KOtBu-Promoted C4 Selective Coupling Reaction of Phenols and [60

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KOtBu-Promoted C4 Selective Coupling Reaction of Phenols and [60]Fullerene: One-Pot Synthesis of 4[60]Fullerephenols under Transition Metal-Free Conditions Fei Li, Jun Xuan, Shu Zhang, Boxiang Liu, Jianxiao Yang, Kai-Qing Liu, Dandan Liu, Qiong Zhang, Hongping Zhou, Jieying Wu, and Yupeng Tian J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00261 • Publication Date (Web): 26 Apr 2018 Downloaded from http://pubs.acs.org on April 26, 2018

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The Journal of Organic Chemistry

KOtBu-Promoted C4 Selective Coupling Reaction of Phenols and [60]Fullerene: One-Pot Synthesis of 4[60]Fullerephenols under Transition Metal-Free Conditions Fei Li,*,†,‡ Jun Xuan,† Shu Zhang,† Boxiang Liu,† Jianxiao Yang,† Kaiqing Liu,‡ Dandan Liu,† Qiong Zhang,† Hongping Zhou,† Jieying Wu,† and Yupeng Tian*,† †

Department of Chemistry, Key Laboratory of Functional Inorganic Materials of Anhui Province,

Anhui University, Hefei 230039, P. R. China ‡

Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026,

P. R. China

ABSTRACT A KOtBu-promoted direct coupling reaction of phenols and [60]fullerene was disclosed. The reaction occurs exclusively at the C4-position of phenols with high regioselectivity and provides an efficient and inexpensive manner to various 4-[60]fullerephenols in good yields. The electrochemical properties of the products render the method attractive and valuable. INTRODUCTION Phenols are key structures of in many pharmaceuticals, polymers, bioactive natural products as well as functional materials.1 Consequently, numerous novel and efficient methods have been developed for the preparation and modification of phenols in the past several years.1-2 Multi-additive fullerephenol derivatives, which are candidates as new hybrid antioxidants able to work at high-temperature,3 were synthesized by multiaddition of organocopper reagents to C603 or electrophilic addition of 2,6-dimethylphenol to C60 in the presence of AlCl3.3,4 The former method requires protection and deprotection of hydroxyl group and the latter one afforded polyphenolfullerenes with a variety of structures. One-pot direct synthesis of fullerephenol mono-adduct by simply reacting pristine fullerenes with phenols remains unknown and very challenging. In recent years, metal salts-mediated or -catalyzed reactions have dramatically changed the fate of fullerene chemistry.5 A broad range of novel fullerene derivatives

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with diversified potential applications can be easily assessed by using various metal salts.6 Along this line, the development of new coupling reactions between C60 and phenols has gained great interest. For instance, in 2017, we realized a new method for the synthesis of [60]fullerene-fused benzofurans via a palladium-catalyzed heteroannulation of phenols (Scheme 1).7 It is worth noting that the reaction occurred with high C2-selectivity of phenols. Recognizing the importance of phenolics, and the lack of sufficient methods for the synthesis of fullerephenol derivatives, we hoped to switch the reactivity of phenols and realized the direct C4 selective coupling reaction of phenols and C60. Inspired by our recent work in KOtBu-mediated coupling reactions of C60 and indoles,8 we proposed that KOtBu might also be an effective promoter to generate reactive phenoxide anion as key nucleophilic carbanion via resonance from a range of phenols (Scheme 1). The formed phenoxide anion then underwent nucleophilic addition to C60, thus realizing the direct C4 selective coupling of phenols with C60. The reaction run under transition metal-free conditions and provided a robust manner to the synthesis of various fullerephenol mono-adducts. Herein, we reported our preliminary results of this study. Scheme 1. Site-Selective Reactions of Phenols and C60

RESULTS AND DISCUSSION Reaction development began using readily available phenol (1a) and the initial conditions from the KOtBu mediated coupling reactions of C60 and indoles developed in our lab (Table 1, Entry 1).8a Using C60 (0.05 mmol, 1 equiv.), phenol 1a (1.2 or 2 equiv.) and KOtBu (2.5 or 5 equiv.) in chlorobenzene(PhCl)/DMSO (4:1) did not result in any product formation (Table 1, entries 1 and 2). Further condition optimization revealed that the polarity of the solvent has a significant influence for the formation of product


