Rhodium-Catalyzed Chemo- and Regioselective Intermolecular Cross

Sep 29, 2017 - It has been established that a cationic rhodium(I)/BIPHEP complex is able to catalyze the unprecedented intermolecular ...
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Article Cite This: J. Org. Chem. 2017, 82, 11117-11125

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Rhodium-Catalyzed Chemo- and Regioselective Intermolecular Cross-Cyclotrimerization of Nonactivated Terminal and Internal Alkynes Shuhei Nishigaki, Yu Shibata, and Ken Tanaka* Department of Chemical Science and Engineering, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo 152-8550, Japan S Supporting Information *

ABSTRACT: It has been established that a cationic rhodium(I)/BIPHEP complex is able to catalyze the unprecedented intermolecular cross-cyclotrimerization of nonactivated terminal and internal alkynes at room temperature. In this transformation, the use of arylacetylenes as terminal alkynes and 1,4-butynediol derivatives as internal alkynes afforded the cross-cyclotrimerization products with good chemo- and regioselectivity. The present study clearly demonstrated that an electronically biased combination of nonactivated and electron-deficient alkynes is not necessary to realize good chemo- and regioselectivity in the cationic rhodium(I) complex-catalyzed intermolecular cross-cyclotrimerization.

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INTRODUCTION The transition-metal-catalyzed alkyne cyclotrimerization1,2 is a useful method for the synthesis of substituted benzenes because of its high atom economy and convergent nature. Numbers of transition-metal complexes are known to catalyze the alkyne cyclotrimerization, but it has been difficult to carry out the highly chemo- and regioselective intermolecular cross-cyclotrimerization of two or three different alkynes to produce densely substituted benzenes.3 A successful solution to minimize the chemo- and regioselectivity problems includes temporary connections of two or three different monoynes with disposable tether groups, such as boron4 and silyl5 groups. A practical solution to control both chemo- and regioselectivity in the completely intermolecular cross-cyclotrimerization of alkynes without the use of tether groups is the use of two or three different alkynes possessing different electronic properties.6−13 For example, our research group reported the highly chemo- and regioselective cross-cyclotrimerization of nonactivated terminal alkynes and electron-deficient internal alkynes (dialkyl acetylenedicarboxylates) to produce 3,6disubstituted phthalates, catalyzed by a cationic rhodium(I)/ H8-BINAP complex at room temperature (Scheme 1, top).7b,c This method has been successfully applied to the synthesis of paracyclophanes7c including cycloparaphenylenes.14 However, the chemo- and regioselective cross-cyclotrimerization without employing an electronically biased combination of alkynes has not been reported to date. In this paper, we have found that electronic bias is not necessary to realize good chemo- and regioselectivity in the cationic rhodium(I) complex-catalyzed intermolecular cross-cyclotrimerization of alkynes. Thus, we have established that a cationic rhodium(I)/BIPHEP complex is able to catalyze the intermolecular cross-cyclotrimerization of © 2017 American Chemical Society

Scheme 1. Rhodium-Catalyzed Intermolecular CrossCyclotrimerization of Terminal and Internal Alkynes

nonactivated terminal and internal (1,4-butynediol derivatives) alkynes at room temperature (Scheme 1, bottom).

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RESULTS AND DISCUSSION We first investigated the reaction of nonactivated terminal [phenylacetylene (1a), 1 equiv] and internal [1,4-diacetoxy-2butyne (2a), 0.5 equiv] alkynes in the presence of a cationic rhodium(I) complex with a simple biarylbisphosphine ligand (BIPHEP, 10 mol %). Surprisingly, despite the absence of electronic bias between these two alkynes, the intermolecular Received: August 22, 2017 Published: September 29, 2017 11117

DOI: 10.1021/acs.joc.7b02121 J. Org. Chem. 2017, 82, 11117−11125

Article

The Journal of Organic Chemistry Table 1. Optimization of Reaction Conditions for Rhodium-Catalyzed Cross-Cyclotrimerization of 1a and 2aa

entry

ligand

2a (equiv)

yield (%) 3aa + 4aa + 5aab

ratio of 3aa/4aa/5aac

1 2 3 4 5d 6 7 8d 9d 10d 11d 12d 13 14e

BIPHEP BIPHEP BIPHEP BIPHEP BIPHEP BIPHEP BIPHEP MeO-BIPHEP Difluorophos Segphos BINAP H8-BINAP dppb BIPHEP

0.5 1.0 1.5 2.0 2.5 3.0 3.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5

75 76 71 74 73 69 66 71 69 71 73 73 0 63

46:8:46 66:9:25 74:8:18 80:7:13 83:6:11 83:7:10 85:6:9 82:6:12 85:7:8 85:5:10 79:12:9 80:11:9 − 82:6:12

a [Rh(cod)2]BF4 (0.020 mmol), ligand (0.020 mmol), 1a (0.20 mmol), 2a (0.10−0.70 mmol), and CH2Cl2 (2.0 mL) were used. bIsolated as a mixture of 3aa, 4aa, 5aa, and 2a. The yield of 3aa + 4aa + 5aa, based on 1a, was determined by 1H NMR. cDetermined by 1H NMR. dAverage of three runs (see Table S1). e[Rh(cod)2]BF4 (0.010 mmol) and BIPHEP (0.010 mmol) were used.

The substrate scope is shown in Table 2. With respect to internal alkynes, the use of sterically demanding 1,4dibenzoyloxy-2-butyne (2b) in place of 1,4-diacetoxy-2-butyne (2a, entry 1) increased the product yield as well as the regioselectivity (entry 2). The use of electron-poor pentafluorophenyl derivative 2c retained the regioselectivity, but lowered the product yield (entry 3). More coordinative carbonate 2d with more electron-rich carbonyl oxygen was an equally suitable substrate (entry 4), but less coordinative phenyl ether 2e with no carbonyl group showed lower chemoselectivity than benzoate 2b (entry 5). With respect to terminal alkynes, not only nonsubstituted phenylacetylene (1a) but also para-substituted phenylacetylenes 1b−d and 3,5-dimethoxyphenylacetylene (1e) reacted with 2b to give the corresponding cross-cyclotrimerization products with high yields and regioselectivity (entries 6−9). Sterically demanding 2,5dimethoxyphenylacetylene (1f) and ortho-tolylacetylene (1g) could also react with 2b to give the corresponding crosscyclotrimerization products in good yields, although regioselectivity could not be determined by 1H NMR due to complex signals as a result of the presence of two pseudoaxial chiralities (entries 10 and 11). Other than the arylacetylenes, alkenyl- (1h, entry 12) and trimethylsilyl- (1i, entry 13) acetylenes could be employed for this process to give the corresponding crosscyclotrimerization products in moderate to good yields with high regioselectivity. However, the reaction of alkylacetylene 1j and 2a afforded the corresponding cross-cyclotrimerization products in moderate yield with low regioselectivity (entry 14). The use of MeO-BIPHEP as a ligand improved the product yield, but the regioselectivity was unchanged (entry 15). Importantly, increasing the amount of 1a (5 equiv) improved the selectivity for 3ja and decreased that of 5ja (entry 16). This effect of the amount of alkylacetylene 1j is the same as that of arylacetylene 1a shown in entries 1−7 of Table 1. As the combination of 4-methoxyphenylacetylene (1c) and 1,4dibenzoyloxy-2-butyne (2b) afforded the cross-cyclotrimeriza-

2:1 (1a/2a) cross-cyclotrimerization proceeded at room temperature in good yield,15 although the observed regioselectivity was low. Not only para-regioisomer 3aa but also a small amount of meta-regioisomer 4aa and a significant amount of ortho-regioisomer 5aa were generated (Table 1, entry 1). The amount of internal alkyne 2a was examined (entries 1−7), which revealed that increasing the amount of 2a increased the ratio of 3aa and decreased the ratio of 5aa. Interestingly, the ratio of 4aa was almost unchanged. The use of 2.5 equiv of 2a afforded 3aa in the highest yield (entry 5). Next, various biaryl bisphosphine ligands (Figure 1) were screened (entries 5 and

Figure 1. Structures of bisphosphine ligands.

