Sequential- and tandem-oxidation-epoxidation reactions employing guanidine bases

Article abstract of DOI:10.1016/j.tet.2013.05.036

1,5,7-Triazabicyclo[4.4.0]dec-1-ene (TBD) and 7-methyl-1,5,7- triazabicyclo[4.4.0]dec-1-ene (MTBD) promote the efficient formation of sulfonium ylides from sulfonium salts in the Corey-Chaykovsky epoxidation of aldehydes and provide excellent yields of the corresponding epoxides. This reaction protocol can be further adapted to allow for the development of both sequential and tandem-oxidation-epoxidation protocols from aldehydes generated in situ by manganese dioxide (MnO₂) or barium manganate (BaMnO ₄) mediated oxidation reactions.

Full text of DOI:10.1016/j.tet.2013.05.036

Tetrahedron 69 (2013) 6196e6202
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Sequential- and tandem-oxidationeepoxidation reactions
employing guanidine bases
*
David J. Phillips, Joseline L. Kean, Andrew E. Graham
Department of Science and Sport, University of Glamorgan, Pontypridd CF37 4AT, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
1,5,7-Triazabicyclo[4.4.0]dec-1-ene (TBD) and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-1-ene (MTBD)
promote the efficient formation of sulfonium ylides from sulfonium salts in the CoreyeChaykovsky
epoxidation of aldehydes and provide excellent yields of the corresponding epoxides. This reaction
protocol can be further adapted to allow for the development of both sequential and tandem-oxida-
tioneepoxidation protocols from aldehydes generated in situ by manganese dioxide (MnO2) or barium
manganate (BaMnO4) mediated oxidation reactions.
Received 20 February 2013
Received in revised form 30 April 2013
Accepted 13 May 2013
Available online 18 May 2013
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
in Michael additions.10 We required an efficient method for the
generation of sulfonium ylides for the synthesis of structurally
Epoxides are highly versatile reagents, which undergo a range of
synthetic transformations, including stereospecific nucleophilic
ring-opening to yield bifunctional compounds, and rearrangement
reactions to give cyclised products or carbonyl compounds.1
Amongst the most effective and widely used non-oxidative route
to epoxides developed to date has been by the reaction of sulfo-
nium ylides generated in the presence of carbonyl compounds, the
so-called CoreyeChaykovsky epoxidation.2 Since its initial disclo-
sure, this area has developed into a vibrant research field, with
subsequent work leading to the development of effective protocols
for the asymmetric synthesis of epoxides.3 While there have been
some elegant strategies for the generation of the required sulfo-
nium ylides,4 typical protocols rely on the use of basic reagents to
generate the sulfonium ylide by deprotonation of a sulfonium salt.
In general, this has meant employing bases, which are either air-
and moisture-sensitive or inorganic in nature and, which require
biphasic or aqueous conditions. It is surprising therefore that the
use of moisture tolerant, non-ionic organic bases has received rel-
atively little attention given their successful application in related
synthetic transformations.5 Previous work has demonstrated that
reagents, such as 1,8-diazabicyclo[5.4.1]undec-7-ene (DBU), 1,5,7-
triazabicyclo[4.4.0]dec-1-ene (TBD), 7-methyl-1,5,7-triazabicyclo
[4.4.0]dec-1-ene (MTBD) and tetramethyl guanidine are highly ef-
fective reagents for the generation of anions from a range of acti-
vated substrates,6 including phosphonium salts and phosphonates
in olefination reactions,7 sulfoxonium salts in cyclopropanation
reactions,8 nitroalkanes in Henry reactions9 and dialkyl phosphites
diverse epoxides, and were attracted to the potential of extending
the range of these organic bases to encompass sulfonium ylide-
mediated epoxidation procedures. Herein we report the success-
ful application of TBD and MTBD for the generation of sulfonium
ylides in CoreyeChaykovsky epoxidation procedures, and the
extension of this methodology to the development of sequential
and tandem oxidationeepoxidation procedures.
2. Results and discussion
We initially assessed the ability of a range of organic bases to
generate sulfonium ylides from sulfonium salt 1a in the presence of
benzaldehyde 2, and were gratified to observe that both TBD and
MTBD were highly effective promoters of the epoxidation reaction,
providing high conversions to the epoxide product (Table 1, entries
3 and 4). These conversions could be improved to near quantitative
by employing a two-fold excess of the base and sulfonium salt to
provide stilbene oxide 3 as the only observable product in im-
pressively short reaction times. Analysis of these crude reaction
mixtures indicated that the epoxide was formed with high to ex-
cellent selectivity for the expected trans isomer.
The scope and generality of this protocol was next investigated
using sulfonium salts 1a and 1b with a range of structurally diverse
aldehydes. The reaction of the unsubstituted sulfonium salt 1a with
para-nitrobenzaldehyde led to an excellent yield of the epoxide
with high selectivity for the trans product (Table 2, entry 2).
