Chiral synthesis via organoboranes. 46. An efficient preparation of chiral pyridino- and thiopheno-18-crown-6 ligands from enantiomerically pure C2-symmetric pyridine- and thiophenediols

Article abstract of DOI:10.1021/jo980899r

Asymmetric reduction of 2,6-diacylpyridines with B- chlorodiisopinocampheylborane provides the corresponding C₂-symmetric diols in very high de and ee. Asymmetric allylboration of 2,6- pyridinedicarboxaldehyde and 2,5-thiophenedicarboxaldehyde

Full text of DOI:10.1021/jo980899r

J . Org. Chem. 1999, 64, 721-725
721
Ch ir a l Syn th esis via Or ga n obor a n es. 46. An Efficien t P r ep a r a tion
of Ch ir a l P yr id in o- a n d Th iop h en o-18-cr ow n -6 Liga n d s fr om
En a n tiom er ica lly P u r e C2-Sym m etr ic P yr id in e- a n d
Th iop h en ed iols1
Guang-Ming Chen,2 Herbert C. Brown,* and P. Veeraraghavan Ramachandran*
H. C. Brown and R. B. Wetherill Laboratories of Chemistry, Purdue University,
West Lafayette, Indiana 47907
Received May 11, 1998
Asymmetric reduction of 2,6-diacylpyridines with B-chlorodiisopinocampheylborane provides the
corresponding C2-symmetric diols in very high de and ee. Asymmetric allylboration of 2,6-
pyridinedicarboxaldehyde and 2,5-thiophenedicarboxaldehyde provides the corresponding bis-
homoallylic alcohols in very high de and ee. These optically pure diols were converted to the disodium
or dipotassium salts and treated with tetra(ethylene glycol) ditosylate to obtain the corresponding
chiral pyridino and thiopheno-18-crown-6 ligands. However, the perfluoroalkyl diols failed to provide
the macrocycles.
Attempts to understand the phenomena of molecular
recognition occurring in chemical interactions involving
enzymes, antibodies, antigens, stereoselective catalysts,
etc. led to the rapid development of the area of synthetic
host-guest chemistry.3 Since the serendipitous discovery
of dibenzo-18-crown-6 ether three decades ago,4 system-
atic research by Pederson,5 Cram,6 Lehn,7 Stoddart,8
Bradshaw,9 and others10 has led to the rational synthesis
of receptor molecules with the desired qualities. Pederson
postulated a qualitative relationship between the stabil-
ity of the complex and the ratio of the cation diameter to
the ligand cavity diameter,5 and subsequent research has
revealed the importance of cation and ligand parameters.
Pirkle’s pioneering research involving chiral recognitions
for enantiomer separations in chromatographic columns
containing chiral macrocyclic ligands led to an empirical
three-point rule,11 which states that “chiral recognition
requires a minimum of three simultaneous interactions
between the chiral crown ether and at least one of the
enantiomers, with at least one of the interactions being
stereochemically dependent.”
The preparation and properties of chiral crown ethers
have attracted considerable attention of analytical, bio-
logical, organic, material, and medicinal chemists re-
cently.12 The syntheses of chiral macrocycles for the
selective recognition of enantiomers is an active area of
research.3c Chiral pyridino- and pyrimidino-18-crown-6
ethers (1 and 2) are among them.9
(1) (a) Presented at the 213th National Meeting of the American
Chemical Society (#ORGN 15), Orlando, FL, August 25, 1996. (b) For
a brief discussion of our initial results, see: Ramachandran, P. V.;
Brown, H. C. In Reductions in Organic Synthesis; Abdel-Magid, A. F.,
Ed.; ACS Symposium Series 641; American Chemical Society: Wash-
ington, DC, 1996; Chapter 5.
(2) Postdoctoral research associate on
Research Office.
a grant from the Army
(3) (a) Kilburn, J . D.; Patel, H. K. Contemp. Org. Synth. 1995, 1,
259 and references therein. (b) Perry, J . J . B.; Kilburn, J . D. Contemp.
