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Communication

In(III)-TMSBr-Catalyzed Cascade Reaction of Diarylalkynes with Acrylates for the Synthesis of Aryldihydronaphthalene Derivatives

1
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore
2
BGI, BGI-Shenzhen, Shenzhen 518083, China
3
Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Jiangsu National Synergetic Innovation Center for Advanced Materials, Nanjing Tech University, Nanjing 210009, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Akio Baba and Makoto Yasuda
Received: 20 March 2018 / Revised: 19 April 2018 / Accepted: 20 April 2018 / Published: 23 April 2018
(This article belongs to the Special Issue Indium in Organic Synthesis)

Abstract

A combined Lewis acid system comprising of two or more Lewis acids occasionally exhibits augmented catalytic activity in organic transformations which are otherwise unrealizable by either of the components exclusively. On the other hand, the efficient construction of multiple new C-C bonds and polycyclic structures in minimal steps remains a subject of great interest in both academia and industry. Herein we report an efficient method to assemble aryldihydronaphthalene derivatives via a cascade reaction of diarylalkynes with acrylates under the catalysis of a combined Lewis acid derived from In(III) salt and TMSBr.
Keywords: indium; combined Lewis acid; catalysis; cascade reaction; aryldihydronaphthalene indium; combined Lewis acid; catalysis; cascade reaction; aryldihydronaphthalene

1. Introduction

In the context of green chemistry, efficient methods to forge multiple new C-C bonds and to introduce molecular complexity in minimal steps have been a long-standing and important goal in the development of modern organic chemistry [1,2]. In this regard, aryldihydronaphthalene derivatives are particularly attractive targets mainly due to their widespread occurrence in natural products and bioactive compounds (Figure 1) [3,4,5,6,7]. They are also employed as fluorescent ligands in biochemistry studies or building blocks towards the synthesis of several biologically-active cyclic molecules [8,9,10,11]. Consequently, their significant roles have driven the establishment of several synthetic methodologies for their preparation. Prominently, the intramolecular hydroarylation of 4-phenyl-1-butyne or its derivatives is one of the most versatile protocols for the construction of aryldihydronaphthalene derivatives [12,13,14,15]. Since the pioneering studies by Fujiwara et al. [16,17], numerous catalytic methods have been developed in this field in which a series of transition metals, Lewis and Bronsted acids have been found effective for catalyzing the hydroarylation [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39]. More recently, Corey [24] and Pérez Sestelo and Martínez [38,39] have independently reported the formation of six-membered oxa- and carbocycles by an In(III)-catalyzed hydroarylation of acetylenic substrates.
On the other hand, although indium(III) salts (InX3 (X = Cl, Br, I, OTf, NTf2, etc.)) have been widely applied as Lewis acids in organic synthesis [40,41,42], their relatively weak Lewis acidity nonetheless limit their applications. Unlike other group III elements, such as aluminum and boron, trimethylsilyl halide is often employed together with InX3 as a robust combined Lewis acid catalyst, as observed in various reactions developed by Baba [43,44], Lee [45], Corey [24,46], our group [47,48,49], and others. As a continuation of our research interest in the application of indium in organic synthesis [47,48,49,50,51], herein we wish to report the first example of the In(III)-TMSBr-catalysed cascade reaction of diarylalkynes with acrylates to access a series of dihydronaphthalene derivatives in a one-pot manner (Scheme 1).

2. Results

2.1. Preliminary Result of In(III)-TMSBr-Catalyzed Cascade Reaction of Diarylalkynes with Acrylates

More recently, our group has demonstrated that the combined Lewis acid of In(III) salt and TMSBr could effectively activate acrylate component for the reaction with aryl alkynes [49]. Inspired by this activation mode, we envisaged a cascade reaction between diarylalkyne 1 and acrylate 2 to prepare aryldihydronaphthalene derivatives with this combined Lewis acid via the reaction sequence shown in Scheme 2. Initially, an intramolecular Friedel-Crafts type arylation reaction might occur, to give alkenyl indium species int-1 which will then undergo nucleophilic attack on the activated acrylate 2 to give the dihydronaphthalene enolate int-2. A further enolate protonation will give the final 1,2-dihydronaphthalene derivative 3.
To begin with, the model reaction involving but-1-yne-1,4-diyldibenzene (1a) and methyl acrylate (2a) were investigated to probe the proposed cascade reaction. In the presence of InBr3 and TMSBr, a 1,2-dihydronaphthalene derivative 3aa with two propionate motifs was obtained in moderate yield with trace amounts of intractable mixture of 1,2-dihydronaphthalene derivatives containing more propionate motifs (Scheme 3). Interestingly, no 1,2-dihydronaphthalene derivative with a single propionate motif in original proposal could be obtained.

2.2. Optimization of In(III)-TMSBr-Catalyzed Cascade Reaction of Diarylalkynes with Acrylates

We subsequently optimized the reaction conditions by using but-1-yne-1,4-diyldibenzene (1a) and methyl acrylate (2a) as model substrates. The results are summarized in Table 1. At the outset, it was found that both In(III) catalyst and TMSBr were indispensable for the efficient progress of this reaction, because the reaction could not take place in the absence of either of them (entries 2–3). Among the different indium catalysts studied (entries 1 and 4–8), In(tfacac)3 was found to exhibit the best catalytic activity to afford the desired product 3aa with 61% yield (entry 7). Other common Lewis acid catalysts (e.g., AlBr3 and ZnCl2, entries 9 and 10) were also screened, which mostly resulted in no product formation. In addition, this reaction was found to proceed only in chlorinated solvents, such as CH2Cl2 or 1,2-dichloroethane, with the latter giving a higher yield of 70% (entry 7 vs. entry 11). In comparison, when TMSBr was replaced by TMSCl, the product yield eroded significantly to less than 5% (entry 12). An attempt to decrease the amount of TMSBr or In(tfacac)3 led to lower yields (entries 13–14). Finally, reducing the stoichiometry of methyl acrylate (2a) to only one equivalent resulted in a significantly decreased yield of 3aa, and 1,2-dihydronaphthalene derivative with a single propionate motif remained absent (entry 15).