8−12), which revealed that the effects of ligands on both chemo- and regioselectivities are very small. Therefore, the most simple and cheap BIPHEP was selected as the ligand.16 Importantly, the use of nonbiaryl bisphosphine ligand (dppb) failed to afford the cross-cyclotrimerization products (entry 13). Finally, the cross-cyclotrimerization of 1a and 2a still proceeded under the low catalyst loading (5 mol %) while retaining the regioselectivity but with slight erosion of the product yield (entry 14). 11118

DOI: 10.1021/acs.joc.7b02121 J. Org. Chem. 2017, 82, 11117−11125

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The Journal of Organic Chemistry Table 2. Rhodium-Catalyzed Cross-Cyclotrimerization of Terminal Alkynes 1 and Internal Alkynes 2a

entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15g 16g,h 17i 18i,j 19k

R1 (1) Ph (1a) Ph (1a) Ph (1a) Ph (1a) Ph (1a) p-MeC6H4 (1b) p-MeOC6H4 (1c) p-CF3C6H4 (1d) 3,5-MeOC6H3 (1e) 2,5-MeOC6H3 (1f) o-MeC6H4 (1g) 1-cyclohexenyl (1h) Me3Si (1i) n-C10H21 (1j) n-C10H21 (1j) n-C10H21 (1j) p-MeOC6H4 (1c) p-MeOC6H4 (1c) p-MeOC6H4 (1c)

yield (%) 3 + 4 + 5b

R2 (2)

d

Ac (2a) Bz (2b) COC6F5 (2c) CO2Me (2d) Ph (2e) Bz (2b) Bz (2b) Bz (2b) Bz (2b) Bz (2b) Bz (2b) CO2Me (2d) Ac (2a) Ac (2a) Ac (2a) Ac (2a) Bz (2b) Bz (2b) Bz (2b)

74 (66 ) 84 (76d) 68 (63d) 79 (71d) 68 (59d) 84 (69d) 90e 81 (75d) 86e 86e 65 (51d) 73e 48e 55e 64e 57e 64e 62e 88e

ratio of 3/4/5c 82:7:11 87:6:7 86:6:8 83:5:12 84:8:8 86:8:6 81:13:6 89:7:4 86:8:6 NDf NDf 77:9:14 96:4:0 42:36:22 43:33:24 66:23:11 85:12:3 84:11:5 81:14:5

a

[Rh(cod)2]BF4 (0.020 mmol), BIPHEP (0.020 mmol), 1 (0.20 mmol), 2 (0.50 mmol), and CH2Cl2 (1.5 mL) were used. bIsolated as a mixture of 3, 4, 5, and 2. The yield of 3 + 4 + 5 was determined by 1H NMR. cDetermined by 1H NMR. dYield of a mixture of 3, 4, and 5 after a preparative GPC. eYield of a mixture of 3, 4, and 5. fThe regioisomer ratio could not be determined. gLigand: MeO-BIPHEP. h2a (2.00 mmol) was used. iA solution of 1c was added to a solution of 2b and the Rh catalyst over 2 h, and the mixture was stirred for 1 h. j2b (0.1 mmol) was used. k [Rh(cod)2]BF4 (0.20 mmol), BIPHEP (0.20 mmol), 1c (0.264 g, 2.00 mmol), 2b (1.47 g, 5.00 mmol), and CH2Cl2 (15 mL) were used.

Scheme 2. Influence of Coordinating Groups in the Internal Alkyne

Scheme 3. Influence of Distance between Coordinating Groups and the C−C Triple Bond in The Internal Alkynex

tion products in the highest yield (entry 7), the reaction was conducted by using stoichiometric amounts of 1c and 2b (2:1 molar ratio) to give the cross-cyclotrimerization products in 64% yield while retaining the high regioselectivity (entry 17). Importantly, slow addition of a solution of 1c to a solution of

2b and the Rh catalyst did not increase the yield of 3cb + 4cb + 5cb due to the formation of a significant amount of the 1:2 (1c/2b) cross-cyclotrimerization products (entry 18). The reaction of 1c with 2b was conducted in a preparative scale [2.00 mmol (0.264 g) of 1c]. Pleasingly, the desired 11119

DOI: 10.1021/acs.joc.7b02121 J. Org. Chem. 2017, 82, 11117−11125

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The Journal of Organic Chemistry

cationic rhodium(I)/BIPHEP complex-catalyzed cross-cyclotrimerization between terminal and internal alkynes. Scheme 6 depicts a possible mechanism for the present chemo- and regioselective cross-cyclotrimerization of non-

tetrasubstituted benzenes were obtained with almost the same yield (88%, 0.492 g) and regioselectivity as in the small-scale reaction (entry 19 vs entry 7). The reaction of 1c and unfunctionalyzed nonactivated internal alkyne 2f was also examined as shown in Scheme 2. Surprisingly, the cross-cyclotrimerization proceeded to give the corresponding tetrasubstituted benzenes, although the product yield and regioselectivity were low. Thus, the use of functionalized internal alkynes is preferable to realize good chemo- and regioselectivity in the cationic rhodium(I) complex catalyzed intermolecular cross-cyclotrimerization. The influence of the distance between coordinating groups and the C−C triple bond in the functionalized internal alkyne was also examined as shown in Scheme 3. The reactions of terminal alkynes 1c and 1h with hex-3-yne-1,6-diyl diacetate (2g) afforded the 2:1 (1c/2g) cross-cyclotrimerization products in low yields, and 1,2,4,5-tetra-substituted benzene 5hg was obtained as a major regioisomer from 1h, although the regioselectivity could not be determined in the reaction using 1c. Thus, the appropriate distance between coordinating groups and the C−C triple bond of functionalized internal alkynes is essential to realize good chemo- and regioselectivity. In order to understand the observed good chemo- and regioselectivity in the present intermolecular cross-cyclotrimerization, reactivities of terminal alkynes (1a, 1i, and 1j) and internal alkynes (2a and 2f) were examined in the presence of the cationic rhodium(I)/BIPHEP or MeO-BIPHEP catalyst at room temperature. Homocyclotrimerization of 1a and 1i proceeded to give the corresponding substituted benzenes 6 and 7 with high regioselectivity, although the yield of 6i and 7i was moderate (Scheme 4). On the other hand, the reaction of 1j afforded the corresponding homocyclotrimerization products 6j and 7j with low regioselectivity (Scheme 4).

Scheme 6. Plausible Reaction Mechanism

activated terminal alkynes 1 and nonactivated internal alkynes 2 to form tetrasubstituted benzenes 3−5. According to our previous report of the rhodium(I)/H8-BINAP complexcatalyzed cross-cyclotrimerization of nonactivated terminal alkynes and electron-deficient internal alkynes,7b,c pararegioisomer 3 would be generated from metallacycle A, although the insertion mode of terminal alkyne 1 into metallacycle A is not clear at the present stage. Alternatively, 3 can also be generated from metallacycle E. On the other hand, ortho-regioisomer 5 can be generated from metallacycles C and D. The fact that increasing the amount of 2 increased the yield of 3 and decreased the yield of 5 (Table 1, entries 1−7) suggests that E and D might not be the major intermediates for 3 and 5, respectively, and the increased formation of metallacycle A and decreased formation of metallacycle C might account for the above result. As meta-regioisomer 4 might be generated from both metallacycles A and B, the amount of 2 did not affect the yield of 4. The slow homocyclotrimerization of 1i could account for the observed highly regioselective formation of 3ia as a result of the rapid formation of metallacycle A and the slow formation of metallacycles B and C. Additionally, the lower regioselectivity in the homocyclotrimerization of 1j than that of 1a (71:29 vs 92:8) could account for the observed increased formation of meta-regioisomer 4ja as a result of the increased formation of metallacycle B, which is able to afford 1,3,5-regioisomer 6j. Based on the above mechanism, the use of a highly reactive propargyl ether as the terminal alkyne would decrease the yield of 3 and increase the yields of 4 and 5 as a result of the preferred formation of metallacycles B and C. Indeed, the

Scheme 4. Rhodium-Catalyzed Homo-cyclotrimerization of Terminal Alkynes 1a, 1g, and 1h

In contrast, no reaction was observed in the cases of internal alkynes 2a and 2f, and homocyclotrimerization products 8a and 8f were not obtained at all (Scheme 5). This poor reactivity of the internal alkynes toward the homocyclotrimerization could account for the observed good chemoselectivity in the present Scheme 5. Rhodium-Catalyzed Homo-cyclotrimerization of Internal Alkynes 2a and 2f

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DOI: 10.1021/acs.joc.7b02121 J. Org. Chem. 2017, 82, 11117−11125

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The Journal of Organic Chemistry Scheme 7. Rhodium-Catalyzed Cross-cyclotrimerization of Functionalized Terminal and Internal Alkynes (1k and 2a)

intermolecular cross-cyclotrimerization. It is in sharp contrast to the fact that electronically biased combination of alkynes is necessary in the chemo- and regioselective intermolecular cross-cyclotrimerization catalyzed by other transition-metal complexes, such as iridium,8 ruthenium,9 nickel,10a and palladium.11 Future works will include the application of the present rhodium-catalyzed chemo- and regioselective intermolecular cross-cyclotrimerization to the synthesis of substituted oligo(para-phenylene) derivatives including cycloparaphenylenes.

