Transformations of 1-(oxiranylmethyl)-1,2,3-triazoles into 2-(Oxiranylmethyl)-1,2,3-triazoles and alkanenitriles

Article abstract of DOI:10.1055/s-0032-1317937

New reactions for the transformation of 1-(oxiranylmethyl)-1,2,3-triazoles into 2-(oxiranylmethyl)-1,2,3-triazoles or alkanenitriles were established. Successive treatment of the substrate with triflic acid and t-BuOH afforded 4,6-dihydro-5-hydroxy-1,3a,6a-triazapentalene derivative. Under the influence of NaH, the bicyclic compound was converted into a 2-(oxiranylmethyl)-1,2,3- triazole or an alkanenitrile. The reaction pathway depends on the substituent pattern of the epoxide side chain. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0032-1317937

LETTER
▌207
letter
Transformations of 1-(Oxiranylmethyl)-1,2,3-triazoles into 2-(Oxiranyl-
methyl)-1,2,3-triazoles and Alkanenitriles
Transformations of 1-(Oxiranylmethyl)-1,2,3-triazoles
Ayumi Osawa, Akane Mera, Kosuke Namba,* Keiji Tanino*
Department of Chemistry, Graduate School of Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan
Fax +81(11)7064920; E-mail: namba@mail.sci.hokudai.ac.jp; E-mail: ktanino@sci.hokudai.ac.jp
Received: 08.11.2012; Accepted after revision: 02.12.2012
would give 1-(oxiranylmethyl)-1,2,3-triazole 5 which
may undergo a cyclization reaction to afford bicyclic tri-
azolium ion B′. The formation of alkoxide ion at B′ would
not induce the elimination to afford 1,3a,6a-triazapen-
Abstract: New reactions for the transformation of 1-(oxiranyl-
methyl)-1,2,3-triazoles into 2-(oxiranylmethyl)-1,2,3-triazoles or
alkanenitriles were established. Successive treatment of the sub-
strate with triflic acid and t-BuOH afforded 4,6-dihydro-5-hydroxy-
1,3a,6a-triazapentalene derivative. Under the influence of NaH, the talenes and reform the epoxide ring at the C4 position to
bicyclic compound was converted into a 2-(oxiranylmethyl)-1,2,3-
triazole or an alkanenitrile. The reaction pathway depends on the
substituent pattern of the epoxide side chain.
give 2-oxylanylmethyl-1,2,3-triazole 6 (Scheme 1, b).
However, the alternative epoxide ring-closing mode at the
C6 position is also possible, which convert back into the
1-oxylanylmethyl-1,2,3-triazole 5. Therefore, the control
Key words: 1,2,3-triazole, 2-substituted 1,2,3-triazole, click reac-
tion
of regioselectivity in the epoxide ring-closing reaction is
an important issue of this conversion strategy giving 2-
substituted 1,2,3-triazoles (Scheme 1, b).
The copper-mediated Huisgen cycloaddition reaction de-
veloped by Sharpless and co-workers has received a great
a) direct synthesis of fluorescent 1,3a,6a-triazapentalene
6
5
deal of attention as one of the most powerful click reaction
applicable to the area of material science, drug discovery,
polymer chemistry, bioconjugation, etc.1,2 The reaction
consists of Cu(I)-catalyzed azide–alkyne condensation to
regioselectively provide 1-substituted 1H-1,2,3-triazoles
under mild conditions, and a large number of 1-substitut-
ed 1H-1,2,3-triazole derivatives have been reported as
useful compounds.3 In contrast, much less attention has
been paid to 2-substituted 2H-1,2,3-triazoles due to its dif-
ficulty of preparation. Therefore, development of an effi-
cient synthetic method for the 2-substituted 1,2,3-
triazoles has recently been an active research area.4 Mean-
while, inspired by the click reaction, we have recently es-
tablished the direct synthesis of 1,3a,6a-triazapentalene,
an excellent fluorescent chromophore with a compact
structure, from an alkyne and azide 1.5 The click reaction
of azide 1 possessing two triflates at each of the C2 and C3
positions afforded triazole A, which underwent cycliza-
tion to give triazolium ion B. In the presence of triethyl-
amine, the intermediate B was subsequently converted
into triazapentalene 3 by a sequential reaction of E2 elim-
ination and deprotonation (Scheme 1, a). Furthermore, the
5-methoxy analogue of B was found to be stable enough
for isolation, and a strong base was necessary for the elim-
ination of the methoxy group to give 1,3a,6a-triazapen-
talenes.6 Based on these synthetic studies of 1,3a,6a-
triazapentalenes, we newly planned the direct synthesis of
2-substituted 2H-1,2,3-triazoles, that is, the use of oxira-
nylmethyl azides 4 as an azide fragment (Scheme 1, b).
