A new synthesis of trans-2,3-diaryloxiranes and 2-(1 H -benzo[ d ][1,2,3]-triazol-1-yl)-1-arylethanols via the reactions of 1-benzyl-3- methylbenzo-triazolium ylide with aryl aldehydes

Article abstract of DOI:10.1055/s-0031-1289555

1-Benzyl-3-methylbenzotriazolium ylide was formed by the reaction of 1-benzyl-3-methylbenzotriazolium iodide with t-BuOK. Subsequently it reacted with various aryl aldehydes to give the corresponding trans-2,3-diaryloxiranes and 2-(1H-benzo-[d][1,2,3]triazol-1-yl)-1-arylethanols in moderate to high yields. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1289555

LETTER
2823
A New Synthesis of trans-2,3-Diaryloxiranes and 2-(1H-Benzo[d][1,2,3]-
triazol-1-yl)-1-arylethanols via the Reactions of 1-Benzyl-3-methylbenzo-
triazolium Ylide with Aryl Aldehydes
New
Synthesis of
t
i
rans-2
aoiranes hui Xiao,* Daqin Lin, Shuitian Tong, Hailan Mo
Department of Chemistry, Zhejiang Normal University, 688 Yingbing Road, Jinhua, Zhejiang 321004, P. R. of China
Fax +86(579)82282610; E-mail: xxh@zjnu.cn
Received 29 July 2011
BMeBt iodide (1) and benzaldehyde (2a) were dissolved
in DMSO and then added slowly to the solution of t-
BuOK in t-BuOH (Table 1, entry 5).6 As expected, the
formation of 1,2-diphenylethene was successfully avoid-
ed, and the yield of 3a and 4a was slightly increased. With
this method, further investigations were focused on the
base and ratio of the starting materials (Table 1, entries 6–
14). As shown in Table 1, a molar ratio of 1:2:2 for 1/2a/
t-BuOK gave 3a (70%) and 4a (90%) in good yield
(Table 1, entry 8). Both one equivalent and three equiva-
lents of base decreased the yield of 3a and 4a (Table 1, en-
Abstract: 1-Benzyl-3-methylbenzotriazolium ylide was formed by
the reaction of 1-benzyl-3-methylbenzotriazolium iodide with t-
BuOK. Subsequently it reacted with various aryl aldehydes to give
the corresponding trans-2,3-diaryloxiranes and 2-(1H-benzo-
[d][1,2,3]triazol-1-yl)-1-arylethanols in moderate to high yields.
Key words: ammonium ylide, 2,3-diaryloxirane, benzotriazole,
Darzens reaction, 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1-arylethanol
Epoxidation of sulfur ylide with carbonyl compound has
been widely investigated and has become one of the most
important methods for the synthesis of oxiranes,1 but only
a few successful examples on ammonium ylides have
been reported due to their instability and poor leaving
ability of the corresponding ammonium group.2 Previous
works on the epoxidation of ammonium ylide with carbo-
nyl compounds clearly showed that the yield and diastereo-
selectivity of epoxides are strongly influenced by the
nature of amine and the stability of ylide.2d Compared
with the benzyl-stabilized ammonium ylides which are
derived from benzylammonium salts of quinuclidine, tri-
ethylamine (TEA) and 1,4-diazabicyclo[2.2.2]octane
(DABCO), 1-benzyl-3-methylbenzotriazolium (BMeBt)
ylide is more stable due to the stabilization of aromatic
benzotriazole and phenyl group. Furthermore, the leaving
ability of 1-methylbenzotriazole (1-MeBt) (gas phase ba-
sicity: GB = 898.7 kJ mol–1)3 is better than that of quinu-
clidine (GB = 952.5 kJ mol–1)3, triethylamine (GB = 951
kJ mol–1)3 and DABCO (GB = 934.6 kJ mol–1).3 However,
the reactivity of BMeBt ylide is still unexplored. Recent-
ly, we had successfully synthesized stilbenes from the ho-
mocoupling of 1,3-dibenzylbenzotriazolium bromides.4
Encouraged by this work, we tried to develop the epoxi-
dation of BMeBt ylide with aryl aldehydes.
Table 1 Screening of Conditions for the Reaction of 1 and 2a
Me
N
N
N
N+I–
base
O
N
+
PhCHO
+
N
Ph
Ph
3a
OH
Ph
2a
Ph
1
4a
Entry Base
Solvent
Ratio (1/ Yield of Yield of
2a/base) 3a (%)a 4a (%)a
1b
2b
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
NaH
THF
1:1:1
1:1:1
1:1:1
1:1:1
1:1:1
1:1:2
1:2:1
1:2:2
1:2:3
1:3:3
1:2:2
1:2:2
1:2:2
1:2:2
trace
trace
15
10
47
42
43
51
54
68
90
85
87
88
56
0
t-BuOH
DMSO
3b
4b
mixed solventsc
mixed solventsc
mixed solventsc
mixed solventsc
mixed solventsc
mixed solventsc
mixed solventsc
mixed solventsc
mixed solventsc
mixed solventsc
mixed solventsc
18
5d
26
6d
28
7d
44
8d
70
9d
65
Initially, BMeBt iodide (1; 3 mmol), benzaldehyde (2a; 3
mmol), t-BuOK (3 mmol) and solvent (10 mL) were
mixed together and stirred at room temperature (Table 1,
entries 1–4).5 After the reaction finished, 1,2-diphe-
nylethene, small amounts of trans-2,3-diphenyloxirane
(3a) and an unexpected by-product 4a were isolated by
column chromatography. In order to avoid the formation
of 1,2-diphenylethene and improve the yield of 3a and 4a,
10d
11d
12d
13d
14d
68
71
NaOH
trace
0
K2CO3
Et3N
0
0
a Isolated yield.
b Process A.5
SYNLETT 2011, No. 19, pp 2823–2826
Advanced online publication: 25.10.2011
DOI: 10.1055/s-0031-1289555; Art ID: W16611ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
1
1
c Mixed solvents: t-BuOH–DMSO = 1:1.
d Process B.6

