Ozone Oxidation of Silylalkene: Mechanistic Study and Application for the Synthesis of Silacarboxylic Acid Derivatives

Article abstract of DOI:10.1021/acs.joc.9b03350

The addition-type ozone oxidation of silylalkenes is a highly efficient reaction to provide synthetically versatile α-silylperoxy carbonyl compounds. To gain insight into the reaction mechanism, we performed a computational study, which revealed that the

Full text of DOI:10.1021/acs.joc.9b03350

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Ozone Oxidation of Silylalkene: Mechanistic Study and Application
for the Synthesis of Silacarboxylic Acid Derivatives
Kazunobu Igawa, Yuuya Kawasaki, Sora Nozaki, Naoto Kokan, and Katsuhiko Tomooka*
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ABSTRACT: The addition-type ozone oxidation of silylalkenes is a highly
efficient reaction to provide synthetically versatile α-silylperoxy carbonyl
compounds. To gain insight into the reaction mechanism, we performed a
computational study, which revealed that the reaction proceeds via [1,2]-
Brook rearrangement-type silyl migration of primary ozonide. In sharp
contrast to the addition-type reactions, the ozone oxidation of α-
alkoxysilylalkenes proceeds in a cleavage-type manner to afford excellent
yields of silacarboxylic acid esters via the 1,3-cycloelimination of primary
ozonide prior to 1,2-silyl migration.
silylperoxy carbonyl compound 2a is the primary product.
However, 2a is too unstable to be isolated; thus, it is difficult to
clarify the reaction mechanism.4,5
In 2006, we explored this reaction during our study on
silylalkenes, finding that the ozone oxidation of alkenes 1 with
sterically hindered silyl groups, such as SiEt3, Sii-Pr3, and Sit-
BuPh2, provides easily isolable α-silylperoxy carbonyl com-
pounds 2 (Scheme 1).6−8
INTRODUCTION
The oxidative cleavage of the carbon−carbon double bond of
alkenes using ozone, namely, “ozonolysis” (eq 1),1 is one of the
■
We coined this reaction “addition-type ozone oxidation” and
speculated that it proceeds via the 1,3-silyl migration of POZ.
α-Silylperoxy carbonyl compounds 2 are quite unique
functionalized silylperoxide derivatives9 and versatile precur-
sors for a variety of oxygen-functionalized compounds:
hydrogenation with Pd/C or phosphite ester reduction of 2
gives acyloin 3 and O-silyl acyloin 4,10 respectively; reduction
with L-selectride occurs at the carbonyl group in 2 with high
diastereoselectivity, giving α-silylperoxy alcohol (R*,R*)-5,
with the silylperoxy group being intact.11 The silylperoxyme-
thine group in 2 can be converted into a carbonyl group via the
β-elimination of the siloxy group by treatment with an amine
base to afford 1,2-diketone 6.
most famous textbook oxidation reactions to be widely utilized
as a highly reliable transformation. Bond dissociation during
ozonolysis proceeds via the 1,3-dipolar cycloaddition of ozone
to an alkene followed by the ozonide rearrangement of the
primary ozonide (POZ) to the thermodynamically stable
secondary ozonide (SOZ).2
However, depending on the reaction conditions and the
structure of the alkene, a different type of oxidationthe so-
called “anomalous ozone oxidation”can often occur.1b For
Furthermore, we have investigated and developed efficient
methods for the preparation of silylalkenes to facilitate
addition-type ozone oxidation: (i) hydroalumination of γ-silyl
propargylic alcohols 7 with aluminum hydride reagents
example, Buchi and Wuest (1978) reported on the ozone
̈ ̈
oxidation of trimethylsilyl (TMS)-substituted alkenes 1a,
resulting in acyloins 3 (eq 2).3 They assumed that α-
Received: December 13, 2019
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© XXXX American Chemical Society
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Scheme 1. Synthesis and Transformation of α-Silylperoxy
a
Carbonyl Compounds
To gain insight into the reaction mechanism, we performed
a computational study using a combination of the density
functional theory (DFT) and CBS-Q methods.15 These
calculations reveal that the key to this reaction is the [1,2]-
Brook rearrangement-type silyl migration of POZ, promoted
by the high oxophilicity of silicon [eq 7, path a (X = R2)].
a
Reagents: (a) H2, Pd/C; (b) P(OMe)3; (c) L-selectride; (d) Et3N.
(MAlH2L2) providing γ-silyl allylic alcohols 1b (eq 3),12 which
can be converted into α-silylperoxy aldehydes 2b by ozone
Interestingly enough, the calculations suggest that the geminal
