Gold-Catalyzed Synthesis of 6-Hydroxy Indoles ... - ACS Publications

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Gold-Catalyzed Synthesis of 6-Hydroxy Indoles from Alkynyl Cyclohexadienones and Substituted Amines VEERABHUSHANAM KADIYALA, Perla Bharath Kumar, Sridhar Balasubramanian, and Galla V. Karunakar J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02023 • Publication Date (Web): 28 Aug 2019 Downloaded from pubs.acs.org on August 28, 2019

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The Journal of Organic Chemistry

Gold-Catalyzed Synthesis of 6-Hydroxy Indoles from Alkynyl Cyclohexadienones and Substituted Amines Veerabhushanam Kadiyala,†‡ Perla Bharath Kumar,†‡ Sridhar Balasubramanian ǁ and Galla V. Karunakar*†‡ †

Fluoro and Agrochemicals Department, ‡Academy of Scientific and Innovative Research, Ghaziabad-

201002, India, and ǁCenter for X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India. [email protected]

ABSTRACT: An efficient gold-catalyzed formation of 6-hydroxy indoles from substituted alkynyl cyclohexadienones and amines have been developed. In this reaction two new C-N bonds were formed, and moderate to very good yields of the 6-hydroxy indole derivatives were obtained in one-pot. This organic transformation tolerates a range of substituted alkynyl cyclohexadienones and amines, which resulted 6-hydroxy indole derivatives selectively. Nature is an abundant source for collection of different varieties of alkaloids.1 The nitrogen containing heterocyclic molecules such as indole alkaloids gained very important role in recent years due to their numerous biological and pharmacological properties.2 Among them, hydroxy substituted indoles3 exhibits potential biological properties (Figure 1). For example, the natural product like 6-hydroxydiscodermindole exhibits cytotoxic effects on murine leukemia cell line P3884 and trachycladiindoles C & D, exhibits cytotoxic activity on few cancer cell lines such as MDA-MB-231, A549 and HT-29.5 Hyrtinadine A showed cytotoxic activity towards murine leukemia L1210 as well as epidermoid carcinoma KB cells.6,7 Further, 6-hydroxy indole derivatives such as BODIPY-OH are useful molecules in

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material chemistry.8 Synthesis of 4-hydroxy and 5-hydroxy substituted indoles are easy to access by commercially available starting materials. Whereas, synthesis of 6-hydroxy indoles are quite difficult to achieve.9 The recent literature evidencing that there is increasing interest for synthesis of 6hydroxy indoles10 due to their application in medicinal chemistry and material science. Hence, the making of versatile building blocks and development of new synthetic methods for the generation of 6-hydroxy indoles is limitless frontier.

Figure 1. Selected examples of important molecules containing 6-hydroxy indole core skeleton. It was reported that Liu and co-workers synthesized tropone derivatives and 1,2-diones by utilizing alkynyl quinols in the presence of gold-catalyst (Scheme 1, a ).11 Recently, Kim et al. reported that the synthesis of 4-alkynylazobenzenes from alkynyl quinols,12a and (Scheme 1, b ) they have also reported that the synthesis of 5-hydroxybenzofurans through 5-endo-dig cyclization reaction of alkynyl quinols in the presence of platinum-catalyst.12b


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Scheme 1. Selected previous reports: (a) synthesis of tropones and 1,2-diones; (b) synthesis of 4-alkynylazobenzenes and benzo furans; (c) synthesis of 6-hydroxy indoles under goldcatalysis.

Gold-catalysed13 organic transformations are an emerging as an important tool in synthetic organic chemistry for generation of desired valuable heterocyclic molecules.14 Our current research efforts focused mainly towards exploration of substituted alkynes in the presence of gold-catalysis.15 Recently, 6-hydroxy indoles were achieved by reaction of carboxymethyl cyclohexadienones with amines under metal-free reaction conditions.9 We are interested to aim our focus on the reactivity of alkynyl substituted cyclohexadienones 1 with amines 2 in the presence of gold-catalyst.



Initially, we anticipated that the reaction of alkynyl cyclohexadienone (1) with substituted aniline (2) in the presence of gold-catalyst would produce in situ generated intermediate IM-I which would further give 6-hydroxy indole derivatives 3 (Scheme 1, c ) via aza-Michael addition followed by rearrangement. Accordingly, a reaction was performed by utilizing 4-hydroxy-4-(phenylethynyl)cyclohexa-2,5-dien-1-one 1a and aniline 2a in the presence of AuCl3 (5 mol %). Very interestingly, we have isolated the product 1,2-diphenyl-1H-indol-6-ol 3a in 22% yield (Scheme 2). Scheme 2. Reaction of alkynyl cyclohexadienones (1a) with aniline (2a)

This experiment inspired us to conduct few more experiments in the presence of different catalysts and solvents to get the better yields of indole derivative 3a. The product 3a was obtained in poor yields, when the reaction was conducted in the presence KAuCl4 and AuClPPh3 (Table 1, entry 1 and 2). We have conducted a reaction without utilizing catalyst, it was observed that this reaction was not forwarded (Table 1, entry 3). Product 3a was observed in good yields, when a reaction was conducted in the presence of IPrAuCl (Table 1, entry 4). A moderate yield of product 3a was obtained when this reaction was performed in the presence of CyJohnPhosAuCl, gold-catalyst A and gold-catalyst B (Table 1, entries 5-7). Very good yield (84%) of product 3a was observed when the reaction was conducted by utilizing gold-catalyst C (Table 1, entry 8). Reactions were conducted by using 2.5 mol % and 1 mol % of gold-catalyst C, which produced the product 3a in 82% and 71% yields, respectively (Table 1, entries 9 and 10).


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Table 1.Optimization of the reaction conditionsa

entry catalyst (mol %)

solvent

temp (oC)

time(h)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN THF DMF EtOH 1,4 Dioxane Toluene DCE DMSO

80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80 80

12 12 12 12 12 12 12 12 26 32 12 12 12 26 26 26 26 26 26 26

KAuCl4 (5) Au(Ph3P)3Cl(5) No catalyst IPrAuCl (5) CyJohnPhos AuCl (5) Gold-catalyst A (5) Gold-catalyst B (5) Gold-catalyst C (5) Gold-catalyst C (2.5) Gold-catalyst C (1) AgSbF6 (5) AgBF4 (5) AgOTf (5) Gold-catalyst C (2.5) Gold-catalyst C (2.5) Gold-catalyst C (2.5) Gold-catalyst C (2.5) Gold-catalyst C (2.5) Gold-catalyst C (2.5) Gold-catalyst C (2.5)

yield (%)b 12 25 nrd 68 42 46 35 84 82 71 25 27 23 72 32 65 34 71 60 24

a

Reaction conditions: all reactions were carried out under nitrogen atmosphere with 1a (0.238 mmol), and 2a (0.262 mmol) and solvent (2 mL); bYields are for isolated products 3a; eq: equivalent; ccm: complex mixture; d nr: no reaction.

