A highly enantioselective access to chiral 1-(β-arylalkyl)-1H-1,2,4- triazole derivatives as potential agricultural bactericides

Article abstract of DOI:10.1002/cbdv.201000180

A series of chiral 1-(β-arylalkyl)-1H-1,2,4-triazole derivatives has been designed as potential antifungal agents. The target triazoles have been synthesized by using a chiral auxiliary as a controlling reagent. All of the compounds were obtained with hig

Full text of DOI:10.1002/cbdv.201000180

CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
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A Highly Enantioselective Access to Chiral 1-(b-Arylalkyl)-1H-1,2,4-triazole
Derivatives as Potential Agricultural Bactericides
by Wen-Chang Lua)b), Xiu-Fang Caoc), Ming Hua), Fei Lia), Guang-Ao Yua), and Sheng-Hua Liu*a)
a) Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry,
Central China Normal University, Wuhan 430079, P. R. China (e-mail: chshliu@mail.ccnu.edu.cn)
b) Periodical Agency of Huazhong Agricultural University, Wuhan 430070, P. R. China
c) College of Science, Huazhong Agricultural University, Wuhan 430070, P. R. China
A series of chiral 1-(b-arylalkyl)-1H-1,2,4-triazole derivatives has been designed as potential
antifungal agents. The target triazoles have been synthesized by using a chiral auxiliary as a controlling
reagent. All of the compounds were obtained with high ee values, reaching up to 99%. Preliminary
bioassay results have revealed that most of the synthesized compounds display significantly higher
fungicidal activities against the species Fusarium oxysporium, Rhizoctonia solani, Botrytis cinereapers,
Gibberella zeae, Dothiorella gregaria, and Colletotrichum gossypii than the commercial agent
triadimefon. Moreover, some of the enantiomers have been found to display significant differences in
activity.
Introduction. – Chirality is an important factor in pharmaceuticals, agrochemicals,
and the life sciences, in general, since the living body is a highly chiral environment.
Many biologically active molecules are chiral, including both naturally occurring
compounds and synthetic drugs [1–4]. Nowadays, several synthetic agrochemicals,
such as pyrethroid insecticides, triazole fungicides, and (aryloxy)propanoate herbicides,
are marketed as their most biologically active isomers. Numerous reports describing
the relative biological activities, preparations, and analyses of enantiomerically pure
agrochemicals are available [5–8].
At present, a high percentage of pharmaceutical compounds are pure enantiomers,
and many of them show significant enantioselective differences in their pharmacoki-
netics and pharmacodynamics [9][10]. There are ca. 650 pesticides on the market, a
quarter of which exist as enantiomers [11]. Different enantiomers of chiral compounds
often have different effects as drugs, and many chiral drugs must be produced with high
enantiomeric purity due to potential side-effects of the other enantiomer [12][13].
The use of optically active pesticides has led to research aimed at finding new and
effective methods of resolving enantiomeric mixtures. Triazole derivatives such as
diniconazole, triadimefon, tebuconazole, and hexaconazole represent the most
important category of fungicides to date [14–17]. These compounds are effective
against a wide spectrum of crop diseases, and they all possess a stereogenic C-atom
leading to two enantiomers. The influence of the configuration upon biological activity
is, therefore, of particular interest in this study.
Heeres and Backx reported the preparation and biological activity of racemic 1-(b-
arylalkyl)-1H-1,2,4-triazole analogs [18]; however, the goal of developing safer and
ꢀ 2011 Verlag Helvetica Chimica Acta AG, Zꢁrich

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CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
more effective chiral drugs, including medicines and agrochemicals, encouraged us to
synthesize pure active enantiomers. As part of our agrochemistry program aimed at
devising new routes to active chiral triazole derivatives 5 [19], we report here that
exceptionally high levels of stereoselectivity can be easily achieved by steric control
under standard conditions in the asymmetric alkylation of N-acylsultams derived from
Oppolzerꢂs 10,2-camphorsultam, as depicted in Scheme 1. Furthermore, we have
investigated the in vitro fungicidal activities of the resulting series of chiral 1-(b-
arylalkyl)-1H-1,2,4-triazole derivatives. Preliminary in vitro assays have shown that
almost all of the compounds 5a–5i have higher fungicidal activities than the
commercial agent triadimefon under the same conditions.
Scheme 1. Synthesis of 1-(b-Arylalkyl)-1,2,4-triazole Derivatives 5
i) 1. Et3N; 2. Me3CCOCl, toluene, 80–1108. ii) 1. BuLi, THF, ꢀ788; 2. hexamethylphosphoric triamide
(HMPA)/RX (MeI, PrI, BuI, PhCH2Br, CH2¼CHCH2Br). iii) NaBH4, aq. THF. iv) HBr. v) 1H-1,2,4-
Triazole, K2CO3, MeCN, reflux, 5–7 h.
Results and Discussion. – 1. Synthesis and Physicochemical Properties. The
pioneering work of Oppolzer et al. resulted in the development of 10,2-camphorsultam
as a popular and widely used chiral auxiliary in asymmetric synthesis. The asymmetric

CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
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induction achieved by using this auxiliary is widely applied in C,C bond-formation
reactions such as alkylations [20], aldol reactions [21], 1,4-additions [22], and
DielsꢀAlder reactions [23]. Thus, we have applied Oppolzerꢂs 10,2-camphorsultam as
a chiral auxiliary in a series of reactions under mild conditions to obtain the chiral
triazole derivatives 5 with high enantiomeric purity.
The synthetic route to 1-(b-arylalkyl)-1H-1,2,4-triazoles 5 is outlined in Scheme 1.
The key to the synthesis of 5 with a high enantiomeric purity was to establish the
stereogenic center in the stable C(a)-alkylation products 2. The a-alkylation reaction is
most probably initiated by the chelated lithium (Z)-enolate intermediate, with
subsequent nucleophilic attack of the alkylating reagent leading to the formation of
chiral intermediates 2. The possible mechanism of the monoalkylation reaction is
depicted in Scheme 2 [20].
Scheme 2. Possible Mechanism of Monoalkylation Reaction with Various Alkyl Halides to Afford
Compounds 2 with High Enantiomeric Purity
N-Acylsultams 1 were readily obtained by acylation of camphorsultam with
phenylacetic acid in the presence of pivaloyl chloride and Et3N [24]. Deprotonation of
1 with BuLi in THF, followed by monoalkylation with benzylic or allylic halides, or
even with non-activated primary alkyl iodides, in the presence of hexamethylphos-
phoric triamide (HMPA) at ꢀ788, followed by crystallization, gave products 2 in high
yields and with high diastereomeric purities [19]. Non-destructive removal of the chiral
auxiliary camphorsultam under mild conditions using NaBH4 in aqueous THF
furnished the sultam and the alcohols 3 [25], which were then brominated with HBr.
The bromo derivatives 4 were then treated with 1H-1,2,4-triazole in MeCN in the
presence of K2CO3 at 60–708 for 5–7 h to give the chiral 1-(b-arylalkyl)-1H-1,2,4-
triazoles 5 [26]. Under the experimental conditions described herein, the pure (R)- and
(S)-derivatives were conveniently obtained with ee values up to 99%. The ee values
and optical rotations of the target compounds are compiled in Table 1. The structures of
1
all of the newly synthesized compounds were elucidated on the basis of their H- and
13C-NMR data, and elemental analyses. A detailed methodology to obtain each of the
compounds 1 to 4 is given in the Exper. Part.
It can be seen from Table 1 that different substituents and configurations lead to
different ee values. When Ar¼4-chlorophenyl, 5c bearing a benzyl moiety was
obtained with the highest ee value. However, when Ar¼2,4-dichlorophenyl, the
compounds bearing Me and Bu substituents, i.e., 5f and 5g, respectively, were obtained
with higher ee values. Furthermore, for a common R substituent such as Bu, the
compounds bearing 4-fluorophenyl and 2,4-dichlorophenyl moieties, 5e and 5g,

