Synthesis and characterization of bis-cyclopropanated 1,3,5-tricarbonyl compounds. A combined synthetic, spectroscopic and theoretical study

Article abstract of DOI:10.1039/c1ob05455d

Bis-cyclopropanated 1,3,5-tricarbonyl compounds were prepared by a sequence of Claisen condensations and cyclopropanations. The optimization of the conditions proved to be very important to suppress retro-Claisen reactions. The conformation of these molec

Full text of DOI:10.1039/c1ob05455d

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PAPER
Synthesis and characterization of bis-cyclopropanated 1,3,5-tricarbonyl
compounds. A combined synthetic, spectroscopic and theoretical study†
Thomas Rahn,a,b Franziska Bendrath,a Martin Hein,a Wolfgang Baumann,b Haijun Jiao,b Armin Bo¨rner,a,b
Alexander Villingera and Peter Langer*a,b
Received 22nd March 2011, Accepted 26th April 2011
DOI: 10.1039/c1ob05455d
Bis-cyclopropanated 1,3,5-tricarbonyl compounds were prepared by a sequence of Claisen
condensations and cyclopropanations. The optimization of the conditions proved to be very important
to suppress retro-Claisen reactions. The conformation of these molecules was studied by experimental
and computational methods. The syn/syn;syn/syn conformation is present for all derivatives. It is
exclusively present in the case of the derivative containing a phenyl group located at the terminal
carbon atom. In most cases, equilibria with other conformers are found.
Introduction
A great variety of pharmacologically important natural products
are biosynthetically derived from poly(b-oxo)carboxylic acids
(polyketides).1 Polyketides also represent important synthetic
building blocks.2 Harris and coworkers reported the biomimetic
synthesis of various 1,3,5-tricarbonyl compounds A based on
condensations of 1,3-dicarbonyl dianions or 1,3,5-tricarbonyl tri-
anions with carboxylic acid derivatives (Fig. 1).3 1,3,5-Tricarbonyl
compounds also are available by reaction of 1,3-bis(silyloxy)-1,3-
butadienes, masked 1,3-dicarbonyl dianions, with acid chlorides.4
We were attracted by the beautiful and interesting structure of
Fig. 1 Structures of 1,3,5-tricarbonyl compounds A–D.
open-chained bis-cyclopropanated 1,3,5-tricarbonyl compounds
B. Like their permethylated analogues C, they are lacking
preliminary communication, we greatly extended the scope for
the CH-acidic methylene groups.5,6 Cyclopropyl-based molecular
the synthesis of bis-cyclopropanated 1,3,5-triketones and also
architectures have recently gained considerable theoretical and
successfully extended our synthetic strategy to the preparation of
structural interest.7 For example, versatile synthetic approaches
various bis-cyclopropanated triketides (i.e., bis-cyclopropanated
to open-chain oligocyclopropanes8 and s-[n]helicenes9 have been
3,5-dioxoesters). In addition, we have found that the direct
developed.
cyclopropanation of 3,5-dioxoesters resulted in the formation of
Cyclic cyclopropanated 1,3,5-triketone
D was prepared
cyclopropanated dihydrofurans which are interesting in their own
right. The structure and the conformation of the products, con-
taining different substitution patterns, were thoroughly analyzed
by spectroscopic methods and by DFT calculations.
in low yield by a Zn/Cu mediated transformation of 1-
bromocyclopropanecarboxylic acid chloride.10 Open-chained
1,3,5-tricarbonyl compounds of type B had not been prepared
until our recent short communication,11 and their synthesis is
a difficult task because 1,3,5-tricarbonyl compounds containing
quaternary carbons easily undergo fragmentations (by means
of retro-Claisen reactions). Herein, we report a comprehensive
synthetic, structural and theoretical study. With regard to our
Results and discussion
Synthesis
Our first target was the synthesis of bis-cyclopropanated 1,3,5-
triketones. We chose a synthetic strategy based on a straight-
forward sequence of Claisen condensation and cyclopropanation
(Scheme 1, Table 1). The K2CO3-mediated12 cyclopropanation
of 1-(cyclopropyl)butane-1,3-dione and benzoylacetone with 1,2-
dibromoethane afforded the known cyclopropanes 2a and 2b.13
The LDA-mediated reaction of 2a with cyclopropanecarboxylic
aInstitut fu¨r Chemie, Universita¨t Rostock, Albert Einstein Str. 3a, 18059,
Rostock, Germany. E-mail: peter.langer@uni-rostock.de; Fax: +49 381
4986412
bLeibniz-Institut fu¨r Katalyse an der Universita¨t Rostock e.V., Albert Einstein
Str. 29a, 18059, Rostock, Germany
† Electronic supplementary information (ESI) available. CCDC reference
numbers 818768 and 818769. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c1ob05455d
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Table 1 Synthesis of cyclopropyl-triketones 4a–f,h
Table 2 Synthesis of cyclopropyl-triketides 8a–h
2
3,4
R1
R2
% (2)a
% (3)a
% (4)a
7,8
R
% (7)a
% (8)a
a
b
b
b
b
b
b
b
b
a
b
c
d
e
f
g
h
i
cPr
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
cPr
70
75
75
75
75
75
75
75
75
65
47
31
22
31
21
18
25
63
30
64
42
30
34
33
0
a
b
c
d
e
f
cPr
40
58
44
51
32
40
48
52
18b
37
67
37
44
34
67
48
cPr
Me
tBu
Ph
OMe
Ph
4-MeC6H4
4-(MeO)C6H4
4-(ClCH2)C6H4
4-tBuC6H4
3-ClC6H4
1-Naphthyl
cHex
g
h
4-(MeO)C6H4
5
30
0
h -Ferrocenyl
a Isolated yields. b Stirring for 8 h instead of 12 h.
a Isolated yields.
Table 3 Optimization of the synthesis of cyclopropyl-triketide 7b
T [◦C]
Time (heating) + time (20 ◦C) [h]a
% (7b)
30
30
45
3 + 0
5 + 12
5 + 12
24
28
58
a Reaction time: heating at the indicated temperature + stirring at 20 ◦C.
Scheme 1 Synthesis of cyclopropyl-triketones 4a–f,h. Conditions: i,
1,2-dibromoethane (2.0 equiv.), K2CO3 (4.0 equiv.), DMSO, 8 h, 20 ◦C;
ii, 1) LDA (1.2 equiv.), THF, 1 h, -78 ◦C, 2) acid chloride, -78 → 20 ◦C,
12 h.
acid chloride gave 3a in up to 65% yield. Subsequent cyclopropa-
nation gave bis-cyclopropanated 1,3,5-triketone 4a. Likewise, the
condensation of 2b with cyclopropanecarboxylic acid chloride or
pivaloyl chloride afforded 3b and 3c which were transformed into
4b and 4c, respectively. The reaction of 2b with various aroyl
chlorides afforded products 3c–i. The cyclopropanation of 3c–
f and 3h afforded products 4c–f and 4h. The cyclopropanation
of derivatives 3g and 3i, containing electron-withdrawing groups,
failed.
Scheme 2 Synthesis of cyclopropyl-triketides 8a–h. Conditions: i, 1)
NaOMe (2.0 equiv.), MTBE, 5 h, 50 ◦C, 2) 12 h, 22 ◦C, 3) HCl (10%),
brine; ii, 1,2-dibromoethane (2.0 equiv.), K2CO3 (4.0 equiv.), DMSO,
12 h, 22 ◦C.
unsuccessful as it resulted in a retro-Claisen reaction. Moreover,
we found that the reaction time and the temperature had a great
effect on the yield. The best yields were obtained when the reaction
As mentioned above, compounds
4
represent bis-
◦
cyclopropanated 1,3,5-triketones. Our next goal was to prepare
bis-cyclopropanated 3,5-dioxoesters (triketides) which are, to
the best of our knowledge, also unknown to date. The strategy
depicted in Scheme 1 for the synthesis of 1,3,5-triketones 4
proved to be not applicable to the synthesis of triketides 8,
due to decomposition by retro-Claisen reaction. However, the
synthesis of triketides 8 could be realized by a slightly different
strategy (Scheme 2, Table 2). The Claisen condensation of
dimethyl cyclopropane-1,1-dicarboxylate (5), which is readily
available in large scale, with ketones 6a,b,d–h afforded the mono-
cyclopropanated triketides 7a,b,d–h which were transformed by
cyclopropanation into the desired bis-cyclopropanated triketides
8a,b,d–h. Likewise, the reaction of 5 with methyl acetate (6c) and
subsequent cyclopropanation afforded the symmetrical, hitherto
unknown bis-cyclopropanated diester 8c.
was carried out at 45–50 C for a minimum reaction time of 5 h
(Table 3). A lower temperature or shorter reaction time led to a
decrease in the yield.
Compounds 7a,b,d–h exist as a mixture of keto and enol
tautomers. According to the NMR experiments, the enol tautomer
is generally preferred, except for 7c which exclusively exists in the
keto form. For compound 7e, we were able to grow crystals and to
study the molecular structure by X-ray crystal structure analysis
(Fig. 2).
The NaOMe-mediated reaction of 5 with 2a afforded the bis-
cyclopropanated tetraketide 9 which represents a rare example
of an open-chained tetraketide (Scheme 3). Unfortunately, the
cyclopropanation of 9 proved to be unsuccessful under various
conditions, due to decomposition by retro-Claisen reactions.
In an attempt to facilitate the synthesis of bis-cyclopropanated
1,3,5-tricarbonyl compounds, we studied the direct twofold
cyclopropanation of 1,3,5-tricarbonyl derivatives (Scheme 4,
Table 4). The cyclopropanation of 1,3,5-tricarbonyl compounds
The best yields of mono-cyclopropanated triketides 7 were
obtained when sodium methoxide and MTBE were used as base
and solvent, respectively. The use of KOtBu or LDA proved to be
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Table 4 Synthesis of dihydrofurans 13
a,b
13
R
%
(12)
%a (13)
a
b
c
d
e
cPr
91
63
42
58
64
32
35
15
21
17
Ph
4-(MeO)C6H4
4-MeC6H4
3-ClC6H4
a Yields of isolated products. b Keto/enol = 0 : 100
cyclopropanated triketides 8. The relatively low yields can be
explained by practical problems during the chromatographic
purification and by partial decomposition, due to retro-Claisen
reactions. The formation of products 13 was not unexpected,
since a competition of cyclopropanation and dihydrofuran for-
mation has been previously reported for the reaction of 1,2-
dibromoethane with simple 1,3-dicarbonyl derivatives.14 The
synthesis of cyclopropanated dihydrofurans related to products
13 has, to the best of our knowledge, not been previously
reported.
Fig. 2 Molecular structure of 7e.
1
A H NOESY experiment was performed on 13a to confirm
the identity of compounds 13a–e (Fig. 3). It is important to note
that the cyclopropylidene moiety is located next to the ester group
and the cyclopropyl adjacent to the keto group. The regioisomeric
products iso-13a–e could not be isolated.
Scheme 3 Synthesis of cyclopropanated tetraketide 9. Conditions: i, 1)
NaOMe, MTBE, 3 h, 30 ◦C, 2) HCl (10%).
Fig. 3 Diagnostic NOESY interactions of compound 13a.
Conformations
The conformations of bis-cyclopropanated 1,3,5-triketones 4a and
4d were already studied in our preliminary communication from
both X-ray structural analysis and B3LYP/6-311+G(d,p) density
functional theory computation.11 For clarity and comparison, we
herein refer to those findings. In the case of 4d, only one conformer
(syn/syn;syn/syn) is present in the solid state and in solution, and
this is also confirmed by computation, and the second conformer
(syn/syn; anti/anti) is found less stable by 9.32 kcal mol-1 (Fig. 4).
In the more stable conformer, the two cyclopropyl rings possess a
syn conformation to the central carbonyl group; and the carbonyl
groups of the benzoyl groups also exist in a syn conformation to
the cyclopropyl rings.
Scheme 4 Synthesis of dihydrofurans 13a–e. Conditions: i, 1) CH2Cl2,
-87 → 20 ◦C; 2) NaHCO3, H2O; ii, 1,2-dibromoethane (2.5 equiv.), K2CO3
(5.0 equiv.), DMSO, 8 h, 20 ◦C.
has, to the best of our knowledge, not been studied so far.
The methyl 3,5-dioxoalkanoates 12a–e were prepared, using
our previously reported procedure,4a by condensation of 1,3-
bis(silyloxy)-1,3-butadiene 11 with acid chlorides 10. The syn-
thesis of derivatives 12a,b has been previously reported.4a The
reaction of 12a–e with 2.5 equiv. of 1,2-dibromoethane afforded
the cyclopropanated dihydrofurans 13a–e rather than the bis-
The predominance of the syn/syn;syn/syn conformer in the case
of 4d might be explained by the fact that the molecule contains two
phenyl groups and a stabilizing intramolecular p-stacking effect
might play a role. We tried to gain more insight by NMR. For the
apparently C2v-symmetric triketone 4a, only one set of signals and
thus no individual conformers were observed even at temperatures
down to -100 ◦C.11 For the non-symmetrical bis-cyclopropanated
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Fig. 6 Relaxed scan along the O1–C2–C3–C4 torsional angle at
HF/6-31G(d) for 4c.
