Abstract
A new Fe(III)-catalyzed bicyclization reaction of yne-allenones with indoles has been established, enabling the direct construction of cyclobuta[a]naphthalen-4-ols with an all-carbon quaternary center in good to excellent yields. This reaction was performed by using low-cost FeCl3 as the catalyst and EtOH as the environmentally benign solvent, providing a green protocol for constructing the cyclobutarene framework with a high degree of atom economy and functional group compatibility. The reaction mechanism was proposed to proceed through a [2 + 2] cycloaddition/1,6-conjugate addition cascade.
Introduction
Development of practical and sustainable synthetic methods for the rapid construction of valuable cyclic target molecules, along with minimum environmental impacts, represents an endeavor of utmost importance in both academia, and industry (Anastas and Warner, ; Bruckmann et al., ; Martins et al., 2009; Jiang et al., 2010; Huang et al., 2018a). In this context, chemical transformations following the principles of atom-economy are generally believed to be green since such reactions enable different molecular fragments into integrated cyclic frameworks by recombining chemical bonds with maximum atom utilization and minimum generation of the chemical waste (Trost, 1995, 2002; Trost et al., 2003; Banert and Plefka, ; Kotha et al., 2013). The key to realize this goal is to implement reaction cascades, which allow the direct formation of multiple chemical bonds in a one-pot operation and can lead to a remarkable increase in resource efficiency for the overall process (Barluenga et al., ; Fuerstner, ; Tietze et al., 2009; Jones et al., 2010; Wang et al., 2015; Sugimoto and Matsuya, 2017; Zhang et al., 2017). Specifically, bicyclization cascades have emerged as an important platform for the synthesis of bioactive small-molecule libraries for their SAR studies (Dömling et al., ; Brauch et al., ; Vlaar et al., 2013; Koopmanschap et al., 2014; Rotstein et al., 2014; Huang et al., 2018b). Due to their annulation efficiency, economic and environmental aspects, and ease of operation as well as diminished waste disposals (Jia et al., 2014; Su et al., 2014; Tian et al., 2015; Chen et al., ; Huang et al., 2017; Liu et al., 2017b,c; Wang L. et al., 2017). In view of the environmental awareness of the chemical community, the combination of the presented bicyclization strategy and the use of environmentally benign solvents will furnish the transformations under avoidance of potential pollutants (Bihani et al., ; Wang J.-Y. et al., 2017; Sha et al., 2018a). Nevertheless, the design and development of environmentally compatible bicyclization cascades without generation of toxic waste and by-products holds considerable challenges.
Cyclobutarenes are a class of structurally unique bicarbocyclic molecules which show a wide spectrum of biological activity (Christophe et al., ; Sadana et al., 2003). Due to the thermodynamic stability associated with the aromatic system and the kinetic reactivity of the strained cyclobutene ring (Cava and Napier, ; Mehta and Kotha, 2001), these molecules behave as reliable and synthetically useful feedstocks (Christophe et al., ) and have been extensively applied in natural product syntheses (Funk and Vollhardt, , ; Grieco et al., 1980; Taber et al., 1987; Nemoto et al., 1995; Michellys et al., 2001). With these contributions in mind, great efforts to establish synthetic protocols for cyclobutarene synthesis have been developed which include 1,4-elimination-cycloaddition of functionalized arenes (Gray et al., 1978; Schirch et al., 1979; Sekine et al., 1979; Lenihan and Shechter, 1994, 1998; Chou et al., ), Parham cyclization (Bradsher and Hunt, ; Buchwald et al., ,; Beak and Selling, ; Aidhen and Ahuja, ), photo-induced cycloadditions (Parham et al., 1976; Kaneko and Naito, 1979; Neckers and Wagenaar, 1981; Kaneko et al., 1982; Kanao et al., 1983; Sato et al., 1987; Hoffmann and Pete, 1996), thermal extrusion reactions (Toda et al., 1988; D'Andrea et al., ; Hickman et al., 1991; Shimada et al., 1993; Andersen et al., ; Craig et al., ), intramolecular addition of carbanions to benzynes (Bunnett and Skorcz, ; Krohn et al., 1978; Gowland and Durst, 1979), [2 + 2 + 2] cycloadditions of 1,5-hexadiyne (Peter and Vollhardt, 1977, 1984; Funk and Vollhardt, ; McNichols and Stang, 1992), ring expansion of cycloproparenes (Birch et al., ; Iskander and Stansfield, 1965; Buckland et al., ; Kagabu and Saito, 1988; Müller et al., 1989), and [2 + 2] cycloadditions of allene precursors (Inanaga et al., 1992; Ezcurra and Moore, ; Toda et al., 1994) and other methods (Markgraf et al., 1969; Garratt and Nicolaides, , ; Bilyard et al., ; Warrener et al., 1993). However, these methods encounter some drawbacks such as high temperatures (400°C-800°C), strong bases (n-BuLi and NaNH2), multiple steps, or a narrow substrate range. Moreover, indole derivatives stand for another important class of heterocyclic compounds present in a myriad of bioactive substances and natural products. Therefore, the development of general and sustainable entries toward cyclobutarene-indole pairs in atom- and pot-economic manner is of potential significance. Recently, we reported the combination of [2 + 2] cycloaddition with 1,4-radical addition reaction by treating yne-allenones with aryldiazonium salts and DABCO-bis(sulfur dioxide) (DABSO), affording functional cyclobuta[a]naphthalen-4-ols (Scheme 1a, Liu et al., 2017a). Subsequently, we developed a BF3•Et2O-catalyzed double [2 + 2] cycloaddition relay between yne-allenones and unactivated alkenes, enabling C-C triple bond cleavage to access phenanthren-9-ols (Scheme 1b, Li et al., 2018a). To continue our efforts in this project (Liu et al., 2017a; Wang J.-Y. et al., 2017; Li et al., 2018a,b; Sha et al., 2018b; Wang et al., 2018), we attempted to employ indoles 2 to be subjected with the reaction of yne-allenones 3 under our previous conditions (Li et al., 2018a) to assemble naphtho[1,2-a]carbazol-5-ols 4 (Scheme 1d), owing to indoles with C2 and C3 reactive sites could acted as C2 synthons for the synthesis of fused indoles (Haibach et al., 2011; Li et al., 2015; Liu et al., 2016; Ozaki et al., 2017). Unexpectedly, a double [2 + 2] cycloaddition relay did not occur. Instead, the reaction involved another [2 + 2] cycloaddition /1,6-addtition cascade to furnish 3-indolyl substituted cyclobuta[a]naphthalen-4-ols 3 by suitably adjusting the catalysts and solvents (Scheme 1c). Notably, the current green protocol represents an atom-economic and eco-friendly entry to structurally unique cyclobutarene-indole pairs through the combination of [2 + 2] cycloaddition with 1,6-conjugate addition by FeCl3 as a low-cost catalyst and EtOH as an environmentally benign solvent. Herein, we elaborate this attractive and benign transformation.
Scheme 1
Results and Discussion
At the beginning of our studies, yne-allenone 1a and N-methylindole (2a) were chosen as the model substrates to explore the feasibility of double [2 + 2] cycloaddition relay reaction with our previous conditions (Table 1, entry 1). Instead of the expected naphtho[1,2-a]carbazol-5-ol 4a, 3-indolyl substituted cyclobuta[a]naphthalen-4-ol 3a was obtained in 60% yield. The following screening of solvents, such as N,N-dimethylformamide (DMF), 1,4-dioxane, tetrahydrofuran (THF), MeOH, and EtOH, showed that use of DMF and 1,4-dioxane as reaction media completely suppressed the reaction process (entries 2–3) whereas the latter three all made the transformations work more efficiently (entries 4–6). Among these, EtOH proved to be the best choice, providing the product 3a with the highest yield of 76% (entry 6). Increasing the component ratio to 1:2 is not beneficial for this transformation as a lower conversion was observed (63%, entry 7). In contrast, fine-tuning the component ratio to 1:1.2 could improve the reaction efficiency, resulting in a higher yield of 3a (81%, entry 8). As the next optimization step, we conducted the screening of a variety of Lewis acid catalysts, such as ZnCl2, Y(OTf)3 and FeCl3 that are often employed in the catalytic transformations, for this cyclization-addition cascade by using EtOH as the reaction media. The former two led to remarkably lower conversions (entries 9–10). Delightingly, the latter one showed the best catalytic performance in this transformation, delivering higher yield of 3a as compared with BF3•Et2O (85%, entry 11 vs. 8). It is found that the reaction efficiency was proven to display an important dependence on the loading of the Fe-catalyst. An increase in the FeCl3 loading had a detrimental impact on the reaction yield (entry 12) whereas reducing the catalytic amount of FeCl3 to 10 mol% could accelerate the conversion into 3a in an increased the yield to 88%. When the reaction temperature was elevated to 70°C, the reaction process was inhibited in some extent (entry 14). On the contrary, decreasing the reaction temperature to 30°C facilitated the current transformation and gave a higher yield of 90% (entry 15).