Interestingly, when the substituted sulfonium salt 1b is employed
in the corresponding reaction with benzaldehyde (entry 3), the
epoxide is again produced in excellent isolated yield but with
enhanced selectivity for the trans isomer. Most gratifying and
* Corresponding author. E-mailaddress:AEGraham@Glamorgan.ac.uk(A.E. Graham).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.036

D.J. Phillips et al. / Tetrahedron 69 (2013) 6196e6202
6197
Table 1
Optimisation of epoxidation protocol
Base (2.2 equiv)
O
O
S
+
Br
CH2Cl2, rt
1a
2
3
Entrya
Time
Base
Conversion (%)b
trans:cisb
1
2
3
4
24 h
24 h
10 min
10 min
Et3N
DBU
TBD
0
71
100
100
d
95:5
92:8
94:6
MTBD
a
Procedure: benzaldehyde (1 equiv), S-benzyltetrahydrothiophenium bromide 1a (2 equiv) and TBD (2.2 equiv) in dichloromethane (10 mL) at room temperature.
b
Determined by 1H NMR analysis of the crude reaction mixture.
Table 2
TBD-mediated CoreyeChaykovsky epoxidation
O
R2
O
TBD (2.2 equiv)
CH2Cl2, rt
S
R2
H
+
Br
R1
R1
1a R1 = H
1b R1 = NO2
Entry
1
Aldehydea
Salt
Product
Yield (%)b
88
trans:cisc
O
Ph
3
1a
92:8
2
Ph
O
Ph
O
Ph
Ph
4
O
2
3
1a
93
91
91:9
5
O2N
O2N
O2N
O
1b
>98:2
5
2
Ph
O
O
7
4
5
1a
1b
84
84
54:46
6
6
Ph
Ph
O
O
Ph
NO2
>98:2
O
Ph
8
Ph
O
EtO2C
6
1b
80
93:7
O
EtO2C
9
NO2
NO2
10
O
EtO2C
O
7
8
9
1b
1a
1b
1a
36
100c
38
95:5
EtO2C
11
12
O
14
>98:2
>98:2
95:5
13
Ph
Ph
O
Ph
NO2
15
13
O
Ph
O
Ph
O
Ph
O
16
10
68
17
O
O
a
Procedure: aldehyde (1 equiv), S-benzyltetrahydrothiophenium bromide 1a (2 equiv) and TBD (2.2 equiv) in dichloromethane (10 mL) at room temperature.
All compounds gave satisfactory spectroscopic data.
b
c
Determined by 1H NMR analysis of the crude reaction mixture.

6198
D.J. Phillips et al. / Tetrahedron 69 (2013) 6196e6202
unexpected was the observation that this protocol is compatible
with enolisable aldehydes. The range of carbonyl substrates
employed in ylide-mediated epoxidation reactions has traditionally
been limited to non-enolisable aldehydes, since the basic condi-
tions required for ylide generation precludes the use of aldehydes,
which are prone to enolisation and subsequent aldol condensation
or elimination reactions.3,11 We were therefore delighted to observe
that high isolated yields of the corresponding epoxides were pro-
duced from 3-phenylpropionaldehyde 6 in reactions employing
sulfonium salts 1a or 1b (entries 4 and 5).
These examples further highlight the importance of electronic
factors in ylide-mediated epoxidation reactions, as reduced cis:-
trans selectivity is observed for the reaction employing sulfonium
salt 1a. In contrast, reactions employing the ylide generated from
sulfonium salt 1b, provide the epoxide with excellent selectivity for
the trans product. The enhanced cis:trans selectivity in this case,
and also the reactions of benzaldehyde with 1a and 1b, reflects the
increased stability of the sulfonium ylide derived from 1b leading to
formation of the anti-betaine.3d
carried out to completion before the addition of the sulfonium salt
and base. Due to the limited range of substrates oxidised by MnO2,
we initial chose to study the reactions of a series of activated al-
cohols to give the corresponding stilbene oxide products. Thus,
benzyl alcohol 18 was subjected to an initial MnO2-mediated oxi-
dation step performed using an excess of activated MnO2 in chlo-
roform at reflux. On completion of the oxidation step, the reaction
mixture was cooled to room temperature and an excess of sulfo-
nium salt 1a and TBD were added. Gratifyingly, this strategy pro-
vided excellent conversions of the alcohol to give stilbene oxide in
good isolated yield with high selectivity for the expected trans
product (Table 3, entry 1). The generality of this process was
demonstrated using a range of substituted benzyl alcohols, which
gave the corresponding stilbene oxides in high overall yields and
with good to excellent selectivity for the trans product (entries
2e8). The methodology is tolerant of a variety of substituents,
giving high yields of mono- and di-substituted symmetrical and
unsymmetrical stilbene oxides even in the case of para-methox-
ybenzaldehyde (entry 7).16 In line with our previous observations,
the stereochemical outcome of this epoxidation protocol mirrors
that of reactions employing aldehydes, giving the trans isomer with
high selectivity from sulfonium salt 1a (entries 1, 3 and 4), and
enhanced selectivity from sulfonium salt 1b (entries 2, 5e8).
