Synthesis of hetero atom modified pyrromethenones

Article abstract of DOI:10.1002/ejoc.200700656

A series of six heteroaromatic compounds, ethyl-/methyl-and dimethylfuranones, thiophenones, and cyclopentenones, was synthesized and condensed with a methyl methylpropionate substituted pyrrole, yielding the "right" half of open-chain tetrapyrroles. These compounds serve as light-inducible chromophores in the plant photoreceptor phytochrome. Three-dimensional structure analysis of the 10-oxapyrromethen-1-one 25 revealed a planar conformation, similar to the dipyrromethenone parent compound, stabilized by a hydrogen bond formed between the pyrrole proton and the furanone oxygen atom. All six pyrrole-substituted heteroaromatic derivatives 25-30 show absorbances in the visible spectrum with high molar extinction coefficients. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200700656

FULL PAPER
DOI: 10.1002/ejoc.200700656
Synthesis of Hetero Atom Modified Pyrromethenones
Christian Bongards[a] and Wolfgang Gärtner*[a]
Keywords: Tetrapyrrole chromophore / Phytochrome / Bilin / Phycocyanobilin
A series of six heteroaromatic compounds, ethyl-/methyl-
and dimethylfuranones, thiophenones, and cyclopentenones,
was synthesized and condensed with a methyl methylpropi-
onate substituted pyrrole, yielding the “right” half of open-
chain tetrapyrroles. These compounds serve as light-induc-
ible chromophores in the plant photoreceptor phytochrome.
Three-dimensional structure analysis of the 10-oxapyrro-
methen-1-one 25 revealed a planar conformation, similar to
the dipyrromethenone parent compound, stabilized by a
hydrogen bond formed between the pyrrole proton and the
furanone oxygen atom. All six pyrrole-substituted heteroaro-
matic derivatives 25–30 show absorbances in the visible
spectrum with high molar extinction coefficients.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
mation and allows one to understand why ring D of the
chromophore (see Figure 1) selectively undergoes a Z/E
double bond photoisomerization as the primary response
to incident light (“Pr-to-Pfr” photoconversion).[13,14] Since
the D-ring is not substituted by very polar groups, but only
Introduction
Abbreviations: BR: bilirubin, BV: biliverdin, PCB: phyco-
cyanobilin, PEB: phycoerythrobilin, PΦB: Phytochromobi-
lin, Pr, Pfr: red-, far-red absorbing forms of plant photo-
receptor phytochrome.
Bile pigments like biliverdin and bilirubin and their de-
rivatives, e.g. phycocyanobilin, phycoerythrobilin or phy-
tochromobilin (PΦB, 1) are compounds which are ubiqui-
tous in all living organisms (see Figure 1). On the one hand,
they represent intermediates in the metabolism of heme
groups[1] and on the other hand, they are important light-
detecting chromophores in many biological photoreceptors.
In particular their photobiological importance as chromo-
phores of light-harvesting antenna in photosynthetic organ-
isms[2] and their role as chromophores in the plant and bac-
terial light-sensing phytochromes[3,4] has raised much inter-
est in modified bilin compounds. In contrast to their bio-
chemical generation (via oxidative cleavage of heme
groups), the highly variable substitution pattern represents
great challenge for chemists working in the field of synthe-
sis. Many efforts have been reported to synthesize the origi-
nal compounds as well as some substitutent-modified open-
chain tetrapyrroles.[5–9] We are mainly interested in the role
of these compounds as chromophores in phyto-
chromes.[10,11] Recently, a three-dimensional structure of the
chromophore-binding domain of a bacterial phytochrome
has been reported which demonstrates the stunning number
of interactions between chromophore and protein.[12] This
network of hydrogen bonds and polar and electrostatic in-
teractions keeps the tetrapyrrole moiety in a bent confor-
[a] Max-Planck-Institute for Bioinorganic Chemistry,
45413 Mülheim an der Ruhr, Germany
Figure 1. Kekulé formula of phytochromobilin (PΦB, 1) in its
ZZZ,asa state. The photoisomerization of the C(15)–C(16) double
bond is indicated by an arrow. Additionally, the novel, structurally
modified chromophores 2–7 are mapped.
E-mail: gaertner@mpi-muelheim.mpg.de
Supporting information for this article is available on the
WWW under http://www.eurjic.org or from the author.
Eur. J. Org. Chem. 2007, 5749–5758
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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C. Bongards, W. Gärtner
FULL PAPER
Figure 2. Preparation of novel ring-D-modified chromophores 2–7 following the convergent synthesis-strategy of open-chain tetrapyrroles
established by Gossauer et al.[6;15]
by a methyl, a vinyl (or ethyl) and the carbonyl function,
the pyrrole nitrogen atom might play an important role in
fixing the conformation of this ring in both Pr- and Pfr-
form. We therefore report here on the synthesis of modified
pyrromethenones as ring-C,D building blocks for open-
chain tetrapyrroles in which the N atom of ring D (N10 in
pyrromethene; nomenclature according to the complete
bilin chromophores) is replaced by an oxygen or a sulfur
atom, or a methylene group (see Figure 2). Since according
to the established convergent synthesis[6,15] the “left” and
the “right” half of an open-chain tetrapyrrole are synthe-
sized separately, and as the final reaction the central coup-
ling is performed, we report here on the hetero atom-modi-
fied “right halves” of novel tetrapyrroles.
Figure 3. Synthesis of the furanones 10 and 11 according to De-
Graw.[16]
Results and Discussion
Syntheses
Synthesis of 3-Ethyl-4-methyl- (10) and 3,4-Dimethylfu-
ranones (11):[16] Ethyl (R,S)-2-bromobutyrate was converted
by Reformatsky reaction into its Zn derivative and allowed
to react with acetoxyacetone to yield lactone 8 in 38%. Eli-
mination of acetic acid upon the addition of TosH·H2O
gave furanone 10 in an overall yield of 22%. The same reac-
tion, using ethyl (R,S)-2-bromopropionate led to furanone
9 (26%, Figure 3).
Synthesis of 3-Ethyl-4-methyl- (14) and 3,4-Dimethylthio-
phenones (15):[17] Thiophenones 14 and 15 were synthesized
(Figure 4) from the same starting material (3-methylthio-
phene). Oxidation yielded a mixture of methyl thio-
phenones 12 and 13 in a ratio of 22.5:77.5 (yield of 18 and
62%, respectively). Both compounds could be separated by
chromatography. Treatment of 13 with either ethyl or
Figure 4. Synthesis of the thiophenones 14 and 15 according to
Kiesewetter et al.[17]
Synthesis of 3-Ethyl-2-methyl-4-(diethoxyphosphoryl)-
methyl iodide yielded the target compounds 14 and 15 in (22) and 2,3-Dimethyl-4-(diethoxyphosphoryl)cyclopen-
33 and 37%, respectively. tenones (23): 2-Ethyl-4-hydroxy-3-methylcyclopent-2-en-1-
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Eur. J. Org. Chem. 2007, 5749–5758

Synthesis of Hetero Atom Modified Dipyrromethenones
one (18) and its 2,3-dimethyl derivative 19 were synthesized at the unsubstituted α-position with the aldehyde function
starting from ethyl 3-oxohexanoate or methyl 3-oxopen- of ring C (Figure 6),[21] whereas the condensation of the
tanoate (Figure 5). Each of these compounds was allowed cyclopentenones could be performed in a Horner–Emmons
to react with pyruvaldehyde, yielding racemic 3-hydroxy- reaction. In all six cases, excellent to moderate yields were
2,5-dioxooctane (16) or -heptane (17), respectively.[18–20] In- observed for the remarkably stable products 25–30.
tramolecular condensation reaction to the hydroxycy-
clopentenones 18 and 19, respectively, was successful in 47
and 50% yield. The hydroxy substituents were transiently
Three-Dimensional Structure of 25
The three-dimensional structure of some of the novel
structures 25–30 could be determined. Compound 25, for
example, forms highly defracting crystals that allow three-
dimensional structure determination (Figure 7). The crystal
structure (resolution 0.7 Å) reveals a nearly planar arrange-
ment of both rings. The small torsion angle C(6)–C(5)–
N–H of –3.39° is probably the result of a hydrogen bond
that is formed between the pyrrole N–H atom and the lone
electron pair of the furan oxygen. Both atoms show a dis-
tance of 2.24 Å which is considerably smaller than the sum
of their van der Waals radii (2.60 Å) and thereby a strong
argument for the assumed hydrogen bond. Additional evi-
dence for a direct interaction between these two atoms can
converted into the chlorides 20 and 21, from which phos-
phonates 22 and 23 were obtained in an Michaelis–Arbuzov
reaction with triethyl phosphite. The generation of phos-
phonates was assumed to be required in order to direct re-
activity to the 4-position of the novel cyclopentenones.
While the furanones 10, 11 and the thiophenones 14, 15 are
supposed to react with the C-ring building block utilizing
the acidic protons in the unsubstituted α-position, in the
case of the cyclopentenones the α-position with respect to
the carbonyl group (C-5) is considered the most reactive
part in the molecule for the anticipated Knoevenagel reac-
tion.
1
be deduced from the IR and the H NMR spectra. The
position of the N–H stretching vibration band for an un-
substituted pyrrole building block is found at 3324 cm–1,
whereas for 25 in which, as proposed, a hydrogen bond for-
Figure 5. Synthesis of the cyclopentenones 22 and 23.
Condensation of Furanones, Thiophenones, and Cyclopen-
tenones 10, 11, 14, 15, 22, and 23 with the C-Ring Building
Block 24: The generation of the “right” half of the tetrapyr-
role derivatives was accomplished by condensation of the
novel furanones, thiophenones, and cyclopentenones with
the C-ring building block 24. As mentioned above, the fu-
Figure 7. X-ray crystal structure (resolution 0.7 Å) and Kekulé for-
mula of the pyrromethen-furanone 25. Due to the intramolecular
hydrogen bond between the 1s orbital of the pyrrole hydrogen atom
and the sp3 hybrid orbital of the furanone oxygen atom the C(6)–
C(7) double bond shows Z configuration while the C(5)–C(6) single
ranones and thiophenones reacted via their acidic proton bond shows syn conformation.
