Oxidative Synthesis of α,β-Unsaturated Ketone from α-Iodo Ketone Using Peracid

Article abstract of DOI:10.1055/s-2003-44371

Oxidation of α-iodo ketone in CH₂Cl₂ using m-chloro-perbenzoic acid yields α,β-unsaturated ketone by β-H elimination in good yield. This reaction affords a new and convenient synthetic method for α,β-unsaturated ketone from α-iodo ketone.

Full text of DOI:10.1055/s-2003-44371

202
SHORT PAPER
Oxidative Synthesis of , -Unsaturated Ketone from -Iodo Ketone Using
Peracid
O
xidative Synthe
.
sis of
,
-UnA
saturated Ketone kira Horiuchi,*a Shun-Jun Ji,b Masatoshi Matsushita,a Wen Chaia
a
Department of Chemistry, Rikkyo (St. Paul’s) University, Nishi-Ikebukuro, Toshima-Ku, Tokyo 171-8501, Japan
Fax +81(3)39852397; E-mail: horiuchi@rikkyo.ac.jp
b
Department of Chemistry and Chemical Engineering, Suzhou University, 1 Shizi St. Suzhou, Jiangsu 215006, P. R. China
Received 29 August 2003; revised 6 October 2003
curred to afford the corresponding , -dialkoxyalkanoic
ester.13 In this paper, we report that the oxidation of -io-
docycloalkanones 1–6 and steroidal -iodo ketones 7,8
with MCPBA in CH2Cl2 yields the corresponding , -un-
saturated ketone (Scheme 1). These results are summa-
rized in Table 1.
Abstract: Oxidation of -iodo ketone in CH2Cl2 using m-chloro-
perbenzoic acid yields , -unsaturated ketone by -H elimination in
good yield. This reaction affords a new and convenient synthetic
method for , -unsaturated ketone from -iodo ketone.
Key words: -iodo ketone, oxidation, elimination reaction , -un-
saturated ketone
O
O
I
MCPBA
Synthesis of , -unsaturated ketones is an important pro-
cess for organic synthetic chemistry. They are usually pre-
pared by one of the following methods: direct oxidation of
ketones using the Collins reagent,1 dehydrobromination
of -bromo ketones by treatment of nitrogenous bases and
by lithium salts,2 -elimination of -phenylseleno carbon-
oyl compounds,3 dehydrogenation of steroidal ketone us-
ing DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)
in boiling benzene,4 dehydrogenation of 3-oxo steroids
using selenium dioxide in tert-butyl alcohol,5 or allylic
oxidation of 5-steroids.6 However, in the case of steroi-
dal , -unsaturated ketones, it is known that these reac-
R2
R1
CH2Cl2
78-90%
(
)
n
R1
(
)
n
R2
1-6
13-18
R3
19
20
MCPBA
O
H
O
R4
CH2Cl2
68-98%
R4
R3
H
7,8
O
tions tend to give abnormal products, i.e.,
, -
unsaturated ketones. It is difficult to separate these iso-
MCPBA
mers having similar properties.7
O
O
R5
R6
R5
R6
CH2Cl2
11-28%
Reaction of alkyl iodides with peracetic acid has been in-
vestigated by Ogata and his co-workers.8 More recently,
Beeley and Sutherland have proposed an elimination of
hypoiodous acid to account for olefin formation during
the Baeyer–Villiger oxidation of an iodonorbornanone.9
Reich et al., 10 reported that the oxidation of acyclic alkyl
iodides bearing strong electron-attracting substituents
such as carbomethoxy and sulfonyl gives the unsaturated
compounds. However, the oxidation of -iodocyclo-
alkanone with peracid (MCPBA) has not been reported
until now.
I
11,12
23,24
Scheme 1
As can be seen from Table 1, it was found that this method
is applicable to -iodocycloalkanones and steroidal
iodo ketones.
-
It is known that oxidative elimination of alkyl iodide and
-carbomethoxy iodide affords olefins by a syn elimina-
tion process.10 The most reasonable explanation for the
original observation is that the iodide is oxidized to an io-
doso-intermediate which then eliminates ‘HOI’ to yield
the unsaturated compounds.8,9 In the present case, it seems
that the oxidation of -iodocycloalkanones with peracid
(MCPBA) undergoes also the same process of elimination
of ‘HOI’. However, in the case of 3,4-dihydro-2-iodo-
1(2H)-naphthalenone (9),14 1-naphthol (21) was obtained
in 75% yield (Table 1, entry 18). Moreover, the reaction
of -iodo acyclic ketones 11 and 12 gave the correspond-
ing (E)- , -unsaturated ketones in low yields. Apparent-
-Iodocycloalkanones are important intermediates in or-
ganic synthesis, which have been investigated by our lab-
oratory with a new method.11 During the course of our
investigations to prepare useful products from these iodo
compounds, we found that irradiation of -iodocycloal-
kanone with a high-pressure mercury lamp in hexane gave
the corresponding , -unsaturated ketone,12 and in aque-
ous alcohol, photocleavage of the carbon–carbon bond oc-
SYNTHESIS 2004, No. 2, pp 0202–0204
x
x
.
x
x
.2
0
0
4
Advanced online publication: 09.12.2003
DOI: 10.1055/s-2003-44371; Art ID: F07503SS
© Georg Thieme Verlag Stuttgart · New York

