Asymmetric ozone oxidation of silylalkenes using a C2- symmetrical dialkoxysilyl group as a chiral auxiliary

Article abstract of DOI:10.1002/chem.201402996

Ozone oxidation of silyl-substituted alkenes, namely silylalkenes, proceeds in an addition-type manner to afford α-silylperoxy carbonyl compounds in good to excellent yields, without the formation of normal ozonolysis products. Herein the ozone oxidation

Full text of DOI:10.1002/chem.201402996

DOI: 10.1002/chem.201402996
Communication
&
Asymmetric Oxidation
Asymmetric Ozone Oxidation of Silylalkene Using a C2-
Symmetrical Dialkoxysilyl Group as a Chiral Auxiliary
[
a]
[a]
[b]
[b]
Kazunobu Igawa, Yuuya Kawasaki, Kosuke Nishino, Naoto Mitsuda, and
[a]
Katsuhiko Tomooka*
Abstract: Ozone oxidation of silyl-substituted alkenes,
namely silylalkenes, proceeds in an addition-type manner
to afford a-silylperoxy carbonyl compounds in good to ex-
cellent yields, without the formation of normal ozonolysis
products. Herein the ozone oxidation of chiral alkenylsi-
lanes prepared from alkynes and a newly designed chiral
hydrosilane is reported. The reaction affords silylperoxides
with high diastereoselectivity (up to 94% d.r.). The silylper-
oxides are convertible into enantioenriched chiral acyloins
in a stereospecific manner.
Stereoselective oxidation of alkenes is one of the most impor-
[1]
tant and widely utilized methods in asymmetric synthesis.
Scheme 1. Ozonolysis and addition-type ozone oxidation of alkene.
However, handling explosive peroxides or highly toxic transi-
tion-metal reagents is a fundamental problem in these reac-
tions. On the other hand, ozone is a prominent oxidant that
can be easily prepared from and is re-convertible to safe and
clean oxygen. Despite this substantial advantage, ozone has
not been applied to the asymmetric oxidation of alkenes, be-
cause the reactions generally involve the cleavage of
a carbon–carbon double bond to afford achiral carbonyl com-
pounds, which is widely known as “ozonolysis” (path a in
action mechanism clearly suggests that the stereochemistry of
the newly generated a-carbonyl stereogenic center is deter-
mined in the 1,3-dipolar cycloaddition step to form ozonide i.
Thus, we envisioned that asymmetric ozone oxidation would
be realized by attaching the appropriately chosen chiral auxili-
[5–7]
ary to a silylalkene.
We planned the introduction of a chiral
auxiliary (CA*) on the silyl group to efficiently construct a chiral
environment around the alkene moiety that is easily removed
from the oxidation product (Scheme 2). The details are provid-
ed below.
[
2]
Scheme 1).
To this end, we recently found that ozone oxidation of silyl-
substituted alkenes, namely silylalkenes, proceeds in an addi-
tion-type manner to afford a-silylperoxy carbonyl compounds
in good to excellent yields, without the formation of normal
[
3,4]
ozonolysis products (path b in Scheme 1).
The key step in
this unique oxidation is the migration of the silyl group from
carbon to oxygen in the primary ozonide i, which prevents 1,3-
dipolar cycloelimination, including CÀC bond cleavage to form
secondary ozonide ii. The resulting a-silylperoxy carbonyl com-
pounds are easily and efficiently convertible into synthetically
[
3]
valuable acyloins, 1,2-diketones, 1,2-diols, and so on. The re-
Scheme 2. Concept of asymmetric ozone oxidation.
[
a] Dr. K. Igawa, Dr. Y. Kawasaki, Prof. Dr. K. Tomooka
Institute for Materials Chemistry and Engineering, Kyushu University
Kasuga, Fukuoka 816-8580 (Japan)
Fax: (+81)92-583-7810
E-mail: ktomooka@cm.kyushu-u.ac.jp
At the outset, we designed silylalkenes 2 having a chiral
[8]
alkoxy moiety on silicon. These silylalkenes were prepared by
the reaction of chlorosilane 1 and a variety of chiral alcohols,
in good to excellent yields (85–98%), as shown in Scheme 3.
Ozone oxidation of 2 was performed as per our standard pro-
[b] K. Nishino, N. Mitsuda
Department of Molecular and Material Sciences, Kyushu University
Kasuga, Fukuoka 816-8580 (Japan)
cedure: bubbling about 1.2 v/v% O /O gas in AcOEt at
3
2
[3]
À788C. The reactions of 2a–c afforded the corresponding a-
silylperoxy ketones 3a–c in quantitative yields, although the
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402996.
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Scheme 3. Preparation and ozone oxidation of chiral silylalkene 2.
migrating silyl groups were bulky. However, the diastereoselec-
tivity of the reactions, which is our main concern, was poor
(
54–64% d.r.).
Scheme 5. Preparation and ozone oxidation of 6, followed by transformation
to acyloin 9.
Because of these disappointing results, we recognized the
need to redesign the chiral auxiliary. After several attempts, we
found that the novel C -symmetrical dialkoxysilyl group A is
2
suitable for this purpose and that it can be easily introduced
With this promising result in hand, we focused on the influ-
ence of the structure of the dialkoxysilyl group A on the ste-
reoselectivity. The stereoselectivity was slightly improved by
the use of 5ba (R=3,5-xylyl) as the dialkoxyhydrosilane: the
oxidation of 6ba afforded (R)-7ba in 76% d.r. The highest ste-
reoselectivity was obtained by the use of 5bb having bulky R
and R’ groups: the oxidation of 6bb afforded (R)-7bb in 94%
d.r. Interestingly, the dialkoxysilane with a benzyl group as R
provided the opposite stereoselectivity: the oxidation of 6ca
afforded (S)-7ca in 91% d.r.
into alkynes by hydrosilylation with dialkoxyhydrosilane 5 pre-
pared
from
a,a,a’,a’-tetraaryl-1,3-dioxolan-4,5-dimethanol
[
9]
[10,11]
(TADDOL; 4) and R’SiCl H, in excellent yield (Scheme 4).
2
Notably, compound 5 is stable under the standard operation
conditions, including purification by silica-gel chromatography.
In particular, 5aa (R=Ph, R’=Me) has good crystallinity and
hence can be purified by recrystallization.
To gain insight into the observed stereoselectivity, we com-
puted the transition states for the 1,3-dipolar cycloaddition of
ozone with a simplified silylalkene 6d at the RHF/6-31G(d)
level of theory, in which the conformation of 5aa in the crys-
talline state, revealed by the X-ray crystallographic analysis,
was used for the initial conformation of the dialkoxysilyl group
[18,19]
of 6d (Figure 1).
Assuming that the ozone accesses the
alkene moiety from the opposite side of the methyl group on
silicon to avoid steric repulsion, we estimated four types of
transition states TS1–TS4 with differences in the Re/Si face se-
lection and endo/exo modes in 1,3-dipolar cycloaddition. The
calculation results showed that TS1, in which ozone reacts
with the alkene moiety from the Re-face in the endo-cyclization
mode to form a silylperoxide with R configuration at the car-
bonyl a-position, is the most favorable. Although the calcula-
tion level is too low to discuss the result in detail, the models
seem to adequately show the effect of the asymmetric envi-
Scheme 4. Preparation of hydrosilane 5.
The hydrosilylation of 5 and 4-octyne in the presence of 1,3-
divinyl-1,1,3,3-tetramethyldisiloxaneplatinum(0)—[Pt(dvds)]—
afforded 6aa–ca in good yields (83–89%) with excellent E se-
lectivities (>99% E) (Scheme 5). Ozone oxidation of silylal-
kenes 6 was performed by the above-mentioned standard pro-
cedure. The reaction of 6aa afforded the corresponding a-silyl-
peroxy ketone 7aa in 94% yield with good diastereoselectivity
[
12]
[20]
ronment created by the chiral silyl group A.
