Axially chiral synthons for dendrimer synthesis

Article abstract of DOI:10.1135/cccc19970925

Axially chiral synthons for chiral dendrimer construction based on 2,2′-dihydroxy-1, 1′-binaphthalene-3,3′-dicarboxylic acid were prepared, namely, chiral connecting units (3, 6, 8), chiral branching units(10, 12, 14), and chiral surface units (5, 17). Re

Full text of DOI:10.1135/cccc19970925

Axially Chiral Synthons
925
AXIALLY CHIRAL SYNTHONS FOR DENDRIMER SYNTHESIS
1
2,
Vit LELLEK and Ivan STIBOR *
Department of Organic Chemistry, Prague Institute of Chemical Technology, 166 28 Prague 6,
Czech Republic; e-mail: 1 vit.lellek@vscht.cz, 2 stibori@vscht.cz
Received November 15, 1996
Accepted January 27, 1997
Axially chiral synthons for chiral dendrimer construction based on 2,2′-dihydroxy-1,1′-binaphthalene-
3,3′-dicarboxylic acid were prepared, namely, chiral connecting units (3, 6, 8), chiral branching units
(10, 12, 14), and chiral surface units (5, 17). Regioselective chloromethylation of methyl 3′-acetoxy-
methyl-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (7) was also studied.
Key words: Dendrimers; Chiral synthons; Binaphthols.
Chemists have long sought ways to control the molecular structure of synthetic high-
molecular weight compounds at a level comparable to that realized in biological mac-
romolecules. Having such methods available might make it possible to finely tune the
properties of materials thus obtained. One method recently discovered has already re-
sulted in a new set of materials called dendrimers (Fig. 1) as wittnessed by numerous
review articles1–8. Some of these materials are now available commercially9. Den-
drimers as highly ordered polymers are believed to provide solutions to a wide variety
of technological and ecological problems, from removal of heavy metals pollutants
from industrial wastes to their use as highly efficient drug delivery systems and even
G-0
FIG. 1
G-1
G-2
G-3
G-4
G-5
Dendrimer with triple-branched core (G-0), up to generation five (G-5)
* The author to whom correspondence should be addressed.
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

926
Lellek, Stibor:
the formation of artificial chemical cells and tissues5,7. Very recently dendrimers have
been used as haemoprotein mimics10,11, protein labels in electron microscopy12, plat-
form for deposition of monolayers13, chemical sensors14, light harvesting antennae15,
saccharide “sponge”16, molecular architecture for photoinduced electron transfer17, and
unimolecular micelles18.
Since the first synthesis of these multibranched cascade molecules has been published by
Vögtle in 1978 (ref.19), numerous synthetic approaches to dendritic macromolecules
have been developed, including divergent and convergent syntheses as well as one-step
routes7. Recently self-assembly has been successfully used for a very efficient synthesis
of dendrimers20,21. Not surprisingly, chiral dendrimers have attracted the attention of
synthetic chemists as a model for biopolymers. As a matter of fact, the first “real”
dendrimer of Denkewalter22 was based on an amino acid and this type of building block
has been used many times later23–28. Recently carbohydrates have been also used for the
synthesis of chiral dendrimers29–31 as well as non-natural building blocks32–34. Chiral den-
drimers have been used as polymeric liquid crystals35 and polymeric asymmetric cata-
lysts36,37
.
The extraordinary activity in the field of dendrimers, and of chiral dendrimers in
particular, prompted us to disclose our synthetic approach to axially chiral building
blocks well-suited for construction of chiral dendrimers. Here, we report on the syn-
thesis of three types of 2,2′-binaphthalene-1,1′-diol (binaphthol) derivatives. They are
currently used as axially chiral connectors, branching and finally surface units in the
synthesis of axially chiral dendrimers which is under way in our laboratory.
RESULTS AND DISCUSSION
The synthesis starts from racemic or optically active 2,2′-dihydroxy-1,1′-binaph-
thalene-3,3′-dicarboxylic acid (1) prepared by modification of a solid-phase coupling
reaction38 followed by known resolution procedure39.
The free R- and S-hydroxy acids (1) were tetramethylated with methyl iodide in
anhydrous dimethylformamide in the presence of potassium carbonate. The method is a
modification of known procedure40 and diester 2 was isolated in 88% yield for R-2, and
93% yield for S-2. Racemic 2 was prepared from known dimethyl 2,2′-dihydroxy-1,1′-
binaphthalene-3,3′-dicarboxylate39 using methyl iodide and potasium carbonate in an-
hydrous acetone. Diester 2 was partially hydrolyzed following the method published for
dimethyl terephthalate41 and desired monoester 3 was isolated along with correspond-
ing acid 1 and recovered diester 2 in 49, 45, and 50% yields for R,S-, R-, and S-3,
respectively. The monoester R,S-3 was alternatively prepared by deprotection of methyl
phenacyl ester (see below). Analogously, methylation of known racemic42–44 as well as
chiral45 2,2′-dihydroxy-1,1′-binaphthalene-3-carboxylic acid its methyl ester proceed
under known40 conditions giving R,S-, R-, and S-4 in 89, 94, and 83% yields, respec-
tively. Hydrolyses of esters were performed using potassium hydroxide in methanol.
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Axially Chiral Synthons
927
R,S- and S-5 were isolated in 95 and 99% yields, respectively. Reduction of carboxyl
group of 3 with the diborane–THF complex using known procedure46,47 yielded alco-
hols 6 R,S, R, and S in 97, 81, and 87%, respectively. Acetylation of both racemic and
chiral alcohols 6 with acetyl chloride proceeded very smoothly giving R,S-, R-, and S-7
in 97, 94, and 99% yields, respectively. Racemic 6 was transformed to chloromethyl
derivative R,S-8 by treatment with excess of thionyl chloride in almost quantitative
yield. Analogously, benzoate R,S-9 was prepared using benzoyl chloride and 4-(di-
methylamino)pyridine in dichloromethane again in quantitative yield. The key-step of
our synthetic appropach was chloromethylation48 of acetate 7. We have reasoned that
electron-donating group in 3′-position of binaphthalene moiety should direct the reac-
tion regioselectively to 6′-position and it is exactly what we have observed. We have
also found that chloromethylation of acetoxymethyl derivatives R,S- and S-7 is accom-
panied by nucleophilic displacement of acetoxy group giving bis(chloromethyl) deriva-
tives R,S- and S-10, both isolated in 50% yield. We have found that composition of
reaction products mixtures obtained from the chloromethylation of 6–9 could be ana-
lysed by NMR spectroscopy only. The course of reaction can be expressed by the reac-
R3
R1
OR
OR
R4
R2
R1
R2
R3
R4
R
(R,S), (R), (S)
(R,S), (R), (S)
H
COOH
COOH
COOMe
COOH
H
H
H
H
H
1
2
CH
COOMe
3
(R,S), (R), (S) 3
H
H
H
H
H
H
H
H
CH COOMe
3
(R,S), (R), (S)
(R,S), (S)
4
5
6
CH
CH
CH
COOMe
COOH
3
3
3
H
(R,S), (R), (S)
COOMe
CH OH
2
(R,S), (R), (S) 7
H
H
H
CH
CH
CH
COOMe
COOMe
COOMe
CH OAc
H
H
H
3
2
(R,S)
8
9
CH Cl
3
3
2
(R,S)
CH OCOPh
2
(R,S), (S)
(R,S), (S)
(R,S), (S)
(R,S), (S)
(R,S), (S)
(R,S)
H
10
CH
COOMe
COOMe
CH Cl
CH Cl
2
3
3
2
11 CH
CH Cl
CH Cl
CH Cl
2
2
2
H
H
CH
CH
COOMe
COOH
CH OCH CH OH CH OCH CH OH
2 2 2 2 2 2
12
13
3
3
CH OCH CH OH CH OCH CH OH
2
2
2
2
2
2
H
H
H
H
14 CH COOCH COPh CH OCH CH OH CH OCH CH OH
3
3
3
3
2
2
2
2
2
2
2
H
CH
CH
CH
COOMe
COOCH COPh
2
15
16
17
(R,S), (S)
(R,S), (S)
COOMe
COOH
CH OMe
2
CH OMe
2
CH OMe
2
CH OMe
2
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

928
Lellek, Stibor:
tion sequence shown in Scheme 1, where bold arrows indicate independently proven
reactions, normal arrows indicate reactions deduced from NMR spectra, and dotted
arrow indicates possible reaction. Compound 7 is chloromethylated in position 6′ first,
then acetoxymethyl group is converted to chloromethyl group giving 10 as main pro-
duct. At the same time the chloromethylation is proceeding further to position 6 and the
intermediate thus formed is converted to tris(chloromethyl) derivative 11. This com-
pound is always present in reaction mixture and makes the purification of 10 difficult.
