Full text of DOI:10.1002/jhet.5570380208

Mar-Apr 2001 The Chemistry of the Highly Reactive 2,6-Bis(bromomethyl)-4-pyrone
365
Werner Löwe* and Stefanie A. Brätter
Institut für Pharmazie I, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany
Manuela Weber and Peter Luger
Institut für Kristallographie, Freie Universität Berlin, Takustr. 6, 14195 Berlin, Germany
Joachim Buddrus
Institut für Spektroskopie und Angewandte Spektroskopie, Bunsen-Kirchhoff-Str. 11, 44139 Dortmund, Germany
Received February 9, 2000
Dedicated to Professor F. Eiden, München, on the occasion of his seventy fifth birthday
Under basic conditions 2,6-bis(bromomethyl)-4-pyrone 8 reacts with tetraethylene glycol to yield the
unexpected macrocycle 9, which is related to the antibiotic Kjellmanianone 10. We propose that this ring
transformation proceeds via the cyclopropyl intermediate d (Scheme 2), which undergoes a ring opening
reaction comparable to the Favorskii rearrangement. Also, 8 reacts with methanol/sodium methoxide to
yield the 3(2H)-furanone derivative 11, the formation of which is suggested to proceed via the intermediate
k with a carbenium-oxonium-ion subunit (Scheme 3). The structure of the 3(2H)-furanone derivative was
confirmed by X-ray analysis.
J. Heterocyclic Chem., 38, 365 (2001).
Introduction.
Although many crown ether-related compounds with a
heterocycle such as the furan ring in 1 have been
synthesized [1], the presence of a 4-pyrone ring subunit
has been described in only one case [2]. Our initial aim
was to synthesize the polyether 2 under basic conditions,
starting with 2,6-bis(bromomethyl)-4-pyrone 8 and
tetraethylene glycol. However, the reaction took an
unexpected turn yielding 9, a macrocycle with a cyclo-
pentenone ring. To better understand this reaction, we also
studied the reaction of 8 with methanol/sodium methoxide
and isolated 11, a compound with a carbon skeleton
completely different from that of 9. In the following
sections, we will describe a method for improved synthesis
of the starting compound 8 and will discuss its reactivity
towards alkoxide ions.
Improved Synthesis of 2,6-Bis(bromomethyl)-4-pyrone (8).
The synthesis of 8 is outlined in Scheme 1. The diethyl
ester 4 is prepared using chelidonic acid 3 [3,4] as the starting
material. The ester 4 is then reduced with sodium borohydride
to yield 7 (38%) and the by-product 5 (29%). Even more by-
products are formed in the reduction of the dimethyl ester of 3

366
W. Löwe, S. A. Brätter, M. Weber, P. Luger and J. Buddrus
Vol. 38
[5]. The conversion of 3 directly into 7 by THF-BH was not
3
performed, since 3 is only partially THF-soluble at lower
temperatures. Compound 7 is then transformed into the
dibromide 8 or the tosylate 6 by standard procedures. This
method of synthesizing 8 is preferred over the Wohl-Ziegler
method for bromination of 2,6-dimethyl-4-pyrone, which has
a much lower yield (3.2%) [2].
Reaction of 8 with Tetraethylene Glycol: 4-Pyrone/-
2-Cyclopentenone Ring Transformation.
Compound 8 was reacted with tetraethylene glycol (TEG)
in the presence of base. We were unable to isolate 2 despite
the use of various solvents (t-BuOH, MeOH, acetone, MeCN,
THF, toluene) and bases (potassium tert-butoxide, potassium
hydride, potassium carbonate, cesium carbonate, sodium,
sodium hydride). Attempts to synthesize 2 using starting
compounds such as 6 or 7 combined with TEG, its bischloro
derivative [6] or TEG ditosylate under identical conditions
were also unsuccessful. By reacting compound 8 and TEG in
the presence of t-BuOH and potassium tert-butoxide under
high-dilution conditions, we unexpectedly isolated low yields
(4.5%) of the macrocycle 9. The unchanged compound 8 was
also detected by tlc and other long-chain ethers may be
formed; that for example, compounds derived from 8 and
TEG through an intermolecular version of the Williamson
synthesis.
The structure of 9 was established by nmr and the infrared
spectra as well as elemental analysis. The β-methoxy-
1
cyclopentenone subunit was identified based on the H-nmr
and C-nmr spectra, which were in excellent agreement with
those of Kjellmanianone 10 [7].
