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Article

Lewis-Acid-Catalyzed (3+2) Annulation of 2-Indolylmethanols with Propargylic Alcohols to Access Cyclopenta[b]indoles

by
Teng-Fei Wu
†,
Zhao-Jie Fu
†,
Yi-Rui Zhang
,
Zong-Wang Qiu
,
Bao Qiong Li
*,
Shao-Shuai Chen
,
Han-Peng Pan
,
Ai-Jun Ma
and
Xiang-Zhi Zhang
*
Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Molecules 2024, 29(6), 1251; https://doi.org/10.3390/molecules29061251
Submission received: 31 January 2024 / Revised: 29 February 2024 / Accepted: 4 March 2024 / Published: 12 March 2024
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Abstract

:
Herein, a Sc(OTf)3-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel–Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon. This method provides a direct and high-yield pathway for synthetically useful cyclopenta[b]indoles. In general, the method features easily accessible substrates with broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up.

1. Introduction

Cyclopenta[b]indoles, as privileged heterocyclic skeletons, are present in numerous natural alkaloids and pharmaceuticals possessing a wide range of biological activities [1,2,3,4,5,6,7,8]. Accordingly, bruceollines are traditionally used to treat parasitic diseases and malaria [5,6]. Scytonemin is a small-molecule inhibitor of polo-like kinase and has the potential to inhibit other cell cycle regulators (Figure 1) [8]. Additionally, this type of fused tricyclic structure has been used as an intermediate in pharmaceutical chemistry and in the total synthesis of natural products, such as arborisidine and 19-epi-arborisidine [9]. Owing to their important biological properties, various synthetic protocols have been developed for preparing cyclopenta[b]indoles. Among these protocols, the (3+2) annulation of 2-indolylmethanols and olefins is an atom-economic strategy for the synthesis of these fused indole derivatives [10,11,12,13,14,15,16,17,18]. In recent years, 2-indolylmethanols have become intriguing reactants because of their unique properties of electrophilicity and nucleophilicity at the C3 position [19,20,21,22,23,24,25,26,27,28]. Despite these impressive achievements, a more efficient and diversity-oriented approach for cyclopenta[b]indoles is still required.
Propargylic alcohols have shown promise as feedstocks for the synthesis of carbo- and heterocyclic compounds. Recently, a number of studies have specifically focused on Lewis- or Brønsted-acid-catalyzed tandem annulations of propargylic alcohols to construct diversely structured indole derivatives [29,30,31,32,33,34,35]. However, there have been limited studies on the annulations of propargylic alcohols with 2-indolylmethanols. In 2014, Wang [36] reported a Lewis-acid-catalyzed (3+3) annulation of propargylic alcohols and 2-indolylmethanols, providing an effective approach to obtain polysubstituted carbazole derivatives (Scheme 1a). Recently, our group developed a Brønsted-acid-catalyzed (3+4) annulation of 2-indolylmethanols and propargylic alcohols, providing a convenient method to obtain structurally diverse indole-fused oxepines (Scheme 1b) [37]. However, to the best of our knowledge, no method has been reported for the synthesis of 1,2,3-trisubstituted cyclopenta[b]indoles by formal (3+2) annulation between 2-indolylmethanols and propargylic alcohols. With our continuing research interest in propargylic alcohols [38,39,40,41] and the importance of cyclopenta[b]indoles, herein, we describe a Sc(OTf)3-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols to synthesize cyclopenta[b]indoles (Scheme 1c).

2. Results

Initially, 2-indolylmethanol 1a and propargylic alcohol 2a were selected as the model substrates to explore the reaction conditions in 1,2-dichloroethane (DCE) at 100 °C (Table 1). First, a range of Lewis acids (entries 1–6) were tested. When Zn(OTf)2 was used as the catalyst, the desired cyclopenta[b]indole 3a was isolated in a moderate yield (entry 1, 62%). The fused tricyclic skeleton of product 3a was determined by X-ray crystallographic analysis (CCDC 2,313,081 (3a) contains the supplementary crystallographic data for this paper; for details, see the Supporting Information). Other common triflates, such as Bi(OTf)3, Yb(OTf)3, Cu(OTf)2, and AgNTf2, all promoted the reaction and gave the desired cyclopenta[b]indole product in moderate yields (entries 2–5, 13–70%). Sc(OTf)3 was found to be the best catalyst, and we then further evaluated the effect of the solvent (entries 6–17). Apart from dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) (entries 14 and 15), many common solvents worked well, providing 3a in moderate yields ranging from 41% to 78% (entries 8–16). Pleasingly, toluene improved the efficiency of the reaction (entry 17, 30 min, 80% yield). Increasing the equivalent amount of propargylic alcohol 2a had a positive effect on the reaction yield (entry 18, 87% yield). Decreasing the equivalent amount of the catalyst had a negative effect on the reaction yield (entry 19, 44% yield).
With the optimized conditions in hand, we studied the substrate scope of propargylic alcohols 2. Various propargylic alcohols bearing different aromatic substituents gave the corresponding cyclopenta[b]indoles in good yields (Scheme 2). Both electron-withdrawing (Cl and F) and electron-donating (Me, Et, n-Bu, t-Bu, and MeO) groups were compatible with the reaction, affording the desired products 3a–3h in yields ranging from 68% to 87%. Adjacent steric hindrance is unfavorable for this reaction (2i, 2-FC6H4, 65% yield). Propargylic alcohols with a heteroaryl group (2-thienyl) were also compatible with the reaction, yielding product 3g in an 83% yield. Alkyl-substituted propargyl alcohols 2k and 2l (R1= t-Bu, cyclopropyl) gave the desired products 3k and 3l in a 50% yield. Moreover, propargylic alcohols 2m–2q, which contained the same aromatic groups (R2 = R3), were compatible with the reaction, yielding the corresponding products 3m–3q in moderate-to-good yields (43–80% yield). Propargylic alcohols with different aromatic groups (2r–2u, R2 ≠ R3) provided the E and Z isomers of products 3r–3u (Z:E = 1.1:1 to 1.3:1). Notably, when R2 or R3 was an alkyl group, no products were detected (for details of the examples, see the Supporting Information).
Next, we assessed the substrate scope of 2-indolylmethanols 1 in the (3+2) annulation catalyzed by Sc(OTf)3 (Scheme 3). A series of indolylmethanols (1b–1j) containing electronically diverse groups at different positions of the indole ring served as appropriate reaction partners in the tandem reaction, giving products 4a–4i in moderate-to-good yields (37–93% yield). Moreover, indolylmethanols 1k–1r, bearing electron-donating or electron-withdrawing Ar groups with para-or meta-substitution patterns, acted as suitable substrates, undergoing (3+2) annulation with propargylic alcohol 2a to produce hydrobenzo[b]carbazoles 4j–4q in moderate-to-high yields. Notably, when R was an alkyl group, no product was obtained.
To explore the utility of this methodology, a gram-scale reaction of 3a was carried out, affording the product 3a in an 83% yield (Scheme 4). Treatment of 3a with LiAlH4 produced compound 5 in a 99% yield. Compound 6 was obtained in an 81% yield through the Suzuki coupling reaction of 4c and 9-phenanthrenylboronic acid.
A plausible mechanism for the reaction is proposed in Scheme 5. First, propargylic alcohol 2 is converted to allene carbocation I under Sc(OTf)3 catalysis. This carbocation then undergoes a Friedel–Crafts-type reaction with indolylmethanol 1 to give the allene intermediate II. This intermediate is transformed to benzylic carbocation III. Intermediate III undergoes 5-exo-annulation to give the final cyclopenta[b]indole product.
In conclusion, we have developed a Sc(OTf)3-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols for the synthesis of cyclopenta[b]indoles. A Friedel–Crafts-type allenylation/5-exo-annulation cascade is involved in the reaction. This method provides a direct and high-yield pathway to synthesize useful cyclopenta[b]indoles. In general, this method features easily accessible substrates with a broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up. This work not only confirms that indolylmethanol is a good three-carbon synthon, but it also enriches the chemistry of propargyl alcohol as a two-carbon synthon.

3. Materials and Methods

Unless otherwise noted, all reagents were purchased as commercial grade (Bide, Energy Chemica, Adamas in China) and used without further purification. All products were purified by flash column chromatography using 200–300 mesh silica gel as a stationary phase. NMR spectra were recorded on a Bruker AVANCE III HD 500 device (500 MHz), using CDCl3. Chemical shifts were denoted in ppm (δ) and calibrated by using residual undeuterated solvent CHCl3 (7.27 ppm for 1H NMR, 77.00 ppm for 13C {1H} NMR) with Me4Si (0.00 ppm) as an internal reference. High-resolution mass spectral analysis (HRMS) data were obtained using an Orbitrap instrument equipped with an ESI source. The 2-indolylmethanols and propargylic alcohols 2 were prepared according to the literature-reported procedures [42,43].