Three reactions were conducted by utilizing different silver catalysts such as AgSbF6, AgBF4 and AgOTf. All these cases moderate yields of product 3a observed (Table 1



entries 11-13). Then, reactions were conducted by using gold-catalyst C in different solvents such as THF, DMF, EtOH, 1,4-dioxane, toluene, DCE and DMSO (Table 1, entries 14-20), moderate to good yields of product 3a was observed in these cases. These optimization result conclude that 2.5 mol % of gold-catalyst C in MeCN at 80 o

C is best for this organic transformation (Table 1, entry 9). Then, experiments were

performed to check substrate scope of this organic reaction. When the reaction was conducted by utilizing 1a with electron donating functional group containing amine like 2b, produced 78% yields of product 3b (Table 2, entry 2). Whereas the electron withdrawing functional group containing aniline 2c reacted with 1a gave 65% yield of product 3c. Then the substrate 1a was tested with hydroxy substituted aniline 2d produced the indole derivative 3d in 82% yield. Two reactions were conducted by utilizing substituted hydroxy anilines such as 2e and 2f gave the corresponding indole derivatives 3e and 3f in 89% and 73% yields, respectively (Table 2, entries 5 and 6). Electron donating functional group substituted at R1 position containing substrate like 1b (R1 = 4-CH3-C6H4) was tested with hydroxy anilines such as 2d, 2e and 2f produced the corresponding substituted indoles 3g, 3h and 3i in very good yields, respectively (Table 2, entries 7-9). The product 3i structure was further analysed by single crystal X-ray data.16 The substrate which was substituted by electron donating functional group at R1 position like 1c (R1 = 4-OCH3-C6H4) was reacted with substituted anilines as 2d, 2e and 2f produced the corresponding indole derivatives such as 3j, 3k and 3l in 94%, 87% and 86% yields, respectively (Table 2, entries 10-12). The substrate which is bearing electron withdrawing functional group at R1 position such as 1d (R1 = 4-F-C6H4) was tested with 2d and 2e produced the corresponding indole derivatives 3m and 3n in very good yields, respectively (Table 2, entries 13 and 14).


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Table 2. Scope of substituted 6-hydroxy indoles (3)a

a

Reaction conditions: all reactions were carried out at 80 °C under nitrogen atmosphere with

1 (1 equiv.), 2 (1.1 equiv.), gold-catalyst C (2.5 mol % ) and solvent (3 mL); bYields are for isolated products 3.

Further, experiments were conducted to test the scope of this reaction. The substrate 1a was tested with methylamine 2g gave the substituted indole 3o in 72% yield (Table 3, entry 1). Benzylamine 2h and cyclohexylamine 2i were tested with 1a produced the corresponding products 3p and 3q in 64% and 21% yields, respectively (Table 3, entries 2 and 3).



Table 3. Scope of substituted 6-hydroxy indoles (3)a

a

Reaction conditions: all reactions were carried out at 80 °C under nitrogen atmosphere with

1 (1 equiv.), 2 (1.1 equiv.), gold-catalyst C (2.5 mol % ) and solvent (3 mL); bYields are for isolated products 3.

In the case of pyridine 4-amine 2j did not give desired product, the starting materials remained intact. Moderate yield (55%) of product 3s was observed when the reaction was conducted with furfurylamine 2k (Table 3, entry 5). Different substituted amines like 2d, 2e and 2f were tested with alkyl substituted cyclohexadienone 1e gave the corresponding substituted indoles 3t, 3u and 3v in 83%, 86% and 48% yields, respectively (Table 3, entries 6-8). Substituted cyclohexadienones such as 1a, 1b and 1c were tested with diamine 2l gave the corresponding indole derivatives 3w, 3x and 3y in 71%, 68% and 57% yields,


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respectively (Table 3, entries 9-11). The substrate 1a was tested with an electron withdrawing aniline derivative such as 4-aminobenzonitrile 2m gave the corresponding substituted indole derivative 3z in 67% yield (Table 3, entry 12). A following tentative reaction mechanism can be proposed for this organic transformation

(Scheme

3).

Initially,

gold-catalyst

coordinates

with

alkynyl

cyclohexadienone 1a, it may react with aniline 2a by following Meyer-Schuster rearrangement17 to give enamine intermediate IM-I, which would further generate IM-II via aza-Michael addition,9 followed by a rearrangement to provide 6-hydroxy indole derivative 3a. Scheme 3. A plausible reaction mechanism.

EXPERIMENTAL SECTION General Information All the reactions were carried out in oven dried reaction flasks under nitrogen atmosphere and also solvents and reagents were transferred by oven-dried syringes to ambient temperature. TLC was performed on Merck silica gel aluminium sheets using UV as a visualizing agent. Solvents were removed under reduced pressure. Columns were packed as slurry of silica gel in hexane and ethyl acetate solvent mixture. The elution was assisted by applying pressure with an air pump.

13

C NMR spectra were recorded on 75, 100 and 125 MHz spectrometers.



1

HNMR spectra were recorded on 300, 400 and 500 MHz spectrometers in appropriate

solvents using TMS as internal standard. The following abbreviations were used to explain multiplicities: s = singlet, d = doublet, dd = double doublet, dt = doublet of triplet, t = triplet, m = multiplet, br s = broad singlet. All reactions were performed under nitrogen atmosphere with freshly distilled and dried solvents. All solvents were distilled using standard procedures. Unless otherwise noted, reagents were obtained from Aldrich, Alfa Aesar, and TCI used without further purification. The starting material (1a-1e) were synthesized by the reported procedure.12

General procedure for synthesis of 3a To a 10 mL round-bottomed flask equipped with magnetic stir bar the substrates 4-hydroxy4-(phenylethynyl)cyclohexa-2,5-dien-1-one 1a (0.476 mmol, 100 mg, 1 equiv.) and Aniline 2a (0.524 mmol, 0.05 mL, 1.1 equiv.), was taken and dissolved in dry CH3CN (3 mL) at 80 o

C (oil bath). To this reaction mixture gold catalyst C (2.5 mol %, 9 mg) was added and

stirred at 80 °C for 26 h under nitrogen atmosphere. Progress of the reaction was monitored by using TLC. After completion of the reaction, the reaction mixture was filtered through celite plug and washed with ethyl acetate. The ethyl acetate layer was concentrated under reduced pressure to get crude residue which was purified by column chromatography through silica gel using hexane and ethyl acetate as eluent (10:1.5) to give product 1,2-diphenyl-1Hindol-6-ol 3a in 112 mg (82%). The same reaction was conducted in gram scale by utilizing 1a (1g) and 2a (0.5 mL) produced the corresponding product 3a in 84% yield (1.13 g). Similar experimental procedure was adopted for the synthesis of 6-hydroxy indole derivatives (3b-z). 1,2-Diphenyl-1H-indol-6-ol (3a) Rf: 0.4; Hexane: Ethyl acetate mixture (10 : 1.5); Light yellow solid with 112 mg (82%) yield; Melting Point: 152-154 °C; 1 H NMR (400 MHz, CDCl3): δ 7.51 (dd, J = 7.9, 0.9 Hz,


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1H), 7.43-7.37 (m, 2H), 7.36-7.30 (m, 1H), 7.26-7.18 (m, 8H), 6.73 (d, J = 7.9, 2H), 4.61 (br s, 1H), ppm; 13C {1 H} NMR (100 MHz, CDCl3): δ 152.0, 139.8, 138.4, 132.5, 129.2, 128.5, 128.0, 127.8, 127.1, 126.9, 122.6, 121.2, 110.5, 103.5, 96.5 ppm; IR(KBr): ΰ = 3539, 3056, 1618, 149, 1165, 761 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C20H15ONH: 286.1226, found 286.1221. 2-Phenyl-1-(p-tolyl)-1H-indol-6-ol (3b) Following the general procedure, 100 mg (0.476 mmol, 1.0 equiv.) of 1a, 0.05 mL (0.524 mmol, 1.1 equiv) of 2b and 9 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 111 mg of 3b was obtained in 78% yield as brown solid. Melting Point: 92-93 °C; 1 H NMR (400 MHz, CDCl3): δ 7.50 (d, J = 9.0 Hz, 1H), 7.26-7.18 (m, 7H), 7.11 (d, J = 8.2, 2H), 6.74-6.70 (m, 3H), 4.61 (br s, 1H), 2.39 (s, 3H) ppm; 13C {1 H} NMR (100 MHz, CDCl3): δ 152.1, 140.0, 139.9, 136.9, 135.8, 132.6, 129.8, 128.5, 128.0, 127.6, 126.9, 122.5, 121.1, 110.4, 103.2, 96.5, 21.1 ppm; IR(KBr): ΰ = 3356, 3238, 2920, 1619, 1513, 1177, 758 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C21H17ONH: 300.1382, found 300.1376. 1-(4-Bromophenyl)-2-phenyl-1H-indol-6-ol (3c) Following the general procedure, 100 mg (0.476 mmol, 1.0 equiv.) of 1a, 90 mg (0.524 mmol, 1.1 equiv) of 2c and 9 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 113 mg of 3c was obtained in 65% yield as light yellow solid. Melting Point: 128-130 °C; 1 H NMR (400 MHz, CDCl3): δ 7.54-7.49 (m, 2H), 7.28-7.20 (m, 6H), 7.10 (d, J = 8.6, 2H), 6.76-6.71 (m, 3H), 4.64 (br s, 1H) ppm;