The carbon skeleton of 9 represents a higher homologue
of the antibiotic 10. Whether or not 9 has antibiotic
properties, remains to be determined.
13
Reaction of 8 with Methanol: 4-Pyrone/3-Furanone Ring
Transformation.
In addition to being reacted with TEG, 8 was also reacted
with methanol/sodium methoxide. Besides the expected
compound 12 (12% yield) compound 11, which has a 3(2H)-
furanone ring, was also formed (14% yield). The structure of
11 was deduced from the uv, infrared and nmr spectra and
confirmed by X-ray analysis. The uv spectrum displays a
broad band at λ (MeOH) = 328 nm, which is typical of a
max
Further information on the five-membered ring was
derived from the H-nmr spectrum, which displayed
signals at 2.58-2.89 corresponding to an ABCDE spin
system resulting from the cycloaliphatic ring protons and
dienone structure [10]. The ir spectrum shows bands at 1697
1
-1
-1
1
cm (C=O) and 1617 cm (C=C). The H-nmr spectrum is
characterized by six singlets. Figure 1 shows the results of
X-ray analysis together with the numbering scheme.
the adjacent CH protons.
2
We propose that 9 is formed according to the pathway
described in Scheme 2. The reaction starts with the
Michael-like addition of an alkoxide ion. The resulting
enolate a is transformed into the cyclopropanone ketal b.
Addition of the second TEG-alkoxide ion yields the
enolate of the crown type compound c. The latter is
transformed to d, which undergoes a Favorskii-like ring
opening reaction to yield e [8,9]. Compound e is
eventually transformed to the macrocycle 9. Altogether,
two nucleophilic additions, two ring closure reactions and
two ring opening reactions take place.
Figure 1. Structure of compound 11, generated with ORTEP [13].

Mar-Apr 2001
The Chemistry of the Highly Reactive 2,6-Bis(bromomethyl)-4-pyrone
367
Table 1
Atomic Coordinates (x 10 ) and Equivalent Isotropic Displacement
Table 4
4
Torsion angles (°) of Compound 11.
2.
3
Parameters (Å 10 ) for Compound 11. U (eq) is defined as
one third of the trace of the orthogonalized Uij tensor.
C (1) – O (1) – C (2) – C (4)
1.4 (3)
C (1) – O (1) – C (2) – C (3)
O (1) – C (2) – C (4) – O (5)
C (3) – C (2) – C (4) – O (5)
C (2) – C (4) – C (5) – C (6)
C (2) – C (4) – C (5) – O (8)
O (8) – C (5) – C (6) – C (7)
C (4) – C (5) – C (6) – C (7)
C (5) – C (6) – C (7)– O (7)
C (5) – C (6) – C (7) – C (8)
O (7) – C (7) – C (8) – O (9)
C (6) – C (7) – C (8) – O (9)
O (7) – C (7) – C (8) – O (8)
C (6) – C (7) – C (8) – O (8)
C (6) – C (5) – O (8) – C (8)
C (4) – C (5) – O (8) – C (8)
O (9) – C (8) – O (8) – C (5)
C (7) – C (8) – O (8) – C (5)
O (8) – C (8) – O (9) – C (10)
C (7) – C (8) – O (9) – C (10)
-179.2 (2)
178.59 (19)
-0.7 (4)
-176.6 (2)
2.6 (3)
x
y
z
U (eq)
60 (1)
56 (1)
46 (1)
62 (1)
45 (1)
43 (1)
47 (1)
48 (1)
65 (1)
48 (1)
51 (1)
57 (1)
72 (1)
C (1)
O (1)
C (2)
C (3)
C (4)
C (5)
C (6)
C (7)
O (7)
C (8)
O (8)
O (9)
C (10)
2550 (8)
3482 (4)
2888 (5)
4073 (8)
1423 (5)
609 (5)
-1011 (5)
-1391 (5)
-2782 (4)
364 (5)
4680 (2)
3545 (1)
2467 (2)
1404 (2)
2428 (2)
1352 (2)
1335 (2)
92 (2)
-363 (1)
-680 (2)
213 (1)
-1531 (1)
-2501 (3)
5735 (1)
5441 (1)
5749 (1)
5372 (1)
6304 (1)
6665 (1)
7209 (1)
7403 (1)
7850 (1)
6923 (1)
6461 (1)
6617 (1)
6295 (2)
-0.9 (3)
178.42 (19)
-177.2 (2)
2.7 (2)
57.1 (3)
-122.83 (19)
176.5 (2)
-3.4 (2)
1456 (3)
-1667 (3)
-45 (9)
-1.4 (2)
179.22 (18)
122.67 (17)
2.9 (2)
80.3 (2)
-163.9 (2)
Table 2
Bond Lengths [Å] and Angles [°] for Compound 11.