Finally, we investigated the development of a tandem oxida-
tioneepoxidation reaction variant, in which the oxidation step and
the deprotonation of the sulfonium salt occur in the presence of
an excess of MnO2 and TBD. Our initial reactions employed
4-nitrobenzyl alcohol in the presence of an excess of sulfonium salt
1a, TBD and 20 equiv of MnO2, and were performed in chloroform at
room temperature. These reactions, however, proceeded slowly and
required extended reaction times, typically 24 h, to achieve sig-
nificant conversion to the stilbene oxide products. Reaction times
could be considerably reduced by carrying out the reaction at reflux
temperatures and, under these conditions, high isolated yields of
the epoxide were achieved with cis/trans selectivities similar to
those observed previously (Scheme 2). Reactions employing benzyl
alcohol with sulfonium salt 1a, however, gave only moderate con-
versions to stilbene oxide 3 under a variety of reaction conditions.
Further analysis of these crude reaction mixtures revealed that,
in addition to the expected stilbene oxide and small quantities of
benzaldehyde, an additional product identified as sulfide 28 was
We next considered the reaction of the a,b-unsaturated esters 9
and 11, which also contain enolisable aldehydes, and, which un-
dergo reaction to give the corresponding epoxides. In the case of 9
(entry 6), in which a substituted alkene is present, the reaction
proceeds to give the epoxide 10 as the only observable product in
good yield with high selectivity for the trans product.3d In the case
of aldehyde 11 (entry 7), the isolated yield of epoxide 12 is low,
which may be due either to a competing cyclopropanation reaction
or to decomposition of the product during purification.4b,12 Simi-
larly, reaction of cinnamaldehyde 13 (entries 8 and 9) with sulfo-
nium salts 1a or 1b led to complete conversion of the aldehyde to
give the corresponding epoxide but with poor isolated yields. It has
been noted that these materials are particularly acid sensitive and
therefore no further purification of these crude reaction mixtures
was attempted.4b Disappointingly, and in line with previous stud-
ies,4b,5a the reaction of ketone substrates, such as acetophenone
and cyclohexanone, gave only trace quantities of epoxide products.
With conditions for the efficient generation of sulfonium ylides
in place, we next explored the feasibility of employing alcohols
as substrates and incorporating a manganese dioxide (MnO2)
mediated oxidation step into the reaction sequence to produce
the corresponding aldehydes in situ (Scheme 1). Such one-pot
O
MnO2 (10 equiv)
Base
S
OH
+
Br
1a
18
3
Scheme 1.
preparative procedures, in which multiple reactions are combined
into a single synthetic operation, offer significant potential ad-
vantages over traditional methodology in terms of efficiency and
operational simplicity.13 A further benefit of this strategy is that
unstable products need not be isolated, as they are rapidly trans-
formed by a subsequent reaction into more stable products. Tan-
dem oxidation protocols employing MnO2 are well documented in
a range of chemical transformations, and take advantage of the
mild, heterogeneous nature of this oxidant.14 It has already been
demonstrated that organic bases efficiently generate both phos-
phonium and sulfoxonium ylides from the corresponding salts in
the presence of MnO2,8,15 suggesting that the corresponding
deprotonation of sulfonium salts should be an achievable goal, and
might provide a highly efficient and general protocol for the gen-
eration of epoxides.
also present. This product is generated as a result of the ylide de-
rived from 1a undergoing a competing SommeleteHauser rear-
rangement reaction, and indeed, treatment of salt 1a with a small
excess of TBD led to the rapid and complete formation of 28
(Scheme 3).