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2a. Switching to more polar organic solvent PhCl/DMSO (2:1) yielded trace amounts of 2a (Table 1, entry 3), while replacing PhCl/DMSO (1:1) as the reaction media increased the yield to 7% (Table 1, entry 4). To our delight, the use of pure aprotic polar solvents, such as DMSO and DMF, the yields of 2a were drastically increased to 30% and 33%, respectively (Table 1, entries 5 and 6). Raising the temperature from rt to 60 ℃ led to an improvement of the yield of 2a to 38% (Table 1, entry 7). Further optimization showed that the yield of 2a can be increased to 56% when 5 equiv. of phenol was used (Table 1 entry 8). (Table 1, entry 8). It was found that other solvents such as PhCl, CH3CN, DME, 1,4-dioxane and CHCl3 under other identical conditions did not produce any 2a (Table 1, entries 9-13), further documenting DMF was the best choice. It is important to note that the reaction did not provide any product 2a under air, an inert gas atmosphere was vital to this reaction. Table 1. Optimization of the Reaction Conditionsa

entry

Molar ratiob

solvent (v/v)

tempc ( ℃)

yield (%)d

1

1 : 1.2: 2.5

PhCl/DMSO (4:1)

rt

NR

2

1 : 2: 5

PhCl /DMSO (4:1)

rt

NR

3

1:2:5

PhCl /DMSO (2:1)

rt

trace

4

1:2:5

PhCl /DMSO (1:1)

rt

7

5

1:2:5

DMSO

rt

30

6

1:2:5

DMF

rt

33 38

7

1:2:5

DMF

60

8

1:5:5

DMF

60

56

9

1:5:5

PhCl

60

NR

10

1:5:5

CH3CN

60

NR

11

1:5:5

DME

60

NR

12

1:5:5

1,4-dioxane

60

NR

13

1:5:5

CHCl3

60

NR

a

Reaction condition: (1) C60 (0.05 mmol)/1a/KOtBu in a designated molar ratio in Schlenk tubes under Ar, solvent (8 mL). (2) CF3COOH (0.1 mmol, 20 equiv). The residue was separated on a silica gel column with disulfide/dichloromethane (5:1) as the eluent to give 2a. bMolar ratio refers to C60/1a/KOtBu. cOil temperature. d Isolated yield by column chromatography.

With the optimal reaction conditions in hand, we then investigated the substrate scope of the process by employing different phenols. As shown in Table 2, phenols with various substituents reacted efficiently to afford the desired 4-[60]fullerephenols in good yields. Both electron-donating (Table 2, entries 1-4) and electronwithdrawing (Table 2, entries 5 and 6) substituents on the phenyl ring of phenols



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could be successfully transformed into the desired products in 51-62% yields. 2,6Bisubsituted phenols could also be employed and provided products 2g–j in good yields (Table 2, entries 7-10, 52–60%). It should be noted that electron-donating substituted and 2,6-bisubsituted phenols were found to be good substrates for this transformation. It was found that 2 equivalents of these phenols were sufficient for this transformation (Table 2, entries 2-4 and 7-10). Notably, all of the above mentioned processes are highly regioselective with the products formed at the C4position of the phenols. Table 2. KOtBu-Promoted C4 Selective Coupling Reaction of Phenols and C60a

entry

substrate 1

product 2

Yield(%)b

1c

56(72)

2

58(73)

3

60(71)

4

62(75)

5c

53(66)

6c

51(64)


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7

60(73)

8

57(70)

9

54(67)

10

52(65)

a

Reaction conditions: (1) C60 (0.05 mmol)/1/KOtBu in a designated molar ratio in Schlenk tubes under Ar, solvent (8 mL). (2) CF3COOH (0.1 mmol, 20 equiv). bIsolated yield by column chromatography. Values in parentheses were based on consumed C60. cThe reaction was carried out with 1 (0.25 mmol, 5 equiv).

The structures of 2a-j were confirmed by 1H NMR, 13C NMR, MALDITOF MS, UV−vis and FT-IR spectroscopy. All of the mass spectra of these products exhibited the correct [M]- peaks. Their 1H NMR spectra displayed all expected chemical shifts. The 13C NMR spectra of 2a-j gave 27-29 peaks in the 135.71-154.44 ppm region for the 58 sp2-carbons of the C60cage and two peaks at 66.40-67.21 ppm and 63.19-63.62 ppm for the two sp3-carbons of C60, which were close to those of the previously reported hydrofullerene derivatives.8a,9 The UV-vis spectra of 2a-j exhibited a peak at 428-434 nm, which is a diagnostic absorption for the C60 1,2-adducts. To gain some mechanistic insight into this transformation, a vis-NIR spectrum study was carried out. First, the reaction was performed with C60 (0.05 mmol) and 1a (0.25 mmol, 5.0 equiv) in DMF (8 mL) in Schlenk tubes under argon atmosphere. C60 was insoluble in DMF at room temperature. However, treatment of KOtBu gave rise to a significant color change of the solution from turbid brown to dark green within 10 min. As revealed in Figure 1, two strong absorption bands at 620 and 984 nm can be observed at the vis-NIR spectrum of the corresponding dark green solution, which is very similar to the RC60− derivatives.8a,10 The green color was rapidly replaced by the formation of a red-brown precipitate since the addition of CF3COOH. The resulting red-brown deposition was soluble in carbon disulfide and then separated on a silica



gel column to give 2a. The deprotonation of 2a with KOtBu in DMF generated the same vis-NIR absorption which indicated that the intermediate should be a C60 anion with a phenoxide anion moiety.

