Synthesis of C2-symmetric chiral amino alcohols: Their usage as organocatalysts for enantioselective opening of epoxide ring

Article abstract of DOI:10.1080/00397910903419878

A series of -amino alcohols derivatives were synthesized from (R)-2-amino-1-butanol and (S)-1,2-propanediol, and they have been used as organocatalaysts in the racemic ring opening of epoxide in good yields with high enantiomeric excess (up to 97%). Copyright

Full text of DOI:10.1080/00397910903419878

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Synthesis of C 2-Symmetric Chiral Amino
Alcohols: Their Usage as Organocatalysts
for Enantioselective Opening of Epoxide
Ring
Yilmaz Turgut a , Tarik Aral a , Mehmet Karakaplan a , Pinar Deniz a &
Halil Hosgoren a
a Faculty of Science, Department of Chemistry, University of Dicle,
Diyarbakir, Turkey
Published online: 15 Oct 2010.
To cite this article: Yilmaz Turgut , Tarik Aral , Mehmet Karakaplan , Pinar Deniz & Halil Hosgoren
(2010): Synthesis of C 2-Symmetric Chiral Amino Alcohols: Their Usage as Organocatalysts for
Enantioselective Opening of Epoxide Ring, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 40:22, 3365-3377
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Synthetic Communications1, 40: 3365–3377, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903419878
SYNTHESIS OF C2-SYMMETRIC CHIRAL AMINO
ALCOHOLS: THEIR USAGE AS ORGANOCATALYSTS
FOR ENANTIOSELECTIVE OPENING OF EPOXIDE RING
Yilmaz Turgut, Tarik Aral, Mehmet Karakaplan, Pinar Deniz,
and Halil Hosgoren
Faculty of Science, Department of Chemistry, University of Dicle,
Diyarbakir, Turkey
A series of b-amino alcohols derivatives were synthesized from (R)-2-amino-1-butanol and
(S)-1,2-propanediol, and they have been used as organocatalaysts in the racemic ring open-
ing of epoxide in good yields with high enantiomeric excess (up to 97%).
Keywords: Asymmetric ring opening; chiral amino alcohol; epoxide; organo catalysis
INTRODUCTION
The development of new methodologies, characterized by operational sim-
plicity and the use of easily available catalysts, is the main target of modern organic
synthesis.[1] Optically active compounds are important building blocks for the
synthesis of pharmaceuticals, pesticides, pheromones, flavors, fragrances, and liquid
crystals.
Catalytic enantioselective reactions constitute important tools in the synthesis
of chiral molecules. Chiral b-amino alcohols are useful building blocks for biologi-
cally active compounds[2] as well as important auxiliaries and ligands in asymmetric
synthesis.[3]
Also, amino alcohols continue to be of importance in modern synthetic chem-
istry, not least because of their biological properties, but also because of wide range
of synthetic applications.[4] Hence, the asymmetric synthesis of enantiomerically
enriched amino alcohols has been extensively studied.
Asymmetric organocatalysis is recognized as an efficient and reliable strategy
for the stereoselective preparation of valuable chiral compounds.The use of purely
organic molecules as chiral catalysts complements the traditional organometallic
and biological approaches to asymmetric catalysis, thus enabling synthetic chemists
to move closer to being able to construct any chiral scaffold in an efficient, rapid,
and stereoselective manner.[5–8]
Received August 4, 2009.
Address correspondence to Yilmaz Turgut, Faculty of Science, Department of Chemistry,
University of Dicle, 21280, Diyarbakir, Turkey. E-mail: yturgut@dicle.edu.tr
3365

