Synthesis and Mechanistic Study of Cyclic Oxoguanidines via Zn(OTf)2-Catalyzed Guanylation/Amidation from Readily Available Amino Acid Esters and Carbodiimides

Article abstract of DOI:10.1002/chem.201500573

The Zn(OTf)₂-catalyzed guanylation/amidation from readily available amino acid esters and carbodiimides is achieved to provide efficiently various cyclic oxoguanidines, including 2-amino-1H-imidazol-5(4H)-ones and 2-aminoquinazolin-4(3H)-ones i

Full text of DOI:10.1002/chem.201500573

DOI: 10.1002/chem.201500573
Full Paper
&
Cyclic Oxoguanidines
Synthesis and Mechanistic Study of Cyclic Oxoguanidines via
Zn(OTf)2-Catalyzed Guanylation/Amidation from Readily Available
Amino Acid Esters and Carbodiimides
Yue Chi,[a] Ling Xu,[a] Shanshan Du,[a] Haihan Yan,[a] Wen-Xiong Zhang,*[a, b] and Zhenfeng Xi[a]
Abstract: The Zn(OTf)2-catalyzed guanylation/amidation
from readily available amino acid esters and carbodiimides is
achieved to provide efficiently various cyclic oxoguanidines,
including 2-amino-1H-imidazol-5(4H)-ones and 2-aminoqui-
nazolin-4(3H)-ones in medium-to-high yields. It is the first
time that an ammonium salt has been used in a guanylation
reaction. The application of cyclic oxoguanidines to provide
the conjugated heterocyclic compounds via oxidative CÀN
formation or aldol reaction is explored. The reaction mecha-
nism is well elucidated by the isolation and characterization
of three important intermediates.
Introduction
Recent years have witnessed a rapid growth in the area of the
catalytic guanylation reaction of amines with carbodiimides
(CGAC reaction).[1] This is because CGAC reaction provides
a straightforward and atom-economical method to prepare
substituted guanidines (RN=C(NR’R’’)NHR), which have unique
value in pharmaceutical chemistry,[2] organometallic and coor-
dination chemistry,[3] and organic synthesis.[4] Very recently,
tandem guanylation/cyclization reaction became a hot field
because of the fast and efficient construction of N-containing
heterocycles through the transformation of NÀH, CÀN, and C=
N bonds of guanidines.[1a,5–7] Three important strategies in
these two-component CGAC reactions have been applied to
the synthesis of cyclic guanidines: 1) Cu-catalyzed guanylation/
N-arylation cyclization of amines with o-haloarylcarbodiimides
(Scheme 1a);[5] 2) Cu-catalyzed guanylation/N-arylation cycliza-
tion of o-haloanilines with carbodiimides (Scheme 1b);[6] and
3) Ti-catalyzed guanylation/metathesis cyclization of diamines
with carbodiimides (Scheme 1c).[7] Our group is interested in
the synthesis of guanidines by using the CGAC reaction,[8,9]
and the reactivity research of carbodiimides.[10] Herein we
report a tandem Zn(OTf)2-catalyzed guanylation/amidation pro-
cess from readily available amino acid ester hydrochlorides
and carbodiimides to efficiently construct five-membered
Scheme 1. Models of two-component guanylation/cyclization for the synthe-
sis of cyclic guanidines.
cyclic oxoguanidines (Scheme 1d). It is the first time to use the
ammonium salt in guanylation reaction, and this type of heter-
ocyclic compound was reported to show good bioactivity[11] or
could be used as ligands.[12] In addition, an ethyl 2-aminoben-
zoate can also act as a suitable partner to efficiently construct
six-membered cyclic oxoguanidines.
[a] Y. Chi, L. Xu, S. Du, H. Yan, Prof. Dr. W.-X. Zhang, Prof. Dr. Z. Xi
Beijing National Laboratory for Molecular Sciences (BNLMS)
Key Laboratory of Bioorganic Chemistry and
Molecular Engineering of Ministry of Education
College of Chemistry, Peking University, Beijing 100871 (P. R. China)
Fax: (+86)10-62751708
Results and Discussion
Synthesis of cyclic oxoguanidines
Condition screening for cyclic oxoguanidines
E-mail: wx_zhang@pku.edu.cn
[b] Prof. Dr. W.-X. Zhang
State Key Laboratory of Elemento-Organic Chemistry
Nankai University, Tianjin 300071 (P. R. China)
The reaction of glycine ethyl ester hydrochloride (1a) with
N,N’-diisopropylcarbodiimide (iPrN=C=NiPr, DIC) was first ex-
amined under various conditions. As a control experiment, DIC
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201500573.
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Table 1. Optimization of the reaction conditions.
Entry
Catalyst
Base
(equiv)
Solvent
2a yield
[%][a]
1
2
3
4
5
6
7
8
9
none
none
none
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
ZnCl2
CoCl2
PdCl2
CuCl
CuCl2
none
Et3N (1.05)
Et3N (2)
C6H6
C6H6
C6H6
C6H6
C6H6
THF
toluene
C6H6
C6H6
C6H6
C6H6
C6H6
0
6
8
none
0
Et3N (1.05)
Et3N (1.05)
Et3N (1.05)
Et3N (1.05)
Et3N (1.05)
Et3N (1.05)
Et3N (1.05)
Et3N (1.05)
78[b]
59
56
41
0
10
11
12
60
29
0
Scheme 2. Synthesis of cyclic oxoguanidines 2a–d and 3a–d.
[a] GC yield. [b] Isolated yield.
reason may be the conjugated effect between C=N double
bond and aryl substituent. It should be noted that OMe and
OH group are tolerated (3c,d). When an unsymmetric carbodii-
mide (DippN=C=NBn) was utilized, the regioselective isomer
3b was produced, probably due to the steric hindrance of the
Dipp group. Single-crystal X-ray diffraction analysis of 3b
shows that the nitrogen atom adjoining the less steric Bn
group connects with the C=O group, and the C=N double
bond is outside of the five-membered ring (Figure 1).
was heated with 1a in benzene at 808C, but no reaction was
observed in 8 h (Table 1, entry 1). When 1–2 equiv of Et3N were
added, only a small amount of cyclic oxoguanidine (2a) was
obtained (Table 1, entries 2 and 3). Because this reaction
needed a long time and gave a low yield without catalyst,[13]
we tried various metal salts, such as Zn(OTf)2, CuCl, CuCl2,
CoCl2 and PdCl2 in this system (Table 1, entries 4–12). The
amino acid ester hydrochloride salt has poor solubility in
common solvents, such as THF, benzene and toluene. However,
Et3N is required in this methodology to neutralize hydrochloric
acid to liberate the free amino acid ester, which has the better
solubility in common solvents (Table 1, entry 4). These reaction
conditions show the present reaction is not a simple proton-
promoted reaction. Finally, we found that 2a could be ob-
tained in 78% isolated yield by using Zn(OTf)2 (5 mol%) as
a catalyst and benzene as solvent at 808C for 8 h (Table 1,
entry 5). THF could be the alternative solvent instead of ben-
zene (Table 1, entry 6).