Table 5
C (1) – O (1)
O (1) – C (2)
C (2) – C (4)
C (2) – C (3)
C (4) – C (5)
C (5) – C (6)
C (5) – O (8)
C (6) – C (7)
C (7) – O (7)
C (7) – C (8)
C (8) – O (9)
C (8) – O (8)
C (9) – C (10)
1.435 (2)
1.360 (2)
1.338 (3)
1.493 (3)
1.436 (3)
1.353 (3)
1.357 (2)
1.414 (3)
1.229 (2)
1.523 (3)
1.373 (2)
1.453 (2)
1.435 (3)
C (2) – O (1) – C (1)
C (4) – C (2) – O (1)
C (4) – C (2) – C (3)
O (1) – C (2) – C (3)
C (2) – C (4) – C (5)
C (6) – C (5) – O (8)
C (6) – C (5) – C (4)
O (8) – C (5) – C (4)
C (5) – C (6) – C (7)
O (7) – C (7) – C (6)
O (7) – C (7) – C (8)
C (6) – C (7) – C (8)
O (9) – C (8) – O (8)
O (9) – C (8) – C (7)
O (8) – O (8) – C (7)
C (5) – O (8) – C (8)
C (8) – O (9) – C (10)
118.07 (16)
122.59 (17)
127.72 (19)
109.70 (18)
127.63 (18)
113.69 (17)
126.46 (18)
119.85 (17)
108.73 (18)
131.43 (19)
123.04 (17)
105.53 (16)
110.67 (17)
111.14 (16)
104.56 (14)
107.38 (14)
114.16 (19)
Crystal Data Collection and Structure
Refinement Parameters of Compound 11
3
Crystal dimensions (mm )
0.34 x 0.18 x 0.14
293
Measuring temperature (K)
Formula
M
C H O
9 12 4
184.19
Crystal system/Space group
monoclinic/P2 /n
1
a (Å)
b (Å)
c (Å)
b (°)
4.159(1)
10.812(2)
20.696(3)
94.07(1)
928.3(3)
4
1.318
392
w -2q scan
0.876
3
V (Å )
Z
-3
D (g.m )
c
F(000)
Data collection method
Linear absorption
-1
coefficient (mm )
2
2
2
Weighting scheme
1/[s (F +0.0397P) +0.1365P
2
2
with P=(F +2F )/3
1948
Table 3
Reflection measured
q Range (°)
4
Hydrogen Coordinates (x 10 ) and Isotropic Displacement Parameters
4.28 - 64.99
2.
3
(Å 10 ) for Compound 11.
Independent reflections/R
1577/0.0777
0.0330/0.0865
0.0775/0.0912
SIR-92[15]
int
R (obs.)/R (all refl.)
1
1
x
y
z
U (eq)
59 (6)
67 (7)
wR (obs.)/wR (all refl.)
2
2
H (11)
H (12)
H (13)
H (31)
H (32)
H (33)
H (4)
3100 (5)
3720 (5)
180 (6)
2530 (9)
4560 (7)
5730 (7)
620 (4)
5344 (19)
4760 (2)
4670 (2)
1120 (3)
700 (3)
1670 (3)
3174 (18)
2004 (18)
-1045 (17)
-2940 (3)
-2120 (3)
-3010 (3)
5433 (10)
6158 (12)
5776 (11)
5070 (18)
5618 (16)
5113 (16)
6482 (9)
7402 (9)
7126 (9)
6590 (16)
5984 (15)
6057 (15)
Goof (F2)
Programs used
SHELXL-93 [16]
76 (8)
136 (15)
129 (12)
112 (10)
48 (5)
44 (5)
51 (6)
114 (12)
105 (10)
114 (11)
Except for the methoxy group at C8, the molecule is
completely planar. By positioning a least squares plane through
the five-member ring atoms C5-C8 and O8, the average
deviation of the contributing atoms in the plane was found to be
0.012 Å. The C1,O1,C2,C3,C4 fragment around the double bond
C2=C4, which was confirmed by the bond length of 1.338 (3) Å,
H (6)
H (8)
H (101)
H (102)
H (103)
-1800 (5)
2310 (5)
1360 (8)
1340 (7)
-1700 (7)

368
W. Löwe, S. A. Brätter, M. Weber, P. Luger and J. Buddrus
Vol. 38
EXPERIMENTAL
is also planar. All deviations remained within 0.012 Å. When a
least squares plane is placed through all non-H atoms except O9
and C10, the average deviation from planarity is 0.04 Å. The
s-trans arrangement of the two double bonds C2=C4 and C5=C6
with respect to C4-C5 is clearly demonstrated in Figure 1 and
was confirmed by the fact that the torsion angle C2-C4-C5-C6 =
-176.6 (2)°. X-ray analysis also revealed that the methoxy group
at the double bond has a trans configuration.