3366
Y. TURGUT ET AL.
Asymmetric organocatalysis offers most of these advantages, as metal-free and
environmentally friendly conditions have been developed for many transformations
by using small organic molecules as chiral promoters.[9,10] Because of the great
synthetic versatility and the pharmaceutical importance of enantiomerically enriched
epoxides, different approaches have been used to access these compounds.
Chirality, in the context of biological activity, is an important phenomenon
because great differences in activities are observed for enantiomers of bioactive sub-
stance. For example, the (S)-isomer of all aryloxypropanolamine-type b-blockers is
clinically useful, whereas the corresponding (R)-isomer has undesirable properties.[11]
Enantiopure aryloxy alcohols are valuable targets for asymmetric synthesis as
a result of their role as key synthetic intermediates in a variety of pharmaceutically
important compounds.[12] In principle, access to these building blocks may be
provided by several routes, including asymmetric reduction of aryloxy ketones[13,14]
or the ring opening of enantiopure terminal epoxides with phenols. Of these, the lat-
ter is probably the most versatile and direct, but available methods for the addition
of phenols to epoxides are extremely limited. No catalytic methods have been devised
for phenolic opening of terminal epoxides, and forcing conditions are required for
the uncatalyzed reaction, such as heating the epoxide in the presence of a phenoxide
salt to high temperatures in a polar solvent.
Many protocols have been developed—for example, Sharpless asymmetric
epoxidation[15,16]—for the synthesis of racemic and nonracemic aryl glycidyl ethers.
However, the technique of hydrolytic kinetic resolution of terminal epoxide recently
reported by Tokunaga et al.[17] has been unexplored. The hydrolytic kinetic
resolution is highly enantioselective, but most importantly, extremely simple to work
with compared to other approaches for chiral glycidyl ether.
Epoxides are versatile reactive intermediates from which diols, ketones, or
alcohols could be obtained as appropriate reagents. Ring opening of epoxides is
an important method of making alcohols. To the best of our knowledge, the use
of chiral amino alcohols derivatives as catalyst in the ring opening of glycidol
with phenols has not been reported to date. It should be interesting to investigate
the catalytic ability of amino alcohol derivatives in the same reactions.
The C2 as well as C1 symmetric prolinamides were shown to be able to promote
the direct aldol condensation of acetone, methoxyacetone, or cyclohexanone and
different aldehydes in very good yields and high enantioselectivities.[18]
C2-Symmetric amino alcohols derivatives catalysts have also received much
attention and have been used in many asymmetric catalysis reactions, and they
have shown powerful utilities in the epoxidation reaction, Diels–Alder reaction,
asymmetric reduction of prochiral ketons, and others.[19]
It has been suggested that the C2-symmetric catalysts enhance the enantioselec-
tivity of the reaction by reducing the number of competing diasteromeric pathways
because of the homotopic nature of the ring coordination sites of the complexes
formed by the catalysts. It is expected that C2-symmetric chiral amino alcohols in
the new ligands may result in unique properties for suitable catalytic reactions.
Because C2-symmetric chiral amino alcohols often give high levels of enantioselec-
tivity in an asymmetric reaction, it was our aim to synthesize novel C2-symmetric
chiral amino alcohols and use them as catalysts in the enantioselective ring opening
of racemic glycidol with phenols.

ENANTIOSELECTIVE OPENING OF EPOXIDE RING
3367
RESULTS AND DISCUSSION
In this study, we demonstrate an efficient synthesis of novel chiral ligands, N-
phenylethyl amino alcohols 3,4, and N-a-pyridylmethyl-b-amino alcohols 7–10
including 2,20-bispyridine and a,0-xylene through a two-step reaction approach and
their application to the enantioselective ring opening of racemic glycidol with phe-
nol, p-methoxy, and p-methyl phenol derivatives. The results are listed in Table 1.
Initially, phenol and (S)-glycidol were transformed into their diols, which were
then tosylated to give 1b. Compounds 1a and 1b were reacted with excess of (S)-a-
phenyl ethylamine to obtaine 2a and 2b in yields of 65% and 63% respectively
(Scheme 1). The C2-symmetric chiral amino alcohols 3 and 4 were synthesized from
ditosylate with excess of 2a and 2b in the presence of Na2CO3 in yields of 46% and
48% respectively.
Table 1. Enantioselective opening of epoxide ring with chiral amino alcohols
Catalyst
R-
Temp. (ꢀC)
Yield (%)a
eeb
Config.c
Time (h)
3
H-
50
50
50
50
50
50
50
50
40
50
50
50
50
50
40
50
50
50
50
50
50
50
50
50
40
40
40
75
85
85
66
69
50
55
55
40
55
50
35
40
45
50
55
60
90
45
50
55
rac-
rac-
6
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
Methoxy-
Methyl-
H-
S
S
S
S
S
4
96
77
Methoxy-
Methyl-
H-
6
70
5
Methoxy-
Methyl-
H-
rac-
14
R
S
S
R
S
S
S
R
6
72
Methoxy-
Methyl-
H-
rac-
13
7
97
30
Methoxy-
Methyl-
H-
14
14
8
Methoxy-
Methyl-
H-
rac-
rac-
10
9
R
R
Methoxy-
Methyl-
H-
57
rac-
4
10
R
Methoxy-
Methyl-
rac-
rac-
aIsolated yield by preparative TLC.
bDetermined by HPLC analysis on a Chiralcel OD-H column.
cAbsolute configuration was determined by comparison of HPLC retention times with those of products
of chiral molecules.

3368
Y. TURGUT ET AL.
Scheme 1. Reagents and conditions: (i) piperidine hydrochloride, 75 ꢀC, (ii) tosyl chloride, dichloro-
methane–pyridine, ꢁ25 ꢀC, (iii, iv) Na2CO3, 14 h, 120 ꢀC.
The C2-symmetric chiral amino alcohols 5 and 6 were synthesized from
commercially and inexpensive (R)-2-amino-1-butanol by our previously reported
method.[20,21]
Recently, pyridine-derived C2-symmteric chiral ligands such as 2,20-
bispyridines, 2,6-disubstituted pyridines, and pyridyl alcohols have been developed
as chiral ligands. Because C2-symmetric chiral amino alcohols often give high
levels of enantioselectivity in asymmetric reactions, herein we demonstrate an
efficient synthesis of novel C2-symmetric chiral ligands, N-a-pyridylmethyl-b-amino
alcohols, and their application to the enantioselective ring opening of epoxide.
Scheme 2. Reagents and conditions: (i) benzyl chloride, Na2CO3, 12 h, 110 ꢀC, (ii) Na2CO3, 14 h, 110 ꢀC.