The copper-mediated click reaction of 4 with an alkyne
+
OTf
N
–
CuI (5 mol%)
4
N 1
R
+
N
R
OTf
N3
Et3N (5 equiv)
THF (0.2 M)
3
2
1
2
3
‘click’ reaction
1,3a,6a-triazapentalene
NEt3
OTf
TfO
H
TfO
N+
5
N+
N+
N–
N
N
H
N
N
N
N
R
N
N
NEt3
R
R
R
A
B
C
D
b) synthetic plan of 2-substituted 1,2,3-triazoles
O
O
–O
O
N3
5
6
4
4
N
+
N
N
N
N
+
N
N
N
N
R
R
R
R
2
6
5
2-oxiranylmethyl-
1,2,3-triazole
B'
1-oxiranylmethyl-
1,2,3-triazole
Scheme 1 Synthetic approach to the 2-substituted 1,2,3-triazoles
We undertook the investigation with the simplest oxira-
nylmethyl azide (4) in order to elucidate the regioselectiv-
ity of the epoxide-reforming reaction. The click reaction
of oxiranylmethyl azide (4), generated in situ from epi-
chlorohydrin (7) with 1-pentadecyne afforded the triazole
5a in 81% yield.7 Since the cascade cyclization of 5a after
triazole formation was not occurred, the activation of the
epoxide ring was examined. Initial attempts to activate the
SYNLETT 2013, 24, 0207–0210
Advanced online publication: 19.12.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1317937; Art ID: ST-2012-U0964-L
© Georg Thieme Verlag Stuttgart · New York

208
A. Osawa et al.
LETTER
epoxide moiety of 5a by using a catalytic amount of Brøn- the same nitrile 10 in 60% yield (Table 1, entry 3). Since
sted or Lewis acids were fruitless due to the basicity of the the hydrogen atom at C4 position was considered to be an
triazole ring. On the other hand, treatment of 5a with 2.0 important factor affecting the nitrile-forming reaction, the
equivalents of trifluoromethanesulfonic acid (TfOH) in gem-dimethyl-substituted analogue 5e was examined. In-
dichloromethane unexpectedly afforded triflate 8a terestingly, the desired epoxide formation occurred to pre-
through an regioselective epoxide-opening reaction.8,9 dominantly give 2-oxiranlymethyl-1,2,3-triazole 6e in
Since oxiranes are known to easily undergo ring-opening 93% yield without the formation of nitrile 10 (Table 1, en-
polymerization in the presence of a strong acid, formation try 4). On the other hand, treatment of 5f, possessing the
of triflate 8a may come from the positive charge on the gem-dimethyl group at the opposite side, with TfOH af-
protonated triazole ring which prevents the dimerization forded ketone 11f through rapid hydride transfer (Table 1,
or origomerization of 5a.10 Although the protonated tri- entry 5).
