One-pot chemoenzymatic synthesis of chiral disubstituted 1,2,3-triazoles in aqueous media

Article abstract of DOI:10.1016/j.molcatb.2013.03.004

A one-pot, two-step procedure combining 1,3-dipolar cycloaddition and an enantioselective reduction mediated by Daucus carota (carrot root) is described. The synthesis was accomplished by first employing the biocatalyst followed by a "click" reaction unde

Full text of DOI:10.1016/j.molcatb.2013.03.004

Accepted Manuscript
Title: One-pot chemoenzymatic synthesis of chiral
disubstituted 1,2,3-triazoles in aqueous media
Author: <ce:author id="aut0005"> Camila de Souza de
Oliveira<ce:author id="aut0010"> Kleber Tellini de
Andrade<ce:author id="aut0015"> Alvaro Takeo Omori
PII:
S1381-1177(13)00075-1
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcatb.2013.03.004
MOLCAB 2644
To appear in:
Journal of Molecular Catalysis B: Enzymatic
Received date:
Revised date:
Accepted date:
6-12-2012
6-3-2013
6-3-2013
Please cite this article as: C.S. Oliveira, K.T. Andrade, A.T. Omori, One-
pot chemoenzymatic synthesis of chiral disubstituted 1,2,3-triazoles in
aqueous media, Journal of Molecular Catalysis B: Enzymatic (2013),
http://dx.doi.org/10.1016/j.molcatb.2013.03.004
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Graphical Abstract
Page 1 of 12

*Research Highlights
HIGHLIGHTS




1,3-dipolar cycloaddition reaction and bioreduction with carrot bits in one-pot.
Excellent enantiomeric excesses were obtained for all reactions (>99%).
Only water as solvent was needed for all reactions.
Cheap catalysts were employed.
Page 2 of 12

*Manuscript
1
One-pot chemoenzymatic synthesis of chiral disubstituted 1,2,3-triazoles in
aqueous media
2
3
Camila de Souza de Oliveira, Kleber Tellini de Andrade, Alvaro Takeo Omori*
4
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6
Laboratório de Compostos Bioativos, Centro de Ciências Naturais e Humanas,
Universidade Federal do ABC, R. Santa Adélia, 166, 09210-170, Santo André, Brazil.
*E-mail: alvaro.omori@ufabc.edu.br Fax +5511-4996-0090; Tel:+5511-4996-8384
7
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9
ABSTRACT: A one-pot, two-step procedure combining 1,3-dipolar cycloaddition and
an enantioselective reduction mediated by Daucus carota (carrot root) is described. The
synthesis was accomplished by first employing the biocatalyst followed by a “click”
reaction under very mild conditions to yield the corresponding chiral disubstituted
1,2,3-triazoles.
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KEYWORDS: Daucus carota, Biocatalysis, Click chemistry, Water chemistry.
1. Introduction
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In organic chemistry, the development of one-pot multistep synthetic methods
deserves attention because it minimizes the time and cost of complex molecule
synthesis. This continuously challenging area can be more powerful if we consider
sustainable aspects.[1] The creation of methods with all catalytic steps (Tandem
Catalysis)[2] is one example. In addition to sustainability, aspects such as the simplicity
and efficiency of the method and the usefulness of the product determine the potential
and importance of the synthetic method and therefore must be also considered.
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The “click” chemistry concept brings together a universe of reliable, quick and
highly selective reactions.[3] The most recognized is the copper(I)-catalyzed 1,3-dipolar
cycloaddition of azides and alkynes to form 1,4-disubstituted-1,2,3-triazoles.[4] Given
the ease in achieving these products, a growing interest from many chemical fields in
this type of compound has been noted.[5] As such, the range of applications of 1,2,3-
triazoles involves many chemical fields, including drug discovery,[6] medicinal[7] and
coordination chemistry,[8] chemosensors,[9] material and polymer chemistry[10] and
many others.
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Another interesting and emerging synthetic method is the enzymatic reduction of
prochiral ketones using pieces of Daucus carota (carrot root). Although evidence for
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endophytic microorganisms being the source of activity has been reported,[11] the use
of the plant tissue is cheaper and easier to handle. Additionally, this biocatalyst often
offers high levels of enantioselectivity and the reaction is carried out under milder
conditions and has easier work-up and eco-friendly procedures in comparison with other
catalytic systems.[12] Acetophenones, α-azido aryl ketones, β-ketoesters, aliphatic
acyclic and cyclic ketones were converted to their corresponding optically active
secondary alcohols using this method.[13] This achievement is significant because
chiral alcohols are important intermediates for the synthesis of a vast range of
compounds, including fragrances, flavors and chiral auxiliaries.