Fig. 4 Conformation and energy of 4d (see ref. 11).
1,3,5-triketones 4c, 4e, 4f and 4h, 1H NOESY measurements
were carried out in CD2Cl2. Here, individual observation of
all molecular positions is possible and qualitative conclusions
are straightforward. The following spectroscopic patterns were
similar for all four derivatives. We find four signals (each of
them representing two protons), two AA¢XX¢ patterns, for the
cyclopropylidene groups. This proves averaged mirror symmetry
for the molecules, however, the preferred conformation is not the
planar (Cs) one. We find a positive NOE between the phenyl ortho
protons and both types of protons at the adjacent three-membered
ring (which is not surprising) and another positive NOE between
the phenyl ortho protons and one type of proton at the remote
cyclopropylidene. The latter indicates a significant contribution
of a syn/anti conformation (with respect to the central carbonyl
group). In such an arrangement, the substituents at both ends
of the chain should be able to approach each other. This can in
particular be observed for 4c by a positive NOE between the phenyl
ortho protons and the tert-butyl group (see ESI†). Unfortunately,
the resonances of the aromatic proton at the terminal residues are
insufficiently separated to observe this also for 4e, 4f and 4h.
To elucidate the change of the conformations of compound 4c,
we carried out density functional theory computations using the
B3LYP/6-311+G(d,p) method,15,16 and used the same procedure
for 4d.11 For 4c, we have found an energy minimum structure with
the phenyl and tert-butyl groups in syn/syn;syn/syn conformation
(Fig. 5). To search for the potential energy surface, we have rotated
the torsional angle of O1–C2–C3–C4 by 360◦ for a relaxed scan
at the HF/6-31G(d) level (Fig. 6). Two minimum structures very
close in energy are found: one corresponds to the syn/syn;syn/syn
conformation and the other one to a syn/anti;syn/syn confor-
mation (Fig. 5). The rotational barrier is lower than 7 kcal
mol-1 which indicates a free rotation and equilibrium of both
conformers. The structure of the syn/anti;syn/syn conformation
was further refined at B3LYP/6-311+G(d,p) and characterized as
a true energy minimum; the torsional angle of O1–C2–C3–C4 is
-152.8◦. At B3LYP/6-311+G(d,p), under the consideration of the
thermal correction to Gibbs free energy at 298 K from frequency
calculations, we have found that the syn/syn;syn/syn confor-
mation (-962.82571 au) and the syn/anti;syn/syn conformation
(-962.82577 au) of 4c are nearly identical in Gibbs free energy.
This reveals that both conformers are nearly equally populated
in solution. All observed NOEs (vide supra) are compatible
with the syn/anti;syn/syn conformation. The syn/syn;syn/syn
conformation is characterized by large distances between the H-
bearing groups and thus does not give rise to specific cross peaks
in the NOESY spectrum.
Finally, the conformation of bis-cyclopropanated triketides
8 was studied. Unfortunately, NMR experiments remained in-
conclusive, due to signal overlap. However, we were able to
study the structure of 8g in the solid state by X-ray crystal
structure analysis (Fig. 7). In the solid state, a syn/syn;syn/syn
conformation is adopted (like in the case of compound 4d). Of
course, this result does not necessarily reflect the situation in
solution and the conformation might be a result of crystal packing
effects.
Conclusions
In conclusion, we have reported the synthesis of various symmet-
rical and unsymmetrical bis-cyclopropanated 1,3,5-tricarbonyl
Fig. 5 The B3LYP/6-311+G(d,p) optimized energy minimum structures of 4c.
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was removed by filtration. The solid was thoroughly washed
with diethyl ether. The filtrate was washed with water until
the yellow colour disappeared, dried (Na2SO4) and concentrated
in vacuo. The residue was purified by column chromatography
(hexane/EtOAc = 2 : 1) to give product 2. The synthesis of 2a,b
has been previously reported.13
General procedure for the synthesis of cyclopropylketides 3
To a solution of LDA (1.2 equiv.) in THF (2 mL mmol-1) was
added 2 (1 equiv.) at -78 ◦C. The reaction mixture was stirred for
1 h and acid chloride (1.1 equiv.) was added dropwise at -78 ◦C.
The reaction mixture was stirred for 12 h and allowed to warm
to 20 ◦C. After aqueous workup with saturated NH4Cl solution,
the aqueous phase was extracted with diethyl ether. The combined
organic layers were dried (Na2SO4) and concentrated in vacuo. The
residue was purified by column chromatography (hexane/EtOAc =
2 : 1) to give product 3.
Fig. 7 Molecular structure of 8g.
1-(1-(Cyclopropanecarbonyl)cyclopropyl)-3-cyclopropylpropane-
1,3-dione (3a)
compounds. While the direct cyclopropanation of 3,5-dioxoesters
resulted in the formation of mono-cyclopropanated dihydro-
furans, the target molecules could be prepared by a stepwise
strategy of Claisen condensation and cyclopropanation. The
optimization of the reaction conditions played an important
role in order to suppress the decomposition by retro-Claisen
reactions. The conformations of these molecules were studied
using a combined approach of X-ray crystal structure analysis,
NOE-experiments and computational methods. In the solid state,
only one conformation (syn/syn;syn/syn) was present in the case
of the symmetrical bis-cyclopropanated 1,3,5-triketone 4d and of
the bis-cyclopropanated triketide 8g. In the case of derivative 4d,
containing two phenyl groups located at the terminal positions
of the chain, this conformation is by far more stable than the
syn/syn;anti/anti conformation and is likely to be exclusively
present in solution. In the case of 4a, containing two cyclopropyl
groups located at the terminal positions of the chain, two main
conformations (syn/syn;syn/syn and syn/syn;anti/anti), which
are similar in Gibbs free energy, were found to coexist in solution.
Only one conformation (syn/syn;syn/syn) was present in the case
of the bis-cyclopropanated 1,3,5-triketones 4a and 4c.
Starting with 2a (1.000 g, 6.57 mmol) dissolved in a solution of
LDA (9.86 mmol) in THF (13 ml) and cyclopropanecarbonyl
chloride (0.824 g, 7.89 mmol), 3a was isolated as a yellow oil
1
(0.94 g, 65%). H NMR (300 MHz, CDCl3, keto/enol = 25 : 75):
d (enol) = 0.94–1.15 (m, 10H, CH/CH2), 1.40–1.48 (m, 4H, CH2),
5.90 (s, 1H, CH), 15.89 (s, 1H, OH). 13C NMR (75 MHz, CDCl3):
d (enol) = 10.7, 12.6, 17.7 (CH2), 18.5, 19.8 (CH), 38.9 (C), 99.7
(CH), 187.2, 196.9, 206.4 (CO). IR (neat., cm-1) 2999 (m), 2970
(w), 1749 (m), 1683 (s), 1623 (s, br), 1443 (s), 1386 (s), 1296 (m),
1265 (m), 1197 (m), 1137 (s), 1106 (m), 1062 (s), 951 (m), 910 (m),
892 (m). MS (EI, 70 eV) m/z = 220 (M+, 2.5), 205 (2.0), 192 (8.6),
152 (23.9), 137 (5.9), 69 (100). Anal. calcd. for C13H16O3 (220.26):
C, 70.89; H, 7.32. Found: C, 70.60; H, 7.71.
1-(1-Benzoylcyclopropyl)-3-cyclopropylpropane-1,3-dione (3b)
Starting with 2b (1.000 g, 5.31 mmol) dissolved in a solution of
LDA (6.38 mmol) in THF (11 ml) and cyclopropanecarbonyl
chloride (0.611 g, 5.84 mmol), 3b was isolated as a yellow oil
(0.64 g, 47%). 1H NMR (300 MHz, CDCl3, keto/enol = 50 : 50): d
(enol) = 0.82–1.02 (m, 4H, CH2), 1.38 (m, 1H, CH), 1.50–1.58 (m,
4H, CH2), 5.36 (s, 1H, CH), 7.34–8.00 (m, 5H, Ph), 15.91 (s, 1H,
OH); d (keto) = 0.82–1.02 (m, 4H, CH2), 1.50–1.66 (m, 4H, CH2),
1.69 (m, 1H, CH), 2.06 (s, 2H, CH2), 7.34–8.00 (m, 5H, Ph). 13C
NMR (75 MHz, CDCl3): d (enol) = 10.0, 16.4 (CH2), 17.2 (CH),
37.0 (C), 98.5 (CH), 128.6, 129.2, 133.3 (Ph), 136.3 (C), 191.0,
192.4, 196.2 (CO). IR (ATR, cm-1) 3085 (w), 3061 (w) 3010 (w),
2970 (w), 2933 (w), 2873 (w), 1673 (s), 1596 (s), 1581 (s), 1449
(m), 1369 (m), 1321 (s), 1295 (s) 1195 (s), 1176 (s), 1133 (m), 1075
(m), 1028 (m), 1002 (s), 945 (m), 928 (s), 895 (m). MS (EI, 70 eV)
m/z = 256 (M+, 7.1), 187 (33.4), 145 (9.8), 105 (100), 77 (51.5),
69 (69.3). HRMS (EI, 70 eV): cacld. for C16H16O3 (M+) 256.1094,
found 256.1096.
Experimental section
General comments
All solvents were dried by standard methods and all reactions
were carried out under an inert atmosphere. For 1H and 13C
NMR spectra the deuterated solvents indicated were used. Mass
spectrometric data (MS) were obtained by electron ionization
(EI, 70 eV), chemical ionization (CI, isobutane) or electrospray
ionization (ESI). For preparative scale chromatography silica gel
60 (0.063-0.200 mm, 70–230 mesh) was used.
General procedure for the synthesis of cyclopropylketides 2
To a suspension of K2CO3 (4.0 equiv.) in DMSO (0.3–
0.5 mL mmol-1) was added 1 (1.0 equiv.). To the reaction
mixture dibromoethane (2.0 equiv.) was added dropwise at 20 ◦C
with vigorous stirring. After stirring at 20 ◦C for 8 h, K2CO3
1-(1-Benzoylcyclopropyl)-4,4-dimethylpentane-1,3-dione (3c)
Starting with 2b (2.000 g, 10.63 mmol) dissolved in a solution of
LDA (12.76 mmol) in THF (20 ml) and acid chloride (1.44 ml,
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1
11.69 mmol), 3c was isolated as a yellow oil (0.90 g, 31%). H
11.69 mmol), 3f was isolated as a yellow oil (0.72 g, 21%). 1H NMR
(300 MHz, CDCl3, keto/enol = 10 : 90): d (enol) = 1.56–1.74 (m,
4H, CH2), 3.77 (s, 3H, CH3), 5.81 (s, 1H, CH), 6.82 (d, 3J = 9.03
Hz, 2H, Ar), 7.40–7.49 (m, 3H, Ph), 7.56 (d, 3J = 9.06 Hz, 2H, Ar),
NMR (300 MHz, CDCl3, keto/enol = 0 : 100): d (enol) = 0.94 (s,
9H, C(CH3)3), 1.54–1.72 (m, 4H, CH2), 5.24 (s, 1H, CH), 7.29–
7.57 (m, 3H, Ph), 7.89–7.93 (m, 2H, Ph), 15.50 (s, 1H, OH). 13C
NMR (75 MHz, CDCl3): d (enol) = 17.2 (CH2), 27.2 (CH3), 37.7,
3
8.00 (d, J = 6.96 Hz, 2H, Ph), 16.13 (s, 1H, OH). 13C NMR (75
38.6 (C), 96.3 (CH), 128.5, 129.0, 133.2 (Ar), 136.8 (C), 194.1,
MHz, CDCl3): d (enol) = 16.8 (CH2), 38.5 (C), 55.4 (CH3), 95.4
-1
˜
196.2, 196.8 (CO). IR (ATR, cm ): n = 3064 (w), 2968 (m), 2935
(CH), 113.9 (Ar), 125.9 (C), 128.8, 128.9, 129.1, 133.3 (Ar), 136.5,
-1
˜
(w), 2908 (w), 2872 (w), 1748 (w), 1678 (m), 1596 (s), 1480 (m),
1449 (m), 1395 (w), 1363 (m), 1320 (m), 1294 (m, br), 1202 (m),
1178 (w), 1131 (s), 1075 (w), 1035 (m), 1001 (m), 964 (m), 916
(m), 877 (w), 785 (s). MS (EI, 70 eV) m/z = 272 (M+, 1.8), 215
(65.0), 187 (9.7), 173 (70.4), 105 (100), 77 (34.4). Anal. calcd.
for C17H20O3 (272.34): C, 74.97; H, 7.40. Found: C, 75.13; H,
7.45.