3.1. General Procedure for the Synthesis of 3a–4q

Sc(OTf)3 (0.04 mmol, 20 mol%) was added to a solution of 2-indolylmethanols 1 (0.2 mmol, 1.0 equiv) and propargylic alcohol 2 (0.3 mmol, 1.5 equiv) in toluene (2.0 mL) in a glass pressure tube (10 mL). The resulting mixture was stirred vigorously at 100 °C. The solvent was concentrated under reduced pressure, and the resulting residue was purified by flash column chromatography on silica gel eluting with petroleum ether/ethyl acetate, giving the corresponding products 3a–4q.

3.2. Spectroscopic Data for the Products 3a–4q

2-(Diphenylmethylene)-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (3a): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 30 min, red foam solid, 95.0 mg, 87% yield, mp 270–274 °C). 1H NMR (500 MHz, CDCl3) δ 7.64 (d, J = 7.5 Hz, 1H), 7.60–7.54 (m, 2H), 7.49 (d, J = 7.8 Hz, 1H), 7.42–7.34 (m, 4H), 7.29–7.23 (m, 1H), 7.20–7.04 (m, 9H), 7.01 (t, J = 7.3 Hz, 1H), 6.95 (t, J = 7.5 Hz, 1H), 6.88–6.80 (m, 5H), 6.77 (t, J = 7.8 Hz, 2H), 6.57 (d, J = 7.2 Hz, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.4, 162.9, 156.9, 152.2, 148.0, 142.4, 142.02, 141.97, 141.9, 141.8, 135.3, 130.8, 129.7, 129.6, 129.2, 129.0, 128.6, 127.9, 127.6, 127.4, 127.2, 126.7, 126.2, 125.2, 123.8, 123.0, 120.8, 62.3. IR: ῡ = 2921, 2853, 1640, 1400, 1190, 1134, 1077, 756, 686, 626, 467 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H30N: 548.2373; found: 548.2371.
2-(Diphenylmethylene)-1-(4-fluorophenyl)-3,3-diphenyl-2,3-dihydrocyclopenta[b]indole (3b): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 30 min, red foam solid, 85.9 mg, 76% yield). 1H NMR (500 MHz, CDCl3) δ 7.59 (d, J = 7.6 Hz, 1H), 7.57–7.50 (m, 2H), 7.49 (d, J = 7.8 Hz, 1H), 7.41–7.33 (m, 4H), 7.27 (td, J = 7.7, 1.0 Hz, 1H), 7.16–7.05 (m, 6H), 7.01 (t, J = 7.5 Hz, 1H), 6.95 (t, J = 7.4 Hz, 1H), 6.92–6.81 (m, 7H), 6.77 (t, J = 7.7 Hz, 2H), 6.57 (d, J = 8.0 Hz, 2H). 13C NMR (126 MHz, CDCl3) δ 188.3, 188.2, 163.0, 161.8 (d, JC-F = 248.1 Hz), 161.7 (d, JC-F = 247.3 Hz), 156.5, 156.2, 152.6, 152.5, 146.6, 146.5, 142.1, 142.11, 142.09, 141.8, 141.7, 138.5, 138.0, 135.2, 132.5, 132.4, 130.94, 130.87, 130.7, 129.80, 129.77, 129.5, 129.2, 128.9, 128.7, 128.6, 128.0, 127.9, 127.7, 127.6, 127.5, 127.4, 127.3, 126.9, 126.4, 126.2, 125.2, 125.1, 123.8, 123.0, 120.9, 114.3, 114.19, 114.15, 114.0, 62.3. 19F NMR (471 MHz, CDCl3) δ –111.3. IR: ῡ = 2920, 2851, 1646, 1528, 1401, 1188, 1135, 1075, 757, 672, 469 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H29FN: 566.2279; found: 566.2273.
1-(D-chlorophenyl)-2-(diphenylmethylene)-3,3-diphenyl-2,3-dihydrocyclopenta[b]indole (3c): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 30 min, red foam solid, 79.0 mg, 68% yield). 1H NMR (500 MHz, CDCl3) δ 7.64 (d, J = 7.4 Hz, 1H), 7.60–7.53 (m, 2H), 7.48 (d, J = 7.8 Hz, 1H), 7.42–7.34 (m, 4H), 7.30–7.22 (m, 1H), 7.21–7.05 (m, 9H), 7.03–6.99 (m, 1H), 6.98–6.92 (m, 1H), 6.88–6.80 (m, 5H), 6.77 (t, J = 7.8 Hz, 2H), 6.60–6.54 (m, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.3, 163.0, 155.0, 152.0, 148.0, 142.2, 142.1, 141.69, 141.65, 134.2, 133.8, 130.7, 130.2, 130.0, 129.5, 129.1, 128.1, 127.6, 127.51, 127.47, 127.2, 126.8, 126.3, 125.0, 123.9, 122.9, 121.0, 62.3. IR: ῡ = 2920, 2851, 1646, 1534, 1463, 1402, 1188, 1135, 1075, 758, 669, 474cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H29ClNO: 582.1983; found: 582.1978.
2-(Diphenylmethylene)-3,3-diphenyl-1-(p-tolyl)-2,3-dihydrocyclopenta[b]indole (3d): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 40 min, red foam solid, 93.1 mg, 83% yield). 1H NMR (500 MHz, CDCl3) δ 7.67 (d, J = 7.5 Hz, 1H), 7.51–7.42 (m, 3H), 7.42–7.33 (m, 4H), 7.24 (td, J = 7.7, 1.3 Hz, 1H), 7.16–7.03 (m, 6H), 7.00 (t, J = 7.3 Hz, 1H), 6.97–6.89 (m, 3H), 6.86–6.79 (m, J = 3.0 Hz, 5H), 6.76 (t, J = 7.7 Hz, 2H), 6.57 (dd, J = 8.0, 1.4 Hz, 2H), 2.23 (s, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.3, 162.9, 157.1, 152.2, 147.9, 142.4, 142.1, 141.9, 141.4, 138.6, 132.3, 130.8, 129.53, 129.45, 129.2, 129.0, 128.5, 127.5, 127.2, 127.1, 127.0, 126.6, 126.1, 125.3, 123.6, 123.0, 120.7, 62.3, 21.3. IR: ῡ = 2922, 2852, 1645, 1530,1401, 1191, 1134, 1075, 758, 672, 573, 473 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C43H32N: 562.2529; found: 562.2524.
2-(Diphenylmethylene)-1-(4-ethylphenyl)-3,3-diphenyl-2,3-dihydrocyclopenta[b]indole (3e): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 30 min, red foam solid, 96.6 mg, 84% yield). 1H NMR (500 MHz, CDCl3) δ 7.68 (d, J = 7.3 Hz, 1H), 7.52–7.44 (m, 3H), 7.42–7.32 (m, 4H), 7.25 (td, J = 7.7, 1.1 Hz, 1H), 7.17–7.03 (m, 6H), 7.01 (td, J = 7.6, 0.9 Hz, 1H), 6.99–6.90 (m, 3H), 6.86–6.79 (m, 5H), 6.76 (t, J = 7.8 Hz, 2H), 6.57 (dd, J = 8.2, 1.1 Hz, 2H), 2.53 (q, J = 7.6 Hz, 2H), 1.15 (t, J = 7.6 Hz, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.4, 162.9, 157.1, 152.3, 147.9, 145.0, 142.3, 142.1, 141.9, 141.5, 132.5, 130.8, 129.6, 129.5, 129.21, 129.15, 127.6, 127.4, 127.21, 127.15, 126.6, 126.1, 125.3, 123.7, 123.0, 120.8, 62.3, 28.8, 15.5. IR: ῡ = 2921, 2852, 1647, 1529, 1400, 1191, 1133, 1075, 759, 671, 521, 471 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C44H34N: 576.2686; found: 576.2685.