Figure 6. Synthesis of the ring-C,D units 25–30 by Knoevenagel[21] or Horner–Emmons reaction.
Eur. J. Org. Chem. 2007, 5749–5758
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C. Bongards, W. Gärtner
FULL PAPER
mation would be possible, this band shifts to higher energy for the thiophenones 27 and 28, respectively, and
(3448 cm–1), indeed indicative of the formation of a hydro- 27800 –1 cm–1 (369 nm) and 21400 –1 cm–1 (368 nm) for
1
gen bond. A similar conclusion can be drawn from the H the cyclopentenone derivatives 29 and 30 (see Table 1) (Fig-
NMR spectroscopic data: whereas the signal of the pyrrole ure 8). Compared to the data from the dipyrromethenone
hydrogen atom in the unformylated precursor of 24 is found (Figure 6, X = NH), 25500 –1 cm–1 (393 nm), the auxo-
at 8.8 ppm, it is shifted upon formylation (compound 24) chromic effect of the hetero atom is clearly seen by a mo-
to lower field (δ = 9.4 ppm), and experiences an additional notonous increase of the absorption maxima (369–389–
downfield shift in the furanone 25 to 9.7 ppm. All these 393–401 nm).
NMR measurements were performed under identical condi-
tions, allowing a direct comparison of the chemical shifts
obtained (see also Exp. Section).
Conclusion
Aza-, thia- and carba-analogues of pyrromethenone were
synthesized in order to serve as building blocks for the
planned construction of open-chain tetrapyrroles with dif-
ferent hetero atoms in the D-ring moiety. Crystal structure
analysis revealed that the two-ring building blocks adapt
the same configuration and conformation as the all-N par-
ent compound. Since bilins serve as chromophores in plant
photoreceptor phytochrome, the changed reactivity of D-
ring-modified systems will reveal new insight into the chro-
mophore-protein interactions that are essential for the func-
tion of biological photoreceptors.
UV/Vis Absorption Properties of Compounds 25–30
Condensation of the novel five-membered ring com-
pounds with the pyrrole 24 generates an extended π-elec-
tron system. Comparison of the absorbance maxima for 25–
30 reveals the effect of the oxygen, sulfur, or carbon (as
methylene group) on the π-electron system compared to the
parent pyrromethenone (Figure 6, X = NH). All novel com-
pounds show characteristic absorption spectra with a peak
in the UV region and a more intense, structured band in
the visible range. The highest extinction coefficients for this
long-wavelength band is found for both furanones 25 and
26 with 48100 –1 cm–1 (389 nm) and 44400 –1 cm–1
(387 nm). The thiophenones and also the cyclopentenone
Experimental Section
General Methods: Column chromatographical purifications were
performed on Merck silica gel 60 (230–400 mesh) under slightly
increased pressure. HPLC: Purifications were carried out on Krom-
asil C18 ODS-5–100 columns (RP-C18, 5 µm, 250 mmϫ21 mm) at
a flow rate of 0.8 mLmin–1. NMR: Spectra were recorded on
Bruker ARX 250, DRX 400, or DRX 500 spectrometers in CDCl3;
chemical shifts (δ) are given in ppm relative to TMS, coupling con-
stants (J) in Hz. The solvent signals were used as references and
derivatives
show
lower
extinction
coefficients:
21800 –1 cm–1 (401 nm) and 29300 –1 cm–1 (400 nm)
Table 1. UV/Vis absorption parameters for the compounds 25–30
(all values were determined in n-hexane).
Substance
λmax [nm] (ε [–1 cm–1])
25
26
27
28
29
30
254 (32000)
254 (30400)
267 (12900)
267 (16700)
253 (23500)
252 (15500)
389 (48100)
387 (44400)
401 (21800)
400 (29300)
369 (27800)
368 (21400)
409 (45200)
407 (41100)
419 (21300)
418 (29100)
388 (19600)
387 (17700)
the chemical shifts converted into the TMS scale (CDCl3: δC
=
77.0 ppm; residual CHCl3 in CDCl3: δH = 7.24 ppm). IR: Perkin–
Elmer System 2000 spectrometer; wavenumbers ν are given. UV/
˜
Vis: Shimadzu UV-2401 PC spectrometers; the solvents applied
were of appropriated quality (Uvasol). MS (EI): Finnigan MAT
8200, or MAT 8400 (70 eV). ESI-MS: Bruker Esquire 3000, or HP
Quadrupol MS Engine; accurate mass determinations (HRMS):
Finnigan MAT 95. Melting points: Reichert melting point micro-
scope (uncorrected).
Although the nomination of the ring-C,D building blocks 25–30
correlates to the IUPAC rules, for prudential reasons, the assign-
ment of the hydrogen and carbon atoms for NMR analysis follows
the Kekulé formula displayed in Figure 7.
4-Ethyl-3-methyl-5-oxotetrahydrofuran-3-yl Acetate (8): A suspen-
sion of acetoxyacetone (27.5 mL, 254.6 mmol), zinc powder (20.0 g,
305.9 mmol) and a catalytic amount of iodine in benzene (300 mL)
was refluxed under argon with vigorous stirring. Within 45 min
ethyl (R,S)-2-bromobutyrate (41.4 mL, 280.2 mmol) was added in
such a way that simmering was maintained. The dispersion was
refluxed for additional 45 min, cooled externally with ice, then
mixed with ice/water (200 mL). After addition of hydrochloric acid
(60 mL, 6 ), the slurry was stirred until two almost clear phases
had formed. These were separated and the aqueous phase was ex-
tracted with diethyl ether (2ϫ75 mL). The combined organic
phases were washed with saturated NaHCO3 solution (100 mL)
and dried with Na2SO4. Evaporation of the solvent yielded the
Figure 8. UV/Vis absorption spectra of selected furanone- (25),
thiophenone- (27), and cyclopentenone-substituted (29) ring-C,D
building blocks (n-hexane).
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Eur. J. Org. Chem. 2007, 5749–5758

Synthesis of Hetero Atom Modified Dipyrromethenones
crude product (28.53 g) which was purified by fractional distillation
in vacuo. The product 8 was obtained as a mixture of its stereoiso-
mers (17.90 g, 96.1 mmol, 38%) in the form of a yellowish liquid,
= 15.85 Hz, C-31), 45.43 (d, 1JC,H = 91.12 Hz, C-4), 73.35 (d, 1JC,H
= 54.19 Hz, C-2), 83.69 (d, JC,H = 12.60 Hz, C-3), 170.54 (d, JC,H
= 3.99 Hz, acetoxy CO2CH3), 177.08 (d, JC,H = 61.30 Hz, C-5)
b.p. 124–126 °C (4.4 mbar). 1H NMR (400 MHz, CDCl3): δ = 1.06– ppm. IR (KBr): ν = 2985, 2945, 2909, 1786, 1741, 1452, 1372, 1235,
˜
1.12 (m, 3 H, 42-CH3), 1.54–1.82 (m, 2 H, 41-CH2), 1.48 (s, 1.1 H,
1149, 1133, 1098, 1032, 1014, 942, 857, 817, 668, 610, 557, 543
31-CH3), 1.64 (s, 1.9 H, 31-CH3), 1.98 (s, 1.7 H, acetoxy CO2CH3), cm–1. MS (GC-EI): m/z (%) = 130 (17), 114 (2), 112 (30), 99 (8),
1.99 (s, 1.3 H, acetoxy CO2CH3), 2.21 (t, 3J = 6.83 Hz, 1.9 H, 4- 84 (7), 83 (9), 72 (8), 68 (3), 67 (2), 56 (17), 55 (9), 45 (2), 43 (100),
CH), 2.65 (t, 3J = 7.20 Hz, 1.1 H, 4-CH), 4.06 (d, AЈBЈ system,
JAЈBЈ = 10.82 Hz, 0.6 H, 2-CHAЈ), 4.26 (d, AЈЈBЈЈ system, JAЈЈBЈЈ
39 (6), 27 (10), 26 (2).
=
3,4-Dimethylfuran-2(5H)-one (11): A mixture of the lactone 9
(11.27 g, 65.5 mmol) and 4-toluenesulfonic acid monohydrate
(0.56 g, 2.9 mmol) was heated under argon at 150 °C for 19 h such
that slight reflux was observable. The accrued dark brown mixture
was purified by fractional distillation in vacuo. Thereby, the reac-
tion product 11 (6.43 g, 57.4 mmol, 88%) was obtained as colour-
less crystals, m.p. 28 °C, b.p. 71–72 °C (0.22 mbar). 1H NMR
(250 MHz, CDCl3): δ = 1.75–1.76 (m, 3 H, 31-CH3), 1.94–1.96 (m,
3 H, 41-CH3), 4.54–4.57 (m, 2 H, 5-CH2) ppm. 13C NMR (63 MHz,
CDCl3): δ = 8.68 (C-31), 12.61 (C-41), 72.92 (C-5), 123.56 (C-3),
9.96 Hz, 0.4 H, 2-CHAЈЈ), 4.42 (d, AЈЈBЈЈ system, JAЈЈBЈЈ = 9.98 Hz,
0.4 H, 2-CHBЈЈ), 4.72 (d, AЈBЈ system, JAЈBЈ = 10.83 Hz, 0.6 H, 2-
1
CHBЈ) ppm. 13C NMR (101 MHz, CDCl3): δ = 11.94 (d, JC,H
=
59.49 Hz, C-42), 17.58 (d, JC,H = 44.71 Hz, C-41), 18.57 (acetoxy
1
1
1
CO2CH3), 21.44 (d, JC,H = 15.65 Hz, C-31), 51.02 (d, JC,H
=
159.81 Hz, C-4), 73.29 (C-2), 83.49 (d, JC,H = 6.29 Hz, C-3), 170.06
(d, JC,H = 4.75 Hz, acetoxy CO2CH3), 175.98 (d, JC,H = 129.88 Hz,
C-5) ppm. IR (KBr): ν = 2972, 2940, 2881, 1783, 1740, 1458, 1371,
˜
1258, 1231, 1149, 1133, 1023, 946 cm–1. MS (GC-EI): m/z (%) =
158 (3), 144 (5), 126 (14), 113 (2), 99 (3), 98 (3), 86 (4), 71 (8), 70
(9), 67 (5), 58 (2), 45 (3), 43 (100), 41 (22), 40 (3), 39 (12).
