Piancatelli Reaction vs Cross-Dehydrative Coup - ACS Publications

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Catalyst-Controlled Chemodivergent Modification of Indoles with 2Furylcarbinols: Piancatelli Reaction vs. Cross-Dehydrative Coupling Reaction Jianfeng Xu, Yi Luo, Huaping Xu, Zhengkai Chen, Maozhong Miao, and Hongjun Ren J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b00090 • Publication Date (Web): 28 Feb 2017 Downloaded from http://pubs.acs.org on February 28, 2017

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The Journal of Organic Chemistry

Catalyst-Controlled

Chemodivergent

Modification

of

Indoles

with

2-Furylcarbinols:

Piancatelli Reaction vs. Cross-Dehydrative Coupling Reaction

Jianfeng Xu, Yi Luo, Huaping Xu, Zhengkai Chen, Maozhong Miao* and Hongjun Ren Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018 (P. R. China) [email protected]

Abstract: A divergent synthetic strategy to functionalize the indole nucleus with readily available 2-furylcarbinols was developed. It was found that the 3-(4-oxo-2-cyclopentenyl)indoles were obtained in moderate to good yields (up to 89%) through Piancatelli reaction catalyzed by ZnCl2, whereas employment of Brønsted acid TFA afforded directly coupled product 3-(2-furyl)indoles in moderate to good yields (up to 87%) via deprotonation-rearomatization route.

INTRODUCTION Indoles are a class of nitrogen heterocycles that play a significant role in both chemistry and biology.1 Particularly, indoles with substitution at the C3 position are commonly found in a number of biologically active natural products and important pharmaceuticals2 (Figure 1), and represent as privileged scaffolds in drug discovery3 since they are capable of binding many receptors with high affinity.4 So far, much work has been directed to catalytic Friedel-Crafts reactions of indoles at C3

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with active carbonyl compounds,5 epoxides,6 olefins,7 imines,8 and allyl compounds,9 etc. However, despite the abundant selections of activated electrophiles, it is necessary to further explore new electrophilic synthons from easily available reagents to meet the challenge of diverse synthesis.

Figure 1. Natural products or pharmaceuticals containing a C3-substituted indole framework 2-Furylcarbinols, a subclass of furan derivates have emerged as important building blocks in contemporary synthesis10 and a variety of important cyclic systems have been successfully constructed from 2-furylcarbinols.11 With promotion by Lewis or Brønsted acids, 2-furylcarbinols are readily transformed into furfuryl cations in situ which have served as highly reactive electron-deficient intermediates.12 In recent years, there have been a number of developments in applications of these interesting intermediates in organic synthesis. For instance, the Piancatelli reaction proceeding through the furfuryl cations has gained a renewed interest in the past decade (Scheme 1, eq 1). Several notable reports have shown that the conversions are compatible with oxygen- or nitrogen-containing nucleophiles such as H2O,13 alcohols14 or amines13a, 15 in an inter- or intramolecular fashion, however, less emphasis has been placed on the selections of carbon-nucleophiles.16 Especially, the carbo-Piancatelli reaction that directly utilizing the aromatic heterocycles as carbon-nucleophiles have been relatively underexplored. On the other hand, we have recently disclosed a new carbon−carbon bond forming strategy to functionalize β-keto amides or


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4-hydroxycoumarins with 2-furylcarbinols via furfuryl cation intermediates, which afforded (Z)-furyl-enols or 3-furyl-4-hydroxycoumarins with high selectivity (Scheme 1, eq 2).17 Moreover, the development of cross-coupling reaction of furfuryl cations with other heterocyclic partners to build bis-heterocyles remains of practical significance. Continuing with our interest in furfuryl cation chemistry, we herein disclose our investigation on catalyst-controlled divergent synthesis of 3-(4-oxo-2-cyclopentenyl)indole or 3-(2-furyl)indole compounds through Piancatelli reaction or cross-dehydrative coupling reaction employing indoles as the nucleophiles (Scheme 1, eq 3). Scheme 1. Profile of the Strategy for Chemoselective Derivatization of Indoles-Involved 2-Furylcarbinols

RESULTS AND DISCUSSION Our initial experiment was performed with indole 1a and furan-2-yldiphenylmethanol 2a in the presence of BiCl3 (10 mol%) in DCE at 80 oC (Table 1, entry 1). Gratifyingly, the desired Piancatelli reaction product 3a and cross-dehydrative coupling product 4a were obtained in 31% and 36% yields, respectively. The structures of 3a and 4a have been unequivocally corroborated by X-ray diffractions (see the Supporting Information). We then focused on optimizing the Piancatelli reaction for the



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formation of product 3a. Various Lewis acid catalysts such as FeCl3, CeCl3·6H2O, CuCl2, Montmorillonite K10, Dy(OTf)3, Zn(OTf)2 and ZnCl2 were screened (Table 1, entries 2−8), the ZnCl2 was found to be the best catalyst for the Piancatelli reaction and the expected 3a was produced in 77% yield (Table 1, entry 8). Solvent effects were examined, and the reactions worked poorly in other solvents such as toluene, dioxane and THF (Table 1, entries 9−11). Next, we made efforts to optimize the cross-dehydrative coupling reaction for affording 4a. The choice of Brønsted acid catalysts could significantly inhibit the formation of Piancatelli reaction product 3a (Table 1, entries 12 and 13). The strong acid TFA gave the best performance, and 4a was formed in 62% yield. Replacing the DCE to the other common solvents such as MeCN, cyclohexane, and toluene resulted in diminished yields (Table 1, entries 14−16). Note that further decreasing the reaction temperature to 40 °C led to a higher yield of 4a (Table 1, entry 17). Table 1. Optimization of the Reaction Conditionsa

entry

cat. (10 mol%)

solvent

t (oC)

time (h)

3a

4a

1 2 3 4 5 6 7

BiCl3 FeCl3 CeCl3·6H2O CuCl2 Montmorillonite K10 Dy(OTf)3 Zn(OTf)2

DCE DCE DCE DCE DCE DCE DCE

80 80 80 80 80 80 80

3 0.5 7 0.2 15 6 5

31 17 0 trace 0 42 69

36 57 55 57 42 29 13

8 9 10 11 12 13 14

ZnCl2 ZnCl2 ZnCl2 ZnCl2 AcOH TFA TFA

DCE toluene dioxane THF DCE DCE MeCN

80 80 80 80 80 80 80

2 6 13 10 7 0.5 3

77 53 28 0 0 trace 0

3 trace trace 0 42 62 56


yield (%)b

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a

15 16 17

TFA TFA TFA

cyclohexane toluene DCE

80 80 40

0.5 1.5 2

0 0 trace

37 61 68

18

TFA

DCE

20

7

trace

50

Reaction conditions (unless otherwise specified): 1a (0.3 mmol), 2a (0.3 mmol), and 10 mol% of acid catalyst in 3 mL of solvent in

N2 atmosphere. bIsolated yields.

After optimizing the reaction conditions for the Piancatelli reaction, we investigated the scope of the reaction by varying the substrates (Scheme 2). Indoles 1 bearing various substituents could smoothly react with furan-2-yldiphenylmethanol (2a). When 2-methylindole and 2-phenylindole were employed, both products 3b and 3c were obtained in 80% yield. The reaction of N-methyl substituted indole with 2a afforded the product 3d in 70% yield. Indoles bearing electron-donating and weak electron-withdrawing substituents including methoxy (3e), benzyloxy (3d), halogens (3g−i), and methyl (3j) groups at the C5−C7 positions underwent facile carbo-Piancatelli reaction to furnish the corresponding products in moderate to good yields. Obviously, it was found that indoles with electron-donating groups gave better results than those with electron-withdrawing groups (3e−j). In contrast, the reaction of indoles with strong electron-withdrawing groups at C5 position such as nitro and methoxycarbonyl failed to generate the products. It also should be note that when N-Boc protected indole was employed, only trace amount of product was obtained. Furthermore, we examined the reaction of unsubstituted indole 1a with various diaryl-2-furylmethanol 2. In the case of symmetric diaryl-2-furylcarbinol (meta-OMe, -F and para-Ph, -But, -Cl), the reaction proceeded smoothly to give the expected compounds 3k−o in moderate to good yields (54−89%). The nonsymmetric diaryl-2-furylcarbinol (R1 = Me, R2 = H) afforded equal amounts of the diasteroisomers 3p in 79% yield. Scheme 2. The Scope of the Reaction for the Effective Formation of 3a



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a

Reaction conditions (unless otherwise specified): 1 (0.3 mmol), 2 (0.3 mmol), ZnCl2 (10 mol%), DCE (3 mL), 80 oC, in N2

atmosphere. bIsolated yields. cThe coupling products were also isolated together with 3h, 3i or 3n in 16%, 9% or 25% yields.