Synthesis of cyclic oxoguanidines including 2-aminoimidazo-
lones (2) or 2-iminoimidazolidin-4-ones (3)
As summarized in Scheme 2, this method could be applied in
different amino acid ester hydrochlorides, such as 1a, alanine
ethyl ester hydrochloride (1b) and phenylalanine ethyl ester
hydrochloride (1c). Different carbodiimides (iPrN=C=NiPr, CyN=
C=NCy, TolN=C=NTol, and DippN=C=NBn) could also be uti-
lized to provide cyclic oxoguanidines 2a–d or 3a–d in
medium to high yields. When R1 and R2 in the carbodiimides
are alkyl groups, 2-aminoimidazolones 2a–d, in which the C=N
double bond is within the five-membered ring, were exclusive-
ly observed. The solid-state structure of 2c has been confirmed
by previous work.[14] In contrast, when R2 in the carbodiimides
are aryl groups, 2-iminoimidazolidin-4-ones 3a–d were exclu-
sively obtained as an isomer of 2-aminoimidazolones. The
Figure 1. ORTEP drawing of 3b with 30% thermal ellipsoids. Hydrogen
atoms, except that of the nitrogen atom N5, are omitted for clarity.
When cyclic amino acid ester hydrochlorides 4 were applied
to the present conditions, the bicyclic-fused 2-iminoimidazoli-
din-4-ones 5a–g could be synthesized (Scheme 3). Similar to
the regioselectivity of 3b in Scheme 2, 5c could be exclusively
obtained when the unsymmetric carbodiimide DippN=C=NBn
was utilized. In case of tBuN=C=NEt, the products were a pair
of isomers 5 f and 5 f’.
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in this method and the yields are high (7a–c). Halogen atoms
were also be tolerated under these conditions (7d–f). The
structure of 7c was confirmed by X-ray crystallographic analy-
sis (Figure 2). It clearly shows the core structure of 2-aminoqui-
nazolinone with the inner C=N bond in the six-membered ring.
Scheme 3. Synthesis of bicycle-fused 2-iminoimidazolidin-4-ones 5a–g.
There are some previous reports on the synthesis of 2-imi-
noimidazolidin-4-ones.[15] However, they usually need ester-
substituted carbodiimides as starting materials, which are not
commercially available, and difficult to prepare. What is more,
these methods could not be applied in the synthesis of bicy-
clic-fused 2-iminoimidazolidin-4-ones like 5 in Scheme 3. The
present method provides a convenient way to build these
cyclic oxoguanidines 5.
Figure 2. ORTEP drawing of 7c with 30% thermal ellipsoids. Hydrogen
atoms, except that of the nitrogen atom N3, are omitted for clarity.
Synthesis of 2-aminoquinazolinones
Application of cyclic oxoguanidines
The above guanylation/amidation process of amino acid ester
hydrochlorides 1 or 4 with carbodiimides provided various
five-membered cyclic oxoguanidines. Similarly, changing 1 to
ethyl 2-aminobenzoates 6, a series of six-membered cyclic oxo-
guanidines 7a–e could be obtained. These results were sum-
marized in Scheme 4. Various carbodiimides could be applied
Further transformation of these products was explored. Be-
cause there is a free NÀH bond in these cyclic oxoguanidines,
it could easily be applied in oxidative CÀN bond formation.
When 3a or 7b were treated with one equivalent of PhI(OAc)2,
the ring-closed products 8 or 9 could be obtained in 84 and
60%, respectively [Eqs. (1) and (2)].[16] Single-crystal X-ray dif-
fraction analysis of 8 reveals it is a highly conjugated molecule
with nearly all the atoms in one plane (Figure 3). This method
provides a new route for the synthesis of conjugated heterocy-
clic compounds by mean of a two-step procedure from easily
Figure 3. ORTEP drawing of 8 with 30% thermal ellipsoids. Hydrogen atoms
Scheme 4. Synthesis of 2-aminoquinazolinones 7a–f.
are omitted for clarity.
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available reagents. These compounds were reported to have
potential value in material science.[17]
Compound 2c could be also applied in an aldol reaction to
prepare 10 [Eq. (3)], which is similar to Leucettamine, isolated
from marine sponges. Such structures have drawn much atten-
tion based on their bioactivity.[18]
Figure 4. ORTEP drawing of 11 with 30% thermal ellipsoids. Hydrogen
atoms, except those on nitrogen atoms, are omitted for clarity. The trifluoro-
methyl part of 11 is disordered. The major part is shown above. Selected
bond lengths [Š]: Zn1ÀN1 2.045(5), Zn1ÀO2 2.219(5), Zn1ÀO3 2.120(0), C6À
O1 1.301(8), C6ÀO2 1.195(7), S1ÀO3 1.428(5), S1ÀO4 1.425(8), S1ÀO5
1.393(5). Hydrogen bonds: dH1’···O5 =2.102 Š, dN1’···O5 =2.973 Š, ]N1’À
H1’···O5=159.98; dH1···O5’ =2.102 Š, dN1···O5’ =2.973 Š, ]N1ÀH1··O5’=159.98.
Mechanistic study
Isolation and reaction of three important intermediates
Catalytic guanylation reaction of amines with carbodiimides
(CGAC reaction) is an atom-economical reaction for the prepa-
ration of guanidines. From experimental evidence to theoreti-
cal chemistry,[19] the mechanistic study has received much at-
tention. Different types of reaction mechanisms have been re-
ported.[1] To gain information on the reaction mechanism, the
stoichiometric reaction was carried out to isolate and charac-
terize some important intermediates. When ethyl 2-piperidine-
carboxylate was mixed with one equivalent of Zn(OTf)2 and
stirred in benzene at 808C for 1 h, a Zn complex 11 was ob-
tained in 96% yield [Eq. (4)]. This structure was confirmed by
X-ray crystallographic analysis (Figure 4). It adopts a monomer
structure that is totally different to the intermediate of other
Zn-catalyzed guanylation reactions.[8e] The zinc center is encap-
sulated in an octahedral ligand field with C2 symmetry in the
solid state. Two amino acid esters coordinate to the zinc
center as chelating ligands in a five-membered ring, while an-
other two OTf groups coordinate to it at the ortho-position. In-
terestingly, the length between H1 and O5’ (2.012 Š), and the
bond angle of N1’-H1’-O5 (159.98) clearly show the OTf groups
from hydrogen-bonding interactions with the NH groups in
the six-membered rings. These hydrogen bonds may weaken
the NÀH bond and promote the protonation process during
the reaction.