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C {1 H} NMR (125

MHz, CDCl3): δ 152.2, 139.6, 137.5, 132.4, 132.2, 129.3, 128.6, 128.2, 127.1, 122.7, 121.3,



120.7, 110.7, 104.1, 96.3 ppm; IR(KBr): ΰ = 3331, 3056, 1618, 1490, 1171, 818 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C20H14ONBrH: 364.0331, found 364.0329. 1-(2-Hydroxyphenyl)-2-phenyl-1H-indol-6-ol (3d) Following the general procedure, 100 mg (0.476 mmol, 1.0 equiv.) of 1a, 57 mg (0.524 mmol, 1.1 equiv) of 2d and 9 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 118 mg of 3d was obtained in 82% yield as light pink solid. Melting Point: 158-160 °C; 1 H NMR (500 MHz, CDCl3): δ 7.52 (d, J = 8.4 Hz, 1H), 7.337.28 (m, 1H), 7.27-7.20 (m, 5H), 7.08 (dd, J = 8.2, 1.4 Hz, 1H), 7.02-6.99 (m, 1H), 6.92-6.88 (m, 1H), 6.80 (d, J = 0.6, Hz, 1H), 6.75 (dd, J = 8.4, 2.1 Hz, 1H), 6.47 (d, J = 2.1 Hz, 1H), 5.19 (br s, 1H), 4.66 (br s, 1H) ppm;

C {1 H} NMR (125 MHz, CDCl3): δ 152.5, 152.2,

13

140.3, 139.9, 131.7, 129.9, 129.4, 128.3, 127.8, 127.4, 124.9, 122.9, 121.5, 121.1, 116.6, 111.0, 104.0, 96.6 ppm; IR(KBr): ΰ = 3471, 3357, 2924, 1492, 1165, 756 cm-1; HRMS (ESITOF) m/z: [M+H]+ calcd for C20H15NO2H: 302.1183, found 302.1178. 1-(2-Hydroxy-5-methylphenyl)-2-phenyl-1H-indol-6-ol (3e) Following the general procedure, 100 mg (0.476 mmol, 1.0 equiv.) of 1a, 64 mg (0.524 mmol, 1.1 equiv) of 2e and 9 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 134 mg of 3e was obtained in 89% yield as light pink solid. Melting Point: 184-186 °C; 1 H NMR (400 MHz, CDCl3): δ 7.50 (d, J = 8.4 Hz, 1H), 7.297.20 (m, 5H), 7.10 (dd, J = 8.3, 1.7 Hz, 1H), 6.96 (d, J = 8.3, Hz, 1H), 6.82 (d, J = 1.7 Hz, 1H), 6.78 (d, J = 0.3 Hz, 1H), 6.73 (dd, J = 8.4, 2.2 Hz, 1H), 6.46 (d, J = 2.2 Hz, 1H), 5.03 (br s, 1H), 4.68 (br s, 1H), 2.20 (s, 3H) ppm; 13C {1 H} NMR (75 MHz, DMSO-d6 & CDCl3): δ 153.0, 150.7, 140.1, 139.2, 132.5, 129.5, 129.0, 128.2, 127.4, 127.0, 125.9, 124.8, 121.0,


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120.0, 116.1, 110.1, 101.9, 96.2, 19.6 ppm; IR(KBr): ΰ = 3490, 3384, 2923, 1510, 1171, 763 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C21H17NO2H: 316.1336, found 316.1331. 1-(5-Chloro-2-hydroxyphenyl)-2-phenyl-1H-indol-6-ol (3f) Following the general procedure, 100 mg (0.476 mmol, 1.0 equiv.) of 1a, 75 mg (0.524 mmol, 1.1 equiv) of 2f and 9 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 116 mg of 3f was obtained in 73% yield as light pink solid. Melting Point: 166-168 °C; 1 H NMR (400 MHz, CDCl3): δ 7.51 (d, J = 8.4 Hz, 1H), 7.317.23 (m, 6H), 7.07-6.98 (m, 2H), 6.83-6.72 (m, 2H), 6.46 (s, 1H), 5.20-4.66 (m, 2H) ppm; 13C {1 H} NMR (75 MHz, DMSO-d6 & CDCl3): δ 152.8, 151.8, 139.3, 138.4, 131.7, 128.3, 127.7, 126.9, 126.3, 125.7, 125.6, 121.8, 120.3, 119.5, 117.0, 109.7, 101.7, 95.3 ppm; IR(KBr): ΰ = 3495, 3363, 2923, 1491, 1168, 761 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C20H14ClNO2H: 336.0794, found 336.0791. 1-(2-Hydroxyphenyl)-2-(p-tolyl)-1H-indol-6-ol (3g) Following the general procedure, 100 mg (0.446 mmol, 1.0 equiv.) of 1b, 54 mg (0.491 mmol, 1.1 equiv) of 2d and 8.5 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 135 mg of 3g was obtained in 90% yield as light pink solid. Melting Point: 192-194 °C; 1 H NMR (500 MHz, CDCl3): δ 7.51 (d, J = 8.4 Hz, 1H), 7.337.29 (m, 1H), 7.16-7.14 (m, 2H), 7.09 (dd, J = 8.2, 1.2 Hz, 1H), 7.04 (d, J = 8.2 Hz, 2H), 7.02 (dd, J = 7.9, 1.6 Hz, 1H), 6.93-6.89 (m, 1H), 6.77-6.73 (m, 2H), 6.47 (d, J = 2.1 Hz, 1H), 5.19 (br s, 1H), 4.69 (br s, 1H), 2.29 (s, 3H) ppm;

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C {1 H} NMR (75 MHz, DMSO-d6 &

CDCl3): δ 152.9, 152.7, 139.5, 138.9, 135.2, 129.3, 129.1, 128.1, 127.8, 126.6, 125.0, 120.6, 119.5, 118.6, 116.0, 109.7, 101.1, 95.9, 20.1 ppm; IR(KBr): ΰ = 3514, 3348, 2920, 1500,



1159, 754 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C21H17NO2H: 316.1337, found 316.1332. 1-(2-Hydroxy-5-methylphenyl)-2-(p-tolyl)-1H-indol-6-ol (3h) Following the general procedure, 100 mg (0.446 mmol, 1.0 equiv.) of 1b, 60 mg (0.491 mmol, 1.1 equiv) of 2e and 8.5 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 124 mg of 3h was obtained in 79% yield as light pink solid. Melting Point: 154-156 °C; 1 H NMR (400 MHz, CDCl3): δ 7.49 (d, J = 8.4 Hz, 1H), 7.17 (d, J = 8.3 Hz, 2H), 7.10 (dd, J = 8.4, 1.8 Hz, 1H), 7.04 (d, J = 8.4 Hz, 2H), 6.96 (d, J = 8.3 Hz, 1H), 6.84 (s,1H), 6.75-6.70 (m, 2H), 6.46 (s, 1H), 4.99 (br s, 1H), 4.64 (br s, 1H), 2.29 (s, 3H), 2.22 (s, 3H) ppm;