2824
X. Xiao et al.
LETTER
tries 7 and 9). It seemed reasonable that one equivalent of ture. It is still a puzzle to us why only a trace of 3a and rea-
base was insufficient because some of the base may be sonable yield of 4a were obtained with NaOH as the base.
consumed by homocoupling of BMeBt iodide or other
Under the optimized conditions (Table 1, entry 8), the
side reactions. The excessive base could accelerate the
scope of this method was further investigated with various
formation of BMeBt ylide which was beneficial to the for-
aryl aldehydes (Table 2). As shown in Table 2, the corre-
mation of 3a and 4a, and also to the formation of 1,2-
sponding trans-2,3-diaryloxiranes 3 and 2-(1H-ben-
diphenylethene. Using t-BuOK and NaH as the base, good
zo[d][1,2,3]triazol-1-yl)-1-arylethanols 4 were isolated in
yields of 3a and 4a were obtained, but no products 3a and
good yields. More intriguingly, all these reactions showed
4a could be isolated with K2CO3 and Et3N as the base. It
high trans-selectivity in the formation of trans-2,3-diaryl-
illustrated that the basicities of K2CO3 and Et3N were not
oxiranes.
strong enough to generate BMeBt ylide at room tempera-
Table 2 The Reaction of 1-Benzyl-3-methylbenzotriazolium Iodide (1) with Various Aryl Aldehydes 2
Me
N
N
N+I–
KOt-Bu
O
ArCHO
Ar
+
2
+
N
N
Ph
Ar
OH
N
Ph
1
2
3
4
Entry
2
3
Yield (%)a (trans/cis)b
4
Yield (%)a
90
CHO
O
1
2
3
70 (>99:1)
N
N
OH
N
3a
3b
3c
2a
4a
Cl
CHO
CHO
Cl
O
O
Cl
76 (96:4)
60 (98:2)
76
77
N
N
OH
OH
N
N
2b
4b
4c
Cl
N
N
Cl
Cl
Cl
2c
CHO
Cl
O
4
5
6
67 (>99:1)
47 (>99:1)
64 (98:2)
89
56
78
N
N
OH
Cl
N
N
N
3d
3e
3f
4d
4e
4f
2d
Br
CHO
Br
O
O
Br
N
N
OH
2e
2f
CHO
Br
Br
N
N
OH
Br
Synlett 2011, No. 19, 2823–2826 © Thieme Stuttgart · New York