When compound 11 was allowed to react with carbodiimide
[Eq. (5)], a guanidinium trifluoromethanesulfonate salt 12 was
isolated. The structure of 12 was confirmed by X-ray crystallo-
graphic analysis (Figure 5). Compound 12 has one crystallo-
graphically independent cation–anion pair in the asymmetric
unit. The sum of the angles at central carbon equals 3608 indi-
cating complete planarity within the range of errors. The CÀN
bond lengths are in the range of 1.32–1.38 Š within the “CN3”
core suggesting the delocalization within the p-system of the
“CN3” core of the guanidinium cation.
When 11 was allowed to react with carbodiimide at 408C,
an open guanidine intermediate 13 could be isolated in 29%
yield with the concomitant formation of the final ring-closed
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Figure 5. ORTEP drawing of 12 with 30% thermal ellipsoids. Hydrogen
atoms, except that on nitrogen atom N3, are omitted for clarity. Selected
bond lengths [Š] and angles [8]: N1ÀC7 1.383 (4), N2ÀC7 1.325(4), N3ÀC7
1.309(4), N1-C7-N2 110.2(3), N1-C7-N3 121.3(3), N2-C7-N3 128.4(3).
product 5d. Increasing the temperature, 13 could be trans-
formed to 5d (Scheme 5). It clearly shows that the guanyla-
tion/amidation reaction proceeds via the open guanidine inter-
mediate.
Scheme 5. Isolation and reaction of the opening guanidine intermediate 13.
Three possible mechanisms
Generally, Zn(OTf)2 is regarded as a Lewis acid. Therefore, it is
possible for Zn(OTf)2 to act as a Lewis acid to activate the car-
bodiimide. Followed by nucleophilic addition/intramolecular
proton transfer, the catalytic cycle is completed by releasing
guanidines and regenerating Zn(OTf)2 as shown in pathway a
in Scheme 6. Similarly, a proton acid-catalyzed mechanism is
also proposed. However, this mechanism could not explain the
formation of trifluoromethanesulfonate salt 12. In addition,
some other Lewis acids show lower catalytic activity than
Zn(OTf)2 (Table 1). Therefore, we think it is not a simple Lewis
acid catalyzed reaction, and pathway a could be excluded.
The formation of 12 reveals Zn(OTf)2 should go through
a ligand exchange step in this reaction. Based on the isolation
and features of two important intermediates 11 and 12, we
proposed two other possible mechanisms: 1) Concerted
protonation/nucleophilic addition/disassociation mechanism
(Scheme 6, pathway b). Ligand substitution by the coordina-
tion of the carbodiimide and the disassociation of OTf anion
would yield the zinc salt intermediate B. After nucleophilic ad-
dition step/protonation, B might change to intermediate C.
Followed by the amidation step, C could release E and inter-
mediate D, which could in turn react with another molecule of
Scheme 6. Three possible mechanisms for the formation of 2.
1 to finish the catalytic cycle. 2) ZnÀN bond formation/inser-
tion/protonation mechanism (Scheme 6, pathway c). The elimi-
nation of HOTf followed by neutralization would generate in-
termediate F, which contains the active ZnÀN bond and in-
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creases the nucleophilicity on the N atom. Coordination of car-
bodiimide to F/intramolecular insertion might provide inter-
mediate H. Intramolecular nucleophilic amidation in H should
release 2 and yield intermediate D. The interaction between D
with amino acid ester hydrotrifluoromethanesulfonate would
regenerate A to complete the catalytic cycle.
Typical procedure for the preparation of 2-aminoimidazo-
lones 2a–d or 2-iminoimidazolidin-4-ones 3a–d by the reac-
tion of amino acid ester hydrochloride and carbodiimide
In a 25 mL of flask, triethylamine (1.05 mmol, 106 mg) was added
to an amino acid ester hydrochloride (1.05 mmol) in benzene
(5 mL). Then Zn(OTf)2 (0.05 mmol, 18 mg) and carbodiimide
(1.00 mmol) were added to the flask, and the mixture was stirred
at 808C for 8 h. The solvent of the reaction mixture was evaporat-
ed under vacuum. The residue was purified by chromatography to
give products 2a–d or 3a–d.
Data for 2a: Yellow oil, isolated yield 78% (143 mg); 1H NMR
(400 MHz, CDCl3, TMS): d=1.24 (d, J=6.5 Hz, 6H; CH3), 1.42, (d,
J=7.0 Hz, 6H; CH3), 3.92–3.94 (m, 3H; 1CH2, 1CH), 4.15–4.22 (m,
1H; CH), 4.79 ppm (brs, 1H; NH); 13C NMR (100 MHz, CDCl3, TMS):
d=20.06, 22.75, 43.46, 43.57, 56.19, 155.55, 180.31 ppm; IR (film):
n˜ =3387 (NÀH), 1676 cmÀ1 (C=O); HRMS: m/z calcd for C9H18N3O
[M+H]+: 184.1449; found: 184.1439.
Data for 2b: Yellow oil, isolated yield 67% (132 mg); 1H NMR
(400 MHz, CDCl3, TMS): d=1.12 (d, J=6.4 Hz, 3H; CH3), 1.23 (brs,
3H; CH3), 1.34, (d, J=7.2 Hz, 3H; CH3), 1.40–1.43 (m, 6H; CH3),
3.86–3.94 (m, 2H; CH), 4.19 (brs, 1H; CH), 5.00–5.01 ppm (m, 1H;
NH); 13C NMR (100 MHz, CDCl3, TMS): d=17.95, 19.74, 22.93, 23.09,
23.30, 41.44, 43.49, 157.26, 174.82 ppm; IR (film): n˜ =3282 (NÀH),
1672 cmÀ1 (C=O); HRMS: m/z calcd for C10H20N3O [M+H]+:
198.1606; found: 198.1596.