ENANTIOSELECTIVE OPENING OF EPOXIDE RING
3369
The compounds 7 and 9 were prepared from (R)-2-amino-1-butanol, 2,6-
pyridinedimethyl ditosylate and a,a0-dibromo-m-xylene in 72% and 75% yields,
respectively. In the same way, the compounds 8 and 10 were obtained from (R)-
N-benzyl-2-amino-1-butanol, 2,6-pyridinedimethyl ditosylate, and a,a0-dibromo-m-
xylene in 49% and 58% yields, respectively. The syntheses of these ligands are shown
in Scheme 3. The novel chiral ligands 3–10 were prepared, and their asymmetric
catalysis was investigated.
To find out the optimum reaction conditions, the C2-symmetric chiral ligand 4
was first evaluated in the catalytic enantioselective ring opening of racemic glycidol
under various experimental conditions. The results are shown in Table 2.
The good reaction yields and enantiomeric excess were obtained when toluene
was replaced with other solvents such as chloroform, acetonitrile, and ethanol in
the same temperature. Polar protic solvent (ethanol) was chosen for this purpose.
Optimization of reaction temperature indicated that 50 ꢀC favored a higher
enantiomeric excess. Neither the reaction yield nor the enantiomeric excess can be
satisfactory when the reaction temperature was elevated or decreased.
Under the optimized reaction condition (EtOH, 50 ꢀC, 10 mol% catalyst load-
ing), catalyst 7 gave 97% ee with phenol (yield 55%). However, when catalyst 8 was
used for ring opening, p-methoxy phenol and p-methyl phenol were racemized except
Scheme 3. Reagents and conditions: (i) Benzyl chloride, Na2CO3, 12 h, 110 ꢀC; (ii) Na2CO3, 12 h, 100 ꢀC.

3370
Y. TURGUT ET AL.
Table 2. Solvent optimization on reaction conditions for catalyst 4
Solvent
R-
T (ꢀC)
Yield (%)
ee (%)
EtOH
H-
H-
H-
H-
50
50
50
50
75
53
51
47
96
94
92
90
CH3CN
CHCl3
Ar-CH3
for phenol (with 14% ee). In contrast, when catalyst 9 was employed as ligand, the ee
value of the ring opening of racemic glycidol with phenol and p-methoxy phenol was
found to be less than 10%, but p-methyl phenol did not give any ee. The same results
were found for catalyst 10.
It has been found that the highest enantioselectivity was observed when
the catalyst contained a bis-pyridine secondary amine alcohol, as can be seen in 7
(up to 97% ee, Fig. 1).
This result shows that the –NH group of the catalyst had a significant effect on
the reaction. Even though it is quite difficult to extract any clear reason for this
result, the hydrogen bonding of the oxygen or hydroxyl of racemic glycidol with
the –NH and nitrogen of pyridine could play important roles in enantioselective ring
opening of epoxide. It is well known that the stereochemical outcome is mainly con-
trolled by the hydroxyl group, thus, the C-O stereocenter position is a fundamental
parameter in the 3-aryloxy-1,2-propandiol enantiomeric excess.
Also as shown in Table 1, we found that the nature of catalyst has a dramatic
influence on the catalytic activity. For example, use of the optimum reaction con-
dition in the presence of 10 mol% C2-symmetric catalysts 3 and 8–10 gave good
chemical yields but with lower enantioselectivities or racemate. On the other hand,
the catalyst 4 was applied to the ring opening of racemic glycidol with phenol deri-
vatives with ee up to 96%, and the results are also shown in Table 1. It is interesting
Figure 1. Enantioselective ring opening of glycidol with 7.