Org. Synth. 1997, 4, 61 and references therein. (c) Whitlock, B. J .;
Ehitlock, H. W. In Supramolecular Stereochemistry; Siegel, J . S., Ed.;
Kluwer Academic: Netherlands, 1995. (d) Webb, T. H.; Wilcox, C. S.
Chem. Soc. Rev. 1993, 383. (e) Crown Ethers: Toward Future Applica-
tions; Cooper, S. R., Ed.; VCH: New York, 1992.
(4) Pederson, C. J . J . Am. Chem. Soc. 1967, 89, 2945.
(5) Pederson, C. J . Angew. Chem., Int. Ed. Engl. 1988, 27, 1021.
(6) (a) Cram, D. J . Angew. Chem., Int. Ed. Engl. 1988, 27, 1009. (b)
Cram, D. J . Science 1983, 219, 1177. (c) Cram, D. J . Science 1988,
240, 760.
The remarkable achievements of organic chemists over
the past two decades in developing new chiral reagents
and asymmetric synthetic methodologies13 to prepare
most types of organic molecules have made the synthesis
of chiral receptor molecules relatively simple. We made
our own contributions to the asymmetric synthetic pro-
gram on the basis of the application of our chiral
organoboranes to the synthesis of enantiomerically pure
molecules.14 Our approaches include asymmetric hy-
droboration, asymmetric reduction, asymmetric allyl- and
(7) (a) Lehn, J . M. Angew. Chem., Int. Ed. Engl. 1988, 27, 90. (b)
Lehn, J . M. Science 1985, 227, 846.
(8) Stoddart, J . F. Top. Stereochem. 1988, 17, 207.
(9) (a) Bradshaw, J . S.; Izatt, R. M. Acc. Chem. Res. 1997, 30, 338.
(b) Bradshaw, J . S.; Huszthy, P.; Ty Redd, J .; Zhang, X. X.; Wang, T.;
Hathaway, J . K.; Young, J .; Izatt, R. M. Pure Appl. Chem. 1995, 67,
691.
(10) (a) Host-Guest Complex Chemistry-I. Topics in Current Chem-
istry Vol. 98; Springer-Verlag: Berlin, 1981. (b) Host-Guest Complex
Chemistry-II. Topics in Current Chemistry Vol. 101; Springer-Verlag:
Berlin, 1982.
(12) Lehn, J . M. Supramolecular Chemistry; VCH: Weinheim, FRG,
1995.
(13) Procter, G. Asymmetric Synthesis; Oxford University Press:
Oxford, England, 1996.
(14) (a) Brown, H. C.; Ramachandran, P. V. In Advances in Asym-
metric Synthesis; Hassner, A., Ed.; J AI Press: Greenwich, CT, 1995;
Chapter 4. (b) Brown, H. C.; Ramachandran, P. V. J . Organomet. Chem.
1995, 500, 1.
(11) Pirkle, W. H.; Pochapsky, T. C. Chem. Rev. 1989, 89, 347.
10.1021/jo980899r CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/15/1999

722 J . Org. Chem., Vol. 64, No. 3, 1999
Chen et al.
Sch em e 1
crotylboration, asymmetric enolboration, asymmetric
ring-opening of epoxides, asymmetric homologation, etc.
Recently, we applied our asymmetric reduction proce-
dure using B-chlorodiisopinocampheylborane (DIP-Chlo-
ride) (3)15 to the reduction of diketones, including several
2,6-diacylpyridines (4a -d ), and achieved the synthesis
of the corresponding C2-symmetric diols in very high
diastereo- and enantiomeric excess (de and ee) (eq 1).16
dimethyl-, 2,16-di-tert-butyl-, and 2,16-diallyl-pyridino-
18-crown-6 ligands (11-13) and 2,16-diallyl-thiopheno-
18-crown-6 ligand (16). Our attempts to prepare the
corresponding 2,16-ditrifluoromethyl- and 2,16-dipen-
tafluoroethyl-pyridino-18-crown-6 ligands (14 and 15)
have been unsuccessful thus far.
Preliminary results of our success have been reported
earlier.1 Recently, Bradshaw and co-workers have re-
ported the preparation and properties of three of the
pyridinyl crown ethers (11-13) via a cumbersome resolu-
tion of racemic 5a , 5b, and 9.21 Our methodologies involve
the asymmetric syntheses of the required diols. The
details of our study follows.
