Chemodivergent Tandem Cyclizations of 2-Indolylmethanols with

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Chemodivergent Tandem Cyclizations of 2-Indolylmethanols with Tryptophols: C–N versus C–C Bond Formation Jing-Yi Wang, Ping Wu, Jia-Le Wu, Guang-Jian Mei, and Feng Shi J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00414 • Publication Date (Web): 07 May 2018 Downloaded from http://pubs.acs.org on May 7, 2018

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The Journal of Organic Chemistry

Chemodivergent Tandem Cyclizations of 2-Indolylmethanols with Tryptophols: C–N versus C–C Bond Formation Jing-Yi Wang‡, Ping Wu‡, Jia-Le Wu, Guang-Jian Mei* and Feng Shi* School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, China E-mail: [email protected]; [email protected] ‡

These authors contributed equally to the work.

Abstract: A chemodivergent reaction of 2-indolylmethanols with tryptophols has been established via an interrupted Nazarov-type cyclization in the presence of Brønsted acid, leading to the efficient synthesis of two series of cyclopenta[b]indole derivatives in a broad substrate scope with high yields and excellent diastereoselectivities (42 examples, up to 99% yield, all >95:5 dr). It was found that the presence or absence of molecular sieves played an important role in controlling the chemoselectivity of the reaction. In the presence of 3 Å molecular sieves, tryptophol would utilize the nucleophilicity of its nitrogen atom to form a new C-N bond; while in the absence of molecular sieves, tryptophol would utilize the nucleophilicity of its C2-position to generate a new C-C bond. So, this reaction will provide a good example for additives-controlled chemoselectivity. In addition, this approach not only provides a useful strategy for the synthesis of structurally diversified cyclopenta[b]indoles, but also demonstrates the practicability of 2-indolylmethanols in organic synthesis.

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Introduction Fused-polycyclic indoles represent one of the most important class of heterocyclic compounds due to their versatile bioactivities.1 Among them, cyclopenta[b]indole frameworks are widely featured in biologically active natural products and synthetic compounds (Figure 1).2-3 For instance, the core structures of natural alkaloids Bruceolline J and Yeuhchukene are cyclopenta[b]indole frameworks. In addition, Yeuhchukene was reported to possess potent anti-implantation activity.2 Moreover, synthetic compounds I–IV exhibit a broad scope of bioactivities such as antioxidant, being antagonist of prostaglandin D2 receptor and being agonist of progesterone receptor.3 As a result, continuous attentions from the chemistry community have been paid to the synthesis of cyclopenta[b]indole derivatives.4

Figure 1. Natural alkaloids and synthetic compounds containing the cyclopenta[b]indole scaffold. Chemodivergent reaction has proven to be one of the most important strategies for the generation of molecular diversity and complexity.5 From the same starting materials, chemodivergent reactions lead to different chemoselective processes.6 This chemodivergent strategy has not only been recognized as one of the most promising paradigms in drug discovery, but also becomes one of the main challenges in organic synthesis. In this regard, it is highly desired to develop chemodivergent reactions for the synthesis of cyclopenta[b]indole derivatives.


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Recently, indolylmethanols have emerged as versatile synthons in organic synthesis.7-8 Especially, 2-indolylmethanol-involved reactions have been widely employed in the synthesis of indole derivatives or indole-fused cyclic frameworks.9-10 However, the investigations on 2-indolymethannols are only limited to substitutions or cyclizations (Scheme 1a and 1b). To the best of our knowledge, there is no report on the chemodivergent reactions of 2-indolymethannols. a) Substitution patterns of 2-indolylmethanols

N H

Nu R 2' Ar

Nu R=H C2'-position

3 N H

OH R 2' Ar

Nu R = Ar C3-position

Nu 3 N H

R Ar

b) Cyclization patterns of 2-indolylmethanols R Nu

Nu E N H

R1 R2

R3

E R3 = H 3C synthon

N H

Nu OH R1 R2

E R3 = H NCC synthon

N E

R1

R2

Nu

Scheme 1. Profile of 2-indolymethanol-involved reactions. Recently, we established catalytic asymmetric interrupted Nazarov-Type cyclizations of C3-alkenyl-substituted 2-indolymethanols with nucleophiles such as indoles (Scheme 2a).11-12 When we utilize tryptophols as nucleophiles, we find a chemodivergent reaction of C3-alkenyl-substituted 2-indolylmethanols with tryptophols via an interrupted Nazarov-type cyclization process,13-16 leading to the synthesis of two series of cyclopenta[b]indole derivatives via carbon-nitrogen (C-N) or carbon-carbon (C-C) bond formation (Scheme 2b).

Scheme 2. Chemodivergent reaction of C3-alkenyl-substituted 2-indolymethanols.



Herein, we report the details on the chemodivergent reaction of 2-indolylmethanols with tryptophols in the presence of Brønsted acid, which led to the efficient synthesis of two series of cyclopenta[b]indole derivatives in a broad substrate scope with high yields and excellent diastereoselectivities (42 examples, up to 99% yield, all >95:5 dr). It should be noted that N-unprotected indole derivatives have two nucleophilic sites: one is indole C3 or C2-position, another is indole N1-position. So, how to control the chemoselectivity of the reaction is a great challenge. In this work, we find the chemoselectivity of the reaction between 2-indolylmethanols and tryptophols can be controlled by adding 3 Å molecular sieves.

Results and Discussion

Our investigation was initiated by the model reaction between 2-indolylmethanol 1a and tryptophol 2a under Brønsted acid catalysis17 (Table 1). First, the solvent effect was examined by screening a series of solvents under the catalysis of phosphoric acid 5a at 30 ℃ in the presence of 3 Å molecular sieves (MS) because water would be generated during the reaction process (entries 1-6). To our delight, the interrupted Nazarov-type cyclization of 2-indolylmethanols 1a with tryptophols 2a occurred smoothly in toluene or chloroform, affording N-alkylation product 3aa through C-N bond formation in moderate yields (entries 5-6). It should be noted that the N-alkylation of indole derivatives have remained underdeveloped, possibly due to the low nucleophilicity of the N-H motif.18 So, inspired by this preliminary result, a series of Brønsted acids 5 were screened in chloroform (entries 6-11). The results revealed that Brønsted acids with strong acidity could successfully catalyze the reaction (entries 6-9), and Brønsted acid 5c was the best catalyst in terms of the yield (entry 8). However, Brønsted acids 5e-5f with weak acidity


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failed to catalyze the reaction (entries 10-11). So, 5c was selected as the optimal catalyst for subsequent condition optimization. It was found that additives had a significant effect on the reaction (entries 12-16). The reaction could not occur with 4 Å molecular sieves (entry 12). When employing 5 Å MS, MgSO4 and Na2SO4 as additives, a mixture of products 3aa (generated via C-N bond formation) and 4aa (generated via C-C bond formation) was observed (entries 13-15). Interestingly, in the absence of additives, 4aa was isolated as the sole product (entry 16). So, this result provided a good opportunity for us to control the chemoselectivity of the reaction by adding 3 Å MS as additives or removing the additives. Subsequently, we were pleased to find that the yield of product 3aa or 4aa could be improved to an excellent or good level by increasing the equivalent ratio of substrate 1a (entries 17-19 and entries 20-22). In addition, the yield of 4aa could be further improved at a higher temperature or using a larger amount of catalyst 5c (entries 23-24), but furhter elevating the reaction temperature led to a slight decrease in the yield (entry 25). Finally, the optimal reaction conditions for this chemodivergent cyclization of 2-indolylmethanol 1a with tryptophol 2a were selected as those shown in entry 18 (for C-N bond formation) and entry 24 (for C-C bond formation), which afforded the corresponding products 3aa and 4aa in excellent yields of 97% and 83%, respectively. Table 1. Optimization of the reaction conditionsa

entry

5

solvent

T (oC)

1a:2a

additives

product

yield (%)b

1

5a

acetone

30

1:1.2

3 Å MS

-

-

2

5a

CH3CN

30

1:1.2

3 Å MS

-

-

3

5a

THF

30

1:1.2

3 Å MS

-

-



4

5a

EtOAc

30

1:1.2

3 Å MS

-

-

5

5a

toluene

30

1:1.2

3 Å MS

3aa

54

6

5a

CHCl3

30

1:1.2

3 Å MS

3aa

60

7

5b

CHCl3

30

1:1.2

3 Å MS

3aa

58

8

5c

CHCl3

30

1:1.2

3 Å MS

3aa

79

9

5d

CHCl3

30

1:1.2

3 Å MS

3aa

49

10

5e

CHCl3

30

1:1.2

3 Å MS

-

-

11

5f

CHCl3

30

1:1.2

3 Å MS

-

-

12

5c

CHCl3

30

1:1.2

4 Å MS

-

-

13

5c

CHCl3

30

1:1.2

5 Å MS

3aa/4aa

46/12

14

5c

CHCl3

30

1:1.2

MgSO4

3aa/4aa

15/48

15

5c

CHCl3

30

1:1.2

Na2SO4

3aa/4aa

47/24

16

5c

CHCl3

30

1:1.2

-

4aa

50

17

5c

CHCl3

30

1.2:1

3 Å MS

3aa

87

18

5c

CHCl3

30

1.5:1

3 Å MS

3aa

97

19

5c

CHCl3

30

1.8:1

3 Å MS

3aa

91

20

5c

CHCl3

30

1.2:1

-

4aa

58

21

5c

CHCl3

30

1.5:1

-

4aa

63

22

5c

CHCl3

30

1.8:1

-

4aa

74

23

5c

CHCl3

40

1.8:1

-

4aa

79

c

5c

CHCl3

40

1.8:1

-

4aa

83

c

5c

CHCl3

40

1.8:1

-

4aa

78

24 25 a

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Unless indicated otherwise, the reaction was carried out at 0.05mmol scale and catalyzed by 10 mol % 5 in a

solvent (1 mL) for 8 h. bIsolated yield and only one diastereomer was observed in all cases. cCatalyzed by 20 mol % 5c.

With the optimal reaction conditions in hand, we then carried out the investigation on the substrate scope of the interrupted Nazarov-type cyclization of 2-indolylmethanols 1 with tryptophols 2 through a C-N bond formation. As shown in Table 2, all reactions between various 2-indolylmethanols 1 and tryptophols 2 worked smoothly, providing tryptophol-substituted cyclopenta[b]indoles 3 via C-N bond formation in moderate to excellent yields (57-99%). It seemed that the position and the electronic nature of the substituents (R/R1/R2) of 2-indolylmethanols 1 had some delicate impacts on the yield. For instance, when R was a substituted phenyl group, a slightly decrease in the yield was observed (entry 1 vs entries 2-3). Moreover, various substituted aryl groups (R1) at the terminal position of the alkenyl groups were


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tolerated (entries 4-10). It seemed that the electronic nature of the R2 group had some influence on the yield because 2-indolylmethanols 1m-1n bearing electron-donating groups on the indole ring were superior to their counterpart 1l substituted with an electron-withdrawing group in terms of the yield (entry 11 vs entries 12-13). However, changing the position of the chloro group (entry 11 vs 14), the corresponding products 3la and 3oa were obtained in the same level of yield. Besides, a wide range of tryptophols 2 bearing various substituents on the benzene ring could be successfully employed to this reaction (entries 15-22). Among them, an excellent yield of 99% was obtained in the reaction of C5-fluoro-substituted tryptophol 2d (entry 17). It should be noted that only one diastereomer of products 3 was observed in all cases (all >95:5 dr). Table 2. Chemoselective synthesis of products 3 via C-N bond formationa

entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

3 3aa 3ba 3ca 3ea 3fa 3ga 3ha 3ia 3ja 3ka 3la 3ma 3na 3oa 3ab 3ac 3ad 3ae 3af 3ag 3ah

R/R1/R2(1) Ph/Ph/H(1a) p-FC6H4/Ph/H(1b) p-MeC6H4/Ph/H(1c) Ph/p-ClC6H4/H(1e) Ph/p-FC6H4/H(1f) Ph/p-MeOC6H4/H(1g) Ph/m-ClC6H4/H(1h) Ph/m-MeC6H4/H(1i) Ph/o-FC6H4/H(1j) Ph/o-MeC6H4/H(1k) Ph/Ph/5-Cl(1l) Ph/Ph/5-Me(1m) Ph/Ph/5-MeO(1n) Ph/Ph/6-Cl(1o) Ph/Ph/H(1a) Ph/Ph/H(1a) Ph/Ph/H(1a) Ph/Ph/H(1a) Ph/Ph/H(1a) Ph/Ph/H(1a) Ph/Ph/H(1a)

R3(2) H(2a) H(2a) H(2a) H(2a) H(2a) H(2a) H(2a) H(2a) H(2a) H(2a) H(2a) H(2a) H(2a) H(2a) 5-Br(2b) 5-Cl(2c) 5-F(2d) 5-Me(2e) 5-MeO(2f) 6-Cl(2g) 6-F(2h)


drb >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5

yield (%)c 97 78 81 94 67 91 85 69 74 78 62 99 95 70 80 88 99 84 77 57 63


22 a

3ak

Ph/Ph/H(1a)

7-MeO(2k)

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>95:5

61

Unless indicated otherwise, the reaction was carried out at 0.1mmol scale and catalyzed by 10 mol % 5c in CHCl3

(1 mL) with 3 Å MS (50 mg) at 30 ℃ for 3 h, and the molar ratio of 1:2 was 1.5:1. bDetermined by 1H NMR. c

Isolated yield.