Figure 1. Vis-NIR spectrum study of the KOtBu-promoted coupling reaction of phenols and C60.

Some control experiments were conducted to get deep insights into the reaction mechanism. Hydrogen/deuterium exchange experiments by addition of a small amount of CD3OD or D2O to the reaction were carried out to check for the formation and protonation of fullerene carbanion. In the presence of D2O or CD3OD in the reaction, we supposed that carbanion of C60 could capture a deuterium from D2O or CD3OD to give rise to deuterium incorporation on the fullerene core. As shown in Scheme 2, when added D2O or CD3OD to the reaction, experiment results show ratios of 2a/2a-d1 in 1/4 and 1/2 respectively, indicating that a C60 anion pathway might be involved. Ratios of 2a/2a-d1 were determined by the integral areas of the C60-bonded hydrogen signals at 6.81 ppm in the 1H NMR spectra of products 2a and 2a-d1 obtained from H/D exchange experiments(See SI). The incomplete deuteration on C60 is assumed to arise from the presence of tBuOH which was produced by the reaction of phenol and KOtBu in the first step of the proposed mechanism. The diversity of the 2a/2a-d1 ratios may due to the different reactivity of D2O and CD3OD to fullerene carbanion. It is worthy to point out that no product 2a can be obtained in the absence of CF3COOH or addition of only 1 equiv of CF3COOH under otherwise identical conditions. Further check results indicated that excess acid relative to the base(KOtBu) used in the first step was required to provide 2a. Fullerephenol 2a is slightly acidic. The pH value of a saturated CS2 solution of


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2a is around 5.3 by PH measurement using a pH meter. Therefore, addition of excess CF3COOH to quench the base is critical for the formation of 2a as a redbrown precipitate in DMF. Scheme 2. Hydrogen/Deuterium Exchange Experiments

Based on the above experimental results and our previous reports,8 a plausible reaction pathway was outlined in Scheme 3. Initially, phenol 1 is transformed to its phenoxide anion A with the assistance of KOtBu, which can transfer to phenolic carbanion B as a resonance structure. Then, nucleophilic attack of B to C60 leads to the formation of intermediate C. C could be transformed into a C60 anion with a phenoxide anion intermediate D in the presence of excess base. Further protonation of D under acidic conditions affords the desired product 2. Scheme 3. Proposed Reaction Mechanism



The obtained products 2a-j exhibited high C4 regioselectivity on the phenols and we did not observe any products with phenols in C2-(ortho) position. Computational study at the B3LYP/6-31G(d) level using the Gaussian 09 program for the reaction was performed to further probe the reaction pathway. The result of structural optimization of phenoxide anion A-1a shows that the negative charge is mainly concentrated in the C4 and C2 position of phenol (see SI), which indicated the nucleophilicity of C4 and C2. As shown in Scheme 4, the formation of the C2bonding transition state TS-o requires an activation energy of 5.4 kcal mol-1, 2.8 kcal mol-1 higher than that required for the formation of C4-bonding transition state TS-p. Furthermore, the C4-coupled fullerene anion INT-p is more stable than C2-coupled fullerene anion INT-o by 5.1 kcal mol-1. In addition, the steric hindrance of C2coupling pathway was increased compared with C4-coupling pathway. Our attempts to employ 3-methylphenol failed to generate C2-coupling product and only trace C4coupling product was detected by TLC. It seems that the steric hindrance is crucial for the coupling of phenol and C60. Therefore, the product formation via C4-coupling should be more favourable. Scheme 4. Computational Calculation Result

The electrochemical properties of representative fullerephenols, C60, PCBM and


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fulleroindoles 3a-b8a were also studied by cyclic voltammetry (CV) (Table 3). It should be noted that phenol group on the 2a reduces the first reduction potential by 55 mV and 29 mV relative to that of PCBM (-1.158 V) and fulleroindole 3a (-1.158 V). Furthermore, strong electron-donating methoxy group on the phenol ring resulted in further decrease of the first reduction potential from −1.213 V (2a) to −1.125 V (2d). It means that these fullerephenols possess higher LUMO levels than that of PCBM and fulleroindoles. Therefore, the obtained products may have potential application in organic solar cells as acceptors. Table 3. Reduction Potentials and LUMO Levels for 4-[60]fullerephenols.a

LUMO level (eV)b

compd

E1

E2

C60

-1.078

-1.463

-3.722

PCBM

-1.158

-1.537

-3.642

3a

-1.187

-1.561

-3.613

3b

-1.201

-1.578

-3.599 -3.587

2a

-1.213

-1.569

2d

-1.225

-1.578

-3.575

2e

-1.187

-1.562

-3.613

2f

-1.192

-1.564

-3.608

2g

-1.193

-1.565

-3.607

2h

-1.204

-1.566

-3.596

2j

-1.182

-1.567

-3.618

a

Versus ferrocene/ferrocenium. The measurements were carried out under an argon atmosphere using anhydrous o-dichlorobenzene of 1 mM samples and 0.1 M n-Bu4NClO4 as a supporting electrolyte; scanning rate: 50 mV·s−1; working electrode: Pt; auxiliary electrode: Pt wire; reference electrode: SCE. bEstimated using the following equation:11 LUMO level = −(4.8 + E1) eV.