SHORT PAPER
Oxidative Synthesis of , -Unsaturated Ketone
203
a
Table 1 Oxidative Elimination of -Iodo Cyclic Ketone with MCPBA in CH2Cl2
Entry
Substrate
Temp (°C)
Time (h)
Product (%)b
GLC Yield (Isolated)
1
2
1
2
3
4
5
6
6
6
6
6
6
7
7
7
7
8
8
9
(n = 1, R1 = R2 = H)
(n = 1, R1 = Me, R2 = H)
(n = 1, R1 = H, R2 = Me)
(n = 2, R1 = R2 = H)
(n = 3, R1 = R2 = H)
(n = 7, R1 = R2 = H)
(n = 7, R1 = R2 = H)
(n = 7, R1 = R2 = H)
(n = 7, R1 = R2 = H)
(n = 7, R1 = R2 = H)
(n = 7, R1 = R2 = H)
(5 , R3 = I, R4 = H)
(5 , R3 = I, R4 = H)
(5 , R3 = I, R4 = H)
(5 , R3 = I, R4 = H)
(5 , R3 = H, R4 = I)
(5 , R3 = H, R4 = I)
0
13
13
13
15
15
15
15
12
8
13
14
15
16
17
18
18
18
18
18
18
19
19
19
19
20
20
21
78 (61)16a
79 (66)16b
79 (69)16b
78 (65)16c
81 (70)16d
63 (50)16e
90 (83)
79 (71)
61 (49)
75 (62)
67 (53)
(98)15
0
3
0
4
0
5
0
6
0c
0
7
8
r.t.
reflux
0d
r.t.d
0
9
10
11
12
13
14
15
16
17
18
15
15
4
r.t.
0d
r.t.d
0
4
(68)
10
10
6
(66)
(60)
(75)16f
r.t.
0
6
(69)
20
75 (67)
O
I
19
20
9
r.t.
0 e
20
20
21
60 (55)
50 (46)
10
22
O
O
I
I
2
2
21
22
23
10
11
12
r.t.e
r.t.
r.t.
20
4
22
45 (40)
(11)
(R5 = C4H9, R6 = C2H5)
(R5 = C4H9, R6 = C3H7)
23
24
4
(28)
a All reactions were carried out in the dark.
b Determined by GLC analysis using n-dodecane as an internal hydrocarbon standard and isolated yields are given in parentheses. All products
were characterized by IR, NMR, and HRMS and the superscript is the reference number.
c 0.5 molar equiv. MCPBA was employed.
d MeCN was employed.
e 2-Cyclohepten-1-one (16) and cycloheptanone were also obtained.
ly, -iodo acyclic ketones are more unstable than
iodocycloalkanones.
-
results, it was found that either the reaction temperature or
the molar ratio of the oxidizing agent shows important ef-
fects. For example, low temperature is more favorable for
the same content of the oxidizing agent (Table 2, entries
3–5). On the other hand, 2 molar equivalents of the oxidiz-
ing agent is required under these conditions (Table 2, en-
tries 1–3).10
In order to discuss the reaction conditions, oxidation reac-
tion of -iodocyclododecanone (6) as a model compound
was carried out. The oxidation of -iodocyclododecanone
with MCPBA gave cyclododecenone (18) in 90% yield at
0 °C. The results are summarized in Table 2. From these
Synthesis 2004, No. 2, 202–204 © Thieme Stuttgart · New York