Next, the generality of the interrupted Nazarov-type cyclization of 2-indolylmethanols 1 with tryptophols 2 through a C-C bond formation was examined (Table 3). First, this reaction was applicable to a variety of 2-indolylmethanols 1 with distinct R/R1/R2 substituents (entries 1-8). Among them, R groups could be various aryl groups bearing different substituents, which gave the corresponding products 4 in generally good yields (entries 2-4). Besides, excellent yields could be obtained when R1 substituents were electron-poor aryl groups (entries 5-6). The electronic nature of the R2 substituents might have a significant impact on the reactivity. For example, when R2 substituent was a methyl group, an excellent yield could be observed (entry 7). However, there was a significant decrease in the yield when R2 substituent was a strong electron-rich methoxy group (entry 8). Then, the applicability of tryptophols 2 was examined (entries 9-16). The results indicated that tryptophols 2 bearing electron-withdrawing substituents (2c-2d, 2g and 2j) were superior to their counterparts (2e-2f, 2i and 2k) substituted with electron-donating groups at the same position in terms of the yield (entries 9-10 vs 11-12; entry 13 vs 14; entry 15 vs 16). Furthermore, all reactions proceeded with excellent diastereoselectivities (all >95:5 dr). Table 3. Chemoselective synthesis of products 4 via C-C bond formationa

entry 1 2 3 4 5

4 4aa 4ba 4ca 4da 4fa

R/R1/R2(1) Ph/Ph/H(1a) p-FC6H4/Ph/H(1b) p-MeC6H4/Ph/H(1c) m-FC6H4/Ph/H(1d) Ph/p-FC6H4/H(1f)

R3(2) H(2a) H(2a) H(2a) H(2a) H(2a)


drb >95:5 >95:5 >95:5 >95:5 >95:5

yield (%)c 83 92 80 95 99

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6 7 8 9 10 11 12 13 14 15 16 a

4ha 4ma 4na 4ac 4ad 4ae 4af 4ag 4ai 4aj 4ak

Ph/m-ClC6H4/H(1h) Ph/Ph/5-Me(1m) Ph/Ph/5-MeO(1n) Ph/Ph/H(1a) Ph/Ph/H(1a) Ph/Ph/H(1a) Ph/Ph/H(1a) Ph/Ph/H(1a) Ph/Ph/H(1a) Ph/Ph/H(1a) Ph/Ph/H(1a)

H(2a) H(2a) H(2a) 5-Cl(2c) 5-F(2d) 5-Me(2e) 5-MeO(2f) 6-Cl(2g) 6-Me(2i) 7-Me(2j) 7-MeO(2k)

>95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5 >95:5

99 99 47 79 97 77 67 99 75 91 66

Unless indicated otherwise, the reaction was carried out at 0.1mmol scale and catalyzed by 20 mol % 5c in CHCl3

(1 mL) at 40 ℃ for 8 h, and the molar ratio of 1:2 was 1.8:1. bDetermined by 1H NMR. cIsolated yield.

It was worth-noting that 3-(1H-indol-3-yl)propan-1-ol 2l could also be employed as a suitable substrate for this chemodivergent interrupted Nazarov-type cyclization of 2-indolylmethanol. As shown in Scheme 3a, the reaction of 2-indolylmethanol 1a with substrate 2l occurred smoothly under optimal reaction conditions, affording cyclopenta[b]indole products 3al and 4al in a chemodivergent manner with moderate to good yields and excellent diastereoselectivities. Moreover, N-methyl 2-indolylmethanol 1p could also be utilized for this reaction, which generated the corresponding products 3pa and 4pa in high yields and excellent diastereoselectivities (Scheme 3b).

Scheme 3. Further substrate expansion.



The structures of all products 3 and 4 were unambiguously assigned by 1H and 13C NMR, IR and HRMS. Moreover, the relative configurations of products 3aa and 4aa were unambiguously determined to be trans by single-crystal X-ray diffraction analysis (Figure S1-S2 in the supporting information).19 The relative configurations of other products 3 and 4 were assigned by analogy. In addition, to further explore the scope and limitation of this chemodivergent reaction, 2-indolylmethanols 1q and 1r bearing a methyl group adjacent to the hydroxy functionality were employed as subtrates to react with tryptophol 2a under the two standard conditions (Scheme 4). In the case of 2-indolylmethanols 1q, tryptophol 2a failed to participate in the reaction, and only a self-dimerization product 6 of substrate 1q was generated (Scheme 4a). While in the case of 2-indolylmethanols 1r, only a self-cyclization product 7 of substrate 1q was observed (Scheme 4b), which might be formed via a dehydration/cyclization/oxidation sequence (Scheme 4c). These results implied that the two phenyl groups adjacent to the hydroxy functionality in the structures of 2-indolylmethanols 1 were necessary for perfoming the reaction between substrates 1 and 2.

Scheme 4. Using 2-indolylmethanols 1q and 1r as substrates. Moreover, other aromatic nucleophiles such as pyrrole 2m, benzofuran 2n and benzothiophene 2o were utilized as substrates to react with 2-indolylmethanol 1a under the two


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standard conditions (Scheme 5). However, none of them could take part in the reaction, and only a byproduct 8 was generated by the Nazarov cyclization of substrate 1a. These outcomes demonstrated that the selection of a suitable aromatic nucleophile is very important for accomplishing the interrupted Nazarov-type cyclization. Ph

a)

Ph OH Ph Ph

10 mol% 5c 8 61%

3Å MS CHCl3, 30 °C

N H

57%

OH Ph Ph

10 mol% 5c 3Å MS CHCl3, 30 °C

N H

CHCl3, 40 °C

20 mol% 5c

+ O

CHCl3, 40 °C

S

CHCl3, 40 °C

Ph N Ph H 8 63%

8 55%

2n

1a Ph OH Ph Ph

10 mol% 5c 37%

N H 2m

Ph

c)

8

+

1a

b) 8

20 mol% 5c


N H 1a

20 mol% 5c

+

8 48%

2o

Scheme 5. Using other aromatic nucleophiles 2 as substrates. In order to gain some insights into the activation mode of the catalyst to substrates 2, we performed some control experiments (Scheme 6). When using tryptamine 2p and TBS-protected tryptophol 2q to replace tryptophol 2a as substrates to react with 2-indolylmethanol 1a under the two standard conditions, both of the two substrates 2p and 2q failed to participate in the reaction, and only the byproduct 8 was generated. These phenomena indicated that the existence of the OH group in the structure of substrates 2 played a crucial role in controlling the reactivity.

Scheme 6. Control experiments.



Based on the experimental results and previous reports on the effect of molecular sieves,20 a possible reaction pathway was suggested to explain the observed chemoselectivity (Scheme 7). As exemplified by the formation of products 3aa and 4aa, under the catalysis of Brønsted acid 5c, the active carbocations A and B were generated from 2-indolylmethanol 1a via dehydration. Then, the sequential 4π electrocyclization of the carbocation intermediate resulted in a cyclopenta[b]indole carbocation intermediate C, which would be trapped by tryptophol 2a in a chemodivergent manner. In the presence of 3 Å MS (path A), the water molecules generated from dehydration would be absorbed by 3 Å MS, which would not affect the nucleophilicity of the nitrogen atom in the indole ring. In addition, the anion of catalyst 5c would act as a base to deprotonate the N-H group, thus increasing the nucleophilicity of the nitrogen atom. At the same time, the anion of catalyst 5c simultaneously generated a hydrogen bond with the OH group of tryptophol 2a and produced an ion pair interaction with the carbocation intermediate C, which facilitated a chemoselective nucleophilic attack of the nitrogen atom to carbocation C and led to the formation of product 3aa via C-N bond formation. On the contrary, in the absence of molecular sieves (path B), the water molecules generated from dehydration would form a hydrogen bond with the nitrogen atom in the indole ring, thus greatly decreasing the nucleophilicity of the nitrogen atom. So, in this case, tryptophol 2a would utilize its C2-nucleophilicity to attack carbocation C via a dual activation mode of the anion of catalyst 5c to substrate 2a and intermediate C, thus leading to the generation of product 4aa via C-C bond formation. The observed trans-configuration of products might be attributed to avoiding the steric hindrance between the indole ring and the adjacent phenyl group.


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Scheme 7. Suggested reaction pathway. Besides, to demonstrate the utility of this chemodivergent interrupted Nazarov-type cyclization, two one-mmol scale reactions of 2-indolylmethanols with tryptophols were performed under the standard conditions, which generated the corresponding cyclopenta[b]indole products 3ad and 4ad in high yields and with excellent diastereoselectivities (Scheme 8). F Ph OH Ph Ph

OH F

10 mol% 5c

+

N H 1a 1.5 mmol

OH N

N H

Ph


2d 1 mmol

N H

Ph Ph

3ad 87% (490 mg), >95:5 dr F

Ph

OH HO

N H 1a 1.8 mmol

OH Ph Ph

20 mol% 5c

F + N H 2d 1 mmol

NH Ph

CHCl3, 40 °C

Ph Ph

N H 4ad 78% (440 mg), >95:5 dr

Scheme 8. One mmol scale synthesis. Finally, we carried out a preliminary investigation on the catalytic asymmetric version of this chemodivergent reaction. It was found either in the presence or in the absence of 3 Å MS, the



Page 14 of 57

reaction of 1a with 2a under the catalysis of chiral phosphoric acid (CPA) 9a could only generate product 3aa, and no product 4aa was observed. So, we screened a series of CPAs 9 in the presence of 3 Å MS. As shown in Table 4, most of CPAs 9 could catalyze the reaction apart from 9c and 9e (entries 3 and 5). Among them, CPA 9d bearing two 3,3’-(9-phenanthrenyl) groups displayed the highest capability in controlling the enantioselectivity of the reaction, which could afford product 3aa in a moderate enantioselectivity of 50% ee (entry 4). This result indicated that it is promising to develop a catalytic asymmetric version of this reaction after further optimization of reaction conditions. Table 4. Preliminary investigation on the catalytic asymmetric versiona

Cat.

yield (%)b

1

9a

68

>95:5

4

2

9b

58

>95:5

29

3

9c

trace

-

-

entry

a

drc

ee (%)d

4

9d

58

>95:5

50

5

9e

trace

-

-

6

9f

47

>95:5

20

7

9g

36

>95:5

33

Unless indicated otherwise, the reaction was carried out at 0.1mmol scale and catalyzed by 20 mol % 9 in CHCl3

(1 mL) with 3 Å MS (50 mg) at 30 ℃ for 4 h, and the molar ratio of 1a:2a was 1.5:1. bIsolated yield. cDetermined by 1H NMR and HPLC. dDetermined by HPLC.