Coordination of the nitrogen atom of amino acid ester to
zinc in A would decrease the nucleophilicity of amine com-
pared to the free uncoordinated amine.[9c] The coordination of
carbodiimide to zinc might overcompensate this negative
effect of zinc coordination to amine in B (Scheme 6, path-
way b). Therefore, the nucleophilic addition/protonation step
from B to C should be a rate-determining step. The hydrogen
bonds in 11 show the interaction between H atom on the N
atom of piperidine ring and O atom of OTf group (Figure 4).
The interaction of hydrogen bonds could weaken the strength
of the NÀH bond, and promote the elimination of HOTf yield-
ing the active ZnÀN bond (Scheme 6, pathway c). The forma-
tion of ZnÀN bond is useful for the nucleophilic addition into
carbodiimides. This also explains why ZnCl2 has the lower cata-
lytic activity (Table 1, entry 6) because the Cl atom is difficult to
form the hydrogen bond like Zn complex 11. For these rea-
sons, we consider that pathway c might be more reasonable
than pathway b.
Data for 2c: Yellow solid, isolated yield 91% (239 mg); m.p. 86.6–
1
87.68C; H NMR (400 MHz, CDCl3, TMS): d=1.17–1.42 (m, 8H; CH2),
1.62–1.75 (m, 6H; CH2), 1.85–2.05 (m, 6H; CH2), 3.69 (brs, 1H; CH),
3.95 (s, 2H; CH2), 4.10 ppm (brs, 1H; CH); 13C NMR (100 MHz,
CDCl3, TMS): d=24.72, 25.05, 25.56, 25.93, 30.25, 33.31, 50.33,
52.05, 56.19, 155.64, 180.28 ppm; IR (film): n˜ =3326 (NÀH),
1620 cmÀ1 (C=O); HRMS: m/z calcd for C15H26N3O [M+H]+:
264.2076; found: 264.2067. The single-crystal structure 2c was con-
sistent with that reported.[14]
Conclusion
We have developed an efficient method to synthesize a series
of cyclic oxoguanidines, including 2-amino-1H-imidazol-5(4H)-
ones and 2-aminoquinazolin-4(3H)-ones in medium to high
yields by means of Zn(OTf)2-catalyzed guanylaion/amidation.
These cyclic oxoguanidines could have the potential bioactivi-
ties or could be used as ligands. All the starting materials, in-
cluding carbodiimides, amino acid esters, and Zn(OTf)2, are
cheap and commercially available. It is the first time that am-
monium salts have been applied in a guanylation reaction. Fur-
ther application of cyclic oxoguanidines was carried out to pro-
vide the conjugated heterocyclic compounds. In addition,
three important intermediates were isolated and characterized
from the reaction system. These are very useful in helping us
to understand the catalytic mechanism.
Data for 2d: Yellow solid, isolated yield 82% (290 mg); m.p. 96.7–
1
97.68C; H NMR (400 MHz, CDCl3, TMS): d=1.13–1.27 (m, 7H; CH2),
1.34–1.43 (m, 3H; CH2), 1.61–1.71 (m, 8H; CH2), 1.92–2.02 (m, 2H;
CH2), 3.14 (d, J=6.4 Hz, 2H; CH2), 3.36 (brs, 1H; CH), 3.73 (brs, 2H;
CH), 4.20 (brs, 1H; NH), 7.10–7.18 ppm (m, 5H; CH); 13C NMR
(100 MHz, CDCl3, TMS): d=14.00, 24.40, 24.59, 24.97, 25.51, 25.76,
29.64, 33.06, 33.83, 37.79, 40.98, 51.54, 55.67, 60.73, 126.76, 127.57,
128.50, 129.28, 130.19, 136.12, 137.26, 175.00 ppm; IR (film): n˜ =
3378 (NÀH), 1680 cmÀ1 (C=O); HRMS: m/z calcd for C22H32N3O [M+
H]+: 354.2545; found: 354.2544.
Data for 3a: Yellow solid, isolated yield 94% (262 mg); m.p. 147.6–
1
148.58C; H NMR (400 MHz, CDCl3, TMS): d=2.33 (s, 3H; CH3), 2.42
(brs, 3H; CH3), 3.94 (brs, 1H; CH2), 4.26 (brs, 1H; CH2), 4.92 (brs,
1H; NH), 6.85–6.87 (m, 1H; CH), 7.12 (d, J=7.9 Hz„ 2H; CH),
7.33 ppm (brs, 5H; CH); 13C NMR (100 MHz, CDCl3, TMS): d=20.73,
21.16, 46.95, 119.45, 122.02, 127.07, 129.71, 130.98, 132.45, 138.27,
144.78, 150.73, 170.66 ppm; IR (film): n˜ =3325 (NÀH), 1687 (C=O);
HRMS: m/z calcd for C17H18N3O [M+H]+: 280.1450; found:
280.1442.
Experimental Section
General methods
Unless otherwise noted, all starting materials were commercially
available and were used without further purification. Solvents were
purified by an Mbraun SPS-800 Solvent Purification System and
dried over fresh Na chips in the glovebox. All reactions were car-
ried out under air atmosphere. 1H and 13C NMR spectra were re-
corded on a Bruker ARX400 spectrometer (FT, 400 MHz for 1H;
100 MHz for 13C) at room temperature, unless otherwise noted.
High-resolution mass spectra (HRMS) were recorded on a Bruker
Apex IV FTMS mass spectrometer using ESI (electrospray ioniza-
tion).
Data for 3b: Yellow solid, isolated yield 73% (255 mg); m.p. 166.5–
167.58C; 1H NMR (400 MHz, CDCl3, TMS): d=1.08–1.10 (m, 12H;
CH3), 2.82–2.89 (m, 2H; CH), 3.86 (s, 2H; CH2), 4.25 (brs, 1H; NH),
4.91 (s, 2H; CH2), 7.00–7.10 (m, 3H; CH), 7.26–7.34 (m, 3H; CH),
7.50–7.52 ppm (m, 2H; CH); 13C NMR (100 MHz, CDCl3, TMS): d=
23.39, 23.42, 28.08, 42.61, 46.90, 123.20, 123.51, 127.59, 128.34,
128.63, 136.48, 139.81, 142.02, 147.92, 170.98 ppm; IR (film): n˜ =
3282 (NÀH), 1671 cmÀ1 (C=O); HRMS: m/z calcd for C22H28N3O [M+
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H]+: 350.2232; found: 350.2226. Single crystals of 3b suitable for
X-ray analysis were grown in ethyl acetate/hexane at room temper-
ature for three days.