C {1 H} NMR (100 MHz, CDCl3): δ 152.3, 149.9, 140.3, 140.0,

13

137.2, 130.5, 130.4, 129.5, 129.0, 128.9, 127.6, 124.7, 122.8, 121.2, 116.3, 110.9, 103.3, 96.6, 21.1, 20.3 ppm; IR(KBr): ΰ = 3475, 3381, 2921, 1509, 1176, 816 cm-1; HRMS (ESITOF) m/z: [M+H]+ calcd for C22H19NO2H: 330.1488, found 330.1489. 1-(5-Chloro-2-hydroxyphenyl)-2-(p-tolyl)-1H-indol-6-ol (3i) Following the general procedure, 100 mg (0.446 mmol, 1.0 equiv.) of 1b, 70 mg (0.491 mmol, 1.1 equiv) of 2f and 8.5 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 122 mg of 3i was obtained in 73% yield as light pink solid. Melting Point: 159-161 °C; 1 H NMR (400 MHz, CDCl3): δ 7.49 (d, J = 8.3 Hz, 1H), 7.27 (dd, J = 8.8, 2.5 Hz, 1H), 7.14 (d, J = 8.3 Hz, 2H), 7.09-6.99 (m, 4H), 6.74 (dd, J = 8.3, 2.2 Hz, 2H), 6.45 (d, J = 2.2 Hz, 1H), 5.25 (br s, 1H), 4.72 (br s, 1H), 2.31 (s, 3H) ppm; 13C {1 H} NMR (100 MHz, CDCl3): 152.4, 151.1, 140.2, 139.7, 137.5, 129.9, 129.2, 128.4, 127.6, 126.0, 125.3, 122.9, 121.4, 117.7, 111.2, 103.9, 96.5, 21.1 ppm; IR(KBr): ΰ = 3511, 3369,


Page 14 of 28

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2923, 1492, 1171, 818 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C21H16ClNO2H: 350.0942, found 350.0949. Crystal Data 3i: C23H22ClNO3 (M =395.89 g/mol): monoclinic, space group P21/n (no. 14), a = 11.0192(2) Å, b = 10.5869(2) Å, c = 17.8709(4) Å, β = 100.0058(9)°, V = 2053.09(7) Å3, Z = 4, T = 294.15 K, μ(Mo Kα) = 0.209 mm-1, Dcalc = 1.2807 g/cm3, 39699 reflections measured (4.48° ≤ 2Θ ≤ 52.5°), 4138 unique (Rint = 0.0934, Rsigma = 0.0814) which were used in all calculations. The final R1 was 0.0560 (I>2u(I)) and wR2 was 0.1499 (all data). CCDC1940475 contains supplementary Crystallographic data for the structure. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre (CCDC), 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0) 1223 336 033; email: [email protected]]. 1-(2-Hydroxyphenyl)-2-(4-methoxyphenyl)-1H-indol-6-ol (3j) Following the general procedure, 100 mg (0.416 mmol, 1.0 equiv.) of 1c, 50 mg (0.458 mmol, 1.1 equiv) of 2d and 8 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 148 mg of 3j was obtained in 94% yield as light yellow solid. Melting Point: 156-158 °C; 1 H NMR (400 MHz, CDCl3): δ 7.46 (d, J = 8.4 Hz, 1H), 7.29 (t, J = 8.1, Hz, 1H), 7.16 (d, J = 8.6, Hz, 2H), 7.06 (d, J = 0.069 Hz, 1H), 6.99 (d, J = 8.1 Hz, 1H), 6.90 (t, J = 7.4, Hz, 1H), 6.78-6.67 (m, 4H), 6.42 (d, J = 1.1 Hz, 1H), 5.55-4.20 (m, 2H), 3.74 (s, 3H) ppm;

13

C {1 H} NMR (75 MHz, DMSO-d6 & CDCl3): δ 157.6, 153.1, 152.6,

139.5, 138.9, 129.3, 128.2, 125.1, 124.9, 120.8, 119.6, 118.8, 116.2, 112.7, 109.8, 100.7, 96.0, 54.2 ppm; IR(KBr): ΰ = 3477, 3375, 2928, 1500, 1158, 752 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C21H17NO3H: 332.1286, found 332.1281.



Page 16 of 28

1-(2-Hydroxy-5-methylphenyl)-2-(4-methoxyphenyl)-1H-indol-6-ol (3k) Following the general procedure, 100 mg (0.416 mmol, 1.0 equiv.) of 1c, 56 mg (0.458 mmol, 1.1 equiv) of 2e and 8 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 143 mg of 3k was obtained in 87% yield as brown solid. Melting Point: 140-142 °C; 1 H NMR (400 MHz, CDCl3): δ 7.48 (d, J = 8.4 Hz, 1H), 7.227.18 (m, 2H), 7.11 (dd, J = 8.4, 1.6 Hz, 1H), 6.96 (d, J = 8.4, Hz, 1H), 6.84 (d, J = 1.6 Hz, 1H), 6.79-6.76 (m, 2H), 6.72 (dd, J = 8.4, 2.2 Hz, 1H), 6.69 (d, J = 0.5 Hz, 1H), 6.45 (d, J = 2.2 Hz, 1H), 5.11-4.52 (m, 2H), 3.76 (s, 3H), 2.22 (s, 3H) ppm;

13

C {1 H} NMR (125 MHz,

CDCl3): δ 158.8, 152.1, 149.9, 140.1, 139.8, 130.5, 130.4, 129.6, 129.0, 124.6, 124.4, 122.7, 121.0, 116.3, 113.7, 110.8, 102.7, 96.6, 55.1, 20.3 ppm; IR(KBr): ΰ = 3484, 3397, 2925, 1505, 1178, 816 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C22H19NO3H: 346.1437, found 346.1440. 1-(5-Chloro-2-hydroxyphenyl)-2-(4-methoxyphenyl)-1H-indol-6-ol (3l) Following the general procedure, 100 mg (0.416 mmol, 1.0 equiv.) of 1c, 65 mg (0.458 mmol, 1.1 equiv) of 2f and 8 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 150 mg of 3l was obtained in 86% yield as brown solid. Melting Point: 93-95 °C; 1 H NMR (500 MHz, CDCl3): δ 7.48 (d, J = 8.4 Hz, 1H), 7.28 (dd, J = 8.7, 2.3 Hz, 1H), 7.18 (d, J = 8.7 Hz, 2H), 7.05 (d, J = 2.3 Hz, 1H), 7.01 (d, J = 8.7 Hz, 1H), 6.80 (d, J = 8.7 Hz, 2H), 6.74 (d, J = 8.7 Hz, 1H), 6.70-6.69 (m, 1H), 6.45 (s, 1H), 5.354.53 (m, 2H), 3.78 (s, 3H) ppm;

C {1 H} NMR (75 MHz, DMSO-d6 & CDCl3): δ 158.3,

13

153.3, 152.4, 139.9, 139.4, 129.3, 128.7, 126.6, 125.0, 123.3, 121.6, 120.3, 117.9, 115.7, 113.4, 110.6, 101.9, 96.4, 54.8 ppm; IR(KBr): ΰ = 3484, 3377, 2931, 1498, 1178, 819 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C21H16ClNO3H: 366.0891, found 366.0901.


