Concave pyridines for selective acylations of polyols

Article abstract of DOI:10.1002/(SICI)1099-0690(199806)1998:6<1077::AID-EJOC1077>3.0.CO;2-6

Selectivity enhancements in the base-catalyzed acylation of polyols (1,2- or 1,3-alkanediol, partially protected glucoside) have been found with (bi)macrocyclic pyridines 2 and 9 as catalysts. The different selectivities obtained for concave pyridines of varying ring sizes (1 vs. 2) are probably caused by their different geometries as a number of X-ray analyses (1a, 1b, 2a, 2b, 2e, 9) indicate. The methyl glucoside 7 can selectively be acylated in 2-position.

Full text of DOI:10.1002/(SICI)1099-0690(199806)1998:6<1077::AID-EJOC1077>3.0.CO;2-6

FULL PAPER
Concave Reagents, 26[᭛]
Concave Pyridines for Selective Acylations of Polyols
a
a
b
a
a
c
Ulrich Lüning* , Sönke Petersen , Wolfgang Schyja , Wolfgang Hacker , Torsten Marquardt , Kerstin Wagner
c
and Michael Bolte
Institut für Organische Chemiea,
Olshausenstraße 40, D-24098 Kiel, Germany,
Fax: (internat.) ϩ49-431-880-1558
E-mail: luening@oc.uni-kiel.de
Institut für Organische Chemie und Biochemieb,
Albertstraße 21, D-79104 Freiburg i. Br., Germany
Institut für Organische Chemie, Johann Wolfgang Goethe-Universitätc,
Marie-Curie-Straße 11, D-60439 Frankfurt am Main, Germany
Received December 1, 1997
Keywords: Carbohydrates / Catalysis / General base / Macrocycles / Molecular recognition / Hydrogen bond
Selectivity enhancements in the base-catalyzed acylation of
polyols (1,2- or 1,3-alkanediol, partially protected glucoside)
have been found with (bi)macrocyclic pyridines 2 and 9 as
ridines of varying ring sizes (1 vs. 2) are probably caused by
their different geometries as a number of X-ray analyses (1a,
1b, 2a, 2b, 2e, 9) indicate. The methyl glucoside 7 can selecti-
catalysts. The different selectivities obtained for concave py- vely be acylated in 2-position.
Two major goals of synthetic chemistry are the develop-
ment of new reactions and the optimization of the yields.
In organic chemistry most unsatisfying yields are caused by
side reactions, rather than by uncomplete turnover due to
the formation of equilibria. The challenge is therefore to
avoid side reactions and thus many selective reagents have
been developed. But it is still difficult to distinguish very
similar functional groups in intramolecular competitions,
e. g. to acylate one OH group in carbohydrates selectively,
especially when secondary OH groups shall be dis-
tinguished from one another.
By using catalysts like 2 in reaction mixtures containing
primary and secondary hydroxyl groups, the primary al-
Promising selectivities in the preferred acylation of pri-
mary alcohols in the presence of secondary ones have been
found when the OH groups have been functionalized by
reaction with a ketene in the presence of a pyridine cata-
[
1][2]
lyst.
In principle, two mechanisms are conceivable for a
pyridine catalyzed addition of alcohols to ketenes: a nucleo-
philic attack of the pyridine on the ketene forming a beta-
[
3]
ine, and the formation of a hydrogen bond between the
alcohol and the pyridine nitrogen atom which activates the
[
4]
alcohol.
In the case of concave pyridines, the latter
mechanism, the increase of the nucleophilicity of the oxy-
gen atom of the alcohol is responsible[ for the catalysis
because the 2,6-disubstitution of the pyridine does not al-
low the nucleophilic attack of the betaine pathway. A hy-
drogen bond to an alcohol, however, can be formed. In this
case, the substitution pattern of the pyridine determines its
reactivity and selectivity.
2]
[
᭛]
Part 25: M. Gelbert, U. Lüning, Supramol. Chem., in press.
Eur. J. Org. Chem. 1998, 1077Ϫ1084

WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1434Ϫ193X/98/0606Ϫ1077 $ 17.50ϩ.50/0
1077

U. Lüning, S. Petersen, W. Schyja, W. Hacker, T. Marquardt, K. Wagner, M. Bolte
FULL PAPER
cohols have been acylated in selectivities exceeding 12:1.[1]
These selectivities have been found for intermolecular
(
EtOH/iPrOH) and intramolecular competition (1,2-pro-
[
1]
panediol, 3). In the present work we have extended the
acylation reaction to 1,3-butanediol (5) and to the glucose
derivative 7. In 7, the two OH groups to be differentiated
are extremely similar, they are both secondary and equa-
torial!
Selectivity Measurements
As described in the literature or analogously (see Scheme
[
5][6]
1
and Experimental), the catalysts 1 and 2
and di- of the chloropyridine derivative 10. Total reduction to the
[
7]
phenylketene have been synthesized. To synthesize 1c bisalcohol 11 and selective oxidation with SeO afforded the
2
and 2c, first an ethoxy group was introduced in 4-position dialdehyde 12 which was cyclized with a diamine 13 or 14
Scheme 1
1078
Eur. J. Org. Chem. 1998, 1077Ϫ1084

Concave Reagents, 26
FULL PAPER
Table 1. Selectivities of the base-catalyzed acylation of different
hydroxyl groups with diphenylketene in four sets of experiments:
Intermolecular competition: EtOH/iPrOH, intramolecular compe-
In addition to 1 and 2, the monomacrocyclic catalyst 9
was investigated, which contains a dioxaoctane chain be-
tween the amide nitrogen atoms as the smaller bimacrocycle
tition: 3, 5 and 7[
a]
1
. But in 9 there is no second macrocycle. This results in
Alcohol(s)
R
2
9
1
increased selectivities as shown in Table 1.
To elucidate the geometry of the catalysts X-ray analyses
were carried out on single crystals of 1a, 1b, 2a, 2b, 2e and
EtOH/iPrOH[b][8]
a H
7.9
10.0
10.5
3.5
4.1
4.0
b OMe
c OEt
12.8
9
(Figures 1Ϫ3), and the conformer distribution was inves-
[1]
d NEt
2
12
tigated in CDCl solution. All catalysts 1 and 2 contain two
3
[
c][9]
dendrimer A
11.6
11.4
9.5
amide groups with hindered rotation along the COϪNH
axis.[ Therefore, ZZ, ZE and EE conformers exist (Table
2). In the monomacrocyclic pyridine 9, the barrier to ro-
tation is smaller. In the NMR spectra, amide conformers
were only found below room temperature.
