Synthesis of self-folded molecular rotors controlled by edge-to-face CH/π aromatic interactions

Article abstract of DOI:10.1055/s-0029-1217528

A series of novel self-folded molecular rotors were synthesized and characterized by ¹H NMR, ¹³C NMR, HRMS, and IR data. All but two compounds were also studied by X-ray crystallography. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1217528

LETTER
2028
Synthesis of Self-Folded Molecular Rotors Controlled by Edge-to-Face
CH/p Aromatic Interactions
S
ynthesisof Self-F
i
olded
t
a
la
r
R
otors o Li, Yanping Zhu, Jing Qin, Huizhen Guo, Lin Li, Anxin Wu*
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, Central China Normal University, Wuhan 430079,
P. R. of China
E-mail: chwuax@mail.ccnu.edu.cn
Received 25 March 2009
sized as reported previously.15 Intermediates 5h and 5i
were produced from 5g through Sonogashira cross-cou-
pling reactions (see Supporting Information). The reac-
tion of intermediates 5a–i with commercial aliphatic
amines 6a–d in DMF, in the presence of formaldehyde,
resulted in the formation of clip molecules 7a–l (Table 1).
Much to our satisfaction, the experimental results showed
that most substrates afforded the expected products in
good yields. The series inspired us to research the influ-
ence of the substituents of flexible side walls (R5–R9) and
rigid side walls (R1–R4) on the edge-to-face aromatic in-
teraction.
All compounds 7a–l gave satisfying 1H NMR, 13C NMR,
HRMS, and IR data. For all but compounds 7h and 7i,
crystals of appropriate size and quality for single crystal
X-ray diffraction studies were obtained. It was found that
all compounds adopted a conformation in which the flex-
ible side walls and the rigid side walls were almost orthog-
onal, and the crystal structures contained weak CH/π
interactions of the edge-to-face type (Figure 1). Such
CH/π interaction is known to arise from hydrogen bond-
ing between soft acids and soft bases. Modifying the elec-
tronic properties of the aromatic substituents allows the
strength of such interactions to be varied. However, ac-
cording to the 1H NMR spectra of these compounds (see
Supporting Information), the peaks attributed to H-1 and
H-2 appeared at the same position (Figure 1). It could
therefore be concluded that the C–C bond adjacent to the
aromatic ring could freely rotate in solution state but was
fixed by intramolecular CH/π interaction in the solid state.
Abstract: A series of novel self-folded molecular rotors were syn-
thesized and characterized by 1H NMR, 13C NMR, HRMS, and IR
data. All but two compounds were also studied by X-ray crystallog-
raphy.
Key words: self-folded, molecular rotors, CH/π interactions,
molecular clips, diethoxycarbonyl glycoluril
Edge-to-face orientations between aromatic rings were
initially observed almost 50 years ago in the herringbone
structure of crystalline benzene.1 However, the signifi-
cance of these relatively weak edge-to-face CH/π aromat-
ic interactions did not become evident until 1985 when
Burley and Petsko, and Singh and Thornton presented ev-
idence that they played a significant role in protein struc-
ture.2 Edge-to-face aromatic interactions can also be
important in such diverse areas as crystal packing and
crystal engineering,3,4 supramolecular assemblies and
host-guest binding,5 drug–receptor interactions,6 and oth-
er areas of molecular recognition.7 Examples have
emerged where intramolecular edge-to-face interactions
have a considerable role in determining the conformation
of flexible organic molecules in solution and in the crys-
talline state.8
In addition, facing the challenge of constructing nanoscale
machines, it has been noted that molecular motors stand
out as essential components to provide power to such sys-
tems.9 The diversity of fascinating biological motors, such
as the kinesin or myosin linear and ATP-ase rotary motor
systems,10 has been a source of inspiration for the devel-
opment of artificial molecular mechanical devices (such
as switches, shuttles, and muscles)11 and a variety of ele-
gant rotor systems.12 A number of systems have been de-
signed in which movement or change in shape occurs in
response to external chemical, electrochemical, or photo-
chemical stimuli.13 Until now, few rotor systems that are
controlled by CH/π aromatic interactions have been re-
ported. Following our previous work,14 herein we report
the synthesis of self-folded molecular rotors controlled by
edge-to-face CH/π aromatic interactions.