128.56, 136.96, 137.91, 139.82, 142.60, 148.17, 173.42 ppm; IR
(film): n˜ =1672 cmÀ1 (C=O); HRMS: m/z calcd for C25H32N3O [M+
H]+: 390.2545; found: 390.2546.
Data for 3c: Yellow solid, isolated yield 87% (262 mg); m.p. 156.5–
157.48C; H NMR (400 MHz, CDCl3, TMS): d=3.68 (s, 3H; CH3), 3.81
Data for 5d: Colorless solid, isolated yield 64% (152 mg); m.p.
49.9–50.58C; H NMR (400 MHz, CDCl3, TMS): d=1.12–1.15 (m, 6H;
1
1
(s, 3H; CH3), 4.33 (brs, 2H; CH2), 6.78–7.80 (m, 1H; CH), 6.94–6.96
(m, 2H; CH), 7.06–7.10 (m, 2H; CH), 7.28–7.29 (m, 1H; CH), 7.46
(brs, 1H; CH), 8.33 ppm (brs, 1H; CH); 13C NMR (100 MHz, CDCl3,
TMS): d=55.80, 55.84, 57.39, 109.96, 112.46, 118.57, 120.02, 121.20,
121.41, 122.52, 128.12, 130.07, 131.41, 147.65, 152.35, 155.31,
178.85 ppm; IR (film): n˜ =3336 (NÀH), 1655 cmÀ1 (C=O); HRMS: m/z
calcd for C18H22N3O3 [M+H]+: 328.1661; found: 328.1656.
CH3), 1.28–1.29 (m, 1H; CH2), 1.35–1.38 (m, 6H; CH3), 1.45–1.52 (m,
2H; CH2), 1.65–1.68 (m, 1H; CH2), 1.93–1.96 (m, 1H; CH2), 2.07–2.10
(m, 1H; CH2), 3.04–3.10 (m, 1H; CH2), 3.47–3.50 (m, 1H; CH2), 3.99–
4.02 (m, 1H; CH), 4.15–4.18 (m, 1H; CH), 4.45–4.49 ppm (m, 1H;
CH); 13C NMR (100 MHz, CDCl3, TMS): d=19.04, 19.14, 22.96, 25.57,
25.62, 25.82, 27.83, 43.37, 44.44, 45.02, 59.33, 141.13, 172.63 ppm;
IR (film): n˜ =1668 cmÀ1 (C=O); HRMS: m/z calcd for C13H24N3O [M+
H]+: 238.1919; found: 238.1913.
Data for 3d: Colorless solid, isolated yield 56% (216 mg); m.p.
176.8–178.68C; 1H NMR (400 MHz, CDCl3, TMS): d=2.28 (s, 6H;
CH3), 2.98–3.09 (m, 2H; CH2), 4.30 (brs, 1H; CH), 4.79 (brs, 1H; NH),
6.63 (d, J=8.0 Hz, 2H; CH), 6.74 (d, J=7.7 Hz, 2H; CH), 6.98 (d, J=
7.9 Hz, 2H; CH), 7.07–7.09 (m, 4H; CH), 7.16 ppm (d, J=7.9 Hz, 2H;
CH); 13C NMR (100 MHz, CDCl3, TMS): d=20.80, 21.18, 37.41, 58.58,
115.54, 122.12, 125.80, 127.18, 129.12, 129.75, 129.84, 129.97,
130.75, 132.73, 132.79, 138.55, 144.45, 150.36, 155.68, 172.60 ppm;
IR (film): n˜ =3317 (NÀH), 1660 cmÀ1 (C=O); HRMS: m/z calcd for
C24H24N3O2 [M+H]+: 386.1868; found: 386.1876.
Data for 5e: Colorless solid, isolated yield 60% (191 mg); m.p.
36.0–36.88C; 1H NMR (400 MHz, CDCl3, TMS): d=1.23–1.39 (m,
10H; CH2), 1.57–1.59 (m, 6H; CH2), 1.72–1.78 (m, 6H; CH2), 1.92–
1.95 (m, 1H; CH2), 2.06–2.10 (m, 1H; CH2), 2.21–2.33 (m, 2H; CH2),
3.02–3.08 (m, 1H; CH), 3.46–3.50 (m, 1H; CH), 3.63 (brs, 1H; CH),
4.05–4.10 ppm (m, 2H; CH2); 13C NMR (100 MHz, CDCl3, TMS): d=
23.01, 24.29, 24.40, 25.37, 25.56, 25.93, 26.11, 26.15, 27.90, 28.64,
28.67, 35.56, 35.78, 44.39, 51.49, 52.76, 59.32, 140.99, 172.74 ppm;
IR (film): n˜ =1632 cmÀ1 (C=O); HRMS: m/z calcd for C19H32N3O [M+
H]+: 318.2545; found: 318.2536.
Data for 5 f+5 f’: Colorless oil, isolated yield 63% (152 mg);
1H NMR (400 MHz, CDCl3, TMS): d=0.94 (t, J=7.3 Hz, 2H; CH3,
5 f’), 1.10 (t, J=7.1 Hz, 3H; CH3, 5 f), 1.25 (s, 6H; CH3, 5 f’), 1.35–
1.36 (m, 3H; CH2, 5 f+5 f’), 1.44 (s, 9H; CH3, 5 f), 1.60–1.68 (m, 6H;
CH2, 5 f+5 f’), 1.90–2.20 (m, 1H; CH2, 5 f+5 f’), 2.45–2.53 (m, 1H;
CH2, 5 f+5 f’), 2.95–3.09 (m, 1H; CH, 5 f+5 f’), 3.46–3.54 (m, 3H;
CH2, 5 f+5 f’), 3.69–3.73 (m, 2H; CH2, 5 f+5 f’), 3.84 ppm (q, J=
7.1 Hz, 2H; CH3, 5 f); 13C NMR (100 MHz, CDCl3, TMS): d=13.40,
13.42, 13.67, 15.77, 19.38, 19.94, 22.08, 24.02, 29.84, 30.00, 31.05,
32.24, 34.43, 36.57, 40.58, 42.10, 51.73, 53.11, 129.50, 144.08,
158.73, 173.55 ppm; IR (film): n˜ =1678 cmÀ1 (C=O); HRMS: m/z
calcd for C13H24N3O [M+H]+: 238.1919; found: 238.1912.