Next, we evaluated the reaction of mono-aryl substituted 2-furylcarbinols with free indole 1a catalyzed by ZnCl2 in DCE at 80 oC (Scheme 3). The cross-dehydrative coupling product 4p was isolated in 48% yield without observing Piancatelli reaction product when the bulky substituent But was installed at C6 position of 2-furylcarbinol (eq 4). Interestingly, switching the But to less sterically crowded methyl or hydrogen, the direct nucleophilic substitution of the hydroxyl group took place to furnish 5a and 5b in 97% and 84% yield, respectively (eq 5).15f, 18 Thus, the di-aryl group attaching to 2-furylcarinol was a necessity for the Piancatelli reaction. Scheme 3. Reaction of Indoles with Monoaromatic Group Substituted 2-Furylcarbinols in the Presence of ZnCl2


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Subsequently, we examined the scope of Brønsted acid catalyzed cross-dehydrative coupling reaction for the formation of various 3-(2-furyl)indoles (Scheme 4). Different substituted indole nucleophiles were tested (4b−h). Generally, using electron-withdrawing group functionalized indoles gave higher yields than electron-donating indoles. For examples, as for indoles with C2-COOEt (4b), C5-Br, -COOMe, -NO2 (4d−f), and C6-Cl (4g) substituents participated in this reaction providing the compounds in more moderate to good yields (68−87%), whereas the reaction of 5-methoxy and 7-methyl indoles furnished the products 4c and 4h in moderate yields. Then, the conversion of various diaryl-2-furylmethanols 2 with indole 1a was also checked. The nature of substituents on the aromatic ring has little effect on this reaction, and the coupling products 4i−o were obtained in moderate yields (42-68%). Finally, N-protected indoles were employed in this reaction, and the negative results were given. Scheme 4. The Scope of the Reaction for the Effective Formation of 4a



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a

Reaction conditions (unless otherwise specified): 1 (0.3 mmol), 2 (0.3 mmol), TFA (10 mol%), DCE (3 mL), 40 oC, in N2 atmosphere.

b

Isolated yields. c5-methoxy-1H-indole (0.36 mmol), 2a (0.3 mmol), TFA (10 mol%), DCE (3 mL), 80 oC, in N2 atmosphere. d1a (0.45

mmol), bis(3-fluorophenyl)(furan-2-yl)methanol (0.3 mmol), TFA (10 mol%), DCE (3 mL), 80 oC, in N2 atmosphere.

Similarly, the reaction of mono-aryl substituted 2-furylcarbinols with indole 1a in the presence of TFA at 40 oC was checked (Scheme 5). When 2-furylcarbinol bearing Ph and But group was employed, the desired 4p could be obtained in 65% yield as the sole product (eq 6). Interestingly, the in-situ substitution product 5a and cross-dehydrative coupling product 4q were produced in 51% and 26% yields when the less steric substrate methyl-phenyl substituted 2-furylcarbinol 2j was employed (eq 7). The hydrogen substituted 2-furylcarbinols 2k gave the direct substitution product 5b in 90% yield (eq 8). So the steric hindrance at C6 position of 2-furylcarbinols was important for such C2 selective cross-dehydrative coupling reaction. Scheme 5. Reaction of Indoles with Monoaromatic Group Substituted 2-Furylcarbinols in the


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Presence of TFA But + N H

O

But OH Ph

TFA(10 mol%)

Ph

(6)

N H 4p, 65%, 1.5 h

2i 1 equiv

1a 0.3 mmol

O

DCE, 40 oC

Ph

TFA(10 mol%) + N H

O

o OH DCE, 40 C, 1.5 h Ph

O

2j 1 equiv

1a 0.3 mmol

O N H 5a, 51% +

N H

(7)

Ph

4q, 26% Ph

OH

+ N H 1a 0.3 mmol

O Ph 2k 1 equiv

TFA (10 mol%) DCE, 40 oC

O N H 5b, 90%, 1.5 h

(8)

Synthetic application of newly modified indoles 3a and 4a had been briefly demonstrated (Scheme 6). Michael addition of 3a with dimethyl malonate in the presence of Cs2CO3 afforded multifunctionalized cyclopentanone substrate 6 in 83% yield with complete stereoselectivities (eq 9). The acid catalyzed furan ring-opening of 4a was realized by treatment with concentrated hydrochloric acid in methanol to produce indole substituted 1,4-dione 7 in 71% yield (eq 10). Scheme 6. Chemical Derivatization of 3a and 4a

To elucidate the mechanism, several controlled experiments were further performed as shown in Scheme 7. We were pleased to find that the unrearranged product 8 was trapped in 38% yield when employing indole 1a to react with furan-2-yldiphenylmethanol 2a in the presence of ZnCl2 at decreasing temperature (40 oC) (eq 11). The parallel transformations of 8 were carried out in the



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optimized reaction conditions to furnish 3a and 4a in 67% and 45% yield, respectively (eq 12 and 13). These results indicated that compound 8 was a valuable intermediate in Piancatelli reaction as well as cross-dehydrative coupling reaction. Scheme 7. Control Experiments Ph + N H 1a 1 mmol

O Ph

Ph ZnCl2 (10 mol%) OH DCE, 40 oC, 1.5 h

O

2a 1 mmol Ph O

N H

Ph

N H

Ph

(12)

Ph

3a, 67% Ph

O

(11)

O

ZnCl2 (10 mol%) DCE, 80 oC, 0.5 h

8 0.2 mmol

Ph

Ph TFA (10 mol%)

O

DCE, 40 oC, 1.5 h

N H

Ph

N H 8, 38%

8 0.2 mmol

N H

Ph

(13)

4a, 45%

On the basis of the above results and previous work, a possible reaction mechanism was proposed in Scheme 8. The carbocation A or highly reactive oxocarbenium ion B was generated in the presence of acidic media, which upon treatment with indole 1 underwent regioselective intramolecular addition converting to 2,5-dihydrofuran intermediate C. When the acidic media was a LA such as Zn(OTf)2 or ZnCl2, which might be difficult to generate Brønsted acid species by hydrolysis or hydration. The oxygen of 2,5-dihydrofuran preferentially attacked LA leading to the ring opening of intermediate C to furnish pentadienyl carbocation D (path a). Subsequent 4 Π-electrocyclic ring closure afforded 3-(4-oxo-2-cyclopentenyl)indole 3. In contrast, in the case of Brønsted acid or Lewis acid assisted Brønsted acid (LBA), the electron-rich double bond of intermediate C selectively attacked to proton to form intermediate E (path b). Then, the oxocarbenium intermediate E underwent deprotonation and rearomatization to produce 3-(2-furyl)indoles 4. Scheme 8. Proposed Mechanism


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CONCLUSION In conclusion, we have developed a practical and chemoselective method for the functionalization of indoles with available 2-furylcarbinols via tandem Piancatelli reaction or cross-dehydrative coupling reaction

in

the

catalyst-controlled

manner.

Various

3-(4-oxo-2-cyclopentenyl)indole

or

3-(2-furyl)indole compounds are obtained in moderate to good yields with high selectivities by tuning the catalyst. Furthermore, application of the modified indoles are both achieved, indole substituted multifunctionalized cyclopentanone and indole substituted 1,4-dione are afforded in 87% and 71% yield, respectively. Extensive studies including the isolation of unarranged 2,5-dihydrofuran intermediate and transformation experiments provide insight into the possible reaction mechanism. EXPERIMENTAL SECTION 1. General Methods. The 1H NMR (400 MHz) chemical shifts were reported in parts per million (δ) relative to internal standard TMS (0 ppm). The coupling constants, J values are reported in Hertz (Hz). The

13

C NMR

(100 MHz) chemical shifts were referenced to the internal solvent signals (central peak is 77.0 ppm in CDCl3). High-resolution mass spectra (HRMS) were recorded using electrospray ionization (ESI) method on a TOF analyzer. Melting points were not corrected. All commercial reagents and solvents were used without additional purification. Petroleum ether refers to the fraction with boiling point in the range 60−90 °C. All reac6ons were monitored by TLC with GF 254 silica gel coated plates.