reaction of 3-methoxyprop-1-yne (1k) and 2a afforded the 2:1 (1k/2a) cross-cyclotrimerization products in low yield and not 3ka but 4ka was the major regioisomer (Scheme 7). The synthetic utility of the present cross-cyclotrimerization product 3 is shown in Scheme 8. 3,5-DimethoxyphenylScheme 8. Synthetic Applications

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EXPERIMENTAL SECTION

General. CH2Cl2 (No. 041-32345) was obtained from Wako Pure Chemical Industries, Ltd., and used as received. H8-BINAP and Segphos were obtained from Takasago International Corporation. MeO-BIPHEP was obtained from Solvias AG. [Rh(cod)2]BF4 was obtained from Umicore AG. Terminal alkyne 1f20 and internal alkynes 2b21 and 2e21 were prepared according to literatures. All other reagents were obtained from commercial sources and used as received. 1 H (400 MHz), 13C{1H} (100 MHz), and 19F{1H} (377 MHz) NMR data were collected on a Bruker AVANCE III HD 400at ambient temperature unless otherwise specified. HRMS data were obtained on a Bruker micrOTOF Focus II. All reactions were carried out under an atmosphere of argon in oven-dried glassware with magnetic stirring. [1,1′:4′,1″-Terphenyl]-2′,3′-diylbis(methylene) Bis(2,3,4,5,6pentafluorobenzoate) (2c). To a solution of but-2-yne-1,4-diol (0.430 g, 4.99 mmol) in Et3N (2.80 mL, 20.1 mmol) and CH2Cl2 (40 mL) was added 2,3,4,5,6-pentafluorobenzoyl chloride (1.40 mL, 10.1 mmol). The resulting mixture was stirred at room temperature for 3 h. The reaction was quenched with water and extracted with CH2Cl2. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chlomatography (eluent: n-hexane/EtOAc/CH2Cl2 = 15:1:1) to give 2c (2.29 g, 4.83 mmol, 97% isolated yield) as a colorless solid. Mp 84.4−85.3 °C; 1H NMR (CDCl3, 400 MHz) δ 5.04 (s, 4H); 13C{1H} NMR (CDCl3, 100 MHz) δ 58.5 (d, 1.4 Hz), 80.8, 140.5 54.0; 19F{1H} NMR (CDCl3, 377 MHz) δ (−137.5)−(−137.6) (m, 2F), (−147.6)−(−147.8) (m, 1F), (−160.2)−(−160.4) (m, 2F); HRMS (ESI) calcd for C18H4O4F10Na [M + Na]+ 496.9842, found 496.9825. But-2-yne-1,4-diyl Dimethyl Bis(carbonate) (2d). To a solution of but-2-yne-1,4-diol (0.172 g, 2.00 mmol) in pyridine (0.97 mL, 12 mmol) and CH2Cl2 (16 mL) was added methyl carbonochloridate (0.37 mL, 4.8 mmol). The resulting mixture was stirred at 0 °C for 1 h. The reaction was quenched with saturated NH4Cl and extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chlomatography (eluent: n-hexane/EtOAc = 3:1) to give 2d (0.372 g, 1.84 mmol, 92% isolated yield) as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 4.78 (s, 4H), 3.782 (s, 6H); 13C{1H} NMR (CDCl3, 100 MHz) δ 155.1, 80.9, 55.3 55.2; HRMS (ESI) calcd for C8H10O6Na [M + Na]+ 225.0370, found 225.0359. General Procedure for Rhodium-Catalyzed Cross-Cyclotrimerization of Terminal Alkynes and Internal Alkynes (3aa, Table 2, Entry 1). BIPHEP (10.5 mg, 0.0201 mmol) and [Rh(cod)2]BF4 (8.1 mg, 0.020 mmol) were dissolved in CH2Cl2

acetylene (1e) and 2,5-dimethoxyphenylacetylene (1f) reacted with 2b in preparative scales to give the corresponding crosscyclotrimerization products without erosion of the product yields. Treatment of a mixture of the cross-cyclotrimerization products 3eb + 4eb + 5eb with BF3·OEt2 at 80 °C afforded the double Friedel−Crafts alkylation17 product, 1,3,8,10-tetramethoxy-11,12-dihydroindeno[2,1-a]fluorene (9), potential applications of which are the organic electronics [e.g., organic light emitting devices (OLEDs)],18 in 59% yield. Interestingly, a mixture of the cross-cyclotrimerization products 3fb + 4fb + 5fb was treated with BF3·OEt2 at 60 °C to give not the double Friedel−Crafts alkylation product but the demethylative etherification product,19 2,11-dimethoxy-6,7-dihydrobenzo[2,1-c:3,4-c′]dichromene (10), in 35% yield.

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CONCLUSION In conclusion, we have established that a cationic rhodium(I)/ BIPHEP complex is able to catalyze the unprecedented intermolecular cross-cyclotrimerization of nonactivated terminal and internal alkynes at room temperature. In this transformation, the use of arylacetylenes as terminal alkynes and 1,4-butynediol derivatives as internal alkynes afforded the cross-cyclotrimerization products [(3,6-diaryl-1,2-phenylene)dimethanol derivatives] with good chemo- and regioselectivity. The present study clearly demonstrated that electronically biased combination of nonactivated and electron-deficient alkynes is not necessary to realize good chemo- and regioselectivity in the cationic rhodium(I) complex-catalyzed 11121