COOMe
COOMe
COOMe
OMe
OMe
OMe
OMe
OMe
OMe
Cl
Cl
O
O
Cl
O
O
Me
Me
7
10
COOMe
COOMe
COOMe
Cl
Cl
Cl
Cl
OMe
OMe
OMe
OMe
OMe
OMe
Cl
Cl
O
O
Me
8
11
SCHEME 1
Bischloromethyl ester 10 was used as starting material for preparation of dendrimer
branching unit. Reaction with silver oxide in ethylene glycol afforded a mixture of ester
R,S- and S-12 contaminated with ethylene glycol esters in total 77 and 78% yield,
respectively. The mixture of both esters was found to be easily hydrolyzed with potas-
sium hydroxide in water–methanol–THF mixture giving pure acids R,S- and S-13 in 88
and 90% yields, respectively. These acids were further transformed to carboxyl-pro-
tected phenacyl esters R,S- and S-14 by reaction49 with (bromoacetyl)benzene in 73 and
78% isolated yields, respectively. Analogously, diester 15 was prepared in 91% yield
from 3 and was found to be easily and selectively reduced with Zn in acetic acid back
into starting R,S-3 in quantitative isolated yield. This procedure will be useful in the
later stages of dendrimer synthesis. Finally, bis(chloromethyl) ester was transformed to
esters R,S- and S-16 (yields 98 and 85%, respectively) using reaction with methanol
and silver oxide. These ester were finally hydrolyzed to corresponding acids R,S- and
S-17 in 93 and 98%, respectively.
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Axially Chiral Synthons
929
Thus, compounds 3, 6, and 8 can be regarded as axially chiral connecting units of
type A, compounds 10, 12, and 14 as axially chiral branching units of type B and
finally compounds 5 and 17 as axially chiral dendrimer surface-unit of type C as shown
in Scheme 2. All these synthons are now used in our laboratory to construct chiral
dendrimers.
OMe
OMe
OMe
OMe
OMe
OMe
A
B
C
axially chiral
connecting unit
axially chiral
branching units
axially chiral
surface-unit
SCHEME 2
EXPERIMENTAL
Melting points were taken on a Boetius apparatus and temperature data are uncorrected. NMR spectra
(δ, ppm; J, Hz) with TMS as internal standard were measured on a Varian Gemini 300 HC spec-
trometer in CDCl3 solutions at 298 °C. Mass spectra were recorded on a Jeol DX 303/DA 5000 mass
spectrometer and infrared spectra (ν, cm–1) on a Nicolet 750 FT IR spectrometer. Optical rotations
were obtained with a JASCO Digital Polarimetr DIP370 in a 1 dm thermostatted cell. All solvents
were distilled and dried before use.
(R,S)-2,2′-Dihydroxy-1,1′-binaphthalene-3,3′-dicarboxylic Acid (R,S-1)
A mixture of finely ground 3-hydroxy-2-naphthoic acid (45.0 g, 239 mmol) and ferric chloride hexa-
hydrate (130.0 g, 478 mmol) was heated to 60 °C (hydrogen chloride was evolved) for 25 h, cooled
to ambient temperature. Hydrochloric acid (1 mol l–1, 500 ml) was added and solid phase was filtered
off and dissolved in 3% sodium hydroxide (1 000 ml). Cold aqueous solution was extracted with
diethyl ether (100 ml) and then acidified with concentrated hydrochloric acid to pH 1. The solid
phase was collected by filtration and washed with cold water. Raw acid was dried (8 h, 60 °C), dis-
solved by refluxing in tetrahydrofuran (200 ml). Triethylamine (40 ml) was added dropwise to the
hot solution and set aside. Crystalline salt was collected after standing 2 days at ambient temperature
and one day at –18 °C, the salt was redissolved in a minimum volume of 5% sodium hydroxide and
the solution was acidified with concentrated hydrochloric acid to pH 1. The solid was filtered off,
washed with water and dried in vacuo (250 Pa, 120 °C). In this way 40.2 g (90%) of acid 1 was
obtained. This acid was again crystallized as salt with triethylamine (prepared as above using 35 g
triethylamine in 180 ml tetrahydrofuran) and after the work-up described above, 30.0 g (67%) of pure
yellow R,S-1 was isolated (m.p. 337–340 °C with decomposition; ref.39 gives m.p. > 285 °C).
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

930
Lellek, Stibor:
Dimethyl (R,S)-2,2′-Dimethoxy-1,1′-binaphthalene-3,3′-dicarboxylate (2)
Procedure A: To dimethyl 2,2′-dihydroxy-1,1′-binaphthalene-3,3′-dicarboxylate (25.0 g, 62 mmol)
in anhydrous acetone (100 ml) solid anhydrous K2CO3 (34.1 g, 247 mmol) was added followed by
methyl iodide (19 ml, 308 mmol). The reaction mixture was refluxed with stirring and every 24 h
new portion of methyl iodide (19 ml, 308 mmol) was added until the fourth day when again K2CO3
(17.1 g, 123 mmol) was added and mixture was stirred and refluxed for the last 24 h, cooled, eva-
porated in vacuo diluted with water (100 ml) and left standing at 0 °C for 2 h. Filtration and drying
at 70 °C yielded 26.58 g (100%) of pure R,S-2, m.p. 108–111 °C.
Procedure B: Pure acid 1 (24.0 g, 64 mmol) was suspended in dry DMF (250 ml) and anhydrous
powdered K2CO3 (44.3 g, 320 mmol) was added at once with stirring. Evolution of carbon dioxide
subsided within 20 min and was followed by addition of methyl iodide (31 ml, 500 mmol). Stirring
was continued for next 24 h and the reaction was quenched by pouring onto mixture of ice and water
(500 ml). The mixture was extracted with diethyl ether (3 × 250 ml) and combined organic phases
were washed with ice water (250 ml), dried with MgSO4 and evaporated in vacuo yielding 27.2 g of
crude 2. It was purified by column chromatography (150 g silica gel, elution with chloroform) and
25.7 g (93%) of pure 2 was isolated after drying in vacuo (250 Pa) at 70 °C (m.p. 108–111 °C).
