Ceric ammonium nitrate (CAN) as a green and highly efficient promoter for the 1,4-addition of thiols and benzeneselenol to α,β-unsaturated ketones

Article abstract of DOI:10.1016/j.tet.2006.12.018

A mild and efficient process for the 1,4-addition of thiols and benzeneselenols to various α,β-unsaturated ketones using a catalytic amount of CAN with excellent product yields is described. This inexpensive, nontoxic, and readily available catalytic ceric(IV) ammonium nitrate system efficiently catalyzes conjugate addition reactions between thiol derivatives and various α,β-unsaturated ketones under solvent-free conditions. A plausible mechanism for the role of CAN, both as a promoter in free radical chain addition reactions as well as a catalyst for the conjugate addition process is proposed.

Full text of DOI:10.1016/j.tet.2006.12.018

Tetrahedron 63 (2007) 1863–1871
Ceric ammonium nitrate (CAN) as a green and highly
efficient promoter for the 1,4-addition of thiols and
benzeneselenol to a,b-unsaturated ketones
Cheng-Ming Chu, Shijay Gao, M. N. V. Sastry, Chun-Wei Kuo, Chaowei Lu,
*
Ju-Tsung Liu and Ching-Fa Yao
Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road, Taipei 116, Taiwan, ROC
Received 7 August 2006; revised 8 October 2006; accepted 11 December 2006
Available online 8 January 2007
Abstract—A mild and efficient process for the 1,4-addition of thiols and benzeneselenols to various a,b-unsaturated ketones using a catalytic
amount of CAN with excellent product yields is described. This inexpensive, nontoxic, and readily available catalytic ceric(IV) ammonium
nitrate system efficiently catalyzes conjugate addition reactions between thiol derivatives and various a,b-unsaturated ketones under solvent-
free conditions. A plausible mechanism for the role of CAN, both as a promoter in free radical chain addition reactions as well as a catalyst for
the conjugate addition process is proposed.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
It also has been reported that the addition of a thiol, includ-
ing aryl and alkyl thiols, to different alkenes can complete
very fast under different conditions.9 Evidence for a free rad-
ical chain reaction mechanism is based on the fact that the
reaction rate is accelerated or initiated by the addition of
free radical initiators or the presence of an excess of oxygen
or under conditions of photolysis. Although the addition of
oxidant-initiated mercaptans to various olefins is one of
the most straightforward methods for generating monoad-
ducts, undesired b-hydroxy sulfides or diadducts are gener-
ated in the synthesis of multifunctional compound in some
cases.9a–c However, only few of these reactions have the rad-
ical character of an alkene with a different substituted group
and examples of the addition of thiols to a,b-unsaturated ke-
tones or reactions involving oxidation addition are scarce or
have not been reported.
The base catalyzed 1,4-addition of thiols to a,b-unsaturated
carbonyl compounds to form carbon–sulfur bonds constitutes
a key reaction in various biosynthetic processes as well as in
organic synthesis.1,2 The 1,4-addition of mercaptans can
be catalyzed by strong bases such as alkali metal alkoxides,
hydroxides,3 and amines.4 Alternatively, the use of Lewis
acids such as Hf(OTf)3,5a InBr3,5b Bi(NO3)3,5c Bi(OTf)3,5d
InCl3,5e Cu(BF4)2,5f and Zn(ClO4)2$6H2O5g has been inves-
tigated. However, the use of either strongly acidic or basic
conditions typically leads to the formation of undesirable
side products owing to side reactions, such as polymerization,
self-condensation, and rearrangements.6 Chakraborti et al.
recently reported on the 1,4-conjugate addition of thiols to
a,b-unsaturated carbonyl compounds in water at room
temperature, without any metal catalyst leading to the facile
and highly efficient synthesis of a-sulfido carbonyl com-
pounds. However, therehasbeennostraightforwardsynthesis
of these uncomplicated enones and methyl acrylate leading to
the preparation of typical enones (e.g., chalcone, trans-4-
phenyl-3-buten-2-one, etc.), which cannot react in water
even under forcible conditions.7 In addition, these reactions
are well documented in the literature with several hetero-
geneous systems such as zeolites and others.8
Among the electron transfer oxidizing agents, ceric(IV) am-
monium nitrate is a convenient and widely used reagent for
affecting a wide array of synthetic transformations due to its
many advantages such as solubility in organic solvents, low
toxicity, high reactivity, and ease of handling. A preliminary
report on the use of Ce(IV) salts for the preparation of car-
bon-centered radicals dates back to the pioneering work of
Heiba and Dessau in 1971.10 Nair et al. developed a facile
CAN-mediated protocol for the thiocyanation and seleno-
cyanation of olefins, which led to different products under
different conditions.11 In recent years, several synthetic
transformations involving both C–C as well as C–X
(X¼hetero atom) bond-forming reactions facilitated by
Keywords: 1,4-Addition; Thiol and benzeneselenol; a,b-Unsaturated
ketones; Solvent free; Ceric ammonium nitrate (CAN).
* Corresponding author. Tel.: +886 2 29350749; fax: +886 2 29324249;
e-mail: cheyaocf@scc.ntnu.edu.tw
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.12.018

1864
C.-M. Chu et al. / Tetrahedron 63 (2007) 1863–1871
catalytic amounts of CAN have been reported.12 In a contin-
uation of our ongoing investigations of radical-mediated
mechanistic pathways, we were prompted to explore the
CAN-mediated conjugate addition of thiol and benzenesele-
nol compounds to a,b-unsaturated ketones and to explore
the mechanism of CAN-mediated reactions. Herein, we
wish to report on the simple and efficient 1,4-addition of
thiols and benzeneselenols to a,b-unsaturated ketones medi-
ated by CAN and a plausible mechanism for the reaction
(Scheme 1).
atmospheres such as Ar, air, and O2. It was also observed
that the reaction proceeded, to a small extent, under photo-
lytic conditions even in different atmospheres. An identical
reaction conducted in the presence of a free radical initiator
such as AIBN and illuminating the system with an ultraviolet
light resulted in the formation of the 1,4-conjugate addition
product 3da in 20% yield (entry 5). The same reaction under
both thermal and photochemical conditions (90 ꢀC) afforded
the conjugate addition product only in good yield, without
1
the 1:1 adduct being detected by H NMR and GC–MS.
However, the literature revealed that the radical addition of
thiols to a,b-unsaturated esters and nitriles involves the for-
mation of both the 1,4-conjugate addition product along with
the 1:1 adduct with the RS group attached to the b-carbon
atom (Scheme 2).9 This clearly demonstrates the difference
between conjugate addition reactions of thiols with a,b-un-
saturated enones and a,b-unsaturated esters and nitriles.
O
O
R3
R2
R3
CAN
neat
R
R
R4XH
+
R1
R1
XR4
R2
X = S or Se
1
2, 4
3, 5
1a: R + R1 = -(CH2)3- , R2 = R3 = H
1b: R + R1 = -(CH2)2- , R2 = R3 = H
1c: R = Me, R1 = R2 = R3 = H
2a: R4 = Ph
2b: R4 = c-C6H11
2c: R4 = C6H5CH2
2d: R4 = C3H7
O
OMe
1d: R = Me, R2 = Ph, R1 = R3 = H
1e: R = Ph, R2 = Ph, R1 = R3 = H
1f: R = Ph, R1 = R2 = Me, R3 = H
1g: R = Me, R2 + R3 = -(CH2)4- , R1 = H
1h: R = CH2=CHCH2O, R1 = R2 = R3 = H
H
EtS
n
2e: R4 = CH2=CHCH2
Peroxide
UV
O
EtS
O
+
OMe
1:1 adduct
OMe
O
EtSH
+
1i: R = CH2=CHC(CH3)2O, R1 = R2 = R3 = H
OMe
Ionic
EtS
O
Scheme 1.
OMe
1,4-addition
2. Results and discussion
2.1. CAN promotes thiol addition
Scheme 2.