1-(4-Butylphenyl)-2-(diphenylmethylene)-3,3-diphenyl-2,3-dihydrocyclopenta[b]indole (3f): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 30 min, red foam solid, 98.9 mg, 82% yield). 1H NMR (500 MHz, CDCl3) δ 7.68 (d, J = 7.4 Hz, 1H), 7.53–7.44 (m, 3H), 7.44–7.32 (m, 4H), 7.24 (td, J = 7.7, 1.0 Hz, 1H), 7.17–7.03 (m, 6H), 7.00 (td, J = 7.6, 1.1 Hz, 1H), 6.98–6.90 (m, 3H), 6.88–6.78 (m, 5H), 6.76 (t, J = 7.8 Hz, 2H), 6.60–6.54 (m, 2H), 2.50 (t, J = 7.5 Hz, 2H), 1.58–1.44 (m, 2H), 1.33–1.22 (m, 2H), 0.94 (t, J = 7.3 Hz, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.4, 162.9, 157.2, 152.3, 147.8, 143.6, 142.4, 142.1, 141.9, 141.4, 132.5, 130.8, 129.5, 129.4, 129.2, 129.0, 128.0, 127.5, 127.2, 127.1, 126.6, 126.1, 125.3, 123.6, 123.0, 120.8, 62.3, 35.4, 33.3, 22.0, 13.9. IR: ῡ = 2921, 2852, 1646, 1530, 1465, 1400, 1188, 1135, 1075, 756, 672, 470 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C46H38N: 604.2999; found: 604.2996.
1-(4-(tert-Butyl)phenyl)-2-(diphenylmethylene)-3,3-diphenyl-2,3-dihydrocyclopenta[b]indole (3g): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 2 h, red foam solid, 100.0 mg, 83% yield). 1H NMR (500 MHz, CDCl3) δ 7.71 (d, J = 7.3 Hz, 1H), 7.53–7.45 (m, 3H), 7.41–7.34 (m, 4H), 7.32–7.22 (m, 1H), 7.18–7.04 (m, 8H), 7.03 (td, J = 7.5, 0.9 Hz, 1H), 6.98–6.91 (m, 1H), 6.84–6.73 (m, 7H), 6.57 (dd, J = 8.3, 1.3 Hz, 2H), 1.25 (s, 9H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.4, 162.9, 157.0, 152.4, 151.6, 147.8, 142.3, 142.1, 141.9, 141.4, 132.1, 130.8, 129.6, 129.5, 129.2, 129.0, 127.6, 127.2, 126.6, 126.1, 125.4, 124.8, 123.7, 123.1, 120.8, 62.3, 34.6, 31.0. IR: ῡ = 2921, 2852, 1647, 1399, 1188, 1135, 1075, 757, 672, 576, 471 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. For C46H38N: 604.2999; found: 604.2998.
2-(Diphenylmethylene)-1-(4-methoxyphenyl)-3,3-diphenyl-2,3-dihydrocyclopenta[b]indole (3h): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 40 min, red foam solid, 100.4 mg, 87% yield). 1H NMR (500 MHz, CDCl3) δ 7.70 (d, J = 7.5 Hz, 1H), 7.56–7.51 (m, 2H), 7.49 (d, J = 7.8 Hz, 1H), 7.39–7.34 (m, 4H), 7.30–7.23 (m, 1H), 7.15–7.04 (m, 6H), 7.03 (td, J = 7.6, 0.9 Hz, 1H), 6.99–6.91 (m, 1H), 6.90–6.79 (m, 5H), 6.77 (t, J = 7.8 Hz, 2H), 6.72–6.66 (m, 2H), 6.57 (dd, J = 8.1, 1.2 Hz, 2H), 3.76 (s, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.2, 162.9, 159.8, 156.8, 152.3, 147.9, 142.5, 142.2, 142.0, 140.9, 130.9, 130.8, 129.6, 129.4, 129.3, 127.7, 127.6, 127.3, 127.20, 127.17, 126.7, 126.1, 125.4, 123.6, 122.9, 120.8, 113.5, 62.4, 55.3. IR: ῡ = 3117, 2920, 2852, 1647, 1529, 1401, 1188, 1135, 1074, 757, 670, 472 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C43H32NO: 578.2478; found: 578.2473.
2-(Diphenylmethylene)-1-(2-fluorophenyl)-3,3-diphenyl-2,3-dihydrocyclopenta[b]indole (3i): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 20 min, red foam solid, 73.4 mg, 65% yield). 1H NMR (500 MHz, CDCl3) δ 7.56 (td, J = 7.4, 1.8 Hz, 2H), 7.50–7.30 (m, 5H), 7.30–7.25 (m, 1H), 7.20–7.07 (m, 7H), 7.07–6.97 (m, 2H), 6.97–6.81 (m, 6H), 6.80–6.72 (m, 3H), 6.57 (d, J = 7.5 Hz, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.5, 163.0, 158.1 (d, JC-F = 249.8 Hz), 151.7, 149.9, 147.7, 143.2, 141.7, 141.6, 130.8, 130.7, 130.44, 130.4, 130.3, 129.9, 129.6, 128.9, 128.4, 127.60, 127.42, 127.2, 126.6, 126.2, 125.0, 123.9, 123.8, 123.63, 123.60, 123.4, 120.9, 115.9, 115.8, 62.2.19F NMR (471 MHz, CDCl3) δ -108.4. IR: ῡ = 2920, 2851, 1646, 1528, 1399, 1188, 1135, 1075, 756, 672, 471 cm−1 HRMS (ESI) m/z: [M + H]+ calcd. for C42H29FN 566.2279; found: 566.2276.
2-(Diphenylmethylene)-3,3-diphenyl-1-(thiophen-2-yl)-2,3-dihydrocyclopenta[b]indole (3j): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 1 h, red foam solid, 96.2 mg, 87% yield). 1H NMR (500 MHz, CDCl3) δ 8.11 (d, J = 7.6 Hz, 1H), 7.50 (d, J = 7.8 Hz, 1H), 7.36 (d, J = 7.3 Hz, 4H), 7.34–7.24 (m, 3H), 7.14–7.02 (m, 7H), 6.99–6.90 (m, 6H), 6.81–6.73 (m, 3H), 6.60 (d, J = 8.0 Hz, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.3, 162.7, 152.5, 149.0, 147.6, 143.2, 142.2, 141.9, 139.8, 136.7, 131.8, 130.6, 129.7, 129.5, 128.6, 127.6, 127.4, 127.3, 127.1, 126.9, 126.2, 124.8, 123.8, 123.7, 120.8, 62.9. IR: ῡ = 2923, 2853, 1693, 1648, 1528, 1399, 1192, 1134, 1075, 757, 671, 474 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C40H28NS: 554.1937; found: 554.1934.
1-(tert-Butyl)-2-(diphenylmethylene)-3,3-diphenyl-2,3-dihydrocyclopenta[b]indole (3k): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 30 min, red foam solid, 52.6 mg, 50% yield). 1H NMR (500 MHz, CDCl3) δ 7.81 (d, J = 7.5 Hz, 1H), 7.53 (d, J = 7.7 Hz, 1H), 7.42–7.23 (m, 7H), 7.23–6.86 (m, 12H), 6.74 (s, 3H), 1.31 (s, 9H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.5, 176.7, 162.3, 153.8, 146.7, 145.6, 143.0, 142.6, 142.2, 132.1, 130.1, 128.72, 128.70, 128.24, 128.16, 127.4, 126.9, 126.0, 125.6, 125.5, 123.4, 120.7, 65.7, 37.4, 31.0. IR: ῡ = 2921, 2852, 1647, 1529,1401, 1192, 1134, 1074, 758, 671, 566, 468 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C40H34N: 528.2686; found: 528.2682.
1-Cyclopropyl-2-(diphenylmethylene)-3,3-diphenyl-2,3-dihydrocyclopenta[b]indole (3l): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 20 min, red foam solid, 51.1 mg, 50% yield). 1H NMR (500 MHz, CDCl3) δ 7.61 (d, J = 7.5 Hz, 1H), 7.47 (d, J = 7.7 Hz, 1H), 7.34–7.16 (m, 10H), 7.15–6.99 (m, 7H), 6.98–6.88 (m, 1H), 6.76 (t, J = 7.8 Hz, 2H), 6.58–6.54 (m, 2H), 1.49–1.31 (m, 3H), 0.99–0.82 (m, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.4, 167.1, 162.3, 154.6, 145.8, 144.0, 142.0, 141.8, 138.7, 130.4, 129.6, 129.2, 128.6, 128.02, 128.00, 127.5, 127.2, 126.7, 126.0, 124.4, 123.8, 123.5, 120.7, 62.1, 16.1, 13.0. IR: ῡ =2921, 2852, 1646, 1529, 1402, 1191, 1134, 1075, 758, 671, 563, 471 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C39H30N: 512.2373; found: 512.2368.