CONCLUSION In conclusion, we have developed a C4 selective coupling reaction of phenols and [60]fullerene promoted by inexpensive KOtBu. The method provides an efficient route to various 4-[60]fullerephenol derivatives in average good yields and high regioselectivity. The solvent plays a key role in achieving the present high efficiency for the product formation. An inert gas atmosphere and the addition of excess acid were also found to be critical in terms of the formation of fullerephenols. Moreover, a plausible reaction pathway is proposed and the electrochemical properties of the products further renders the method valuable. The further application of this method to the synthesis of



more structural complex [60]fullerephenol derivatives is currently underway in our laboratory. EXPERIMENTAL SECTION General Methods. All reactions were performed under inert atmosphere (argon or nitrogen) using standard Schlenk technique. 1H NMR and 13C NMR spectra were obtained in CS2/d6-DMSO with TMS as internal standard (400 MHz 1H and 100 MHz 13

C) at room temperature. 1H NMR spectra were referenced to residual DMSO at 2.50 ppm, and 13C NMR spectra were referenced to residual DMSO at 39.52 ppm. HRMS data were obtained by a TOF mass analyzer. Silica gel G was used for column chromatography. Cyclic Voltammetry of 2a-j. The measurements were carried out under an argon atmosphere using anhydrous o-dichlorobenzene of 1 mM samples and 0.1 M nBu4NClO4 as a supporting electrolyte; scanning rate: 50 mV•s−1; working electrode: Pt; auxiliary electrode: Pt wire; reference electrode: SCE. General Procedure for the Synthesis of 2a, 2e-f. DMF (8 mL) was added to the mixture of C60 (0.05 mmol), phenol (0.25 mmol) and KOtBu (0.25 mmol) in a Schlenk vessel at room temperature under Ar atmosphere. Then, the Schlenk vessel was allowed to stir at 60 °C for 60 minutes. CF3COOH (75 µL, 1.0 mmol) was added next, the mixture was stirred for 10 minutes. After the mixture was cooled to room temperature, 20 mL carbon disulfide was added. Resulting reddish brown solution was washed with water and concentrated, then the residue was subjected to column chromatography on silica gel with carbon disulfide as the eluent to give unreacted C60 subsequent elution with carbon disulfide/dichloromethane afforded 2 as an amorphous black solid. General Procedure for the Synthesis of 2b-d, 2g-j. DMF (8 mL) was added to the mixture of C60 (0.05 mmol), phenol (0.1 mmol) and KOtBu (0.25 mmol) in a Schlenk vessel at room temperature under Ar atmosphere. Then, the Schlenk vessel was allowed to stir at 60 °C for 60 minutes. CF3COOH (75 µL, 1.0 mmol) was added next, the mixture was stirred for 10 minutes. After the mixture was cooled to room temperature, 20 mL carbon disulfide was added. Resulting reddish brown solution was washed with water and concentrated, then the residue was subjected to column chromatography on silica gel with carbon disulfide as the eluent to give unreacted C60 subsequent elution with carbon disulfide/dichloromethane afforded 2 as an amorphous black solid. Procedure for the hydrogen/deuterium exchange experiments. DMF (8 mL) was added to the mixture of C60 (0.05 mmol), phenol (0.1 mmol) and KOtBu (0.25 mmol) in a Schlenk vessel at room temperature under Ar atmosphere. After being


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stirred at 60 °C for 60 minutes, D2O (0.18 mL, 10 mmol) or CD3OD (0.4 mL, 10 mmol) was added to the mixture and stirred for 10 minutes. CF3COOH (75 µL, 1.0 mmol) was added next, the mixture was stirred for another 10 minutes. After the mixture was cooled to room temperature, 20 mL carbon disulfide was added. Resulting reddish brown solution was washed with water and concentrated, then the residue was subjected to column chromatography on silica gel with carbon disulfide as