These investigations prompted us to consider the use of CAN
as a catalyst for the conjugate addition of thiophenol 2a with
enones. Thus in the presence of 5 mol % CAN under solvent-
free conditions, the reaction of thiophenol 2a with cyclo-
hexenone 1a proceeded smoothly within 10 min to afford
the conjugate addition products exclusively and in quantita-
tive yields (Fig. 1). Analogously, a decrease in the amount of
CAN led to the partial recovery of the starting material, even
when the reaction time was prolonged. A further series of
experiments revealed that the optimal molar ratio of enone,
thiol, and CAN was 1:1.1:0.05. The yield of product was not
improved when 5 or 10 mol % CAN was used as a promoter,
suggesting that 5 mol % of CAN is appropriate for the
reaction.
Several blank reactions were conducted at this stage between
1d and 1.1 equiv of thiophenol 2a at different temperatures
under different atmospheres. Under these conditions, the
yield of 3da was negligible, demonstrating that the rate
of the uncatalyzed reaction is unfavorable for 1,4-addition
(Table 1). No significant change in the reaction mixture
was observed, when it was conducted under different
Table 1. The 1,4-addition of thiophenol 2a to enone 1d under solvent-free
condition at different temperatures
Entry Additive (mol %) Conditiona
Time 1db (%) 3dab (%)
1
2
3
4
5
6
7
8
—
—
—
—
AIBN (5)
—
—
—
Ar, 25 ꢀC
Air, 25 ꢀC
O2, 25 ꢀC
3 h
3 h
3 h
99
98
96
96
80
84
82
87
tr
2
4
4
We subsequently examined the effect of solvent on the cat-
alytic activity of CAN during the reaction of 1d with 2a
Ar, 25 ꢀC, hvc 3 h
Ar, 25 ꢀC, hvc 3 h
20
12
18
13
29
21
44
tr
13
17
41
62
Ar, 35 ꢀC
Ar, 35 ꢀC
Ar, 50 ꢀC
Ar, 50 ꢀC
3 h
8 h
3 h
120
100
9
—
—
16 h 71
10
11
12
13
14
15
16
Ar, 50 ꢀC, hvc 3 h
Ar, 50 ꢀC, hvc 3 h
79
56
99
85
64
59
38
>99
>99
>99
93
AIBN (5)
80
60
40
20
0
Galvinoxyl (10)d Ar, 50 ꢀC, hvc 4 h
Air, 50 ꢀC
O2, 50 ꢀC
Ar, 90 ꢀC
Ar, 90 ꢀC
3 h
3 h
3 h
3 h
65
—
—
—
AIBN (5)
a
Conditions: enone 1d (2.0 mmol) and 2a (2.2 mmol) were mixed together
under different atmospheres at different temperatures.
Yields were determined by 1H NMR and GC.
The photochemical reactions were performed using a 275 W general
electric sunlamp at about a 20 cm distance.
Reaction was carried out in 0.5 mL of CHCl3.
b
c
0.0
1.0
2.5
5.0
10.0
100.0
mol % of CAN for 2 mmol of enone 1a
d
Figure 1.

C.-M. Chu et al. / Tetrahedron 63 (2007) 1863–1871
1865
Table 2. Reaction of 1d with 2a in various solvents under the catalytic
influence of CAN
Table 3. Cerium(IV) ammonium nitrate (CAN) promoted 1,4-addition of
thiols to enonesa
O
O
Entry
1
2
Temp (ꢀC)/
time
Product 3
Yieldb
(%)
CAN
condition
+
PhSH
1
2
3
4
5
2a rt/10 min
2b rt/1 h
2c rt/40 min
2d rt/40 min
2e rt/20 min
3aa 98
Ph
Ph
SPh
3da
O
O
3ab 95
3ac 98
3ad 95
3ae 99
1d
2a
3dab Recovered
(%)
SR4
Entry CAN
Solvent
Conditiona
(mol %)
1db (%)
O
O
O
1
2
3
4
5
6
7
8
5
5
5
5
5
5
5
5
5
5
5
5
10
10
10
CH2Cl2
CH3CN
Air, rt, 3 h
Air, rt, 3 h
CH3COCH3 Air, rt, 3 h
C2H5OC2H5 Air, rt, 3 h
47
71
57
61
47
68
86
80
56
99
94
53
29
43
39
53
25
14
20
18
—
6
6
2a rt/20 min
3ba 98
SPh
7
8
9
10
11
2a rt/40 min
2b rt/20 min
2c rt/40 min
2d rt/20 min
2e rt/20 min
3ca 99
3cb 96
3cc 98
3cd 86
3ce 90
C6H6
CH3OH
—
Air, rt, 3 h
Air, rt, 3 h
Ar, rt, 1 h
Air, rt, 1 h
O2, rt, 1 h
Ar, 50 ꢀC, 1 h
Air, 50 ꢀC, 1 h
O
—
—
—
—
—
—
—
—
SR4
9
10
11
12
13
14
15
O
O
O2, 50 ꢀC, 0.5 h 86
10
9
19
18
12
13
2a rt/3 h
2a 50/1 h
3da 86
90
Ar, 50 ꢀC, 1 h
Air, 50 ꢀC, 1 h
92
81
Ph
Ph
SPh
SPh
SPh
O2, 50 ꢀC, 0.5 h 82
O
O
a
All reactions were performed using 2 mmol of 1d and 2.2 mmol of 2a in
2 mL of degassed solvent under different atmospheres.
Yields were determined by 1H NMR.
14c,d Ph
2a 50/30 min
2a 50/4 h
Ph
Ph
3ea 80
3fa 82
3ga 86e
b
Ph
Ph
O
O
15d
Ph
(Table 2). The type of solvent had little effect and almost all
of the solvents tested afforded the product in moderate to
high yields. Good product yields were obtained in polar sol-
vents whereas only moderate yields were obtained when
benzene and dichloromethane were used. The reduced cata-
lytic activity is most probably due to the poor solubility of
CAN in these solvents. Moreover, the reaction was promoted
under an atmosphere of argon, compared to an O2 or air at-
mosphere at ambient temperature (entries 7–15). However,
at elevated temperature (50 ꢀC) the yield of the addition
product (3da) was practically quantitative and only a slight
difference was observed in terms of both yield and reaction
rate either in an Ar or an air atmosphere (entries 10 and 11).
On the other hand, no substance containing two or more mol-
ecules of 1:1 adduct was detected, except when the addition
was carried out in an O2 atmosphere, in which some of enone
1d underwent reduction to produce a ketone and the transfor-
mation to a sulfonate by itself (Table 1, entry 14 and Table 2,
entry 9).13d
O
O
16d
2a 50/4 h
PhS
PhS
H
O
17
18
2a 0/2 h
2a 50/30 min
3ha 14f
98g
H
H
H
H
O
O
O
H
PhS
19
2a 50/2 h
3ia 60
Me
Me
Me
Me
O
O
O
O
a
All reactions were performed using 1 equiv (2 mmol) of enone 1 and
1.1 equiv (2.2 mmol) of mercaptan 2 in the presence of 5 mol % of
CAN under solvent-free condition in air atmosphere.
Isolated yields.
b
c
d
e
Reaction was carried out in 1 mL of CH3CN.
Compound 2a (2 equiv, 4 mmol) and 10 mol % of CAN were used.
The two diastereomers formed in 98:2 (trans:cis) and were separated by
column chromatography.
f
Eight percent of 1:1 adduct product 3ha0 and 40% of di-addition 3ha00
were isolated.
To demonstrate the versatility of CAN-promoted 1,4-addi-
tion reactions, a variety of enones 1a–g were reacted with
both aliphatic and aromatic thiols 2a–e in the presence of
CAN, giving good to practically quantitative yields of the ra-
cemic product as confirmed by HPLC analysis (Table 3).14
The product also could be easily isolated by simple purifica-
tion by flash column chromatography. It is noteworthy that
the highly steric cyclohexanethiol 2b and the unstable allyl
mercaptan 2e also afforded the 1,4-adduct in 95% and
99% yield, respectively, after isolation (entries 2 and 5). In
other cases, steric effects were observed when bulkier
enones were used, and in such reactions, more driving con-
ditions were required. Both an increase in the reaction tem-
perature as well as the amount of CAN were needed in cases
of sterically bulkier substrates such as 1d–g (entries 13–16).