2-(Bis(4-fluorophenyl)methylene)-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (3m): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 20 min, red foam solid, 86.2 mg, 74% yield). 1H NMR (500 MHz, CDCl3) δ 7.65 (d, J = 7.3 Hz, 1H), 7.57–7.52 (m, 2H), 7.48 (d, J = 7.8 Hz, 1H), 7.42–7.34 (m, 4H), 7.31–7.08 (m, 11H), 7.05–6.98 (m, 1H), 6.82–6.76 (m, 2H), 6.59–6.43 (m, 6H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.2, 163.0, 161.9 (d, JC-F = 248.5 Hz), 161.8 (d, JC-F = 247.4 Hz), 155.9, 153.0, 145.2, 142.3, 141.7, 138.3, 137.8, 135.1, 132.5, 132.4, 131.0, 130.9, 129.9, 129.5, 128.9, 128.8, 128.1, 127.7, 126.5, 125.1, 123.9, 123.1, 120.9, 114.5, 114.33, 114.28, 114.2, 62.3.19F NMR (471 MHz, CDCl3) δ –113.7, –114.6. IR: ῡ = 2921, 2851, 1647, 1528, 1400, 1192, 1134, 1075, 757, 671, 471 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H28F2N: 584.2184; found: 584.2178.
2-(Bis(4-chlorophenyl)methylene)-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (3n): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 20 min, red foam solid, 65.2 mg, 53% yield). 1H NMR (500 MHz, CDCl3) δ 7.64 (d, J = 7.4 Hz, 1H), 7.55–7.49 (m, 2H), 7.48 (d, J = 7.8 Hz, 1H), 7.41–7.33 (m, 4H), 7.27 (td, J = 7.7, 1.1 Hz, 1H), 7.24–7.19 (m, 3H), 7.19–7.09 (m, 6H), 7.02 (td, J = 7.6, 0.9 Hz, 1H), 6.83–6.70 (m, 6H), 6.52–6.46 (m, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.0, 163.1, 155.5, 153.5, 144.6, 142.5, 141.5, 140.3, 140.0, 134.9, 133.5, 133.1, 131.9, 130.5, 130.1, 129.5, 128.9, 128.8, 128.2, 127.8, 127.6, 127.5, 126.5, 125.1, 124.0, 123.2, 121.0, 62.3. IR: ῡ = 3118, 2920, 2850, 1646, 1528, 1402, 1191, 1136, 1075, 755, 670, 470 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H28Cl2N: 616.1593; found: 616.1589.
2-(Bis(4-bromophenyl)methylene)-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (3o): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 20 min, red foam solid, 60.4 mg, 43% yield). 1H NMR (500 MHz, CDCl3) δ 7.64 (d, J = 7.4 Hz, 1H), 7.55–7.45 (m, 3H), 7.40–7.32 (m, 4H), 7.31–7.26 (m, 1H), 7.24–7.19 (m, 3H), 7.20–7.08 (m, 6H), 7.05–7.01 (m, 1H), 6.98–6.88 (m, 4H), 6.68 (d, J = 8.4 Hz, 2H), 6.43 (d, J = 8.5 Hz, 2H).13C {1H} NMR (126 MHz, CDCl3) δ 187.9, 163.1, 155.4, 153.5, 144.6, 142.6, 141.5, 140.6, 140.3, 134.9, 132.1, 130.7,130.52, 130.46,130.1, 129.5, 128.9, 128.8, 128.2, 127.8, 126.6, 125.1, 124.0, 123.2, 121.9, 121.3, 121.0, 62.3. IR: ῡ = 2920, 2851, 1647, 1529, 1401, 1195, 1135, 1073, 756, 670, 472 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H28Br2N: 706.0563; found: 706.0561.
2-(Di-p-tolylmethylene)-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (3p): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 20 min, red foam solid, 92.0 mg, 80% yield). 1H NMR (500 MHz, CDCl3) δ 7.64 (d, J = 7.5 Hz, 1H), 7.60–7.51 (m, 2H), 7.48 (d, J = 7.8 Hz, 1H), 7.38 (d, J = 7.1 Hz, 4H), 7.24 (td, J = 7.7, 1.2 Hz, 1H), 7.19–7.04 (m, 9H), 6.99 (t, J = 7.5 Hz, 1H), 6.71 (d, J = 8.0 Hz, 2H), 6.59 (t, J = 7.8 Hz, 4H), 6.46 (d, J = 8.0 Hz, 2H), 2.16 (s, 3H), 2.04 (s, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.5, 162.9, 157.3, 151.7, 148.4, 142.0, 141.5, 139.7, 139.3, 137.1, 136.5, 135.5, 130.8, 129.6, 129.4, 129.2, 129.0, 128.1, 127.9, 127.8, 127.5, 126.1, 125.3, 123.6, 122.9, 120.7, 62.3, 21.0, 20.9. IR: ῡ = 3122, 2920, 2852, 1648, 1527, 1401, 1190, 1136, 1074, 756, 671, 471 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C44H34N: 576.2686; found: 576.2678.
2-(Bis(4-methoxyphenyl)methylene)-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (3q): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 30 min, red foam solid, 91.0 mg, 75% yield). 1H NMR (500 MHz, CDCl3) δ 7.67 (d, J = 7.5 Hz, 1H), 7.61–7.55 (m, 2H), 7.48 (d, J = 7.8 Hz, 1H), 7.43–7.34 (m, 4H), 7.24 (td, J = 7.7, 1.2 Hz, 1H), 7.19 (t, J = 7.5 Hz, 2H), 7.17–7.05 (m, 7H), 7.00 (td, J = 7.5, 1.0 Hz, 1H), 6.75 (d, J = 8.7 Hz, 2H), 6.51 (d, J = 8.7 Hz, 2H), 6.38–6.29 (m, 4H), 3.65 (s, 3H), 3.58 (s, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.6, 162.7, 158.9, 158.7, 157.5, 151.4, 147.8, 142.1, 141.1, 137.6, 135.5, 135.4, 134.8, 132.4, 131.6, 130.8, 129.5, 129.3, 129.0, 128.5, 128.4, 128.3, 128.2, 127.9, 127.5, 127.3, 126.1, 125.3, 123.6, 122.8, 120.7, 113.8, 113.4, 112.7, 112.5, 62.4, 55.10, 55.07. IR: ῡ = 2921, 2851, 1649, 1529, 1400, 1195, 1135, 1073, 756, 669, 481 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C44H34NO2: 608.2584; found: 608.2578.
2-((4-Fluorophenyl)(phenyl)methylene)-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (3r): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 30 min, red foam solid, 87.0 mg, 77% yield, Z/E = 1.1:1) 1H NMR (500 MHz, CDCl3) δ 7.64 (dd, J = 7.5, 2.8 Hz, 1H), 7.61–7.52 (m, 2H), 7.48 (d, J = 7.8 Hz, 1H), 7.45–7.34 (m, 4H), 7.26 (t, J = 7.6 Hz, 1H), 7.25–7.05 (m, 9H), 7.04–6.93 (m, 2H), 6.83 (s, 2H), 6.83–6.75 (m, 2H), 6.60–6.42 (m, 4H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.3, 188.2, 162.99, 162.97, 161.8 (d, JC-F = 248.1 Hz), 161.7 (JC-F = 247.3 Hz), 156.5, 156.2, 152.6, 152.5, 146.6, 146.5, 142.2, 142.13, 142.11, 141.8, 141.7, 138.50, 138.47, 138.04, 138.02, 135.2, 132.5, 132.4, 131.0, 130.9, 130.8, 129.81, 129.79, 129.5, 129.2, 128.9, 128.7, 128.6, 128.1, 127.9, 127.8, 127.7, 127.6, 127.5, 127.4, 127.3, 126.9, 126.4, 126.3, 125.18, 125.16, 123.9, 123.1, 120.9, 114.3, 114.20, 114.15, 114.0, 62.3. 19F NMR (471 MHz, CDCl3) δ -114.0, -114.9. IR: ῡ = 2920, 2851, 1647, 1531, 1401, 1188, 1134, 1075, 758, 672, 471 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H29FN: 566.2279; found: 566.2271.