As shown for compounds 7a–d in Figure 2, substitution of
the hydrogen atoms in the π-aromatic ring by electron-do-
nating groups [7b (CH3) and 7c (OCH3)] or an electron-
withdrawing group [7d (Br)] was accompanied, respec-
The synthetic route used to obtain clip molecules 7a–l is
shown in Scheme 1. Compounds 4 and 5a–g were synthe-
SYNLETT 2009, No. 12, pp 2028–2034
x
x
.x
x
.2
0
0
9
Advanced online publication: 01.07.2009
DOI: 10.1055/s-0029-1217528; Art ID: W04209ST
© Georg Thieme Verlag Stuttgart · New York
Figure 1 Fast rotation in solution and fixed conformation in solid
state of clip molecules

LETTER
Synthesis of Self-Folded Molecular Rotors
2029
tively, by an increase or decrease in the degree of the con- substituted analogue 7a (3.077 Å), and longer in 7d (3.260
formational folding. The distance between the aromatic Å) than in 7a.
CH and the best plane of the phenyl ring was found to be
shorter in 7b (2.835 Å) and 7c (2.905 Å) than in the non-
Table 1 Isolated Yields and Products in the Synthesis of Clip Molecules from Various Substrates
Entry
5a–j
6a–d
Product (R = COOEt)
Yield (%)a
O
O
O
N
N
N
N
N
N
NH
COOEt
R
EtOOC
R
N
1
58
H2N
NH
6a
O
7a
7b
5a
5b
O
O
O
N
N
NH
COOEt
N
N
N
EtOOC
R
R
N
2
3
4
5
6
7
45
67
45
50
52
56
H2N
NH
N
6a
O
O
O
MeO
MeO
MeO
MeO
N
N
N
N
NH
COOEt
NH
R
EtOOC
R
N
H2N
N
N
6a
O
O
5c
7c
O
N
O
O
Br
Br
NH
N
N
N
EtOOC
COOEt
NH
R
R
N
H2N
N
O
N
6a
Br
Br
5d
7d
O
O
N
N
N
NH
COOEt
NH
N
N
EtOOC
R
R
N
N
N
H2N
N
6a
NO2
NO2
O
O
5e
7e
O
O
OMe
OMe
N
N
NH
N
N
N
N
EtOOC
COOEt
NH
R
R
H2N
6a
NO2
NO2
O
O
O
O
5f
7f
N
N
NH
COOEt
NH
N
N
N
N
EtOOC
R
R
H2N
6a
I
I
O
O
5g
7g
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2030
Y. Li et al.
LETTER
Table 1 Isolated Yields and Products in the Synthesis of Clip Molecules from Various Substrates (continued)
Entry
5a–j
6a–d
Product (R = COOEt)
Yield (%)a
O
O
N
N
NH
COOEt
NH
N
N
N
N
EtOOC
R
R
N
8
82
H2N
O
O
O
O
6a
TMS
TMS
5h
7h
N
N
N
N
N
N
NH
COOEt
NH
R
EtOOC
R
N
9
58
H2N
O
O
O
O
6a
5i
7i
N
N
NH
COOEt
N
N
N
N
CF3
CF3
EtOOC
EtOOC
EtOOC
R
R
R
R
R
R
N
N
N
10
11
12
25
65
72
H2N
NH
6b
O
O
O
O
5a
5a
5a
7j
7k
7l
N
N
NH
N
N
N
N
COOEt
H2N
NH
6c
O
O
O
O
OMe
OMe
OMe
OMe
OMe
OMe
N
N
NH
N
N
N
N
COOEt
NH
H2N
O
O
6d
a Isolated yield of last step.