163.0 (C), 178.7, 195.4, 196.4 (CO). IR (ATR, cm ): n = 3084 (w),
3061 (w), 3008 (w), 2978 (w), 2940 (w), 2910 (w), 2842 (w), 1675
(m), 1607 (s), 1588 (s), 1556 (s), 1505 (s), 1446 (s), 1435 (s), 1319
(m), 1300 (m), 1248 (s), 1201 (m), 1174 (s), 1133 (m), 1118 (s),
1074 (m), 1036 (m), 1018 (s), 1001 (s), 966 (m), 933 (m), 873 (m),
859 (w), 841 (s), 812 (m), 780 (s). MS (EI, 70 eV) m/z = 322 (M+,
7.1), 187 (8.4), 177 (7.1), 135 (100), 105 (28.6), 77 (28.5), 69 (11.5).
Anal. calcd. for C20H18O4 (322.35): C, 74.52; H, 5.63. Found: C,
74.82; H, 5.58.
1-(1-Benzoylcyclopropyl)-3-phenylpropane-1,3-dione (3d)
Starting with 2b (1.000 g, 5.31 mmol) dissolved in a solution of
1-(1-Benzoylcyclopropyl)-3-(4-(chloromethyl)phenyl)propane-1,3-
dione (3g)
LDA (6.38 mmol) in THF (11 ml) and benzoyl chloride (0.7 ml,
1
5.84 mmol), 3d was isolated as a yellow oil (0.34 g, 22%). H
NMR (300 MHz, CDCl3, keto/enol = 0 : 100): d = 1.59–1.77 (m,
4H, CH2), 5.87 (s, 1H, CH), 7.34–8.01 (m, 10H, Ph), 15.85 (s, 1H,
OH). 13C NMR (75 MHz, CDCl3): d = 17.5 (CH2), 39.3 (C), 96.9
(CH), 127.1, 128.9, 129.1, 129.5, 132.6, 133.8, (Ph), 133.9, 136.9
(C), 178.5, 196.7, 197.2 (CO). IR (ATR, cm-1) 3084 (w), 3062 (w)
3034 (w) 1719 (w, br), 1677 (m), 1596 (m), 1567 (s), 1492 (m), 1456
(m), 1421 (m) 1296 (m), 1249 (m), 1203 (m), 1177 (m), 1133 (m),
1097 (w), 1074 (m), 1026 (m), 998 (s), 930 (m, br), 901 (w), 868
(w), 795 (m). MS (EI, 70 eV) m/z = 392 (M+, 8.3), 187 (32.0), 147
(8.1), 105 (100), 77 (41.9), 69 (16.2). HRMS (EI, 70 eV): cacld for
C19H16O3 (M+) 292.1094, found 292.1096.
Starting with 2b (2.000 g, 10.63 mmol) dissolved in a solution of
LDA (12.76 mmol) in THF (20 ml) and acid chloride (2.00 g,
1
11.63 mmol), 3g was isolated as a yellow oil (0.65 g, 18%). H
NMR (300 MHz, CDCl3, keto/enol = 0 : 100): d (enol) = 1.50–
1.77 (m, 4H, CH2), 2.06 (s, 2H, CH2), 5.81 (s, 1H, CH), 7.34–7.59
(m, 7H, Ph/Ar), 7.91–8.00 (m, 2H, Ph/Ar), 15.80 (s, 1H, OH).
13C NMR (75 MHz, CDCl3): d (enol) = 17.1, 17.3 (CH2), 39.0,
41.9 (C), 45.3 (CH2), 96.8 (CH), 127.7, 128.4, 128.6, 133.5, 133.5
(Ar), 136.5, 136.8, 141.5, 177.2 (C), 196.3, 197.1, 203.9 (CO). IR
-1
˜
(ATR, cm ): n = 3084 (w), 3062 (w), 3010 (w), 2963 (w), 2871 (w),
1672 (s), 1597 (s), 1556 (s), 1508 (m), 1448 (m), 1359 (w), 1321
(s), 1296 (s, br), 1266 (s), 1204 (m), 1177 (m), 1135 (m), 1113 (m),
1074 (m), 1035 (m), 1002 (s), 898 (w), 854 (w), 785 (s). MS (EI, 70
eV) m/z = 340 (M+, 34.5), 305 (23.0), 195 (17.5), 187 (99.7), 153
(100), 145 (18.8), 135 (11.8), 125 (16.0), 119 (15.4), 112 (12.9), 105
(81.8), 91 (15.5), 77 (74.4), 69 (26.4). HRMS (EI, 70 eV): cacld.
for C20H17ClO3 (M+) 340.08607, found 340.085130.
1-(1-Benzoylcyclopropyl)-3-p-tolylpropane-1,3-dione (3e)
Starting with 2b (2.000 g, 10.63 mmol) dissolved in a solution of
LDA (12.76 mmol) in THF (20 ml) and acid chloride (1.63 ml,
11.69 mmol), 3e was isolated as a colourless solid (1.00 g, 31%);
◦
1
mp 89 C. H NMR (300 MHz, CDCl3, keto/enol = 0 : 100): d
(enol) = 1.58 (q, 3J = 3.83 Hz, 2H, CH2), 1.75 (q, 3J = 3.83 Hz, 2H,
CH2), 2.42 (s, 3H, CH3), 5.85 (s, 1H, CH), 7.13 (d, 3J = 7.91 Hz,
2H, Ar), 7.41–7.53 (m, 5H, Ar/Ph), 7.98–8.01 (m, 2H, Ph), 15.94
(s, 1H, OH). 13C NMR (75 MHz, CDCl3): d (enol) = 17.1 (CH2),
21.6 (CH3), 38.9 (C), 96.2 (CH), 126.8, 128.7, 129.2, 129.4 (Ar),
1-(1-Benzoylcyclopropyl)-3-(4-tert-butylphenyl)propane-1,3-dione
(3h)
Starting with 2b (2.000 g, 10.63 mmol) dissolved in a solution of
130.8 (C), 133.4 (Ar), 136.6, 143.1 (C), 178.6, 196.4, 196.5 (CO).
LDA (12.76 mmol) in THF (20 ml) and acid chloride (2.30 g,
11.69 mmol), 3h was isolated as an orange oil (0.93 g, 25%). H
-1
1
˜
IR (ATR, cm ): n = 3079 (w), 3060 (w), 3030 (w), 2966 (w), 2920
(w), 1716 (m), 1675 (m), 1596 (s), 1557 (s, br), 1508 (m), 1446 (m),
1342 (m), 1317 (m), 1290 (m), 1266 (s), 1207 (m), 1190 (m), 1178
(m), 1097 (s), 1066 (m), 1031 (m), 1017 (m), 1007 (m), 990 (m), 951
(m), 937 (m), 905 (m), 885 (m), 866 (m), 841 (m), 828 (m), 772 (s).
MS (EI, 70 eV) m/z = 306 (M+, 36.2), 187 (76.2), 161 (27.3), 145
(12.9), 119 (100), 105 (82.3), 91 (45.2), 77 (55.3), 69 (46.6). Anal.
calcd. for C20H18O3 (306.36): C, 78.41; H, 5.92. Found: C, 78.47;
H, 5.95.
NMR (300 MHz, CDCl3, keto/enol = 0 : 100): d (enol) = 1.29 (s,
9H, C(CH3)3), 1.59 (q, 3J = 3.82 Hz, 2H, CH2), 1.75 (q, 3J = 3.83
Hz, 2H, CH2), 5.85 (s, 1H, CH), 7.35–8.02 (m, 9H, Ar/Ph), 15.89
(s, 1H, OH). 13C NMR (75 MHz, CDCl3): d (enol) = 17.1 (CH2),
31.1 (CH3), 35.0, 38.9 (C), 96.4 (CH), 125.6, 126.7, 128.7, 129.2
(Ar), 130.8 (C), 133.4 (Ar), 136.6, 156.1 (C), 178.4, 180.0, 196.5
-1
˜
(CO). IR (ATR, cm ): n = 3062 (w), 2963 (m), 2906 (w), 2869
(w), 1719 (w), 1676 (m), 1597 (s), 1557 (m), 1508 (m), 1448 (m),
1363 (m), 1320 (m), 1297 (m, br), 1268 (s), 1201 (m), 1178 (m),
1140 (w), 1112 (m), 1097 (m), 1071 (m), 1032 (m), 1015 (m), 1001
(m), 934 (m), 904 (m), 848 (m), 783 (s). MS (EI, 70 eV) m/z = 348
(M+, 10.8), 187 (23.5), 161 (100), 145 (9.7), 105 (34.9), 77 (21.3),
69 (9.7). HRMS (EI, 70 eV): calcd. for C23H24O3 (M+) 348.17200,
found 348.172840.
1-(1-Benzoylcyclopropyl)-3-(4-methoxyphenyl)propane-1,3-dione
(3f)
Starting with 2b (2.000 g, 10.63 mmol) dissolved in a solution
of LDA (12.76 mmol) in THF (20 ml) and acid chloride (1.99 g,
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1-(1-Benzoylcyclopropyl)-3-(3-chlorophenyl)propane-1,3-dione (3i)
MS (EI, 70 eV) m/z = 282 (M+, 4.3), 254 (22.4), 293 (10.7), 213
(11.4), 207 (11.4), 191 (18.5), 163 (14.4), 105 (100), 77 (60.7), 69
(45.0). HRMS (EI, 70 eV): cacld. for C18H18O3 (M+) 281.1172,
found 281.1174.
Starting with 2b (2.000 g, 10.63 mmol) dissolved in a solution of
LDA (12.76 mmol) in THF (20 ml) and acid chloride (1.50 ml,
11.◦69 mmol), 3i was isolated as an orange oil (2.20 g, 63%); mp
89 C. 1H NMR (300 MHz, CDCl3, keto/enol = 0 : 100): d (enol) =
1.60–1.79 (m, 4H, CH2), 5.83 (s, 1H, CH), 7.24–7.57 (m, 6H,
Ar/Ph), 7.97–8.00 (m, 2H, Ph), 15.74 (s, 1H, OH). 13C NMR (75
MHz, CDCl3): d (enol) = 17.5 (CH2), 39.1 (C), 96.9 (CH), 124.8,
1-(1-(1-Benzoylcyclopropanecarbonyl)cyclopropyl)-2,2-
dimethylpropan-1-one (4c)
Starting with 3c (0.24 g, 0.88 mmol) dissolved in a suspension
of K2CO3 (0.49 g, 3.52 mmol) in DMSO (0.5 ml) and 1,2-
dibromoethane (0.15 ml, 1.76 mmol) added dropwise, 4c was
126.9, 128.8, 129.2, 129.9, 132.1, 133.6 (Ar/Ph), 134.8, 135.5, 136.5
-1
˜
(C), 176.5, 196.2, 197.3 (CO). IR (ATR, cm ): n = 3068 (w), 3011
1
(w), 1724 (w), 1676 (m), 1598 (m), 1561 (s, br), 1448 (m), 1320
(m), 1292 (m), 1244 (m), 1202 (m), 1177 (m), 1132 (m), 1096 (m),
1075 (m), 1034 (m), 1000 (m), 933 (m), 907 (m), 843 (w), 804
(w), 776 (s). MS (EI, 70 eV) m/z = 326 (M+, 5.8), 187 (49.5), 139
(78.7), 105 (100), 77 (55.6), 69 (24.3). HRMS (EI, 70 eV): calcd.
for C19H15ClO3 (M+) 326.07042, found 326.06966.
isolated as an orange oil (0.11 g, 42%). H NMR (300 MHz,
CDCl3): d = 0.95 (m, 2H, CH2), 1.14 (s, 9H, C(CH3)3), 1.25 (m,
2H, CH2), 1.54 (q, 3J = 3.79 Hz, 2H, CH2), 1.71 (q, 3J = 3.80 Hz,
2H, CH2), 7.30–7.89 (m, 5H, Ph). 13C NMR (75 MHz, CDCl3):
d = 16.0, 18.1 (CH2), 28.4 (CH3), 41.1, 43.6, 45.5 (C), 128.5, 129.4,
133.4 (Ph), 137.3 (C), 195.6, 200.8, 211.0 (CO). IR (ATR, cm-1):
˜
n = 3063 (w), 2970 (w), 2935 (w), 2908 (w), 2872 (w), 1730 (w),
1666 (s), 1598 (m), 1480 (m), 1449 (m), 1395 (w), 1365 (w), 1320
(m), 1296 (m), 1202 (m), 1177 (m), 1146 (m, br), 1073 (s), 1049
(m), 1014 (m), 993 (s), 938 (m), 882 (m), 785 (m). MS (EI, 70 eV)
m/z = 297 (M+, 1.0), 241 (100), 213 (12.6), 173 (21.7), 105 (79.6),
77 (34.2). HRMS (ESI): cacld. for C19H23O3 ([M+1]+) 299.16417,
found 299.16443.
Procedure for the synthesis of cyclopropylketides 4
To a suspension of K2CO3 (4.0 equiv.) in DMSO (0.3–
0.5 mL mmol-1) was added 3 (1.0 equiv.). To the reaction
mixture dibromoethane (2.0 equiv.) was added dropwise at 20 ◦C
with vigorous stirring. After stirring at 20 ◦C for 8 h, K2CO3
was removed by filtration. The solid was thoroughly washed
with diethyl ether. The filtrate was washed with water until
the yellow colour disappeared, dried (Na2SO4) and concentrated
in vacuo. The residue was purified by column chromatography
(hexane/EtOAc = 2 : 1) to give product 4.
