Synthesis of Enantiomerically Pure Thiocrown Ethers Derived from 1,1'-Binaphthalene-2,2'-diol

Article abstract of DOI:10.1021/jo952107o

Synthetic methodology is given for the preparation of two different types of thiocrown ethrs from optically pure 1,1'-binaphthalene-2,2'-diol (10).The conceptually simplest approach starts from optically pure 10 itself, which is alkylated (4 equiv of K2CO3 in DMF at 110 deg C) with 2-chloroethanol followed by mesylation to provide 2,2'-bis(2-mesyloxy)ethoxy)-1,1'-binaphthyl (14).When allowed to react with ethane-1,2-dithiol, propane-1,3-dithiol, 1,4,7--trithiaheptane, 1,4,8,11-tetrathiaundecane, 2,2-dimethylpropane-1,3-dithiol, 2-(mercaptomethyl)-1-propene-3-thiol, and 1,2-benzenedithiol in the presence of Cs2CO3 in DMF at 60 deg C the corresponding thiocrown ethers 22-25, 28, 30, and 32 are formed in 30-54percent yields.Test reactions were carried out to establish that no racemization occurs during alkylation under these conditions.Reaction of optically pure 10 with tetrahydropyranyl (THP)-protected 3-chloropropanol under similar conditions for the preparation of 14 proceeded more sluggishly but cleanly.Removal of the THP protecting groups afforded 2,2'-bis(3-bromopropoxy)-1,1'-binaphthyl (20), which on reaction with propane-1,3-dithiol, 1,5,9-trithianonane, 2,2-dimethylpropane-1,3-dithiol, 2-(mercaptomethyl)-1-propene-3-thiol, and 1,2-bis(mercaptomethyl)benzene provided the respective thiocrown ethers 26, 27, 29, 31, and 33 in 24-68percent yields.Another class of thiocrown ethers was prepared from optically active 10, which converted via ortho-lithiation to 3,3'-bis(bromomethyl)-2,2'-dimethoxy-1,1'-binaphthyl (39) by means of methylation (K2CO3/CH3I)), ortho-lithiation followed by formylation (n-C4H9Li/N,N,N',N'-tetramethylethylenediamine (TMEDA)/ether followed by DMF and H2O workup) followed by reduction (NaBH4) followed by bromination (PBr3 in C5H5N).Reaction (Cs2CO3 in DMF at 60 deg C) with 1,4,7-trithiaheptane, 1,4,8-trithiaoctane, 1,4,7,10-tetrathiadecane, 1,4,8,11-tetrathiaundecane, and 1,5,10,14-tetrathiatetradecane afforded the corresponding thiocrown ethers 40-44 in 40-75percent yields.Despite repeated attempts using a wide range of reagents, demethylation of the methoxy ether functionalities failed.Attempts to prepare the free phenol derivatives of the latter type of grown ethers by oxuidative coupling of two naphthol units failed.

Full text of DOI:10.1021/jo952107o

J . Org. Chem. 1996, 61, 3093-3105
3093
Syn th esis of En a n tiom er ica lly P u r e Th iocr ow n Eth er s Der ived
fr om 1,1′-Bin a p h th a len e-2,2′-d iol
H. Thijs Stock and Richard M. Kellogg*
Department of Organic and Molecular Inorganic Chemistry, University of Groningen,
Groningen 9747 AG, The Netherlands
Received November 28, 1995X
Synthetic methodology is given for the preparation of two different types of thiocrown ethers from
optically pure 1,1′-binaphthalene-2,2′-diol (10). The conceptually simplest approach starts from
optically pure 10 itself, which is alkylated (4 equiv of K2CO3 in DMF at 110 °C) with 2-chloroethanol
followed by mesylation to provide 2,2′-bis(2-(mesyloxy)ethoxy)-1,1′-binaphthyl (14). When allowed
to react with ethane-1,2-dithiol, propane-1,3-dithiol, 1,4,7-trithiaheptane, 1,4,8,11-tetrathiaundec-
ane, 2,2-dimethylpropane-1,3-dithiol, 2-(mercaptomethyl)-1-propene-3-thiol, and 1,2-benzenedithiol
in the presence of Cs2CO3 in DMF at 60 °C the corresponding thiocrown ethers 22-25, 28, 30, and
32 are formed in 30-54% yields. Test reactions were carried out to establish that no racemization
occurs during alkylation under these conditions. Reaction of optically pure 10 with tetrahydro-
pyranyl (THP)-protected 3-chloropropanol under similar conditions for the preparation of 14
proceeded more sluggishly but cleanly. Removal of the THP protecting groups afforded 2,2′-bis-
(3-bromopropoxy)-1,1′-binaphthyl (20), which on reaction with propane-1,3-dithiol, 1,5,9-trithianonane,
2,2-dimethylpropane-1,3-dithiol, 2-(mercaptomethyl)-1-propene-3-thiol, and 1,2-bis(mercaptomethyl)-
benzene provided the respective thiocrown ethers 26, 27, 29, 31, and 33 in 24-68% yields. Another
class of thiocrown ethers was prepared from optically active 10, which was converted via ortho-
lithiation to 3,3′-bis(bromomethyl)-2,2′-dimethoxy-1,1′-binaphthyl (39) by means of methylation (K2-
CO3/CH3I), ortho-lithiation followed by formylation (n-C4H9Li/N,N,N′,N′-tetramethylethylenediamine
(TMEDA)/ether followed by DMF and H2O workup) followed by reduction (NaBH4) followed by
bromination (PBr3 in C5H5N). Reaction (Cs2CO3 in DMF at 60 °C) with 1,4,7-trithiaheptane, 1,4,8-
trithiaoctane, 1,4,7,10-tetrathiadecane, 1,4,8,11-tetrathiaundecane, and 1,5,10,14-tetrathiatetra-
decane afforded the corresponding thiocrown ethers 40-44 in 40-75% yields. Despite repeated
attempts using a wide range of reagents, demethylation of the methoxy ether functionalities failed.
Attempts to prepare the free phenol derivatives of the latter type of crown ethers by oxidative
coupling of two naphthol units failed.
In tr od u ction
thiolates, which carry out nucleophilic substitutions on
an appropriate chloride, bromide, mesylate, or other
leaving group, has provided a satisfactory solution to the
synthesis of many thiocrown ethers.7,8 The method is
illustrated in eq 1 for the synthesis of thio-18-crown-6
(3).
Investigations of crown ethers have been biased toward
oxygen (ether) and nitrogen (amine) linkages at the cost
of other heteroatoms like sulfur (sulfide).1,2 In large part
this state of affairs comes about from the lack, at least
until fairly recently, of generally applicable and high yield
syntheses for thiocrown ethers. The templated cycliza-
tions3 of ω-substituted alcohols and amines that work so
well for the preparation of oxo- and azacrown ethers
generally fail when thiolate is the nucleophile and the
intermediate chain contains sulfide linkages. Attempts
to use transition metals as synthetic templates for
obtainment of thiocrown ethers have in general not been
too successful.4-6 In our hands, however, the use of Cs2-
CO3 in dimethylformamide (DMF) to generate cesium
(1)
Thiocrown ethers have been studied chiefly for their
capacity to ligate transition metal ions.9 They bind
second- and third-row transition metal ions and generally
stabilize the lower oxidation states of these ions. Al-
though sulfide linkages should have a significant affinity
* To whom correspondence should be addressed: Phone: +31-50-
363 42 35. Fax: +31-50-363 42 96. E-mail: <R.M.Kellogg@
rugch4.chem.rug.nl>.
X Abstract published in Advance ACS Abstracts, April 1, 1996.
(1) Crown Compounds. Towards Future Applications; Cooper, S. R.,
Ed.; VCH Publishers: New York, 1992.
(6) Recently, we demonstrated that boric acid and
a borium/
(2) For a review on the synthesis of crown ether compounds see:
Okahara, M.; Nakatsuji, Y. In Crown Ethers and Analogous Com-
pounds; Hiraoka, M., Ed.; Elsevier: Amsterdam, 1992; Chapter 2.
(3) (a) Mandolini, L.; Masci, B. J . Am. Chem. Soc. 1977, 99, 7709.
(b) Ercolani, G.; Mandolini, L.; Masci, B. J . Am. Chem. Soc. 1981, 103,
2780. (c) Bowsher, B. R.; Rest, A. J . Inorg. Chim. Acta 1980, 45, L5.
(d) Cacciapaglia, R.; Mandolini, L. Chem. Soc. Rev. 1993, 221.
(4) For a review on early thiocrown ether syntheses see: Bradshaw,
J . S.; Hui, J . Y. K. J . Heterocycl.Chem. 1974, 11, 649.
(5) (a) Dietrich, B.; Lehn, J .-M.; Sauvage, J . P. J . Chem. Soc., Chem.
Commun. 1970, 1055. (b) Alberts, A. H.; Annunziata, R.; Lehn, J .-M.
J . Am. Chem. Soc. 1977, 99, 8502. (c) Vo¨gtle, F.; Neumann, P.; Zuber,
M. Chem. Ber. 1972, 105, 2955.
aluminum isoproxide cocktail are effective templates in several
thiocrown ether syntheses: (a) Edema, J . J . H.; Stock, H. T.; Buter,
J .; Kellogg, R. M.; Smeets, W. J . J .; Spek, A. L. Tetrahedron 1993, 49,
4355. (b) Edema, J . J . H.; Stock, H. T.; Buter, J .; Kellogg, R. M.; Smeets,
W. J . J .; Spek, A. L.; Van Bolhuis, F. Angew. Chem., Int. Ed. Engl.
1993, 32, 436.
(7) Buter, J .; Kellogg, R. M. J . Chem. Soc., Chem. Commun. 1980,
466.
(8) (a) Buter, J .; Kellogg, R. M. J . Org. Chem. 1981, 46, 4481. (b)
Buter, J .; Kellogg, R. M. Org. Synth. 1987, 65, 1550.
(9) For reviews see: (a) Cooper, S. R. Acc. Chem. Res. 1988, 21, 141.
(b) Cooper, S. R.; Rawle, S. C. Struct. Bond. (Berlin) 1990, 72, 1. (c)
Blake, A. J .; Schro¨der, M. Adv. Inorg. Chem. 1990, 35, 1.
S0022-3263(95)02107-4 CCC: $12.00 © 1996 American Chemical Society

3094 J . Org. Chem., Vol. 61, No. 9, 1996
Stock and Kellogg
(2)
isopropylmagnesium bromide to cyclohexenone (not il-
lustrated).15 In this reaction 4b and 6 were applied as
ligands resulting in asymmetric inductions of 16 and 17%
ee, respectively. These results are promising in terms
of chemical reactivity but the challenge of obtaining high
ee’s is at the same time clear.
We describe here the syntheses of two new families of
chiral nonracemic thiocrown ethers derived from 1,1′-
binaphthalene-2,2′-diol.
F igu r e 1.
Resu lts
for such transition metal ions, the observed stability
constants are often disappointingly small.9 In general,
thiocrown ethers show smaller macrocyclic effects than
their corresponding oxo- and aza-analogs.10,11 This is
chiefly due to the tendency of the sulfide linkages to
arrange themselves outside (exodentate) of the cavity.12
The unit -SCH2CH2S- tends toward an anticonforma-
tion rather than the gauche conformation favored by
-N(R)CH2CH2N(R)- and -OCH2CH2O- segments.
Despite these conformational problems and their effect
on complexation behavior, thiocrown ethers remain an
interesting class of ligands. Both the capacity of sulfides
to stabilize lower oxidation states of transition metal ions
as well as the relative stability of sulfides compared to
the more often used phosphines toward oxidation are
obvious plus points. Moreover, sulfide linkages do not
readily participate in protic equilibria as do amines. The
possibility of “tuning” the coordination chemistry of
thiocrown ethers by varying the ring size and the number
of complexation sites is well within synthetic reach.13
Application of chiral nonracemic thiocrown ethers as
ligands for asymmetric syntheses catalyzed by a transi-
tion metal is also a potent area for application of these
compounds, and the present work is intended as a step
toward that goal.
Axially dissymmetric 1,1′-binaphthalene-2,2′-diol (10)
has been used as the chiral component for the prepara-
tion of all the compounds described here. There are two
obvious retrosynthetic approaches to simple thiocrown
ethers derived from 10 (Scheme 1, eq 3).
Path A is less attractive because of the need for
â-chloro sulfides as the chain components; such com-
pounds are powerful vesicants and in our experience
dangerous. In our experience the use of leaving groups
other than chloride does not provide a viable remedy to
this problem. Attachment of two functionalized arms as
shown in path B allows one to avoid this complication.
Path B requires that bis-alkylation of 10 be achieved. We
wanted to use commercially available enantiomerically
pure 10, rather than to synthesize racemic thiocrown
ethers followed by optical resolution. For this reason
racemization during the synthetic steps must be avoided.
We noted, however, the report by Cram that enantiomer-
ically pure 10 is 69% racemized when it is stirred for 23
h in a 0.67 M KOH solution in n-butanol at 118 °C and
72% racemized in a 1:1 mixture of dioxane and 20%
aqueous HCl at 100 °C, but is optically stable under
neutral conditions in dioxane-water at 100 °C.16 Under
sufficiently acidic or basic conditions the phenolic groups
in 10 are charged, resulting in elongation of the biaryl
bond, thereby diminishing the rotational barrier along
this axis, making the molecule more prone to racemiza-
tion. The possibility of racemization of 10 during alkyla-
tion (under basic conditions) obviously has to be checked.
Enantiomerically pure 10 (ee >99.9%, determined by
HPLC) was alkylated by stirring a mixture of 1 equiv of
10 (0.067 M) and 4 equiv of ethyl bromide in the presence
of 3 equiv of base at various temperatures in THF, DMF,
acetone, acetonitrile, and DMF as solvents. Potassium
tert-butoxide, NaH, and K2CO3 were used as bases. Both
the ratio of monoalkylated product 11 to dialkylated 12
and the ee of 12 were examined (eq 4).
At the time this work was initiated (1990) the only
chiral nonracemic thiocrown ethers known were 4-6
(Figure 1).
Compounds 4 and 5 had been applied as ligands in the
Ni(II)-catalyzed cross-coupling reaction of Grignard re-
agent 7 with vinyl bromide 8 (eq 2).14 Although the
chemical yields of 9 in this reaction were good to
excellent, the asymmetric induction was only moderate.
In the presence of 0.3 mol % thiocrown ether 5 the
enantiomeric excess (ee) of 9 was 46%.
Chiral nonracemic thiocrown ethers have also been
applied in the Zn(II)-catalyzed conjugate addition of
Under several conditions conversion to 12 was incom-
plete. However, to our relief, under none of the applied
conditions was there more than 2% racemization. Even
application of basic conditions at elevated temperatures
did not result in substantial racemization. Under all
investigated reaction conditions the first alkylation step,
to give 11, proceeds rapidly, whereas the second alkyla-
(10) (a) Smith, G. F.; Margerum, D. W. J . Chem. Soc., Chem.
Commun 1975, 807. (b) Sokol, L. S. W. S.; Ochrymowycz, L. A.;
Rorabacher, D. B. Inorg. Chem. 1981, 20, 3189. (c) Bach, R. D.;
Vardhan, H. B. J . Org. Chem. 1986, 51, 1609.
(11) Microwave heating is sometimes required for effectuation of
complex formation of thiocrown ethers: Baghurst, D. R.; Cooper, S.
R.; Greene, D. L.; Mingos, D. M. P.; Reynolds, S. M. Polyhedron 1990,
9, 893.
(12) DeSimone, R. E.; Glick, M. D. J . Am. Chem. Soc. 1976, 98, 762.
(13) Konno, T.; Heeg, M. J .; Deutsch, E. Inorg. Chem. 1988, 27, 4113.
(14) (a) Lemaire, M.; Buter, J .; Vriesema, B. K.; Kellogg, R. M. J .
Chem. Soc., Chem. Commun. 1984, 309. (b) Vriesema, B. K.; Lemaire,
M.; Buter, J .; Kellogg, R. M. J . Org. Chem. 1986, 51, 5169. (c) Vriesema,
B. K. Ph.D. Thesis, University of Groningen, the Netherlands, 1986,
Chapter 4.
(15) J ansen, J . F. G. A.; Feringa, B. L. J . Org. Chem. 1990, 55, 4168.
(16) (a) Kyba, E. B.; Koga, K.; Sousa, L. R.; Siegel, M. G.; Cram, D.
J . J . Am. Chem. Soc. 1973, 95, 2692. (b) Kyba, E. P.; Gokel, G. W.; De
J ong, F.; Koga, K.; Sousa, L. R.; Siegel, M. G.; Kaplan, L.; Sogah, G.
D. Y.; Cram, D. J . J . Org. Chem. 1977, 42, 4173.