Our proposal for the formation of 11 is described in
Scheme 3. Again, the reaction starts with a Michael-like
addition at the double bond. Further steps are described in
the reaction scheme. Since compound h is not stable under
basic conditions, its deprotonation leads to the enolate i,
which gives rise to k' by loss of the bromide ion. Having a
carbenium-oxonium-ion subunit k, smoothly rationalises
why 11 is formed by reaction with sodium methoxide.
General Methods.
The melting points are uncorrected. The infrared spectra were
obtained using dispersions in KBr and the H-nmr and C-nmr
spectra were recorded on a 400 MHz Bruker spectrometer.
Chemical shifts are reported in ppm downfield from tetramethyl-
silane (TMS). Electron impact mass spectra were obtained at 70
eV. The uv spectrum was recorded with a Hewlett Packard
8451A Diode Array Spectrophotometer.
Silica gel 60 (Merck, 230-400 mesh) and silica gel plates
(Merck, 60 F ) were used for flash chromatography and tlc.
The petroleum ether, used for recrystallization, had a bp of
40-70 °C. Dichloromethane was distilled from P O . Anhydrous
1
13
254
2
5
MeOH and EtOH were obtained after reflux over small amounts
of magnesium and distillation. All other reagents were obtained
from commercial suppliers and used without further purification.
Conclusion.
Diethyl 4-Oxo-4H-pyran-2,6-dicarboxylate (4).
The 4-pyrone derivative 8 is a highly reactive compound
containing five reactive centers, all of which are susceptible
to nucleophilic attack. Under basic conditions the attack at
the double bond competes with the attack at the bromine-
bearing carbon atom. The enolate ion that emerges from the
double bond attack undergoes various reactions and yields
a compound with an unexpected carbon skeleton. We
predict, that nucleophiles other than alkoxide ions (amines,
Grignard compounds, cuprates etc.) will also give rise to
compounds with unexpected structures.
Compound 4 was prepared from 3 [3]. The crude product
was purified by flash chromatography using ethyl acetate
(EtOAc) as the eluent. Recrystallization from EtOAc/n-hexane
(1:1) yielded white crystals, corresponding to compound 4.
Yield 68%, mp 63 °C, R = 0.57 (EtOAc); ir (potassium
f
-1
1
bromide): ν 1740, 1658 (C=O), 1621 cm ; H-nmr (deuterio-
chloroform): δ 1.42 (t, 6H, J = 7.1), 4.45 (q, 4H, J = 7.1), 7.15
+
(s, 2H) ppm; ms (m/z) 240 (M ).
Anal. Calcd. for C H O (240.2): C, 55.00 H, 5.04. Found:
11 12
6
C, 54.89 H, 4.94.

Mar-Apr 2001
The Chemistry of the Highly Reactive 2,6-Bis(bromomethyl)-4-pyrone
369
Ethyl 4-Hydroxy-6-hydroxymethyl-5,6-dihydro-4H-pyran-2-
carboxylate (5) and 2,6-Bis(hydroxymethyl)-4-pyrone (7).
2,5,8,11,14-Pentaoxa-bicyclo[15.2.1]-eicosa-1(19)-ene-15,18-
dione (9).