It is noteworthy that no byproducts resulting from 1,2-
g
Trace of 1:1 adduct product 3ha0 was isolated.
1
additions or bis-additions were observed by H NMR and
GC. Moreover, the reactions are clean, high yielding, and
sometimes quantitative. Compared to conventional methods,
enhanced reaction rates, improved yields, and excellent 1,4-
selectivity are the main features of these CAN catalyzed
reactions. The CAN-mediated generation of a radical by
single electron transfer has also been investigated.13,16d
Indeed, we also observed the exclusive formation of disul-
fides, when thiols were treated with 1 equiv of CAN. Based
on our investigations, we propose a plausible mechanism for
this reaction (Scheme 3).

1866
C.-M. Chu et al. / Tetrahedron 63 (2007) 1863–1871
could be used as antioxidants, enzyme inhibitors, antitumor,
O
and anti-infective agents, cytokine inducers, and immuno
modulators.17 Furthermore, the biochemical role of sele-
nium in mammals was clearly established by the discovery
that it is a component of the active site of the antioxidant en-
zyme glutathione peroxidase (GPx).18 Increased interest in
the use of organoselenium compounds in biochemistry has
generated a growing demand for their synthesis as well as
their pharmacological activity.
enones: 1a - 1i
Ce(IV) Ce(III)
neat
-H+
RS
O
RSH
RSH
RS
We further examined the addition of benzeneselenols to a,b-
unsaturated ketones (Table 4). In an initial experiment, a
blank reaction was run with benzeneselenol 4 and enones
1a–g in the absence of CAN at 0 ꢀC or room temperature.
Surprisingly, the reaction afforded the b-seleno adduct 5
in poor to moderate yields along with detectable amounts
of the reduction product 6. The results for chalcone 1e
were also examined in the addition reactions using ethanol
without the aid of a catalyst.19 In addition to 1,4-addition
products, saturated ketones were produced as competitive
products depending on the nature of the substrate, which
was identified by GC–MS and compared with authentic stan-
dards.20 It is noteworthy that reactions using complicated
enones 1d–f resulted in the formation of the reduced product
as the major component and the 1,4-addition product as a
minorcomponent. Thereasonfortheformationofthereduced
product may be due to simple hydrogenationvia a free radical
intermediate in the presence of the less acidic hydrogen of
benzeneselenolandthemore electrophilic enone. This is most
probably due to the fact that the photolysis of selenols yields
hydrogen radicals H.20a This is probably due to competitive
addition and reduction in the presence of the less steric of
b-carbon. Therefore, inferior results are obtained for a b-carbon
containing a bulky substituent (entries 4–6 and 10–13).
RS
O
HSR
3
2
Scheme 3. Plausible mechanism for the role of CAN as a promoter of free
radical chain reactions of 1,4-addition.
During the reaction, CAN converts the thiol to a thiyl radical
cation, and subsequently to a thiyl radical from the fragmen-
tation of the radical cation. This thiyl radical then undergoes
a radical chain addition to the enone to form the final 1,4-ad-
dition product. Furthermore, another mechanistic rationale
for this reaction is based on the oxidizing nature of CAN.
The use of a strong oxidizing catalyst such as CAN could
easily form a strong coordinate bond with the carbonyl oxy-
gen of the a,b-unsaturated ketone, which in turn, would in-
crease the electrophilicity of the b-carbon thus permitting
the conjugate addition reaction to proceed under mild condi-
tions in a short time.
Encouraged by these results, we examined the scope of CAN
as a catalyst for the 1,4-addition of thiols to diene esters
such as 1h–i (Table 3, entries 17–19). As expected, the reac-
tion proceeded smoothly in the case of 1h at 50 ꢀC to afford
the 1,4-addition product in excellent yield with only a trace
of dimerized product. Conversely, only a moderate yield was
obtained when a sterically hindered substrate such as 1i was
used, with undetectable amounts of 1:1 adduct. The lower
yield of 1i (60% isolated yield) may be explained on the
basis of the lower electrophilicity of the vinyl ester 1i, which
has a poor reactivity, as well as the steric hindrance associ-
ated with the gem-dimethyl allyl group, which would hinder
the nucleophilic thiyl addition to the electrophilic b-carbon.
In fact a g-lactone product resulting from exocyclization
was not observed, as anticipated during the reaction of a thiol
with a sterically hindered gem-dialkyl ester15 such as acrylic
acid 1,1-dimethyl-allyl ester 1i. Presumably, the rate at
which the radical intermediate traps the hydrogen from thio-
phenol is much faster than the rate of cyclization of the same
radical.16 Furthermore, regioselectivity is an important crite-
rion for the addition to occur exclusively on the conjugated
double bond. Most probably, the RS radical is an electro-
philic species and the reverse might be expected, since the
conjugated double bond is more electron poor. It is also sig-
nificant that a 1:1 adduct with an RS group on the b-carbon
atom of 3ha0 was observed along with the normal 1,4-
adducts 3ha and 3ha00 when the reaction involved heating
or the use of a sunlamp, which is due to CAN-promoted
free radical chain reactions.9
Table 4. Comparison of the results of the CAN-promoted conjugate addition
of benzeneselenol 4 to a,b-unsaturated ketones
O
O
O
R3
SePh
R3
R2
R3
R2
condition
R
PhSeH
+
R
R
+
R1
R1
R1
R2
1
4
5
6
Entry
1
CAN (mol %) Conditiona
5b (%)
6b (%)
1
1a
1c
1d
1d
1d
1d
1d
1d
1d
1e
1e
1f
—
—
—
—
—
—
2
Air, 0 ꢀC, 10 min 5a (94)
Air, 0 ꢀC, 20 min 5c (95)
6a (tr)
6c (tr)
6d (32)
6d (42)
6d (42)
6d (39)
2
3c
4
Ar, rt, 24 h
5d (40)
5d (20)
5d (10)
5d (7)
Air, rt, 24 h
Air, rt, 24 h
O2, rt, 24 h
Ar, rt, 5 min
Air, rt, 5 min
O2, rt, 5 min
Air, rt, 24 h
Air, rt, 20 min
Air, rt, 24 h
Air, rt, 40 min
Air, rt, 24 h
5c
6c
7
5d (>99) 6d (—)
5d (>99) 6d (—)
5d (>99) 6d (—)
8
9
2
2
10d
11e
12
13e
14
—
—
—
—
—
5e (13)
5e (44)
5f (17)
5f (6)
6e (17)
6e (12)
6f (45)
6f (44)
6g (tr)
1f
1g
5g (75)
a
All chemicals and glassware were degassed thoroughly using argon prior
to use and the reactions were carried out by using 2 mmol of 1d and
3 mmol of 4 under different conditions.
2.2. CAN promotes benzeneselenol addition
Yields were determined by 1H NMR.
b
c
d
e
Phenylselenol 4 (2.2 mmol, 1.1 equiv) was used.
Reaction was carried out in 1 mL of CH3CN.
Reaction was carried out in 1.7 mL of EtOH.
During the past decade, many efforts have been directed to-
ward the synthesis of stable organoselenium compounds that

C.-M. Chu et al. / Tetrahedron 63 (2007) 1863–1871
1867
As indicated in entries 7–9, various types of atmospheres,
including oxygen, air and argon, were investigated for the
reaction of 1d with 4 in the presence of CAN. The procedure
is very simple, and it should be noted that CAN is able to
promote these reactions under different atmospheres. This
is probably due to the strong oxidizing nature of CAN. How-
ever, the reaction is efficient under different atmospheres.
When the reaction was carried out under an atmosphere of
O2, no significant change in the reaction, compared with
that for an Ar atmosphere. This may be due to the fact that
the reaction, when run in an atmosphere of O2 is inhibited
and the reactant is oxidized to diphenyl-diselane from ben-
zeneselenol.21 Indeed; diphenyl diselenide was detected in
this reaction.
observed (Table 5, entries 3–5). To apply this method, diene
esters 1h–i were reacted with benzeneselenol in the presence
of CAN under similar conditions. Unfortunately, the reac-
tions did not proceed and only unreacted starting materials
were recovered.