Typical procedure for the preparation of bicycle-fused 2-imi-
noimidazolidin-4-ones 5a–g by the reaction of amino acid
ester hydrochloride and carbodiimide
In a 25 mL of flask, triethylamine (1.05 mmol, 106 mg) was added
to an amino acid ester hydrochloride (1.05 mmol) in benzene
(5 mL). Then Zn(OTf)2 (0.05 mmol, 18 mg) and carbodiimide
(1.00 mmol) were added to the flask, and the mixture was stirred
at 808C for 8 h. The solvent of the reaction mixture was evaporat-
ed under vacuum. The residue was purified by chromatography to
give products 5a–g.
Data for 5a: Colorless solid, isolated yield 71% (215 mg); m.p.
28.7–29.38C; H NMR (400 MHz, CDCl3, TMS): d=1.25–1.34 (m, 6H;
Data for 5g: Colorless solid, isolated yield 84% (307 mg); m.p.
123.4–124.38C; 1H NMR (400 MHz, CDCl3): d=1.22–1.25 (m, 1H;
CH2), 1.50–1.61 (m, 3H; CH2), 1.99–2.02 (m, 1H; CH2), 2.18–2.23 (m,
1H; CH2), 2.81–2.86 (m, 1H; CH), 3.63 (s, 3H; CH3), 3.70 (s, 3H;
CH3), 3.86–3.93 (m, 1H; CH2), 4.07–4.16 (m, 1H; CH2), 6.35–6.36 (m,
1H; CH), 6.57–6.73 (m, 5H; CH), 6.99–7.07 ppm (m, 2H; CH);
13C NMR (100 MHz, CDCl3): d=13.99, 20.83, 55.56 (2C), 55.61,
57.14, 60.16, 109.71, 112.23, 118.38, 120.96, 121.19, 122.25, 127.79,
129.84, 131.21, 147.37, 152.15, 155.07, 170.90, 178.65 ppm; IR
(film): n˜ =1687 cmÀ1 (C=O); HRMS: m/z calcd for C21H24N3O3 [M+
H]+: 366.1818; found: 366.1811.
1
CH2), 1.41–1.49 (m, 1H; CH2), 1.54–1.63 (m, 5H; CH2), 1.67–1.79 (m,
6H; CH2), 1.91–1.97 (m, 2H; CH2), 2.17–2.35 (m, 4H; CH2), 3.10–3.17
(m, 1H; CH), 3.43–3.52 (m, 2H; CH2), 3.90 (t, J=7.9 Hz, 1H; CH),
3.97–4.03 ppm (m, 1H; CH); 13C NMR (100 MHz, CDCl3, TMS): d=
24.34, 24.73, 25.12, 25.75, 25.77, 25.85, 26.76, 28.25, 28.28, 30.66,
34.65, 35.74, 51.79, 52.18, 55.69, 64.28, 151.04, 173.97 ppm; IR
(film): n˜ =1670 cmÀ1 (C=O); HRMS: m/z calcd for C18H30N3O [M+
H]+: 304.2389; found: 304.2379.
Data for 5b: Colorless solid, isolated yield 74% (215 mg); m.p.
1
88.9–89.88C; H NMR (400 MHz, CDCl3, TMS): d=1.24–1.27 (m, 1H;
CH2), 1.84–1.98 (m, 2H; CH2), 2.29–2.30 (m, 1H; CH2), 2.94 (brs, 2H;
CH2), 4.26 (t, J=8.0 Hz, 1H; CH), 6.93–7.01 (m, 3H; CH), 7.22–7.26
(m, 2H; CH), 7.32–7.34 (m, 1H; CH), 7.46 ppm (brs, 4H; CH);
13C NMR (100 MHz, CDCl3, TMS): d=27.23, 28.63, 50.20, 64.76,
122.17, 122.34, 127.14, 128.00, 128.70, 128.84, 132.87, 147.81,
152.39, 172.77 ppm; IR (film): n˜ =1689 (C=O); HRMS: m/z calcd for
C18H18N3O [M+H]+: 292.1450; found: 292.1440.
Typical procedure for the preparation of 2-aminoquinazoli-
nones 7a–f by the reaction of 2-aminobenzoate and carbo-
diimide
In a 25 mL of flask, Zn(OTf)2 (0.05 mmol, 18 mg) was added to a 2-
aminobenzoates (1.05 mmol) in benzene (5 mL). Then carbodiimide
(1.00 mmol) were added to the flask, and the mixture was stirred
at 808C for 8 h. The solvent of the reaction mixture was evaporat-
ed under vacuum. The residue was purified by chromatography to
give products 7a–f.
Data for 5c: Colorless solid, isolated yield 58% (226 mg); m.p.
125.9–126.38C; 1H NMR (400 MHz, CDCl3, TMS): d=0.97 (d, J=
6.8 Hz, 3H; CH3), 1.06–1.12 (m, 6H; CH3), 1.19 (d, J=6.8 Hz, 3H;
CH3), 1.72–1.74 (m, 2H; CH2), 2.12–2.14 (m, 2H; CH2), 2.50 (brs, 1H;
CH), 2.82–2.86 (m, 2H; CH2), 2.95–3.00 (m, 1H; CH), 4.06–4.08 (m,
1H; CH), 4.77–4.91 (m, 2H; CH2), 6.98–7.07 (m, 3H; CH), 7.25–7.36
(m, 3H; CH), 7.44–7.45 ppm (m, 2H; CH); 13C NMR (100 MHz,
CDCl3, TMS): d=22.11, 22.78, 23.60, 24.48, 27.25, 28.06, 28.21,
28.81, 43.15, 47.77, 64.76, 122.36, 122.89, 123.28, 127.50, 128.42,
Data for 7a: Colorless solid, isolated yield 91% (223 mg); m.p.
1
97.9–98.78C; H NMR (400 MHz, CDCl3): d=1.21 (d, J=6.3 Hz, 6H;
CH3), 1.45 (d, J=7.2 Hz, 6H; CH3), 4.24–4.33 (m, 2H; CH), 5.27 (brs,
1H; NH), 6.99–7.03 (m, 1H; CH), 7.18 (d, J=7.9 Hz, 1H; CH), 7.41–
7.44 (m, 1H; CH), 7.92 ppm (dd, J=8.0 Hz, J=1.3 Hz, 1H; CH);
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13C NMR (100 MHz, CDCl3, TMS): d=20.14, 22.77, 43.51 (2C),
117.48, 122.07, 124.47, 126.92, 133.88, 148.83, 148.95, 163.11 ppm;
IR (film): n˜ =3367 (NÀH), 1649 cmÀ1 (C=O); HRMS: m/z calcd for
C14H20N3O [M+H]+: 246.1606; found: 246.1600.
808C for 2 h. The solvent of the reaction mixture was evaporated
under vacuum. The residue was purified by chromatography to
give products 8 or 9.
