Monosubstituted

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Metal-Free Synthesis of N-Alkyl-2,5-Unsubstituted/ Monosubstituted Fulleropyrrolidines: Reaction of [60]Fullerene with Paraformaldehyde and Amines Yun-Fei Li, Duo Zhang, Hui-Juan Wang, Fa-Bao Li, Liang Sun, Li Liu, Chao-Yang Liu, Abdullah M. Asiri, and Khalid A. Alamry J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00083 • Publication Date (Web): 07 Feb 2019 Downloaded from http://pubs.acs.org on February 7, 2019

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The Journal of Organic Chemistry

Metal-Free Synthesis of N-Alkyl-2,5-Unsubstituted/Monosubstituted Fulleropyrrolidines: Reaction of [60]Fullerene with Paraformaldehyde and Amines Yun-Fei Li,† Duo Zhang,† Hui-Juan Wang,‡ Fa-Bao Li,*,† Liang Sun,† Li Liu,† Chao-Yang Liu,*,‡ Abdullah M. Asiri,§ and Khalid A. Alamry§ †Hubei

Collaborative Innovation Center for Advanced Organic Chemical Materials,

Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Key Laboratory of Green Preparation and Application for Functional Materials, Ministry of Education, and School of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, People’s Republic of China ‡State

Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics,

Wuhan Center for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, People’s Republic of China §Department

of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia E-mail: [email protected]; [email protected]

ACS Paragon Plus Environment

The Journal of Organic Chemistry 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

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____________________________________________________________________

R2 R1

R2

NH2

N R1

(CH2O)n , air

R3

N

R4

21 examples up to 65% yield

H free-metal excellent yields wide structural diversities readily available starting materials

N

R4

R3 8 examples up to 51% yield

ABSTRACT: A series of scarce N-alkyl-2,5-unsubstituted/monosubstituted fulleropyrrolidines were synthesized in moderate to excellent yields by the simple one-step thermal reaction of [60]fullerene with primary/secondary amines in the presence of paraformaldehyde without the addition of valuable metal salts. Intriguingly, the reaction with primary amines unexpectedly afforded N-alkyl-2,5-unsubstituted fulleropyrrolidines instead of the anticipated 2,5-monosubstituted fulleropyrrolidines. A plausible reaction pathway is proposed to elucidate the above-mentioned reaction process based on the experimental results. _____________________________________________________________________ INTRODUCTION Due to the outstanding properties,1,2 fullerenes as novel carbon materials have received wide attention over the past 30 years. However, the poor solubility of fullerenes in polar organic solvents and water has hampered their applications in many fields. Therefore, the functionalization of fullerenes by chemical modification to introduce versatile functional groups onto fullerene skeletons is an important aspect


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of fullerene research. By using chemical modification method,2,3 a large variety of fullerene derivatives with structural and functional diversities have been prepared, of which have displayed a broad range of valuable properties and have thus been utilized in many fields including materials science, bio-medical application, and nanotechnology,2 exhibiting great advantages over traditional non-fullerene manners in many cases.4 Although many synthetic strategies including cycloadditions, nucleophilic additions, radical additions, and asymmetric catalysis have been developed to functionalize fullerenes,2,3 the known protocols still meet a great challenge in preparing N-alkyl-2,5-unsubstituted/monosubstituted fulleropyrrolidines. Fulleropyrrolidines are a kind of important fullerene compound,3g,5-10 and have attracted extensive attention among scientific community due to their promising applications in many fields such as modern drug synthesis,8 organic solar cells,9 and light-controlled field effect transistors.10 General speaking, fulleropyrrolidines were synthesized by two main strategies, that is, the best-known Prato reaction5a,b together with the newly-developed reaction based on aldehydes and amines.6f,7 However, these known methods still have great difficulty in the preparation of fulleropyrrolidines with specific structural motifs. For example, N-alkyl-2,5-unsubstituted/monosubstituted fulleropyrrolidines is not easy to obtain by Prato reaction due to the very limited substrate scope of N-substituted amino acids.6b To the best of our knowledge, only a few N-alkyl-2,5-unsubstituted/monosubstituted fulleropyrrolidines were reported by different groups.6 Nevertheless, these reported methods have their own limitations including hardly available starting materials, poor product selectivity, low product



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yields, and complex reaction system. On the other hand, the substitutes on the pyrrolidine ring were found to have a great correlation with the properties of fulleropyrrolidines in many fields.5a,b Accordingly, the further exploration and development

of

new

synthetic

methods

for

the

preparation

of

scarce

N-alkyl-2,5-unsubstituted/monosubstituted fulleropyrrolidines in a straightforward and practical manner with a broad substrate scope are still in strong demand. The newly-developed strategy to functionalize fullerenes by using inexpensive and readily available aldehydes and amines6f,7,11-14 is a potential option due to its high efficiency

in

preparing

fulleropyrrolines,11

organofullerenes

including

tetrahydropyridinofullerenes,12

fulleropyrrolidines,6f,7

cyclopentafullerenes,13

and

fulleropyrrolidin-2-ols.14 In efforts to extend the reactions of [60]fullerene (C60) with aldehydes and amines,6f,7,11-14 we found that the thermal reaction of C60 with paraformaldehyde

and

benzylamine

afforded

N-benzyl-2,5-unsubstituted

fulleropyrrolidine instead of the expected N-unsubstituted-2-phenyl fulleropyrrolidine (Scheme 1). Considering the easy availability, inexpensive price, and versatility of paraformaldehyde and primary amines, this above-mentioned synthetic route would provide a potentially synthetic strategy to generate novel N-alkyl-2,5-unsubstituted fulleropyrrolidines.

In

this

paper,

we

N-alkyl-2,5-unsubstituted/monosubstituted

reported

the

synthesis

fulleropyrrolidines

in

of

scarce

moderate

to

excellent yields by a simple and efficient one-step reaction of C60 with paraformaldehyde and primary/secondary amines without the use of expensive metal salts.


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Scheme 1. Reaction of C60 with Paraformaldehyde and Benzylamine failed

(CH2O)n

NH2

N H

, air

N

RESULTS AND DISCUSSION At the onset, paraformaldehyde and benzylamine (1a) were chosen as the model substrates to screen the reaction conditions. To our disappointment, only a trace amount of desired product 2a was obtained when the reaction of C60 with paraformaldehyde and benzylamine (1a) was performed in a molar ratio of 1:5:5 in o-dichlorobenzene (ODCB) at 180 °C for 120 min under air conditions (entry 1, Table 1). To improve the yield of 2a, various reaction conditions have been examined. We found the yield of 2a could be gradually improved from a trace amount to 61% when the molar ratio of reaction was changed from 1:5:5 to 1:15:25 (entries 1-7, Table 1). Further variation of the equivalents of paraformaldehyde and 1a had no benefit to the yield of product 2a (entries 8-10, Table 1). Decreasing the reaction temperature resulted in the obvious reduction in product yield (entry 11, Table 1). Almost the same yield of 2a under nitrogen or dark conditions indicated that oxygen in air has no influence on the reaction (entries 12 and 13, Table 1). Accordingly, the reagent molar ratio of C60, paraformaldehyde, and 1a as 1:15:25, the reaction temperature as 180 °C together with the air conditions were selected as the optimized reaction conditions



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(entry 7, Table 1). It should be noted that the above-mentioned reaction with the addition of 4-dimethylaminopyridine (DMAP), acetic acid (HOAc), and Mg(ClO4)2 were also examined due to the previous confirmation that their presence has the positive effect on the formation of fulleropyrrolidines based on amines and aldehydes.7a,e Unfortunately, no improvement for the yield of 2a could be observed when the reaction was respectively conducted in the presence of DMAP, HOAc, and Mg(ClO4)2 under the optimized conditions (entries 14-16, Table 1).

Table 1. Optimization of Reaction Conditions for the Reaction of C60 with Paraformaldehyde and Benzylamine 1aa NH2

(CH2O)n

additive

1a

N

Δ, air 2a

entry

additive

molar ratiob

temp. (oC)

time (min)

yield (%) of 2ac

1

none

1:5:5:0

180

120

trace

2

none

1:10:10:0

180

45

19 (59)

3

none

1:10:15:0

180

30

38 (54)

4

none

1:10:20:0

180

35

48 (98)

5

none

1:10:25:0

180

32

57 (86)

6

none

1:10:30:0

180

40

56 (86)

7

none

1:15:25:0

180

20

61 (84)

8

none

1:20:25:0

180

20

45 (75)

9

none

1:5:25:0

180

30

28 (82)

10

none

1:25:15:0

180

15

29 (38)

11

none

1:15:25:0

160

40

38 (75)

12

none

1:15:25:0

180

20

59 (69)

13

none

1:15:25:0

180

20

59 (71)

14

DMAP

1:15:25:2

180

25

61 (84)

15

HOAc

1:15:25:2

180

25

57 (80)

16

Mg(ClO4)2

1:15:25:2

180

25

54 (98)

d e


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aUnless

otherwise indicated, all reactions were performed in o-dichlorobenzene (ODCB, 6 mL)

under air conditions. bMolar ratio refers to C60/(CH2O)n/1a/additive. cIsolated yield; those in parentheses were based on consumed C60.

dThe

reaction was conducted under nitrogen

atmosphere. eThe reaction was performed in the dark.

With the reliable and optimal conditions in hand, we started to explore the scope of arylmethanamines for this type of reaction. The reaction conditions and yields were summarized in Table 2. As can be seen from Table 2, typical arylmethanamines including benzylamines (1a-f) with both electron-donating and electron-withdrawing groups, 2-thiophenemethylamine (1g), α-substituted benzylamines (1h,i), and naphthylmethanamine (1j) could readily react with paraformaldehyde to produce the desired N-alkyl-2,5-unsubstituted fulleropyrrolidines 2a-j in moderate to good yields. In general, α-unsubstituted arylmethanamines (1a-g,j) displayed higher reaction efficiency (30-65%) as compared with those bearing α-substitutes (1h,i) with yields of 16-23%. This observation could be explained by the great steric hindrance from α-substituted benzylamines (1h,i). In addition, 2,4-dimethoxybenzylamine (1b) and 2-chlorobenzylamine (1e) gave the obviously higher product yields (~65%) than other arylmethanamines (1c,d,f), which should be attributed to the ortho-substitution effect.