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In this contribution, we report a tandem catalysis protocol based on the
combination of chemical and enzymatic catalysis[14] for the preparation of chiral
disubstituted 1,2,3-triazoles from azidoacetophenones in water.
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45
2. Experimental
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2.1. General Methods
All reagents and chemicals were purchased from Sigma–Aldrich and used directly
without further purification. Solvents (reagent grade) were used for extraction and flash
chromatography. The solvent compositions reported for all chromatographic separations
are on a volume/volume (v/v) basis. 1H NMR spectra were recorded at either 300 or 500
MHz and are reported in parts per million (ppm) on the δ scale relative to
tetramethylsilane (TMS) as an internal standard. 13C NMR spectra were recorded at
either 75 or 125 MHz and are reported in parts per million (ppm) on the δ scale relative
to CDCl3 (δ 77.00). High-resolution mass spectrometry (HRMS) data were recorded on
a MicroTOF instrument (Bruker Daltonics) with ion mass/charge (m/z) ratios as values
in atomic mass units. Optical rotation values were measured on a Perkin-Elmer
Polarimeter. The FT-IR spectra were recorded with a Bomem MB100 instrument in the
wavenumber range 4,000 cm-1 to 400 cm-1. GC/MS was acquired on a GC-17A
instrument (Shimadzu) equipped with a GCMS-QP5050A MS detector operating at 70
eV. All melting points were recorded on a Büchi Melting Point B-540 melting point
apparatus. Chiral GC-FID analyses were recorded on a GC-17A instrument (Shimadzu)
with a Chirasil-Dex CB--cyclodextrin (25 m x 0.25 mm) column using H2 as carrier
gas. The enantiomeric excess values of the samples of alcohol 5 and 6 were determined
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according to the following conditions: (i) compound 5: rate 1 ◦C/min; oven 100–180 °C
(30 min); retention time [(R)-isomer: 12.0 min; (S)-isomer: 12.8 min].(ii) compound 6: :
rate 1 ◦C/min; oven 100–180 °C (30 min); retention time [(R)-isomer: 9.6 min; (S)-
isomer: 10.1 min].
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General procedure for the synthesis of 3, 4, 5 and 6 and respective analytical data
are specified in Supplementary information.
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2.2. General procedure for biocatalytic reduction of azidoacetophenones mediated
by Daucus carota bits
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75
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82
Compounds (S)-(5) and (S)-(6) were prepared from the corresponding ketone
precursors following the procedure reported previously [15].
2.2.1. (S)-3-azido-α-methyl-benzenemethanol (S)-(5): 0.494g, yield 53%.
(c. 3.1, CHCl3).
: -51°
: -12º
2.2.2. (S)-4-azido-α-methyl-benzenemethanol (S)-(6): 0.410g, yield 44%.
(c. 0.7, CHCl3).
2.3. Cyclization of (6) with phenylacetylene
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To a solution of compound (S)-(6) (0.252 g, 1.55 mmol) and phenylacetylene (0.158 g,
1.55 mmol) in n-butanol and water (1:1) was added 0.148 g (0.93 mmol, 0.6 equiv.) of
copper sulfate (CuSO4) and 0.327 g (1.86 mmol) of ascorbic acid. The mixture was
stirred at room temperature until complete conversion, as indicated by TLC. After
extraction with dichloromethane (3 x 50 mL), the organic phases were combined and
dried over MgSO4. The solvent was removed under vacuum, and a brown solid was
obtained by crystallization as compound (S)-(12).
2.3.1. (S)-1-(4-(4-phenyl-1H-1,2,3-triazol-1-yl)phenyl)ethanol (S)-(12): Yellow solid,
0.399 g, yield 97%. mp: 156 oC. 1H NMR (300 MHz, CDCl3): δ 8.18 (s, 1H), 7.92 (d, J
= 6.0 Hz, 2H), 7.78 (d, J = 9.0 Hz, 2H), 7.56 (d, J = 9.0 Hz, 2H), 7.47 (t, J = 6.0 Hz,
2H), 7.38 (t, J = 6.0 Hz, 1H), 5.01 (q, J = 6.0 Hz, 1H), 1.55 (s, 3H). 13C NMR (75MHz,
CDCl3): δ 148.3, 146.8, 136.1, 130.2, 128.9, 128.4, 126.7, 125.8, 120.5, 117.6, 69.5,
25.4. IR (cm-1, KBr): 3409, 2921, 1741, 1594, 1446, 1255, 1087. GCMS (70 eV,
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EI): m/z (%) 237 (21) [M-28]+, 222 (42), 194 (31), 193 (100), 165 (16), 116 (28).