1,1¢-Carbonylbis(cyclopropane-1,1-diyl)bis(phenylmethanone) (4d)
Starting with 3d (0.280 g, 0.96 mmol) dissolved in a suspension of
K2CO3 (0.530 g, 3.83 mmol) in DMSO (0.5 ml) and dibromoethane
(0.17 ml, 1.92 mmol), 4d was isolated as a colorless solid (0.17 g,
◦
1
30%). MP: 144–145 C. H NMR (300 MHz, CDCl3): d = 1.18–
1.41 (m, 4H, CH2), 7.41–7.77 (m, 5H, Ph). 13C NMR (75 MHz,
CDCl3): d = 19.1 (CH2), 43.0 (C), 128.8, 129.4, 133.6 (Ph), 138.0
(C), 196.2, 202.2 (CO). IR (ATR, cm-1) 3094 (w), 3054 (w) 3017
(w) 1723 (w, br), 1666 (m), 1647 (s), 1597 (m), 1579 (m), 1451 (m),
1416 (w) 1320 (s), 1295 (s), 1203 (m), 1173 (m), 1067 (s), 1037 (m),
1027 (m), 1001 (m), 985 (m), 929 (w), 866 (m), 841 (w), 805 (w).
MS (EI, 70 eV) m/z = 318 (M+, 5.3), 290 (12.4), 227 (5.6), 213
(10.2), 199 (13.4), 105 (100), 77 (62.3). Anal. calcd. for C21H18O3
(318.37): C, 79.22; H, 5.70. Found: C, 79.04; H, 5.59.
1,1¢-Carbonylbis(cyclopropane-1,1-diyl)bis(cyclopropylmethanone)
(4a)
Starting with 3a (0.500 g, 2.27 mmol) dissolved in a suspension of
K2CO3 (0.784 g, 5.68 mmol) in DMSO (0.7 ml) and dibromoethane
(0.2 ml, 2.27 mmol), 4a was isolated as a colorless oil (0.17 g, 30%).
1H NMR (400 MHz, CDCl3): d = 0.86–1.04 (m, 4H, CH2), 1.63 (m,
4H, CH2), 1.83–1.89 (m, 2H, CH). 13C NMR (100 MHz, CDCl3):
d = 12.3 (CH2), 17.9 (CH), 19.6 (CH2), 43.5 (C), 202.4, 205.8 (CO).
IR (neat., cm-1) 3096 (m), 3011 (s) 1681 (s, br), 1570 (m), 1444 (s),
1392 (s, br) 1319 (s), 1280 (s), 1198 (m), 1107 (s), 1085 (s), 1061
(s), 1006 (s), 953 (m), 936 (w), 922 (w), 893 (m), 841 (w). MS (EI,
70 eV) m/z = 246 (M+, 0.3), 218 (82.9), 203 (17.7), 177 (19.4), 121
(15.0), 69 (100). Anal. calcd. for C15H18O3 (246.30): C, 73.15; H,
7.37. Found: C, 73.30; H, 7.36.
(1-(1-Benzoylcyclopropanecarbonyl)cyclopropyl)(p-tolyl)-
methanone (4e)
Starting with 3e (0.27 g, 0.88 mmol) dissolved in a suspension
of K2CO3 (0.49 g, 3.52 mmol) in DMSO (0.5 ml) and 1,2-
Dibromoethane (0.15 ml, 1.76 mmol) added dropwise, 4e was
(1-(1-Benzoylcyclopropanecarbonyl)cyclopropyl)(cyclopropyl)-
methanone (4b)
◦
1
isolated as a colourless solid (0.10 g, 34%); mp 96 C. H NMR
(300 MHz, CDCl3): d = 1.15–1.23 (m, 4H, CH2), 1.35–1.44 (m, 4H,
CH2), 2.42 (s, 3H, CH3), 7.23 (d, 3J = 8.06 Hz, 2H, Ar), 7.41–7.46
Starting with 3b (0.200 g, 0.78 mmol) dissolved in a suspension of
K2CO3 (0.43 g, 3.12 mmol) in DMSO (0.5 ml) and dibromoethane
(0.13 ml, 1.56 mmol), 4b was isolated as a colorless oil (0.14 g,
64%). 1H NMR (400 MHz, CDCl3): d = 0.80–0.97, (m, 4H, CH2),
1.19–1.41 (m, 4H, CH2), 1.62 (m, 1H, CH), 1.70–1.75 (m, 4H,
CH2), 7.27–7.72 (m, 5H, Ph). 13C NMR (100 MHz, CDCl3): d =
12.9 (CH2), 18.3 (CH), 19.8, 20.7 (CH2), 42.5, 44.1 (C), 128.6,
129.1, 133.1 (Ph), 138.5 (C), 197.1, 202.4, 205.2 (CO). IR (ATR,
cm-1) 3087 (w), 3063 (w), 3011 (w), 1731 (w), 1666 (s, br), 1598
(w), 1580, (w), 1449 (m), 1387 (m, br) 1320 (s), 1202 (m), 1165
(m), 1108 (w), 1078 (s), 1049 (s), 1008 (m), 993 (s), 906 (m, br).
3
(m, 2H, Ph), 7.54–7.58 (m, 1H, Ph), 7.66 (d, J = 8.16 Hz, 2H,
Ar), 7.74–7.77 (m, 2H, Ph). 13C NMR (75 MHz, CDCl3): d = 18.7,
18.8 (CH2), 21.8 (CH3), 42.5, 42.6 (C), 128.4, 129.1, 129.2, 129.2,
133.23 (Ar/Ph), 135.1, 137.8, 144.1 (C), 195.2, 195.9, 202.1 (CO).
-1
˜
IR (ATR, cm ): n = 3090 (w), 3053 (w), 3011 (w), 2923 (w), 2862
(w), 1722 (w), 1664 (s), 1650 (s), 1604 (s), 1578 (m), 1509 (w), 1450
(m), 1418 (w), 1317 (s), 1296 (s), 1202 (m), 1172 (s), 1119 (w), 1099
(m), 1069 (s), 1046 (m), 1001 (m), 988 (s), 914 (w), 864 (m), 840
(m), 819 (m), 782 (s). MS (EI, 70 eV) m/z = 332 (M+, 22.5), 304
(61.9), 276 (9.0), 227 (36.4), 213 (34.8), 199 (19.5), 171 (11.3), 157
5178 | Org. Biomol. Chem., 2011, 9, 5172–5184
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(10.2), 119 (100), 105 (96.4), 91 (71.2), 77 (52.6). HRMS (ESI):
cacld. for C22H21O3 ([M+1]+) 333.14852, found 333.14868.
7. Starting with 5 (3.95 g, 25.00 mmol) dissolved in a suspension
of sodium methoxide (5.40 g, 100.00 mmol) in MTBE (25.0 ml)
and 6 (4.20 g, 50.00 mmol), 7 was isolated as a orange oil (2.09 g,
40%). 1H NMR (300 MHz, CDCl3, keto/enol = 45 : 55): d (enol) =
0.98–1.18 (m, 4H, CH2), 1.57 (m, 4H, CH2), 1.68 (m, 1H, CH),
3.77 (s, 3H, CH3), 6.27 (s, 1H, CH), 16.01 (s, 1H, OH); d (keto) =
0.98–1.18 (m, 4H, CH2), 1.63 (m, 4H, CH2), 2.04 (m, 1H, CH),
3.74 (s, 3H, CH3), 4.21 (s, 2H, CH2). 13C NMR (75 MHz, CDCl3):
d (enol) = 10.4 (CH2), 18.2 (CH), 18.7 (CH2), 30.3 (C), 52.6 (CH3),
99.4 (CH), 171.6, 187.1, 195.2 (CO); d (keto) = 11.7 (CH2), 21.4
(CH), 21.6 (CH2), 35.1 (C), 52.5 (CH3), 57.3 (CH2), 171.6, 200.1,
205.0 (CO). IR (neat., cm-1) 3011 (m), 2950 (m) 2848 (m) 1732 (s),
1653 (m), 1594 (m, br), 1559 (m), 1442 (m), 1382 (m), 1319 (m, br)
1201 (m), 1155 (m), 1119 (m), 1072 (m), 1027 (w), 967 (m), 944
(m), 915 (w), 900 (w). MS (EI, 70 eV) m/z = 210 (M+, 5.4), 182
(19.8), 178 (11.5), 137 (9.5), 127 (15.1), 111 (10.5), 69 (100). Anal.
calcd. for C11H14O4 (210.23): C, 62.85; H, 6.71. Found: C, 63.23;
H, 6.78.
(1-(1-Benzoylcyclopropanecarbonyl)cyclopropyl)(4-methoxy-
phenyl)methanone (4f)
Starting with 3f (0.31 g, 0.96 mmol) dissolved in a suspension
of K2CO3 (0.53 g, 3.83 mmol) in DMSO (0.5 ml) and 1,2-
dibromoethane (0.17 ml, 1.92 mmol) added dropwise, 4f was
isolated as a colourless solid (0.11 g, 33%); mp 105 ◦C. 1H NMR
(300 MHz, CDCl3): d = 1.15 (q, 3J = 3.86 Hz, 2H, CH2), 1.24 (q,
3J = 3.86 Hz, 2H, CH2), 1.35 (q, 3J = 3.86 Hz, 2H, CH2), 1.44 (q,
3J = 3.86 Hz, 2H, CH2), 3.88 (s, 3H, CH3), 6.91 (m, 2H, Ar), 7.41–
7.60 (m, 4H, Ar/Ph), 7.73–7.77 (m, 3H, Ph). 13C NMR (75 MHz,
CDCl3): d = 18.5, 18.7 (CH2), 42.3, 42.6 (C), 55.5 (CH3), 113.6
(Ar), 128.4, 129.1 (Ar/Ph), 130.5 (C), 131.3, 133.2 (Ar), 137.7,
-1
˜
163.6 (C), 193.9, 195.8, 202.2 (CO). IR (ATR, cm ): n = 3088 (w),
3054 (w), 3013 (w), 2966 (w), 2938 (w), 2912 (w), 1663 (m), 1648
(s), 1596 (s), 1573 (s), 1510 (m), 1450 (m), 1300 (s), 1253 (s), 1204
(s), 1168 (s), 1116 (m), 1069 (s), 1029 (s), 1000 (m), 985 (s), 864
(w), 844 (s), 807 (m), 781 (s). MS (EI, 70 eV) m/z = 348 (M+, 30.6),
320 (64.8), 243 (20.2), 229 (18.1), 187 (23.4), 159 (12.3), 135 (100),
105 (79.9), 92 (25.3), 77 (77.6). Anal. calcd. for C22H20O4 (348.39):
C, 75.84; H, 5.79. Found: C, 75.81; H, 5.87.
General procedure for the synthesis of cyclopropylketides 7b–h
To a suspension of sodium methoxide (2.0 equiv.) in MTBE
(0.75 mL mmol-1 ketone) was added 6 (1.0 equiv.) at 50 ◦C.
After stirring for 10 min 5 (1.0 equiv.) was added dropwise over
a period of 30 to 60 min at 45–50 ◦C with vigorous stirring.
Then stirring was continued for 5 h at the same temperature
and then for a further for 12 h at 22 ◦C. After neutralization
with 10% HCl solution with ice cooling and addition of saturated
NaCl solution, the organic layer was separated and washed with
water. The aqueous phase was extracted with diethyl ether. The
combined organic layers were dried (Na2SO4) and concentrated
in vacuo. The residue was purified by column chromatography
(heptane/EtOAc = 100/1 → 20/1) to give product 7.