156.58 (C-4), 175.77 (C-2) ppm. IR (KBr): ν = 2955, 2928, 2865,
˜
1752, 1682, 1449, 1385, 1351, 1326, 1188, 1081, 1031, 887, 760,
660, 577, 480 cm–1. MS (EI, –10 °C): m/z (%) = 112 (80) [M+], 83
(80), 82 (3), 55 (100), 54 (11), 53 (11), 52 (3), 51 (5), 50 (4), 39 (16),
38 (2), 29 (12), 27 (11), 26 (2). HRMS (EI): m/z: calcd. for C6H8O2:
112.052430; found: 112.052443.
3-Ethyl-4-methylfuran-2(5H)-one (10): A mixture of the lactone 8
(7.46 g, 51.7 mmol) and 4-toluenesulfonic acid monohydrate
(0.29 g, 1.5 mmol) was heated under argon at 150 °C for 19 h such
that slight reflux was observable. The accrued dark brown mixture
was purified by fractional distillation in vacuo. Thereby, the reac-
tion product 10 (3.70 g, 29.3 mmol, 57%) was obtained as slightly
yellow liquid, b.p. 51–54 °C (0.010 mbar). 1H NMR (250 MHz,
4-Methylthiophen-2(5H)-one (13): A solution of n-butyllithium in
n-hexane (69.8 mL, 111.7 mmol, 1.6 ) was added to a solution of
3-methylthiophene (10.0 mL, 102 mmol) in absolute diethyl ether
(100 mL) under argon. After refluxing for 30 min, the solution was
cooled down to –63 °C. Within 30 min a solution consisting of tri-
methyl borate (12.8 mL, 111.0 mmol) and absolute diethyl ether
(100 mL) was added. The resulting mixture was stirred for 4 h at
–67 °C. Warming up to ambient temperature induced the formation
of a colourless precipitation. Within 30 min an aqueous solution
of hydrogen peroxide (17.6 mL, 204.7 mmol, 35%) was added to
the dispersion which was refluxed for 1 h afterwards. The layers
were separated from each other, and the aqueous phase was ex-
tracted with diethyl ether (4ϫ50 mL). After combining, the or-
ganic layers were dried with Na2SO4. Evaporation of the solvent
yielded the raw material (10.02 g) which was purified by fractional
distillation in vacuo. Subsequent column chromatography of the
remaining mixture of the regioisomers 4-methyl-2(5H)-thio-
phenone (13) and 3-methyl-2(5H)-thiophenone (12) with n-pentane
und ethyl acetate (4:1) yielded the desired reaction product 13
(7.22 g, 63.2 mmol, 62%) as a slight yellow-brown liquid. 1H NMR
(400 MHz, CDCl3): δ = 2.17 (m, 3 H, 41-CH3), 3.92–3.93 (m, 2 H,
5-CH2), 6.05–6.06 (m, 1 H, 3-CH) ppm. 13C NMR (101 MHz,
CDCl3): δ = 18.94 (C-41), 40.90 (C-5), 129.19 (C-3), 167.55 (C-4),
3
CDCl3): δ = 1.03 (t, J = 7.57 Hz, 3 H, 32-CH3), 1.97 (s, 3 H, 41-
CH3), 2.23 (q, 3J = 7.56 Hz, 2 H, 31-CH2), 4.56 (s, 2 H, 5-CH2)
ppm. 13C NMR (63 MHz, CDCl3): δ = 11.99 (C-32), 12.51 (C-31),
16.66 (C-41), 72.32 (C-5), 128.57 (C-3), 155.82 (C-4), 174.88 (C-2)
ppm. IR (KBr): ν = 2973, 2936, 2877, 1758, 1744, 1679, 1453, 1390,
˜
1341, 1190, 1093, 1065, 1035, 948, 773 cm–1. MS (EI, –15 °C): m/z
(%) = 126 (60) [M+], 97 (38), 80 (4), 79 (8), 77 (2), 69 (52), 68 (6),
67 (20), 63 (2), 59 (2), 51 (7), 50 (4), 43 (11), 41 (100), 40 (8), 39
(38), 38 (5), 29 (16). HRMS (EI): m/z: calcd. for C7H10O2:
126.068080; found: 126.068038.
3,4-Dimethyl-5-oxotetrahydrofuran-3-yl Acetate (9): A dispersion
consisting of acetoxyacetone (25.0 mL, 226.8 mmol), zinc powder
(18.8 g, 287.6 mmol) and a catalytic amount of iodine in benzene
(270 mL) was refluxed under argon with vigorous stirring. Within
75 min ethyl (R,S)-2-bromopropionate (32.8 mL, 250.0 mmol) was
added such that simmering was afforded. The dispersion was re-
fluxed for additional 60 min, cooled on ice, and mixed with ice-
water (380 mL). After addition of hydrochloric acid (80 mL, 6 )
the slurry was stirred until two almost clear phases occurred. They
were separated from each other and the aqueous phase was ex-
tracted with diethyl ether (3ϫ120 mL). The combined organic
phases were washed with a saturated NaHCO3 solution (300 mL)
and dried with Na2SO4. Evaporation of the solvent yielded the
crude product (17.57 g) which was purified by fractional distillation
in vacuo. The product 9 of the reaction was obtained as a mixture
of its stereoisomers (11.27 g, 65.5 mmol, 29%) in form of a yellow-
199.73 (C-2) ppm. IR (KBr): ν = 3073, 2982, 2946, 2915, 1678,
˜
1659, 1634, 1434, 1404, 1378, 1310, 1228, 1156, 1098, 1017, 881,
833, 766, 656, 566, 484, 437 cm–1. MS (GC-EI): m/z (%) = 114
(100) [M+], 86 (26), 85 (34), 82 (2), 71 (26), 69 (17), 58 (4), 53 (24),
51 (5), 50 (6), 47 (2), 46 (11), 45 (23), 41 (12), 40 (8), 39 (28), 38
(7), 37 (4), 27 (10).
1
ish oil, b.p. 76–78 °C (0.23 mbar). H NMR (250 MHz, CDCl3): δ
= 1.17 (d, 3J = 2.99 Hz, 1.4 H, 41-CH3), 1.20 (d, 3J = 2.77 Hz, Additionally, the byproduct 12 (2.04 g, 17.9 mmol, 18%) was ob-
1.6 H, 41-CH3), 1.44 (s, 1.4 H, 31-CH3), 1.61 (s, 1.6 H, 31-CH3), tained in the form of yellow-brown coloured crystals, m.p. 35 °C.
1.97 (s, 1.6 H, acetoxy CO2CH3), 1.99 (s, 1.4 H, acetoxy CO2CH3), 1H NMR (400 MHz, CDCl3): δ = 1.89–1.91 (m, 3 H, 31-CH3),
2.40 (q, J = 7.26 Hz, 0.5 H, 4-CH), 2.83 (q, J = 7.42 Hz, 0.5 H, 4-
CH), 4.04 (d, AЈBЈ system, JAЈBЈ = 10.90 Hz, 0.6 H, 2-CHAЈ), 4.29
3.90–3.92 (m, 2 H, 5-CH2), 7.16–7.18 (m, 1 H, 4-CH) ppm.
13C NMR (101 MHz, CDCl3): δ = 11.78 (C-31), 34.93 (C-5), 141.50
(d, AЈЈBЈЈ system, JAЈЈBЈЈ = 10.04 Hz, 0.4 H, 2-CHAЈЈ), 4.44 (d, (C-3), 147.04 (C-4), 200.57 (C-2) ppm. IR (KBr): ν = 3053, 2986,
˜
AЈЈBЈЈ system, JAЈЈBЈЈ = 10.03 Hz, 0.4 H, 2-CHBЈЈ), 4.80 (d, AЈBЈ
system, JAЈBЈ = 10.91 Hz, 0.6 H, 2-CHBЈ) ppm. 13C NMR (63 MHz,
CDCl3): δ = 17.96 (C-41), 20.50 (acetoxy CO2CH3), 21.90 (d, 1JC,H
2951, 2919, 2871, 1794, 1666, 1638, 1432, 1412, 1404, 1370, 1300,
1191, 1041, 1024, 988, 897, 811, 748, 678, 670, 592, 476, 423 cm–1.
MS (GC-EI): m/z (%) = 114 (100) [M+], 113 (2), 88 (2), 87 (6), 86
Eur. J. Org. Chem. 2007, 5749–5758
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5753

C. Bongards, W. Gärtner
FULL PAPER
(54), 85 (78), 82 (2), 81 (2), 69 (13), 58 (7), 53 (41), 52 (5), 51 (11), some thiophenone 13 (0.27 g, 2.38 mmol, 9% of the starting mate-
50 (11), 49 (2), 47 (3), 46 (19), 45 (29), 41 (19), 39 (27), 38 (4), 27 rial) was recovered, m.p. 38–39 °C. 1H NMR (400 MHz, CDCl3): δ
(20), 26 (6).
