Asymmetric synthesis of new chiral 1,2- and 1,3-diols

Article abstract of DOI:10.1007/s00706-012-0792-7

Seven chiral 1,2-diols and six chiral 1,3-diols were synthesized by the asymmetric reduction of the corresponding 1,2-diketones and 1,3-diketones using oxazaborolidine-BH₃ catalyst. The 13 corresponding racemic 1,2- and 1,3-diols were synthesized by reducing the diketones with NaBH₄ and they were used for determining the ee values through their chiral resolution on HPLC and GC. Five starting diketones, four racemic 1,2-diols, five chiral 1,2-diols, and two chiral 1,3-diols are novel compounds. The new chiral compounds were characterized by IR, ¹H and ¹³C NMR, MS, and elemental analysis. The asymmetric reduction method, oxazaborolidine-BH ₃, was applied to these diketones for the first time in this study. The relationship between the structure of the diketone and the yield, diastereoselectivity, and enantiomeric excess was discussed.

Full text of DOI:10.1007/s00706-012-0792-7

Monatsh Chem (2013) 144:183–190
DOI 10.1007/s00706-012-0792-7
ORIGINAL PAPER
Asymmetric synthesis of new chiral 1,2- and 1,3-diols
•
˘
Tu¨lay Yıldız Ays¸e Yusufoglu
Received: 4 November 2011 / Accepted: 8 May 2012 / Published online: 12 June 2012
Ó Springer-Verlag 2012
Abstract Seven chiral 1,2-diols and six chiral 1,3-diols
were synthesized by the asymmetric reduction of the
corresponding 1,2-diketones and 1,3-diketones using
oxazaborolidine–BH3 catalyst. The 13 corresponding racemic
1,2- and 1,3-diols were synthesized by reducing the dike-
tones with NaBH4 and they were used for determining the
ee values through their chiral resolution on HPLC and
GC. Five starting diketones, four racemic 1,2-diols, five
chiral 1,2-diols, and two chiral 1,3-diols are novel com-
pounds. The new chiral compounds were characterized
prochiral diketones by chiral catalysts and reagents. During
the past few years, a large number of reducing agents and
chiral catalysts have been developed that facilitate the
reduction reaction under a wide range of conditions [1–3].
Although hydrogenation in the presence of diphosphine–
Ru (or Rh) complexes [4, 5] and hydride reduction pro-
moted by chiral organoboranes [6–8] have been reported to
be very effective on a broad range of ketones, only a
limited number of examples have been applied for the
enantio- and diastereoselective reduction of diketones
of different structure. Amongst them the development of
methods for the diastereoselective reduction of carbonyl
groups continues to be of interest in organic chemistry
[9, 10]. In particular, chemical routes towards vicinal diols
in terms of stereospecificity and enantioselectivity include
the catalytic cis-dihydroxylation of olefins with OsO4
[11, 12] and the catalytic asymmetric transfer hydrogenation
of diketones [13]. Biocatalytic methods for the synthesis of
diols are the kinetic resolution of racemic diols achieved by
enzymatic oxidation [14] and the enzymatic and microbial
reduction of diketones [15, 16].
1
by IR, H and 13C NMR, MS, and elemental analysis. The
asymmetric reduction method, oxazaborolidine–BH3, was
applied to these diketones for the first time in this study.
The relationship between the structure of the diketone and
the yield, diastereoselectivity, and enantiomeric excess was
discussed.
Keywords Asymmetric synthesis Á Chiral 1,2-diol Á
Chiral 1,3-diol Á Diketone Á Reduction
Introduction
The oxazaborolidine-mediated enantioselective reduction
of ketones with borane is a well-established methodology.
Since the famous CBS (Corey–Bakshi–Shibata) oxaza-
borolidine catalyst was obtained by Corey et al. [17, 18]
from (R)- or (S)-proline, a number of new chiral oxaz-
aborolidines have been synthesized and used widely in
asymmetric reductions. Among the characteristics of the
CBS-catalyzed enantioselective reduction of prochiral
ketones are its high reaction rate and high enantioselec-
tivity. Recently, we successfully reported the asymmetric
reduction of prochiral monoketones by (R)-(?)-2-methyl-
CBS-oxazaborolidine (R-Me-CBS) [19]. The R-Me-CBS
reduction was applied to biphenyl alkyl diketones (lignin
models) [20], 1,3-ferrocenyldiketones [21], and tetralin-
Chiral diols are structural motifs often found in various
important natural products and have also been proven
valuable as chiral ligands and auxiliaries in stereoselec-
tive organic syntheses. The enantioselective synthesis of
chiral diols is still a stimulating subject. One of the most
successful methods is the enantioselective reduction of
˘
T. Yıldız Á A. Yusufoglu (&)
Department of Chemistry, University of Istanbul,
Istanbul, Turkey
e-mail: ayseserg@istanbul.edu.tr
123

˘
184
T. Yıldız, A. Yusufoglu
1,4-dione [22]. Additionally, some C2-symmetric diketones
were reduced with erythro-diphenyl oxazaborolidine [23].