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CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
Table 1. The ee and [a]2D5 Values of 1-(b-Arylalkyl)-1H-1,2,4-Triazole Derivatives 5
Entry
Compound
R
Ar
Yielda) [%]
[a]2D5 (c¼1, CH2Cl2)
ee [%]b)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
(R)-5a
(S)-5a
(R)-5b
(S)-5b
(R)-5c
(S)-5c
(R)-5d
(S)-5d
(R)-5e
(S)-5e
(R)-5f
(S)-5f
(R)-5g
(S)-5g
(R)-5h
(S)-5h
(R)-5i
(S)-5i
Pr
Pr
4-ClꢀC6H4
4-ClꢀC6H4
4-ClꢀC6H4
4-ClꢀC6H4
4-ClꢀC6H4
4-ClꢀC6H4
4-FꢀC6H4
73
71
75
73
60
58
58
60
57
59
54
56
65
69
59
62
51
58
þ83.7
ꢀ82.8
þ67.5
ꢀ69.7
þ19.7
ꢀ23.1
þ70.2
ꢀ70.7
þ59.9
ꢀ68.8
þ13.5
ꢀ13.2
þ20.7
ꢀ20.9
þ27.4
ꢀ28.4
þ8.3
99
94
87
95
98
99
90
89
98
99
99
97
98
99
88
90
93
99
Bu
Bu
Bn
Bn
Pr
Pr
4-FꢀC6H4
Bu
Bu
Me
Me
Bu
Bu
Allyl
Allyl
Bn
Bn
4-FꢀC6H4
4-FꢀC6H4
2,4-Cl2ꢀC6H3
2,4-Cl2ꢀC6H3
2,4-Cl2ꢀC6H3
2,4-Cl2ꢀC6H3
2,4-Cl2ꢀC6H3
2,4-Cl2ꢀC6H3
2,4-Cl2ꢀC6H3
2,4-Cl2ꢀC6H3
ꢀ11.3
a) Yields of isolated products. b) Determined by HPLC analysis (Chiralcel OJ-H or OD-H).
respectively, exhibited the highest ee values. The configurations of compounds 5 were
assigned on the basis of the absolute configurations of compounds 2. The crystal
structures of molecules (2’R)-2a and (2’S)-2a were established by X-ray crystallo-
graphic analysis and are shown in the Figure1).
2. Antifungal Activity. The antifungal activities of the 1-(b-arylalkyl)-1H-1,2,4-
triazole derivatives 5 were evaluated by using in vitro agar diffusion assays, the results
of which are presented in Tables 2 and 3. Most of the compounds showed activities in
preliminary screening tests against fungal cultures when deployed at a concentration of
50 mg/ml in agar diffusion assays. All of the synthesized chiral triazole derivatives
showed significant inhibitory activities against the growth of the species Fusarium
oxysporium, Rhizoctonia solani, Botrytis cinereapers, Gibberella zeae, Dothiorella
gregaria, and Colletotrichum gossypii compared with the commercial fungicide
triadimefon.
As shown in Table 2, all activity screenings were performed using commercial
triadimefon as a reference. Triadimefon, a broad-spectrum fungicide, was first
introduced as a triazole fungicide in 1976. We used this compound as a reference to
evaluate the potential activity of 1-(b-arylalkyl)-1H-1,2,4-triazole derivatives 5. All of
the synthesized compounds displayed inhibitory activities against Botrytis cinereapers,
1
)
Crystallographic data for (R)-2a and (S)-2a have been deposited with the Cambridge Crystal-
lographic Data Centre as supplementary publication (CCDC-715349 and CCDC-715350). This data
can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK (fax: þ441223/336033; e-
mail: deposit@ccdc.cam.ac.uk).

CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
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Figure. The molecular structure of a) (2’R)-2a and b) (2’S)-2a
Table 2. In vitro Fungicidal Activities of Compounds 5 at 50 mg/l Concentrationa)b)
Compound
R
Ar
Inhibition of growth [%]
F. oxy-
sporium
R. solani B. cine- G. zeae D. gregaria C. gossypii
reapers
(R)-5a
(S)-5a
(R)-5b
(S)-5b
(R)-5c
(S)-5c
(R)-5d
(S)-5d
(R)-5e
(S)-5e
(R)-5f
(S)-5f
(R)-5g
(S)-5g
(R)-5h
(S)-5h
(R)-5i
(S)-5i
Pr
Pr
4-ClꢀC6H4
4-ClꢀC6H4
4-ClꢀC6H4
4-ClꢀC6H4
4-ClꢀC6H4
4-ClꢀC6H4
4-FꢀC6H4
4-FꢀC6H4
4-FꢀC6H4
4-FꢀC6H4
91
95
73
82
71
63
98
95
95
77
98
99
99
99
86
86
99
99
99
96
97
98
99
100
90
99
94
90
91
100
100
100
100
98
85
70
78
74
73
70
100
89
98
74
74
74
96
81
77
81
78
73
59
95
100
100
100
86
100
100
100
100
100
96
100
100
100
100
98
100
100
100
100
100
98
Bu
Bu
Bn
Bn
Pr
79
73
100
100
100
98
100
89
100
100
100
100
100
79
100
100
98
98
57
Pr
Bu
Bu
Me
Me
Bu
Bu
2,4-Cl2ꢀC6H3 90
2,4-Cl2ꢀC6H3 93
2,4-Cl2ꢀC6H3 91
2,4-Cl2ꢀC6H3 91
98
100
100
100
100
67
Allyl 2,4-Cl2ꢀC6H3 92
Allyl 2,4-Cl2ꢀC6H3 98
Bn
Bn
2,4-Cl2ꢀC6H3 68
2,4-Cl2ꢀC6H3 75
91
91
14
92
98
Triadimefon
78
a) Mean values for relative inhibitions calculated from at least three determinations. b) Standard
deviations are within the range of 1–4.
Gibberella zeae, and Dothiorella gregaria better than triadimefon at a concentration of
50 mg/l. In particular, for the fungus Dothiorella gregaria, triadimefon was found to
exhibit a weak inhibition rate of only 14%, which was lower than the inhibition rates of
the synthesized chiral triazole derivatives 5. Moreover, all of the compounds, except
(S)-5c and (S)-5i, showed higher inhibitory activities against Colletotrichum gossypii
than the reference compound. The inhibitory activity of triadimefon against
Rhizoctonia solani is lower than those of almost all of the synthesized chiral triazole
derivatives, except (R)-5c, (S)-5c, (R)-5h, and (S)-5i. From these preliminary results, it

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CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
can be seen that most of the synthesized compounds exhibit high and broad-spectrum
antifungal activities against the six strains tested, and the activity differences between
the compounds of different configurations are insignificant. To further investigate the
activity differences of the enantiomers, the test concentration was decreased to
12.5 mg/l. The inhibitory activities of compounds 5a, 5b, 5d, 5e, 5f, and 5g against the
Table 3. In vivo Fungicidal Activities of Compounds 5 at 12.5 mg/l Concentrationa)b)
Compound
R
Ar
Inhibition of growth [%]
F. oxy-
R. solani B. cine- G. zeae D. gregaria C. gossypii
sporium
reapers
(R)-5a
(S)-5a
(R)-5b
(S)-5b
(R)-5d
(S)-5d
(R)-5e
(S)-5e
(R)-5f
(S)-5f
Pr
Pr
4-ClꢀC6H4
4-ClꢀC6H4
61
63
38
54
88
71
79
29
86
97
91
92
87
95
83
90
73
82
80
88
86
92
57
22
87
78
39
26
9
70
22
98
100
15
61
31
34
38
66
55
62
21
31
45
69
62
29
61
68
0
91
88
87
87
96
92
98
75
38
92
88
96
78
Bu 4-ClꢀC6H4
Bu 4-ClꢀC6H4
68
55
73
45
36
14
77
45
95
10
Pr
Pr
4-FꢀC6H4
4-FꢀC6H4
Bu 4-FꢀC6H4
Bu 4-FꢀC6H4
Me 2,4-Cl2ꢀC6H3 67
Me 2,4-Cl2ꢀC6H3 79
Bu 2,4-Cl2ꢀC6H3 79
Bu 2,4-Cl2ꢀC6H3 63
65
(R)-5g
(S)-5g
Triadimefon
a) Mean values for relative inhibitions calculated from at least three determinations. b) Standard
deviations are within the range of 1–4.
various fungi at this concentration are collected in Table 3. The results evidence that the
synthesized triazole derivatives 5 exhibit higher inhibition activities than the
commercial triadimefon under the same conditions. More importantly, the enantiomers
display some differences in activity. For example, compound 5b exhibits significant
activity differences against Dothiorella gregaria and Botrytis cinereapers, with (S)-5b
showing inhibition rates of 87 and 68%, respectively, whereas (R)-5b exhibiting
inhibition rates of 22 and 0%, respectively. Enantiomers of 5a also show distinctly
different inhibition rates against Botrytis cinereapers and Gibberella zeae, with the (R)-
enantiomer (R)-5a displaying better inhibition activity than the (S)-enantiomer. The
activity of (R)-5e is far higher than that of (S)-5e; the inhibition rate against Fusarium
oxysporium of the (R)-enantiomer is 50% higher than that of the (S)-enantiomer. The
inhibitory activities of the enantiomers of compound 5f against Dothiorella gregaria are
also distinctly different, with the activity of (S)-5f being about five-fold higher than that
of (R)-5f.
Conclusions. – In summary, we have achieved a highly enantioselective synthesis of
1-(b-arylalkyl)-1H-1,2,4-triazole derivatives utilizing camphorsultam as a chiral
auxiliary. All of the compounds were obtained with high ee values reaching 87–
99%. Preliminary bioassay results have demonstrated that most of these compounds

CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
1503
display significant wide-spectrum fungicidal activities against the species Fusarium
oxysporium, Rhizoctonia solani, Botrytis cinereapers, Gibberella zeae, Dothiorella
gregaria, and Colletotrichum gossypii. On the basis of the above results, the optically
pure enantiomers (R)-5a, (S)-5a, (R)-5d, (S)-5d, (R)-5e, (S)-5f, (R)-5g, (S)-5g, and
(S)-5h exhibited higher activities than the commercial fungicide triadimefon, and,
therefore display the potential to be developed as highly potent antifungal agents.
The authors acknowledge financial support from the National Natural Science Foundation of China
(Nos. 20572029 and 20772039) and the Science Foundation for the New Teacher at the University of China
(No. 20070511006).
Experimental Part
1. General. Unless otherwise noted, all materials were commercially available and were used directly
without further purification. All solvents were redistilled before use. Fusarium oxysporium, Rhizoctonia
solani, Botrytis cinereapers, Gibberella zeae, Dothiorella gregaria, and Colletotrichum gossypii were
provided by the Center for Bioassay, Central China Normal University. The enantiomeric ratio was
determined by using HPLC on Chiralcel OD-H column and OJ-H column, with hexane and iPrOH as the
eluent. M.p.: Bꢀchi B-545 melting point apparatus; uncorrected. Optical rotations: Jasco P-1010
1
polarimeter. H- and 13C-NMR spectra: Varian Mercury Plus 400 spectrometer (400 MHz) or Varian
Mercury Plus 600 spectrometer (600 MHz), resp.; the chemical shifts d rel. to CDCl3 with TMS as the
internal reference. MS: TraceMS-2000 organic mass spectrometer. Elemental analyses: Vario ElIII
CHNSO elemental analysis instrument.
2. Synthesis of 1. To a mixture of the (ꢀ)-d-10,2-camphorsultam (30 mmol) and (4-chlorophenyl)-
acetic acid (60 mmol) in toluene (48 ml) was added Et3N (120 mmol). The mixture was heated to an
internal temp. of 808. To the mixture was added a soln. of pivaloyl chloride (60 mmol) in toluene
(6 mmol) at a rate to maintain an internal temp. of 808. The mixture was then heated to 1108 and stirred at
this temp. for 24 h. The mixture was cooled to r.t. and was washed with 2n HCl, 5% Na2CO3, and brine,
dried (Na2SO4), and filtered. The filtrate was concentrated, and the crude product was purified by
crystallization or SiO2 chromatography to afford the desired product 1 as a white solid. The analogous
procedure with (þ)-l-10,2-camphorsultam gave the enantiomeric products.
(þ)-(1S)-N-[2-(4-Chlorophenyl)acetyl]bornane-10,2-sultam (¼2-(4-Chlorophenyl)-1-[(3aS)-tetra-
hydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]ethanone; (1S)-1a). Yield
10.5 g (95%). 1H-NMR (400 MHz, CDCl3): 0.90 (s, Me); 1.05 (s, Me); 1.27–1.37 (m, 2 H); 1.78–1.87 (m,
3 H); 1.95–1.97 (m, 2 H); 3.44 (d, J¼13.5, 2 H); 3.81–3.84 (m, 1 H); 3.87–3.99 (m, COCH2); 7.16–7.23
(m, 4 arom. H). 13C-NMR (100 MHz, CDCl3): 19.73; 20.70; 38.17; 40.85; 41.06; 44.22; 44.62; 47.64; 48.35;
52.86; 65.22; 127.70; 128.49; 131.01; 131.10; 131.65; 132.95; 169.30. EI-MS: 367 (Mþ ). Anal. calc. for
C18H22ClNO3S (367.89): C 58.77, H 6.03, N 3.81, S 8.72; found: C 58.53, H 5.79, N 3.69, S 8.72.
(þ)-(1S)-N-[2-(4-Fluorophenyl)acetyl]bornane-10,2-sultam (¼2-(4-Fluorophenyl)-1-[(3aS)-tetra-
hydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]ethanone; (1S)-1b). Yield
8.43 g (80%).1H-NMR (400 MHz, CDCl3): 0.97 (s, Me); 1.12 (s, Me); 1.34–1.42 (m, 2 H); 1.85–1.93 (m,
3 H); 2.02–2.04 (m, 2 H); 3.51 (d, J¼13.5, 2 H); 3.88–3.91 (m, 1 H); 3.95–4.06 (m, COCH2); 6.98–7.02
(m, 2 arom. H); 7.25–7.29 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 19.77; 20.73; 38.22; 40.95; 41.18;
44.26; 44.67; 47.67; 48.38; 52.92; 65.23; 114.99; 115.23; 115.46; 128.90; 131.28; 161.94; 169.66. EI-MS: 351
(Mþ ). Anal. calc. for C18H22FNO3S (351.44): C 61.52, H 6.31, N 3.99, S 9.12; found: C 61.57, H 6.40, N
3.86, S 8.92.
(þ)-(1S)-N-[2-(2,4-Dichlorophenyl)acetyl]bornane-10,2-sultam
(¼2-(2,4-Dichlorophenyl)-1-
[(3aS)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]ethanone;
1
(1S)-1c). Yield 10.26 g (85%). H-NMR (400 MHz, CDCl3): 0.99 (s, Me); 1.21 (s, Me); 1.35–1.43 (m,
2 H); 1.88–1.94 (m, 3 H); 2.04–2.06 (m, 1 H); 2.14–2.15 (m, 1 H); 3.52 (q, J¼13.7, 2 H); 3.90–3.93 (m,
1 H); 4.04–4.28 (m, COCH2); 7.18–7.23 (m, 2 arom. H); 7.41 (s, 1 arom. H). 13C-NMR (100 MHz,

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CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
CDCl3): 19.70; 20.54; 20.68; 38.06; 39.34; 44.21; 44.61; 47.63; 48.51; 52.72; 65.17; 127.04; 129.12; 130.56;
132.62; 133.69; 135.21; 167.83. EI-MS: 401 (Mþ ). Anal. calc. for C18H21Cl2NO3S (402.34): C 53.73, H 5.26,
N 3.48, S 7.97; found: C 53.61, H 4.98, N 3.35, S 8.07.
3. Synthesis of 2. A soln. of (1R)-1 (0.02 mol) in anh. THF (60 ml) under N2 was cooled to ꢀ788, to
which BuLi (9 ml, 2.5m in hexane) was added dropwise. After stirring for 1 h, the alkylating agents
(0.1 mol) and HMPA (0.1 mol) in THF were added, then the mixture was stirred at ꢀ788 for 6–8 h. The
mixture was slowly warmed up to r.t., before the reaction was quenched by the addition of H2O, and the
mixture was extracted with Et2O (3ꢁ60 ml). The combined org. phases were washed with brine, dried
(MgSO4), and concentrated to yield a crude oil, which was purified by crystallization or by SiO2
chromatography to afford the desired product 2. The enantiomeric products were prepared according to
the same procedure [19].
N-(þ)-[(2S)-2-(4-Chlorophenyl)pentanoyl]bornane-10,2-sultam (¼(2S)-2-(4-Chlorophenyl)-1-
[(3aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]pentan-1-one;
(2’S)-2a). White solid. M.p. 182–1848. Yield 7.79 g (95%). 1H-NMR (600 MHz, CDCl3): 0.90 (t, J ¼ 7.2,
3 H); 0.98 (s, Me); 1.21 (s, Me); 1.28–1.34 (m, 4 H); 1.76–1.79 (m, 1 H); 1.84–1.90 (m, 3 H, ); 2.04–2.10
(m, 2 H); 2.13–2.14 (m, 1 H); 3.41 (d, J¼13.8, 1 H); 3.53 (d, J¼13.8, 1 H); 3.83–3.85 (m, 1 H); 4.27 (t,
J ¼ 7.5, COCH); 7.27 (d, J ¼ 7.6, 2 arom. H); 7.39 (d, J ¼ 7.6, 2 arom. H). 13C-NMR (100 MHz, CDCl3):
13.65; 19.78; 20.56; 20.82; 26.26; 32.75; 38.13; 38.44; 44.52; 47.61; 48.15; 50.12; 53.00; 65.41; 128.19;
130.14; 132.86; 136.51; 173.05. EI-MS: 409 (Mþ ). Anal. calc. for C21H28ClNO3S (409.97): C 61.52, H 6.88,
N 3.42, S 7.82; found: C 61.75, H 6.89, N 3.30, S 8.14.
(þ)-N-[(2R)-2-(4-Chlorophenyl)pentanoyl]bornane-10,2-sultam (¼(2R)-2-(4-Chlorophenyl)-1-
[(3aS)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]pentan-1-one;
(2’R)-2a). White solid. M.p. 182–1848. Yield 7.62 g (93%). Spectroscopic data: identical to those of (2’S)-
2a.
(þ)-N-[(2S)-2-(4-Chlorophenyl)hexanoyl]bornane-10,2-sultam (¼(2S)-2-(4-Chlorophenyl)-1-
[(3aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]hexan-1-one;
(2’S)-2b). White solid. M.p. 129–1318. Yield 7.97 g (94%). 1H-NMR (400 MHz, CDCl3): 0.84 (t, J ¼ 7.2,
3 H); 0.98 (s, Me); 1.21 (s, Me); 1.24–1.35 (m, 6 H); 1.78–1.82 (m, 1 H); 1.84–1.90 (m, 3 H, ); 2.05–2.13
(m, 3 H); 3.41 (d, J¼14.0, 1 H); 3.52 (d, J¼14.0, 1 H); 3.82–3.84 (m, 1 H); 4.25 (t, J ¼ 7.2, COCH); 7.26
(d, J ¼ 8.4, 2 arom. H); 7.39 (d, J ¼ 8.4, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 13.80; 19.88; 20.87;
22.28; 26.35; 29.55; 32.90; 35.83; 38.53; 44.62; 47.71; 48.52; 50.38; 53.15; 65.54; 128.31; 130.21; 133.01;
136.55; 173.22. EI-MS: 423 (Mþ ). Anal. calc. for C22H30ClNO3S (424.0): C 62.32, H 7.13, N 3.30, S 7.56;
found: C 62.43, H 6.91, N 3.09, S 7.58.
(þ)-N-[(2R)-2-(4-Chlorophenyl)hexanoyl]bornane-10,2-sultam (¼(2R)-2-(4-Chlorophenyl)-1-
[(3aS)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]hexan-1-one;
(2’R)-2b). White solid. M.p. 129–1318. Yield 7.97 g (94%). Spectroscopic data: identical to those of (2’S)-
2b.
(þ)-N-[(2S)-2-(4-Chlorophenyl)-3-phenylpropanoyl]bornane-10,2-sultam (¼(2S)-2-(4-Chloro-
phenyl)-1-[(3aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]-3-
phenylpropan-1-one; (2’S)-2c). White solid. M.p. 205–2068. Yield 7.14 g (78%). 1H-NMR (400 MHz,
CDCl3): 0.63 (s, Me); 0.87 (s, Me); 1.25–1.27 (m, 2 H); 1.73–1.82 (m, 4 H); 1.92–1.98 (m, 1 H); 3.04–
3.08 (m, 1 H, PhCH2); 3.29–3.41 (m, 3 H); 3.72–3.75 (m, 1 H); 4.60–4.64 (m, COCH); 7.14–7.48 (m, 9
arom. H). 13C-NMR (100 MHz, CDCl3): 19.74; 20.42; 26.30; 32.76; 38.23; 42.50; 44.53; 47.47; 48.03;
51.95; 52.97; 65.30; 126.67; 128.28; 128.38; 129.37; 130.20; 133.22; 136.08; 137.60; 171.97. EI-MS: 457
(Mþ ). Anal. calc. for C25H28ClNO3S (458.01): C 65.56, H 6.16, N 3.06, S 7.00; found: C 65.59, H 5.65, N
3.26, S 7.28.
(þ)-N-[(2R)-2-(4-Chlorophenyl)-3-phenylpropanoyl]bornane-10,2-sultam (¼(2R)-2-(4-Chloro-
phenyl)-1-[(3aS)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]-3-
phenylpropan-1-one; (2’R)-2c). White solid. M.p. 205–2068. Yield 6.96 g (76%). Spectroscopic data:
identical to those of (2’S)-2c.
(þ)-N-[(2S)-2-(4-Fluorophenyl)pentanoyl]bornane-10,2-sultam (¼(2S)-2-(4-Fluorophenyl)-1-
[(3aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]pentan-1-one;
1
(2’S)-2d). White solid. M.p. 161–1638. Yield 7 g (89%). H-NMR (600 MHz, CDCl3): 0.91 (t, J ¼ 7.2,

CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
1505
3 H); 0.98 (s, Me); 1.21 (s, Me); 1.31–1.34 (m, 4 H); 1.76–1.79 (m, 1 H); 1.84–1.90 (m, 3 H, ); 2.04–2.10
(m, 2 H); 2.13–2.14 (m, 1 H); 3.44 (d, J¼13.8, 1 H); 3.53 (d, J¼13.8, 1 H); 3.83–3.85 (m, 1 H); 4.28 (t,
J ¼ 7.2, COCH); 6.98–7.00 (m, 2 arom. H); 7.41–7.43 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3):
13.62; 19.74; 20.54; 20.78; 26.23; 32.70; 38.20; 38.43; 44.50; 47.57; 48.11; 49.93; 52.96; 65.36; 114.71;
114.92; 130.24; 130.32; 133.71; 161.87; 173.3. EI-MS: 393 (Mþ ). Anal. calc. for C21H28FNO3S (393.52): C
64.10, H 7.17, N 3.56, S 8.15; found: C 64.36, H 6.86, N 3.40, S 8.10.
(þ)-N-[(2R)-2-(4-Fluorophenyl)pentanoyl]bornane-10,2-sultam (¼(2R)-2-(4-Fluorophenyl)-1-
[(3aS)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]pentan-1-one;
(2’R)-2d). White solid. M.p. 161–1638. Yield 7.16 g (91%). Spectroscopic data: identical to those of (2’S)-
2d.
(þ)-N-[(2S)-2-(4-Fluorophenyl)hexanoyl]bornane-10,2-sultam (¼(2S)-2-(4-Fluorophenyl)-1-
[(3aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]hexan-1-one;
(2’S)-2e). White solid. M.p. 134–1368. Yield 7.09 g (87%). 1H-NMR (600 MHz, CDCl3): 0.85 (t, J ¼ 7.0,
3 H); 0.98 (s, Me); 1.21 (s, Me); 1.25–1.34 (m, 6 H); 1.78–1.82 (m, 1 H); 1.84–1.90 (m, 3 H, ); 2.06–2.10
(m, 2 H); 2.14–2.17 (m, 1 H); 3.42 (d, J¼13.8, 1 H); 3.53 (d, J¼13.8, 1 H); 3.83–3.85 (m, 1 H); 4.24 (t,
J ¼ 7.0, COCH); 6.97–7.00 (m, 2 arom. H); 7.41–7.43 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3):
13.75; 19.80; 20.79; 22.22; 26.28; 29.50; 32.78; 35.88; 38.46; 44.56; 47.63; 48.17; 50.13; 53.05; 65.43; 114.99;
130.28; 130.36; 133.71; 161.87; 173.3. EI-MS: 407 (Mþ ). Anal. calc. for C22H30FNO3S (407.54): C 64.84, H
7.42, N 3.44, S 7.87; found: C 64.63, H 7.14, N 3.34, S 8.00.
(þ)-N-[(2R)-2-(4-Fluorophenyl)hexanoyl]bornane-10,2-sultam (¼(2R)-2-(4-Fluorophenyl)-1-
[(3aS)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]hexan-1-one;
(2’R)-2e). White solid. M.p. 134–1368. Yield 6.85g (84%). Spectroscopic data: identical to those of (2’S)-
2e.
(þ)-N-[(2S)-2-(2,4-Dichlorophenyl) ethanoyl]bornane-10,2-sultam (¼(2S)-2-(2,4-Dichlorophenyl)-
1-[(3aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]propan-1-
1
one; (2’S)-2f). White solid. M.p. 129–1308. Yield 7.66 g (92%). H-NMR (600 MHz, CDCl3): 0.97 (s,
Me); 1.17 (s, Me); 1.33–1.40 (m, 2 H); 1.56 (d, J ¼ 6, 3 H); 1.88–2.06 (m, 3 H); 2.07 (d, J ¼ 7.2, 2 H); 3.47
(d, J ¼ 7.2, 2 H); 3.76 (s, 1 H); 4.85 (d, J ¼ 6.6, COCH); 7.23 (d, J ¼ 8.4, 1 arom. H); 7.39 (s, 1 arom. H);
7.43 (d, J ¼ 8.4, 1 arom. H). 13C-NMR (100 MHz, CDCl3): 19.03; 19.73; 20.57; 25.85; 26.24; 29.17; 38.24;
44.42; 47.65; 48.34; 52.82; 65.26; 126.88; 129.13; 129.67; 133.25; 134.36; 135.73; 172.73. EI-MS: 415 (Mþ ).
Anal. calc. for C19H23Cl2NO3S (416.36): C 54.81, H 5.57, N 3.36, S 7.70; found: C 55.08, H 5.77, N 3.19, S
7.62.
(þ)-N-[(2R)-2-(2,4-Dichlorophenyl)ethanoyl]bornane-10,2-sultam (¼(2R)-2-(2,4-Dichlorophen-
yl)-1-[(3aS)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]propan-
1-one; (2’R)-2f). White solid. M.p. 129–1308. Yield 7.58 g (91%). Spectroscopic data: identical to those
of (2’S)-2f.
(þ)-N-[(2S)-2-(2,4-Dichlorophenyl)hexanoyl]bornane-10,2-sultam (¼(2S)-2-(2,4-Dichlorophenyl)-
1-[(3aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]hexan-1-
one; (2’S)-2g). White solid. M.p. 149–1528. Yield 8.52 g (93%). 1H-NMR (600 MHz, CDCl3): 0.86 (t, J ¼
7.2, 3 H); 0.98 (s, Me); 1.20 (s, Me); 1.24–1.36 (m, 6 H); 1.72 (br., 1 H); 1.89 (br., 3 H); 2.11 (br., 1 H);
2.12 (br., 2 H); 3.38 (d, J¼13.8, 1 H); 3.50 (d, J¼13.8, 1 H); 3.89 (br., 1 H); 4.79 (br., COCH); 7.20 (d,
J¼8.4, 1 arom. H); 7.39 (s, 1 arom. H); 7.53 (d, J ¼ 8.4, 1 arom. H). 13C-NMR (100 MHz, CDCl3): 13.77;
19.80; 20.74; 22.10; 26.31; 29.54; 32.75; 35.49; 38.47; 44.58; 46.40; 47.68; 48.29; 52.99; 65.39; 126.92;
129.27; 129.69; 133.06; 134.68; 134.89; 171.96. EI-MS: 458 ([Mþ1]þ ). Anal. calc. for C22H29Cl2NO3S
(458.44): C 56.74, H 6.38, N 3.06, S 6.99; found: C 57.13, H 6.20, N 2.81, S 6.91.
(þ)-N-[(2R)-2-(2,4-Dichlorophenyl)hexanoyl]bornane-10,2-sultam (¼(2R)-2-(2,4-Dichlorophen-
yl)-1-[(3aS)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]hexan-1-
one; (2’R)-2g). White solid. M.p. 149–1528. Yield 8.16 g (89%). Spectroscopic data: identical to those of
(2’S)-2g.
(þ)-N-[(2S)-2-(2,4-Dichlorophenyl)pent-4-enoyl]bornane-10,2-sultam (¼(2S)-2-(2,4-Dichloro-
phenyl)-1-[(3aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]-
pent-4-en-1-one; (2’S)-2h). White solid. M.p. 172–1748. Yield 7.16 g (81%). 1H-NMR (600 MHz, CDCl3):
0.97 (s, Me); 1.19 (s, Me); 1.35 (br., 2 H); 1.88 (br., 3 H); 2.10 (br., 2 H); 2.49–2.51 (m, 1 H); 2.74–2.76