2-((4-Bromophenyl)(phenyl)methylene)-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (3s): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 15 min, red foam solid, 85.1 mg, 68% yield, Z/E = 1.1:1). 1H NMR (500 MHz, CDCl3) δ 7.64 (t, J = 6.6 Hz, 1H), 7.58–7.50 (m, 2H), 7.48 (dd, J = 7.7, 1.9 Hz, 1H), 7.43–7.33 (m, 4H), 7.26 (td, J = 7.7, 1.0 Hz, 1H), 7.25–7.05 (m, 9H), 7.01 (t, J = 7.5 Hz, 1H), 6.99–6.88 (m, 3H), 6.83 (s, 2H), 6.78 (t, J = 7.8 Hz, 1H), 6.73–6.65 (m, 1H), 6.58–6.52 (m, 1H), 6.45 (d, J = 8.5 Hz, 1H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.2, 188.1, 163.0, 156.3, 156.0, 152.8, 152.8, 146.2, 142.3, 141.7, 141.7, 141.4, 141.3, 140.9, 135.1, 132.2, 130.8, 130.7 130.4, 130.3, 129.9, 129.5, 129.2, 128.9, 128.7, 128.1, 127.9, 127.8, 127.7, 127.5, 127.5, 127.3, 126.9, 126.5, 126.3, 125.2, 123.9, 123.1, 121.7, 121.1, 120.9, 62.3. IR: ῡ = 2920, 2852, 1646, 1531, 1464, 1395, 1190, 1134, 1075, 759, 516, 468 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H29BrNO: 626.1478; found: 626.1469.
2-((4-Methoxyphenyl)(phenyl)methylene)-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (3t): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 15 min, red foam solid, 94.6 mg, 82% yield, Z/E = 1.3:1). 1H NMR (500 MHz, CDCl3) δ 7.65 (t, J = 7.5 Hz, 1H), 7.60–7.54 (m, 2H), 7.48 (d, J = 7.8 Hz, 1H), 7.44–7.33 (m, 4H), 7.25 (td, J = 7.7, 1.1 Hz, 1H), 7.24–7.04 (m, 9H), 7.04–6.93 (m, 2H), 6.88–6.80 (m, 3H), 6.81–6.72 (m, 2H), 6.57 (dd, J = 8.2, 1.3 Hz, 1H), 6.53–6.47 (m, 1H), 6.38–6.28 (m, 2H), 3.71 (s, 3H), 3.64 (s, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.54, 188.50, 162.9, 158.9, 158.7, 157.1, 152.1, 151.6, 148.0, 147.8, 142.7, 142.1, 142.0, 141.9, 141.6, 135.5, 135.4, 135.1, 134.7, 132.2, 130.9, 130.7, 129.54, 129.51, 129.3, 129.0, 128.5, 128.4, 127.9, 127.8, 127.6, 127.5, 127.4, 127.3, 127.1, 126.7, 126.2, 126.1, 125.28, 125.25, 123.7, 122.9, 120.8, 112.8, 112.6, 62.4, 62.3, 55.10, 55.08. IR: ῡ = 2920, 2852, 1645, 1532, 1465, 1395, 1189, 1134, 1075, 758, 672, 468 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C43H32NO: 578.2478; found: 578.2470.
4-(Phenyl(1,3,3-triphenylcyclopenta[b]indol-2(3H)-ylidene)methyl)phenol (3u): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 3 h, red foam solid, 38.3mg, 34% yield, Z/E = 1.2:1). 1H NMR (500 MHz, CDCl3) δ 7.71–7.54 (m, 5H), 7.52–7.45 (m, 2H), 7.45–7.40 (m, 2H), 7.38–7.32 (m, 2H), 7.32–7.24 (m, 5H), 7.22–7.15 (m, 2H), 7.09–6.95 (m, 4H), 6.94–6.86 (m, 1H), 6.85–6.74 (m, 1H), 6.72–6.66 (m, 1H), 6.58–6.39 (m, 3H), 4.55 (s, 1H). 13C NMR (126 MHz, CDCl3) δ 153.4, 149.0, 145.7, 145.5, 142.8, 142.3, 141.2, 139.0, 134.3, 133.5, 128.02, 127.96, 127.93, 127.85, 127.4, 127.20, 127.15, 127.1, 126.4, 126.2, 125.6, 122.1, 120.6 119.9, 115.9, 114.3, 111.0, 82.5, 81.5. IR: ῡ = 2920, 2851, 1646, 1528, 1401, 1193, 1134, 1073, 755, 670, 471 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H29NO: 564.2319; found: 564.2322.
2-(Biphenylmethylene)-7-fluoro-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (4a): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 30 min, red foam solid, 102.8 mg, 91% yield). 1H NMR (500 MHz, CDCl3) δ 7.57–7.48 (m, 2H), 7.42–7.33 (m, 5H), 7.32 (dd, J = 8.6, 2.5 Hz, 1H), 7.22–7.06 (m, 9H), 7.00–6.92 (m, 2H), 6.88–6.81 (m, 5H), 6.78 (t, J = 7.8 Hz, 2H), 6.57 (d, J = 7.2 Hz, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.38, 188.36, 159.9 (JC-F = 240.8 Hz), 159.02, 159.01, 158.0, 152.0, 149.0, 142.2, 141.8, 141.7 141.6, 141.5, 135.0, 130.8, 129.5, 129.2, 128.9, 128.8, 128.1, 127.7, 127.5, 127.4, 127.2, 126.9, 126.3, 126.23, 126.15, 121.14, 121.07, 116.0, 115.8, 110.2, 110.0, 62.4. 19F NMR (471 MHz, CDCl3) δ -119.2. IR: ῡ = 2920, 2851, 1645, 1531, 1407, 1188, 1135, 1073, 755, 672, 470 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H29FN: 566.2279; found: 566.2275.
7-Chloro-2-(diphenylmethylene)-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (4b): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 20 min, red foam solid, 96.4 mg, 83% yield). 1H NMR (500 MHz, CDCl3) δ 7.57 (s, 1H), 7.54 (d, J = 7.3 Hz, 2H), 7.43–7.31 (m, 5H), 7.27–7.05 (m, 10H), 7.00–6.92 (m, 1H), 6.84 (s, 5H), 6.81–6.73 (m, 2H), 6.60– 6.51 (m, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.7, 161.3, 158.5, 152.0, 149.3, 142.2, 141.8, 141.6, 141.1, 135.0, 130.8, 129.5, 129.3, 129.20, 129.17, 129.0, 128.9, 128.1, 127.7, 127.6, 127.4, 127.2, 126.9, 126.6, 126.3, 122.9, 121.5, 62.4. IR: ῡ = 2920, 2851, 1646, 1530, 1465, 1404, 1190, 1134, 1074, 759, 672,470 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H29ClN: 582.1983; found: 582.1979.
7-Bromo-2-(diphenylmethylene)-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (4c): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 30 min, red foam solid, 116.4 mg, 93% yield). 1H NMR (500 MHz, CDCl3) δ 7.72 (d, J = 1.6 Hz, 1H), 7.57–7.51 (m, 2H), 7.39–7.30 (m, 6H), 7.19 (t, J = 7.5 Hz, 2H), 7.17–7.05 (m, 7H), 6.95 (t, J = 7.5 Hz, 1H), 6.87–6.80 (m, 5H), 6.77 (t, J = 7.8 Hz, 2H), 6.57 (dd, J = 8.0, 1.1 Hz, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.5, 161.6, 158.6, 152.0, 149.3, 142.1, 141.7, 141.5, 140.9, 134.9, 132.0, 130.8, 129.4, 129.1, 129.0, 128.8, 128.1, 127.7, 127.5, 127.4, 127.2, 127.1, 126.9, 126.3, 125.7, 121.9, 117.0, 62.4. IR: ῡ = 2920, 2850, 1646, 1529, 1464, 1400, 1188, 1135, 1074, 758, 672, 578, 470 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H29BrN: 626.1478; found: 626.1472.
2-(diphenylmethylene)-7-methyl-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (4d): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 20 min, red foam solid, 64.0 mg, 57% yield). 1H NMR (500 MHz, CDCl3) δ 7.60–7.52 (m, 2H), 7.43 (s, 1H), 7.41–7.32 (m, 5H), 7.17 (t, J = 7.5 Hz, 2H), 7.15–7.04 (m, 8H), 6.94 (t, J = 7.5 Hz, 1H), 6.88–6.79 (m, 5H), 6.76 (t, J = 7.8 Hz, 2H), 6.57 (dd, J = 8.1, 1.1 Hz, 2H), 2.27 (s, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 187.7, 160.9, 156.2, 152.2, 147.6, 142.4, 142.1, 142.00, 141.95, 135.4, 133.4, 130.8, 130.4, 129.5, 129.2, 129.0, 128.5, 127.9, 127.6, 127.30, 127.26, 127.2, 126.7, 126.1, 125.3, 123.6, 120.4, 62.2, 21.4. IR: ῡ = 2920, 2851, 1646, 1530, 1405, 1190, 1133, 1074, 758, 673, 519, 469 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C43H32N: 562.2529; found: 562.2524.