azole ring of 8a did not attack the triflate moiety in situ,
formation of the desired bicyclic triazolium ion 9a in 87%
NMR yield was observed after extraction of 8a with wa-
ter. In contrast, one-pot neutralization of the reaction mix-
Table 1 Conversions of the Various Oxiranymethyl-1,2,3-triazoles
5 into Nitrile 10 and 2-Oxiranylmethyl-1,2,3-triazoles 6
R3
R3
R4
O
O
R4
R2
ture by adding a base merely induced reformation of the
starting material 5a. These results led us to explore neutral
proton acceptors other than water, and addition of an ex-
cess amount of t-BuOH was found to effect the desired
transformation (Scheme 2). Having established the proce-
dure for preparing 5-hydroxy-intermediate 9a, direct
transformation into 2-oxylanylmethyl-1,2,3-triazole 6a
under basic conditions was examined. After removal of
dichloromethane and t-BuOH under reduced pressure, the
crude 9a was diluted with THF, and to this was carefully
added 3.5 equivalents of sodium hydride. The reaction
proceeded smoothly at room temperature, but we were
surprised to find that the product was nitrile 10 (70% yield
from 5a, Scheme 2). Meanwhile, direct treatment of 5a
with sodium hydride never gave nitrile 10.11
TfOH (2.0 equiv), CH2Cl2, 10 min
then, t-BuOH, 2 h, evaporation
R2
R1
R1
N
N
N
N
N
N
then NaH (3.5 equiv), THF
C13H27
6
C13H27
5
Entry Substrate
Product
Yield (%)a
O
N
N
N
1
2
3
4
10
51
C13H27
5b
O
N
N
N
OTf
10
10
73
60
93
O
HO
TfOH
C13H27
(2.0 equiv)
i) NaN3, DMSO
O
N
N
Cl
+
NH
–OTf
5c
CH2Cl2
N
N
C13H27
ii)
N
7
CuSO4, i-Pr2NEt,
sodium ascorbate,
H2O
O
C13H27
C13H27
5a
8a
N
81%
Ph
N
N
C13H27
OTf
HO
HO
+
t-BuOH
(excess)
5d
–OTf
N
HOt-Bu
N+
NC
NaH, THF
r.t.
N
O
O
C13H27
10
70% from 5a
N
H
N
N
or
H2O
C13H27
N
N
C13H27
9a
87% (NMR yield)
N
N
N
N
8a'
C13H27
C13H27
Scheme 2 Synthesis of 5-hydroxy intermediate 9a and its conver-
sion into nitrile 10
5e
6e
O
O
Although the mechanistic details of the surprising reac-
tion is not clear, we investigated the substituent effect of
the epoxide side chain (Table 1). The direct sequential
treatment of the methyl-substituted analogue 5b with
TfOH, t-BuOH, and NaH also afforded the same nitrile 10
in 51% yield (Table 1, entry 1). The reaction of the corre-
sponding diastereomer 5c also gave 10 in 73% yield, indi-
cating that the stereochemistry at the side chain of the
triazole do not affect the nitrile formation reactions. The
phenyl substituent instead of a methyl group also afforded
N
N
N
N
N
N
5b
quant.
C4H9
C4H9
11f
5f
a Isolated yield.
b Treatment with only TfOH (2 equiv).
Synlett 2013, 24, 207–210
© Georg Thieme Verlag Stuttgart · New York

LETTER
Transformations of 1-(Oxiranylmethyl)-1,2,3-triazoles
209
O–
These results led us to examine a similar transformation
using several analogues of 5e (Table 2). The conversion of
1-(oxiranylmethyl)-1,2,3-triazole 5g possessing a phenyl
group at the C2 position also smoothly proceeded to give
2-(oxiranylmethyl)-1,2,3-triazole 6g in 97% yield (Table
2, entry 1). The 1-(oxiranylmethyl)-1,2,3-triazoles pos-
sessing a functional group such as methyl ether (5h), ben-
zyl ether (5i), and chloride (5j) also afforded the desired
products 6h, 6i, and 6j in 42%, 80%, and 57% yields, re-
spectively (Table 2, entries 2–4). It was therefore con-
firmed that the novel conversion method from 1-
(oxiranylmethyl)-1,2,3-triazoles to the corresponding 2-
(oxiranylmethyl)-1,2,3-triazoles is applicable to various
triazoles.
OH
O
O
K2CO3
Cl
Cl
Cl
Cl
Cl
Cl
+
MeOD
quant.
12
12'
13
(6:1)
14
Scheme 3 Epoxide-forming reaction of 12
In conclusion, novel transformation of 1-(oxiranylmeth-
yl)-1,2,3-triazoles 5 into alkanenitrile 10 or 2-oxiranyl-
methyl-1,2,3-triazoles 6 were discovered. The reaction
pathway leading to 6 or 10 depends on the substituent pat-
tern of the epoxide side chain. The present transformation
of 5 into 6 provides a new entry for the synthesis of 2-sub-
stituted 1,2,3-triazoles.13,14
Table 2 Synthesis of the Various 2-Oxiranylmethyl-1,2,3-triazoles 6
Acknowledgment
–O
O
O
This work was partially supported by the Global COE program
(Project No. B01: Catalysis as the Basis for Innovation in Material
Science), Grant-in-Aid for Scientific Research (Grant No.