Thiocrown Ethers Derived from 1,1′-Binaphthalene-2,2′-diol
Sch em e 1
J . Org. Chem., Vol. 61, No. 9, 1996 3095
(3)
tion step, giving 12, is much slower. Thus, during the
reaction there is a high concentration of 11. Apparently,
A somewhat higher yield (89%) of bis-alkylated product
was obtained by using THP-protected 2-chloroethanol as
alkylating agent, but after deprotection with HCl the
total yield of 13 was not higher than the single step
shown in eq 5. Bis-mesylation of 13 was achieved by
reaction with mesyl chloride and triethylamine in the
presence of 4-(N,N-dimethylamino)pyridine (DMAP) as
nucleophilic catalyst.
The ligating properties of thiocrown ether ligands can
be tuned by varying both the ring-size and the positioning
of the heteroatoms within the crown ether. To prepare
more flexible thiocrown ethers dibromide 20, a homologue
of 14 with a chain length of three carbon atoms instead
of two was required. The synthesis of 20 turned out to
be troublesome. The routes examined are summarized
in eq 6 (Scheme 2).
(4)
Alkylation of 10 was carried out with 3-chloro-1-
propanol in DMF at 110 °C. Although 4 equiv of chloride
and of base was used, considerable amounts of mono-
alkylated product 16 were obtained. The yield of bis-
alkylated 15 after purification could not be raised above
59%. The problem was traced to the competitive forma-
tion of 7-chloro-4-oxaheptanol (17). This complication
was avoided by use of THP-protected 18; bis-alkylated
product 19 was obtained as a mixture of diastereomers
in 89% yield and the deprotection step delivered 15 in
95% yield. Bromination of 15 with PBr3/pyridine was,
however, unsatisfactory and provided 20 in only 19%
yield. Reaction of THP ethers with LiBr/BF3‚Et2O or
LiBr/ClSiMe3 are reported to provide directly the ha-
lides;18 however, with 19 only undefinable products were
found. An excellent solution to this problem was found
in the method of Schwarz et al.19 whereby THP ether 19
was brominated directly with triphenylphosphonium
bromide; the dibromide 20 was isolated in 73% yield. A
disadvantage of this reaction, especially when performed
on larger scale, is the huge amount of triphenylphosphine
oxide produced. This byproduct can be removed, how-
ever, by crystallization from toluene/n-octane. The triph-
enylphosphine oxide is washed thoroughly with n-hexane
to recover any remaining 20, which is then purified by
column chromatography.
the rate of racemization of mono-alkylated 11 under basic
conditions at elevated temperatures is very low and the
rate of mono-alkylation of 10 is much higher than its rate
of racemization. After considerable experimentation17 it
was found that the optimized reaction conditions for bis-
ethylation of 10 are the use of K2CO3 as base in DMF at
a temperature of 110 °C. Under these conditions 12 was
obtained in 100% yield and 99.6% ee.
(5)
The procedure used for ring-closure is illustrated for
the preparation of 22 in eq 7. Cyclization of 14 with 1,3-
On applying these reaction conditions to the reaction
of 10 with 2-chloroethanol as alkylating agent 13 was
obtained in 77% yield (eq 5).
(18) (a) Vankar, Y. D.; Shah, K. Tetrahedron Lett. 1991, 32, 1081.
(b) Sato, T.; Tada, T.; Otera, J .; Nozaki, H. Tetrahedron Lett. 1989,
30, 1665.
(19) Schwarz, M.; Oliver, J . E.; Sonnet, P. E. J . Org.Chem. 1975,
40, 2410.
(17) Full details of the investigated procedures can be found in:
Stock, H. T. Ph.D. Thesis, University of Groningen, the Netherlands,
1994.

3096 J . Org. Chem., Vol. 61, No. 9, 1996
Stock and Kellogg
Sch em e 2
(6)
propanedithiol by use of the Cs2CO3/DMF method7,8
afforded thiocrown ether 22 in 30% yield. Ring strain
in 22 is probably the reason for the only moderate yield.
Change of leaving group did not help; analogous cycliza-
tion of dibromide 21, obtained from 14 by reaction with
LiBr in DMSO at 60 °C, gave 22 in essentially the same
yield (eq 7).
1 equiv of ethanol on recrystallization from that solvent.
The structure of the complex is not known. The ethanol
could be removed by column chromatography over silica
gel using toluene/n-hexane as eluent. Macrocycles 30-
33, with other incorporated units, were prepared starting
from either 14 or 20.
In order to check whether racemization had occurred
during any of the synthetic steps used in preparation of
the thiocrown ethers the ee of 24 was determined. HPLC
analysis on a Daicel OT+ column showed the ee be 99.5%,
so no racemization had occurred. We assume this to be
general for all thiocrown ether syntheses described here,
especially since the conditions for alkylation have been
shown not to lead to racemization.
With the intention of maintaining the phenolic groups
of 10 for binding, the synthesis from 10 of 3,3′-substituted
bis-naphthol systems 34 was examined. A simple ret-
rosynthesis is given in eq 8.
(7)
Cram has described the synthesis of racemic 3,3′
disubstituted 35 (X ) morpholine, R ) H) by a Mannich
reaction, but the prolonged high temperatures required
(5 days at 160 °C) would lead to racemization of optically
active 10.21,22 Cram has also reported the preparation
of enantiomerically pure 35 (X ) OH, R ) H) via an
oxidative coupling of 2-hydroxynaphthalene-3-carboxylic
acid followed by resolution and reduction. The overall
yield (21%) is low, however, and we sought an alternative
approach to enantiomerically pure 35.
In initial attempts to achieve 3,3′ functionalization of
10 Vilsmeier-Haack conditions (POCl3/DMF), the Rei-
mer-Tiemann reaction (75% NaOH/CHCl3), reaction
with paraformaldehyde, SnCl4, and 2,6-lutidine,23 and the
Fries rearrangement of the bis-benzoate24 of 10 were
tried. All these approaches in our hands failed.25 More
The thiocrown ethers 23-25 were synthesized in an
analogous manner by cyclization of bis-mesylate 14.
Isolated yields are given in parentheses. The propylene
bridged thiocrown ethers 26 and 27 were prepared from
20. The appropriate dithiols were either commercially
available or were prepared by routes well described in
the literature (Figure 2).
Desper and Gellman have used gem-dimethyl units in
the backbone of thiocrown ethers to achieve rigidity and
preorganization for complexation of metal ions.20 Analo-
gously, we prepared 28 and 29. Compound 29 complexed
(21) (a) Koenig, K. E.; Helgeson, R. C.; Cram, D. J . J . Am. Chem.
Soc. 1976, 98, 4018. (b) Helgeson, R. C.; Tarnowski, T. L.; Cram, D. J .
J . Org. Chem. 1979, 44, 2538.
(22) Cram, D. J .; Helgeson, R. C.; Peacock, S. C.; Kaplan, L. J .;
Domeier, L. A.; Moreau, P.; Koga, K.; Mayer, J . M.; Chao, Y.; Siegel,
M. G.; Hoffman, D. H.; Sogah, G. D. Y. J . Org. Chem. 1978, 43, 1930.
(23) Casiraghi; Casnati; Puglia; Sartori; Terenghi J . Chem. Soc.,
Perkin Trans. 1 1980, 1862.
(20) (a) Desper, J . M.; Gellman, S. H. J . Am. Chem. Soc. 1990, 112,
6732. (b) Desper, J . M.; Gellman, S. H. J . Am. Chem. Soc. 1991, 113,
704. (c) Desper, J . M.; Gellman, S. H.; Wolf, R. E.; Cooper, S. R. J .
Am. Chem. Soc. 1991, 113, 8663. (d) Nazarenko, A. Y.; Izatt, R. M.;
Lamb, J . D.; Desper, J . M.; Matysik, B. E.; Gellman, S. H. Inorg. Chem.
1992, 31, 3990. (e) Desper, J . M.; Vyvyan, J . R.; Mayer, M. J .;
Ochrymowycz, L. A.; Gellman, S. H. Inorg. Chem. 1993, 32, 381.

Thiocrown Ethers Derived from 1,1′-Binaphthalene-2,2′-diol
J . Org. Chem., Vol. 61, No. 9, 1996 3097
F igu r e 2.
To achieve lithiation O-methylation (96%) of 10 was
necessary. Ortho-lithiation of 36 with n-BuLi in the
presence of N,N,N′,N′-tetramethylethylenediamine (TME-
DA) in THF at 0 °C led to the desired product 37, but
the yield was only 24%. Contemporary with our work
Naruta and co-workers27 described the synthesis of the
3,3′-bis-carboxylate of 36 via ortho-lithiation of 36 in
refluxing diethyl ether as solvent. When these conditions
were applied and the bis-lithiated 36 was allowed to react
with DMF, bis-aldehyde 37 was obtained in 76% yield.
HPLC analysis established that 37 was enantiomerically
pure. Reduction to 38 (95%) and bromination (91%) (eq
10) provided dibromide 39 in 63% overall yield starting
from 10.
(8)
success was obtained via an ortho-lithiation route as
illustrated in eq 9.26
(10)
The thiocrown ethers 40-44 were prepared in 40-76%
yield using the cesium thiolate approach described previ-
ously (Figure 3).
Unfortunately, we were completely stymied in our
attempts to demethylate these thiocrown ethers. A brief
description is given of the attempts that have been made
following many of the known protocols for demethylating
(24) Badr, M. Z. A.; Aly, M. M.; Abdel-Latif, F. F. J . Org. Chem.
1979, 44, 3244.
(25) See also: Moneta, W.; Baret, P.; Pierre, J .-L. Bull. Soc. Chim.
Fr. 1988, 995.
(9)
(26) (a) Narasimhan, N. S.; Mali, R. S. Synthesis 1983, 957. (b)
Gschwend, H. W.; Rodriquez, H. R. Org. React. 1979, 26, 35.
(27) Naruta, Y.; Tani, F.; Ishihara, N.; Maruyama, K. J . Am. Chem.
Soc. 1991, 113, 6865.