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Conclusions

In summary, we have established a chemodivergent reaction of 2-indolylmethanols with tryptophols via an interrupted Nazarov-type cyclization in the presence of Brønsted acid, leading to the efficient synthesis of two series of cyclopenta[b]indole derivatives in a broad substrate scope with high yields and excellent diastereoselectivities (42 examples, up to 99% yield, all >95:5 dr). It was found that the presence or absence of molecular sieves played an important role in controlling the chemoselectivity of the reaction. In the presence of 3 Å molecular sieves, tryptophol would utilize the nucleophilicity of its nitrogen atom to form a new C-N bond; while in the absence of molecular sieves, tryptophol would utilize the nucleophilicity of its C2-position to generate a new C-C bond. So, this reaction will provide a good example for additives-controlled chemoselectivity. In addition, this approach not only provides a useful strategy for the synthesis of structurally diversified cyclopenta[b]indoles, but also demonstrates the practicability of 2-indolylmethanols in organic synthesis, which will greatly enrich the chemistry of 2-indolylmethanols. Experimental Section 1

H and 13C NMR spectra were measured at 400 and 100 MHz, respectively. The solvent used

for NMR spectroscopy were acetone-d6 and CDCl3, using tetramethylsilane as the internal reference. HRMS (ESI) was determined by a HRMS/MS instrument. The X-ray source used for the single crystal X-ray diffraction analysis of compounds 3aa and 4aa was MoKα (λ = 0.71073), and the thermal ellipsoid was drawn at the 30% probability level. Analytical grade solvents for the column chromatography were used after distillation, and commercially available reagents were used as received. Substrates 1 were prepared according to the procedures in the literature.11



Page 16 of 57

General procedure for the synthesis of products 3 To the mixture of 2-indolylmethanols 1 (0.15 mmol), tryptophols 2 (0.1 mmol), catalyst 5c (0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction which was indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography to afford pure products 3. 2-(1-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethanol (3aa): Following the general procedure, to the mixture of (E)-diphenyl(3-styryl-1H-indol-2-yl)methanol 1a (60.2 mg, 0.15 mmol), 2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3aa (52.7 mg) in 97% yield as white solid. m.p. 94-95 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.25 (s, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.52 (d, J = 7.6 Hz, 2H), 7.41 (d, J = 8.4 Hz, 1H), 7.34 (t, J = 7.6 Hz, 2H), 7.28 (d, J = 7.2 Hz, 1H), 7.25 – 7.21 (m, 1H), 7.18 – 7.12 (m, 2H), 7.11 – 6.98 (m, 9H), 6.90 (s, 1H), 6.79 (d, J = 7.2 Hz, 2H), 6.55 (d, J = 7.6 Hz, 2H), 6.29 (d, J = 5.4 Hz, 1H), 5.18 (d, J = 4.0 Hz, 1H), 3.80 – 3.74 (m, 2H), 2.91 (t, J = 6.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 147.3, 144.8, 142.7, 141.0, 136.6, 129.8, 129.7, 128.7, 127.7, 127.7, 127.5, 127.02, 126.9, 126.7, 123.5, 122.4, 121.5, 120.7, 119.3, 118.9, 118.7, 116.5, 112.2, 110.7, 68.5, 62.6, 61.7, 28.7; IR (KBr): 3299, 3053, 2920, 1491, 1458, 1034, 742, 702 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H32N2ONa 567.2407, found 567.2425. 2-(1-(3,3-bis(4-fluorophenyl)-2-phenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3 -yl)ethanol

(3ba):

Following

the

general

procedure,


to

the

mixture

of

Page 17 of 57 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


(E)-bis(4-fluorophenyl)(3-styryl-1H-indol-2-yl)methanol

1b

(65.6

mg,

0.15

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ba (45.2 mg) in 78% yield as white solid. m.p. 98-99 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.46 – 7.39 (m, 3H), 7.25 – 7.21 (m, 1H), 7.14 (d, J = 7.6 Hz, 1H), 7.10 – 7.03 (m, 4H), 7.02 (d, J = 1.6 Hz, 2H), 7.00 (s, 1H), 6.96 (t, J = 5.6 Hz, 2H), 6.86 (s, 1H), 6.79 – 6.67 (m, 4H), 6.50 – 6.37 (m, 2H), 6.24 (d, J = 5.6 Hz, 1H), 5.05 (s, 1H), 3.83 – 3.71 (m, 2H), 2.97 – 2.85 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 161.6 (J = 245 Hz), 141.1, 140.4, 138.2, 136.7, 131.2 (J = 8 Hz), 129.7, 129.3 (J = 8 Hz), 128.0, 127.2, 123.5, 122.7, 121.6, 121.0, 119.4, 119.0, 118.9, 116.6, 115.6 (J = 21 Hz), 114.3 (J = 21 Hz), 112.2, 110.9, 68.9, 62.6, 60.8, 54.7, 28.7; IR (KBr): 3256, 3058, 2916, 1601, 1506, 1458, 1225, 1161, 738 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H30F2N2ONa 603.2219, found 603.2232. 2-(1-(2-phenyl-3,3-di-p-tolyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethano l

(3ca):

Following

the

general

procedure,

to

the

mixture

of

(E)-(3-styryl-1H-indol-2-yl)di-p-tolylmethanol 1c (64.4 mg, 0.15 mmol), 2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ca (46.2 mg) in 81% yield as white solid. m.p. 83-84 oC; >95:5 dr; 1H NMR (400 MHz, Acetone-d6) δ 10.35 (s, 1H), 7.54 (d, J = 8.4 Hz,



Page 18 of 57

3H), 7.45 (d, J = 8.0 Hz, 1H), 7.16 (d, J = 8.0 Hz, 2H), 7.14 – 7.09 (m, 1H), 7.07 (d, J = 8.0 Hz, 1H), 7.05 – 6.92 (m, 7H), 6.91 – 6.83 (m, 5H), 6.45 – 6.23 (m, 3H), 5.26 (d, J = 6.4 Hz, 1H), 3.73 – 3.63 (m, 2H), 3.43 (t, J = 5.4 Hz, 1H), 2.86 – 2.82 (m, 2H), 2.31 (s, 3H), 2.22 (s, 3H); 13C NMR (100 MHz, Acetone-d6) δ 147.7, 142.3, 141.7, 140.4, 139.2, 136.7, 136.0, 135.8, 130.1, 129.5, 128.9, 128.0, 127.9, 127.4, 126.6, 123.4, 121.6, 120.8, 119.8, 118.7, 118.6, 118.5, 116.1, 112.4, 110.2, 68.8, 62.4, 61.1, 54.6, 28.6, 20.1, 19.9; IR (KBr): 3252, 3053, 2924, 1579, 1452, 1256, 1009, 744, 708 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C41H36N2ONa 595.2721, found 595.2713. 2-(1-(2-(4-chlorophenyl)-3,3-diphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3yl)ethanol

(3ea):

Following

the

general

(E)-(3-(4-chlorostyryl)-1H-indol-2-yl)diphenylmethanol

procedure, 1e

(65.3

to

the mg,

mixture 0.15

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ea (54.4 mg) in 94% yield as white solid. m.p. 72-73 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.10 (s, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.49 – 7.40 (m, 3H), 7.33 (t, J = 7.4 Hz, 2H), 7.28 (d, J = 7.6 Hz, 1H), 7.24 – 7.20 (m, 1H), 7.17 – 7.11 (m, 2H), 7.09 – 7.03 (m, 4H), 7.02 – 6.91 (m, 4H), 6.87 (s, 1H), 6.68 (d, J = 8.0 Hz, 2H), 6.51 (d, J = 7.6 Hz, 2H), 6.19 (d, J = 5.6 Hz, 1H), 5.10 (s, 1H), 3.83 – 3.73 (m, 2H), 2.91 (t, J = 6.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 144.5, 142.4, 141.1, 132.8, 131.1, 129.7, 128.8, 127.9, 127.7, 127.6, 127.2, 127.0, 123.5, 122.6, 121.6, 120.8, 119.3, 119.1, 118.9, 116.3, 112.2, 111.0, 110.4, 67.8, 62.7, 61.7, 55.6, 28.7; IR (KBr): 3278, 3056, 2923, 2852, 1706, 1458, 1288,


Page 19 of 57 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


741, 701 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31ClN2ONa 601.2018, found 601.2033. 2-(1-(2-(4-fluorophenyl)-3,3-diphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3yl)ethanol

(3fa):

Following

the

general

procedure,

(E)-(3-(4-fluorostyryl)-1H-indol-2-yl)diphenylmethanol

1f

to

(62.8

the mg,

mixture 0.15

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3fa (37.4 mg) in 67% yield as white solid. m.p. 98-99 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.47 (d, J = 7.6 Hz, 2H), 7.42 (d, J = 8.0 Hz, 1H), 7.34 (t, J = 7.6 Hz, 2H), 7.28 (d, J = 7.2 Hz, 1H), 7.25 – 7.20 (m, 1H), 7.17 – 7.11 (m, 2H), 7.09 – 7.03 (m, 4H), 7.02 – 6.92 (m, 2H), 6.89 (s, 1H), 6.74 – 6.65 (m, 4H), 6.51 (d, J = 7.6 Hz, 2H), 6.20 (d, J = 5.6 Hz, 1H), 5.12 (s, 1H), 3.82 – 3.72 (m, 2H), 2.92 (t, J = 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 161.8 (J = 240 Hz), 144.6, 142.6, 141.1, 136.7, 131.3 (J = 8 Hz), 129.7, 128.8, 127.7, 127.6, 127.1, 127.0, 123.5, 122.5, 121.6, 120.8, 119.3, 119.0, 118.9, 116.3, 114.6 (J = 21 Hz), 112.2, 110.9, 110.4, 67.7, 62.7, 61.6, 54.6, 28.7; IR (KBr): 3289, 3056, 2956, 1698, 1603, 1509, 1459, 1229, 833, 746, 701 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C39H32FN2O 563.2493, found 563.2487. 2-(1-(2-(4-methoxyphenyl)-3,3-diphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol3-yl)ethanol

(3ga):

Following

the

general

procedure,

(E)-(3-(4-methoxystyryl)-1H-indol-2-yl)diphenylmethanol

1g

to

(64.6

the mg,

mixture 0.15

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50



Page 20 of 57

mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ga (52.5 mg) in 91% yield as white solid. m.p. 90-91 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.10 (s, 1H), 7.58 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.4 Hz, 1H), 7.34 (t, J = 7.6 Hz, 2H), 7.28 (d, J = 7.2 Hz, 1H), 7.23 – 7.19 (m, 1H), 7.16 – 7.09 (m, 2H), 7.08 – 7.02 (m, 4H), 6.97 (d, J = 3.6 Hz, 2H), 6.91 (s, 1H), 6.62 (t, J = 9.4 Hz, 2H), 6.55 – 6.47 (m, 4H), 6.17 (d, J = 5.6 Hz, 1H), 5.10 (d, J = 4.8 Hz, 1H), 3.82 – 3.72 (m, 2H), 3.68 (s, 3H), 2.92 (t, J = 6.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 158.5, 144.8, 142.8, 141.0, 136.8, 136.5, 130.9, 129.7, 128.7, 128.5, 127.8, 127.6, 127.0, 126.8, 123.6, 122.5, 122.4, 122.2, 121.5, 120.7, 119.5, 119.3, 118.9, 118.8, 116.6, 113.1, 112.2, 111.2, 110.7, 67.8, 62.6, 61.5, 55.1, 54.9, 28.7; IR (KBr): 2359, 1245, 1035, 1005, 800, 744, 707, 668 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2O2Na 597.2513, found 597.2533. 2-(1-(2-(3-chlorophenyl)-3,3-diphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3yl)ethanol

(3ha):

Following

the

general


procedure, 1h

(65.3

to

the mg,

mixture 0.15

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford >95:5 dr 3ha (49.4 mg) in 85% yield as white solid. m.p. 68-69 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.60 (d, J = 7.6 Hz, 1H), 7.51 – 7.39 (m, 3H), 7.34 (t, J = 7.4 Hz, 2H), 7.28 (d, J = 7.2 Hz, 1H), 7.25 – 7.20 (m, 1H), 7.18 – 7.12 (m, 2H), 7.10 – 6.95 (m, 7H), 6.94 – 6.89 (m, 1H), 6.86 (s, 1H), 6.68 (d, J =


Page 21 of 57 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


7.2 Hz, 2H), 6.54 (d, J = 7.6 Hz, 2H), 6.23 (d, J = 5.2 Hz, 1H), 5.09 (s, 1H), 3.83 – 3.71 (m, 2H), 2.91 (t, J = 6.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 147.0, 144.5, 142.4, 141.2, 136.6, 133.6, 129.8, 129.6, 128.9, 128.8, 128.5, 128.0, 127.7, 127.6, 127.5, 127.2, 127.0, 125.4, 123.5, 122.6, 121.7, 120.9, 119.3, 119.1, 118.9, 116.2, 112.2, 111.0, 110.5, 68.0, 62.7, 61.9, 55.1, 28.7; IR (KBr): 3407, 3236, 3055, 2922, 1458, 1036, 742, 706 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31ClN2ONa 601.2018, found 601.2014. 2-(1-(3,3-diphenyl-2-(m-tolyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethan ol

(3ia):

Following

the

general

procedure,

(E)-(3-(3-methylstyryl)-1H-indol-2-yl)diphenylmethanol

1i

to (62.2

the

mixture

mg,

0.15

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ia (38.4 mg) in 69% yield as white solid. m.p. 81-82 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.26 (s, 1H), 7.63 (d, J = 7.6 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.27 (s, 2H), 7.25 (s, 1H), 7.21 – 7.09 (m, 5H), 7.07 – 7.01 (m, 2H), 7.00 – 6.89 (m, 4H), 6.88 – 6.82 (m, 2H), 6.79 (s, 1H), 6.73 (d, J = 7.2 Hz, 2H), 6.67 (s, 1H), 6.25 (d, J = 2.0 Hz, 1H), 5.28 (d, J = 3.2 Hz, 1H), 3.79 – 3.65 (m, 2H), 2.97 – 2.77 (m, 2H), 1.94 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 149.4, 145.6, 142.2, 141.5, 136.4, 129.8, 129.0, 128.4, 127.8, 127.2, 126.8, 126.5, 125.5, 124.7, 123.6, 122.5, 121.6, 120.9, 119.4, 119.1, 118.8, 115.9, 112.2, 110.4, 110.1, 64.6, 62.8, 62.4, 54.4, 28.6, 20.6; IR (KBr): 3546, 3285, 3057, 2920, 1700, 1487, 1451, 703 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2ONa 581.2564, found 581.2555.