ENANTIOSELECTIVE OPENING OF EPOXIDE RING
3371
to note that aryloxy group in 4 plays a very important role for the enantioselectivity
of the reaction. Thus, it may be concluded that bulky aryloxy group on the a-carbon
at amino alcohols is required for the high enantioselective reaction. The results show
that not only was higher enantioselectivity obtained but also chemical yield was high.
CONCLUSIONS
In conclusion, a series of novel C2-symmetric chiral amino alcohols has been
conveniently prepared. The catalytic activity for the enantioselective ring opening
of phenols with racemic glycidol was investigated, and excellent enantioselectivities
were obtained (up to 97% ee). This protocol provides a highly practical and pure ring
opening. In generally, the catalysts 4 and 7 demonstrated better enantioselectivity
than other amino alcohols. These results should provide useful information for
the design of new types of catalysts. The advantages of these chiral amino alcohols
in asymmetric organocatalysis is that the reaction metal free and environmentally
friendly.
EXPERIMENTAL
General Methods
All chemicals were reagent grade unless otherwise specified. (S)-a-Phenyl ethyl-
amine was purchased from Fluka chemical company. Silica gel 60 (Merck,
0.040–0.063 mm) and silica gel=thin-layer chrometo graphy (TLC) cards (F254) were
used for flash column chromatography and TLC. Melting points were determined
with a Gallenkamp apparatus with open capillaries. Infrared (IR) spectra were
recorded on a Mattson 1000 Fourier transform (FT)–IR model spectrometer.
Elemental analyses were performed with a Carlo-Erba 1108 model apparatus.
Optical rotations were taken on a Perkin-Elmer model 341 polarimeter. 1H
(400-MHz) and 13C (100-MHz) NMR spectra were recorded on a Bruker
DPX-400 high-performance digital FT-NMR spectrometer. The chemical shifts (d)
and coupling constants (J) were expressed in parts per million and hertz.
The ee value determination was carried out using chiral high-performance
liquid chromatography (HPLC) on a Daicel1 Chiralcel OD column on Biorad model
2800 pump and Biorad ultraviolet (UV) detector. Separation was carried out on a
250 ꢂ 460 mm Daicel1 Chiralcel OD with hexane=ethanol (90=10) as an eluent.
(S)-(þ)-2-Hydroxypropyl P-Toluenesulfonate 1a
p-Toluenesulfonylchloride (12.97 g, 68.06 mmol) dissolved in 10 mL CH Cl
2
¨
2
was added dropwise over a period of 2 h to a stirred solution of (S)-2-propanediol
(5.18 g, 68.06 mmol) in dichlorometane–pyridine (10:10 V=V) at ꢁ25 ꢀC under argon.
The mixture was stirred at ꢁ25 ꢀC for 4 h and then at rt for 2 h. After the reaction
was completed, 150 mL of CH2Cl2 were added, and the mixture was shaken succes-
sively with ice-cold water, 1 N 40 mL aqueous HCl, 75 mL water, saturated
NaHCO3, and water respectively. The organic phase was dried with MgSO4 and fil-
tered, and the solvent was removed under reduced pressure. The residue was purified

3372
Y. TURGUT ET AL.
by chromatography over silica gel using toluene–EtOAc (5=1) to give 1a (9.00 g,
25
58%) as white crystal: mp 33–35 ꢀC (lit.[22] 34–35 ꢀC), ½aꢃD þ 12.05o (c 1, CHCl3);
IR: n 3558, 3430, 1363, 1183 cmꢁ1 1H NMR (CDCl3): d (ppm) 1.17 (d, 3H,
;
J ¼ 7.2 Hz), 2.12 (s, 1H), 2.47 (s, 3H), 3.84–3.89 (m, 1H), 3.99–4.08 (m, 2H), 7.37
(d, 2H, J ¼ 8.0 Hz), 7.82 (d, 2H, J ¼ 8.0 Hz).
(R)-1-(p-Toluenesulfonate)-3-phenoxy-2-propanole 1b
p-Toluenesulfonylchloride (5.67 g, 29 mmol) dissolved in 20 mL CH2Cl2 was
added dropwise over
a period of 2 h to a stirred solution of (S)-3-
phenoxypropane-1,2-diol[23] (5.00 g, 29 mmol) in dichlorometane–pyridine
(10:10 V=V) at ꢁ25 ꢀC under argon. The mixture was stirred at ꢁ25 ꢀC for 4 h and
then rt for 2 h. After the reaction was completed, 150 mL of CH2Cl2 were added,
and the mixture was shaken successively with ice-cold water, 1 N 40 mL aqueous
HCl, 75 mL water, saturated NaHCO3, and water. The organic phase was dried with
MgSO4 and filtered, and the solvent was removed under reduced pressure. The resi-
due was purified by chromatography over silica gel using toluene–EtOAc (5=1) to
25
give 1b (7.00 g, 75%) as white crystal; mp: 83–84 ꢀC ½aꢃD ꢁ10.00 (c 1, MeOH); IR:
n 3560, 3091, 2950, 2860, 1940, 1600, 1560, 1488, 1250, 1265, 1170, 1110, 1038
1
cmꢁ1; H NMR (CDCl3): d (ppm) 2.50 (s, 3H), 4.16 (d, 2H, J ¼ 4.9 Hz), 4.23–4.29
(m, 3H), 6.94 (d, 2H, J ¼ 9.6 Hz), 7.35 (d, 2H, J ¼ 8.4 Hz), 7.81 (d, 2H, J ¼ 8.4 Hz),
8.20 (d, 2H, J ¼ 7.8 Hz), 13C NMR (CDCl3): d (ppm) 21.54, 68.00, 68.80, 69.80,
114.64, 125.84, 127.94, 129.98, 132.85, 142.33, 145.30, 163.00. Anal. calcd. for
C16H18SO5: C, 59:63; H, 5.59; S, 9.94. Found: C, 59.64; H, 5.60: S, 7.01.
(S)-1-[N-(S)-a-Phenyl Ethyl]amino-2-propanole 2a
(S)-a-Phenylethylamine (18.97 g, 156.52 mmol), (S)-(þ)-2-hydroxypropyl-p-
toluenesulfonate (9.00 g, 39.13 mmol), and Na2CO3 (4.77 g, 45.00 mmol) were stirred
at 110 ꢀC for 12 h under argon. The mixture was cooled, and 100 mL CHCl3 were
added to the mixture and refluxed for 2 h. The organic phase was separated from
the solid phase. The remaining solid was re-extracted with CHCl3 (3 ꢂ 50 mL).
The combined CHCl3 layers were dried with Na2SO4, and the organic phase was
removed under reduced pressure. The excess (S)-a-phenyl ethylamine was distilled
at 90–95 ꢀC=1 mmHg, and the product was distilled at 140–141 ꢀC=1 mmHg to give
34
2a (4.52 g, 65%) as oil:½aꢃD þ 25.40 (c 1, CHCl3); IR: n 3364, 2980, 2928, 1651, 1452,
1380, 1138, 1061 cmꢁ1; 1H NMR (CDCl3): d (ppm) 1.10 (d, 3H, J ¼ 6.4 Hz), 1.40 (d,
3H, J ¼ 6.8 Hz), 2.26 (q, 1H, J ¼ 4.0 Hz), 2.52 (bs, 2H), 2.63 (q, 1H, J ¼ 8.8 Hz), 3.82
(q, 2H, J ¼ 6.4 Hz), 7.25 (m, 5H). 13C NMR (CDCl3): d (ppm) 20.41, 24.46, 54.40,
57.68, 65.79, 126.54, 129.09, 128.56, 144.98. Anal. calcd. for C11H17NO: C, 73.74;
H, 9.49; N, 7.82. Found: C, 74.00; H, 9.70; N, 7.80.
(S)-1-[N-(S)-a-Phenyl Ethyl]amino-3-phenoxy-2-propanole 2b
(S)-a-Phenylethylamine (3.75 g, 31.05 mmol), (R)-1-(p-toluenesulfonate)-3-
phenoxy-2-propanole 1b (2.00 g, 6.21 mmol), and Na2CO3 (0.65 g, 6.13 mmol)
were stirred at 110 ꢀC for 12 h under argon. Then the mixture was cooled, d