Dimethyl (R)-2,2′-Dimethoxy-1,1′-binaphthalene-3,3′-dicarboxylate (R-2)
The diester R-2 was prepared from pure R-1 in 88% yield using procedure B as a glass39, [α]D25
+43.3° (c 1.0, THF); ref.50 gives [α]2D3 +43.0° (c 1.0, THF).
Dimethyl (S)-2,2′-Dimethoxy-1,1′-binaphthalene-3,3′-dicarboxylate (S-2)
The diester S-2 was prepared from pure S-1 in 94% yield using procedure B as a glass39, [α]D25 –43.3°
(c 1.0, THF).
Methyl Hydrogen (R,S)-2,2′-Dimethoxy-1,1′-binaphthalene-3,3′-dicarboxylate (3)
Procedure A: A solution of potassium hydroxide (3.58 g, 63.9 mmol) in 66% aqueous MeOH (30 ml)
was added dropwise at ambient temperature to diester 2 (25.0 g, 58.1 mmol) dissolved in a mixture
of THF (30 ml) and MeOH (40 ml). The reaction mixture was refluxed for 5 h, cooled and most of
the solvents was evaporated, diluted with cold water (500 ml) and acidified with HCl (1 : 1) to pH ≈ 1.
Solid products were collected by filtration, dried at 50 °C and chromatographed (silica gel, toluene–
3% acetone).
Compound 3 was isolated in 49% yield; RF 0.5 (chloroform–acetone 10 : 1). 1H NMR spectrum
(CDCl3): 3.45 s, 3 H (OCH3); 3.47 s, 3 H (OCH3); 4.02 s, 3 H (COOCH3); 7.12–7.55 m, 6 H (arom. H);
8.02 d, 1 H, J = 7.7 (arom. H); 8.06 d, 1 H, J = 8.8 (arom. H); 8.62 s, 1 H (arom. H); 8.94 s, 1 H
(arom. H). 13C NMR spectrum, APT (CDCl3): CH3 and CH: 53.16, 62.70, 63.08, 125.91, 126.12,
126.49, 126.82, 129.63, 129.95, 130.39, 134.70, 136.20; CH2 and C: 122.15, 125.41, 125.83, 126.03,
130.20, 130.62, 136.07, 136.97, 154.31, 155.09, 167.28, 167.46. IR spectrum (CHCl3): 1 733 (C=O);
3 205 (OH). Mass spectrum (EI), m/z (rel. int., %): 416 (M+, 40); 384 (M – OCH+3, 100). For C25H20O6
(416.4) calculated: 72.11% C, 4.84% H; found: 72.12% C, 5.11% H.
Ester 2 was obtained in 24% yield (5.95 g, 13.8 mmol); RF 0.8 (chloroform–acetone 10 : 1).
Acid 1 was obtained in 24% yield (5.66 g, 14 mmol); RF 0.2 (chloroform–acetone 10 : 1).
Procedure B: Diester R,S-15 (20.0 mg, 37 µmol) was dissolved in warm glacial acetic acid (2 ml)
and treated with zinc powder (5 mg, 76 µmol) at 20 °C. The reaction mixture was vigorously stirred
for 5 h, then second portion of zinc powder (15 mg, 228 µmol) was added at once and stirring was
continued for additional 15 h. All solids were filtered off and clear solution was evaporated in vacuo
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Axially Chiral Synthons
931
to dryness giving R,S-3 in almost quantitative yield with chromatographic and spectral properties
identical with the product obtained by procedure A.
Methyl Hydrogen (R)-2,2′-Dimethoxy-1,1′-binaphthalene-3,3′-dicarboxylate (R-3)
Compound R-3 was prepared using procedure A from R-2 in 45% yield. Spectral data were in agree-
ment with the data of racemic compound. For C25H20O6 (416.4) calculated: 72.11% C, 4.84% H;
found: 71.62% C, 5.09% H. [α]2D5 +46.5° (c 1.0, THF).
Methyl Hydrogen (S)-2,2′-Dimethoxy-1,1′-binaphthalene-3,3′-dicarboxylate (S-3)
Compound S-3 was prepared using the same procedure as above for R-3 from S-2 in 50% yield.
Spectral data correspond to those of racemic compound. For C25H20O6 (416.4) calculated: 72.11% C,
4.84% H; found: 71.79% C, 5.10% H; [α]2D5 –47.6° (c 1.0, THF).
Methyl (R,S)-2,2′-Dimethoxy-1,1′-binaphthalene-3-carboxylate (R,S-4)
The mixture of R,S-methyl 2,2′-dihydroxy-1,1′-binaphthalene-3-carboxylate44,45 (20.0 g, 58 mmol)
and anhydrous K2CO3 (19.0 g, 137 mmol) in anhydrous acetone (200 ml) was stirred for 15 min, then
methyl iodide (25 ml, 400 mmol) was added dropwise and the mixture was refluxed for 12 h. Addi-
tional methyl iodide (15 ml, 240 mmol) was added and the mixture was refluxed with stirring for
total 120 h, cooled, the solid was filtered off, the filtrate evaporated and residual solid was crystal-
lized from toluene–petroleum ether (1 : 1, 100 ml) giving 16.78 g (78%) of pure ester. The mother
liquor was evaporated, chromatographed on silica gel using toluene–3% acetone and recrystallized
giving second crop (2.53 g, 12%). Total yield was 89%, m.p. 99–102 °C. 1H NMR spectrum
(CDCl3): 3.47 s, 3 H (CH3); 3.80 s, 3 H (CH3); 4.00 s, 3 H (COOCH3); 7.06–7.51 m, 7 H (arom. H);
7.85–8.06 m, 3 H (arom. H); 8.52 s, 1 H (arom. H). 13C NMR spectrum, APT (CDCl3): CH3 and CH:
52.95, 57.08, 62.34, 114.08, 124.31, 125.73, 126.08, 126.21, 127.41, 128.63, 128.85, 129.69, 130.64,
133.44; CH2 and C: 119.14, 125.67, 127.85, 130.42, 134.62, 136.54, 155.01, 155.60, 167.79. IR spec-
trum (CHCl3): 1 724 (C=O). Mass spectrum, m/z (rel. int., %): 372 (M+, 100). For C24H20O4 (372.4)
calculated: 77.40% C, 5.41% H; found: 77.55% C, 5.52% H.
Methyl (R)-2,2′-Dimethoxy-1,1′-binaphthalene-3-carboxylate (R-4)
To (R)-2,2′-dihydroxy-1,1′-binaphthalene-3-carboxylic acid47 (6.5 g, 19.7 mmol) in anhydrous
acetone (70 ml), dry potassium carbonate (10.8 g, 79 mmol) was gradually added followed by methyl
iodide (25 ml, 0.4 mol). The reaction mixture was stirred for 3 days at ambient temperature, then
refluxed 12 h, additional portions of methyl iodide (6 ml, 96 mmol) and potassium carbonate (5.4 g,
38.3 mmol) were added and stirring under reflux was continued for another 24 h. The reaction mix-
ture was cooled and the solid was filtered off. The filtrate was evaporated in vacuo, diluted with ice
water (200 ml) and extracted with ether (3 × 100 ml). Combined organic layers were washed with
water (150 ml), dried with MgSO4, evaporated and dried for 2 h at 55 °C and 2 kPa yielding 6.86 g
(94%) of glassy R-4. Its spectral data correspond to those of the racemic compound. For C24H20O4
(372.4) calculated: 77.40% C, 5.41% H; found: 77.65% C, 5.51% H. [α]2D0 +87.9° (c 1.0, THF).