Page 22 of 57

2-(1-(2-(2-fluorophenyl)-3,3-diphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3yl)ethanol

(3ja):

Following

the

general

procedure,


1j

to

(62.8

the mg,

mixture 0.15

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ja (41.9 mg) in 74% yield as white solid. m.p. 88-89 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.27 (s, 1H), 7.60 (d, J = 7.6 Hz, 1H), 7.47 – 7.41 (m, 3H), 7.31 – 7.27 (m, 2H), 7.23 (t, J = 7.2 Hz, 3H), 7.13 – 7.07 (m, 3H), 7.06 – 7.00 (m, 5H), 6.80 (t, J = 7.4 Hz, 1H), 6.78 – 6.70 (m, 3H), 6.67 (d, J = 8.0 Hz, 2H), 6.33 (d, J = 4.4 Hz, 1H), 5.47 (d, J = 4.4 Hz, 1H), 3.78 – 3.68 (m, 2H), 2.95 – 2.80 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 160.7 (J = 240 Hz), 148.1, 144.8, 142.5, 141.3, 136.6, 130.5, 129.6, 128.8, 128.6, 128.5, 127.7, 127.5, 127.0, 126.8, 124.6, 123.5, 123.4, 122.6, 120.8, 119.3, 119.0, 118.9, 116.2, 115.0 (J = 23 Hz), 112.2, 110.7, 110.2, 67.6, 62.7, 62.1, 54.1, 28.7; IR (KBr): 2917, 2849, 1511, 1459, 1254, 1178, 743, 704 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31FN2ONa 585.2313, found 585.2335. 2-(1-(3,3-diphenyl-2-(o-tolyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethan ol

(3ka):

Following

the

general

procedure,

(E)-(3-(2-methylstyryl)-1H-indol-2-yl)diphenylmethanol

1k

to

the

mixture

(62.2

mg,

0.15

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative


Page 23 of 57 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


thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ka (43.3 mg) in 78% yield as white solid. m.p. 86-87 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.15 (s, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H), 7.30 – 7.27 (m, 2H), 7.25 (s, 1H), 7.22 – 7.16 (m, 3H), 7.15 – 7.08 (m, 2H), 7.04 (t, J = 7.6 Hz, 2H), 6.97 (t, J = 7.4 Hz, 2H), 6.91 (t, J = 8.6 Hz, 2H), 6.86 – 6.80 (m, 2H), 6.79 – 6.69 (m, 3H), 6.66 (s, 1H), 6.24 (d, J = 2.4 Hz, 1H), 5.27 (d, J = 3.2 Hz, 1H), 3.79 – 3.67 (m, 2H), 2.94 – 2.78 (m, 2H), 1.92 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 149.5, 145.6, 142.2, 141.5, 136.4, 129.8, 129.0, 128.4, 127.8, 127.2, 126.8, 126.5, 125.5, 123.6, 122.5, 121.6, 120.9, 119.4, 119.1, 118.8, 115.9, 112.2, 110.4, 110.1, 64.6, 62.8, 62.4, 55.3, 28.6, 20.6; IR (KBr): 3395, 3056, 2928, 1700, 1455, 1033, 740, 702, 657 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2ONa 581.2564, found 581.2572. 2-(1-(7-chloro-2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethan ol

(3la):

Following

the

general

procedure,

(E)-(5-chloro-3-styryl-1H-indol-2-yl)diphenylmethanol

1l

to

the

(65.3

mg,

mixture 0.15

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3la (36.0 mg) in 62% yield as white solid. m.p. 91-92 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 7.6 Hz, 2H), 7.40 – 7.27 (m, 4H), 7.20 – 7.10 (m, 3H), 7.08 – 7.01 (m, 4H), 7.00 – 6.88 (m, 4H), 6.82 (s, 1H), 6.71 (d, J = 6.8 Hz, 2H), 6.46 (d, J = 7.6 Hz, 2H), 6.20 (s, 1H), 5.13 (s, 1H), 3.85 – 3.67 (m, 2H), 2.91 (t, J = 6.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 144.5, 142.5, 139.3, 136.6, 129.8, 129.6, 128.8, 127.8, 127.7, 127.6, 127.2, 127.0, 126.9, 126.5, 124.6,



Page 24 of 57

122.8, 121.6, 119.1, 118.9, 118.8, 116.3, 113.1, 111.1, 110.5, 68.1, 62.6, 61.6, 54.6, 28.7; IR (KBr): 3379, 3056, 2923, 1669, 1457, 1355, 1081, 742 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31ClN2ONa 601.2018, found 601.2014. 2-(1-(7-methyl-2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)etha nol

(3ma):

Following

the

general

procedure,

(E)-(5-methyl-3-styryl-1H-indol-2-yl)diphenylmethanol

1m

to

the

(62.2

mg,

mixture 0.15

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ma (65.1 mg) in 99% yield as white solid. m.p. 62-63 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 7.6 Hz, 2H), 7.36 – 7.30 (m, 3H), 7.27 (s, 1H), 7.11 (t, J = 7.4 Hz, 1H), 7.08 – 6.98 (m, 6H), 6.97 – 6.94 (m, 4H), 6.87 (s, 1H), 6.73 (d, J = 7.2 Hz, 2H), 6.51 (d, J = 7.6 Hz, 2H), 6.22 (d, J = 4.4 Hz, 1H), 5.09 (s, 1H), 3.81 – 3.71 (m, 2H), 2.96 – 2.87 (m, 2H), 2.34 (s, 3H); 13

C NMR (100 MHz, CDCl3) δ 142.8, 139.4, 136.4, 135.7, 130.2, 129.9, 129.7, 128.7, 128.5,

127.7, 127.5, 126.9, 126.8, 126.7, 123.9, 123.8, 122.5, 122.2, 121.5, 119.5, 119.0, 118.9, 118.8, 118.7, 116.0, 111.8, 111.2, 66.3, 62.6, 61.7, 54.2, 28.7, 21.4; IR (KBr): 3381, 3059, 2924, 2854, 1713, 1620, 1453, 1186, 703 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2ONa 581.2564, found 581.2558. 2-(1-(7-methoxy-2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)eth anol

(3na):

Following

the

general

procedure,

(E)-(5-methoxy-3-styryl-1H-indol-2-yl)diphenylmethanol

1n


to (64.6

the

mixture

mg,

0.15

of

mmol),

Page 25 of 57 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


2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3na (54.4 mg) in 95% yield as white solid. m.p. 80-81 oC; >95:5 dr; 1H NMR (400 MHz, Acetone-d6) δ 10.30 (s, 1H), 7.62 (d, J = 7.2 Hz, 2H), 7.54 (d, J = 8.0 Hz, 1H), 7.39 – 7.30 (m, 3H), 7.27 – 7.23 (m, 1H), 7.12 – 7.08 (m, 1H), 7.06 – 6.93 (m, 8H), 6.92 – 6.84 (m, 3H), 6.82 – 6.77 (m, 1H), 6.52 (t, J = 5.0 Hz, 3H), 6.31 (d, J = 6.0 Hz, 1H), 5.23 (d, J = 6.0 Hz, 1H), 3.73 – 3.64 (m, 2H), 3.58 (s, 3H), 3.41 (t, J = 5.2 Hz, 1H), 2.87 (s, 1H), 2.84 (s, 1H); 13C NMR (100 MHz, Acetone-d6) δ 154.5, 148.1, 145.3, 143.6, 139.5, 136.7, 130.0, 129.6, 129.1, 128.3, 128.1, 127.5, 127.3, 126.6, 126.5, 126.4, 123.8, 120.8, 118.7, 118.5, 115.9, 113.0, 111.7, 111.6, 110.3, 100.9, 67.8, 62.4, 61.8, 54.9, 54.6, 31.1; IR (KBr): 3585, 2924, 2853, 1716, 1495, 1450, 1186, 1080, 996, 740 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2O2Na 597.2513, found 597.2532. 2-(1-(6-chloro-2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethan ol

(3oa):

Following

the

general

procedure,

(E)-(6-chloro-3-styryl-1H-indol-2-yl)diphenylmethanol

1o

to

the

(65.3

mg,

mixture 0.15

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3oa (40.5 mg) in 70% yield as white solid. m.p. 106-107 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 7.57 (d, J = 7.6 Hz, 1H), 7.49 (d, J = 7.6 Hz, 2H), 7.38 (s, 1H), 7.34 (t, J = 7.4 Hz, 2H), 7.28 (d, J = 7.2 Hz,



Page 26 of 57

1H), 7.13 (t, J = 7.2 Hz, 1H), 7.09 – 6.94 (m, 10H), 6.83 (s, 1H), 6.73 (d, J = 7.2 Hz, 2H), 6.48 (d, J = 7.6 Hz, 2H), 6.22 (d, J = 4.4 Hz, 1H), 5.15 (s, 1H), 3.82 – 3.67 (m, 2H), 2.90 (t, J = 6.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 144.5, 142.4, 141.3, 136.6, 129.8, 129.6, 128.8, 128.5, 128.3, 127.8, 127.7, 127.6, 127.2, 127.0, 126.9, 125.4, 122.1, 121.6, 121.5, 120.1, 119.1, 118.8, 116.6, 112.2, 110.9, 110.7, 70.5, 62.6, 61.7, 28.7; IR (KBr): 3380, 3050, 2920, 1669, 1457, 1360, 1080, 742 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31ClN2ONa 601.2018, found 601.2013. 2-(1-(4-methyl-2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)etha nol

(3pa):

Following

the

general

procedure,


1p

to

the

(62.2

mg,

mixture 0.15

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3pa (43.6 mg) in 78% yield as white solid. m.p. 84-85 oC; >95:5 dr; 1H NMR (400 MHz, Acetone-d6) δ 7.71 – 7.67 (m, 2H), 7.55 – 7.51 (m, 1H), 7.46 – 7.40 (m, 3H), 7.36 – 7.32 (m, 1H), 7.25 (s, 1H), 7.22 – 7.17 (m, 3H), 7.11 – 7.06 (m, 3H), 7.03 – 6.98 (m, 2H), 6.97 – 6.88 (m, 4H), 6.85 – 6.81 (m, 2H), 6.51 – 6.46 (m, 2H), 6.42 (d, J = 7.2 Hz, 1H), 5.19 (d, J = 7.6 Hz, 1H), 3.75 – 3.68 (m, 2H), 3.46 (t, J = 5.4 Hz, 1H), 3.20 (s, 3H), 2.91 – 2.87 (m, 2H); 13C NMR (100 MHz, Acetone-d6) δ 148.0, 143.7, 141.9, 138.8, 138.4, 136.8, 130.2, 130.0, 129.1, 128.9, 128.4, 127.6, 127.3, 127.1, 127.0, 126.8, 123.0, 121.6, 120.4, 119.9, 118.8, 118.7, 118.5, 116.1, 112.2, 110.3, 110.2, 74.2, 62.4, 61.9, 54.6, 29.8, 29.2; IR (KBr): 3381, 3059, 2924, 2854, 1713, 1453, 1186, 970, 703 cm-1; HRMS (ESI-TOF) m/z: [M +


Page 27 of 57 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


Na]+ Calcd for C40H34N2ONa 581.2564, found 581.2578. 2-(5-bromo-1-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethan ol

(3ab):

Following

the

general

(E)-diphenyl(3-styryl-1H-indol-2-yl)methanol

procedure, 1a

to

(60.2

the mg,

mixture 0.15

of

mmol),

2-(5-bromo-1H-indol-3-yl)ethanol 2b (24.0 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ab (49.7 mg) in 80% yield as white solid. m.p. 86-87 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 7.69 (d, J = 2.0 Hz, 1H), 7.50 (d, J = 7.6 Hz, 2H), 7.42 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 7.6 Hz, 2H), 7.28 (d, J = 7.2 Hz, 1H), 7.25 – 7.21 (m, 1H), 7.17 – 6.95 (m, 9H), 6.88 (s, 1H), 6.81 (d, J = 8.4 Hz, 1H), 6.72 (d, J = 7.2 Hz, 2H), 6.50 (d, J = 7.6 Hz, 2H), 6.19 (d, J = 5.6 Hz, 1H), 5.09 (s, 1H), 3.76 – 3.68 (m, 2H), 2.84 (t, J = 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 147.2, 144.6, 142.6, 141.0, 138.5, 135.2, 129.9, 129.7, 128.8, 127.8, 127.7, 127.6, 127.1, 126.9, 124.3, 123.4, 122.6, 121.4, 120.9, 119.2, 116.1, 112.4, 112.3, 110.6, 68.3, 62.5, 61.6, 28.5; IR (KBr): 3284, 3057, 2927, 1700, 1598, 1493, 1453, 1034, 861, 791, 703 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31BrN2ONa 645.1512, found 645.1513. 2-(5-chloro-1-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethan ol