In this study we applied this stereoselective (R)-oxaza-
borolidine–borane reduction to 1,2-diketones 1a–1g and
1,3-diketones 1h–1p, in order to prepare chiral 1,2-diols
2a–2g and 1,3-diols 2h–2p, and NaBH4 for the synthesis of
racemic 1,2- and 1,3-diols. 2b, 2c, 2d, and 2e are new
racemic diols. Amongst the chiral 1,2-diols the five chiral
1,2-diols 2a–2e and two chiral 1,3-diols 2m and 2n are
novel.
60 mol% of R-Me-CBS in THF at 0 °C to rt, the reduction
was completed within 1 h according to the known stereo-
chemical course of CBS-catalyzed reduction of ketones
[17]. In order to compare and determine the ee values of
the chiral diols, the corresponding diketones were reduced
by NaBH4 to racemic diols that were resolved on chiral
HPLC or GC. Newly synthesized 1,2- and 1,3-diols were
characterized according to their 1H NMR and HPLC or GC
spectra.
The syn and anti diastereoisomers of the diols and their
1
diastereomeric ratios were defined by H NMR (Table 1).
The HPLC traces of the racemic diols contained four peaks
and those of meso diols three peaks. The retention times of
the syn and anti enantiomers, which were resolved on
chiral HPLC, are given in the ‘‘Experimental’’ section.
Since no similar standards were available for 2a–2e, 2g,
and 2k–2p, the absolute configurations of these compounds
could not be determined. The configurations of the diols 2f,
2h, and 2j were established via literature data. The
reduction with NaBH4 gave the racemic diols in high yields
by slightly favoring the syn diastereoisomer as shown in
Table 2.
Results and discussion
Thirteen chiral diols 2a–2p with alkyl and aryl, substituted
aryl, hetero aryl, and biaryl groups were synthesized for the
first time in this study by asymmetric CBS–BH3 reduction
of the corresponding diketones 1a–1p. The five new 1,2-
diketones 1a–1e were synthesized by oxidation of their
corresponding alkenes using KMnO4 and a phase transfer
agent (Scheme 1) [24].
In the literature survey R-Me-CBS was the best reducing
catalyst [9] exposing very high ee values for the ketones.
The (S) enantiomers of some aryl–alkyl substituted sec-
ondary carbinols were synthesized with excellent ee values
by us via asymmetric reduction method with R-Me-CBS
[19]. In this study, the five new 1,2-diketones 1a–1e, two
commercially available 1,2-diketones 1f, 1g, and all six
purchased 1,3-diketones 1h–1p of different structure were
reduced to the corresponding diols 2a–2p using R-Me-CBS
for the first time. When diketones 1a–1p were treated with
BH3ÁMe2S (1:2 diketone/borane ratio) in the presence of
The influence of substrate structure on the stereoselec-
tivity of the reaction was examined using the catalyst
R-Me-CBS. Unsymmetrical 1,2-diols with different aro-
matic groups showed similar stereoselectivity. The best
results were obtained for 2d with a dr ratio of 84:16
(Table 1, entry 4). Amongst 1,3-diols the best dr ratio was
obtain for 2m (dr = 92:8) (Table 1, entry 11).
The 1,2-diketones 1a–1g and 1,3-diketones 1k–1p,
which have no rotation between the two carbonyl groups,
exhibited syn diastereoselectivity. The 1,3-diketones with
Scheme 1
O
OH
NaBH4
Amberlist 15
Heat
(CH2)nCH3
(CH2)nCH3
(CH2)nCH3
Ar
Ar
Ar
O
KMnO4
(CH2)nCH3
(CH2)nCH3
Ar
Ar
Phase transfer agent
O
1a-1e
Diketone
Diol
2a
Ar
n
1a
1b
1c
1d
1e
Ph
15
10
11
13
10
2b
p-MeC6H4
2c
2d
2e
p-MeOC6H4
2-Thienyl
2-Naphthyl
123

Asymmetric synthesis of new chiral 1,2- and 1,3-diols
185
Table 1 Asymmetric reduction of prochiral diketones with R-Me-CBS
Entry
1
Substrate
Yielda/%
50
drb (syn/anti)
eec (syn/anti)
Conf.d (syn/anti)
72/28
n.d./50
n.d.