These pyridinediols (5a -d ) have been examined as chiral
tridentate ligands for catalytic asymmetric reactions.17
We have since applied enantioselective allylboration with
B-allyldiisopinocampheylborane18 (6) to dicarboxalde-
hydes, including 2,6-pyridine- and 2,5-thiophenedicar-
boxaldehydes (7 and 8, respectively), for the preparation
of C2-symmetric bis-homoallylic diols 9 and 10, respec-
tively (Scheme 1).19
Resu lts a n d Discu ssion
On the basis of a recent report by Lehn and co-workers
on the synthesis of helical macrocycles from (+)-(S,S)-
bipyridine-6,6′-diethanol and bromomethylbipyridine (eq
2),20 we envisaged the synthesis of a series of chiral
Either enantiomer of the necessary diols 5a -d was
obtained by the asymmetric reduction of the correspond-
ing diketones with the enantiomers of 3, as described by
us earlier.16 We obtained 5a in 59% yield as a 90:10
mixture of the dl and meso components, which were
separated as the bis-3,5-dinitrobenzoate via crystalliza-
tion from chloroform. Enantiomerically pure 5b, 5c, and
5d were obtained in 57%, 72%, and 75% yields, respec-
tively.
During this study, we developed an improved proce-
dure to prepare the diketone 4b. Sharpless and Hawkins
reported a 35% yield of racemic 5b by treating the 2,6-
dilithiopyridine with pivalaldehyde at -78 °C, with
subsequent oxidation to 4b in 80% yield.22 Our experi-
ences in the synthesis of several of these types of pyridyl
ketones from the lithiopyridines suggested that the poor
(17) (a) Ishizaki, M.; Fujita, K.; Shimamoto, M.; Hoshino, O.
Tetrahedron: Asymmetry 1994, 5, 411. (b) J iang, Q.; Plew, D. V.;
Murtuza, S.; Zhang, X.; Guo, C. Tetrahedron Lett. 1996, 37, 797. (c)
Sablong, R.; Osborn, J . A. Tetrahedron Lett. 1996, 37, 4937. (d) Brown,
H. C.; Chen, G. M.; Ramachandran, P. V. Chirality 1997, 9, 506.
(18) Brown, H. C.; J adhav, P. K. J . Am. Chem. Soc. 1983, 105, 2092.
(19) Ramachandran, P. V.; Chen, G. M.; Brown, H. C. Tetraedron
Lett. 1997, 38, 2417.
(20) Zarges, W.; Hall, J .; Lehn, J . M.; Bolm, C. Helv. Chim. Acta
1991, 74, 1843.
(21) Habata, Y.; Bradshaw, J . S.; Young, J . J .; Castle, S. L.; Huszthy,
P.; Pyo, T.; Lee, M. L.; Izatt, R. M. J . Org. Chem. 1996, 61, 8391.
(22) Hawkins, J .; Sharpless, B. K. Tetrahedron Lett. 1987, 28, 2825.
pyridino- and thiopheno-crown ligands where the chiral-
ity arose from the pyridine and thiophenedimethanols.
We succeeded in the synthesis of the crown ethers 2,16-
(15) Brown, H. C.; Chandrasekharan, J .; Ramachandran, P. V. J .
Am. Chem. Soc. 1988, 110, 1539. DIP-Chloride is a trademark of the
Aldrich Chemical Co.
(16) Ramachandran, P. V.; Chen, G. M.; Lu, Z. H.; Brown, H. C.
Tetrahedron Lett. 1996, 37, 3795.

Chiral Synthesis via Organoboranes
J . Org. Chem., Vol. 64, No. 3, 1999 723
Sch em e 2
Sch em e 3
yield might be the result of the instability of the dilithio
salt. Accordingly, we conducted the preparation at -100
°C and realized an 83% yield of racemic 5b. Subsequent
oxidation provided an 80% yield of the necessary diketone
4b, as reported previously.22
ecules in 11-48% yields. The reaction of the disodium
salt of 5a showed only one major product by TLC (eq 3).