(1-(1-Benzoylcyclopropanecarbonyl)cyclopropyl)(4-tert-butyl-
phenyl)methanone (4h)
Starting with 3h (0.31 g, 0.88 mmol) dissolved in a suspension
of K2CO3 (0.49 g, 3.52 mmol) in DMSO (0.5 ml) and 1,2-
Dibromoethane (0.15 ml, 1.76 mmol) added dropwise, 4h was
1
isolated as a pale yellow oil (0.10 g, 30%). H NMR (300 MHz,
CDCl3): d = 1.16–1.21 (m, 4H, CH2) 1.35 (s, 9H, C(CH3)3), 1.37–
3
1.41 (m, 4H, CH2), 7.34–7.41 (m, 2H, Ph), 7.45 (d, J = 8.58
3
Hz, 2H, Ar), 7.52–7.59 (m, 1H, Ph), 7.70 (d, J = 8.58 Hz, 2H,
Methyl 1-(3-oxobutanoyl)cyclopropanecarboxylate (7b)
Ar), 7.74–7.77 (m, 1H, Ph), 7.99–8.01 (m, 1H, Ph). 13C NMR (75
MHz, CDCl3): d = 18.5, 18.6 (CH2), 31.1 (CH3), 35.2, 42.6, 42.7
Starting with 5 (6.90 mL, 50.00 mmol) dissolved in a suspension
of sodium methoxide (5.402 g, 100 mmol) in MTBE (37.0 ml)
and 6b (2.904 g, 50 mmol), 7b was isolated as a light-yellow oil
(5.400 g, 58%). 1H NMR (300 MHz, CDCl3,keto/enol = 1: 2): d
(enol) = 1.52 (s, 4H, CH2CH2), 2.04 (s, 3H, CH3), 3.70 (s, 3H,
OCH3), 6.10 (s, 1H, CH), 15.42 (s, 1H, OH); d (keto) = 1.59 (s,
4H, CH2CH2), 2.23 (s, 3H, CH3), 3.67 (s, 3H, OCH3), 4.02 (s, 2H,
CH2). 13C NMR (75 MHz, CDCl3): d (enol) = 18.8 (CH2CH2),
23.5 (CH3), 31.2 (Cq), 52.2 (OCH3), 99.8 (CH), 171.1 (COOCH3),
186.2 (COH), 192.5 (CO); d (keto) = 21.4 (CH2CH2), 30.4 (CH3),
(C), 125.4, 126.7, 128.4, 129.1, 133.2 (Ar/Ph), 135.1, 137.8, 157.1
-1
˜
(C), 195.4, 195.9, 202.1 (CO). IR (ATR, cm ): n = 3061 (w), 2963
(w), 2906 (w), 2869 (w), 1722 (w), 1665 (s), 1604 (m), 1507 (w),
1448 (m), 1409 (w), 1364 (w), 1319 (s), 1268 (s), 1202 (m), 1185
(m), 1111 (m), 1066 (s), 1039 (w), 989 (s), 878 (w), 847 (m), 836
(m), 785 (s). MS (EI, 70 eV) m/z = 374 (M+, 14.7), 373 (27.3), 346
(31.8), 331 (27.0), 317 (17.0), 269 (11.9), 255 (17.8), 227 (15.3), 213
(19.1), 199 (16.2), 162 (12.7), 161 (100), 146 (16.6), 118 (23.4), 115
(17.9), 105 (99.5), 91 (16.8), 77 (57.0). Anal. calcd. for C25H26O3
(374.47): C, 80.18; H, 7.00. Found: C, 80.23; H, 7.06.
34.4 (Cq), 57.2 (CH2), 171.1 (COOCH3), 199.6 (CO), 202.4 (CO).
-1
˜
IR (ATR, cm ): n = 3116 (w), 3011 (w), 2956 (m), 2848 (w), 1723
(s), 1692 (w), 1605 (s). MS (EI, 70 eV): m/z = 184 (M+, 30), 156
(57), 127 (88), 85 (71), 43 (100). Anal. calcd. for C9H12O4 (184.189):
C, 58.69; H, 6.57; Found: C, 58.316; H, 6.338.
Synthesis of methyl 1-(3-cyclopropyl-3-oxopropanoyl)cyclo-
propanecarboxylate (7a)
To a suspension of sodium methoxide (4.0 equiv.) in MTBE
(1.0 mL mmol-1) was added 6 (2.0 equiv.) at 30 ◦C. To the
reaction mixture 5 (1.0 equiv.) was added dropwise at 30 ◦C with
vigorous stirring. After stirring at 30 ◦C for 3 h and aqueous
workup with 10% HCl solution with ice cooling, the organic layer
was separated and washed with water. The aqueous phase was
extracted with MTBE. The combined organic layers were dried
(Na2SO4) and concentrated in vacuo. The residue was purified by
column chromatography (hexane/EtOAc = 2 : 1) to give product
Methyl 1-(3-methoxy-3-oxopropanoyl)cyclopropanecarboxylate
(7c)
Starting with 5 (6.90 mL, 50.00 mmol) dissolved in a suspension
of sodium methoxide (5.402 g, 100 mmol) in MTBE (37.0 ml)
and 6c (2.904 g, 50 mmol), 7c was isolated as a colourless liquid
(5.400 g, 58%). 1H NMR (300 MHz, CDCl3, keto/enol = 1: 0) d
(keto) = 1.61 (s, 4H, CH2CH2), 3.71, 3.72 (s, 3H, OCH3), 3.94 (s,
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1
2H, CH2). 13C NMR (75 MHz, CDCl3) d (keto) = 21.4 (CH2), 34.3
40%). H NMR (300 MHz, CDCl3, keto/enol = 1: 3) d (enol) =
1.23–1.89 (m, 14H, CH2), 2.14–2.21 (m, 1H, CHCH2), 3.71 (s,
3H, OCH3), 6.13 (s, 1H, C[O]CH), 15.56 (s, 1H, OH); d (keto) =
1.23–1.89 (m, 14H, CH2), 2.45–2.71 (m, 1H, CHCH2), 3.67 (s,
3H, OCH3), 4.01 (s, 2H, C[O]CH2).13C NMR (75 MHz, CDCl3) d
(enol) = 18.9, 25.7, 29.7 (CH2), 31.3 (Cq), 45.4 (CH), 52.2 (OCH3),
97.4 (CH), 171.3 (COOCH3), 192.8, 193.1 (CO); d (keto) = 21.5,
(Cq), 48.7 (C[O]CH2), 52.2, 52.2 (OCH3), 168.1, 171.0 (COOCH3),
-1
˜
198.1 (CO). IR (ATR, cm ): n = 3111 (w), 3006 (w), 2956 (m), 2848
(w), 1725 (s), 1694 (s). MS (EI, 70 eV): m/z = 200 (M+, 2), 172
(24), 127 (100), 101 (24), 59 (43). HRMS (ESI, 70 eV) calcd. for
C16H23O4 (223.05769 [M+Na]+): 223.05771.
25.5, 28.2 (CH2), 34.5 (Cq), 51.0 (CH), 52.1 (OCH3), 54.5 (CH2),
Methyl 1-(3-phenyl-3-oxopropanoyl)cyclopropanecarboxylate (7d)
-1
˜
171.4 (COOCH3), 200.4, 208.0 (CO). IR (ATR, cm ): n = 3013
Starting with 5 (2.76 mL, 20.00 mmol) dissolved in a suspension
of sodium methoxide (2.160 g, 40 mmol) in MTBE (15.0 ml) and
6d (2.33 mL, 20 mmol), 7d was isolated as a yellow liquid (2.488 g,
(w), 2929 (s), 2854 (m), 2668 (w), 1717 (s), 1693 (w), 1592 (s). MS
(EI, 70 eV): m/z = 252 (M+, 6), 169 (93), 127 (100), 83 (36), 69 (24).
Anal. calcd. for C14H20O4 (252.306): C, 66.65; H, 7.99; Found: C,
66.761; H, 8.061.
1
51%). H NMR (300 MHz, CDCl3, keto/enol = 1: 5) d (enol) =
1.59–1.69 (m, 4H, CH2CH2), 3.76 (s, 3H, OCH3), 6.90 (s, 1H,
C[O]CH), 7.42–7.59 (m, 3H, PhH), 7.88–7.96 (m, 2H, PhH), 16.04
(s, 1H, OH); d (keto) = 1.59–1.69 (m, 4H, CH2CH2), 3.62 (s, 4H,
OCH3), 4.62 (s, 2H, C[O]CH2), 7.42–7.59 (m, 3H, PhH), 7.88–
7.96 (m, 2H, PhH).13C NMR (75 MHz, CDCl3) d (enol) = 19.4
(CH2CH2), 31.8 (Cq), 52.3 (OCH3), 96.6 (C[O]CH), 126.919 (Ph,
Ph), 128.6 (Ph, Ph), 132.1 (Ph), 134.2 (Cq,Ar), 171.3 (COOCH3),
179.4 (COH), 194.1 (CO); d (keto) = 21.7 (CH2CH2), 34.6 (Cq),
52.2 (OCH3), 52.8 (C[O]CH2), 128.3 (Ph, Ph), 128.7 (Ph, Ph),
Methyl 1-(3-(4-methoxyphenyl)-3-oxopropanoyl)cyclopropane-
carboxylate (7g)
Starting with 5 (3.50 mL, 25.00 mmol) dissolved in a suspension
of sodium methoxide (2.701 g, 50 mmol) in MTBE (19 ml) and 6g
(3.754 g, 25 mmol), 7g was isolated as a light-yellow oil (3.307 g,
1
48%). H NMR (300 MHz, CDCl3, keto/enol = 1: 5) d (enol) =
1.59–1.66 (m, 4H, CH2CH2), 3.75 (s, 3H, ArOCH3), 3.87 (s, 3H,
COOCH3), 6.81 (s, 1H, C[O]CH), 6.93–6.96 (m, 2H, PhH), 7.86–
7.94 (m, 2H, PhH), 16.27 (s, 1H, OH); d (keto) = 1.59–1.66 (m,
4H, CH2CH2), 3.63 (s, 3H, ArOCH3), 3.87 (s, 3H, COOCH3),
4.57 (s, 2H, C[O]CH2), 6.93–6.96 (m, 2H, PhH), 7.86–7.94 (m,
2H, PhH).13C NMR (75 MHz, CDCl3) d (enol) = 19.0 (CH2CH2),
31.4 (Cq), 52.2, 55.3 (OCH3), 95.5 (C[O]CH), 113.9 (PhH), 126.7
(CAr,q), 129.0 (PhH), 163.0 (Cq-OCH3), 171.4 (COOCH3), 180.4,
192.2 (CO); d (keto) = 21.4 (CH2CH2), 34.6 (Cq), 52.1 (OCH3),
52.5 (C[O]CH2), 55.4 (OCH3), 113.8 (PhH), 129.4 (CAr,q), 130.6
133.5 (Ph), 136.4 (Cq), 171.3 (COOCH3), 194.7 (CO), 200.2 (CO).
-1
˜
IR (ATR, cm ): n = 3151 (w), 3062 (w), 3021 (w), 2953 (m), 2845
(w), 1724 (s), 1683 (w), 1598 (s), 1565 (s). MS (EI, 70 eV): m/z =
246 (M+, 29), 147 (42), 105 (100), 77 (45), 69 (33). Anal. calcd.
for C14H14O4 (246.259): C, 68.28; H, 5.73; Found: C, 68.294; H,
5.678.
Methyl 1-(3-(1-napththyl)-3-oxopropanoyl)cyclopropanecarboxy-
late (7e)
(PhH), 163.8 (Cq-OCH3), 171.3 (COOCH3), 193.1, 200.3 (CO).
Starting with 5 (2.76 mL, 20.00 mmol) dissolved in a suspension
of sodium methoxide (2.160 g, 40 mmol) in MTBE (30.0 ml) and
6e (2.33 mL, 20 mmol), 7e was isolated as a yellow solid (1.667 g,
32%). mp 67–69 ◦C; 1H NMR (300 MHz, CDCl3, keto/enol = 1: 5)
d (enol) = 1.62–1.73 (m, 4H, CH2CH2), 3.35 (s, 3H, OCH3), 6.68 (s,
1H, C[O]CH), 7.48–7.60 (m, 3H, ArH), 7.75–7.97 (m, 3H, ArH),
8.46–8.49 (m, 1H, ArH), 16.07 (s, 1H, OH); d (keto) = 1.62–1.73
(m, 4H, CH2CH2), 3.75 (s, 3H, OCH3), 4.74 (s, 2H, C[O]CH2),
7.48–7.60 (m, 3H, ArH), 7.75–7.97 (m, 3H, ArH), 8.46–8.49 (m,
1H, ArH).13C NMR (75 MHz, CDCl3) d (enol) = 19.4 (CH2CH2),
31.8 (Cq), 52.4 (OCH3), 101.8 (C[O]CH), 124.8 (Ph), 125.5 (Ph),
126.3 (Ph), 127.1 (Ph), 127.2 (Ph), 128.6 (Ph), 130.2 (Cq), 131.6
(Ph), 133.4 (Cq), 133.8 (Cq), 171.1 (COOCH3), 183.1 (COH), 193.6
(CO); d (keto) = 21.8 (CH2CH2), 34.6 (Cq), 52.2 (OCH3), 55.9
(C[O]CH2), 124.3 (Ph), 125.8 (Ph), 126.5 (Ph), 128.2 (Ph), 128.4
-1
˜
IR (ATR, cm ): n = 3005 (w), 2953 (m), 2840 (m), 1723 (s),
1672 (m), 1599 (s), 1563 (m), 1507 (s). MS (EI, 70 eV): m/z =
276 (M+, 15), 248 (11), 177 (12), 135 (100), 77 (11). Anal. calcd.
for C15H16O5 (276.285): C, 65.21; H, 5.84. Found: C, 65.530; H,
6.009.