O
(CH2)15CH3
Ph
O
1a
2
40
78/22
54/60
n.d.
O
(CH2)10CH3
p-MeC6H4
O
1b
3
70
75/25
62/54
n.d.
O
(CH2)11CH3
p-MeOC6H4
O
1c
4
25
84/16
70/42
n.d.
O
(CH2)13CH3
S
O
1d
5
64
72/28
68/54
n.d.
O
(CH2)10CH3
2-Naphth
O
1e
6
95
100/0
0
meso
O
Ph
Ph
O
1f
123

˘
186
T. Yıldız, A. Yusufoglu
Table 1 continued
Entry
7
Substrate
Yielda/%
83
drb (syn/anti)
eec (syn/anti)
Conf.d (syn/anti)
75/25
22/n.d.
n.d.
O
O
1g
8
9
22
20
17/83
30/70
0/66
meso/(S,S)
(S,S)/(R,S)
O
O
Ph
Ph
Ph
1h
20/87
O
O
Me
1j
10
20
68/32
[99/[99
n.d.
O
O
Ph
1k
11
21
92/8
72/[99
n.d.
O
O
1m
12
13
40
60
77/23
64/36
85/12
n.d.
n.d.
O
O
1n
[99/83
O
O
1p
a
Isolated yield of products
b
c
d
1
The dr was determined by H NMR
The ee was determined by HPLC or GC analysis
Absolute configurations could not be determined (n.d.) except of 2f, 2h, and 2j
123

Asymmetric synthesis of new chiral 1,2- and 1,3-diols
187
using known methods. The racemic diols were prepared by
the reduction of the corresponding diketones with NaBH4
in methanol/THF. The reactions were monitored by TLC
using silica gel plates and the products were purified by
flash column chromatography on silica gel (Merck,
230–400 mesh) with hexane/ethyl acetate. NMR spectra
Table 2 Comparison of dr rates in the racemic and asymmetric
reductions
Entry
Substrate
Racemic
reduction
dr (syn/anti)
Asymmetric
reduction
dr (syn/anti)
Asymmetric
reduction
ee (syn/anti)
1
1a
1b
1c
1d
1e
1f
58/42
60/40
65/35
60/40
55/45
66/34
57/53
46/54
47/53
54/46
50/50
58/42
50/50
72/28
78/22
75/25
84/16
72/28
100/0
75/25
17/83
30/70
68/32
92/8
n.d./50
54/60
62/54
70/42
68/54
0
1
were recorded at 500 MHz for H and 125 MHz for 13C
2
using Me4Si as the internal standard in CDCl3. GC–MS
spectra were recorded on a Shimadzu QP2010 Plus. IR
spectra were recorded on a Mattson 1000. Melting points
were determined with a Bu¨chi Melting Point B-540.
Enantiomeric excess (ee) of the chiral alcohols was deter-
mined with a Shimadzu DGU-20A5 HPLC apparatus fitted
with a 25 cm Chiralcel OD chiral column. The enantio-
meric excess of diols 2n and 2p was determined by GC on
a 25 m 9 0.25 mm CP Cyclodex B 236M column.
3
4
5
6
7
1g
1h
1j
2/n.d.
0/66
8
9
20/87
[99/[99
72/[99
85/12
[99/83
10
11
12
13
1k
1m
1n
1p
77/23
64/36
General procedure for synthesis of diketones 1a–1e
Alkene (10 mmol) was dissolved in 25 cm3 of methylene
chloride and 5 cm3 of acetic acid in a three-necked, round-
bottomed flask equipped with a mechanical stirrer. About
0.5 g of phase transfer agent (benzyl triethyl ammonium
chloride was used in this study, different from the literature
[24]) dissolved in 20 cm3 of methylene chloride was
added, followed by powdered potassium permanganate
(30 mmol) in small portions over 2 h. An ice bath was used
to maintain the temperature below 30 °C. The mixture was
then stirred vigorously overnight, cooled, and treated with
20 cm3 of water and 1 g of sodium bisulfite to reduce any
excess oxidant. After 20 min the solution was acidified
with concentrated HCl and the excess potassium per-
manganate was reduced by addition, in small portions, of
the required amount of sodium bisulfide. Any solid car-
boxylic acids which precipitated were collected by
filtration, and the organic layer was separated. The
aqueous layer was saturated with sodium chloride and
extracted with ether (2 9 30 cm3) and the aqueous layer
was separated. The ether layers were combined, washed
once with 30 cm3 of 5 % NaOH solution and water, then
dried over anhydrous Na2SO4. Evaporation was carried
out under reduced pressure after filtration. The crude
yellow product was purified by column chromatography
(n-hexane/EtOAc 8:2).