3. Conclusion
In summary, we successfully developed a general synthetic
protocol for the mild and efficient 1,4-addition of thiols
and selenophenols to various a,b-unsaturated ketones using
a catalytic amount of CAN. The reaction is simple, conve-
nient and can be applied to a wide variety of substrates
with excellent product yields under solvent-free conditions.
We also examined various parameters such as solvent, tem-
perature, and additives to achieve maximum yields of 1,4-
addition products. A plausible mechanism is proposed for
the role of CAN, both as a promoter in free radical chain ad-
dition reactions as well as a catalyst in the conjugate addition
process. This inexpensive catalyst not only offers advantages
such as high catalytic activity, operational simplicity, and the
broadest substrate scope with excellent product yields but
also stands as an alternative to conventional methods, which
involve the use of expensive, noxious, and/or air-sensitive
catalysts. We are currently in the process of expanding the
scope of these reactions and to elucidate more aspects re-
garding the reaction mechanism.
Under optimized reaction conditions, the 1,4-addition of
various a,b-unsaturated ketones with benzeneselenol was
investigated and the results are summarized in Table 5. We
attempted a variety of reactions between benzeneselenol 4
and enones 1 with catalytic amounts of CAN (2–5 mol %),
which afforded various b-seleno adducts in excellent yields.
It is noteworthy that reduction products were predominantly
formed in the absence of CAN with these substrates. No
apparent significant steric effect of b-site substituents was
Table 5. Cerium(IV) ammonium nitrate (CAN)-catalyzed 1,4-addition of
benzeneselenol 4 to various enones 1a–ga
Entry
1
CAN
(mol %) time
Temp (ꢀC)/
5
Yieldb
(%)
4. Experimental section
4.1. General methods
O
O
5a
1
2
2
2
5
0/5 min
98
99
98
99
SePh
All reactions were performed in oven-dried glassware and
some reactions were carried out under a positive pressure
of argon when the reactions were sensitive to moisture
or oxygen. Analytical thin layer chromatography was per-
formed with E. Merck silica gel 60F glass plates and
flash chromatography based E. Merck silica gel 60 (230–
400 mesh). GC was measured by a SHIMADZU GC-14B
instrument. MS or HRMS were measured using a JEOL
O
O
5c
2
0/5 min
rt/5 min
rt/10 min
Me
Me
Ph
Me
SePh
O
O
5d
3
Me
Ph
Ph
Ph
Ph
O
SePh
JMS-D300 or JEOL JMS-HX110 spectrometer. 1H and 13
NMR spectra were recorded with a Varian Gemini-200 or
Bruker Avance EX 400 FT NMR.
C
O
4c
5e
Ph
SePh
4.2. Typical experimental procedure for the 1,4-addition
of thiophenol 2a to cyclohexenone 1a in the presence of
ceric(IV) ammonium nitrate (CAN) to generate 3-phe-
nylthiocyclohexanone (3aa)22
O
O
5
5
5
rt/15 min
rt/40 min
98
5f
Ph
Ph
6d
47e
Me
SePh
Me
Me
Me
In a 10 mL round bottom flask were first added cyclohexe-
none 1a (0.198 g, 2 mmol) and thiophenol 2a (0.249 g,
2.2 mmol). The mixture was thoroughly degassed using vac-
uum and argon purge cycles, and ceric ammonium nitrate
(CAN) (0.0548 g, 0.1 mmol) was then added under a dry
air atmosphere, which was passed through CaCl2. The mix-
ture was stirred at room temperature for 10 min. After
completion of the reaction (monitored by TLC and GC),
the crude product was purified by flash column chromato-
graphy (ethyl acetate–hexanes 1:20) to give the pure product
3aa in 98% (0.404 g) isolated yield as a colorless oil:
1H NMR (400 MHz, CDCl3) d 7.429 (dt, J¼8.0, 1.6 Hz,
O
O
5g
7
5
rt/10 min
Me
PhSe
98
Me
a
All Reactions were carried out using 1 equiv (2 mmol) of enone 1 and
1.5 equiv (3 mmol) of benzeneselenol 4 in the presence of 2–5 mol %
of CAN under solvent-free condition in air atmosphere.
Isolated yields.
Reaction was carried out in 1 mL of CH3CN.
Reaction was carried out in 1.7 mL of EtOH.
Twenty nine percent of unreacted 1f and 17% of reduction product ketone
were isolated.
b
c
d
e

1868
C.-M. Chu et al. / Tetrahedron 63 (2007) 1863–1871
2H), 7.34–7.21 (m, 3H), 3.47–3.39 (m, 1H), 2.68 (dd,
J¼14.4, 4.4 Hz, 1H), 2.41–2.29 (m, 3H), 2.16–2.12 (m,
2H), 1.76–1.70 (m, 2H); 13C NMR (100 MHz, CDCl3)
d 208.90, 133.41, 133.19, 129.24, 127.97, 47.95, 46.30,
41.05, 31.43, 24.22; m/z (relative intensity) 206 (M+, 60),
110 (100), 109 (42), 97 (57), 96 (30), 84 (18), 77 (19), 69
(100), 68 (85), 66 (34), 65 (34), 55 (38). HRMS calcd for
C12H14OS 206.0760, found 206.0770.
(44), 83 (24), 77 (10), 69 (10), 68 (57), 65 (23), 55 (100).
HRMS calcd for C11H12OS 192.0609, found 192.0610.
4.2.6. 4-Phenylsulfanyl-butan-2-one (3ca).26 Colorless oil:
1H NMR (400 MHz, CDCl3) d 7.35–7.26 (m, 4H), 7.18 (tt,
J¼7.2, 1.3 Hz, 1H), 3.12 (t, J¼7.2 Hz, 2H), 2.74 (t,
J¼7.2 Hz, 2H), 2.13 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 206.70, 135.81, 129.62, 129.13, 126.42, 43.17, 30.20,
27.56; m/z (relative intensity) 180 (M+, 5), 179 (8), 178
(65), 163 (100), 135 (45), 134 (12), 110 (20), 109 (55),
101 (20), 91 (45), 77 (15), 69 (16), 65 (27). HRMS calcd
for C10H12OS 180.0609, found 180.0422.
4.2.1. 3-Cyclohexylsulfanyl-cyclohexanone (3ab).23 Col-
orless oil: H NMR (400 MHz, CDCl3) d 3.12–3.07 (m,
1
1H), 2.75–2.62 (m, 2H), 2.38–2.22 (m, 3H), 2.15–2.04
(m, 2H), 1.94–1.82 (m, 2H), 1.78–1.52 (m, 5H), 1.34–1.13
(m, 5H); 13C NMR (100 MHz, CDCl3) d 209.12, 48.95,
42.48, 41.22, 41.05, 34.09, 34.04, 32.29, 26.14, 26.11,
25.85, 24.48; m/z (relative intensity) 212 (M+, 35), 116
(22), 115 (52), 114 (27), 97 (75), 96 (79), 83 (43), 82 (48),
81 (29), 69 (50), 68 (70), 67 (85), 55 (100). HRMS calcd
for C12H20OS 212.1229, found 212.1252. Anal. Calcd for
C12H20OS: C, 67.87; H, 9.49; S, 15.10. Found: C, 67.87;
H, 9.09; S, 14.84.