This finding was consistent with the expectation that in- fect of the iodine atom. For compounds 7j, 7k and 7l, elec-
creasing the π-electron density of the aromatic ring will tron-donating groups [7k (CH3) and 7l (OCH3)] or an
favor the CH/π-interacting conformation.16 For 7e, the in- electron-withdrawing group [7j (CF3)] were incorporated
corporation of an ortho-nitro group into molecule 7b was into the CH aromatic ring, respectively. It was found that
found to be unfavorable to the CH/π systems. In this case, a stronger electron-donating effect resulted in weaker
the CH/π distance now became 2.895 Å, so the strength of CH/π interactions, which is in agreement with the hydro-
the interaction was much weaker than that of 7b. When in- gen bond nature of the CH/π interaction. Surprisingly, the
troducing an ortho-nitro and an ortho-methoxy to 7a si- CH/π hydrogen bond in 7j was a little weaker than that
multaneously, the π-system of 7f was found to be more found in 7a, according to the distance between the CH and
electron-deficient than that of 7a as a longer distance be- the π-ring (3.157 Å). This may be due to the special chem-
tween the CH and the π-ring was noted (3.144 Å). The dis- ical properties of the fluorine atom.
tance in 7g was similar to that found in 7a (2.949 Å),
which may be due to the weak electron-withdrawing ef-
Synlett 2009, No. 12, 2028–2034 © Thieme Stuttgart · New York

LETTER
Synthesis of Self-Folded Molecular Rotors
2031
O
O
HO
O
HN
EtOOC
NH
COOEt
NH
O
O
CO2Et
CO2Et
(iii)
(i), (ii)
(iv)
OH
HO
HN
OH
O
1
2
3
O
O
R1
R1
R5
R2
R3
R2
R3
N
N
N
R6
R7
N
N
NH
(v)
R
R
N
R
R
N
NH
R9
R4
R4
R8
O
O
R = COOEt
R = COOEt
5
7
R1
R6
R7
R8
R5
R2
R3
X
X
H2N
R9
R4
4
6
X = Cl
X = Br
Scheme 1 Reagents and conditions: (i) AcOH, Br2, H2O; (ii) EtOH, HCl (g), 0 °C; (iii) PhH, H2NCONH2, TFA, reflux; (iv) 4, t-BuOK,
DMSO; (v) 6, HCHO (37%), DMF.
In summary, we reported the synthesis of a series of novel
self-folded molecular rotors in which the conformation
was controlled by the intramolecular CH/π interac-
tion.17,18 In addition, the 1H NMR spectra and the crystal
structure analysis provide strong evidence for the substit-
uent effects on CH/π interaction. The exact mechanism
and the development of a controllable molecular rotor are
under investigation.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
We gratefully acknowledge the financial support of this work by
Central China Normal University and the National Natural Science
Foundation of China (Grant Number 20672042 and Grant Number
20872042).
References and Notes
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Figure 2 Substituent effects on CH/π interactions in the solid state
Synlett 2009, No. 12, 2028–2034 © Thieme Stuttgart · New York

2032
Y. Li et al.
LETTER
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cross-coupling reactions. Thus, a suspension of 5 (5 mmol)
in 37% aq formaldehyde (3.5 mL) and DMF (30 mL) was
brought to reflux under magnetic stirring. A solution of
aliphatic amine (5 mmol) in DMF (20 mL) was added
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compound 7 as a solid.
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(18) Compound 7a: Yield: 58%; white solid; mp 159–160 °C; IR
(KBr): 2960, 2923, 2852, 1737, 1635, 1377, 1267, 752, 722
cm–1; 1H NMR (CDCl3, 400 MHz): d = 7.50–7.47 (m, 2 H),
7.30–7.19 (m, 5 H), 6.88–6.85 (m, 2 H), 4.86 (d, J = 15.6
Hz, 2 H), 4.65 (d, J = 15.2 Hz, 4 H), 4.39–4.25 (m, 6 H),
2.88 (s, 2 H), 1.38–1.25 (m, 6 H); 13C NMR (CDCl3,100
MHz): d = 165.9, 165.6, 156.9, 136.2, 130.0, 129.0, 128.0,
127.4, 114.2, 80.3, 75.9, 63.3, 63.2, 59.8, 53.7, 45.5, 14.0,
13.9; HRMS: m/z [M + H]+ calcd for C27H29N5O6: 519.2118;
found: 520.2191.