= 1.79–1.81 (m, 3 H, 31-CH3), 2.09–2.10 (m, 3 H, 41-CH3), 3.80–
3.82 (m, 2 H, 5-CH2) ppm. 13C NMR (101 MHz, CDCl3): δ = 10.12
(C-31), 17.51 (C-41), 38.78 (C-5), 135.13 (C-3), 158.45 (C-4), 200.47
3-Ethyl-4-methylthiophen-2(5H)-one (14): Ethyl iodide (3.35 mL,
41.0 mmol) was added to a solution consisting of the thiophenone
13 (3.00 g, 26.3 mmol) and chloroform (27.3 mL) under argon and
exclusion of light. After addition of a solution of tetrabutylammo-
nium hydrogen sulfate (8.97 g, 26.4 mmol) and sodium hydroxide
(2.14 g, 53.5 mmol) in water (27.3 mL), the resulting slurry was
stirred at ambient temperature for 70 h. The reaction was quenched
by addition of hydrochloric acid (25.7 mL, 2 ), the aqueous layer
was extracted with chloroform (3ϫ20 mL), and the solvent of the
combined organic phases was removed by evaporation in vacuo.
Upon addition of diethyl ether (200 mL) to the remaining brown
oil, the ammonium salt formed, which was separated from the solu-
tion by filtration. After drying the filtrate over Na2SO4, the solvent
was evaporated in vacuo. The residue was purified by fractional
distillation in vacuo and subsequently by column chromatography
with n-pentane and ethyl acetate (9:1). The product 14 (1.21 g,
8.5 mmol, 33%) was obtained as an orange, clear liquid, b.p. 54–
57 °C. 1H NMR (400 MHz, CDCl3): δ = 1.00 (t, 3J = 7.56 Hz, 3 H,
32-CH3), 2.11 (s, 3 H, 41-CH3), 2.29 (q, 3J = 7.53 Hz, 2 H, 31-CH2),
3.80 (q, 4J = 0.80 Hz, 2 H, 5-CH2) ppm. 13C NMR (101 MHz,
CDCl3): δ = 12.75 (C-32), 17.28 (C-31), 18.33 (C-41), 38.74 (C-5),
(C-2) ppm. IR (KBr): ν = 2980, 2943, 2923, 2856, 1678, 1655, 1437,
˜
1409, 1377, 1297, 1231, 992, 936, 827, 766, 677, 632, 536, 474, 430
cm–1. MS (GC-EI): m/z (%) = 128 (100) [M+], 113 (3), 99 (25), 85
(56), 83 (7), 71 (3), 67 (34), 65 (9), 59 (12), 55 (16), 45 (15), 41
(14), 39 (25), 29 (3), 27 (13). HRMS (EI): m/z: calcd. for C6H8OS:
128.029588; found: 128.029781.
3-Hydroxyoctane-2,5-dione (16): Ethyl butyrylacetate (20.0 mL,
123.9 mmol) cooled down to 0 °C was dosed with a chilled solution
of potassium hydroxide (8.33 g, 137.3 mmol) in water (50 mL). The
resulting slurry was stirred for 30 min and subsequently stored at
5 °C for 8 d. At ambient temperature carbon dioxide was passed
into for 2 h. Afterwards a solution of pyruvaldehyde in water
(22.3 mL, 40%) was added, the mixture was stirred for 24 h and
extracted with diethyl ether (5ϫ70 mL). The combined organic
layers were washed with brine (170 mL) and dried with Na2SO4.
Evaporation of the solvent yielded 18.04 g of the crude material
which was purified by fractional distillation under reduced pres-
sure. The product 16 of the reaction was obtained (12.05 g,
76.2 mmol, 62%) as a yellowish, clear, and slightly viscous oil, b.p.
1
1
77–79 °C. H NMR (400 MHz, H/1H-COSY, CDCl3): δ = 0.85 (t,
140.75 (C-3), 158.37 (C-4), 200.16 (C-2) ppm. IR (KBr): ν = 2970,
˜
3J = 7.42 Hz, 3 H, 8-CH3), 1.54 (tq, Jt = 7.26, Jq = 7.35 Hz, 2 H,
3
3
2934, 2875, 1675, 1651, 1456, 1409, 1380, 1334, 1297, 1222, 1155,
1112, 1023, 916, 847, 761, 707, 658, 623, 543, 472 cm–1. MS (EI,
10 °C): m/z (%) = 142 (100) [M+], 127 (17), 114 (6), 109 (8), 101
(2), 99 (39), 97 (6), 86 (2), 81 (23), 79 (9), 77 (3), 69 (10), 66 (2), 65
(7), 58 (2), 50 (2), 45 (10), 41 (18), 39 (15), 38 (2), 29 (2). HRMS
(EI): m/z: calcd. for C7H10OS: 142.045238; found: 142.045368.
7-CH2), 2.20 (s, 3 H, 1-CH3), 2.39 (t, 3J = 7.27 Hz, 2 H, 6-CH2),
3
2.76 (dd, ABX system, JAB = 17.12, JAX = 6.38 Hz, 1 H, 4-CHA),
2.88 (dd, ABX system, JAB = 17.12, JBX = 3.85 Hz, 1 H, 4-CHB),
3
3
3
3.45 (br. s, 1 H, OH), 4.29 (dd, ABX system, JAX = 6.37, JBX
=
3.85 Hz, 1 H, 3-CHX) ppm. 13C NMR (101 MHz, 1H/13C-COSY,
CDCl3): δ = 13.47 (C-8), 16.81 (C-7), 25.28 (C-2), 45.19 (C-4),
Additionally, the byproduct 3-ethyl-4-methyl-2(3H)-thiophenone
(0.13 g, 0.9 mmol, 4%) was isolated in the form of a yellow liquid.
1H NMR (400 MHz, CDCl3): δ = 0.98 (t, 3J = 1.25 Hz, 3 H, 32-
CH3), 1.64–1.75 (m, 1 H, 31-CH2), 2.05–2.15 (m, 1 H, 31-CH2), 2.09
45.46 (C-6), 73.72 (C-3), 209.30 (C-2,-5) ppm. IR (KBr): ν = 3458,
˜
2965, 2937, 2878, 1713, 1459, 1407, 1359, 1248, 1181, 1128, 1106,
1017, 967, 904, 617, 529 cm–1. MS (EI, –2 °C): m/z (%) = 158 (1)
[M+], 143 (1), 115 (37), 97 (9), 87 (1), 71 (95), 55 (5), 43 (100),
41 (13), 27 (11). HRMS (CI, isobutane): m/z: calcd. for C8H15O3
[M + H]+: 159.102292; found: 159.102117.
4
4
4
(dd, Jd = 1.25, Jd = 0.47 Hz, 3 H, 41-CH3), 4.24 (dq, Jd = 3.58,
3
4
4Jq = 0.67 Hz, 0.5 H, 3-CH), 4.26 (dq, Jd = 3.47, Jq = 0.73 Hz,
0.5 H, 3-CH), 6.00 (q, 4J = 1.30 Hz, 1 H, 5-CH) ppm. 13C NMR
(101 MHz, CDCl3): δ = 10.85 (C-32), 17.13 (C-31), 25.71 (C-41),
57.82 (C-3), 129.80 (C-5), 170.36 (C-4), 198.79 (C-2) ppm. MS
(GC-EI): m/z (%) = 142 (100) [M+], 127 (6), 113 (48), 109 (6), 99
(15), 85 (57), 81 (22), 79 (11), 73 (10), 69 (32), 65 (8), 59 (7), 53
(13), 45 (33), 39 (34), 27 (14). HRMS (EI): m/z: calcd. for C7H10OS:
142.045238; found: 142.045472.
2-Ethyl-4-hydroxy-3-methylcyclopent-2-enone (18): A solution of
the dione 16 (12.05 g, 76.2 mmol) in methanol (55 mL, 1.4 mol)
was cooled to 0 °C. Within 2 h an aqueous solution of K2CO3
(332 mL, 20%) was added such that the temperature of the re-
sulting mixture did not exceed 5 °C. It was stirred for 2 h at 0 °C,
for additional 24 h at ambient temperature, and afterwards was
neutralised by addition of hydrochloric acid (2 ). The solution was
3,4-Dimethylthiophen-2(5H)-one (15): Methyl iodide (3.45 mL, extracted with dichloromethane (4ϫ440 mL) and the combined or-
54.9 mmol) was added to a solution consisting of the thiophenone
13 (3.00 g, 26.3 mmol) and chloroform (27.0 mL) under argon and
exclusion of light. After addition of a solution composed of tetra-
butylammonium hydrogen sulfate (8.93 g, 25.8 mmol) and sodium
hydroxide (2.12 g, 52.4 mmol) in water (27.0 mL), the resulting
slurry was stirred at ambient temperature for 76 h. The reaction
was quenched by addition of hydrochloric acid (25.0 mL, 2 ). The
aqueous layer was extracted with chloroform (3ϫ20 mL), and the
solvent of the combined organic phases was removed by evapora-
tion in vacuo. Upon addition of diethyl ether (200 mL) to the resi-
due, the ammonium salt formed, which was separated from the
solution by filtration. After drying the filtrate over MgSO4, the
solvent was evaporated in vacuo. The residue was purified by frac-
tional distillation in vacuo and subsequently by column chromatog-
raphy with n-pentane and ethyl acetate (9:1). The product 15
(1.14 g, 8.9 mmol, 34% isolated yield, 37% concerning converted
thiophenone 13) was obtained as an orange, clear liquid. Also,
ganic layers were dried with Na2SO4. Removal of the solvent by
evaporation in vacuo yielded 9.22 g of the crude material which was
purified by column chromatography with chloroform and methanol
(99:1). The product 18 (5.00 g, 35.7 mmol, 47%) was obtained as
1
an auburn coloured, clear liquid. H NMR (500 MHz, CDCl3): δ
3
= 0.96 (t, J = 7.60 Hz, 3 H, 22-CH3), 2.06 (s, 3 H, 31-CH3), 2.16
(q, 3J = 7.56 Hz, 2 H, 21-CH2), 2.23 (dd, ABX system, 3JAX = 1.76,
JAB = 18.35 Hz, 1 H, 5-CHA), 2.57 (br. s, 1 H, OH), 2.72 (dd, ABX
3
system, JAB = 18.35, JBX = 6.12 Hz, 1 H, 5-CHB), 4.67 (d, ABX
3
system, JBX = 5.94 Hz, 1 H, 4-CHX) ppm. 13C NMR (126 MHz,
BB, CDCl3): δ = 12.37 (C-22), 13.18 (C-31), 15.94 (C-21), 44.18 (C-
5), 71.25 (C-4), 143.22 (C-2), 168.07 (C-3), 205.31 (C-1) ppm. IR
(KBr): ν = 3411, 2971, 2936, 2876, 1694, 1646, 1463, 1384, 1348,
˜
1311, 1262, 1238, 1192, 1148, 1095, 1048, 1012, 938, 918, 849, 777,
616, 579 cm–1. MS (EI, 14 °C): m/z (%) = 40 (100) [M+], 125 (50),
111 (59), 107 (6), 97 (70), 95 (19), 93 (7), 83 (17), 79 (41), 77 (18),
67 (38), 55 (54), 53 (33), 43 (90), 41 (75), 39 (47), 29 (20), 27 (30).