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Flash column chromatography was carried out using 200−300 mesh silica gel.

2. Procedure and experiment data for 3, 4 and 5 (1) General procedure for the synthesis of 3 Indoles 1 (0.3 mmol, 1.0 equiv), ZnCl2 (0.03 mmol, 10 mol %) and 2-furylcarbinols 2 (0.3 mmol, 1.0 equiv) were dissolved in 3 mL of DCE in sequence. The mixture was then stirred at 80 oC for 2-5 h under N2. After completion of the reaction, the solvent was removed in vacuo, and the residue was purified with flash silica gel chromatography to afford 3. Experiment data for 3 4-(1H-indol-3-yl)-5,5-diphenylcyclopent-2-enone (3a) A mixture of 1H-indole 1a (34 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (75 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 2 h to afford 3a (78 mg, 77%) as a white solid; M.p. 209-210 oC (Petroleum ether/EtOAc); Rf = 0.18 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.94-7.84 (m, 2H), 7.48 (d, J = 6.8 Hz, 2H), 7.39-7.22 (m, 4H), 7.14-7.00 (m, 2H), 6.94 (t, J = 7.0 Hz, 1H), 6.88-6.75 (m, 5H), 6.44-6.36 (m, 2H), 5.41 (s, 1H);

13

C NMR (100 MHz, CDCl3): δ 209.4, 164.6, 142.3, 142.2, 135.7, 131.3, 130.0, 128.3,

127.01, 126.97, 126.7, 125.7, 123.4, 121.9, 119.2, 118.9, 113.6, 110.9, 67.0, 51.0; HRMS (ES+-TOF) calcd for C25H20NO ([M+H]+): 350.1545, found 350.1548. 4-(2-methyl-1H-indol-3-yl)-5,5-diphenylcyclopent-2-enone (3b) A mixture of 2-methyl-1H-indole 1b (38 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (76 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 2 h to afford 3b (84 mg, 80%) as a white solid; M.p. 215-216 oC (Petroleum ether/EtOAc); Rf = 0.20 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.95 (dd, J = 5.6 Hz, 2.4 Hz, 1H), 7.60 (s, 1H), 7.37-7.27 (m, 4H), 7.27-7.17 (m, 2H), 7.02 (d, J = 8.0 Hz, 1H), 6.96 (t, J = 7.4 Hz, 1H), 6.91-6.78 (m, 6H), 6.47 (dd, J = 5.4 Hz, 1.8 Hz, 1H), 5.38 (s, 1H), 1.96 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 209.4, 166.3, 142.9, 141.0, 134.7, 133.0, 131.6, 129.9, 128.5, 128.3, 128.0, 126.8, 126.6, 125.9, 120.8, 119.1, 118.5, 109.9, 108.0, 66.7, 52.4, 12.4; HRMS (ES+-TOF) calcd for C26H22NO ([M+H]+): 364.1701, found 364.1686. 5,5-diphenyl-4-(2-phenyl-1H-indol-3-yl)cyclopent-2-enone (3c) A mixture of 2-phenyl-1H-indole 1c (59 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv)


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and furan-2-yldiphenylmethanol 2a (76 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 3 h to afford 3c (103 mg, 80%) as a yellow solid; M.p. 197-198 oC (Petroleum ether/EtOAc); Rf = 0.21 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.98 (s, 1 H), 7.93 (d, J = 3.6 Hz, 1H), 7.39-7.28 (m, 5H), 7.25-7.14 (m, 5H), 7.11 (d, J = 8.4 Hz, 1H), 7.05 (d, J = 8.0 Hz, 1H), 7.01-6.94 (m, 3H), 6.84-6.73 (m, 4H), 6.48 (d, J = 4.0 Hz, 1H), 5.49 (s, 1H);

13

C NMR (100 MHz, CDCl3): δ 209.5,

166.8, 142.9, 140.2, 136.3, 135.5, 132.3, 131.7, 130.4, 128.8, 128.23, 128.20, 128.1, 128.0, 126.7, 126.0, 121.8, 120.6, 119.1, 110.3, 109.4, 66.5, 53.3; HRMS (ES+-TOF) calcd for C31H24NO ([M+H]+): 426.1858, found 426.1849. 4-(1-methyl-1H-indol-3-yl)-5,5-diphenylcyclopent-2-enone (3d) A mixture of 1-methyl-1H-indole 1d (38 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (76 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 2 h to afford 3d (74 mg, 70%) as a yellow solid; M.p. 57-58 oC (Petroleum ether/EtOAc); Rf = 0.11 (Petroleum ether/EtOAc 10/1); 1H NMR (400 MHz, CDCl3): δ 7.88 (dd, J = 5.8 Hz, 2.6Hz, 1H), 7.48 (d, J = 7.6 Hz, 2H), 7.37-7.21 (m, 4H), 7.07 (d, J = 3.2 Hz, 2H), 6.70-6.91 (m, 1H), 6.87-6.82 (m, 2H), 6.81-6.76 (m, 3H), 6.40-6.37 (m, 1H), 6.26 (s, 1H) , 5.40 (s, 1H) , 3.50 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 209.4, 164.5, 142.33, 142.30, 136.5, 131.1, 130.0, 128.3, 128.22, 128.18, 127.5, 126.9, 126.6, 125.7, 121.4, 118.9, 118.7, 111.9, 108.9, 66.9, 50.9, 32.5; HRMS (ES+-TOF) calcd for C26H22NO ([M+H]+): 364.1701, found 364.1695. 4-(5-methoxy-1H-indol-3-yl)-5,5-diphenylcyclopent-2-enone (3e) A mixture of 5-methoxy-1H-indole 1e (45 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (76 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 2 h to afford 3e (75 mg, 65%) as a yellow solid; M.p. 175-176 oC (Petroleum ether/EtOAc); Rf = 0.14 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.95 (s, 1H), 7.87 (dd, J = 5.6 Hz, 2.4 Hz, 1H), 7.46 (d, J = 7.2 Hz, 2H), 7.34-7.20 (m, 3H), 6.94 (d, J = 8.8 Hz, 1H), 6.86-6.76 (m, 5H), 6.73-6.65 (m, 2H), 6.38-6.34 (m, 2H), 5.33 (s, 1H) , 3.71 (s, 3H);

13

C NMR (100

MHz, CDCl3): δ 209.5, 164.5, 153.6, 142.2, 142.1, 131.3, 130.9, 130.0, 128.32, 128.25, 127.4, 127.0, 126.7, 125.8, 124.1, 113.3, 111.9, 111.6, 101.0, 67.0, 55.8, 51.1; HRMS (ES+-TOF) calcd for C26H22NO2 ([M+H]+): 380.1651, found 380.1640. 4-(5-(benzyloxy)-1H-indol-3-yl)-5,5-diphenylcyclopent-2-enone (3f) A mixture of 5-(benzyloxy)-1H-indole 1f (67 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1