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Compound 7b: Yield: 45%; white solid; mp 160–161 °C; IR
(KBr): 3064, 2973, 2938, 1738, 1718, 1452, 1414, 1263, 752
cm–1; 1H NMR (CDCl3, 400 MHz): d = 7.24–7.18 (m, 5 H),
6.85–6.82 (m, 2 H), 4.77 (d, J = 15.6 Hz, 2 H), 4.62 (d,
J = 13.6 Hz, 2 H), 4.57 (d, J = 15.6 Hz, 2 H), 4.37–4.24 (m,
6 H), 2.87 (s, 2 H), 2.22 (s, 6 H), 1.36–1.28 (m, 6 H); 13
C
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Mottier, L.; Paolucci, F.; Roffia, S.; Wurpel, G. W. H.
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L. H. Chem. Commun. 2007, 1349. (b) Zheng, X. L.;
Mulcahy, M. E.; Horinek, D.; Galeotti, F.; Magnera, T. F.;
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NMR (CDCl3, 100 MHz): d = 165.9, 165.7, 156.9, 136.5,
136.0, 133.4, 131.2, 128.9, 127.9, 127.2, 80.4, 75.9, 63.1,
63.0, 59.8, 53.7, 45.0, 19.1, 13.9, 13.8; HRMS: m/z [M + H]+
calcd for C29H33N5O6: 547.2431; found: 548.2504.
Compound 7c: Yield: 67%; white solid; mp 228–229 °C; IR
(KBr): 3069, 2957, 2936, 2852, 1762, 1718, 1465, 1417,
1282, 741 cm–1; 1H NMR (CDCl3, 400 MHz): d = 7.21–7.19
(m, 3 H), 7.00–6.91 (m, 4 H), 4.78 (d, J = 16.0 Hz, 2 H),
4.68 (d, J = 14.0 Hz, 2 H), 4.61 (d, J = 16.0 Hz, 2 H), 4.40–
4.28 (m, 6 H), 3.91 (s, 6 H), 2.94 (s, 2 H), 1.38–1.30 (m,
6 H); 13C NMR (CDCl3, 100 MHz): d = 165.9, 165.7, 156.9,
147.7, 136.3, 128.9, 128.7, 127.9, 127.2, 113.3, 80.3, 76.0,
63.2, 63.1, 59.8, 56.0, 53.6, 45.1, 13.9, 13.8; HRMS: m/z
[M + H]+ calcd for C29H33N5O8: 579.2329; found: 580.2402.
Compound 7d: Yield: 45%; yellow solid; mp 247–248 °C;
IR (KBr): 3061, 2927, 2852, 1761, 1743, 1721, 1457, 1420,
1251, 752 cm–1; 1H NMR (CDCl3, 400 MHz): d = 7.42–7.21
(m, 5 H), 6.95 (d, J = 6.8 Hz, 2 H), 5.67 (d, J = 16.0 Hz,
2 H), 4.68 (d, J = 13.6 Hz, 2 H), 4.57 (d, J = 16.0 Hz, 2 H),
4.40–4.26 (m, 6 H), 3.00 (s, 2 H), 1.38–1.30 (m, 6 H); 13
C
NMR (CDCl3, 100 MHz): d = 165.7, 165.5, 156.7, 137.8,
136.2, 133.9, 129.1, 128.1, 127.4, 124.2, 79.0, 76.4, 63.4,
63.2, 59.9, 54.0, 44.9, 14.0, 13.9; HRMS: m/z [M + H]+ calcd
for C27H27Br2N5O6: 675.0328; found: 676.0401. Compound
7e: Yield: 50%; white solid; mp 163–165 °C; IR (KBr):
3448, 2984, 1772, 1619, 1533, 1459, 1420, 1368, 1319,
1259, 1224, 1154, 1099, 1077, 1027, 980, 914, 852, 815
cm–1; 1H NMR (CDCl3, 400 MHz): d = 7.44 (s, 1 H), 7.29–
7.23 (m, 3 H), 6.93–6.92 (d, J = 6.8 Hz, 2 H), 4.93 (d,
J = 16.0 Hz, 1 H), 4.87 (d, J = 16.0 Hz, 1 H), 4.85–4.53 (m,
4 H), 4.37–4.25 (m, 6 H), 2.90 (s, 2 H), 2.33 (s, 3 H), 2.20 (s,
3 H), 1.37–1.29 (m, 6 H); 13C NMR (CDCl3, 150 MHz): d =
165.6, 165.4, 156.9, 156.4, 152.1, 138.5, 136.3, 135.0,
133.2, 129.1, 128.1, 127.4, 126.3, 79.7, 76.0, 63.4, 63.2,
59.9, 59.8, 53.9, 45.2, 39.7, 19.9, 14.5, 13.9, 13.8; HRMS:
m/z [M + H]+ calcd for C29H32N6O8: 592.2282; found:
593.2354.