free rotation 1h and 1j, which have one methylene group
between the two carbonyl groups, exhibited anti diastere-
oselectivity. In this work all substrates 1a–1p have two
prochiral centers. The absolute configurations of the chiral
diols 2a–2p could not be determined in this study because
of the lack of the similar diols with fixed configuration.
Conclusion
The synthesized chiral 1,2-diols 2a–2g and 1,3-diols 2h–2p
are new compounds and they are valuable intermediates in
the preparation of new ligands and in the synthesis of
several natural molecules. These chiral diols were obtained
by the diastereoriched reduction of 13 prochiral diketones
of different structure via the R-Me-CBS catalyst. Accord-
ing to the literature survey, this catalyst has not previously
been applied to the asymmetric reduction of the 1,2 and
1,3-diketones achieved in this study. The diastereomeric
ratios of the new chiral diols were determined by chiral
1
HPLC or GC and their structures were analyzed by IR, H
and 13C NMR, MS, and elemental analysis. The five new
1,2-diketones 1a–1e were synthesized for the first time in
this study by oxidation of the corresponding alkenes
(Scheme 1) [24].
1-Phenyl-1,2-octadecanedione (1a, C24H38O2)
M.p.: 31.2–32.4 °C; 25 % yield; IR (KBr): vꢀ = 3,082,
2,953, 2,860, 1,715, 1,700, 1,607, 1,456, 1,407, 1,302,
1,153, 1,078, 708, 698 cm-1; 1H NMR (500 MHz, CDCl3):
d = 0.80 (t, 3H, J = 7.3 Hz), 1.12–1.62 (m, 28H), 2.79 (t,
2H, J = 7.3 Hz), 7.20–7.90 (m, 5H) ppm; 13C NMR
(125 MHz, CDCl3): d = 13.60, 22.11, 24.57, 26.85, 28.34,
29.63, 36.85, 37.51, 128.51, 129.10, 132.58, 132.70,
Experimental
The majority of the chemicals used in this work were
commercially available from Merck or Aldrich. The
alkenes used for the synthesis of diketones were obtained
from the corresponding alcohols by elimination of water
123

˘
188
T. Yıldız, A. Yusufoglu
190.71, 202.78 ppm; MS: m/z = 43, 57, 77, 97, 108, 117,
134, 254, 282, 328, 358 (M?).
General procedure for reduction of prochiral diketones
by (R)-(?)-2-methyl-CBS-oxazaborolidine (R-Me-CBS)
1-(4-Methylphenyl)-1,2-tridecanedione (1b, C20H30O2)
M.p.: 24.3–25.5 °C; 16 % yield; IR (KBr): vꢀ = 3,038,
2,938, 2,853, 1,746, 1,700, 1,615, 1,461, 1,384, 1,238,
In a typical procedure, to a solution of R-Me-CBS
(0.36 mmol, 0.36 cm3 of 1 M solution in toluene) was
added BH3ÁMe2S (2 M in THF, 1.5 mmol, 0.75 cm3) and
the mixture was stirred under nitrogen atmosphere, then
cooled to 0 °C. After 10 min of stirring, a solution of
diketone (0.6 mmol) in 5 cm3 of THF was added within
40 min at 0 °C. The reaction mixture was maintained at rt
for 1 h and then quenched with 2 M HCl. The solution was
extracted with 30 cm3 ether. The aqueous layer was sepa-
rated and was extracted once more with 80 cm3 ether. The
ether layers were combined, washed once with water, and
dried over anhydrous Na2SO4. Evaporation was carried out
under reduced pressure after filtration. The residue was
purified by column chromatography (n-hexane/EtOAc).