The allylboration of a series of dicarboxaldehydes,
including 2,6-pyridinedicarboxaldehyde (7), with 6 was
reported by us recently.19 The reaction in THF at -100
°C provides the product diol (9) in 92% yield and 96%
de. The dl portion was enantiomerically pure, separated
from the meso (2%) over silica gel. Compared to this, the
earlier procedure (Scheme 2)21 using allylmagnesium
bromide and 7 provided a mixture of the meso and dl
components, separated by column chromatography in
20% and 24% yields, respectively. The dl component was
then acetylated and resolved using a Regis-Pirkle
column. The experimental procedure involves repeated
injections of 20 µL each of the sample to obtain (-)-9 in
46% yield and 92.8% ee, and (+)-9 in 17% yield and 99%
ee (Scheme 2).
We isolated 28% of 11 by column chromatography.
Bradshaw et al. reported a 1.5% and 0.4% yield, respec-
tively, of 11 and a dimeric compound, (S,S,S,S)-2,16,22,-
36-tetramethyl-3,6,9,12,15,23,26,29,32,35-decaoxa-41,42-
diazatricyclo[36.3.1.117,21]dotetraconta-1(41),17,19,21,37,39-
hexaene, from the same reaction. We did not attempt to
isolate any of the side products from the residue which
may have contained the dimer. The reaction of the
disodium salt of 5b provided a 48% of the desired aza-
crown ether 12 (eq 3).
2,6-Thiophenedicarboxaldehyde (8) was allylborated
with 6 at -100 °C to obtain 10 in 93% yield and 92% de.
Enantiomerically pure 10 was separated from the meso
compound by crystallizing the bis-3,5-dinitrobenzoate
from hexane/ethyl acetate, followed by hydrolysis (Scheme
1).
A similar reaction with the dipotassium salt of the
diallyl diol 9 with 17 showed two major and several minor
products by TLC. We separated the major products by
column chromatography, which revealed them to be the
required pyridino-18-crown-6 13 and the dimeric com-
pound 18 (Scheme 3).
Our attempts to prepare the CF3 and C2F5 analogues
14 and 15, respectively, have not succeeded thus far.
When we applied the same reaction procedure in eq 5 to
P r ep a r a tion of Aza -Cr ow n Eth er s. The aza-crown
ethers 11-13 were prepared using standard proce-
dures.23 The 2,6-pyridinedimethanols were converted to
the corresponding disodium salt with NaH, followed by
treatment with the ditosylate (17) of the tetra(ethylene
glycol) to provide the chiral pyridino-18-crown-6 mol-
(23) Redd, J . T.; Bradshaw, J . S.; Huszthy, P.; Izatt, R. M. J .
Heterocycl. Chem. 1994, 31, 1047.

724 J . Org. Chem., Vol. 64, No. 3, 1999
Chen et al.
prepare 14, the TLC of the reaction mixture revealed that
no reaction had taken place. Indeed, we recovered 85%
of the starting diol after workup. Conducting the reaction
under varying conditions of temperature, time, and
solvents was not fruitful. With an intention of facilitating
the displacement, we attempted the coupling by prepar-
ing and utilizing the bis-p-nitrobenzenesulfonate of the
tetra(ethylene glycol) but failed to achieve the coupling.
Exp er im en ta l Section
Gen er a l Meth od s. All operations were carried out under
an inert atmosphere. Techniques for handling air- and moisture-
sensitive materials have been previously described.24 The H,
1
11B, and 19F NMR spectra were plotted on a Varian Gemini-
300 spectrometer with a Nalorac-Quad probe. The optical
rotations were measured using a Rudolph Autopol III pola-
rimeter.