Table 1
 | |||||
|---|---|---|---|---|---|
| Entry | Ratio (1a:2a) | Cat. (mol%) | Solvent | Temp (°C) | Yield (%)[b] |
| 1 | 1:1.5 | BF3•Et2O (15) | DCE | 50 | 60 |
| 2 | 1:1.5 | BF3•Et2O (15) | DMF | 50 | N.D. |
| 3 | 1:1.5 | BF3•Et2O (15) | 1,4-dioxane | 50 | N.D. |
| 4 | 1:1.5 | BF3•Et2O (15) | THF | 50 | 66 |
| 5 | 1:1.5 | BF3•Et2O (15) | MeOH | 50 | 62 |
| 6 | 1:1.5 | BF3•Et2O (15) | EtOH | 50 | 76 |
| 7 | 1:2 | BF3•Et2O (15) | EtOH | 50 | 63 |
| 8 | 1:1.2 | BF3•Et2O (15) | EtOH | 50 | 81 |
| 9 | 1:1.2 | ZnCl2 (15) | EtOH | 50 | 60 |
| 10 | 1:1.2 | Y(OTf)3 (15) | EtOH | 50 | 25 |
| 11 | 1:1.2 | FeCl3 (15) | EtOH | 50 | 85 |
| 12 | 1:1.2 | FeCl3 (20) | EtOH | 50 | 74 |
| 13 | 1:1.2 | FeCl3 (10) | EtOH | 50 | 88 |
| 14 | 1:1.2 | FeCl3 (10) | EtOH | 70 | 72 |
| 15 | 1:1.2 | FeCl3 (10) | EtOH | 30 | 90 |
Optimization of Reaction Conditions[a].
Reaction conditions: Benzene-tethered yne-allenone (1a, 0.1 mmol, 1.0 equiv), N-methylindole (2a, x mmol), catalyst (y mol%), solvent (5.0 mL), air, 8 h
Isolated yield based on 1a.
With these optimal conditions in hand (Table 1, entry 15), we set out to examine the scope of this Fe-catalyzed [2 + 2] cycloaddition /1,6-addition cascade by using a variety of yne-allenones and indoles. As depicted in Scheme 2, N-methylindole (2a) was first selected to evaluate the influence of substituents (R1) in the arylalkynyl moiety of yne-allenone 1. Both electron-poor and electron-rich groups at different positions of the arylalkynyl moiety (R1) can all tolerate this catalytic system, efficiently accessing the corresponding products 3b-3j in 75–98% yields. Diverse substituents, such as fluoro (1b), chloro (1c and 1d), bromo (1e), methyl (1f and 1g), methoxy (PMP = p-methoxyphenyl, 1h), ethyl(1i), t-butyl (1j) were suitable for this transformation. The presence of soft electron-withdrawing substituents (chloro, 1c and bromo, 1e) at the para-positions seemed to result in higher reactivity than that of electron-donating counterparts (3c and 3e vs. 3f and 3h-3j). Moreover, a sterically encumbered 1-naphthyl (1-Np) analog 1k was an effective candidate, which proceeded through a similar cyclization-addition process to give the corresponding product 3k in 77% yield. Besides, 2-thienyl counterpart 1l still showed high reactivity, delivering 2-thienyl product 3l in 91% yield. Next, we placed different functional groups (R2) including methoxy, methyl, and fluoro into the C4 or C5 position of the internal arene ring of substrates 1 and explored the synthetic utility of these substrates. Satisfyingly, all those substituents (1m−1u) would be compatible in the present reaction protocol, and the corresponding functionalized cyclobuta[a]naphthalen-4-ols 3m-3u in 72–92% yields were produced. Interestingly, the pyridine-tethered yne-allenone 1v could be successfully converted into cyclobutarene product 3v in 68% yield.
Scheme 2
Next, the scope with respect to indoles components was evaluated. As anticipated, the different substituents including methoxy (2b), chloro (1c and 1d), bromo (1e), methyl (1f and 1g), located at different positions of the indole ring would be accommodated, confirming the reaction efficiency, as the cyclobuta[a]naphthalen-4-ol products 3w-3bb were offered in 76–92% yields. Finally, the free indole turned out to be a suitable reaction partner, leading to the formation of products 3cc and 3dd in 78 and 81% yields, respectively. Products 3 were fully characterized by their NMR and HR-MS spectral analysis. In the case of product 3a, its structure was further confirmed by X-ray crystallography (Figure 1).
Figure 1
Mechanism
Based on the above experimental observations and literature reports (Haibach et al., 2011; Li et al., 2015, 2018a; Liu et al., 2016, 2017a; Ozaki et al., 2017; Sha et al., 2018b), a feasible mechanism for forming products 3 was proposed in Scheme 3. Initially, the intramolecular [2 + 2] cycloaddition of yne-allenones 1 rapidly occurs to yield cyclobutene intermediate A. In the presence of Fe-catalyst, 1,6-addition of indoles into intermediate B gives intermediate C, which converts into the final products 3 through proton transfer (PT), together with the regeneration of Fe-catalyst.
Scheme 3
Conclusion
In summary, starting from readily available yne-allenones and indoles, we have established a new Fe-catalyzed [2 + 2] cycloaddition/1,6-conjugate addition cascade for the high-efficient and benign synthesis of a variety of 3-indolyl cyclobuta[a]naphthalen-4-ols with good to excellent yields. The current green protocol has the advantages of broad scope of substrates, good tolerance of functional group and high atom utilization as well as mild reaction conditions. Further application of the resulting cyclobutarenes is underway in our laboratory.
Materials and Methods
General
All melting points are uncorrected. The NMR spectra were recorded in CDCl3 or DMSO-d6 on a 400 MHz instrument with TMS as internal standard. Chemical shifts (δ) were reported in ppm with respect to TMS. Data are represented as follows: chemical shift, mutiplicity (s = singlet, d = doublet, t = triplet, m = multiplet), coupling constant (J, Hz) and integration. HRMS analyses were carried out using a TOF-MS instrument with an ESI source. X-Ray crystallographic analysis was performed with a SMART CCD and a P4 diffractometer (the copies of NMR see Supplementary Material). All yne-allenones 1 are known compounds and their preparation followed the previously reported procedures (Wei et al., 2009; Liu et al., 2017a; Li et al., 2018b).
General Procedure for the Synthesis of 3
Example for the Synthesis of 3a
1-(2-(Phenylethynyl)phenyl)buta-2,3-dien-1-one (1a, 0.3 mmol, 73.2 mg) was added to a 10-mL reaction tubing under the air conditions. Then, N-methylindole (2a, 0.36 mmol, 47.2 mg) and EtOH (5 mL) were continuously added into the above reaction mixture. Subsequently, FeCl3 (10 mol%, 4.8 mg) was added to the reaction system. Then the mixture was stirred at 30°C for 8 h until complete consumption of 1a as monitored by TLC analysis. After the reaction was finished, the reaction mixture was concentrated in vacuum, and the resulting residue was purified by column chromatography on silica gel (eluent, petroleum ether/ethyl acetate = 20:1) to afford the desired product 3a as a white solid.
1-(1-methyl-1H-indol-3-yl)-1-phenyl-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3a)
White solid, 102 mg, 90% yield; mp 179-181°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.23 (s, 1H), 8.24 (d, J = 8.0 Hz, 1H), 7.51 (d, J = 7.6 Hz, 1H), 7.38 (m, 5H), 7.29 (m, 2H), 7.21 (m, 1H), 7.07 (m, 1H), 6.91-6.78 (m, 4H), 3.88 (m, 2H), 3.68 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.8, 146.1, 140.3, 137.7, 137.0, 130.1, 128.5, 128.1, 127.5, 127.4, 126.8, 126.5, 125.2, 124.4, 123.9, 122.4, 121.5, 120.1, 119.0, 118.8, 110.3, 104.9, 54.4, 47.7, 32.7; IR (KBr, ν, cm−1) 3341, 3044, 1579, 1474, 1228, 1181, 1024, 905, 806, 738; HRMS (APCI-TOF) m/z calcd for C27H20NO [M-H]− 374.1545; found 374.1546.
1-(4-fluorophenyl)-1-(1-methyl-1H-indol-3-yl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3b)
White solid, 97 mg, 83% yield; mp 160-162°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.24 (s, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.43-7.34 (m, 5H), 7.11 (m, 3H), 6.87 (m, 4H), 3.88 (m, 2H), 3.68 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 162.2 (1JCF = 240.5 Hz), 159.8, 154.9, 142.3 (4JCF = 2.9 Hz), 142.2, 140.3, 137.7, 136.8, 129.9, 129.4 (3JCF = 7.9 Hz), 129.3, 128.1, 127.5, 126.7, 125.2, 124.4, 123.9, 122.2, 121.6, 120.0, 119.1, 118.6, 115.3 (2JCF = 21.0 Hz), 115.1, 110.4, 105.0, 53.7, 47.9, 32.7; IR (KBr, ν, cm−1) 3399, 3051, 1573, 1464, 1226, 1188, 1014, 904, 808, 748; HRMS (APCI-TOF) m/z calcd for C27H19FNO [M-H]− 392.1451; found 392.1453.
1-(4-chlorophenyl)-1-(1-methyl-1H-indol-3-yl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3c)
White solid, 114 mg, 93% yield; mp 170-172°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.27 (s, 1H), 8.24 (d, J = 8.0 Hz, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.44-7.31 (m, 7H), 7.12-7.06 (m, 1H), 6.93 (s, 1H), 6.87 (m, 3H), 3.82 (m, 2H), 3.69 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.9, 145.1, 140.3, 137.7, 136.5, 131.0, 129.9, 129.3, 128.5, 128.2, 127.6, 126.7, 125.2, 124.4, 124.0, 122.1, 121.6, 120.0, 119.1, 118.2, 110.4, 104.9, 53.7, 47.8, 32.7; IR (KBr, ν, cm−1) 3407, 3031, 1563, 1441, 1223, 1103, 1012, 909, 838, 741; HRMS (APCI-TOF) m/z calcd for C27H19ClNO [M-H]− 408.1156; found 408.1143.