DOI: 10.1021/acs.joc.7b02121 J. Org. Chem. 2017, 82, 11117−11125

Article

The Journal of Organic Chemistry (2.0 mL), and the mixture was stirred at room temperature for 10 min. H2 was introduced to the resulting solution in a Schlenk tube. After stirring at room temperature for 30 min, the resulting mixture was concentrated under reduced pressure. The residue was dissolved in CH2Cl2 (0.3 mL). To the solution was added a solution of alkynes 1a (20.4 mg, 0.200 mmol) and 2a (85.1 mg, 0.500 mmol) in CH2Cl2 (1.2 mL). The mixture was stirred at room temperature for 1 h. The resulting solution was concentrated, and the residue was purified by silica gel preparative thin layer chromatography (eluent: n-hexane/ EtOAc/CH2Cl2 = 10:1:5), which furnished a mixture of 3aa, 4aa, 5aa, and 2a (85.7 mg, (3aa + 4aa + 5aa)/2a = 18:82, 3aa + 4aa + 5aa: 0.0741 mmol, 74% yield, 3aa/4aa/5aa = 82:7:11) as a colorless oil. Further purification by a preparative GPC furnished a mixture of 3aa, 4aa, and 5aa (24.8 mg, 66% isolated yield, 3aa/4aa/5aa = 83:6:11) as a colorless oil. [1,1′:4′,1″-Terphenyl]-2′,3′-diylbis(methylene) Diacetate (3aa, Table 2, Entry 1). 1H NMR (CDCl3, 400 MHz) δ 7.47− 7.32 (m, 12H), 5.10 (s, 4H), 2.03 (s, 6H); partial protons of 4aa: δ 7.68 (d, J = 1.8 Hz, 1H), 7.61 (d, J = 7.4 Hz, 2H), 7.54 (d, J = 1.9 Hz, 1H), 5.31 (s, 2H), 5.10 (s, 2H), 2.13 (s, 3H), 2.04 (s, 3H); partial protons of 5aa: δ 7.47 (s, 2H), 5.27 (s, 4H), 2.11 (s, 6H); 13C{1H} NMR (CDCl3, 100 MHz) δ 170.3, 144.0, 140.5 133.1, 130.8, 129.2, 128.3, 127.6, 61.6; HRMS (ESI) calcd for C24H22O4Na [M + Na]+ 397.1410, found 397.1415. [1,1′:4′,1″-Terphenyl]-2′,3′-diylbis(methylene) Dibenzoate (3ab, Table 2, Entry 2). The title compound was isolated as a mixture of 3ab, 4ab, 5ab, and 2b. Colorless oil, 145.3 mg, (3ab + 4ab + 5ab)/2b = 20:80, 3ab + 4ab + 5ab: 0.0842 mmol, 84% NMR yield, 3ab/4ab/5ab = 87:6:7. Further purification by a preparative GPC furnished a mixture of 3ab, 4ab, and 5ab. Colorless solid, 38.0 mg, 0.0763 mmol, 76% isolated yield, 3ab/4ab/5ab = 86:7:7, mp 41.3− 46.1 °C; 1H NMR (CDCl3, 400 MHz) δ 7.90 (d, J = 7.5 Hz, 4H), 7.67−7.12 (m, 18H), 5.41 (s, 4H); partial protons of 4ab: δ 5.64 (s, 2H), 5.43 (s, 2H); partial protons of 5ab: δ 5.61 (s, 2H); 13C{1H} NMR (CDCl3, 100 MHz) δ 165.9, 144.2, 140.5, 133.5, 132.8, 130.8, 129.9, 129.6, 129.2, 128.3, 128.2, 127.6, 62.1; HRMS (ESI) calcd for C34H26O4Na [M + Na]+ 521.1723, found 521.1728. [1,1′:4′,1″-Terphenyl]-2′,3′-diylbis(methylene) Bis(2,3,4,5,6pentafluorobenzoate) (3ac, Table 2, Entry 3). The title compound was isolated as a mixture of 3ac, 4ac, 5ac, and 2c. Pale yellow solid, 238.6 mg, (3ac + 4ac + 5ac)/2c = 15:85, 3ac + 4ac + 5ac: 0.0684 mmol, 68% NMR yield, 3ac/4ac/5ac = 86:6:8. Further purification by a preparative GPC furnished a mixture of 3ac, 4ac, and 5ac. Colorless solid, 41.5 mg, 0.0632 mmol, 63% isolated yield, 3ac/ 4ac/5ac = 86:6:8, mp 120.9−123.9 °C; 1H NMR (CDCl3, 400 MHz) δ 7.50−7.34 (m, 12H), 5.45 (s, 4H); partial protons of 4ac: δ 5.65 (s, 2H), 5.47 (s, 2H); partial protons of 5ac: δ 5.63 (s, 4H); 13C{1H} NMR (CDCl3, 100 MHz) δ 144.6, 140.0, 132.0, 131.4, 129.2, 128.5, 127.9, 63.6; HRMS (ESI) calcd for C34H16O4F10Na [M + Na]+ 701.0781, found 701.0801. [1,1′:4′,1″-Terphenyl]-2′,3′-diylbis(methylene) Dimethyl Bis(carbonate) (3ad, Table 2, Entry 4). The title compound was isolated as a mixture of 3ad, 4ad, 5ad, and 2d. Colorless solid, 69.5 mg, (3ad + 4ad + 5ad)/2d = 30:70, 3ad + 4ad + 5ad: 0.0790 mmol, 79% NMR yield, 3ad/4ad/5ad = 83:5:12. Further purification by a preparative GPC furnished a mixture of 3ad, 4ad, and 5ad. Colorless solid, 28.9 mg, 0.0712 mmol, 71% isolated yield, 3ad/4ad/5ad = 83:4:13, mp 136.3−142.6 °C; 1H NMR (CDCl3, 400 MHz) δ 7.47− 7.32 (m, 12H), 5.20 (s, 4H), 3.76 (s, 6H); partial protons of 4ad: δ 7.71 (d, J = 1.9 Hz, 1H), 7.61 (d, J = 7.1 2H), 7.54 (d, J = 2.0 Hz, 1H), 7.26 (td, J = 7.9, 1.7 Hz, 1H), 5.40 (s, 2H), 5.20 (s, 2H), 3.81 (s, 3H), 3.76 (s, 3H); partial protons of 5ad: δ 7.50 (s, 2H), 5.35 (s, 4H), 3.80 (s, 6H); 13C{1H} NMR (CDCl3, 100 MHz) δ 155.2, 144.1, 140.3, 132.5, 131.0, 129.3, 128.3, 127.6, 64.8, 54.8; HRMS (ESI) calcd for C24H22O6Na [M + Na]+ 429.1309, found 429.1309. 2′,3′-Bis(phenoxymethyl)-1,1′:4′,1″-terphenyl (3ae, Table 2, Entry 5). The title compound was isolated as a mixture of 3ae, 4ae, 5ae, and 2e. Pale yellow solid, 56.6 mg, (3ae + 4ae + 5ae)/2e = 38:62, 3ae + 4ae + 5ae; 0.0678 mmol, NMR 68% yield, 3ae/4ae/5ae = 84:8:8. Further purification by a preparative GPC furnished a mixture

of 3ae, 4ae, and 5ae. Colorless solid, 25.9 mg, 0.0586 mmol, 59% isolated yield (3ae/4ae/5ae = 85:7:8), mp 146.4−150.6 °C; 1H NMR (CDCl3, 400 MHz) δ 7.54−6.79 (m, 22H), 5.05 (s, 4H); partial protons of 4ae: δ 7.85 (d, J = 1.8 Hz, 1H), 7.62 (d, J = 7.1 Hz, 2H), 7.58 (d, J = 2.0 Hz, 1H), 5.31 (s, 2H), 5.02 (s, 2H); partial protons of 5ae: δ 7.60 (s, 2H), 5.23 (s, 4H); 13C{1H} NMR (CDCl3, 100 MHz) δ 158.5, 143.8, 140.6, 134.2, 130.9, 129.44, 129.39, 128.2, 127.4, 121.0, 114.9, 65.0; HRMS (ESI) calcd for C32H26O2Na [M + Na]+ 465.1825, found 465.1830. (4,4″-Dimethyl-[1,1′:4′,1″-terphenyl]-2′,3′-diyl)bis(methylene) Dibenzoate (3bb, Table 2, Entry 6). The title compound was isolated as a mixture of 3bb, 4bb, 5bb, and 2b. Colorless oil, 144.2 mg, (3bb + 4bb + 5bb)/2b = 20:80, 3bb + 4bb + 5bb: 0.0837 mmol, 84% NMR yield, 3cb/4cb/5cb = 86:8:6. Further purification by a preparative GPC furnished a mixture of 3bb, 4bb, and 5bb. Colorless solid, 36.3 mg, 0.0690 mmol, 69% isolated yield 3bb/ 4bb/5bb = 85:8:7, mp 49.2−56.2 °C; 1H NMR (CDCl3, 400 MHz) δ 7.91 (d, J = 7.1, 4H), 7.59−7.01 (m, 16H), 5.40 (s, 4H), 2.36 (s, 6H); partial protons of 4bb: δ 5.62 (s, 2H), 5.42 (s, 2H), 2.38 (s, 3H); partial protons of 5bb: δ 5.59 (s, 4H), 2.30 (s, 6H); 13C{1H} NMR (CDCl3, 100 MHz) δ 165.9, 144.1, 137.6, 137.2, 133.5, 132.8, 130.9, 129.9, 129.6, 129.1, 129.0, 128.2, 62.3, 21.1 ; HRMS (ESI) calcd for C36H30O4Na [M + Na]+ 549.2036, found 549.2051. (4,4″-Dimethoxy-[1,1′:4′,1″-terphenyl]-2′,3′-diyl)bis(methylene) Dibenzoate (3cb, Table 2, Entry 7). The title compound was isolated as a mixture of 3cb, 4cb, and 5cb. Pale yellow solid, 50.5 mg, 0.0905 mmol, 90% isolated yield, 3cb/4cb/5cb = 81:13:6, mp 124.6−134.0 °C; 1H NMR (CDCl3, 400 MHz) δ 7.91 (d, J = 7.1 Hz, 4H), 7.48−7.41 (m, 4H), 7.34 (d, J = 8.7 Hz, 4H), 7.27 (t, J = 7.2 Hz, 4H), 6.91 (d, J = 8.8 Hz, 4H), 5.41 (s, 4H), 3.80 (s 6H); partial protons of 4cb: δ 5.61 (s, 2H), 5.43 (s, 2H); partial protons of 5cb: δ 5.59 (s, 4H); 13C{1H} NMR (CDCl3, 100 MHz) δ 165.9, 159.1, 143.7, 133.6, 132.9, 132.8, 131.0, 130.3, 129.6, 128.2, 113.8, 62.4, 55.3; HRMS (ESI) calcd for C36H30O6Na [M + Na]+ 581.1935, found 581.1942. (4,4″-Bis(trifluoromethyl)-[1,1′:4′,1″-terphenyl]-2′,3′-diyl)bis(methylene) Dibenzoate (3db, Table 2, Entry 8). The title compound was isolated as a mixture of 3db, 4db, 5db, and 2b. Colorless oil, 148 mg, (3db + 4db + 5db)/2b = 20:80, 3db + 4db + 5db: 0.0807 mmol, 81% NMR yield, 3db/4db/5db = 89:7:4. Further purification by a preparative GPC furnished a mixture of 3db, 4db, and 5db. Colorless solid, 47.3 mg, 0.0745 mmol, 75% isolated yield, 3db/ 4db/5db = 89:7:4, mp 128.1−138.0 °C; 1H NMR (CDCl3, 400 MHz) δ 7.88 (d, J = 7.1 Hz, 4H), 7.67 (d, J = 8.1 Hz, 4H), 7.56 (d, J = 8.0 Hz, 4H), 7.50−7.43 (m, 4H), 7.28 (t, J = 7.8 Hz, 4H), 5.41 (s, 4H); partial protons of 4db: δ 5.67 (s, 2H), 5.43 (s, 2H); partial protons of 5db: δ 5.63 (s, 4H); 13C{1H} NMR (CDCl3, 100 MHz) δ 165.8, 144.05, 144.04, 143.3, 133.8, 133.1, 130.8, 129.62, 129.59, 129.5 128.3, 125.4 (q, J = 3.6 Hz), 61.8; HRMS (ESI) calcd for C36H24O4F6Na [M + Na]+ 657.1471, found 657.1494. (3,3″,5,5″-Tetramethoxy-[1,1′:4′,1″-terphenyl]-2′,3′-diyl)bis(methylene) Dibenzoate (3eb, Table 2, Entry 9). The title compound was isolated as a mixture of 3eb, 4eb, and 5eb. Colorless solid, 53.4 mg, 0.0863 mmol, 86% isolated yield, 3eb/4eb/5eb = 86:8:6, mp 142.1−151.1 °C; 1H NMR (CDCl3, 400 MHz) δ 7.92 (dd, J = 8.2, 1.1 Hz, 4H), 7.48−7.40 (m, 4H), 7.26 (t, J = 7.8 Hz, 4H), 6.57 (d, J = 2.3 Hz, 4H), 6.46 (t, J = 2.2 Hz, 2H), 5.43 (s, 4H), 3.67 (s 12H); partial protons of 4eb: δ 5.62 (s, 2H), 5.45 (s, 2H); partial protons of 5eb: δ 5.60 (s, 4H); 13C{1H} NMR (CDCl3, 100 MHz) δ 165.9, 160.5, 144.3, 142.4, 133.4, 132.9, 130.5, 129.8, 129.6, 128.2, 100.1, 77.4, 77.3, 77.1, 76.7, 62.1, 55.3; HRMS (ESI) calcd for C38H34O8Na [M + Na]+ 641.2146, found 641.2147. (2,2″,5,5″-Tetramethoxy-[1,1′:4′,1″-terphenyl]-2′,3′-diyl)bis(methylene) Dibenzoate (3fb, Table 2, Entry 10). The title compound was isolated as a mixture of 3fb, 4fb, and 5fb. Yellow sticky oil, 53.5 mg, 0.0865 mmol, 86% isolated yield (regioselectivity could not be determined); 1H NMR (CDCl3, 400 MHz) δ 8.08−7.80 (m, 4H), 7.63−7.15 (m, 8H), 6.93−6.64 (m, 6H), 5.72−5.27 (m, 4H), 3.78−3.45 (m, 12H); 13C{1H} NMR (CDCl3, 100 MHz) δ 166.3, 166.0, 153.4, 153.3, 153.1, 150.61, 150.55, 140.0, 139.8, 134.13, 11122