Table 2. Reaction Conditions and Yields for the Reaction of C60 with Paraformaldehyde and Arylmethanamines 1a R (CH2O)n

Ar 1

R

, air NH2

N

ODCB

Ar 2



amine 1

product 2

time (min)

yieldb (%)

2a

20

61 (84)

2b

15

65 (73)

15

53 (95)

20

51 (67)

35

40 (62)

20

22 (67)

2e

25

64 (84)

1f

2f

35

46 (96)

NH2 1g

2g

30

49 (94)

2h

20

23 (82)

2i

20

16 (27)

2j

15

30 (55)

NH2 1a

NH2 OCH3 1b OCH3 NH2

2c

1c OCH3 NH2

2d

1d Cl NH2 Cl 1e

NH2

Br

S

NH2 1h

H NH2 1i NH2 1j

aAll

reactions were performed in ODCB (6 mL) under air conditions at 180 oC unless otherwise

indicated, molar ratio refers to C60/(CH2O)n/1 = 1:15:25. bIsolated yield, those in parentheses were based on consumed C60.

To expand the scope of the reaction, the substrates were further extended from


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arylmethanamines to other representative primary amines. The reaction conditions and

yields

were

listed

in

Table

3.

As

shown

in

Table

3,

electron-donating/withdrawing phenethylamines (3a-f), 2-thiophene ethylamine (3g), 3-phenyl-1-propylamine (3h), aliphatic amine (3i,j), and 2,2-diphenylethylamine (3k) could readily react with paraformaldehyde to afford the expected fulleropyrrolidines 4a-k with yields of 21-65%. Compared with aryl/benzyl-substituted ethylamines (3a-h,k), alkyl-substituted ethylamines (3i,j) obviously decreased the product yields (21-36% vs 42-65%), probably due to the inherently low reactivity of 3i,j with an inactive alkyl substituent in the current reaction system. Furthermore, the electronic effect of substitutes on aryl ring had no obvious impact on product yields. For instance, only slightly decreased product yields for electron-donating substituted 3b,c were observed as compared with those for electron-withdrawing substituted 3d-f (52-53% vs 53-57%). As for 2,2-diphenylethanamine (3k), its product yield was remarkably increased as compared with that from aminodiphenylmethane (1h) by adopting the similar reaction conditions (53% vs 23%), probably due to the lower steric hindrance of 3k than 1h. It should be noted that aromatic amines including aniline, 4-methoxyaniline, 3-methoxyaniline, 2-chloroaniline, and 4-chloroaniline were also investigated under standard reaction conditions. However, no desired product was detected probably due to the decreased nucleophilicity of NH2 by the direct conjugation between the aryl and amine groups.

Table 3. Reaction Conditions and Yields for the Reaction of C60 with



Paraformaldehyde and Inactive Amines 3a (CH2O)n

, air

R2

NH2 R1 3

R2

N

ODCB

R1 4

amine 3

product 4

time (min)

yieldb (%)

20

63 (93)

15

53 (95)

4b

15

53 (77)

4c

35

52 (79)

25

53 (79)

15

45 (98)

4e

25

56 (70)

4f

25

57 (98)

4g

20

42 (78)

4h

15

52 (85)

4i

20

36 (84)

4j

15

21 (60)

4k

15

53 (90)

NH2

4a 3a

NH2

3b OCH3 NH2

3c H3CO NH2

4d

3d Cl

NH2

3e F NH2 Cl 3f Cl NH2 3g

S

3h

H3CO 3i

3j

NH2

NH2

NH2

NH2

3k

aAll


indicated, molar ratio refers to C60/(CH2O)n/3 = 1:15:25. bIsolated yield, those in parentheses were


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based on consumed C60.

It is worth to mention that some controlled experiments were conducted to test the effect of substituents on the reaction rate with primary amines. Representative benzylamine (1a), 4-methoxybenzylamine (1c), and 4-chlorobenzylamine (1d) as well as

typical

phenethylamine

(4a),

4-methoxyphenethylamine

(4b),

and

4-chlorophenethylamine (4d) were selected as model substrates to react with C60 and paraformaldehyde under the optimized reaction conditions for 20 min and 15 min, respectively. Experimental results indicated that electron-donating substituted 4-methoxybenzylamine (1c) and 4-methoxyphenethylamine (4b) exhibited the obviously higher reaction rate than the corresponding electron-withdrawing substituted 4-chlorobenzylamine (1d) and 4-chlorophenethylamine (4d) by comparing with their consumption of C60 probably due to the higher nucleophilicity of NH2 from amines 1c and 4b as compared to 1d and 4d. As for the unsubstituted benzylamine (1a) and phenethylamine (4a), the reaction rate is between electron-donating 1c,4b and electron-withdrawing 1d,4d, agreeing well with their nucleophilic ability. Secondary amines were also applied to the above-mentioned reaction system. We first studied the reaction with N-methylbenzylamine (5a), N-ethylbenzylamine (5b), N,N-dibenzylamine (5c), diethylamine (5d), dipropylamine (5e), and dibutylamine (5f) under the optimized reaction conditions. Experimental results indicated that all of the six representative amines could react with paraformaldehyde to generate the desired N-alkyl-2-substituted fulleropyrrolidines 6a-f with yields of 31-51% (Table



Page 12 of 44

4). It should be noted that two fulleropyrrolidine isomers should be theoretically formed for unsymmetrical amines (5a,b). However, only the N-alkyl-2-phenyl fulleropyrrolidines

instead

of

N-benzyl-2-alkyl

fulleropyrrolidines

were

experimentally obtained, probably due to the higher reactivity at the benzylic position of 5a,b. Unsymmetrical ethylbutylamine (5g) was also investigated and both N-butyl-2-methyl fulleropyrrolidine (6g) and N-ethyl-2-propyl fulleropyrrolidine (6g') were isolated with yields of 25% and 18%, respectively (Scheme2). The lower yield of 6g' as compared to 6g might be ascribed to the great steric hindrance of propyl group relative to methyl group in 5g. It is worth to mention that the relatively high reaction rate for primary/secondary amines 1/3/5 was probably due to the less steric hindrance of paraformaldehyde relative to other aldehydes.7c,f

Table 4. Reaction Conditions and Yields for the Reaction of C60 with Paraformaldehyde and Secondary Amines 5a (CH2O)n

R1

N H

amine 5

5a

6a

25

31 (97)

5b

6b

15

51 (94)

6c

15

40 (98)

5d

6d

15

42 (95)

5e

6e

15

36 (78)

N

N H 5c

N

R2

R1 6 R1 = phenyl for 6a-c

yieldb (%)

H

H

N

time (min)

N

H

, air

5

product 6

H

N

R2


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N H

aAll

6f

5f

15

33 (77)


indicated, molar ratio refers to C60/(CH2O)n/5 = 1:15:25. bIsolated yield, those in parentheses were based on consumed C60.

Scheme 2. Reaction of C60 with Paraformaldehyde and Ethylbutylamine 5g

(CH2O)n

5g

N

6g

ODCB, air

H

N

25%

180 oC, 15 min

N 6g' 18%

Fulleropyrrolidines 2a,6b,d-fc,6d,ee,6fg,6fh,6e 4a,6eb,6ee,6ej,6f and 6a,6ab,6cc,6bd6b are known compounds, and their identities were confirmed by comparison of their spectral data with those reported previously in the literature. As for new compounds 2b,d,f,i,j, 4c,d,f-i,k, and 6e-g,g', their structures were unambiguously characterized by their MALDI-TOF MS, FT-IR, UV-vis,

1H

and

13C

NMR spectra. All

MALDI-TOF MS of these new compounds gave the correct [M]− peaks. FT-IR spectra exhibited the characteristic absorptions of C60 skeleton at about 527, 574, 1184, and 1427 cm-1. Their UV-vis spectra showed a diagnostic absorption at 431 nm for the 1,2-adducts of C60. Expected chemical shifts and splitting patterns for all protons were also displayed in their 1H NMR spectra. In their

13C

NMR spectra,

2b,d,f,j and 4c,d,f-i,k exhibited no more than 16 lines for the 58 sp2-carbons of the



C60 skeleton and one peak at 69.23-69.74 ppm for the two sp3-carbons of the C60 cage, agreeing well with their C2v molecular symmetry, whereas 2i displayed 23 lines including some overlapping ones for the 58 sp2-carbons of the C60 moiety and one peak at 69.28 ppm for the two sp3-carbons of the C60 skeleton, consistent with its Cs symmetry. As for 6e-g,g', there were at least 44 peaks including some overlapped ones for the 58 sp2-carbons of the C60 cage, agreeing well with the C1 symmetry of their molecular structures. On the basis of the previously reported mechanisms7 together with the experimental observations, we proposed a plausible reaction pathway for the formation of N-alkyl-2,5-unsubstituted/monosubstituted fulleropyrrolidines 2/4/6. As depicted in Scheme 3, paraformaldehyde first reacts with amines 1/3/5 to produce a bis-hydroxymethylation intermediate I (R2 = H) or a mono-hydroxymethylation intermediate IX (R2 = alkyl). In the case of intermediate I, a subsequent dehydrogenation with the aid of an excess of 1/3 as a base leads to the formation of an anionic intermediate II. It is worth mentioning that the preferred dehydrogenation site of intermediate I is located in the α-hydrogen rather than more acidic hydroxyl hydrogen probably due to the existence of two OH···O intramolecular hydrogen bonds between two hydroxyl groups (OH), which can increase the stability of hydroxyl hydrogen. Protonation of intermediate II by the proton delivery of base·H+ to the OH group produces a 1,2-dipole III or a 1,3-dipole IV accompanied by the elimination of one molecule of H2O. Cycloaddition of III or IV to C60 generates a fulleropyrrolidin-2-ol intermediate V, followed by dehydration by the same way as for


Page 14 of 44

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intermediate II to produce an iminium intermediate VI. Subsequent hydride transfer from amines 1/3 to VI forms N-alkyl-2,5-unsubstituted fulleropyrrolidines 2/4 as well as another iminium intermediate VII, which can undergo deprotonation and subsequent hydrolysis to attain an aldehyde intermediate VIII. The successful detection of benzaldehyde (see Figure S1 in Supporting Information) from the reaction mixture of C60, paraformaldehyde, and benzylamine (1a) for 20 min under the optimized conditions confirms the plausibility of the above-mentioned reaction pathway although the existence of benzaldehyde in the reaction solution is quite low probably due to the further condensation reaction of benzaldehyde with benzylamine. As for intermediate IX, dehydration under the assistance of 5 results in the generation of a 1,2-dipole X or a 1,3-dipole XI, followed by a concerted 1,3-dipolar cycloaddition to C60 to give N-alkyl-2-substituted fulleropyrrolidines 6.