24310162), and Grant-in-Aid for Scientific Research on Innovative
Areas (Project No. 2105: Organic Synthesis Based on Reaction In-
tegration and No. 2301: Chemical Biology of Natural Products)
from the Ministry of Education, Culture, Sports, Science, and Tech-
nology, Japan.
TfOH (2 equiv), CH2Cl2
then t-BuOH, evaporation
N
N+
N
N
N
N
N
N
N
then NaH, THF, time
R
R
R
5
9
6
Entry
R
NaH (equiv)
Time (h) Yield (%)a
1
2
3
4
5g Ph
6.5
3.5
5
9
97
42
80
57
References and Notes
5h CH2OMe
5i (CH2)3OBn
5j (CH2)3Cl
3.5
6
(1) (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem.
Int. Ed. 2001, 40, 2004. (b) Rostovtsev, V. V.; Green, L. G.;
Fokin, V. V.; Sharpless, K. B. Angew. Chem. Int. Ed. 2002,
41, 25969. (c) Tornøe, C. W.; Christensen, C.; Meldal, M.
J. Org. Chem. 2002, 67, 3057.
3.5
3
a Isolated yield.
(2) For reviews, see: (a) Fan, W. Q.; Katritzky, A. R. In
Comprehensive Heterocyclic Chemistry II; Vol. 4;
We were curious about the preferential formation of 2-
(oxiranylmethyl)-1,2,3-triazole 6 rather than reformation
of 1-(oxiranylmethyl)-1,2,3-triazole 5 from the alkoxide
intermediate generated from bicyclic triazolium ion 9.
The results indicate that the epoxide-forming reaction oc-
curred through attack of the alkoxide ion moiety on the
more sterically hindered carbon atom. With a view to ob-
taining information about general tendency for this type of
reaction, the epoxide-forming reaction of a simple sub-
strate was examined. Thus, 1,3-dihloro-3-methyl-2-buta-
nol (12) was treated with potassium carbonate in
deuterated methanol. The epoxide-forming reaction of 12
resulted in the formation of a 6:1 regioisomeric mixture in
favor of trisubstituted oxirane 13 (Scheme 3). This result
strongly suggested that the ring-closing reactions of alco-
hols possessing a β-leaving group tend to give multisub-
stituted epoxides despite the large steric hindrance at the
reaction site. To our knowledge, this is the first example
of the simple comparison of the reactivity between the ter-
tiary and primary chlorides in epoxide ring-closing reac-
tion.12
Katritzky, A. R.; Rees, C. W.; Scriven, C. W. V., Eds.;
Elsevier: Oxford, 1996, 1–126. (b) Hein, C. D.; Liu, X.-M.;
Wan, D. Pharm. Res. 2008, 25, 2216. (c) Struthers, H.;
Mindt, T. L.; Schibli, R. Dalton Trans. 2010, 39, 675.
(3) For recent reviews, see: (a) Ling, R.; Yoshida, M.; Mariano,
P. S. J. Org. Chem. 1996, 61, 4439. (b) Kvivopalov, V. P.;
Shkurko, O. P. Russ. Chem. Rev. 2005, 74, 339. (c) Bock, V.
D.; Hiemstra, H.; Maarseveen, J. H. Eur. J. Org. Chem.
2006, 1, 51. (d) Wu, P.; Fokin, V. V. Aldrichimica Acta
2007, 40, 7.
(4) For recent examples, see: (a) Kamijo, S.; Jin, T.; Huo, Z.;
Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 7786.
(b) Kamijo, S.; Jin, T.; Huo, Z.; Yamamoto, Y. J. Org.
Chem. 2004, 69, 2386. (c) Kalisiak, J.; Sharpless, B.; Fokin,
V. V. Org. Lett. 2008, 10, 3171. (d) Chen, Y.; Liu, Y.;
Petersen, J. L.; Shi, X. Chem. Commun. 2008, 3254. (e) Liu,
Y.; Yan, W.; Chen, Y.; Petersen, J. L.; Shi, X. Org. Lett.