(3ac):

Following

the

general


procedure, 1a

(60.2

to

the mg,

mixture 0.15

of

mmol),

2-(5-chloro-1H-indol-3-yl)ethanol 2c (19.6 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for



Page 28 of 57

4 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ac (51.0 mg) in 88% yield as white solid. m.p. 103-104 oC; >95:5 dr; 1H NMR (400 MHz, Acetone-d6) δ 10.47 (s, 1H), 7.68 (d, J = 7.6 Hz, 2H), 7.56 (d, J = 2.0 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.39 – 7.34 (m, 2H), 7.30 – 7.25 (m, 1H), 7.17 – 7.08 (m, 3H), 7.06 – 7.01 (m, 4H), 7.00 – 6.95 (m, 4H), 6.90 – 6.87 (m, 2H), 6.86 – 6.81 (m, 1H), 6.48 (d, J = 7.6 Hz, 2H), 6.35 (d, J = 6.8 Hz, 1H), 5.27 (d, J = 6.4 Hz, 1H), 3.71 – 3.65 (m, 2H), 3.54 (t, J = 5.4 Hz, 1H), 2.86 – 2.80 (m, 2H); 13C NMR (100 MHz, Acetone-d6) δ 147.4, 145.0, 143.3, 141.8, 138.9, 130.1, 129.6, 128.5, 128.1, 127.6, 127.4, 126.8, 126.7, 126.5, 123.8, 123.3, 121.9, 120.8, 120.0, 118.7, 118.3, 115.9, 112.5, 112.0, 111.6, 67.8, 62.4, 61.7, 28.7; IR (KBr): 3427, 3252, 3053, 2924, 1579, 1495, 1452, 1256, 708 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31ClN2ONa 601.2017, found 601.2018. 2-(5-fluoro-1-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethan ol

(3ad):

Following

the

general


procedure, 1a

(60.2

to

the mg,

mixture 0.15

of

mmol),

2-(5-fluoro-1H-indol-3-yl)ethanol 2d (17.9 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ad (64.9 mg) in 99% yield as white solid. m.p. 93-94 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.07 (s, 1H), 7.48 (d, J = 7.6 Hz, 2H), 7.43 (d, J = 8.4 Hz, 1H), 7.34 (t, J = 7.6 Hz, 2H), 7.28 (d, J = 7.2 Hz, 1H), 7.25 – 7.17 (m, 2H), 7.16 – 7.11 (m, 2H), 7.10 – 6.96 (m, 6H), 6.90 (s, 1H), 6.83 – 6.80 (m, 1H), 6.77 – 6.61 (m, 3H), 6.49 (d, J = 7.6 Hz, 2H), 6.18 (d, J = 6.0 Hz, 1H), 5.08 (s, 1H), 3.75 – 3.71(m, 2H),


Page 29 of 57 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


2.84 (t, J = 6.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 157.6 (J = 224 Hz), 144.2, 142.6, 141.1, 138.7, 138.2, 129.9, 129.7, 128.8, 127.8, 127.7, 127.6, 127.1, 126.8, 123.5, 122.5, 120.8, 119.2, 116.2, 112.3, 111.3, 110.7, 109.8 (J = 26 Hz), 103.7 (J = 23 Hz), 68.2, 62.5, 61.6, 28.6; IR (KBr): 3292, 3056, 2975, 2929, 1692, 1455, 1170, 741, 702 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31FN2ONa 585.2313, found 585.2308. 2-(5-methyl-1-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)etha nol

(3ae):

Following

the

general


procedure, 1a

(60.2

to

the mg,

mixture 0.15

of

mmol),

2-(5-methyl-1H-indol-3-yl)ethanol 2e (17.5 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ae (46.8 mg) in 84% yield as white solid. m.p. 115-116 oC; >95:5 dr; 1H NMR (400 MHz, Acetone-d6) δ 10.43 (s, 1H), 7.66 (d, J = 7.6 Hz, 2H), 7.46 (d, J = 8.0Hz, 1H), 7.39 – 7.31 (m, 3H), 7.29 – 7.24 (m, 1H), 7.15 – 7.08 (m, 2H), 7.07 – 7.01 (m, 3H), 7.00– 6.91 (m, 6H), 6.89 (d, J = 6.8 Hz, 2H), 6.72 (d, J = 7.6 Hz, 1H), 6.49 (d, J = 7.6 Hz, 2H), 6.31 (d, J = 6.4 Hz, 1H), 5.30 (d, J = 6.4 Hz, 1H), 3.75 – 3.60 (m, 2H), 3.44 (t, J = 5.4 Hz, 1H), 2.87 – 2.78 (m, 2H), 2.35 (s, 3H); 13C NMR (100 MHz, Acetone-d6) δ 147.2, 145.2, 143.4, 141.8, 139.2, 135.1, 130.0, 129.6, 128.4, 128.1, 127.5, 127.3, 127.2, 126.6, 126.4, 123.4, 122.4, 121.7, 119.8, 118.7, 118.5, 116.4, 112.4, 67.7, 62.4, 61.7, 54.1, 29.0, 20.6; IR (KBr): 3228, 3029, 2902, 1716, 1491, 1453, 1053, 862, 797, 744, 701 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2ONa 581.2564, found 581.2559. 2-(5-methoxy-1-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)eth



anol

(3af):

Following

the

general


procedure, 1a

Page 30 of 57

to

(60.2

the

mg,

mixture 0.15

of

mmol),

2-(5-methoxy-1H-indol-3-yl)ethanol 2f (19.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3 Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3af (44.3 mg) in 77% yield as white solid. m.p. 96-97 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.49 (d, J = 7.6 Hz, 2H), 7.42 (d, J = 8.0 Hz, 1H), 7.39 – 7.27 (m, 3H), 7.24 – 7.20 (m, 1H), 7.17 (d, J = 7.6 Hz, 1H), 7.14 – 7.06 (m, 2H), 7.05 – 6.99 (m, 5H), 6.98 – 6.96 (m, 1H), 6.84 (d, J = 8.0 Hz, 2H), 6.73 (d, J = 7.2 Hz, 2H), 6.64 – 6.58 (m, 1H), 6.51 (d, J = 7.6 Hz, 2H), 6.18 (d, J = 5.2 Hz, 1H), 5.11 (s, 1H), 3.83 (s, 3H), 3.78 – 3.69 (m, 2H), 2.92 – 2.81 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 153.7, 144.8, 142.7, 141.1, 131.9, 129.9, 129.7, 128.7, 127.7, 127.6, 127.5, 127.0, 126.9, 126.7, 123.6, 122.4, 121.7, 120.8, 119.4, 116.5, 112.2, 111.6, 100.6, 68.3, 62.6, 61.7, 55.8, 28.7; IR (KBr): 3027, 2921, 1611, 1509, 1457, 1357, 996, 698 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2O2Na 597.2513, found 597.2512. 2-(6-chloro-1-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethan ol

(3ag):

Following

the

general


procedure, 1a

(60.2

to

the mg,

mixture 0.15

of

mmol),

2-(6-chloro-1H-indol-3-yl)ethanol 2g (19.6 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford >95:5 dr 3ag (32.9


Page 31 of 57 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


mg) in 57% yield as white solid. m.p. 112-113 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.51 (d, J = 7.2 Hz, 2H), 7.44 (t, J = 8.2 Hz, 2H), 7.36 (t, J = 7.4 Hz, 2H), 7.29 (d, J = 7.2 Hz, 1H), 7.25 – 7.21 (m, 1H), 7.18 – 7.11 (m, 2H), 7.10 – 7.08 (m, 1H), 7.07 – 6.97 (m, 6H), 6.93 (s, 1H), 6.86 (s, 1H), 6.72 (d, J = 7.2 Hz, 2H), 6.49 (d, J = 7.6 Hz, 2H), 6.16 (d, J = 6.4 Hz, 1H), 5.07 (d, J = 6.0 Hz, 1H), 3.80 – 3.67 (m, 2H), 2.88 (t, J = 6.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 147.3, 144.7, 142.6, 141.0, 138.4, 137.1, 129.9, 129.7, 128.8, 127.8, 127.7, 127.6, 127.5, 127.2, 127.1, 126.9, 123.4, 122.6, 120.8, 119.7, 119.6, 119.2, 116.1, 112.3, 111.3, 110.6, 68.5, 62.7, 61.6, 28.6; IR (KBr): 3581, 3404, 3253, 2919, 2535, 1451, 1034, 803, 707 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31ClN2ONa 601.2017, found 601.2018. 2-(6-fluoro-1-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethan ol

(3ah):

Following

the

general


procedure, 1a

(60.2

to

the mg,

mixture 0.15

of

mmol),

2-(6-fluoro-1H-indol-3-yl)ethanol 2h (17.9 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ah (35.2 mg) in 63% yield as white solid. m.p. 89-90 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 7.52 (d, J = 7.6 Hz, 2H), 7.47 – 7.41 (m, 2H), 7.35 (t, J = 7.4 Hz, 2H), 7.29 (d, J = 7.2 Hz, 1H), 7.25 – 7.20 (m, 1H), 7.16 – 7.12 (m, 2H), 7.10 – 6.98 (m, 6H), 6.90 (s, 1H), 6.82 – 6.77 (m, 1H), 6.73 (d, J = 7.4 Hz, 2H), 6.60 (d, J = 10.0 Hz, 1H), 6.50 (d, J = 7.2 Hz, 2H), 6.14 (d, J = 6.4 Hz, 1H), 5.11 (d, J = 5.6 Hz, 1H), 3.81 – 3.70 (m, 2H), 2.88 (t, J = 6.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 159.7 (J = 236 Hz), 147.2, 144.7, 142.6, 141.0, 138.5, 136.6, 129.8 (J = 20 Hz), 128.8, 127.8,



Page 32 of 57

127.7, 127.6, 127.2, 126.8, 125.1, 123.5, 122.5, 120.8, 119.5, 119.3 (J = 10 Hz), 116.2, 112.3, 107.7 (J = 24 Hz), 68.2, 62.6, 61.6, 28.7; IR (KBr): 3290, 3058, 2919, 2852, 2333, 1701, 1452, 1229, 1039, 701 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31FN2ONa 585.2313, found 585.2328. 2-(7-methoxy-1-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)eth anol

(3ak):

Following

the

general


procedure, 1a

to

(60.2

the

mg,

mixture 0.15

of

mmol),

2-(7-methoxy-1H-indol-3-yl)ethanol 2k (19.1 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 3 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3ak (35.2 mg) in 61% yield as white solid. m.p. 99-100 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.46 – 7.38 (m, 3H), 7.28 (d, J = 6.8 Hz, 1H), 7.25 – 7.20 (m, 4H), 7.16 (d, J = 7.6 Hz, 1H), 7.10 – 7.05 (m, 2H), 7.03 – 7.00 (m, 1H), 6.99 – 6.89 (m, 6H), 6.80 – 6.75 (m, 2H), 6.66 (s, 1H), 6.60 – 6.55 (m, 2H), 6.50 (d, J = 7.6 Hz, 1H), 5.06 (d, J = 4.0 Hz, 1H), 3.72 – 3.62 (m, 2H), 3.36 (s, 3H), 2.86 – 2.72 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 147.8, 147.5, 145.1, 143.0, 141.2, 140.1, 130.6, 129.8, 129.7, 128.4, 127.9, 127.3, 127.1, 126.8, 126.4, 126.3, 126.0, 124.9, 123.6, 122.3, 120.6, 119.4, 119.3, 118.1, 112.1, 111.5, 110.8, 102.2, 69.8, 62.6, 62.2, 61.9, 54.4, 28.8; IR (KBr): 3277, 3058, 2930, 1695, 1479, 1451, 1249, 1034, 703 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2O2Na 597.2513, found 597.2533. 3-(1-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)propan-1-ol (3al):