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CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
(m, 1 H); 3.37 (d, J¼13.8, 1 H); 3.50 (d, J¼13.8, 1 H); 3.88 (br., 1 H); 4.92 (br., COCH); 5.03 (d, J ¼
10.2, 1 H); 5.13 (d, J ¼ 16.8, 1 H); 5.80 (br., 1 H); 7.20 (d, J¼8.4, 1 arom. H); 7.39 (s, 1 arom. H); 7.55 (d,
J ¼ 8.4, 1 arom. H). 13C-NMR (100 MHz, CDCl3): 19.70; 20.69; 26.20; 32.60; 38.21; 39.07; 44.47; 45.83;
47.56; 48.21; 52.83; 62; 29; 117.74; 126.87; 129.24; 129.68; 133.15; 134.02; 134.48; 170.93. EI-MS: 441 (Mþ
). Anal. calc. for C21H25Cl2NO3S (442.4): C 57.01, H 5.70, N 3.17, S 7.25; found: C 56.79, H 5.76, N 3.15, S
7.13.
(þ)-N-[(2R)-2-(2,4-Dichlorophenyl)pent-4-enoyl]bornane-10,2-sultam (¼(2R)-2-(2,4-Dichloro-
phenyl)-1-[(3aS)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-yl]-
pent-4-en-1-one; (2’R)-2h). White solid. M.p. 172–1748. Yield 7.43 g (84%). Spectroscopic data: identical
to those of (2’S)-2h.
(þ)-N-[(2S)-2-(2,4-Dichlorophenyl)-3-Phenylpropanoyl]bornane-10,2-sultam (¼(2S)-2-(2,4-Di-
chlorophenyl)-1-[(3aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-
yl]-3-phenylpropan-1-one; (2’S)-2i). White solid. M.p. 228–2308. Yield 7.98 g (81%). 1H-NMR
(600 MHz, CDCl3): 0.61 (s, Me); 0.86(s, Me); 1.26 (br., 2 H); 1.65–1.71 (m, 2 H); 1.81 (br., 2 H);
1.92–1.96 (m, 1 H); 3.06–3.08 (m, 1 H, PhCH2); 3.16–3.25 (m, 1 H, PhCH2); 3.26(d, J¼13.8, 1 H); 3.36
(d, J¼13.8, 1 H); 3.76 (br., 1 H); 5.18 (br., COCH); 7.18–7.29 (m, 6 arom. H); 7.41 (s, 1 arom. H); 7.65 (d,
J ¼ 8.4, 1 arom. H). 13C-NMR (100 MHz, CDCl3): 19.61; 20.20; 26.19; 32.57; 38.04; 41.29; 44.47; 47.36;
47.99; 48.26; 52.77; 65.00; 126.61; 127.03; 128.19; 129.12; 129.41; 133.27; 134.10; 134.39; 137.59; 170.61. EI-
MS: 492 (Mþ ). Anal. calc. for C25H27Cl2NO3S (492.46): C 60.97, H 5.53, N 2.84, S 6.51; found: C 60.55, H
5.61, N 2.81, S 6.78.
(þ)-N-[(2R)-2-(2,4-Dichlorophenyl)-3-Phenylpropanoyl]bornane-10,2-sultam (¼(2R)-2-(2,4-Di-
chlorophenyl)-1-[(3aS)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzothiazol-1(3H,4H)-
yl]-3-phenylpropan-1-one; (2’R)-2i). White solid. M.p. 228–2308. Yield 7.68 g (78%). Spectroscopic
data: identical to those of (2’S)-2i.
4. Synthesis of 3. A soln. of NaBH4 (40 mmol; 4 equiv.) in H2O (10 ml) was added dropwise to a
cooled (ice-water) soln. of 2 (10 mmol) in THF (30 ml). The mixture was stirred at r.t., and the
completion of the reaction was monitored by TLC. To the mixture was added 2m HCl at a rate to
maintain the internal temp. at 20–258. The mixture was extracted with AcOEt (2ꢁ50 ml). The combined
org. layers were washed with brine (50 ml), concentrated, and purified by SiO2 chromatography to afford
the desired products 3, using 10% AcOEt/petroleum ether (60–908) as an eluent. The enatiomeric
products were prepared according to the same procedure [25].
(2R)-2-(4-Chlorophenyl)pentan-1-ol ((R)-3a). Colorless oil. Yield 1.85 g (93%). 1H-NMR
(400 MHz, CDCl3): 0.85 (t, J ¼ 7.4, Me); 1.14–1.19 (m, CH2); 1.44–1.48 (m, 1 H of CH2); 1.59–1.64
(m, 1 H of CH2); 2.35 (br., OH); 2.67 (br., CH); 3.54 (br., CH2OH); 7.09 (d, J ¼ 8.0, 2 arom. H); 7.25 (d,
J ¼ 8.0, 2 arom. H).
(2S)-2-(4-Chlorophenyl)pentan-1-ol ((S)-3a). Colorless oil. Yield 1.89 g (95%). Spectroscopic data:
identical to those of (R)-3a.
(2R)-2-(4-Chlorophenyl)hexan-1-ol ((R)-3b). Colorless oil. Yield 1.91 g (90%). 1H-NMR
(400 MHz, CDCl3): 0.84 (t, J ¼ 7.2, Me); 1.13–1.21 (m, CH2); 1.22–1.30 (m, CH2, OH); 1.51–1.58 (m,
1 H of CH2); 1.66–1.69 (m, 1 H of CH2); 2.75 (br., CH); 3.69–3.76 (m, CH2OH); 7.15 (d, J ¼ 8.2, 2 arom.
H); 7.30 (d, J ¼ 8.2, 2 arom. H).
(2S)-2-(4-Chlorophenyl)hexan-1-ol ((S)-3b). Colorless oil. Yield 1.96 g (92%). Spectroscopic data:
identical to those of (R)-3b.
(2R)-2-(4-Chlorophenyl)-3-phenylpropan-1-ol ((R)-3c). Colorless oil. Yield 2.05 g (83%). 1H-NMR
(400 MHz, CDCl3): 1.28 (br., OH); 2.82–2.85 (m, 1 H of CH2); 2.98–3.07 (m, 1 H of CH2); 3.71–3.75 (m,
CH2OH); 7.03–7.26 (m, 9 arom. H).
(2S)-2-(4-Chlorophenyl)-3-phenylpropan-1-ol ((S)-3c). Colorless oil. Yield 2.12 g (86%). Spectro-
scopic data: identical to those of (R)-3c.
(2R)-2-(4-Fluorophenyl)pentan-1-ol ((R)-3d). Colorless oil. Yield 1.57 g (86%). 1H-NMR
(400 MHz, CDCl3): 0.87 (t, J ¼ 7.4, Me); 1.18–1.26 (m, OH, CH2); 1.49–1.56 (m, 1 H of CH2); 1.61–
1.68 (m, 1 H of CH2); 2.77–2.81 (m, CH); 3.66–3.74 (m, CH2OH); 7.00–7.04 (m, 2 arom. H); 7.16–7.19
(m, 2 arom. H).

CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
1507
(2S)-2-(4-Fluorophenyl)pentan-1-ol ((S)-3d). Colorless oil. Yield 1.6 g (88%). Spectroscopic data:
identical to those of (R)-3d.
(2R)-2-(4-Fluorophenyl)hexan-1-ol ((R)-3e). Colorless oil. Yield 1.63 g (83%). 1H-NMR (400 MHz,
CDCl3): 0.84 (t, J ¼ 7.2, Me); 1.10–1.20 (m, CH2); 1.22–1.37 (m, CH2); 1.39 (br., OH); 1.41–1.56 (m, 1 H
of CH2); 1.64–1.71 (m, 1 H of CH2); 2.73–2.78 (m, CH); 3.64–3.76 (m, CH2OH); 7.00–7.04 (m, 2 arom.
H); 7.15–7.18 (m, 2 arom. H).
(2S)-2-(4-Fluorophenyl)hexan-1-ol ((S)-3e). Colorless oil. Yield 1.63 g (83%). Spectroscopic data:
identical to those of (R)-3e.
(2R)-2-(2,4-Dichlorophenyl)propan-1-ol ((R)-3f). Colorless oil. Yield 1.74 g (85%). 1H-NMR
(600 MHz, CDCl3): 1.27 (d, J¼7.6, Me); 1.38 (s, OH); 3.47–3.51 (m, CH); 3.69–3.73 (m, 1 H of
CH2OH); 3.76–3.79 (m, 1 H of CH2OH); 7.24 (d, J ¼ 9.6, 2 arom. H); 7.40 (s, 1 arom. H).
(2S)-2-(2,4-Dichlorophenyl)propan-1-ol ((S)-3f). Colorless oil. Yield 1.66 g (81%). Spectroscopic
data: identical to those of (R)-3f.
(2R)-2-(2,4-Dichlorophenyl)hexan-1-ol ((R)-3g). Colorless oil. Yield 2.3 g (93%). 1H-NMR
(600 MHz, CDCl3): 0.86 (t, J ¼ 7.2, Me); 1.16 (br., OH); 1.21–1.31 (m, 2 CH2); 1.56–1.59 (m, 1 H of
CH2); 1.76–1.77 (m, 1 H of CH2); 3.40–3.42 (m, CH); 3.75–3.77 (m, CH2OH); 7.20–7.25 (m, 2 arom. H);
7.40 (s, arom. H).
(2S)-2-(2,4-Dichlorophenyl)hexan-1-ol ((S)-3g). Colorless oil. Yield 2.32 g (94%). Spectroscopic
data: identical to those of (R)-3g.
(2R)-2-(2,4-Dichlorophenyl)pent-4-en-1-ol ((R)-3h). Colorless oil. Yield 1.89 g (82%). 1H-NMR
(600 MHz, CDCl3): 1.36 (s, OH); 2.37–2.42 (m, 1 H of CH2); 2.52–2.56 (m, 1 H of CH2); 3.49–3.51 (m,
CH); 3.79–3.81 (m, CH2OH); 4.99–5.05 (m, CH2); 5.68–5.74 (m, CH); 7.21–7.25 (m, 2 arom. H); 7.41 (s,
1 arom. H).
(2S)-2-(2,4-Dichlorophenyl)pent-4-en-1-ol ((S)-3h). Colorless oil. Yield 2.0 g (87%). Spectroscopic
data: identical to those of (R)-3h.
(2R)-2-(2,4-Dichlorophenyl)-3-phenylpropan-1-ol ((R)-3i). Colorless oil. Yield 2.47 g (88%).
1H-NMR (400 MHz, CDCl3): 1.31 (s, OH); 2.93–2.95 (m, 1 H of CH2); 3.01–3.03 (m, 1 H of CH2Ph);
3.71 (br., CH); 3.80 (br., CH2); 7.14–7.38 (m, 8 arom. H).
(2S)-2-(2,4-Dichlorophenyl)-3-phenylpropan-1-ol ((S)-3i). Colorless oil. Yield 2.39 g (85%).
Spectroscopic data: identical to those of (R)-3i.
5. Synthesis of 4. A 100-ml round-bottom flask equipped with a stir bar was charged with 10 mmol of
3 and 30 ml (0.21 mol) of HBr. The mixture was refluxed and stirred for 10–12 h at 100–1108. After
completion of the reaction, the mixture was extracted with CHCl3 (40ꢁ3 ml). The combined org. phases
were washed with H2O, NaHCO3 (aq. sat.), and brine (50 ml), dried (Na2SO4), and concentrated to yield
a crude oil, which was purified by SiO2 chromatography with petroleum ether (60–908) to give pure 4 as a
colorless oil. The enantiomeric products were prepared according to the same procedure.
(2R)-1-Bromo-2-(4-chlorophenyl)pentane ((R)-4a). Colorless oil. Yield 1.54 g (59%). 1H-NMR
(400 MHz, CDCl3): 0.85 (t, J ¼ 7.2, Me); 1.16–1.20 (m, MeCH2); 1.55–1.59 (m, 1 H of CH2); 1.79–1.85
(m, 1 H of CH2); 2.90–2.94 (m, CH); 3.45–3.54 (m, CH2Br); 7.10 (d, J ¼ 8.4, 2 arom. H); 7.27 (d, J ¼ 8.4,
2 arom. H).
(2S)-1-Bromo-2-(4-chlorophenyl)pentane ((S)-4a). Colorless oil. Yield 1.57 g (60%). Spectroscopic
data: identical to those of (R)-4a.
(2R)-1-Bromo-2-(4-chlorophenyl)hexane ((R)-4b). Colorless oil. Yield 1.63 g (59%). 1H-NMR
(400 MHz, CDCl3): 0.84 (t, J ¼ 7.2, Me); 1.10–1.32 (m, 2 CH2); 1.57–1.61 (m, 1 H of CH2); 1.84–1.89 (m,
1 H of CH2); 2.89–2.93 (m, CH); 3.47–3.57 (m, CH2Br); 7.11 (d, J ¼ 8.6, 2 arom. H); 7.30 (d, J ¼ 8.6, 2
arom. H).
(2S)-1-Bromo-2-(4-chlorophenyl)hexane ((S)-4b). Colorless oil. Yield 1.52 g (55%). Spectroscopic
data: identical to those of (R)-4b.
(2R)-1-Bromo-2-(4-chlorophenyl)-3-phenylpropane ((R)-4c). Colorless oil. Yield 1.52 g (49%).
1H-NMR (400 MHz, CDCl3): 2.92–2.95 (m, 1 H, PhCH2); 3.13–3.16 (m, 1 H, PhCH2); 3.18–3.24 (m,
CH2Br); 3.53–3.60 (m, CH); 7.04–7.33 (m, 9 arom. H).
(2S)-1-Bromo-2-(4-chlorophenyl)-3-phenylpropane ((S)-4c). Colorless oil. Yield 1.61 g (52%).
Spectroscopic data: identical to those of (R)-4c.

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CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
(2R)-1-Bromo-2-(4-fluorophenyl)pentane ((R)-4d). Colorless oil. Yield 1.44 g (59%). 1H-NMR
(400 MHz, CDCl3): 0.87 (t, J ¼ 7.2, Me); 1.16–1.22 (m, CH2); 1.55–1.61 (m, 1 H of CH2); 1.82–1.87
(m, 1 H of CH2); 2.92–2.96 (m, CH); 3.48–3.57 (m, CH2Br); 6.99–7.04 (m, 2 arom. H); 7.12–7.16 (m, 2
arom. H).
(2S)-1-Bromo-2-(4-fluorophenyl)pentane ((S)-4d). Colorless oil. Yield 1.42 g (58%). Spectroscopic
data: identical to those of (R)-4d.
(2R)-1-Bromo-2-(4-fluorophenyl)hexane ((R)-4e). Colorless oil. Yield 1.37 g (53%). 1H-NMR
(400 MHz, CDCl3): 0.84 (t, J ¼ 7.2, Me); 1.11–1.33 (m, 2 CH2); 1.56–1.61 (m, 1 H, CH2); 1.85–1.91 (m,
1 H, CH2); 2.90–2.94 (m, CH); 3.48–3.57 (m, CH2Br); 7.00–7.04 (m, 2 arom. H); 7.12–7.16 (m, 2 arom.
H).
(2S)-1-Bromo-2-(4-fluorophenyl)hexane ((S)-4e). Colorless oil. Yield 1.45 g (56%). Spectroscopic
data: identical to those of (R)-4e.
(2R)-1-Bromo-2-(2,4-dichlorophenyl)propane ((R)-4f). Colorless oil. Yield 1.34 g (50%). 1H-NMR
(600 MHz, CDCl3): 1.40 (d, J ¼ 7.2, Me); 3.48–3.50 (m, 1 H of CH2); 3.60–3.61 (m, 1 H of CH2); 3.64–
3.68 (m, CH); 7.19–7.21 (m, 1 arom. H); 7.21–7.22 (m, 1 arom. H); 7.40 (s, 1 arom. H).
(2S)-1-Bromo-2-(2,4-dichlorophenyl)propane ((S)-4f). Colorless oil. Yield 1.31 g (49%). Spectro-
scopic data: identical to those of (R)-4f.
(2R)-1-Bromo-2-(2,4-dichlorophenyl)hexane ((R)-4g). Colorless oil. Yield 1.8 g (58%). 1H-NMR
(600 MHz, CDCl3): 0.89 (t, J ¼ 7.2, Me); 1.20–1.36 (m, 4 H); 1.65 (d, J ¼ 9, 1 H); 1.84–1.86 (m, 1 H);
3.56–3.59 (m, CH2Br, CH); 7.17 (d, J ¼ 7.8, 1 arom. H); 7.25 (d, J ¼ 9, 1 arom. H); 7.40 (d, J ¼ 7.8, 1 arom.
H).
(2S)-1-Bromo-2-(2,4-dichlorophenyl)hexane ((S)-4g). Colorless oil. Yield 1.86 g (60%). Spectro-
scopic data: identical to those of (R)-4g.
(2R)-5-Bromo-4-(2,4-dichlorophenyl)pent-1-ene ((R)-4h). Colorless oil. Yield 1.23 g (42%).
1H-NMR (600 MHz, CDCl3): 2.44–2.49 (m, 1 H, CH2); 2.59–2.66 (m, 1 H, CH2); 3.60–3.66 (m, CH2Br,
CH); 5.03–5.10 (m, CH2¼CH); 5.62–5.69 (m, CH2¼CH); 7.16 (d, J ¼ 8.4, 1 arom. H); 7.25 (d, J ¼ 8.4, 1
arom. H); 7.41 (s, 1 arom. H).
(2S)-5-Bromo-4-(2,4-dichlorophenyl)pent-1-ene ((S)-4h). Colorless oil. Yield 1.53 g (52%). Spec-
troscopic data: identical to those of (R)-4h.
(2R)-1-Bromo-2-(2,4-dichlorophenyl)-3-phenylpropane ((R)-4i). Colorless oil. Yield 1.93 g (56%).
1H-NMR (400 MHz, CDCl3): 2.97–3.02 (m, 1 H, PhCH2); 3.09–3.14 (m, 1 H, PhCH2); 3.53–3.63 (m,
CH2Br); 3.84–3.87 (m, CH); 7.13–7.38 (m, 8 arom. H).
(2S)-1-Bromo-2-(2,4-dichlorophenyl)-3-phenylpropane ((S)-4i). Colorless oil. Yield 1.86 g (54%).
Spectroscopic data: identical to those of (R)-4i.
6. Synthesis of 5. A mixture of 4 (5 mmol), K2CO3 (25 mmol), and 1H-1,2,4 triazole (6 mmol) in
MeCN (25 ml) was stirred at 60–708 for 5–7 h. After completion of the reaction, the mixture was cooled
to r.t. and filtered. The filtrate was washed with H2O (5 ml), dried (Na2SO4), and filtered. The filtrate was
concentrated under reduced pressure to give a crude product, which was purified by SiO2
chromatography to give compounds 5, with Et2O as an eluent. The enantiomeric products were
prepared according to the same procedure [26].
1-[(2R)-2-(4-Chlorophenyl)pentyl]-1H-1,2,4-triazole ((R)-5a). Colorless oil. Yield 0.91 g (73%).
[a]2D5 ¼ þ83.7 (c¼1.0, CH2Cl2). 99% ee (HPLC: tR 16.91 (minor); 11.28 (major)). 1H-NMR (400 MHz,
CDCl3): 0.85 (t, J ¼ 7.2, Me); 1.17–1.23 (m, CH2Me); 1.61–1.67 (m, CH2CH2Me); 3.19–3.23 (m, CH);
4.15–4.21 (m, 1 H, CH2); 4.34–4.39 (m, 1 H, CH2); 6.93–7.03(m, 4 arom. H); 7.61 (s, 1 triazole H); 7.89 (s,
1 triazole H). 13C-NMR (100 MHz, CDCl3): 13.56; 19.94; 34.51; 45.20; 55.24; 128.51; 128.63; 132.51;
139.23; 143.00; 151.55. EI-MS: 250 ([Mþ1]þ ). Anal. calc. for C13H16ClN3 (249.74): C 62.52, H 6.46, N
16.83; found: C 62.33, H 6.58, N 16.38.
1-[(2S)-2-(4-Chlorophenyl)pentyl]-1H-1,2,4-triazole ((S)-5a). Colorless oil. Yield 0.89 g (71%).
[a]2D5 ¼ ꢀ82.8 (c¼1.0, CH2Cl2). 94% ee (HPLC: tR 11.96 (minor); 15.23 (major)). Spectroscopic data:
identical to those of (R)-5a.
1-[(2R)-2-(4-Chlorophenyl)hexyl]-1H-1,2,4-triazole ((R)-5b). Colorless oil. Yield 0.99 g (75%).
1
[a]2D5 ¼ þ67.5 (c¼1.0, CH2Cl2). 87% ee (HPLC: tR 13.71 (minor); 10.31 (major)). H-NMR (400 MHz,
CDCl3): 0.82(t, J ¼ 7.2, Me); 1.13–1.31 (m, 2 CH2); 1.63–1.69 (m, CH2CH2Me); 3.19 (t, J ¼ 6.8, CH);

CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
1509
4.15–4.21 (m, 1 H, CH2); 4.35–4.40 (m, 1 H, CH2); 6.93–7.03 (m, 4 arom. H); 7.70 (s, 1 triazole H); 7.89
(s, 1 triazole H). 13C-NMR (100 MHz, CDCl3): 13.58; 22.18; 28.97; 33.24; 45.34; 55.51; 115.26; 115.47;
128.61; 128.68; 136.49; 143.01; 151.51; 161.45. EI-MS: 264 ([Mþ1]þ ). Anal. calc. for C13H16ClN3
(263.77): C 62.52, H 6.46, N 16.83; found: C 62.33, H 6.58, N 16.38.
1-[(2S)-2-(4-Chlorophenyl)hexyl]-1H-1,2,4-triazole ((S)-5b). Colorless oil. Yield 0.96 g (73%).
[a]2D5 ¼ ꢀ69.7 (c¼1.0, CH2Cl2). 95% ee (HPLC: tR 11.46 (minor); 13.96 (major)). Spectroscopic data:
identical to those of (R)-5b.
1-[(2R)-2-(4-Chlorophenyl)-3-phenylpropyl]-1H-1,2,4-triazole ((R)-5c). Colorless oil. Yield 0.89 g
(60%). [a]2D5 ¼ þ19.7 (c¼1.0, CH2Cl2). 98% ee (HPLC: tR 33.60 (minor); 21.45 (major)). 1H-NMR
(400 MHz, CDCl3): 2.97–3.00 (m, PhCH2); 3.53 (d, J ¼ 7.2, CH); 4.23–4.29 (m, 1 H, CH2); 4.40–4.45 (m,
1 H, CH2); 7.07 (d, J ¼ 8.4, 2 arom. H); 7.16–7.26 (m, 5 arom. H); 7.60 (s, 1 triazole H); 7.90 (s, 1 triazole
H). 13C-NMR (100 MHz, CDCl3): 39.41; 47.33; 54.36; 126.55; 127.47; 128.49; 128.81; 128.91; 128.94;
130.33; 133.06; 138.16; 138.80; 143.37; 151.97. EI-MS: 297 (Mþ ). Anal. calc. for C17H16ClN3 (297.78): C
68.57, H 5.42, N 14.11; found: C 68.19, H 5.47, N 14.02.
1-[(2S)-2-(4-Chlorophenyl)-3-phenylpropyl]-1H-1,2,4-triazole ((S)-5c). Colorless oil. Yield 0.86 g
(58%). [a]2D5 ¼ ꢀ23.1 (c¼1.0, CH2Cl2). 99% ee (HPLC: tR 21.10 (minor); 34.03 (major)). Spectroscopic
data: identical to those of (R)-5c.
1-[(2R)-2-(4-Fluorophenyl)pentyl]-1H-1,2,4-triazole ((R)-5d). Colorless oil. Yield 0.68 g (58%).
1
[a]2D5 ¼ þ70.2 (c¼1.0, CH2Cl2). 90% ee (HPLC: tR 18.91 (minor); 17.29 (major)). H-NMR (400 MHz,
CDCl3): 0.86 (t, J ¼ 7.2, Me); 1.17–1.24 (m, CH2Me); 1.61–1.67 (m, CH2CH2Me); 3.19–3.23 (m, CH);
4.15–4.21 (m, 1 H, CH2); 4.34–4.39 (m, 1 H, CH2); 6.93–7.03 (m, 4 arom. H); 7.61 (s, 1 triazole H); 7.89
(s, 1 triazole H). 13C-NMR (100 MHz, CDCl3): 13.57; 19.97; 34.67; 45.08; 55.48; 115.26; 115.47; 128.26;
128.70; 136.43; 140.01; 151.54; 161.49. EI-MS: 234 ([Mþ1]þ ). Anal. calc. for C13H16FN3 (233.28): C
66.93, H 6.91, N 18.01; found: C 66.72, H 7.21, N 18.35.
1-[(2S)-2-(4-Fluorophenyl)pentyl]-1H-1,2,4-triazole ((S)-5d). Colorless oil. Yield 0.7 g (60%).
[a]2D5 ¼ ꢀ70.7 (c¼1.0, CH2Cl2). 89% ee (HPLC: tR 17.29 (minor); 18.99 (major)). Spectroscopic data:
identical to those of (R)-5d.
1-[(2R)-2-(4-Fluorophenyl)hexyl]-1H-1,2,4-triazole ((R)-5e). Colorless oil. Yield 0.7 g (57%).
[a]2D5 ¼ þ59.9 (c¼1.0, CH2Cl2). 98% ee (HPLC: tR 35.36 (minor); 41.33 (major)). 1H-NMR (400 MHz,
CDCl3): 0.81 (d, J ¼ 6.8, Me); 1.17–1.26 (m, 2 CH2); 1.66 (d, J ¼ 6.4, CH2CH2Me); 3.19 (s, CH); 4.19 (t,
J ¼ 8.8, 1 H, CH2); 4.35–4.40 (m, 1 H, CH2); 6.93–7.01 (m, 4 arom. H); 7.63 (s, 1 triazole H); 7.89 (s, 1
triazole H). 13C-NMR (100 MHz, CDCl3): 13.57; 19.97; 34.67; 45.08; 54.48; 115.26; 115.47; 128.62; 128.70;
136.43; 143.01; 151.54; 161.49. EI-MS: 248 ([Mþ1]þ ). Anal. calc. for C13H16FN3 (247.31): C 67.99, H 7.34,
N 16.99; found: C 67.64, H 7.58, N 17.24.
1-[(2S)-2-(4-Fluorophenyl)hexyl]-1H-1,2,4-triazole ((S)-5e). Colorless oil. Yield 0.73 g (59%).
[a]2D5 ¼ ꢀ68.8 (c¼1.0, CH2Cl2). >99% ee (HPLC: tR 42.17(major)). Spectroscopic data: identical to
those of (R)-5e.
1-[(2R)-2-(2,4-Dichlorophenyl)propyl]-1H-1,2,4-triazole ((R)-5f). Colorless oil. Yield 0.69 g
(54%). [a]2D5 ¼ þ13.5 (c¼1.0, CH2Cl2). 99% ee (HPLC: tR 18.46 (minor); 16.14 (major)). 1H-NMR
(600 MHz, CDCl3): 1.31 (d, J ¼ 7.2, Me); 3.87–3.88 (m, CH); 4.25–4.29 (m, CH2); 4.37–4.40 (m, 1 H,
CH2); 7.10 (d, J ¼ 7.8, 1 arom. H); 7.23 (d, J ¼ 7.8, 1 arom. H); 7.39 (s, 1 arom. H); 7.81 (s, 1 triazole H);
7.92 (s, 1 triazole H). 13C-NMR (100 MHz, CDCl3): 17.41; 36.17; 54.50; 127.57; 128.34; 129.71; 133.41;
134.50; 137.92; 143.17; 151.88. EI-MS: 256 (Mþ ). Anal. calc. for C11H11Cl2N3 (256.13): C 51.58, H 4.33, N
16.41; found: C 51.3, H 4.19, N 15.71.
1-[(2S)-2-(2,4-Dichlorophenyl)propyl]-1H-1,2,4-triazole ((S)-5f). Colorless oil. Yield 0.72 g (56%).
[a]2D5 ¼ ꢀ13.2 (c¼1.0, CH2Cl2). 97% ee (HPLC: tR 18.86 (minor); 15.19 (major)). Spectroscopic data:
identical to those of (R)-5f.
1-[(2R)-2-(2,4-Dichlorophenyl)hexyl]-1H-1,2,4-triazole ((R)-5g). Colorless oil. Yield 0.97 g (65%).
[a]2D5 ¼ þ20.7 (c¼1.0, CH2Cl2). 98% ee (HPLC: tR 39.31 (minor); 35.83 (major)). 1H-NMR (400 MHz,
CDCl3): 0.83 (t, J ¼7.2, Me); 1.14–1.32 (m, 2 CH2); 1.68–1.74 (m, CH2); 3.77 (t, J¼7.2, CH); 4.33–4.39
(m, CH2); 7.05 (d, J ¼ 8.0, 1 arom. H); 7.21–7.23 (m, 1 arom. H); 7.36 (d, J ¼ 2.0, 1 arom. H); 7.71 (s, 1
triazole H); 7.89 (s, 1 triazole H). 13C-NMR (100 MHz, CDCl3): 13.72; 22.36; 28.87; 31.55; 41.64; 53.78;