The production of such rearrangement products in sulfonium
ylide-mediated reactions is well documented,17 and probably
reflects the relatively slow rate of oxidation of benzyl alcohol to
benzaldehyde by MnO2. In the absence of significant quantities of
the aldehyde, the competing rearrangement reaction leads to
complete consumption of the ylide, and hence conversions to the
epoxide are severely limited. To overcome this limitation, we rea-
soned that a more powerful oxidant would be required, which
would ensure that significant quantities of benzaldehyde were
produced more rapidly, so ensuring the epoxidation reaction is the
predominant pathway. With this in mind, we turned our attention
to the use of barium manganate (BaMnO4), a more powerful
Our initial goal considered the development of a sequential
oxidationeepoxidation process in which the oxidation step is

D.J. Phillips et al. / Tetrahedron 69 (2013) 6196e6202
6199
Table 3
Sequential oxidationeepoxidation reactions of alcohols
R1
R1
O
R2
S
(i) MnO2 (10 equiv), CHCl3,
(ii) TBD (2.2 equiv), rt
Δ
R2
OH
+
Br
1a R1 = H
1b R1 = NO2
Entry
1
Alcohola
Salt
Product
Yield (%)b
trans:cisc
O
Ph
3
1a
1b
68
70
92:8
18
18
Ph
Ph
OH
OH
Ph
O
Ph
2
>98:2
5
O2N
O
Ph
19
OH
3
4
5
1a
1a
1b
71
79
85
95:5
5
O2N
O2N
O
20
21
Ph
OH
91:9
NO2
20
O
OH
22
>98:2
NO2
O
19
OH
23
6
7
1b
81
>98:2
O2N
O2N
NO2
25
24
O
OH
OH
1b
1b
62
84
>98:2
>98:2
MeO
MeO
MeO
NO2
O
26
27
8
MeO
a
Procedure: alcohol (1 equiv), S-benzyltetrahydrothiophenium bromide 1a (2 equiv), BaMnO2 (4 equiv) and TBD (2.2 equiv) in acetonitrile (10 mL) at 60 ꢀC.
All compounds gave satisfactory spectroscopic data.
b
c
Determined by 1H NMR analysis of the crude reaction mixture.
R1
O
S
OH
MnO2 (20 equiv), CHCl3, Δ
+
Br
R1
TBD (2.2 equiv)
1
1a
19
5 R1 = NO2 = 77%
R1 = NO2
R = H
18
3 R1 = H
= 43%
Scheme 2.
Base
Sommelet-Hauser
S
S
S
81%
Br
1a
28
Scheme 3.

6200
D.J. Phillips et al. / Tetrahedron 69 (2013) 6196e6202
oxidant than activated MnO2,18 and, which has previously been
successfully employed in a number of tandem oxidation pro-
tocols.19 Our initial studies investigated the reaction of benzyl al-
cohol with salt 1 employing a two-fold excess of BaMnO4 in
chloroform at reflux, which resulted in moderate conversions to
stilbene oxide. On changing the solvent to acetonitrile, and carrying
out the reaction with a four-fold excess of BaMnO4, we were grat-
ified to observe that high yields of epoxide were achieved within
1 h (Table 4, entry 1). Analysis of these crude reaction mixtures
indicated that the SommeleteHauser rearrangement was almost
unsymmetrical epoxides. The presence of this material suggests
that some of the sulfonium salt 1b is undergoing hydrolysis to
generate quantities of 4-nitrobenzyl alcohol or 4-nitrobenzyl bro-
mide, which are subsequently oxidised to 4-nitrobenzaldehyde by
BaMnO4, which subsequently reacts with the ylide derived from 1b
to generate the symmetrical epoxide. In the case of 4-methylbenzyl
alcohol 20, where the oxidation of the alcohol is slow, a significant
quantity of bis-2,3-(4-nitrophenyl) oxirane 23 is produced, and
hence a significant quantity of ylide is consumed limiting yields of
the desired unsymmetrical product.
Table 4
Tandem oxidationeepoxidation reactions of alcohols
R2
BaMnO2 (4 equiv) CH3CN, 60 oC
TBD (2.2 equiv), 1 or 2 (2 equiv)
O
OH
R1
R1
R2 = H or NO2
R1 = H, NO2 or Me
Entry
1
Alcohola
Salt
Time (h)
1
Product
Yield (%)b
78
trans:cisc
>98:2
O
3
1a
1b
18
Ph
Ph
Ph
OH
Ph
O
Ph
Ph
2
3
0.5
0.5
71d
>98:2
>98:2
5
18
OH
O2N
O2N
O
19
OH
1a
1b
83
5
O2N
O2N
NO2
O
19
OH
23
4
5
0.5
85
>98:2
O2N
O
20
21
Ph
OH
1a
1b
1
1
81
>98:2
>98:2
NO2
20
O
OH
55e
22
6
a
Procedure: alcohol (1 equiv), S-benzyltetrahydrothiophenium bromide 1a (2 equiv), BaMnO2 (4 equiv) and TBD (2.2 equiv) in acetonitrile (10 mL) at 60 ꢀC.
All compounds gave satisfactory spectroscopic data.
b
c
Determined by 1H NMR analysis of the crude reaction mixture.
d
e
Crude reaction contains w20% trans 2,3-bis-(4-nitrophenyl) oxirane 23.