3098 J . Org. Chem., Vol. 61, No. 9, 1996
Stock and Kellogg
any reaction.30 The same is true of (CH3)3SiI (Table 1,
entries 8 and 9).31 Attempted reactions using other
nucleophiles (Table 1, entries 10-13) either led to
destruction of the ring system or no reaction.32-34
McKervey et al. found that oxocrown ethers are readily
demethylated by LiI in what appears to be an example
of catalysis by a crown ether.35 Reinhoudt et al. report,
however, that larger ring crown ethers fail to demethyl-
ate under these conditions.36,37 When these conditions
were applied to thiocrown ether 42 no reaction took place
(Table 1, entry 14). Attempts to use cations other than
lithium (Table 1, entries 15-17) were to no avail.
Bartsch et al. have reported the use of LiAlH4 in refluxing
THF for deprotection of aryl methyl ethers incorporated
in oxocrown ethers.38 Unfortunately, no reaction was
obtained using these conditions (Table 1, entries 18 and
19).
In view of these failures we turned to routes whereby
methyl ethers are not used for protection of the phenolic
groups. To check whether it is necessary to protect the
phenolic groups 45 was prepared by deprotection of 39
with BBr3 (eq 11). Not unsurprisingly, attempts to
F igu r e 3.
Ta ble 1. Attem p ted Dem eth yla tion of In tr a a n n u la r
Meth oxy Gr ou p s
(11)
entry substrate
conditions
product(s)
1
2
3
4
40
40
42
40
48% HBr, AcOH, reflux, 1 h complex mixture
48% HBr, AcOH, 50 °C, 6 h starting material
48% HBr, AcOH, 100 °C, 1 h complex mixture
2 equiv of BBr3, CH2Cl2,
0 °C, 4 h
starting material
starting material
starting material
starting material
starting material
starting material
cyclize 45 to 46 failed. Reaction took place readily, but
a complex mixture was obtained, from which no products
could be characterized.
The MOM protective group was next investigated as
summarized in eq 12.
Preparation of the bromide 50 (other leaving groups
were also examined) fails undoubtedly because of its
intrinsic instability due to intramolecular participation
5
6
7
8
9
40
40
42
40
42
12 equiv of BBr3, CH2Cl2,
reflux, 18 h
12 equiv of BBr3, CCl4,
reflux, 18 h
12 equiv of BBr3, CH2Cl2,
reflux, 18 h
KI, Me3SiCl, CH3CN,
reflux, 44 h
KI, Me3SiCl, CH3CN,
reflux, 20 h
10
11
12
13
14
15
16
17
42
40
43
40
42
42
40
40
pyridine‚HCl, reflux, 3 h
EtSNa, DMF, reflux, 2 h
EtSNa, DMF, 100 °C, 2 h
NaCN, DMSO, 180 °C, 16 h starting material
LiI, pyridine, reflux, 3 d
AgI, pyridine, reflux, 24 h
complex mixture
complex mixture
starting material
(29) Kawasaki, I.; Matsuda, K.; Kaneko, T. Bull. Chem. Soc. J pn.
1971, 44, 1986.
(30) (a) McOmie, J . F. W.; West, D. E. Organic Synthesis; Wiley:
New York, 1973; p 412. (b) Akimoto, H.; Yamada, S. Tetrahedron 1971,
27, 5999. (c) Te´treau, C.; Lavalette, D.; Cabaret, D.; Geraghty, N.;
Welvart, Z. J . Phys. Chem. 1983, 87, 3234. (d) McOmie, J . W. F.; Watts,
M. L.; West, D. E. Tetrahedron 1968, 24, 2289.
(31) (a) J ung, M. E.; Lyster, M. A. J . Org. Chem. 1977, 42, 3761. (b)
Olah, G. A.; Narang, S. C. Tetrahedron 1982, 38, 2225. (c) Olah, G. A.;
Narang, S. C.; Balaram Gupta, B. G.; Malhotra, R. J . Org. Chem. 1979,
44, 1247.
(32) Curphey, T. J .; Hoffman, E. J .; McDonald, C. Chem. Ind. 1967,
1138.
starting material
starting material
AgCN, DMSO, 100 °C, 48 h starting material
AgCN, DMSO, reflux, 72 h
complex mixture,
containing 37
starting material
starting material
18
19
40
42
LiAlH4, THF, reflux, 20 h
LiAlH4, THF, reflux, 20 h
(33) a) Feutrill, G. I.; Mirrington, R. N. Aust. J . Chem. 1972, 25,
1719. (b) Feutrill, G. I.; Mirrington, R. N. Tetrahedron Lett. 1970, 1327.
(34) McCarthy, J . R.; Moore, J . L.; Crege, R. J . Tetrahedron Lett.
1978, 5183.
(35) Browne, C. M.; Ferguson, G; McKervey, M. A.; Mulholland, D.
L.; O’Connor, T.; Parvez, M. J . Am. Chem. Soc. 1985, 107, 2703.
(36) Van der leij, M.; Oosterink, H. J .; Hall, R. H.; Reinhoudt, D. N.
Tetrahedron 1981, 37, 3661.
aryl methyl ethers.28 Various conditions used for at-
tempted demethylation are summarized in Table 1.
HBr and acetic acid (Table 1, entries 1-3) led either
to no reaction or destruction of the ring systems.29 BBr3
(Table 1, entries 4-7) even in large excess failed to cause
(37) De J ong, F.; Reinhoudt, D. N. Adv. Phys. Org. Chem. 1980, 17,
279.
(28) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd ed.; Wiley & Sons: New York, 1991; Chapter 3, pp 145-
149.
(38) (a) Czech, B. P.; Huh, H.; Bartsch, R. A. J . Org. Chem. 1992,
57, 725. (b) Czech, A.; Czech, B. P.; Desai, D. H.; Hallman, J . L.;
Phillips, J . B.; Bartsch, R. A. J . Heterocycl. Chem. 1986, 23, 1355.

Thiocrown Ethers Derived from 1,1′-Binaphthalene-2,2′-diol
J . Org. Chem., Vol. 61, No. 9, 1996 3099
result in formation of the desired 54, but of 56 (eq 14).
Owing to the low yield of 56 together with the large size
of its protective group45 this compound was considered
to be unsuitable for further exploration in the synthesis
of thiocrown ethers of type 34.
(12)
of oxygen from the MOM group to form the six-membered
oxonium ion. The methylene protective group was also
examined as shown in eq 13.
(13)
Methylene-protected derivative 51 is known,39 but
ortho-lithiation of this material turned out to be very
difficult. The best result obtained even under forcing
conditions was a mixture of monosubstituted 52 in 18%
yield and the desired disubstituted 53 in 29% yield, which
had to be separated by tedious column chromatography.
The approach was abandoned. Apparently, the oxygen
atoms in 51 are improperly oriented for stabilization of
o-lithiums. Various attempts to prepare acetonides
(acetone/acid, trimethyl orthoformate/acid) of 10 also
failed.40-42
Application of phosphepane 5746 (eq 15) and bis-allyl
ether 59 (eq 16) as protected derivatives of 10 failed since
both compounds were unstable under ortho-lithiation
conditions. Bis-allyl derivative 59 seemed most promis-
ing since allyl groups have been successfully applied for
protection of intraannular phenolic groups in oxocrown
ethers.36 Unfortunately, under the strongly basic condi-
tions required for ortho-lithiation of 59 extensive rear-
rangement (not investigated further) occurs.
Several other protecting groups for 10 were examined.
Protection of 10 with dichloro dimethylsilane43,44 did not
An alternative approach to thiocrown ethers bearing
intraannular phenolic groups is by oxidative coupling of
(39) (a) Daub, G. H. J . Org Chem. 1973, 38, 1771. b)Te´treau, C.;
Lavalette, D.; Cabaret, D.; Geraghty, N.; Welvart, Z. J . Phys. Chem.
1983, 87, 3234.
(40) Clode, D. M. Chem. Rev. 1979, 79, 491.
(45) We anticipated difficulties in the ring closing reaction when
large substituents on the phenolic groups are present.
(46) (a) Hulst, A. J . R. L. Ph.D. Thesis, Groningen, the Netherlands,
1994, Chapter 3. (b) Van Basten, A.; Hulst, R.; Kellogg, R. M. J . Chem.
Soc., Perkin Trans. 1, in press.
(41) Lipshutz, B. H.; Barton, J . C. J . Org. Chem. 1988, 53, 4495.
(42) Amarnath, V.; Broom, A. D. Chem. Rev. 1977, 77, 183.
(43) Furusawa, K. Chem. Lett. 1989, 509.
(44) Trost, B. M.; Caldwell, C. G. Tetrahedron Lett. 1981, 22, 4999.

3100 J . Org. Chem., Vol. 61, No. 9, 1996
Stock and Kellogg
Sch em e 3
Ta ble 2. Attem p ted Oxid a tive P h en ol Cou p lin g of 63
entry
oxidant
solvent
water
T (°C)
product(s)
starting material
a
1
2
3
4
5
6
7
8
9
FeCl3
FeCl3
FeCl3
100
reflux
50
reflux
reflux
16
19
18
23
a
MeOH/EtOH 1:2
starting material
starting material
starting material
starting material
polymeric material
polymeric material
polymeric material
polymeric material
b
a
K3Fe(CN)6
MeOH
MeOH
Bu4NI/CH3CN
KOH/water
KOH/MeOH
NiCl2/MeOH
b
Cu(II)(RNH2)4
- e-, 6.0 V
- e-, 3.5 V
- e-, 4.0 V
- e-, 7.5 V
a
b
1.1 equiv of oxidant. 2 equiv of oxidant.
two naphthol units already bearing the thiocrown ether
chain. One such attempt is outlined in eq 17 (Scheme
3).
Starting material 61 was prepared by known proce-
dures47 and was readily converted to 63 in two steps.
Oxidative cyclization of 63 to (racemic) 64 failed under
all conditions examined. The results are summarized in
Table 2.
2,2′-diol have been achieved. These enantiomerically
pure thiocrown ethers are being investigated as ligands
in asymmetric catalysis.17,52 This work will be reported
in due course.
Exp er im en ta l Section
Gen er a l Rem a r k s. All reactions were performed in a
nitrogen atmosphere, unless otherwise stated. Melting points
are uncorrected. Optical rotations were measured at room
temperature (20 °C) at the sodium D line (589 nm) and at the
mercury lines (578, 546, 436, 365 nm). 1H NMR spectra were
recorded at 60, 200, or 300 MHz. 13C NMR spectra were
recorded at 50.3 or 75.4 MHz. Mass spectra were recorded by
Mr. A. Kiewiet. Elemental analyses were performed in the
Microanalytical Department of this laboratory by Mr. H.
Draayer, J . Ebels, J . Hommes, and J . E. Vos. All solvents and
reagents were purified and dried, following standard proce-
dures.53 Reagents were purchased from J anssen Chimica,
Aldrich Chemical Co., and Fluka. 1,1′-Binaphthalene-2,2′-diol
(10) was purchased from Syncom BV. 1,4,7-Trithiaheptane
was purchased from Aldrich Chemical Co. Compounds 36,27
39,27 51,39 61,47 and dithiols 1,5,9-trithianonane,54 1,4,7,10-
tetrathiadecane,55 1,4,8,11-tetrathiaundecane,8b 1,5,10,14-
tetrathiatetradecane,55 2-(mercaptomethyl)-1-propene-3-thiol,56
1,2-benzenedithiol,57 1,2-bis(mercaptomethyl)benzene,58 and
2,2-dimethyl-1,3-propanedithiol56,59 were prepared according
to literature procedures. Compound 5746 was kindly donated
by Dr. R. Hulst. In some substitution reactions 4-(N,N-
Reaction of 63 with oxidants, like FeCl3,48 K3Fe(CN)6,49
and Cu(II)(RNH2)4,50 known to couple efficiently 2-naph-
thol to 1,1′-binaphthalene-2,2′-diol, failed to effect cou-
pling to give 64 (Table 2, entries 1-5). In all these
attempts only starting material was recovered. Our
hopes that transition metals like Fe(III) would act both
as oxidant and template were unfortunately not re-
warded. Attempts to accomplish coupling via electro-
chemical oxidation51 also failed; all attempts resulted in
formation of polymeric material (Table 2, entries 6-9).
In view of the number of unsuccessful efforts to
synthesize thiocrown ethers containing intraannular
phenolic groups we gave up further attempts to prepare
these compounds.
Con clu sion
The syntheses of two types of new and enantiomerically
pure thiocrown ethers derived from 1,1′-binaphthalene-
(47) (a) Yamamoto, K.; Fukushima, H.; Yumioka, H.; Nakazaki, M.
Bull. Chem. Soc. J pn. 1985, 58, 3633. (b) Huisgen, R.; Nakaten, H.
Liebegs Ann. Chem. 1954, 586, 84. (c) Werner, A.; Seybold, W. Ber.
Deutsch. Chem. Ges. 1904, 37, 3661.
(48) (a) Pummerer, R.; Prell, E.; Rieche, A. Chem. Ber. 1926, 59,
2159. (b) Toda, F.; Tanaka, K.; Iwata, S. J . Org. Chem. 1989, 54, 3007.
(49) McDonald, P. D.; Hamilton, G. A. Mechanisms of Phenolic
Oxidative Coupling Reactions. In Oxidation in Organic Chemistry;
Trahanovsky, W. S. Ed.; Academic Press: New York, 1973.
(50) (a) Brussee, J .; Groenendijk, J . L. G.; Te Koppele, J . M.; J ansen,
A. C. A. Tetrahedron 1985, 41, 3313. (b) Feringa, B.; Wynberg, H.
Bioorg. Chem. 1978, 7, 397.
(52) Thiocrown ethers 26 and 42 have been tested as ligands in Ni-
(II)-catalyzed conjugate addition reactions: De Vries, A. H. M.; J ansen,
J . F. G. A.; Feringa, B. L. Tetrahedron 1994, 50, 4479.
(53) Vogel’s Textbook of Practical Organic Chemistry, 4th ed.;
Longman: London, 1978.
(54) Setzer, W. N.; Afshar, S.; Burns, N. L.; Ferrante, L. A.; Hester,
A. M.; Meehan J r., E. J .; Grant, G. J .; Isaac, S. M.; Laudeman, C. P.;
Lewis, C. M.; VanDerveer, D. G. Heteroatom. Chem. 1990, 1, 375.
(55) Wolf, R. E., J r.; Hartman, J .-A. R.; Storey, J . M. E.; Foxman,
B. M.; Cooper, S. R. J . Am. Chem. Soc. 1987, 109, 4328.
(56) Houk, J .; Whitesides, G. M. J . Am. Chem. Soc. 1987, 109, 6825.
(57) Giolando, D. M.; Kirschbaum, K. Synthesis 1992, 451.
(58) Mayerle, J . J .; Denmark, S. E.; DePamphilis, B. V.; Ibers, J .
A.; Holm, R. H. J . Am. Chem. Soc. 1975, 97, 1032.
(51) (a) Kashiwagi, Y.; Ono, H.; Osa, T. Chem. Lett. 1993, 81. (b)
Zweig, A.; Maurer, A. H.; Roberts, B. G. J . Org. Chem. 1967, 32, 1322.
(c) Papouchado, L.; Sandford, R. W.; Petrie, G.; Adams, R. N. J .
Electroanal. Chem. 1975, 65, 275.
(59) Eliel, E. L.; Rao, V. S.; Smith, S.; Hutchins, R. O. J . Org. Chem.
1975, 40, 524.