ENANTIOSELECTIVE OPENING OF EPOXIDE RING
3373
50 mL CHCl3 were added to the mixture and refluxed for 2 h. The organic phase was
separated from the solid phase. The remaining solid was re-extracted with CHCl3
(3 ꢂ 25 mL). The combined CHCl3 layers were dried with Na2SO4, and the organic
phase was removed under reduced pressure. The excess (S)-a-phenylethylamine
was distilled at 90–95 ꢀC=1 mmHg, and the residue was purified by chromatography
over silica gel using EtOAc=n-hexane=Et3N (7=5=1) to give 2b (1.00 g, 63%) as yellow
34
oil: ½aꢃD þ35.4o (c 1.68, CHCl3); IR: n 3326, 3058, 3031, 2967, 2929, 2877, 1741,
1606, 1587, 1490, 1452, 1375, 1297, 1247, 1170, 1085, 1047 cmꢁ1; 1H NMR (CDCl3):
d (ppm) 1.44 (d, 3H, J ¼ 7.0 Hz), 2.63 (bs, 2H, NH and OH), 2.73 (m, 2H), 3.83 (q,
1H, J ¼ 7.0 Hz), 3.97 (m, 3H), 6.95 (m, 3H), 7.39 (m, 10H). 13C NMR (CDCl3): d
(ppm) 24.23, 50.12, 58.74, 68.95, 70.61, 115.65, 121.07, 126.69, 127.15, 128.61,
129.53, 145.15, 158.72. Anal. calcd. for C17H21NO2: C, 75.27; H, 7.75; N, 5.16.
Found: C, 75.25; H, 7.59; N, 5.18.
(2S,9S)-4,7-[N-(S)-a-Phenyl Ethyl]diaza-2,9-decanediol 3
(S)-1-[N-(S)-a-Phenyl ethyl] amino-2-propanole (9.00, 50.28 mmol), ethylene
glycol ditosylate (3.10 g, 8.38 mmol), and Na2CO3 (1.5 g, 14.15 mmol) were stirred
at 110 ꢀC for 12 h under argon. Then the mixture was cooled, and 100 mL CHCl3
were added to the mixture, which was refluxed for 2 h. The organic phase was sepa-
rated from the solid phase. The remaining solid was re-extracted with CHCl3
(3 ꢂ 50 mL). The combined CHCl3 layers were dried with Na2SO4, and the organic
phase was removed under reduced pressure. The excess (S)-1-[N-(S)-a-phenyl ethyl]
amino-2-propanole was distilled at 140–141 ꢀC=1 mmHg. The residue was purified
by chromatography over silica gel using EtOAc=hexane=Et3N (10=30=2) to give 3
25
(1.50 g, 46.00%) as yellow oil: ½aꢃD -72.87o (c 3.4, CHCl3). IR: n 3428, 3070, 3031,
1
2979, 2831, 1740, 1458, 1375, 1075 cmꢁ1; H NMR (CDCl3): d (ppm) 1.12 (d, 6H,
J ¼ 8.0 Hz), 1.48 (d, 6H, J ¼ 8.0 Hz), 2.24 (t, 4H, J ¼ 12.0 Hz), 2.43 (q, 2H,
J ¼ 4.0 Hz), 2.71–2.76 (m, 2H), 2.76–3.90 (m, 4H), 3.76–3.80 (m, 4H), 4.78
(bs, 2H), 7.18–7.37 8 m, 10H).13C NMR (CDCl3): d (ppm) 18.67, 20.25, 48.70,
58.56, 59.48, 63.57, 127.24, 128.18, 141.08. Anal. calcd. for C24H36O2N2: C, 75.00;
H, 9.37; N, 7.29. Found: C, 75.20; H, 9.45; N, 7.18.
(1S,8S)-3,6-[N-(S)-a-Phenyl Ethyl]diaza-1,8-diphenoxymethyl-1,8-
decanediol 4
(S)-1-[N-(S)-a-Phenyl
ethyl]amino-3-phenoxy-2-propanole
2b
(5.60 g,
20.6 mmol), ethylene glycol ditosylate (1.27 g, 3.43 mmol), and Na2CO3 (1.00 g,
9.40 mmol) were stirred at 120 ꢀC for 12 h under argon. Then the mixture was cooled,
and 100 mL CHCl3 were added to the mixture and refluxed for 2 h. The organic
phase was separated from the solid phase. The remaining solid was re-extracted with
CHCl3 (3 ꢂ 50 mL). The combined CHCl3 layers were dried with Na2SO4, and the
organic phase was removed under reduced pressure. The residue was purified by
chromatography over silica gel using EtOAc=petroleum ether=Et3N (2=12=1) to give
34
4 (1.90 g, 48.71%) as yellow oil: ½aꢃD ꢁ40.5o(c 0.74, CHCl3); IR: n 3411, 3070, 3031,
2973, 2935, 2877, 1741, 1697, 1600, 1496, 1452, 1380, 1303, 1247, 1182, 1047 cmꢁ1
;
1H NMR (CDCl3): d (ppm) 1.40 (d, 6H, J ¼ 6.9 Hz), 2.51–2.65 (m, 5H), 2.77–2.84