1-(2-chlorophenyl)-1-(1-methyl-1H-indol-3-yl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3d)
White solid, 92 mg, 75% yield; mp 177-179°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.31 (s, 1H), 8.30-8.19 (m, 1H), 7.65 (d, J = 7.6 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.44-7.28 (m, 6H), 6.99 (m, 1H), 6.93 (s, 1H), 6.79 (s, 1H), 6.69 (m, 1H), 6.60 (d, J = 8.0 Hz, 1H), 4.32 (d, J = 14.4 Hz, 1H), 3.71 (s, 1H), 3.66 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 155.2, 143.4, 140.3, 137.7, 135.9, 134.0, 131.0, 130.5, 130.1, 128.9, 127.9, 127.6, 127.4, 126.2, 125.2, 124.4, 123.9, 122.2, 121.1, 119.3, 118.9, 116.1, 110.2, 104.7, 55.3, 47.5, 32.7; IR (KBr, ν, cm−1) 3442, 3022, 1533, 1421, 1203, 1123, 1010, 903, 834, 721; HRMS (APCI-TOF) m/z calcd for C27H19ClNO [M-H]− 408.1156; found 408.1162.
1-(4-bromophenyl)-1-(1-methyl-1H-indol-3-yl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3e)
White solid, 133 mg, 98% yield; mp 166-168°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.26 (s, 1H), 8.24 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 8.4 Hz, 3H), 7.43-7.34 (m, 3H), 7.30 (d, J = 8.4 Hz, 2H), 7.09 (m, 1H), 6.93 (s, 1H), 6.92-6.83 (m, 3H), 3.81 (m, 2H), 3.69 (s, 3H). 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.9, 145.5, 140.3, 137.7, 136.5, 131.5, 129.9, 129.7, 128.2, 127.6, 126.7, 125.3, 124.4, 124.0, 122.1, 121.6, 120.0, 119.6, 119.1, 118.1, 110.4, 104.9, 53.8, 47.8, 32.7. IR (KBr, ν, cm−1) 3412, 3021, 1538, 1391, 1202, 1129, 1017, 906, 818, 733; HRMS (APCI-TOF) m/z calcd for C27H19BrNO [M-H]− 452.0651; found 452.0634.
1-(1-methyl-1H-indol-3-yl)-1-(p-tolyl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3f)
White solid, 94 mg, 80% yield; mp 155-157°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.20 (s, 1H), 8.23 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.42-7.34 (m, 3H), 7.26 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 3H), 6.92-6.79 (m, 4H), 3.80 (m, 2H), 3.68 (s, 3H), 2.26 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.7, 143.0, 140.3, 137.7, 137.2, 135.3, 130.0, 129.1, 128.0, 127.4, 127.3, 126.8, 125.2, 124.3, 123.8, 122.4, 121.5, 120.2, 119.0, 118.9, 110.3, 105.0, 54.0, 47.8, 32.7, 21.1; IR (KBr, ν, cm−1) 3418, 3009, 1541, 1401, 1192, 1121, 1012, 916, 813, 730; HRMS (APCI-TOF) m/z calcd for C28H22NO [M-H]− 388.1702; found 388.1723.
1-(1-methyl-1H-indol-3-yl)-1-(m-tolyl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3g)
White solid, 99 mg, 85% yield; mp 149-151°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.20 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.38 (m, 3H), 7.23 (s, 1H), 7.18 (d, J = 5.6 Hz, 2H), 7.09-7.01 (m, 2H), 6.85 (m, 4H), 3.82 (m, 2H), 3.68 (s, 3H), 2.22 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.7, 146.0, 140.3, 137.7, 137.4, 137.1, 128.4, 128.0, 127.4, 127.2, 126.8, 125.2, 124.8, 124.3, 123.8, 120.1, 118.9, 110.3, 105.0, 54.3, 47.7, 32.7, 21.8; IR (KBr, ν, cm−1) 3411, 2966, 1511, 1406, 1162, 1091, 1015, 911, 833, 727; HRMS (APCI-TOF) m/z calcd for C28H22NO [M-H]− 388.1702; found 388.1720.
1-(4-methoxyphenyl)-1-(1-methyl-1H-indol-3-yl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3h)
White solid, 105 mg, 86% yield; mp 167-169°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.19 (s, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.42-7.33 (m, 3H), 7.29 (d, J = 8.8 Hz, 2H), 7.07 (m, 1H), 6.91-6.81 (m, 6H), 3.79 (m, 2H), 3.70 (s, 3H), 3.67 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 157.9, 154.7, 140.3, 138.1, 137.7, 137.3, 130.0, 128.5, 128.0, 127.3, 126.8, 125.2, 124.4, 123.8, 122.4, 121.5, 120.2, 119.2, 118.9, 113.8, 110.3, 105.0, 55.4, 53.7, 47.9, 32.7; IR (KBr, ν, cm−1) 3417, 2996, 1517, 1403, 1177, 1096, 1013, 914, 845, 720; HRMS (APCI-TOF) m/z calcd for C28H22NO2 [M-H]− 404.1651; found 404.1638.
1-(4-ethylphenyl)-1-(1-methyl-1H-indol-3-yl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3i)
White solid, 97 mg, 80% yield; mp 165-167°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.19 (s, 1H), 8.24 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.42-7.33 (m, 3H), 7.29 (d, J = 8.0 Hz, 2H), 7.13-7.04 (m, 3H), 6.90-6.77 (m, 4H), 3.80 (m, 2H), 3.68 (s, 3H), 2.56 (m, 2H), 1.15 (m, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.7, 143.3, 141.7, 140.3, 137.7, 137.2, 130.0, 128.0, 127.9, 127.4, 127.4, 126.8, 125.2, 124.3, 123.8, 122.4, 121.5, 120.2, 119.0, 118.9, 110.3, 105.0, 54.0, 47.8, 32.7, 28.2, 16.0; IR (KBr, ν, cm−1) 3387, 3013, 1510, 1406, 1167, 1091, 1012, 918, 832, 722; HRMS (APCI-TOF) m/z calcd for C29H24NO [M-H]− 402.1858; found 402.1874.
1-(4-(tert-butyl)phenyl)-1-(1-methyl-1H-indol-3-yl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3j)
White solid, 104 mg, 80% yield; mp 178-180°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.19 (s, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.35 (m, 7H), 7.07 (m, 1H), 6.93-6.78 (m, 4H), 3.81 (m, 2H), 3.68 (s, 3H), 1.25 (s, 9H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.7, 148.5, 143.0, 140.3, 137.7, 137.1, 130.1, 128.0, 127.4, 127.2, 126.8, 125.3, 125.2, 124.3, 123.8, 122.5, 121.5, 120.2, 119.0, 118.9, 110.3, 104.9, 54.0, 47.7, 34.5, 32.7, 31.6; IR (KBr, ν, cm−1) 3402, 3010, 1512, 1423, 1177, 1093, 1018, 933, 814, 711; HRMS (APCI-TOF) m/z calcd for C31H28NO [M-H]− 430.2171; found 430.2187.
1-(1-methyl-1H-indol-3-yl)-1-(naphthalen-1-yl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3k)
White solid, 98 mg, 77% yield; mp 162-164°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.25 (s, 1H), 8.27 (d, J = 8.0 Hz, 1H), 7.89-7.81 (m, 3H), 7.71 (d, J = 7.2 Hz, 1H), 7.57 (m, 2H), 7.47-7.34 (m, 5H), 7.08 (m, 1H), 6.95 (s, 1H), 6.91 (d, J = 6.0 Hz, 2H), 6.81 (m, 1H), 3.93 (s, 2H), 3.69 (m, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.9, 143.7, 140.4, 137.8, 137.1, 133.3, 132.1, 130.1, 128.2, 128.1, 127.8, 127.5, 126.9, 126.6, 126.5, 126.0, 125.3, 125.2, 124.4, 123.9, 122.3, 121.5, 120.1, 119.0, 118.6, 110.4, 105.1, 54.5, 47.5, 32.7; IR (KBr, ν, cm−1) 3422, 3014, 1510, 1413, 1171, 1088, 1015, 937, 825, 727; HRMS (APCI-TOF) m/z calcd for C31H22NO [M-H]− 424.1702; found 424.1713.
1-(1-methyl-1H-indol-3-yl)-1-(thiophen-2-yl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3l)
White solid, 104 mg, 91% yield; mp 158-160°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.26 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.48 (m, 1H), 7.43-7.36 (m, 2H), 7.31 (d, J = 4.8 Hz, 1H), 7.12 (m, 2H), 6.99 (d, J = 5.6 Hz, 2H), 6.92 (m, 2H), 6.85 (s, 1H), 3.98 (d, J = 13.6 Hz, 1H), 3.77 (d, J = 13.6 Hz, 1H), 3.69 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 155.0, 151.2, 140.1, 137.6, 136.8, 129.5, 127.5, 126.9, 126.6, 125.3, 124.6, 124.5, 124.4, 124.0, 122.4, 121.6, 120.2, 119.1, 119.0, 110.4, 105.0, 50.9, 48.9, 32.7; IR (KBr, ν, cm−1) 3427, 3050, 1517, 1421, 1178, 1068, 1020, 936, 821, 734; HRMS (APCI-TOF) m/z calcd for C25H18NOS [M-H]− 380.1110; found 380.1108.