[d]
dendrimer B
5]
[e][11]
soluble polymer
insoluble polymer[
f]
7.4
Ǟ 4a/4b[g]
3
a H
10.3
13
13.2
15.2
16.2
10.6
10.8
4.0
4.5
5.0
b OMe
c OEt
24
Table 2. Conformer distribution of concave pyridines due to E- and
Z-amide conformations
d NEt
2
[e]
soluble polymer
[f]
insoluble polymer
insoluble polymer[
h]
ZZ
ZE
EE
5
7
Ǟ 6a/6b
b OMe
23
21
4.2
3
[5]
1
a
63
54
34
75
68
68
71
66
66
61
62
25
28
46
12
18
20
<5
5
[5]
Ǟ 8a/8b[i]
[j]
1b
1c
2a
2b
2c
a H
ϱ
[
[
j]
j]
b OMe
c OEt
ϱ
ϱ
4.8
[5]
[5]
ഠ23
[e]
27
27
23
28
28
33
33
soluble polymer
>50
insoluble polymer[ >30
f]
5
[6]
2
d
e
6
[10]
2
6
[
a]
[10]
All experiments were repeated several times. When in doubt, the
2f
6
[
b]
[10]
[10]
smaller selectivities are always listed. Ϫ The reaction conditions dendrimer A
6
[1]
were chosen as in ref. . A mixture of EtOH, iPrOH and tBuOH
dendrimer B
5
[c]
was used, the tert-butyl ester was not detected. Ϫ Dendrimer with
[
9][10]
four 2e units bound as ethers, molecular weight: 2557, ref.
. Ϫ
[
d]
Dendrimer with six 2e units bound as ethers, molecular weight:
The NMR data and the X-ray structures show that the
small bimacrocycles 1 differ from the large ones 2: While
both macrocyclic classes 1 and 2 crystallize as ZZ conform-
[
9][10]
[e]
3
863, ref.
. Ϫ Soluble polymer from poly(vinylbenzyl chlo-
ride) and 2e, containing 60 weight% of 2f. Remaining chlorine
[11]
[f]
atoms had been substituted by NaOMe.
Ϫ Insoluble polymer
from a Merrifield resin (3.9 mmol Cl/g) and 2e, containing 20 ers, the conformer distribution in solution shows a higher
weight% of 2f. Remaining chlorine atoms had been substituted by
[
11]
[g]
tendency for 1 to build E-amide groups. In Figure 1 the X-
NaOMe.
Batch reaction. Ϫ Reaction conditions were chosen
[
1]
[h]
as in ref. . Ϫ An HPLC column was packed with the insoluble ray structures for 1 and 2 are compared. As observed in the
[
f]
polymer , and the reaction mixture was slowly pressed through
selectivities, a 4-substitution of the pyridine also had only
a small influence on the overall structures. These are pri-
marily determined by the length of the polyether chains.
The polyether and the polymethylene chains of 2a, 2b and
2e form a relatively flat macrocycle over which the pyridine
[
11]
[i]
[j]
the column.
be detected.
Ϫ 8c could never be detected. Ϫ Only 8a could
in the presence of a template metal ion Mg2ϩ or Ca2ϩ
.
Obeying the high dilution principle a second cyclization ring is oriented almost perpendicular (Figure 1b). In this
with decanedicarbonyl dichloride gave the products 1c and conformation a coordination of a substrate molecule is eas-
2
c.
ily possible by the formation of a hydrogen bond. In the
9
was synthesized by reaction of pivaloyl chloride with acylation experiments this hydrogen bond will activate the
[5]
the macrocyclic diamine
precursor. Reaction of di- alcohol molecule. In the X-ray structure of 2e, such a hydro-
phenylketene with the diols 3, 5 and 7 afforded mixtures of gen bond was formed between the acidic hydrogen atom
the products 4a/4b, 6a/6b and 8aϪ8c. The selectivities were of a chloroform molecule and the pyridine nitrogen atom
determined by GC (4a/4b and 6a/6b as trimethylsilyl ethers) (Figure 2).
1
or by H-NMR (8aϪ8c). The selectivities found for various
catalysts 1, 2 and 9 are compared in Table 1.
In contrast to 2a, 2b and 2e, the smaller bimacrocycles 1
adopt a different geometry. The macrocycle formed by the
For each acylation reaction of Table 1, drastically larger polyether and the polymethylene chains is not flat resulting
selectivities were found with the larger concave pyridines 2 in a stronger shielding of the pyridine nitrogen atom (Fig-
in comparison to the smaller bimacrocycles 1. In most ure 1a). The hydrogen bond discussed above cannot be
cases, substitution of the pyridine unit in 4-position had formed easily resulting in a lower reactivity of these cata-
only small influences on the selectivities, as did a fixation lysts.[ In fact the reactivity of 1a is close to the catalytic
2]
[2]
of the concave pyridines 2 to polymers or dendrimers. The power of an amide. Therefore the amide groups contrib-
reduced selectivities of 2a in comparison to 2bϪd reflect its ute to the catalysis and cause the smaller selectivities.
smaller basicity which causes a lower reactivity and allows
the less selective uncatalyzed reaction to occur partially.
The monomacrocycle 9 possesses the short dioxaoctane
chain of the small bimacrocycles 1 but shows selectivities
Eur. J. Org. Chem. 1998, 1077Ϫ1084
1079

U. Lüning, S. Petersen, W. Schyja, W. Hacker, T. Marquardt, K. Wagner, M. Bolte
FULL PAPER
Figure 1a. Superimposed X-ray structures of 1a (solid bonds) and 1b (open bonds). Atoms of the pyridine rings were fitted.
Figure 1b. Superimposed X-ray structures of 2a (dotted lines), 2b (full lines) and 2e (dashed lines). The atoms of the pyridine rings were
fitted.