Thiocrown Ethers Derived from 1,1′-Binaphthalene-2,2′-diol
J . Org. Chem., Vol. 61, No. 9, 1996 3101
dimethylamino)pyridine (DMAP) was added as hypernucleo-
philic catalyst.60
mmol) and K2CO3 (19.4 g, 140 mmol) were dissolved in DMF
(250 mL) and stirred at 110 °C for 17 h. The reaction mixture
was filtered and concentrated under reduced pressure. The
residue was taken up in CH2Cl2 (300 mL) and washed with
water (100 mL) and 4 N NaOH (2 × 150 mL). The organic
layer was dried (MgSO4) and concentrated under reduced
pressure to give a pale yellow oil (21.05 g). The oil was heated
in a bulb to bulb distillation apparatus (0.1 mmHg, 225 °C) to
remove dimeric byproduct 17. The residue of distillation
(16.25 g) was purified by column chromatography (silica gel,
Et2O) to give the mono-alkylated product (16, 21%). Further
elution (EtOAc) gave 15 (59%) as a white foam.
Compound 16: mp 179.6-181.0 °C; [R]578 ) +30.4 (c )
0.938, THF), [R]546 ) +39.6, [R]436 ) +152.5, [R]365 ) +843.4;
1H NMR (CDCl3, 300 MHz) δ 1.65-1.71 (m, 2 H), 1.95 (s, br,
1 H), 3.28-3.30 (m, 2 H), 4.08-4.15 (m, 2 H), 5.94 (s, br, 1 H),
7.16 (d, J ) 8.8 Hz, 1 H), 7.27-7.47 (m, 7 H), 7.92-7.96 (m, 3
H), 8.04 (d, J ) 9.5 Hz, 1 H); 13C NMR (CDCl3, 75.4 MHz) δ
31.3 (t), 59.7 (t), 67.2 (t), 114.9 (d), 116.8 (s), 117.5 (d), 123.1
(d), 124.0 (d), 124.5 (d), 124.9 (d), 126.2 (d), 126.9 (d), 127.9
(d), 128.0 (d), 128.8 (s), 129.3 (s), 129.6 (d), 130.4 (d), 133.6
(s), 133.8 (s), 151.1 (s), 154.7 (s); HRMS m/ e (M+) calcd
344.141, obsd 344.142.
2,2′-Dieth oxy-1,1′-bin a p h th yl (12).61 Op tim ized Rea c-
tion Con d ition s.17 A solution of (R)-10 (286 mg, 1.00 mmol),
K2CO3 (0.41 g, 3.0 mmol), and ethyl bromide (0.30 mL, 4.0
mmol) in DMF (15 mL) was stirred at 110 °C for 24 h. The
reaction mixture was cooled to rt, filtered, and concentrated
under reduced pressure to give a white solid (330 mg). The
crude product was filtered over a short silica gel column (CH2-
1
Cl2) to give 12 (100%): mp 135.1-136.2 °C; H NMR (CDCl3,
200 MHz) δ 1.10 (t, J ) 7.0 Hz, 6 H), 4.09 (q, J ) 7.0 Hz, 4 H),
7.17-7.49 (m, 8 H), 7.90 (d, J ) 7.9 Hz, 2 H), 7.98 (d, J ) 9.0
Hz, 2 H); 13C NMR (CDCl3, 50.3 MHz) δ 15.0 (q), 65.2 (t), 115.9
(d), 120.7 (s), 123.4 (d), 125.5 (d), 126.1 (d), 127.8 (d), 129.1
(d), 129.3 (s), 134.2 (s), 154.3 (s); ee 99.6%, as determined by
HPLC.62
(R)-(-)-2,2′-Bis(2-h yd r oxyeth oxy)-1,1′-bin a p h th yl (13).
The literature procedure for preparation of the (S)-enanti-
omer16 was improved and applied for preparation of both (R)-
and (S)-13: (R)-(+)-10 (8.62 g, 30.1 mmol), 2-chloroethanol (8.0
mL, 119 mmol), and K2CO3 (16.6 g, 120 mmol) were dissolved
in DMF (250 mL) and stirred at 110 °C for 17 h. The reaction
mixture was filtrated and concentrated under reduced pres-
sure. The residue was taken up in CH2Cl2 (150 mL) and
washed with water (2 × 100 mL) and 2 N NaOH (100 mL).
The organic layer was dried (MgSO4) and concentrated under
reduced pressure to give a pale yellow oil (12.15 g). The crude
product was purified by column chromatography (silica gel,
Et2O) giving 13 (77%) as a white foam: mp 130-134 °C; [R]578
) -26.4 (c ) 0.762, THF), [R]546 ) -26.6; [R]436 ) +14.0; [R]365
) +543.8; 1H NMR (CDCl3, 200 MHz) δ 2.42 (s, br, 2 H), 3.45-
3.70 (m, br, 4 H), 3.98-4.07 (m, 2 H), 4.18-4.28 (m, 2 H), 7.13-
7.48 (m, 8 H), 7.91 (d, J ) 7.3 Hz, 2 H), 8.00 (d, J ) 9.0 Hz, 2
H); 13C NMR (CDCl3, 50.3 MHz) δ 61.2 (t), 71.7 (d), 115.9 (d),
120.3 (s), 124.1 (d), 125.2 (d), 126.7 (d), 128.2 (d), 129.6 (s),
129.8 (d), 133.8 (s), 153.5 (s); HRMS m/ e (M+) calcd 374.152,
obsd 374.152.
Compound 15: mp 66.3-68.3 °C; [R]589 ) +41.0 (c ) 0.442,
THF), [R]578 ) +50.2, [R]546 ) +60.9, [R]436 ) +172.0, [R]365
)
+716.1; 1H NMR (CDCl3, 200 MHz) δ 1.56-1.80 (m, 4 H), 2.06
(s, br, 2 H), 3.29-3.31 (m, br, 4 H), 4.02-4.27 (m, 4 H), 7.13-
7.49 (m, 8 H), 7.90 (d, J ) 7.7 Hz, 2 H), 8.00 (d, J ) 9.0 Hz, 2
H); 13C NMR (CDCl3, 50.3 MHz) δ 31.5 (t), 60.1 (t), 67.6 (t),
114.8 (d), 119.7 (s), 123.7 (d), 125.1 (d), 126.3 (d), 127.9 (d),
129.3 (s), 129.5 (d), 133.7 (s), 153.7 (s); HRMS m/ e (M+) calcd
402.183, obsd 402.183.
(S)-15 by Hyd r olysis of (a S)-19. To a stirred solution of
(aS)-19 (10.18 g, 17.9 mmol) in acetone (200 mL) at rt was
added 6 N HCl (23 mL, 138 mmol). After 17 h the reaction
mixture was neutralized with Na2CO3 and concentrated under
reduced pressure. The residue was taken up in CH2Cl2 (300
mL) and washed with water (2 × 150 mL) and 0.5 N NaOH
(100 mL). The organic layer was dried (MgSO4) and concen-
trated under reduced pressure to give a yellow foam (7.14 g).
The crude product was purified by column chromatography
(silica gel, EtOAc) to give 15 (95%) as a white foam: mp 66.7-
68.2 °C; [R]D ) -40.8 (c ) 0.526, THF), [R]578 ) -49.7, [R]546
) -60.4, [R]436 ) -170.7, [R]365 ) -709.2. The NMR data were
in accord with the data for the product obtained from 10 (vide
supra).
(a S)-2,2′-Bis(3-(p yr a n yl-2-oxy)p r op oxy)-1,1′-b in a p h -
th yl (19). (S)-(-)-10 (5.72 g, 20.0 mmol), 2-(3-chloro-1-
propoxy)pyran63 (7.50 g, 42.0 mmol), and K2CO3 (5.80 g, 42
mmol) were dissolved in DMF (150 mL) and stirred at 110 °C
for 4 h. The reaction mixture was concentrated under reduced
pressure, and the residue was taken up in CH2Cl2 (200 mL)
and washed with water (2 × 150 mL), 2 N NaOH (2 × 150
mL), and brine (150 mL). The organic layer was dried (MgSO4)
and concentrated under reduced pressure to give a brown oil
(10.61 g). The crude product was purified by column chroma-
tography (silica gel, Et2O) to give 19 (89%) as a yellow oil: 1H
NMR (CDCl3, 300 MHz) δ 1.38-1.78 (m, 16 H), 2.87-3.06 (m,
2 H), 3.33- 3.45 (m, 4 H), 3.65-3.75 (m, 2 H), 4.03-4.16 (m, 5
H), 4.28-4.31 (m, 1 H), 7.15-7.47 (m, 8 H), 7.88 (d, J ) 8.1
Hz, 2 H), 7.96 (d, J ) 9.2 Hz, 2 H); 13C NMR (CDCl3, 75.4
MHz) δ 19.4 (t), 19.6 (t), 25.3 (t), 29.5 (t), 29.6 (t), 30.4 (t), 61.9
(t), 62.0 (t), 62.1 (t), 63.6 (t), 63.7 (t), 63.8 (t), 66.2 (t), 66.3 (t),
66.4 (t), 98.6 (d), 98.7 (d), 115.4 (d), 120.2 (s), 120.3 (s), 123.2
(d), 123.3 (d), 125.2 (d), 125.2 (d), 125.9 (d), 127.6 (d), 127.6
(d), 128.9 (d), 129.0 (s), 133.9 (s), 154.0 (s), 154.1 (s); HRMS
m/ e (M+) calcd 570.298, obsd 570.298.
(S)-(+)-13.16 By the same procedure (S)-13 (71%) was ob-
tained: mp 131-134 °C; [R]578 ) +25.1 (c ) 0.958, THF), [R]546
) +25.4 (lit.16 [R]546 ) +23.2 (c ) 1.05, THF)); [R]436 ) -13.4;
[R]365 ) +522.6.
(R)-(-)-2,2′-Bis(2-(m esyloxy)eth oxy)-1,1′-bin aph th yl (14).
To a solution of (R)-13 (1.87 g, 5.0 mmol), triethylamine (1.5
mL, 11 mmol), and DMAP (20 mg, 0.16 mmol) in CH2Cl2 (75
mL) was dropwise added methanesulfonyl chloride (0.85 mL,
11.0 mmol) at 0 °C. The reaction mixture was stirred at room
temperature for 17 h and subsequently washed with water (2
× 50 mL). The organic layer was dried (MgSO4) and concen-
trated under reduced pressure to give a viscous, slightly yellow
oil (2.80 g). The crude product was crystallized from toluene/
n-hexane to give 14 (95%) as white crystals: mp 143-144 °C;
[R]578 ) -30.5 (c ) 0.650, THF); [R]546 ) -32.8; [R]436 ) -24.3;
[R]365 ) +237; 1H NMR (CDCl3, 300 MHz) δ 1.83 (s, 6 H), 3.93-
4.11 (m, 8 H), 6.90-7.25 (m, 8 H), 7.66-7.71 (m, 2 H), 7.77-
7.82 (m, 2 H); 13C NMR (CDCl3, 75.4 MHz) δ 35.9 (q), 67.0 (t),
68.7 (t), 114.8 (d), 119.7 (s), 124.1 (d), 125.0 (d), 126.7 (d), 127.8
(d), 129.3 (s), 129.6 (d), 133.7 (s), 153.2 (s); HRMS m/ e (M+)
calcd 530.107, obsd 530.106. Anal. Calcd (found) for
C26H26O8S2: C, 58.85 (58.67); H, 4.94 (5.03); S, 12.09 (11.98).
(S)-(+)-14. By the same procedure (S)-14 (92%) was
obtained: mp 142-143 °C; [R]578 ) +30.4 (c ) 0.834, THF);
[R]546 ) +32.6; [R]436 ) +24.4; [R]365 ) -234.
(R)-(+)-2,2′-Bis(3-h yd r oxyp r op oxy)-1,1′-bin a p h th yl (15)
an d (R)-(+)-2-(3-Hydr oxypr opoxy)-2′-h ydr oxy-1,1′-bin aph -
th yl (16). (R)-15 a n d (R)-16 by a lk yla tion of (R)-(+)-10.
(R)-(+)-10 (10.0 g, 35.0 mmol), 3-chloro-1-propanol (13.2 g, 100
2,2′-Bis(3-br om op r op oxy)-1,1′-bin a p h th yl (20). (S)-20
F r om 19. Triphenylphosphine (21.2 g, 81 mmol) was dissolved
in CH2Cl2 (150 mL) and cooled to 0 °C. Bromine (4.14 mL, 81
mmol) was slowly added, initially forming a white precipitate
that turns orange upon further adding. After all the bromine
had been added the reaction mixture was stirred at 0 °C for
(60) (a) Scriven, E. F. V. Chem. Soc. Rev. 1983, 13, 129. (b) Ho¨fle,
G.; Steglich, W.; Vorbru¨ggen, H. Angew. Chem., Int. Ed. Engl. 1978,
17, 569.
(61) Zinke, A.; Dengg, R. Monatsh. Chem. 1922, 43, 127.
(62) A water-cooled 250 × 4.6 mm (+)-poly(triphenylmethyl meth-
acrylate) column (DAICEL OT+) was used, with n-hexane/2-propanol
100:1 as eluent (flow 0.5 mL/min); retention times: (S)-12, 34.76 min;
(R)-12, 42.95 min. (a) Okamoto, Y.; Honda, S.; Okamoto, I.; Yuki, K.;
Murata, S.; Noyori, R.; Takaya, H. J . Am. Chem. Soc. 1981, 103, 6971.
(b) Okamoto, Y.; Hatada, K. J . Liq. Chromatogr. 1986, 9, 369.
(63) Parham, W. E.; Anderson, E. L. J . Am. Chem. Soc. 1948, 70,
4187.