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equiv) and furan-2-yldiphenylmethanol 2a (76 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 2 h to afford 3f (119 mg, 87%) as a white solid; M.p. 173-174 oC (Petroleum ether/EtOAc); Rf = 0.07 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.88 (dd, J = 5.6 Hz, 2.4 Hz, 1H), 7.78 (s, 1H), 7.45 (d, J = 7.2 Hz, 2H), 7.40 (d, J = 7.6 Hz, 2H), 7.37-7.23 (m, 6H), 7.00 (d, J = 8.4 Hz, 1H), 6.81-6.73 (m, 7H), 6.42 (d, J = 1.6 Hz, 1H), 6.38 (d, J =4.8 Hz, 1H), 5.31 (s, 1H), 5.01 (d, J = 12.0 Hz, 1H), 4.96 (d, J = 12.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 209.4, 164.5, 152.6, 142.2, 142.0, 137.6, 131.3, 131.00, 129.98, 128.5, 128.28, 128.25, 127.7, 127.4, 127.0, 126.7, 125.7, 124.1, 113.3, 112.8, 111.6, 102.7, 70.8, 66.9, 51.1; HRMS (ES+-TOF) calcd for C32H26NO2 ([M+H]+): 456.1964, found 456.1949. 4-(5-chloro-1H-indol-3-yl)-5,5-diphenylcyclopent-2-enone (3g) A mixture of 5-chloro-1H-indole 1g (45 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (76 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 5 h to afford 3g (69 mg, 61%) as a yellow solid; M.p. 193-194 oC (Petroleum ether/EtOAc); Rf = 0.20 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.10 (s, 1H), 7.89 (dd, J = 5.6 Hz, 2.4 Hz, 1H), 7.44 (d, J = 7.6 Hz, 2H), 7.35-7.22 (m, 4H), 7.00-6.93 (m, 2H), 6.85-6.77 (m, 5H), 6.46 (d, J = 1.6 Hz, 1H), 6.38 (d, J = 4.8 Hz, 1H), 5.31 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 209.3, 164.1, 141.9, 141.8, 134.0, 131.5, 130.0, 128.3, 128.2, 128.0, 127.1, 126.8, 125.9, 124.80, 124.77, 122.1, 118.3, 113.4, 111.9, 67.0, 50.8; HRMS (ES+-TOF) calcd for C25H19ClNO ([M+H]+): 384.1155, found 384.1157. 4-(5-bromo-1H-indol-3-yl)-5,5-diphenylcyclopent-2-enone (3h) A mixture of 5-bromo-1H-indole 1h (58 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (76 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 5 h to afford 3h (47 mg, 37%) as a dark solid; M.p. 198-199 oC (Petroleum ether/EtOAc); Rf = 0.11 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.01 (s, 1H), 7.89 (dd, J = 5.6 Hz, 2.8 Hz, 1H), 7.45 (d, J = 7.2 Hz, 2H), 7.39 (s, 1H), 7.36-7.23 (m, 3H), 7.09 (d, J = 8.4 Hz, 1H), 6.96 (d, J = 8.8 Hz, 1H), 6.85-6.77 (m, 5H), 6.46 (d, J = 1.2 Hz, 1H), 6.39 (d, J = 4.4 Hz, 1H), 5.31 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 209.2, 164.1, 141.9, 141.8, 134.3, 131.5, 130.0, 128.6, 128.3, 128.2, 127.1, 126.8, 125.9, 124.6, 121.4, 113.3, 112.4, 67.0, 50.8; HRMS (ES+-TOF) calcd for C25H19BrNO ([M+H]+): 428.0650, found 428.0629. 4-(6-chloro-1H-indol-3-yl)-5,5-diphenylcyclopent-2-enone (3i) A mixture of 6-chloro-1H-indole 1i (45 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv)


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and furan-2-yldiphenylmethanol 2a (76 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 4 h to afford 3i (55 mg, 48%) as a purple solid; M.p. 194-195 oC (Petroleum ether/EtOAc); Rf = 0.15 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.97 (s, 1H), 7.89 (dd, J = 5.4 Hz, 2.6 Hz, 1H), 7.44 (d, J = 7.6 Hz, 2H), 7.35-7.24 (m, 3H), 7.21 (d, J = 8.8 Hz, 1H), 7.08 (s, 1H), 6.88 (d, J = 8.4 Hz, 1H), 6.84-6.77 (m, 5H), 6.44 (s, 1H), 6.39 (d, J = 5.6 Hz, 1H), 5.35 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 209.2, 164.1, 141.98, 141.95, 136.1, 131.5, 129.9, 128.3, 128.2, 127.7, 127.1, 126.8, 125.9, 125.6, 124.0, 119.9, 119.8, 113.9, 110.8, 67.0, 50.9; HRMS (ES+-TOF) calcd for C25H19ClNO ([M+H]+): 384.1155, found 384.1158. 4-(7-methyl-1H-indol-3-yl)-5,5-diphenylcyclopent-2-enone (3j) A mixture of 7-methyl-1H-indole 1j (39 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (76 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 2 h to afford 3j (85 mg, 79%) as a white solid; M.p. 82-83 oC (Petroleum ether/EtOAc); Rf = 0.09 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.88 (dd, J = 5.6 Hz, 2.4Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.33-7.20 (m, 4H), 6.90-6.77 (m, 7H), 6.39-6.35 (m, 2H), 5.40 (s, 1H), 2.27 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 209.6, 164.9, 142.3, 142.2, 135.3, 131.1, 130.0, 128.3, 128.2, 126.9, 126.7, 126.6, 125.8, 123.2, 122.4, 120.0,119.4, 116.5, 113.9, 66.8, 51.2, 16.4; HRMS (ES+-TOF) calcd for C26H22NO ([M+H]+): 364.1701, found 364.1694. 4-(1H-indol-3-yl)-5,5-bis(3-methoxyphenyl)cyclopent-2-enone (3k) A mixture of 1H-indole 1a (36 mg, 0.3 mmol, 1.0 equiv) ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-ylbis(3-methoxyphenyl)methanol 2b (94 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 2 h to afford 3k (90 mg, 72%) as a yellow solid; M.p. 62-63 oC (Petroleum ether/EtOAc); Rf = 0.06 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.06 (s, 1H), 7.85 (dd, J = 5.8 Hz, 2.6 Hz, 1H), 7.36 (d, J = 7.2 Hz, 1H), 7.23 (t, J = 8.0 Hz, 1H), 7.07-6.99 (m, 4H), 6.93 (t, J = 7.6 Hz, 1H), 6.80 (dd, J = 8.2 Hz, 1.4 Hz, 1H), 6.73 (t, J = 7.8 Hz, 1H), 6.50 (d, J = 6.8 Hz, 1H), 6.35-6.31 (m, 4H), 5.36 (s, 1H), 3.70 (s, 3H), 3.18(s, 3H); 13C NMR (100 MHz, CDCl3): δ 209.2, 164.8, 159.3, 157.9, 143.7, 143.2, 135.6, 131.1, 129.1, 127.6, 127.1, 123.4, 122.3, 121.7, 120.6, 119.2, 118.7, 115.6, 114.8, 113.3, 112.4, 111.8, 111.0, 66.8, 55.1, 54.6, 51.3; HRMS (ES+-TOF) calcd for C27H24NO3 ([M+H]+): 410.1756, found 410.1744. 5,5-bis(3-fluorophenyl)-4-(1H-indol-3-yl)cyclopent-2-enone (3l) A mixture of 1H-indole 1a (36 mg, 0.3 mmol, 1.0 equiv) ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and



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bis(3-fluorophenyl)(furan-2-yl)methanol 2c (89 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 2 h to afford 3l (106 mg, 89%) as a white solid; M.p. 135-136 oC (Petroleum ether/EtOAc); Rf = 0.12 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.03 (s, 1H), 7.91 (dd, J = 5.6 Hz, 2.4 Hz, 1H), 7.32-7.22 (m, 3H), 7.17 (d, J = 7.4 Hz, 1H), 7.11 (d, J = 8.0 Hz, 1H), 7.05 (t, J = 7.6 Hz, 1H), 7.00-6.93 (m, 2H), 6.78-6.71 (m, 1H), 6.60 (d, J = 8.4 Hz, 2H), 6.48 (t, J = 7.8 Hz, 2H), 6.38 (t, J = 6.0 Hz, 1H), 5.32(s, 1H); 13C NMR (100 MHz, CDCl3): δ 208.2, 164.6, 163.2 (d, J = 121.7 Hz), 160.8 (d, J = 120.0 Hz), 144.2 (d, J = 7.1 Hz), 143.8 (d, J = 7.2 Hz), 135.7, 131.0, 129.8 (d, J = 7.7 Hz), 128.1 (d, J = 8.6 Hz), 126.6, 125.7 (d, J = 2.6 Hz), 123.8 (d, J = 3.3 Hz), 123.4, 122.1, 119.3, 118.6, 117.0 (d, J = 22.5 Hz), 115.4 (d, J = 22.4 Hz), 114.2 (d, J = 21.5 Hz), 112.88 (d, J = 20.8 Hz), 112.86, 110.0, 66.3, 50.9; HRMS (ES--TOF) calcd for C25H16F2NO ([M-H]-): 384.1200, found 384.1196. 5,5-di(biphenyl-4-yl)-4-(1H-indol-3-yl)cyclopent-2-enone (3m) A mixture of 1H-indole 1a (36 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and dibiphenyl-4-yl(furan-2-yl)methanol 2d (124 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 2 h to afford 3m (122 mg, 79%) as a white solid; M.p. 228-229 oC (Petroleum ether/EtOAc); Rf = 0.06 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.89 (dd, J = 5.6 Hz, 2.4 Hz, 1H), 7.85 (s, 1H), 7.62-7.56 (m, 6H), 7.46-7.38 (m, 3H), 7.37-7.21 (m, 6H), 7.11-6.91 (m, 7H), 6.46-6.40 (m, 2H), 5.46 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 209.5, 164.7, 141.3, 141.2, 140.7, 140.5, 139.8, 138.4, 135.7, 131.4, 130.4, 128.74, 128.71, 128.5, 127.3, 127.02, 126.98, 126.9, 126.8, 125.4, 123.4, 122.0, 119.3, 118.9, 113.6, 110.9, 66.7, 51.0; HRMS (ES+-TOF) calcd for C37H28NO ([M+H]+): 502.2171, found 502.2166. 5,5-bis(4-tert-butylphenyl)-4-(1H-indol-3-yl)cyclopent-2-enone (3n) A mixture of 1H-indole 1a (36 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and bis(4-tert-butylphenyl)(furan-2-yl)methanol 2e (109 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 2 h to afford 3n (75 mg, 54%) as a purple solid; M.p. 115-116 oC (Petroleum ether/EtOAc); Rf = 0.19 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.90 (dd, J = 5.6 Hz, 2.8 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 7.2 Hz, 1H), 7.06 (d, J = 8.0 Hz, 1H), 6.98 (t, J = 7.6 Hz, 1H), 6.85 (d, J = 7.4 Hz, 1H), 6.75-6.68 (m, 4H), 6.44 (d, J = 2.4 Hz, 1H), 6.38 (dd, J = 5.6 Hz, 1.6 Hz, 1H), 5.35 (s, 1H), 1.31 (s, 9H), 0.99 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 210.1, 164.2, 149.6, 148.3, 138.94, 138.86, 135.8, 131.5, 129.7, 128.0, 126.9, 125.1, 123.3, 123.1, 121.7, 119.1, 118.8, 114.1, 110.5, 66.7, 51.0, 34.3, 33.9, 31.3, 31.0; HRMS (ES+-TOF) calcd for