Figure 2. In the crystal, 2e forms a hydrogen bond between its pyridine nitrogen atom and the acidic hydrogen atom of a chloroform
molecule (dashed line). The hydroxyl group forms an intermolecular hydrogen bond to one of the carbonyl oxygen atoms.
close to those of the large bimacrocycles 2. In the NMR to the catalyst and one complex where the 3-OH group is
spectra only one conformer is observed, and in the crystal, bound. To form the acylated products these complexes must
9
exists as a ZE conformer (Figure 3). Thus the confor- react with the ketene. The rate of formation of a specific
mation of 9 is different from 1 and 2 but in contrast to 1 product (e. g. 8a or 8b) is then determined by the rate with
where the pyridine nitrogen atom hardly can form the hy- which the complex can be attacked by the ketene. For a
drogen bond required for the catalysis, one bridge is missing selective catalyst (2 or 9) these rates differ strongly for dif-
in 9. In addition, the monomacrocycle is bent allowing the ferent OH groups which means that the accessibility of the
pyridine nitrogen atom to form the hydrogen bond to the oxygen atom of each alcohol in each complex is different
alcohol(s).
depending on the chain(s) of the pyridine catalysts. Accord-
For the reactive catalysts, the first step of the reaction is ing to the selectivities listed in Table 1 the shielding of the
probably the formation of complexes between the different oxygen atom in 3-position of the carbohydrate 7 by the hy-
OH groups in the substrates and the catalyst, e. g. one com- drogen bonded catalyst must therefore be much larger than
plex where the 2-OH group of the carbohydrate 7 is bound the shielding of the oxygen atom in 2-position.
1080
Eur. J. Org. Chem. 1998, 1077Ϫ1084

Concave Reagents, 26
FULL PAPER
Figure 3. Superimposed X-ray structures of the bimacrocycle 1b (open bonds), and the monomacrocycle 9 (solid bonds) both containing
a dioxaoctane chain. Atoms of the pyridine rings were fitted. In contrast to the bimacrocycles 1, the nitrogen atom of 9 is less shielded
allowing catalysis by hydrogen bond formation to a hydroxyl group.
These assumptions are supported by experiments in solution. The slightly brown solution was heated at reflux for 2 h
and was then extracted continuously for 20 h with chloroform. The
which the size of the ketene was varied (e. g. diphenylketene,
[13]
solvents were evaporated in vacuo yielding 7.0 g (88%) of a slightly
bis(2,4,6-trimethylphenyl)ketene).
When the sterical de-
o
1
brown solid, m. p. 115Ϫ116 C. Ϫ H-NMR (200 MHz,
]DMSO): δ ϭ 1.34 (t, 6.8 Hz, 3 H), 4.11 (q, 6.8 Hz, 2 H), 4.45
d, 5.9 Hz, 4 H), 5.39 (t, 5.9 Hz, 2 H, exchangeable with D O),
.83 (s, 2 H). Ϫ IR (KBr): ν˜ ϭ 3340 cm (br., OϪH), 1604
mand of the ketene was increased the overall rate dropped
drastically and the selectivity vanished.
This leads to the conclusion that for an optimal selec-
tivity the catalyst must be optimized in such a way that only
one of the two possible reaction pathways is slowed down
[D
6
(
6
2
Ϫ1
ϩ
(
arom.), 1577. Ϫ MS (EI, 70 eV); m/z (%): 183 (50) [M ], 182 (100),
1
64 (14), 154 (22), 139 (10), 138 (20), 137 (34), 136 (40), 125 (18).
ϩ
by the concave shielding. If the shielding is not sufficient Ϫ MS (CI, isobutane); m/z (%): 185 (10), 184 (100) [M ϩ H], 139
the selectivity will only be small, but if the shielding is ex- (17) [M ϩ HϪOCH CH ]. Ϫ C H NO (183.1): calcd. C 59.00,
ϩ
2
3
9
13
3
treme both reactions pathways are hindered and if products H 7.15, N 7.65, found C 58.56, H 7.05, N 7.52.
are formed at all the selectivity will be determined by other
4
-Ethoxypyridine-2,6-dicarbaldehyde (12): To a suspension of
factors, for instance by a non-catalyzed background reac-
tion.
4
2
.20 g (38.2 mmol) of SeO in 150 ml of 1,4-dioxane, 7.00 g (38.2
mmol) of 11 was added. The reaction mixture was slowly heated
The results of Table 1 demonstrate that concave reagents to 70 C. Then the mixture turned dark red and elemental selenium
are a powerful tool for selective acylation of very similar precipitated. Stirring was continued at 90 C until no further reac-
o
o
hydroxyl groups. Future work will concentrate on the devel- tion was detected by TLC (reaction time 5 to 10 h). Towards the
2
end of the reaction two times 250 mg of SeO were added. Precipi-
opment of tailored concave bases for the selective acylation
of other carbohydrates.
tated selenium was removed by filtration of the hot reaction mix-
ture through several layers of sand and MgSO . The filter pad was
4
This work is supported by the Deutsche Forschungsgemeinschaft
washed intensively with hot 1,4-dioxane. After evaporation of the
solvents in vacuo, the yellow residue was purified by chromatogra-
(Lu 378/12Ϫ1) and the Fonds der Chemischen Industrie. W. S. is
grateful for a Landes-Graduierten-Stipendium des Landes Baden-
Württemberg.
phy (silica gel, 100 g, diameter 4 cm, ethyl acetate/dichloromethane,
o
3
:1) yielding 5.4 g (78%) of a slightly yellow solid, m. p. 90Ϫ92 C.
1
Ϫ H-NMR (200 MHz, CDCl
7
3
): δ ϭ 1.50 (t, 7.0 Hz, 3 H), 4.22 (q,
.0 Hz, 2 H), 7.63 (s, 2 H), 10.11 (s, 2 H). Ϫ C-NMR (50 MHz,
Experimental Section
General Remarks: See ref.[1] Radial chromatography was carried
out with chromatotron from Harrison Research Co. (silica gel lay-
ers with a thickness of 2 mm were used).
13
CDCl ): δ ϭ 14.2 (q), 64.9 (t), 111.3 (d), 154.7 (s), 166.9 (s), 192.3
3
Ϫ1
(
(
d). Ϫ IR (KBr): ν˜ ϭ 3084 cm
(arom.), 1710 (CϭO), 1595
arom.), 1556 (arom.). Ϫ MS (EI, 70 eV); m/z (%): 180 (9), 179 (70)
ϩ
ϩ
[M ], 151 (100) [M ϪCO], 123 (35), 95 (47). Ϫ MS (CI, isobut-
4-Ethoxy-2,6-bis(hydroxymethyl)pyridine (11): 1.13
g
(50.0
ϩ
ane); m/z (%): 181 (10), 180 (100) [M ϩ H]. Ϫ HR-MS: C
calcd. 179.0582 found 179.0581; C
found 180.0616. Ϫ C NO
9
H
9
NO
calcd. 180.0616
(179.1): calcd. C 60.33, H 5.06, N
.82, found C 60.16, H 5.16, N 7.62.