2.3. Substrate Scope of In(III)-TMSBr-Catalysed Cascade Reaction of Diarylalkynes with Acrylates

With the optimized reaction conditions in hand (Table 1, entry 11), the generality of diarylalkyne substrate scope of this reaction with respect to methyl acrylate (2a) was investigated, and the results are listed in Figure 2a. Various substituted but-1-yne-1,4-diyldibenzene derivatives on the phenyl ring were well suited for this protocol, producing the corresponding product 3 in 47% to 73% yields (3aa-ja). Expectedly, substrates with orth-substituent on phenyl ring gave respective products in lower yields than those with meta- or para-substituents (3ga vs. 3ba and 3ha, 3fa vs. 3ia) and no cyclization product could be detected when 1l was used under the same conditions. Additionally, the incompatibility of 4-phenyl-1-butyne (1k) with the current transformation emphasized the importance of the phenyl ring moiety for this reaction. Finally, a substrate with a strong aryl electron-withdrawing substituent (e.g., 1m) was also unsuitable for this reaction.
With but-1-yne-1,4-diyldibenzene (1a) as the standard coupling partner, next, the scope of acrylate 2 in the present protocol was examined (Figure 2b). In addition to methyl acrylate (3a), acrylates carrying longer O-alkyl chains also reacted smoothly to give 1,2-dihydronaphthalene products 3ab-ad, albeit in relatively low yields (37–60%). Aside from the alkyl chain, reactions of acrylates tethering the chloroethyl group proceeded well to give 3ae in moderate yield (50%). However, the use of other olefinic substrates, such as ethyl methacrylate (2g), ethyl but-2-enoate (2h), and but-3-en-2-one (2i), could not provide any desired product.

3. Discussion

On the basis of above experimental results and precedent literature reports [38,39,43,44,49], a plausible reaction pathway for this In(tfacac)3-TMSBr-catalyzed cascade reaction of diarylalkynes with acrylates was put forward in Scheme 4: In(tfacac)3 and TMSBr would first form a combined Lewis acid complex (LA) with heightened acidity than either of them solely; second, an intramolecular Friedel-Crafts type arylation reaction takes place to generate an alkenyl indium species int-1; this is followed by a nucleophilic attack of int-1 onto activated acrylate 2, giving rise to int-2, which subsequently attacks another molecule of acrylate to give int-3; finally, the int-3 is quenched by the proton generated from the first step to furnish the final product 3.

4. Materials and Methods

4.1. General Information

Unless otherwise noted, all reagents and solvents were purchased from commercial sources and used as received. The TMSBr and InBr3 used was purchased from Sigma-Aldrich, Singapore. The In(tfacac)3 used was purchased from Strem Chemicals (Newburyport, MA, USA) and its purity is 99%. Thin layer chromatography (TLC) was used to monitor the reaction progress on Merck (Frankfurter Strasse, Darmstadt, Germany) 60 F254 precoated silica gel plates (0.2 mm thickness). TLC spots were visualized by UV-light irradiation on a Spectro line model ENF-24061/F (Spectroline, Westbury, NY, USA) at 254 nm. Anther visualization method was staining with a basic solution of potassium permanganate or acidic solution of ceric molybdate, followed by heating. Flash column chromatography was performed using Merck silica gel 60 (Frankfurter Strasse, Darmstadt, Germany) with analytical grade solvents as eluents. 1H-NMR, 13C-NMR, and 2D NMR spectra were recorded using Bruker Avance 400 MHz spectrometers (Bruker Corporation, Billerica, MA, USA). Corresponding chemical shifts are reported in ppm downfield relative to TMS and were referenced to the signal of chloroform-d (δ = 7.26, singlet). Multiplicities were given as: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, brs = broad singlet, dd = doublet of doublets, and td = triplet of doublets. Values of coupling constants are reported as J in Hz.

4.2. General Procedure for In(III)-TMSBr-Catalysed Cascade Reaction of Diarylalkyne with Acrylates

A dry reaction tube was charged with aryl alkyne 1 (0.4 mmol), acrylate 2 (1.2 mmol), indium(III) trifluoroacetylacetonate (In(tfacac)3, 20 mol %, 0.08 mmol, 45.9 mg) and DCE (1 mL) under N2 atmosphere at 0 °C. Bromotrimethylsilane (TMSBr, 3 equiv, 1.2 mmol, 183.6 mg) was added and the reaction mixture was stirred at room temperature for 2 h. Upon completion of the reaction as indicated by TLC analysis, the residue was directly purified by flash column chromatography on silica gel (eluent: hexane/ethyl acetate 10:1) to afford the desired product 3.