Following

the

general

procedure,


to

the

mixture

of

Page 33 of 57 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



1a

(60.2

mg,

0.15

mmol),

3-(1H-indol-3-yl)propan-1-ol 2l (17.5 mg, 0.1 mmol), catalyst 5c (1.8 mg, 0.01 mmol) and 3Å MS (50 mg), was added chloroform (1 mL). Then, the reaction mixture was stirred at 30 oC for 4 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography (toluene/ethyl acetate = 10/1) to afford 3al (34.9 mg) in 63% yield as white solid. m.p. 105-106 oC; >95:5 dr; 1H NMR (400 MHz, Acetone-d6) δ 10.43 (s, 1H), 7.68 (d, J = 7.6 Hz, 2H), 7.54 (d, J = 7.6 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.36 (t, J = 7.6 Hz, 2H), 7.27 (t, J = 7.2 Hz, 1H), 7.15 – 7.09 (m, 2H), 7.08 – 7.01 (m, 4H), 7.00 – 6.92 (m, 6H), 6.91 – 6.85 (m, 3H), 6.49 (d, J = 7.2 Hz, 2H), 6.36 (d, J = 6.4 Hz, 1H), 5.31 (d, J = 5.6 Hz, 1H), 3.57 – 3.49 (m, 2H), 3.43 (t, J = 5.2 Hz, 1H), 2.72 (t, J = 7.4 Hz, 2H), 1.82 – 1.74 (m, 2H); 13C NMR (100 MHz, Acetone-d6) δ 147.2, 145.2, 143.4, 141.8, 139.2, 136.7, 130.0, 129.6, 128.9, 128.4, 128.1, 127.4, 127.1, 126.7, 126.4, 123.4, 121.8, 120.8, 119.9, 118.8, 118.6, 118.4, 116.4, 115.0, 112.4, 110.2, 67.8, 61.8, 61.2, 54.5, 33.4, 21.2; IR (KBr): 3269, 3058, 2923, 1704, 1452, 1185, 792, 744 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2ONa 581.2564, found 581.2578. Typical procedure for the synthesis of products 4

To the mixture of 2-indolymethanols 1 (0.18 mmol), tryptophols 2 (0.1 mmol) and catalyst 5c (0.02 mmol), was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by preparative thin layer chromatography to afford products 4.

2-(2-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethanol (4aa):



Page 34 of 57

Following the general procedure, to the mixture of (E)-diphenyl(3-styryl-1H-indol-2-yl)methanol 1a (72.2 mg, 0.18 mmol), 2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol), was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4aa (45.1 mg) in 83% yield as white solid. m.p. 94-95 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 11.6 Hz, 2H), 7.67 – 7.61 (m, 2H), 7.50 (d, J = 7.6 Hz, 1H), 7.41 (t, J = 7.8 Hz, 3H), 7.33 – 7.28 (m, 1H), 7.22 – 7.14 (m, 3H), 7.13 – 6.97 (m, 9H), 6.72 (d, J = 7.2 Hz, 2H), 6.47 – 6.38 (m, 2H), 5.07 (d, J = 8.4 Hz, 1H), 4.99 (d, J = 8.4 Hz, 1H), 3.50 – 3.39 (m, 1H), 2.99 – 2.88 (m, 1H), 2.77 – 2.66 (m, 1H), 2.59 – 2.46 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 147.0, 144.7, 142.7, 140.8, 138.3, 136.3, 135.7, 130.5, 129.8, 129.0, 128.8, 127.8, 127.6, 127.5, 127.0, 126.8, 122.1, 121.4, 120.5, 119.3, 119.2, 118.6, 117.6, 112.1, 110.8, 109.1, 68.4, 63.1, 62.1, 42.1, 27.9; IR (KBr): 3436, 3269, 2554, 1530, 1226, 1002, 834, 738, 699 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H32N2ONa 567.2408, found 567.2432. 2-(2-(3,3-bis(4-fluorophenyl)-2-phenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3 -yl)ethanol

(4ba):

Following

the

general


procedure, 1b

(78.7

to

the mg,

mixture 0.18

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol) was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4ba (53.4 mg) in 92% yield as white solid. m.p. 98-99 oC; >95:5 dr; 1H NMR (400 MHz, Acetone-d6) δ 10.14 (s, 1H), 10.05 (s, 1H), 7.92 –


Page 35 of 57 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


7.79 (m, 2H), 7.46 (d, J = 7.6 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.24 – 7.16 (m, 3H), 7.10 – 7.02 (m, 4H), 7.01 – 6.92 (m, 3H), 6.91 – 6.84 (m, 5H), 6.44 – 6.22 (m, 2H), 5.35 (d, J = 9.2 Hz, 1H), 5.06 (d, J = 9.2 Hz, 1H), 3.65 – 3.53 (m, 1H), 3.45 (t, J = 5.4 Hz, 1H), 3.33 – 3.18 (m, 1H), 2.86 – 2.61 (m, 2H); 13C NMR (100 MHz, Acetone-d6) δ 161.6 (J = 242 Hz), 161.5 (J = 242 Hz), 146.2, 141.3, 140.6, 138.8, 138.2, 136.5, 136.0, 131.4 (J = 8 Hz), 130.5 (J = 8 Hz), 130.2, 128.8, 127.5, 126.9, 124.0, 121.3, 120.6, 119.5, 118.7, 118.2 (J = 12 Hz), 114.9 (J = 21 Hz), 114.1 (J = 21 Hz), 112.2, 110.7, 109.2, 68.4, 62.6, 61.1, 40.9, 28.1; IR (KBr): 3287, 2921, 2882, 1457, 1026, 739, 702, 529 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H30F2N2ONa 603.2219, found 603.2226. 2-(2-(2-phenyl-3,3-di-p-tolyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethano l

(4ca):

Following

the

general

procedure,

to

the

mixture

of

(E)-(3-styryl-1H-indol-2-yl)di-p-tolylmethanol 1c (77.2 mg, 0.18 mmol), 2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol) was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4ca (45.5 mg) in 80% yield as white solid. m.p. 77-78 o

C; >95:5 dr; 1H NMR (400 MHz, Acetone-d6) δ 10.02 (d, J = 4.4 Hz, 2H), 7.68 (d, J = 8.4 Hz,

2H), 7.45 (d, J = 7.6 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.25 – 7.20 (m, 3H), 7.07 – 7.02 (m, 2H), 7.01 – 6.93 (m, 5H), 6.92 – 6.86 (m, 3H), 6.85 – 6.82 (m, 2H), 6.25 (d, J = 8.4 Hz, 2H), 5.30 (d, J = 9.2 Hz, 1H), 5.01 (d, J = 9.2 Hz, 1H), 3.63 – 3.54 (m, 1H), 3.52 – 3.34 (m, 1H), 3.31 – 3.22 (m, 1H), 2.84 – 2.72 (m, 2H), 2.34 (s, 3H), 2.27 (s, 3H); 13C NMR (100 MHz, Acetone-d6) δ 147.0, 142.0, 141.2, 140.0, 138.7, 136.5, 136.3, 135.9, 135.8, 130.4, 129.6, 128.9, 128.8, 128.5, 127.9,



Page 36 of 57

127.2, 126.6, 124.0, 121.0, 120.5, 119.3, 118.5, 118.2, 118.0, 112.1, 110.7, 109.0, 68.1, 62.6, 61.4, 41.1, 28.2, 20.1, 20.0; IR (KBr): 3397, 3027, 2920, 1699, 1509, 1454, 1038, 821, 743, 702 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C41H36N2ONa 595.2721, found 595.2731. 2-(2-(3,3-bis(3-fluorophenyl)-2-phenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3 -yl)ethanol

(4da):

Following

the

general


procedure, 1d

to

(78.7

the mg,

mixture 0.18

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol) was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4da (55.3 mg) in 95% yield as white solid. m.p. 113-114 oC; >95:5 dr; 1H NMR (400 MHz, Acetone-d6) δ 10.22 (s, 1H), 10.09 (s, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.57 – 7.53 (m, 1H); 7.52 – 7.46 (m, 2H), 7.42 (d, J = 8.0 Hz, 1H), 7.23 (d, J = 7.6 Hz, 1H), 7.18 – 7.02 (m, 6H), 7.01 – 6.87 (m, 7H), 6.24 – 6.22 (m, 1H), 6.10 – 5.99 (m, 1H), 5.38 (d, J = 9.2 Hz, 1H), 5.13 (d, J = 9.2 Hz, 1H), 3.66 – 3.56 (m, 1H), 3.53 – 3.38 (m, 1H), 3.36 – 3.25 (m, 1H), 2.87 – 2.74 (m, 2H); 13C NMR (100 MHz, Acetone-d6) δ 162.9 (J = 242 Hz), 162.3 (J = 242 Hz), 147.1 (J = 6 Hz), 145.6 (J = 6 Hz), 145.2, 141.3, 138.0, 136.5, 135.8, 130.2, 129.2 (J = 8 Hz), 128.8, 127.5, 127.0, 125.5, 125.4, 124.5, 124.4, 123.9, 121.5, 120.6, 119.6, 118.8, 118.3, 118.2, 116.5 (J = 22 Hz), 115.6 (J = 22 Hz), 113.6 (J = 14 Hz), 113.5 (J = 14 Hz), 112.2, 110.7, 109.3, 68.2, 62.5, 61.9, 40.9, 28.1; IR (KBr): 3399, 3025, 2919, 2342, 1509, 1452, 1039, 743 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H30F2N2ONa 603.2219, found 603.2213. 2-(2-(2-(4-fluorophenyl)-3,3-diphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3yl)ethanol

(4fa):

Following

the

general

procedure,


to

the

mixture

of

Page 37 of 57 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



1f

(75.4

mg,

0.18

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol), was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4fa (55.6 mg) in 99% yield as white solid. m.p. 95-96 oC; >95:5 dr; 1H NMR (400 MHz, Acetone-d6) δ 10.10 (s, 1H), 10.03 (s, 1H), 7.84 – 7.77 (m, 2H), 7.48 – 7.38 (m, 4H), 7.34 – 7.29 (m, 1H), 7.25 – 7.18 (m, 2H), 7.15 – 7.09 (m, 2H), 7.08 – 7.04 (m, 1H), 7.01 – 6.92 (m, 3H), 6.90 – 6.80 (m, 3H), 6.79 – 6.71 (m, 2H), 6.43 – 6.33 (m, 2H), 5.37 (d, J = 9.2 Hz, 1H), 4.99 (d, J = 9.6 Hz, 1H), 3.63 – 3.53 (m, 1H), 3.46 (t, J = 5.0 Hz, 1H), 3.30 – 3.18 (m, 1H), 2.82 – 2.71 (m, 2H); 13C NMR (100 MHz, Acetone-d6) δ 161.6 (J = 240 Hz), 146.3, 144.7, 143.2, 141.3, 136.5, 136.0, 134.8, 134.7, 132.0 (J = 8 Hz), 129.6, 128.8, 128.5, 128.4, 127.4, 126.6, 123.9, 121.1, 120.6, 119.4, 118.6, 118.3, 118.2, 118.1, 114.0 (J = 21 Hz), 112.1, 110.8, 109.1, 66.7, 62.6, 61.9, 41.6, 28.1; IR (KBr): 3834, 3735, 2466, 1698, 1490, 1472, 1450, 704 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31FN2ONa 585.2313, found 585.2301. 2-(2-(2-(3-chlorophenyl)-3,3-diphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3yl)ethanol

(4ha):

Following

the

general


procedure, 1h

(78.3

to

the mg,

mixture 0.18

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol) was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4ha (58.6) in 99% yield as white solid. m.p.