3
mmol) of sodium was dissolved in 200 ml of dry ethanol and 10.0 g
13
8 9 3
CH NO
12]
(
43.6 mmol) of dimethyl 4-chloro-2,6-pyridinedicarboxylate (10)[
9
H
9
3
was added in portions. The reaction mixture turned yellow and
7
turbid. After 6 h at reflux temperature, the mixture was cooled to
o
0
C and 10.0 g (260 mmol) of sodium borohydrate was added in
Syntheses of Monomacrocyclic Pyridinediamines. Ϫ General Pro-
cedure: One equivalent of 4-ethoxypyridine-2,6-dicarbaldehyde (12)
at room temperature for 1 h and then was refluxed for additional and one equivalent of the template salt MCl were dissolved in 150
portions. After a strong development of gas, the mixture was stirred
2
1
5 h. After cooling, 100 ml of acetone was added and the mixture
ml of dry methanole. Under nitrogen, one equivalent of the diamin
13 or 14, dissolved in 30 ml of dry methanole, was added within
30 min. The mixture was stirred for 1 h at room temperature and
was refluxed for 2 h. The solvents were evaporated in vacuo and
the brown residue was mixed with 120 ml of saturated Na CO
2 3
Eur. J. Org. Chem. 1998, 1077Ϫ1084
1081

U. Lüning, S. Petersen, W. Schyja, W. Hacker, T. Marquardt, K. Wagner, M. Bolte
FULL PAPER
o
.
heated at reflux for 2.5 h. After cooling to 0 C, sodium borohyd-
C
27
H
43
N
3
O
5
2
0.5 H O (498.3): calcd. C 65.03, H 8.89, N 8.43,
ride was added. The mixture was stirred for 15 h at room tempera- found C 65.54, H 8.73, N 8.49.
ture, 50 ml of water was added, and stirring was continued for
2
9-Ethoxy-17,20,23-trioxa-1,14,33-triazatricyclo[12.11.7.127,31]-
additional 6 h. The mixture was concentrated to 100 ml. Precipitat-
ing borates formed a strong turbidity. After filtration, the solution
was extracted four times with 100 ml of dichloromethane. The com-
tritriaconta-27(33),28,30-trien-2,13-dione (2c): Starting materials:
2
.78 g (8.2 mmol) of 19-ethoxy-6,9,12-trioxa-3,15,21-triazabicy-
clo[15.3.1]heneicosa-1(20),17(21),18-triene (16), 2.19 g (8.2 mmol)
of decanedicarbonyl dichloride, 4.97 g (49.2 mmol) of NEt . Yield:
.00 g (46%), m. p. 122Ϫ124 C. Ϫ H-NMR (500 MHz, CDCl ):
δ ϭ 0.9Ϫ1.8 (m, ca. 23 H), 2.1Ϫ2.4 (m, ca. 4 H), 3.2Ϫ4.3 (m, ca.
4 H), 4.6Ϫ5.4 (m, ca. 4 H), 6.45 (d, 2.2 Hz, 0.27 H, Py-HZE), 6.54
s, 1.36 H, Py-CHZZ), 6.66 (d, 2.2 Hz, 0.27 H, Py-HZE), 6.93 (s, 0.1
4
bined organic layer was sucked through a MgSO pad, the solvents
3
were evaporated and the residue was dried in vacuo.
o
1
2
3
1
6-Ethoxy-6,9-dioxa-3,12,18-triazabicyclo[12.3.1]octadeca-
(17),14(18),15-triene (15): Starting materials: 0.85 g (4.7 mmol)
of 4-ethoxypyridine-2,6-dicarbaldehyde (12), 0.70 g (4.7 mmol) of
,8-diamino-3,6-dioxaoctane (13), 1.00 g (4.7 mmol) of MgCl ·6
O, 1.90 g (29.1 mmol) of NaBH . Yield: 1.27 g (92%), yellow
): δ ϭ 1.41 (t, 7.1 Hz, 3 H), 2.82
, 4 H), 3.70 (t, 4.9 Hz, 4 H), 3.5Ϫ4.0 (br.
s, ca. 2 H, exchangeable with D O), 3.84 (m , 4 H), 4.05 (q, 7.1 Hz,
H), 6.54 (s, 2 H). Ϫ IR (KBr): ν˜ ϭ 3300 cm (br., NH), 1600
1
1
(
1
2
˜
Ϫ1
H, Py-HEE). Ϫ IR (KBr): ν ϭ 1652 cm (CϭO), 1631, 1600
H
2
4
ϩ
(
5
arom.), 1575 (arom.). Ϫ MS (EI, 70 eV); m/z (%): 533 (100) [M ],
05 (23), 503 (37), 444 (37), 428 (25), 415 (38), 151 (71). Ϫ
(533.3): calcd. C 65.26, H 8.88, N 7.87, found C 64.98,
1
oil. Ϫ H-NMR (200 MHz, CDCl
t, 4.9 Hz, 4 H), 3.65 (m
3
(
c
29 47 3 6
C H N O
2
c
H 8.81, N 7.63.
Ϫ1
2
ϩ
3,12-Bis(2,2-dimethyl-propionyl)-16-methoxy-6,9-dioxa-3,12,18-
triazabicyclo[12.3.1]octadeca-1(17),14(18),15-triene (9): 1.25 g
(4.5 mmol) of 16-methoxy-6,9-dioxa-3,12,18-triazabicyclo-
12.3.1]octadeca-1(17),14(18),15-triene and 2.70 g (26.7 mmol) of
NEt were dissolved in 100 ml of dry dichloromethane. 1.21 g (9.8
mmol) of pivaloyl chloride in 25 ml of dry dichloromethane was
slowly added during 1 h while stirring. After 15 h of stirring at
room temperature the solution was concentrated to 50 ml and ex-
tracted with 15 ml of 2  NaOH. The aqueous layer was extracted
three times with 100 ml of dry dichloromethane. The organic layers
(
2
arom.), 1571 (arom.). Ϫ MS (EI, 70 eV); m/z (%): 295 (30) [M ],
33 (26), 220 (25), 192 (57), 178 (100), 151 (53). Ϫ MS (CI, iso-
ϩ
ϩ
butane); m/z (%): 296 (100) [M ϩ H], 295 (13) [M ], 294 (12),
[5]
[
2
82 (16), 192 (13), 178 (12).
9-Ethoxy-6,9,12-trioxa-3,15,21-triazabicyclo[15.3.1]heneicosa-
(20),17(21),18-triene (16): Starting materials: 1.50 g (8.4 mmol)
3
1
1
of 4-ethoxypyridine-2,6-dicarbaldehyde (12), 1.60 g (8.4 mmol) of
,11-diamino-3,6,9-trioxaundecane (14), 0.93 g (8.4 mmol) of
CaCl , 2.10 g (55.5 mmol) of NaBH . Yield: 2.78 g (98%), yellow
): δ ϭ 1.41 (t, 6.8 Hz, 3 H), 2.85
, 12 H), 3.5Ϫ4.0 (br. s, ca. 2 H, exchange-
, 4 H), 4.06 (q, 6.8 Hz, 2 H), 6.59 (s, 2 H).
1
2
4
1
oil. Ϫ H-NMR (200 MHz, CDCl
t, 5.7 Hz, 4 H), 3.66 (m
able with D O), 3.80 (m
Ϫ IR (KBr): ν˜ ϭ 3380 cm (br., NH), 1599 (arom.), 1571 (arom.).
Ϫ MS (EI, 70 eV); m/z (%): 339 (25) [M ], 281 (11), 279 (10), 233
3
4
were combined, dried with MgSO , and the solvent was evapo-
(
c
rated. The remaining oil was purified by chromatography (silica
gel, 100 g, diameter 4 cm, dichloromethane/ethanol, 10:1; Chroma-
totron, dichloromethane) yielding 1.21 g (61%) of 9 as a slightly
yellow solid, m. p.: 153Ϫ154 C. Ϫ H-NMR (300 MHz, CDCl
δ ϭ 1.35 (s, 18 H), 3.47 (br. s, 4 H), 3.63 (br. s, 8 H), 3.80 (s, 3 H),
.78 (br. s, 4 H), 6.72 (s, 2 H). Ϫ H NMR (200 MHz, CDCl
eq. of picric acid): δ ϭ 1.35 (s, 18 H), 3.30 (s, 4 H), 3.35 (t, 5.0 Hz,
H), 3.88 (t, 5.0 Hz, 4 H), 4.07 (s, 3 H), 4.89 (s, 4 H), 7.10 (s, 2
H), 9.10 (br. s, ca. 8.2 H, picric acid). Ϫ IR (KBr): ν˜ ϭ 3440 cm
618 (CϭO), 1597 (arom.), 1570 (arom.). Ϫ MS (EI, 70 eV); m/z
%): 450 (5), 449 (20) [M ], 393 (18), 392 (77) [M Ϫ C
23), 364 (100) [M Ϫ COC(CH
37 (42). Ϫ MS (CI, isobutane); m/z (%): 451 (28), 450 (100) [M
ϩ H], 392 (3) [M Ϫ C
MS;
24
2313CH39
2
c
Ϫ1
ϩ
o
1
3
):
(
47), 222 (23), 220 (22), 206 (25), 192 (100), 178 (71), 166 (45). Ϫ
ϩ
MS (CI, isobutane); m/z (%): 340 (100) [M ϩ H], 326 (15).
1
4
3
, 4.0
Syntheses of Bimacrocyclic Pyridinebislactames. Ϫ General Pro-
cedure: To a well stirred solution (KPG stirrer, > 500 r/min) of six
equivalents of triethylamine in 500 ml of dry dichloromethane, one
equivalent of the pyridinediamine 15 or 16 in 200 ml of dichloro-
methane, and one equivalent of decanedicarbonyl dichloride in 250
ml of dry dichloromethane were dropped synchronically within 7
h. Stirring was continued for additional 30 min. Then the reaction
mixture was allowed to stand for 15 h. The solution was concen-
trated to 150 ml and was washed with 50 ml 2  NaOH. The aque-
ous layer was extracted three times with 100 ml of dichloromethane.
4
Ϫ1
,
1
(
(
ϩ
ϩ
ϩ
4
H
9
], 365
ϩ
3 3
) ], 323 (18), 248 (14), 177 (15),
ϩ
1
ϩ
ϩ
ϩ
4
H
9
], 364 (3) [M Ϫ COC(CH
calcd. 449.2890, found
39 3 5
: calcd. 450.2923, found 450.2920. Ϫ C24H N O
3
)
3
]. Ϫ HR-
449.2887;
39 3 5
C H N O :
C
(
N
3
O
5
449.3): calcd. C 64.12, H 8.74, N 9.35, found C 63.43, H 8.68,
N 9.16.
4
The combined organic layer was dried with MgSO and filtered.
After evaporation of the solvents, the remaining oil was purified by
chromatography (silica gel, 100 g, diameter 4 cm, dichloromethane/
ethanol, 10:1).
3
-Hydroxybutyl Diphenylacetate (6a) and 3-Hydroxy-1-meth-
ylpropyl Diphenylacetate (6b): 1.00 g (4.3 mmol) of diphenylacetyl
chloride was dissolved in 10 ml of dry dichloromethane, and 5.00
ml (55.3 mmol) of butane-1,3-diol (5) and 1 ml of pyridine were
2
6-Ethoxy-17,20-dioxa-1,14,30-triazatricyclo[12.8.7.124,28]-
triaconta-24(30),25,27-trien-2,13-dione (1c): Starting materials:
1
3
.27 g (4.3 mmol) of 16-ethoxy-6,9-dioxa-3,12,18-triazabicyclo[12.- added. The reaction mixture was stirred for 15 h at room tempera-
.1]octadeca-1(17),14(18),15-triene (15), 1.15 g (4.3 mmol) of de-
. Yield: 0.98
ture, then 20 ml of water was added and the mixture was extracted
twice with 20 ml of dichloromethane. The combined organic layer
canedicarbonyl dichloride, 2.61 g (25.8 mmol) of NEt
g (46%), colourless oil, slowly crystallizing, m. p. 98Ϫ102 C. Ϫ
3
o
4
was dried with MgSO and filtered. Evaporation of the solvent in
1
H-NMR (200 MHz, CDCl
3
): δ ϭ 1.1Ϫ1.8 (m, ca. 23 H), 2.2Ϫ2.5 vacuo yielded a colourless oil, which was dissolved in little di-
(
(
m, ca. 4 H), 3.0Ϫ4.1 (m, ca. 8 H), 4.13 (q, 7.0 Hz, 2 H), 4.4Ϫ4.9 chloromethane and purified twice by chromatography (silica gel,
m, ca. 4 H), 6.54 (d, 2.4 Hz, ca. 0.46 H, Py-HEZ), 6.55 (s, 0.69 H, 100 g, diameter 2 cm, ethyl acetate). Yield: 0.7 g (57%) of 6a/6b in
1
Py-HZZ), 6.80 (s, 0.39 H, Py-HEE), 6.87 (d, 2.4 Hz, ca. 0.46 H, Py- a 9:1 ratio (NMR) as colourless oil. Ϫ H NMR (300 MHz,
H
1
4
1
4
Ϫ1
EZ). Ϫ IR (KBr): ν˜ ϭ 3431 cm , 1647 (CϭO), 1600 (arom.),
CDCl
576 (arom.). Ϫ MS (EI, 70 eV); m/z (%): 489 (98) [M ], 459 (52), s, 1 H), 7.2Ϫ7.4 (m, 10 H), signals for 6a: δ ϭ 1.15 (d, 6.2 Hz, 2.7
44 (38), 294 (20), 234 (20), 220 (22), 206 (39), 192 (35), 178 (54), H), 3.7Ϫ3.8 (m, 0.9 H), 4.1Ϫ4.3 (m, 0.9 H), 4.3Ϫ4.5 (m, 0.9 H),
51 (100). HR-MS: calcd. 489.3203 found 5.01 (s, 0.9 H), signals for 6b: δ ϭ 1.27 (d, 6.4 Hz, 0.3 H), 3.3Ϫ3.6
3
): signals for 6a and 6b: δ ϭ 1.6Ϫ1.9 (m, ca. 2 H) 1.80 (br.