Scheme 3. Possible Formation Mechanism for Fulleropyrrolidines 2/4/6



Page 16 of 44

protonation R2 = H

O HN H O

alkyl R = aryl

1/3 as base

1

R

base H

R1 O HN II H O

H

I H hydrogen bond

1

H2O

hydrogen bond OH

N

HO R1

2

R1 (CH2O)n

R N H 1/3/5 heating

H

N

HO

III

H

C60

base H

N

H2O

R1

IV

R1

V H R1 1/3

H2N N

N R1

H2N

VI

R1 VII 2/4

H

1

R

HN

alkyl R = aryl 1

H

N

H H2O

R1 VIII

O

H

OH

R2 = alkyl

R1

R1

5 as base

H

H2O

R2 IX

C60

N

R1

R2 X

H

N

R1

R2 XI

N R2 6

R1

Besides the detection experiments of benzaldehyde from the reaction mixture of C60, paraformaldehyde, and benzylamine (1a) under standard reaction conditions, other controlled experiments by utilizing the reaction of C60 with paraformaldehyde and 1a in the presence/absence of tert-butylamine were also carried out under various conditions (Table 5). We first investigated the reaction of C60 with paraformaldehyde and tert-butylamine in the absence of 1a, and found that no desired N-tert-butyl-2,5-unsubstituted fulleropyrrolidine was formed even by increasing the amount of tert-butylamine and prolonging the reaction time (entries 1 and 2, Table 5), agreeing well with our suggested reaction mechanism because the reduction of iminium VI by hydrogen transfer to produce the expected fulleropyrrolidine was hampered when tert-butylamine without α-hydrogen was employed. Furthermore, we


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also studied the reaction of C60 with paraformaldehyde and 1a in a molar ratio of 1:15:8 (entry 3, Table 5). The reduction of the equivalent of 1a from 25 to 8 could meet the molar ratio of paraformaldehyde to 1a as 2:1 based on our proposed mechanism. However, the yield of 2a was found to be dramatically reduced from 61% to 9% (entry 7, Table 1 vs entry 3, Table 5), indicating that an excess of 1a might have multiple roles in the high efficient synthesis of 2a. On the basis of the successful detection of benzaldehyde from the reaction mixture of C60, paraformaldehyde, and 1a under the optimized conditions (see Figure S1 in Supporting Information), 1a as a reductant to result in the generation of 2a has been well established. Additionally, 1a as a base might be another major reason for the synthesis of 2a with a high yield. Controlled experiments indicated that the addition of tert-butylamine could improve the yield of 2a from 9% to 30% (entries 4-8, Table 5), showing that the presence of a base had a positive effect on the formation of 2a. It is worth to mention that a large excess of tert-butylamine was required probably due to its low boiling point (about 45 oC).

Based on the above experimental facts, 1a might serve as reactant, reductant, and

organic base, consistent with our suggested mechanism shown in Scheme 3. It should be noted that controlled experiments by increasing the amount of paraformaldehyde (from 15 to 40 equiv.) were also conducted. Experimental results indicated that the yield of 2a could be gradually decreased from 9% to 5% (entries 3 and 9-11, Table 5), excluding the possibility of paraformaldehyde as a reductant to afford product 2a.

Table 5. Controlled Experiments for Mechanistic Studya



NH2

(CH2O)n 1a

additive

Page 18 of 44

N

Δ, air 2a

entry

additive

molar ratiob

time (min)

yield (%) of 2ac

1

(CH3)3CNH2

1:15:0:25

240

none

2

(CH3)3CNH2

1:15:0:50

300

none

3

none

1:15:8:0

30

9 (22)

4

(CH3)3CNH2

1:15:8:10

40

13 (29)

5

(CH3)3CNH2

1:15:8:20

35

23 (70)

6

(CH3)3CNH2

1:15:8:30

35

25 (77)

7

(CH3)3CNH2

1:15:8:40

35

30 (73)

8

(CH3)3CNH2

1:15:8:50

35

29 (75)

9

none

1:20:8:0

30

8 (18)

10

none

1:30:8:0

25

7 (14)

11

none

1:40:8: 0

20

5 (8)

aUnless

otherwise indicated, all reactions were performed at 180 oC in ODCB (6 mL) under air

conditions.

bMolar

ratio refers to C60/(CH2O)n/1a/(CH3)3CNH2.

cIsolated

yield; those in

parentheses were based on consumed C60.

CONCLUSION In summary, the simple one-step thermal reaction of C60 with paraformaldehyde and primary/secondary amines in the absence of metal salts successfully afforded a series of scarce N-alkyl-2,5-unsubstituted/monosubstituted fulleropyrrolidines in moderate to excellent yields. The current method for the preparation of fulleropyrrolidines by using inexpensive and easily available paraformaldehyde and primary/secondary amines is obviously more straightforward and practical than the previous ones.6 Furthermore, the current synthetic protocol also displays a broad substrate scope and excellent functional group tolerance, providing a good opportunity for researchers to


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design and synthesize a large variety of novel organic photovoltaic materials. An unusual mechanism for the formation of N-alkyl-2,5-unsubstituted fulleropyrrolidines was suggested by utilizing primary amines as reactant, reductant, and organic base based on our experimental observations.

EXPERIMENTAL SECTION General Methods. Reagents and solvents employed were commercially available without further purification. Purified fullerene products were obtained by flash chromatography over silica gel. The UV-vis spectra were performed in CHCl3. IR spectra were taken with KBr pellets. NMR spectra (1H and 13C NMR) were recorded on a 500 or 800 MHz NMR spectrometer. Chemical shifts in 1H NMR spectra were referenced to tetramethylsilane (TMS) at 0.00 ppm, while chemical shifts in 13C NMR spectra were referenced to residual DMSO at 39.52 ppm. High-resolution mass spectrometry

(HRMS)

by

MALDI-TOF

was

obtained

by

using

4-hydroxy-α-cyanocinnamic acid as the matrix in negative-ion mode. General Synthetic Procedure for Fulleropyrrolidines 2/4/6. C60 (36.0 mg, 0.05 mmol), paraformaldehyde (22.5 mg, 0.75 mmol) and amines 1/3/5 (1.25 mmol) were added to a 50 mL round-bottom flask equipped with a reflux condenser and a magnetic stirrer. After they were completely dissolved in 6 mL of o-dichlorobenzene (ODCB) by sonication, the resulting solution was put into an oil bath preset at 180 oC and stirred under air conditions. Thin-layer chromatography (TLC, CS2/CH2Cl2 as developing solvent, Rf (C60) = 1.0) was employed to carefully monitor the reaction



and to stop the reaction at the designated time. The reaction mixture was filtered through a silica gel plug to remove any insoluble material. After the solvent evaporation in vacuo was completed, the residue was separated on a silica gel column with carbon disulfide/dichloromethane as the eluent to afford first unreacted C60 and then fulleropyrrolidines 2/4/6. Fulleropyrrolidine 2a: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 1a (137 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 20 min afforded first unreacted C60 (9.8 mg, 27%) and then 2a6b,d-f (26.2 mg, 61%, Rf = 0.3) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. Fulleropyrrolidine 2b: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 1b (185 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 15 min afforded first unreacted C60 (4.1 mg, 11%) and then 2b (29.7 mg, 65%, Rf = 0.1) as amorphous brown solid with CS2/CH2Cl2 as the eluent (V/V = 10/1): mp > 300 °C. 2b: 1H NMR (800 MHz, CS2/DMSO-d6) δ 7.51 (d, J = 8.3 Hz, 1H), 6.49 (dd, J = 8.3, 2.0 Hz, 1H), 6.46 (d, J = 2.0 Hz, 1H), 4.38 (s, 4H), 4.21 (s, 2H), 3.91 (s, 3H), 3.79 (s, 3H); 13C{1H} NMR (125 MHz, CS2/DMSO-d6) (all 4C unless indicated) δ 159.47 (1C, aryl C), 157.65 (1C, aryl C), 154.32, 146.21 (2C), 145.23, 145.20, 145.00, 144.70 (2C), 144.42, 144.23, 143.56, 142.07 (2C), 141.60, 141.29, 141.07, 140.87, 139.15, 135.38, 130.33 (1C, aryl C), 116.60 (1C, aryl C), 103.91 (1C, aryl C), 97.96 (1C, aryl C), 69.74 (2C, sp3-C of C60), 66.13 (2C), 54.52 (1C), 54.27 (1C), 50.49 (1C); FT-IR ν/cm-1 (KBr) 2922,