Methyl (S)-2,2′-Dimethoxy-1,1′-binaphthalene-3-carboxylate (S-4)
Compound S-4 was prepared analogously from corresponding S-acid using the same procedure as
above in 84% yield. Its spectral data correspond to those of racemic compound. For C24H20O4 (372.4)
calculated: 77.40% C, 5.41% H; found: 77.78% C, 5.63% H. [α]2D0 –93.6° (c 1.0, THF).
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

932
Lellek, Stibor:
(R,S)-2,2′-Dimethoxy-1,1′-binaphthalene-3-carboxylic Acid (R,S-5)
Ester R,S-4 (11.6 g, 31 mmol) was dissolved in methanol (150 ml) and treated with KOH (17.5 g,
311 mmol) with stirring. The resulting solution was refluxed for 4 h, cooled to ambient temperature
and stirred for additional 16 h and then evaporated in vacuo. The residue was redissolved in water
(400 ml), carefully acidified with 0.5 M HCl to pH 1, cooled in ice (2 h), precipitate collected,
washed with water and dried at 50 °C for 5 h. Crystallization from acetone (50 ml) and toluene (5 ml)
1
yielded (after 24 h drying in vacuo at 70 °C) 10.6 g (95%) of beige crystals, m.p. 197–200 °C. H NMR
spectrum (CDCl3): 3.50 s, 3 H (OCH3); 3.83 s, 3 H (OCH3); 7.09 d, 1 H, J = 8.7 (arom. H); 7.19 d,
1 H, J = 8.8 (arom. H); 7.30 m, 1 H (arom. H); 7.39 m, 1 H (arom. H); 7.51 m, 2 H (arom. H); 7.92 d,
1 H, J = 7.7 (arom. H); 8.07 m, 2 H (arom. H), 8.93 s, 1 H (arom. H). 13C NMR spectrum, APT
(CDCl3): CH3 and CH: 57.00, 62.76, 113.86, 124.855, 125.26, 126.14, 126.72, 127.79, 128.79,
129,73, 130.29, 131.37, 135.84; CH2 and C: 117.79, 121.42, 126.65, 129.65, 130.81, 134.20, 137.13,
154.08, 155.54, 167.30. IR spectrum (CHCl3): 1 737 (C=O). Mass spectrum, m/z (rel. int., %): 358
(M+, 100). For C23H18O4 (358.4) calculated: 77.08% C, 5.06% H; found: 77.14% C, 5.07% H.
(S)-2,2′-Dimethoxy-1,1′-binaphthalene-3-carboxylic Acid (S-5)
The chiral acid was prepared from S-4 in 99% yield as amorphous solid using the same method as
described for the racemic compound. 1H NMR, IR a MS data correspond to those of the racemic
compound. For C23H18O4 (358.4) calculated: 77.08% C, 5.06% H; found: 76.59% C, 5.14% H.
[α]2D0 –62.2° (c 0.29, chloroform).
Methyl (R,S)-3′-Hydroxymethyl-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (R,S-6)
Compound R,S-3 (11.4 g, 27.4 mmol) was dissolved in anhydrous tetrahydrofuran (70 ml) under dry
nitrogen and 1.0 M solution of BH3 . THF complex in THF (41.0 ml) was added during 15 min main-
taining temperature at –16 °C with stirring. Reaction mixture was stirred at –10 °C for 2 h and at 10 °C
for another 2 h, then carefully quenched with ice–water (10 ml) followed by saturated NaHCO3 (10 ml).
Most of THF was evaporated in vacuo and the residue was partitioned between water (100 ml) and
diethyl ether (50 ml). Aqueous phase was extracted twice with diethyl ether (50 ml), combined
extracts were dried with MgSO4, evaporated in vacuo and the crude product was chromatographed on
silica gel using toluene–10% acetone. Methyl (R,S)-3′-hydroxymethyl-2,2′-dimethoxy-1,1′-binaphthalene-
1
3-carboxylate (R,S-6) 10.7 g (97%) was isolated as white solid, m.p. 127.5–131 °C. H NMR spectrum
(CDCl3): 2.86 s, 1 H (OH); 3.34 s, 3 H (OCH3); 3.43 s, 3 H (OCH3); 3.99 s, 3 H (COOCH3); 4.93 d,
1 H, J = 13.7 (OCH-H); 5.03 d, 1 H, J = 13.7 (OCH-H); 7.11–7.46 m, 6 H (arom. H); 7.87 d, 1 H,
J = 8.2 (arom. H); 7.96 d, 1 H, J = 8.2 (arom. H); 8.03 s, 1 H (arom. H); 8.55 s, 1 H (arom. H). 13C NMR
spectrum, APT (CDCl3): CH3 and CH: 53.05, 61.49, 62.52, 125.60, 125.97, 126.20, 126.36, 126.96,
128.69, 128.89, 129.17, 129.71, 133.92; CH2 and C: 62.56, 124.30, 127.22, 130.16, 131.21, 134.31,
134.72, 136.48, 154.96, 155.25, 167.60. IR spectrum (CHCl3): 1 726.5 (C=O); 3 608 (OH). Mass
spectrum, m/z (rel. int., %): 402 (M+, 100). For C25H22O5 (402.4) calculated: 74.61% C, 5.51% H;
found: 74.37% C, 5.57% H.
Methyl (R)-3′-Hydroxymethyl-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (R-6)
R-6 was prepared using the same procedure as above and was isolated as a colourless glass in 81%
yield. 1H NMR, IR a MS data were identical with those of the racemic compounds. For C25H22O5
(402.4) calculated: 74.61% C, 5.51% H; found: 74.94 %C, 5.62% H. [α]2D0 +5.9° (c 1.0, THF).
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Axially Chiral Synthons
933
Methyl (S)-3′-Hydroxymethyl-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (S-6)
S-6 was prepared using the same procedure as above and was isolated as a colourless glass in 87%
yield. 1H NMR, IR a MS data were identical with those of the racemic compounds. For C25H22O5
(402.4) calculated: 74.61% C, 5.51% H; found: 74.42 %C, 5.79% H. [α]2D0 –5.9° (c 1.0, THF).
Methyl (R,S)-3′-Acetoxymethyl-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (R,S-7)
Pure R,S-6 (4.90 g, 12.2 mmol) was dissolved in acetyl chloride (50 ml, 70 mmol) the mixture was
refluxed for 2 h, coolled and evaporated in vacuo to dryness. The crude product was partitioned be-
tween diethyl ether (150 ml) and saturated solution of NaHCO3 (50 ml). The aqueous phase was ex-
tracted with 50 ml of diethyl ether, combined extracts were dried with MgSO4 and, after evaporation,
subjected to column chromatography (50 g silica gel, toluene–5% acetone). After 2 h at 50 °C/2 kPa,
1
5.26 g (97%) of colourless glass R,S-7 was obtained. RF 0.5 (toluene–acetone 3 : 97). H NMR spec-
trum (CDCl3): 2.18 s, 3 H (COCH3); 3.35 s, 3 H (OCH3); 3.45 s, 3 H (OCH3); 3.99 s, 3 H
(COOCH3); 5.38 d, 1 H, J = 13.2 (OCH-H); 5.43 d, 1 H, J = 13.2 (OCH-H); 7.12 d, 1 H, J = 8.3
(arom. H); 7.18 d, 1 H, J = 8.8 (arom. H); 7.23–7.48 m, 4 H (arom. H); 7.91 d, 1 H, J = 8.2 (arom. H);
7.97 d, 1 H, J = 8.2 (arom. H); 8.03 s, 1 H (arom. H); 8.55 s, 1 H (arom. H). 13C NMR spectrum,
APT (CDCl3): CH3 and CH: 21.17, 52.47, 61.27, 61.99, 125.13, 125.44, 125.61, 125.76, 126.76,
128.19, 128.58, 129.14, 129.97, 133.39; CH2 and C: 62.43, 124.26, 125.05, 126.50, 129.43, 129.57,
130.40, 134.10, 135.85, 154.41, 154.79, 167.02, 170,91. IR spectrum (CHCl3): 1 732 (C=O). Mass
spectrum, m/z (rel. int., %): 444 (M+, 100). For C27H24O6 . 1.5 H2O (471.5) calculated: 68.78% C,
5.77% H; found: 68.82% C, 5.77% H.
