reduction in the number of steps for the synthesis of aryl- and heteroaryl-annulated[a]carbazoles. Furthermore, utilization of the Fischer indole synthesis for efficient supply of the substrates, 2-aryl- and 2-heteroarylindoles, is another important factor shortening the overall process. The development of the annulation with a wide substrate scope provided a unique opportunity to evaluate photophysical properties of a series of aryl- and heteroaryl-annulated[a]carbazoles. Almost all the compounds evaluated in this study were found to emit purple to green light in the visible region. Some interesting structure-property correlations are also described.

Friedel–Crafts alkenylation of arenes using alkynes catalysed by metal trifluoromethanesulfonates

Metal trifluoromethanesulfonates [M(OTf)n; M = Sc, Zr, In] catalyse the Friedel–Crafts alkenylation of arenes using alkynes, including internal alkynes, to give, through an alkenyl cation intermediate, 1,1-diarylalkenes in high to excellent yields.

Indium-Catalyzed Reductive Alkylation of Pyrroles with Alkynes and Hydrosilanes: Selective Synthesis of β-Alkylpyrroles

Mixing readily available alkynes, pyrroles, and triethylsilane along with an indium catalyst was found to be an efficient procedure to introduce alkyl groups onto a beta-position of pyrroles in a complete regioselective manner. This is the first demonstration of catalytic beta-alkylation of pyrroles in a single step.

Reductive alkylation of indoles with alkynes and hydrosilanes under indium catalysis.

Under Indium catalysis, diverse alkylindoles were successfully prepared with a flexible combination of indoles and alkynes in the presence of hydrosilanes. In addition to the hydrosilane, carbon nucleophiles are also available. This new method generates alkylindoles in yields over 70% with a broad scope of functional group compatibility.

Zinc-Catalyzed Dehydrogenative N-Silylation of Indoles with Hydrosilanes

Due to their importance as nitrogen-protected indoles, Nsilylindoles are recognized as indispensable synthetic platforms that can be used to construct valuable indole-based organic molecules. N-Silylation of indoles is generally performed by a two-step sequence consisting of N-metalation of indoles with strong metallic bases (met–base), such as LiBu, KN ACHTUNGTRENNUNG(SiMe3)2, or NaH, and then treatment of the resulting N-metal indoles with halosilanes (X Si). This strategy requires handling of moisture-sensitive reagents, that is, met–base and X Si, the use of which also results in the production of stoichiometric amounts of the waste products H base and X met. Moreover, indoles with baseor nucleophile-sensitive functional groups are incompatible with the reaction conditions. We envisaged that exploitation of a catalytic one-step N-silylation, independent of both the met–base and X Si, would avoid the aforementioned issues, thus establishing a more widespread applicability for N-silylindoles in organic synthesis. Herein, we disclose the first example of a Lewis acid catalyzed dehydrogenative Nsilylation of indoles with hydrosilanes as a simple and practical system, in which ZnACHTUNGTRENNUNG(OTf)2 (Tf =SO2CF3) exhibits outstanding catalytic performance. Initially, we examined the effect of using different Lewis acid catalysts in the reaction of indole (1 a) with methyldiphenylsilane (2 a ; Table 1). Treating 1 a and 2 a with In ACHTUNGTRENNUNG(OTf)3 (10 mol %) in EtCN at 80 8C for 15 h gave ACHTUNGTRENNUNG (methyldiphenylsilyl)indole (3 a), albeit in a low yield, as well as a significant amount of indoline (4 a ; Table 1, entry 1). None of the triflate salts based on a Bi, Cu, Ag, or Sc metal provided improvements in the yield (Table 1, entries 2–5). In sharp contrast, ZnACHTUNGTRENNUNG(OTf)2 showed excellent catalytic activity, providing 3 a in 99 % yield, although a small amount of 4 a was again formed (Table 1, entry 6). It is worth noting that no C-silylation was observed. On the basis of this result, we tested other zinc catalysts. The nonaflate salt Zn ACHTUNGTRENNUNG(ONf)2 also catalyzed the Nsilylation, but the reaction was slower (Table 1, entry 7). Zinc halides, however, were totally inactive (Table 1, entries 8 and 9). With the use of Zn ACHTUNGTRENNUNG(OTf)2 as a catalyst, a survey of different solvents clearly showed that nitriles are essential for providing 3 a (Table 1, entries 6 and 10–15). We next focused on screening organic bases to allow the loading of Zn ACHTUNGTRENNUNG(OTf)2 to be reduced, as well as to inhibit the formation of 4 a. In the case without the use of a base, lowering the loading of ZnACHTUNGTRENNUNG(OTf)2 to 5 mol % made the Nsilylation much slower (Table 1, entry 16). Although the addition of Et3N, 4-(di ACHTUNGTRENNUNGmethyl ACHTUNGTRENNUNGamino)pyridine (DMAP), or 2,6lutidine had detrimental effects, we found that the exclusive and quantitative synthesis of 3 a can be achieved by using pyridine as the base (Table 1, entries 17–21). When using pyridine, replacing EtCN with other solvents was again inef[a] Prof. Dr. T. Tsuchimoto, Y. Iketani, M. Sekine Department of Applied Chemistry, School of Science and Technology Meiji University 1-1-1 Higashimita, Tama-ku, Kawasaki 214-8571 (Japan) Fax: (+81) 44-934-7228 E-mail : tsuchimo@isc.meiji.ac.jp Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201200651. Table 1. Lewis acid catalyzed dehydrogenative N-silylation of indole with methyldiphenylsilane.