DOI: 10.1021/acs.joc.7b02121 J. Org. Chem. 2017, 82, 11117−11125

Article

The Journal of Organic Chemistry

a Schlenk tube. After stirring at room temperature for 30 min, H2 was introduced to the resulting solution in a Schlenk tube again. After stirring at room temperature for more 30 min, the resulting mixture was concentrated under reduced pressure. The residue was dissolved in CH2Cl2 (3.0 mL). To the solution was added a solution of alkynes 1c (264 mg, 2.00 mmol) and 2b (1.47 g, 5.00 mmol) in CH2Cl2 (12 mL). The mixture was stirred at room temperature for 1 h. The resulting solution was concentrated, and the residue was purified by a silica gel column chromatography (eluent: n-hexane/EtOAc = 8:1 to 6:1), which furnished a mixture of 3cb, 4cb, and 5cb (492 mg, 0.881 mmol, 88% yield, 3cb/4cb/5cb = 81:14:5) as a pale yellow solid. 4,4″-Dimethoxy-2′,3′-dipentyl-1,1′:4′,1″-terphenyl (3cf, Scheme 2). The title compound was isolated as a mixture of 3cf, 4cf, and 5cf. Colorless oil, 11.4 mg, 0.0265 mmol, 27% isolated yield, 3cf/4cf/5cf = 57:18:25; 1H NMR (CDCl3, 400 MHz) δ 7.26 (d, J = 8.7, 4H), 7.00 (s, 2H), 6.94 (d, J = 8.7, 4H), 3.86 (s, 6H), 2.73−2.52 (m, 4H), 1.73−0.74 (m, 18H); partial protons of 4cf: δ 7.53 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 2.1 Hz, 1H), 7.21 (d, J = 2.1 Hz, 1H), 3.86 (s, 2H), 3.83 (s, 2H); partial protons of 5cf: δ 7.16 (s, 2H), 7.06 (d, J = 8.8 Hz, 4H), 6.76 (d, J = 8.8 Hz, 4H), 3.77; 13C{1H} NMR (CDCl3, 100 MHz) δ 158.9, 158.42, 158.36, 158.1, 142.7, 141.6, 141.1, 139.6, 139.2, 137.5, 137.4, 137.3, 135.53, 135.46, 134.3, 133.7, 132.6, 131.2, 130.9, 130.4, 128.0, 127.5, 126.6, 126.5, 114.1, 113.31, 113.28, 55.3, 55.2, 33.3, 32.4, 32.3, 32.21, 32.18, 32.1, 31.6, 31.1, 31.0, 30.8, 29.9, 29.3, 22.62, 22.61, 22.2, 22.1, 14.08, 14.06, 13.9; HRMS (ESI) calcd for C30H38O2Na [M + Na]+ 453.2764, found 453.2773. (4,4″-Dimethoxy-[1,1′:4′,1″-terphenyl]-2′,3′-diyl)bis(ethane2,1-diyl) Diacetate (3cg, Scheme 3). The title compound was isolated as a mixture of 3cg, 4cg, and 5cg. Colorless sticky oil, 8.3 mg, 0.018 mmol, 18% isolated yield (regioselectivity could not be determined); 1H NMR (CDCl3, 400 MHz) δ7.55−6.74 (m, 10H), 4.40−3.94 (m, 4H), 3.90−3.75 (m, 6H), 3.18−2.46 (m, 4H), 2.10− 1.93 (m, 6H); 13C{1H} NMR (CDCl3, 100 MHz) δ 171.0, 170.9, 170.8, 159.3, 158.8, 158.7, 158.3, 143.8, 142.5, 138.9, 138.7, 137.3, 134.9, 134.5, 134.4, 134.3, 133.6, 132.9, 132.2, 132.1, 130.8, 130.2, 128.9, 128.0, 127.6, 127.3, 114.2, 113.7, 113.4, 64.9, 64.7, 64.1, 64.0, 62.6, 55.4, 55.3, 55.2, 32.3, 31.5, 28.9, 28.3, 21.01, 20.96, 20.88, 19.2; HRMS (ESI) calcd for C28H30O6Na [M + Na]+ 485.1935, found 485.1953. (2,2″,3,3″,4,4″,5,5″-Octahydro-[1,1′:4′,1″-terphenyl]-2′,3′diyl)bis(ethane-2,1-diyl) Diacetate (3hg, Scheme 3). Colorless sticky oil, 2.6 mg, 0.0063 mmol, 6% isolated yield; 1H NMR (CDCl3, 400 MHz) δ 6.89 (s, 2H), 5.58−5.52 (m, 2H), 4.12 (t, J = 8.0 Hz, 4H), 3.03 (t, J = 8.0 Hz, 4H), 2.24−2.12 (m, 8H), 2.05 (s, 6H), 1.81− 1.64 (m, 8H); 13C{1H} NMR (CDCl3, 100 MHz) δ 170.9, 144.6, 138.8, 133.2, 127.3, 126.2, 65.0, 31.4, 29.2, 25.3, 23.2, 22.1, 21.1; HRMS (ESI) calcd for C26H34O4Na [M + Na]+ 433.2349, found 433.2364. (2,2″,3,3″,4,4″,5,5″-Octahydro-[1,1′:2′,1″-terphenyl]-4′,5′diyl)bis(ethane-2,1-diyl) Diacetate (5hg, Scheme 3). The title compound was isolated as a mixture of 4hg and 5hg. Colorless sticky oil, 10.3 mg, 0.0251 mmol, 25% isolated yield, 4hg/5hg = 21:79; 1H NMR (CDCl3, 400 MHz) δ 6.93 (s, 2H), 5.68−5.61 (m, 2H), 4.25 (t, J = 7.5 Hz, 4H), 2.95 (t, J = 7.5 Hz, 4H), 2.41−2.09 (m, 8H), 2.09− 2.01 (m, 6H), 1.82−1.59 (m, 8H); partial protons of 4hg: δ 7.11 (d, J = 2.0 Hz, 1H), 6.98 (d, J = 2.0 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 171.0, 141.4, 139.0, 133.8, 130.2, 126.0, 64.8, 31.4, 29.5, 25.7, 23.3, 22.2, 21.0; HRMS (ESI) calcd for C26H34O4Na [M + Na]+ 433.2349, found 433.2359. (3,5-Bis(methoxymethyl)-1,2-phenylene)bis(methylene) Diacetate (4ka, Scheme 7). The title compound was isolated as a mixture of 3ka, 4ka, and 5ka. Colorless oil, 6.5 mg, 0.0210 mmol, 21% isolated yield, 3ka/4ka/5ka = 18:72:10; 1H NMR (CDCl3, 400 MHz) δ 7.39−7.36 (m, 1H), 7.36−7.34 (m, 1H), 5.27 (s, 2H), 5.23 (s, 2H), 4.56 (s, 2H), 4.46 (s, 2H), 3.43−3.38 (m, 6H), 2.12−2.02 (m, 6H); partial protons of 3ka: δ 7.41 (s, 2H), 5.31 (s, 4H), 4.45 (s, 4H); partial protons of 5ka: δ 7.43 (s, 4H), 5.18 (s, 4H), 4.51 (s, 4H); 13 C{1H} NMR (CDCl3, 100 MHz) δ 170.7, 170.6, 139.3, 138.6, 138.3, 136.9, 136.4, 134.6, 133.9, 132.1, 130.2, 129.9, 128.8, 128.7, 74.0, 72.6, 72.5, 71.7, 64.0, 63.6, 59.7, 59.5, 58.5, 58.43, 58.39, 58.36, 52.2, 51.1,