Data for 8: Yellow solid, isolated yield 84% (72 mg); m.p. 146.9–
147.88C; 1H NMR (400 MHz, CDCl3): d=2.40 (s, 3H; CH3), 2.46 (s,
3H; CH3), 4.63 (s, 2H; CH2), 7.03–7.05 (m, 2H; CH), 7.32 (d, J=
8.3 Hz, 2H; CH), 7.55 (d, J=8.1 Hz, 1H; CH), 7.70 ppm (d, J=8.4 Hz,
2H; CH); 13C NMR (100 MHz, CDCl3): d=21.16, 21.62, 47.41, 108.70,
119.01, 123.49, 123.67, 129.84, 129.97, 131.56, 132.38, 137.92,
142.06, 153.55, 169.96 ppm; IR (film): n˜ =1675 cmÀ1 (C=O); HRMS:
m/z calcd for C17H16N3O [M+H]+: 278.1293; found: 278.1302.
Single crystals of 8 suitable for X-ray analysis were grown in ethyl
acetate/hexane at room temperature for three days.
Data for 7b: Colorless solid, isolated yield 85% (266 mg); m.p.
112.6–113.28C; 1H NMR (400 MHz, CDCl3, TMS): d=5.95 (brs, 1H;
NH), 7.07–7.10 (m, 1H; CH), 7.24–7.33 (m, 3H; CH), 7.41–7.43 (m,
2H; CH), 7.52–7.54 (m, 3H; CH), 7.60–7.67 (m, 4H; CH), 8.18 ppm
(d, J=7.8 Hz, 1H; CH); 13C NMR (100 MHz, CDCl3, TMS): d=118.40,
120.75, 123.63, 123.96, 125.59, 127.13, 128.83, 129.00, 130.22,
130.79, 134.51, 134.66, 137.78, 146.25, 148.46, 162.44 ppm; IR
(film): n˜ =3334 (NÀH), 1675 cmÀ1 (C=O); HRMS: m/z calcd for
C20H14N3O [M+H]+: 314.1289; found: 314.1282. This compound
has been reported previously.[20a]
Data for 9: Yellow solid, isolated yield 60% (46 mg); m.p. 158.8–
159.78C; 1H NMR (400 MHz, CDCl3): d=7.29–7.31 (m, 2H; CH),
7.41–7.50 (m, 4H; CH), 7.54–7.57 (m, 2H; CH), 7.65–7.67 (m, 1H;
CH), 7.83–7.88 (m, 1H; CH), 7.99–8.01 (m, 1H; CH), 8.23 (d, J=
8.4 Hz, 1H; CH), 8.43 ppm (dd, J=7.9 Hz, J=1.4 Hz, 1H; CH);
13C NMR (100 MHz, CDCl3): d=112.35, 114.45, 117.04, 119.90,
120.78, 122.48, 124.15, 125.02, 128.46, 129.38, 129.85, 130.53,
135.29, 135.36, 137.22, 142.55, 147.54, 159.70 ppm; IR (film): n˜ =
1750 cmÀ1 (C=O); HRMS: m/z calcd for C20H14N3O [M+H]+:
312.1137; found: 312.1134.
Data for 7c: Colorless solid, isolated yield 89% (303 mg); m.p.
132.5–133.38C; 1H NMR (400 MHz, CDCl3, TMS): d=2.27 (s, 3H;
CH3), 2.40 (s, 3H; CH3), 5.96 (brs, 1H; NH), 7.05–7.08 (m, 2H; CH),
7.15–7.22 (m, 3H; CH), 7.34–7.37 (m, 4H; CH), 7.45–7.47 (m, 1H;
CH), 7.56–7.60 (m, 1H; CH), 8.11–8.13 ppm (m, 1H; CH); 13C NMR
(100 MHz, CDCl3, TMS): d=20.80, 21.32, 118.32, 121.11, 123.66,
125.51, 127.13, 128.66, 129.33, 131.43, 131.77, 133.68, 134.54,
135.21, 140.40, 146.76, 148.64, 162.62 ppm; IR (film): n˜ =3319 (NÀ
H), 1660 cmÀ1 (C=O); HRMS: m/z calcd for C22H20N3O [M+H]+:
342.1606; found: 342.1596. Single crystals of 7a suitable for X-ray
analysis were grown in ethyl acetate/hexane at room temperature
for three days. This compound has been reported previously.[20b]
Data for 7d: Colorless solid, isolated yield 85% (276 mg); m.p.
132.5–133.38C; 1H NMR (400 MHz, CDCl3): d=1.11 (d, J=6.3 Hz,
6H; CH3), 1.35 (d, J=7.2 Hz, 6H; CH3), 4.13–4.24 (m, 2H; CH), 5.24
(brs, 1H; NH), 6.98 (d, J=8.7 Hz, 1H; CH), 7.38 (dd, J=8.7 Hz, J=
2.2 Hz, 1H; CH), 7.99 ppm (d, J=2.1 Hz, 1H; CH); 13C NMR
(100 MHz, CDCl3): d=20.17, 22.81, 43.69 (2C), 114.60, 118.84,
126.47, 129.37, 136.92, 147.94, 149.04, 162.04 ppm; IR (film): n˜ =
3414 (NÀH), 1625 cmÀ1 (C=O); HRMS: m/z calcd for C14H19BrN3O
[M+H]+: 324.0712; found: 324.0706.
Typical procedure for the preparation of compound 10 by
the reaction of benzaldehyde and 2c
In a 25 mL of flask, potassium tert-butylate (0.33 mmol, 37 mg) was
added to a benzaldehyde (0.30 mmol, 32 mg) in THF (3 mL). Then
compound 2c (0.30 mmol, 79 mg) were added to the flask, and
the mixture was stirred at 608C for 2 h. The solvent of the reaction
mixture was evaporated under vacuum. The residue was purified
by chromatography to give products 10. Yellow solid, isolated
yield 72% (76 mg); m.p. 89.1–89.88C; 1H NMR (400 MHz, CDCl3,
TMS): d=1.25–1.52 (m, 10H; CH2), 1.71–1.94 (m, 8H; CH2), 2.14–
2.18 (m, 2H; CH2), 3.76–3.82 (m, 1H; CH), 4.06–4.79 (m, 1H; CH),
4.50 (d, J=7.7 Hz, 1H; NH), 6.64 (s, 1H; CH), 7.23–7.26 (m, 1H; CH),
7.36 (t, J=7.7 Hz, 2H; CH), 8.07 ppm (t, J=7.4 Hz, 2H; CH);
13C NMR (100 MHz, CDCl3, TMS): d=24.71, 25.18, 25.55, 26.03,
30.78, 33.15, 50.88, 51.98, 115.94, 127.72, 128.34, 130.63, 135.88,
139.23, 156.60, 170.28 ppm; IR (film): n˜ =3296 (NÀH), 1666 cmÀ1
(C=O); HRMS: m/z calcd for C22H30N3O [M+H]+: 352.2389; found:
352.2383.