4.3. Product Characterization

Dimethyl 2-((1-phenyl-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate (3aa). Colorless oil, 106.2 mg, 0.281 mmol, 70% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.45–7.41 (m, 2H), 7.38–7.34 (m, 1H), 7.18–7.10 (m, 4H), 7.05–7.02 (m, 1H), 6.58 (d, J = 7.5 Hz, 1H), 3.67 (s, 3H), 3.65 (s, 3H), 2.91 (t, J = 7.7 Hz, 2H), 2.66–2.61 (m, 1H), 2.44–2.31 (m, 4H), 2.22–2.18 (m, 2H), 1.79–1.76 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 175.4, 173.3, 139.2, 136.7, 136.3, 135.2, 134.3, 130.2, 128.4, 127.0, 126.9, 126.4, 126.2, 125.8, 51.6, 51.5, 43.5, 37.0, 31.6, 28.4, 27.4, 26.7.
Dimethyl 2-((1-(p-tolyl)-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate (3ba). Colorless oil, 114.5 mg, 0.292 mmol, 73% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.24–7.22 (m, 2H), 7.17–7.12 (m, 1H), 7.11–7.08 (m, 1H), 7.05–7.01 (m, 3H), 6.60 (d, J = 7.0 Hz, 1H), 3.67 (s, 3H), 3.65 (s, 3H), 2.89 (t, J = 7.8 Hz, 2H), 2.66–2.62 (m, 1H), 2.44 (s, 3H), 2.43–2.35 (m, 4H), 2.22–2.18 (m, 2H), 1.79–1.74 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 175.5, 173.3, 136.8, 136.4, 136.2, 136.0, 135.2, 134.2, 130.1, 129.1, 127.0, 126.3, 126.2, 125.9, 51.6, 51.5, 43.4, 37.0, 31.6, 28.4, 27.4, 26.6, 21.2.
Dimethyl 2-((1-([1,1′-biphenyl]-4-yl)-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate (3ca). Colorless oil, 116.3 mg, 0.256 mmol, 64% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.71–7.66 (m, 4H), 7.51–7.47 (m, 2H), 7.44–7.37 (m, 2H), 7, 23 (brs, 2H), 7.15–7.11 (m, 1H), 7.08–7.04 (m, 1H), 6.67 (d, J = 7.6 Hz, 1H), 3.66 (s, 3H), 3.65 (s, 3H), 2.94–2.90 (m, 2H), 2.70–2.66 (m, 1H), 2.50–2.41 (m, 4H), 2.25–2.19 (m, 2H), 1.83–1.77 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 175.5, 173.3, 140.9, 139.6, 138.2, 136.7, 135.9, 135.2, 134.5, 130.7 (×2), 128.8, 127.3, 127.1 (×2), 126.4, 126.2, 125.9, 51.7, 51.6, 43.5, 37.0, 31.6, 28.4, 27.4, 26.6.
Dimethyl 2-((1-(4-fluorophenyl)-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate (3da). Colorless oil, 90.3 mg, 0.228 mmol, 57% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.18–7.16 (m, 1H), 7.14–7.10 (m, 5H), 7.07–7.03 (m, 1H), 6.56–6.54 (d, J = 7.5 Hz, 1H), 3.68 (s, 3H), 3.65 (s, 3H), 2.90 (t, J = 7.9 Hz, 2H), 2.66–2.61 (m, 1H), 2.44–2.29 (m, 4H), 2.24–2.19 (m, 2H), 1.80–1.73 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 175.3, 173.3, 161.9 (d, JC-F = 243.7 Hz), 136.5, 135.3, 135.2, 134.9 (d, JC-F = 4.0 Hz), 134.8, 131.8 (d, JC-F = 7.8 Hz), 127.1, 126.5, 126.2, 125.7, 115.3 (d, JC-F = 21.1 Hz), 51.7, 51.6, 43.4, 37.0, 31.5, 28.3, 27.4, 26.7.
Dimethyl 2-((1-(4-chlorophenyl)-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate (3ea). Colorless oil, 107.1 mg, 0.26 mmol, 65% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.61–7.59 (m, 2H), 7.22–7.14 (m, 3H), 7.10–7.06 (m, 2H), 6.58 (d, J = 7.6 Hz, 1H), 3.72 (s, 3H), 3.69 (s, 3H), 2.93 (t, J = 7.8 Hz, 2H), 2.71–2.67 (m, 1H), 2.48–2.41 (m, 4H), 2.37–2.32 (m, 2H), 1.83–1.77 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 175.3, 173.2, 138.1, 136.2, 135.2, 135.1, 134.8, 132.0, 131.6, 127.1, 126.6, 126.3, 125.7, 121.0, 51.7, 51.6, 43.3, 37.0, 31.5, 28.3, 27.3, 26.7.
Dimethyl 2-((1-(4-bromophenyl)-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate (3fa). Colorless oil, 122.2 mg, 0.268 mmol, 67% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.41–7.39 (m, 2H), 7.17–7.02 (m, 5H), 6.54 (d, J = 7.6 Hz, 1H), 3.67 (s, 3H), 3.65 (s, 3H), 2.89 (t, J = 7.9 Hz, 2H), 2.68–2.61 (m, 1H), 2.43–2.26 (m, 4H), 2.24–2.19 (m, 2H), 1.79–1.75 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 175.3, 173.2, 137.6, 136.3, 135.1, 134.9, 132.9, 131.7, 128.7 (×2), 127.1, 126.6, 126.3, 125.7, 51.7, 51.6, 43.3, 37.0, 31.5, 28.3, 27.3, 26.7.
Dimethyl 2-((1-(o-tolyl)-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate (3ga). Colorless oil, 73.7 mg, 0.188 mmol, 47% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.28–7.22 (m, 3H), 7.18–7.17 (m, 1H), 7.12–7.08 (m, 2H), 7.03–7.00 (m, 1H), 6.49 (d, J = 7.4 Hz, 1H), 3.66 (s, 3H), 3.65 (s, 3H), 2.92–2.90 (m, 2H), 2.64–2.61 (m, 1H), 2.46–2.29 (m, 4H), 2.19–2.15 (m, 2H), 2.05 (s, 3H), 1.79–1.72 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 175.7, 173.3, 138.3, 136.8, 135.8, 135.4, 135.1, 134.2, 130.6, 130.4, 130.1, 127.3, 127.0, 126.4, 125.8, 125.1, 51.6, 51.5, 43.3, 36.8, 31.5, 28.4, 27.1, 26.5, 19.3.