134.08, 133.4, 133.0, 132.7, 132.6, 132.5, 130.9, 130.5, 130.14, 130.11, 130.07, 130.0, 129.74, 129.71, 129.6, 129.5, 128.33, 128.27, 128.2, 128.1, 128.0, 117.2, 117.1, 116.8, 114.12, 114.09, 113.8, 111.8, 111.7, 111.5, 64.4, 62.7, 55.9, 55.71, 55.66, 55.62, 55.5 ; HRMS (ESI) calcd for C38H34O8Na [M + Na]+ 641.2146, found 641.2161. (2,2″-Dimethyl-[1,1′:4′,1″-terphenyl]-2′,3′-diyl)bis(methylene) Dibenzoate (3gb, Table 2, Entry 11). The title compound was isolated as a mixture of 3gb, 4gb, 5gb, and 2b. Pale yellow sticky oil, 147.2 mg, (3gb + 4gb + 5gb)/2b = 15:85, 3gb + 4gb + 5gb: 0.0653 mmol, 65% NMR yield (regioselectivity could not be determined). Further purification by a preparative GPC furnished a mixture of 3gb, 4gb, and 5gb. Pale yellow sticky oil, 26.6 mg, 0.0506 mmol, 51% isolated yield (regioselectivity could not be determined); 1 H NMR (CDCl3, 400 MHz) δ 7.88−7.77 (m, 4H), 7.46−7.39 (m, 2H), 7.35−7.13 (m, 14H), 5.42−5.13 (m, 4H), 2.15 (s, 3H), 2.13 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 165.87, 165.86, 143.2, 139.923, 139.916, 136.0, 135.8, 133.71, 133.70, 132.7, 132.4, 130.4, 130.1, 130.0, 129.89, 129.88, 129.8, 129.6, 129.3, 128.4, 128.31, 128.28, 128.1, 127.86, 127.85, 125.52, 125.47, 62.01, 61.96; HRMS (ESI) calcd for C36H30O4Na [M + Na]+ 549.2036, found 549.2032. Dimethyl [(2,2″,3,3″,4,4″,5,5″-octahydro-[1,1′:4′,1″-terphenyl]-2′,3′-diyl)bis(methylene)] Bis(carbonate) (3hd, Table 2, Entry 12). The title compound was isolated as a mixture of 3hd, 4hd, and 5hd. Colorless sticky oil, 30.2 mg, 0.0730 mmol, 73% isolated yield, 3hd/4hd/5hd = 77:9:14; 1H NMR (CDCl3, 400 MHz) δ 7.10 (s, 2H), 5.59−5.53 (m, 2H), 5.27 (s, 4H) 3.78 (s, 6H), 2.25−2.09 (m, 8H), 1.81−1.59 (m, 8H); partial protons of 4hd: δ 7.33 (d, J = 1.9 Hz, 1H), 7.15 (d, J = 2.0 Hz, 1H); partial protons of 5hd: δ 7.16 (s, 2H); 13 C{1H} NMR (CDCl3, 100 MHz) δ 155.5, 145.7, 137.4, 131.8, 129.3, 127.3, 64.9, 54.8, 31.3, 25.3, 23.0, 22.0; HRMS (ESI) calcd for C24H30O6Na [M + Na]+ 437.1935, found 437.1951. [3,6-Bis(trimethylsilyl)-1,2-phenylene]bis(methylene) Diacetate (3ia, Table 2, Entry 13). The title compound was isolated as a mixture of 3ia and 4ia. Colorless solid, 17.6 mg, 0.0480 mmol, 48% isolated yield, 3ia/4ia = 96:4, mp 106.0−108.0 °C; 1H NMR (CDCl3, 400 MHz) δ 7.58 (s, 2H), 5.23 (s, 4H), 2.07 (s, 6H), 0.34 (s, 18H); partial protons of 4ia: δ 7.72 (d, J = 1.2 Hz, 2H); 13C{1H} NMR (CDCl3, 100 MHz) δ 170.7, 143.6, 140.1, 134.9, 64.0, 21.0, 0.42; partial carbons: δ 0.68, 0.53, 0.12, 0.16, −1.2; HRMS (ESI) calcd for C18H30O4Si2Na [M + Na]+ 389.1575, found 389.1576. Procedure for 3ja (Table 2, Entry 16). MeO-BIPHEP (11.7 mg, 0.0200 mmol) and [Rh(cod)2]BF4 (8.1 mg, 0.020 mmol) were dissolved in CH2Cl2 (2.0 mL), and the mixture was stirred at room temperature for 10 min. H2 was introduced to the resulting solution in a Schlenk tube. After stirring at room temperature for 30 min, the resulting mixture was concentrated under reduced pressure. The residue was dissolved in CH2Cl2 (0.3 mL). To the solution was added a solution of alkynes 1j (33.3 mg, 0.200 mmol) and 2a (340 mg, 2.00 mmol) in CH2Cl2 (1.2 mL). The mixture was stirred at room temperature for 1 h. The resulting solution was concentrated, and the residue was purified by silica gel preparative thin layer chromatography (eluent: n-hexane/EtOAc = 5:1), which a furnished mixture of 3ja, 4ja, and 5ja (28.6 mg, 0.0569 mmol, 57%, 3ja/4ja/5ja = 66:23:11) as a colorless solid. (3,6-Didecyl-1,2-phenylene)bis(methylene) Diacetate (3ja, Table 2, Entry 16). Mp 38.8−42.2 °C; 1H NMR (CDCl3, 400 MHz) δ 7.17 (s, 2H), 5.23 (s, 4H), 2.65 (t, J = 7.9 Hz, 4H), 2.06 (s, 6H), 1.69−1.18 (m, 32H), 0.88 (t, J = 6.8 Hz, 6H); partial protons of 4ja: δ 7.06 (s, 1H), 7.04 (s, 1H), 5.17 (s, 2H), 5.14 (s, 2H); partial protons of 5ja: δ 7.16 (s, 2H), 5.20 (s, 4H); 13C{1H} NMR (CDCl3, 100 MHz) δ 170.9, 170.79, 170.76, 170.7, 143.9, 143.7, 141.5, 141.3, 135.7, 133.2, 131.8, 131.2, 130.5, 130.4, 129.2, 128.2, 64.7, 64.0, 60.4, 59.9, 35.7, 33.2, 32.4, 32.1, 32.0, 31.9, 31.3, 31.2, 29.8, 29.7, 29.62, 29.60, 29.56, 29.53, 29.50, 29.4, 29.3, 22.7, 21.03, 21.01, 20.98, 14.1; HRMS (ESI) calcd for C32H54O4Na [M + Na]+ 525.3914, found 525.3930. Large Scale Procedure (3cb, Scheme 2). BIPHEP (105 mg, 0.201 mmol) and [Rh(cod)2]BF4 (81.2 mg, 0.200 mmol) were dissolved in CH2Cl2 (4.0 mL), and the mixture was stirred at room temperature for 10 min. H2 was introduced to the resulting solution in 11123

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thin layer chromatography (eluent: n-hexane/EtOAc/CH2Cl2 = 8:1:2), which furnished a mixture of 3fb, 4fb, and 5fb (108 mg, 0.174 mmol, 87%, regioselectivity was not detected) as a yellow sticky oil. To a solution of a portion of the above mixture of 3fb, 4fb, and 5fb (27.2 mg, 0.0440 mmol) in CH2Cl2 (10 mL) was added 46% BF3·OEt2 (47 μL, 0.18 mmol). The resulting mixture was stirred at 60 °C for 18 h. The reaction was quenched with water and extracted with CH2Cl2. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel preparative thin layer chromatography (eluent: n-hexane/ CH2Cl2 = 1:4) to give 10 (5.8 mg, 0.015 mmol, 35% isolated yield) as a pale yellow solid. Mp: 141.1−142.4 °C; 1H NMR (CDCl3, 400 MHz) δ 7.68 (s, 2H), 7.25 (d, J = 2.9 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 6.82 (dd, J = 8.8, 2.9 Hz, 2H), 5.09 (s, 4H), 3.85 (s, 6H); 13 C{1H} NMR (CDCl3, 100 MHz) δ 155.0, 148.4, 129.9, 127.4, 123.4, 122.0, 117.9, 115.2, 108.4, 64.5, 55.9; HRMS (APCI) calcd for C22H17O4 [M − H]+ 345.1121, found 345.1101.