4.2.7. 4-Cyclohexylsulfanyl-butan-2-one (3cb).23 Color-
less oil: H NMR (400 MHz, CDCl3) d 2.78–2.69 (m, 4H),
1
2.64–2.60 (m, 1H), 2.17 (s, 3H), 2.02–1.90 (m, 2H), 1.82–
1.71 (m, 2H), 1.65–1.58 (m, 1H), 1.38–1.15 (m, 5H);
13C NMR (100 MHz, CDCl3) d 207.00, 44.05, 43.84,
33.63, 30.11, 26.09, 25.83, 23.84; m/z (relative intensity)
186 (M+, 48), 116 (17), 115 (68), 114 (38), 83 (40), 82
(33), 81 (42), 71 (56), 67 (70), 55 (100). HRMS calcd for
C10H18OS 168.1073, found 168.1083. Anal. Calcd for
C10H18OS: C, 64.46; H, 9.74; S, 17.21. Found: C, 64.17;
H, 9.77; S, 17.06.
1
4.2.2. 3-Benzylthiocyclohexanone (3ac). Colorless oil: H
NMR (400 MHz, CDCl3) d 7.37–7.21 (m, 5H), 3.76 (dd,
J¼15.2, 13.6 Hz, 2H), 2.96–2.89 (m, 1H), 2.69 (dd,
J¼14.4, 4.4 Hz, 1H), 2.41–2.30 (m, 3H), 2.11–2.07 (m,
2H), 1.75–1.60 (m, 2H); 13C NMR (100 MHz, CDCl3)
d 208.86, 138.08, 128.91, 128.79, 127.33, 48.00, 42.15,
41.12, 35.12, 31.49, 24.30; m/z (relative intensity) 220
(M+, 5), 124 (15), 123 (15), 97 (29), 96 (13), 91 (100), 77
(10), 69 (12), 68 (35), 65 (20), 55 (10). HRMS calcd for
C13H16OS 220.0916, found 220.0920.
4.2.8. 4-Benzylsulfanyl-butan-2-one (3cc). Colorless oil:
1H NMR (400 MHz, CDCl3) d 7.30–7.19 (m, 5H), 3.69
(s, 2H), 2.65–2.58 (m, 4H), 2.07 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 206.60, 138.25, 128.78, 128.48,
127.00, 43.25, 36.61, 29.92, 25.17; m/z (relative intensity)
194 (M+, 17), 160 (5), 124 (14), 123 (18), 92 (12), 91
(100), 77 (7), 65 (21), 63 (7), 55 (10). HRMS calcd for
C11H14OS 194.0760, found 194.0773.
4.2.3. 3-n-Propylthio-1-cyclohexanone (3ad).24 Colorless
oil: 1H NMR (400 MHz, CDCl3) d 3.15–3.00 (m, 1H),
2.72 (d, J¼14.1 Hz, 1H), 2.53 (dt, J¼7.4, 2.5 Hz, 2H),
2.42–2.30 (m, 3H), 2.20–2.13 (m, 2H), 1.75–1.70 (m, 2H),
1.70–1.55 (m, 2H), 0.99 (dt, J¼7.4, 2.9 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 208.90, 48.32, 42.80, 41.01, 32.62,
31.74, 24.30, 23.12, 13.57; m/z (relative intensity) 172
(M+, 60), 119 (8), 115 (20), 110 (14), 98 (23), 97 (100), 96
(81), 76 (18), 74 (19), 69 (100), 68 (86), 67 (30), 55 (62).
HRMS calcd for C9H16OS 172.0916, found 172.0926.
4.2.9. 4-Propylsulfanyl-butan-2-one (3cd).27 Colorless oil:
1H NMR (400 MHz, CDCl3) d 2.75–2.71 (m, 4H), 2.50 (t,
J¼7.2 Hz, 2H), 2.17 (s, 3H), 1.61 (sext, J¼7.2 Hz, 2H),
0.98 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 206.95, 43.80, 34.48, 30.11, 25.77, 22.91, 13.48; m/z
(relative intensity) 146 (M+, 100), 117 (10), 104 (5), 103
(30), 83 (40), 89 (7), 71 (45), 61 (20), 55 (3). HRMS calcd
for C7H14OS 146.0760, found 146.0772.
4.2.10. 4-Allylmercapto-butan-2-one (3ce). Colorless oil:
1H NMR (400 MHz, CDCl3) d 5.84–5.73 (m, 1H), 5.15–
5.08 (m, 2H), 3.15 (d, J¼7.2 Hz, 2H), 2.75–2.65 (m, 4H),
2.17 (s, 3H); 13C NMR (100 MHz, CDCl3) d 206.78,
134.27, 117.16, 43.44, 35.08, 30.08, 24.46; m/z (relative in-
tensity) 144 (M+, 100), 103 (35), 101 (8), 85 (12), 74 (13), 73
(27), 71 (20), 59 (5), 55 (5). HRMS calcd for C7H12OS
144.0603, found 144.0613.
4.2.4. 3-Allylsulfanyl-cyclohexanone (3ae). Colorless oil:
1H NMR (400 MHz, CDCl3) d 5.80–5.67 (m, 1H), 5.15–
5.00 (m, 2H), 3.15 (d, J¼7.0 Hz, 2H), 3.05–2.95 (m, 1H),
2.65 (d, J¼14.2 Hz, 1H), 2.36–2.26 (m, 3H), 2.13–2.02
(m, 2H), 1.74–1.60 (m, 2H); 13C NMR (100 MHz, CDCl3)
d 208.76, 134.33, 117.25, 47.97, 41.53, 41.01, 33.64,
31.42, 24.25; m/z (relative intensity) 170 (M+, 51), 129
(18), 98 (18), 114 (27), 97 (100), 96 (30), 69 (86), 68 (57),
67 (35), 55 (54). HRMS calcd for C9H14OS 170.0760, found
170.0769. Anal. Calcd for C9H14OS: C, 63.48; H, 8.29; S,
18.83. Found: C, 63.03; H, 8.13; S, 18.94.
4.2.11. 4-Phenyl-4-phenylsulfanyl-butan-2-one (3da).23,28
Colorless oil: 1H NMR (400 MHz, CDCl3) d 7.31–7.24
(m, 6H), 7.24–7.16 (m, 4H), 4.70 (dd, J¼7.8, 6.8 Hz, 1H),
3.08 (dd, J¼14.0, 7.8 Hz, 1H), 3.02 (dd, J¼14.0, 6.8 Hz,
1H), 2.05 (s, 3H); 13C NMR (100 MHz, CDCl3) d 205.64,
141.24, 134.25, 133.08, 129.02, 128.67, 127.89, 127.80,
127.61, 49.71, 48.26, 30.87; m/z (relative intensity) 256
(M+, 71), 148 (11), 147 (99), 135 (9), 111 (11), 109
(100), 105 (14), 104 (41), 103 (41), 91 (18), 77 (44), 65
(37), 51 (23). HRMS calcd for C16H16OS 256.0922, found
256.0915.
4.2.5. 3-(Phenylthio)cyclopentanone (3ba).25 Colorless
oil: 1H NMR (400 MHz, CDCl3) d 7.39 (dt, J¼7.7, 1.6 Hz,
2H), 7.34–7.22 (m, 3H), 3.92–3.84 (m, 1H), 2.55 (dd,
J¼18.4, 7.2 Hz, 2H), 2.52–2.40 (m, 1H), 2.37–2.15 (m,
3H), 2.05–1.95 (m, 1H); 13C NMR (100 MHz, CDCl3) d
216.27, 134.31, 131.94, 129.15, 127.42, 45.25, 43.38, 36.78,
29.36; m/z (relative intensity) 192 (M+, 36), 110 (23), 109

C.-M. Chu et al. / Tetrahedron 63 (2007) 1863–1871
1869
4.2.12. 1,3-Diphenyl-3-phenylsulfanyl-propan-1-one
(3ea).29 White solid; mp 118–119 ꢀC: 1H NMR (400 MHz,
CDCl3) d 7.86 (d, J¼8.56 Hz, 2H), 7.49 (t, J¼7.3 Hz, 1H),
7.37 (t, J¼7.8 Hz, 2H), 7.35–7.27 (m, 4H), 7.25–7.13 (m,
6H), 4.96 (dd, J¼8.0, 6.1 Hz, 1H), 3.65 (dd, J¼17.0,
8.0 Hz, 1H), 3.56 (dd, J¼17.0, 6.1 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 197.08, 141.36, 136.87, 134.42,
133.37, 132.87, 128.99, 128.74, 128.59, 128.19, 127.95,
127.66, 127.50, 48.38, 44.85; m/z (relative intensity) 319
(M+1, 21), 318 (M+, 85), 209 (67), 207 (11), 110 (18), 109
(78), 106 (80), 105 (100), 104 (46), 103 (47), 78 (49), 77
(97), 65 (30), 51 (51). HRMS calcd for C21H18OS
318.1078, found 318.1072.