(17) Synthesis of 7; General Procedure
DMF and the aliphatic amines had to be freshly distilled or
recrystallized under nitrogen. Compounds 4 and 5a–g were
synthesized as reported previously.15 The intermediates 5h
and 5i were then produced from 5g through Sonogashira
Compound 7f: Yield: 52%; white solid; mp 158–160 °C; IR
(KBr): 3062, 2977, 2937, 2847, 1754, 1718, 1520, 1470,
1423, 1276, 814, 744 cm–1; 1H NMR (CDCl3, 400 MHz):
d = 7.86 (d, J = 9.2 Hz, 1 H), 7.28–7.22 (m, 3 H), 6.93–6.89
Synlett 2009, No. 12, 2028–2034 © Thieme Stuttgart · New York

LETTER
(m, 3 H), 5.80 (d, J = 16.8 Hz, 1 H), 5.74 (d, J = 16.0 Hz,
Synthesis of Self-Folded Molecular Rotors
2033
(KBr): 3053, 2992, 2966, 2906, 1761, 1715, 1416, 1415,
1254, 820, 739 cm–1; 1H NMR (CDCl3, 400 MHz): d = 7.49–
7.46 (m, 2 H), 7.29–7.26 (m, 2 H), 7.01 (d, J = 7.6 Hz, 2 H),
6.75 (d, J = 8.0 Hz, 2 H), 4.86 (d, J = 16.0 Hz, 2 H), 4.64 (d,
J = 16.0 Hz, 2 H), 4.37–4.27 (m, 6 H), 2.84 (s, 2 H), 2.27 (s,
3 H), 1.38–1.30 (m, 6 H); 13C NMR (CDCl3, 100 MHz): d =
166.0, 165.7, 156.9, 136.8, 136.2, 133.4, 130.0, 128.9,
128.7, 128.0, 80.3, 76.0, 63.2, 63.1, 59.8, 53.5, 45.4, 21.0,
14.0, 13.9; HRMS: m/z [M + H]+ calcd for C28H31N5O6:
533.2274; found: 534.2347.
1 H), 4.68 (d, J = 14.0 Hz, 1 H), 4.62 (d, J = 16.8 Hz, 1 H),
4.52 (d, J = 14.4 Hz, 1 H), 4.40 (d, J = 14.0 Hz, 1 H), 4.38–
4.21 (m, 6 H), 4.00 (s, 3 H), 2.99 (d, J = 13.2 Hz, 1 H), 2.66
(d, J = 13.6 Hz, 1 H), 1.38–1.25 (m, 6 H); 13C NMR (CDCl3,
100 MHz): d = 165.7, 165.5, 160.3, 156.7, 144.2, 136.2,
133.5, 129.1, 128.1, 127.5, 126.9, 126.0, 110.6, 79.3, 63.4,
63.2, 60.6, 58.9, 56.8, 53.9, 38.6, 36.7, 13.9, 13.8; HRMS:
m/z [M + H]+ calcd for C28H30N6O9: 594.2074; found:
595.2147.