1,053, 830, 738 cm-1 1H NMR (500 MHz, CDCl3):
;
d = 0.80 (t, 3H, J = 6.8 Hz), 1.18–1.79 (m, 18H), 2.08
(t, 2H, J = 3.9 Hz), 2.30 (s, 3H), 7.20 (d, 2H, J = 7.8 Hz),
7.80 (d, 2H, J = 8.3 Hz) ppm; 13C NMR (125 MHz,
CDCl3): d = 14.14, 21.49, 23.26, 24.57, 26.96, 28.02,
29.62, 37.51, 130.39, 130.49, 132.44, 146.19, 190.71,
202.75 ppm; MS: m/z = 41, 57, 77, 97, 107, 118, 122, 134,
145, 183, 223, 237, 288, 302 (M?).
1-(4-Methoxyphenyl)-1,2-tetradecanedione
(1c, C21H32O3)
M.p.: 35.4–36.7 °C; 20 % yield; IR (KBr): vꢀ = 3,038,
2,923, 2,861, 1,715, 1,669, 1,615, 1,469, 1,438, 1,323,
1,269, 1,184, 869, 723 cm-1; 1H NMR (500 MHz, CDCl3):
d = 0.80 (t, 3H, J = 7.3 Hz), 1.10–1.70 (m, 22H), 2.78 (t,
2H, J = 7.8 Hz), 3.80 (s, 3H), 6.90 (d, 2H, J = 9.2 Hz),
7.90 (d, 2H, J = 9.2 Hz) ppm; 13C NMR (125 MHz,
CDCl3): d = 13.96, 22.44, 24.57, 26.85, 28.02, 29.63,
37.51, 55.30, 130.00, 131.40, 162.94, 190.71, 202.78 ppm;
MS: m/z = 41, 57, 77, 97, 107, 108, 122, 136, 145, 164,
223, 226, 302, 318, 332 (M?).
1-Phenyl-1,2-octadecanediol (2a, C24H42O2)
M.p.: 72.2–73.2 °C; 50 % yield; ee not determined for syn,
50 % ee for anti, syn/anti = 72:28; HPLC analysis:
Chiralcel OD chiral column, mobile phase i-PrOH/hexane
5:95, flow rate 0.5 cm3/min, wavelength 210 nm; tR: tanti
(major) = 16.249 min, tanti (minor) = 17.049 min, tsyn
(major ? minor) = 18.611 min; IR (KBr): vꢀ = 3,353,
3,069, 2,915, 2,861, 1,500, 1,476, 1,376, 1,246, 1,084,
1,061, 769, 707 cm-1 1H NMR (500 MHz, CDCl3):
;
1-(2-Thienyl)-1,2-hexadecanedione (1d, C20H32O2S)
M.p.: 28.3–29.1 °C; 15 % yield; IR (KBr): vꢀ = 3,100, 2,930,
2,853, 1,715, 1,638, 1,461, 1,415, 1,362, 1,261, 1,046, 753,
d = 0.82 (t, 3H, J = 6.8 Hz), 1.12–1.42 (m, 32H), 3.75
(m, 1H), 4.60 (d, 1H, J = 4.3 Hz), 7.22–7.32 (m, 5H) ppm;
13C NMR (125 MHz, CDCl3): d = 13.10, 21.60, 24.60,
24.80, 28.20, 30.01, 30.60, 31.00, 31.60, 74.20, 76.00,
125.80, 126.80, 127.40, 139.50 ppm; MS: m/z = 43, 57,
77, 97, 108, 117, 131, 207, 253, 328, 341 (M?-H2O).
1
698 cm-1; H NMR (500 MHz, CDCl3): d = 0.80 (t, 3H,
J = 6.8 Hz), 1.14–1.38 (m, 22H), 1.68 (pent, 2H,
J = 7.3 Hz), 2.82 (t, 2H, J = 7.8 Hz), 7.05 (dd, 1H,
J1 = 3.9 Hz, J2 = 4.8 Hz), 7.52 (dd, 1H, J1 = 0.9 Hz,
J2 = 4.8 Hz), 7.62 (dd, 1H, J1 = 0.9 Hz, J2 = 3.9 Hz)
ppm; 13C NMR (125 MHz, CDCl3): d = 13.60, 22.11,
24.20, 26.85, 28.02, 29.63, 30.85, 37.58, 129.61, 131.70,
132.33, 145.74, 186.09, 201.87 ppm; MS: m/z = 43, 57, 69,
85, 108, 112, 136, 140, 154, 223, 254, 302, 322, 336 (M?).