8.0 Hz, 1H), 3.05 (dd, J¼13.4, 6.1 Hz, 1H), 2.70 (m, 1H),
2.37 (m, 2H); 2.03 (m, 2H); 13C NMR (100 MHz, CDCl3)
d 173.57, 172.44, 135.53, 132.26, 132.13, 130.59, 129.24,
126.91, 118.77, 118.57, 65.69, 65.46, 44.95, 36.25, 31.79,
26.78; m/z (relative intensity) 334 (M+, 5), 332 (10), 222
(25), 150 (20), 149 (30), 135 (30), 123 (30), 117 (40), 110
(100), 110 (100), 109 (50), 77 (30), 69 (32), 66 (32), 55
(51). HRMS calcd for C18H22O4S 334.1239, found 334.0889.
4.2.18. 1-(2-Phenylsulfanyl-cyclohexyl)-ethanone (3ia).
Colorless oil: 1H NMR (400 MHz, CDCl3) d 7.37 (dt,
J¼7.4, 1.5 Hz, 2H), 7.31–7.17 (m, 3H), 6.10 (dd, J¼17.44,
10.84 Hz, 1H), 5.19 (dd, J¼17.48, 10.92 Hz, 2H), 3.13 (dd,
J¼7.52, 7.36 Hz, 2H), 2.56 (dd, J¼7.36, 7.52 Hz, 2H), 1.51
(s, 6H); 13C NMR (100 MHz, CDCl3) d 170.80, 142.55,
135.67, 130.20, 129.18, 126.64, 113.01, 81.49, 35.55,
29.34, 26.64; m/z (relative intensity) 250 (M+, 17), 182
(100), 181 (40), 163 (15), 137 (25), 135 (20), 123 (90), 110
(47), 109 (58), 77 (20), 69 (64), 65 (34), 55 (20), 53 (25).
HRMS calcd for C14H18O2S 250.1022, found 222.1033.
4.2.13. 3-Phenylthio-3-methyl-butyrophenone (3fa).29
Colorless oil: 1H NMR (400 MHz, CDCl3) d 7.88 (d,
J¼8.8 Hz, 2H), 7.58–7.52 (m, 3H), 7.45–7.32 (m, 5H),
3.22 (s, 2H), 1.46 (s, 6H); 13C NMR (100 MHz, CDCl3)
d 198.31, 138.19, 137.98, 133.20, 131.75, 129.33, 128.88,
128.76, 128.31, 49.12, 48.00, 28.57; m/z (relative intensity)
270 (M+, 11), 161 (30), 110 (10), 109 (14), 106 (12), 105
(100), 77 (47), 65 (7), 51 (11). HRMS calcd for C17H18OS
270.1078, found 270.1084.
4.2.19. 3-Phenyl selenocyclohexanone (5a).30 Colorless
oil: 1H NMR (400 MHz, CDCl3) d 7.59 (dt, J¼7.4, 1.8 Hz,
2H), 7.36–7.26 (m, 3H), 3.52–3.44 (m, 1H), 2.68 (ddd,
J¼14.4, 4.4, 2.0 Hz, 1H), 2.49 (dd, J¼14.3, 11 Hz, 1H),
2.41–2.07 (m, 4H), 1.86–1.64 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 208.98, 135.88, 129.35, 128.38,
127.68, 48.93, 41.04, 40.42, 32.28, 25.42; m/z (relative
intensity) 254 (M+, 30), 158 (45), 157 (30), 156 (25), 155
(20), 154 (15), 117 (10), 97 (65), 96 (25), 78 (100), 77
(60), 69 (80), 68 (85), 55 (33), 51 (41). HRMS calcd for
C12H14OSe 254.0204, found 204.0201. Anal. Calcd for
C12H14OSe: C, 56.92; H, 5.57. Found: C, 56.69; H, 5.36.
4.2.14. trans-1-(2-Phenylsulfanyl-cyclohexyl)-ethanone
1
(3ga). Major product: white solid; mp 76–78 ꢀC; H NMR
(400 MHz, CDCl3) d 7.40 (d, J¼8.2 Hz, 2H), 7.28 (t,
J¼6.9 Hz, 2H), 7.20 (tt, J¼6.9, 1.1 Hz, 1H), 3.80–3.77 (dt,
J¼7.6, 3.8 Hz, 1H), 2.73–2.68 (dt, J¼10.2, 4.0 Hz, 1H),
2.16 (s, 3H), 2.06–1.99 (m, 1H), 1.88–1.68 (m, 5H), 1.53–
1.30 (m, 1H), 1.33–1.20 (m, 1H); 13C NMR (100 MHz,
CDCl3) d 209.07, 135.93, 131.95, 129.16, 127.15, 54.16,
49.05, 31.59, 28.35, 24.58, 24.11, 21.52; m/z (relative inten-
sity) 234 (M+, 77), 125 (18), 110 (100), 109 (20), 81 (26), 79
(10), 77 (10), 65 (11). HRMS calcd for C14H18OS 234.1078,
found 234.1072. Anal. Calcd for C14H18OS: C, 71.75; H,
7.74; S, 13.68. Found: C, 71.57; H, 7.61; S, 13.94.
4.2.20. 4-(Benzoseleno)-butan-2-one (5c).31 Colorless oil:
1H NMR (400 MHz, CDCl3) d 7.59 (dt, J¼7.7, 1.8 Hz,
2H), 7.28–7.23 (m, 3H), 3.05 (t, J¼7.2 Hz, 2H), 2.84 (t,
J¼7.2 Hz, 2H), 2.11 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 207.15, 132.98, 129.84, 129.28, 127.25, 44.22, 30.12,
20.61; m/z (relative intensity) 228 (M+, 48), 226 (23), 185
(20), 178 (30), 158 (34), 157 (53), 155 (30), 149 (17), 91
(37), 79 (28), 78 (100), 77 (100), 69 (37), 68 (27), 67 (28),
57 (38), 55 (86), 51 (64). HRMS calcd for C10H12OSe
228.0048, found 228.0051. Anal. Calcd for C10H12OSe: C,
52.87; H, 5.32. Found: C, 52.87; H, 5.07.
4.2.15. cis-1-(2-Phenylsulfanyl-cyclohexyl)-ethanone
(3ga). Minor product: colorless oil; H NMR (400 MHz,
1
CDCl3) d 7.42 (d, J¼8.2 Hz, 2H), 7.30–7.20 (m, 3H), 3.19
(td, J¼11.0, 3.8 Hz, 1H), 2.53 (dt, J¼11.0, 3.6 Hz, 1H),
2.22 (s, 3H), 2.11–2.06 (m, 1H), 1.92–1.87 (m, 1H), 1.75–
1.67 (m, 2H), 1.43–1.28 (m, 4H); 13C NMR (100 MHz,
CDCl3) d 210.62, 133.91, 133.13, 128.88, 127.45, 55.95,
47.82, 33.56, 29.99, 29.70, 25.88, 24.84.
4.2.21. 4-Phenyl-4-phenylselenyl-butan-2-one (5d).32
1
4.2.16. 3-Phenylsulfanyl-propionic acid allyl ester (3ha).
Colorless oil: 1H NMR (400 MHz, CDCl3) d 7.38 (dt,
J¼8.0, 1.6 Hz, 2H), 7.31–7.18 (m, 3H), 5.95–5.85 (m, 1H),
5.33–5.21 (m, 2H), 4.59 (d, J¼5.8 Hz, 2H), 3.17
(t, J¼7.4 Hz, 2H), 2.65 (t, J¼7.4 Hz, 2H); 13C NMR
(100 MHz, CDCl3) d 171.52, 135.34, 132.13, 130.32, 129.19,
126.75, 118.58, 65.54, 34.54, 29.21; m/z (relative intensity)
222 (M+, 80), 165 (30), 163 (30), 139 (40), 137 (50), 135
(55), 123 (45), 110 (55), 109 (100), 77 (38), 69 (53), 65
(44), 55 (58). HRMS calcd for C12H14O2S 222.0709, found
222.0717.