Compound 7g: Yield: 56%; white solid; mp 233–234 °C; IR
(KBr): 3448, 2979, 2935, 2825, 1950, 1754, 1721, 1585,
1558, 1497, 1465, 1417, 1372, 1301, 1277, 1252, 1213,
1168, 1141, 1110, 1073, 1029, 986, 961, 910, 862, 828
cm–1; 1H NMR (CDCl3, 400 MHz): d = 7.83 (d, J = 8.0 Hz,
1 H), 7.47 (d, J = 8.0 Hz, 1 H), 6.94–6.88 (m, 3 H), 5.45 (d,
J = 16.0 Hz, 1 H), 4.88 (d, J = 16.0 Hz, 1 H), 4.68–4.39 (m,
4 H), 4.37–4.26 (m, 6 H), 2.94 (d, J = 14.0 Hz, 1 H), 2.88 (d,
J = 14.0 Hz, 1 H), 1.38–1.30 (m, 6 H); 13C NMR (CDCl3,
150 MHz): d = 165.7, 165.5, 156.9, 156.7, 139.9, 139.4,
136.8, 136.3, 130.8, 129.3, 129.0, 128.0, 127.3, 100.6, 79.4,
76.2, 63.2, 63.1, 60.0, 59.6, 53.8, 49.7, 46.0, 13.4, 13.8;
HRMS: m/z [M + H]+ calcd for C27H28IN5O6: 645.1084;
found: 646.1157.
Compound 7h: Yield: 82%; white solid; mp 212–213 °C; IR
(KBr): 3448, 3066, 2960, 2930, 2851, 2153, 1772, 1652,
1587, 1544, 1461, 1419, 1368, 1318, 1254, 1223, 1157,
1098, 1098, 1077, 1027, 987, 919, 905, 859 cm–1; 1H NMR
(CDCl3, 400 MHz): d = 7.44 (d, J = 7.6 Hz, 2 H), 7.29–7.20
(m, 4 H), 6.93 (d, J = 7.6 Hz, 2 H), 5.73 (d, J = 16.0 Hz,
1 H), 4.84 (d, J = 16.0 Hz, 1 H), 4.70 (d, J = 14.4 Hz, 1 H),
4.62 (d, J = 14.4 Hz, 1 H), 4.60 (d, J = 16.4 Hz, 1 H), 4.49
(d, J = 16.4 Hz, 1 H), 4.38–4.25 (m, 6 H), 3.02 (d, J = 13.2
Hz, 1 H), 2.87 (d, J = 13.2 Hz, 1 H), 1.38–1.26 (m, 6 H),
0.30 (s, 9 H); 13C NMR (CDCl3, 150 MHz): d = 166.1, 165.8,
157.1, 156.6, 138.5, 136.6, 132.4, 130.3, 129.2, 128.9,
128.2, 128.0, 127.5, 127.3, 123.9, 102.3, 99.6, 80.1, 76.1,
63.3, 63.1, 60.4, 59.5, 54.0, 45.7, 42.5, 14.0, 13.9; HRMS:
m/z [M + H]+ calcd for C32H37N5O6Si: 615.2513; found:
616.2586.
Compound 7i: Yield: 58%; white solid; mp 288–289 °C; IR
(KBr): 3424, 3059, 2983, 2930, 2846, 1739, 1721, 1588,
1545, 1460, 1420, 1368, 1315, 1259, 1224, 1172, 1148,
1080, 1026, 984, 917, 905, 854, 802 cm–1; 1H NMR (CDCl3,
400 MHz): d = 8.63 (d, J = 8.4 Hz, 1 H), 7.90–7.84 (m, 2 H),
7.65–7.45 (m, 5 H), 7.33–7.29 (m, 2 H), 7.25–6.97 (m, 3 H),
6.95–5.90 (m, 2 H), 5.95 (d, J = 16.0 Hz, 1 H), 4.90 (d,
J = 16.0 Hz, 1 H), 4.75–4.63 (m, 4 H), 4.57–4.26 (m, 6 H),
3.06 (d, J = 13.6 Hz, 1 H), 2.97 (d, J = 13.6 Hz, 1 H), 1.38–
1.25 (m, 6 H); 13C NMR (CDCl3, 150 MHz): d = 165.9,
165.6, 156.9, 156.6, 137.8, 136.8, 133.3, 133.1, 132.3,
130.9, 130.3, 129.3, 128.9, 127.8, 127.5, 126.9, 126.5,
126.4, 125.3, 124.2, 120.7, 92.3, 91.6, 80.1, 75.9, 63.4, 63.3,
59.4, 53.9, 45.7, 42.8, 13.9 cm–1. HRMS: m/z [M + H]+ calcd
for C39H35N5O6: 669.2587; found: 670.2660.