Methyl 1-(3-(g5-ferrocenyl)-3-oxopropanoyl)cyclopropane-
carboxylate (7h)
Starting with 5 (1.582 g, 10.00 mmol) dissolved in a suspension of
sodium methoxide (1.084 g, 20 mmol) in MTBE (7.5 mL) and 6h
(2.281 g, 10.00 mmol), 7h was isolated as a dark-red oil (1.824 g,
1
52%). H NMR (300 MHz, CDCl3, keto/enol = 3: 5) d (enol) =
1.58–1.64 (m, 4H, CH2CH2), 3.75 (s, 3H, OCH3), 4.19 (s, 5H,
CH), 4.49–4.50 (m, 2H, CH), 4.79–4.80 (m, 2H, CH), 6.39 (s, 1H,
C[O]CH), 16.06 (s, 1H, OH); d (keto) = 1.58–1.64 (m, 4H, CH2),
3.68 (s, 3H, OCH3), 4.24 (s, 5H, CH), 4.40 (s, 2H, C[O]CH2),
4.52–4.53 (m, 2H, CH), 4.76–4.78 (m, 2H, CH).13C NMR (75
MHz, CDCl3) d = 18.6 (CH2), 30.5 (Cq), 52.2 (OCH3), 68.5, 70.0,
70.3 (CH), 78.6 (Cq), 96.8 (C[O]CH), 171.4 (COOCH3), 187.6,
200.1 (CO); d (keto) = 21.0 (CH2), 34.9 (Cq), 52.1 (OCH3), 53.4
(Ph), 128.5 (Ph), 128.6 (Ph), 130.2 (Cq), 134.0 (Cq), 134.6 (Cq),
-1
˜
171.4 (COOCH3), 197.8 (CO), 200.2 (CO). IR (ATR, cm ): n =
3048 (w), 3012 (w), 2951 (w), 2844 (w), 1723 (s), 1675 (w), 1598 (w),
1567 (s), 1508 (m). MS (EI, 70 eV): m/z = 296 (M+, 21), 197 (20),
168 (22), 155 (100), 127 (64). Anal. calcd. for C18H16O4 (296.317):
C, 72.96; H, 5.44; Found: C, 73.005; H, 5.435.
(C[O]CH2), 69.5, 71.9, 72.6 (CH), 77.2 (Cq), 170.1 (COOCH3),
Methyl 1-(3-cyclohexyl-3-oxopropanoyl)cyclopropanecarboxylate
(7f)
-1
˜
188.8, 198.1 (CO). IR (ATR, cm ): n = 3100 (w), 3014 (w), 2953
(w), 1725 (s), 1661 (m), 1651 (m), 1520 (s), 1504 (s). MS (EI, 70
eV): m/z = 253 ([M-H]+, 3), 228 (100), 185 (56), 129 (28), 56 (17).
HRMS (ESI, 70 eV) calcd. for C18H19FeO4 ([M+H]+, 355.0627):
355.0627.
Starting with 5 (1.40 mL, 10.00 mmol) dissolved in a suspension
of sodium methoxide (1.800 g, 20 mmol) in MTBE (7.5 ml) and 6f
(1.262 g, 10 mmol), 7f was isolated as a colourless liquid (1.008 g,
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Synthesis of methyl 1-(1-(cyclopropanecarbonyl)cyclopropane-
carbonyl)-cyclopropanecarboxylate (8a)
liquid (0.597 g, 67%).1H NMR (300 MHz, CDCl3) d = 1.56 (s, 8H,
CH2), 3.67 (s, 6H, OCH3). 13C NMR (75 MHz, CDCl3) d = 20.2
(CH2), 34.8 (Cq), 52.0 (OCH3), 171.6 (COOCH3), 199.4 (CO). IR
To a suspension of K2CO3 (4.0 equiv.) in DMSO (0.3–
0.5 mL mmol-1) was added 7 (1.0 equiv.). To the reaction mixture
dibromoethane (2.0 equiv.) was added dropwise at 20 ◦C with
vigorous stirring. After stirring at 20 ◦C for 8 h, K2CO3 was
removed by filtration. The solid was thoroughly washed diethyl
ether. The filtrate was washed with water until the yellow colour
disappears, dried (Na2SO4) and concentrated in vacuo. The residue
was purified by column chromatography (hexane/EtOAc = 2 : 1)
to give product 8. Starting with 7 (1.500 g, 7.14 mmol) dissolved
in a suspension of K2CO3 (2.47 g, 17.84 mmol) in DMSO (2.1
ml) and dibromoethane (0.6 ml, 7.14 mmol), 8 was isolated as
-1
˜
(ATR, cm ): n = 3111 (w), 3012 (w), 2958 (m), 2847 (w), 1723 (s),
1677 (s). MS (EI, 70 eV): m/z = 226 (M+, 7), 198 (90), 127 (100), 95
(32), 59 (41). HRMS (ESI, 70 eV) calcd. for C11H14O5 (226.08358):
226.083021.
Methyl 1-(1-benzoylcyclopropanecarbonyl)cyclopropanecarboxy-
late (8d)
Starting with 7d (1.500 g, 6.00 mmol) dissolved in a suspension
of K2CO3 (3.320 g, 24.00 mmol) in DMSO (5.0 ml) and dibro-
moethane (1.60 ml, 12.00 mmol), 8d was isolated as a colourless
oil (0.593 g, 37%). 1H NMR (300 MHz, CDCl3) d = 1.15–1.40 (m,
4H, CH2CH2), 1.70–1.71 (m, 4H, CH2CH2), 3.59 (s, 3H, OCH3),
7.39–7.44 (m, 2H, PhH), 7.50–7.56 (m, 1H, PhH), 7.67–7.70 (m,
2H, PhH). 13C NMR (75 MHz, CDCl3) d = 19.5, 22.2 (CH2), 35.1,
1
a colorless oil (0.30 g, 18%). H NMR (300 MHz, CDCl3): d =
0.81–0.98 (m, 4H, CH2), 1.52–1.55 (m, 8H, CH2), 1.75–1.80 (m,
1H, CH), 3.59 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3): d = 12.0
(CH2), 17.7 (CH), 19.1, 21.3 (CH2), 35.2, 43.5 (C), 52.4 (CH3),
171.6, 201.2, 206.1 (CO). IR (neat., cm-1) 3011 (m), 2954 (m) 1733
(s), 1674 (s), 1570 (w), 1540 (w), 1506 (w), 1437 (m), 1400 (m, br)
1324 (s), 1199 (m), 1164 (m), 1079 (s), 1048 (m), 1009 (m), 954 (w),
911 (w), 889 (w), 835 (w), 751 (w), 735 (w). MS (EI, 70 eV) m/z =
236 (M+, 7.9), 208 (100), 193 (15.7), 179 (27.9), 177 (32.2), 167
(34.7), 149 (21.8), 137 (22.1), 109 (14.3), 95 (25.3), 69 (98.8). Anal.
calcd. for C13H16O4 (236.26): C, 66.09; H, 6.83. Found: C, 66.14; H,
6.78.
42.2 (Cq), 52.1 (OCH3), 128.4, 128.4, 132.8 (Ph), 138.2 (Cq,Ph),
-1
˜
170.5 (COOCH3), 196.9, 201.0 (CO). IR (ATR, cm ): n = 3061
(w), 3011(w), 2952 (w), 2846 (w), 1728 (s), 1663 (s), 1598 (m), 1579
(w). MS (EI, 70 eV): m/z = 271 ([M-H]+, 244 (29), 181 (42), 105
(100), 77 (59). Anal. calcd. for C16H16O4 (272.296): C, 70.57; H,
5.92; Found: C, 70.723; H, 5.917.
Methyl 1-(1-(1-naphthoyl)cyclopropanecarbonyl)cyclopropane-
carboxylate (8e)
General procedure for the synthesis of cyclopropylketides 8b–h
To a suspension of K2CO3 (4.0 equiv.) in DMSO (1.2 mL mmol-1
tricarbonyl) was added 7 (1.0 equiv.). To the reaction mixture
dibromoethane (2.0 equiv.) was dropwise added at 0 ◦C with
vigorous stirring. After 30 min the mixture was warmed to
22 ◦C and then stirring was continued for 12 h. Subsequently
K2CO3 was removed by filtration and the solid was thoroughly
washed with diethyl ether. The filtrate was washed two times
with saturated NaCl-solution, dried (Na2SO4) and concentrated
in vacuo. The residue was purified by column chromatography
(heptane/EtOAc = 30 : 1 → 5 : 1) to give products 8.
Starting with 7e (0.200 g, 0.67 mmol) dissolved in a suspension of
K2CO3 (0.370 g, 2.68 mmol) in DMSO (1.0 ml) and dibromoethane
(0.14 ml, 1.34 mmol), 8e was isolated as a white solid (0.096 g,
44%). mp 98–100 C; H NMR (300 MHz, CDCl3) d = 0.96–
1.22 (m, 4H, CH2CH2), 1.78–1.92 (m, 4H, CH2CH2), 3.32 (s,
3H, OCH3), 7.41–7.71 (m, 3H, ArH), 7.85–7.88 (m, 1H, ArH),
7.95–7.97 (m, 1H, ArH), 8.39–8.42 (m, 1H, ArH). 13C NMR (75
MHz, CDCl3) d = 21.3, 22.1 (CH2), 34.6, 44.0 (Cq), 51.7 (OCH3),
124.0, 125.7, 126.5, 127.6, 128.1, 128.3 (Ar), 130.1 (Cq,Ar), 132.4
◦
1
(Ar), 133.8, 135.8 (Cq,Ar), 170.6 (COOCH3), 199.0, 201.1 (CO). IR
-1
˜
(ATR, cm ): n = 3089 (w), 3048 (w), 3011 (w), 2952 (w), 2848 (w),
Methyl 1-(1-acetylcyclopropanecarbonyl)-cyclopropanecarboxy-
late (8b)
1723 (s), 1661 (s), 1592 (w), 1574 (w), 1508 (m). MS (EI, 70 eV):
m/z = 322(M+, 33), 181 (14), 179 (10), 155 (100), 127 (78). Anal.
calcd. for C20H18O4 (322.355): C, 74.52; H, 5.63; Found: C, 74.249;
H, 5.471.
Starting with 7b (0.921 g, 5.00 mmol) dissolved in a suspension
of K2CO3 (2.764 g, 20.00 mmol) in DMSO (6.0 ml) and dibro-
moethane (0.9 ml, 10.00 mmol), 8b was isolated as a light-yellow
1
oil (0.388 g, 37%). H NMR (300 MHz, CDCl3) d = 1.46–1.50
Methyl 1-(1-(cyclohexanecarbonyl)cyclopropanecarbonyl)cyclo-
propanecarboxylate (8f)
(m, 4H, CH2), 1.55–1.60 (m, 4H, CH2), 2.08 (s, 3H, CH3), 3.65
(s, 3H, OCH3). 13C NMR (75 MHz, CDCl3) d = 18.0, 20.6 (CH2),
Starting with 7f (0.757 g, 3.00 mmol) dissolved in a suspension
of K2CO3 (1.658 g, 12.00 mmol) in DMSO (4.0 ml) and dibro-
moethane (0.60 ml, 6.00 mmol), 8f was isolated as a colourless
liquid (0.279 g, 34%). 1H NMR (300 MHz, CDCl3) d = 1.18–1.79
(m, 18H, CH2), 2.38–2.48 (m, 1H, CH), 3.65 (s, 3H, OCH3). 13C
NMR (63 MHz, CDCl3) d = 17.7, 20.9, 25.7, 29.2 (CH2), 34.7,
26.0 (CH3), 34.2, 42.9 (Cq), 52.0 (OCH3), 171.4 (COOCH3), 200.8,
-1
˜
203.9 (CO). IR (ATR, cm ): n = 3099 (w), 3013 (w), 2954 (m),
2848 (w), 1724 (s), 1681 (s), 1582 (s). MS (EI, 70 eV): m/z = 210
(M+, 6), 182 (100), 127 (32), 69 (36), 43 (60). HRMS (ESI, 70 eV)
calcd. for C11H15O4 (211.0965 [M+H]+): 211.0966.
41.8 (Cq), 47.5 (CH), 52.2 (OCH3), 171.1 (COOCH3), 201.1, 208.5
Dimethyl 1,1¢-carbonyldicyclopropanecarboxylate (8c)
-1
˜
(CO). IR (ATR, cm ): n = 3096 (w), 3013 (w), 2931 (s), 2854 (m),
Starting with 7c (0.800 g, 4.00 mmol) dissolved in a suspension
of K2CO3 (2.211 g, 16.00 mmol) in DMSO (3.0 ml) and dibro-
moethane (0.8 ml, 6.00 mmol), 8c was isolated as a colourless
1728 (s), 1677 (s). MS (EI, 70 eV): m/z = 278 (M+, 1), 195 (100),
127 (38), 83 (18), 55 (17). HRMS (ESI, 70 eV) calcd. for C16H23O4
(279.1591 [M+H]+): 279.1593.
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Methyl 1-(1-(4-methoxybenzoyl)cyclopropanecarbonyl)cyclopro-
panecarboxylate (8g)
95 (19.7), 69 (100). Anal. calcd. for C15H18O5 (278.30): C, 64.74;
H, 6.52. Found: C, 64.99; H, 7.03.