3102 J . Org. Chem., Vol. 61, No. 9, 1996
Stock and Kellogg
45 min. A solution of 19 (8.6 g, 15.1 mmol) in CH2Cl2 (30 mL)
was added in 15 min at 0 °C, and the reaction mixture was
stirred at room temperature for 17 h. CH2Cl2 (100 mL) was
added, and the reaction mixture was washed twice with water.
The organic layer was dried (MgSO4) and concentrated under
reduced pressure to give a light brown solid (22.3 g). The solid
was recrystallized from toluene/n-octane to give white crystals
(7.28 g, triphenylphosphine oxide). The mother liquor was
concentrated under reduced pressure and purified by column
chromatography (silica gel, CH2Cl2/n-hexane 1:1) to give a
yellowish brown oil (7.00 g). This oil was boiled in methanol
and decanted while hot. The decantate was concentrated
under reduced pressure to give 20 (73%) as a yellow oil.
Analytically pure material was obtained by additional column
chromatography (silica gel, toluene) to give 20 as a colorless
H), 7.98 (d, J ) 8.8 Hz, 2 H); 13C NMR (CDCl3, 75.4 MHz): δ
30.0 (t), 30.3 (t), 31.2 (t), 70.5 (t), 116.8 (d), 121.2 (s), 123.8
(d), 125.3 (d), 126.2 (d), 127.8 (d), 129.3 (d), 129.6 (s), 133.9
(s), 154.1 (s); HRMS m/ e (M+) calcd 446.137, obsd 446.136.
(R)-22 fr om (R)-21 a n d 1,3-P r op a n ed ith iol. Reaction of
(R)-21 (500 mg, 1.00 mmol) and 1,3-propanedithiol (100 mg,
1.00 mmol) afforded (R)-22 in 31% yield: mp 64.3-64.6 °C;
[R]578 ) +204.8 (c ) 0.968, THF), [R]546 ) +242.0, [R]436
+538.0, [R]365 ) +1624.
)
(S)-(-)-2,3:4,5-Di(1,2-n a p h th o)-1,6-d ioxa -9,12-d ith ia cy-
clotetr a d eca -2,4-d ien e (23). According to the procedure
described for the synthesis of 22, from (S)-14 and 1,2-
ethanedithiol: yield 32%; mp 75.7-76.2 °C; [R]578 ) -153.5 (c
) 0.998, THF), [R]546 ) -183.0, [R]436 ) -444.6, [R]365 ) -1576;
1H NMR (CDCl3, 300 MHz) δ 2.47-2.88 (m, 8 H), 4.06-4.41
(m, 4 H), 7.12-7.53 (m, 8 H), 7.90 (d, J ) 8.1 Hz, 2 H), 7.99
(d, J ) 8.8 Hz, 2 H); 13C NMR (CDCl3, 75.4 MHz) δ 30.2 (t),
31.5 (t), 72.3 (t), 117.3 (d), 121.3 (s), 124.0 (d), 125.1 (d), 126.3
(d), 127.8 (d), 129.4 (d), 129.7 (s), 133.8 (s), 153.9 (s); HRMS
m/ e (M+) calcd 432.122, obsd 432.122.
(R)-(+)-23: yield 30%; mp 74.8-75.9 °C; [R]578 ) +156.6 (c
) 0.554, THF), [R]546 ) +186.4, [R]436 ) +455.0, [R]365 ) +1612.
(R)-23 fr om (R)-21 a n d 1,2-eth a n ed ith iol: yield 33%; mp
75.4-76.4 °C; [R]578 ) +156.0 (c ) 0.660, THF), [R]546 ) +186.1,
[R]436 ) +455.1, [R]365 ) +1608.
oil: [R]D ) -46.5 (c ) 0.400, THF), [R]578 ) -49.8, [R]546
)
-59.8, [R]436 ) -145.5, [R]365 ) -442.0; 1H NMR (CDCl3, 300
MHz) δ 1.92-1.99 (m, 4 H), 2.84-3.02 (m, 4 H), 4.06-4.20
(m, 4 H), 7.22-7.48 (m, 8 H), 7.92 (d, J ) 8.1 Hz, 2 H), 8.00
(d, J ) 9.2 Hz, 2 H); 13C NMR (CDCl3, 75.4 MHz) δ 30.0 (t),
32.4 (t), 66.8 (t), 115.3 (d), 120.3 (s), 123.6 (d), 125.2 (d), 126.3
(d), 127.7 (d), 129.2 (s), 129.3 (d), 133.8 (s), 153.7 (s); HRMS
m/ e (M+) calcd 526.014, obsd 526.013. Anal. Calcd (found)
for C26H24O2Br2: C, 59.11 (59.19); H, 4.58 (4.58); Br, 30.25
(30.15).
(R)-20 fr om 15. Compound 15 (7.93 g, 19.7 mmol) was
dissolved in THF (150 mL). Pyridine (0.61 mL, 7.5 mmol) was
added, and the reaction mixture was cooled to 0 °C. Phos-
phorus tribromide (2.0 mL, 21.3 mmol) was added in 5 min,
giving a white precipitate. The reaction mixture was allowed
to warm to room temperature. After being stirred at ambient
temperature for 20 h the reaction mixture was concentrated
under reduced pressure. The residue was taken up in benzene
(100 mL) and water (150 mL). The benzene layer was
separated, and the water layer was extracted with benzene (2
× 75 mL). The combined organic layers were dried (MgSO4)
and concentrated under reduced pressure to give a yellow oil
(16.17 g). The crude product was purified by column chroma-
tography (silica gel, toluene) to give 20 (19%) as a colorless
(R)-(+)-2,3:4,5-Di(1,2-n a p h th o)-1,6-d ioxa -9,12,15-tr ith i-
a cycloh ep ta d eca -2,4-d ien e (24). According to the procedure
described for the synthesis of 22, from (R)-14 and 1,4,7-
trithiaheptane: yield 58%; mp 54.3-56.1 °C; [R]578 ) +90.7 (c
) 1.060, THF), [R]546 ) +109.6, [R]436 ) +283.8, [R]365 ) +1065;
1H NMR (CDCl3, 300 MHz) δ 2.28-2.97 (m, 12 H), 3.85-4.02
(m, 4 H), 6.97-7.32 (m, 8 H), 7.72 (d, J ) 8.0 Hz, 2 H), 7.81
(d, J ) 8.8 Hz, 2 H); 13C NMR (CDCl3, 75.4 MHz) δ 30.9 (t),
31.2 (t), 32.2 (t), 71.4 (t), 116.6 (d), 121.0 (s), 123.9 (d), 125.3
(d), 126.3 (d), 127.8 (d), 129.5 (d), 129.6 (s), 133.9 (s), 153.9
(s); HRMS m/ e (M+) calcd 492.125, obsd 492.126. Anal. Calcd
(found) for C28H28O2S3: C, 68.26 (67.83); H, 5.73 (5.69); S, 19.52
(19.24).
(S)-24 fr om (S)-14 a n d 1,4,7-tr ith ia h ep ta n e: yield 52%;
oil: [R]D ) +46.0 (c ) 0.544, THF), [R]578 ) +49.1, [R]546
)
mp 54.8-56.1 °C; [R]578 ) -91.7 (c ) 0.542, THF), [R]546
)
+58.9, [R]436 ) +144.0, [R]365 ) +436.9; 1H NMR and 13C NMR
spectra were identical to the spectra of (S)-20 obtained from
19.
-110.6, [R]436 ) -287.2, [R]365 ) -1081; ee > 99.5% as
determined by HPLC.64
(R)-(+)-2,3:4,5-Di(1,2-n a p h th o)-1,6-d ioxa -9,12,16,19-tet-
r a th ia cyclou n eicosa -2,4-d ien e (25). According to the pro-
cedure described for the synthesis of 22, from (R)-14 and
1,4,8,11-tetrathiaundecane: yield 54% as a colorless oil; [R]D
) +130.3 (c ) 0.284, THF), [R]578 ) +141.9, [R]546 ) +168.0,
[R]436 ) +376.1, [R]365 ) +1081; 1H NMR (CDCl3, 200 MHz) δ
1.86 (quintet, J ) 6.8 Hz, 2 H), 2.39-2.74 (m, 16 H), 4.05-
4.35 (m, 4 H), 7.16-7.50 (m, 8 H), 7.90 (d, J ) 7.8 Hz, 2 H),
8.00 (d, J ) 9.0 Hz, 2 H); 13C NMR (CDCl3, 50.3 MHz) δ 29.8
(t), 30.6 (t), 31.2 (t), 32.4 (t), 32.5 (t), 70.5 (t), 115.7 (d), 120.7
(s), 124.0 (d), 125.4 (d), 126.5 (d), 127.9 (d), 129.6 (d), 134.1
(s), 153.9 (s); HRMS m/ e (M+) calcd 566.144, obsd 566.144.
(S)-(-)-2,3:4,5-Di(1,2-n a p h t h o)-1,6-d ioxa -10,14-d it h ia -
cycloh ep ta d eca -2,4-d ien e (26). According to the procedure
described for the synthesis of 22, from (S)-20 and 1,3-
propanedithiol: yield 61%; mp 107.6-109.9 °C; [R]578 ) -163.7
(R)-(+)-2,2′-Bis(2-br om oeth oxy)-1,1′-bin a p h th yl (21). A
solution of (R)-14 (2.43 g, 4.58 mmol) and anhydrous lithium
bromide (1.20 g, 13.8 mmol) in DMSO (40 mL) was stirred at
60 °C for 20 h. Water (50 mL) was added, and the mixture
was extracted with Et2O (3 × 50 mL). The combined Et2O
layers were washed with brine (75 mL), dried (MgSO4), and
concentrated under reduced pressure to give a yellow oil (2.25
g). The crude product was purified by column chromatography
(silica gel, CH2Cl2) to give 21 (94%) as colorless crystals.
Recrystallization from CH2Cl2/n-hexane afforded very long
needles: mp 91.2-92.4 °C; [R]D ) +45.6 (c ) 0.296, THF), [R]578
1
) +50.3, [R]546 ) +59.8, [R]436 ) +150.0, [R]365 ) +552.4; H
NMR (CDCl3, 200 MHz) δ 3.31 (t, J ) 6.6 Hz, 4 H), 4.21-4.42
(m, 4 H), 7.26; 13C NMR (CDCl3, 50.3 MHz) δ 29.5 (t), 70.0 (t),
116.4 (d), 121.1 (s), 124.3 (d), 125.5 (d), 126.7 (d), 128.1 (d),
129.8 (d), 129.9 (s), 134.1 (s), 153.7 (s); HRMS m/ e (M+) calcd
497.983, obsd 497.983.
(c ) 1.098, THF), [R]546 ) -193.8, [R]436 ) -446.2, [R]365
)
-1433; 1H NMR (CDCl3, 300 MHz) δ 1.69-1.78 (m, 6 H), 2.25-
2.40 (m, 4 H), 2.53 (t, J ) 7.0 Hz, 4 H), 3.83-3.90 (m, 2 H),
4.27-4.34 (m, 2 H), 7.10-7.47 (m, 8 H), 7.88 (d, J ) 8.0 Hz, 2
H), 7.96 (d, J ) 8.8 Hz, 2 H); 13C NMR (CDCl3, 75.4 MHz) δ
27.6 (t), 29.3 (t), 29.6 (t), 30.4 (t), 67.5 (t), 115.5 (d), 120.4 (s),
123.4 (d), 125.2 (d), 126.1 (d), 127.7 (d), 129.1 (d), 129.2 (s),
134.0 (s), 154.1 (s); HRMS m/ e (M+) calcd 474.169, obsd
474.169.
(S)-(-)-2,3:4,5-Di(1,2-n a p h th o)-1,6-d ioxa -10,14,18-tr ith i-
a cyclou n eicosa -2,4-d ien e (27). According to the procedure
described for the synthesis of 22, from (S)-20 and 1,5,9-
trithianonane: yield 47% as a colorless oil; [R]D ) -130.7 (c
(S)-(-)-2,3:4,5-Di(1,2-n a p h th o)-1,6-d ioxa -9,13-d ith ia cy-
clop en ta d eca -2,4-d ien e (22). Typ ica l P r oced u r e. A solu-
tion of (S)-14 (2.65 g, 5.0 mmol) and 1,3-propanedithiol (0.51
g, 5.1 mmol) in DMF (150 mL) was added dropwise to a stirred
suspension of Cs2CO3 (3.43 g, 10.5 mmol) in DMF (600 mL) at
60 °C over a period of 10-18 h. The reaction mixture was
filtered and concentrated under reduced pressure. The residue
was taken up in CH2Cl2 (100 mL) and washed with water (2
× 100 mL) and 2 N NaOH (2 × 100 mL). The organic layer
was dried (MgSO4) and concentrated under reduced pressure
to give a yellow foam (2.64 g). The crude product was purified
by column chromatography (silica gel, toluene) to give 22 (30%)
as a white foam: mp 64.2-64.6 °C; [R]578 ) -201.9 (c ) 1.054,
THF), [R]546 ) -238.4, [R]436 ) -530.8, [R]365 ) -1596; 1H NMR
(CDCl3, 300 MHz) δ 1.73-1.88 (m, 2 H), 2.44-2.68 (m, 8 H),
4.08-4.20 (m, 4 H), 7.15-7.47 (m, 8 H), 7.89 (d, J ) 7.7 Hz, 2
(64) A water-cooled DAICEL OT+ column was used, with n-hexane/
2-propanol 9:1 as eluent (flow 1.0 mL/min); a solution of 24 in
2-propanol was injected; retention times: (S)-24, 28.3 min; (R)-24, 48.0
min.