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CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
127.46; 128.71; 129.63; 133.16; 135.13; 136.73; 143.03; 151.67. EI-MS: 298 ([Mþ1]þ ). Anal. calc. for
C14H17Cl2N3 (298.21): C 56.39, H 5.75, N 14.09; found: C 56.76, H 5.36, N 14.24.
1-[(2S)-2-(2,4-Dichlorophenyl)hexyl]-1H-1,2,4-triazole ((S)-5g). Colorless oil. Yield 1.03 g (69%).
[a]2D5 ¼ ꢀ26.9 (c¼1.0, CH2Cl2). >99% ee (HPLC: tR 39.60 (major)). Spectroscopic data: identical to
those of (R)-5g.
1-[(2R)-2-(2,4-Dichlorophenyl)pent-4-enyl]-1H-1,2,4-triazole ((R)-5h). Colorless oil. Yield 0.83 g
(59%). [a]2D5 ¼ þ27.4 (c¼1.0, CH2Cl2). 88% ee (HPLC: tR 15.91 (minor); 9.85 (major)). 1H-NMR
(400 MHz, CDCl3): 2.46–2.53 (m, CH2); 3.87 (t, J ¼7.2, CH); 4.35–4.46 (m, CH2); 5.03–5.09 (m,
CH¼CH2); 5.62–5.69 (m, CH¼CH2); 7.02 (d, J ¼ 8.4, 1 arom. H); 7.19–7.22 (m, 1 arom. H); 7.37 (d, J ¼ 2,
1 arom. H); 7.74 (s, 1 triazole H); 7.90 (s, 1 triazole H). 13C-NMR (100 MHz, CDCl3): 35.91; 41.17; 52.57;
118.05; 127.39; 128.92; 133.40; 134.02; 134.85; 136.08; 143.19; 151.73. EI-MS: 282 ([Mþ1]þ ). Anal. calc.
for C13H13Cl2N3 (282.17): C 55.34, H 4.64, N 14.89; found: C 55.07, H 5.12, N 15.29.
1-[(2S)-2-(2,4-Dichlorophenyl)pent-4-enyl]-1H-1,2,4-triazole ((S)-5h). Colorless oil. Yield 0.87 g
(62%). [a]2D5 ¼ ꢀ28.4 (c¼1.0, CH2Cl2). 90% ee (HPLC: tR 9.04 (minor); 16.33 (major)). Spectroscopic
data: identical to those of (R)-5h.
1-[(2R)-2-(2,4-Dichlorophenyl)-3-phenylpropyl]-1H-1,2,4-triazole ((R)-5i). Colorless oil. Yield
0.85g (51%). [a]2D5 ¼ þ8.3 (c¼1.0, CH2Cl2). 93% ee (HPLC: tR 22.18 (minor); 17.77 (major)).
1H-NMR (400 MHz, CDCl3): 3.01–3.08 (m, PhCH2); 4.11 (t, J ¼ 6.8, CH); 4.40–4.41 (m, CH2); 6.98 (d,
J ¼ 8.4, 2 arom. H); 7.12–7.32 (m, 7 arom. H); 7.66 (s, 1 triazole H); 7.88 (s, 1 triazole H). 13C-NMR
(100 MHz, CDCl3): 18.10; 37.94; 43.12; 52.03; 126.56; 127.30; 128.43; 129.64; 133.37; 134.71; 135.99;
137.71; 143.20; 151.68. EI-MS: 332 ([Mþ1]þ ). Anal. calc. for C17H15Cl2N3 (332.23): C 61.46, H 4.55, N
12.65; found: C 61.18, H 4.98, N 112.29.
1-[(2S)-2-(2,4-Dichlorophenyl)-3-phenylpropyl]-1H-1,2,4-triazole ((S)-5i). Colorless oil. Yield
0.96 g (58%). [a]2D5 ¼ ꢀ11.3 (c¼1.0, CH2Cl2). 99% ee (HPLC: tR 17.75 (minor); 22.12 (major)).
Spectroscopic data: identical to those of (R)-5i.
7. Antifungal-Activity Determination. The in vitro fungicidal activities against Fusarium oxysporium,
Rhizoctonia solani, Botrytis cinereapers, Gibberella zeae, Dothiorella gregaria, and Colletotrichum
gossypii were tested according to the method reported in [27]. The medium was amended with aliquots of
each tested compound soln. to provide concentration of 50 and 12.5 mg/l. The tested compounds were
dissolved in 0.3 ml of DMF and added aseptically to molten agar after autoclaving, when the agar had
cooled to ca. 45–508.The concentration of solvent never exceeded 0.1 mg/l. The mixed medium without
sample was used as the blank control. The inocula, 5 mm in diameter, were removed from the margins of
actively growing colonies of mycelium, placed in the centers of the above plates. Three replicates were
conducted for each concentration, and the control plates were sealed with parafilm and incubated at 268
in darkness. The diameter of the mycelium was measured for 48 h. The inhibition percent was used to
describe the efficiency of the compounds: inhibition percent [%]¼(hyphal diameter in the control ꢀ
hyphal diameter in the treatment)/hyphal diameter in the control.
REFERENCES
[1] H. Caner, E. Groner, L. Levy, I. Agranat, Drug Discovery Today 2004, 9, 105.
[2] T. P. Yoon, E. N. Jacobsen, Science 2003, 299, 1691.
[3] B. Jiang, H. Wang, Q.-M. Fu, Z.-Y. Li, Chirality 2008, 20, 96.
[4] K. M. Koeller, C.-H. Wong, Nature 2001, 409, 232.
[5] W. Liu, J. J. Gan, J. Agric. Food Chem. 2004, 52, 736.
[6] W. Liu, S. Qin, J. Gan, J. Agric. Food Chem. 2005, 53, 3814.
[7] M. T. Martin, R. J. Brennan, W. Hu, E. Ayanoglu, C. Lau, H. Ren, C. R. Wood, J. C. Corton, R. J.
Kavlock, D. J. Dix, Toxicol. Sci. 2007, 97, 595.
[8] X. Cai, W. Liu, G. Sheng, J. Agric. Food Chem. 2008, 56, 2139.
[9] E. L. Izake, J. Pharm. Sci. 2007, 96, 1659.
[10] A. Shafaati, Iran. J. Pharm. Res. 2007, 6, 73.
[11] A. W. Garrison, Environ. Sci. Technol. 2006, 40, 16.

CHEMISTRY & BIODIVERSITY – Vol. 8 (2011)
1511
[12] N. Kurihara, J. Miyamoto, G. D. Paulson, B. Zeeh, M. W. Skidmore, R. M. Hollingworth, H. A.
Kuiper, Pure Appl. Chem. 1997, 69, 1335.
[13] R. Shimazawa, N. Nagai, S. Toyoshima, H. Okuda, J. Health Sci. 2008, 54, 23.
[14] ꢃModern Crop Protectionꢂ, Eds. W. Krꢄmer, U. Schirmer, Wiley-VCH, Weinheim, Germany, 2007.
[15] S. Cairoli, A. Arnoldi, S. Pagani, J. Agric. Food Chem. 1996, 44, 3849.
[16] A. Arnoldi, R. Carzaniga, G. Morini, L. Merlini, G. Farina, J. Agric. Food Chem. 2000, 48, 2547.
[17] A. Arnoldi, S. Dallavalle, L. Merlini, L. Musso, G. Farina, M. Moretti, L. Jayasinghe, J. Agric. Food
Chem. 2007, 55, 8187.
[18] J. Heeres, L. Backx, Ger. Offen. 1978; Chem. Abstr. 1978, 88, 190842.
[19] S. Liu, W. Lu, G. Yu, M. Hu, S. Jin, X. Cao, Faming Zhuanli Shenqing Gongkai Shuomingshu 2009;
Chem. Abstr. 2009, 150, 306655.
[20] W. Oppolzer, R. Moretti, S. Thomi, Tetrahedron Lett. 1989, 30, 5603.
[21] W. Oppolzer, J. Blagg, I. Rodriguez, E. Walther, J. Am. Chem. Soc. 1990, 112, 2767.
[22] W. Oppolzer, G. Poli, A. J. Kingma, C. Starkemann, G. Bernadinelli, Helv. Chim. Acta 1987, 70, 2201.
[23] W. Oppolzer, Pure Appl. Chem. 1990, 62, 1241.
[24] M. Prashad, H.-Y. Kim, D. Har, O. Repic, T. Blacklock, Tetrahedron Lett. 1998, 39, 9369.
[25] X. Cao, F. Liu, W. Lu, G. Chen, G.-A. Yu, S. H. Liu, Tetrahedron 2008, 64, 5629.
[26] X. Cao, F. Li, M. Hu, W. Lu, G.-A. Yu, S. H. Liu, J. Agric. Food Chem. 2008, 56, 11367.
[27] J. M. Clough, C. R. A. Godfrey, ꢃThe strobilurin fungicidesꢂ, in ꢃFungicidal Activity, Chemical and
Biological Approaches to Plant Protectionꢂ, Eds. D. H. Hutson, J. Miyamoto, Wiley Series in
Agrochemicals and Plant Protection, John Wiley & Sons, Surrey, United Kingdom, 1998, p. 109.
Received June 28, 2010