Starting with 7g (1.381 g, 5.00 mmol) dissolved in a suspension
of K2CO3 (2.764 g, 20.00 mmol) in DMSO (5.0 ml) and dibro-
moethane (1.20 ml, 7.50 mmol), 8g was isolated as a light-yellow
solid (0.909 g, 61%). mp 52–53 ◦C; 1H NMR (300 MHz, CDCl3)
d = 1.18–1.41 (m, 4H, CH2), 1.63–1.67 (m, 4H, CH2), 3.59 (s, 3H,
OCH3), 3.85 (s, 3H, OCH3), 6.87–6.90 (m, 2H, PhH), 7.68–7.71
(m, 2H, PhH). 13C NMR (75 MHz, CDCl3) d = 19.0, 21.7 (CH2),
35.2, 41.8 (Cq), 52.1, 55.4 (OCH3), 113.6 (Ph), 130.7 (Cq,Ph), 130.8
General procedure for the synthesis of tricarbonyl compounds 12
To a suspension of 11 (2.0 equiv.) in CH2Cl2 (2 mL mmol-1)
10 (1.0 equiv.) was added at -78 ◦C. The reaction mixture
was allowed to warm to 20 ◦C and stirred for 12 h. After
aqueous workup with saturated NaHCO3-solution the aqueous
phase was extracted with CH2Cl2. The combined organic layers
were dried (Na2SO4) and concentrated in vacuo. The residue
was purified by column chromatography (hexane/EtOAc = 2 : 1)
to give product 9. The synthesis of 12a,b has been previously
reported.4a
(Ph), 163.4 (Cq,Ph), 170.5 (COOCH3), 194.9, 201.3 (CO). IR (ATR,
-1
˜
cm ): n = 3054 (w), 3020 (w), 2968 (w), 2935 (w), 2843 (w), 1711
(s), 1677 (m), 1656 (s), 1596 (s), 1506 (s). MS (EI, 70 eV): m/z =
302 (M+, 8), 274 (31), 172 (11), 135 (100), 77 (13). Anal. calcd.
for C17H18O5 (302.322): C, 67.54; H, 6.00. Found: C, 67.209; H,
5.990.
Methyl 5-(4-methoxyphenyl)-3,5-dioxopentanoate (12c)
Starting with p-anisoyl chloride (0.8 ml, 5.76 mmol)
and 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene (3.00 g,
11.52 mmol), dissolved in CH2Cl2 (10 mL), 12c was isolated as
an orange solid (0.60 g, 42%); mp 133 C. H-NMR (300 MHz,
CDCl3, keto/enol = 0 : 100): d (enol) = 3.46 (s, 2H, CH2), 3.76 (s,
3H, OCH3), 3.86 (s, 3H, ArOCH3), 6.21 (s, 1H, CH), 6.93 (d, 3J =
8.97 Hz, 2H, Ar), 7.86 (d, 3J = 9.00 Hz, 2H, Ar), 16.00 (s, 1H, OH).
13C-NMR (75 MHz, CDCl3): enol: d = 45.3 (CH2), 52.5 (OCH3),
Methyl 1-(1-(g5-ferrocenoyl)cyclopropanecarbonyl)cyclopropane-
carboxylate (8h)
◦
1
Starting with 7h (0.708 g, 2.00 mmol) dissolved in a suspension of
K2CO3 (1.106 g, 8.00 mmol) in DMSO (2.0 ml) and dibromoethane
(0.40 ml, 4.00 mmol), 8h was isolated as a red solid (0.361 g, 48%).
◦
mp 128–130 C;1H NMR (300 MHz, CDCl3) d = 1.32–1.69 (m,
8H, CH2), 3.54 (s, 3H, OCH3), 4.13 (s, 5H, CH), 4.46–4.47 (m,
2H, CH), 4.72–4.73 (m, 2H, CH2). 13C NMR (75 MHz, CDCl3)
d = 18.3, 22.0 (CH2), 35.1, 42.6 (Cq), 52.0 (OCH3), 70.1, 70.3, 71.7
55.5 (OCH3), 95.9 (CH), 114.1 (Ar), 126.6 (C), 129.3 (Ar), 163.5
-1
˜
(CAr), 168.3, 183.4, 187.1 (CO). IR (ATR, cm ): n = 3470 (w),
2981 (w), 2846 (w), 2629 (w, br), 2559 (w, br), 1751 (s), 1738 (m),
1675 (m, br), 1600 (s), 1577 (s), 1513 (m), 1465 (m), 1442 (m), 1427
(s), 1299 (s), 1254 (s), 1190 (s), 1178 (s), 1142 (s), 1118 (s), 1106 (s),
1010 (s), 953 (m), 934 (m), 874 (m), 845 (s), 822 (s), 783 (s), 766 (s).
MS (EI, 70 eV): m/z (%) = 250 (M+, 9.0), 218 (8.8), 190 (8.7), 177
(15.4), 152 (39.5), 135 (100), 107 (8.6), 92 (6.4), 77 (12.1), 69 (8.3).
Anal. calcd. for C13H14O5 (250.25): C, 62.39; H, 5.64. Found: C,
62.44; H, 5.44.
(CH), 79.6 (Cq), 170.4 (COOCH3), 200.1, 201.1 (CO). IR (ATR,
-1
˜
cm ): n = 3097 (w), 3009 (w), 2956 (w), 1723 (s), 1673 (w), 1652 (s),
1569 (w), 1553 (w), 1537 (w), 1504 (w). MS (EI, 70 eV): m/z = 381
(24), 280 (M+, 100), 283 (6), 257 (8), 247 (7), 121 (13). Anal. calcd.
for C20H20FeO4 (380.215): C, 63.18; H, 5.30. Found: C, 62.808; H,
5.447.
Synthesis of methyl 1-(3-(1-(cyclopropanecarbonyl)cyclopropyl)-3-
oxopropanoyl)-cyclopropanecarboxylate (9)
Methyl 3,5-dioxo-5-p-tolylpentanoate (12d)
To a suspension of sodium methoxide (2.0 equiv.) in MTBE
(1.33 mL mmol-1) was added 2a (1.0 equiv.) at 30 ◦C. To the
reaction mixture 5 (1.0 equiv.) was added dropwise at 30 ◦C with
vigorous stirring. After stirring at 30 ◦C for 3 h and aqueous
workup with 10% HCl-solution with ice cooling, the organic layer
was separated and washed with water. The aqueous phase was
extracted with MTBE. The combined organic layers were dried
(Na2SO4) and concentrated in vacuo. The residue was purified by
column chromatography (hexane/EtOAc = 2 : 1) to give product
9. Starting with 5 (1.830 g, 12.00 mmol) dissolved in a suspension
of sodium methoxide (1.30 g, 24.00 mmol) in MTBE (9.0 ml) and
2a (1.90 g, 12.00 mmol), 9 was isolated as a orange oil (1.29 g,
39%). 1H NMR (300 MHz, CDCl3): d = 0.91–1.15 (m, 8H, CH2),
1.47–1.50 (m, 4H, CH2), 2.21 (m, 1H, CH), 3.77 (s, 3H, CH3), 5.80
(s, 1H, CH), 15.50 (s, 1H, OH). 13C NMR (75 MHz, CDCl3): d =
12.6, 17.0, 17.9 (CH2), 17.9 (CH), 28.1, 40.3 (C), 52.9 (CH3), 100.3
(CH), 170.5, 188.3, 193.4, 206.3 (CO). IR (neat, cm-1) 3101 (w),
3003 (m), 2954 (m), 1733 (s), 1684 (s), 1653 (m), 1616 (s), 1559
(m), 1540 (m), 1522 (m), 1507 (m), 1437 (s), 1419 (s), 1388 (s),
1321 (s), 1216 (m), 1135 (m), 1063 (s), 1009 (m), 948 (m), 885 (w),
783 (w), 754 (w). MS (EI, 70 eV) m/z = 278 (M+, 8.7), 263 (20.8),
150 (23.0), 246 (15.1), 179 (11.3), 151 (12.6), 137 (33.0), 127 (100),
Starting with p-methylbenzoyl chloride (0.89 g, 5.76 mmol)
and 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene (3.00 g,
11.52 mmol), dissolved in CH2Cl2 (10 mL), 12d was isolated as a
yellow oil (0.78 g, 58%). 1H-NMR (300 MHz, CDCl3, keto/enol =
0 : 100): d (enol) = 2.41 (s, 3H, CH3), 3.48 (s, 2H, CH2), 3.76 (s,
3
3H, OCH3), 6.26 (s, 1H, CH), 7.25 (d, J = 8.46 Hz, 2H, Ar),
7.78 (d, 3J = 8.28 Hz, 2H, Ar), 15.86 (s, 1H, OH). 13C-NMR (75
MHz, CDCl3): enol: d = 21.7 (CH3), 45.6 (CH2), 52.5 (OCH3),
96.4 (CH), 127.2, 129.5 (Ar), 131.3, 143.6 (C), 168.1, 183.1, 188.5
-1
˜
(CO). IR (ATR, cm ): n = 3032 (w), 2999 (w), 2953 (w), 2923 (w,
br), 2846 (w, br), 1739 (s), 1606 (s), 1506 (m), 1435 (s), 1254 (s),
1184 (s), 1147 (s), 1076 (m), 1017 (s), 954 (m), 832 (m), 780 (s). MS
(EI, 70 eV): m/z (%) = 234 (M+, 46.0), 202 (22.4), 174 (68.1), 161
(81.5), 119 (100), 91 (57.4), 69 (75.5). HRMS (EI, 70 eV): calcd.
for C13H14O4 (M+) 234.08866, found 234.088131.
Methyl 5-(3-chlorophenyl)-3,5-dioxopentanoate (12e)
Starting with m-chlorobenzoylchloride (0.7 ml, 5.76 mmol)
and 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene (3.00 g,
11.52 mmol), dissolved in CH2Cl2 (10 mL), 12e was isolated
as a yellow oil (0.94 g, 64%). 1H-NMR (300 MHz, CDCl3,
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keto/enol = 0 : 100): d (enol) = 3.50 (s, 2H, CH2), 3.77 (s, 3H,
(m, 2H, Ph). 13C NMR (75 MHz, CDCl3): d = 17.1 (CH2), 29.6
(C), 30.3 (CH2), 50.6 (CH3), 70.5 (OCH2), 105.5 (C), 127.8, 127.9,
131.9 (Ph), 137.8 (C), 165.1, 168.4, 197.4 (CO). IR (ATR, cm-1):
3
3
OCH3), 6.26 (s, 1H, CH), 7.39 (dd, J = 7.86 Hz, J = 7.92 Hz,
1H, Ar), 7.50 (ddd, 3J = 7.91 Hz, 4J = 2.07 Hz, 4J = 1.13 Hz, 1H,
Ar), 7.74 (ddd, 3J = 7.83 Hz, 4J = 1.50 Hz, 4J = 1.13 Hz, 1H, Ar),
7.74 (dd, 4J = 1.86 Hz, 4J = 1.88 Hz, 1H, Ar), 15.63 (s, 1H, OH).
13C-NMR (75 MHz, CDCl3): enol: d = 45.7 (CH2), 52.6 (OCH3),
˜
n = 3061 (w), 3013 (w), 2949 (w), 2904 (w), 2870 (w), 1693 (s), 1628
(m), 1598 (w), 1581 (w), 1437 (m), 1387 (m), 1355 (w), 1321 (w),
1289 (m), 1208 (m), 1189 (m), 1155 (m), 1108 (s), 1045 (s), 991 (s),
939 (m), 882 (w), 849 (w, br), 795 (m), 783 (m), 763 (m). MS (EI,
70 eV) m/z = 272 (M+, 33.0), 271 (34.2), 240 (9.9), 239 (10.5), 213
(14.2), 212 (14.3), 185 (6.4), 181 (10.2), 105 (100), 77 (55.2). Anal.
calcd. for C16H16O4 (272.30): C, 70.57; H, 5.92. Found: C, 70.14;
H, 5.90.
97.1 (CH), 125.2, 127.2, 130.0, 132.6 (Ar), 135.0, 135.9 (C), 167.8,
-1
˜
181.0, 189.5 (CO). IR (ATR, cm ): n = 3070 (w), 3002 (w), 2953
(w), 2844 (w, br), 1738 (s), 1602 (s), 1563 (s), 1503 (m), 1435 (s),
1324 (m), 1251 (s), 1198 (s), 1145 (s), 1099 (m), 1078 (m), 1011
(m), 954 (m), 897 (m), 768 (s). MS (EI, 70 eV): m/z (%) = 254 (M+,
48.8), 222 (32.4), 196 (57.1), 195 (23.1), 194 (93.7), 183 (66.0), 182
(20.3), 181 (98.0), 141 (76.7), 140 (17.2), 139 (100), 111 (71.0), 101
(22.6), 89 (10.7), 75 (33.8), 69 (91.2). HRMS (EI, 70 eV): calcd.
for C12H11ClO4 (M+) 254.03404, found 254.033453.