Data for 7e: Colorless solid, isolated yield 64% (251 mg); m.p.
154.0–154.68C; 1H NMR (400 MHz, CDCl3): d=5.95 (brs, 1H; NH),
7.07–7.10 (m, 1H; CH), 7.24–7.33 (m, 3H; CH), 7.41–7.43 (m, 2H;
CH), 7.50–7.54 (m, 3H; CH), 7.60–7.67 (m, 3H; CH), 8.18 ppm (d, J=
2.3 Hz, 1H; CH); 13C NMR (100 MHz, CDCl3): d=116.31, 119.72,
120.93, 124.22, 127.41, 128.83, 128.85, 129.42, 130.36, 130.84,
134.13, 137.45, 137.61, 146.58, 147.40, 161.20 ppm; IR (film): n˜ =
3415 (NÀH), 1681 cmÀ1 (C=O); HRMS: m/z calcd for C20H15BrN3O
[M+H]+: 392.0398; found: 392.0393.
Data for 7 f: Colorless solid, isolated yield 60% (229 mg); m.p.
1
161.3–164.18C; H NMR (400 MHz, CDCl3, TMS): d=5.88 (brs, 1H;
NH), 7.08 (d, J=7.8 Hz, 1H; CH), 7.22–7.24 (m, 1H; CH), 7.30–7.35
(m, 3H; CH), 7.45 (brs, 1H; CH), 7.55–7.57 (m, 1H; CH), 7.60–7.62
(m, 2H; CH), 7.68–7.72 (m, 2H; CH), 8.17 ppm (d, J=7.8 Hz, 1H;
CH); 13C NMR (100 MHz, CDCl3, TMS): d=118.38, 118.86, 120.93,
124.17, 124.28, 125.83, 127.22, 127.29, 129.57, 129.83, 130.85,
131.78, 134.58, 135.05, 135.51, 136.59, 138.83, 145.33, 148.05,
162.18 ppm; IR (film): n˜ =3315 (NÀH), 1667 cmÀ1 (C=O); HRMS: m/z
calcd for C20H14Cl2N3O [M+H]+: 382.0514; found: 382.0509.
Isolation of 11 from the reaction of Zn(OTf)2 with ethyl nico-
tinate
In a 25 mL of flask, Zn(OTf)2 (0.30 mmol, 109 mg) was added to an
ethyl nicotinate (0.30 mmol, 32 mg) in benzene (5 mL), and the
mixture was stirred at 808C for 1 h. After filtration, the reaction
mixture was left to evaporate under a nitrogen atmosphere for five
days to give single crystals of 11 suitable for X-ray analysis. Color-
less solid, isolated yield 96% (199 mg); 1H NMR (400 MHz, C6D6):
d=0.96 (t, J=7.1 Hz, 3H; CH3), 1.13–1.16 (m, 1H; CH2), 1.28–1.30
(m, 2H; CH2), 1.48–1.53 (m, 2H; CH2), 1.84–1.87 (m, 1H; CH2), 2.44–
2.45 (m, 1H; CH2), 2.91–2.94 (m, 1H; CH2), 3.23–3.25 (m, 1H; CH),
3.46 (brs, 1H; NH), 3.95 ppm (q, J=7.1 Hz, 2H; CH2); 13C NMR
(100 MHz, C6D6): d=13.11, 23.02, 24.70, 27.97, 44.60, 57.53, 59.65,
171.94 ppm.
Typical procedure for the preparation of conjugated hetero-
cyclic compounds 8 or 9 by the reaction of PhI(OAc)2 with
cyclic oxoguanidines 3a or 7b
In a 25 mL of flask, iodobenzene diacetate (0.33 mmol, 107 mg)
was added to a cyclic oxoguanidines 3a (0.30 mmol, 84 mg) or 7b
(0.30 mmol, 94 mg) in MeCN (3 mL), and the mixture was stirred at
Chem. Eur. J. 2015, 21, 10369 – 10378
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Full Paper
Isolation of 12 from the reaction of Zn(OTf)2, ethyl nicoti-
nate and DIC
Acknowledgements
This work was supported by the Natural Science Foundation of
China, and the 973 Program from National Basic Research Pro-
gram of China (2011CB808600).
In a 25 mL of flask, 11 (0.30 mmol, 109 mg) was added to DIC
(0.60 mmol, 75 mg) in benzene (5 mL), and the mixture was stirred
at 808C for 3 h. After filtration, the reaction mixture was left to
evaporate under a nitrogen atmosphere to give 12. Single crystals
of 12 suitable for X-ray analysis were grown in ethyl acetate/
hexane at room temperature for 3 days. Colorless solid, isolated
Keywords: amino acid esters
·
carbodiimides
·
cyclic
1
oxoguanidines · cyclization · guanylation
yield 34% (131 mg); H NMR (400 MHz, CDCl3, TMS): d=1.13–1.15
(m, 1H; CH2), 1.29–1.32 (m, 2H; CH2), 1.46–1.54 (m, 12H; CH3),
1.61–1.70 (m, 1H; CH2), 2.01–2.07 (m, 1H; CH2), 2.30–2.33 (m, 1H;
CH2), 3.45–3.51 (m, 1H; CH), 3.98–4.12 (m, 2H; CH2), 4.21–4.25 (m,
1H; CH), 4.36–4.41 (m, 1H; CH), 7.87 ppm (d, J=8.3 Hz, 1H; NH);
13C NMR (100 MHz, CDCl3, TMS): d=19.09, 19.34, 21.58, 22.82,
23.33, 25.18, 27.59, 45.54, 48.41, 49.24, 59.63, 153.74, 171.27 ppm.
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24.87, 25.71, 27.92, 44.56, 47.60, 47.79, 59.46, 147.29, 172.66 ppm;
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calculated positions and were included in the structure calculation
without further refinement of the parameters. CCDC 1045541 (3b),
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data for this paper. These data can be obtained free of charge
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Received: February 11, 2015
Published online on May 26, 2015
Chem. Eur. J. 2015, 21, 10369 – 10378
www.chemeurj.org
10378
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim