Addition-type oxidation of silylalkene using ozone: An efficient approach for acyloin and its derivatives

Article abstract of DOI:10.1246/cl.2011.233

Acyloins are efficiently synthesized in three steps from alkynes via ydrosilylation followed by an addition-type ozone oxidation and hydrogenation. The key intermediate α-silylperoxy ketone is convertible to not only acyloin but also O-silylated acyloin and diketone.

Full text of DOI:10.1246/cl.2011.233

doi:10.1246/cl.2011.233
Published on the web February 5, 2011
233
Addition-type Oxidation of Silylalkene Using Ozone:
An Efficient Approach for Acyloin and Its Derivatives
Kazunobu Igawa,1 Yuuya Kawasaki,2 and Katsuhiko Tomooka*1
1Institute for Materials Chemistry and Engineering, Kyushu University,
6-1 Kasuga-koen, Kasuga, Fukuoka 816-8580
2Interdisciplinary Graduate School of Engineering Science, Kyushu University,
6-1 Kasuga-koen, Kasuga, Fukuoka 816-8580
(Received November 29, 2010; CL-101007; E-mail: ktomooka@cm.kyushu-u.ac.jp)
Acyloins are efficiently synthesized in three steps from
alkynes via hydrosilylation followed by an addition-type ozone
oxidation and hydrogenation. The key intermediate ¡-silylper-
oxy ketone is convertible to not only acyloin but also O-silylated
acyloin and diketone.
oxy aldehydes 3 (R2 = H) introducing silylperoxy and carbonyl
moieties on vicinal carbons without normal fission of the
carbon-carbon double bond.4 This result clearly suggests that a
similar ozone oxidation of silyl-substituted internal alkene 2
(R2 = alkyl) should yield the corresponding ¡-silylperoxy
ketone 3 (R2 = alkyl), which has versatile functional groups
for synthesis of a variety of oxy-functionalized compounds
containing acyloin.5-8 Herein, we report a new efficient synthetic
approach for acyloins and their derivatives from alkynes 4 via
sequential hydrosilylation followed by addition-type ozone
oxidation (Scheme 1, Method B).9
First, we performed (E)- or (Z)-selective hydrosilylation of
4-octyne (4a) and 1,8-diphenyl-4-octyne (4b) by previously
reported procedures.10 The hydrosilylation of 4a and 4b in the
presence of platinum(0)-1,3-divinyl-1,1,3,3-tetramethyldisilox-
ane [Pt(DVDS)] afforded (E)-2a-2d in good yields with
excellent E-selectivities (>99% E).11 On the other hand,
Yamamoto and Asao’s Lewis acid-promoted hydrosilylation
of 4a afforded (Z)-2a and -2b as the sole isomer (>99% Z)
(Scheme 2).12
Acyloins, namely ¡-hydroxy ketones 1 are important as key
structural components of biologically active natural products and
as synthetic building blocks owing to their versatile bifunction-
ality.1,2 Therefore, thus far, several synthetic approaches to
acyloins have been developed. Among these approaches, acyloin
condensation is one of the most widely used approaches,
however, proper choice of substrate and harsh conditions are
requisite for the reductive dimerization of esters.2a,2b As an
alternative approach, a sequential method involving the oxida-
tion of alkenes or alkynes and further transformation of the
resulting oxy-functionalized intermediates such as epoxide, diol,
or diketone is also commonly used.3 However, in this method, it
is rather complicated to control the oxidation level of vicinal
carbons having the same oxy-functionality, which often leads
to the formation of a regioisomer of acyloin (Scheme 1,
Method A). To avoid these longstanding problems, a more
efficient synthetic approach for acyloin is needed.
R3SiH
Pt(DVDS)
(0.2 mol%)
SiR3
R1
THF, reflux
R1
(E)-2a: R1 = H, R = Ph (90%)
(E)-2b: R1 = H, R = Et (78%)
(E)-2c: R1 = H, R = i-Pr (97%)
(E)-2d: R1 = Ph, R = i-Pr (85%)
OH
R2
O
O
R1
HO
O
Method A
R2
R2
R1
R1
R1
R1
4a: R1 = H
4b: R1 = Ph
R3SiH
addition-type
oxidation of
control of
SiR3
AlCl3 (20 mol%)
oxidation level
alkene or alkyne
toluene
O
R = Ph: reflux
R = Et : 0 °C
(Z)-2a: R = Ph (16%)
(Z)-2b: R = Et (78%)
HO
R1
R2
R2
R1
4
1
Scheme 2. Hydrosilylation of alkyne 4a and 4b.
hydrosilylation
of alkyne
O-O bond
cleavage
Ozone oxidation of silylalkenes 2 was performed by
bubbling ca. 1.2 v/v% O3/O2 gas in AcOEt at ¹78 °C.13 The
reactions of (E)-2a-2d afforded the corresponding ¡-silylperoxy
ketones 3a-3d in excellent yields, regardless of the different
silyl groups [TPS (R = Ph), TES (R = Et), and TIPS (R = i-Pr)]
(Scheme 3).14
SiR3
R2
O
O3
O
R3SiO
R2
Method B
R1
R1
2
3
In sharp contrast, a similar oxidation of (Z)-2a (R3Si =
TPS) afforded 3a in a very low yield (9%) (Scheme 4).15 The
remarkable difference between (E)-2a and (Z)-2a is probably
due to the steric repulsion of the bulky silyl group with the ¢-
cis-substituent in the silyl migration stage of primary ozonide i,
as shown in Scheme 4. On the basis of this working hypothesis,
Scheme 1. Synthetic approach to acyloin based on oxidation of
an unsaturated carbon-carbon bond.
To this end, we recently found that ozone oxidation of 1-
silyl-substituted terminal alkenes 2 (R2 = H) affords ¡-silylper-
Chem. Lett. 2011, 40, 233-235
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

234
SiR3
O
Table 1. Synthesis of O-silylated acyloins 5e-5h from alkyne
O3
R1
O
R1
4e-4h
R3SiO
R1
AcOEt, –78 °C
O
R1
TIPSO
RO
OR
3a: R1 = H, R = Ph (97%)
3b: R1 = H, R = Et (84%)
3c: R1 = H, R = i-Pr (86%)
3d: R1 = Ph, R = i-Pr (92%)
OR
(E)-2a-d
RO
4e–h
5e–h
TIPS-H
Pt(DVDS) /
neat, 80 °C
P(OMe)3
t-BuOH, 50 °C
/
Scheme 3. Ozone oxidation of (E)-silylalkenes [(E)-2a-2d].
SiR3
O
O
TIPS
O3
O
O3
O
OR
OR
R3SiO
TIPSO
AcOEt, –78 °C
AcOEt, –78 °C
RO
RO
(Z)-2a,b
3a: R = Ph (9%)
3b: R = Et (48%)
2e–h
3e–h
Entry
4
R
Yields of 2a/% Yields of 5b/%
O3
O
O
1
2
3
4
4e TBS
75 (2e)
(>99% E)
95 (2f)
64 (5e)
57 (5f)
45 (5g)
53 (5h)
R
α
O
β
Si
H
R
4f Bn
R
(E/Z = 95/5)c
99 (2g)
i
4g p-ClC6H4CH2
(E/Z = 89/11)c
94 (2h)
Scheme 4. Ozone oxidation of (Z)-silylalkenes [(Z)-2a and
-2b].
4h p-CNC6H4CH2
(E/Z = 85/15)c
c
aIsolated yields. Isolated yields from 2. Determined by GLC
analysis.
b
we anticipated that a decrease in the bulkiness of the silyl group
would improve the efficiency of the addition-type ozone
oxidation of (Z)-2. As we expected, a similar reaction of (Z)-
2b with a smaller silyl group (R3Si = TES) afforded 3b in a
considerably better yield (48%) than that of (Z)-2a.
The ¡-silylperoxy ketones 3 thus obtained are easily and
efficiently convertible into free or O-silylated acyloins. As
shown in Scheme 5, hydrogenation of 3d catalyzed by Pd/C
afforded free acyloin 1d in 78% yield by reductive O-O bond
cleavage.8a To transform 3d into O-silylated acyloin 5d, we
examined conventional methods for the reduction of the silyl
peroxide moiety using PPh3 or PMe3.4,8,16,17 However, the
reactions involved in these methods required a long time along
with partial decomposition of 3d. After several attempts, we
found that the reaction of 3d with P(OMe)3 in t-BuOH smoothly
afforded 5d in good yield (76%). Furthermore, we successfully
converted 3d to 1,2-diketone 6d in 90% yield by Et3N treatment.
For example, the sequential reaction of the disilyl ether of 2-
butyne-1,4-diol 4e with hydrosilylation and ozone oxidation
followed by phosphite reduction afforded O-silylated acyloin 5e
with oxy-functions on all the carbons, in good yield (Table 1,
Entry 1).18 Similar reactions of dibenzyl ether derivatives 4f-4h
also afforded O-silylated acyloins 5f-5h in moderate yields,
regardless of the functional groups on the aromatic ring
(Table 1, Entries 2-4).19,20 These results clearly show that the
present sequential conversion of alkyne is an efficient approach
for synthetically variable multifunctionalized acyloin deriva-
tives.
In summary, we have described a new synthetic approach
for acyloin and its derivatives using the addition-type ozone
oxidation of silylalkene. In the described approach, easily
available and chemically stable silylalkene moieties serve as
synthetic equivalents of acyloin moieties. Further applications of
the present synthetic method to natural product synthesis are in
progress.
O
HO
Ph
H2, Pd/C
cOEt, rt
A
Ph
1d (78%)
This research was supported in part by MEXT, Japan [Grant-
in-Aid for Scientific Research on Innovative Areas (Project
No. 2105: Organic Synthesis Based on Reaction Integration),
Global COE Program (Kyushu Univ.), and MEXT Project of
Integrated Research on Chemical Synthesis] and Industrial Tech-
nology Research and Development Project (No. 09C46622a)
from NEDO, Japan. We thank Y. Tanaka (IMCE, Kyushu Univ.)
for HRMS measurements.
O
P(OMe)3
TIPSO
Ph
Ph
Ph
3d
t-BuOH, 50 °C
5d (76%)
O
Et3N
O
THF, rt
Ph
6d (90%)
References and Notes
Scheme 5. Transformation of ¡-silylperoxy ketone 3d.
1
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Chem. Lett. 2011, 40, 233-235
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

235
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19 Ozone oxidations of 2f-2h were performed without separa-
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20 Although, ozone is capable of oxidizing benzylic carbon, no
such products were observed in the ozone oxidation of 2f-
2h.
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6
7
8
21 Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
Chem. Lett. 2011, 40, 233-235
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/