Compound 7j: Yield: 25%; white solid; mp 177–179 °C; IR
(KBr): 3066, 2956, 2922, 1737, 1716, 1460, 1416, 1266,
850, 750 cm–1; 1H NMR (CDCl3, 400 MHz): d = 7.51–7.45
(m, 4 H), 7.32–7.29 (m, 2 H), 6.94 (d, J = 2.0 Hz, 2 H), 4.86
(d, J = 15.6 Hz, 2 H), 4.64 (d, J = 15.6 Hz, 2 H), 4.60 (d,
J = 14.0 Hz, 2 H), 4.39–4.28 (m, 6 H), 2.90 (s, 2 H), 1.38–
1.25 (m, 6 H); 13C NMR (CDCl3, 100 MHz): d = 165.8,
165.6, 157.0, 140.5, 136.2, 130.0, 129.1, 128.0, 125.0,
122.8, 80.3, 75.9, 63.3, 59.9, 53.2, 45.5, 29.7, 14.0; HRMS:
m/z [M + H]+ calcd for C28H28F3N5O6: 587.1992; found:
588.2064.
Compound 7l: Yield: 72%; white solid; mp 190–192 °C; IR
(KBr): 3068, 2981, 2954, 2841, 1766, 1738, 1719, 1466,
1421, 1226, 736 cm–1; 1H NMR (CDCl3, 400 MHz): d =
7.47–7.43 (m, 2 H), 7.27–7.24 (m, 2 H), 6.12 (s, 2 H), 4.86
(d, J = 16.0 Hz, 2 H), 4.65 (d, J = 15.6 Hz, 4 H), 4.38–4.29
(m, 6 H), 3.81 (s, 6 H), 3.79 (s, 3 H), 2.81 (s, 2 H), 1.38–1.31
(m, 6 H); 13C NMR (CDCl3, 100 MHz): d = 165.8, 165.5,
156.9, 152.5, 136.6, 136.2, 131.8, 129.7, 127.8, 105.7, 80.2,
75.8, 63.2, 63.1, 60.6, 59.6, 55.8, 54.0, 45.3, 13.9, 13.8;
HRMS: m/z [M + H]+ calcd for C30H35N5O9: 609.2435;
found: 610.2508.
(19) Crystal data for compound 7a: C27H29N5O6; MW = 519.55;
monoclinic; a = 15.655(4), b = 8.752(2), c = 19.427(5) Å,
b = 110.550(5)°; V = 2492.4(11) Å3; T = 292(2) K; space
group P21/n; Z = 4; m(Mo-Ka) = 0.100 mm–1; 13703
reflections measured, 4889 unique (Rint = 0.0476) which
were used in all calculations. The final wR2 (F2) was 0.1980
(all data).
For compound 7b: C29H33N5O6; MW = 547.60; monoclinic;
a = 9.9597(9), b = 23.109(2), c = 12.4028(11) Å,
b = 101.193(2)°; V = 2800.3(4) Å3; T = 292(2) K; space
group P21/c; Z = 4; m(Mo-Ka) = 0.092 mm–1; 14003
reflections measured, 4926 unique (Rint = 0.0343) which
were used in all calculations. The final wR2 (F2) was 0.1755
(all data).
For compound 7c: C29H33N5O8; MW = 579.60; monoclinic;
a = 8.1464(6), b = 23.9524(17), c = 15.0281(11) Å,
b = 104.7310(10)°; V = 2836.0(4) Å3; T = 292(2) K; space
group P21/n; Z = 4; m(Mo-Ka) = 0.100 mm–1; 33110
reflections measured, 6772 unique (Rint = 0.0987) which
were used in all calculations. The final wR2 (F2) was 0.1729
(all data).