5754
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5749–5758

Synthesis of Hetero Atom Modified Dipyrromethenones
HRMS (EI): m/z: calcd. for C8H12O2: 140.083733; found:
140.083832.
fied by fractional distillation in vacuo. The product 17 was ob-
tained (9.25 g, 64.2 mmol, 41%) as a colourless, clear, and slightly
viscous oil, b.p. 54–56 °C. 1H NMR (400 MHz, CDCl3): δ = 1.02
4-Chloro-2-ethyl-3-methylcyclopent-2-enone (20): Thionyl chloride
(2.5 mL, 33.2 mmol) was slowly added under argon to the alcohol
18 (1.98 g, 14.1 mmol) at 0 °C. The solution was stirred for 15 min
at ambient temperature and the excess of thionyl chloride was re-
moved by distillation under reduced pressure (27–4 mbar). Purifi-
cation of the residual solution by fractional distillation in vacuo
yielded the product 20 (1.18 g, 7.5 mmol, 53%) in the form of a
clear, yellow and slightly viscous oil, b.p. 51 °C (0.76 mbar).
1H NMR (400 MHz, CDCl3): δ = 0.98 (t, 3J = 7.60 Hz, 3 H, 22-
3
(t, J = 7.29 Hz, 3 H, 7-CH3), 2.22 (s, 3 H, 1-CH3), 2.45 (q, 3J =
3
7.31 Hz, 2 H, 6-CH2), 2.78 (dd, ABX system, JAB = 17.02, JAX
=
=
3
6.39 Hz, 1 H, 4-CHA), 2.91 (dd, ABX system, JAB = 17.01, JBX
3.82 Hz, 1 H, 4-CHB), 3.70 (br. s, 1 H, OH), 4.31 (dd, ABX system,
3
3JAX = 6.32, JBX = 3.87 Hz, 1 H, 3-CH) ppm. 13C NMR
(101 MHz, 1H/13C-COSY, CDCl3): δ = 7.45 (C-7), 25.30 (C-1),
36.87 (C-6), 44.88 (C-4), 73.81 (C-3), 209.24 (C-2), 209.72 (C-5)
ppm. IR (KBr): ν = 3450, 2979, 2941, 1714, 1460, 1411, 1359, 1242,
˜
1183, 1114, 1003, 967, 616 cm–1. MS (GC-EI): m/z (%) = 126 (1),
108 (1), 101 (20), 83 (7), 79 (1), 73 (9), 69 (7), 57 (100), 55 (10), 43
(45), 29 (20), 27 (4). HRMS (CI, isobutane): m/z: calcd. for
C7H13O3 [M + H]+: 145.086470; found: 145.086323.
3
CH3), 2.09 (s, 3 H, 31-CH3), 2.21 (q, J = 7.61 Hz, 2 H, 21-CH2),
3
2.60 (dd, ABX system, JAB = 19.05, JAX = 1.65 Hz, 1 H, 5-CHA),
3
2.94 (dd, ABX system, JAB = 19.03, JBX = 6.45 Hz, 1 H, 5-CH2),
3
3
4.81 (dd, ABX system, JAX = 1.83, JBX = 6.47 Hz, 1 H, 4-CHX)
ppm. 13C NMR (101 MHz, CDCl3): δ = 12.42 (C-22), 14.24 (C-31),
16.50 (C-21), 45.03 (C-5), 57.85 (C-4), 145.07 (C-2), 165.36 (C-3),
4-Hydroxy-2,3-dimethylcyclopent-2-enone (19): A solution of the di-
one 17 (4.02 g, 27.9 mmol) in methanol (20 mL, 0.49 mol) was
cooled to 0 °C. An aqueous solution of K2CO3 (121 mL, 20%) was
added within 1 h such that the temperature of the resulting mixture
did not exceed 3 °C. It was stirred for 2 h at 0 °C for additional
24 h at ambient temperature, and was afterwards neutralised by
addition of hydrochloric acid (2 ). The solution was extracted
with dichloromethane (4ϫ110 mL) and the combined organic lay-
ers were dried with Na2SO4. Removal of the solvent by evaporation
in vacuo yielded 2.47 g of the raw material which was purified by
column chromatography with chloroform and methanol (99:1). The
product 19 (1.74 g, 13.8 mmol, 50%) was obtained as an auburn,
clear liquid. 1H NMR (500 MHz, CDCl3): δ = 1.69 (s, 3 H, 31-
CH3), 2.06 (s, 3 H, 21-CH3), 2.19 (br. s, 1 H, OH), 2.25 (d, ABX
system, JAB = 18.38 Hz, 1 H, 5-CHA), 2.75 (dd, ABX system, JAB
203.46 (C-1) ppm. IR (KBr): ν = 2973, 2936, 2877, 1712, 1647,
˜
1461, 1386, 1346, 1249, 1222, 1183, 1086, 1057, 930, 899, 781, 718,
658, 587 cm–1. MS (EI, –7 °C): m/z (%) = 158 (52) [M+], 138 (2),
123 (85), 115 (2), 107 (2), 95 (100), 93 (8), 79 (17), 67 (30), 65 (8),
55 (19), 39 (21), 27 (13). HRMS (EI): m/z: calcd. for C8H11ClO:
158.049956; found: 158.049842.
Diethyl (3-Ethyl-2-methyl-4-oxocyclopent-2-enyl)phosphonate (22):
A mixture of the chloride 20 (1.18 g, 7.5 mmol) and triethyl phos-
phite (1.4 mL, 7.7 mmol) was heated under argon to 75–80 °C for
45 min and was subsequently refluxed at 160 °C for 5 h. Purifica-
tion of the resulting solution by fractional distillation in vacuo
yielded the product 22 (0.86 g, 3.3 mmol, 44% isolated yield, 73%
concerning converted chloride 20) as a yellow, clear liquid. Ad-
ditionally, some chloride 20 (0.46 g, 2.9 mmol, 39% of the starting
material) was recovered, b.p. 123–124 °C (0.76–0.82 mbar).
1H NMR (400 MHz, 1H/1H-COSY, CDCl3): δ = 0.93 (t, 3J =
7.57 Hz, 3 H, 32-CH3), 1.21 [t, 3J = 7.05 Hz, 3 H, PO(OCH2-
3
3
= 18.38, JBX = 6.09 Hz, 1 H, 5-CHB), 4.70 (d, 4-CHX, JBX
=
5.50 Hz, 1 H, ABX system) ppm. 13C NMR (126 MHz, BB,
CDCl3): δ = 7.67 (C-31), 13.39 (C-21), 44.00 (C-5), 71.40 (C-4),
137.90 (C-2), 168.00 (C-3), 205.41 (C-1) ppm. IR (KBr): ν = 3411,
˜
2978, 2923, 1699, 1648, 1437, 1386, 1327, 1242, 1195, 1149, 1085,
1050, 1006, 946, 903, 836, 717, 661, 590, 508 cm–1. MS (EI, 15 °C):
m/z (%) = 126 (94) [M+], 111 (89), 98 (100), 93 (5), 83 (85), 81 (20),
79 (31), 71 (5), 69 (16), 65 (10), 55 (86), 53 (39), 43 (89), 41 (44),
39 (56), 29 (28), 27 (47). HRMS (EI): m/z: calcd. for C7H10O2:
126.068082; found: 126.068227.