ϩ
Ϫ
27 43 3 5
C H N O
13
89.3202. C26 CH43
N
O
3 5
calcd. 490.3236 found 490.3235. Ϫ (m, 0.2 H), 5.01 (s, 0.1 H), 5.1Ϫ5.3 (m, 0.1 H). Ϫ IR (KBr): ν˜ ϭ
1082
Eur. J. Org. Chem. 1998, 1077Ϫ1084

Concave Reagents, 26
FULL PAPER
3
7
411 cmϪ1 (br., OH), 1732 (CϭO), 1600 (arom.), 1496. Ϫ MS (EI,
using SADABS (Sheldrick, 1996), structure solution by direct
methods, structure refinement: full-matrix least-squares on F ,
data/parameter-ratio: 5084/198, goodness-of-fit ϭ 1.065, final R in-
ϩ
ϩ
2
0 eV); m/z (%): 284 (2) [M ], 195 (3), 194 (17), 167 (100) [M
Ϫ
ϩ
COOR]. Ϫ MS (CI, isobutane); m/z (%): 286 (9), 285 (47) [M
ϩ
ϩ
20 3
H], 167 (5) [M Ϫ COOR], 117 (100). Ϫ C18H O (284.1): calcd. dices (all data): R ϭ 0.063, wR2 ϭ 0.177, largest difference peak
˚
Ϫ3
C 76.03, H 7.09, found C 75.59, H 7.09.
and hole: 0.279 and Ϫ1.041 eA .
8
aϪc: The diphenylacetyl derivatives of methyl 4,6-O-benzylid-
1
b: C26
41 3 5 r
H N O , M ϭ 475.62 g/mol. Crystal data: orthorhom-
ene-α--glucopyranoside (7) were isolated from the competition
experiments and separated (1.03 mmol of 7, catalysis by pyridine).
bic, space group Pccn, Z ϭ 8, unit cell: a ϭ 21.0473(1), b ϭ
3.4133(1), c ϭ 10.4790(2) A, V ϭ 5163.91(6) A , calcd. density
d ϭ 1.224 gcm . Data collection: Siemens CCD three-circle dif-
fractometer, graphite-monochromated Mo-K radiation; colourless
crystal, 0.6 x 0.5 x 0.3 mm, T ϭ 153 K, ω-scans in the 2θ range
Ϫ53 , index ranges Ϫ25 Յ h Յ 25, Ϫ29 Յ k Յ 29, Ϫ13 Յ l
Յ 12; total of 50744 reflections, 5301 independent (Rint ϭ 0.103),
absorption coefficient ϭ 0.085 mm , empirical absorption correc-
tion using SADABS (Sheldrick, 1996), structure solution by direct
˚ ˚
3
2
Separation and chromatography (silica gel with 5% H
CH Cl /EtOH, 20:1) gave 68 mg of pure 8a (R ϭ 0.76) and 87 mg
of pure 8c (R ϭ 0.81), a mixture of 8a and 8c (106 mg), and a
mixture of 8a and 8b (111 mg) which was separated by a second
chromatography (silica gel with 5% H O w/w, cyclohexane/ethyl
acetate, 20:1) yielding pure 8a (20 mg, R ϭ 0.72) and pure 8b (67
mg, R ϭ 0.48).
2
O, w/w,
Ϫ3
2
2
f
α
f
o
3
2
Ϫ1
f
f
2
1
methods, structure refinement: full-matrix least-squares on F ,
data/parameter-ratio: 5301/308, goodness-of-fit ϭ 1.152, final R in-
dices (all data): R ϭ 0.106, wR2 ϭ 0.163, largest difference peak
8
a: M. p. 151Ϫ152°C. Ϫ H NMR (400 MHz, CDCl
s, 3 H, OCH ), 3.55 (t, 10 Hz, 1 H, 3-H), 3.75 (t, 10 Hz, 1 H, 6-
H), 3.81 (dt, J ϭ 4.5 Hz, J ϭ 10 Hz, 1 H, 5-H), 4.15 (t, 10 Hz, 1
H, 4-H), 4.27 (dd, 4.5 Hz, 10 Hz, 1 H, 6-H), 4.83 (dd, 4 Hz, 10
Hz, 1 H, 2-H), 4.94 (d, 4 Hz, 1 H, 1-H), 5.14 (s, 1 H, 2-COCHPh ),
3
): δ ϭ 3.29
(
3
d
t
˚
Ϫ3
and hole: 0.236 and Ϫ0.266 eA
.