Methyl (R)-3′-Acetoxymethyl-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (R-7)
R-7 was prepared in 94% yield using the same method as described for the racemic compound. Using
diffusion of heptane into toluene solution of pure R-7, a crystalline product having m.p. 89–91 °C
was obtained after three months at ambient temperature. 1H NMR and IR data were identical with
those of the racemic compound. For C27H24O6 (444.5) calculated: 72.96% C, 5.44% H; found:
73.04% C, 5.46% H. [α]2D0 +6.0° (c 1.06, THF).
Methyl (S)-3′-Acetoxymethyl-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (S-7)
S-7, m.p. 89.5–91 °C was prepared in 99% yield by the same method as described for racemic com-
pound. 1H NMR and IR data were identical with those of the racemic compound. For C27H24O6
(444.5) calculated: 72.96% C, 5.44% H; found: 72.83% C, 5.51% H. [α]2D0 –5.9° (c 1.13, THF).
Methyl (R,S)-3′-Chloromethyl-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (R,S-8).
Thionyl chloride (3 ml, 41 mmol) and R,S-6 (1 g, 2.48 mmol) was slowly heated to reflux and then
refluxed for 2 h. All volatiles were evaporated in vacuo and the solid residue was chromatographed
on silica gel–chloroform. The amorphous product was obtained in nearly quantitative yield (1.05 g).
RF 0.8 (toluene–acetone 3 : 97). 1H NMR spectrum (CDCl3): 3.39 s, 3 H (OCH3); 3.45 s, 3 H
(OCH3); 4.00 s, 3 H (COOCH3); 4.81 d, 1 H, J = 11.5 (OCH-H); 5.01 d, 1 H, J = 11.5 (OCH-H);
7.16 d, 1 H, J = 8.7 (arom. H); 7.22 d, 1 H, J = 8.8 (arom. H); 7.26–7.48 m, 4 H (arom. H); 7.90 d,
1 H, J = 8.2 (arom. H); 7.98 d, 1 H, J = 8.2 (arom. H); 8.10 s, 1 H (arom. H); 8.57 s, 1 H (arom. H).
13C NMR spectrum, APT (CDCl3): CH3 and CH: 53.08, 62.09, 62.59, 125.83, 126.05, 126.26,
126.38, 127.61, 128.81, 129.26, 129.76, 131.52, 134.05; CH2 and C: 42.83, 124.98, 125.72, 127.04,
130.19, 131.05, 131.68, 134.93, 136.43, 155.02, 155.25, 167.59. IR spectrum (CHCl3): 1 732 (C=O).
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934
Lellek, Stibor:
Mass spectrum, m/z (rel. int., %): 420 (M+, 100), 422 (M+ + 2, 30). For C25H21ClO4 (420.9) calcu-
lated: 71.34% C, 5.03% H, 8.42% Cl; found: 71.00% C, 5.14% H, 8.61% Cl.
Methyl (R,S)-3′-(Benzoyloxymethyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (R,S-9)
Pure 7 (0.5 g, 1.24 mmol) was dissolved in dry dichloromethane (5 ml) along with 4-(dimethyl-
amino)pyridine (1.52 g, 12.4 mmol) and cooled to 0 °C. Benzoyl chloride (1.44 ml, 12.42 mmol) in
dry dichloromethane (5 ml) was added dropwise with cooling. The reaction mixture was stirred for
additional 2 h and temperature was allowed to rise to ambient and stirring was continued for 48 h,
then poured into 10% aqueous solution of potassium carbonate (50 ml) and extracted with chloro-
form (3 × 20 ml). Combined organic phases were washed with 3% HCl (30 ml), dried with magne-
sium sulfate and evaporated. The crude material was subjected to chromatography on silica
gel–chloroform and after 2 h of drying in vacuo at 50 °C glassy methyl (R,S)-3′-(benzoyloxymethyl)-
2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (R,S-9) in nearly quantitative yield (629 mg) was
obtained. RF 0.7 (toluene–acetone 3 : 97). 1H NMR spectrum (CDCl3): 3.40 s, 3 H (OCH3); 3.47 s,
3 H (OCH3); 4.00 s, 3 H (COOCH3); 5.68 d, 1 H, J = 13.2 (OCH-H); 5.73 d, 1 H, J = 13.2 (OCH-H);
7.13–7.60 m, 9 H (arom. H); 7.92 d, 1 H, J = 8.4 (arom. H); 7.98 d, 1 H, J = 8.2 (arom. H); 8.14 m, 3 H
(arom. H); 8.56 s, 1 H (arom. H). 13C NMR spectrum, APT (CDCl3): CH3 and CH: 53.09, 62.04,
62.66, 125.77, 126.10, 126.24, 126.45, 127.42, 128.89, 129.11, 129.23, 129.78, 130.38, 130.74,
133.72, 134.04; CH2 and C: 63.52, 124.95, 127.18, 130.16, 130.23, 131.09, 134.79, 136.52, 155.08,
155.55, 167.08, 167.64. IR spectrum (CHCl3): 1 719 (C=O). Mass spectrum, m/z (rel. int., %): 506
(M+, 46). For C32H26O6 (506.6) calculated: 75.88% C, 5.17% H; found: 75.58% C, 5.19% H.
Methyl (R,S)-3′,6′-Bis(chloromethyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (R,S-10)
Solution of R,S-7 (2.2 g, 5.0 mmol) in anhydrous dichloromethane (20 ml) was treated successively
with methoxymethyl chloride (1.6 g, 24.8 mmol) at –20 °C under vigorous stirring, then solution of
SnCl4 (1.43 ml, 12.42 mmol) in dichloromethane (15 ml) was added dropwise within 5 min. The
reaction mixture was stirred for 3.5 h, allowed to warm to ambient temperature (1 h) and stirred
another 30 min at this temperature. After quenching by addition of 5% HCl (10 ml), the organic layer
was extracted with water (5 ml) and 3% aqueous solution of NaHCO3 (5 ml), dried with MgSO4,
evaporated in vacuo and chromatographed on silica gel (toluene–3% acetone). Slow diffusion of hex-
ane in toluene solution afforded crystalline crude material (1.8 g) that was recrystallized (the only
procedure for separation of undesired methyl (R,S)-3′,6,6′-tris(chloromethyl)-2,2′-dimethoxy-1,1′-bi-
naphthalene-3-carboxylate) giving 1.17 g (50%) of white crystals (m.p. 176–182 °C). RF 0.7 (toluene–
acetone 3 : 97). 1H NMR spectrum (CDCl3): 3.36 s, 3 H (OCH3); 3.44 s, 3 H (OCH3); 4.00 s, 3 H
(COOCH3); 4.71 s, 2 H (CH2Cl); 4.72 s, 2 H (CH2Cl); 4.83 d, 1 H, J = 11.5 (OCH-H); 4.96 d, 1 H,
J = 11.5 (OCH-H); 7.10 d, 1 H, J = 8.8 (arom. H); 7.18 d, 1 H, J = 8.8 (arom. H); 7.26–7.40 m, 3 H
(arom. H); 7.89 s, 1 H (arom. H); 7.96 s, 1 H (arom. H); 8.07 s, 1 H (arom. H); 8.53 s, 1 H (arom. H).