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C33H36NO ([M+H]+): 462.2797, found 462.2794. 5,5-bis(4-chlorophenyl)-4-(1H-indol-3-yl)cyclopent-2-enone (3o) A mixture of 1H-indole 1a (36 mg, 0.3 mmol, 1.0 equiv) ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and bis(4-chlorophenyl)(furan-2-yl)methanol 2f (96 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 2 h to afford 3o (98 mg, 78%) as a white solid; M.p. 247-248 oC (Petroleum ether/EtOAc); Rf = 0.12 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.92 (dd, J = 6.0 Hz, 2.8 Hz, 1H), 7.89 (s, 1H), 7.40-7.29 (m, 5H), 7.19 (d, J = 8.0 Hz, 1H), 7.10 (t, J = 7.4 Hz, 1H), 6.98 (t, J = 7.6 Hz, 1H), 6.80-6.73 (m, 4H), 6.47 (d, J = 2.0 Hz, 1H), 6.41 (dd, J = 5.6 Hz, 1.6 Hz, 1H), 5.35 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 208.4, 164.4, 140.5, 135.8 , 133.3, 131.9, 131.3, 131.2, 129.5, 128.5, 127.0, 126.8, 123.3, 122.3, 119.6, 118.6, 113.3, 111.1, 65.9, 50.8; HRMS (ES--TOF) calcd for C25H16Cl2NO ([M-H]-): 416.0609, found 416.0601. 4-(1H-indol-3-yl)-5-phenyl-5-p-tolylcyclopent-2-enone (3p) A mixture of 1H-indole 1a (36 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yl(phenyl)(p-tolyl)methanol 2g (80 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 o

C for 2 h to afford 3p (87 mg, 79%, dr = 1 : 1) as a yellow solid; M.p. 168-169 oC (Petroleum

ether/EtOAc); Rf = 0.13 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.90-7.86 (m, 2H), 7.47-7.45 (m, 1H), 7.36-7.29 (m, 3H), 7.25-6.71 (m, 8H), 6.61-6.59 (m, 1H), 6.40-6.36 (m, 2H), 5.39-5.38 (m, 1H), 2.33-2.00 (m, 3H);

13

C NMR (100 MHz, CDCl3): δ 209.85, 209.80, 164.8, 164.6,

142.4, 142.3, 139.21, 139.16, 136.7, 135.64, 135.60, 135.2, 131.22, 131.16, 129.9, 129.7, 129.0, 128.23, 128.21, 128.1, 127.4, 127.0, 126.95, 126.87, 126.7, 125.7, 123.4, 123.3, 121.74, 121.72, 119.14, 119.09, 118.9, 118.8, 113.6, 113.5, 110.91, 110.86, 66.7, 66.6, 51.0, 50.9, 20.9, 20.7; HRMS (ES--TOF) calcd for C26H20NO ([M-H]-): 362.1545, found 362.1536.

(2) General procedure for the synthesis of 4 indole 1 (0.3 mmol, 1.0 equiv), TFA (0.03 mmol, 10 mol %) and 2-furylcarbinols 2 (0.3 mmol, 1.0 equiv) were dissolved in 3 mL of DCE in sequence. The mixture was then stirred at 40 oC for 0.5-4 h under N2. After completion of the reaction, the solvent was removed in vacuo, and the residue was purified with flash silica gel chromatography to afford 4. Experiment data for 4 3-(5-benzhydrylfuran-2-yl)-1H-indole (4a)



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A mixture of 1H-indole 1a (34 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (75 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 oC for 2 h to afford 4a (69 mg, 68%) as a white solid; M.p. 113-114 oC (Petroleum ether/EtOAc); Rf = 0.30 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.97 (s, 1H), 7.83 (d, J = 7.6 Hz, 1H), 7.34-7.27 (m, 6H), 7.26-7.13 (m, 8H), 6.46 (d, J = 2.8 Hz, 1H), 5.98 (d, J = 2.8 Hz, 1H), 5.53 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 154.1, 149.8, 142.1, 136.1, 128.8, 128.4, 126.6, 124.1, 122.5, 121.0, 120.4, 120.1, 111.3, 110.0, 109.0, 103.9, 50.9; HRMS (ES+-TOF) calcd for C25H20NO ([M+H]+): 350.1545, found 350.1541. Ethyl 3-(5-benzhydrylfuran-2-yl)-1H-indole-2-carboxylate (4b) A mixture of ethyl 1H-indole-2-carboxylate 1k (57 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (75 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 oC for 3 h to afford 4b (86 mg, 68%) as a white solid; M.p. 145-146 oC (Petroleum ether/EtOAc); Rf = 0.15 (Petroleum ether/EtOAc 10/1); 1H NMR (400 MHz, CDCl3): δ 8.91 (s, 1 H), 7.83 ( d, J = 8.4 Hz, 1H), 7.37-7.23 (m, 12H), 7.16 (s, 1H), 7.02 (t, J = 7.2 Hz, 1H), 6.12 (s, 1H), 5.59 (s, 1H), 4.39 (q, J = 6.4 Hz, 2H), 1.39 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 161.2, 155.8, 148.2, 141.9, 135.5, 128.9, 128.4, 126.7, 126.1, 125.9, 124.0, 121.1, 121.0, 113.9, 111.6, 111.3, 110.0, 61.1, 51.1, 14.4; HRMS (ES+-TOF) calcd for C28H24NO3 ([M+H]+): 422.1756 , found 422.1750. 3-(5-benzhydrylfuran-2-yl)-5-methoxy-1H-indole (4c) A mixture of 5-methoxy-1H-indole 1e (53 mg, 0.36 mmol, 1.2 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (75 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 0.5 h to afford 4c (67 mg, 59%) as a yellow solid; M.p. 107-108 oC (Petroleum ether/EtOAc); Rf = 0.23 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.03 (s, 1H), 7.37-7.21 (m, 13H), 6.86 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 6.40 (d, J = 2.8 Hz, 1H), 5.99 (d, J = 3.2 Hz, 1H), 5.54 (s, 1H), 3.72 (s, 3H);