Page 20 of 44

Page 21 of 44 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


2852, 1608, 1583, 1510, 1459, 1418, 1331, 1286, 1266, 1206, 1184, 1155, 1108, 1034, 831, 768, 638, 574, 526; UV-vis (CHCl3) λmax/nm 257, 305, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C71H15NO2 913.1103; Found 913.1093. Fulleropyrrolidine 2c: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 1c (163 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 15 min afforded first unreacted C60 (15.8 mg, 44%) and then 2c6d,e (23.2 mg, 53%, Rf = 0.3) as amorphous brown solid with CS2/CH2Cl2 as the eluent (V/V = 10/1): mp > 300 °C. Fulleropyrrolidine 2d: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 1d (152 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 35 min afforded first unreacted C60 (12.7 mg, 35%) and then 2d (17.9 mg, 40%, Rf = 0.7) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. 2d: 1H NMR (500 MHz, CS2/DMSO-d6) δ 7.61 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 4.40 (s, 4H), 4.25 (s, 2H); 13C{1H} NMR (125 MHz, CS2/DMSO-d6) (all 4C unless indicated) δ 153.85, 146.19 (2C), 145.18, 145.05, 144.98, 144.61 (2C), 144.42, 144.20, 143.50, 142.04 (2C), 141.58, 141.19, 141.02, 140.84, 139.14, 135.70 (1C, aryl C), 135.28, 132.51 (1C, aryl C), 129.26 (2C, aryl C), 128.00 (2C, aryl C), 69.58 (2C, sp3-C of C60), 66.43 (2C), 57.05 (1C); FT-IR ν/cm-1 (KBr) 2917, 2850, 1508, 1487, 1464, 1426, 1336, 1183, 1156, 1088, 1013, 893, 805, 769, 669, 574, 527; UV-vis (CHCl3) λmax/nm 256, 307, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C69H10ClN 887.0502; Found 887.0502. Fulleropyrrolidine 2e: According to the general synthetic procedure, the reaction



of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 1e (151 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 25 min afforded first unreacted C60 (8.7 mg, 24%) and then 2e6f (28.6 mg, 64%, Rf = 0.6) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. Fulleropyrrolidine 2f: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 1f (158 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 35 min afforded first unreacted C60 (18.6 mg, 52%) and then 2f (21.2 mg, 46%, Rf = 0.4) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. 2f: 1H NMR (800 MHz, CS2/DMSO-d6) δ 7.55 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 4.40 (s, 4H), 4.23 (s, 2H); 13C{1H} NMR (125 MHz, CS2/DMSO-d6) (all 4C unless indicated) δ 153.89, 146.22 (2C), 145.21, 145.08, 145.01, 144.64 (2C), 144.45, 144.23, 143.53, 142.07 (2C), 141.60, 141.22, 141.05, 140.87, 139.17, 136.25 (1C, aryl C), 135.31, 130.98 (2C, aryl C), 129.63 (2C, aryl C), 120.90 (1C, aryl C), 69.62 (2C, sp3-C of C60), 66.45 (2C), 57.10 (1C); FT-IR ν/cm-1 (KBr) 2916, 2850, 1511, 1485, 1427, 1338, 1185, 1154, 1113, 1069, 1011, 803, 768, 574, 527; UV-vis (CHCl3) λmax/nm 256, 307, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C69H10BrN 930.9997; Found 930.9997. Fulleropyrrolidine 2g: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 1g (128 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 30 min afforded first unreacted C60 (17.4 mg, 48%) and then 2g6f (21.0 mg, 49%, Rf = 0.3) as amorphous brown solid with CS2 as the eluent: mp > 300 °C.


Page 22 of 44

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Fulleropyrrolidine 2h: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 1h (215 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 20 min afforded first unreacted C60 (26.0 mg, 72%) and then 2h6e (10.9 mg, 23%, Rf = 0.85) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. Fulleropyrrolidine 2i: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 1i (159 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 20 min afforded first unreacted C60 (14.3 mg, 40%) and then 2i (6.8 mg, 16%, Rf = 0.5) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. 2i: 1H NMR (800 MHz, CS2/DMSO-d6) δ 7.62 (dd, J = 8.1, 1.2 Hz, 2H), 7.37 (t, J = 7.7 Hz, 2H), 7.27 (t, J = 7.4 Hz, 1H), 4.43 (d, J = 8.5 Hz, 2H ), 4.28 (d, J = 8.5 Hz, 2H ), 3.92 (q, J = 6.6 Hz, 1H), 1.80 (d, J = 6.6 Hz, 3H );

13C{1H}

NMR (125 MHz, CS2/DMSO-d6) (all 2C unless indicated) δ 154.07,

154.03, 146.18, 145.16 (4C), 145.11, 145.06, 144.97 (4C), 144.63, 144.41, 144.39, 144.18 (4C), 143.51, 143.50, 143.20 (1C, aryl C), 142.02, 141.55 (4C), 141.23, 141.18, 141.01 (4C), 140.83, 140.81, 139.13, 139.11, 135.33 (4C), 128.05 (aryl C), 126.77 (1C, aryl C), 126.25 (aryl C), 69.28 (sp3-C of C60), 65.26, 62.96 (1C), 22.55 (1C); FT-IR ν/cm-1 (KBr) 2920, 2851, 1429, 1182, 1153, 1122, 1024, 699, 527, UV-vis (CHCl3) λmax/nm 257, 305, 431; HRMS (MALDI-TOF) m/z: [M] − Calcd for C70H13N 867.1048; Found 867.1048. Fulleropyrrolidine 2j: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 1j



(183 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 15 min afforded first unreacted C60 (16.3 mg, 45%) and then 2j (13.4 mg, 30%, Rf = 0.8) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. 2j: 1H NMR (500 MHz, CS2/DMSO-d6) δ 8.63 (d, J = 8.4 Hz, 1H ), 7.84 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 6.8 Hz, 1H), 7.57 (t, J = 7.5 Hz, 1H), 7.48 (t, J = 7.3 Hz, 2H), 4.70 (s, 2H), 4.48 (s, 4H); 13C{1H}

NMR (125 MHz, CS2/DMSO-d6) (all 4C unless indicated) δ 153.55, 145.70

(2C), 144.68, 144.62, 144.49, 144.14 (2C), 143.91, 143.71, 143.02, 141.54 (2C), 141.07, 140.74, 140.54, 140.34, 138.64, 134.78, 132.64 (1C, aryl C), 132.36 (1C, aryl C), 130.94 (1C, aryl C), 127.56 (1C, aryl C), 127.47 (1C, aryl C), 125.74 (1C, aryl C), 125.00 (1C, aryl C), 124.90 (1C, aryl C), 124.33 (1C, aryl C), 123.42 (1C, aryl C), 69.23 (2C, sp3-C of C60), 66.31 (2C), 55.74 (1C); FT-IR ν/cm-1 (KBr) 2899, 2779, 1509, 1462, 1426, 1335, 1268, 1166, 1111, 1074, 892, 791, 779, 768, 574, 527, UV-vis (CHCl3) λmax/nm 257, 305, 431; HRMS (MALDI-TOF) m/z: [M] − Calcd for C73H13N 903.1048; Found 903.1044. Fulleropyrrolidine 4a: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 3a (157 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 20 min afforded first unreacted C60 (11.4 mg, 32%) and then 4a6e (27.4 mg, 63%, Rf = 0.2) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. Fulleropyrrolidine 4b: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 3b (183 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 15 min afforded first unreacted


Page 24 of 44

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C60 (11.2 mg, 31%) and then 4b6e (23.7 mg, 53%, Rf = 0.3) as amorphous brown solid with CS2/CH2Cl2 as the eluent (V/V = 10/1): mp > 300 °C. Fulleropyrrolidine 4c: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 3c (183 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 35 min afforded first unreacted C60 (12.2 mg, 34%) and then 4c (23.3 mg, 52%, Rf = 0.3) as amorphous brown solid with CS2/CH2Cl2 as the eluent (V/V = 10/1): mp > 300 °C. 4c: 1H NMR (500 MHz, CS2/DMSO-d6) δ 7.15 (t, J = 7.8 Hz, 1H), 6.90 (t, J = 7.6 Hz, 2H), 6.67 (d, J = 8.0 Hz, 1H), 4.43 (s, 4H), 3.76 (s, 3H), 3.30 (t, J = 7.8 Hz, 2H), 3.15 (t, J = 7.8 Hz, 2H); 13C{1H}

NMR (125 MHz, CS2/DMSO-d6) (all 4C unless indicated) δ 158.72 (1C, aryl

C), 154.07, 146.16 (2C), 145.15, 145.11, 144.95, 144.62 (2C), 144.38, 144.18, 143.50, 142.03 (2C), 141.55, 141.18, 141.02, 140.82, 140.39 (1C, aryl C), 139.10, 135.28, 128.61 (1C, aryl C), 120.34 (1C, aryl C), 113.89 (1C, aryl C), 110.94 (1C, aryl C), 69.63 (2C, sp3-C of C60), 66.88 (2C), 55.41 (1C), 54.00 (1C), 34.85 (1C); FT-IR ν/cm-1 (KBr) 2927, 1584, 1487, 1462, 1453, 1429, 1343, 1259, 1188, 1156, 1115, 1057, 873, 768, 696, 575, 527; UV-vis (CHCl3) λmax/nm 257, 306, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C71H15NO 897.1154; Found 897.1154. Fulleropyrrolidine 4d: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 3d (176 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 25 min afforded first unreacted C60 (11.9 mg, 33%) and then 4d (23.7 mg, 53%, Rf = 0.5) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. 4d: 1H NMR (500 MHz, CS2/DMSO-d6) δ 7.35



(d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 4.44 (s, 4H), 3.30 (t, J = 7.6 Hz, 2H), 3.18 (t, J = 7.6 Hz, 2H);

13C{1H}

NMR (125 MHz, CS2/DMSO-d6) (all 4C unless

indicated) δ 154.00, 146.18 (2C), 145.17, 145.09, 144.97, 144.63 (2C), 144.40, 144.20, 143.51, 142.05 (2C), 141.58, 141.19, 141.03, 140.84, 139.13, 137.60 (1C, aryl C), 135.25, 131.31 (1C, aryl C), 129.59 (2C, aryl C), 127.74 (2C, aryl C), 69.62 (2C, sp3-C of C60), 66.83 (2C), 53.20 (1C), 34.08 (1C); FT-IR ν/cm-1 (KBr) 2920, 2850, 1581, 1489, 1466, 1426, 1384, 1183, 1159, 1115, 1091, 813, 769, 597, 574, 527; UV-vis (CHCl3) λmax/nm 256, 306, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C70H12ClN 901.0658; Found 901.0658. Fulleropyrrolidine 4e: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 3e (164 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 25 min afforded first unreacted C60 (7.2 mg, 20%) and then 4e6e (25.0 mg, 56%, Rf = 0.2) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. Fulleropyrrolidine 4f: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 3f (188 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 25 min afforded first unreacted C60 (15.1 mg, 42%) and then 4f (26.8 mg, 57%, Rf = 0.4) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. 4f: 1H NMR (500 MHz, CS2/DMSO-d6) δ 7.50 (d, J = 8.2 Hz, 1H), 7.37 (d, J = 2.0 Hz, 1H), 7.23 (dd, J = 8.2, 2.0 Hz, 1H), 4.47 (s, 4H), 3.31 (s, 4H); 13C{1H} NMR (125 MHz, CS2/DMSO-d6) (all 4C unless indicated) δ 153.94, 146.16 (2C), 145.15, 145.05, 144.95, 144.61 (2C), 144.38, 144.17, 143.48,