13C NMR spectrum, APT (CDCl3): CH3 and CH: 53.24, 62.23, 62.76, 126.77, 127.12, 128.16,
128.50, 129.28, 129.78, 131.67, 134.16; CH2 and C: 42.65, 46.63, 46.87, 124.80, 126.88, 129.97,
130.82, 132.44, 134.56, 134.99, 135.47, 136.04, 155.65, 155.84, 167.40. IR spectrum (CHCl3): 1 727
(C=O). Mass spectrum, m/z (rel. int., %): 468 (M+, 100), 470 (M+ + 2, 70). For C26H22O4Cl2 (469.4)
calculated: 66.53% C, 4.72% H, 15.11% Cl; found: 66.55% C, 4.79% H, 15.11% Cl.
Methyl (S)-3′,6′-Bis(chloromethyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (S-10)
Solution of S-7 (2.0 g, 4.5 mmol) in anhydrous dichloromethane (7 ml) was treated successively with
methoxymethyl chloride (1.45 g, 22.5 mmol) at –60 °C under vigorous stirring. Then solution of
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Axially Chiral Synthons
935
SnCl4 (2.6 ml, 22.5 mmol) in dichloromethane (15 ml) was added within 5 min and the reaction mix-
ture was stirred for 3.5 h, allowed to warm to ambient temperature (1 h) and stirred another 30 min.
The mixture was quenched by addition of 5% HCl (10 ml). The organic layer was extracted with
water (5 ml) and 3% aqueous solution of NaHCO3 (5 ml), dried with MgSO4, evaporated in vacuo
and chromatographed on silica gel (dichloromethane) giving 1.65 g of yellowish material. Fourfold
chromatography on silica gel (Kieselgel 60H) using heptane–ether–acetone–methanol (80 : 10 : 10 : 0.5)
led to separation of following compounds:
Amorphous colourless methyl (S)-3′,6′-bis(chloromethyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-car-
boxylate (S-10), 1.12 g (50%). 1H NMR and IR data correspond to those of racemic compound. For
C26H22Cl2O4 (469.4) calculated: 66.53% C, 4.72% H, 15.11% Cl; found: 66.55% C, 4.79% H,
15.11% Cl. [α]2D5 –7.2° (c 1, THF).
Methyl (S)-3′,6,6′-tris(chloromethyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (S-11) 130 mg
1
(5%), RF 0.6 (toluene–acetone 3 : 97). H NMR spectrum (CDCl3): 3.38 s, 3 H (OCH3); 3.44 s, 3 H
(OCH3); 4.00 s, 3 H (COOCH3); 4.72 s, 2 H (CH2Cl); 4.84 d, 1 H, J = 11.4 (OCH-H); 4.98 d, 1 H,
J = 11.4 (OCH-H); 7.14 d, 1 H, J = 8.7 (arom. H); 7.18 d, 1 H, J = 8.4 (arom. H); 7.26–7.50 m, 3 H
(arom. H); 7.90 s, 1 H (arom. H); 7.98 d, 1 H, J = 8.2 (arom. H); 8.08 s, 1 H (arom. H); 8.56 s, 1 H
(arom. H). 13C NMR, APT (CDCl3): CH3 and CH: 53.19, 62.18, 62.74, 126.36, 126.42, 126.94,
128.08, 128.50, 129.46, 129.89, 131.55, 134.31; CH2 and C: 42.75, 46.95, 125.09, 125.75, 126.83,
130.23, 130.85, 132.47, 134.73, 134.95, 136.42, 155.12, 155.87, 167.64. IR spectrum (CHCl3): 1 727
(C=O). Mass spectrum, m/z (rel. int., %): 515 (M+, 30), 517 (M+ + 2, 28), 517 (M+ + 4, 10). [α]2D5
+42.6° (c 0.23, chloroform).
General Procedure for Monochloromethylation of Binaphthalenes 6–9
3,3′-Disubstituted binaphthol (0.3 mmol) was dissolved in dry dichloromethane (2 ml) and treated
with methoxymethyl chloride (97 mg, 1.5 mmol). The solution was cooled to –15 °C and SnCl4 (85 µl,
0.75 mmol) dissolved in dry dichloromethane (4 ml) was added dropwise. The reaction mixture was
stirred at –15 °C for 3.5 h, then at ambient temperature for 2 h and quenched by pouring onto a silica
gel column. Fractions with intense blue luminiscence (excitation at 254 nm) eluated with dichloro-
methane were collected, evaporated and analyzed by NMR spectroscopy.
Methyl (R,S)-3′,6′-Bis(4-hydroxy-2-oxabutyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (R,S-12)
R,S-10 (470 mg, 1 mmol) and silver oxide (580 mg, 2.5 mmol) was refluxed in dry ethylene glycol
(5 ml) with stirring for 1 h under nitrogen. The excess of ethylene glycol was distilled off under
vacuum and residual material was chromatographed on silica gel (Kieselgel 60 H, chloroform–5%
methanol) giving pure R,S-12 (210 mg, 40%) and about 37% of 2-hydroxyethyl (R,S)-3′,6′-bis(4-hy-
droxy-2-oxabutyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (in a mixture with another un-
1
identified product). H NMR spectrum (CDCl3): 2.27 s, 2 H (OH); 3.33 s, 3 H (OCH3); 3.43 s, 3 H
(OCH3); 3.63 t, 2 H, J = 4.5 (CH2); 3.77 t, 4 H, J = 4.4 (CH2); 3.83 t, 2 H, J = 4.4 (CH2); 3.99 s,
3 H (COOCH3); 4.67 s, 2 H (ArCH2O); 4.82 d, 1 H, J = 12.2 (OCH-H); 4.86 d, 1 H, J = 12.2
(OCH-H); 7.09–7.27 m, 3 H (arom. H); 7.33 t, 1 H, J = 7.6 (arom. H); 7.42 t, 1 H, J = 7.8 (arom. H);
7.86 s, 1 H (arom. H); 7.96 d, 1 H, J = 8.2 (arom. H); 8.05 s, 1 H (arom. H); 8.53 s, 1 H (arom. H).
13C NMR spectrum, APT (CDCl3): CH3 and CH: 53.06, 61.75, 62.54, 126.20, 126.33, 126.41,
126.96, 127.42, 129.16, 129.72, 129.75, 133.91; CH2 and C: 62.48, 62.49, 69.58, 72.21, 72.62, 73.79,
124.61, 125.62, 127.19, 130.16, 130.98, 132.35, 133.99, 135.26, 136.44, 154.95, 155.39, 167.63. IR
spectrum (CHCl3): 3 599 (OH); 3 479 (OH); 1 725 (C=O). Mass spectrum, m/z (rel. int., %): 520
(M+, 100). For C30H32O8 . H2O (538.6) calculated: 66.90% C, 6.36% H; found: 66.79% C, 6.40% H.