21.0, 20.95, 20.91, 20.88; HRMS (ESI) calcd for C16H22O6Na [M + Na]+ 333.1309, found 333.1300. General Procedure for Rhodium-Catalyzed Homo-cyclotrimerization of Terminal Alkynes (Scheme 4, 6a and 7a). BIPHEP (10.5 mg, 0.0201 mmol) and [Rh(cod)2]BF4 (8.1 mg, 0.020 mmol) were dissolved in CH2Cl2 (2.0 mL), and the mixture was stirred at room temperature for 10 min. H2 was introduced to the resulting solution in a Schlenk tube. After stirring at room temperature for 30 min, the resulting mixture was concentrated under reduced pressure. The residue was dissolved in CH2Cl2 (0.3 mL). To the solution was added a solution of alkyne 1a (20.4 mg, 0.200 mmol) in CH2Cl2 (1.2 mL). The mixture was stirred at room temperature for 1 h. The resulting solution was concentrated, and the residue was purified by silica gel preparative thin layer chromatography (eluent: nhexane/EtOAc = 50:1), which furnished a mixture of 6a and 7a (19.8 mg, 0.0646 mmol, 97%, 6a/7a = 92:8) as a colorless solid. 4′-Phenyl-1,1′:2′,1″-terphenyl (6a, Scheme 4): 22 1H NMR (CD2Cl2, 400 MHz) δ 7.66−7.00 (m, 18H); partial protons of 7a: δ 7.73 (s, 3H). Benzene-1,2,4-triyltris(trimethylsilane) (6i, Scheme 4): 23 The title compound was isolated as a mixture of 6i and 7i. Colorless solid, 8.4 mg, 0.0285 mmol, 43% isolated yield, 6i/7i = 90:10; 1H NMR (CDCl3, 400 MHz) δ 7.85−7.82 (m, 1H), 7.65 (dd, J = 7.4, 0.5 Hz, 1H), 7.49 (dd, J = 7.4, 1.4 Hz, 1H), 0.37 (s, 9H), 0.36 (s, 9H), 0.27 (s, 9H); 7i: δ 7.68 (s, 3H), 0.28 (s, 27H). 1,2,4-Tris(decyl)benzene (6j, Scheme 4): 24 The title compound was isolated as a mixture of 6j and 7j. Colorless solid, 30.6 mg, 0.0613 mmol, 92% isolated yield, 6j/7j = 71:29; 1H NMR (CDCl3, 400 MHz) δ 7.03 (d, J = 7.6, 1H), 6.96−6.89 (m, 2H), 2.61−2.47 (m, 6H), 1.65− 1.48 (m, 6H), 1.44−1.17 (m, 42H), 0.88 (t, J = 7.6, Hz, 9H); partial protons of 7j: δ 6.80 (s, 3H). 1,3,8,10-Tetramethoxy-11,12-dihydroindeno[2,1-a]fluorine (9, Scheme 8). BIPHEP (20.9 mg, 0.0400 mmol) and [Rh(cod)2]BF4 (16.2 mg, 0.0399 mmol) were dissolved in CH2Cl2 (2.0 mL), and the mixture was stirred at room temperature for 10 min. H2 was introduced to the resulting solution in a Schlenk tube. After stirring at room temperature for 30 min, the resulting mixture was concentrated under reduced pressure. The residue was dissolved in CH2Cl2 (0.3 mL). To the solution was added a solution of alkynes 1e (64.9 mg, 0.400 mmol) and 2b (294 mg, 1.00 mmol) in CH2Cl2 (1.2 mL). The mixture was stirred at room temperature for 1 h. The resulting solution was concentrated, and the residue was purified by silica gel preparative thin layer chromatography (eluent: n-hexane/EtOAc/CH2Cl2 = 8:1:2), which furnished a mixture of 3eb, 4eb, and 5eb (114 mg, 0.180 mmol, 90%, 3eb/4eb/5eb = 85:10:5) as a colorless solid. To a solution of a portion of the above mixture of 3eb, 4eb, and 5eb (29.0 mg, 0.0468 mmol, 3eb/4eb/5eb = 85:10:5) in CH2Cl2 (10 mL) was added 46% BF3·OEt2 (50 μL, 0.19 mmol). The resulting mixture was stirred at 80 °C for 5 h. The reaction was quenched with water and extracted with CH2Cl2. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel preparative thin layer chromatography (eluent: n-hexane/CH2Cl2 = 1:2) to give 9 (10.4 mg, 0.0278 mmol, 59% isolated yield) as a colorless solid. Mp 209 °C (decomposition); 1 H NMR (CDCl3, 400 MHz) δ 7.72 (s, 2H), 6.95 (d, J = 2.0 Hz, 2H), 6.43 (d, J = 2.0 Hz, 2H), 3.91 (s, 12H), 3.79 (s, 4H); 13C{1H} NMR (CDCl3, 100 MHz) δ 161.1, 156.8, 144.0, 141.0, 140.3, 123.0, 118.5, 97.4, 96.5, 55.7, 55.4, 32.2; HRMS (APCI) calcd for C24H23O4 [M + H]+ 375.1591, found 375.1576. 2,11-Dimethoxy-6,7-dihydrobenzo[2,1-c:3,4-c′]dichromene (10, Scheme 8). BIPHEP (20.9 mg, 0.0400 mmol) and [Rh(cod)2]BF4 (16.2 mg, 0.0399 mmol) were dissolved in CH2Cl2 (2.0 mL), and the mixture was stirred at room temperature for 10 min. H2 was introduced to the resulting solution in a Schlenk tube. After stirring at room temperature for 30 min, the resulting mixture was concentrated under reduced pressure. The residue was dissolved in CH2Cl2 (0.3 mL). To the solution was added a solution of alkynes 1f (64.9 mg, 0.400 mmol) and 2b (294 mg, 1.00 mmol) in CH2Cl2 (1.2 mL). The mixture was stirred at room temperature for 1 h. The resulting solution was concentrated, and the residue was purified by silica gel preparative

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02121. Copies of 1H and 13C NMR spectra (PDF)

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AUTHOR INFORMATION

Corresponding Author

* E-mail: [email protected]. ORCID

Ken Tanaka: 0000-0003-0534-7559 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported partly by ACT-C (No. JPMJCR1122YR) from Japan Science and Technology Agency (JST, Japan) and Grants-in-Aid for Scientific Research (Nos. 15H03775 and JP26102004) from Japan Society for the Promotion of Science (JSPS, Japan). We thank Takasago for the gift of H8-BINAP and Segphos, and Solvias and Umicore for generous support in supplying MeO-BIPHEP and the rhodium complex, respectively.