Page 26 of 44

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142.02 (2C), 141.55, 141.16, 141.01, 140.82, 139.10, 135.29 (1C, aryl C), 135.23, 133.97 (1C, aryl C), 132.10 (1C, aryl C), 131.34 (1C, aryl C), 128.30 (1C, aryl C), 126.39 (1C), 69.60 (2C, sp3-C of C60), 66.76 (2C), 53.22 (1C), 31.59 (1C); FT-IR ν/cm-1 (KBr) 2921, 2849, 1512, 1470, 1427, 1343, 1184, 1163, 1115, 1103, 1051, 897, 864, 816, 769, 574, 527; UV-vis (CHCl3) λmax/nm 255, 307, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C70H11Cl2N 935.0269; Found 935.0269. Fulleropyrrolidine 4g: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 3g (146 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 20 min afforded first unreacted C60 (16.6 mg, 46%) and then 4g (18.5 mg, 42%, Rf = 0.3) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. 4g: 1H NMR (500 MHz, CS2/DMSO-d6) δ 7.13 (d, J = 4.6 Hz, 1H), 6.97 (s, 1H), 6.91 (t, J = 3.7 Hz, 1H), 4.48 (s, 4H), 3.42 (t, J = 6.4 Hz, 2H), 3.37 (t, J = 6.4 Hz, 2H); 13C{1H} NMR (125 MHz, CS2/DMSO-d6) (all 4C unless indicated) δ 153.83, 146.01 (2C), 144.99, 144.93, 144.80, 144.47 (2C), 144.23, 144.02, 143.34, 141.87 (2C), 141.40, 141.04 (5C), 140.87, 140.67, 138.95, 135.15, 125.84 (1C, aryl C), 124.25 (1C, aryl C), 123.22 (1C, aryl C), 69.45 (2C, sp3-C of C60), 66.66 (2C), 55.09 (1C), 28.79 (1C); FT-IR ν/cm-1 (KBr) 2921, 2849, 1515, 1466, 1428, 1382, 1344, 1183, 1161, 1116, 847, 819, 769, 694, 574, 527; UV-vis (CHCl3) λmax/nm 256, 305, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C68H11NS 873.0612; Found 873.0612. Fulleropyrrolidine 4h: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 3h



(178 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 15 min afforded first unreacted C60 (13.7 mg, 39%) and then 4h (22.9 mg, 52%, Rf = 0.25) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. 4h: 1H NMR (500 MHz, CS2/DMSO-d6) δ 7.27-7.21 (m, 4H), 7.12 (t, J = 7.0 Hz, 1H), 4.38 (s, 4H), 3.06 (t, J = 7.1 Hz, 2H), 2.95 (t, J = 7.1 Hz 2H), 2.24-2.19 (m, 2H); 13C{1H} NMR (125 MHz, CS2/DMSO-d6) (all 4C unless indicated) δ 153.93, 146.00 (2C), 144.99, 144.95, 144.80, 144.46 (2C), 144.22, 144.02, 143.34, 141.87 (2C), 141.40, 141.05, 140.86, 140.67, 140.48 (1C, aryl C), 138.96, 135.09, 127.62 (2C, aryl C), 127.52 (2C, aryl C), 125.03 (1C, aryl C), 69.46 (2C, sp3-C of C60), 66.63 (2C), 52.69 (1C), 32.77 (1C), 29.59 (1C); FT-IR ν/cm-1 (KBr) 2880, 1510, 1450, 1426, 1340, 1184, 1115, 897, 769, 745, 696, 597, 574, 527; UV-vis (CHCl3) λmax/nm 256, 306, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C71H15N 881.1205; Found 881.1205. Fulleropyrrolidine 4i: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 3i (109 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 20 min afforded first unreacted C60 (20.6 mg, 57%) and then 4i (14.7 mg, 36%, Rf = 0.08) as amorphous brown solid with CS2/CH2Cl2 as the eluent (V/V = 10/1): mp > 300 °C. 4i: 1H NMR (500 MHz, CS2/DMSO-d6) δ 4.46 (s, 4H), 3.86 (t, J = 5.2 Hz, 2H), 3.46 (s, 3H), 3.26 (t, J = 5.2 Hz, 2H);

13C{1H}

NMR (125 MHz, CS2/DMSO-d6) (all 4C unless indicated) δ

154.06, 146.03 (2C), 145.02 (8C), 144.83, 144.52 (2C), 144.25, 144.05, 143.38, 141.91 (2C), 141.43, 141.08, 140.90, 140.70, 138.98, 135.15, 71.30 (1C), 69.62 (2C, sp3-C of C60), 67.46 (2C), 57.81 (1C), 53.36 (1C); FT-IR ν/cm-1 (KBr) 2920, 1510,


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1428, 1383, 1341, 1182, 1117, 770, 670, 573, 527; UV-vis (CHCl3) λmax/nm 256, 306, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C65H11NO 821.0841; Found 821.0841. Fulleropyrrolidine 4j: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 3j (124 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 15 min afforded first unreacted C60 (23.3 mg, 65%) and then 4j6f (8.6 mg, 21%, Rf = 0.4) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. Fulleropyrrolidine 4k: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 3k (237 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 15 min afforded first unreacted C60 (14.9 mg, 41%) and then 4k (24.9 mg, 53%, Rf = 0.55) as amorphous brown solid with CS2 as the eluent): mp > 300 °C. 4k: 1H NMR (500 MHz, CS2/DMSO-d6) δ 7.41 (d, J = 7.5 Hz, 4H), 7.27 (t, J = 7.5 Hz, 4H), 7.15 (t, J = 7.3 Hz, 2H), 4.56 (t, J = 7.5 Hz, 1H), 4.39 (s, 4H), 3.71 (d, J = 7.5 Hz, 2H);

13C{1H}

NMR (125 MHz,

CS2/DMSO-d6) (all 4C unless indicated) δ 153.82, 145.96 (2C), 144.95, 144.91, 144.76, 144.42 (2C), 144.15, 143.98, 143.30, 142.13 (2C, aryl C), 141.81 (2C), 141.35, 140.99, 140.82, 140.61, 138.87, 135.02, 127.51 (aryl C), 127.40 (aryl C), 125.58 (2C, aryl C), 69.48 (2C, sp3-C of C60), 66.63 (2C), 58.12 (1C), 49.43 (1C); FT-IR ν/cm-1 (KBr) 2964, 2847, 1507, 1463, 1450, 1426, 1345, 1184, 1118, 1029, 893, 753, 736, 696, 574, 527; UV-vis (CHCl3) λmax/nm 257, 306, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C76H17N 943.1361; Found 943.1361.



Fulleropyrrolidine 6a: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 5a (161 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 25 min afforded first unreacted C60 (24.4 mg, 68%) and then 6a6a (13.4 mg, 31%, Rf = 0.4) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. Fulleropyrrolidine 6b: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 5b (186 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 15 min afforded first unreacted C60 (16.7 mg, 46%) and then 6b6c (22.0 mg, 51%, Rf = 0.8) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. Fulleropyrrolidine 6c: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 5c (240 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 15 min afforded first unreacted C60 (21.3 mg, 59%) and then 6c6b (18.8 mg, 40%, Rf = 0.9) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. Fulleropyrrolidine 6d: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 5d (129 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 15 min afforded first unreacted C60 (20.2 mg, 56%) and then 6d6b (17.0 mg, 42%, Rf = 0.25) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. Fulleropyrrolidine 6e: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 5e


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(171 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 15 min afforded first unreacted C60 (19.3 mg, 54%) and then 6e (15.1 mg, 36%, Rf = 0.5) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. 6e: 1H NMR (500 MHz, CS2/DMSO-d6) δ 4.89 (d, J = 9.8 Hz, 1H), 4.11-4.08 (m, 2H), 3.46-3.41 (m, 1H), 2.84-2.79 (m, 1H), 2.52-2.43 (m, 2H), 1.97-1.91 (m, 2H), 1.39 (t, J = 7.4 Hz, 3H), 1.22 (t, J = 7.3 Hz, 3H);

13C{1H}

NMR (125 MHz, CS2/DMSO-d6) (all 1C unless indicated) δ 155.47,

153.96, 153.85, 152.66, 145.91, 145.90, 145.56, 145.31, 145.14, 145.03 (2C), 144.92, 144.90, 144.81, 144.76, 144.72, 144.71, 144.56, 144.54, 144.36, 144.21, 144.17, 144.07 (2C), 144.01 (2C), 144.00, 143.93, 143.51, 143.38, 143.21, 143.18, 141.98, 141.86, 141.45, 141.43, 141.42, 141.39, 141.05 (2C), 141.01, 140.95 (2C), 140.92, 140.88, 140.86, 140.83, 140.62, 140.57, 140.51, 139.06, 139.00, 138.72, 138.47, 135.92, 135.12, 134.52, 134.32, 77.16, 74.98, 69.48 (sp3-C of C60), 65.62 (sp3-C of C60), 53.41, 23.09, 21.49, 11.52, 11.19; FT-IR ν/cm-1 (KBr) 2921, 1540, 1457, 1427, 1184, 890, 673, 526; UV-vis (CHCl3) λmax/nm 256, 308, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C67H15N 833.1205; Found 833.1205. Fulleropyrrolidine 6f: According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 5f (211 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 15 min afforded first unreacted C60 (20.6 mg, 57%) and then 6f (14.1 mg, 33%, Rf = 0.65) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. 6f: 1H NMR (500 MHz, CS2/DMSO-d6) δ 4.87 (d, J = 9.9 Hz, 1H), 4.12 (t, J = 5.5 Hz, 1H), 4.09 (d, J = 9.9 Hz, 1H), 3.52-3.46 (m, 1H), 2.86-2.81 (m, 1H), 2.45-2.30 (m, 2H), 1.95-1.81 (m, 4H), 1.73-1.56 (m, 2H),