Crude reaction contains w40% trans 2,3-bis-(4-nitrophenyl) oxirane 23.
completely suppressed in this solvent, leading to reduced con-
3. Conclusions
sumption of the ylide derived from 1a. Furthermore, it was ob-
served that cis/trans ratios of the resulting epoxides were also
enhanced. With effective conditions for the tandem-oxidation
protocol established, we next turned our attention to tandem oxi-
dationeepoxidation reactions employing 4-nitrobenzyl alcohol.
The oxidation step in these reactions proceeded more rapidly than
with benzyl alcohol, and in these cases, shorter reaction times can
be employed (entries 3 and 4).
We have developed a highly efficient procedure for the pro-
duction of epoxides from aldehydes and sulfonium ylides in the
presence of guanidine bases, such TBD and MTBD. These epoxides
are rapidly produced in high yields with excellent selectivity for the
trans product. In contrast to previously reported methodology, this
protocol is applicable to both non-enolisable and enolisable alde-
hydes and a,b-unsaturated aldehydes, considerably extending the
Interestingly, reactions employing sulfonium salt 1b (entries 2
and 6) also produced quantities of the symmetrical bis-2,3-(4-
nitrophenyl) oxirane product 23 in addition to the expected
scope of this synthetic approach. This methodology has been fur-
ther extended to encompass both sequential- and tandem-oxida-
tioneepoxidation protocols, which exploit the ability to generate

D.J. Phillips et al. / Tetrahedron 69 (2013) 6196e6202
6201
sulfonium ylides in situ from sulfonium salts and a strong guani-
dine base, such as TBD and MTBD, in the presence of an oxidising
agent. In the case of the sequential oxidationeepoxidation protocol,
high yields of epoxides are produced employing MnO2 as the oxi-
dant. However, due to rapid consumption of the sulfonium ylide by
(2.2 equiv, 376 mg, 2.70 mmol) and activated MnO2 (20 equiv,
2.12 g, 24.65 mmol) in chloroform (10 mL) was stirred for 6 h at
reflux. At this time, the reaction mixture was cooled to room
temperature and the MnO2 removed by filtration through a Celite
pad, which was washed with additional chloroform (2ꢁ20 mL). The
combined organic fractions were washed with water (2ꢁ20 mL)
and the aqueous layer extracted with dichloromethane (3ꢁ20 mL).
The organic fractions were combined, dried over magnesium sul-
fate and the solvent removed to give an orange oil, which was
purified by column chromatography (2% ethyl acetate:hexane) to
give the product as a pale yellow solid (228 mg, 77%; trans:cis 98:2);
a
competing SommeleteHauser reaction, the more powerful
BaMnO4 is the preferred oxidant in tandem oxidationeepoxidation
protocols. We are currently seeking to exploit the wider substrate
range displayed by BaMnO4 to consider the reactions of alkyl al-
cohols, which produce enolisable aldehydes, in both sequential-
and tandem-protocols.
1H NMR (400 MHz; CDCl3)
d
¼3.85 (1H, d, J¼2.0 Hz), 4.00 (1H, d,
4. Experimental
J¼2.0 Hz), 7.35e7.45 (5H, m), 7.55 (2H, d, J¼9.0 Hz), 8.25 (2H, d,
J¼9.0 Hz); 13C NMR (100 MHz; CDCl3)
¼147.9, 144.4, 136.1, 128.9,
d
4.1. Typical experimental procedure for the preparation of
epoxides from aldehydes
128.4, 126.3, 125.6, 123.9, 63.4, 61.7; MS (ES, NH3) m/z 259
(MþNH4)þ; HRMS (ES, NH3) calculated for C14H15N2O3 (MþNH4)þ
259.1077, found 259.1082; nmax/cmꢂ1 (neat) 1600, 1513, 1340,
1106, 838.
4.1.1. 2,3-Diphenyl oxirane.4b A mixture of benzaldehyde (76 mg,
0.72 mmol), S-benzyltetrahydrothiophenium bromide 1a (2 equiv,
370 mg, 1.44 mmol) and TBD (2.2 equiv, 220 mg, 1.58 mmol) in
dichloromethane (10 mL) was stirred for 10 min at room temper-
ature. At this time, the reaction mixture was washed with water
(2ꢁ20 mL) and the aqueous layer extracted with dichloromethane
(3ꢁ20 mL). The organic layers were combined, dried over magne-
sium sulfate and the solvent removed to give a colourless oil, which
was purified by column chromatography (2% ethyl acetate:hexane)
to give the product as a white solid (124 mg, 88%; trans:cis 92:8); 1H
4.4. Typical procedure for the preparation of epoxides by
a tandem oxidationeCoreyeChaykovsky epoxidation em-
ploying barium manganate
4.4.1. 2-(4-Nitrophenyl)-3-phenyl oxirane 5.4b A mixture of benzyl
alcohol (36 mg, 0.33 mmol), S-(4-nitrobenzyl)-tetrahy-
drothiophenium bromide 1b (2 equiv, 201 mg, 0.66 mmol), TBD
(2.2 equiv, 101 mg, 0.73 mmol) and BaMnO4 (4 equiv, 90%, 372 mg,
1.32 mmol) in acetonitrile (10 mL) was stirred for 30 min at 60 ꢀC.