6-methoxy-1-(1-methyl-1H-indol-3-yl)-1-phenyl-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3m)
White solid, 110 mg, 90% yield; mp 172-174°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.11 (s, 1H), 7.58 (d, J = 2.4 Hz, 1H), 7.43 (d, J = 8.8 Hz, 1H), 7.37 (m, 3H), 7.29 (m, 2H), 7.20 (m, 1H), 7.11-7.05 (m, 2H), 6.88-6.79 (m, 4H), 3.87 (d, J = 13.2 Hz, 1H), 3.84 (s, 3H), 3.76 (d, J = 13.6 Hz, 1H), 3.68 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 156.1, 153.7, 146.1, 137.7, 137.3, 137.2, 128.5, 128.1, 127.5, 126.8, 126.4, 126.2, 125.5, 124.0, 121.5, 120.1, 119.6, 118.9, 110.3, 105.4, 103.2, 55.5, 54.3, 47.7, 32.7; IR (KBr, ν, cm−1) 3387, 3045, 1507, 1422, 1172, 1058, 1011, 932, 827, 739; HRMS (APCI-TOF) m/z calcd for C28H22NO2 [M-H]− 404.1651; found 404.1630.
1-(4-chlorophenyl)-6-methoxy-1-(1-methyl-1H-indol-3-yl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3n)
White solid, 121 mg, 92% yield; mp 175-177°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.15 (s, 1H), 7.59 (d, J = 2.4 Hz, 1H), 7.44-7.31 (m, 6H), 7.13-7.05 (m, 2H), 6.94-6.81 (m, 4H), 3.85 (s, 3H), 3.83-3.72 (m, 2H), 3.68 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 156.2, 153.9, 145.1, 137.7, 137.2, 136.7, 131.0, 129.3, 128.5, 128.1, 126.7, 126.3, 125.3, 123.8, 121.6, 120.0, 119.7, 119.1, 118.3, 110.4, 105.4, 103.2, 55.5, 53.7, 47.7, 32.7. IR (KBr, ν, cm−1) 3382, 3025, 1523, 1421, 1192, 1074, 1008, 934, 828, 736. HRMS (APCI-TOF) m/z calcd for C28H21NClO2 [M-H]− 438.1261; found 438.1277.
6-methoxy-1-(1-methyl-1H-indol-3-yl)-1-(p-tolyl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3o)
White solid, 102 mg, 81% yield; mp 170-172°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.09 (s, 1H), 7.59 (d, J = 2.4 Hz, 1H), 7.43 (d, J = 9.2 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.26 (d, J = 8.0 Hz, 2H), 7.07 (m, 4H), 6.89-6.80 (m, 4H), 3.84 (s, 3H), 3.83-3.72 (m, 2H), 3.67 (s, 3H), 2.26 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 156.1, 153.6, 143.1, 137.7, 137.4, 137.3, 135.3, 129.1, 128.0, 127.4, 126.8, 126.2, 125.5, 124.0, 121.5, 120.2, 119.5, 119.1, 118.9, 110.2, 105.4, 103.1, 55.5, 54.0, 47.7, 32.6, 21.1; IR (KBr, ν, cm−1) 3387, 3022, 1521, 1425, 1202, 1094, 1016, 942, 835, 721; HRMS (APCI-TOF) m/z calcd for C29H24NO2 [M-H]− 418.1808; found 418.1822.
7-methyl-1-(1-methyl-1H-indol-3-yl)-1-phenyl-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3p)
White solid, 84 mg, 72% yield; mp 147-149°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.12 (s, 1H), 8.14 (d, J = 8.8 Hz, 1H), 7.38 (m, 3H), 7.32-7.26 (m, 3H), 7.20 (m, 2H), 7.08 (m, 1H), 6.88 (d, J = 4.4 Hz, 2H), 6.86-6.77 (m, 2H), 3.86 (d, J = 13.6 Hz, 1H), 3.73 (d, J = 13.6 Hz, 1H), 3.69 (s, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.8, 146.2, 140.5, 137.7, 136.6, 136.3, 130.4, 128.5, 128.1, 127.5, 126.8, 126.4, 126.0, 124.3, 123.5, 121.5, 121.3, 120.2, 118.9, 118.9, 110.3, 104.2, 54.4, 47.9, 32.7, 22.0; IR (KBr, ν, cm−1) 3507, 3052, 1522, 1420, 1201, 1098, 1015, 944, 841, 727; HRMS (APCI-TOF) m/z calcd for C28H22NO [M-H]− 388.1702; found 388.1727.
1-(4-chlorophenyl)-7-methyl-1-(1-methyl-1H-indol-3-yl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3q)
White solid, 114 mg, 90% yield; mp 152-154°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.16 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 7.40-7.33 (m, 5H), 7.25 (s, 1H), 7.19 (d, J = 8.8 Hz, 1H), 7.09 (m, 1H), 6.94-6.83 (m, 3H), 6.79 (s, 1H), 3.85 (d, J = 13.6 Hz, 1H), 3.73 (s, 1H), 3.70 (s, 3H), 2.33 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.9, 145.2, 140.4, 137.7, 136.7, 135.9, 131.0, 130.2, 129.4, 128.5, 128.2, 126.7, 126.1, 124.4, 123.5, 121.6, 121.1, 120.1, 119.1, 118.3, 110.4, 104.2, 53.7, 47.9, 32.7, 22.0; IR (KBr, ν, cm−1) 3495, 3042, 1520, 1402, 1221, 1084, 1016, 947, 831, 709; HRMS (APCI-TOF) m/z calcd for C28H21ClNO [M-H]− 422.1312; found 422.1314.
7-methyl-1-(1-methyl-1H-indol-3-yl)-1-(p-tolyl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3r)
White solid, 96 mg, 79% yield; mp 153-155°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.10 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 7.26 (d, J = 8.0 Hz, 3H), 7.18 (d, J = 8.8 Hz, 1H), 7.08 (m, 3H), 6.90 (d, J = 8.8 Hz, 2H), 6.83 (m, 1H), 6.79 (s, 1H), 3.88-3.69 (m, 2H), 3.68 (s, 3H), 2.32 (s, 3H), 2.26 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.7, 143.1, 140.4, 137.7, 136.5, 136.5, 135.3, 130.3, 129.1, 128.0, 127.4, 126.9, 126.0, 124.3, 123.4, 121.5, 121.3, 120.3, 119.0, 118.9, 110.3, 104.2, 54.0, 47.9, 32.7, 22.0, 21.1; IR (KBr, ν, cm−1) 3490, 3031, 1500, 1422, 1213, 1090, 1012, 948, 843, 719; HRMS (APCI-TOF) m/z calcd for C29H24NO [M-H]− 402.1858; found 402.1844.
7-fluoro-1-(1-methyl-1H-indol-3-yl)-1-phenyl-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3s)
White solid, 96 mg, 81% yield; mp 144-146°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.36 (s, 1H), 7.87 (m, 1H), 7.55 (m, 1H), 7.33 (m, 6H), 7.21 (m, 1H), 7.08 (m, 1H), 6.93 (s, 1H), 6.91-6.77 (m, 3H), 3.84 (m, 2H), 3.68 (s, 3H). 13C NMR (100 MHz, DMSO-d6; δ, ppm) 160.3 (1JCF = 239.4 Hz), 157.9, 154.2, 154.1, 145.8, 139.7 (6JCF = 2.4 Hz), 139.6, 137.7, 137.3, 128.6, 128.1, 127.5, 127.2, 126.8, 126.7 (3JCF = 19.7 Hz), 125.9 (5JCF = 8.1 Hz), 125.8, 125.1 (4JCF = 8.4 Hz), 125.0, 121.5, 120.0, 119.0, 118.6, 117.5, 117.3, 110.3, 108.0 (2JCF = 21.7 Hz), 107.8, 106.0, 54.4, 47.8, 32.7; IR (KBr, ν, cm−1) 3501, 3021, 1502, 1421, 1215, 1099, 1014, 962, 883, 712; HRMS (APCI-TOF) m/z calcd for C27H19FNO [M-H]− 392.1451; found 392.1459.
1-(4-chlorophenyl)-7-fluoro-1-(1-methyl-1H-indol-3-yl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3t)
White solid, 117 mg, 91% yield; mp 149-151°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.44 (s, 1H), 8.30 (m, 1H), 7.41-7.32 (m, 5H), 7.24 (m, 1H), 7.12-7.04 (m, 2H), 6.98 (s, 1H), 6.86 (d, J = 13.2 Hz, 3H), 3.82 (m, 2H), 3.71 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 160.0 (1JCF = 231.6 Hz), 157.1, 155.3, 144.8, 142.4, 137.8, 136.2 (6JCF = 3.4 Hz), 136.1, 131.1, 130.5 (5JCF = 9.6 Hz), 130.4, 129.3, 128.6, 128.2, 127.8 (4JCF = 9.9 Hz), 126.6, 122.4, 121.6, 119.9, 119.2, 117.8, 113.9 (2JCF = 24.1 Hz), 113.6, 110.5, 105.5 (3JCF = 20.3 Hz), 105.3, 104.5, 53.7, 47.7, 32.7; IR (KBr, ν, cm−1) 3512, 3020, 1505, 1411, 1210, 1095, 1010, 966, 861, 740; HRMS (APCI-TOF) m/z calcd for C27H18ClFNO [M-H]− 426.1061; found 426.1066.