2
2
a: C27H
43
N
3
O
5
, M
r
ϭ 489.64 g/mol. Crystal data: monoclinic,
5
3
.53 (s, 1 H, PhCH), 7.2Ϫ7.4 (m, 15 H, Ar-H). Ϫ IR (KBr): ν˜ ϭ
450 cm (br., OH), 1735 (CϭO), 750, 700. Ϫ MS (EI, 70 eV):
m/z (%): 476 (44), [M ], 167 (100), 152 (41), 149 (24), 107 (42), 91
32), 69 (37). Ϫ C28
space group P2
1
˚
/n, Z ϭ 4, unit cell: a ϭ 15.5325(1), b ϭ 10.3881(1),
Ϫ1
o
˚
3
c ϭ 16.3564(1) A, β ϭ 90.766(1) , V ϭ 2638.92(3) A , calcd. density
d ϭ 1.232 gcm . Data collection: Siemens CCD three-circle dif-
fractometer, graphite-monochromated Mo-K radiation; colourless
α
crystal, 1.0 x 0.9 x 0.4 mm, T ϭ 173 K, ω-scans in the 2θ range
ϩ
Ϫ3
(
7
H
28
O
7
(476.5): calcd. C 70.58 H 5.92, found C
0.71 H 5.98.
1
o
8
b: M. p. 185Ϫ187°C. Ϫ H-NMR (400 MHz, CDCl
3
): δ ϭ 3.45 3Ϫ60 , index ranges Ϫ21 Յ h Յ 20, Ϫ13 Յ k Յ 14, Ϫ22 Յ l
(
1
1
s, 3 H, OCH
H, 2-H), 3.71 (t, 10 Hz, 1 H, 6-H), 3.87 (dt, J
0 Hz, 1 H, 5-H), 4.28 (dd, 4.5 Hz, 10 Hz, 1 H, 6-H), 4.78 (d, 4 tion using SADABS (Sheldrick, 1996), structure solution by direct
3
), 3.55 (t, 10 Hz, 1 H, 4-H), 3.66 (dd, 4 Hz, 10 Hz, Յ 20; total of 39970 reflections, 7102 independent (R ϭ 0.025),
int
Ϫ1
d
ϭ 4.5 Hz, J
t
ϭ
absorption coefficient ϭ 0.085 mm , empirical absorption correc-
2
Hz, 1 H, 1-H), 5.12 (s, 1 H, 3-COCHPh
2
), 5.40 (s, 1 H, PhCH), methods, structure refinement: full-matrix least-squares on F ,
5
.44 (t, 10 Hz, 1 H, 3-H), 7.1Ϫ7.4 (m, 15 H, Ar-H). Ϫ IR (KBr): data/parameter-ratio: 7102/317, goodness-of-fit ϭ 1.045, final R in-
Ϫ1
ν˜ ϭ 3450 cm (br., OH), 1740 (CϭO), 710. Ϫ MS (EI, 70 eV):
m/z (%): 476 (33), [M ], 167 (100), 159 (42), 141 (23), 107 (33), 99
dices (all data): R ϭ 0.045, wR2 ϭ 0.107, largest difference peak
ϩ
˚
Ϫ3
and hole: 0.381 and Ϫ0.163 eA .
(
28 7 2
35), 69 (63). Ϫ C28H O ·0.5 H O (476.5 ϩ 9.0): calcd. C 69.26
2
b: C28
45 3 6 r
H N O , M ϭ 519.67 g/mol. Crystal data: triclinic,
H 6.02, found C 68.16 H 5.87.
¯
space group P1, Z ϭ 2, unit cell: a ϭ 8.990(4), b ϭ 10.070(6), c ϭ
6.145(5) A, α ϭ 74.78(5), β ϭ 86.74(4), γ ϭ 77.72(4) , V ϭ
378.1(1) A , calcd. density d ϭ 1.252 gcm . Data collection: En-
raf-Nonius CAD4 four-circle diffractometer, graphite-monochro-
mated Cu-K radiation; colourless crystal, 0.6 x 0.5 x 0.3 mm, T ϭ
23 K, ω-scans in the 2θ range 5Ϫ110 , index ranges Ϫ9 Յ h Յ 2,
Ϫ10 Յ k Յ 10, Ϫ17 Յ l Յ 17; total of 4331 reflections, 3468 inde-
pendent (Rint ϭ 0.056), absorption coefficient ϭ 0.710 mm , no
absorption correction, structure solution by direct methods, struc-
ture refinement: full-matrix least-squares on F , data/parameter-
ratio: 3468/333, goodness-of-fit ϭ 1.100, final R indices (all data):
R ϭ 0.046, wR2 ϭ 0.113, largest difference peak and hole: 0.418
and Ϫ0.345 eA
1
8
c: M. p. 155Ϫ156°C. Ϫ H-NMR (400 MHz, CDCl
3
): δ ϭ 3.22
˚
o
1
1
(
s, 3 H, OCH
H), 3.92 (dt, J
0 Hz, 1 H, 6-H), 4.85 (s, 1 H, 2-COCHPh
Hz, 1 H, 2-H), 4.94 (d, 4 Hz, 1 H, 1-H), 4.95 (s, 1 H, 3-COCHPh
.38 (s, 1 H, PhCH), 5.75 (t, 10 Hz, 1 H, 3-H), 7.0Ϫ7.4 (m, 25 H,
3
), 3.57 (t, 10 Hz, 1 H, 4-H), 3.72 (t, 10 Hz, 1 H, 6-
ϭ 4.5 Hz, J ϭ 10 Hz, 1 H, 5-H), 4.37 (dd, 4.5 Hz,
), 4.88 (dd, 4 Hz, 10
),
˚
3
Ϫ3
d
t
1
2
α
o
2
1
5
Ϫ1
Ar-H). Ϫ IR (KBr): ν˜ ϭ 1730 cm (CϭO), 1150, 755, 700. Ϫ MS
Ϫ1
ϩ
(
1
EI, 70 eV): m/z (%): 670 (37), [M ], 353 (16), 194 (93), 165 (100),
09 (81), 91 (97). Ϫ C46 (670.8): calcd. C 75.21 H 5.71, found
C 75.67 H 6.20.
H
38
O
8
2
X-ray Analyses: Crystallographic data (excluding structure fac-
tors) for the structures reported in this paper have been deposited
with the Cambridge Crystallographic Data Centre (No 100803).
Copies of the data can be obtained free of charge on application
to The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK (fax: int. code ϩ(1223)336Ϫ033, e-mail: teched@ccdc.cam.a-
c.uk).
˚
Ϫ3
.