HRMS: m/z calcd for C16H16N3O [M+H]+ 266.1293, found 266.1296 [M+1]+.
: -
99
20° (c. 0.82, CHCl3).
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2.4. General Procedure for one-pot synthesis of chiral 1,2,3-Triazoles
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To a 125 mL Erlenmeyer flask was added 40 mL of distilled water, 10 g of fresh
carrot (cut into small, thin slices, 5 mm) and 50 mg (0.72 mmol) of azidoacetophenone.
The mixture was incubated in an orbital shaker (200 rpm) at room temperature for 48 h.
Alkyne (0.72 mmol, 1 equiv.), CuSO4 (0.064 g, 0.4 mmol) and ascorbic acid (0.176 g,
0.9 mmol) were then added to the Erlenmeyer Flask, and the reaction was stirred in an
orbital shaker and monitored by TLC. After completion, the suspension was filtered off,
and the carrot root was washed three times with water (3 x 15 mL) and dichloromethane
(3 x 20 mL). Filtrates were then extracted with more dichloromethane (3 x 125 mL).
The organic phases were combined, dried (Na2SO4) and then evaporated under vacuum.
The final products were purified by flash chromatography when necessary.
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2.4.1.
(S)-1-(3-(4-pentyl-1H-1,2,3-triazol-1-yl)phenyl)ethanol
(7):
Eluent:
1
EtOAc/hexane (2:3), pale yellow oil, 0.106 g, yield 57%. H NMR (300 MHz, CDCl3):
δ 7.77 (t, J = 1.8 Hz, 1H), 7.73 (s, 1H), 7.63 (dt, J = 2.1, 2.1 Hz, 2H), 7.49 (t, J = 7.8
Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 5.01 (q, J = 6.3 Hz, 1H), 2.80 (t, J = 7.5 Hz, 2H),
1.74 (qn, J = 7.5 Hz, 2H), 1.56~1.31 (m, 7H), 0.92 (t, J = 7.2 Hz, 3H). 13C NMR
(75MHz, CDCl3): δ 148.0, 130.2, 129.7, 125.4, 119.3, 118.9, 117.4, 69.8, 31.4, 29.1,
27.2, 26.6, 25.4, 22.4, 14.0. HRMS: m/z calcd for C15H22N3O [M+H]+ 260.1763, found
260.1750.
-5° (c 1.4, CHCl3). IR (cm-1, KBr): 3363, 2919, 1741,1612, 1454,
1226, 1047.
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123
124
125
126
127
2.4.2.
(S)-1-(4-(4-pentyl-1H-1,2,3-triazol-1-yl)phenyl)ethanol
(8):
Eluent:
1
EtOAc/hexane (2:3), orange oil, 0.127 g, yield 68%. H NMR (500 MHz, CDCl3): δ
7.63 (d, J = 8.5 Hz, 3H), 7.45 (d, J = 5.5 Hz, 2H), 4.92 (m, 1H), 2.72 (t, J = 8 Hz, 2H),
1.66 (qn, J = 1.0 Hz, 2H), 1.46 (d, J = 6.5 Hz, 3H), 1.30 (qn, J = 8.5 Hz, 4H), 0.84 (t, J
= 1.5 Hz, 3H). 13C NMR (75MHz, CDCl3): δ 146.3, 126.7, 120.5, 31.5, 25.6, 22.4, 14.0.
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HRMS: m/z calcd for C15H22N3O [M+H]+ 260.1763, found 260.1750.
0.63, CHCl3). IR (cm-1, KBr): 3367, 2929, 1743, 1592, 1452, 1230, 1049.