204
C. A. Horiuchi et al.
SHORT PAPER
Table 2 Oxidation of -Iodocyclododecanone (6) with MCPBAa
References
Entry Solvent
MCPBA Temp
Time
(h)
Product
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(molar
equiv.)
(°C)
(18)/% b
GLC Yield
(Isolated)
1
2
3
4
5
6
7
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
CH3CN
0.5
1.0
2.0
2.0
2.0
2.0
2.0
0
15
15
15
12
8
63 (50)
75 (65)
90 (83)
79 (71)
61 (49)
75 (62)
67 (53)
0
0
r.t.
reflux
0
15
15
r.t.
a Solvent (30 mL) was employed.
b GLC yield and isolated yield in parentheses.
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In conclusion, this method is simple and convenient for
the synthesis of , -unsaturated ketone. It is particularly
noteworthy that this reaction affords a new synthetic
method for , -unsaturated ketone.
Melting points are uncorrected and were measured by a Yanaco
Mp-52777 (Yanaco Co. Ltd, Kyoto, Japan). IR spectra were record-
ed using a JASCO FT/IR-230 grating infrared spectrometer. 1H and
13C NMR spectra were measured using a JEOL GSX 400 Model
spectrometer in CDCl3 with TMS as an internal standard. HRMS
were recorded at 75 eV on a JEOL JMS-01SG-2 instrument with a
direct inlet.
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Oxidative Elimination of 7 with m-Chloroperbenzoic Acid;
Typical Procedure
(14) The starting material -iodo cyclic ketones used in our
experiments were prepared according to the literature
procedures.11 The physical data of typical compound 3,4-
dihydro-2-iodo-1(2H)-naphthalenone (9) is listed.
Colorless needles; mp 78.5–79.6 °C.
MCPBA (0.135 g, 0.78 mmol) in CH2Cl2 solution (10 mL) was add-
ed dropwise into a CH2Cl2 solution (20 mL) of 2 -iodo-5 -
cholestan-3-one (7) (0.20 g, 0.39 mmol) at 0 °C over a period of 1
h and the mixture was stirred for 4 h. The mixture was diluted with
water (5 mL). The organic phase was washed with aq Na2S2O3 to re-
move the iodine produced, and dried (Na2SO4) and then concentrat-
ed. The resulting solid was separated by column chromatography on
silica gel, eluting with hexane–Et2O (5:1, 150 mL) to give 5 -
cholest-1-en-3-one (19) (0.148 g, 98%). Colorless needles were ob-
tained from EtOH; mp 97–99 °C (lit.15 99 °C).
IR (KBr): 1672, 1593 cm–1.
1H NMR (CDCl3): = 5.02 (t, J = 3.7 Hz, 1 H, C2), 7.31 (m,
2 H), 7.51 (m, 1 H), 8.09 (d, J = 7.7 Hz, 1 H).
13C NMR (CDCl3): = 27.8, 30.7, 32.7, 127.0, 128.7, 128.8,
129.4, 134.0, 142.8, 191.8.
HRMS: m/z calcd for C10H9OI [M]: 271.9699; found:
271.9734.
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Synthesis 2004, No. 2, 202–204 © Thieme Stuttgart · New York