1-(4-Methylphenyl)-1,2-tridecanediol (2b, C20H34O2)
M.p.: 31.3–32.6 °C; 40 % yield; 54 % ee for syn, 60 % ee for
anti, syn/anti = 78:22; HPLC analysis: Chiralcel OD chiral
column, mobile phase i-PrOH/hexane 7:93, flow rate
0.8 cm3/min, wavelength 210 nm; tR: tanti (major) =
16.162 min, tanti (minor) = 17.316 min, tsyn (minor) =
18.160 min, tsyn (major) = 18.847 min; IR (KBr):
vꢀ = 3,423, 3,292, 3,023, 2,930, 2,846, 1,538, 1,469, 1,269,
1,107, 1,046, 807, 730 cm-1; 1H NMR (500 MHz, CDCl3):
d = 0.82 (t, 3H, J = 6.3 Hz), 1.12–1.32 (m, 18H), 1.48–1.52
(m, 4H), 2.30 (s, 3H), 3.75 (m, 1H), 4.60 (d, 1H, J = 4.3 Hz),
7.08–7.22 (m, 4H) ppm; 13C NMR (125 MHz, CDCl3):
d = 13.09, 21.30, 21.69, 23.91, 23.94, 28.14, 28.69, 30.93,
33.12, 33.17, 63.31, 63.37, 125.80, 128.13, 168.05,
173.31 ppm; MS: m/z = 43, 57, 77, 97, 107, 117, 122, 131,
145, 183, 207, 272 (M?-H2O).
1-(2-Naphthyl)-1,2-tridecanedione (1e, C23H30O2)
M.p.: 19.2–20.1 °C; 30 % yield; IR (KBr): vꢀ = 3,053,
2,930, 2,860, 1,711, 1,680, 1,600, 1,507, 1,300, 1,287,
1,248, 1,040, 793, 746 cm-1; 1H NMR (500 MHz, CDCl3):
d = 0.80 (t, 3H, J = 6.9 Hz), 1.10–1.70 (m, 18H), 2.90 (t,
2H, J = 7.8 Hz), 7.40–8.90 (m, 7H) ppm; 13C NMR
(125 MHz, CDCl3): d = 14.14, 23.26, 24.60, 26.96, 28.02,
29.61, 32.40, 37.51, 125.10, 128.00, 130.80, 132.52,
133.72, 134.35, 190.71, 202.77 ppm; MS: m/z = 44, 57,
69, 82, 96, 129, 156, 165, 184, 212, 281, 308, 338 (M?).
123

Asymmetric synthesis of new chiral 1,2- and 1,3-diols
189
1-(4-Methoxyphenyl)-1,2-tetradecanediol
(2c, C21H36O3)
tanti = 20.480 and 21.070 min (not observed), tsyn
(meso) = 22.380 min.
M.p.: 72.5–73.2 °C; 70 % yield; 62 % ee for syn, 54 % ee for
anti, syn/anti = 75:25; HPLC analysis: Chiralcel OD chiral
column, mobile phase i-PrOH/hexane 7:93, flow rate 1 cm3/
min, wavelength210 nm;tR: tanti (minor) = 21.317 min, tanti
(major) = 22.742 min, tsyn (minor) = 24.185 min, tsyn
(major) = 25.199 min; IR (KBr): vꢀ = 3,273, 3,195, 3,008,
2,914, 2,848, 1,614, 1,470, 1,284, 1,176, 1,106, 1,028, 827,
1,2-Dihydro-1,2-acenaphthylenediol (2g)
M.p.: 207.2–209.4 °C (Ref. [26] 208.5–209.5 °C); 83 %
yield; 22 % ee for syn, not determined for anti, syn/
anti = 75:25; HPLC analysis: the enantiomeric excess was
determined by HPLC analysis using a chiral column after
derivatization to the corresponding diacetate, Chiralcel OD
chiral column, mobile phase i-PrOH/hexane 1:99, flow rate
1 cm3/min, wavelength 210 nm; tR: tanti (minor) = 10.848
min, tanti (major) = 11.728 min, tsyn (major ? minor) =
16.627 min.
1
718 cm-1; H NMR (500 MHz, CDCl3): d = 0.81 (t, 3H,
J = 6.8 Hz), 1.11–1.45 (m, 22H), 1.50 (s, 1H), 1.70 (s, 1H),
3.50 (m, 1H), 3.71 (s, 3H), 4.54 (d, 1H, J = 3.5 Hz), 6.71–
7.42 (m, 4H) ppm; 13C NMR (125 MHz, CDCl3): d = 16.19,
23.01, 24.60, 29.20, 30.01, 32.00, 32.50, 55.52, 75.00, 78.00,
114.01, 128.02, 133.00, 160.05 ppm; MS: m/z = 43, 57, 69,
77, 121, 137, 147, 161, 302, 318 (M?-H2O).