A solution of tetraethylene glycol (TEG) (2.25 g, 11.58
mmoles) and t-BuOH (20 ml) was added dropwise to a mixture of
potassium tert-butoxide (2.6 g, 23.17 mmoles) and t-BuOH
Sodium borohydride (3.2 g, 84.59 mmoles) was gradually
added to a solution of 4 (10.0 g, 41.63 mmoles) in dry MeOH
(100 ml), cooled to -20 °C in an ice/NaCl bath and the hetero-
geneous reaction mixture was stirred at -20 °C for 1 hour. After
removal of the solvent, the orange colored residue was
(40 ml) at 30 °C under N . The resulting mixture was stirred at
2
30 °C for 12 hours. The yellow solution was filtered and then
diluted with t-BuOH (60 ml). Another solution was prepared by
dissolving 8 (2.0 g, 7.14 mmoles) in t-BuOH (120 ml). Both
solutions were simultaneously added dropwise to refluxing
t-BuOH (400 ml). The reaction mixture was heated for an
additional 2 hours under reflux and filtered. The solvent was
removed in vacuo. The product was purified by flash chroma-
tography using EtOAc/MeCN (1:1) as the eluent. This yielded
the macrocycle 9 as a white solid, which was recrystallised from
EtOAc/n-hexane (1:1) to give colourless crystals. Yield: 100 mg
dissolved in H O (100 ml), then neutralized with 10% aqueous
2
H SO . Evaporation to dryness afforded an orange colored
2
4
solid product, which was dissolved in EtOH/EtOAc (9:1,
150 ml) and the reaction mixture was filtered. The solvent was
evaporated to yield an amorphous light brown solid. Flash
chromatography (eluent: EtOAc/EtOH (9:1)) of the crude
reaction product yielded the pure compounds 5 and 7.
Recrystallization from ethanol/petroleum ether (2:1) yielded 5
as white crystals: 2.4 g (29%), mp 93 °C, R = 0.12 (EtOAc); ir
f
(4.5%), mp 83 °C, R = 0.16 (EtOAc/MeCN (1:1)); ir (potassium
-1
1
f
(potassium bromide): ν 3402, 1718, 1646, 1267 cm ; H-nmr
(deuteriochloroform): δ 1.32 (t, 3H, J = 7.1), 1.82 (m, 1H),
2.15 (m, 1H), 2.71 (s, 2H), 3.80 (m, 2H), 4.21 (m, 1H), 4.29 (q,
2H, J = 7.1), 4.57 (m, 1H), 6.03 (t, 1H, J = 0,9) ppm; ms: (m/z)
-1
1
bromide): ν 3079, 2961-2860, 1729, 1686, 1596 cm ; H-nmr
(deuteriochloro-form): δ 2.59-2.89 (m, 5H), 3.59-3.86 (m, 12H),
4.13 (m, 2H), 4.26 (m, 1H), 4.34 (m, 1H), 5.33 (s, 1H) ppm;
C-nmr (deuteriochloroform): δ 33.8, 34.6, 42.0, 63.0, 68.0,
69.0, 70.4, 70.5, 70.8, 70.9, 71.0, 104.0, 171.0, 189.0, 205.0 ppm;
13
+
202 (M ).
Anal. Calcd for C H O (202.2): C, 53.46 H, 6.98. Found: C,
9
14
5
+
ms (m/z) 314 (M ).
53.61 H, 6.98.
Compound 7 was recrystallized from EtOAc/n-hexane (5:1) to
Anal. Calcd for C H O (314.3): C, 57.32 H, 7.05. Found: C,
15 22
7
57.25 H, 7.03.
yield colorless needles: 2.5 g (38%), mp 107 °C, R = 0.02
f
-1
E-2-Methoxy-5-(2-methoxy-1-propenyl)-3(2H)-furanone (11)
and 2,6-Bis(methoxy-methyl)-4-pyrone (12).
(EtOAc); ir (potassium bromide): ν 3345-3229, 1666, 1603 cm ;
H-nmr (DMSO-d ): δ 4.36 (d, 4H, J = 5.9), 5.72 (t, 2H, J = 5.9),
1
6
+
6.24 (s, 2H) ppm; ms (m/z) 156 (M ).
Sodium methoxide (400 mg, 7.4 mmoles) was gradually added
to a solution of 8 (1.0 g, 3.57 mmoles) and dry MeOH (50 ml).
The reaction mixture was stirred at room temperature for 1 hour,
and DME (1 ml) was subsequently added. The mixture was
warmed to 60 °C and stirred for an additional 12 hours before the
solid was filtered off. Evaporation of the solvent yielded a deep
brown oil, which was purified by flash chromatography (EtOAc
as eluent) to yield compound 11 as yellow crystals: 90 mg (14%),
Anal. Calcd for C H O (156.1): C, 53.85 H, 5.16. Found: C,
7
8 4
53.66 H, 5.08.
2,6-Bis(tosyloxymethyl)-4-pyrone (6).