2008, 10, 5389. (f) Wang, X.-J.; Zhang, L.; Lee, H.; Haddad,
N.; Krishnamurthy, D.; Senanayake, C. H. Org. Lett. 2009,
11, 5026. (g) Wang, X.-J.; Sidhu, K.; Zhang, L.; Campbell,
S.; Haddad, N.; Reeves, D. C.; Krishnamurthy, D.;
Senanayake, C. H. Org. Lett. 2009, 23, 5490. (h) Yamauchi,
M.; Miura, T.; Murakami, M. Heterocycles 2010, 80, 177.
(i) Wang, X.-J.; Zhang, L.; Krishnamurthy, D.; Senanayake,
C. H.; Wipf, P. Org. Lett. 2010, 12, 4632. (j) Ueda, S.; Su,
M.; Buchwald, S. L. Angew. Chem. Int. Ed. 2011, 50, 8944.
(k) Zhang, Y.; Li, X.; Li, J.; Chen, J.; Meng, X.; Zhao, M.;
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 207–210

210
A. Osawa et al.
LETTER
(13) Typical Procedure for the Transformation of 5a into
Chen, B. Org. Lett. 2012, 14, 26. (l) Guru, M. M.;
Punniyamurthy, T. J. Org. Chem. 2012, 77, 5063.
Nitrile 10
(5) Namba, K.; Osawa, A.; Ishizaka, S.; Kitamura, N.; Tanino,
K. J. Am. Chem. Soc. 2011, 133, 11466.
(6) Namba, K.; Mera, A.; Osawa, A.; Sakuda, E.; Kitamura, N.;
Tanino, K. Org. Lett. 2012, 14, 5554.
(7) One-pot click reaction of alkyl halide, see: Kacprzak, K.
Synlett 2005, 943.
(8) 4-Tridecyl triazole 5a was employed for the structural
analysis of the reactive intermediate cation 8a because
corresponding butyl or phenyl compounds are insoluble
amorphous materials in CDCl3.
(9) Other Brønsted and Lewis acids such as BF3·OEt2, Et2AlCl,
TiCl4, Hg(OTf)2, and TFA could not activate the epoxide.
However, TBSOTf and TMSOTf also gave the intermediate
8a due to in situ generated TfOH.
(10) We confirmed that the internal 1,2,3-triazole ring is
necessary for the ring-opening reaction of oxirane leading to
triflate alcohol 8. Treatment of oxirane 15 with TfOH (2.0
equiv) gave a complex mixture. Similar treatment in the
presence of triazole 16 (1 equiv) also afforded the complex
mixture (Scheme 4).
To a solution of 5a (43 mg, 0.14 mmol) in CH2Cl2 (0.7 mL)
was added TfOH (25 μL, 0.28 mmol) at 0 °C. After the
mixture was stirred at r.t. for 30 min, t-BuOH (1 mL) was
added. The mixture was stirred for 3 h and concentrated
under reduced pressure to give crude 9a. To a suspension of
NaH (21 mg, 0.49 mmol) in THF (0.5 mL) was added a
solution of crude 9a in THF (2.3 mL) through a cannula at 0
°C. The mixture was stirred for 3.5 h, and the reaction was
quenched with sat. aq NH4Cl solution. The mixture was
extracted with EtOAc (3×). The combined organic layers
were washed with brine, dried over MgSO4, filtered, and
concentrated under reduced pressure. The residue was
purified by flash silica gel column chromatography
(hexane–EtOAc, 4:1) to give nitrile 10 (22 mg, 70%) as a
colorless oil.
Compound 9a: 1H NMR (500 MHz, CDCl3): δ = 8.13 (s, 1
H), 5.47 (br, 1 H), 4.92 (dd, J = 14.0, 4.9 Hz, 1 H), 4.86 (dd,
J = 13.2, 5.2 Hz, 1 H), 4.72 (d, J = 13.7 Hz, 1 H), 4.64 (d, J
= 13.2 Hz, 1 H), 2.76 (t, J = 8.0 Hz, 2 H), 1.70–1.64 (m, 2
H), 1.36–1.26 (m, 20 H), 0.87 (t, J = 6.9 Hz, 3 H)..
(14) The transformation of 1-(oxiranylmethyl)-1,2,3-triazoles 5
into 2-(oxiranylmethyl)-1,2,3-triazoles 6 is conducted in the
same manner as the above-mentioned typical procedure.