the

eluent

to

give

unreacted

C60

subsequent

elution

with

carbon

disulfide/dichloromethane afforded 2a and 2a-d1 as an amorphous black solid. 1,2-(4-phenol)(hydro)[60]fullerene 2a. Following the general procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with 1a (25.0 mg, 0.25 mmol) and KOtBu (28.0 mg, 0.25 mmol) afforded first unreacted C60 (8.1 mg, 23%) and then 2a (22.8 mg, 56%) as an amorphous black solid: mp >300 °C; 1H NMR (400 MHz, CS2/d6-DMSO) δ 9.46 (s, O-H, 1H), 8.18 (d, J = 8.8 Hz, 2H), 7.14(d, J = 8.8 Hz，2H), 6.82 (s, 1H); C NMR (100 MHz, CS2/ d6-DMSO) (all 2C unless indicated) δ 157.4(aryl C, 1C), 154.2, 13C NMR (100 MHz, CS2/ d6-DMSO) (all 2C unless indicated) δ 157.4(1C, aryl C), 154.2, 152.6, 146.9(1C), 146.7(1C), 146.5, 145.8, 145.7, 145.59, 145.57, 145.56, 145.3, 144.93, 144.86, 144.80, 144.78, 144.1, 144.0, 142.7, 141.98, 141.96, 141.8, 141.50(4C), 141.47, 141.1, 141.0, 139.7(4C), 137.6, 136.0, 135.1(1C, aryl C), 128.0(aryl C), 116.6(aryl C), 66.9(1C, sp3-C of C60), 63.5(1C, sp3-C of C60); FT-IR (KBr) v 3445, 1608, 1501, 1425, 1166, 831, 762, 526 cm-1; UV-vis (CHCl3) λmax (log ε) 256 (5.05), 408 (4.75), 434 (4.31), 681 (2.01) nm; HRMS (MALDI-TOF-MS, DCTB as matrix, negative mode): m/z [M]- calcd for C66H6O 814.0419; found 814.0423.

13

1,2-(4-phenol)(hydro)[60]fullerene 2b. According to the general procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with 1b (15.0 mg, 0.1 mmol) and KOtBu (28.0 mg, 0.25 mmol) afforded first unreacted C60 (7.1 mg, 20%) and then 2b (24.1 mg, 58%) as an amorphous black solid: mp >300 °C; 1H NMR (400 MHz, CS2/d6-DMSO) δ 9.34 (s, O-H, 1H), 8.05 (d, J = 2.3 Hz, 1H), 7.96 (dd, J = 2.3, 8.3 Hz, 1H), 7.13 (d, J = 8.3 Hz, 1H), 6.79 (s, 1H); 13C NMR (100 MHz, CS2/ d6-DMSO) (all 2C unless indicated) δ 155.4(1C, aryl C), 154.3, 152.6, 146.9(1C), 146.6(1C), 146.5, 145.8, 145.7, 145.60, 145.57, 145.55, 145.3, 144.9, 144.82, 144.76(4C), 144.1, 144.0, 142.7, 141.96, 141.93, 141.8, 141.49(4C), 141.45, 141.1, 141.0, 139.7, 139.6, 137.6, 135.9, 135.0(1C, aryl C), 129.3(1C, aryl C), 125.6(1C, aryl C), 125.3(1C, aryl C), 115.7(1C, aryl C), 66.9(1C, sp3-C of C60), 63.5(1C, sp3-C of C60), 16.4(1C, -CH3); FT-IR (KBr) v 3446, 1692, 1507, 1426, 1353, 1190, 1021, 871, 762, 526 cm-1; UV-vis (CHCl3) λmax (log ε) 256 (5.02), 408 (4.76), 434 (4.28), 682 (1.98) nm; HRMS (MALDI-TOFMS, DCTB as matrix, negative mode): m/z [M]- calcd for C67H8O 828.0575; found 828.0580. 1,2-(4-phenol)(hydro)[60]fullerene 2c. Following the general procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with 1c (11.0 mg, 0.1 mmol) and KOtBu (28.0 mg, 0.25 mmol) afforded first unreacted C60 (5.6 mg, 16%) and then 2c (26.2 mg, 60%) as an amorphous black solid: mp >300 °C; 1H NMR (400 MHz, CS2/d6-DMSO) δ 9.43 (s, O-H, 1H), 8.18 (d, J = 2.7 Hz, 1H), 7.97 (dd, J = 2.7, 8.3 Hz, 1H), 7.15(d, J = 8.3 Hz, 1H), 6.80 (s, 1H), 1.60 (s, 9H); 13C NMR (100 MHz, CS2/ d6-DMSO) (all 2C unless indicated) δ 155.8(1C, aryl C), 154.4, 152.6, 146.8(1C), 146.6(1C), 146.5, 145.8, 145.7, 145.59, 145.56, 145.5, 145.3, 144.9, 144.79, 144.76(4C), 144.1, 144.0,