3374
Y. TURGUT ET AL.
(m, 3H), 3.83–4.07 (m, 8H), 6.93–7.00 (m, 5H), 7.30–7.33 (m, 15H). 13C NMR
(CDCl3): d (ppm) 13.92, 49.76, 53.59, 59.43, 67.63, 70.10, 114.67, 120.92, 127.73,
128.20, 128.33, 129.50, 142.20, 158.88. Anal. calcd. for C36H44O4N2: C, 76.05; H,
7.75; N, 4.93. Found: C, 76.10; H, 7.85; N, 4.98.
(3R,8R)-Dihydroxymethyl-4,7-diazadecane 5
(R)-(ꢁ)-Amino-1-butanol (73.3 g, 800 mmol), 1,2-dibromoethane (18.8 g,
100 mmol), and Na2CO3 (10.6 g, 100 mmol) were stirred at 100 ꢀC for 12 h under
argon. Then the mixture was cooled, and 100 mL CHCl3 were added to the mixture
and refluxed for 2 h. The organic phase was separated from the solid phase. The
remaining solid was re-extracted with CHCl3 (3 ꢂ 50 mL). The combined CHCl3
layers were dried over anhydrous Na2SO4. The solvent was evaporated under
reduced pressure. The excess (R)-(ꢁ)-amino-1-butanol was distilled at 50 ꢀC=0.1
mmHg, and the residue was recrystallized with THF–EtOAc (8:1) to afford 5
20
(16 g, 79%) as white solid Mp: 88–89 ꢀC ½aꢃD þ28.75o (c 0.8, EtOH); IR: n 3296,
1
3142, 2958, 2931, 1469, 1377, 1353, 1091, 1064 cmꢁ1; H NMR (CDCl3): d (ppm)
0.96 (t, 6H, J ¼ 7.5 Hz), 1.39–1.54 (m, 4H), 2.54–2.88 (m, 6H), 3.37–3.45 (m, 2H),
AB system (dd, A part: 3.39, J ¼ 7 Hz and J ¼ 4 Hz, 2H; B part: dd, 3.65, J ¼ 7 Hz
and J ¼ 4 Hz, 2H) 13C NMR (CDCl3): d (ppm) 10.50, 24.30, 46.85, 60.63, 63.31.
Anal. calcd. for C10H24O2N2: C, 58.80; H, 11.86; N, 13.70. Found: C, 58.92; H,
12.11; N, 13.44.
(3R,8R)-Dihydroxymethyl-N,N’-dibenzyl-4,7diazadecane 6
(R)-N-Benzyl-2-amino-1-butanol (22.00 g, 120 mmol), 1,2-dibromoethane
(3.83 g, 20 mmol), and Na2CO3 (2.17 g, 20 mmol) were stirred at 110 ꢀC for 12 h
under argon. Then the mixture was cooled, and 100 mL CHCl3 were added to the
mixture and refluxed for 2 h. The organic phase was separated from the solid phase.
The remaining solid was re-extracted with CHCl3 (3 ꢂ 50 mL). The combined CHCl3
layers were dried with Na2SO4, and the organic phase was removed under reduced
pressure. The excess amine was distilled at 98–100 ꢀC=0.1 mmHg. The residue was
purified by chromatography over silica gel using EtOAc=n-hexane (1=2) to give 6
25
(6.2 g, 79%) as yellow oil. ½aꢃD ꢁ58.00o (c 1.2, CHCl3); IR: n 3326, 3108, 2975,
2937, 1497, 1464, 1335, 1214. 1109 cmꢁ1: 1H NMR (CDCl3): 0.87 (t, 6H, J ¼ 8.0 Hz),
), 1.09–1.14 (m, 2H), 1.60 (bs, 2H), 1.61–1.64 (m, 2H), 2.37–2.67 (m, 6H), 3.26–3.70
(m, 8H), 7.11–7.31 (m, 10H); 13C NMR (CDCl3): d (ppm) 11.80, 17.74, 47.80, 54.39,
60.81, 62.51, 127.14, 128.45, 129.24, 139.21. Anal. calcd. for C24H36O2N2: C, 74.96;
H, 9.44; N, 7.28. Found: C, 74.21; H, 9.68; N, 6.98.
(R,R)-Bis(2,6-pyridyldimethyl)-2-aminobutan-1-ol 7
(R)-2-Amino-1-butanol (6.37 g, 71.50 mmol), 2,6-pyridinedimethyl ditosy-
late[24] (4.00 g, 8.95 mmol), and Na2CO3 (2 g, 17.88 mmol) were stirred at 100 ꢀC
for 12 h under argon. Then the mixture were cooled and 100 mL CHCl3 were added
to the mixture and refluxed for 2 h. The organic phase was separated from the solid
phase. The remaining solid was re-extracted with CHCl3 (3 ꢂ 50 mL). The combined