Dimethyl 2-((1-(m-tolyl)-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate (3ha). Colorless oil, 90.9 mg, 0.232 mmol, 58% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm)7.32–7.30 (m, 1H), 7.17–7.15 (m, 2H), 7.12–7.08 (m, 1H), 7.05–7.01 (m, 1H), 6.97–6.93 (m, 2H), 6.59 (d, J = 7.5 Hz, 1H), 3.66 (s, 3H), 3,65 (s, 3H), 2.91–2.87 (m, 2H), 2.65–2.62 (m, 1H), 2.43–2.34 (m, 4H), 2.39 (s, 3H), 2.22–2.17 (m, 2H), 1.79–1.76 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 175.6, 173.3, 139.0, 136.7, 136.3, 135.1, 134.1, 130.8, 128.2, 127.6 (×2), 127.2, 127.0, 126.3, 126.2, 125.9, 51.6, 51.5, 43.4, 36.9, 31.6, 28.4, 27.3, 26.6, 21.5.
Dimethyl 2-((1-(4-bromo-2-methylphenyl)-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate (3ia). Colorless oil, 97.8 mg, 0.208 mmol, 52% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.44 (s, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.17 (d, J = 7.1 Hz, 1H), 7.13–7. 10 (m, 1H), 7.04–7.00 (m, 1H), 6.97 (d, J = 8.1 Hz, 1H), 6.45 (d, J = 7.4 Hz, 1H), 3.67 (s, 3H), 3.66 (s, 3H), 2.92–2.88 (m, 2H), 2.64–2.62 (m, 1H), 2.46–2.34 (m, 4H), 2.22–2.11 (m, 2H), 2.03 (s, 3H), 1.80–1.70 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 175.5, 173.2, 139.4, 137.3, 135.3, 135.1, 134.8, 134.3, 133.0, 132.1, 129.0, 127.2, 126.6, 126.4, 124.9, 121.1, 51.7, 51.6, 43.2, 36.9, 31.5, 28.3 (×2), 27.0, 26.5.
Dimethyl 2-((1-(3,5-dimethylphenyl)-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate (3ja). Colorless oil, 89.4 mg, 0.220 mmol, 55% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.17–7.15 (m, 1H), 7.12–7.08 (m, 1H), 7.06–7.02 (m, 1H), 6.98 (s, 1H), 6.78 (s, 1H), 6.73 (s, 1H), 6.62 (d, J = 7.5 Hz, 1H), 3.67 (s, 3H), 3.66 (s, 3H), 2.91–2.86 (m, 2H), 2.66–2.61 (m, 1H), 2.44–2.37 (m, 4H), 2.35 (s, 6H), 2.24–2.14 (m, 2H), 1.81–1.75 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 175.7, 173.3, 139.0, 137.7, 136.8, 136.4, 135.1, 133.9, 128.4, 127.9, 126.9, 126.2, 126.1, 125.9, 51.6, 51.5, 43.5, 37.0, 31.6, 28.4, 27.3, 26.6, 21.3.
Diethyl 2-((1-phenyl-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate (3ab). Colorless oil, 97.5 mg, 0.240 mmol, 60% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.44–7.40 (m, 2H), 7.37–7.33 (m 1H), 7.18–7.16 (m, 3H), 7.12–7.09 (m, 1H), 7.05–7.01 (m, 1H), 6.58 (d, J = 7.6 Hz, 1H), 4.17–4.08 (m, 4H), 2.90 (t, J = 8.3 Hz, 1H), 2.65–2.58 (m, 1H), 2.43–2.30 (m, 4H), 2.21–2.14 (m, 2H), 1.79–1.74 (m, 2H), 1.29–1.27 (m, 6H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 175.1, 172.9, 139.2, 136.7, 136.2, 135.2, 134.5, 130.3, 128.4, 127.0, 126.8, 126.3, 126.2, 125.8, 60.4, 60.3, 43.5, 37.0, 31.8, 28.4, 27.4, 26.8, 14.2.
Dibutyl 2-((1-phenyl-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate(3ac). Colorless oil, 96.2 mg, 0.208 mmol, 52% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.44–7.40 (m, 2H), 7.37–7.33 (m, 1H), 7.17–7.09 (m, 4H), 7.05–7.01 (m, 1H), 6.58 (d, J = 7.0 Hz, 1H), 4.07–4.03 (m, 4H), 2.91 (t, J = 8.1 Hz, 2H), 2.66–2.57 (m, 1H), 2.47–2.30 (m, 4H), 2.21–2.12 (m, 2H), 1.81–1.73 (m, 2H), 1.65–1.54 (m, 4H), 1.42–1.29 (m, 4H), 0.97–0.89 (m, 6H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 175.1, 173.0, 139.2, 136.7, 136.2, 135.1, 134.4, 130.3, 128.4, 127.0, 126.8, 126.3, 126.2, 125.8, 64.4, 64.3, 43.5, 37.0, 31.9, 30.7, 30.6, 28.4, 27.4, 26.8, 19.1 (×2), 13.7, 13.6.
Dihexyl 2-((1-phenyl-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate(3ad). Colorless oil, 66.1 mg, 0.148 mmol, 37% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.44–7.40 (m, 2H), 7.37–7.35 (m, 1H), 7.17–7.16 (m, 3H), 7.12–7.08 (m, 1H), 7.05–7.01 (m, 1H), 6.57 (d, J = 7.5 Hz, 1H), 4.09–4.02 (m, 4H), 2.92–2.88 (m, 2H), 2.64–2.62 (m, 1H), 2.45–2.32 (m, 4H), 2.22–2.16 (m, 2H), 1.79–1.71 (m, 2H), 1.65–1.56 (m, 6H), 1.32–1.28 (m, 10H), 0.93–0.87 (m, 6H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 175.1, 173.0, 139.2, 136.7, 136.2, 135.1, 134.4, 130.3, 128.4, 127.0, 126.8, 126.3, 126.2, 125.8, 64.7, 64.6, 43.5, 37.0, 31.8, 31.4, 31.3, 28.6, 28.5, 28.4, 27.4, 26.7, 25.6 (×2), 22.5, 22.4, 14.0 (×2).
Bis(2-chloroethyl) 2-((1-phenyl-3,4-dihydronaphthalen-2-yl)methyl)pentanedioate (3ae). Colorless oil, 89.2 mg, 0.200 mmol, 50% yield. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.45–7.43 (m, 2H), 7.38–7.36 (m, 1H), 7.18–7.10 (m, 4H), 7.06–7.02 (m, 1H), 6.58 (d, J = 7.6 Hz, 1H), 4.35–4.29 (m, 4H), 3.70–3.63 (m, 4H), 2.94–2.89 (m, 2H), 2.73–2.67 (m, 1H), 2.50–2.33 (m, 4H), 2.31–2.26 (m, 2H), 1.84–1.79 (m, 2H); 13C-NMR (100 MHz, CDCl3): δ (ppm) 174.6, 172.4, 139.1, 136.6, 136.4, 135.1, 134.0, 130.2, 128.4, 127.0, 126.9, 126.4, 126.2, 125.9, 64.0, 63.9, 43.2, 41.5, 41.4, 36.9, 31.5, 28.4, 27.4, 26.4.
Product characterization data, and 1H- and 13C-NMR spectra are available from supplementary material.