Thiocrown Ethers Derived from 1,1′-Binaphthalene-2,2′-diol
) 0.668, THF), [R]578 ) -142.2, [R]546 ) -167.4, [R]436
J . Org. Chem., Vol. 61, No. 9, 1996 3103
)
(S)-(-)-2,3:4,5-Di(1,2-n a p h t h o)-1,6-d ioxa -10,15-d it h ia -
12,13-(1,2-ben zo)cycloocta d eca -2,4-d ien e (33). According
to the procedure described for the synthesis of 22, from (S)-20
and 1,2-bis(mercaptomethyl)benzene: yield 61%; mp 75.9-
77.8 °C; [R]D ) -160.8 (c ) 0.306, THF), [R]578 ) -177.8, [R]546
1
-368.1, [R]365 ) -1060; H NMR (CDCl3, 200 MHz) δ 1.73-
1.94 (m, 8 H), 2.32 (t, J ) 7.1 Hz, 4 H), 2.48-2.63 (m, 4 H),
2.68 (t, J ) 7.1 Hz, 4 H), 3.97-4.07 (m, 2 H), 4.19-4.30 (m, 2
H), 7.22-7.45 (m, 6 H), 7.54 (d, J ) 9.0 Hz, 2 H), 7.96 (d, J )
7.8 Hz, 2 H), 8.04 (d, J ) 9.0 Hz, 2 H); 13C NMR (CDCl3, 50.3
MHz) δ 28.3 (t), 29.4 (t), 29.7 (t), 30.3 (t), 30.8 (t), 68.0 (t), 115.8
(d), 120.6 (s), 123.7 (d), 125.5 (d), 126.4 (d), 128.0 (d), 129.4
(d), 129.5 (s), 134.2 (s), 154.3 (s); HRMS m/ e (M+) calcd
548.188, obsd 548.188.
1
) -210.8, [R]436 ) -491.5, [R]365 ) -1587; H NMR (CDCl3,
200 MHz) δ 1.85-2.02 (m, 4 H), 2.44-2.67 (m, 4 H), 3.98 (AB-
system, J 1 ) 62.0 Hz, J 2 ) 12.0 Hz, 4 H), 3.97-4.08 (m, 2 H),
4.35-4.47 (m, 2 H), 7.34-7.51 (m, 10 H), 7.54 (d, J ) 9.0 Hz,
2 H), 8.03 (d, J ) 8.1 Hz, 2 H), 8.09 (d, J ) 9.0 Hz, 2 H); 13C
NMR (CDCl3, 50.3 MHz): δ 29.3 (t), 29.6 (t), 34.4 (t), 67.6 (t),
115.2 (d), 120.4 (s), 123.7 (d), 125.5 (d), 126.5 (d), 127.8 (d),
128.1 (d), 129.4 (s), 129.5 (d), 130.6 (d), 134.4 (s), 136.4 (s),
154.1 (s); HRMS m/ e (M+) calcd 536.184, obsd 536.184.
(R)-(+)-2,3:4,5-Di(1,2-n a p h t h o)-1,6-d ioxa -9,13-d it h ia -
11,11-d im eth ylcyclotetr a d eca -2,4-d ien e (28). According to
the procedure described for the synthesis of 22, from (R)-14
and 2,2-dimethyl-1,3-propanedithiol: yield 37%; mp 89.2-89.9
°C; [R]D ) +257.6 (c ) 0.304, THF), [R]578 ) +286.2, [R]546
)
(R)-(-)-2,2′-Dim eth oxy-1,1′-bin a p h th yl-3,3′-d ica r ba ld e-
h yd e (37). A solution of (R)-36 (12.56 g, 40.0 mmol) and
TMEDA (31.4 mL, 209 mmol) in Et2O (600 mL) was cooled to
0 °C. A 2.0 M solution of n-BuLi in hexanes (87 mL, 174 mmol)
was added dropwise over a period of 30 min. The mixture was
stirred at 0 °C for 1 h and was then slowly warmed to reflux.
After being refluxed for 16 h the resulting pale brown suspen-
sion was cooled to 0 °C and DMF (25 mL, 320 mmol) was added
dropwise. The mixture was stirred at 0 °C for 90 min, and
then 4 N HCl (120 mL, 480 mmol) was added slowly under
vigorous stirring. The resulting two-phase system was stirred
for 30 min. The organic layer was separated, washed with
0.5 N HCl (200 mL), a saturated NaHCO3 solution (200 mL),
and brine (200 mL), dried (Na2SO4), and concentrated under
reduced pressure to give a yellow solid (14.36 g). The crude
product was filtered over a short column (silica gel, Et2O) and
then recrystallized from 96% EtOH to give 37 (76%) as pale
yellow crystals: mp 156.5-158.3 °C (lit.65 racemate, mp 150
+335.2, [R]436 ) +716.1, [R]365 ) +1981; 1H NMR (CDCl3, 200
MHz) δ 1.05 (s, 6 H), 2.36 (d, J ) 12.6 Hz, 2 H), 2.48-2.60 (m,
2 H), 2.78 (d, J ) 12.6 Hz, 2 H), 2.71-2.96 (m, 2 H), 4.12-
4.30 (m, 4 H), 7.21-7.50 (m, 8 H), 7.93 (d, J ) 7.7 Hz, 2 H),
8.02 (d, J ) 9.0 Hz, 2 H); 13C NMR (CDCl3, 50.3 MHz) δ 27.8
(q), 31.6 (t), 36.4 (s), 41.1 (t), 68.0 (t), 115.7 (d), 123.7 (d), 125.5
(d), 126.4 (d), 128.0 (d), 128.0 (s), 129.4 (d), 134.2 (s), 153.8
(s); HRMS m/ e (M+) calcd 474.169, obsd 474.169.
(S)-(-)-2,3:4,5-Di(1,2-n a p h t h o)-1,6-d ioxa -10,14-d it h ia -
12,12-d im eth ylcycloh ep ta d eca -2,4-d ien e (29). According
to the procedure described for the synthesis of 22, from (S)-20
and 2,2-dimethyl-1,3-propanedithiol: yield 24%; mp 174.6-
176.6 °C; [R]D ) -145.3 (c ) 0.298, THF), [R]578 ) -159.7, [R]546
1
) -189.3, [R]436 ) -434.6, [R]365 ) -1427; H NMR (CDCl3,
200 MHz) δ 1.03 (s, 6 H), 1.72-1.85 (m, 4 H), 2.34-2.72 (m, 8
H), 3.88-3.98 (m, 2 H), 4.22-4.34 (m, 2 H), 7.13-7.39 (m, 6
H), 7.47 (d, J ) 8.9 Hz, 2 H), 7.90 (d, J ) 7.7 Hz, 2 H), 7.98 (d,
J ) 8.9 Hz, 2 H); 13C NMR (CDCl3, 50.3 MHz) δ 27.6 (q), 29.3
(t), 29.5 (t), 35.9 (s), 42.9 (t), 67.4 (t), 115.2 (d), 120.2 (s), 123.4
(d), 125.3 (d), 126.2 (d), 127.9 (d), 129.1 (s), 129.2 (d), 134.1
(s), 154.2 (s); HRMS m/ e (M+) calcd 502.200, obsd 502.200.
(S)-(-)-2,3:4,5-Di(1,2-n a p h th o)-1,6-d ioxa -9,13-d ith ia -11-
m eth ylen ecyclop en ta d eca -2,4-d ien e (30). According to the
procedure described for the synthesis of 22, from (S)-14 and
2-(mercaptomethyl)-1-propene-3-thiol: yield 20%; mp 54.5-
55.6 °C; [R]578 ) -176.6 (c ) 0.988, THF), [R]546 ) -208.8, [R]436
) -468.6, [R]365 ) -1423; 1H NMR (CDCl3, 300 MHz) δ 2.55-
2.68 (m, 4 H), 3.28 (AB system, J 1 ) 62.6 Hz, J 2 ) 13.9 Hz, 4
H), 4.15-4.31 (m, 4 H), 5.08 (s, 2 H), 7.17-7.43 (m, 8 H), 7.91
(d, J ) 8.1 Hz, 2 H), 7.99 (d, J ) 9.2 Hz, 2 H); 13C NMR (CDCl3,
75.4 MHz) δ 31.4 (t), 36.4 (t), 69.3 (t), 114.8 (t), 115.1 (d), 120.2
(s), 123.5 (d), 125.2 (d), 126.2 (d), 127.8 (d), 129.2 (d), 134.0
(s), 142.6 (s), 153.8 (s); HRMS m/ e (M+) calcd 458.137, obsd
458.136.
°C); [R]D ) -29.1 (c ) 0.850, CH2Cl2), [R]578 ) -31.8, [R]546
)
-37.9, [R]436 ) -83.2; 1H NMR (CDCl3, 200 MHz) δ 3.52 (s, 6
H), 7.17-7.55 (m, 6 H), 8.08 (d, J ) 7.3 Hz, 2 H), 8.64 (s, 2 H),
10.58 (s, 2 H); 13C NMR (CDCl3, 50.3 MHz) δ 63.1 (q), 124.9
(s), 125.5 (d), 126.1 (d), 128.5 (s), 129.6 (d), 129.9 (s), 130.5
(d), 132.3 (d), 137.0 (s), 156.5 (s), 190.3 (d).
(S)-(+)-37. By the same procedure (S)-37 (75%) was
obtained: mp 156.3-157.7 °C; [R]D ) +28.6 (c ) 1.210, CH2-
Cl2), [R]578 ) +30.9, [R]546 ) +38.1, [R]436 ) +79.9.
Deter m in a tion of th e Exten t of Ra cem iza tion in th e
Syn th esis of 37. (R)-37 (5 mg) and (S)-37 (9 mg) were
dissolved in n-hexane/2-propanol 9:1 (2 mL). A sample of this
mixture was analyzed by HPLC on a OT-column (eluent
n-hexane/2-propanol 9:1, flow 0.5 mL/min). The retention
times of the enantiomers were (R) 34.39 min, (S) 36.83 min.
From analogous HPLC-analysis of (S)-37, purified by col-
umn chromatography, but not crystallized, it was observed
that this material was enantiomerically pure.
(S)-(-)-2,3:4,5-Di(1,2-n a p h t h o)-1,6-d ioxa -10,14-d it h ia -
12-m eth ylen ecycloh ep ta d eca -2,4-d ien e (31). According to
the procedure described for the synthesis of 22, from (S)-20
and 2-(mercaptomethyl)-1-propene-3-thiol: yield 68%; mp
69.8-70.4 °C; [R]578 ) -138.5 (c ) 0.960, THF), [R]546 ) -165.6,
[R]436 ) -399.1, [R]365 ) -1377; 1H NMR (CDCl3, 300 MHz) δ
1.72-1.87 (m, 4 H), 2.23-2.45 (m, 4 H), 3.22 (AB system, J 1
) 24.0 Hz, J 2 ) 14.5 Hz, 4 H), 3.86-3.93 (m, 2 H), 4.20-4.27
(m, 2 H), 5.04 (s, 2 H), 7.09-7.45 (m, 8 H), 7.87 (d, J ) 8.1 Hz,
2 H), 7.96 (d, J ) 9.2 Hz, 2 H); 13C NMR (CDCl3, 75.4 MHz) δ
28.5 (t), 29.2 (t), 36.2 (t), 67.7 (t), 114.8 (t), 115.2 (d), 120.1 (s),
123.4 (d), 125.1 (d), 126.1 (d), 127.7 (d), 129.0 (d), 129.1 (s),
134.0 (s), 140.9 (s), 153.9 (s); HRMS m/ e (M+) calcd 486.169,
obsd 486.169.
(R)-(-)-3,3′-Bis(h yd r oxym eth yl)-2,2′-d im eth oxy-1,1′-bi-
n a p h th yl (38).27 (R)-38 was prepared by a modified procedure
as described for the synthesis of (S)-38.27 To a solution of (R)-
37 (6.15 g, 16.6 mmol) in a mixture of absolute ethanol (130
mL) and THF (20 mL) was added NaBH4 (1.25 g, 33.0 mmol)
at room temperature. After being stirred for 4 h the reaction
mixture was concentrated under reduced pressure. The
residue was taken up in CH2Cl2 (200 mL) and 3 N HCl (200
mL) and was vigorously stirred untill all solid material was
dissolved. The organic layer was separated, and the aqueous
layer was extracted with CH2Cl2 (2 × 150 mL). The combined
organic layers were dried (MgSO4) and concentrated under
reduced pressure to give 38 (95%) as a white foam: mp 182.6-
184.2 °C; [R]D ) -46.8 (c ) 0.602, THF), [R]578 ) -53.8, [R]546
) -63.1, [R]436 ) -123.6, [R]365 ) -188.2; 1H NMR (CDCl3,
200 MHz) δ 2.79 (s, br, 2 H), 3.30 (s, 6 H), 4.97 (AB-system, J 1
) 28.2 Hz, J 2 ) 13.2 Hz, 4 H), 7.15-7.44 (m, 6 H), 7.89 (d, J
) 88.3 Hz, 2 H), 8.03 (s, 2 H); 13C NMR (CDCl3, 50.3 MHz) δ
60.8 (q), 62.0 (t), 124.0 (s), 125.0 (d), 125.6 (d), 126.5 (d), 128.1
(d), 128.3 (d), 130.6 (s), 133.9 (s), 134.0 (s), 154.7 (s).
(R)-(+)-2,3:4,5-Di(1,2-n a p h t h o)-1,6-d ioxa -9,12-d it h ia -
10,11-(1,2-ben zo)cyclotetr a d eca -2,4-d ien e (32). According
to the procedure described for the synthesis of 22, from (R)-
21 and 1,2-dimercaptobenzene: yield 72%; mp 222.2-223.9
°C; [R]D ) +345.6 (c ) 0.544, THF), [R]578 ) +381.6, [R]546
)
+448.9, [R]436 ) +981.8, [R]365 ) +2873; 1H NMR (CDCl3, 200
MHz) δ 2.94-3.09 (m, 2 H), 3.18-3.30 (m, 2 H), 4.13-4.33
(m, 4 H), 7.06-7.47 (m, 12 H), 7.86 (d, J ) 8.0 Hz, 2 H), 7.92
(d, J ) 9.0 Hz, 2 H); 13C NMR (CDCl3, 50.3 MHz) δ 34.8 (t),
67.6 (t), 100.1 (s), 115.5 (d), 120.1 (s), 123.6 (d), 125.4 (d), 126.3
(d), 127.7 (d), 127.8 (d), 129.3 (s), 129.3 (s), 133.4 (d), 134.1
(s), 138.6 (s), 154.0 (s); HRMS m/ e (M+) calcd 480.122, obsd
480.122.
(S)-(+)-38.27 By the same procedure (S)-38 (91%) was
obtained: mp 181.8-183.9 °C (lit.27 mp 183-185 °C); [R]D
)
(65) Moneta, W.; Baret, P.; Pierre, J .-L. Bull. Soc. Chim. Fr. 1988,
995.