White solid; mp 53–54 ꢀC: H NMR (400 MHz, CDCl3)
d 7.59 (dt, J¼8, 1.4 Hz, 2H), 7.30–7.15 (m, 8H), 4.79 (dd,
J¼8.6, 6.4 Hz, 1H), 3.26 (dd, J¼17.1, 8.6 Hz, 1H), 3.10
(dd, J¼17.1, 6.4 Hz, 1H), 2.04 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 206.02, 141.61, 135.94, 129.12,
129.04, 128.61, 128.38, 127.73, 127.36, 49.74, 41.84,
30.67; m/z (relative intensity) 304 (M+, 5), 302 (3), 234
(3), 158 (32), 157 (25), 156 (17), 147 (35), 146 (51), 145
(50), 131 (84), 104 (17), 103 (100), 102 (16), 78 (75), 77
(96), 76 (16), 51 (59). HRMS calcd for C16H16OSe
304.0361, found 304.0369. Anal. Calcd for C16H16OSe: C,
63.37; H, 5.32. Found: C, 63.32; H, 5.11.
4.2.17. Diallyl 2-(phenylthiomethyl)pentanedioate (3ha0).
Colorless oil: 1H NMR (400 MHz, CDCl3) d 7.38 (dt, J¼7.6,
1.4 Hz, 2H), 7.31–7.21 (m, 3H), 5.93–5.83 (m, 2H), 5.35–
5.21 (m, 4H), 4.58 (m, J¼6.0 Hz, 4H), 3.25 (dd, J¼13.4,
4.2.22. 1,3-Diphenyl-3-phenylselenyl-propan-1-one
1
(5e).19 White solid; mp 120–121 ꢀC: H NMR (400 MHz,
CDCl3) d 7.87 (dt, J¼7.9, 1.4 Hz, 2H), 7.52 (tt, J¼7.4,

1870
C.-M. Chu et al. / Tetrahedron 63 (2007) 1863–1871
4. (a) Zhu, S.; Cohen, T. Tetrahedron 1997, 53, 17607; (b)
Hiemstra, H.; Wiberg, H. J. Am. Chem. Soc. 1981, 103, 417;
(c) Suzuki, K.; Ikekawa, A.; Mukaiyama, T. Bull. Soc. Chem.
Jpn. 1982, 55, 3277; (d) Yamashita, H.; Mukaiyama, T.
Chem. Lett. 1985, 363; (e) Emori, E.; Arai, T.; Sasai, H.;
Shibasaki, M. J. Am. Chem. Soc. 1998, 120, 4043.
5. (a) Kobayashi, S.; Ogawa, C.; Kawamura, M.; Sugiura, M.
Synlett 2001, 983; (b) Bandini, M.; Cozzi, P. G.; Giacomini,
M.; Melchiorre, P.; Selva, S.; Umani-Ronchi, A. J. Org.
Chem. 2002, 67, 3700; (c) Srivastava, N.; Banik, B. K.
J. Org. Chem. 2003, 68, 2109; (d) Alam, M. M.; Varala, R.;
Adapa, S. R. Tetrahedron Lett. 2003, 44, 5115; (e) Ranu,
B. C.; Dey, S. S.; Samanta, S. ARKIVOC 2005, 44; (f) Garg,
S. K.; Kumar, R.; Chakraborti, A. K. Tetrahedron Lett. 2005,
46, 1721; (g) Garg, S. K.; Kumar, R.; Chakraborti, A. K.
Synlett 2005, 1370.
1.2 Hz, 1H), 7.43–7.37 (m, 4H), 7.28–7.13 (m, 8H), 5.03
(dd, J¼8.4, 6.0 Hz, 1H), 3.85 (dd, J¼17.3, 8.5 Hz, 1H),
3.66 (dd, J¼17.3, 6.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3) d 197.51, 141.80, 136.90, 135.88, 133.41, 129.27,
129.15, 128.80, 128.59, 128.33, 128.23, 127.84, 127.31,
44.91, 42.29. Anal. Calcd for C21H18OSe: C, 69.04; H,
4.97. Found: C, 68.87; H, 4.64.
4.2.23. 3-Methyl-1-phenyl-3-phenylselenyl-butan-1-one
(5f). Pale yellow oil: H NMR (400 MHz, CDCl3) d 7.87
1
(dt, J¼7.2, 1.4 Hz, 2H), d 7.68 (dt, J¼7.9, 1.4 Hz, 2H), d
7.56–7.30 (m, 6H), 3.34 (s, 2H), 1.57 (s, 6H); 13C NMR
(100 MHz, CDCl3) d 198.37, 138.62, 138.08, 133.21,
129.04, 128.99, 128.76, 128.28, 127.89, 50.38, 44.29,
29.80; m/z (relative intensity) 318 (M+, 2), 243 (5), 161
(7), 160 (20), 159 (28), 145 (25), 131 (7), 117 (8), 105
(100), 83 (15), 78 (17), 77 (63), 55 (13), 51 (28). HRMS
calcd for C17H18OSe 318.0517, found 318.0527. Anal.
Calcd for C17H18OSe: C, 63.37; H, 5.32. Found: C, 62.59;
H, 5.36.
6. Novak, L.; Kolontis, P.; Szantay, C.; Aszodi, D.; Kajtar, M.
Tetrahedron 1982, 38, 153.
7. Our recent study found that only 35% or 20% of addition prod-
uct was observed when the reaction of chalcone or trans-4-
phenyl-3-butene-2-one with thiophenol was conducted under
the same conditions as literature reported for 24 h after the crude
mixture was analyzed by NMR or GC, respectively. Khatik,
G. L.; Kumar, R.; Chakraborti, A. K. Org. Lett. 2006, 8, 2433.
8. (a) Shinde, P. D.; Mahajan, V. A.; Borate, H. B.; Tillu, V. H.;
Bal, R.; Chandwadkar, A.; Wakharkar, R. D. J. Mol. Catal.
A: Chem. 2004, 216, 115; (b) Sreekumar, R.; Rugmini, P.;
Padmakumar, R. Tetrahedron Lett. 1997, 38, 6557.
9. (a) Harris, J. F.; Stacey, F. W. Organic Reactions; Adams, R.,
Ed.; Wiley: New York, NY, 1963; Vol. 13, Chapter 4; (b)
Kharasch, M. S.; Fuchs, C. F. J. Org. Chem. 1948, 13, 97;
(c) Griesbaum, K. Angew. Chem., Int. Ed. Engl. 1970, 9, 27;
(d) Kharasch, M. S.; Nudenberg, W.; Mantell, G. J. J. Org.
Chem. 1954, 16, 524; (e) Oswald, A. A. J. Org. Chem. 1961,
26, 842; (f) Bredereck, H.; Wagner, A.; Kottenhahn, A.
Chem. Ber. 1960, 93, 2415; (g) Harman. Chem. Abstr. 1950,
44, 8942; (h) Oswald, A. A.; Noel, F. J. Org. Chem. 1961,
26, 3948.
4.2.24. 1-(2-Phenylselenyl-cyclohexyl)-ethanone (5g).
1
White solid; mp 67–69 ꢀC; H NMR (400 MHz, CDCl3)
d 7.55–7.51 (m, 2H), d 7.28–7.23 (m, 3H), 3.77–3.75 (m,
1H), 2.76–2.73 (m, 1H), 2.11 (s, 3H), 2.13–1.30 (m, 8H);
13C NMR (100 MHz, CDCl3) d 209.14, 134.41, 130.66,
129.24, 127.63, 54.90, 46.74, 33.02, 28.15, 25.30, 24.43,
22.90; m/z (relative intensity) 282 (M+, 60), 280 (30), 158
(85), 157 (38), 156 (46), 155 (30), 154 (25), 125 (45), 124
(30), 109 (43), 81 (98), 79 (60), 78 (100), 77 (76), 53 (32),
51 (43). HRMS calcd for C14H18OSe 282.0517, found
282.0521. Anal. Calcd for C14H18OSe: C, 59.79; H, 6.45.
Found: C, 59.85; H, 6.39.