: -13° (c
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2.4.3. (S)-1-(3-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)phenyl)ethanol (9): Eluent:
1
EtOAc/hexane (4:1), orange oil, 0.039 g, yield 25%. H NMR (500 MHz, CDCl3): δ
8.01 (s, 1H), 7.78 (s, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.45 (d, 7.0
13
Hz, 1H), 5.01 (q, J = 6.5 Hz, 1H), 4.89 (s, 2H), 1.55 (d, J = 6.5 Hz, 3H). C NMR
(75MHz, CDCl3): δ 175.5, 148.1, 136.9, 129.6, 127.5, 125.9,119.2, 117.5, 69.5, 55.9,
22.6. HRMS: m/z calcd for C11H14N3O2 [M+H]+ 220.1086, found 220.1072.
-11°
(c 0.4, CHCl3). IR (cm-1, KBr): 3370, 2921, 2107, 1614, 1452, 1220, 1058.
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2.4.4.
(S)-1-(4-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)phenyl)ethanol
(10):
1
Eluent: EtOAc/hexane (2:3), orange oil, 0.111 g, yield 71%. H NMR (500 MHz,
CDCl3): δ 7.89 (s, 1H), 7.63 (d, J = 9.0 Hz, 2H), 7.47 (d, J = 9.5 Hz, 2H), 4.92 (q, J =
6.5 Hz, 1H), 4.81 (s, 2H), 1.47 (d, J = 6.5 Hz, 3H). 13C NMR (75MHz, CDCl3): δ 148.2,
146.8, 136.1, 126.9, 120.7, 129.9, 69.7, 56.6, 25.4. HRMS: m/z calcd for C11H14N3O2
[M+H]+ 220.1086, found 220.1071.
-8º (c 0.8, CHCl3). IR (cm-1, KBr): 3409,
2921, 1741, 1594, 1446, 1255, 1087.
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147
148
149
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2.4.5.
(S)-1-(3-(4-phenyl-1H-1,2,3-triazol-1-yl)phenyl)ethanol
(11):
Eluent:
1
EtOAc/hexane (1:4), orange oil, 0.097 g, yield 51%. H NMR (500 MHz, CDCl3): δ
8.15 (s, 1H), 7.84 (d, J = 8.0 Hz, 2H), 7.77 (s, 1H), 7.64 (d, J = 6.5 Hz, 1H), 7.45 (t, J =
10.0 Hz, 1H), 7.41 (m, 3H), 7.31 (t, J = 6.0 Hz, 1H), 4.97 (d, J = 6.0 Hz, 1H), 1.5 (d, J
13
= 7.0 Hz, 3H). C NMR (75MHz, CDCl3): δ 148.1, 137.2, 130.2, 129.9, 128.9, 128.4,
125.9, 125.7, 119.4, 117.6, 117.5, 69.8, 25.58. HRMS: m/z calcd for C16H16N3O
[M+H]+ 266.1293, found 266.1295.
: -15° (c 0.67, CDCl3). IR (cm-1, KBr): 3407,
2924, 2102, 1587, 1449, 1260, 1070.
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2.4.6. (S)-1-(4-(4-phenyl-1H-1,2,3-triazol-1-yl)phenyl)ethanol (S)-(12): Yellow solid,
0.094 g, yield 51%. The analytical data of compound (12) was consistent with those
obtained for the compound isolated from the step-wise synthesis.
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3. Results and Discussion
The preparation of azidoacetophenones is straightforward and can be achieved
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simply by diazotation of the amino group followed by substitution with sodium
azide.[16] Thus, starting from commercially available meta- and para-substituted
aminoacetophenones, azides 3 and 4 were obtained (Scheme 1).
O
O
OH
1)NaNO , HCl
2
(aq)
2) NaN , H O
Daucus carota
H O
3
2
2
H2N
N3
N3
1 (meta)
2 (para)
3 (meta), 64%
4 (para), 91%
(S)-5 (meta) >99% ee, (53%)*
(S)-6 (para) >99% ee, (44%)*
*isolated yields
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Scheme 1. Synthesis and bioreduction of azidoacetophenones 3 and 4.
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To verify the influence of the azido group, the prepared azidoacetophenones 3
and 4 were first reacted with carrot bits in water (Scheme 1). The progress of the
reaction was followed by TLC analysis, and the corresponding secondary alcohols 5 and
6 were obtained in the S configuration[17],[18] with high enantioselectivity (>99% ee)
and moderate isolated yield. As expected, the enantioselectivity agreed with Prelog´s
rule.[19]
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To ensure the success and the regioselectivity of the cycloaddition reaction,
compound 6 was reacted following the cyclization protocol with phenylacetylene. In
this control experiment, the chiral disubstituted 1,2,3-triazole 12 was isolated as a single
product (Scheme 2).