LETTER
New Synthesis of trans-2,3-Diaryloxiranes
2825
Table 2 The Reaction of 1-Benzyl-3-methylbenzotriazolium Iodide (1) with Various Aryl Aldehydes 2 (continued)
Me
N
N
N+I–
KOt-Bu
O
Ar
ArCHO
+
2
+
N
N
Ph
Ar
OH
N
Ph
1
2
3
4
Entry
2
3
Yield (%)a (trans/cis)b
4
Yield (%)a
80
Me
CHO
CHO
Me
O
O
Me
7
8
41 (94:6)
N
N
OH
N
N
2g
3g
3h
4g
4h
Me
52 (>99:1)
65 (>99:1)
82
80
N
N
Me
F
OH
OH
Me
2h
CHO
O
9
N
N
F
N
F
3i
4i
2i
a Isolated yield.
b Determined by GC–MS.
It was reported that 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1- iranes is determined by ring-closure step or addition step.
phenylethanol (4a) could be easily prepared by the reac- Further investigations on determination step are in
tion of 1-MeBt with 2a in the presence of n-BuLi.7 How- progress.
ever, no product 4a was found in the stirred mixture of 1-
In addition, 1,3-dibenzylbenzotriazolium bromide (5) was
MeBt, 2a and t-BuOK (or NaOH) at room temperature. It
also subjected to this reaction. As we expected, trans-2,3-
illustrated that the product 4a was not derived from 1-
diphenyloxirane 3a and two possible diastereomers of 2-
MeBt. The possible mechanism for the formation of 3 and
4 is described in Scheme 1. Firstly, BMeBt iodide reacts
–
with t-BuOK to form ylides A and B. Ylide B is more ac-
CH2
Me
N
N
N+I-
Me
N
N
N+
N+
N
tive than ylide A, so it preferentially reacts with aryl alde-
hyde to give intermediate C. Subsequently ylide D is
formed by the intramolecular deprotonation of intermedi-
ate C, and it reacts with another equivalent of aromatic al-
dehyde to form intermediate E. Finally, intermediate E
undergoes ring closure to give 3 and 4.
ArCHO
KOt-Bu
N
Ph
Ph
Ph
ylide A
ylide B
1
OH
Ar
O–
Ar
OH
Aggarwal and co-workers proved that the addition of ben-
zyl-stabilized ammonium ylide to aryl aldehyde was re-
versible and nonselective. The high trans-selectivity was
determined by ring-closure step owing to the poor leaving
ability of ammonium group.2d In this case, ylide D was
more stable than the general benzyl-stabilized ammonium
ylide because of the stabilization of aromatic benzotriaz-
ole and phenyl group. Therefore, the addition of ylide D
to aryl aldehyde may also be reversible (Scheme 2). How-
ever, 1-substituted benzotriazole is a good leaving group.
It may reduce the enthalpy of ring closure. Furthermore,
the steric hindrance of 1-substituted benzotriazole may in-
crease the enthalpic barrier to the formation of syn-be-
taine. Therefore, it is still uncertain that the high trans-
selectivity for the formation of trans-2,3-diphenylox-
N
Ar
ArCHO
N+
N
N
N
N+
N
N
N+
Ar
Ph
O–
Ph
Ph
intermediate C
ylide D
intermediate E
Ar
O
OH
N
N
+
N
Ph
Ar
3
4
Scheme 1 The proposed mechanism for the reaction of 1-benzyl-3-
methylbenzotriazolium iodide (1) with aryl aldehydes 2
Synlett 2011, No. 19, 2823–2826 © Thieme Stuttgart · New York