13

C NMR (100 MHz, CDCl3): δ 154.5, 154.1, 150.1, 142.0, 131.1, 128.8,

128.4, 126.6, 124.6, 121.5, 112.9, 112.0, 109.9, 108.8, 103.4, 101.7, 55.6, 51.0; HRMS (ES+-TOF) calcd for C26H22NO2 ([M+H]+): 380.1651, found 380.1653. 3-(5-benzhydrylfuran-2-yl)-5-bromo-1H-indole (4d) A mixture of 5-bromo-1H-indole 1h (59 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (75 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 oC for 1 h to afford 4d (101 mg, 79%) as a white solid; M.p. 184-185 oC (Petroleum ether/EtOAc); Rf =


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0.26 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.18 (s, 1H), 7.94 (s, 1H), 7.41 (d, J = 2.4 Hz, 1H), 7.36-7.29 (m, 5H), 7.28-7.22 (m, 7H), 6.44 (d, J = 3.2 Hz, 1H), 6.01 (d, J = 2.0 Hz, 1H), 5.53 (s, 1H);

13

C NMR (100 MHz, CDCl3): δ 154.4, 149.0, 142.0, 134.7, 128.8, 128.4, 126.7, 125.9,

125.5, 122.9, 121.9, 113.8, 112.6, 109.9, 109.0, 104.3, 50.9; HRMS (ES+-TOF) calcd for C25H19BrNO ([M+H]+): 428.0650, found 428.0640. Methyl 3-(5-benzhydrylfuran-2-yl)-1H-indole-5-carboxylate (4e) A mixture of methyl 1H-indole-5-carboxylate 1l (52 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (75 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 oC for 2 h to afford 4e (105 mg, 87%) as a purple solid; M.p. 149-150 oC (Petroleum ether/EtOAc); Rf = 0.19 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.60 (s, 1H), 8.45 (s, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.39 (s, 1H), 7.34-7.28 (m, 5H), 7.27-7.21 (m, 6H), 6.54 (s, 1H), 6.00 (s, 1H), 5.52 (s, 1H), 3.92 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 168.1, 154.5, 148.9, 142.0, 138.7, 128.8, 128.4, 126.6, 123.85, 123.77, 123.0, 122.3, 122.2, 111.0, 110.3, 110.1, 104.8, 52.0, 50.9; HRMS (ES+-TOF) calcd for C27H22NO3 ([M+H]+): 408.1600, found 408.1590. 3-(5-benzhydrylfuran-2-yl)-5-nitro-1H-indole (4f) A mixture of 5-nitro-1H-indole 1m (48 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (76 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 oC for 3 h to afford 4f (91 mg, 78%) as a red solid; M.p. 173-174 oC (Petroleum ether/EtOAc); Rf = 0.15 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.79 (s, 1H), 8.50 (s, 1H), 8.13 (d, J = 8.4 Hz, 1H), 7.53 (s, 1H), 7.42-7.32 (m, 5H), 7.30-7.25 (m, 6H), 6.57 (s, 1H), 6.07 (s, 1H), 5.55 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 155.2, 148.1, 142.3, 141.8, 138.9, 128.8, 128.5, 126.8, 123.7, 123.3, 118.3, 117.8, 111.6, 111.3, 110.1, 105.4, 51.0; HRMS (ES+-TOF) calcd for C25H19N2O3 ([M+H]+): 395.1396 , found 395.1388. 3-(5-benzhydrylfuran-2-yl)-6-chloro-1H-indole (4g) A mixture of 6-chloro-1H-indole 1i (45 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (76 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 oC for 0.5 h to afford 4g (84 mg, 74%) as a white solid; M.p. 121-122 oC (Petroleum ether/EtOAc); Rf = 0.35 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.98 (s, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.36-7.20 (m, 12H), 7.10 (d, J = 8.4 Hz, 1H), 6.42 (s, 1H), 5.99 (s, 1H), 5.52 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 154.5, 149.3, 142.1, 136.5, 128.8, 128.5, 128.4, 126.7, 122.8, 121.4, 121.2, 111.2, 110.0,



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

109.4, 104.2, 51.0; HRMS (ES+-TOF) calcd for C25H19ClNO ([M+H]+): 384.1155, found 384.1143. 3-(5-benzhydrylfuran-2-yl)-7-methyl-1H-indole (4h) A mixture of 7-methyl-1H-indole 1j (39 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (75 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 oC for 1 h to afford 4h (64 mg, 59%) as a white solid: M.p. 174-175 oC (Petroleum ether/EtOAc); Rf = 0.36 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.02 (s, 1H), 7.69 (d, J = 7.2 Hz, 1H), 7.40 (s, 1H), 7.34-7.28 (m, 4H), 7.27-7.20 (m, 6H), 7.09 (t, J = 7.4 Hz, 1H), 7.02 (d, J = 7.2 Hz, 1H), 6.47 (d, J = 3.2 Hz, 1H), 5.98 (d, J = 2.4 Hz, 1H), 5.53 (s, 1H) , 2.46 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 154.0, 150.0, 142.2, 135.7, 128.9, 128.4, 126.6, 123.7, 123.1, 120.6, 120.4, 117.9, 110.0, 109.6, 103.9, 50.9, 16.6; HRMS (ES+-TOF) calcd for C26H22NO ([M+H]+): 364.1701 , found 364.1699. 3-(5-(bis(2-methoxyphenyl)methyl)furan-2-yl)-1H-indole (4i) A mixture of 1H-indole 1a (35 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-ylbis(2-methoxyphenyl)methanol 2h (93 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 oC for 1 h to afford 4i (77 mg, 63%) as a white solid; M.p. 149-150 oC (Petroleum ether/EtOAc); Rf = 0.21 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.01 (s, 1H), 7.83 (d, J = 7.6 Hz, 1H), 7.35-7.27 (m, 2H), 7.24-7.17 (m, 3H) , 7.17-7.11 (m, 1H), 7.02 (d, J = 7.2 Hz, 2H), 6.89-6.84 (m, 4H), 6.43 (d, J = 2.8 Hz, 1H), 6.28 (s, 1H), 5.87 (d, J = 2.4 Hz, 1H), 3.73 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 157.1, 154.3, 149.4, 136.2, 130.8, 129.5, 127.5, 124.2, 122.4, 120.9, 120.3, 120.2, 111.2, 110.8, 109.5, 109.3, 103.9, 55.8, 37.4; HRMS (ES+-TOF) calcd for C27H24NO3 ([M+H]+): 410.1756, found 410.1754. 3-(5-(bis(3-fluorophenyl)methyl)furan-2-yl)-1H-indole (4j) A mixture of 1H-indole 1a (53 mg, 0.45 mmol, 1.5 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and bis(3-fluorophenyl)(furan-2-yl)methanol 2g (86 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 4 h to afford 4j (61 mg, 53%) as a brown oil; Rf = 0.32 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.39-7.15 (m, 6H), 7.02 (d, J = 8.0 Hz, 2H), 6.98-6.92 (m, 4H), 6.47 (d, J = 3.2 Hz, 1H), 6.03 (d, J = 2.8 Hz, 1H), 5.50 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 162.9 (d, J = 245.0 Hz), 152.5, 150.3, 144.0 (d, J = 6.7 Hz), 136.1, 130.0 (d, J = 3.3 Hz), 124.5 (d, J = 3.3 Hz), 124.1, 122.7, 121.1, 120.5, 120.1, 115.8 (d, J = 21.9 Hz), 113.9 (d, J = 20.4 Hz), 111.3, 110.4, 108.9, 103.9, 50.2; HRMS (ES+-TOF) calcd for C25H18F2NO ([M+H]+): 386.1356, found 386.1357.