1,3-Diphenylpropane-1,3-diol (2h)
M.p.: 148.8–149.9 °C (Ref. [25] 160–161 °C); 22 % yield;
0 % ee for meso, 66 % ee (S,S) for anti, syn/anti = 17:83;
HPLC analysis: Chiralcel OD chiral column, mobile phase i-
PrOH/hexane 10:90, flow rate 1 cm3/min, wavelength
210 nm; tR: tanti (major) = 10.767 min for (S,S)-isomer, tanti
(minor) = 12.370 min for (R,R)-isomer, tsyn (meso) =
14.771 min.
1-(2-Thienyl)-1,2-hexadecanediol (2d, C20H36O2S)
M.p.: 55.2–56.9 °C; 25 % yield; 70 % ee for syn, 42 % ee for
anti, syn/anti = 84:16; HPLC analysis: Chiralcel OD chiral
column, mobile phase i-PrOH/hexane 7:93, flow rate 1 cm3/
min, wavelength210 nm;tR: tanti (minor) = 12.299 min, tanti
(major) = 15.317 min, tsyn (minor) = 16.852 min, tsyn
(major) = 19.086 min; IR (KBr): vꢀ = 3,200, 3,195, 3,047,
2,914, 2,847, 1,671, 1,511, 1,299, 1,176, 1,135, 1,061, 771,
1-Phenyl-1,3-butanediol (2j)
M.p.: 64.2–65.5 °C (Ref. [27] 65 °C); 20 % yield; 20 % ee
for syn, 87 % ee for anti, syn/anti = 30:70; HPLC analysis:
Chiralcel OD chiral column, mobile phase i-PrOH/hexane
5:95, flow rate 1 cm3/min, wavelength 210 nm; tR: tanti
(minor) = 15.417 min for (S,R)-isomer, tanti (major) =
16.913 min for (R,S)-isomer, tsyn (major) = 17.974 min for
(S,S)-isomer, tsyn (minor) = 24.189 min for (R,R)-isomer.
1
690 cm-1; H NMR (500 MHz, CDCl3): d = 0.81 (t, 3H,
J = 6.3 Hz), 1.13–1.52 (m, 28H), 3.70 (m, 1H), 4.81 (d, 1H,
J = 3.9 Hz), 6.81–7.42 (m, 3H) ppm; 13C NMR (125 MHz,
CDCl3): d = 14.31, 22.89, 25.97, 29.29, 29.90, 32.13, 32.56,
73.71, 74.98, 124.70, 125.85, 126.74, 143.38 ppm; MS:
m/z = 43, 57, 69, 85, 97, 114, 225, 267, 306, 322, 341 (M?).
a-(2-Hydroxycyclohexyl)benzenemethanol
(2k, C13H18O2)
1-(2-Naphthyl)-1,2-tridecanediol (2e, C23H34O2)
M.p.: 78–79.3 °C; 64 % yield; 68 % ee for syn, 54 % ee for
anti, syn/anti = 72:28; HPLC analysis: Chiralcel OD chiral
column, mobile phase i-PrOH/hexane 10:90, flow rate 1 cm3/
min, wavelength 210 nm; tR: tsyn (minor) = 6.518 min, tsyn
(major) = 9.431 min, tanti (major) = 12.063 min, tanti (min-
or) = 21.389 min; IR (KBr): vꢀ = 3,353, 3,276, 3,052, 2,912,
2,847, 1,616, 1,456, 1,232, 1,164, 1,099, 1,059, 778,
M.p.: 89.2–90.5 °C; 20 % yield;[99 % ee for syn,[99 % ee
for anti, syn/anti = 68:32; HPLC analysis: Chiralcel OD
chiral column, mobile phase i-PrOH/hexane 5:95, flow rate
1 cm3/min, wavelength 210 nm; tR: tsyn (minor) = 12.859
min (not observed), tsyn (major) = 13.596 min, tanti
(minor) = 15.099 min (not observed), tanti (major) =
31.282 min; IR (KBr): vꢀ = 3,346, 3,061, 3,030, 2,930,
1
735 cm-1; H NMR (500 MHz, CDCl3): d = 0.81 (t, 3H,
2,853, 1,453, 1,415, 1,330, 1,192, 1,076, 761, 707 cm-1
;
J = 6.8 Hz), 1.12–1.60 (m, 20H), 1.80 (br s, 1H), 2.70 (br s,
1H), 4.01 (m, 1H), 5.52 (d, 1H, J = 4.3 Hz), 7.38–8.43 (m,
7H) ppm; 13C NMR (125 MHz, CDCl3): d = 13.10, 22.01,
25.60, 28.20, 29.01, 30.00, 31.00, 32.40, 73.00, 75.00,
122.00, 128.00, 129.80, 132.70, 135.50 ppm; MS:
m/z = 44, 57, 69, 82, 96, 129, 158, 167, 207, 281, 308, 341
(M?).