Page 38 of 57

71-72 oC; >95:5 dr; 1H NMR (400 MHz, Acetone-d6) δ 10.11 (s, 1H), 10.04 (s, 1H), 7.82 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 7.6 Hz, 1H), 7.45 – 7.39 (m, 3H), 7.32 (t, J = 7.2 Hz, 1H), 7.26 – 7.19 (m, 2H), 7.16 – 7.04 (m, 4H), 7.03 – 6.92 (m, 4H), 6.91 – 6.77 (m, 3H), 6.40 (d, J = 7.6 Hz, 2H), 5.39 (d, J = 8.8 Hz, 1H), 5.02 (d, J = 9.2 Hz, 1H), 3.70 – 3.55 (m, 1H), 3.48 (s, 1H), 3.39 – 3.27 (d, 1H), 2.85 – 2.73 (m, 2H); 13C NMR (100 MHz, Acetone-d6) δ 146.2, 144.5, 142.9, 141.3, 141.2, 136.5, 135.8, 132.8, 130.2, 129.6, 128.9, 128.8, 128.5, 128.4, 127.5, 126.8, 126.7, 123.9, 121.2, 120.6, 119.4, 118.6, 118.3, 118.2, 118.1, 112.2, 110.8, 109.2, 67.0, 62.6, 62.1, 41.4, 29.7; IR (KBr): 3397, 3027, 2920, 1699, 1509, 1454, 1304, 1038, 821, 743, 702 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C39H32ClN2O 579.2198, found 579.2193. 2-(2-(7-methyl-2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)etha nol

(4ma):

Following

the

general

procedure,

to

the

mixture

of

(E)-(5-methyl-3-styryl-1H-indol-2-yl)diphenylmethanol 1m (74.7 mg, 0.18 mmol), 2a (16.1 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol), was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4ma (57.6 mg) in 99% yield as white solid. m.p. 102-103 oC; >95:5 dr; 1

H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 7.86 (s, 1H), 7.62 (d, J = 7.2 Hz, 2H), 7.52 (d, J = 7.6

Hz, 1H), 7.40 (t, J = 7.6 Hz, 2H), 7.32 – 7.28 (t, J = 7.4 Hz, 2H), 7.24 – 7.22 (d, J = 7.6 Hz, 1H), 7.17 – 7.09 (m, 3H), 7.08 – 6.93 (m, 6H), 6.92 (s, 1H), 6.70 (d, J = 7.2 Hz, 2H), 6.46 – 6.31 (m, 2H), 5.03 (d, J = 8.4 Hz, 1H), 4.95 (d, J = 8.4 Hz, 1H), 3.49 – 3.36 (m, 1H), 2.96 – 2.83 (m, 1H), 2.78 – 2.64 (m, 1H), 2.55 – 2.45 (m, 1H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 147.2, 144.8, 142.8, 139.1, 138.3, 136.5, 135.6, 130.6, 130.0, 129.8, 129.1, 128.8, 127.8, 127.5, 127.0,


Page 39 of 57 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


126.8, 124.0, 123.6, 121.3, 119.1, 118.9, 118.6, 117.0, 111.7, 110.9, 108.9, 68.3, 63.0, 62.0, 42.1, 27.9, 21.3; IR (KBr): 3261, 3057, 2961, 1702, 1611, 1095, 797, 702 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2ONa 581.2564, found 581.2588. 2-(2-(7-methoxy-2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)eth anol

(4na):

Following

the

general

procedure,

(E)-(5-methoxy-3-styryl-1H-indol-2-yl)diphenylmethanol

1n

to (77.6

the

mixture

mg,

0.18

of

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol) was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4na (26.7 mg) in 47% yield as white solid. m.p. 84-84 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 7.99 (s, 1H), 7.82 (s, 1H), 7.61 (d, J = 7.6 Hz, 2H), 7.50 (d, J = 7.6 Hz, 1H), 7.39 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 8.0 Hz, 2H), 7.21 (d, J = 7.6 Hz, 1H), 7.18 – 7.10 (m, 2H), 7.09 – 6.98 (m, 6H), 6.87 – 6.83 (m, 1H), 6.71 (d, J = 7.2 Hz, 2H), 6.55 (d, J = 2.4 Hz, 1H), 6.44 – 6.35 (m, 2H), 5.03 (d, J = 8.4 Hz, 1H), 4.95 (d, J = 8.4 Hz, 1H), 3.65 (s, 3H), 3.46 – 3.39 (m, 1H), 2.91 – 2.83 (m, 1H), 2.75 – 2.66 (m, 1H), 2.54 – 2.47 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 154.6, 147.9, 144.7, 142.8, 138.3, 136.3, 135.8, 135.6, 130.6, 129.7, 129.0, 128.8, 127.7, 127.5, 127.0, 126.8, 124.2, 121.4, 119.1, 118.6, 117.2, 112.7, 111.7, 110.8, 108.9, 101.5, 68.2, 63.0, 62.0, 56.1, 42.1, 28.0; IR (KBr): 3290, 3056, 2955, 1698, 1603, 1509, 1459, 1229, 833, 746, 701 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2O2Na 597.2513, found 597.2508. 2-(2-(4-methyl-2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)etha nol

(4pa):

Following

the

general

procedure,


to

the

mixture

of



1p

Page 40 of 57

(74.7

mg,

0.18

mmol),

2-(1H-indol-3-yl)ethanol 2a (16.1 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol), was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4pa (61.6 mg) in 99% yield as white solid. m.p. 67-68 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.15 (s, 1H), 7.65 (d, J = 7.6 Hz, 2H), 7.51 (d, J = 7.6 Hz, 1H), 7.40 – 7.27 (m, 5H), 7.25 – 7.11 (m, 5H), 7.10 – 7.00 (m, 6H), 6.68 (d, J = 7.2 Hz, 2H), 6.45 (d, J = 7.6 Hz, 2H), 5.04 (d, J = 8.8 Hz, 1H), 4.98 (d, J = 8.8 Hz, 1H), 3.55 – 3.45 (m, 1H), 3.14 (s, 3H), 3.04 – 2.96 (m, 1H), 2.85 – 2.76 (m, 1H), 2.64 – 2.55 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 148.6, 143.6, 141.6, 138.7, 138.4, 136.9, 135.6, 130.4, 129.2, 128.3, 127.5, 127.3, 127.2, 126.9, 126.8, 123.2, 121.5, 121.4, 119.9, 119.3, 119.2, 118.6, 116.6, 110.8, 109.8, 108.9, 75.2, 63.1, 62.6, 40.8, 30.2, 28.1; IR (KBr): 3387, 3057, 2924, 1697, 1451, 1034, 745, 703 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2ONa 581.2564, found 581.2571. 2-(5-chloro-2-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethan ol

(4ac):

Following

the

general


procedure, 1a

(72.2

to

the mg,

mixture 0.18

of

mmol),

2-(5-chloro-1H-indol-3-yl)ethanol 2c (19.6 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol) was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4ac (45.6 mg) in 79% yield as white solid. m.p. 105-106 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.00 (s, 1H), 7.96


Page 41 of 57 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


(s, 1H), 7.64 – 7.60 (m, 2H), 7.45 (d, J = 2.0 Hz, 1H), 7.44 – 7.38 (m, 3H), 7.33 – 7.29 (m, 1H), 7.22 – 7.14 (m, 2H), 7.12 – 6.99 (m, 9H), 6.71 (d, J = 7.2 Hz, 2H), 6.44 – 6.37 (m, 2H), 5.04 (d, J = 8.4 Hz, 1H), 4.95 (d, J = 8.4 Hz, 1H), 3.42 – 3.34 (m, 1H), 2.96 – 2.88 (m, 1H), 2.69 – 2.60 (m, 1H), 2.51 – 2.44 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 147.1, 144.6, 142.6, 140.7, 138.1, 137.9, 130.5, 130.1, 129.7, 128.9, 127.7, 127.6, 127.5, 127.1, 127.0, 126.9, 125.0, 123.7, 122.2, 121.6, 120.6, 119.1, 118.2, 117.3, 112.1, 111.7, 109.0, 68.3, 62.8, 62.1, 42.1, 27.7; IR (KBr): 3232, 3054, 2923, 1716, 1494, 1459, 1338, 1080, 799 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31ClN2ONa 601.2018, found 601.2011. 2-(5-fluoro-2-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethan ol

(4ad):

Following

the

general


procedure, 1a

(72.2

to

the mg,

mixture 0.18

of

mmol),

2-(5-fluoro-1H-indol-3-yl)ethanol 2d (17.9 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol) was added chloroform (1 mL). Then, the reaction mixture at 40 oC and stirred for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4ad (54.7 mg) in 97% yield as white solid. m.p. 85-86 oC; >95:5 dr; 1H NMR (400 MHz, Acetone-d6) δ 10.12 (d, J = 8.0 Hz, 2H), 7.82 – 7.78 (m, 2H), 7.44 – 7.38 (m, 3H), 7.33 – 7.29 (m, 1H), 7.22 – 7.14 (m, 3H), 7.11 – 7.04 (m, 4H), 7.01 – 6.95 (m, 3H), 6.90 – 6.86 (m, 1H), 6.84 – 6.80 (m, 2H), 6.79 – 6.74 (m, 1H), 6.38 – 6.32 (m, 2H), 5.33 (d, J = 9.2 Hz, 1H), 5.01 (d, J = 9.2 Hz, 1H), 3.59 – 3.38 (m, 2H), 3.27 – 3.17 (m, 1H), 2.78 – 2.64 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 157.7 (J = 232 Hz), 147.1, 144.6, 142.7, 140.7, 138.4 (J = 19 Hz), 132.1, 130.5, 129.8, 129.3, 128.9, 127.7, 127.6 (J = 13 Hz) 127.1, 127.0, 126.9, 123.7, 122.1, 120.6, 119.1, 117.4, 112.1, 111.3 (J = 10 Hz), 109.5 (J =



Page 42 of 57

22 Hz), 109.4, 103.8, 103.6, 68.3, 62.8, 62.1, 42.1, 27.9; IR (KBr): 3393, 3055, 2929, 1459, 1222, 836, 745, 705 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31FN2ONa 585.2313, found 585.2320. 2-(5-methyl-2-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)etha nol

(4ae):

Following

the

general


procedure, 1a

(72.2

to

the mg,

mixture 0.18

of

mmol),

2-(5-methyl-1H-indol-3-yl)ethanol 2e (17.5 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol) was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4ae (42.8 mg) in 77% yield as white solid. m.p. 68-69 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 7.91 (s, 1H), 7.89 (s, 1H), 7.62 (d, J = 7.6 Hz, 2H), 7.40 (t, J = 7.4 Hz, 3H), 7.34 – 7.27 (m, 3H), 7.21 – 7.14 (m, 2H), 7.11 – 7.04 (m, 4H), 7.03 – 6.95 (m, 3H), 6.94 (d, J = 8.4 Hz, 1H), 6.69 (d, J = 7.2 Hz, 2H), 6.41 (d, J = 7.6 Hz, 2H), 5.05 (d, J = 8.4 Hz, 1H), 4.95 (d, J = 8.8 Hz, 1H), 3.46 – 3.38 (m, 1H), 2.96 – 2.88 (m, 1H), 2.72 – 2.64 (m, 1H), 2.55 – 2.47 (m, 1H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 146.9, 144.8, 142.8, 140.8, 138.3, 136.5, 134.0, 130.6, 129.8, 129.2, 128.8, 128.5, 127.8, 127.6, 127.5, 127.0, 126.8, 123.8, 122.9, 122.0, 120.5, 119.3, 118.4, 117.7, 112.0, 110.5, 108.6, 68.4, 63.1, 62.1, 42.1, 27.9, 21.5; IR (KBr): 2961, 1689, 1489, 1457, 1295, 1260, 1204, 800, 703 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2ONa 581.2564, found 581.2578. 2-(5-methoxy-2-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)eth anol

(4af):

Following

the

general


procedure, 1a

(72.2


to mg,

the

mixture 0.18

of

mmol),

Page 43 of 57 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


2-(5-methoxy-1H-indol-3-yl)ethanol 2f (19.1 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol) was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4af (38.2 mg) in 67% yield as white solid. m.p. 95-96 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 7.93 (s, 1H), 7.87 (s, 1H), 7.62 (d, J = 7.6 Hz, 2H), 7.42 – 7.36 (m, 3H), 7.30 (t, J = 7.4 Hz, 1H), 7.21 – 6.94 (m, 11H), 6.80 – 6.68 (m, 3H), 6.45 – 6.37 (m, 2H), 5.06 (d, J = 8.4 Hz, 1H), 4.95 (d, J = 8.4 Hz, 1H), 3.82 (s, 3H), 3.45 – 3.36 (m, 1H), 2.93 – 2.85 (m, 1H), 2.73 – 2.64 (m, 1H), 2.54 – 2.46 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 153.9, 147.0 144.7, 142.7, 140.8, 138.3, 137.3, 130.7, 130.5, 129.8, 129.4, 128.8, 127.8, 127.5, 127.0, 126.8, 123.8, 122.1, 120.5, 119.2, 117.6, 112.1, 111.5, 111.3, 108.9, 100.8, 68.4, 63.0, 62.1, 56.0, 31.4, 30.2; IR (KBr): 2962, 1699, 1583, 1489, 1458, 1261, 1036, 802, 743, 703 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2O2Na 597.2513, found 597.2529. 2-(6-chloro-2-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)ethan ol

(4ag):

Following

the

general


procedure, 1a

(72.2

to

the mg,

mixture 0.18

of

mmol),

2-(6-chloro-1H-indol-3-yl)ethanol 2g (19.6 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol) was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4ag (58.1 mg) in 99% yield as white solid. m.p. 97-98 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 7.2 Hz, 2H), 7.63 (d, J = 7.6 Hz, 2H), 7.44 – 7.36 (m, 4H), 7.31 (t, J = 7.2 Hz, 1H), 7.21 – 7.15 (m, 2H),