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3-(5-(bis(3-methoxyphenyl)methyl)furan-2-yl)-1H-indole (4k) A mixture of 1H-indole 1a (35 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-ylbis(3-methoxyphenyl)methanol 2f (93 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 oC for 0.5 h to afford 4k (67 mg, 55%) as a red oil; Rf = 0.16 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.05 (s, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.34-7.27 (m, 2H), 7.24-7.12 (m, 4H), 6.87-6.75 (m, 6H), 6.44 (d, J = 3.6 Hz, 1H), 6.03 (d, J = 2.8 Hz, 1H), 5.46 (s, 1H), 3.72 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 159.6, 153.8, 149.9, 143.6, 136.1, 129.3, 124.2, 122.5, 121.3, 121.0, 120.4, 120.2, 114.8, 111.8, 111.2, 110.0, 109.1, 103.9, 55.1, 50.9; HRMS (ES+-TOF) calcd for C27H24NO3 ([M+H]+): 410.1756, found 410.1747. 3-(5-(dibiphenyl-4-ylmethyl)furan-2-yl)-1H-indole (4l) A mixture of 1H-indole 1a (35 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and dibiphenyl-4-yl(furan-2-yl)methanol 2b (120 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 oC for 1 h to afford 4l (101 mg, 67%) as a white solid; M.p. 203-204 oC (Petroleum ether/EtOAc); Rf = 0.26 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.11 (s, 1H), 7.88 (d, J = 7.2 Hz, 1H), 7.63-7.54 (m, 8H), 7.48-7.30 (m, 12H), 7.26-7.14 (m, 2H), 6.52 (d, J = 3.2 Hz, 1H) , 6.10 (d, J = 2.8 Hz, 1H), 5.62 (s, 1H);

13

C NMR (100 MHz, CDCl3): δ 153.9, 150.0, 141.2, 140.8, 139.5, 136.1,

129.2, 128.7, 127.1, 127.0, 124.1, 122.6, 121.0, 120.5, 120.1, 111.3, 110.1, 109.0, 103.9, 50.3; HRMS (ES+-TOF) calcd for C37H28NO ([M+H]+): 502.2171, found 502.2169. 3-(5-(bis(4-tert-butylphenyl)methyl)furan-2-yl)-1H-indole (4m) A mixture of 1H-indole 1a (35 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and bis(4-tert-butylphenyl)(furan-2-yl)methanol 2c (108 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 oC for 1 h to afford 4m (94 mg, 68%) as a white solid; M.p. 183-184 oC (Petroleum ether/EtOAc); Rf = 0.19 (Petroleum ether/EtOAc 10/1); 1H NMR (400 MHz, CDCl3): δ 8.01 (s, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.38-7.29 (m, 6H), 7.23-7.13 (m, 6H), 6.45 (d, J = 2.8 Hz, 1H), 6.01 (d, J = 2.8 Hz, 1H), 5.47 (s, 1H), 1.30 (s, 18H); 13C NMR (100 MHz, CDCl3): δ 154.6, 149.6, 149.2, 139.3, 136.1, 128.4, 125.2, 124.2, 122.5, 120.9, 120.3, 120.2, 111.2, 109.6, 109.2, 103.9, 50.0, 34.4, 31.4; HRMS (ES+-TOF) calcd for C33H36NO ([M+H]+): 462.2797, found 462.2799. 3-(5-(bis(4-chlorophenyl)methyl)furan-2-yl)-1H-indole (4n) A mixture of 1H-indole 1a (35 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and bis(4-chlorophenyl)(furan-2-yl)methanol 2d (95 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE



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at 40 oC for 4 h to afford 4n (52 mg, 42%) as a white solid; M.p. 154-155 oC (Petroleum ether/EtOAc); Rf = 0.35 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.11 (s, 1H), 7.82 (d, J = 6.8 Hz, 1H), 7.41-7.10 (m, 12H), 6.49-6.44 (m, 1H) , 5.99-5.94 (m, 1H), 5.45 (s, 1H);

13

C NMR (100 MHz,

CDCl3): δ 152.9, 150.3, 140.1, 136.1, 132.7, 130.1, 128.6, 124.1, 122.7, 121.0, 120.6, 120.1, 111.3, 110.3, 108.9, 103.9, 49.6; HRMS (ES+-TOF) calcd for C25H18Cl2NO ([M+H]+): 418.0765, found 418.0748. 3-(5-(phenyl(p-tolyl)methyl)furan-2-yl)-1H-indole (4o) A mixture of 1H-indole 1a (35 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yl(phenyl)(p-tolyl)methanol 2e (80 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 o

C for 0.5 h to afford 4o (74 mg, 68%) as a white solid; M.p. 100-101 oC (Petroleum ether/EtOAc); Rf

= 0.32 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 6.4 Hz, 2H), 7.31-7.07 (m, 13H), 6.44 (d, J = 3.2 Hz, 1H), 5.99-5.95 (m, 1H) , 5.48 (s, 1H); 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 154.3, 149.8, 142.4, 139.2, 136.2, 136.0, 129.1, 128.8, 128.7, 128.4, 126.5, 124.0, 122.5, 121.0, 120.4, 120.1, 111.3, 109.9, 108.9, 103.8, 50.5, 21.0; HRMS (ES+-TOF) calcd for C26H22NO ([M+H]+): 364.1701, found 364.1701. 3-(5-(2,2-dimethyl-1-phenylpropyl)furan-2-yl)-1H-indole (4p) Methond A: a mixture of 1H-indole 1a (35 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and 1-(furan-2-yl)-2,2-dimethyl-1-phenylpropan-1-ol 2i (69 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 2 h to afford 4p (47mg, 48%); Methond B: a mixture of 1H-indole 1a

(36

mg,

0.3

mmol,

1.0

equiv),

TFA

(4

mg,

0.03

mmol,

0.1

equiv)

and

1-(furan-2-yl)-2,2-dimethyl-1-phenylpropan-1-ol 2i (69 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 oC for 1.5 h to afford 4p (64mg, 65%) as a brown oil; Rf = 0.22 (Petroleum ether/EtOAc 10/1). 1H NMR (400 MHz, CDCl3): δ 8.07 (s, 1H), 7.95 (d, J = 6.8 Hz, 1H), 7.47 (d, J = 7.2 Hz, 2H), 7.42 (d, J = 2.0 Hz, 1H), 7.36-7.32 (m, 1H), 7.31-7.17 (m, 5H), 6.44 (d, J = 2.8 Hz, 1H), 6.23 (d, J = 2.8 Hz, 1H), 3.83 (s, 1H), 1.05 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 154.3, 148.9, 140.5, 136.2, 130.0, 127.7, 126.2, 124.2, 122.5, 120.7, 120.4, 120.2, 111.3, 109.6, 108.8, 103.9, 56.8, 35.2, 28.7; HRMS (ES+-TOF) calcd for C23H24NO ([M+H]+): 330.1858, found 330.1861.

(3) Procedure for the synthesis of 5 3-(1-(furan-2-yl)-1-phenylethyl)-1H-indole (5a)


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Method A: 1H-indole 1a (36 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and 1-(furan-2-yl)-1-phenylethanol 2j (57 mg, 0.3 mmol, 1.0 equiv) were dissolved in 3 mL of DCE in sequence. The mixture was then stirred at 80 oC for 2 h under N2. After completion of the reaction, the solvent was removed in vacuo, and the residue was purified with flash silica gel chromatography to 5a (84mg, 97%) as a yellow oil; Rf = 0.45 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.66 (s, 1H), 7.32 (s, 1H), 7.27-7.07 (m, 8H), 6.95-6.88 (m, 1H), 6.64-6.61 (m, 1H), 6.29-6.25 (m, 1H), 6.02-5.97 (m, 1H), 2.13 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 160.7, 146.6, 141.3, 136.8, 127.9, 127.4, 126.2, 126.1, 122.8, 122.6, 121.63, 121.60, 119.1, 111.1, 109.8, 106.6, 44.8, 27.6; HRMS (ES+-TOF) calcd for C20H18NO ([M+H]+): 288.1388, found 288.1394. Byproduct: 3-(1-(furan-2-yl)-1-phenylethyl)-1H-indole (4q) Method B: 1H-indole 1a (35 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and 1-(furan-2-yl)-1-phenylethanol 2j (56 mg, 0.3 mmol, 1.0 equiv) were dissolved in 3 mL of DCE in sequence. The mixture was then stirred at 40 oC for 1.5 h under N2. After completion of the reaction, the solvent was removed in vacuo, and the residue was purified with flash silica gel chromatography to 5a (43mg, 51%) and 4q (22mg, 26%), respectively. The data of 4q: a yellow solid, M.p. 83-84 oC (Petroleum ether/EtOAc); Rf = 0.38 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 8.12 (s, 1H), 7.98 (d, J = 7.6 Hz, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.33-7.30 (m, 3H), 7.26-7.16 (m, 4H), 6.45 (d, J = 2.8 Hz, 1H), 6.13 (d, J = 2.8 Hz, 1H), 4.21 (q, J = 6.8 Hz, 1H), 1.67 (d, J = 7.2 Hz, 3H);

13

C NMR (100 MHz, CDCl3): δ 156.6, 149.2, 144.4, 136.1, 128.4, 127.5, 127.4, 126.4,