142.7, 142.0, 141.9, 141.8, 141.53, 141.47, 141.4, 141.1, 141.0, 139.6(4C), 137.4, 136.5, 135.9(1C, aryl C), 135.0(1C, aryl C), 125.3(1C, aryl C), 125.2(1C, aryl C), 117.3(1C, aryl C), 67.2(1C, sp3-C of C60), 63.6(1C, sp3-C of C60), 34.4(1C), 29.1(1C, -CH3); FT-IR (KBr) v 3521, 2931, 1625, 1486, 1434, 1385, 1198, 1021, 823, 770, 526 cm-1; UV-vis (CHCl3) λmax (log ε) 258 (4.98), 408 (4.65), 434 (3.80), 685 (2.12) nm; HRMS (MALDI-TOF-MS, DCTB as matrix, negative mode): m/z [M]- calcd for C70H14O 870.1045; found 870.1049. 1,2-(4-phenol)(hydro)[60]fullerene 2d. Following the general procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with 1d (12.5 mg, 0.1 mmol) and KOtBu (28.0 mg, 0.25 mmol) afforded first unreacted C60 (6.3 mg, 18%) and then 2d (26.1 mg, 62%) as an amorphous black solid: mp >300 °C; 1H NMR (400 MHz, CS2/d6-DMSO) δ 8.75 (s, O-H, 1H), 7.84 (d, J = 2.4 Hz, 1H), 7.79 (dd, J = 2.4 Hz, 8.0 Hz，1H), 7.15 (d, J = 8.0 Hz, 1H), 6.84 (s, 1H), 4.11 (s，3H); 13C NMR (100 MHz, CS2/ d6-DMSO) (all 2C unless indicated) δ 154.1(1C, aryl C), 152.6(1C, aryl C), 148.5, 147.1, 147.0(1C), 146.7(1C), 146.6, 145.9, 145.8, 145.7(6C), 145.4, 145.0, 144.93, 144.86, 144.8, 144.2, 144.1, 142.8, 142.1, 142.0, 141.9, 141.6(6C), 141.2, 141.1, 139.74, 139.72, 138.2, 135.9, 135.2(1C, aryl C), 120.1(1C, aryl C), 116.6(1C, aryl C), 111.5(1C, aryl C), 67.1(1C, sp3-C of C60), 63.5(1C, sp3-C of C60), 55.7(1C, -OCH3); FT-IR (KBr) v 3533, 1652, 1506, 1471, 1449, 1178, 1019, 868, 725, 526 cm-1; UV-vis (CHCl3) λmax (log ε) 257 (5.10), 408 (4.81), 434 (4.45), 686 (2.08) nm; HRMS (MALDI-TOF-MS, DCTB as matrix, negative mode): m/z [M]- calcd for C67H8O2 844.0524; found 844.0528. 1,2-(4-phenol)(hydro)[60]fullerene 2e. Following the general procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with 1e (42.5 mg, 0.25 mmol) and KOtBu (28.0 mg, 0.25 mmol) afforded first unreacted C60 (7.2 mg, 20%) and then 2e (23.5 mg, 53%) as an amorphous black solid: mp >300 °C; 1H NMR (400 MHz, CS2/d6-DMSO) δ 9.67 (s, O-H, 1H), 8.22 (s, 1H), 8.16 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 7.6 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.35 (d, J = 8.4 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 6.89 (s, 1H); 13 C NMR (100 MHz, CS2/ d6-DMSO) (all 2C unless indicated) δ 154.3(1C, aryl C), 154.1, 152.5, 146.9(1C), 146.6(1C), 146.5, 145.8, 145.7, 145.6, 145.5(4C), 145.3, 144.90, 144.86, 144.77, 144.75, 144.1, 144.0, 142.7, 142.0, 141.9, 141.8, 141.49, 141.47, 141.45, 141.1, 141.0, 139.7, 139.6, 138.2, 138.1, 135.8(1C, aryl C), 135.1(1C, aryl C), 129.13(aryl C), 129.10(1C, aryl C), 129.08(1C, aryl C), 127.5(aryl C), 126.9(1C, aryl C), 126.4(1C, aryl C), 117.3(1C, aryl C), 66.9(1C, sp3-C of C60), 63.5(1C, sp3-C of C60); FT-IR (KBr) v 3517, 1679, 1457, 1316, 1227, 1125, 828, 770, 526 cm-1; UV-vis (CHCl3) λmax (log ε) 254 (4.96), 408 (4.23), 434 (3.25), 686 (2.02) nm; HRMS (MALDI-TOF-MS, DCTB as matrix, negative mode): m/z [M]- calcd for C72H10O 890.0732; found 890.0737. 1,2-(4-phenol)(hydro)[60]fullerene 2f. Following the general procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with 1f (32.5 mg, 0.25 mmol) and KOtBu (28.0 mg, 0.25 mmol) afforded first unreacted C60 (7.4 mg, 21%) and then 2f (21.6 mg, 51%) as an amorphous black solid: mp >300 °C; 1H NMR (400 MHz, CS2/d6-DMSO) δ 10.23 (s, O-H, 1H), 8.26(d, J = 2.4 Hz, 1H), 8.11(dd, J = 2.4, 8.4 Hz, 1H), 7.34(d, J = 8.4, 1H), 6.81 (s, 1H); 13C NMR (100 MHz, CS2/ d6-DMSO) (all 2C unless indicated) δ153.4(1C, aryl C), 153.2, 152.3, 146.9(1C), 146.7(1C), 146.4, 145.8, 145.8, 145.6, 145.6, 145.4, 145.3, 144.97, 144.94, 144.84, 144.80, 144.1, 144.00, 142.7, 142.0(4C), 141.8, 141.51, 141.49, 141.4, 141.1, 141.0, 139.73, 139.68, 138.6,