5. Conclusions

In a nutshell, we described an efficient method to assemble aryldihydronaphthalene derivatives via the cascade reaction of diarylalkynes with acrylates employing the catalysis of a combined Lewis acid system formed from In(III) salt and TMSBr. Both indium(III) and TMSBr are indispensable for the efficient progress of the reaction. In most cases, the reaction proceeded efficiently to afford the corresponding aryldihydronaphthalene derivatives in moderate to good yields. With reference to current experimental observations and literature reports, a possible mechanistic pathway for this reaction was also provided.

Supplementary Materials

Supplementary materials are available online: general experimental procedures, product characterization data, and 1H- and 13C-NMR spectra.

Acknowledgments

We are grateful to Nanjing Tech University, the SICAM Fellowship from the Jiangsu National Synergetic Innovation Center for Advanced Materials, Nanyang Technological University, Singapore Ministry of Education Academic Research Fund (Tier 1: MOE2015-T1-001-070 (RG5/15) and MOE2014-T1-001-102 (RG9/14)), and the Singapore National Research Foundation (NRF2015NRF-POC001-024) for generous financial support. W.W.Z. thanks BGI for financial support.

Author Contributions

W.W.Z. and T.-P.L. conceived and designed the experiments; L.S. and Q.-C.Z. performed the experiments; L.S. and Z.L.S wrote the paper; and W.W.Z. and L.S. analysed the data.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. James, M.J.; O’Brien, P.; Taylor, R.J.K.; Unsworth, W.P. Synthesis of spirocyclic indolenines. Chem. Eur. J. 2016, 22, 2856–2881. [Google Scholar] [CrossRef] [PubMed]
  2. Nicolaou, K.C.; Edmonds, D.J.; Bulger, P.G. Cascade reactions in total synthesis. Angew. Chem. Int. Ed. 2006, 45, 7134–7186. [Google Scholar] [CrossRef] [PubMed]
  3. Pan, J.-Y.; Chen, S.-L.; Yang, M.-H.; Wu, J.; Sinkkonen, J.; Zou, K. An update on lignans: Natural products and synthesis. Nat. Prod. Rep. 2009, 26, 1251–1292. [Google Scholar] [CrossRef] [PubMed]
  4. Teponno, R.B.; Kusari, S.; Spiteller, M. Recent advances in research on lignans and neolignans. Nat. Prod. Rep. 2016, 33, 1044–1092. [Google Scholar] [CrossRef] [PubMed]
  5. Yang, X.; Reinhold, A.R.; Rosati, R.L.; Liu, K.K.C. Enzyme-catalyzed asymmetric deacylation for the preparation of Lasofoxifene (CP-336156), a selective estrogen receptor modulator. Org. Lett. 2000, 2, 4025–4027. [Google Scholar] [CrossRef] [PubMed]
  6. Haq, A.-U.; Malik, A.; Anis, I.; Khan, S.B.; Ahmed, E.; Ahmed, Z.; Nawas, S.A.; Choudhary, M.I. Enzymes inhibiting lignans from Vitex Negundo. Chem. Pharm. Bull. 2004, 52, 1269–1272. [Google Scholar] [CrossRef]
  7. Kocsis, L.S.; Brummond, K.M. Intramolecular dehydro-Diels–Alder reaction affords selective entry to arylnaphthalene or aryldihydronaphthalene lignans. Org. Lett. 2014, 16, 4158–4161. [Google Scholar] [CrossRef] [PubMed]
  8. Magoulas, G.E.; Papaioannou, D. Bioinspired syntheses of dimeric hydroxycinnamic acids (lignans) and hybrids, using phenol oxidative coupling as key reaction, and medicinal significance thereof. Molecules 2014, 19, 19769–19835. [Google Scholar] [CrossRef] [PubMed]
  9. Silva, L.F.; Siqueira, F.A.; Pedrozo, E.C.; Vieira, F.Y.M.; Doriguetto, A.C. Iodine(III)-promoted ring contraction of 1,2-dihydronaphthalenes: Adiastereoselective total synthesis of (±)-Indatraline. Org. Lett. 2007, 9, 1433–1436. [Google Scholar] [CrossRef] [PubMed]
  10. Scribner, A.W.; Haroutounian, S.A.; Carlson, K.E.; Katzenellenbogen, J.A. 1-Aryl-2-pyridyl-3,4-dihydronaphthalenes: photofluorogenic ligands for the estrogen receptor. J. Org. Chem. 1997, 62, 1043–1057. [Google Scholar] [CrossRef]
  11. Marieke, V.; Iris, A.; Christiane, S.; Ursula, M.-V.; Klaus, B.; Sandrine, M.-O.; Rolf, W.H. Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes:  Potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis. J. Med. Chem. 2006, 49, 2222–2231. [Google Scholar] [CrossRef]