124.2, 122.5, 120.7, 120.4, 120.2, 111.2, 109.3, 106.5, 103.8, 39.3, 20.7; HRMS (ES+-TOF) calcd for C20H18NO ([M+H]+): 288.1388, found 288.1382. 3-(furan-2-yl(phenyl)methyl)-1H-indole (5b) Method A: a mixture of 1H-indole 1a (36 mg, 0.3 mmol, 1.0 equiv), ZnCl2 (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yl(phenyl)methanol 2k (53 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 80 oC for 2 h to afford 5b (70mg, 84%); Method B: a mixture of 1H-indole 1a (35 mg, 0.3 mmol, 1.0 equiv), TFA (4 mg, 0.03 mmol, 0.1 equiv) and furan-2-yl(phenyl)methanol 2k (52 mg, 0.3 mmol, 1.0 equiv) was stirred in 3 mL of DCE at 40 oC for 1.5 h to afford 5b (75mg, 90%) as a green solid; M.p. 46-47 oC (Petroleum ether/EtOAc); Rf = 0.15 (Petroleum ether/EtOAc 10/1); 1H NMR (400 MHz, CDCl3): δ 7.75 (s, 1H), 7.35-7.31 (m, 2H), 7.29-7.18 (m, 6H), 7.13 (t, J = 7.4 Hz, 1H), 7.00 (t, J = 7.4 Hz, 1H), 6.67-6.64 (m, 1H), 6.28-6.25 (m, 1H), 5.97-5.94 (m, 1H), 5.64 (s, 1H); 13C NMR (100 MHz, CDCl3):



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δ 156.8, 141.8, 141.6, 136.4, 128.40, 128.37, 126.62, 126.58, 123.2, 122.1, 119.5, 119.4, 117.3, 111.1, 110.1, 107.3, 42.6; HRMS (EI-TOF) calcd for C19H15NO ([M]+): 273.1154, found 273.1151.

3. Chemical derivatization of 3a and 4a for the synthesis of trans-6 and 7 Dimethyl 2-(2-(1H-indol-3-yl)-4-oxo-3,3-diphenylcyclopentyl)malonate (trans-6) A mixture of 4-(1H-indol-3-yl)-5,5-diphenylcyclopent-2-enone 3a (105 mg, 0.3 mmol, 1.0 equiv), dimethyl malonate (60 mg, 0.45 mmol, 1.5 equiv) and Cs2CO3 (10 mg, 0.03 mmol, 0.1 equiv) was stirred in 3 mL of t-BuOH at room temperature under ambient atmosphere for 12 h. After completion of the reaction, the solvent was removed in vacuo, and the residue was purified with flash silica gel chromatography to afford trans-6 (120 mg, 83%) as a white solid; M.p. 191-192 oC (Petroleum ether/EtOAc); Rf = 0.14 (Petroleum ether/EtOAc 3/1); 1H NMR (400 MHz, CDCl3): δ 8.03 (s, 1H), 7.55 (d, J = 8.0 Hz, 2H), 7.40 (s, 1H), 7.40-7.04 (m, 9H), 6.69 (d, J = 7.6 Hz, 2H), 5.78 (s, 1H), 4.73 (d, J = 12.0 Hz, 1H), 3.68 (s, 3H), 3.43 (d, J = 4.8 Hz, 1H), 3.37 (s, 3H), 3.20-3.38 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 217.0, 169.1, 168.5, 142.1, 141.8, 135.3, 130.4, 129.0, 127.9, 127.4, 127.0, 126.8, 124.4, 121.8, 119.6, 118.9, 111.1, 111.0, 67.7, 52.4, 52.3, 51.6, 46.4, 42.0; HRMS (ES+-TOF) calcd for C30H28NO5 ([M+H]+): 482.1967, found 482.1971 1-(1H-indol-3-yl)-5,5-diphenylpentane-1,4-dione (7) The concentrated HCl (1.25 ml, 15 mmol, 50 equiv) was added to the solution of 3-(5-benzhydrylfuran-2-yl)-1H-indole 4a (105 mg, 0.3 mmol, 1.0 equiv) in 3mL of MeOH. Then, the mixture was stirred at 80 oC under ambient atmosphere for 5 h. After completion of the reaction, the solvent was removed in vacuo, and the residue was purified with flash silica gel chromatography to afford 7 (78 mg, 71%) as a white solid: M.p. 168-169 oC (Petroleum ether/EtOAc); Rf = 0.13 (Petroleum ether/EtOAc 3/1); 1H NMR (400 MHz, CDCl3): δ 8.74 (s, 1H), 8.32 (d, J = 7.6 Hz, 1H), 7.80 (s, 1H), 7.36-7.30 (m, 5H), 7.29-7.23 (m, 8H), 5.34 (s, 1H), 3.18 (t, J = 6.4 Hz, 2H), 3.02 (t, J = 6.0 Hz, 2H);

13

C NMR (100 MHz, CDCl3): δ 208.6, 194.0, 146.6, 138.3, 136.2, 131.3, 129.1, 128.7, 127.2,

125.3, 123.6, 122.6, 122.2, 111.4, 64.5, 36.9, 33.8; HRMS (ES+-TOF) calcd for C25H22NO2 ([M+H]+): 368.1651, found 368.1655. 4. Control experiments 3-(5-(diphenylmethylene)-2,5-dihydrofuran-2-yl)-1H-indole (8)


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A mixture of 1H-indole 1a (119 mg, 1 mmol, 1.0 equiv), ZnCl2 (14 mg, 0.1 mmol, 0.1 equiv) and furan-2-yldiphenylmethanol 2a (250 mg, 1 mmol, 1.0 equiv) was stirred in 5 mL of DCE at 40 oC for 1.5 h to afford 8 (134 mg, 38%) as a white solid; M.p. 154-155 oC (Petroleum ether/EtOAc); Rf = 0.28 (Petroleum ether/EtOAc 5/1); 1H NMR (400 MHz, CDCl3): δ 7.99 (s, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.40-7.28 (m, 6H) ,7.23-7.12 (m, 4H) ,7.12-7.03 (m, 2H), 6.55 (s, 1H), 6.43-6.36 (m, 2H);

13

C NMR (100 MHz, CDCl3): δ 158.1, 141.2, 139.5, 136.5, 135.2, 131.3, 129.2, 128.2, 127.7,

126.5, 126.2, 125.8, 125.5, 123.0, 122.5, 120.1, 119.6, 113.6, 111.8, 111.3, 84.6; HRMS (ES+-TOF) calcd for C25H20NO ([M+H]+): 350.1545, found 350.1547. 4-(1H-indol-3-yl)-5,5-diphenylcyclopent-2-enone (3a) 3-(5-(diphenylmethylene)-2,5-dihydrofuran-2-yl)-1H-indole 8 (70 mg, 0.2 mmol, 1.0 equiv) and ZnCl2 (3 mg, 0.02 mmol, 0.1 equiv) were dissolved in 2 mL of DCE in sequence. The mixture was then stirred at 80 oC under N2 for 0.5 h. After completion of the reaction, the solvent was removed in vacuo, and the residue was purified with flash silica gel chromatography to afford 3a (47 mg, 67%). 3-(5-benzhydrylfuran-2-yl)-1H-indole (4a) 3-(5-(diphenylmethylene)-2,5-dihydrofuran-2-yl)-1H-indole 8 (69 mg, 0.2 mmol, 1.0 equiv) and TFA (3 mg, 0.02 mmol, 0.1 equiv) were dissolved in 2 mL of DCE in sequence. The mixture was then stirred at 40 oC under N2 for 1.5 h. After completion of the reaction, the solvent was removed in vacuo, and the residue was purified with flash silica gel chromatography to afford 4a (31 mg, 45%).

Supporting Information NOE spectra of 6; copies of NMR (1H, 13C) spectra for 3a-3p, 4a-4q, 5a, 5b, 6, 7 and 8; X-ray crystallographic data for compound 3a; X-ray crystallographic data for compound 4a;

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]



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Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENT:

We are grateful to the National Natural Science Foundation of China (21302169, 21602202, 21602203), the Science Foundation of Zhejiang Sci-Tech University (Grant Nos. 13062121-Y, 1206820-Y and 1206821-Y) and the program for innovative research team of Zhejiang Sci-Tech University (Grant Nos. 13060052-Y) for financial support.

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