Compound 6e: white amorphous solid. 1H NMR (500 MHz,
CDCl3): δ = 7.38 (s, 1 H), 4.55 (dd, J = 14.4, 6.3 Hz, 1 H),
4.48 (dd, J = 14.3, 6.3 Hz, 1 H), 3.23 (t, J = 6.0 Hz, 1 H), 2.66
(t, J = 7.7 Hz, 2 H), 1.68–1.62 (m, 2 H), 1.43 (s, 3 H), 1.36
TfOH
N
O
(2.0 equiv)
N
N
complex mixture
+
C12H25
CH2Cl2
(0.2 M)
C4H9
15
16
(s, 3 H), 1.34–1.26 (m, 20 H), 0.88 (t, J = 6.9 Hz, 4 H). 13
NMR (125.8 MHz, CDCl3): δ = 149.20, 133.00, 60.86,
58.65, 53.92, 31.88, 29.64, 29.62, 29.61, 29.59, 29.51,
29.32, 29.23, 29.21, 25.44, 24.37, 22.65, 18.86, 14.08.
C
Scheme 4
HRMS (EI): m/z calcd for: 335.2936 [M+]; found: 335.2946.
Compound 6g: 1H NMR (500 MHz, CDCl3): δ = 7.86 (s, 1
H), 7.77 (d, J = 6.9 Hz, 2 H), 7.41 (t, J = 7.4 Hz, 2 H), 7.34
(t, J = 7.4 Hz, 1 H), 4.64 (dd, J = 14.3, 5.7 Hz, 1 H), 4.54 (dd,
J = 14.3, 5.7 Hz, 1 H), 3.29 (t, J = 5.7 Hz, 1 H), 1.46 (s, 3 H),
1.36 (s, 3 H).
(11) Treatment of 5a with sodium hydride induced the ring-
opening reaction of epoxide to give the corresponding
enamino alcohol 17 in 23% yield (Scheme 5), along with
recovery of starting material 5a (70%).
N
Compound 6h: 1H NMR (500 MHz, CDCl3): δ = 7.54 (s, 1
H), 4.51 (dd, J = 13.8, 5.8 Hz, 1 H), 4.48 (s, 2 H), 4.47 (dd,
J = 14.3, 5.7 Hz, 1 H), 3.34 (s, 3 H), 3.18 (t, J = 5.7 Hz, 1 H),
1.37 (s, 3 H), 1.29 (s, 3 H), 1.36 (s, 3 H).
N
N
HO
NaH, THF
23%
5a
C13H27
17
E/Z = 2:1
Compound 6i: 1H NMR (500 MHz, CDCl3): δ = 7.37 (s, 1
H), 7.34–7.27 (m, 5 H), 4.53 (dd, J = 14.3, 5.8 Hz, 1 H), 4.52
(s, 2 H), 4.48 (dd, J = 14.3, 5.8 Hz, 1 H), 3.53 (t, J = 6.3 Hz,
2 H), 3.22 (t, J = 5.8 Hz, 1 H), 2.79 (t, J = 5.7 Hz, 2 H), 1.98
(quin, J = 6.3 Hz, 2 H), 1.43 (s, 3 H), 1.36 (s, 3 H).
Compound 6j: 1H NMR (500 MHz, CDCl3): δ = 7.36 (s, 1
H), 4.47 (dd, J = 14.3, 5.8 Hz, 1 H), 4.44 (dd, J = 14.3, 5.7
Hz, 1 H), 3.52 (t, J = 6.3 Hz, 2 H), 3.16 (t, J = 5.7 Hz, 1 H),
2.79 (t, J = 6.9 Hz, 2 H), 2.08 (quin, J = 6.3 Hz, 2 H), 1.36
(s, 3 H), 1.30 (s, 3 H).
Scheme 5
(12) (a) The comparison of halogen atoms in the epoxide ring-
closing reaction of 2,2,6,6-tetrahalogenocyclohexanols, see:
Duhamel, P.; Leblond, B.; Bidois-Séry, L.; Poirier, J.-M.
J. Chem. Soc., Perkin Trans. 1 1994, 16, 2265. (b) Epoxide-
formingreactionof 2-chloro-1-(1-chlorocyclopropyl)ethanol,
see: Sudo, K.; Shimokawara, T.; Imai, E.; Kusano, N.;
Kanno, H.; Miyake, T.; Mori, M.; Saishoji, T. WO
2011070742, 2011.
Synlett 2013, 24, 207–210
© Georg Thieme Verlag Stuttgart · New York