(
73% d.r.). The stereochemistry of the newly generated stereo-
The present asymmetric ozone oxidation has a broad sub-
strate scope. As shown in Scheme 6, the ozone oxidation of 3-
hexyne-, 2-butyne-1,4-diol-, and 6-phenyl-2-hexyn-1-ol-derived
silylalkenes (6e–6g, respectively) afforded the corresponding
a-silylperoxy ketones in 90 (78% d.r.), 85 (91% d.r.), and 86%
genic center of 7aa was determined to be R by transforming
the compound into a stereochemically defined acyloin 9a, as
follows. The reaction of 7aa with P(OMe) in tBuOH proceed-
ed to afford O-silylated acyloin 8aa in 69% yield.
tion of 8aa with tetra-n-butylammonium fluoride (TBAF) af-
forded (R)-9a in 60% yield without loss of enantiopurity along
[
13]
3
[
14,15]
The reac-
[21–23]
yield (89% d.r.), respectively.
Moreover, a similar reaction
of the cyclododecyne-derived cyclic silylalkene 6h proceeded
with good stereoselectivity (82% d.r.).
[
16,17]
with a good deal of TADDOL 4a.
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thesis, along with investigations of the synthetic applications
of the C -symmetrical dialkoxyhydrosilane, are in progress.
2
Acknowledgements
This research was supported by JSPS KAKENHI (grant numbers
24106734 and 24350048) and the MEXT Project of Integrated
Research on Chemical Synthesis. We thank Y. Tokito (Kyushu
Univ.) for assistance in the HRMS measurements.
Keywords: acyloin · alkenes · asymmetric oxidation · ozone ·
silylperoxide
[
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addition of ozone with alkenylsilane 6d. The relative zero-point vibrational
À1
energies in kcalmol
.
1
992, 114, 974–979.
[
7] Few examples of diastereoselective oxidation of alkenes into acyloin
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2
008, 683–686.
[
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[
[
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Scheme 6. Scope and limitation of asymmetric ozone oxidation.
In conclusion, we have developed an unprecedented asym-
metric ozone oxidation of silylalkenes by using a C -symmetri-
2
[
[
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1
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Chem. Eur. J. 2014, 20, 1 – 5
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[
14] Reduction of silylperoxides with phosphite esters would remove the
oxygen adjacent to the silicon as well as with phosphines, thus the
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the reduction with phosphite esters.
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[19] Selected crystallographic data of 5aa and 6ca are described in Sup-
porting Information. CCDC-995038 (5aa) and 995039 (6ca) contain the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
[
[
[
16] Enantiopurity of 9a was determined by GLC analysis, see Supporting In-
formation for details.
[
20] Although the reason for the change in diastereoselectivity when using
a Bn-substituted system has not been clarified, the X-ray crystallograph-
ic analysis of 5aa and 6ca show a substantial difference in the confor-
mation of the dialkoxysilyl group A, see Supporting Information.
21] Silylalkene 6g was prepared by regioselective hydrosilylation using the
dimethylvinylsilyl group as a directing group: Y. Kawasaki, Y. Ishikawa,
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from 6e and 6 f were determined to R at the carbonyl a-position by
derivatization to authentic samples, see Supporting Information for the
details.
17] Hydrogenation of silylperoxides 7 using transition metal catalysts di-
rectly affords acyloins 9, but with loss of stereopurity. Mechanistic stud-
ies for the epimerization are now underway.
[
[
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Received: April 8, 2014
Published online on && &&, 0000
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COMMUNICATION
&
Asymmetric Oxidation
K. Igawa, Y. Kawasaki, K. Nishino,
N. Mitsuda, K. Tomooka*
&& – &&
Asymmetric Ozone Oxidation of
Putting ozone to work: Ozone oxida-
tion of chiral alkenylsilanes prepared
from alkynes and a newly designed
chiral hydrosilane affords silylperoxides
with high diastereoselectivity (up to
94% d.r.; see scheme). The silylperox-
ides are convertible into enantioen-
riched chiral acyloins in a stereospecific
manner.
Silylalkene Using a C -Symmetrical
2
Dialkoxysilyl Group as a Chiral
Auxiliary
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These are not the final page numbers! ÞÞ