OH
OH
CuSO4, Ascorbic acid
N
+
N
n-butanol, H2O (1:1), 1h
N
N3
97%
(S)-6
(S)-12
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Scheme 2. Cycloaddition of phenylacetylene with compound 6.
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Based on the success of the two reactions and considering the use of aqueous
media as solvent in both cases, we investigated the possibility of performing these
reactions in a one-pot protocol. Initial attempts involving the addition of all reagents
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(compound 6 and phenylacetylene) in a single step showed that the cyclization reaction
proceeded faster than the bioreduction reaction. Because of the low solubility of the
acetophenones containing the 1,2,3-triazole core in water, the desired chiral alcohol 12
was not obtained. This result indicated the synthesis should be performed in a stepwise
procedure.
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As expected, when the enzymatic reduction of azidoacetophenone 6 was
performed prior to the copper-catalyzed reaction, we obtained the corresponding chiral
disubstituted 1,2,3-triazole 12 as a single product. This strategy was successfully
applied to three different alkynes, 1-heptyne, phenylacetylene and propargyl alcohol,
reacting with para- and meta-azidoacetophenones (Scheme 3, Table 1).
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Table 1. One-pot synthesis of chiral 1,2,3-triazoles from azidoacetophenones 3 and 4a.
Page 9 of 12

OH
O
i.
bits
D. carota
ii. RCCH, ascorbic acid, CuSO4
H2O, r.t.
(S)
N3
N
R = C5H11, CH2OH, Ph
R
N
7 (meta, R= C5H11
)
3 (meta)
4 (para)
N
8 (para, R= C5H11
)
9
(meta, R= CH2OH)
10
11
12
(para, R= CH2OH)
(meta, R= Ph)
(para, R= Ph)
20
Compound
Product
Time (days) % yieldb
[]D
% eec
>99%
Config.d
OH
N
N
N
6
6
57
68
-5 (c 1.4, CDCl3)
S
7
OH
-13 (c 0.63, CDCl3)
>99%
S
8
N
N
N
OH
N
N
N
4
5
6
25
71
51
-11 (c 0.4, CDCl3)
-8 (c 0.8, CDCl3)
-15 (c 0.67, CDCl3)
>99%
>99%
>99%
S
S
S
9
OH
OH
N
10
N
N
OH
N
OH
N
N
11
12
OH
N
N
N
7
51
-20 (c 0.82, CDCl3)
>99%
S
194
195
196
197
198
199
a. Reaction conditions: azidoacetophenone (0.7 mmol), carrot (10g), water (40 ml) at room temperature for 48 h,
followed by alkyne (0.7 mmol), CuSO4 (0.42 mmol), and ascorbic acid (1 mmol) until completion (analyzed by
TLC). b. Isolated Yield. c. The enantiomeric excess was inferred from the chiral GC analysis of (S)-1-(3-
azidophenyl)ethanol and (S)-1-(4-azidophenyl)ethanol obtained from the bioreduction step. d. The absolute
configurations were inferred from (S)-1-(3-azidophenyl)ethanol and (S)-1-(4-azidophenyl)ethanol obtained from the
bioreduction step (see refs. 15 and 16).
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201
202
203
204
An examination of the results in Table 1 revealed that there was no influence of
the position of the azide group or the R group of the alkyne on the reaction. The only
drawback was observed with the purification of compound 9, which resulted in a low
yield. Interestingly, when the azidoacetophenone was fully converted to the alcohol and
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submitted to cyclization, in most cases the final product precipitated as a single
compound. However, recrystallization attempts were not successful.
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4. Conclusions
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In summary, a useful method for the chemoenzymatic synthesis of chiral disubstituted
1,2,3-triazoles is presented. This procedure consists of the use of cheap, versatile and
readily available reagents (water as solvent and carrot bits as biocatalysts). Moreover,
the bioreduction and Cu-catalyzed Hüisgen 1,3-dipolar cycloaddition can be achieved in
a one-pot sequence to afford the title compounds in moderate yields. Investigations into
improving the yields, the use of more sophisticated terminal alkynes and biological
activities of the products are ongoing.