3
CH3)2], 1.26 [t, J = 7.05 Hz, 3 H, PO(OCH2CH3)2], 2.17 (s, 3 H,
21-CH3), 2.17 (q, 3J = 7.48 Hz, 2 H, 31-CH2), 2.48–2.63 (m, 2 H,
5-CH2), 3.03 (m, 0.5 H, 1-CH), 3.09 (m, 0.5 H, 1-CH), 3.95–4.14
[m, 4 H, PO(OCH2CH3)2] ppm. 13C NMR (101 MHz, DEPT 135,
1
1H/13C-COSY, CDCl3): δ = 12.54 (d, JC,H = 4.25 Hz, C-32), 16.35
[d, 3J = 5.78 Hz, PO(OCH2CH3)2], 16.45 (C-21), 16.45 (C-31), 36.60
4-Chloro-2,3-dimethylcyclopent-2-enone (21): Thionyl chloride
(3.8 mL, 50.5 mmol) was slowly added under argon to the alcohol
19 (1.75 g, 13.9 mmol) at 0 °C. The solution was stirred for 1 h at
0 °C and for another 1 h at ambient temperature. Subsequently, the
excess of thionyl chloride was removed by distillation under re-
duced pressure (11–8 mbar). Purification of the residual solution
by fractional distillation in vacuo yielded the product 21 (0.93 g,
6.4 mmol, 46%) in form of a clear, yellow and slightly viscous oil,
2
1
(d, JC,P = 3.97 Hz, C-5), 41.62 (d, JC,P = 144.47 Hz, C-1), 62.04
2
2
[d, JC,P = 6.83 Hz, PO(OCH2CH3)2], 62.54 [d, JC,P = 6.99 Hz,
PO(OCH2CH3)2], 144.30 (d, 1JC,H = 9.99 Hz, C-3), 164.28 (d, 2JC,P
1
= 8.99 Hz, C-2), 206.05 (d, JC,H = 2.32 Hz, C-4). IR (KBr): ν =
˜
2978, 2935, 2876, 1702, 1641, 1445, 1387, 1348, 1256, 1233, 1209,
1164, 1052, 1024, 966, 800, 615, 570, 534, 489 cm–1. MS (EI, 45 °C):
m/z (%) = 260 (99) [M+], 245 (8), 232 (34), 217 (7), 204 (77), 189
(15), 175 (6), 150 (12), 139 (21), 122 (100), 107 (38), 95 (36), 79
(30), 67 (18), 55 (21), 41 (18), 29 (25). HRMS (ESI pos, methanol
+ dichloromethane): m/z: calcd. for C12H21O4NaP [M + Na]+:
283.107312; found: 283.106969.
1
b.p. 36–40 °C (0.11–0.13 mbar). H NMR (400 MHz, CDCl3): δ =
1.71 (s, 3 H, 21-CH3), 2.07 (s, 3 H, 31-CH3), 2.60 (dd, ABX system,
3
JAB = 19.06, JAX = 1.74 Hz, 1 H, 5-CHA), 2.94 (dd, ABX system,
3
JAB = 19.06, JBX = 6.45 Hz, 1 H, 5-CHB), 4.81 (dd, ABX system,
3
3JAX = 0.75, JBX = 6.40 Hz, 1 H, 4-CHX) ppm. 13C NMR
3-Hydroxyheptane-2,5-dione
(17):
Methyl
propionylacetate
(101 MHz, 1H/13C-COSY, CDCl3): δ = 8.20 (C-31), 14.43 (C-21),
(20.0 mL, 158.3 mmol) was cooled down to 0 °C and was dosed
with a chilled solution of potassium hydroxide (9.80 g, 174.7 mmol)
in water (63 mL). The resulting slurry was stirred for 35 min and
subsequently stored at 5 °C for 6 d. Carbon dioxide was passed
into it at ambient temperature for 2 h. Afterwards, a solution of
pyruvaldehyde in water (28.5 mL, 40%) was added, the mixture
was stirred for 24 h, stored at 5 °C for 17 h, and extracted with
diethyl ether (5ϫ90 mL). The combined organic layers were
washed with brine (230 mL) and dried with Na2SO4. Evaporation
of the solvent yielded 14.14 g of the crude material which was puri-
44.85 (C-5), 57.77 (C-4), 139.68 (C-2), 165.60 (C-3), 203.68 (C-1)
ppm. IR (KBr): ν = 2983, 2924, 2860, 1709, 1652, 1439, 1387, 1326,
˜
1294, 1254, 1225, 1186, 1107, 1071, 925, 872, 725, 690, 659, 560,
537, 478 cm–1. MS (EI, –15 °C): m/z (%) = 144 (46) [M+], 129 (1),
109 (100), 101 (1), 81 (67), 79 (28), 65 (8), 53 (23), 39 (19), 27 (13).
HRMS (EI): m/z: calcd. for C7H9ClO: 144.034192; found:
144.034146.
Diethyl (2,3-Dimethyl-4-oxocyclopent-2-enyl)phosphonate (23): A
mixture of the chloride 21 (0.78 g, 5.4 mmol) and triethyl phosphite
Eur. J. Org. Chem. 2007, 5749–5758
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5755

C. Bongards, W. Gärtner
FULL PAPER
(0.95 mL, 5.4 mmol) was heated under argon to 75–80 °C for
45 min and subsequently refluxed at 160–170 °C for 5.5 h. Purifica-
tion of the resulting solution by fractionating distillation in vacuo,
followed by column chromatography with n-hexane, ethyl acetate,
and 2-propanol (49:49:2) as eluent yielded the product 23 (0.68 g,
2.8 mmol, 51%) as a yellow, clear liquid, b.p. 86 °C (0.032–
0.035 mbar). 1H NMR (400 MHz, CDCl3): δ = 1.22 [t, 3J =
(1.4 mL), to which a small amount of molecular sieves (3 Å) was
added, was refluxed for 19 h in the dark and under argon. The
reaction mixture was decanted from the molecular sieves which was
repeatedly washed with chloroform as long as the solvent showed
colour. The combined organic phases were washed with a solution
of Na2CO3 (2 , 3ϫ100 mL), with a solution of saturated KH2PO4
(3ϫ100 mL), and with
a solution of saturated NaHCO3
7.03 Hz, 3 H, PO(OCH2CH3)2], 1.27 [t, 3J
= 7.07 Hz, 3 H, (3ϫ100 mL). After drying over Na2SO4, the solvent was evapo-
PO(OCH2CH3)2], 1.68 (dq, Jd = 4.91, Jq = 0.93 Hz, 3 H, 31-CH3), rated. Column chromatography of the remaining raw material
2.16 (d, J = 3.33 Hz, 3 H, 21CH3), 2.50–2.65 (m, 2 H, 5-CH2), 3.03– (0.49 g) with dichloromethane and ethyl acetate (49:1) as eluent
3.06 (m, 0.5 H, 1-CH), 3.09–3.12 (m, 0.5 H, 1-CH), 3.97–4.13 [m,
yielded the expected reaction product 26 (0.30 g, 0.8 mmol, 76%)
1
1
4 H, PO(OCH2CH3)2] ppm. 13C NMR (101 MHz, DEPT 135, H/ as yellow crystals, m.p. 151–152 °C. H NMR (400 MHz, CDCl3):
1
13C-COSY, CDCl3): δ = 8.29 (d, JC,H = 1.92 Hz, C-31), 16.40 [d,
δ = 1.57 [s, 9 H, CO2C(CH3)3], 1.93 (s, 3 H, 91-CH3), 2.09 (s, 3 H,
81-CH3), 2.09 (s, 3 H, 41-CH3), 2.52 (t, 3J = 8.00 Hz, 2 H, 32-CH2),
2
3JC,P = 5.49 Hz, PO(OCH2CH3)2], 16.84 (C-21), 36.44 (d, JC,P
=
=
1
2
3
3.83 Hz, C-5), 41.72 (d, JC,P = 144.99 Hz, C-1), 62.12 [d, JC,P
2.99 (t, J = 7.80 Hz, 2 H, 31-CH2), 3.65 (s, 3 H, CO2CH3), 5.88 (s,
6.89 Hz, PO(OCH2CH3)2], 62.60 [d, 2JC,P
=
6.98 Hz,
1 H, 6-CH), 9.69 (br. s, 1 H, NH) ppm. 13C NMR (101 MHz,
PO(OCH2CH3)2], 138.84 (d, 1JC,H = 9.94 Hz, C-3), 164.53 (d, 1JC,H
CDCl3): δ =
8.91 (C-91), 9.87 (C-41), 20.52 (C-81), 28.37
= 8.79 Hz, C-2), 206.37 (d, JC,H = 2.82 Hz, C-4) ppm. IR (KBr): [CO2C(CH3)3], 29.69 (C-31), 34.90 (C-32), 51.48 (CO2CH3), 81.47
1
ν = 2985, 2931, 1702, 1644, 1445, 1388, 1329, 1258, 1236, 1210, [CO2C(CH3)3], 95.81 (C-6), 122.89, 123.08, 126.40, 128.36 (C-2,-4,
˜
1164, 1027, 967, 888, 797, 731, 693, 655, 600, 532, 491 cm–1. MS
-5,-9), 123.17 (C-3), 146.86 (C-7), 147.11 (C-8), 160.11 [CO2C-
(EI, 50 °C): m/z (%) = 246 (74) [M+], 231 (1), 218 (22), 203 (1), 190 (CH ) ], 169.03 (C-10), 173.60 (CO CH ) ppm. IR (KBr): ν = 3447,
˜
3 3
2
3
(72), 173 (14), 162 (5), 136 (12), 108 (100), 92 (15), 81 (37), 65 (9), 3067, 3007, 2974, 2953, 2930, 1758, 1736, 1682, 1653, 1625, 1449,
53 (16), 41 (15), 29 (13). HRMS (ESI pos, methanol + dichloro- 1367, 1272, 1252, 1192, 1171, 1137, 1096, 1007, 946, 845, 809, 753,
methane): m/z: calcd. for C11H19NaO4P [M + Na]+: 269.091319; 712, 678, 603, 571 cm–1. UV/Vis (n-hexane): λmax (ε) = 254 (30400),
found: 269.091189.