2
e: C29
H
47
N
O
3 7
·CHCl
3
r
, M ϭ 669.06 g/mol. Crystal data:
monoclinic, space group P2
2.166(3), c ϭ 15.002(2) A, β ϭ 93.26 (1) , V ϭ 3405.6(7) A , calcd.
density d ϭ 1.305 gcm . Data collection: Enraf-Nonius CAD4
four-circle diffractometer, graphite-monochromated Cu-K radi-
ation; colourless crystal, 0.5 x 0.3 x 0.3 mm, T ϭ 293 K, ω-scans
1
/n, Z ϭ 4, unit cell: a ϭ 10.258(1), b ϭ
˚
o
˚
3
2
Ϫ3
α
41 3 5 r
1a: C25H N O , M ϭ 463.61 g/mol. Crystal data: monoclinic,
o
space group C2/c, Z ϭ 8, unit cell: a ϭ 17.7544(1), b ϭ 17.6531(1), in the 2θ range 7Ϫ120 , index ranges 0 Յ h Յ 11, Ϫ24 Յ k Յ 5,
c ϭ 17.1207(2) A, β ϭ 111.749(1) , V ϭ 4984.00(7) A , calcd. den- Ϫ16 Յ l Յ 16; total of 6757 reflections, 5047 independent (Rint
sity d ϭ 1.236 g·cm . Data collection: Siemens CCD three-circle 0.034), absorption coefficient ϭ 2.830 mm , no absorption correc-
diffractometer, graphite-monochromated Mo-K radiation; colour- tion, structure solution by direct methods, structure refinement:
less crystal, 0.8 x 0.4 x 0.4 mm, T ϭ 143 K, ω-scans in the 2θ range full-matrix least-squares on F , data/parameter-ratio: 5047/384,
˚
o
˚
3
ϭ
Ϫ3
Ϫ1
α
2
o
3
Ϫ53 , index ranges Ϫ22 Յ h Յ 22, -22 Յ k Յ 22, Ϫ21 Յ l Յ 21; goodness-of-fit ϭ 1.038, final R indices (all data): R ϭ 0.103,
total of 43833 reflections, 5084 independent (Rint ϭ 0.047), absorp-
tion coefficient ϭ 0.086 mm , empirical absorption correction
wR2 ϭ 0.261, largest difference peak and hole: 0.508 and Ϫ0.570
eA .
Ϫ1
˚
Ϫ3
Eur. J. Org. Chem. 1998, 1077Ϫ1084
1083

U. Lüning, S. Petersen, W. Schyja, W. Hacker, T. Marquardt, K. Wagner, M. Bolte
FULL PAPER
9
: C24
H
39
N
3
O
5
, M
r
ϭ 449.58 g/mol. Crystal data: triclinic, space
NMR spectroscopy. To remove the catalysts the NMR solvent was
¯
group P1, Z ϭ 2, unit cell: a ϭ 10.2293(1), b ϭ 10.5033(1), c ϭ evaporated. 250 µl of dichloromethane was added and the solution
2.7351(1) A, α ϭ 73.652(1), β ϭ 88.698(1), γ ϭ 65.506(1) , V ϭ was filtered through silica gel and washed with 20 ml of dichloro-
187.86(2) A , calcd. density d ϭ 1.257 gcm . Data collection:
Siemens CCD three-circle diffractometer, graphite-monochromated
Mo-K
˚
o
1
1
˚
3
Ϫ3
methane. After evaporation of the solvent in vacuo, the remaining
residue was analysed by NMR spectroscopy in CDCl and C
radiation; colourless crystal, 0.6 x 0.4 x 0.3 mm, T ϭ 173 With the catalysts 1, 2 and 9, 8c never could be detected.
3
6 6
D .
α
o
K, ω-scans in the 2θ range 4Ϫ52 , index ranges Ϫ12 Յ h Յ 12,
Ϫ13 Յ k Յ 13, Ϫ15 Յ l Յ 15; total of 14355 reflections, 4784
[1]
W. Schyja, S. Petersen, U. Lüning, Liebigs Ann. 1996,
2099Ϫ2105.
Ϫ1
independent (Rint ϭ 0.027), absorption coefficient ϭ 0.088 mm
,
[
[
[
2]
3]
4]
empirical absorption correction using SADABS (Sheldrick, 1996),
structure solution by direct methods, structure refinement: full-ma-
U. Lüning, R. Baumstark, W. Schyja, Liebigs Ann. Chem.
1
991, 999Ϫ1002.
J. Jähme, C. Rüchardt, Angew. Chem. 1981, 93, 919Ϫ921; An-
gew. Chem. Int. Ed. Engl. 1981, 20, 885Ϫ887.
2
trix least-squares on F , data/parameter-ratio: 4784/290, goodness-
of-fit ϭ 1.026, final R indices (all data): R ϭ 0.047, wR2 ϭ 0.095,
H. Pracejus, J. Le sˇ ka, Z. Naturforsch., Teil B, 1966, 21, 30Ϫ32.
U. Lüning, R. Baumstark, K. Peters, H. G. v. Schnering, Liebigs
Ann. Chem. 1990, 129Ϫ143.
˚
Ϫ3
[5]
largest difference peak and hole: 0.290 and Ϫ0.195 eA
.
[6]
Selectivity Measurements
U. Lüning, R. Baumstark, M. Müller, Liebigs Ann. Chem.
1
991, 987Ϫ998.
6
a/6b: The experiments were carried out analogously to 4a/4b
[7]
E. C. Taylor, A. McKillop, G. H. Hawks, Org. Synth. 1972,
52, 36Ϫ38.
1]
(
50 m 5, 50 m catalyst, 4 m Ph
2
CϭCϭO).[ Analysis by GC
[
[
8]
9]
W. Schyja, Ph. D. thesis, University of Freiburg, 1995.
T. Marquardt, U. Lüning, Chem. Commun. 1997, 1681Ϫ1682.
T. Marquardt, diploma thesis, University of Kiel, 1997.
W. Hacker, Ph. D. thesis, University of Freiburg, 1996.
D. G. Markees, G. W. Kidder, J. Am. Chem. Soc. 1956, 78,
after derivatization.
[
[
[
10]
11]
12]
8a/b: 1 mmol of 7 was dissolved in 2 ml of dry dichloromethane
and 0.01 to 1.00 mmol of the catalyst was added. Then 1.25 mmol
of diphenylketene was added with an Eppendorf pipette. The vial
was flushed with nitrogen and closed. After 15 h at room tempera-
ture the mixtures were concentrated in vacuo and analysed by
4
130Ϫ4135.
[13]
S. Petersen, Ph. D. thesis, University of Kiel, 1998.
[97366]
1084
Eur. J. Org. Chem. 1998, 1077Ϫ1084