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2-(4-Fluorophenyl)-1-(2-hydroxyphenyl)-1H-indol-6-ol (3m) Following the general procedure, 100 mg (0.438 mmol, 1.0 equiv.) of 1d, 52 mg (0.482 mmol, 1.1 equiv) of 2d and 8.5 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 119 mg of 3m was obtained in 78% yield as light yellow solid. Melting Point: 160-162 °C; 1 H NMR (400 MHz, CDCl3): δ 7.50 (d, J = 8.4 Hz, 1H), 7.34-7.29 (m, 1H), 7.24-7.18 (m, 2H), 7.08 (dd, J = 8.2, 0.8 Hz, 1H), 7.00-6.89 (m, 4H), 6.76-6.72 (m, 2H), 6.45 (d, J = 1.8 Hz, 1H), 5.20 (br s, 1H), 4.70 (br s, 1H), ppm; 13C {1 H} NMR (100 MHz, CDCl3): δ 162.1 (d, 3JC-F = 247.214 Hz), 152.5, 152.2, 139.8, 139.3, 130.0, 129.6 (d, 2JC-F = 8.0 Hz), 129.5, 127.9, 124.7, 122.7, 121.4, 121.2, 116.7, 115.3 (d, 1JC-F = 21.274 Hz), 111.1, 103.8, 96.5 ppm; IR(KBr): ΰ = 3476, 3381, 2931, 1495, 1159, 822 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C20H14FNO2H: 320.1081, found 320.1102. 2-(4-Fluorophenyl)-1-(2-hydroxy-5-methylphenyl)-1H-indol-6-ol (3n) Following the general procedure, 100 mg (0.438 mmol, 1.0 equiv.) of 1d, 60 mg (0.482 mmol, 1.1 equiv) of 2e and 8.5 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 125 mg of 3n was obtained in 79% yield as light pink solid. Melting Point: 104-106 °C; 1 H NMR (400 MHz, CDCl3): δ 7.51 (d, J = 8.4 Hz, 1H), 7.257.21 (m, 2H), 7.11 (dd, J = 8.4, 1.8 Hz, 1H), 7.00-6.90 (m, 3H), 6.81 (d, J = 1.8 Hz, 1H), 6.77-6.72 (m, 2H), 6.47 (d, J = 2.1 Hz, 1H), 4.96 (br s, 1H), 4.68 (br s, 1H), 2.22 (s, 3H) ppm; 13C {1 H} NMR (75 MHz, CDCl3): δ 162.1 (d, 3JC-F = 247.581 Hz), 152.4, 149.9, 139.9, 139.2, 130.7, 130.6, 129.5 (d, 2JC-F = 7.703 Hz), 128.0,124.4, 122.7, 121.4, 116.4, 115.3 (d, 1

JC-F = 21.457 Hz), 111.1, 103.7, 96.6, 20.3 ppm; IR(KBr): ΰ = 3422, 3381, 2923, 1501,

1179, 819 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C21H16FNO2H: 334.1237, found 334.1237.



1-Methyl-2-phenyl-1H-indol-6-ol (3o)18 Following the general procedure, 100 mg (0.476 mmol, 1.0 equiv.) of 1a, 0.02 mL (0.524 mmol, 1.1 equiv) of 2g and 9 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 18h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 77 mg of 3o was obtained in 72% yield as pale yellow solid. Melting Point: 152-154 °C; 1 H NMR (400 MHz, CDCl3): δ 7.50-7.42 (m, 5H), 7.40-7.34 (m, 1H), 6.80 (d, J = 2.2 Hz, 1H), 6.69 (dd, J = 8.4, 2.2 Hz, 1H), 6.47 (d, J = 0.6 Hz, 1H), 4.80 (br s, 1H), 3.65 (s, 3H). ppm; 13C {1 H} NMR (75 MHz, DMSO-d6 & CDCl3): δ 152.8, 139.4, 139.1, 132.4, 128.4, 127.9, 126.8, 120.8, 120.2, 109.8, 100.8, 94.9, 30.7 ppm; IR(KBr): ΰ = 3241, 3052, 1621, 1493, 1205, 815 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C15H12ONH: 224.1069, found 224.1068. 1-Benzyl-2-phenyl-1H-indol-6-ol (3p) Following the general procedure, 100 mg (0.476 mmol, 1.0 equiv.) of 1a, 0.057 mL (0.524 mmol, 1.1 equiv) of 2h and 9 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 91 mg of 3p was obtained in 64% yield as pale yellow solid. Melting Point: 151-153 °C; 1 H NMR (400 MHz, CDCl3): δ 7.49 (d, J = 8.4 Hz, 1H), 7.437.20 (m, 8H), 7.03 (d, J = 6.8 Hz, 2H), 6.69 (dd, J = 8.4, 2.2 Hz, 1H), 6.60 (d, J = 2.2 Hz, 1H), 6.57 (d, J = 0.6 Hz, 1H), 5.27 (s, 2H), 4.63 (br s, 1H). ppm; 13C {1 H} NMR (100 MHz, CDCl3): δ 151.7, 141.0, 138.9, 137.9, 132.6, 128.9, 128.7, 128.4, 127.7, 127.1, 125.9, 122.7, 121.2, 110.0, 102.1, 96.4, 47.7 ppm; IR(KBr): ΰ = 3497, 3039, 1619, 1487, 1161, 784 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C21H16ONH: 300.1383, found 300.1389. 1-Cyclohexyl-2-phenyl-1H-indol-6-ol (3q) Following the general procedure, 100 mg (0.476 mmol, 1.0 equiv.) of 1a, 0.06 mL (0.524 mmol, 1.1 equiv) of 2i and 9 mg (2.5 mol %,) of gold catalyst C was used and the reaction


Page 18 of 28

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time was 12h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 29 mg of 3q was obtained in 21% yield as light brown solid. Melting Point: 166-168 °C; 1 H NMR (400 MHz, CDCl3): δ 7.47-7.36 (m, 6H), 7.13 (d, J = 1.9 Hz, 1H), 6.66 (dd, J = 8.4, 1.9 Hz, 1H), 6.38 (s, 1H), 4.65 (br s, 1H), 4.20-4.10 (m, 1H), 2.40-2.26 (m, 2H), 1.93-1.82 (m, 4H), 1.73-1.64 (m, 1H), 1.32-1.20 (m, 3H) ppm; 13C {1 H} NMR (100 MHz, CDCl3): δ 150.6, 140.8, 136.6, 133.8, 129.3, 128.3, 127.6, 123.4, 121.1, 109.2, 102.1, 98.7, 56.2, 31.1, 26.1, 25.4 ppm; IR(KBr): ΰ = 3386, 2928, 1618, 1484, 1182, 758 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C20H20ONH: 292.1696, found 292.1708. 1-(Furan-3-ylmethyl)-2-phenyl-1H-indol-6-ol (3s) Following the general procedure, 100 mg (0.476 mmol, 1.0 equiv.) of 1a, 0.05 mL (0.524 mmol, 1.1 equiv) of 2k and 9 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 76 mg of 3s was obtained in 55% yield as light yellow solid. Melting Point: 116-118 °C; 1 H NMR (400 MHz, CDCl3): δ 7.54-7.51 (m, 2H), 7.48-7.33 (m, 5H), 6.86 (d, J = 2.2 Hz, 1H), 6.70 (dd, J = 8.4, 2.2 Hz, 1H), 6.50 (d, J = 0.7 Hz, 1H), 6.28 (dd, J = 3.2, 1.8 Hz, 1H), 6.07 (dd, J = 3.2, 0.7 Hz, 1H), 5.15 (s, 2H), 4.73 (br s, 1H). ppm; C {1 H} NMR (100 MHz, CDCl3): δ 151.7, 150.9, 142.1, 140.7, 139.0, 132.6, 129.3, 128.5,

13

127.8, 122.7, 121.1, 110.3, 110.1, 107.5, 102.3, 96.4, 41.7 ppm; IR(KBr): ΰ = 3465, 3290, 1617, 1335, 1194, 752 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C19H15O2NH: 290.1175, found 290.1195. 1-(2-Hydroxyphenyl)-2-propyl-1H-indol-6-ol (3t) Following the general procedure, 100 mg (0.568 mmol, 1.0 equiv.) of 1e, 68 mg (0.625 mmol, 1.1 equiv) of 2d and 11 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 106 mg of 3t was obtained in 83% yield as light brown solid.