For compound 7d: C27H27Br2N5O6; MW = 677.36; triclinic;
a = 9.136(3), b = 10.144(3), c = 15.028(4) Å,
a = 90.784(5)°, b = 94.628(5)°, g = 94.984(5)°;
V = 1382.6(7) Å3; T = 292(2) K; space group P1, Z = 2;
m(Mo-Ka) = 2.983 mm–1; 13279 reflections measured, 5386
unique (Rint = 0.1158) which were used in all calculations.
The final wR2 (F2) was 0.1795 (all data).
For compound 7e: C29H32N6O8; MW = 592.61; monoclinic;
a = 7.9571(4), b = 15.6173(6), c = 22.8959(10) Å,
b = 94.0820(10)°; V = 2838.0(2) Å3; T = 292(2) K; space
group P21/c; Z = 4; m(Mo-Ka) = 0.103 mm–1; 21931
reflections measured, 4992 unique (Rint = 0.0254) which
were used in all calculations. The final wR2 (F2) was 0.1761
(all data).
For compound 7f: C56H64N12O19; MW = 1209.19;
tetragonal; a = 15.9660(6), b = 15.9660(6), c = 11.1270(9)
Å, a = b = g = 90.00°; V = 2836.4(3) Å3; T = 292(2) K;
space group P43; Z = 2; m(Mo-Ka) = 0.108 mm–1; 32120
reflections measured, 6183 unique (Rint = 0.1055) which
were used in all calculations. The final wR2 (F2) was 0.1147
(all data).
For compound 7g: C27H28IN5O6; MW = 645.44;
monoclinic; a = 9.0743(10), b = 25.339(3), c = 11.6956(13)
Å, b = 90.212(2)°; V = 2689.2(5) Å3; T = 292(2) K; space
group P21/c; Z = 4; m(Mo-Ka) = 1.242 mm–1; 30097
Compound 7k: Yield: 65%; white solid; mp136–139 °C; IR
Synlett 2009, No. 12, 2028–2034 © Thieme Stuttgart · New York

2034
Y. Li et al.
LETTER
reflections measured, 5852 unique (Rint = 0.0924) which
were used in all calculations. The final wR2 (F2) was 0.1632
(all data).
For compound 7j: C28H28F3N5O6; MW = 587.55; triclinic;
a = 9.2056(13), b = 12.8972(18), c = 13.3762(19) Å,
a = 113.437(2)°, b = 98.874(2)°, g = 99.525(2)°;
V = 1393.8(3) Å3; T = 292(2) K; space group P1; Z = 2;
m(Mo-Ka) = 0.113 mm–1; 14646 reflections measured, 5445
unique (Rint = 0.0559) which were used in all calculations.
The final wR2 (F2) was 0.1554 (all data).
For compound 7k: C28H31N5O6; MW = 533.58;
orthorhombic; a = 18.049(4), b = 18.263(4), c = 8.0492(17)
Å, a = b = g = 90.00°; V = 2653.3(10) Å3; T = 292(2) K;
space group Pna21; Z = 4; m(Mo-Ka) = 0.096 mm–1; 26452
reflections measured, 3099 unique (Rint = 0.0885) which
were used in all calculations. The final wR2 (F2) was 0.1101
(all data).
For compound 7l: C30H35N5O9; MW = 613.63; monoclinic;
a = 8.9216(5), b = 29.5203(17), c = 11.5079(6) Å,
b = 90.5000(10)°; V = 3030.7(3) Å3; T = 292(2) K; space
group P21/n; Z = 4; m(Mo-Ka) = 0.101 mm–1; 23651
reflections measured, 5919 unique (Rint = 0.0768) which
were used in all calculations. The final wR2 (F2) was 0.2164
(all data).
CCDC-724320 (7a); CCDC-724321 (7b); CCDC-724322
(7c); CCDC-724323 (7d); CCDC-724324 (7e); CCDC-
724325 (7f); CCDC-724326 (7g); CCDC-724327 (7j);
CCDC-724328 (7k); CCDC-724329 (7l). These data can be
obtained free of charge at www.ccdc.cam.ac.uk/conts/
retrieving.html [or from the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
+44(1223)336033; email: deposit@ccdc.cam.ac.uk].
Synlett 2009, No. 12, 2028–2034 © Thieme Stuttgart · New York

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