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REFERENCES

(1) For selected recent reviews of the transition-metal-catalyzed alkyne cyclotrimerization, see: (a) Transition-Metal-Mediated Aromatic Ring Construction; Tanaka, K., Ed.; John Wiley & Sons: Hoboken, USA, 2013. (b) Broere, D. L. J.; Ruijter, E. Synthesis 2012, 44, 2639. (c) Domínguez, G.; Pérez-Castells. Chem. Soc. Rev. 2011, 40, 3430. (2) For selected recent reviews of the application of the transitionmetal-catalyzed alkyne cyclotrimerization, see: (a) Tanaka, K.; Kimura, Y.; Murayama, K. Bull. Chem. Soc. Jpn. 2015, 88, 375. (b) Tanaka, K. Chem. - Asian J. 2009, 4, 508. (c) Kotha, S.; Brahmachary, E.; Lahiri, K. Eur. J. Org. Chem. 2005, 2005, 4741. (3) For reviews of the transition-metal-catalyzed intermolecular cross-cyclotrimerization of two or three different alkynes, see: Galan, B. R.; Rovis, T. Angew. Chem., Int. Ed. 2009, 48, 2830. (4) (a) Yamamoto, Y.; Ishii, J.; Nishiyama, H.; Itoh, K. J. Am. Chem. Soc. 2004, 126, 3712. (b) Yamamoto, Y.; Ishii, J.; Nishiyama, H.; Itoh, K. J. Am. Chem. Soc. 2005, 127, 9625. (5) Chouraqui, G.; Petit, M.; Aubert, C.; Malacria, M. Org. Lett. 2004, 6, 1519. (6) For the completely intermolecular cross-cyclotrimerization of alkynes using stoichiometric metal complexes, see: (a) Wakatsuki, Y.; Kuramitsu, T.; Yamazaki, H. Tetrahedron Lett. 1974, 15, 4549. (b) Yamazaki, H.; Wakatsuki, Y. J. J. Organomet. Chem. 1977, 139, 157.

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DOI: 10.1021/acs.joc.7b02121 J. Org. Chem. 2017, 82, 11117−11125

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The Journal of Organic Chemistry (c) Takahashi, T.; Xi, Z.; Yamazaki, A.; Liu, Y.; Nakajima, K.; Kotora, M. J. J. Am. Chem. Soc. 1998, 120, 1672. (d) Takahashi, T.; Tsai, F.-Y.; Li, Y.; Nakajima, K.; Kotora, M. J. Am. Chem. Soc. 1999, 121, 11093. (e) Suzuki, D.; Urabe, H.; Sato, F. J. J. Am. Chem. Soc. 2001, 123, 7925. (f) Tanaka, R.; Nakano, Y.; Suzuki, D.; Urabe, H.; Sato, F. J. J. Am. Chem. Soc. 2002, 124, 9682. (7) The rhodium-catalyzed intermolecular cross-cyclotrimerization of two different alkynes has been reported; see: (a) Abdulla, K.; Booth, B. L.; Stacey, C. J. J. Organomet. Chem. 1985, 293, 103. (b) Tanaka, K.; Shirasaka, K. Org. Lett. 2003, 5, 4697. (c) Tanaka, K.; Toyoda, K.; Wada, A.; Shirasaka, K.; Hirano, M. Chem. - Eur. J. 2005, 11, 1145. (d) Konno, T.; Moriyasu, K.; Kinugawa, R.; Ishihara, T. Org. Biomol. Chem. 2010, 8, 1718. (8) The iridium-catalyzed intermolecular cross-cyclotrimerization of two different alkynes has been reported; see: (a) Takeuchi, R.; Nakaya, Y. Org. Lett. 2003, 5, 3659. (b) Onodera, G.; Matsuzawa, M.; Aizawa, T.; Kitahara, T.; Shimizu, Y.; Kezuka, S.; Takeuchi, R. Synlett 2008, 2008, 755. (9) The ruthenium-catalyzed intermolecular cross-cyclotrimerization of two different alkynes has been reported; see: (a) Ura, Y.; Sato, Y.; Shiotsuki, M.; Kondo, T.; Mitsudo, T. J. Mol. Catal. A: Chem. 2004, 209, 35. (b) Kotha, S.; Seema, V.; Mobin, S. M. Synthesis 2011, 2011, 1581. (c) Wu, C.-Y.; Lin, Y.-C.; Chou, P.-T.; Wang, Y.; Liu, Y.-H. Dalton Trans. 2011, 40, 3748. (10) The nickel-catalyzed intermolecular cross-cyclotrimerization of two different alkynes has been reported; see: (a) Mori, N.; Ikeda, S.-I.; Odashima, K. Chem. Commun. 2001, 181. The nickel-catalyzed intermolecular cross-cyclotrimerization of 3-(alkynyl)propargylic alcohols and acetylenes has been reported; see: (b) Sato, Y.; Ohashi, K.; Mori, M. Tetrahedron Lett. 1999, 40, 5231. (11) The palladium-catalyzed intermolecular cross-cyclotrimerization of two different alkynes has been reported; see: tom Dieck, H.; Munz, C.; Müller, C. J. Organomet. Chem. 1990, 384, 243. (12) The transition-metal-catalyzed intermolecular cross-cyclotrimerization of three different alkynes has been reported, while two components should be used in large excess. See: Ura, Y.; Sato, Y.; Tsujita, H.; Kondo, T.; Imachi, M.; Mitsudo, T. J. Mol. Catal. A: Chem. 2005, 239, 166. (13) The transition-metal-catalyzed intermolecular cross-cyclotrimerization of two different alkynes with alkenes has also been reported. For Rh, see: (a) Hara, J.; Ishida, M.; Kobayashi, M.; Noguchi, K.; Tanaka, K. Angew. Chem., Int. Ed. 2014, 53, 2956. (b) Yoshida, T.; Tajima, Y.; Kobayashi, M.; Masutomi, K.; Noguchi, K.; Tanaka, K. Angew. Chem., Int. Ed. 2015, 54, 8241. For Ni, see: (c) Yamasaki, R.; Terashima, N.; Sotome, I.; Komagawa, S.; Saito, S. J. Org. Chem. 2010, 75, 480. (14) (a) Miyauchi, Y.; Johmoto, K.; Yasuda, N.; Uekusa, H.; Fujii, S.; Kiguchi, M.; Ito, H.; Itami, K.; Tanaka, K. Chem. - Eur. J. 2015, 21, 18900. (b) Nishigaki, S.; Miyauchi, Y.; Noguchi, K.; Ito, H.; Itami, K.; Shibata, Y.; Tanaka, K. Eur. J. Org. Chem. 2016, 2016, 4668. (c) Nishigaki, S.; Fukui, M.; Kawauchi, S.; Sugiyama, H.; Uekusa, H.; Shibata, Y.; Tanaka, K. Chem. - Eur. J. 2017, 23, 7227. (d) Hayase, N.; Miyauchi, Y.; Aida, Y.; Sugiyama, H.; Uekusa, H.; Shibata, Y.; Tanaka, K. Org. Lett. 2017, 19, 2993. (15) The intermolecular 1:2 (= 1a/2a) cross-cyclotrimerization product was generated in a low yield of ca. 10%. (16) For the effect of ligands on the course of the cyclotrimerization reactions, see: (a) Fabbian, M.; Marsich, N.; Farnetti, E. Inorg. Chim. Acta 2004, 357, 2881. Kezuka, S.; Tanaka, S.; Ohe, T.; Nakaya, Y.; Takeuchi, R. J. J. Org. Chem. 2006, 71, 543. (c) Matoušová, E.; Gyepes, R.; Císařová, I.; Kotora, M. Adv. Synth. Catal. 2016, 358, 254. (17) Li, G.; Wang, E.; Chen, H.; Liu, Y.; Wang, P. G. Tetrahedron 2008, 64, 9033. (18) For the synthesis and potential applications of 11,12dihydroindeno[2,1-a]fluorenes, see: (a) Thirion, D.; Poriel, C.; Rault-Berthelot, J.; Barriére, F.; Jeannin, O. Chem. - Eur. J. 2010, 16, 13646. (b) Ho, J.-H.; Lin, Y.-C.; Chou, L.-T.; Chen, Y.-Z.; Liu, W.-Q.; Chuang, C.-L. Tetrahedron Lett. 2013, 54, 1991.

(19) Although the same transformation has not been reported, the intramolecular demethylative etherification of a methyl phenyl ether with a tert-benzyl alcohol in the presence of hydrogen iodide and acetic anhydride was reported. See: Minuti, L.; Ballerini, E.; Barattucci, A.; Bonaccorsi, P. M.; Di Gioia, M. L.; Leggio, A.; Siciliano, C.; Temperini, A. Tetrahedron 2015, 71, 3253. (20) Wang, Y.; Wang, C.; Wang, Y.; Dong, L.; Sun, J. RSC Adv. 2015, 5, 12354. (21) Zhang, X.-M.; Wu, G.-Q.; Chen, W.-Z. Chin. J. Chem. 2007, 25, 1722. (22) Ozerov, O. V.; Patrick, B. O.; Ladipo, F. T. J. Am. Chem. Soc. 2000, 122, 6423. (23) Yong, L.; Butenschön, H. Chem. Commun. 2002, 23, 2852. (24) Saito, S.; Kawasaki, T.; Tsuboya, N.; Yamamoto, Y. Chem. Commun. 2002, 576.

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DOI: 10.1021/acs.joc.7b02121 J. Org. Chem. 2017, 82, 11117−11125