At this time, the reaction mixture was cooled to room temperature
and the BaMnO4 removed by filtration through a Celite pad, which
was washed with additional acetonitrile (2ꢁ5 mL). The combined
solvents were removed to give an orange oil, which was purified by
column chromatography (hexane/2% ethyl acetate:hexane) to
give the product as a pale yellow solid (57 mg, 71%; trans:cis 98:2)
with data identical to that above.
NMR (400 MHz; CDCl3)
NMR (100 MHz; CDCl3)
d
¼3.95 (2H, s), 7.40e7.55 (10H, m); 13C
d¼137.1, 128.5, 128.2, 125.5, 62.7; MS (ES,
NH3) m/z 214 (MþNH4)þ; HRMS (ES, NH3) calculated for C14H16NO
(MþNH4)þ 214.1226, found (MþNH4)þ 214.1229; nmax/cmꢂ1 (neat)
1493, 1453, 846, 747, 696.
4.2. Typical procedure for the preparation of epoxides by
a sequential oxidationeCoreyeChaykovsky epoxidation
4.2.1. 2-(4-Nitrophenyl)-3-(4-methylphenyl) oxirane 22. A mixture
of 4-methylbenzyl alcohol (40 mg, 0.33 mmol) and activated MnO2
(10 equiv, 290 mg, 3.30 mmol) in chloroform (10 mL) was stirred
for 2 h at reflux. At this time, the reaction was cooled to room
temperature and TBD (2.2 equiv, 100 mg, 0.73 mmol) and
S-(4-nitrobenzyl)-tetrahydrothiophenium bromide 1b (2 equiv,
200 mg, 0.66 mmol) were added. After stirring for a further 20 min,
the MnO2 was removed by filtration through a Celite pad, which
was then washed with additional chloroform (2ꢁ10 mL). The re-
action mixture was then washed with water (2ꢁ20 mL), the
aqueous layer was then extracted with dichloromethane
(3ꢁ20 mL). The organic layers were combined and dried over
magnesium sulfate. The solvent was then removed to give a yellow
solid, which was purified by column chromatography (2% ethyl
acetate:hexane) to give the product as a pale yellow solid (71 mg,
4.5. Typical procedure for the TBD promoted Somme-
leteHauser rearrangement
4.5.1. 2-(2-Methylphenyl)tetrahydrothiophene 28.17 TBD (53 mg,
0.38 mmol) was added to
a solution of S-benzyltetrahy-
drothiophenium bromide 1a (50 mg, 0.19 mmol) in chloroform
(10 mL) and the reaction stirred at room temperature for 1 h. At this
time, the solvent was removed and the residue purified by column
chromatography (hexane) to give the product as a clear oil (28 mg,
81%); 1H NMR (400 MHz; CDCl3)
d
¼1.85e2.0 (2H, m), 2.15e2.30
(2H, m), 2.35 (1H, s), 2.90e3.00 (1H), 3.05e3.15 (1H, m), 4.65 (1 H,
dd, J¼8.0 and 6.0), 7.05e7.25 (3H, m), 7.60 (1H, d, J¼7.0); 13C NMR
(100 MHz; CDCl3)
d
¼19.7, 30.8, 33.2, 38.6, 48.6, 126.3, 126.7, 126.8,
130.2, 135.8, 140.8; MS (EI) m/z 178 (M)þ; nmax/cmꢂ1 (neat) 2859,
85%; trans:cis 98:2); 1H NMR (400 MHz; CDCl3)
d
¼2.40 (3H, s), 3.85
1603, 1460, 755.
(1H, d, J¼2.0 Hz), 3.95 (1H, d, J¼2.0 Hz), 7.20e7.30 (4H, m), 7.55 (2H,
d, J¼9.0 Hz), 8.25 (2H, d, J¼9.0 Hz); 13C NMR (100 MHz; CDCl3)
Acknowledgements
d
¼147.8, 144.6, 138.8, 133.1, 129.4, 126.2, 125.4, 123.9, 63.4, 61.6,
21.1; MS (EI, perfluorotributylamine) m/z 255 (M)þ, HRMS (EI,
perfluorotributylamine) calculated for C15H13NO3 (M)þ 255.0890,
found 255.0893; nmax/cmꢂ1 (neat) 1602, 1515, 1347, 1108, 845.
The authors thank the Engineering and Physical Sciences
Research Council (EPSRC) for financial support and the EPSRC Na-
tional Mass Spectrometry Service, Swansea University. The authors
also thank Dr. R. Jenkins (School of Chemistry, Cardiff University)
for his help in obtaining high resolution NMR data.