1.13-1.07 (m, 6H);

13C{1H}


indicated) δ 155.45, 153.83, 153.74, 152.55, 145.85 (2C), 145.46, 145.31, 145.09, 144.97 (2C), 144.86 (2C), 144.75, 144.70, 144.66 (2C), 144.50, 144.45, 144.30, 144.13, 144.12 (2C), 144.01 (2C), 143.88, 143.45, 143.32, 143.15, 143.12, 141.92, 141.80, 141.38 (4C), 140.99 (2C), 140.96, 140.90 (2C), 140.84 (2C), 140.81, 140.78, 140.56, 140.50, 140.46, 139.01, 138.96, 138.65, 138.39, 135.88, 135.03, 134.47, 134.28, 75.94, 75.09, 69.50 (sp3-C of C60), 65.60 (sp3-C of C60), 51.20, 32.52, 30.21, 20.23, 20.14, 14.11, 13.64; FT-IR ν/cm-1 (KBr) 2922, 2856, 1536, 1457, 1428, 1181, 676, 571, 526; UV-vis (CHCl3) λmax/nm 256, 308, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C69H19N 861.1518; Found 861.1518. Fulleropyrrolidines 6g and 6g': According to the general synthetic procedure, the reaction of C60 (36.0 mg, 0.05 mmol) with paraformaldehyde (22.5 mg, 0.75 mmol) and 5g (171 μL, 1.25 mmol) in ODCB (6 mL) at 180 oC for 15 min afforded first unreacted C60 (16.3 mg, 45%) and then 6g (10.3 mg, 25%, Rf = 0.6) and 6g' (7.7 mg, 18%, Rf = 0.3) as amorphous brown solid with CS2 as the eluent: mp > 300 °C. 6g: 1H NMR (500 MHz, CS2/DMSO-d6) δ 4.87 (d, J = 9.1 Hz, 1H), 4.01 (q, J = 6.3 Hz, 1H), 3.96 (d, J = 9.1 Hz, 1H), 3.40-3.34 (m, 1H), 2.68-2.63 (m, 1H), 1.98-1.83 (m, 2H), 1.94 (d, J = 6.3 Hz, 3H), 1.76-1.59 (m, 2H), 1.12 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (125 MHz, CS2/DMSO-d6) (all 1C unless indicated) δ 155.48, 153.33, 152.98, 152.21, 146.06 (2C), 145.73, 145.61, 145.45, 145.14, 145.11, 144.98 (2C), 144.91, 144.88, 144.78 (2C), 144.64, 144.51, 144.36 (2C), 144.34, 144.23, 144.15, 144.09 (2C), 144.04, 143.99, 143.61, 143.49, 143.24 (2C), 141.99, 141.88, 141.52, 141.48, 141.45,


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141.43, 141.10 (2C), 141.08, 141.00 (2C), 140.88, 140.76 (3C), 140.57, 140.53, 139.11, 139.03 (2C), 138.59, 136.39, 135.33, 134.87, 134.66, 74.57, 70.77, 68.03 (sp3-C of C60), 65.62 (sp3-C of C60), 50.87, 29.69, 20.44, 16.18, 13.67; FT-IR ν/cm-1 (KBr) 2922, 2854, 1515, 1461, 1428, 1376, 1185, 1077, 676, 597, 526; UV-vis (CHCl3) λmax/nm 256, 306, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C67H15N 833.1205; Found 833.1205. 6g': 1H NMR (500 MHz, CS2/DMSO-d6) δ 4.89 (d, J = 9.8 Hz, 1H), 4.89 (t J = 5.0 Hz, 1H), 4.11 (d, J = 9.8 Hz, 1H), 3.63-3.56 (m, 1H), 2.91-2.83 (m, 1H), 2.46-2.30 (m, 2H), 1.94-1.83 (m, 2H), 1.51 (t, J = 7.2 Hz, 3H), 1.09 (t, J = 7.3 Hz, 3H);

13C{1H}


indicated) δ 155.53, 153.86, 153.76, 152.60, 145.90, 145.88, 145.51, 145.37, 145.16, 145.03, 145.00, 144.91, 144.89, 144.80, 144.75, 144.70, 144.69, 144.56, 144.48, 144.35, 144.18, 144.17, 144.06, 144.05, 144.00 (3C), 143.92, 143.51, 143.36, 143.19, 143.17, 141.96, 141.84, 141.42 (3C), 141.04, 141.01 (2C), 140.94 (2C), 140.88 (2C), 140.85, 140.83, 140.61, 140.54, 140.50, 139.04, 139.00, 138.68, 138.43, 135.98, 135.12, 134.53, 134.33, 75.58, 75.12, 69.38 (sp3-C of C60), 65.25 (sp3-C of C60), 45.62, 32.49, 20.22, 14.16, 13.05; FT-IR ν/cm-1 (KBr) 2921, 2852, 1540, 1510, 1461, 1427, 1376, 1342, 1186, 770, 649, 571, 526; UV-vis (CHCl3) λmax/nm 256, 308, 431; HRMS (MALDI-TOF) m/z: [M]− Calcd for C67H15N 833.1205; Found 833.1205.

Acknowledgements The authors are grateful for the financial support from National Natural Science Foundation of China (nos. 21102041, 21671061, and 11575287), Scientific Research



Foundation of Education Commission of Hubei Province (no. D20161007), Innovation and Entrepreneurship Training Program for Undergraduates of Hubei Province (nos. 201710512044 and 201810512046), and the Open Project of State Key Laboratory of Silicate Materials for Architectures (Wuhan University of Technology) (no. SYSJJ2019-10).

Supporting Information HRMS of 2b, 4k, and 6e, UV-vis spectra of 2d, 4h, and 6b, 1H and 13C NMR spectra of products 2a-j, 4a-k, and 6a-g,g'. This material is available free of charge via the Internet at http://pubs.acs.org.

REFERENCES (1) (a) Kroto, H. W.; Heath, J. R.; O’Brien, S. C.; Curl, R. F.; Smalley, R. E. C60: Buckminsterfullerene. Nature 1985, 318, 162. (b) Kräetschmer, W.; Lamb, L. D.; Fostiropoulos, K.; Huffman, D. R. Solid C60: a New Form of Carbon. Nature 1990, 347, 354. (2) For selected reviews on materials, see: (a) Bendikov, M.; Wudl, F. Tetrathiafulvalenes, Oligoacenenes, and Their Buckminsterfullerene Derivatives: The Brick and Mortar of Organic Electronics. Chem. Rev. 2004, 104, 4891. (b) Giacalone, F.; Martín, N. Fullerene Polymers: Synthesis and Properties. Chem. Rev. 2006, 106, 5136. (c) Zhu, S.-E; Li, F.; Wang, G.-W. Mechanochemistry of Fullerenes and Related Materials. Chem. Soc. Rev. 2013, 42, 7535. (d) Balch, A.


Page 34 of 44

Page 35 of 44 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


L.; Winkler, K. Two-Component Polymeric Materials of Fullerenes and the Transition Metal Complexes: a Bridge between Metal-Organic Frameworks and Conducting Polymers. Chem. Rev. 2016, 116, 3812. (e) Rudolf, M.; Kirner, S. V.; Guldi,

D.

M.

A

Multicomponent

Molecular

Approach

to

Artificial

Photosynthesis-the Role of Fullerenes and Endohedral Metallofullerenes. Chem. Soc. Rev. 2016, 45, 612. For selected reviews and papers on bio-medical applications, see: (f) Nakamura, E.; Isobe, H. Functionalized Fullerenes in Water. The First 10 Years of Their Chemistry, Biology, and Nanoscience. Acc. Chem. Res. 2003, 36, 807. (g) Murata, M.; Murata, Y.; Komatsu, K. Surgery of Fullerenes. Chem. Commun. 2008, 6083. (h) Luczkowiak, J.; Muñoz, A.; Sánchez-Navarro, M.; Ribeiro-Viana, R.; Ginieis, A.; Illescas, B. M.; Martín, N.; Delgado, R.; Rojo, J. Glycofullerenes Inhibit Viral Infection. Biomacromolecules 2013, 14, 431. (i) Muñoz, A.; Sigwalt, D.; Illescas, B. M.; Luczkowiak, J.; Rodríguez-Pérez, L.; Nierengarten, I.; Holler, M.; Remy, J.-S.; Buffet, K.; Vincent, S. P.; Rojo, J.; Delgado, R.; Nierengarten, J.-F.; Martín, N. Synthesis of Giant Globular Multivalent Glycofullerenes as Potent Inhibitors in a Model of Ebola Virus Infection. Nat. Chem. 2016, 8, 50. (j) Illescas, B. M.; Rojo, J.; Delgado, R.; Martín, N. Multivalent Glycosylated Nanostructures to Inhibit Ebola Virus Infection. J. Am. Chem. Soc. 2017, 139, 6018. For selected reviews on nanotechnology, see: (k) Guldi, D. M.; Illescas, B. M.; Atienza, C. M.; Wielopolski, M.; Martín, N. Fullerene for Organic Electronics. Chem. Soc. Rev. 2009, 38, 1587. (l) Sánchez, L.; Otero, R.; Gallego, J. M.; Miranda, R.; Martín, N.



Page 36 of 44

Ordering Fullerenes at the Nanometer Scale on Solid Surfaces. Chem. Rev. 2009, 109, 2081. (m) Vougioukalakis, G. C.; Roubelakis, M. M.; Orfanopoulos, M. Open-Cage Fullerenes: towards the Construction of Nanosized Molecular Containers. Chem. Soc. Rev. 2010, 39, 817. (3) For

selected

reviews,

see:

(a)

Hirsch,

A.