Acknowledgements
Financial support of this work by the National Science
Council of the Republic of China and National Taiwan Nor-
mal University (ORD93-C) is gratefully acknowledged.
10. Heiba, E. I.; Dessau, R. M. J. Am. Chem. Soc. 1971, 93, 524.
11. Nair, V.; Balagopal, L.; Rajan, R.; Mathew, J. Acc. Chem. Res.
2004, 37, 21.
12. (a) Ho, T. L. Synthesis 1973, 347; (b) Ho, T. L. Organic
Synthesis by Oxidation with Metal Compounds; Plenum:
New York, NY, 1986 and references therein; (c) Imamoto, T.
Lanthanide Reagents in Organic Synthesis; Academic:
London, 1994; p 119; (d) Nair, V.; Mathew, J.; Prabhakaran,
J. Chem. Soc. Rev. 1997, 127; (e) Hwu, J. R.; King, K.-Y.
Curr. Sci. 2001, 8, 1043.
Supplementary data
The H and 13C NMR spectra for all compounds are avail-
able. Supplementary data associated with this article can
be found in the online version, at doi:10.1016/j.tet.2006.
12.018.
1
13. (a) Ho, T. L.; Wong, C. M. Synthesis 1972, 561; (b) See
Ref. 12a; (c) Molander, G. A. Chem. Rev. 1992, 92, 29; (d)
Nair, V.; Augustine, A. Org. Lett. 2003, 5, 543.
References and notes
14. The typical enantioselectivity of 3da was determined by chiral
stationary phase HPLC analysis (DAICEL CHIRALCEL
OD-H, i-PrOH–hexane/2:98, flow rate: 0.5 mL/min, retention
time: 16.7 min, 18.4 min).
15. (a) Jung, M. E.; Gervoy, J. J. Am. Chem. Soc. 1991, 113, 224;
(b) Jung, M. E.; Trifunovich, I. D.; Lensen, N. Tetrahedron
Lett. 1992, 33, 6719.
16. The cyclization of ester radicals derived from allyl acrylate
and allyl acetate is known to be very slow compared to the
dramatic effect of gem-dimethyl substitution on the rate of
5-exo-cyclization. The rate constant of gem-dialkyl cyclization
is in the range of 106 sꢁ1. Relatively, the rate constant for the
1. (a) Fluharty, A. L. The Chemistry of the Thiol Group, Part 2;
Patai, S., Ed.; Wiely: New York, NY, 1974; p 589; (b) Fujita,
E.; Nagao, Y. J. Bioorg. Chem. 1977, 6, 287.
2. (a) Julia, M.; Badet, B. Bull. Soc. Chim. Fr. 1975, 1363; (b)
Trost, B. M.; Keeley, D. E. J. Org. Chem. 1975, 40, 2013; (c)
Shono, T.; Matsumura, Y.; Kashimura, S.; Hatanaka, K.
J. Am. Chem. Soc. 1979, 101, 4752; (d) Chang, Y.-H.;
Pinnick, H. W. J. Org. Chem. 1978, 43, 373.
3. (a) Bergman, E. D.; Ginsberg, D.; Rappo, R. Org. React. 1959,
10, 179; (b) Oare, D. A.; Heathcock, C. A. Topics in
Stereochemistry; Eliel, E. L., Wilen, S. H., Eds.; Wiley: New
York, NY, 1989; Vol. 9, p 277.

C.-M. Chu et al. / Tetrahedron 63 (2007) 1863–1871
1871
reduction of alkyl radicals by thiophenol of 1.3ꢂ108 Mꢁ1 sꢁ1
has also been reported: (a) Russell, G. A.; Li, C.; Chen, P.
J. Am. Chem. Soc. 1996, 118, 9831; (b) Curran, D. P.; Tamine,
J. J. Org. Chem. 1991, 56, 2746; (c) Franz, J. A.; Bushaw,
B. A.; Alnajjar, M. S. J. Am. Chem. Soc. 1989, 111, 268; (d)
Free Radical in Organic Chemistry; Fossey, J., Lefort, D.,
Sorba, J., Eds.; Wiely: New York, NY, 1995; p 80 and 99.
17. (a) Levander, O. A. Selenium. In Trace Elements in Human and
Animal Nutrition; Mertz, W., Ed.; Academic: Orlando, 1986;
Vol. 2, p 209; (b) Levander, O. A. A. Ann. Rev. Nutr. 1987, 7,
227; (c) Neve, J. Biological Functions of Selenium. In
Selenium in Medicine and Biology; Neve, J., Favier, A., Eds.;
W. de Gruyter: Berlin, 1988; p 97; (d) Selenium in Biology
and Human Health; Burk, R. F., Ed.; Springer: New York,
NY, 1994; (e) Ganther, H. E. Carcinogenesis 1999, 20, 1657;
(f) Mugesh, G.; du Mont, W.-W.; Sies, H. Chem. Rev. 2001,
101, 2125.
21. Clarembeau, M.; Cravador, A.; Dumont, W.; Hevesi, L.; Krief,
A. Tetrahedron 1985, 41, 4793.
22. Wabnitz, T. C.; Yu, J.-Q.; Spencer, J. B. Chem.—Eur. J. 2004,
10, 484.
23. Firouzabadi, H.; Iranpoor, N.; Jafari, A. A. Synlett 2005, 299.
24. Silva, F. M. D.; Gomes, A. K.; Jones, J. Can. J. Chem. 1999,
77, 624.
25. Flowers, W. T.; Freitas, A. M.; Holt, G.; Purkiss, S. C. J. Chem.
Soc., Perkin Trans. 1 1981, 1119.
26. (a) Wabnitz, T. C.; Spencer, J. B. Org. Lett. 2003, 5, 2141; (b)
Ranu, B. C.; Mandal, T. Synlett 2004, 1239.
27. Sabirov, S. S.; Gnevasheva, L. M.; Ismailov, M. I.; Isobaev,
M. D. J. Org. Chem. USSR 1984, 20, 1239.
28. Bodwell, J. R.; Patwardhan, B. H.; Dittmer, D. C. J. Org. Chem.
1984, 49, 4192.
29. Narasaka, K.; Arai, N.; Okauchi, T. Bull. Chem. Soc. Jpn. 1993,
66, 2995.
ꢀ
€
18. (a) Flohe, L.; Gunzler, E. A.; Schock, H. H. FEBS Lett. 1973,
32, 132; (b) Rotruck, J. T.; Pope, A. L.; Ganther, H. E.;
Swanson, A. B.; Hafeman, D. G.; Hoekstra, W. G. Science
1973, 179, 588.
30. (a) Dieden, R.; Hevesi, L. Synthesis 1988, 8, 616; (b)
Sakakibara, M.; Katsumata, K.; Watanabe, Y.; Toru, T.;
Ueno, Y. Synthesis 1992, 4, 377.
31. (a) Miyoshi, N.; Ishii, H.; Kondo, K.; Murai, S.; Sonoda, N.
Synthesis 1979, 4, 300; (b) Middleton, D. S.; Simpkins,
N. S.; Begley, M. J.; Terrett, N. K. Tetrahedron 1990,
46, 545.
19. Gilman, H.; Cason, L. F. J. Am. Chem. Soc. 1951, 73, 1074.
20. (a) Perkins, M. J.; Smith, B. V.; Turner, E. S. J. Chem. Soc.,
Chem. Commun. 1980, 977; (b) Akiyama, R.; Kobayashi, S.
J. Am. Chem. Soc. 2003, 125, 3412.
32. Miyashita, M.; Yoshikoshi, A. Synthesis 1980, 8, 664.