S. Abe et al. / Tetrahedron: Asymmetry 16 (2005) 15–19
17
OH
HN
9
OH
a
b
OHC
N
+
11
F
CHO
O
O
10
O
N
HN
O
N
Boc
c
OHC
N
O
d
1c
O
HN
12
13
Boc
Scheme 3. Reagents and conditions: (a) K2CO3, DMF; 42%; (b) BocNHOCH2COOH, WSC, CH2Cl2; 89%; (c) C60, MeNHCH2COOH, toluene;
32%; (d) TFA, CH2Cl2; quant.
conditions, which were slightly modified to fit our
experiments.13
Another synthetic strategy was used for the synthesis of
the fullerene-containing pyrrolidines via a process of
1,3-dipolar cycloaddition of azomethine (Scheme 3).14–18
A mixture of compound 9 (1 equiv), compound 10
(1 equiv) and K2CO3 (1.2equiv) in DMF was stirred
for 14 h at room temperature, and then for 12more
hours at 50–60 °C. After the usual treatment, the
product was then purified using chromatography, and
compound 11 was produced in 42% yield. BocNH-
OCH2COOH (2equiv), WSC (3 equiv) and 4-dimethyl-
aminopyridine (0.1 equiv) were added to a solution of
compound 11 (1 equiv) in CH2Cl2, and then stirred for
1.5 h at room temperature. The resulting mixture was
purified by silica gel chromatography to afford com-
pound 12a in 89% yield.§ Compound 12 (5 equiv) and
N-methylglycine (1 equiv) were added to a solution of
C60 (100 mg) in toluene. The solution was then refluxed
for 2h. The product was purified with chromatography
to afford compound 13 (37 mg, 32%).– Finally, removal
of the Boc group in compound 13 was performed using
TFA, to create target compound 1c (20 mg, quant.).
1,8-Diazabicyclo[5,4,0]undec-7-ene (DBU, 5 equiv) had
been added to a solution of C60 (100 mg), 7a (1.1 equiv)
and I2 (3 equiv) in toluene at room temperature. After
the mixture was stirred for 12h, additional portions of
7a (0.5 equiv) and I2 (1 equiv) were added, and the mix-
ture was stirred for another 12h. The product was then
purified by chromatography (compound 8a, 36 mg,
24%).à Finally, removal of the phthaloyl moiety in com-
pound 8a was performed using 40% methylamine/meth-
anol, which resulted in the target compound 1a.
Another target compound, 1b, was synthesized from
compound 2b, instead of 2a. Compound 1b was synthe-
sized according to almost the same procedure as de-
scribed above. The yield of the Bingel reaction for 1b
was 23%. In this synthetic route, there were two key
reactions. When the Cbz group of compound 3a was re-
moved by a catalyst with 10% palladium–carbon, the N–
O bond of compound 3a was cleaved under the reaction
conditions. Therefore, two more reactions (the removal
of the phthaloyl group and the protection with the Boc
group) were required to reach the intermediate 5a. The
second key step was the reaction for the modification
of C60 with the maloimide derivative 7a. When we used
compound 6a instead of compound 7a for the Bingel
reaction, the cycloaddition reaction did not proceed at
all. From this result, it was found that protection of
the oxylamino group with the phthaloyl moiety was suit-
able for this reaction. However, the reaction mechanism
is not completely clear.
Using the fullerenes 1a–c with oxylamino moieties, the
coupling reaction between oxylamino group and sacchar-
ide was performed. In a typical procedure, the oligosac-
charide was dissolved with KH2PO4 buffer solution/
methanol (1:1). The solution was then added to a solu-
tion of C60 derivative in chloroform/methanol (1:1).
§ NMR data for 12: 1H NMR (CDCl3): d 1.3–1.4 (m, 1H), 1.48 (s, 9H),
1.6–1.7 (m, 3H), 1.82(d, H2 ,
J = 12.6 Hz), 2.91 (dt, 2H, J = 2.4,
12.6 Hz), 3.94 (d, 2H, J = 13.2 Hz), 4.27 (t, 2H, J = 6 Hz), 4.44 (s,
2H), 6.90 (d, 2H, J = 12Hz), 7.74 (d, 2H, J = 6 Hz), 9.76 (s, 1H).
– NMR data for 13: 1H NMR (CDCl3): d 1.3–1.45 (m, 2H), 1.47 (s,
9H), 1.47–1.6 (m, 1H), 1.66 (q, 2H, J = 6.6 Hz), 1.75–1.85 (m, 2H),
2.65–2.75 (m, 2H), 2.79 (s, 3H), 3.65–3.75 (m, 2H), 4.22 (d, 1H,
J = 9 Hz), 4.26 (t, 2H, J = 7 Hz), 4.43 (s, 2H), 4.85 (s, 1H), 4.96 (d,
1H, J = 9 Hz), 6.97 (d, 2H, J = 8.4 Hz), 7.65 (s, 2H), 7.72 (s, 1H).
TOF-Mass: 1154 (M+H).
à NMR data for 8a: 1H NMR (CDCl3): d 1.45–1.5 (t, 3H, J = 7.1 Hz),
1.75–1.8 (m, 2H), 1.8–1.9 (m, 4H), 3.65 (q, 2H, J = 6.0 Hz), 4.25 (t,
2H, J = 5.8 Hz), 4.57 (q, 2H, J = 7.1 Hz), 7.7–7.8 (m, 4H). TOF-
Mass: 1080 (M+H).