  12. Bandini, M.; Emer, E.; Tommasi, S.; Umani-Ronchi, A. Innovative catalytic protocols for the ring-closing Friedel–Crafts-typealkylation and alkenylation of arenes. Eur. J. Org. Chem. 2006, 3527–3544. [Google Scholar] [CrossRef]
  13. Kitamura, T. Transition-metal-catalyzed hydroarylation reactions of alkynes through direct functionalization of C–H bonds: a convenient tool for organic synthesis. Eur. J. Org. Chem. 2009, 1111–1125. [Google Scholar] [CrossRef]
  14. Yamamoto, Y. Synthesis of heterocycles via transition-metal catalyzed hydroarylation of alkynes. Chem. Soc. Rev. 2014, 43, 1575–1600. [Google Scholar] [CrossRef] [PubMed]
  15. Namyslo, J.C.; Storsberg, J.; Klinge, J.; Gärtner, C.; Yao, M.-L.; Ocal, N.; Kaufmann, D.E. The hydroarylation reaction—Scope and limitations. Molecules 2010, 15, 3402–3410. [Google Scholar] [CrossRef] [PubMed]
  16. Jia, C.; Lu, W.; Oyamada, J.; Kitamura, T.; Matsuda, K.; Irie, M.; Fujiwara, Y. Novel Pd(II)- and Pt(II)-catalyzed regio- and stereoselective trans-hydroarylation of alkynes by simple arenes. J. Am. Chem. Soc. 2000, 122, 7252–7263. [Google Scholar] [CrossRef]
  17. Jia, C.; Pao, D.; Oyamada, J.; Lu, W.; Kitamura, T.; Fujiwara, Y. Efficient activation of aromatic C-H bonds for addition to C-C multiple bonds. Science 2000, 287, 1992–1995. [Google Scholar] [CrossRef] [PubMed]
  18. Pastine, S.J.; Youn, S.W.; Sames, D. PtIV-catalyzed cyclization of arene−alkyne substrates via intramolecular electrophilic hydroarylation. Org. Lett. 2003, 5, 1055–1058. [Google Scholar] [CrossRef] [PubMed]
  19. Nishizawa, M.; Takao, H.; Yadav, V.K.; Imagawa, H.; Sugihara, T. Mercuric triflate-(TMU)3-catalyzed cyclization of ω-arylalkyne leading to dihydronaphthalenes. Org. Lett. 2003, 5, 4563–4565. [Google Scholar] [CrossRef] [PubMed]
  20. Zhang, L.; Kozmin, S.A. Brønsted acid-promoted cyclizations of siloxyalkynes with arenes and alkenes. J. Am. Chem. Soc. 2004, 126, 10204–10205. [Google Scholar] [CrossRef] [PubMed]
  21. Nevado, C.; Echavarren, A.M. Intramolecular hydroarylation of alkynes catalyzed by platinum or gold: Mechanism and endo selectivity. Chem.–Eur. J. 2005, 11, 3155–3164. [Google Scholar] [CrossRef] [PubMed]
  22. Barluenga, J.; Trincado, M.; Marco-Arias, M.; Ballesteros, A.; Rubio, E.; González, J.M. Intramolecular iodoarylation reaction of alkynes: easy access toderivatives of benzofused heterocycles. Chem. Commun. 2005, 2008–2010. [Google Scholar] [CrossRef] [PubMed]
  23. Gurtis, N.R.; Rassias, P.G.; Walker, A.J. A facile gold(I)-catalysed intramolecular alkyne hydroarylation approach to methyl 5-amino-2H-1-benzopyran-8-carboxylate derivatives. Tetrahedron Lett. 2008, 49, 6279. [Google Scholar] [CrossRef]
  24. Qiu, W.-W.; Surendra, K.; Yin, L.; Corey, E.J. Selective formation of six-membered oxa- and carbocycles by the In(III)-activated ring closure of acetylenic substrates. Org. Lett. 2011, 13, 5893–5895. [Google Scholar] [CrossRef] [PubMed]
  25. Wang, Y.; Ji, K.; Lan, S.; Zhang, L. Rapid access to chroman-3-ones through gold-catalyzed oxidation of propargyl aryl ethers. Angew. Chem. Int. Ed. 2012, 51, 1915–1918. [Google Scholar] [CrossRef] [PubMed]
  26. Arcadi, A.; Blesi, F.; Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Marinelli, F. Gold versus silver catalyzed intramolecular hydroarylation reactions of [(3-arylprop-2-ynyl)oxy]benzene derivatives. Org. Biomol. Chem. 2012, 10, 9700–9708. [Google Scholar] [CrossRef] [PubMed]
  27. Eom, D.; Mo, J.; Lee, P.H.; Gao, Z.; Kim, S. Synthesis of vinyl sulfides and vinylamines through catalytic intramolecular hydroarylation in the presence of FeCl3 and AgOTf. Eur. J. Org. Chem. 2013, 533–540. [Google Scholar] [CrossRef]
  28. Morán-Poladura, P.; Rubio, E.; González, J.M. Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives. Beilstein J. Org. Chem. 2013, 9, 2120–2128. [Google Scholar] [CrossRef] [PubMed]
  29. Eom, D.; Park, S.; Park, Y.; Lee, K.; Hong, G.; Lee, P.H. Brønsted acid catalyzed intramolecular hydroarylation for the synthesis of cycloalkenyl selenides and tellurides. Eur. J. Org. Chem. 2013, 2672–2682. [Google Scholar] [CrossRef]