387 (44400), 407 nm (41100). MS (EI, 130 °C): m/z (%) = 389 (19)
[M+], 333 (100), 302 (9), 289 (11), 288 (11), 273 (24), 272 (2), 260
(11), 258 (2), 256 (4), 255 (4), 242 (7), 230 (9), 227 (5), 216 (7), 214
(3), 186 (4), 144 (2), 128 (4), 57 (2). HRMS (EI): m/z: calcd. for
C21H27NO6: 389.183839; found: 389.183447.
tert-Butyl 5-{[4-Ethyl-3-methyl-5-oxofuran-2(5H)-ylidene]methyl}-3-
[2-(methoxycarbonyl)ethyl]-4-methyl-1H-pyrrole-2-carboxylate (25):
A solution of the pyrrole 24 (0.31 g, 1.1 mmol), the furanone 10
(0.13 g, 1.0 mmol), and DBU (0.36 mL, 2.4 mmol) in absolute THF
(1.4 mL), to which a small amount of molecular sieves (3 Å) was
added, was refluxed for 19 h in the dark and under argon. The
reaction mixture was decanted from the molecular sieves which was
repeatedly washed with chloroform as long as the solvent showed
colour. The combined organic phases were washed with a solution
of Na2CO3 (2 , 3ϫ100 mL), with a solution of saturated KH2PO4
tert-Butyl 5-{[4-Ethyl-3-methyl-5-oxothiophen-2(5H)-ylidene]meth-
yl}-3-[2-(methoxycarbonyl)ethyl]-4-methyl-1H-pyrrole-2-carboxylate
(27): A solution of the pyrrole 24 (0.30 g, 1.0 mmol), the thio-
phenone 14 (0.15 g, 1.1 mmol), and DBU (0.35 mL, 2.3 mmol) in
absolute THF (1.4 mL), to which a small amount of molecular
sieves (3 Å) was added, was refluxed for 19 h in the dark and under
argon. The reaction mixture was decanted from the molecular si-
eves which was repeatedly washed with chloroform, as long as the
solvent showed colour. The combined organic phases were washed
with a solution of Na2CO3 (2 , 3ϫ100 mL), with a solution of
saturated KH2PO4 (3ϫ100 mL), and with a solution of saturated
NaHCO3 (3ϫ100 mL). After drying over Na2SO4, the solvent was
evaporated. Column chromatography of the remaining crude mate-
rial (0.58 g) with dichloromethane and ethyl acetate (19:1) as eluent
yielded the expected reaction product 27 (0.21 g, 0.5 mmol, 49%)
as a yellow-orange solid, m.p. 67–68 °C. 1H NMR (400 MHz,
CDCl3): δ = 1.06 (t, 3J = 7.58 Hz, 3 H, 92-CH3), 1.56 [s, 9 H,
CO2C(CH3)3], 2.12 (s, 3 H, 81-CH3), 2.27 (s, 3 H, 41-CH3), 2.42 (q,
3J = 7.60 Hz, 2 H, 91-CH2), 2.52 (t, 3J = 7.87 Hz, 2 H, 32-CH2),
(3ϫ100 mL), and with
a solution of saturated NaHCO3
(3ϫ100 mL). After drying over Na2SO4, the solvent was evapo-
rated. Column chromatography of the remaining crude material
(0.46 g) with dichloromethane and ethyl acetate (49:1) as eluent
yielded the expected reaction product 25 (0.36 g, 0.9 mmol, 86%)
1
as yellow crystals, m.p. 134–135 °C. H NMR (400 MHz, CDCl3):
δ = 1.12 (t, 3J = 7.61 Hz, 3 H, 92-CH3), 1.57 [s, 9 H, CO2C-
(CH3)3], 2.09 (s, 3 H, 41-CH3), 2.11 (s, 3 H, 81-CH3), 2.37 (q, J =
3
7.66 Hz, 2 H, 91-CH2), 2.52 (t, J = 7.87 Hz, 2 H, 32-CH2), 2.99 (t,
3
3J = 8.00 Hz, 2 H, 31-CH2), 3.65 (s, 3 H, CO2CH3), 5.88 (s, 1 H, 6-
CH), 9.70 (br. s, 1 H, NH) ppm. 13C NMR (101 MHz, CDCl3): δ
= 9.64 (C-41), 12.77 (C-92), 17.28 (C-91), 20.51 (C-81), 28.36
[C(CH3)3], 31.20 (C-31), 34.85 (C-32), 51.47 (CO2CH3), 81.35
[C(CH3)3], 95.90 (C-6), 123.15 (C-3), 125.55, 126.45, 128.37, 128.40
(C-2,-4,-5,-9), 146.59, 146.80 (C-7,-8), 160.07 [CO2C(CH3)3],
3
2.99 (t, J = 7.89 Hz, 2 H, 31-CH2), 3.64 (s, 3 H, CO2CH3), 6.93 (s,
1 H, 6-CH), 8.98 (br. s, 1 H, NH) ppm. 13C NMR (101 MHz,
CDCl3): δ = 9.07 (C-41), 12.66 (C-91), 13.11 (C-92), 18.97 (C-81),
20.35 (C-31), 28.33 [CO2C(CH3)3], 34.64 (C-32), 51.48 (CO2CH3),
81.69 [CO2C(CH3)3], 114.31 (C-6), 124.28, 125.66, 127.87, 129.07,
131.21 (C-2,-3,-4,-5,-7), 139.59 (C-9), 153.09 (C-8), 159.82
168.96 (C-10), 173.61 (CO CH ) ppm. IR (KBr): ν = 3448, 3066,
˜
2
3
2978, 2878, 1759, 1735, 1680, 1622, 1445, 1394, 1367, 1298, 1278,
1268, 1256, 1193, 1172, 1161, 1138, 1131, 1115, 1097, 1006, 944,
848, 673, 613 cm–1. UV/Vis (n-hexane): λmax (ε) = 254 (32000), 389
(48100), 409 nm (45200). MS (EI, 130 °C): m/z (%) = 403 (18) [M+],
347 (100), 316 (7), 303 (10), 287 (20), 286 (2), 274 (9), 272 (3), 270
(3), 269 (2), 256 (5), 254 (2), 244 (7), 241 (3), 230 (5), 228 (3),
226 (2), 200 (3), 135 (3). HRMS (EI): m/z: calcd. for C22H29NO6:
403.199489; found: 403.199617.
[CO C(CH ) ], 173.44 (CO CH ), 192.32 (C-10) ppm. IR (KBr): ν
˜
2
3 3
2
3
= 3429, 2974, 2952, 2934, 2875, 1740, 1675, 1608, 1583, 1537, 1437,
1383, 1368, 1276, 1197, 1165, 1140, 1054, 985, 961, 884, 847, 816,
778, 741, 708, 649, 545, 514, 473 cm–1. UV/Vis (n-hexane): λmax (ε)
= 267 (12900), 401 (21800), 419 nm (21300). MS (EI, 120 °C): m/z
(%) = 419 (26) [M+], 363 (100), 317 (13), 303 (24), 290 (6), 244 (3),
tert-Butyl 5-{[3,4-Dimethyl-5-oxofuran-2(5H)-ylidene]methyl}-3-[2-
(methoxycarbonyl)ethyl]-4-methyl-1H-pyrrole-2-carboxylate (26): A 216 (2), 166 (1), 129 (2), 91 (1), 73 (1), 57 (3). HRMS (ESI pos,
solution of the pyrrole 24 (0.30 g, 1.0 mmol), the furanone 11
(0.11 g, 1.0 mmol), and DBU (0.35 mL, 2.3 mmol) in absolute THF
methanol + dichloromethane): m/z: calcd. for C22H29NNaO5S [M
+ Na]+: 442.166415; found: 442.16614.
5756
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5749–5758

Synthesis of Hetero Atom Modified Dipyrromethenones
tert-Butyl 5-[3,4-Dimethyl-5-oxothiophen-2(5H)-ylidenemethyl]-3-[2- (s, 1 H, 6-CH), 8.67 (br. s, 1 H, NH) ppm. 13C NMR (126 MHz,
(methoxycarbonyl)ethyl]-4-methyl-1H-pyrrole-2-carboxylate (28): A
solution of the pyrrole 24 (0.30 g, 1.0 mmol), the thiophenone 15
(0.13 g, 1.0 mmol), and DBU (0.35 mL, 2.3 mmol) in absolute THF
(1.4 mL), to which a small amount of molecular sieves (3 Å) was
added, was refluxed for 19 h in the dark and under argon. The
reaction mixture was decanted from the molecular sieves which was
repeatedly washed with chloroform as long as the solvent showed
colour. The combined organic phases were washed with a solution
of Na2CO3 (2 , 3ϫ100 mL), with a solution of saturated KH2PO4
BB, 1H/13C-COSY, CDCl3): δ = 8.69 (C-41), 11.47 (C-81), 12.75 (C-
92), 16.69 (C-91), 20.31 (C-31), 28.15 [CO2C(CH3)3], 34.62 (C-32),
38.27 (C-11), 51.25 (CO2CH3), 81.19 [CO2C(CH3)3], 109.81 (C-6),
121.95 (C-2), 122.62 (C-4), 128.46 (C-3), 129.11 (C-5), 133.48 (C-
7), 144.10 (C-9), 160.16 [CO2C(CH3)3], 163.32 (C-8), 173.29
(CO CH ), 202.68 (C-10) ppm. IR (KBr): ν = 3471, 2974, 2933,
˜
2
3
2875, 1739, 1691, 1619, 1439, 1394, 1368, 1275, 1254, 1166,
1137, 1098, 1057, 983, 962, 929, 855, 809, 777, 697, 649 cm–1.
UV/Vis (n-hexane): λmax (ε) = 253 (23500), 369 (27800), 388 nm
(19600). MS (EI, 150 °C): m/z (%) = 401 (27) [M+], 379 (2), 359
(5), 345 (100), 285 (24), 242 (5), 182 (3), 115 (1), 91 (1), 77 (1), 57
(4), 41 (2). HRMS (ESI pos, methanol + dichloromethane):
m/z: calcd. for C23H31NNaO5 [M + Na]+ 424.209440; found:
424.209631.