Ma ter ia ls. Anhydrous ethyl ether (EE) purchased from
Mallinckrodt, Inc. was used as received. THF was distilled
from sodium/benzophenone ketyl. DIP-Chloride, allylmagne-
sium bromide, 2,6-pyridinedicarboxaldehyde, 2,5-thiophene-
dicarboxaldehyde, tetra(ethylene glycol), potassium tert-
butoxide, p-toluenesulfonyl chloride, and 4-nitrobenzenesulfonyl
chloride were all obtained from the Aldrich Chemical Co. The
diols 5a -e were obtained via the asymmetric reduction of the
corresponding diketones with 3.16 The diols 9 and 10 were
obtained via the allylboration of the corresponding dicarbox-
aldehydes with 6.19 (R)-(+)-R-methoxy-R-(trifluoromethyl)-
phenylacetic acid (MTPA) was purchased from the Aldrich
Chemical Co. and converted to the acid chloride using Mosher’s
procedure.25
In contrast, the reaction of the disodium salt of 5d with
the ditosylate or bis-p-nitrobenzenesulfonate of the tetra-
(ethylene glycol) at reflux for 10 days provided a complex
mixture of eight to ten products (TLC). Column chroma-
tography did not provide any of the required ether 15.
The structures of the different products are yet to be
determined. We then attempted the coupling of the
ditosylate of the perfluoroalkyl pyridinediols (19) and the
disodium salt of the tetra(ethylene glycol) (20) (eq 4). This
P r ep a r a tion of R,R′-Dia llyl-2,5-th iop h en ed im eth a n ol
(10). Allylmagnesium bromide (72.6 mL, 1.0 M, 72.6 mmol)
was added dropwise to a well-stirred solution of (-)-3 (24.45
g, 76.2 mmol) in EE (200 mL) at -78 °C. The mixture was
then stirred for 0.5 h at -78 oC, allowed to warm to room
temperature, and stirred for 4 h. The solvent was removed
under aspirator vacuum, and the residue was extracted with
pentane (3 × 150 mL), filtered through a Kramer filter,24 and
concentrated to afford dIpc2BAll (6) (11B NMR δ 79 ppm) in
essentially quantitative yield. The above dIpc2BAll was dis-
solved in THF (100 mL) and cooled to -100 °C. A solution of
2,5-thiophenedicarboxaldehyde (4.06 g, 29.0 mmol) in anhy-
drous THF (50 mL) was added dropwise over 0.5 h, and the
reaction mixture was stirred at -100 °C for 4 h when the
reaction was complete (11B NMR shift from δ 79 to 52 ppm).
Addition of methanol (1 mL) to this intermediate, followed by
alkaline H2O2 oxidation, afforded a crude product which was
chromatographed (ethyl acetate/hexane, 3:7 as eluent) to
provide 6.04 g (93%) of 10. Analysis of the bis-MTPA ester
using 19F NMR spectroscopy showed the diol to be of 92% de.
The dl component revealed g98% ee. 1H NMR (CDCl3) δ
(ppm): 2.32 (d, 2H), 2.57 (m, 4H), 4.88-4.95 (m, 2H), 5.14-
5.23 (m, 4H), 5.75-5.90 (m, 2H), 6.82 (s, 2H). 13C NMR (CDCl3)
also was in vain. We are continuing our efforts to
synthesize 14 and 15.
Th io-Cr ow n Eth er s. We encountered no difficulty in
preparing the new thio-crown ether 16. Thus, the reac-
tion of the dipotassium salt of 10 with the ditosylate of
the tetra(ethylene glycol) in THF at room temperature
for 6 days and workup provided 19% of the product (eq
5). There were a number of side products from this
δ (ppm): 43.66, 69.54, 118.81, 123.33, 133.88, 147.02. [R]24
D
) +19.87 (c 9.4, EtOH).
P r ep a r a tion of Tetr a (eth ylen e glycol) Ditosyla te. Tet-
ra(ethylene glycol) (6.66 g, 34.3 mmol) in 200 mL dry THF
was added dropwise to a vigorously stirred suspension of NaH
(2.64 g, 110 mmol) in dry THF (50 mL) at 0 °C. The reaction
mixture was slowly warmed and refluxed for 4 h and then
cooled to 0 °C, followed by the addition of tosyl chloride (16.38
g, 85.8 mmol) in dry THF (100 mL). The mixture was warmed
to room temperature and stirred for 48 h. The solvent was
removed, and the residue was treated cautiously with water
and extracted with ethyl ether (3 × 100 mL). The organics
were dried over anhydrous MgSO4, concentrated, and purified
by column chromatography (hexane/ethyl acetate, 8:2) to
provide 16.40 g (96%) of the ditosylate as a colorless viscous
oil. 1H NMR (CDCl3) δ (ppm): 2.43 (s, 6H), 3.50-3.60 (m, 8H),
3.68 (t, 4H), 4.15 (t, 4H), 7.33 (d, 4H), 7.79 (d, 4H).
reaction that were not identified.