  30. Walkinshaw, A.J.; Xu, W.; Suero, M.G.; Gaunt, M.J. Copper-catalyzed carboarylation of alkynes via vinyl cations. J. Am. Chem. Soc. 2013, 135, 12532–12535. [Google Scholar] [CrossRef] [PubMed]
  31. Murase, H.; Senda, K.; Senoo, M.; Hata, T.; Urabe, H. Rhodium-catalyzed intramolecular hydroarylation of 1-halo-1-alkynes: regioselective synthesis of semihydrogenated aromatic heterocycles. Chem. Eur. J. 2014, 20, 317–322. [Google Scholar] [CrossRef] [PubMed]
  32. Xu, J.; Wang, Y.-L.; Gong, T.-J.; Xiao, B.; Fu, Y. Copper-catalyzed endo-type trifluoromethyl arylation of alkynes. Chem. Commun. 2014, 50, 12915–12918. [Google Scholar] [CrossRef] [PubMed]
  33. Wang, Y.-L.; Zhang, W.-M.; Dai, J.-J.; Feng, Y.-S.; Xu, H.-J. Cu-catalyzed intramolecular hydroarylation of alkynes. RSC Adv. 2014, 4, 61706–61710. [Google Scholar] [CrossRef]
  34. Fu, L.; Niggemann, M. Calcium-catalyzed carboarylation of alkynes. Chem. Eur. J. 2015, 21, 6367–6370. [Google Scholar] [CrossRef] [PubMed]
  35. Warner, A.J.; Lawson, J.R.; Fasano, V.; Ingleson, M.J. Formation of C(sp2)-boronate esters by borylative cyclization of alkynes using BCl3. Angew. Chem. Int. Ed. 2015, 54, 11245–11249. [Google Scholar] [CrossRef] [PubMed]
  36. Ding, D.; Mou, T.; Feng, M.; Jiang, X. Utility of ligand effect in homogenous gold catalysis: enabling regiodivergent π-bond-activated cyclization. J. Am. Chem. Soc. 2016, 138, 5218–5221. [Google Scholar] [CrossRef] [PubMed]
  37. Lau, V.M.; Pfalzgraff, W.C.; Markland, T.E.; Kanan, M.W. Electrostatic control of regioselectivity in Au(I)-catalyzed hydroarylation. J. Am. Chem. Soc. 2017, 139, 4035–4041. [Google Scholar] [CrossRef] [PubMed]
  38. Alonso-Marañón, L.; Martínez, M.M.; Sarandeses, L.A.; Pérez Sestelo, J. Indium-catalyzed intramolecular hydroarylation ofaryl propargyl ethers. Org. Biomol. Chem. 2015, 13, 379–387. [Google Scholar] [CrossRef] [PubMed]
  39. Alonso-Marañón, L.; Sarandeses, L.A.; Martínez, M.M.; Pérez Sestelo, J. Sequential In-catalyzed intramolecular hydroarylation and Pd-catalyzed cross-coupling reactions using bromopropargyl aryl ethers and amines. Org. Chem. Front. 2017, 4, 500–505. [Google Scholar] [CrossRef]
  40. Li, C.J.; Chan, T.H. Organic synthesis using indium-mediated and catalyzed reactions in aqueous media. Tetrahedron 1999, 55, 11149–11176. [Google Scholar] [CrossRef]
  41. Shen, Z.-L.; Wang, S.-Y.; Chok, Y.-K.; Xu, Y.-H.; Loh, T.-P. Organoindium reagents: the preparation and application in organic synthesis. Chem. Rev. 2013, 113, 271–401. [Google Scholar] [CrossRef] [PubMed]
  42. Zhao, K.; Shen, L.; Shen, Z.-L.; Loh, T.-P. Transition metal-catalyzed cross-coupling reactions using organoindium reagents. Chem. Soc. Rev. 2017, 46, 586–602. [Google Scholar] [CrossRef] [PubMed]
  43. Onishi, Y.; Ito, T.; Yasuda, M.; Baba, A. Indium(III) chloride/chlorotrimethylsilane as a highly active Lewis acid catalyst system for the Sakurai-Hosomi reaction. Eur. J. Org. Chem. 2002, 1578–1581. [Google Scholar] [CrossRef]
  44. Saito, T.; Nishimoto, Y.; Yasuda, M.; Baba, A. Direct coupling reaction between alcohols and silyl compounds: enhancement of Lewis acidity of Me3SiBr using InCl3. J. Org. Chem. 2006, 71, 8516–8522. [Google Scholar] [CrossRef] [PubMed]
  45. Lee, P.H.; Lee, K.; Sung, S.-Y.; Chang, S. The catalytic Sakurai reaction. J. Org. Chem. 2001, 66, 8646–8649. [Google Scholar] [CrossRef] [PubMed]
  46. Surendra, K.; Corey, E.J. Diiodoindium(III) cation, InI2+, a potent yneophile. Generation and application to cationic cyclization by selective ϖ-activation of C≡C. J. Am. Chem. Soc. 2014, 136, 10918–10920. [Google Scholar] [CrossRef] [PubMed]
  47. Liu, F.; Loh, T.-P. Highly stereoselective Prins cyclization of (Z)-and (E)-γ-brominated homoallylic alcohols to 2,4,5,6-tetrasubstituted tetrahydropyrans. Org. Lett. 2007, 9, 2063–2066. [Google Scholar] [CrossRef] [PubMed]