Addition

Reactions

of

Buckminsterfullerene (C60). Synthesis 1995, 895. (b) Thilgen, C.; Diederich, F. Structural Aspects of Fullerene Chemistry-a Journey through Fullerene Chirality. Chem. Rev. 2006, 106, 5049. (c) Yurovskaya, M. A.; Trushkov, I. V. Cycloaddition to Buckminsterfullerene C60: Advancements and Future Prospects. Russ. Chem. Bull., Int. Ed. 2002, 51, 367. (d) Matsuo, Y.; Nakamura, E. Selective Multiaddition of Organocopper Reagents to Fullerenes. Chem. Rev. 2008, 108, 3016. (e) Tzirakis, M. D.; Orfanopoulos, M. Radical Reactions of Fullerenes: from Synthetic Organic Chemistry to Materials Science and Biology. Chem. Rev. 2013, 113, 5262. (f) Delgado, J. L.; Filippone, S.; Giacalone, F.; Herranz, Ma. Á.; Illescas, B.; Pérez, E. M.; Martín, N. Buckyballs. Top. Curr. Chem. 2014, 350, 1. (g) Maroto, E. E.; Izquierdo, M.; Reboredo, S.; Marco-Martínez, J.; Filippone, S.; Martín, N. Chiral Fullerenes from Asymmetric Catalysis. Acc. Chem. Res. 2014, 47, 2660. (h) Bao, L.; Peng, P.; Lu, X. Bonding inside and outside Fullerene Cages. Acc. Chem. Res. 2018, 51, 810. For selected papers, see: (i) Ueda, M.; Sakaguchi, T.; Hayama, M.; Nakagawa, T.; Matsuo, Y.; Munechika, A.; Yoshida, S.; Yasudad, H.; Ryu, I. Regio- and Stereo-Selective Intermolecular [2+2] Cycloaddition

of

Allenol

Esters

with


C60

Leading

to

Page 37 of 44 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


Alkylidenecyclobutane-Annulated Fullerenes. Chem. Commun. 2016, 52, 13175. (j) Minois, P.; Bayardon, J.; Meunier-Prest, R.; Jugé, S. [60]Fullerene l-Amino Acids and Peptides: Synthesis under Phase-Transfer Catalysis Using a Phosphine-Borane Linker. Electrochemical Behavior. J. Org. Chem. 2017, 82, 11358. (k) Wu, S.-L.; Gao, X. Copper-Catalyzed Aerobic Oxidative Reaction of C60 with Aliphatic Primary Amines and CS2. J. Org. Chem. 2018, 83, 2125. (l) Pieper,

P.;

Russo,

V.;

Heinrich,

B.;

Donnio,

B.;

Deschenaux,

R.

Liquid-Crystalline Tris[60]Fullerodendrimers. J. Org. Chem. 2018, 83, 3208. (m) Lukyanov, D. A.; Konev, A. S.; Amsharov, K. Yu.; Khlebnikov, A. F.; Hirsch, A. Diastereospecific and Highly Site-Selective Functionalization of C70 Fullerene by a Reaction with Diethyl N-Arylaziridine-2,3-Dicarboxylates. J. Org. Chem. 2018, 83, 14146. (n) Zhilenkov, A. V.; Peregudov, A. S.; Chernyak, A. V.; Martynenko, V. M.; Troshinc, P. A. Synthesis of Chlorinated Fullerenes C60Cln (n = 2, 4) from C60Cl6 and Their Arbuzov-type Reaction with P(OEt)3. Tetrahedron Lett. 2018, 59, 608. (o) Lim, S. H.; Oh, J.; Nahm, K.; Noh, S.; Shim, J. H.; Kim, C.; Kim, E.; Cho, D. W. Photochemical Approach for the Preparation of N-Alkyl/Aryl Substituted Fulleropyrrolidines: Photoaddition Reactions of Silyl Group Containing α-Aminonitriles with Fullerene C60. J. Org. Chem. 2019, 84, 1407. (4) For selected papers on materials, see: (a) Chen, H.; Liang, Y.; Wang, M.; Lv, P.; Xuan, Y. Reverse ATRP of Ethyl Acrylate with Ionic Liquids as Reaction Medium. Chem. Eng. J. 2009, 147, 297. (b) Liu, X.; Chen, H.; Wang, C.; Qu, R.; Ji, C.; Sun, C.; Zhang, Y. Synthesis of Porous Acrylonitrile/Methyl Acrylate



Copolymer Beads by Suspended Emulsion Polymerization and Their Adsorption Properties after Amidoximation. J. Hazard. Mater. 2010, 175, 1014. (c) Zong, G.; Chen, H.; Qu, R.; Wang, C.; Ji, N. Synthesis of Polyacrylonitrile-Grafted Cross-Linked N-Chlorosulfonamidated Polystyrene via Surface-Initiated ARGET ATRP, and Use of the Resin in Mercury Removal after Modification. J. Hazard. Mater. 2011, 186, 614. For selected papers on nanotechnology, see: (d) Zhang, S.; Zhang, Y.; Liu, J.; Xu, Q.; Xiao, H.; Wang, X.; Xu, H.; Zhou, J. Thiol Modified Fe3O4@SiO2 as a Robust, High Effective, and Recycling Magnetic Sorbent for Mercury Removal. Chem. Eng. J. 2013, 226, 30. (e) Zhang, S.; Zhang, Y.; Bi, G.; Liu, J.; Wang, Z.; Xu, Q.; Xu, H.; Li, X. Mussel-inspired Polydopamine Biopolymer Decorated with Magnetic Nanoparticles for Multiple Pollutants Removal. J. Hazard. Mater. 2014, 270, 27. (5) For selected reviews on fulleropyrrolidines, see: (a) Prato, M.; Maggini, M. Fulleropyrrolidines: a Family of Full-Fledged Fullerene Derivatives. Acc. Chem. Res. 1998, 31, 519. (b) Tagmatarchis, N.; Prato, M. The Addition of Azomethine Ylides to [60]Fullerene Leading to Fulleropyrrolidines. Synlett 2003, 768. For selected papers on fulleropyrrolidines, see: (c) Maggini, M.; Scorrano, G.; Prato, M. Addition of Azomethine Ylides to C60: Synthesis, Characterization, and Functionalization of Fullerene Pyrrolidines. J. Am. Chem. Soc. 1993, 115, 9798. (d) Maggini, M.; Scorrano, G.; Bianco, A.; Toniolo, C.; Sijbesma, R. P.; Wudl, F.; Prato, M. Addition Reactions of C60 Leading to Fulleroprolines. J. Chem. Soc., Chem. Commun. 1994, 305. (e) Lawson, G. E.; Kitayogorodskiy, A.; Ma, B.;


Page 38 of 44

Page 39 of 44 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


Bunker, C. E.; Sun, Y.-P. Photoinduced Inter- and Intra-Molecular Electron Transfer Reactions of [60]Fullerene and a Tertiary Amine. Formation of the Cycloadduct N-Ethyl-trans-2′,5′-Dimethylpyrrolidino[3′,4′:1,2][60]Fullerene. J. Chem. Soc., Chem. Commun. 1995, 2225. (f) Liou, K.-F.; Cheng, C.-H. Photoinduced Reactions of Tertiary Amines with [60]Fullerene; Addition of an α-C–H Bond of Amines to [60]Fullerene. Chem. Commun. 1996, 1423. (g) Gan, L.; Zhou, D.; Luo, C.; Tan, H.; Huang, C.; Lu, M.; Pan, J.; Wu, Y. Synthesis of Fullerene Amino Acid Derivatives by Direct Interaction of Amino Acid Ester with C60. J. Org. Chem. 1996, 61, 1954. (h) Gan, L.; Jiang, J.; Zhang, W.; Su, Y.; Shi, Y.; Huang, C.; Pan, J.; Lu, M.; Wu, Synthesis of Pyrrolidine Ring-Fused Fullerene Multicarboxylates by Photoreaction. Y. J. Org. Chem. 1998, 63, 4240. (i) Filippone, S.; Maroto, E. E.; Martín-Domenech1, Á.; Suarez, M.; Martín. N. An Efficient Approach to Chiral Fullerene Derivatives by Catalytic Enantioselective 1,3-Dipolar Cycloadditions. Nat. Chem. 2009, 1, 578. (j) Maroto, E. E.; Filippone, S.; Suárez, M.; Martínez-Álvarez, R.; de Cózar, A.; Cossío, F. P.; Martín, N. Stereodivergent Synthesis of Chiral Fullerenes by [3 + 2] Cycloadditions to C60. J. Am. Chem. Soc. 2014, 136, 705. (k) Liu, T.‐X.; Hua, S.; Ma, N.; Zhang, P.; Bi, J.; Zhang, Z.; Zhang, G. Reactivity and Synthetic Applications of α–Functionalized Oxime Acetates: Divergent Access to Fulleropyrrolidines and Mono- and Disubstituted

1-Fulleropyrrolines

via

Copper-Catalyzed

Redox-Neutral

N-Heteroannulation with [60]Fullerene. Adv. Synth. Catal. 2018, 360, 142. (6) (a) Jin, B.; Peng, R.-F.; Shen, J.; Chu, S.-J. Synthesis of Fulleropyrrolidines



Page 40 of 44

through the Reaction of [60]Fullerene with Quaternary Ammonium Salts and Amino Acids. Tetrahedron Lett. 2009, 50, 5640. (b) Zhu, S.-E; Cheng, X.; Li, Y.-J.; Mai, C.-K.; Huang, Y.-S.; Wang, G.-W.; Peng, R.-F.; Jin, B.; Chu, S.-J. Study on the Thermal Reactions of [60]Fullerene with Amino Acids and Amino Acid Esters. Org. Biomol. Chem. 2012, 10, 8720. (c) Jin, B.; Shen, J.; Peng, R.-F.; Chen, C.-D.; Chu, S.-J. Reactions of [60]Fullerene with Halides and Amino Acids to Synthesize Fulleropyrrolidines. Eur. J. Org. Chem. 2014, 6252. (d) Lim, S. H.; Jeong, H. C.; Sohn, Y.; Kim, Y.-I.; Cho, D. W.; Woo, H.-J.; Shin, I.-S.; Yoon, U. C.; Mariano, P. S. Single Electron Transfer-Promoted Photochemical Reactions of Secondary