Exclusive Synthesis of β‐Alkylpyrroles under Indium Catalysis: Carbonyl Compounds as Sources of Alkyl Groups

Introduction of alkyl groups onto aromatic rings is among the most important transformations in organic synthesis. Transition-metal-catalyzed cross-coupling must be a leading option to make alkyl–aryl bonds at desired positions. However, pre-activation of both fragments with halides and electropositive metals is required to secure the regioselectivities. A realistic candidate to reduce our dependence on the preactivation would be electrophilic aromatic substitution (EAS), that is, the Friedel–Crafts alkylation that replaces the pre-activated arenes with simple arenes, while the simple arenes for the EAS generally cause non-regioselective reaction, and, in addition, their reaction sites are narrowed to more nucleophilic positions. Therefore, development of EAS enabling regioselective alkylation at desired sites on arenes would be useful over the cross-coupling. In this context, we recently reported the regiospecific b-alkylation of pyrroles through EAS, by the simple assembly of alkynes 1, pyrroles 2, and Et3SiH (3 a) under indium catalysis (Scheme 1). b-Alkylpyrroles are structural motifs found in many natural products and functional organic materials, but b-alkylation of pyrroles by EAS has been a challenging issue, due to dominant a-nucleophilicity of pyrroles. Despite such characteristics of pyrroles, our recent finding, which is the first example of catalytic b-alkylation of pyrroles in one-step, showed that b-alkylpyrroles 4 are formed exclusively, via formation of dipyrrolylalkanes 5 as crucial intermediates. However, the scope of 1 has been restricted mainly to terminal alkynes, the terminal carbon atom of which is inevitably incorporated as a methyl group into 4. We envisioned that replacing 1 with carbonyl compounds 6 would drastically extend the diversity of alkyl groups installable onto 2. Moreover, the use of 6, which is cheaper in general than 1, would make the process highly attractive and practical. Herein we disclose a new method for synthesis of b-alkylpyrroles 4 using 6 as alkyl group suppliers. Due to the potent activity of In ACHTUNGTRENNUNG(NTf2)3 (Tf =SO2CF3) found in our preceding research, research on this topic began with its testing in the reaction of 2-decanone (6 a) and N-methylpyrrole (2 a) with Et3SiH (3 a), by the procedure shown as method A: simultaneous treatment of 6, 2, 3 and In ACHTUNGTRENNUNG(NTf2)3 (Table 1). Thus, the reaction with In ACHTUNGTRENNUNG(NTf2)3 (10 mol%) in 1,4-dioxane at 85 8C for 3 h gave 3-(decan-2yl)-N-methylpyrrole (4 a) as a single isomer in 92 % yield (entry 1). The absence of formation of its a-isomer is particularly noteworthy. Another important aspect is that the use of 6 a allowed to reduce the catalyst loading, compared with reaction of the corresponding alkyne, 1-decyne, requiring 25 mol % of In ACHTUNGTRENNUNG(NTf2)3.[3] The 5-nonyl group, which is difficult to install regioselectively when an unsymmetrical alkyne (4-nonyne) is used, is readily available from 5-nonanone (entry 2). The cyclic structures that are inaccessible from alkynes can be treated with ease (entries 3–5), while 2adamantanol (15 % yield), resulting from direct reduction of [a] Prof. Dr. T. Tsuchimoto, M. Igarashi, K. Aoki Department of Applied Chemistry School of Science and Technology Meiji University, Higashimita Tama-ku, Kawasaki 214-8571 (Japan) Fax: (+81) 44-934-7228 Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201000733. Scheme 1. Indium-catalyzed reductive b-alkylation of pyrroles: alkynes versus carbonyl compounds as sources of alkyl groups ([In] = indium salt).

Indium triflate-catalysed double addition of heterocyclic arenes to alkynes

Indium triflate was found to be a prominent catalyst for addition of heterocyclic arenes to alkynes to afford 2:1 adducts, where two heterocyclic arenes regioselectively attacked the same carbon atom of alkynes.

Indium-catalyzed annulation of 3-aryl- and 3-heteroarylindoles with propargyl ethers: synthesis and photoluminescent properties of aryl- and heteroaryl[c]carbazoles

Treatment of 3-aryl- and 3-heteroarylindoles with propargyl ethers under indium catalysis successfully provided aryl- and heteroaryl[c]carbazoles, which were found to be more efficient emitters compared with the corresponding [a]-analogs.

Palladium-catalysed dimerization of vinylarenes using indium triflate as an effective co-catalyst

A palladium-indium triflate catalyst was found to be much more active for the dimerization of vinylarenes compared with generally used cationic palladium(II) catalysts.

Alkylation-annulation of halo esters with organometallic reagent/SmI2 couple leading to cycloalkanols: A facile cyclopropanol synthesis from a 3-halo ester

Abstract Transformation of a 3-halo ester to cyclopropanols has been accomplished in excellent yields under mild conditions employing a coupled reagent of samarium(II) diiodide with organometallic reagents. 5- and 6- Halo esters were also transformed into cyclopentanols and cyclohexanols, respectively, in low to moderate yields. The reaction with a 4-halo ester gave 2,2-disubstituted tetrahydrofuran as a major product that resulted from double alkylation followed by cyclization; a substituted cyclobutanol was formed in poor yield.