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936
Lellek, Stibor:
Methyl (S)-3′,6′-Bis(4-hydroxy-2-oxabutyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (S-12)
Product S-12 was obtained from S-10 (440 mg, 0.94 mmol) by the procedure described above for
racemic compound. S-12 (238 mg, 49%) was isolated along with 142 mg (29%) of 2-hydroxyethyl (S)-
3′,6′-bis(4-hydroxy-2-oxabutyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (impure). 1H NMR and
IR data of S-12 correspond to those of racemic compound. For C30H32O8 (529.6) calculated: 68.04%
C, 6.28% H; found: 68.21% C, 6.15% H; [a]D20 –6.2° (c 0.5, THF).
(R,S)-3′,6′-Bis(4-hydroxy-2-oxabutyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylic Acid (R,S-13)
A mixture of R,S-12 (300 mg, 0.576 mmol), solution of KOH (323 mg, 5.76 mmol) in water (1.5 ml),
methanol (2.5 ml), and tetrahydrofuran (5 ml) was stirred and refluxed for 1 h. Then it was stirred
for another 12 h at ambient temperature, evaporated in vacuo, diluted with ice water (50 ml) and
acidified with concentrated HCl to pH ≈ 1. The white precipitate obtained was extracted with chlo-
roform (2 × 30 ml), the organic phase was dried with MgSO4 and evaporated in vacuo. The residue
was chromatographed on silica gel (chloroform–5% methanol) giving after drying (24 h, 250 Pa/50 °C)
257 mg (88%) of glassy R,S-13. 1H NMR spectrum (CDCl3): 3.30 s, 3 H (OCH3); 3.38 s, 3 H
(OCH3); 3.64 t, 2 H, J = 4.5 (CH2); 3.78 t, 4 H, J = 4.4 (CH2); 3.83 q, 2 H, J = 3.1 (CH2); 4.67 s,
2 H (ArCH2O); 4.83 d, 1 H, J = 12.6 (OCH-H); 4.88 d, 1 H, J = 12.6 (OCH-H); 5.65 s, 2 H (OH);
7.08 d, 1 H, J = 8.6 (arom. H); 7.17 d, 1 H, J = 8.8 (arom. H); 7.24 d, 1 H, J = 10.4 (arom. H); 7.35 t,
1 H, J = 7.7 (arom. H); 7.47 t, 1 H, J = 7.8 (arom. H); 7.88 s, 1 H (arom. H); 8.00 d, 1 H, J = 8.2
(arom. H); 8.07 s, 1 H (arom. H); 8.83 s, 1 H (arom. H). 13C NMR spectrum, APT (CDCl3): CH3 and
CH: 61.79, 62.79, 126.14, 126.24, 127.24, 127.49, 129.74, 130.15, 130.30, 135.72; CH2 and C: 62.27,
62.29, 69.43, 72.17, 72.56, 73.58, 122.76, 123.89, 126.43, 130.36, 130.95, 132.25, 133.72, 135.39,
136.92, 154.45, 155.39, 168.01. IR spectrum (CHCl3): 1 736 (C=O). Mass spectrum (FAB, glycerol–
thioglycerol), m/z (rel. int., %): 506.2 (M+, 30), 445.2 ([M – C2H5O+2], 100). For C29H30O8 (506.6)
calculated: 68.00% C, 6.11% H; found: 67.95% C, 6.09% H.
(S)-3′,6′-Bis(4-hydroxy-2-oxabutyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylic Acid (S-13)
Procedure A: S-13 was prepared according by the same procedure as racemic compound starting
from S-12. Pure acid was isolated as a glassy material in 98% yield. The product was identical with
that prepared by procedure B.
Procedure B: S-13 was prepared from crude 2-hydroxyethyl (S)-3′,6′-bis(4-hydroxy-2-oxabutyl)-
2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (300 mg, 576 µmol) and a solution of KOH (323 mg,
5.76 mmol) in water (1.5 ml) and methanol (2.5 ml). Pure (S)-3′,6′-bis(4-hydroxy-2-oxabutyl)-2,2′-
dimethoxy-1,1′-binaphthalene-3-carboxylic acid (S-13) was isolated in 90% yield. 1H NMR and IR
data correspond to those of racemic compound. For C29H30O8 (506.6) calculated: 68.00% C, 6.11% H;
found: 67.84% C, 6.09% H.
2-Oxoethyl-2-phenyl (R,S)-3′,6′-Bis(4-hydroxy-2-oxabutyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-car-
boxylate (R,S-14)
To the mixture od phenacyl bromide (110 mg, 217 µmol) and potassium fluoride (28 mg, 0.478 mmol)
in dry DMF (0.5 ml) a solution of acid R,S-13 (43.4 mg, 0.217 mmol) in dry DMF (1.3 ml) was
added dropwise and stirred for 12 h at ambient temperature. The reaction mixture was quenched with
water (15 ml) and extracted with chloroform (3 × 15 ml). The organic phase was dried, evaporated
in vacuo and subjected to chromatography (Kieselgel 60H, chloroform–2% methanol). After drying
for 2 h at 40 °C and 2.5 kPa, 100 mg (73%) of a colourless glassy product was isolated. Using
diffusion of heptane into a benzene solution of pure R,S-14 at ambient temperature the crystalline
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Axially Chiral Synthons
937
product m.p. 116–124 °C was obtained after three days. 1H NMR spectrum (CDCl3): 2.55 s, 2 H
(OH); 3.36 s, 3 H (OCH3); 3.48 s, 3 H (OCH3); 3.60 t, 2 H, J = 4.3 (CH2); 3.77 m, 4 H (CH2); 3.83 t,
2 H, J = 4.4 (CH2); 4.65 s, 2 H (ArCH2O); 4.83 d, 1 H, J = 12.6 (OCH-H); 4.88 d, 1 H, J = 12.6
(OCH-H); 5.63 d, 1 H, J = 16.5 (H-CHCO); 5.70 d, 1 H, J = 16.5 (H-CHCO); 7.11–7.52 m, 7 H (arom. H);
7.61 t, 1 H, J = 7.4 (arom. H); 7.86 s, 1 H (arom. H); 7.98–8.00 m, 3 H (arom. H); 8.06 s, 1 H (arom. H);
8.76 s, 1 H (arom. H). 13C NMR spectrum, APT (CDCl3): CH3 and CH: 61.74, 62.72, 126.19,
126.29, 126.41, 126.92, 127.35, 128.42, 129.31, 129.48, 129.71, 129.88, 134.51, 134.66; CH2 and C:
62.44, 67.19, 69.53, 72.17, 72.58, 73.74, 124.56, 124.67, 127.29, 130.13, 130.95, 132.33, 133.96,
134.89, 135.26, 136.69, 155.14, 155.37, 166.13, 192.81. IR spectrum (CHCl3): 3 598 (OH); 3 467
(OH); 1 735 (C=O); 1 704 (C=O). Mass spectrum, m/z (rel. int., %): 624 (M+, 100). For C37H36O9 (624.7)
calculated: 71.14% C, 5.81% H; found: 70.97% C, 5.97% H.
2-Oxoethyl-2-phenyl (S)-3′,6′-Bis(4-hydroxy-2-oxabutyl)-2,2′-dimethoxy-1,1′-binaphthalene-
3-carboxylate (S-14)
Compound S-14 was prepared using the same procedure as for racemic compound and isolated in
1
78% yield as a glass. H NMR and IR data correspond to those of racemic compound. For C37H 36O9
(624.7) calculated: 71.14% C, 5.81% H; found: 70.81% C, 5.81% H; [α]2D0 –23.6° (c 1, THF).