(3ϫ100 mL), and with
a solution of saturated NaHCO3
(3ϫ100 mL). After drying over Na2SO4, the solvent was evapo-
rated. Column chromatography of the remaining raw material
(0.62 g) with dichloromethane and ethyl acetate (19:1) as eluent
yielded the expected reaction product 28 (0.14 g, 0.3 mmol, 34%
isolated yield, 40% concerning converted pyrrole 24) as a yellow-
orange solid as well as some pyrrole 24 (50 mg, 0.17 mmol, 17%
of the starting material), m.p. 67–69 °C. 1H NMR (400 MHz,
CDCl3): δ = 1.57 [s, 9 H, CO2C(CH3)3], 1.97 (s, 3 H, 21-CH3), 2.13
tert-Butyl 5-[(2,3-Dimethyl-4-oxocyclopent-2-enylidene)methyl]-3-[2-
(methoxycarbonyl)ethyl]-4-methyl-1H-pyrrole-2-carboxylate
(30):
The coupling-reaction was performed in the dark and under argon.
At ambient temperature, a dispersion of NaH in mineral oil (0.07 g,
55–65%) was dispersed in THF (4.9 mL) and was mixed with a
solution of phosphonate 23 (0.38 g, 1.6 mmol) in THF (3.7 mL).
When the mixture was stirred at 60–70 °C for 1 h, development of
hydrogen was observed. After cooling to ambient temperature, a
solution of the pyrrole 24 (0.24 g, 0.8 mmol) and THF (4.8 mL)
was added, and the mixture was stirred for another hour. Thereby
a dark brown solution was formed which was refluxed for 21 h.
After addition of a saturated aqueous solution of NH4Cl (1.8 mL),
the resulting slurry was diluted with 60 mL of ethyl acetate and
water at a time. The phases were separated, the aqueous phase was
extracted with ethyl acetate (5ϫ60 mL), and the combined organic
phases were washed with brine (4ϫ60 mL). After drying over
Na2SO4, evaporation of the solvent yielded the crude product
(0.56 g) which was purified by HPLC with methanol and water
(5:1) as eluent. Evaporation of the methanol and freeze-drying of
the remaining aqueous dispersion resulted in the reaction product
30 (0.11 g, 0.28 mmol, 34%) as a yellow-orange solid, m.p. 111–
112 °C. 1H NMR (500 MHz, CDCl3): δ = 1.56 [s, 9 H, CO2C-
(CH3)3], 1.86 (s, 3 H, 91-CH3), 2.09 (s, 3 H, 41-CH3), 2.17 (s, 3 H,
3
(s, 3 H, 31-CH3), 2.27 (s, 3 H, 71-CH3), 2.53 (t, J = 7.89 Hz, 2 H,
82-CH2), 3.00 (t, 3J = 7.91 Hz, 2 H, 81-CH2), 3.65 (s, 3 H,
CO2CH3), 6.94 (s, 1 H, 5-CH), 8.99 (br. s, 1 H, NH) ppm.
13C NMR (101 MHz, CDCl3): δ = 9.11 (C-41), 10.89 (C-91), 13.03
(C-81), 20.37 (C-31), 28.37 [CO2C(CH3)3], 34.67 (C-32), 51.51
(CO2CH3), 81.74 [CO2C(CH3)3], 114.21 (C-6), 124.31, 125.73,
127.87, 129.11, 131.11 (C-2,-3,-4,-5,-7), 133.98 (C-9), 153.37 (C-8),
159.84 [CO2C(CH3)3], 173.48 (CO2CH3), 192.60 (C-10) ppm. IR
(KBr): ν = 3400, 2968, 2952, 2930, 1737, 1694, 1678, 1610, 1587,
˜
1537, 1438, 1384, 1367, 1274, 1255, 1162, 1138, 1056, 1010, 906,
852, 808, 776, 689, 541, 490, 473 cm–1. UV/Vis (n-hexane): λmax (ε)
= 267 (16700), 400 (29300), 418 nm (29100). MS (EI, 125 °C): m/z
(%) = 405 (28) [M+], 349 (100), 303 (11), 289 (24), 276 (6), 258 (4),
229 (4), 202 (4), 168 (2), 136 (2), 115 (1), 91 (1), 77 (1), 57 (5), 41
(3). HRMS (EI): m/z: calcd. for C21H27NO5S: 405.160996; found:
405.161075.
tert-Butyl 5-[(3-Ethyl-2-methyl-4-oxocyclopent-2-enylidene)methyl]-
3-[2-(methoxycarbonyl)ethyl]-4-methyl-1H-pyrrole-2-carboxylate
(29): The coupling-reaction was performed in the dark and under
argon. A dispersion of NaH in mineral oil (0.10 g, 55–65%) was
dispersed at ambient temperature in THF (8.0 mL) and mixed with
a solution of the phosphonate 22 (0.59 g, 2.3 mmol) in THF
(6.0 mL). When the mixture was stirred at 60–62 °C for 1 h devel-
opment of hydrogen was observed. After cooling to ambient tem-
perature, a solution of the pyrrole 24 (0.35 g, 1.2 mmol) and THF
(8.0 mL) was added, and the mixture was stirred for another hour.
Thereafter, a dark brown solution was formed which was refluxed
for 21 h. After addition of a saturated aqueous solution of NH4Cl
(2.4 mL), the resulting slurry was diluted with 90 mL of ethyl ace-
tate and 90 mL of water. The phases were separated, the aqueous
phase was extracted with ethyl acetate (5ϫ90 mL), and the com-
bined organic phases were washed with brine (4ϫ90 mL). After
drying over Na2SO4, evaporation of the solvent yielded the crude
product (0.67 g) which was purified by HPLC with methanol and
water (5:1) as eluent. Evaporation of the methanol and freeze-dry-
ing of the remaining aqueous dispersion resulted in the reaction
product 29 (0.14 g, 0.34 mmol, 29% isolated yield, 32% concerning
converted pyrrole 24) as a yellow-orange, clear, and viscous oil.
Additionally, some pyrrole 24 (37 mg, 0.12 mmol, 10% of the start-
3
81-CH3), 2.52 (t, J = 7.99 Hz, 2 H, 32-CH2), 2.99 (t, 3J = 8.01 Hz,
2 H, 31-CH2), 3.16 (s, 2 H, 11-CH2), 3.66 (s, 3 H, CO2CH3), 6.47
(s, 1 H, 6-CH), 8.67 (br. s, 1 H, NH) ppm. 13C NMR (126 MHz,
1
BB, H/13C-COSY, CDCl3): δ = 8.52 (C-91), 8.70 (C-41), 11.75 (C-
81), 20.30 (C-31), 28.16 [CO2C(CH3)3], 34.62 (C-32), 38.08 (C-11),
51.24 (CO2CH3), 81.19 [CO2C(CH3)3], 109.64 (C-6), 121.95 (C-2),
122.65 (C-4), 128.46 (C-3), 129.07 (C-5), 133.40 (C-7), 138.54 (C-
9), 160.17 [CO2C(CH3)3], 163.76 (C-8), 173.28 (CO2CH3), 202.94
(C-10) ppm. IR (KBr): ν = 3473, 2975, 2953, 2929, 1737, 1676,
˜
1624, 1595, 1439, 1393, 1368, 1331, 1275, 1256, 1165, 1138, 1091,
1056, 962, 942, 882, 848, 808, 777, 655, 545, 470, 452 cm–1. UV/
Vis (n-hexane): λmax (ε) = 252 (15500), 368 (21400), 387 nm (17700).
MS (EI, 125 °C): m/z (%) = 387 (25) [M+], 331 (100), 300 (9), 271
(24), 258 (7), 228 (5), 212 (4), 184 (4),127 (3), 91 (2), 77 (2), 57 (7),
41 (5). HRMS (ESI pos, methanol + dichloromethane): m/z: calcd.
for C22H29NNaO5 [M + Na]+ 410.193795; found: 410.193322.
X-ray Crystal Structure Analysis of 25: C22H29NO6, Mr = 403.46,
yellow opaque parallelepiped, crystal size 0.34ϫ0.26ϫ0.10 mm,
triclinic, space group P-1, a = 8.4299(3), b = 10.0423(4), c =
13.7683(6) Å, α = 74.765(3), β = 77.259(3), γ = 73.333(3)°, V =
1063.98(8) Å3, T = 100 K, Z = 2, δcalcd. = 1.259 gϫcm–3, λ =
ing material) was recovered. 1H NMR (500 MHz, CDCl3): δ = 1.03
3
(t, J = 7.59 Hz, 3 H, 92-CH3), 1.56 [s, 9 H, CO2C(CH3)3], 2.09 (s, 0.71073 Å, µ(Mo-Kα) = 0.091 mm–1, Bruker–Nonius Kappa-CCD,
3
3 H, 41-CH3), 2.17 (s, 3 H, 81-CH3), 2.33 (q, J = 7.65 Hz, 2 H, 91- 3.69ϽθϽ30.99, 14387 measured reflections, 6735 independent re-
CH2), 2.51 (t, 3J = 7.98 Hz, 2 H, 32-CH2), 2.99 (t, 3J = 8.00 Hz,
2 H, 31-CH2), 3.15 (s, 2 H, 11-CH2), 3.65 (s, 3 H, CO2CH3), 6.47
flections, structure solved by direct methods and refined by full-
matrix least-squares on F2 to R1 = 0.0492 [IϾ2σ(I)], wR2 = 0.1254,
Eur. J. Org. Chem. 2007, 5749–5758
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5757

C. Bongards, W. Gärtner
FULL PAPER
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262 parameters, S = 1.034, residual electron density +0.577/–0.650
e ϫÅ–3.
CCDC-654307 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Supporting Information (see also the footnote on the first page of
this article): Bond lenghts and angles of compound 25.
Acknowledgments
The expert assistance of Dr. Thomas Weyhermüller (Max Planck
Institute for Bioinorganic Chemistry, Mülheim an der Ruhr) in the
three-dimensional structure analysis of compound 25 is greatly ac-
knowledged. This work was financially supported by the Deutsche
Forschungsgemeinschaft (DFG) (GA377/13).
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Received: July 16, 2007
Published Online: September 28, 2007
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