Page 12 of 15

Page 13 of 15 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


135.7, 135.2(1C, aryl C), 128.6(1C, aryl C), 126.2(1C, aryl C), 121.8(1C, aryl C), 117.7(1C, aryl C), 66.4(1C, sp3-C of C60), 63.2(1C, sp3-C of C60); FT-IR (KBr) v 3526, 1683, 1572, 1524, 1465, 1370, 1197, 1121, 1069, 875, 672, 526cm-1; UV-vis (CHCl3) λmax (log ε) 254 (4.95), 407 (4.72), 433(3.28), 684 (1.97) nm; HRMS (MALDI-TOF-MS, DCTB as matrix, negative mode): m/z [M]- calcd for C66H5ClO 848.0029; found 848.0034. 1,2-(4-phenol)(hydro)[60]fullerene 2g. Following the general procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with 1g (12.5 mg, 0.1 mmol) and KOtBu (28.0 mg, 0.25 mmol) afforded first unreacted C60 (6.5 mg, 18%) and then 2g (25.2 mg, 60%) as an amorphous black solid: mp >300 °C; 1H NMR (400 MHz, CS2/d6-DMSO) δ 8.34 (s, O-H, 1H), 7.90 (s, 2H), 6.78 (s, 1H), 2.47 (s, 6H); 13C NMR (100 MHz, CS2/ d6-DMSO) (all 2C unless indicated) δ 154.3(1C, aryl C), 153.2, 152.5, 146.8(1C), 146.6(1C), 146.5, 145.8, 145.7, 145.6, 145.53, 145.51, 145.3, 144.9, 144.8, 144.7(4C), 144.04, 144.00, 142.6, 141.92, 141.89, 141.8, 141.5(4C), 141.4, 141.02, 140.93, 139.61, 139.59, 137.85, 135.88, 135.0(1C, aryl C), 127.0(aryl C), 125.4(aryl C), 66.8(1C, sp3-C of C60), 63.5(1C, sp3-C of C60), 17.0(-CH3); FT-IR (KBr) v 3441, 1617, 1558, 1517, 1433, 1136, 1024, 869, 772, 526 cm-1; UV-vis (CHCl3) λmax (log ε) 257 (5.13), 401 (4.74), 434 (3.53), 687 (2.02) nm; HRMS (MALDI-TOF-MS, DCTB as matrix, negative mode): m/z [M]- calcd for C68H10O 842.0732; found 842.0736. 1,2-(4-phenol)(hydro)[60]fullerene 2h. Following the general procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with 1h (16.5 mg, 0.1 mmol) and KOtBu (28.0 mg, 0.25 mmol) afforded first unreacted C60 (6.8 mg, 19%) and then 2h (25.1 mg, 57%) as an amorphous black solid: mp >300 °C; 1H NMR (400 MHz, CS2/d6-DMSO) δ 8.28 (s, O-H, 1H), 8.07 (d, J = 2.2 Hz), 7.92 (d, J = 2.2 Hz), 6.81(s, 1H), 1.63 (s, 9H); 13C NMR (100 MHz, CS2/ d6-DMSO) (all 2C unless indicated) δ 154.4(1C, aryl C), 153.6, 152.6, 146.9(1C), 146.6(1C), 146.5, 145.8, 145.7, 145.6, 145.6, 145.5, 145.3, 144.9, 144.80, 144.76(4C), 144.1, 144.0, 142.7, 141.96, 141.93, 141.8, 141.53, 141.48, 141.45, 141.1, 141.0, 139.6(4C), 137.8, 137.5, 135.9(1C, aryl C), 135.0(1C, aryl C), 127.3(1C, aryl C), 126.0(1C, aryl C), 123.1(1C, aryl C), 67.2(1C, sp3-C of C60), 63.6(1C, sp3-C of C60), 34.6(1C), 29.4(3C, -CH3), 17.5(1C, -CH3); FT-IR (KBr) v 3443, 1624, 1485, 1197, 1125, 1021, 870, 770, 526 cm-1; UV-vis (CHCl3) λmax (log ε) 254 (4.91), 405 (4.12), 429 (3.20), 680 (1.98) nm; HRMS (MALDI-TOF-MS, DCTB as matrix, negative mode): m/z [M]- calcd for C71H16O 884.1201; found 884.1204. 1,2-(4-phenol)(hydro)[60]fullerene 2i. Following the general procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with 1i (14.5 mg, 0.1 mmol) and KOtBu (28.0 mg, 0.25 mmol) afforded first unreacted C60 (7.0 mg, 19%) and then 2i (23.3 mg, 54%) as an amorphous black solid: mp >300 °C; 1H NMR (400 MHz, CS2/d6-DMSO) δ 9.19 (s, O-H, 1H), 8.12 (s, 1H), 8.05 (s, 1H), 6.79 (s, 1H), 2.53 (s, 3H); 13C NMR (100 MHz, CS2/ d6-DMSO) (all 2C unless indicated) δ 153.33(1C, aryl C), 152.2, 150.9, 146.9(1C), 146.6(1C), 146.4, 145.8(4C), 145.6(4C), 145.4, 145.3, 144.9(4C), 144.8(4C), 144.1, 144.0, 142.7, 142.0(4C), 141.8, 141.5(4C), 141.4, 141.1, 141.0, 139.7(4C), 138.7, 135.7, 135.2(1C, aryl C), 128.2(1C, aryl C), 127.8(1C, aryl C), 125.9(1C, aryl C), 121.8(1C, aryl C), 66.4(1C, sp3-C of C60), 63.2(1C, sp3-C of C60), 17.2(1C, -CH3); FT-IR (KBr) v 3525, 1623, 1525, 1456, 1342, 1235, 1121, 864, 781, 526, cm-1; UV-vis (CHCl3) λmax (log ε) 256 (5.05), 405 (4.45), 428 (3.37), 685 (2.08) nm; HRMS (MALDI-TOF-MS, DCTB as matrix, negative mode): m/z [M]- calcd for C67H7ClO 862.0185; found 862.0191.