2826
X. Xiao et al.
LETTER
(1H-benzo[d][1,2,3]triazol-1-yl)-1,2-diphenylethanol 6a
were obtained (Scheme 3).
Acknowledgment
We gratefully acknowledge the financial support from the Founda-
tion of Science and Technology Department of Zhejiang Province
(2011R09020-07).
O–
Ar
Ph
H
H
OH
N
N
O
Ar
References and Notes
+
N
N
Ph
Ar
N
(1) (a) Li, A.-H.; Dai, L.-X.; Aggarwal, V. K. Chem. Rev. 1997,
97, 234. (b) Aggarwal, V. K.; Ford, J. G.; Fonquerna, S.;
Adams, H.; Jones, R. V. H.; Fieldhouse, R. J. Am. Chem.
Soc. 1998, 120, 8328. (c) Aggarwal, V. K.; Winn, C. L. Acc.
Chem. Res. 2004, 37, 611. (d) McGarrigle, E. M.; Myers,
E. L.; Illa, O.; Shaw, M. A.; Riches, S. L.; Aggarwal, V. K.
Chem. Rev. 2007, 107, 5841. (e) Illa, O.; Arshad, M.; Ros,
A.; McGarrigle, E. M.; Aggarwal, V. K. J. Am. Chem. Soc.
2010, 132, 1828.
(2) (a) Jonczyk, A.; Konarska, A. Synlett 1999, 1085.
(b) Kowalkowska, A.; Sucholbiak, D.; Jonczyk, A. Eur. J.
Org. Chem. 2005, 5, 925. (c) Kimachi, T.; Kinoshita, H.;
Kusaka, K.; Takeuchi, Y.; Aoe, M.; Ju-ichi, M. Synlett 2005,
842. (d) Robiette, R.; Conza, M.; Aggarwal, V. K. Org.
Biomol. Chem. 2006, 4, 621. (e) Alex, A.; Larmanjat, B.;
Marrot, J.; Couty, F.; David, O. Chem. Commun. 2007,
2500. (f) Kinoshita, H.; Ihoriya, A.; Ju-ichi, M.; Kimachi, T.
Synlett 2010, 2330. (g) Waser, M.; Herchl, R.; Mueller, N.
Chem. Commun. 2011, 47, 2170.
OH
Ar
N
3
4
trans-2,3-diaryloxirane
anti betaine
O–
ylide D
Ar
H
Ph
OH
H
Ar
O
+
N
N
N
N
N
Ph
Ar
OH
Ar
N
3
4
cis-2,3-diaryloxirane
syn betaine
Scheme 2 The formation of trans-2,3-diaryloxiranes and cis-2,3-
diaryloxiranes
Ph
N
N
N
(3) Hunter, E. P. L.; Lias, S. G. J. Phys. Chem. Ref. Data 1998,
27, 413.
(4) Xiao, X.-H.; Lin, D.-Q.; Tong, S.-T.; Luo, H.; He, Y.-F.;
Mo, H.-L. Synlett 2011, 1731.
O
KOt-Bu
N
N
+
PhCHO
2
+
N+Br–
Ph
Ph
Ph
Ph
OH
6a 81%
for two possible
diastereomers
Ph
2a
5
3a 66 %
trans/cis > 99:1
(5) Process A: BMeBt iodide (1; 3 mmol), benzaldehyde (2a; 3
mmol), t-BuOK (3 mmol) and solvent (10 mL) were mixed
together and stirred at r.t. After the purple color of the
solution had faded, H2O (25 mL) was added and the products
were extracted with EtOAc (3 × 25 mL). The combined
organic phases were washed with brine (2 × 25 mL) and H2O
(25 mL), and then were dried over anhyd Na2SO4, filtered
and concentrated in vacuo. The residue was separated by
column chromatography.
(6) Process B: A solution of BMeBt iodide (1; 3 mmol) and aryl
aldehyde 2 (6 mmol) in DMSO (5 mL) was added dropwise
to the stirred solution of t-BuOK (6 mmol) in t-BuOH (5 mL)
at r.t. After the purple color of the solution had faded, H2O
(25 mL) was added and the products were extracted with
EtOAc (3 × 25 mL). The combined organic phases were
washed with brine (2 × 25 mL) and H2O (25 mL), and then
were dried over anhyd Na2SO4, filtered and concentrated in
vacuo. The residue was separated by column chromatog-
raphy to afford the corresponding trans-2,3-diaryloxiranes 3
and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1-arylethanol 4.
(7) Katritzky, A. R.; Wu, J.; Kuzmierkiewicz, W.; Rachwal, S.
Liebigs Ann. Chem. 1994, 1.
Scheme 3 The reaction of 1,3-dibenzylbenzotriazolium bromide (5)
with benzaldehyde (2a)
In summary, we have developed a new and convenient
synthesis of trans-2,3-diaryloxiranes and 2-(1H-ben-
zo[d][1,2,3]triazol-1-yl)-1-arylethanols by the reactions
of BMeBt ylide with aryl aldehydes.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Synlett 2011, No. 19, 2823–2826 © Thieme Stuttgart · New York

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