4.3. Typical procedure for the preparation of epoxides by
a tandem oxidationeCoreyeChaykovsky epoxidation em-
ploying manganese dioxide
Supplementary data
4.3.1. 2-(4-Nitrophenyl)-3-phenyl oxirane 5.4b
A
mixture of
4-nitrobenzyl alcohol (189 mg, 1.23 mmol), S-benzyltetrahy-
drothiophenium bromide 1a (2 equiv, 637 mg, 2.46 mmol), TBD
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.05.036.

6202
D.J. Phillips et al. / Tetrahedron 69 (2013) 6196e6202
8. Paxton, R. J.; Taylor, R. J. K. Synlett 2007, 633e637.
References and notes
9. Simoni, D.; Rondanin, R.; Morini, M.; Baruchello, R.; Invidiata, F. P. Tetrahedron
Lett. 2000, 41, 1607e1610.
10. Simoni, D.; Invidiata, F. P.; Manferdini, M.; Lampronti, I.; Rondanin, R.; Roberti,
M.; Pollini, G. P. Tetrahedron Lett. 1998, 39, 7615e7618.
1. (a) Pattenden, G. In Comprehensive Organic Synthesis; Pergamon: Oxford, UK,
1991; Vol. 3, pp 733e775; (b) Pastor, I. M.; Yus, M. Curr. Org. Chem. 2005, 9,
1e29; (c) Robinson, M. W. C.; Davies, A. M.; Mabbett, I.; Davies, T. E.; Apperley,
D. C.; Taylor, S. H.; Graham, A. E. J. Mol. Catal. A 2010, 329, 57e63; (d) Robinson,
M. W. C.; Davies, A. M.; Mabbett, I.; Apperley, D. C.; Taylor, S. H.; Graham, A. E. J.
Mol. Catal. A 2009, 314, 10e14; (e) Smith, B. M.; Skellam, E. J.; Oxley, S. J.;
Graham, A. E. Org. Biomol. Chem. 2007, 5, 1979e1982; (f) Robinson, M. W. C.;
Pillinger, K. S.; Mabbett, I.; Timms, D. A.; Graham, A. E. Tetrahedron 2010, 66,
8377e8382; (g) Robinson, M. W. C.; Davies, A. M.; Mabbett, I.; Taylor, S. H.;
Graham, A. E. Org. Biomol. Chem. 2009, 7, 2559e2564.
11. (a) Julienne, K.; Metzner, P.; Henryon, V. J. Chem. Soc., Perkin Trans. 1 1999,
731e735; (b) Kotoku, N.; Narumi, F.; Kato, T.; Yamaguchi, M.; Kobayashi, K.
Tetrahedron Lett. 2007, 48, 7147e7150.
ꢀ
ꢀ
12. Solladie-Cavallo, A.; Bouerat, L.; Roje, M. Tetrahedron Lett. 2000, 41, 7309e7312.
13. (a) Trost, B. M. Science 1991, 254, 1471e1477; (b) Trost, B. M. Angew.Chem., Int.
Ed. 1995, 34, 259e281; (c) Wasilke, J.-C.; Obrey, S. J.; Baker, R. T.; Bazan, G. C.
Chem. Rev. 2007, 105, 1001e1020; (d) Posner, G. H. Chem. Rev. 1986, 86,
831e844; (e) Ho, T.-L. In Tandem Organic Reactions; Wiley-Interscience: New
York, NY, 1992; (f) Hall, N. Science 1994, 266, 32e34; (g) Tietze, L. F. Chem. Rev.
1996, 96, 115e136; (h) Kubczyk, T. M.; William, S. M.; Kean, J. R.; Davies, T. E.;
Taylor, S. H.; Graham, A. E. Green Chem. 2011, 13, 2320e2325; (i) Smith, B. M.;
Graham, A. E. Tetrahedron Lett. 2011, 52, 6281e6283; (j) Smith, B. M.; Graham,
A. E. Tetrahedron 2012, 68, 7775e7781.
2. Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1964, 87, 1353e1364.
3. (a) McGarrigle, E. M.; Myers, E. L.; Illa, O.; Shaw, M. A.; Riches, S. L.; Aggarwal,
V. K. Chem. Rev. 2007, 107, 5841e5883; (b) Li, A.-H.; Da, L.-X.; Aggarwal, V. K.
Chem. Rev. 1997, 97, 2341e2372; (c) Aggarwal, V. K.; Harvey, J. N.; Richardson, J.
J. Am. Chem. Soc. 2002, 124, 5747e5756; (d) Aggarwal, V. K.; Richardson, J. Chem.
Commun. 2003, 2644e2647; (e) Solladie-Cavallo, A.; Diep-Vohuule, A. J. Org.
Chem. 1995, 60, 3494e3498.