Page 20 of 28

Melting Point: 114-116 °C; 1 H NMR (400 MHz, CDCl3): δ 7.40-7.35 (m, 2H), 7.16-7.10 (m, 2H), 7.05-6.99 (m, 1H), 6.63 (dd, J = 8.4, 2.2 Hz, 1H), 6.35 (d, J = 0.8 Hz, 1H), 6.30 (d, J = 2.2 Hz, 1H), 5.12 (br s, 1H), 4.59 (br s, 1H), 2.44 (t, J = 7.5 Hz, 2H), 1.57 (h, J = 7.5 Hz, 2H), 0.89(t, J = 7 .5 Hz, 3H), ppm;

13

C {1 H} NMR (125 MHz, CDCl3): δ 152.7, 151.5, 141.1,

138.5, 130.2, 129.5, 123.8, 122.7, 121.0, 120.5, 116.6, 110.1, 100.8, 96.1, 28.7, 21.5, 13.8 ppm; IR(KBr): ΰ = 3484, 3344, 2957, 1501, 1162, 756 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C17H17NO2H: 268.1342, found 268.1337. 1-(2-Hydroxy-5-methylphenyl)-2-propyl-1H-indol-6-ol (3u) Following the general procedure, 100 mg (0.568 mmol, 1.0 equiv.) of 1e, 76 mg (0.625 mmol, 1.1 equiv) of 2e and 11 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 116 mg of 3u was obtained in 86% yield as light yellow solid. Melting Point: 98-100 °C; 1 H NMR (500 MHz, CDCl3): δ 7.40 (d, J = 8.4 Hz, 1H), 7.18 (dd, J = 8.4, 1.6 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H), 6.95 (d, J = 1.6 Hz, 1H), 6.67 (dd, J = 8.4, 2.3 Hz, 1H), 6.37-6.35 (m, 2H), 4.81 (br s, 1H), 4.51 (br s, 1H), 2.46 (t, J = 7.6 Hz, 2H), 2.32 (s, 3H), 1.59 (h, J = 7.6 Hz, 2H), 0.91 (t, J = 7.6 Hz, 3H), ppm;

13

C {1 H} NMR (100 MHz,

CDCl3): δ 151.3, 150.3, 141.2, 138.6, 130.7, 130.4, 129.7, 123.4, 122.5, 120.3, 116.4, 110.0, 100.4, 96.1, 28.6, 21.5, 20.3, 13.8 ppm; IR(KBr): ΰ = 3470, 3382, 2928, 1511, 1183, 770 cm1

; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C18H19NO2H: 282.1501, found 282.1498.

1-(5-Chloro-2-hydroxyphenyl)-2-propyl-1H-indol-6-ol (3v) Following the general procedure, 100 mg (0.568 mmol, 1.0 equiv.) of 1e, 89 mg (0.625 mmol, 1.1 equiv) of 2f and 11 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 69 mg of 3v was obtained in 48% yield as light brown solid. Melting Point: 92-94 °C; 1 H NMR (400 MHz, CDCl3): δ 7.39 (d, J = 8.3 Hz, 1H), 7.35 (dd, J


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= 8.8, 2.4 Hz, 1H), 7.17 (d, J = 2.4 Hz, 1H), 7.07 (d, J = 8.8 Hz, 1H), 6.67 (dd, J = 8.3, 2.1 Hz, 1H), 6.39-6.32 (m, 2H), 5.30-4.49 (m, 2H), 2.45 (t, J = 7.3 Hz, 2H), 1.58 (h, J = 7.3 Hz, 2H), 0.92 (t, J = 7.3 Hz, 3H) ppm; 13C {1 H} NMR (125 MHz, CDCl3): δ 151.7, 151.6, 140.8, 138.4, 130.3, 129.3, 125.3, 124.8, 122.7, 117.8, 110.3, 101.4, 95.9, 28.6, 21.5, 13.8 ppm; IR(KBr): ΰ = 3472, 3360, 2930, 1492, 1189, 821 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C17H16ClNO2H: 302.0946, found 302.0942. 1-(2-Aminophenyl)-2-phenyl-1H-indol-6-ol (3w) Following the general procedure, 100 mg (0.476 mmol, 1.0 equiv.) of 1a, 56 mg (0.524 mmol, 1.1 equiv) of 2l and 9 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 102 mg of 3w was obtained in 71% yield as brown solid. Melting Point: 142-144 oC; 1 H NMR (500 MHz, CDCl3): δ 7.51 (d, J = 8.5 Hz, 1H), 7.337.21 (m, 2H), 7.25-7.17 (m, 4H), 6.96 (dd, J = 7.7, 1.3 Hz, 1H), 6.80 (dd, J = 8.8, 1.2 Hz, 1H), 6.76 (d, J = 0.6, 1H), 6.75-6.70 (m, 2H), 6.46 (d, J = 2.1, 1H), 4.76 (br s, 1H), 3.60 (br s, 2H) ppm;

13

C {1 H} NMR (100 MHz, CDCl3): δ 152.2, 14.7, 140.0, 139.5, 132.3, 129.8,

129.3, 128.2, 127.7, 127.1, 124.0, 122.7, 121.2, 118.7, 116.1, 110.6, 103.0, 96.7 ppm; IR(KBr): ΰ = 3475, 3377, 2925, 1619, 1501, 1358, 1151, 757 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C20H16ON2H: 301.1335, found 301.1327. 1-(2-Aminophenyl)-2-(p-tolyl)-1H-indol-6-ol (3x) Following the general procedure, 100 mg (0.446 mmol, 1.0 equiv.) of 1b, 53 mg (0.491 mmol, 1.1 equiv) of 2l and 8.5 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 103 mg of 3x was obtained in 69% yield as light yellow solid. Melting Point: 166-168 °C; 1 H NMR (400 MHz, CDCl3): δ 7.50 (d, J = 8.4 Hz, 1H), 7.237.17 (m, 3H), 7.03 (d, J = 8.1 Hz, 2H), 6.98 (dd, J = 7.8, 1.3 Hz, 1H), 6.82-6.79 (m, 1H),



6.76-6.69 (m, 3H), 6.46 (d, J = 1.9, 1H), 4.66 (br s, 1H), 3.59 (br s, 2H), 2.28 (s, 3H) ppm; C {1 H} NMR (75 MHz, DMSO-d6 & CDCl3): δ 153.0, 149.0, 143.7, 138.8, 138.4, 135.5,

13

128.8, 128.7, 128.1, 127.9, 126.6, 122.9, 120.7, 119.8, 116.7, 115.0, 114.9, 110.1, 101.4, 95.5, 20.1 ppm; IR(KBr): ΰ = 3509, 3382, 2919, 1617, 1503, 1362, 1153, 747 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C21H18ON2H: 315.1491, found 315.1485. 1-(2-Aminophenyl)-2-(4-fluorophenyl)-1H-indol-6-ol (3y) Following the general procedure, 100 mg (0.438 mmol, 1.0 equiv.) of 1d, 57 mg (0.482 mmol, 1.1 equiv) of 2l and 8.5 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 86 mg of 3y was obtained in 57% yield as light yellow solid. Melting Point: 116-118 °C; 1 H NMR (500 MHz, CDCl3): δ 7.51 (d, J = 8.4 Hz, 1H), 7.307.27 (m, 2H), 7.22-7.18 (m, 1H), 6.96-6.90 (m, 3H), 6.82 (dd, J = 8.1, 1.2 Hz, 1H), 6.75-6.70 (m, 3H), 6.47 (d, J = 2.2 Hz, 1H), 4.66 (br s, 1H), 3.60 (br s, 2H) ppm; 13C {1 H} NMR (75 MHz, DMSO-d6 & CDCl3): δ 161.1(d, 3JC-F = 246.214 Hz), 153.5, 149.4, 144.0, 139.2, 137.7, 129.1, 128.9, 128.7(d, 2JC-F = 8.670 Hz), 128.3, 121.0, 120.3, 117.2, 115.4, 115.3, 114.5(d, 1

JC-F = 21.385 Hz),110.6, 102.2, 95.9 ppm; IR(KBr): ΰ = 3363, 3275, 2920, 1615,1497, 1171,