6-fluoro-1-(1-methyl-1H-indol-3-yl)-1-phenyl-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3u)
White solid, 97 mg, 82% yield; mp 148-150°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.41 (s, 1H), 8.30 (m, 1H), 7.38 (d, J = 8.8 Hz, 3H), 7.30 (m, 2H), 7.24 (m, 2H), 7.08 (m, 2H), 6.94 (s, 1H), 6.90-6.79 (m, 3H), 3.84 (m, 2H), 3.70 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 162.3 (1JCF = 243.8 Hz), 160.0, 155.1, 145.8, 142.4, 137.8, 136.7 (6JCF = 5.1 Hz), 130.7 (5JCF = 9.3 Hz), 130.6, 128.6, 128.1, 127.8, 127.7 (4JCF = 9.6 Hz), 127.4, 126.7, 126.6, 122.4, 121.5, 120.0, 119.0, 118.4, 113.8 (2JCF = 24.8 Hz), 113.5, 110.4, 105.7 (3JCF = 20.1 Hz), 105.5, 104.6, 54.3, 47.7, 32.7; IR (KBr, ν, cm−1) 3502, 3047, 1502, 1422, 1235, 1099, 1015, 946, 851, 733; HRMS (APCI-TOF) m/z calcd for C27H19FNO [M-H]− 392.1451; found 392.1450.
8-(1-methyl-1H-indol-3-yl)-8-(p-tolyl)-7,8-dihydrocyclobuta[h]quinolin-5-ol (3v)
White solid, 80 mg, 68% yield; mp 162-164°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.56 (s, 1H), 8.88 (m, 1H), 8.60 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7.41 (dd, J = 8.4, 4.2 Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.07 (d, J = 8.0 Hz, 3H), 7.01 (s, 1H), 6.90 (s, 1H), 6.85 (m, 1H), 3.91 (m, 2H), 3.64 (s, 3H), 2.23 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 155.0, 151.2, 145.1, 143.9, 137.5, 137.1, 135.0, 132.7, 128.8, 128.3, 128.1, 126.5, 121.3, 120.4, 120.3, 120.1, 119.3, 118.8, 110.1, 105.3, 55.2, 46.1, 32.6, 21.1; IR (KBr, ν, cm−1) 3545, 3067, 1552, 1421, 1230, 1129, 1012, 949, 840, 730; HRMS (APCI-TOF) m/z calcd for C27H21N2O [M-H]− 389.1654; found 389.1657.
1-(4-chlorophenyl)-1-(5-methoxy-1-methyl-1H-indol-3-yl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3w)
White solid, 121 mg, 92% yield; mp 166-168°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.27 (s, 1H), 8.27 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.44-7.33 (m, 6H), 7.27 (d, J = 8.8 Hz, 1H), 6.88 (d, J = 10.8 Hz, 2H), 6.74 (m, 1H), 6.24 (d, J = 2.0 Hz, 1H), 3.81 (m, 2H), 3.64 (s, 3H), 3.49 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 155.0, 153.3, 145.0, 140.5, 136.5, 133.1, 131.1, 130.0, 129.4, 128.7, 128.5, 127.6, 127.0, 125.3, 124.4, 124.0, 122.2, 117.6, 111.0, 110.9, 104.8, 102.4, 55.5, 53.8, 47.7, 32.8; IR (KBr, ν, cm−1) 3504, 2997, 1534, 1401, 1233, 1149, 1010, 942, 847, 736; HRMS (APCI-TOF) m/z calcd for C28H21NClO2 [M-H]− 438.1261; found 438.1267.
1-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(p-tolyl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3x)
White solid, 107 mg, 85% yield; mp 170-172°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.21 (s, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.43-7.33 (m, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.8 Hz, 1H), 7.11 (d, J = 7.6 Hz, 2H), 6.88 (s, 1H), 6.82 (s, 1H), 6.72 (m, 1H), 6.22 (d, J = 2.0 Hz, 1H), 3.79 (m, 2H), 3.63 (s, 3H), 3.47 (s, 3H), 2.27 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.8, 153.1, 143.0, 140.5, 137.1, 135.3, 133.1, 130.2, 129.1, 128.6, 127.5, 127.4, 127.1, 125.2, 124.4, 123.8, 122.4, 118.4, 110.8, 110.7, 104.9, 102.6, 55.5, 54.1, 47.7, 32.8, 21.1; IR (KBr, ν, cm−1) 3487, 3022, 1520, 1422, 1200, 1097, 1012, 944, 833, 725; HRMS (APCI-TOF) m/z calcd for C29H24NO2 [M-H]− 418.1808; found 418.1838.
1-(7-chloro-1-methyl-1H-indol-3-yl)-1-(p-tolyl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3y)
White solid, 113 mg, 89% yield; mp 163-165°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.24 (s, 1H), 8.24 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 7.6 Hz, 1H), 7.38 (m, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.4 Hz, 2H), 6.93 (s, 1H), 6.88-6.76 (m, 4H), 3.99 (s, 3H), 3.78 (s, 2H), 2.24 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.8, 142.5, 140.2, 136.9, 135.5, 132.6, 131.2, 130.2, 129.9, 129.2, 127.4, 127.3, 125.2, 124.4, 123.9, 123.0, 122.2, 120.1, 119.6, 119.3, 116.5, 104.9, 53.6, 47.6, 36.5, 21.0; IR (KBr, ν, cm−1) 3505, 3022, 1524, 1400, 1209, 1082, 1012, 945, 833, 719; HRMS (APCI-TOF) m/z calcd for C28H21ClNO [M-H]− 422.1312; found 422.1304.
1-(1,7-dimethyl-1H-indol-3-yl)-1-(p-tolyl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3z)
White solid, 93 mg, 77% yield; mp 165-167°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.17 (s, 1H), 8.23 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.37 (m, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 6.85 (s, 1H), 6.79-6.64 (m, 4H), 3.93 (s, 3H), 3.77 (s, 2H), 2.68 (s, 3H), 2.25 (s, 3H). 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.6, 143.0, 140.3, 137.4, 136.3, 135.3, 129.9, 129.6, 129.1, 128.0, 127.3, 125.2, 124.3, 124.0, 123.8, 122.4, 121.8, 119.1, 118.5, 118.4(5), 118.3(9), 105.0, 53.8, 47.6, 36.6, 21.1, 19.7; IR (KBr, ν, cm−1) 3468, 3056, 1480, 1424, 1203, 1095, 1010, 958, 844, 722; HRMS (APCI-TOF) m/z calcd for C29H24NO [M-H]− 402.1858; found 402.1844.
1-(6-methoxy-1-methyl-1H-indol-3-yl)-1-(p-tolyl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3aa)
White solid, 96 mg, 76% yield; mp 171-173°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.18 (s, 1H), 8.23 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.41-7.32 (m, 2H), 7.26 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 2.0 Hz, 1H), 6.85 (s, 1H), 6.70 (d, J = 10.4 Hz, 2H), 6.48 (m, 1H), 3.81 (m, 2H), 3.75 (s, 3H), 3.63 (s, 3H), 2.26 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 156.0, 154.6, 143.1, 140.3, 138.5, 137.3, 135.3, 130.0, 129.1, 127.4, 127.3, 126.8, 125.2, 124.3, 123.8, 122.4, 121.1, 120.7, 119.1, 109.0, 105.0, 93.6, 55.7, 54.0, 47.8, 32.7, 21.1; IR (KBr, ν, cm−1) 3487, 3020, 1521, 1420, 1212, 1091, 1011, 944, 836, 729; HRMS (APCI-TOF) m/z calcd for C29H24NO2 [M-H]− 418.1808; found 418.1822.
1-(5-bromo-1-methyl-1H-indol-3-yl)-1-(p-tolyl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3bb)
White solid, 121 mg, 76% yield; mp 175-177°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.22 (s, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.40 (m, 3H), 7.25 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.0 Hz, 1H), 7.10 (d, J = 8.0 Hz, 2H), 6.95 (s, 1H), 6.93 (s, 1H), 6.86 (s, 1H), 3.84-3.74 (m, 2H), 3.69 (s, 3H), 2.27 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.8, 142.5, 140.3, 136.8, 136.5, 135.5, 129.9, 129.6, 129.2, 128.4, 127.5, 127.3, 125.2, 124.4, 124.0, 122.2, 118.8, 112.6, 111.6, 104.9, 53.7, 47.8, 32.9, 21.1; IR (KBr, ν, cm−1) 3531, 3050, 1522, 1404, 1242, 1121, 1017, 945, 836, 720; HRMS (APCI-TOF) m/z calcd for C28H21BrNO [M-H]− 466.0807; found 466.0815.
1-(1H-indol-3-yl)-1-(p-tolyl)-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3cc)
White solid, 88 mg, 78% yield; mp 156-158°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.86 (s, 1H), 10.20 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.38 (m, 3H), 7.27 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 7.02 (m, 1H), 6.96-6.88 (m, 3H), 6.81 (m, 1H), 3.82 (m, 2H), 2.25 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.6, 143.2, 140.3, 137.4, 137.4, 135.3, 130.0, 129.1, 127.4, 127.3, 126.6, 125.2, 124.4, 123.8, 123.7, 122.4, 122.0, 121.3, 120.0, 119.7, 118.8, 112.1, 105.0, 54.1, 47.6, 21.1; IR (KBr, ν, cm−1) 3501, 3408, 3051, 1520, 1402, 1240, 1118, 1010, 943, 816, 723; HRMS (APCI-TOF) m/z calcd for C27H20NO [M-H]− 374.1545; found 374.1529.