Con clu sion s
In conclusion, we have successfully synthesized several
pyridino- and thiopheno-18-crown-6 ligands in 11-48%
yield. The possibility of synthesizing several types of
enantiomerically pure diols via the asymmetric reduction
of diketones with the enantiomers of Ipc2BCl and the
asymmetric allylboration of dialdehydes with the enan-
tiomers of Ipc2BAll has provided the opportunity to
synthesize a variety of chiral crown ethers having sub-
stituents differing in their electronic and steric environ-
ments for application in host-guest chemistry. We
believe that this aspect can be exploited in a systematic
study of these chiral crown ethers for molecular recogni-
tion.
Syn th esis of En a n tiom er ica lly P u r e Dim eth ylp yr i-
d in o Cr ow n Eth er . (R,R)-R,R′-Dimethyl-2,6-pyridinedimeth-
anol (1.07 g, 6.4 mmol) in THF (50 mL) was added dropwise
to a vigorously stirred suspension of NaH (0.49 g, 20.4 mmol)
(24) Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M.
Organic Syntheses via Boranes; Wiley-Interscience: New York, 1975;
Reprinted edition, Vol. 1. Aldrich Chemical Co. Inc.: Milwaukee, WI,
1997; Chapter 9.
(25) Dale, J . A.; Dull, D. L.; Mosher, H. S. J . Org. Chem.1969, 34,
2543. As a result of the limitations of the NMR technique, a maximum
of g98% ee is assigned for the products, although none of the peaks
corresponding to the enantiomer was observed.
We are continuing our efforts to synthesize 14 and 15.
We are also synthesizing chiral crown ethers from the
chiral diols 5a -d , 9, and 10 and oligodiols bearing chiral
centers.

Chiral Synthesis via Organoboranes
J . Org. Chem., Vol. 64, No. 3, 1999 725
in dry THF (15 mL) at 0 °C. The mixture was stirred at 0 °C
for 30 min and warmed to reflux. After refluxing for 2 h, the
reaction mixture was cooled to room temperature, followed by
the dropwise addition of tetra(ethylene glycol) ditosylate (3.21
g, 6.4 mmol) in THF (100 mL). The mixture was then stirred
at room temperature for 3 days, after which the solvent was
removed under aspirator vacuum, and the residue was treated
with water and extracted with ethyl ether (3 × 40 mL). The
organics were dried over anhydrous MgSO4, concentrated, and
purified by column chromatography (silica gel; hexane/ethyl
acetate, 8:2) to yield 0.59 g (28%) of the dimethylpyridino
crown ether 11 as a pale yellow oil. 1H NMR (CDCl3) δ (ppm):
1.50 (d, 6H), 3.35-3.75 (m, 16H), 4.69 (q, 2H), 7.37 (d, 2H),
as a pale yellow oil and 0.40 g (15%) of the dimer crown ether
1
18 as a pale yellow oil. 13. H NMR (CDCl3) δ (ppm): (2.46-
2.63 (m, 4H), 3.30-3.85 (m, 16H), 4.50-4.63 (m, 2H), 4.89-
5.10 (m, 4H), 5.67-5.90 (m, 2H), 7.31 (d, 2H), 7.68 (t, 1H).
[R]24 ) -2.58 (c 5.7, CHCl3). 18. 1H NMR (CDCl3) δ (ppm):
D
(2.48-2.75 (m, 8H), 3.40-3.80 (m, 32H), 4.50-4.65 (m, 4H),
4.90-5.12 (m, 8H), 5.62-5.89 (m, 4H), 7.15 (d, 4H), 7.58 (t,
2H). [R]24 ) -47.64 (c 7.2, CHCl3).