3104 J . Org. Chem., Vol. 61, No. 9, 1996
Stock and Kellogg
+47.4 (c ) 0.814, THF) (lit.27 [R]D ) +53.4), [R]578 ) +55.0,
[R]546 ) +65.6, [R]436 ) +127.4, [R]365 ) +195.3.
(d), 126.2 (d), 127.8 (d), 130.2 (d), 130.6 (s), 132.1 (s), 133.6
(s), 155.1 (s); HRMS m/e (M+) calcd 608.191, obsd 608.191.
(S)-(-)-3,3′-Bis(b r om om et h yl)-2,2′-d ih yd r oxy-1,1′-b i-
n a p h th yl (45). To a cooled (0 °C) solution of (S)-39 (0.75 g,
1.50 mmol) in CH2Cl2 (50 mL) was added dropwise BBr3 (1.0
M in CH2Cl2, 4.0 mL, 4.0 mmol). After the mixture was stirred
at room temperature for 4 h a saturated NaHCO3 solution (10
mL) was added. The mixture was poured into water (100 mL)
and was extracted with CH2Cl2 (3 × 75 mL). The combined
organic layers were washed with 2 N HCl (100 mL), dried
(MgSO4), and concentrated under reduced pressure to give 45
1,4,8-Tr ith ia octa n e. This product was obtained as a side
product (8%) in the synthesis of 1,4,8,11-tetrathiaundecane8b
1
bp 120-135 °C (0.35 mm Hg); H NMR (CDCl3, 200 MHz) δ
1.36 (t, J ) 8.1 Hz, 1 H), 1.66-1.84 (m, 3 H), 2.52-2.71 (m, 8
H); 13C NMR (CDCl3, 50.3 MHz) δ 23.4 (t), 24.7 (t), 30.2 (t),
33.3 (t), 36.0 (t).
(S)-(+)-2,3,4:5,6,7-Bis[1,3-(2-m eth oxyn a p h th o)]-9,12,15-
tr ith ia cyclop en ta d eca -3,5-d ien e (40). According to the
procedure described for the synthesis of 22, from (S)-39 and
1,4,7-trithiaheptane: yield 76% as a white solid; mp 272.2-
274.1 °C; [R]578 ) +969 (c ) 0.342, THF), [R]546 ) +1133, [R]436
) +2306, [R]365 ) +4865; 1H NMR (CDCl3, 200 MHz) δ 2.57-
2.68 (m, 2 H), 2.88-3.15 (m, 6 H), 3.07 (s, 6 H), 3.97 (AB-
system, J 1 ) 103.8 Hz, J 2 ) 13.7 Hz, 4 H), 7.22-7.47 (m, 6
H), 7.90 (d, J ) 8.1 Hz, 2 H), 7.96 (s, 2 H); 13C NMR (CDCl3,
50.3 MHz): δ 30.8 (t), 32.1 (t), 32.3 (t), 61.0 (q), 124.1 (s), 124.9
(d), 125.5 (d), 126.4 (d), 128.1 (d), 130.0 (d), 131.2 (s), 133.3
(s), 134.5 (s), 155.1 (s); HRMS m/e (M+) calcd 492.125, obsd
492.125.
(R)-(-)-2,3,4:5,6,7-Bis[1,3-(2-m eth oxyn a p h th o)]-9,12,16-
t r it h ia cycloh exa d eca -3,5-d ien e (41). According to the
procedure described for the synthesis of 22, from (R)-39 and
1,4,8-trithiaoctane: yield 50% as a white solid; mp 215.6-
217.3 °C; [R]D ) -797.5 (c ) 0.276, THF), [R]578 ) -870.7, [R]546
) -1019, [R]436 ) -2089, [R]365 ) -4479; 1H NMR (CDCl3,
200 MHz) δ 1.77-1.92 (m, 2 H), 2.11-2.97 (m, 8 H), 3.10 (s, 3
H), 3.14 (s, 3 H), 3.96 (AB-system, J 1 ) 106.0 Hz, J 2 ) 13.7
Hz, 2 H), 4.01 (AB-system, J 1 ) 125.8 Hz, J 2 ) 13.3 Hz, 2 H),
7.21-7.31 (m, 4 H), 7.37-7.46 (m, 2 H), 7.87-7.92 (m, 2 H),
8.02 (s, 1 H), 8.10 (s, 1 H); 13C NMR (CDCl3, 50.3 MHz) δ 28.2
(t), 29.1 (t), 30.0 (t), 31.4 (t), 31.6 (t), 31.8 (t), 33.9 (t), 60.9 (q),
124.0 (s), 124.1 (s), 124.9 (d), 125.6 (d), 126.4 (d), 128.0 (d),
130.6 (d), 130.8 (d), 131.1 (s), 131.1 (s), 132.9 (s), 133.3 (s),
133.4 (s), 134.5 (s), 155.0 (s), 155.7 (s); HRMS m/e (M+) calcd
506.141, obsd 506.141.
(99%) as a pale yellow foam: mp 186.4-188.6 °C; [R]D
)
-165.9 (c ) 0.340, THF), [R]578
) -175.3, [R]546 ) -207.6, [R]436
1
) -474.4; H NMR (CDCl3, 200 MHz) δ 4.82 (AB-system, J 1
) 11.3 Hz, J 2 ) 10.2 Hz, 4 H), 5.34 (s, 2 H), 7.08-7.13 (m, 2
H), 7.27-7.45 (m, 4 H), 7.88-7.93 (m, 2 H), 8.09 (s, 2 H); 13C
NMR (CDCl3, 50.3 MHz) δ 28.9 (t), 111.4 (s), 124.1 (d), 124.7
(d), 126.6 (s), 128.2 (d), 128.5 (d), 129.1 (s), 132.3 (d), 133.4
(s), 150.8 (s); HRMS m/e (M+) calcd 469.952, obsd 469.951.
(S)-(-)-2,2′-Bis(m eth yoxym eth oxy)-1,1′-din aph th yl (47).
(S)-47 was prepared by a modified procedure as described for
the synthesis of racemic 47.66 To a solution of (S)-10 (2.75 g,
9.62 mmol) in THF (100 mL) was added KOtBu (2.37 g, 21.1
mmol). After the mixture was stirred at room temperature
for 10 min a solution of freshly prepared methoxymethyl
iodide67 (3.64 g, 21.2 mmol) in THF (15 mL) was added
dropwise over a period of 15 min. The mixture was stirred
for 18 h at room temperature and was then concentrated under
reduced pressure. Water (100 mL) was added to the residue,
and the mixture was extracted with CH2Cl2 (3 × 100 mL). The
combined organic layers were washed with 2 N NaOH (100
mL), dried (MgSO4), and concentrated under reduced pressure
to give a viscous yellow oil (3.53 g). The crude product was
purified by column chromatography (silica gel, CH2Cl2) to give
47 (96%) as a pale yellow oil that crystallized on standing: mp
95.1-96.6 °C (lit.66 racemate: mp 93-94 °C); [R]D ) -79.0 (c
) 0.990, THF), [R]578 ) -83.4, [R]546 ) -98.4, [R]436 ) -223.8,
1
[R]365 ) -690.9; H NMR (CDCl3, 200 MHz) δ 3.20 (s, 6 H),
(R)-(-)-2,3,4:5,6,7-Bis[1,3-(2-m et h oxyn a p h t h o)]-9,12,-
15,18-tetr a th ia cycloocta d eca -3,5-d ien e (42). According to
the procedure described for the synthesis of 22, from (R)-39
and 1,4,7,10-tetrathiadecane: yield 44% as a white solid; mp
5.08 (AB-system, J 1 ) 22.2 Hz, J 2 ) 6.2 Hz, 4 H), 7.13-7.44
(m, 6 H), 7.64 (d, J ) 9.2 Hz, 2 H), 7.93 (d, J ) 8.1 Hz, 2 H),
8.00 (d, J ) 9.2 Hz, 2 H); 13C NMR (CDCl3, 50.3 MHz) δ 55.8
(q), 95.2 (t), 117.3 (d), 121.3 (s), 124.1 (d), 125.6 (d), 126.3 (d),
127.9 (d), 129.4 (d), 129.9 (s), 134.1 (s), 152.7 (s); HRMS m/e
(M+) calcd 374.152, obsd 374.152.
182.2-183.5 °C; [R]D ) -590.6 (c ) 0.384, THF), [R]578
)
-642.7, [R]546 ) -750.5, [R]436 ) -1508, [R]365 ) -3077; 1H
NMR (CDCl3, 200 MHz) δ 2.58-2.77 (m, 12 H), 3.29 (s, 6 H),
4.04 (AB-system, J 1 ) 91.2 Hz, J 2 ) 14.2 Hz, 4 H), 7.11-7.28
(m, 4 H), 7.37-7.45 (m, 2 H), 7.91 (d, J ) 8.2 Hz, 2 H), 8.14 (s,
2 H); 13C NMR (CDCl3, 50.3 MHz) δ 29.6 (t), 31.5 (t), 32.00 (t),
32.3 (t), 61.2 (q), 124.4 (s), 125.0 (d), 125.7 (d), 126.4 (d), 127.9
(d), 130.7 (d), 130.9 (s), 133.3 (s), 133.5 (s), 154.8 (s); HRMS
m/e (M+) calcd 552.129, obsd 552.128.
(S)-(-)-2,2′-Bis(m eth yoxym eth oxy)-1,1′-din aph th yl-3,3′-
d ica r ba ld eh yd e (48). To a cooled (0 °C) solution of (S)-47
(2.96 g, 7.91 mmol) and TMEDA (6.0 mL, 39 mmol) in Et2O
(350 mL) was added dropwise n-BuLi (1.6 M in hexanes, 21.2
mL, 33.9 mmol) over a period of 15 min. After being stirred
at 0 °C for 2 h, the mixture was refluxed for 17 h. The
resulting purple-brown suspension was cooled to 0 °C, and
DMF (5.0 mL, 65 mmol) was added. The mixture was stirred
for 2 h at 0 °C, and then a saturated NH4Cl solution (50 mL)
was added dropwise. The organic layer was separated, washed
with water (150 mL), a saturated NaHCO3 solution (150 mL)
and brine (150 mL), dried (MgSO4), and concentrated under
reduced pressure to give an orange oil (2.92 g). The crude
product was purified by column chromatography (silica gel,
CH2Cl2) to give 48 (78%) as a pale yellow solid: mp 126.7-
128.6 °C; [R]D ) -43.9 (c ) 0.440, THF), [R]578 ) -47.4, [R]546
(R)-(-)-2,3,4:5,6,7-Bis[1,3-(2-m et h oxyn a p h t h o)]-9,12,-
16,19-tetr a th ia cyclon on a d eca -3,5-d ien e (43). According to
the procedure described for the synthesis of 22, from (R)-39
and 1,4,8,11-tetrathiaundecane: yield 40% as a white solid;
mp 132.4-133.6 °C; [R]D ) -178.7 (c ) 0.282, THF), [R]578
)
1
-195.4, [R]546 ) -228.7, [R]436 ) -462.1, [R]365 ) -886.2; H
NMR (CDCl3, 200 MHz) δ 1.62 (quintet, J ) 7.5 Hz, 2 H),
1.96-2.10 (m, 2 H), 2.22-2.36 (m, 2 H), 2.51-2.77 (m, 8 H),
3.39 (s, 6 H), 4.04 (AB-system, J 1 ) 71.2 Hz, J 2 ) 14.1 Hz, 4
H), 7.06-7.45 (m, 6 H), 7.90 (d, J ) 7.7 Hz, 2 H), 8.13 (s, 2 H);
13C NMR (CDCl3, 50.3 MHz) δ 29.5 (t), 30.1 (t), 30.3 (t), 30.6
(t), 31.8 (t), 61.2 (q), 124.6 (s), 125.0 (d), 125.6 (d), 126.4 (d),
127.8 (d), 130.6 (d), 130.8 (s), 132.4 (s), 133.6 (s), 155.0 (s);
HRMS m/e (M+) calcd 566.144, obsd 566.144.
1
) -60.2; H NMR (DMSO-d6, 200 MHz) δ 2.67 (s, 6 H), 4.75
(AB-system, J 1 ) 9.4 Hz, J 2 ) 6.0 Hz, 4 H), 7.10 (d, J ) 8.1
Hz, 2 H), 7.43-7.60 (m, 4 H), 8.27 (d, J ) 8.1 Hz, 2 H), 8.70
(s, 2 H), 10.40 (s, 2 H); 13C NMR (CDCl3, 50.3 MHz) δ 57.0 (q),
100.6 (t), 125.9 (s), 126.1 (d), 126.3 (d), 128.9 (s), 129.6 (d),
130.0 (s), 130.3 (d), 132.3 (d), 136.7 (s), 154.0 (s), 190.6 (d);
HRMS m/e (M+) calcd 430.142, obsd 430.142.
(S)-(+)-2,3,4:5,6,7-Bis[1,3-(2-m eth oxyn a p h th o)]-9,13,18,-
22-tetr a th ia cyclod oeicosa -3,5-d ien e (44). According to the
procedure described for the synthesis of 22, from (S)-39 and
1,5,10,14-tetrathiatetradecane: yield 56% as a colorless oil;
[R]D ) +5.7 (c ) 0.246, THF), [R]578 ) +6.1, [R]546 ) +8.9, [R]436
(S )-(+)-3,3′-Bis(h yd r oxym e t h yl)-2,2′-b is(m e t h yoxy-
m eth oxy)-1,1′-d in a p h th yl (49). (S)-49 was prepared by a
different approach as described for the synthesis of racemic
49.21b To a solution of (S)-48 (1.33 g, 3.09 mmol) in absolute
ethanol (100 mL) and THF (20 mL) was added NaBH4 (0.24
1
) +31.7, [R]365 ) +69.1; H NMR (CDCl3, 200 MHz) δ 1.34-
1.57 (m, 4 H), 1.73-1.97 (m, 4 H), 2.20-2.30 (m, 4 H), 2.52 (t,
J ) 7.4 Hz, 4 H), 2.65 (t, J ) 7.2 Hz, 4 H), 3.39 (s, 6 H), 4.03
(AB-system, J 1 ) 35.4 Hz, J 2 ) 13.2 Hz, 4 H), 7.14-7.27 (m,
4 H), 7.36-7.44 (m, 2 H), 7.88 (d, J ) 8.1 Hz, 2 H), 8.04 (s, 2
H); 13C NMR (CDCl3, 50.3 MHz) δ 28.8 (t), 29.9 (t), 30.8 (t),
30.9 (t), 31.2 (t), 31.5 (t), 61.2 (q), 124.6 (s), 124.9 (d), 125.7
(66) Peacock, S. S.; Walba, D. M.; Gaeta, F. C. A.; Helgeson, R. C.;
Cram, D. J . J . Am. Chem. Soc. 1980, 102, 2043.
(67) J ung, M. E.; Mazurek, M. A.; Lim, R. M. Synthesis 1978, 588.