1-(6-methyl-1H-indol-3-yl)-1-phenyl-1,2-dihydrocyclobuta[a]naphthalen-4-ol (3dd)
White solid, 91 mg, 81% yield; mp 172-174°C; 1H NMR (400 MHz, DMSO-d6; δ, ppm) 10.72 (s, 1H), 10.18 (s, 1H), 8.25 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.44-7.34 (m, 4H), 7.26 (m, 3H), 7.18 (m, 1H), 6.86 (d, J = 6.8 Hz, 3H), 6.79 (s, 1H), 3.83 (s, 2H), 2.22 (s, 3H); 13C NMR (100 MHz, DMSO-d6; δ, ppm) 154.6, 146.2, 140.4, 137.5, 135.7, 129.9, 128.5, 127.3, 127.1, 126.9, 126.3, 125.2, 124.4, 123.8, 123.0, 122.4, 119.6, 119.0, 111.9, 105.0, 54.2, 47.5, 21.9; IR (KBr, ν, cm−1) 3518, 3401, 3050, 1570, 1392, 1242, 1110, 1023, 941, 826, 721; HRMS (APCI-TOF) m/z calcd for C27H20NO [M-H]− 374.1545; found 374.1553.
X-Ray Structure of Product 3a (CCDC 1867087)
The crystal of compound 3a belongs to Triclinic, space group P-1 with a = 8.5599(7) Å, b = 12.1512(11) Å, c = 12.5112(12) Å, α = 100.943(2)°, β = 94.2510(10)°, γ = 106.823(3)°, V = 1211.40(19) Å3, Mr = 433.53, Z = 2, Dc = 1.743 g/cm3, μ(MoKα) = 0.074 mm−1, F(000) = 460, the final R = 0.0495 and wR = 0.1118.
Statements
Author contributions
HL, BJ, and GL designed the project. HL performed the experiments. HL, W-JH, and S-JT analyzed the data. HL, BJ, and GL wrote the manuscript.
Funding
We are grateful for financial support from the NSFC (Nos. 21332005, 21472071 and 21871112), the Outstanding Youth Fund of JSNU (YQ2015003) and Robert A. Welch Foundation (D-1361, USA).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fchem.2018.00599/full#supplementary-material
References
1
AidhenI. S.AhujaJ. R. (1992). A novel synthesis of benzocyclobutenones. Tetrahedron Lett.33, 5431–5432. 10.1016/S0040-4039(00)79113-1
2
AnastasP. T.WarnerJ. C. (1998). Green Chemistry: Theory and Practice. New York, NY: Oxford Science Publications.
3
AndersenN. G.MaddafordS. P.KeayB. A. (1996). Synthesis of functionalized naphthalenes from substituted 1-methoxybenzocyclobutenes. J. Org. Chem.61, 2885–2887. 10.1021/jo951978v
4
BanertK.PlefkaO. (2011). Synthesis with perfect atom economy: Generation of diazo ketones by 1,3-dipolar cycloaddition of nitrous oxide at cyclic alkynes under mild conditions. Angew. Chem. Int. Ed. 50, 6171–6174. 10.1002/anie.201101326
5
BarluengaJ.RodriguezF.FananasF. J. (2009). Recent advances in the synthesis of indole and quinoline derivatives through cascade reactions. Chem. Asian J.4, 1036–1048. 10.1002/asia.200900018
6
BeakP.SellingG. W. (1989). Displacements at the nitrogen of lithioalkoxylamides by organometallic reagents. J. Org. Chem.54, 5574–5580. 10.1021/jo00284a034
7
BihaniM.BoraP. P.BezG.AskariH. (2013). Amberlyst A21 catalyzed chromatography-free method for multicomponent synthesis of dihydropyrano [2,3-c] pyrazoles in ethanol. ACS Sustainable Chem. Eng.1, 440–447. 10.1021/sc300173z
8
BilyardK. G.GarrattP. J.UnderwoodA. J.ZahlerR. (1979). Vicinal diester dianions. Annelation with allylic and benzylic αω-dihalides. Synthesis of tricyclobuta[1,2:3,4:6,7]naphthalene. Tetrahedron Lett.20, 1815–1818. 10.1016/S0040-4039(01)86226-2
9
BirchA. J.BrownJ. M.StansfieldF. (1964). Reactions of cyclohexadienes. IV. Some transformations of bisdihalocarbene adducts. J. Chem. Soc.5343–5348. 10.1039/jr9640005343
10
BradsherC. K.HuntD. A. (1981). Novel synthesis of benzo[1,2:4,5]dicyclobutene via a dual Parham cyclialkylation. J. Org. Chem.46, 4608–4610. 10.1021/jo00335a072
11
BrauchS.Van BerkelS.-S.WestermannB. (2013). Higher-order multicomponent reactions: beyond four reactants. Chem. Soc. Rev.42, 4948–4962. 10.1039/c3cs35505e
12
BruckmannA.KrebsA.BolmC. (2008). Organocatalytic reactions. Effects of ball milling, microwave and ultrasound irradiation. Green Chem.10, 1131–1141. 10.1039/b812536h
13
BuchwaldS. L.LucasE. A.DewanJ. C. (1987a). Synthesis, structure, and reactions of a zirconocene-benzdiyne complex. J. Am. Chem, Soc. 109, 4396–4397. 10.1021/ja00248a046
14
BuchwaldS. L.WatsonB. T.LumR. T.NugentW. A. (1987b). A general method for the preparation of zirconocene complexes of substituted benzynes: in situ generation, coupling reactions, and use in the synthesis of polyfunctionalized aromatic compounds. J. Am. Chem. Soc. 109, 7137–7141. 10.1021/ja00257a038
15
BucklandS. J.HaltonB.MeiQ.StangP. J. (1987). Studies in the cycloproparene series: reactions of alkylidenecycloproparenes with electrophiles. Aust. J. Chem.40, 1375–1387. 10.1071/CH9871375
16
BunnettJ. F.SkorczJ. A. (1962). Homocyclic ring closures via benzyne intermediates. A new synthesis of 1-substituted benzocyclobutenes. J. Org. Chem.27, 3836–3843. 10.1021/jo01058a019
17
CavaM. P.NapierD. R. (1956). Benzocyclobutene and benzocyclobutadiene dimer. J. Am. Chem. Soc.78:500. 10.1021/ja01583a071
18
ChenK.LiuS.WangD.HaoW.-J.ZhouP.TuS.-J.et al. (2017). Silver/scandium-cocatalyzed bicyclization of β-Alkynyl ketones leading to benzo[c]xanthenes and naphtho[1,2-b]benzofurans. J. Org. Chem.82, 11524–11530. 10.1021/acs.joc.7b02134
19
ChouC.-H.WuC.-C.ChenW.-K. (1995). Synthesis of Pyrido[b]cyclobuten-5-one and 1-azafulvenallene by flash vacuum pyrolysis of 3-chloroformyl-2-methylpyridine. Tetrahedron Lett.36:5065. 10.1016/0040-4039(95)00940-E
20
ChristopheS.Kuehm-CaubereC.RenardP.PfeifferB.CaubereP. (1998). Design of new anticancer drugs. II. Easy arynic access to benzocyclobutacarbazoles, a new family of antitumor agents. Tetrahedron Lett.39, 7284–7286. 10.1016/S0040-4039(98)02186-8
21
CraigD.RobsonM. J.ShawS. J. (1998). Traceless linkers for solid-phase synthesis. Homo-and hetero-Diels-Alder reactions of o-quinodimethanes. Synlett1998, 1381–1383. 10.1055/s-1998-1968
22
D'AndreaS. V.FreemanJ. P.SzmuszkoviczJ. (1990). Diels-Alder cycloaddition reactions of isobenzofuran and o-quinodimethane with 1, 2-diheteroethylenes. J. Org. Chem.55, 4356–4358. 10.1021/jo00301a028
23
DömlingA.WangW.WangK. (2012). Chemistry and biology of multicomponent reactions. Chem. Rev.112, 3083–3135. 10.1021/cr100233r
24
EzcurraJ. E.MooreH. W. (1993). Synthesis of o-quinodimethanes and benzocyclobutenes from dimethyl squarate. Tetrahedron Lett.34, 6177–6180. 10.1016/S0040-4039(00)73703-8
25
FuerstnerA. (2009). Gold and platinum catalysis-a convenient tool for generating molecular complexity. Chem. Soc. Rev.38, 3208–3221. 10.1039/b816696j
26
FunkR. L.VollhardtK. P. C. (1977). A cobalt-catalyzed steroid synthesis. J. Am. Chem. Soc.99, 5483–5484. 10.1021/ja00458a044
27
FunkR. L.VollhardtK. P. C. (1979). The cobalt way to dl-estrone, a highly regiospecific functionalization of 2, 3-bis (trimethylsilyl) estratrien-17-one. J. Am. Chem. Soc.101, 215–217. 10.1021/ja00495a035
28
FunkR. L.VollhardtK. P. C. (1980). Cooligomerizations of 3-substituted 1, 5-hexadiynes with bis(trimethylsilyl)acetylene catalyzed by cobalt. A general synthesis of tricyclic ring systems from acyclic precursors. J. Am. Chem. Soc.102, 5245–5253. 10.1021/ja00536a022
29
GarrattP. J.NicolaidesD. N. (1972). 3-Thiabicyclo[3.2.0]hepta-1, 4-diene. J. Chem. Soc. Chem. Commun. 1014–1015. 10.1039/c39720001014
30