ENANTIOSELECTIVE OPENING OF EPOXIDE RING
3375
CHCl3 layers were dried over anhydrous Na2SO4. The solvent was concentrated, and
the crude product was purified by column chromatography over silica gel using
EtOAc=Petroleum ether=Et3N (2=12=1) to afford 7 (1.80 g, 72%) as yellow oil.
27
½aꢃD þ13.8 (c 1, EtOH); IR: n 3377, 3070, 3044, 2973, 2935, 1606, 1490, 1465,
1362, 1252, 1053 cmꢁ1
;
1H NMR (CDCl3): d (ppm) 0.96 (t, 6H, J ¼ 7.4 Hz),
1.45–1.60 (m, 4H), 2.63–2.68 (m, 2H), 3.52–3.84 (m, 5H), 3.66–13.71 (m, 3H),
3.86–4.06 (m, 4H), 7.15 (d, 2H, J ¼ 7.6 Hz), 7.62 (t, 1H, J ¼ 7.6 Hz). 13C NMR
(CDCl3): d (ppm) 10.62, 24.38, 51.48, 61.02, 62.86, 120.81, 137.44, 159.0. Anal. calcd.
for: C15H27O2N3: C, 64.05; H, 9.61; N, 14.95. Found: C, 64.00; H, 9.78, N, 14.85.
(R,R)-Bis(2,6-pyridyldimethyl)-2-[N-benzyl]-butan-1-ol 8
(R)-N-Benzyl-2-amino-1-butanol (4.81 g, 26.80 mmol) and 2,6-pyridinedi-
methyl ditosylate (3.00 g, 6.71 mmol) were stirred at 100 ꢀC for 12 h under argon.
Then the mixture was cooled, and 100 mL CHCl3 were added to the mixture and
refluxed for 2 h. The organic phase was separated from the solid phase. The remain-
ing solid was re-extracted with CHCl3 (3 ꢂ 50 mL). The combined CHCl3 layers were
dried over anhydrous Na2SO4. The solvent was concentrated, and the crude product
was purified by column chromatography over silica gel using toluene=EtOAc=Et3N
27
(15=1.5=0.5) to afford 8 (1.5 g, 49%) as yellow oil. ½aꢃD ꢁ10.8o(c 1, EtOH); IR: n
3288, 3072, 3031: 2978, 2935, 1606, 1496, 1458, 1162, 1079 cmꢁ1; 1H NMR (CDCl3):
d (ppm) 0.95 (t, 6H, J ¼ 7.6 Hz), 1.28–1.35 (m, 2H), 1.74–1.81 (m, 2H), 2.79–2.86
(m, 2H), 3.53–3.74 (m, 8H), 3.86 (d, 2H, J ¼ 13.6 Hz), 3.98 (d, 2H, J ¼ 14.0 Hz),
5.07 (bs, 2H), 6.98 (d, 2H, J ¼ 7.6 Hz) 7.16–7.32 (m , 10H), 7.46 (t, 1H, J ¼ 7.6 Hz).
13C NMR (CDCl3): d (ppm) 11.85, 19.34, 54.48, 54.91, 61.64, 63.26, 121.21, 126.93,
128.20, 128.92, 136.89, 139.62, 159.61. Anal. calcd. for C29H39O2N3: C, 75.48; H,
8.46; N, 9.11. Found: C, 75.60; H, 8.58; N, 9.12.
(R,R)-Bis(a,a’-dibromo-m-xylene)-2-aminobutan-1-ol 9
Compound 9 was prepared as described for 7 starting from (R)-2-amino-1-
butanol (10.79 g, 121.30 mmol), a,a0-dibromo-m-xylene (4.0 g, 15.20 mmol), and
Na2CO3 (3.2 g, 30.18 mmol). The crude product was purified by column chromato-
graphy over silica gel using n-hexane=EtOH=Et3N (6=2=1) to afford 9 (3.2 g, 75%) as
27
yellow oil. ½aꢃD ꢁ9.6o (c 5, EtOH); IR: n 3240, 2962, 2930, 2870, 1601, 1575, 1463,
1158, 1053, 802 cmꢁ1; 1H NMR (CDCl3): d (ppm) 0.93 (t, 6H, J ¼ 7.6 Hz), 1.25–1.29
(m, 1H), 1.44–1.58 (m, 3H), 1.74–1.79 (m, 1H), 2.59–2.71 (m, 3H), 3.32–3.36 (m,
4H), 3.44–3.49 (m, 2H), 3.65–3.81 (m,4H), 7.16–7.31 (m, 4H). 13C NMR (CDCl3):
d (ppm) 10.39, 24.21, 51.01, 59.86, 62.67, 126.88, 127.71, 127.87, 128.60. Anal. calcd.
for C16H28O2N2: C, 68.57; H, 10.00; N, 10.00. Found: C, 68.63; H, 10.15; N, 10.08.
(R,R)-Bis(a,a’-dibromo-m-xylene)-2-[N-benzyl]-butan-1-ol 10
Compound 10 was prepared as described for 8 starting from (R)-N-
benzyl-2-amino-1-butanol (8.14 g, 45.40 mmol), a,a0-dibromo-m-xylene (3.00 g,
11.30 mmol), and Na2CO3 (2.39 g, 22.55 mmol). The crude product was purified by
column chromatography over silica gel using toluene=EtOAc=Et3N (13=0.5=0.5) to