N-Trimethylsilylmethyl-N-benzylamines

Leading

to

Aminomethylation of Fullerene C60. J. Org. Chem. 2016, 81, 2460. (e) Jeong, H. C.; Lim, S. H.; Cho, D. W.; Kim, S. H.; Mariano, P. S. Single Electron Transfer Promoted Photoaddition Reactions of α-Trimethylsilyl Substituted Secondary N-Alkylamines with Fullerene C60. Org. Biomol. Chem. 2016, 14, 10502. (f) Tuktarov, A. R.; Shakirova, Z. R.; Dzhemilev, U. M. One-Pot Method for the Synthesis of 2,5-Unsubstituted Pyrrolidino[3′,4′:1,9]Fullerenes. Org. Lett. 2017, 19, 3863. (7) (a) Troshin, P. A.; Peregudov, A. S.; Mühlbacher, D.; Lyubovskaya, R. N. An Efficient [2+3] Cycloaddition Approach to the Synthesis of Pyridyl–Appended Fullerene Ligands. Eur. J. Org. Chem. 2005, 3064. (b) Shi, J.-L.; Li, F.-B.; Zhang, X.-F.; Wu, J.; Zhang, H.-Y.; Peng, J.; Liu, C.-X.; Liu, L.; Wu, P.; Li, J.-X. Synthesis and Functionalization of Symmetrical 2,5-Diaryl Fulleropyrrolidines:


Page 41 of 44 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


Ferric

Perchlorate-Mediated

One-Step

Reaction

of

[60]Fullerene

with

Arylmethanamines. J. Org. Chem. 2016, 81, 1769. (c) Shi, J.-L.; Zhang, X.-F.; Wang, H.-J.; Li, F.-B.; Zhong, X.-X.; Liu, C.-X.; Liu, L.; Liu, C.-Y.; Qin, H.-M.; Huang, Y.-S. A Protocol for the Preparation of 2,5-Diaryl Fulleropyrrolidines: Thermal

Reaction

of

[60]Fullerene

with

Aromatic

Aldehydes

and

Arylmethanamines. J. Org. Chem. 2016, 81, 7662. (d) Yang, H.-T.; Tan, Y.-C.; Ge, J.; Wu, H.; Li, J.-X.; Yang, Y.; Sun, X.-Q.; Miao, C.-B. Reaction of C60 with Inactive Secondary Amines and Aldehydes and the Cu(OAc)2-Promoted Regioselective

Intramolecular

C-H

Functionalization

of

the

Generated

Fulleropyrrolidines. J. Org. Chem. 2016, 81, 11201. (e) Zhang, H.-Y.; Wang, H.-J.; Li, F.-B.; Liu, C.-X.; Zhang, X.-F.; Liu, L.; Liu, C.-Y. Facile Access to 2,5-Diaryl Fulleropyrrolidines: Magnesium Perchlorate-mediated Reaction of [60]Fullerene with Arylmethylamines and Aryl Aldehydes. RSC Adv. 2016, 6, 79095. (f) Zhang, M.; Wang, H.-J.; Li, F.-B.; Zhong, X.-X.; Huang, Y.-S.; Liu, L.; Liu,

C.-Y.;

Asiri,

A.

M.;

2-Aryl-5-alkyl-fulleropyrrolidines:

Alamry,

K.

A.

Metal-Free-Mediated

Synthesis

of

Reaction

of

[60]Fullerene with Aromatic Aldehydes and Inactive Primary Amines. J. Org. Chem. 2017, 82, 8617. (g) Zhang, M.; Wang, H.-J.; Li, F.-B.; Zhong, X.-X.; Huang, Y.-S.; Liu, L.; Liu, C.-Y. Asiri, A. M.; Alamry, K. A. Stereoselective Synthesis of N-ethyl-2-arylvinyl-5-methyl Fulleropyrrolidines: Reaction of [60]Fullerene with Aromatic Aldehydes and Triethylamine/Diethylamine in the Absence or Presence of Manganese(III) Acetate. Org. Biomol. Chem. 2018, 16,



Page 42 of 44

2975. (8) (a) Mateo-Alonso, A.; Sooambar, C.; Prato, M. Synthesis and Applications of Amphiphilic Fulleropyrrolidine Derivatives. Org. Biomol. Chem. 2006, 4, 1629. (b) Lee, C.-M.; Huang, S.-T.; Huang, S.-H.; Lin, H.-W.; Tsai, H.-P.; Wu, J.-Y.; Lin, C.-M.; Chen, C.-T. C60 Fullerene-Pentoxifylline Dyad Nanoparticles Enhance Autophagy to Avoid Cytotoxic Effects Caused by the β-Amyloid Peptide. Nanomedicine 2011, 7, 107. (c) Grinholc, M.; Nakonieczna, J.; Fila, G.; Taraszkiewicz, A.; Kawiak, A.; Szewczyk, G.; Sarna, T.; Lilge, L.; Bielawski, K. P.

Antimicrobial

Photodynamic

Therapy

with

Fulleropyrrolidine:

Photoinactivation Mechanism of Staphylococcus Aureus, in Vitro and in Vivo Studies. Appl. Microbiol. Biotechnol. 2015, 99, 4031. (9) (a) Delgado, J. L.; Espildora, E.; Liedtke, M.; Sperlich, A.; Rauh, D.; Baumann, A.; Deibel, C.; Dyakonov, V.; Martin, N. Fullerene Dimers (C60/C70) for Energy Harvesting. Chem.-Eur. J. 2009, 15, 13474. (b) Matsumoto, K.; Hashimoto, K.; Kamo, M.; Uetani, Y.; Hayase, S.; Kawatsura, M.; Itoh, T. Design of Fulleropyrrolidine Derivatives as an Acceptor Molecule in a Thin Layer Organic Solar Cell. J. Mater. Chem. 2010, 20, 9226. (c) Mumyatov, A. V.; Prudnov, F. A.; Inasaridze, L. N.; Mukhacheva, O. A.; Troshin, P. A. High LUMO Energy Pyrrolidinofullerenes as Promising Electron-Acceptor Materials for Organic Solar Cells. J. Mater. Chem. C 2015, 3, 11612. (d) Sartorio, C.; Campisciano, V.; Chiappara, C.; Cataldo, S.; Scopelliti, M.; Gruttadauria, M.; Giacalone, F.; Pignataro, B. Enhanced Power-Conversion Efficiency in Organic Solar Cells


Page 43 of 44 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


Incorporating Copolymeric Phase-Separation Modulators. J. Mater. Chem. A 2018, 6, 3884. (10)(a) Liddell, P. A.; Kodis, G.; Moore, A. L.; Moore, T. A.; Gust, D. Photonic Switching

of

Photoinduced

Electron

Transfer

in

a

Dithienylethene−Porphyrin−Fullerene Triad Molecule. J. Am. Chem. Soc. 2002, 124, 7668. (b) Kumar, K. S.; Patnaik, A. Tunable Electronic Properties of a Proton−Responsive N,N−Dimethylaminoazobenzene Fullerene (C60) Dyad. ChemPhysChem 2010, 11, 3645. (c) Tuktarov, A. R.; Khuzin, A. A.; Tulyabaev, A. R.; Venidictova, O. V.; Valova, T. M.; Barachevsky, V. A.; Khalilov, L. M.; Dzhemilev, U. M. Synthesis, Structure and Photochromic Properties of Hybrid Molecules Based on Fullerene C60 and Spiropyrans. RSC Adv. 2016, 6, 71151. (11)(a) Wu, J.; Liu, C.-X.; Wang, H.-J.; Li, F.-B.; Shi, J.-L.; Liu, L.; Li, J.-X.; Liu, C.-Y.; Huang, Y.-S. Cu(OAc)2-Mediated Reaction of [60]Fullerene with Aldehydes and Primary Amines for the Synthesis of Fulleropyrrolines. J. Org. Chem. 2016, 81, 9296. (b) Peng, J.; Xiang, J.-J.; Wang, H.-J.; Li, F.-B.; Huang, Y.-S.; Liu, L.; Liu, C.-Y.; Asiri, A. M.; Alamry, K. A. DMAP-Mediated Synthesis of Fulleropyrrolines: Reaction of [60]Fullerene with Aromatic Aldehydes and Arylmethanamines in the Absence or Presence of Manganese(III) Acetate. J. Org. Chem. 2017, 82, 9751. (12)Peng, J.; Huang, G.; Wang, H.-J.; Li, F.-B.; Huang, C.; Xiang, J.-J.; Huang, Y.; Liu, L.; Liu, C.-Y.; Asiri, A. M.; Alamry, K. A. TEMPO-Mediated Synthesis of Tetrahydropyridinofullerenes:

Reaction

of


[60]Fullerene

with


α-Methyl-Substituted Arylmethanamines and Aldehydes in the Presence of 4-Dimethylaminopyridine. J. Org. Chem. 2018, 83, 85. (13)Zhang, M.; Zhang, H.-Y.; Wang, H.-J.; Li, F.-B.; Huang, Y.; Liu, L.; Liu, C.-Y.; Asiri, A. M.; Alamry, K. A. Stereoselective Synthesis of Cyclopentafullerenes: the Reaction of [60]Fullerene with Aldehydes and Triethylamine Promoted by Magnesium Perchlorate. New J. Chem. 2018, 42, 9291. (14)Huang, G.; Zhang, M.; Wang, H.-J.; Li, F.-B.; Yang, F.; Liu, L.; Liu, C.-Y.; Asiri, A. M.; Alamry, K. A. Metal-Free Synthesis of Fulleropyrrolidin-2-ols: a Novel Reaction of [60]Fullerene with Amines and 2,2-Disubstituted Acetaldehydes. Org. Biomol. Chem. 2018, 16, 7648.


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Monosubstituted

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