827 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C20H15ON2FH: 319.1241, found 319.1235. 4-(6-Hydroxy-2-phenyl-1H-indol-1-yl)benzonitrile (3z) Following the general procedure, 100 mg (0.476 mmol, 1.0 equiv.) of 1a, 62 mg (0.524 mmol, 1.1 equiv) of 2m and 9 mg (2.5 mol %,) of gold catalyst C was used and the reaction time was 26h. After flash column chromatography on silica gel (eluted with Rf: 0.4; Hexane: Ethyl acetate mixture 10 : 1.5), 98 mg of 3z was obtained in 67% yield as white solid. Melting Point: 203-205 °C; 1 H NMR (400 MHz, CDCl3): δ 7.70-7-65 (m, 2H), 7.52 (d, J = 8.314 Hz, 1H), 7.32 (d, J = 8.314 Hz, 2H), 7.28-7.24 (m, 3H), 7.20-7.15 (m, 2H), 6.82-6.74


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(m, 3H), 4.92-4.84 (m, 1H) ppm; 13C {1 H} NMR (100 MHz, CDCl3): δ 152.7, 142.6, 139.3, 139.1, 133.1, 131.8, 128.6, 128.4, 128.1, 127.5, 122.9, 121.6, 118.2, 111.2, 110.2, 105.5, 96.2 ppm; IR(KBr): ΰ = 3382, 3060, 2233, 1597, 1373, 1221, 1176, 756 cm-1; HRMS (ESI-TOF) m/z: [M+H]+ calcd for C21H14ON2H: 311.1178, found 311.1201. ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: Copies of 1H, 13C NMR spectra for all new products (3a-3z) (PDF) Single crystal X-ray data for 3i (CIF). AUTHOR INFORMATION Corresponding Author *E-mail: [email protected] Notes The authors declare no competing financial interest. ACKNOWLEDGMENTS We thank Department of Science and Technology (DST) India grant no: DST-SB/EMEQ257/2014 and CSIR, New Delhi for financial support. We are thankful to Director Dr. S. Chandrasekhar CSIR-IICT for his support. We acknowledge our colleagues from CSIR-IICT Dr. S. Suresh, Dr. K. Srinivas and Dr. Rajesh for their encouragement. V. K thanks to UGCSRF, P. B. K thanks to DST for Inspire fellowship and also thanks to AcSIR, manuscript communication number:IICT/pubs.2019/265.



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REFERENCES (1) (a) Handbook of Marine Natural Products; Fattorusso, E., Gerwick, W. H., TaglialatelaScafati, O., Eds.; Springer: Dordrecht, 2012. (b) Cragg, G. M.; Newman, D. J. Antineoplastic Agents from Natural Sources: Achievements and future Directions. Expert Opin. Invest. Drugs. 2000, 9, 2783. (c) (a) Ayres, D.; Loike, J. D. Chemistry and pharmacology of natural products. Lignans: chemical, biological and clinical properties; Cambridge University Press: Cambridge, 1990. (2) (a) Brown, E. G. Ring Nitrogen and Key Biomolecules. The Biochemistry of Nheterocycles, Kluwer Academic, Boston. 1998. (b) Majumdar, K. C.; Karunakar, G. V.; Sinha, B. Formation of Five-and Six-Membered Heterocyclic Rings under Radical Cyclization Conditions. Synthesis 2012, 2475. (c) Eicher, T.; Hauptmann, S. The Chemistry of Heterocycles: Structure, Reactions, Syntheses, and Applications, 2nd ed.; Wiley-VCH: Weinheim, Germany, 2003. (3) (a) Mewshaw, R. E.; Webb, M. B.; Marquis, K. L.; McGaughey, G. B.; Shi, X.; Wasik, T.; Scerni, R.; Brennan, J. A.; Andree, T. H. New Generation Dopaminergic Agents. 6. Structure-Activity Relationship Studies of a Series of 4-(Aminoethoxy)indole and 4(Aminoethoxy)indolone

Derivatives

Based

on

the

Newly

Discovered

3-

Hydroxyphenoxyethylamine D2 Template. J. Med. Chem. 1999, 42, 2007. (b) Grollier, J. F.; Cotteret, J. Process for Dyeing Keratinous Fibres Based on Monohydroxyindole and 5,6disubstituted Hydroxyindole and Composition Employed. FR 2649009, 1991. (c) Sharma, V.; Kumar, P.; Pathak, D. Biological Importance of the Indole Nucleus in Recent Years: A Comprehensive Review. J. Heterocycl. Chem. 2010, 47, 491. (d) MacDonough, M. T.; Strecker, T. E.; Hamel, E.; Hall, J. J.; Chaplin, D. J.; Trawick, M. L.; Pinney, K. G. Synthesis and Biological Evaluation of Indole-based, Anti-Canceragents Inspired by the Vascular


Page 25 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Disrupting

Agent

2-(3’-Hydroxy-4’-Methoxyphenyl)-3-(3’’,4”,5’’-trimethoxybenzoyl)-6-

Methoxyindole(OXi8006). Bioorg. Med. Chem. 2013, 21, 6831. (e) Pare, C. M. B.; Sandler, M.; Stacey, R. S. 5-Hydroxyindoles in Mental Deficiency. J. Neurol., Neurosurg. Psychiatry 1960, 23, 341. (f) Igarashi, S.; Inami, H.; Hara, H.; Koutoku, H.; Oritani, H.; Mase, T. A Novel Class of Inhibitors for Human and Rat Steroid 5alpha-Reductases: Synthesis and Biological Evaluation of Indoline and Aniline Derivatives. III. Chem. Pharm. Bull. 2000, 48, 1689. (4) Cohen, J.; Paul, G.; Gunasekera, S.; Longley, R.; Pomponi, S. A New Discodermindole from the Marine Sponge Discodermia Polydiscus. Pharm. Bol. 2004, 42, 59. (5) Capon, R. J.; Peng, C.; Dooms, C. Trachycladindoles A-G: Cytotoxic heterocycles from an Australian Marine Sponge, Trachycladus laevispirulifer. Org. Biomol. Chem. 2008, 6, 2765. (6) Endo, T.; Tsuda, M.; Fromont, J.; Kobayashi, J. I. Hyrtinadine A, a Bis-indole Alkaloid from a Marine Sponge. J. Nat. Prod. 2007, 70, 423. (7) Jimenez, P. C.; Wilke, D. V.; Ferreira, E. G.; Takeara, R.; de Moraes, M. O.; Silveira, E. R.; da Cruz Lotufo, T. M.; Lopes, N. P.; Costa-Lotufo, L. V. Structure Elucidation and Anticancer Activity of 7-Oxostaurosporine Derivatives from the Brazilian Endemic Tunicate Eudistoma vannamei. Mar. Drugs 2012, 10, 109 (8) (a) Zhao, C.; Feng, P.; Cao, J.; Zhang, Y.; Wang, X.; Yang, Y.; Zhang, Y.; Zhang, J. 6Hydroxyindole-based Borondipyrromethene: Synthesis and Spectroscopic Studies. Org. Biomol. Chem. 2012, 10, 267. (b) Cao, J.; Zhao, C.; Wang, X.; Zhang, Y.; Zhu, W. TargetTriggered Deprotonation of 6-Hydroxyindole-based BODIPY: Specially Switch on NIR Fluorescence upon Selectively Binding to Zn2+. Chem. Commun. 2012, 48, 9897.