Thiocrown Ethers Derived from 1,1′-Binaphthalene-2,2′-diol
J . Org. Chem., Vol. 61, No. 9, 1996 3105
g, 6.3 mmol). After being stirred at room temperature for 17
h the mixture was concentrated under reduced pressure to give
a yellow foam (2.02 g). The crude product was boiled in CH2-
Cl2 (3 × 50 mL) and decanted while hot. The combined organic
layers were concentrated under reduced pressure to give 49
(95%) as a pale yellow foam (lit.21b racemate is a colorless oil):
and concentrated under reduced pressure to give pale yellow
crystals (1.82 g). The crude product was purified by column
chromatography (silica gel, CH2Cl2) to give 59 (99%) as white
crystals: mp 110.1-111.1 °C; [R]D ) +29.3 (c ) 0.382, THF),
[R]578 ) +32.5, [R]546 ) +41.1, [R]436 ) +138.5, [R]365 ) +667.8;
1H NMR (CDCl3, 200 MHz) δ 4.60-4.62 (m, 4 H), 5.06-5.16
(m, 4 H), 5.75-5.94 (m, 2 H), 7.27-7.45 (m, 8 H), 7.49 (d, J )
9.0 Hz, 2 H), 7.96 (d, J ) 8.0 Hz, 2 H), 8.02 (d, J ) 9.0 Hz, 2
H); 13C NMR (CDCl3, 50.3 MHz) δ 70.0 (t), 115.7 (d), 116.5 (t),
120.4 (s), 123.7 (d), 125.6 (d), 126.3 (d), 128.0 (d), 129.2 (d),
129.4 (s), 133.8 (d), 134.2 (s), 154.1 (s); HRMS m/e (M+) calcd
366.162, obsd 366.162.
1,13-Bis[3-(2-m eth oxyn a p h th yl)]-2,5,9,12-tetr a th ia tr i-
d eca n e (62). To a solution of 1,4,8,11-tetrathiaundecane (1.14
g, 5.00 mmol) in THF (50 mL) was added KOtBu (1.40 g, 12.5
mmol). After the mixture was stirred at room temperature
for 20 min 61 (2.51 g, 10.0 mmol) was added. The mixture
was stirred at ambient temperature for 4 h. The resulting
pale brown suspension was concentrated under reduced pres-
sure. 2 N HCl (100 mL) was added to the residue, and the
mixture was extracted with CH2Cl2 (3 × 100 mL). The
combined organic layers were dried (MgSO4) and concentrated
under reduced pressure to give a yellow oil (2.92 g). The crude
product was purified by column chromatography (silica gel,
CH2Cl2) to give 62 (100%) as a colorless oil that solidifies on
standing: mp 78.6-80.4 °C; 1H NMR (CDCl3, 200 MHz) δ 1.75
(quintet, J ) 7.2 Hz, 2 H), 2.54 (t, J ) 7.2 Hz, 4 H), 2.69-2.73
(m, 8 H), 3.93 (s, 4 H), 3.97 (s, 6 H), 7.14 (s, 2 H), 7.32-7.48
(m, 4 H), 7.69 (s, 2 H), 7.72-7.77 (m, 4 H); 13C NMR (CDCl3,
50.3 MHz) δ 29.3 (t), 30.8 (t), 31.1 (t), 31.7 (t), 32.0 (t), 55.5
(q), 105.5 (d), 123.9 (d), 126.2 (d), 126.4 (d), 127.3 (d), 128.3
(s), 128.5 (s), 129.0 (d), 134.0 (s), 155.8 (s); HRMS m/e (M+)
calcd 568.160, obsd 568.160.
1,13-Bis[3-(2-h yd r oxyn a p h th yl)]-2,5,9,12-tetr a th ia tr i-
d eca n e (63). To a cooled (0 °C) solution of 62 (1.58 g, 2.78
mmol) in CH2Cl2 (50 mL) was added BBr3 (1.6 mL, 16.7 mmol)
dropwise over a period of 5 min. After the mixture was stirred
at room temperature for 20 h a saturated NaHCO3 solution
(20 mL) was added. The mixture was stirred for 30 min and
was then poured into water (100 mL). The mixture was
extracted with CH2Cl2 (3 × 50 mL). The combined organic
layers were washed with 3 N HCl (100 mL), dried (MgSO4),
and concentrated under reduced pressure to give a yellow oil
(1.71 g) that solidified on standing. The crude product was
boiled in toluene (50 mL) and decanted while hot. The
decantate was cooled to -20 °C to give 63 (83%) as a white
powder: mp 97.2-99.3 °C; 1H NMR (CDCl3, 200 MHz) δ 1.58
(quintet, J ) 7.1 Hz, 2 H), 2.36 (t, J ) 7.1 Hz, 4 H), 2.64 (s, 8
H), 3.99 (s, 4 H), 6.48 (s, br, 2 H), 7.26 (s, 2 H), 7.27-7.45 (m,
4 H), 7.61-7.74 (m, 6 H); 13C NMR (CDCl3, 50.3 MHz) δ 29.0
(t), 30.6 (t), 30.9 (t), 31.8 (t), 32.6 (t), 111.7 (d), 124.0 (d), 125.3
(s), 126.3 (d), 126.5 (d), 127.4 (d), 128.7 (s), 129.6 (d), 134.3
(s), 152.8 (s); HRMS m/e (M+) calcd 540.129, obsd 540.129.
mp 68.6-69.2 °C; [R]D ) +66.4 (c ) 0.256, THF), [R]578
)
1
+69.9, [R]546 ) +80.9, [R]436 ) +151.6; H NMR (CDCl3, 200
MHz) δ 3.20 (s, 6 H), 3.54 (s, br, 2 H), 4.47 (AB-system, J 1
)
8.3 Hz, J 2 ) 6.2 Hz, 4 H), 4.93 (AB-system, br, J 1 ) 30.5 Hz,
J 2 ) 12.7 Hz, 4 H), 7.14-7.48 (m, 6 H), 7.92 (d, J ) 8.1 Hz, 2
H), 8.04 (s, 2 H); 13C NMR (CDCl3, 50.3 MHz) δ 57.1 (q), 61.8
(t), 99.3 (t), 125.2 (s), 125.4 (d), 125.8 (d), 126.8 (d), 128.2 (d),
129.7 (d), 130.9 (s), 133.8 (s), 134.6 (s), 153.1 (s); HRMS m/e
(M+) calcd 434.173, obsd 434.173.
2,3-[1,2-n a p h th o]4,5-[1,2-(3-for m yln a p h th o)]-1,6-d iox-
a cycloh ep ta -2,4-d ien e (52) a n d 2,3:4,5-Bis[1,2-(3-for m yl-
n a p h th o)]-1,6-d ioxa cycloh ep ta -2,4-d ien e (53). To a cooled
(0 °C) solution of 51 (2.00 g, 6.71 mmol) and TMEDA (5.2 mL,
35 mmol) in Et2O (150 mL) was added dropwise s-BuLi (0.8
M in cyclohexane/isopentane, 34 mL, 27 mmol) over a period
of 15 min. The resulting dark green solution was allowed to
warm to room temperature. After being stirred at ambient
temperature for 17 h the mixture was cooled to 0 °C and DMF
(4.2 mL, 53 mmol) was added. After the mixture was stirred
at 0 °C for 2 h, 4 N HCl (20 mL, 80 mmol) was added dropwise.
The organic layer was washed with water (150 mL), a
saturated NaHCO3 solution (150 mL), and brine (150 mL),
dried (MgSO4), and concentrated under reduced pressure to
give a pale yellow solid (1.82 g). The crude product was
purified by column chromatography over a 30 cm silica gel
column (100 g silica gel, CH2Cl2) to give 52 (18%) as a first
fraction (Rf ) 0.52) and 53 (29%) as a second fraction (Rf )
0.22). Analytically pure 53 was obtained by recrystallization
from CHCl3/n-hexane.
52: mp 182.1-184.0 °C; 1H NMR (CDCl3, 200 MHz) δ 5.81
(AB-system, J 1 ) 4.7 Hz, J 2 ) 3.4 Hz, 2 H), 7.40-7.58 (m, 7
H), 7.95-8.10 (m, 3 H), 8.60 (s, 1 H), 10.62 (s, 1 H); 13C NMR
(DMSO-d6, 50.3 MHz) δ 103.4 (t), 121.1 (d), 124.5 (s), 125.2
(d), 125.6 (d), 125.9 (d), 126.1 (d), 126.6 (d), 126.8 (s), 127.5
(s), 128.7 (d), 129.1 (d), 130.2 (s), 130.8 (d), 131.0 (d), 131.1
(d), 131.3 (s), 131.4 (s), 134.0 (s), 150.8 (s), 151.2 (s), 189.9 (d);
HRMS m/e (M+) calcd 326.094, obsd 326.094.
1
53: mp 238.9-240.7 °C; H NMR (DMSO-d6, 200 MHz) δ
6.04 (s, 2 H), 7.30 (d, J ) 8.1 Hz, 2 H), 7.47-7.64 (m, 4 H),
8.32 (d, J ) 8.1 Hz, 2 H), 8.71 (s, 2 H), 10.51 (s, 2 H); 13C NMR
(DMSO-d6, 50.3 MHz) δ 104.3 (t), 125.8 (d), 126.0 (s), 126.3
(d), 127.3 (s), 129.3 (d), 130.3 (s), 130.8 (d), 131.5 (d), 133.9
(s), 150.9 (s), 189.8 (d); HRMS m/e (M+) calcd 354.089, obsd
354.089. Anal. Calcd (found) for C23H14O4‚CHCl3: C, 60.73
(60.70); H, 3.19 (3.24); Cl, 22.41 (21.03).
7,7,9,9-Tetr a m eth yl-2,3:4,5-d i(1,2-n a ph th o)-1,6,8-tr ioxa -
7,9-d isila cyclon on a -2,4-d ien e (56). To a solution of 10 (2.38
g, 8.32 mmol) in CH2Cl2 (50 mL) were added Et3N (3.5 mL, 25
mmol) and dichlorodimethylsilane (0.93 mL, 7.7 mmol). After
being refluxed for 18 h the reaction mixture was washed with
water (2 × 50 mL), a saturated NH4Cl solution (50 mL), and
2 N NaOH (2 × 50 mL), dried (MgSO4), and concentrated
under reduced pressure to give a brown solid (0.70 g). The
crude product was purified by column chromatography (silica
gel, CH2Cl2) to give 56 (17%) as a pale yellow powder: mp
172.2-174.6 °C; 1H NMR (CDCl3, 200 MHz) δ -0.55 (s, 6 H),
0.27 (s, 6 H), 7.19-7.43 (m, 8 H), 7.89-7.97 (m, 4 H); 13C NMR
(CDCl3, 50.3 MHz) δ -1.3 (q), 0.2 (q), 121.9 (d), 123.4 (s), 124.2
(d), 125.2 (d), 126.6 (d), 127.8 (d), 129.6 (d), 130.0 (s), 134.2
(s), 150.4 (s); HRMS m/e (M+) calcd 416.126, obsd 416.126.
(R)-(+)-2,2′-Bis(2-p r op en -1-yloxy)-1,1′-d in a p h th yl (59).
A solution of (R)-10 (1.43 g, 5.00 mmol), allyl bromide (2.42 g,
20.0 mmol), and K2CO3 (2.76 g, 20.0 mmol) in acetone (150
mL) was refluxed for 70 h. The reaction mixture was filtered
Ack n ow led gm en t. We thank the Dutch Organiza-
tion of Scientific Research (NWO) administered through
the Office for Chemical Research (SON) for financial
support of this work.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of thiocrown ethers 22-33 and 40-44; descriptions
of attempts to demethylate 40, 42, and 43; attempts to
brominate 49 and to cyclize 45; attempted synthesis of 58;
attempts to prepare 64 by oxidative coupling (75 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 O952107O