  48. Hu, X.H.; Liu, F.; Loh, T.-P. Stereoelectronic versus steric tuning in the Prins cyclization Reaction: synthesis of 2,6-trans pyranyl motifs. Org. Lett. 2009, 11, 1741–1743. [Google Scholar] [CrossRef] [PubMed]
  49. Shen, L.; Zhao, K.; Doitomi, K.; Ganguly, R.; Li, Y.-X.; Shen, Z.-L.; Hirao, H.; Loh, T.-P. Lewis acid-catalyzed selective [2 + 2]-cycloaddition and dearomatizing cascade reaction of aryl alkynes with acrylates. J. Am. Chem. Soc. 2017, 139, 13570–13578. [Google Scholar] [CrossRef] [PubMed]
  50. Zhao, J.-F.; Loh, T.-P. Acid-catalyzed intramolecular [2 + 2] cycloaddition of ene-allenones: facile access to bicyclo[n.2.0] frameworks. Angew. Chem. Int. Ed. 2009, 48, 7232–7235. [Google Scholar] [CrossRef] [PubMed]
  51. Li, B.; Lai, Y.-C.; Zhao, Y.J.; Wong, Y.-H.; Shen, Z.L.; Loh, T.-P. Synthesis of 3-oxaterpenoids and its application in the total synthesis of (±)-moluccanic acid methyl ester. Angew. Chem. Int. Ed. 2012, 51, 10619–10623. [Google Scholar] [CrossRef]
Sample Availability: Samples of the compounds 3aaja and 3abae are available from the authors.
Figure 1. Representative natural products and bioactive compounds containing aryldihydronaphthalene structures [3,4,5,6,7].
Figure 1. Representative natural products and bioactive compounds containing aryldihydronaphthalene structures [3,4,5,6,7].
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Scheme 1. In(III)-TMSBr-catalysed cascade reaction of diarylalkynes with acrylates for the synthesis of dihydronaphthalene derivatives.
Scheme 1. In(III)-TMSBr-catalysed cascade reaction of diarylalkynes with acrylates for the synthesis of dihydronaphthalene derivatives.
Molecules 23 00979 sch001
Scheme 2. Proposed In(III)-TMSBr-catalysed cascade reaction of diarylalkynes with acrylates.
Scheme 2. Proposed In(III)-TMSBr-catalysed cascade reaction of diarylalkynes with acrylates.
Molecules 23 00979 sch002
Scheme 3. Initial results of In(III)-TMSBr-catalysed cascade reaction of but-1-yne-1,4-diyldibenzene (1a) with methyl acrylates (2a).
Scheme 3. Initial results of In(III)-TMSBr-catalysed cascade reaction of but-1-yne-1,4-diyldibenzene (1a) with methyl acrylates (2a).
Molecules 23 00979 sch003
Figure 2. Substrate scope for the In(III)-TMSBr-catalysed cascade reaction of diarylalkyne with acrylates a,b. a Unless otherwise noted, all reactions were performed with 1 (0.4 mmol), 2 (1.2 mmol), In(tfacac)3 (20 mol %), TMSBr (3 equiv), 0 °C-rt, N2. b Isolated yields.
Figure 2. Substrate scope for the In(III)-TMSBr-catalysed cascade reaction of diarylalkyne with acrylates a,b. a Unless otherwise noted, all reactions were performed with 1 (0.4 mmol), 2 (1.2 mmol), In(tfacac)3 (20 mol %), TMSBr (3 equiv), 0 °C-rt, N2. b Isolated yields.
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Scheme 4. Plausible reaction mechanism of the In(tfacac)3-TMSBr-catalysed cascade reaction of diarylalkynes with acrylates.
Scheme 4. Plausible reaction mechanism of the In(tfacac)3-TMSBr-catalysed cascade reaction of diarylalkynes with acrylates.
Molecules 23 00979 sch004
Table 1. The In(III)-TMSBr-catalyzed cascade reaction of diarylalkyne 1a with methyl acrylate (2a) a.
Table 1. The In(III)-TMSBr-catalyzed cascade reaction of diarylalkyne 1a with methyl acrylate (2a) a.
Molecules 23 00979 i001
EntryCatalystSolventTMSXYield (%) b
1InBr3CH2Cl2TMSBr50
2InBr3CH2Cl2-0
3-CH2Cl2TMSBr0 c
4InCl3CH2Cl2TMSBr14
5InI3CH2Cl2TMSBr47
6In(OTf)3CH2Cl2TMSBr37
7In(tfacac)3CH2Cl2TMSBr61
8In(acac)3CH2Cl2TMSBr0
9AlBr3CH2Cl2TMSBr0
10ZnCl2CH2Cl2TMSBr0
11In(tfacac)3ClCH2CH2ClTMSBr70
12In(tfacac)3ClCH2CH2ClTMSCl<5
13In(tfacac)3ClCH2CH2ClTMSBr60 c
14In(tfacac)3ClCH2CH2ClTMSBr57 d
15In(tfacac)3ClCH2CH2ClTMSBr33 e
a Unless otherwise noted, all reactions were performed with 1a (0.4 mmol), 2a (1.2 mmol), catalyst (20 mol %), TMSX (3 equiv), 0 °C-rt, 2 h, N2. b Isolated yields. c 2.0 equiv of TMSBr was added. d 10 mol % of In(tfacac)3 was added. e 1.0 equiv of 2a was added.
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