3376
Y. TURGUT ET AL.
27
afford 10 (3.00 g, 58%) as a yellow oil. ½aꢃD þ5.2o (c 5, EtOH); IR: n 3270, 3072,
1
3028, 2976, 2940, 160, 1490, 1460, 1162, 1078, 912, cmꢁ1; H NMR (CDCl3): d
(ppm) 0.94 (t, 6H, J ¼ 7.6 Hz), 1.23–1.31 (m, 2H), 1.74–1.81 (m, 2H), 1.78–1.85
(m, 2H), 2.71–2.76 (m, 2H), 3.22 (bs, 2H), 3.39–3.48 (m, 5H),3.53–3.56 (m, 3H),
3.78–3.85 (m, 4H) 7.17–7.32 (m, 14H), 13C NMR (CDCl3): d (ppm) 11.92, 18.20,
53.32, 53.52, 60.70, 60.99, 127.24, 127.95, 128.55, 128.81, 129.10, 129.69, 139.55,
139.83. Anal. calcd. for C30H40O2N2: C, 78.26; H, 8.69; N, 6.08. Found: C, 78.63;
H, 8.75; N, 6.15.
Typical Procedure for the Ring Opening of Glycidol
with Phenol Derivatives
Catalyst (0.033 mmol) was added to a mixture of phenol derivatives (0.33 mmol)
and racemic glycidol (0.66 mmol) in absolute ethanol (1 mL). The mixture was stirred
at room temperature for 30 min under an inert atmosphere of argon. Then, the reac-
tion mixture was heated for 12 h at 50 ꢀC. After concentration by rotary evaporation,
the product was purified directly by preparative TLC (ethyl acetate–hexane 2:1) to
afford the chiral aryloxy-propanediols. The enantiomeric excess were determined
by HPLC with a chiral coloumn [by chiral HPLC analysis using a Daicel chiralcel
OD-H column, UV detector, 254 nm, ethanol–hexane 10:90, flow rate 1 mL=min).
ACKNOWLEDGMENT
We thank the Scientific and Technological Research Council of Turkey
˙
(TUBITAK) for their financial support (Project No. 107 T 079).
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