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Acknowledgements
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The authors are grateful to FAPESP and CNPq for financial support. Oliveira
recognizes UFABC for a fellowship. Dr. Leandro Helgueira Andrade is thanked for
chiral GC analysis.
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Notes and references
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[2] J.C. Wasilke,S.J. Obrey, T. Baker, G.C. Bazan, Chem. Rev. 105 (2005) 1001-1020.
[3]J.E. Moses, A.D. Moorhouse, Chem. Soc. Rev. 36 (2007) 1249-1262.
[4] K.B. Sharpless, V.V. Rostovtsev, L.G. Green, V.V. Fokin, Angew. Chem. Int. Ed.
41 (2002) 2596-2599; M. Meldal, C.W. Tornøe, Chem. Rev. 108 (2008) 2952-3015.
[5] The Web of Science database showed more than 3000 articles containing the topic
1,2,3-triazole (between 1945 and 2011). Almost half of these were published in the last
5 years.
[6]H. C. Kolb, K. B. Sharpless, Drug Discovery Today 8 (2003) 1128-1137.
[7]S.G. Agalave, S.R. Maujan, V.S. Pore, Chem. Asian J. 6 (2011) 2696-2718; A.J.
McCarroll, C.S. Matthews, G. Wells, T.D. Bradshaw, M.F.G. Stevens, Org. Biomol.
Chem. 8 (2010) 2078-2084.
[8] G. Aromí, L.A. Barrios, O. Roubeau, P. Gamez, Coord. Chem. Rev. 255 (2011)
485-546.
[9] Y.H. Lau, P.J. Rutledge, M. Watkinson, M.H. Todd, Chem. Soc. Rev. 40 (2011)
2848-2866.
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[10] J.-F. Lutz, Angew. Chem. Int. Ed. 46 (2007) 1018-1025.
[11] P. Rodriguez, M. Barton, V. Aldabalde, S. Onetto, P. Panizza, P. Menendez, D.
Gonzalez, S. Rodriguez, J. Mol. Cat. B: Enzymatic 49 (2007) 8-11; P. Rodriguez, B.
Reyes, M. Barton, C. Coronel, P. Menendez, D. Gonzalez, S. Rodriguez, J. Mol. Cat. B:
Enzymatic 71 (2011) 90-94.
[12]N. Blanchard, P. van de Weghe, Org. Biomol. Chem. 4 (2006) 2348-2353 and
references therein; G.A. Cordell, T.L.G. Lemos, F.J.Q. Monte, M.C. Mattos, J. Nat.
Prod. 70 (2007) 478-492.
[13]Recent uses of warrD. carota bits as biocatalyst: M.S. Salvano, J.J. Cantero, A.M.
Vazquez, S.M. Formica, M.L. Aimar, J. Mol. Cat. B: Enzymatic 71 (2011) 16-21; R.
Lacheretz, D.G. Pardo, J. Cossy, Org. Letters 11 (2009) 1245-1248; H.M.C. Ferraz,
G.G.Bianco, F.I. Bombonato, L.H. Andrade, A.L.M. Porto, A. L. M. Quimica Nova 31
(2008) 813-817.
[14] A.C. Marr, S. Liu, Trends Biotechnol. 29 (2011) 199-204.
[15] J.V. Comasseto, A.T. Omori, A.L.M. Porto, L.H. Andrade, Tetrahedron Lett. 45
(2004) 473-476.
[16]M. Warrier, F.K. Lo, H.G. Monbouquette, A.M.G. Garibay, Photochem. Photobiol.
Sci. 3 (2004) 859-863.
[17]The absolute configuration of (S)-1-(3-azidophenyl)ethanol was assigned by
comparison of the sign of the measured optical rotation of the corresponding amine
(after chemical conversion by Staudinger reaction) with those of the literature (T.S.
Kaufman, V.L. Ponzo, Synlett 7 (2002) 1128-1130.
[18] For the (S)-1-(4-azidophenyl)ethanol, the azido group was converted into the
acetamide (A. Kamal, A.V. Ramana, K.S. Reddy, K.V. Ramana, A.H.Babu, B.R.
Prasad, Tetrahedron Lett. 45 (2004) 8187-8190), and the sign of the measured optical
rotation was compared with the literature (J. Wettergren, A. Bogevig, M. Portier, H.
Adolfson, Adv. Synth. Catal. 348 (2006) 1277-1282).
[19]V. Prelog, Pure Appl. Chem. 9 (1964) 119-130.
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