Triethylamine (1.4 ml, 10.24 mmoles) was added to a solution
of the compound 7 (800 mg, 5.12 mmoles) and 4-(dimethyl-
amino)pyridine (62.6 mg, 0.512 mmoles) in dry CH Cl (100 ml)
2
2
at 0 °C, followed by tosyl chloride (1.95 g, 10.24 mmoles). The
mixture was stirred at 0 °C for 2 hours, then treated with 5%
aqueous HCl (3 x 50 ml). The organic layer was washed with
H O (50 ml), dried over Na SO and concentrated. Flash
mp 93 °C, R = 0.4 (EtOAc); uv (methanol) λ
328 nm (br); ir
f
max
1
-1
(potassium bromide): ν 1697, 1616 cm ; H-nmr (deuterio-
chloroform): δ 2.29 (s, 3H), 3.58 (s, 3H), 3.74 (s, 3H), 5.22 (s,
+
2
2
4
1H), 5.34 (s, 1H), 5.37 (s, 1H) ppm; ms (m/z) 184 (M ).
chromatography (eluent: EtOAc) yielded compound 6 as pure
colorless needles: 2.2 g (95%), mp 96 °C, R = 0.4 (EtOAc); ir
Anal. Calcd for C H O (184.2): C, 58.69 H, 6.57. Found: C,
9
12 4
f
58.68 H, 6.37.
Compound 12 was obtained as a yellow oil in 12% yield: R =
-1
1
(potassium bromide): ν 1668, 1364, 1174 cm ; H-nmr
f
(DMSO-d ): δ 2.40 (s, 6H), 4.96 (s, 4H), 6.28 (s, 2H), 7.46 (anal.
-1
1
6
0.15 (EtOAc); ir (film) ν 1670, 1626 cm ; H-nmr (deuterio-
chloroform) δ 3.45 (s, 6H), 4.26 (s, 4H), 6.38 (s, 2H) ppm; ms
as AB, ca. d, 4H, J = 8.2), 7.80 (anal. as AB, ca. d, 4H, J = 8.2)
+
ppm; ms (m/z) 464 (M ).
+
(m/z) 184 (M ).
Anal. Calcd for C H O S (464.5): C, 54.30 H, 4.34. Found:
21 20
8 2
Anal. Calcd for C H O (184.2): C, 58.69 H, 6.57. Found: C,
9
12 4
C, 54.18 H, 4.34.
57.97 H, 6.76.
2,6-Bis(bromomethyl)-4-pyrone (8).
Single Crystal X-ray Analysis of Compound 11.
Compound 7 (4.0 g, 19.78 mmoles) was added to a mixture
Crystals of 11 were grown from EtOAc/n-hexane; only rather
small crystals suited for X-ray analysis could be obtained. Precise
lattice parameters (from 119 high-order reflections with 30 ≤ 2θ
≤ 70) and three-dimensional intensity data were measured on a
STOE diffractometer using Ni-filtered Cu Kα-radiation and the
ω -2θ scan technique. No significant intensity variations were
observed from monitoring three check reflection. Phase determi-
nation was made using direct methods (program SIR92 [11]), and
the data were refined using the least squares program of the
SHELXL program system [12]. All hydrogen atoms were located
of concentrated H SO (5 ml) and 48% aqueous HBr (45 ml)
2
4
at 0 °C. The mixture was warmed to room temperature and
stirred for 12 hours at 60 °C. The reaction mixture was poured
onto ice-cold water (150 ml), neutralized with saturated
Na SO solution and extracted with EtOAc (3 x 100 ml). The
2
3
combined organic layers were dried over Na SO , filtered and
2
4
concentrated. Flash chromatography (eluent: EtOAc)
produced 8 as pale yellow crystals: 4.2 g (58%), mp 91 °C.
(yield 3.2%, mp 91 °C) [2].

370
W. Löwe, S. A. Brätter, M. Weber, P. Luger and J. Buddrus
Vol. 38
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from difference syntheses. Further information about crystal data
and structure refinement are summarized in Table 5. Figure 1
shows the structure of compound 11, which was generated with
ORTEP [13].
REFERENCES AND NOTES
[1] G. R. Newkome, J. D. Sauer, J. M. Roper and D. C. Hager,
Chem. Rev., 77, 513 (1977).
[2] W. Löwe, S. A. Brätter, C. Dietrich, M. Weber and P. Luger, J.
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(1), 133 (1965).
[13] C. K. Johnson, ORTEP II; Report ORNL-5138; Oak Ridge
National Laboratory, Tennessee, USA (1976).
[4] R. F. Toomey and R. Riegel, J. Org. Chem., 17, 1492 (1952).