Methyl (2-Oxoethyl-2-phenyl) (R,S)-2,2′-Dimethoxy-1,1′-binaphthalene-3,3′-dicarboxylate (R,S-15)
A mixture of phenacyl bromide (48 mg, 0.24 mmol), potassium fluoride (31 mg, 0.528 mmol) and
acid R,S-4 (100 mg, 0.24 mmol) in dry DMF (2 ml) was stirred for 20 h at ambient temperature. The
reaction mixture was evaporated in vacuo and chromatographed on a column of silica gel with chloroform
as eluent. The crude product was further purified by preparative TLC (Kieselgel G, chloroform) giving
116 mg (90%) of R,S-15 which, recrystallized from benzene–heptane (1 : 2), had m.p. 173.5–175.5 °C.
1H NMR spectrum (CDCl3): 3.52 s, 3 H (OCH3); 3.54 s, 3 H (OCH3); 3.99 s, 3 H (COOCH3); 5.63 d, 1 H,
J = 16.5 (H-CHCO); 5.70 d, 1 H, J = 16.5 (H-CHCO); 7.15–7.64 m, 9 H (arom. H); 7.96-8.02 m,
4 H (arom. H); 8.57 s, 1 H (arom. H); 8.78 s, 1 H (arom. H). 13C NMR spectrum, APT (CDCl3):
CH3 and CH: 53.00, 62.64, 62.83, 126.15, 126.21, 128.44, 129.14, 129.34, 129.51, 129.70, 129.93,
134.01, 134.52, 134.79; CH2 and C: 67.21, 124.60, 125.51, 126.85, 126.98, 130.18, 134.95, 136.35,
136.61, 154.99, 155.19, 166.09, 167.53, 192.80. IR spectrum (CHCl3): 1 730 (C=O), 1 705 (C=O).
Mass spectrum, m/z (rel. int., %): 430 ([M – 105+], 6), 119 (PhCOCH+2, 15), 105 (PhCO+, 100). For
C33H26O7 (534.6) calculated: 74.15% C, 4.90% H; found: 74.17% C, 5.09% H.
Methyl (R,S)-3′,6′-Bis(methoxymethyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (16)
Procedure A: A stirred suspension of R,S-10 (500 mg, 1.063 mmol) in a mixture of dry methanol
(10 ml) and dioxane (5 ml) was treated with anhydrous AlCl3 (425 mg, 3.19 mmol) under argon. The
reaction mixture was heated to reflux for 20 min and then dry methanol (20 ml) was added. Another
portion of dry methanol (10 ml) was added after 20 h of stirring followed by 5 ml of methanol after
each 24 h until total 96 h of stirring was attained. The reaction mixture was evaporated in vacuo and
filtered through a short column of silica gel using chloroform–acetone (10 : 1) as eluent. The eluated
product was further purified using TLC plate (Kieselgel 60 PF254, chloroform). Pure R,S-16 (480 mg,
98%) was obtained after drying at 250 Pa/50 °C as white powder.
Procedure B: R,S-10 (380 mg, 0.81 mmol) was suspended in dry methanol (6 ml) and silver oxide
(464 mg, 2 mmol) was added under dry nitrogen. The reaction mixture was refluxed for 12 h with
stirring, cooled, evaporated in vacuo and chromatographed on a column of silica gel in chloroform.
After drying 354 mg (95%) of R,S-16 was isolated. After recrystallization from methanol yielded 210 mg
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1
(59%) of white crystals, m.p 118.5–120 °C. H NMR spectrum (CDCl3): 3.34 s, 3 H (OCH3); 3.42 s,
6 H (OCH3); 3.56 s, 3 H (OCH3); 3.99 s, 3 H (COOCH3); 4.57 s, 2 H (CH2); 4.71 d, 1 H, J = 12.6
(OCH-H); 4.78 d, 1 H, J = 12.6 (OCH-H); 7.10–7.46 m, 5 H (arom. H); 7.86 s, 1 H (arom. H); 7.96 d,
1 H, J = 8.24 (arom. H); 8.06 s, 1 H (arom. H), 8.53 s, 1 H (arom. H). 13C NMR spectrum, APT
(CDCl3): CH3 and CH: 53.00, 58.87, 59.03, 61.76, 62.52, 126.15, 126.36, 126.43, 126.89, 127.40,
129.08, 129.58, 129.68, 133,77; CH2 and C: 70.95, 75.30, 124.55, 125.75, 127.37, 130.19, 131.08,
132.57, 133.92, 135.39, 136.53, 155.00, 155.38, 167.67. IR spectrum (CHCl3): 1 726 (C=O). Mass
spectrum, m/z (rel. int., %): 460 (M+, 25). For C28
H 28O6 (460.5) calculated: 73.01% C, 6.13% H;
found: 72.69% C, 6.05% H.
Methyl (S)-3′,6′-Bis(methoxymethyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylate (S-16)
Ester S-16 was prepared from S-10 using procedure B (see above) in 85% yield. 1H NMR and IR
data correspond to those of racemic compound. For C28H28O6 . 0.25 H2O (465.0) calculated: 72.32% C,
6.18% H; found: 72.46% C, 6.28% H. [α]2D0 –7.9° (c 0.97, THF).
(R,S)- 3′,6′-Bis(methoxymethyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylic Acid (R,S-17)
Ester R,S-16 (480 mg, 1.04 mmol) in tetrahydrofuran (5 ml) was hydrolyzed with a solution of KOH
(1.17 g, 20 mmol) in water (1.5 ml) and methanol (2.5 ml) by 30 min reflux. All volatiles were
evaporated in vacuo, water (50 ml) was added to the residue and acidified with concentrated HCl to
pH ≈ 1. The precipitate was collected after two hours, washed with water and dried giving 430 mg
1
(93%) of pure R,S-17. H NMR spectrum (CDCl3): 3.32 s, 3 H (OCH3); 3.41 s, 3 H (OCH3); 3.45 s, 3 H
(OCH3); 3.57 s, 3 H (OCH3); 4.58 s, 2 H (CH2); 4.72 d, 1 H, J = 12.6 (OCH-H); 4.78 d, 1 H, J =
12.6 (OCH-H); 7.10 d, 1 H, J = 8.6 (arom. H); 7.23 d, 1 H, J = 8.2 (arom. H); 7.25–7.53 m, 3 H
(arom. H); 7.89 s, 1 H (arom. H); 8.04 d, 1 H, J = 8.2 (arom. H); 8.10 s, 1 H (arom. H); 8.92 s, 1 H
(arom. H).13C NMR spectrum, APT (CDCl3): CH3 and CH: 59.13, 59.35, 62.01, 63.11, 126.16,
126.52, 126.98, 127.55, 127.63, 130.12, 130.51, 130.55, 136.42; CH2 and C: 70.95, 75.27, 121.66,
123.58, 126.24, 130.77, 131.23, 132.74, 133.70, 135.93, 137.34, 154.19, 155.59, 166.66. IR spectrum
(CHCl3): 3 195 (COOH), 1 737 (C=O). Mass spectrum, m/z (rel. int., %): 446 (M+, 4). For C27H26O6 . 0.25 H2O
(451.0) calculated: 71.91% C, 5.92% H; found: 71.67% C, 5.73% H.
(S)-3′,6′-Bis(methoxymethyl)-2,2′-dimethoxy-1,1′-binaphthalene-3-carboxylic Acid (S-17)
S-17 was prepared in 98% yield from S-16 using the same procedure as for racemic compound. 1H NMR
and IR data correspond to those of racemic compound. [α]2D0 –6.9° (c 0.26, THF). For C27H26O6 . 1.5 H2O
(473.5) calculated: 68.49% C, 6.17% H; found: 68.55% C, 6.16% H.
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