2-(Diphenylmethylene)-7-methoxy-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (4e): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 20 min, red foam solid, 72.6 mg, 63% yield). 1H NMR (500 MHz, CDCl3) δ 7.54 (d, J = 7.2 Hz, 2H), 7.37 (d, J = 6.9 Hz, 5H), 7.22 (d, J = 2.5 Hz, 1H), 7.19–7.05 (m, 9H), 6.98–6.92 (m, 1H), 6.88–6.79 (m, 6H), 6.77 (t, J = 7.8 Hz, 2H), 6.59–6.53 (m, 2H), 3.73 (s, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 187.0, 156.8, 152.2, 142.4, 142.0, 135.3, 130.8, 129.5, 129.2, 128.9, 128.6, 127.9, 127.6, 127.4, 127.2, 126.7, 126.2, 120.8, 114.3, 109.8, 62.2, 55.8. IR: ῡ = 2921, 2821, 1646, 1530, 1399, 1187, 1134, 1074, 760, 672, 468 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C43H32NO: 578.2478; found: 578.2472.
2-(Diphenylmethylene)-6-fluoro-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (4f): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 3 h, red foam solid, 88.0 mg, 78% yield). 1H NMR (500 MHz, CDCl3) δ 7.63–7.49 (m, 3H), 7.39–7.33 (m, 4H), 7.22–7.07 (m, 10H), 6.96 (t, J = 7.4 Hz, 1H), 6.84 (s, 4H), 6.78 (t, J = 7.7 Hz, 2H), 6.75–6.67 (m, 1H), 6.60–6.53 (m, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 190.3,165.0, 164.7, 164.6, 164.0 (d, JC-F = 248.2 Hz), 156.8, 151.9, 148.3, 142.3, 141.9, 141.6, 141.0, 135.2, 130.8, 129.5, 129.2, 128.9, 128.7, 128.0, 127.7, 127.5, 127.4, 127.2, 126.8, 126.4, 123.6, 123.5, 121.4, 110.7, 110.5, 108.8, 108.6, 62.4.19F NMR (471 MHz, CDCl3) δ -109.8. IR: ῡ = 2921, 2851, 1647, 1530, 1400, 1193, 1133, 1073, 757, 671, 567, 519 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H29FN: 566.2279; found: 566.2273.
2-(Diphenylmethylene)-6-methoxy-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (4g): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 2 h, red foam solid, 61.0 mg, 53% yield). 1H NMR (500 MHz, CDCl3) δ 7.57–7.51 (m, 3H), 7.41–7.35 (m, 4H), 7.19–7.05 (m, 10H), 6.94 (t, J = 7.4 Hz, 1H), 6.88–6.79 (m, 5H), 6.77 (t, J = 7.7 Hz, 2H), 6.57 (d, J = 8.2 Hz, 3H), 3.78 (s, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 189.9, 165.0, 161.7, 154.4, 152.0, 146.7, 142.5, 142.1, 141.9, 141.7, 135.5, 130.8, 129.6, 129.3, 128.9, 128.8, 128.5, 128.4, 128.33, 128.27, 127.8, 127.6, 127.3, 127.22, 127.19, 127.16, 126.64, 126.59, 126.2, 123.7, 117.9, 110.3, 106.3, 62.3, 55.5. IR: ῡ = 2920, 2851, 1646, 1531, 1400, 1189, 1135, 1074, 759, 671, 471 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C43H32NO: 578.2478; found: 578.2474.
2-(diphenylmethylene)-8-methyl-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (4h): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 1 h, red foam solid, 41.2 mg, 37% yield). 1H NMR (500 MHz, CDCl3) δ 7.43–7.35 (m, 4H), 7.30 (d, J = 7.7 Hz, 1H), 7.23–7.10 (m, 9H), 7.05–6.98 (m, 3H), 6.91–6.86 (m, 1H), 6.85–6.81 (m, 3H), 6.80–6.76 (m, 2H), 6.75–6.68 (m, 3H), 6.56–6.49 (m, 2H), 1.57 (s, 3H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.7, 163.1, 155.64, 153.58, 148.1, 144.4, 142.4, 142.1, 141.8, 136.7, 135.7, 130.2, 129.6, 129.5, 129.5, 128.3, 127.6, 127.5, 127.2, 126.7, 126.6, 126.5, 126.3, 125.1, 118.3, 61.4, 21.8. IR: ῡ = 2937, 2924, 1553, 1490, 1441, 1392, 1337, 785, 695, 609, 537 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C43H32N: 562.2529; found: 562.2519.
5-chloro-2-(diphenylmethylene)-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (4i): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 2 h, red foam solid, 103 mg, 89% yield). 1H NMR (500 MHz, CDCl3) δ 7.60–7.48 (m, 3H), 7.42–7.36 (m, 4H), 7.28–7.23 (m, 2H), 7.21–7.05 (m, 9H), 7.00–6.90 (m, 2H), 6.84 (s, 5H), 6.78 (t, J = 7.7 Hz, 2H), 6.58–6.52 (m, 2H).13C NMR (126 MHz, CDCl3) δ 188.7, 159.2, 158.6, 152.3, 149.2, 142.3, 142.0, 141.8, 141.6, 135.0, 130.8, 129.9, 129.7, 129.2, 129.0, 128.8, 128.0, 127.6, 127.5, 127.4, 127.22, 127.17, 126.9, 126.31, 125.29, 124.4, 121.2, 62.7. IR: ῡ = 2980, 2977, 1631, 1537, 1393, 1337, 1127, 748, 695, 488, 436 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H29ClN: 582.1983; found: 582.1973.
2-(Diphenylmethylene)-3,3-bis(4-fluorophenyl)-1-phenyl-2,3-dihydrocyclopenta[b]indole (4j): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 1 h, red foam solid, 88.6 mg, 76% yield). 1H NMR (500 MHz, CDCl3) δ 7.66 (d, J = 7.5 Hz, 1H), 7.56–7.52 (m, 2H), 7.49 (d, J = 7.8 Hz, 1H), 7.38–7.26 (m, 5H), 7.20–7.15 (m, 2H), 7.14–7.11 (m, 1H), 7.07–6.98 (m, 2H), 6.89–6.79 (m, 11H), 6.60–6.54(m, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 187.9, 162.8, 161.3 (d, JC-F = 245.9 Hz), 156.6, 151.8, 148.2, 142.0, 141.9, 141.7, 137.60, 137.57, 135.0, 131.7, 131.0, 130.9, 130.7, 129.9, 129.0, 128.9, 128.8, 128.6, 128.24, 128.21, 127.9, 127.6, 127.5, 127.44, 127.38, 127.3, 127.1, 126.0, 125.1, 124.0, 123.1, 120.9, 114.6, 114.4, 61.0.19F NMR (471 MHz, CDCl3) δ -116.2. IR: ῡ = 2922, 2852, 1646, 1529, 1399, 1190, 1134, 757,672, 572, 470 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H28F2N: 584.2184; found: 584.2178.