GarrattP. J.NicolaidesD. N. (1974). Synthesis and some reactions of 3-thiabicyclo [3.2.0] hepta-1, 4-diene. Case for revival of the Mills-Nixon effect. J. Org. Chem.39, 2222–2224. 10.1021/jo00929a018
31
GowlandB. D.DurstT. (1979). Benzocyclobutyl phenyl sulfone. An evaluation of its potential as a precursor to substituted benzocyclobutenes and ortho-quinodimethanes. Can. J. Chem. 57, 1462–1467. 10.1139/v79-239
32
GrayR.HarruffL. G.KrymowskiJ.PetersonJ.BoekelheideV. (1978). Syntheses of benzo[1,2:4,5]dicyclobutene derivatives. J. Am. Chem. Soc.100, 2892–2893. 10.1021/ja00477a054
33
GriecoP. A.TakigawaT.SchillingerW. J. (1980). Bicyclo[2.2.1]heptanes as intermediates in the synthesis of steroids. Total synthesis of estrone. J. Org. Chem.45, 2247–2251. 10.1021/jo01299a042
34
HaibachM. C.DebI.DeC. K.SeidelD. (2011). Redox-neutral indole annulation cascades. J. Am. Chem. Soc.133, 2100–2103. 10.1021/ja110713k
35
HickmanD. N.WallaceT. W.WardleworthJ. M. (1991). The preparation of α-tetralones from benzocyclobutenones via sequential thermal electrocyclic reactions. Tetrahedron Lett.32, 819–822. 10.1016/S0040-4039(00)74896-9
36
HoffmannN.PeteJ.-P. (1996). Acid catalyzed intramolecular photochemical reactions of 3-alkenyloxyphenols. Tetrahedron Lett.37, 2027–2030. 10.1016/0040-4039(96)00190-6
37
HuangM.-H.HaoW.-J.JiangB. (2018a). Radical enabled bicyclization and annulation with 1,n-bifunctionalization: recent advances. Chem. Asian J.13, 2958–2977. 10.1002/asia.201801119
38
HuangM.-H.HaoW.-J.LiG.TuS.-J.JiangB. (2018b). Recent advances in radical transformations of internal alkynes. Chem. Commun.54, 10791–10811. 10.1039/C8CC04618B
39
HuangM.-H.ZhuY.-L.HaoW.-J.WangA.-F.WangD.-C.LiuF.et al. (2017). Visible-light photocatalytic bicyclization of 1,7-enynes toward functionalized sulfone-containing benzo[a]fluoren-5-ones. Adv. Synth. Catal.359, 2229–2234. 10.1002/adsc.201700124
40
InanagaJ.SugimotoY.HanamotoT. (1992). A novel method for the generation of 2, 3-naphthoquinodimethanes utilizing samarium (II) iodide-promoted allene synthesis. Tetrahedron Lett.33, 7035–7038. 10.1016/S0040-4039(00)60926-7
41
IskanderG. M.StansfieldF. (1965). 4-Hydroxybenzocyclobuten-I-one and its derivatives. J. Chem. Soc. 1390–1392. 10.1039/jr9650001390
42
JiaS.SuS.LiC.JiaX.LiJ. (2014). Multicomponent cascade cycloaddition involving tropone, allenoate, and isocyanide: a rapid access to a 7, 6, 5-fused tricyclic skeleton. Org. Lett.16, 5604–5607. 10.1021/ol502656g
43
JiangB.RajaleT.WeverW.TuS.-J.LiG. (2010). Multicomponent reactions for the synthesis of heterocycles. Chem. Asian J.5, 2318–2335. 10.1002/asia.201000310
44
JonesA. C.MayJ. A.SarpongR.StoltzB. M. (2010). Toward a symphony of reactivity: cascades involving catalysis and sigmatropic rearrangements. Angew. Chem. Int. Ed.53, 2556–2591. 10.1002/anie.201302572
45
KagabuS.SaitoK. (1988). Dihalocarbene addition to benzocyclopropene. Tetrahedron Lett.29, 675–676. 10.1016/S0040-4039(00)80181-1
46
KanaoY.IyodaM.OdaM. (1983). The effect of cyclobutene ring annulation on p-benzoquinone: synthesis and properties of 1,2,3,4,5,6-hexahydrobenzo[1,2:4,5]dicyclobutene-3,6-dione([2,3:5,6]dicyclobuta-p-benzoquinone). Tetrahedron Lett.24, 1727–1730. 10.1016/S0040-4039(00)81755-4
47
KanekoC.NaitoT. (1979). Intermolecular photochemical cycloaddition of 4-methoxy-2-quinolone with olefins: a regioselective synthesis of 5-substituted cyclobuta[c]-2-quinolones. Chem. Pharm. Bull.27, 2254–2256. 10.1248/cpb.27.2254
48
KanekoC.NaitoT.MomoseY.FujiiH.NakayamaN.KoizumiI. (1982). Cycloadditions in syntheses. VIII. Synthesis of 1,2-dihydrocyclobuta[c]-pyridine and-quinoline and their 3-substituted derivatives. Chem. Pharm. Bull. 30, 519–525. 10.1248/cpb.30.519
49
KoopmanschapG.RuijterE.OrruR. V. A. (2014). Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics. J. Org. Chem.10, 544–598. 10.3762/bjoc.10.50
50
KothaS.GoyalD.ChavanA. S. (2013). Diversity-oriented approaches to unusual α-amino acids and peptides: step economy, atom economy, redox economy, and beyond. J. Org. Chem. 78, 12288–12313. 10.1021/jo4020722
51
KrohnK.CarbooD.PuttfarckerU. (1978). 1-Phenyl-1,2-dihydrobenzazetes from N-phenylbenzylamines by aryne cyclization. Liebigs Ann. Chem.1978, 608–616. 10.1002/jlac.197819780411
52
LenihanB. D.ShechterH. (1994). Substituted o-[(Trimethylsilyl) methyl] benzyl p-tolyl sulfones: practical reagents for preparing cycloadducts of o-quinodimethanes. Tetrahedron Lett.35, 7505–7508. 10.1016/S0040-4039(00)78329-8
53
LenihanB. D.ShechterH. (1998). Chemistry of Conversions of [o-[1-Halo-1-(p-tolylsulfonyl)alkyl]benzyl]trimethylsilanes to o-Quinodimethanes and Benzocyclobutenes. J. Org. Chem.63, 2086–2093. 10.1021/jo9705935
54
LiH.HaoW.-J.WangM.QinX.TuS.-J.ZhouP.et al. (2018a). Catalytic double [2 + 2] cycloaddition relay enabled C–C triple bond cleavage of Yne–Allenones. Org. Lett.20, 4362–4366. 10.1021/acs.orglett.8b01841
55
LiH.ZhouP.XieF.HuJ.-Q.YangS.-Z.WangY.-J.et al. (2018b). I2-Mediated iodobenzannulation of yne-allenones toward 1-naphthols and their synthetic application. J. Org. Chem.83, 13335–13343. 10.1021/acs.joc.8b02108
56
LiX.LiH.SongW.TsengP.-S.LiuL.GuzeiI. A.et al. (2015). Divergent reactivity of rhodium (I) carbenes derived from indole annulations. Angew. Chem. Int. Ed.54, 12905–12908. 10.1002/anie.201505329
57
LiuC.ZhouL.HuangW.WangM.GuY. (2016). Synthesis of dihydrocarbazoles via (4 + 2) annulation of donor-acceptor cyclopropanes to indoles. Tetrahedron72, 563–570. 10.1016/j.tet.2015.12.023
58
LiuF.WangJ.-Y.ZhouP.LiG.HaoW.-J.TuS.-J.et al. (2017a). Merging [2 + 2] cycloaddition with radical 1,4-addition: metal-free access to functionalized cyclobuta[a]naphthalen-4-ols. Angew. Chem. Int. Ed.56, 15570–15574. 10.1002/anie.201707615
59
LiuS.ChenK.LanX.-C.HaoW.-J.LiG.TuS.-J.et al. (2017b). Synergistic silver/scandium catalysis for divergent synthesis of skeletally diverse chromene derivatives. Chem. Commun.53, 10692–10695. 10.1039/C7CC05563C
60
LiuS.LanX.-C.ChenK.HaoW.-J.LiG.TuS.-J.et al. (2017c). Ag/Brønsted Acid Co-Catalyzed Spiroketalization of β-Alkynyl Ketones toward Spiro [chromane-2, 1′-isochromene] Derivatives. Org. Lett.19, 3831–3834. 10.1021/acs.orglett.7b01705
61
MarkgrafJ. H.KattR. J.ScottW. L.ShefrinR. N. (1969). Strained heterocyclic systems. IV. 1, 2-Dihydrocyclobuta [b] quinoline and derivatives. J. Org. Chem.34, 4131–4133. 10.1021/jo01264a081
62
MartinsM. A. P.FrizzoC. P.MoreiraD. N.BuriolL.MachadoP. (2009). Solvent-free heterocyclic synthesis. Chem. Rev.109, 4140–4182. 10.1021/cr9001098
63
McNicholsA. T.StangP. J. (1992). An improved synthesis of cyclopropa[4,5]benzocyclobutene. Synlett1992, 971–972. 10.1055/s-1992-21549
64
MehtaG.KothaS. (2001). Recent chemistry of benzocyclobutenes. Tetrahedron57, 625–659. 10.1016/S0040-4020(00)00958-3
65
MichellysP.-Y.MaurinP.ToupetL.PellissierH.SantelliM. (2001). A very short synthesis of steroids from 1, 3-butadiene and benzocyclobutenes. J. Org. Chem.66, 115–122. 10.1021/jo001106f
66