4. (a) Aggarwal, V. K.; Winn, C. L. Acc. Chem. Rev. 2004, 37, 611e620; (b) Aggarwal,
V. K.; Alonso, E.; Bae, I.; Hynd, G.; Lydon, K. M.; Palmer, M. J.; Patel, M.; Por-
celloni, M.; Richardson, J.; Stenson, R. A.; Studley, J. R.; Vasse, J.-L.; Winn, C. L. J.
Am. Chem. Soc. 2003, 125, 10926e10940; (c) Forbes, D. C.; Standen, M. C.; Lewis,
D. L. Org. Lett. 2003, 5, 2283e2286; (d) Tanzawa, T.; Shiria, N.; Sato, Y.; Hatano,
K.; Kurono, Y. J. Chem. Soc., Perkin Trans. 1 1995, 2845e2848; (e) Padwa, A.;
Gasdaska, J. R. Tetrahedron 1988, 44, 4147e4156; (f) Okazaki, Y.; Ando, F.; Ko-
ketsu, J. Bull. Chem. Soc. Jpn. 2003, 76, 2155e2165.
5. For the use of phosphazene bases in epoxidation procedures see: (a) Solladie-
Cavallo, A.; Roje, M.; Isarno, T.; Sunjic, V.; Vinkovic, V. Eur. J. Org. Chem. 2000,
1077e1080; (b) Solladie-Cavallo, A.; Diep-Vohuule, A.; Isarno, T. Angew. Chem.,
Int. Ed. 1998, 37, 1689e1691; (c) Kokotos, C. G.; Aggarwal, V. K. Org. Lett. 2007, 9,
2099e2102; (d) Aggarwal, V. K.; Bae, I.; Lee, H.-Y. Tetrahedron 2004, 60,
9725e9733.
ꢀ
14. (a) Taylor, R. J. K.; Reid, M.; Foot, J.; Raw, S. A. Acc. Chem. Res. 2005, 38, 851e869;
(b) Reid, M.; Rowe, D. J.; Taylor, R. J. K. Chem. Commun. 2003, 2284e2285; (c)
Harris, G. H.; Graham, A. E. Tetrahedron Lett. 2010, 51, 6890e6892; (d) Smith, B.
M.; Graham, A. E. Tetrahedron Lett. 2007, 48, 4891e4894.
15. (a) Raw, S. A.; Reid, M.; Roman, E.; Taylor, R. J. K. Synlett 2004, 819e822; (b)
Quesada, E.; Raw, S. A.; Reid, M.; Roman, E.; Taylor, R. J. K. Tetrahedron 2006, 62,
6673e6680; (c) Phillips, D. J.; Pillinger, K. S.; Wei, L.; Taylor, A. E.; Graham, A. E.
Chem. Commun. 2006, 2280e2282; (d) Phillips, D. J.; Pillinger, K. S.; Wei, L.;
Taylor, A. E.; Graham, A. E. Tetrahedron 2007, 63, 10528e10533; (e) Phillips, D. J.;
Graham, A. E. Synlett 2008, 649e652.
ꢀ
16. Winn, C. L.; Bellenie, B. R.; Goodman, J. M. Tetrahedron Lett. 2002, 43, 5427e5430.
17. (a) Aggarwal, V. K.; Smith, H. W.; Hynd, G.; Jones, R. V. H.; Fieldhouse, R.; Spey,
S. E. J. Chem. Soc., Perkin Trans. 1 2000, 3267e3276; (b) Date, S. M.; Singh, R.;
Ghosh, S. K. Org. Biomol. Chem. 2005, 3, 3369e3378.
18. Procter, G.; Ley, S. V.; Castle, G. H. Barium Manganate In Encyclopedia of Re-
agents for Organic Synthesis; John Wiley & Sons: New York, NY, 2001.
19. (a) Shuto, S.; Niizuma, S.; Matsuda, A. J. Org. Chem. 1998, 63, 4489e4493; (b)
Bagley, M. C.; Lin, V.; Phillips, D. J.; Graham, A. E. Tetrahedron Lett. 2009, 50,
6823e6825; (c) Bagley, M. C.; Lin, V.; Pope, S. J. A. Tetrahedron Lett. 2009, 50,
6818e6822.
ꢀ
6. Ishikawa, T. In Superbases for Organic Synthesis: Guanidines, Amidines, Phospha-
zenes and Related Organocatalysts; John Wiley & Sons, Ltd: Chichester, UK, 2009.
7. (a) Simoni, D.; Rossi, M.; Rondanin, R.; Mazzali, A.; Baruchello, R.; Malagutti, C.;
Roberti, M.; Invidiata, F. P. Org. Lett. 2000, 2, 3765e3768; (b) Blackburn, L.; Pei,
C.; Taylor, R. J. K. Synlett 2002, 215e218.