3,3-Bis(4-chlorophenyl)-2-(diphenylmethylene)-1-phenyl-2,3-dihydrocyclopenta[b]indole (4k): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 2 h, red foam solid, 104.4 mg, 85% yield). 1H NMR (500 MHz, CDCl3) δ 7.66 (d, J = 7.6 Hz, 1H), 7.57–7.51 (m, 2H), 7.49 (d, J = 7.8 Hz, 1H), 7.32–7.25 (m, 5H), 7.17 (t, J = 7.3 Hz, 2H), 7.15–7.07 (m, 5H), 7.07–6.98 (m, 2H), 6.88–6.80 (m, 7H), 6.57 (d, J = 7.3 Hz, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 187.2, 162.5, 156.8, 151.2, 148.6, 141.79, 141.75, 140.1, 134.9, 132.4, 130.7, 130.0, 129.0, 128.9, 128.0, 127.9, 127.6, 127.44, 127.38, 127.2, 125.0, 124.2, 123.1, 120.9, 61.3. IR: ῡ = 2919, 2851, 1644, 1540, 1406, 1260, 1190, 1133, 1076, 756, 633, 477 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H28Cl2N: 616.1593; found: 616.1589.
2-(Diphenylmethylene)-1-phenyl-3,3-di-p-tolyl-2,3-dihydrocyclopenta[b]indole (4l): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 1 h min, red foam solid, 83.8 mg, 73% yield). 1H NMR (500 MHz, CDCl3) δ 7.62 (d, J = 7.6 Hz, 1H), 7.57–7.52 (m, 2H), 7.47 (d, J = 7.7 Hz, 1H), 7.29–7.20 (m, 6H), 7.15 (t, J = 7.4 Hz, 2H), 7.12–7.05 (m, 1H), 6.99 (td, J = 7.6, 0.9 Hz, 1H), 6.97–6.90 (m, 5H), 6.86–6.80 (m, 5H), 6.77 (t, J = 7.8 Hz, 2H), 6.58 (dd, J = 8.2, 1.1 Hz, 2H), 2.24 (s, 6H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.7, 163.1, 156.6, 152.4, 147.5, 142.4, 142.1, 141.9, 138.9, 135.6, 135.4, 130.8, 129.6, 129.4, 129.2, 128.9, 128.5, 128.3, 127.8, 127.3, 127.2, 127.0, 126.6, 125.3, 123.6, 122.9, 120.8, 61.8, 20.9. IR: ῡ = 2921, 2852, 1645, 1542, 1398, 1266, 1187, 1135, 1077, 756, 631, 474 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C44H34N: 576.2686; found: 576.2684.
3,3-Bis(4-(tert-butyl)phenyl)-2-(diphenylmethylene)-1-phenyl-2,3-dihydrocyclopenta[b]indole (4m): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 50 min, red foam solid, 105.4 mg, 80% yield). 1H NMR (500 MHz, CDCl3) δ 7.65 (d, J = 7.5 Hz, 1H), 7.57 (d, J = 7.3 Hz, 2H), 7.50 (d, J = 7.8 Hz, 1H), 7.32–7.24 (m, 5H), 7.20–7.14 (m, 2H), 7.13–7.08 (m, 5H), 7.01 (t, J = 7.5 Hz, 1H), 6.93 (t, J = 7.4 Hz, 1H), 6.88–6.79 (m, 5H), 6.75 (t, J = 7.7 Hz, 2H), 6.60–6.53 (m, 2H), 1.26 (s, 18H).13C {1H} NMR (126 MHz, CDCl3) δ 188.8, 163.1, 156.7, 152.6, 148.6, 147.4, 142.5, 142.1, 141.9, 138.8, 135.5, 130.8, 129.6, 129.2, 129.0, 128.5, 127.8, 127.3, 127.2, 127.0, 126.4, 125.4, 124. 4, 123.6, 123.0, 120.8, 61.8, 34.2, 31.3. IR: ῡ = 2920, 2853, 1646, 1529, 1398, 1188, 1135, 1076, 755, 674, 472 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C50H46N: 660.3625; found: 660.3621.
2-(Diphenylmethylene)-3,3-bis(4-methoxyphenyl)-1-phenyl-2,3-dihydrocyclopenta[b]indole (4n): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 2 h, red foam solid, 81.2 mg, 67% yield). 1H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 7.4 Hz, 1H), 7.57–7.52 (m, 2H), 7.48 (d, J = 7.8 Hz, 1H), 7.30–7.24 (m, 6H), 7.16 (t, J = 7.4 Hz, 2H), 7.13–7.05 (m, 1H), 7.03–6.92 (m, 2H), 6.87–6.77 (m, 7H), 6.70–6.63 (m, 4H), 6.60 (dd, J = 8.2, 1.3 Hz, 2H), 3.73 (s, 6H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.8, 163.1, 157.8, 156.5, 152.5, 147.5, 142.4, 142.1, 141.8, 135.4, 134.2, 130.8, 130.5, 129.6, 129.2, 128.9, 128.5, 127.9, 127.30, 127.25, 127.1, 126.7, 125.3, 123.7, 123.0, 120.8, 113.1, 61.0, 55.2. IR: ῡ = 2919, 2850, 1643, 1533, 1399, 1264, 1190, 1134, 1077, 629, 471 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C44H34NO2: 608.2584; found: 608.2580.
3,3-Di([1,1’-biphenyl]-4-yl)-2-(diphenylmethylene)-1-phenyl-2,3-dihydrocyclopenta[b]indole (4o): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 3 h, red foam solid, 103.4 mg, 74% yield). 1H NMR (500 MHz, CDCl3) δ 7.68 (d, J = 7.5 Hz, 1H), 7.64–7.58 (m, 2H), 7.57–7.46 (m, 9H), 7.45–7.34 (m, 8H), 7.34–7.24 (m, 3H), 7.21–7.14 (m, 2H), 7.10 (t, J = 7.4 Hz, 1H), 7.06–6.95 (m, 2H), 6.94–6.85 (m, 2H), 6.85–6.76 (m, 5H), 6.65 (d, J = 7.3 Hz, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.2, 163.0, 156.7, 152.1, 147.9, 142.2, 142.1, 142.0, 141.0, 138.9, 135.3, 130.7, 129.9, 129.8, 129.2, 129.0, 128.7, 127.9, 127.4, 127.17, 127.16, 127.1, 126.9, 126.7, 126.4, 125.3, 123.9, 123.1, 120.9, 61.9. IR: ῡ = 2921, 2851, 1646, 1528, 1401, 1188, 1134, 1071, 756, 673, 470 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C54H38N: 700.2999; found: 700.2996.
2-(Diphenylmethylene)-1-phenyl-3,3-di-m-tolyl-2,3-dihydrocyclopenta[b]indole (4p): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 20 min, red foam solid, 52.8 mg, 46% yield). 1H NMR (500 MHz, CDCl3) δ 7.64 (d, J = 7.5 Hz, 1H), 7.58–7.52 (m, 2H), 7.48 (d, J = 7.8 Hz, 1H), 7.30–7.19 (m, 4H), 7.19–7.14 (m, 4H), 7.10 (t, J = 7.4 Hz, 1H), 7.07–6.98 (m, 3H), 6.95 (s, 1H), 6.90 (d, J = 7.5 Hz, 2H), 6.87–6.75 (m, 7H), 6.59 (d, J = 7.3 Hz, 2H), 2.20 (s, 6H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.6, 163.0, 156.8, 152.4, 147.6, 142.5, 142.0, 141.8, 141.7, 136.8, 135.5, 130.8, 130.6, 129.6, 129.3, 128.9, 128.5, 127.9, 127.5, 127.32, 127.27, 127.02, 126.99, 126.73, 126.67, 125.3, 123.7, 123.0, 120.8, 62.2, 21.5. IR: ῡ = 2921, 2851, 1645, 1531, 1465, 1416, 1190, 1135, 1073, 758,673, 470 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C44H34N: 576.2686; found: 576.2682.
2-(Diphenylmethylene)-3,3-bis(3-methoxyphenyl)-1-phenyl-2,3-dihydrocyclopenta[b]indole (4q): (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 40 min, red foam solid, 35.2 mg, 29% yield). 1H NMR (500 MHz, CDCl3) δ 7.64 (d, J = 7.5 Hz, 1H), 7.59–7.52 (m, 2H), 7.48 (d, J = 7.8 Hz, 1H), 7.31–7.23 (m, 1H), 7.16 (t, J = 7.4 Hz, 2H), 7.13–6.91 (m, 9H), 6.89–6.78 (m, 7H), 6.69–6.61 (m, 4H), 3.67 (s, 6H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.1, 163.0, 158.8, 156.6, 152.0, 147.8, 143.2, 142.3, 142.0, 141.9, 135.3, 130.8, 129.7, 129.2, 129.0, 128.6, 128.5, 127.9, 127.4, 127.1, 126.7, 125.3, 123.8, 123.0, 122.2, 120.9, 115.8, 112.0, 62.3, 55.1. IR: ῡ = 2921, 2852, 1645, 1534, 1405, 1258, 1192, 1133, 1076, 756, 670, 473 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C44H34NO2: 608.2584; found: 608.2575.