Methyl 1-(3-(4-methoxybenzoyl)-4,5-dihydrofuran-2-yl)cyclo-
propanecarboxylate (13c)
Starting with 12c (0.34 g, 1.36 mmol) dissolved in a suspen-
sion K2CO3 (0.94 g, 6.81 mmol) in DMSO (0.4 ml) and 1,2-
dibromoethane (0.29 ml, 3.41 mmol), 13c was isolated as a
General procedure for the synthesis of dihydrofuranes 13
1
To
a
suspension of K2CO3 (5.0 equiv.) in DMSO (0.3-
colourless oil (0.06 g, 15%). H NMR (300 MHz, CDCl3): d =
0.5 mL mmol-1) 12 (1.0 equiv.) was added. To the reaction
mixture was dibromoethane (2.5 equiv.) added dropwise at 20 ◦C
with vigorous stirring. After stirring at 20 ◦C for 8 h, K2CO3
was removed by filtration. The solid was thoroughly washed
with diethyl ether. The filtrate was washed with water until
the yellow colour disappeared, dried (Na2SO4) and concentrated
in vacuo. The residue was purified by column chromatography
(hexane/EtOAc = 2 : 1) to give product 13.
1.41 (m, 2H, (CHaHb)2C), 1.67 (m, 2H, (CHaHb)2C), 2.80 (t,
3J = 9.67 Hz, 2H, CH2), 3.52 (s, 3H, CH3), 3.84 (s, 3H, CH3), 4.42
3
3
(t, J = 9.67 Hz, 2H, CH2), 6.86 (d, J = 9.04 Hz, 2H, Ar), 7.76
(d, 3J = 9.00 Hz, 2H, Ar). 13C NMR (75 MHz, CDCl3): d = 16.6
(CH2), 29.3 (C), 30.4 (CH2), 50.5, 55.4 (CH3), 70.5 (OCH2), 105.2
(C), 113.2, 130.0 (Ar), 130.4, 162.6 (C), 165.1, 168.6, 195.6 (CO).
-1
˜
IR (ATR, cm ): n = 2950 (w), 2904 (w), 2841 (w), 1695 (m), 1673
(m), 1630 (m), 1599 (s), 1576 (m), 1510 (m), 1436 (m), 1419 (w),
1387 (w), 1354 (w), 1295 (m), 1253 (s), 1213 (m), 1167 (s), 1108
(s), 1029 (s), 986 (s), 937 (m), 884 (w), 839 (m), 817 (m), 794 (m),
757 (m). MS (EI, 70 eV) m/z = 302 (M+, 13.7), 301 (23.6), 271
(14.2), 181 (6.7), 135 (100), 107 (7.0), 92 (10.6), 77 (15.6). Anal.
calcd. for C17H18O5 (302.32): C, 67.54; H, 6.00. Found: C, 67.38; H,
6.03.
Methyl 1-(3-(cyclopropanecarbonyl)-4,5-dihydrofuran-2-yl)cyclo-
propanecarboxylate (13a)
Starting with 12a (1.70 g, 9.23 mmol) dissolved in a suspension
of K2CO3 (6.38 g, 46.15 mmol) in DMSO (3 ml) and 1,2-
dibromoethane (1.67 ml, 19.38 mmol), 13a was isolated as an
1
yellow oil (0.70 g, 32%). H NMR (300 MHz, CDCl3): d = 0.76
Methyl 1-(3-(4-methylbenzoyl)-4,5-dihydrofuran-2-yl)cyclo-
propanecarboxylate (13d)
(m, 2H, (CHaHb)2CH), 0.99 (m, 2H, (CHaHb)2CH), 1.25 (m, 2H,
(CHaHb)2C), 1.55 (m, 2H, (CHaHb)2C), 2.03 (m, 1H (CH2)2CH),
3.01 (t, 3J = 9.69 Hz, 2H, CH2), 3.62 (s, 3H, CH3), 4.37 (t, 3J = 9.69
Hz, 2H, CH2). 13C NMR (75 MHz, CDCl3): d = 10.5 (CH2), 17.7
Starting with 12d (0.31 g, 1.36 mmol) dissolved in a suspen-
sion K2CO3 (0.94 g, 6.81 mmol) in DMSO (0.4 ml) and 1,2-
dibromoethane (0.29 ml, 3.41 mmol), 13d was isolated as a pale
yellow oil (0.08 g, 21%). 1H NMR (300 MHz, CDCl3): d = 1.43 (m,
2H, (CHaHb)2C), 1.69 (m, 2H, (CHaHb)2C), 2.36 (s, 3H, CH3),
2.78 (t, 3J = 9.66 Hz, 2H, CH2), 3.52 (s, 3H, CH3), 4.41 (t, 3J = 9.70
(CH2), 19.2 (CH), 23.5 (C), 31.0 (CH2), 52.7 (CH3), 70.3 (OCH2),
-1
˜
115.6 (C), 165.4, 172.0, 196.1 (CO). IR (ATR, cm ): n = 3095 (w),
3007 (w), 2954 (w), 2903 (w), 2871 (w), 1726 (s), 1659 (m), 1615
(m), 1589 (m), 1436 (m), 1402 (s), 1305 (s), 1200 (s), 1174 (s), 1129
(s), 1098 (m), 1070 (m), 1029 (m), 990 (w), 958 (s), 904 (m), 866
(m), 843 (w), 751 (w). MS (EI, 70 eV) m/z = 236 (M+, 83.0), 221
(19.1), 208 (100), 195 (70.3), 189 (50.0), 177 (54.1), 163 (24.4), 135
(22.6), 127 (23.3), 107 (28.6), 95 (26.1), 91 (25.6), 79 (38.6), 77
(32.6), 69 (96.2). Anal. calcd. for C13H16O4 (236.26): C, 66.09; H,
6.83. Found: C, 66.04; H, 6.88.
3
3
Hz, 2H, CH2), 7.16 (d, J = 8.27 Hz, 2H, Ar), 7.66 (d, J = 8.28
Hz, 2H, Ar). 13C NMR (75 MHz, CDCl3): d = 16.9 (CH2), 21.6
(CH3), 29.5 (C), 30.4 (CH2), 50.5 (CH3), 70.5 (OCH2), 105.3 (C),
127.9, 128.7 (Ar), 135.1, 142.5 (C), 165.1, 168.5, 196.8 (CO). IR
-1
˜
(ATR, cm ): n = 2949 (w), 2903 (w), 1695 (m), 1677 (m), 1627 (m),
1607 (m), 1437 (m), 1387 (m), 1355 (w), 1316 (w), 1293 (m), 1204
(m), 1179 (s), 1153 (w), 1108 (s), 1043 (s), 995 (s), 938 (m), 916
(m), 886 (w), 817 (m), 794 (w), 763 (w). MS (EI, 70 eV) m/z = 286
(M+, 22.6), 271 (76.0), 239 (9.3), 226 (16.6), 181 (6.7), 119 (100),
91 (68.2). HRMS (EI, 70 eV): calcd. for C17H18O4 (M+) 286.11996,
found 286.120056.
Methyl 1-(3-benzoyl-4,5-dihydrofuran-2-yl)cyclopropanecarboxy-
late (13b)
Starting with 12b (0.3 g, 1.36 mmol) dissolved in a suspen-
sion K2CO3 (0.94 g, 6.81 mmol) in DMSO (0.4 ml) and 1,2-
dibromoethane (0.29 ml, 3.41 mmol), 13b was isolated as a
Methyl 1-(3-(3-chlorobenzoyl)-4,5-dihydrofuran-2-yl)cyclo-
propanecarboxylate (13e)
1
colourless oil (0.13 g, 35%). H NMR (300 MHz, CDCl3): d =
1.45 (m, 2H, (CHaHb)2C), 1.71 (m, 2H, (CHaHb)2C), 2.76 (t,
3J = 9.66 Hz, 2H, CH2), 3.53 (s, 3H, CH3), 4.41 (t, 3J = 9.70 Hz,
2H, CH2), 7.34–7.39 (m, 2H, Ph), 7.43–7.46 (m, 1H, Ph), 7.73–7.77
Starting with 12e (0.35 g, 1.36 mmol) dissolved in a sus-
pension K2CO3 (0.94 g, 6.81 mmol) in DMSO (0.4 ml) and
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1,2-dibromoethane (0.29 ml, 3.41 mmol), 13e was isolated as a
5 Peralkyl-polyketides were previously prepared in very low yields
based on the base-mediated ring cleavage of 2,2,4-trimethyl-3-hydroxy-
pentenoic acid b-lactone: K. D. Berlin and R. B. Hanson, J. Org. Chem.,
1967, 32, 1763.
6 The formation of a triketide as a side-product was previously claimed,
but the product has not been unambiguously identified: J. M. Stewart
and G. K. Pagenkopf, J. Org. Chem., 1969, 34, 7.
7 A. de Meijere, S. I. Kozhushkov and H. Schill, Chem. Rev., 2006, 106,
4926.
8 M. von Seebach, S. I. Kozhushkov, D. Frank, R. Boese, J. Benet-
Buchholz, D. S. Yufit, H. Schill and A. de Meijere, Chem.–Eur. J.,
2007, 13, 167.
9 (a) A. de Meijere, A. F. Khlebnikov, S. I. Kozhushkov, K. Miyazawa,
D. Frank, P. R. Schreiner, C. Rinderspacher, D. S. Yufit and J. A. K.
Howard, Angew. Chem., 2004, 116, 6715, (Angew. Chem., Int. Ed, 2004,
43, 6553); (b) A. de Meijere, A. F. Khlebnikov, S. I. Kozhushkov, D. S.
Yufit, O. V. Chetina, J. A. K. Howard, T. Kurahashi, K. Miyazawa,
D. Frank, P. R. Schreiner, B. C. Rinderspacher, M. Fujisawa, C.
Yamamoto and Y. Okamoto, Chem.–Eur. J., 2006, 12, 5697.
10 (a) J.-M. Wulff and H. M. R. Hoffmann, Angew. Chem., 1985, 97,
597; (b) H. M. R. Hoffmann, U. Eggert, A. Walenta, E. Weineck, D.
Schomburg, R. Wartchow and F. H. Allen, J. Org. Chem., 1989, 54,
6096; (c) A. Wulferding, J. H. Jankowski and H. M. R. Hoffmann,
Chem. Ber., 1994, 127, 1275.
1
pale yellow oil (0.07 g, 17%). H NMR (300 MHz, CDCl3): d =
1.01 (m, 2H, (CHaHb)2C), 1.21 (m, 2H, (CHaHb)2C), 3.12 (t, 3J =
3
9.57 Hz, 2H, CH2), 3.70 (s, 3H, CH3), 4.51 (t, J = 9.51 Hz, 2H,
3
3
CH2), 7.34 (dd, J = 7.53 Hz, J = 7.62 Hz, 1H, Ar), 7.45 (ddd,
4
4
3J = 7.76 Hz, J = 1.20 Hz, J = 1.20 Hz, 1H, Ar), 7.55 (ddd,
3J = 7.65 Hz, 4J = 1.26 Hz, 4J = 1.44 Hz, 1H, Ar), 7.67 (dd, 4J =
1.69 Hz, 4J = 1.68 Hz, 1H, Ar). 13C NMR (75 MHz, CDCl3): d =
18.2 (CH2), 23.7 (C), 32.0 (CH2), 52.8 (CH3), 70.5 (OCH2), 114.5
(C), 125.9, 128.3, 129.7, 131.4 (Ar), 134.2, 142.4 (C), 167.3, 171.5,
-1
˜
191.1 (CO). IR (ATR, cm ): n = 3066 (w), 2953 (w), 2902 (w),
1727 (m), 1605 (s), 1566 (m), 1474 (w), 1435 (m), 1418 (w), 1383
(m), 1357 (m), 1298 (s), 1262 (m), 1199 (s), 1173 (s), 1125 (s), 1076
(m), 1040 (w), 1026 (w), 999 (w), 954 (w), 901 (m), 858 (m), 802
(m), 737 (s). MS (EI, 70 eV) m/z = 306 (M+, 74.4), 291 (25.7), 280
(38.7), 279 (15.1), 278 (91.5), 275 (30.0), 249 (17.0), 248 (8.2), 247
(30.4), 239 (17.1), 222 (11.5), 221 (7.2), 220 (38.5), 211 (11.8), 195
(19.5), 163 (13.3), 141 (50.6), 140 (10.4), 139 (100), 127 (26.6), 113
(20.9), 112 (5.9), 111 (70.0), 75 (19.5). HRMS (EI, 70 eV): calcd.
for C16H15ClO4 (M+) 306.06400, found 306.064482.
11 T. Rahn, H. Jiao, W. Baumann, A. Spannenberg and P. Langer, Eur. J.
Org. Chem., 2008, 971.
12 N. S. Zefirov, T. S. Kuznetsova, S. I. Kozhushkov, L. S. Surmina and Z.
A. Rashchupkina, J. Org. Chem. USSR (Engl. Transl.), 1983, 19, 474,
(Zh. Org. Khim., 1983, 19, 541).
13 The synthesis of 2a and 2b is known; however, compound 2a was not
completely characterized: N. S. Zefirov, S. I. Kozhushkov and T. S.
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Acknowledgements
Financial support from the DFG (scholarship for T. R.) and by
the State of Mecklenburg-Vorpommern (scholarship for F. B.) is
gratefully acknowledged.
Notes and references
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5184 | Org. Biomol. Chem., 2011, 9, 5172–5184
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