D
Syn th esis of En a n tiom er ica lly P u r e Dia llylth iop h en o
Cr ow n Eth er (16). Enantiomerically pure (S,S)-R,R′-diallyl-
2,6-thiophenedimethanol (0.73 g, 3.26 mmol) in THF (20 mL)
was added to a solution of t-BuOK (0.80 g, 7.17 mmol) in THF
(5 mL) and stirred for 12 h. Tetra(ethylene glycol) ditosylate
(1.64 g, 3.26 mmol) in THF (20 mL) was then added, and the
resulting mixture was stirred at room temperature for 6 days.
The solvent was removed under aspirator vacuum, and the
residue was treated with water and extracted with ethyl ether
(3 × 25 mL). The organics were dried over anhydrous MgSO4
and concentrated, and the residue was purified by column
chromatography (silica gel, hexane/ethyl acetate, 8:2) to
provide 0.15 g of the starting diol and 0.24 g (19%) of the
7.72 (t, 1H). [R]24 ) +2.65 (c 6.5, CHCl3).
D
Syn th esis of En a n tiom er ica lly P u r e Di-ter t-bu tylp y-
r id in o Cr ow n Eth er . This reaction was carried out according
to the above procedure using (R,R)-R,R′-di-tert-butyl-2,6-py-
ridinedimethanol (1.26 g, 5.0 mmol), NaH (0.38 g, 16.0 mmol),
and tetra(ethylene glycol) ditosylate (3.01 g, 6.0 mmol). The
mixture was stirred at room temperature for 6 days, the
solvent was removed under aspirator vacuum, and the residue
was treated with water and extracted with ethyl ether (3 ×
40 mL). The organics were dried over anhydrous MgSO4,
concentrated, and purified by column chromatography (silica
gel; hexane/ethyl acetate, 8:2) to provide 0.98 g (48%) of the
1
diallylthiopheno crown ether 16 as a pale yellow oil. H NMR
(CDCl3) δ (ppm): 2.50-2.75 (m, 4H), 3.50-3.70 (m, 16H),
4.54-4.60 (t, 2H), 5.03-5.13 (m, 4H), 5.75-5.90 (m, 2H), 6.80
(s, 2H). 13C NMR (CDCl3) δ (ppm): 41.25, 67.76, 70.45, 70.68,
77.32, 117.21, 123.81, 134.48, 145.35. Anal. Calcd for
1
di-tert-butyl pyridino crown ether 12 as a pale yellow oil. H
NMR (CDCl3) δ (ppm): (0.92 (s, 18H), 3.39-3.78 (m, 16H), 4.20
C
20H30O5S: C, 62.80; H, 7.91; S, 8.38. Found: C, 63.19; H, 8.16;
(s, 2H), 7.12 (d, 2H), 7.58 (t, 1H). [R]24 ) +27.96 (c 1.37,
S, 8.31. [R]22 ) -24.11 (c 6.0, CHCl3).
D
D
CHCl3).
Syn th esis of En a n tiom er ica lly P u r e Dia llylp yr id in o
Cr ow n Eth er . Enantiomerically pure (S,S)-R,R′-diallyl-2,6-
pyridinedimethanol (1.55 g, 7.1 mmol) in THF (30 mL) was
added to a solution of t-BuOK (1.74 g, 15.5 mmol) in THF (10
mL) and stirred for 12 h. Tetra(ethylene glycol) ditosylate (3.56
g, 7.1 mmol) in THF (40 mL) was then added, and the resulting
mixture was stirred at room temperature for 6 days. The
solvent was removed under aspirator vacumm, and the residue
was treated with water and extracted with ethyl ether (3 ×
40 mL). The organics were dried over anhydrous MgSO4 and
concentrated, and the residue was purified by column chro-
matography (silica gel; hexane/ethyl acetate, 8:2) to provide
0.29 g (11%) of the diallylpyridino crown ether monomer 13
Ack n ow led gm en t . Financial support from the
United States Army Research Office (DAAH-94-G-0313)
is gratefully acknowledged.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds 10 and 16 (4 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
J O980899R