MüllerP.BernardinelliG.JacquierY.RiccaA. (1989). Tricarbonyl-chromium complexes of benzannelated cycloproparenes. Helv. Chim. Acta72, 1618–1626. 10.1002/hlca.19890720722
67
NeckersD. C.WagenaarF. L. (1981). Synthesis of 3, 4-benzo-2-thiabicyclo[3.2.0]hepta-1,3-diene. J. Org. Chem.46, 3939–3940. 10.1021/jo00332a046
68
NemotoH.SatohA.FukumotoK.KabutoC. (1995). A rapid access to both enantiomers of 1,2,3,4-tetranor B-trienic 18,18,18-trifluorosteroids. The first enantiocontrolled total synthesis of 18,18,18-trifluorosteroids. J. Org. Chem.60, 594–600. 10.1021/jo00108a022
69
OzakiK.MatsuokaW.ItoH.ItamiK. (2017). Annulative π-extension (APEX) of heteroarenes with dibenzosiloles and dibenzogermoles by palladium/o-chloranil catalysis. Org. Lett.19, 1930–1933. 10.1021/acs.orglett.7b00684
70
ParhamW. E.JonesL. D.SayedY. A. (1976). Selective halogen-lithium exchange in bromophenylalkyl halides. J. Org. Chem.41, 1184–1186. 10.1021/jo00869a022
71
PeterK.VollhardtC. (1977). Transition-metal-catalyzed acetylene cyclizations in organic synthesis. Acc. Chem. Res.10, 1–8. 10.1021/ar50109a001
72
PeterK.VollhardtC. (1984). Cobalt-mediated [2 + 2 + 2]-cycloadditions: a maturing synthetic strategy [new synthetic methods (43)]. Angew. Chem. Int. Ed.23, 539–556. 10.1002/anie.198405393
73
RotsteinB.-H.ZaretskyS.RaiV.YudinA.-K. (2014). Small heterocycles in multicomponent reactions. Chem. Rev.114, 8323–9359. 10.1021/cr400615v
74
SadanaA. K.SainiR. K.BillupsW. E. (2003). Cyclobutarenes and related compounds. Chem. Rev.103, 1539–1602. 10.1021/cr010022j
75
SatoM.SuzukiT.MorisawaH.FujitaS.InukaiN.KanekoC. (1987). Cycloadditions in syntheses. XXXV. 2-Cyano-1,2-dihydrocyclobuta[a]naphthalene and Its derivatives: synthesis and reaction with olefins. Chem. Pharm. Bull.35, 3647–3657. 10.1248/cpb.35.3647
76
SchirchP. F. T.BoekelheideV.CyclophaneM. (1979). J. Am. Chem. Soc. 101, 3125–3126. 10.1021/ja00505a052
77
SekineY.BrownM.BoekelheideV. (1979). [2.2.2.2.2.2](1,2,3,4,5,6) Cyclophane: superphane. J. Am. Chem. Soc.101, 3126–3127. 10.1021/ja00505a053
78
ShaH.-K.LiuF.LuJ.LiuZ.-Q.HaoW.-J.TangJ.-L.et al. (2018a). Metal-free benzannulation of yne-allenone esters for atom-economic synthesis of functionalized 1-naphthols. Green Chem.20, 3476–348510.1039/C8GC01034J
79
ShaH.-K.XuT.LiuF.TangB.-Z.HaoW.-J.TuS.-J.et al. (2018b). Metal-free naphthannulation reactions of yne-allenone esters for accessing polycyclic aromatic hydrocarbons. Chem. Commun.54, 10415–10418. 10.1039/C8CC05018J
80
ShimadaS.OsodaK.NarasakaK. (1993). Boron compound as a trapping reagent of α-hydroxy o-quinodimethanes in the diels–alder reaction. Bull. Chem. Soc. Jpn.66, 1254–1257. 10.1246/bcsj.66.1254
81
SuS.LiC.JiaX.LiJ. (2014). Isocyanide-based multicomponent reactions: concise synthesis of spirocyclic oxindoles with molecular complexity by using a [1,5]-hydrogen shift as the key step. Chem. Eur. J.20, 5905–5909. 10.1002/chem.201402576
82
SugimotoK.MatsuyaY. (2017). Recent applications of gold-catalyzed cascade reactions in total synthesis of natural product. Tetrahedron Lett.58, 4420–4426. 10.1016/j.tetlet.2017.10.029
83
TaberD. F.RamanK.GaulM. D. (1987). Enantioselective ring construction: synthesis of (+)-estrone methyl ether. J. Org. Chem.52, 28–34. 10.1021/jo00377a005
84
TianY.TianL.HeX.LiC.-J.JiaX.LiJ. (2015). Indium (III) chloride-catalyzed isocyanide insertion reaction to construct complex spirooxindole. Org. Lett.17, 4874–4877. 10.1021/acs.orglett.5b02432
85
TietzeL. F.KinzelT.BrazelC. C. (2009). The domino multicomponent allylation reaction for the stereoselective synthesis of homoallylic alcohols. Acc. Chem. Res.42, 367–378. 10.1021/ar800170y
86
TodaF.TanakaK.SanoI.IsozakiT. (1994). A new synthetic route to 1, 2-dihydrocyclobutaarenes. Angew. Chem. Int. Ed.33, 1757–1758. 10.1002/anie.199417571
87
TodaM.OkadaK.OdaM. (1988). Synthesis of 3, 4; 7, 8; 9, 10-tribenzobicyclo [4.2.2] deca-1,3,7,9-tetraene: a new strained bridgehead olefin. Tetrahedron Lett.29, 2329–2332. 10.1016/S0040-4039(00)86051-7
88
TrostB. M. (1995). Atom economy - a challenge for organic synthesis: homogeneous catalysis leads the way. Angew. Chem. Int. Ed. 34, 259–281. 10.1002/anie.199502591
89
TrostB. M. (2002). On inventing reactions for atom economy. Acc. Chem. Res. 35, 695–70510.1021/ar010068z
90
TrostB. M.TosteF. D.GreenmanK. (2003). Atom economy. palladium-catalyzed formation of coumarins by addition of phenols and alkynoates via a Net C-H insertion. J. Am. Chem. Soc.125, 4518–4526. 10.1021/ja0286573
91
VlaarT.MaesB.-U.RuijterE.OrruR.-V. (2013). Palladium-catalyzed migratory insertion of isocyanides: an emerging platform in cross-coupling chemistry. Angew. Chem. Int. Ed.52, 7084–7097. 10.1002/anie.201300942
92
WangJ.-Y.XieF.-L.HuJ.-Q.YangS.-Z.WangY.-J.HaoW.-J.et al. (2018). Atom-economic synthesis of cyclobuta[a]naphthalen-4-ols via base-promoted [2 + 2] cycloaddition/1,6-nucleophilic addition cascades. Org. Biomol. Chem.16, 7104–7108. 10.1039/C8OB02042F
93
WangJ.-Y.ZhouP.LiG.HaoW.-J.TuS.-J.JiangB. (2017). Synthesis of functionalized benzo[g]indoles and 1-naphthols via carbon-carbon triple bond breaking/rearranging. Org. Lett.19, 6682–6685. 10.1021/acs.orglett.7b03410
94
WangL.ShiL.-X.LiuL.LiZ.-X.XuT.HaoW.-J.et al. (2017). Synthesis of diastereoenriched oxazolo[5,4-b]indoles via catalyst-free multicomponent bicyclizations. J. Org. Chem.82, 3605–3611. 10.1021/acs.joc.7b00129
95
WangY.LuH.XuP.-F. (2015). Asymmetric catalytic cascade reactions for constructing diverse scaffolds and complex molecules. Acc. Chem. Res. 48, 1832–1844. 10.1021/acs.accounts.5b00217
96
WarrenerR. N.PittI. G.RussellR. A. (1993). Reaction of dienophiles with a 5, 6-bismethylenenorborn-2-en-7-one: the synthesis of a stable norborna-2, 5-dien-7-one. Aust. J. Chem.46, 1009–1019. 10.1071/CH9931009
97
WeiH.ZhaiH.XuP.-F. (2009). Novel platinum-catalyzed tandem reaction: an efficient approach to construct naphtho[1,2-b]furan. J. Org. Chem.74, 2224–2226. 10.1021/jo802645s
98
ZhangC.HooperJ. F.LuptonD. W. (2017). N-heterocyclic carbene catalysis via the α, β-unsaturated acyl azolium. ACS Catal. 7, 2583–2596. 10.1021/acscatal.6b03663
Summary
Keywords
Fe(III)-catalysis, bicyclization, 1,6-addition, yne-allenones, cyclobutarenes
Citation
Li H, Hao W-J, Li G, Tu S-J and Jiang B (2018) Fe(III)-Catalyzed Bicyclization of Yne-Allenones With Indoles for the Atom-Economic Synthesis of 3-Indolyl Cyclobutarenes. Front. Chem. 6:599. doi: 10.3389/fchem.2018.00599
Received
12 September 2018
Accepted
19 November 2018
Published
04 December 2018
Volume
6 - 2018
Edited by
Oliver Reiser, University of Regensburg, Germany
Reviewed by
Federica Valentini, Università di Roma Tor Vergata, Italy; Till Opatz, Johannes Gutenberg University Mainz, Germany
Updates
Copyright
© 2018 Li, Hao, Li, Tu and Jiang.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Guigen Li guigen.li@ttu.eduBo Jiang jiangchem@jsnu.edu.cn
This article was submitted to Green and Sustainable Chemistry, a section of the journal Frontiers in Chemistry
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.