(9) Reddy, R. R.; Adlak, K.; Ghorai, P. Catalyst-free Synthesis of 6-Hydroxy Indoles via the Condensation of Carboxymethyl Cyclohexadienones and Amines. J. Org. Chem. 2017, 82, 8426. (10) (a) Lerman, L.; Weinstock-Rosin, M. W.; Nudelman, A. An Improved Synthesis of Hydroxyindoles. Synthesis 2004, 18, 3043. (b) Zhou, B.; Liu, Z. -C.; Qu, W. -W.; Yang, R.; Lin, X. -R.; Yan, S. -J.; Lin, J. An Environmentally Benign, Mild, and Catalyst-free Reaction of Quinones with Heterocyclic Ketene Aminals in Ethanol: Site-Selective Synthesis of Rarely Fused [1,2-a]Indolone Derivatives via an Unexpected Anti-Nenitzescu Strategy. Green Chem. 2014, 16, 4359. (c) Shvedov, V. I.; Panisheva, E. K.; Vlasova, T. F.; Grinev, A. N. Synthesis and Aminomethylation of 6-Hydroxyindoles. Chem. Heterocycl. Compd. 1973, 9, 1225. (d) Gribble, G. W. Recent Developments in Indole Ring Synthesis-Methodology and Applications. J. Chem. Soc., Perkin Trans. 1 2000, 1045. (e) Raucher, S.; Koolpe, G. A. Synthesis of Substituted Indoles via Meerwein Arylation. J. Org. Chem. 1983, 48, 2066. (11) Zhao, J.; Liu, J.; Xie, X.; Li, S.; Liu, Y. Gold-Catalyzed Synthesis of Tropone and Its Analogues via Oxidative Ring Expansion of Alkynyl Quinols. Org. Lett. 2015, 17, 5926. (12) (a) Yoon, S.; Jung, Y.; Kim, I. Catalyst-free Synthesis of 4-Alkynylazobenzenes from Quinols. Tetrahedron Lett. 2017, 58, 1590. (b) Kim, I.; Kim, K.; Choi, J. A direct Approach to 5-Hydroxybenzofurans via a Platinum-Catalyzed Domino Rearrangement/5-Endo-Dig Cyclization Reaction of Quinols. J. Org. Chem. 2009, 74, 8492. (13) (a) Hashmi, A. S. K. Gold-Catalyzed Organic Reactions. Chem. Rev. 2007, 107, 3180. (b) Krause, N.; Winter, C. Gold-Catalyzed Nucleophilic Cyclization of Functionalized Allenes: A Powerful Access to Carbo- and Heterocycles. Chem. Rev. 2011, 111, 1994. (c) Arcadi, A. Alternative Synthetic Methods through New Developments in Catalysis by Gold. Chem. Rev. 2008, 108, 3266. (d) Jiménez-Núñez, E.; Echavarren, A. M. Gold-Catalyzed Cycloisomerizations of Enynes: A Mechanistic Perspective. Chem. Rev. 2008, 108, 3326. (e)


Page 26 of 28

Page 27 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Hashmi, A. S. K.; Hutchings, G. J. Gold Catalysis. Angew. Chem., Int. Ed. 2006, 45, 7896. (f) Fürstner, A.; Davis, P. W. Catalytic Carbophilic Activation: Catalysis by Platinum and Gold pi Acids. Angew. Chem., Int. Ed. 2007, 46, 3410. (g) Gorin, D. J.; Toste, F. D. Relativistic Effects in Homogeneous Gold Catalysis. Nature 2007, 446, 395. (14) (a) Dorel, R.; Echavarren, A. M. Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity. Chem. Rev. 2015, 115, 9028. (b) Asiria, A. M.; Hashmi, A. S. K. Gold-Catalysed Reactions of Diynes. Chem. Rev. 2016, 45, 4471. (c) Hashmi A. S. K.; Toste, F. D. Modern Gold Catalyzed Synthesis. Wiley-VCH, Weinheim. 2012. (d) Rudolph, M.; Hashmi, A. S. K. Heterocycles from Gold Catalysis. Chem. Commun. 2011, 47, 6536. (e) Li, Z.; Brouwer, C.; C. He. Gold-Catalyzed Organic Transformations. Chem. Rev. 2008, 108, 3239. (f) Pflästerer, D.; A. Stephen K. Hashmi, A. S. K. Gold Catalysis in Total Synthesis - Recent Achievements. Chem. Soc. Rev. 2016, 45, 1331. (15) (a) Goutham, K.; Kumar, D. A.; Suresh, S.; Sridhar, B.; Narender, R.; Karunakar, G. V. Gold-Catalyzed Intramolecular Cyclization of N-Propargylic β-Enaminones for the Synthesis of 1,4-Oxazepine Derivatives. J. Org. Chem. 2015, 80, 11162. (b) Mangina, N. S. V. M. R.; Veerabhushanam, K.; Ravinder, G.; Goutham, K.; Sridhar, B.; Karunakar, G. V. GoldCatalyzed Intramolecular Regioselective 7-exo-dig Cyclization To Access 3-Methylene-3,4dihydrobenzo[b]oxepinones. Org. Lett. 2017, 19, 282. (c) Goutham, K.; Kadiyala, V.; Sridhar, B.; Karunakar, G. V. Gold-Catalyzed Intramolecular Cyclization/Condensation Sequence: Synthesis of 1,2-Dihydro[c][2,7]naphthyridines. Org. Biomol. Chem. 2017, 15, 7813. (d) Ravinder, G.; Mangina, N. S. V. M. R.; Sridhar, B.; Karunakar, G. V. Gold-Catalyzed Formation of Aryl-fused Pyrazolooxazepines via Intramolecular Regioselective 7-exo-dig Cyclization. Org. Biomol. Chem. 2019, 17, 2809. (e) Purnachander, D.; Suneel, K.; Sridhar, B.; Karunakar, G. V. Gold-Carbene Assisted Formation of Tetraarylmethane Derivatives: Double X-H Activation by Gold. Org. Biomol. Chem. 2019, 17, 4856. (f) Sunil, K.;



Thummala, Y.; Dalovai, P.; S. Balasubramanian, S.; Karunakar, G. V. A Gold-Catalyzed Facile Intramolecular Rearrangement and Cyclization Sequence for Synthesis of 2,5Dihydrofurans. Org. Biomol. Chem. 2019, 17, 6015. (16) See the Supporting Information for X-ray crystallographic data for compound 3i (17) (a) Swaminathan, S. Narayanan, K. V. The Rupe and Meyer-Schuster Rearrangement. Chem. Rev. 1971, 71, 429. (b) Hansmann, M. M.; Hashmi, A. S. K.; Lautens, M. Gold Meets Rhodium: Tandem One-Pot Synthesis of β-Disubstituted Ketones via Meyer-Schuster Rearrangement and Asymmetric 1,4-Addition. Org. Lett. 2013, 15, 3226. (c) Engel, D. A.; Dudley, G. B.The Meyer-Schuster rearrangement for the Synthesis of α, β-Unsaturated Carbonyl Compounds Org. Biomol. Chem. 2009, 7, 4149. (d) Pennell, M. N.; Kyle, M. P.; Gibson, S. M.; Male, L.; Turner, P. G.; Grainger, R. S.; Sheppard, T. D. Intercepting the Gold-Catalysed Meyer-Schuster Rearrangement by Controlled Protodemetallation: A Regioselective Hydration of Propargylic Alcohols. Adv. Synth. Catal. 2016, 358, 1519. (e) Engel, D. A.; Dudley, G. B. Olefination of Ketones Using a Gold(III)-Catalyzed MeyerSchuster Rearrangement. Org. Lett. 2006, 8, 4027. (f) Sugawara, Y.; Yamada, W.; Yoshida, S.; Ikeno, T.; Yamada, T. Carbon Dioxide-Mediated Catalytic Rearrangement of Propargyl Alcohols into α, β-Unsaturated Ketones J. Am. Chem. Soc. 2007, 129, 12902. (g) Yang, Y.; Hu, W.; Ye, X.; Wang, D.; Shi, X. Preparation of Triazole gold(III) Complex as an Effective Catalyst for the Synthesis of E-α-Haloenones. Adv. Synth. Catal. 2016, 358, 2583. (18) Schraub, M.; Dobelmann-Mara, L.; Riedmueller, S.; Patent WO2018/149852, 2018, A1.


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Gold-Catalyzed Synthesis of 6-Hydroxy Indoles ... - ACS Publications

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