1,2-(4-phenol)(hydro)[60]fullerene 2j. Following the general procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with 1j (24.6 mg, 0.1 mmol) and KOtBu (28.0 mg, 0.25 mmol) afforded first unreacted C60 (7.1 mg, 20%) and then 2j (25.1 mg, 52%) as an amorphous black solid: mp >300 °C; 1H NMR (400 MHz, CS2/d6-DMSO) δ 8.35 (s, O-H, 1H), 8.23 (s, 2H), 7.78 (d, J = 7.6 Hz, 4H), 7.53 (t, J = 7.6 Hz, 4H), 7.42 (t, J = 7.6 Hz, 2H), 7.00 (s, 1H); 13C NMR (100 MHz, CS2/ d6-DMSO) (all 2C unless indicated) δ 153.8(aryl C), 152.5, 150.5, 146.9(1C), 146.7(1C), 146.5, 145.8, 145.7, 145.59, 145.57, 145.5, 145.3, 144.9(4C), 144.80, 144.77, 144.1, 144.0, 142.7, 141.98, 141.96, 141.8, 141.5(6C), 141.1, 141.0, 139.7(4C), 139.3, 138.2, 135.8(1C, aryl C), 135.2(1C, aryl C), 131.8(aryl C), 129.4(4C, aryl C), 128.5(aryl C), 127.9(4C, aryl C), 126.8(aryl C), 66.9(1C, sp3-C of C60), 63.5(1C, sp3-C of C60); FT-IR (KBr) v 3446, 1629, 1524, 1427, 1322, 1229, 1120, 883, 777, 526 cm-1; UV-vis (CHCl3) λmax (log ε) 253 (4.88), 406 (4.21), 434 (3.18), 682 (1.95) nm; HRMS (MALDI-TOF-MS, DCTB as matrix, negative mode): m/z [M]- calcd for C78H14O 966.1045; found 966.1048.

ASSOCIATED CONTENT Supporting Information 1 H-NMR and 13C-NMR spectra of products 2a−j. 1H NMR spectra of products 2a and 2a-d1 obtained from H/D exchange experiments. CVs of compounds 2a−j and 3a−b along with C60 and PCBM. Computational results of mechanistic study. This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION Corresponding Authors *E-mail: [email protected] *E-mail: [email protected] Notes The authors declare no competing financial interest.

ACKNOWLEDGMENTS We acknowledge the financial support for this work from the National NSF of China (51672002, 51372003, and 51432001), Education Committee of Anhui Province (KJ2018A0037), the Research Foundation from College of Chemistry & Chemical Engineering of Anhui University.

REFERENCES (1) (a) Tyman, J. H. P. Synthetic and Natural Phenols; Elsevier: New York, 1996. (b) Fyfe, C. A. In The Chemistry of the Hydroxyl Group; Patai, S., Ed.; Wiley Interscience: New York, 1971; Vol. 1, pp 83-127. (2) For selected examples, see: (a) Hoarau, C.; Pettus, T. R. R. Synlett 2003, 127. (b) Hanson, P.; Jones, J. R.; Taylor, A. B.; Walton, P. H.; Timms, A. W. J. Chem. Soc., Perkin Trans. 2 2002, 1135. (c) George, T.; Mabon, R.; Sweeney, G.; Sweeney, J. B.; Tavassoli, A. J. Chem. Soc., Perkin


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KOtBu-Promoted C4 Selective Coupling Reaction of Phenols and [60

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