1HNMR(500 MHz, CDCl3):d = 0.98–1.80(m, 10H), 3.39–
3.43 (m, 1H), 4.11 (br s, 1H), 4.91 (d, 1H, J = 4.1 Hz), 7.15–
7.35 (m, 5H) ppm; 13C NMR (125 MHz, CDCl3): d = 18.71,
19.91, 25.87, 34.20, 48.15, 71.63, 78.17, 126.11, 127.27,
128.33, 143.44 ppm; MS: m/z = 41, 51, 54, 67, 79, 107, 117,
125, 170, 188, 207 (M?).
1,2,3,4-Tetrahydro-2-(1-hydroxyethyl)-1-naphthalenol
(2m, C12H16O2)
meso-1,2-Diphenylethane-1,2-diol (2f)
M.p.: 145.3–146 °C (Ref. [25] 142–144 °C); 95 % yield;
0 % ee for meso, syn/anti = 100:0; HPLC analysis:
Chiralcel OD chiral column, mobile phase i-PrOH/hexane
1:99, flow rate 1 cm3/min, wavelength 210 nm; tR:
n2D0 = 1.580; 21 % yield; 72 % ee for syn,[99 % ee for anti,
syn/anti = 92:8; HPLC analysis: Chiralcel OD chiral col-
umn, mobile phase i-PrOH/hexane 10:90, flow rate 1 cm3/
min, wavelength 210 nm; tR: tsyn (major) = 8.015 min, tsyn
123

˘
190
T. Yıldız, A. Yusufoglu
(minor) = 10.031 min, tanti (minor) = 10.776 min, tanti
(major) = 12.820 min; IR (KBr): vꢀ = 3,429, 3,062, 3,022,
2,970, 2,928, 1,469, 1,455, 1,397, 1,297, 1,136, 1,062, 740,
31.11, 34.20, 42.39, 72.69, 82.63 ppm; MS: m/z = 43, 55,
67, 83, 93, 111, 129, 136, 154, 171 (M?).
1
662 cm-1; H NMR (500 MHz, CDCl3): d = 1.22 (d, 3H,
Acknowledgments This study was supported by the Istanbul Uni-
˙ ¨
versity Department of Scientific Research Projects (I.U. Bilimsel
J = 23.9 Hz), 1.24–1.30 (m, 3H), 1.82 (br s, 2H), 2.80 (m,
2H), 4.10 (m, 1H), 4.62 (d, 1H, J = 7.1 Hz), 7.01–7.52 (m,
4H) ppm; 13C NMR (125 MHz, CDCl3): d = 20.95, 22.93,
28.21, 48.32, 68.92, 73.06, 125.32, 127.37, 135.38,
138.39 ppm; MS: m/z = 43, 45, 55, 65, 77, 91, 119, 129,
145, 159, 174, 192 (M?).
Aras¸tırma Projeleri Birimi) with Project Number 3099.
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2-(1-Hydroxyethyl)cyclopentanol (2n, C7H14O2)
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2-(1-Hydroxy-2-methylpropyl)cyclohexanol
(2p, C10H20O2)
M.p.: 104.2–105.6 °C; 60 % yield;[99 % ee for syn, 83 %
ee for anti, syn/anti = 64:36; GC analysis: the enantiomeric
excess was determined after derivatization to the correspond-
ing diacetate by GC analysis using a chiral column CP
Cyclodex B 236M capillary column (25 m 9 0.25 mm), at
70 °C then 5 °C/min to 150 °C for 30 min; tR: tanti
(minor) = 13.023 min, tanti (major) = 13.428 min, tsyn
(minor) = 14.623 min (not observed), tsyn (major) =
14.988 min; IR (KBr): vꢀ = 3,353, 2,930, 2,861, 1,415,
˘
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1
1,330, 1,138, 1,084, 915, 738 cm-1; H NMR (500 MHz,
CDCl3): d = 0.87 (d, 6H, J = 6.3 Hz), 1.24–1.45 (m, 11H),
1.50–1.82 (m, 1H), 3.31 (m, 1H), 3.45 (m, 1H) ppm; 13C
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123