Page 44 of 57

7.12 (d, J = 1.6 Hz, 1H), 7.11 – 6.98 (m, 8H), 6.71 (d, J = 7.6 Hz, 2H), 6.41 (d, J = 7.2 Hz, 2H), 5.05 (d, J = 8.8 Hz, 1H), 4.95 (d, J = 8.8 Hz, 1H), 3.41 – 3.30 (m, 1H), 2.93 – 2.83 (m, 1H), 2.72 – 2.62 (m, 1H), 2.52 – 2.45 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 147.1, 144.6, 142.7, 140.8, 138.2, 137.0, 136.0, 130.5, 129.8, 128.9, 127.7, 127.5, 127.4, 127.2, 127.0, 126.9, 123.7, 122.2, 120.6, 119.8, 119.5, 119.1, 117.3, 112.2, 110.7, 109.3, 68.2, 63.0, 62.1, 42.1, 27.8; IR (KBr): 3396, 3270, 2925, 1716, 1541, 1491, 1008, 743, 708 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C39H31ClN2ONa 601.2018, found 601.2035. 2-(6-methyl-2-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)etha nol

(4ai):

Following

the

general


procedure, 1a

(72.2

to

the mg,

mixture 0.18

of

mmol),

2-(6-methyl-1H-indol-3-yl)ethanol 2i (17.5 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol), was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4ai (42.0 mg) in 75% yield as white solid. m.p. 76-77 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 7.93 (s, 1H), 7.63 (d, J = 7.6 Hz, 2H), 7.41 (d, J = 7.2 Hz, 2H), 7.38 (d, J = 5.6 Hz, 2H), 7.32 (d, J = 7.2 Hz, 1H), 7.20 (d, J = 7.2 Hz, 1H), 7.16 (d, J = 7.6 Hz, 1H), 7.13 – 6.95 (m, 9H), 6.91 (d, J = 8.0 Hz, 1H), 6.70 (d, J = 7.2 Hz, 2H), 6.41 (d, J = 7.2 Hz, 2H), 5.05 (d, J = 8.4 Hz, 1H), 4.95 (d, J = 8.8 Hz, 1H), 3.48 – 3.35 (m, 1H), 2.92 (s, 1H), 2.72 – 2.64 (m, 1H), 2.54 – 2.46 (m, 1H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 146.9, 144.8, 142.8, 140.7, 138.3, 136.1, 135.2, 131.2, 130.6, 129.8, 128.8, 127.8, 127.5, 127.4, 127.0, 126.9, 126.8, 123.8, 122.0, 120.8, 120.5, 119.3, 118.3, 117.7, 112.0, 110.8, 108.8, 68.3, 63.1, 62.0, 42.1, 28.0, 21.6; IR (KBr): 3285, 3056, 2923, 2853, 1709, 1458, 1033, 702


Page 45 of 57 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


cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2ONa 581.2564, found 581.2549. 2-(7-methyl-2-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)etha nol

(4aj):

Following

the

general


procedure, 1a

(72.2

to

the mg,

mixture 0.18

of

mmol),

2-(7-methyl-1H-indol-3-yl)ethanol 2j (17.5 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol), was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4aj (51.0 mg) in 91% yield as white solid. m.p. 98-99 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H), 7.81 (s, 1H), 7.67 (d, J = 7.6 Hz, 2H), 7.46 – 7.39 (m, 3H), 7.38 – 7.30 (m, 2H), 7.22 – 7.15 (m, 2H), 7.13 (d, J = 8.0 Hz, 1H), 7.10 – 6.98 (m, 7H), 6.93 (d, J = 7.2 Hz, 1H), 6.73 (d, J = 7.2 Hz, 2H), 6.42 (d, J = 7.6 Hz, 2H), 5.08 (d, J = 8.8 Hz, 1H), 4.99 (d, J = 8.4 Hz, 1H), 3.49 – 3.40 (m, 1H), 2.97 – 2.87 (m, 1H), 2.73 – 2.65 (m, 1H), 2.55 – 2.47 (m, 1H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 146.8, 144.9, 142.9, 140.8, 138.3, 135.8, 135.2, 130.6, 129.8, 128.9, 128.5, 127.8, 127.6, 127.5, 127.0, 126.9, 126.8, 123.8, 122.1, 122.0, 120.5, 120.1, 119.5, 119.2, 117.8, 116.4, 112.1, 109.7, 68.1, 63.1, 62.1, 42.3, 28.1, 16.8; IR (KBr): 3386, 3057, 2925, 1707, 1580, 1452, 1218, 1036, 703 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2ONa 581.2564, found 581.2551. 2-(7-methoxy-2-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)eth anol

(4ak):

Following

the

general


procedure, 1a

(72.2

to mg,

the

mixture 0.18

of

mmol),

2-(7-methoxy-1H-indol-3-yl)ethanol 2k (19.1 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol), was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the



Page 46 of 57

completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4ak (37.9 mg) in 66% yield as white solid. m.p. 75-76 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 8.18 (s, 1H), 8.00 (s, 1H), 7.66 (d, J = 7.6 Hz, 2H), 7.45 – 7.38 (m, 3H), 7.32 (t, J = 7.4 Hz, 1H), 7.22 – 7.16 (m, 2H), 7.14 – 6.98 (m, 9H), 6.72 (d, J = 7.2 Hz, 2H), 6.60 (d, J = 7.6 Hz, 1H), 6.41 (d, J = 7.6 Hz, 2H), 5.09 (d, J = 8.8 Hz, 1H), 4.96 (d, J = 8.8 Hz, 1H), 3.86 (s, 3H), 3.50 – 3.40 (m, 1H), 3.00 – 2.89 (m, 1H), 2.77 – 2.65 (m, 1H), 2.58 – 2.48 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 146.8, 145.9, 144.7, 142.8, 140.8, 138.2, 135.8, 130.6, 130.2, 129.8, 128.8, 127.8, 127.6, 127.5, 127.0, 126.8, 126.0, 123.8, 122.0, 120.4, 119.6, 119.3, 117.8, 112.1, 111.5, 109.7, 101.6, 68.2, 63.1, 62.0, 55.1, 42.1, 28.1; IR (KBr): 3472, 2339, 1640, 1112, 835, 622, 647, 602 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2O2Na 597.2513, found 597.2535. 3-(2-(2,3,3-triphenyl-1,2,3,4-tetrahydrocyclopenta[b]indol-1-yl)-1H-indol-3-yl)propan-1-ol (4al):

Following

the

general


procedure, 1a

(72.2

to

the mg,

mixture 0.18

of mmol),

3-(1H-indol-3-yl)propan-1-ol 2l (17.5 mg, 0.1 mmol), catalyst 5c (3.6 mg, 0.02 mmol), was added chloroform (1 mL). Then, the reaction mixture was stirred at 40 oC for 8 h. After the completion of the reaction indicated by TLC, the reaction mixture was purified by flash column chromatography eluent (petroleum ether/ethyl acetate = 10/1) to afford 4al (45.4 mg) in 81% yield as white solid. m.p. 71-72 oC; >95:5 dr; 1H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H), 7.90 (s, 1H), 7.65 – 7.61 (m, 2H), 7.48 (d, J = 7.6 Hz, 1H), 7.41 (t, J = 7.6 Hz, 3H), 7.31 (t, J = 7.4 Hz, 1H), 7.21 – 7.09 (m, 5H), 7.08 – 7.01 (m, 5H), 7.00 – 6.96 (m, 2H), 6.72 (d, J = 7.2 Hz, 2H), 6.45 – 6.40 (m, 2H), 5.08 (d, J = 8.4 Hz, 1H), 4.99 (d, J = 8.4 Hz, 1H), 3.45 – 3.34 (m, 2H), 2.49 – 2.41 (m, 1H), 2.39 – 2.32


Page 47 of 57 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


(m, 1H), 1.70 – 1.63 (m, 1H), 0.92 – 0.78 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 147.0, 144.9, 142.9, 140.8, 138.7, 135.7, 135.2, 130.6, 129.8, 128.9, 128.8, 127.8, 127.5, 127.4, 127.0, 126.8, 126.7, 123.8, 122.0, 121.2, 120.5, 119.4, 118.9, 118.6, 117.8, 112.8, 112.0, 110.8, 68.4, 62.9, 62.2, 42.1, 33.6, 20.4; IR (KBr): 3390, 3059, 2933, 1717, 1493, 1451, 1304, 1033, 909, 743, 703 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C40H34N2ONa 581.2564, found 581.2575. Characteristic data for compounds 6-8 3,3-dimethyl-2-phenyl-1-((Z)-2-(3-((E)-styryl)-1H-indol-2-yl)prop-1-en-1-yl)-1,2,3,4-tetrahyd rocyclopenta[b]indole (6): white solid; m.p. 108-109 oC; 1H NMR (400 MHz, CDCl3) δ 8.12 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 6.0 Hz, 1H), 7.87 (s, 1H), 7.56 (d, J = 7.6 Hz, 2H), 7.51 – 7.30 (m, 8H), 7.23 – 7.10 (m, 9H), 7.03 – 6.98 (m, 1H), 3.15 (d, J = 12.8 Hz, 1H), 2.86 (d, J = 12.8 Hz, 1H), 2.26 (s, 3H), 1.70 (s, 3H), 1.38 (s, 3H); 13C NMR (100 MHz, Acetone-d6) δ 151.1, 139.9, 139.8, 139.2, 138.6, 135.9, 135.8, 131.2, 131.0, 128.6, 128.3, 127.8, 126.9, 126.2, 126.1, 125.6, 125.5, 124.6, 121.9, 121.4, 121.3, 121.0, 120.4, 120.3, 120.2, 111.6, 111.5, 110.7, 109.8, 104.8, 62.2, 61.6, 38.9, 29.7, 26.4; IR (KBr): 3429, 2968, 2926, 1449, 1310, 956, 740, 694, 544 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C38H34N2Na 541.2615, found 541.2620. 1,3-diphenyl-9H-carbazole (7): white solid; m.p. 97-98 oC; 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 6.4 Hz, 1H), 7.99 (s, 1H), 7.47 – 7.27 (m, 10H), 7.24 – 7.16 (m, 3H), 5.85 (s, 1H), 5.59 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 140.6, 139.8, 138.8, 136.9, 135.9, 128.7, 128.6, 128.5, 128.0, 126.6, 126.5, 126.3, 125.8, 123.1, 122.5, 120.9, 120.7, 118.9, 113.9, 111.1; IR (KBr): 3345, 3054, 1704, 1508, 919, 782, 727, 692 cm-1; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C24H17NNa 342.1254, found 342.1241. 2,3,3-triphenyl-3,4-dihydrocyclopenta[b]indole (8): white solid; m.p. 97-98 oC; 1H NMR (400



MHz, Acetone-d6) δ 10.62 (s, 1H), 7.78 – 7.73 (m, 1H), 7.72 (s, 1H), 7.47 (d, J = 7.6 Hz, 2H), 7.43 – 7.36 (m, 5H), 7.34 – 7.24 (m, 6H), 7.20 (t, J = 7.6 Hz, 2H), 7.16 – 7.07 (m, 3H); 13C NMR (100 MHz, Acetone-d6) δ 157.6, 148.6, 141.0, 136.2, 128.6, 128.3, 127.9, 126.9, 126.1, 125.8, 124.0, 121.6, 121.0, 119.9, 119.2, 119.0, 112.3, 63.3; IR (KBr): 3407, 3029, 1593, 1490, 1249, 783, 761, 746 cm-1; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C29H22N 384.1747, found 384.1760.

Supporting Information Characterization data (including 1H and

13

C NMR spectra) of products 3-4 and 6-8, HPLC

copies of product 3aa, single crystal data of products 3aa and 4aa. This material is available free of charge via the Internet at http://pubs.acs.org.

Acknowledgements

We are grateful for financial support from National Natural Science Foundation of China (21772069 and 21702077), Natural Science Foundation of Jiangsu Province (BK20160003 and BK20170227), Six Kinds of Talents Project of Jiangsu Province (SWYY-025) and Undergraduate Students Project of Jiangsu Province.

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Enantioselective

Friedel–Crafts

Alkylation/N-Hemiacetalization Cascade Reaction with Indoles. Angew. Chem. Int. Ed. 2013, 52, 3250–3336; (c) Chen, M.; Sun, J. Catalytic Asymmetric N-Alkylation of Indoles and Carbazoles through 1, 6-Conjugate Addition of Aza-para-quinone Methides. Angew. Chem. Int. Ed. 2017, 56, 4583–4658. (19) CCDC 1589277 for 3aa and CCDC 1589278 for 4aa, see the Supporting Information for details. (20) Hong, L.; Sun, W.; Yang, D.; Li, G.; Wang, R. Additive Effects on Asymmetric Catalysis. Chem. Rev. 2016, 116, 4006–4123.


Chemodivergent Tandem Cyclizations of 2-Indolylmethanols with

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