3.3. General Procedure for the Gram-Scale Synthesis of 3a

To a solution of Sc(OTf)3 (393.7 mg, 0.8 mmol) in toluene (40 mL) was added of 1a (1.2 g, 4.0 mmol) and 2a (1.7 g, 6 mmol) in glass pressure tube (100 mL). The reaction mixture was stirred for 1.5 h at 100 °C. The solvent was concentrated under reduced pressure, and the resulting residue was purified by flash column chromatography on silica gel eluting with petroleum ether/ethyl acetate (petroleum ether/ethyl acetate 10:1 to 3:1), giving the corresponding product 3a (1.86 g, 83% yield).

3.4. General Procedure for the Synthesis of 5

LiAlH4 (11.4 mg, 0.3 mmol) was added to a solution of 3a (54.7 mg, 0.1 mmol) in dry THF (1 mL) at 0 ℃. The reaction mixture was stirred for 10 min. Then, water (2 mL) was added. The layers were separated, and the aqueous layer was extracted with CH2Cl2 (5 mL × 3). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography on silica gel, giving the product 5 (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 10 min, red foam solid, 54.5 mg, 99% yield).
2-(Diphenylmethylene)-1,3,3-triphenyl-2,3,3a,4-tetrahydrocyclopenta[b]indole (5): 1H NMR (500 MHz, CDCl3) δ 7.64 (s, 1H), 7.41–7.29 (m, 2H), 7.19 (tt, J = 8.2, 6.6 Hz, 7H), 7.11–7.06 (m, 2H), 7.06–6.97 (m, 8H), 6.90 (ddd, J = 15.1, 11.5, 4.2 Hz, 3H), 6.83 (t, J = 7.4 Hz, 1H), 6.72 (t, J = 7.7 Hz, 2H), 6.54 (d, J = 7.2 Hz, 2H), 6.49 (d, J = 7.2 Hz, 2H), 5.65 (s, 1H).13C {1H} NMR (126 MHz, CDCl3) δ 153.0, 147.6, 145.0, 143.9, 143.6, 143.1, 142.9, 141.6, 140.8, 130.0, 128.93, 128.89, 128.8, 128.5, 128.4, 128.1, 127.44, 127.41, 127.3, 126.4, 126.3, 125.7, 125.6, 125.4, 123.3, 121.5, 119.8, 119.4, 119.1, 111.7, 62.3, 49.1. IR: ῡ = 3471, 3110, 2920, 2852, 1648, 1527, 1402, 1243, 1190, 1136, 1073, 1027, 752, 671, 467 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C42H32N: 550.2529; found: 550.2525.

3.5. General Procedure for the Synthesis of 6

Pd(PPh3)4 (46.2 mg, 0.2 mmol), Cs2CO3 (97.7 mg, 0.15 mmol), and phenanthren-9-ylboronic acid(66.6 mg, 0.15 mmol) in 1,4-dioxane (2 mL) were added to a solution of 4c (125.3 mg, 0.3.1.2 mmol). The reaction mixture was stirred for 12 h. The residue was purified by flash chromatography on silica gel, giving the product 6 (eluent: petroleum ether/ethyl acetate 10:1 to 3:1, 12 h, red foam solid, 117.2 mg, 81% yield).
2-(Diphenylmethylene)-7-(phenanthren-9-yl)-1,3,3-triphenyl-2,3-dihydrocyclopenta[b]indole (6): 1H NMR (500 MHz, CDCl3) δ 8.70 (d, J = 8.3 Hz, 1H), 8.65 (d, J = 8.2 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.85–7.77 (m, 2H), 7.67–7.50 (m, 7H), 7.51–7.38 (m, 6H), 7.22–7.07 (m, 7H), 7.01 (t, J = 7.5 Hz, 2H), 6.94 (q, J = 7.4 Hz, 2H), 6.89–6.82 (m, 2H), 6.82–6.74 (m, 5H), 6.61 (d, J = 7.3 Hz, 2H). 13C {1H} NMR (126 MHz, CDCl3) δ 188.8, 162.3, 157.4, 152.3, 148.3, 142.3, 142.0, 141.9, 141.8, 138.7, 136.4, 135.1, 131.5, 131.4, 131.3, 130.8, 130.5, 129.8, 129.6, 129.5, 129.22, 129.17, 128.9, 128.6, 128.5, 127.9, 127.64, 127.58, 127.4, 127.3, 127.2, 126.9, 126.77, 126.75, 126.5, 126.42, 126.39, 126.3, 126.2, 125.4, 124.6, 122.8, 122.4, 120.4, 62.5. IR: ῡ = 3117, 2922, 2852, 1649, 1529, 1400, 1191, 1136, 1073, 755, 671, 469 cm−1. HRMS (ESI) m/z: [M + H]+ calcd. for C56H38N: 724.2999; found: 724.2993.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules29061251/s1, X-ray data for products 3a; copies of 1H NMR, 13C {1H} NMR spectra.

Author Contributions

T.-F.W., Z.-J.F., Y.-R.Z., Z.-W.Q. and X.-Z.Z. performed the project; B.Q.L., A.-J.M. and X.-Z.Z. provided the funds and data analysis; S.-S.C. and H.-P.P. helped in collecting some new compounds; and B.Q.L. and X.-Z.Z. prepared and checked the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

Financial support was obtained from the NSFC (22101213), Department of Education of Guangdong Province (2020KCXTD036; 2021KQNCX101), Hong Kong–Macao Joint Research and Development Fund of Wuyi University (2021WGALH12), and the Science and Technology Planning Project of Guangdong Province (2021B1212040016).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data for the synthesized compounds presented in this study are available in the Supplementary Information.

Conflicts of Interest

The authors declare no conflict of interest.

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Molecules 29 01251 g001
Figure 1. Representative natural product molecules.
Figure 1. Representative natural product molecules.
Molecules 29 01251 g001
Molecules 29 01251 sch001
Scheme 1. Annulation of 2-indolylmethanols with propargylic alcohols.
Scheme 1. Annulation of 2-indolylmethanols with propargylic alcohols.
Molecules 29 01251 sch001
Molecules 29 01251 sch002
Scheme 2. Scope of propargylic alcohols. Performed at 0.2 mmol scale. 1 Ratio of isomers determined by crude 1H NMR.
Scheme 2. Scope of propargylic alcohols. Performed at 0.2 mmol scale. 1 Ratio of isomers determined by crude 1H NMR.
Molecules 29 01251 sch002
Molecules 29 01251 sch003
Scheme 3. Scope of 2-indolylmethols. Performed at 0.2 mmol scale.
Scheme 3. Scope of 2-indolylmethols. Performed at 0.2 mmol scale.
Molecules 29 01251 sch003
Molecules 29 01251 sch004
Scheme 4. Gram-scale reaction and transformations.
Scheme 4. Gram-scale reaction and transformations.
Molecules 29 01251 sch004
Molecules 29 01251 sch005
Scheme 5. Plausible mechanism.
Scheme 5. Plausible mechanism.
Molecules 29 01251 sch005
Table 1. Optimization of the reaction conditions for (3+2) annulation of 1a and 2a.
Table 1. Optimization of the reaction conditions for (3+2) annulation of 1a and 2a.
Molecules 29 01251 i001
EntryCatalystSolvent TimeYield 1 (%)
1Zn(OTf)2DCE2 h62
2Bi(OTf)3DCE3 h70
3Yb(OTf)3DCE2 h64
4Cu(OTf)2DCE2 h63
5AgNTf2DCE6 h13
6Sc(OTf)3DCE2 h74
7Sc(OTf)3CHCl3 1 h74
8Sc(OTf)31,4-dioxane 4 h76
9Sc(OTf)3THF 12 h75
10Sc(OTf)3EtOH1 h41
11Sc(OTf)3MeCN 6 h63
12Sc(OTf)3EA 4 h78
13Sc(OTf)3acetone 12 h58
14Sc(OTf)3DMF 12 hN.R.
15Sc(OTf)3DMSO 12 htrace
16Sc(OTf)3PhCl 40 min78
17Sc(OTf)3toluene 30 min80
18 2Sc(OTf)3toluene 30 min87
19 3Sc(OTf)3toluene24 h44
Performed with 1a (0.1 mmol) and 2a (0.11 mmol) in the presence of catalyst (20 mol %) in solvent at 100 °C. 1 Yield of the isolated product. 2 2a (1.5 equiv) was used. 3 Sc(OTf)3 (10 mol %) was used.
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MDPI and ACS Style

Wu, T.-F.; Fu, Z.-J.; Zhang, Y.-R.; Qiu, Z.-W.; Li, B.Q.; Chen, S.-S.; Pan, H.-P.; Ma, A.-J.; Zhang, X.-Z. Lewis-Acid-Catalyzed (3+2) Annulation of 2-Indolylmethanols with Propargylic Alcohols to Access Cyclopenta[b]indoles. Molecules 2024, 29, 1251. https://doi.org/10.3390/molecules29061251

AMA Style

Wu T-F, Fu Z-J, Zhang Y-R, Qiu Z-W, Li BQ, Chen S-S, Pan H-P, Ma A-J, Zhang X-Z. Lewis-Acid-Catalyzed (3+2) Annulation of 2-Indolylmethanols with Propargylic Alcohols to Access Cyclopenta[b]indoles. Molecules. 2024; 29(6):1251. https://doi.org/10.3390/molecules29061251

Chicago/Turabian Style

Wu, Teng-Fei, Zhao-Jie Fu, Yi-Rui Zhang, Zong-Wang Qiu, Bao Qiong Li, Shao-Shuai Chen, Han-Peng Pan, Ai-Jun Ma, and Xiang-Zhi Zhang. 2024. "Lewis-Acid-Catalyzed (3+2) Annulation of 2-Indolylmethanols with Propargylic Alcohols to Access Cyclopenta[b]indoles" Molecules 29, no. 6: 1251. https://doi.org/10.3390/molecules29061251

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