alkoxyl group (X = OR3) of silylalkenes switches the reaction
course of ozone oxidation from addition-type to cleavage-type
(eq 7, path b), which provides silacarboxylic acid esters 10 (R3
= alkyl) that have been synthesized by quite limited
approaches. The details of the computational study, along
with the efficient synthesis of a variety of silacarboxylic acid 11
(R3 = H) and its ester 10, are provided below.
oxidation with excellent yields and (ii) hydrosilylation of the
dimethylvinylsilyl group attached to unsymmetrical internal
alkynes 8 with a Pt(0) catalyst providing silylalkenes 1c with
high proximal selectivity (eq 4).13 A variety of α-silylperoxy
hydroxyketones 2c were obtained by ozone oxidation of 1c.
RESULTS AND DISCUSSION
■
Computational Study. In this study, the reaction of
trimethylsilylethylene with ozone was used as a simplified
model.16 At the outset, we attempted the 1,3-dipolar
cycloaddition of silylalkenes and ozone, which is the first
step in standard ozonolysis (Figure 1). The transition-state
Addition-type ozone oxidation is applicable to asymmetric
synthesis: (i) ozone oxidation of silylalkenes 1d with a C2-
symmetric chiral auxiliary on a silicon atom gives α-silylperoxy
ketones 2d (up to 94% diastereomeric purity) (eq 5),7a−c
Figure 1. Reaction surface of the 1,3-dipolar cycloaddition of
silylalkenes and ozone with relative zero-point vibrational energies
from i in kcal·mol−1.
which are convertible into enantioenriched acyloin 3, (ii)
ozone oxidation of optically active alkenylsilanes 1e with an
asymmetric silicon atom gives enantioenriched α-silylperoxy
ketones 2e, with the retention of configuration on the silicon
atom (eq 6).14 β-Elimination of 2e gives chiral silanols 9 in an
enantioenriched form.
The aforementioned successful results encourage us to
disclose the detailed reaction mechanism of this addition-type
ozone oxidation of silylalkenes.
structure of the 1,3-dipolar cycloaddition TS1 was calculated
using DFT at the B3LYP/6-311+G(2d,2p) level of theory
followed by the intrinsic reaction coordinate (IRC) calculation
to generate the starting reactant complex i and the product
POZ ii. All of the obtained geometries of the local minimum
states on the potential energy surface and transition states were
optimized with CBS-Q; the CBS-Q energies thus obtained
were used for evaluation. These calculations show that the
energy barrier of the 1,3-dipolar cycloaddition is only 1.1 kcal·
B
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mol−1, and POZ ii is produced with 53.4 kcal·mol−1 of
exothermic heat. To gain information about the driving force
of the 1,3-silyl migration of ii, we performed a natural bond
orbital calculation of ii to analyze the charge distribution at the
B3LYP/6-311+G(2d,2p) level of theory that shows that the
2,4-oxygen atoms have large negative charges (−0.30 and
−0.30) and the silicon atom has a large positive charge
(+1.62). Based on the calculation results, we estimate that the
1,2-silyl migration from 1-carbon to anionic 2-oxygen, namely
the [1,2]-Brook rearrangement-type reaction,17 is prompted by
their electrostatic interaction.
The IRC calculation of TS2 was performed at the B3LYP/6-
311+G(2d,2p) level of theory to gain insight into the reaction
process and products (Figure 3). Reasonably enough,
silylperoxide v was produced from TS2 via 1,2-silyl migration
to form a zwitterionic geometry iii, with silyloxonium and
peroxide anion moieties, followed by a nucleophilic attack of
the peroxide anion toward the silicon atom, as shown with
typified geometry iv without a saddle point. This calculation
reveals that the addition-type ozone oxidation of silylalkenes
proceeds via the [1,2]-Brook rearrangement-type silyl migra-
tion of POZ.
DFT calculations were performed for 1,2-silyl migration and
for the transition-state geometries of the 1,3-dipolar cyclo-
elimination affording SOZ. With regard to the 1,3-dipolar
cycloelimination, four types of transition states were assumed
from the positions of the cleavage bonds and the configuration
of the generated carbonyl oxide moiety. These calculations
afforded the transition-state geometries TS2−TS6 having sole
proper imaginary vibration in the frequency calculation (Figure
2); the geometries of TS2−TS6 were optimized and analyzed
Further computational investigation suggests an interesting
substituent effect: an alkoxy group will lead to cleavage-type
ozone oxidation, namely “normal ozonolysis”. For example, the
transition-state geometries TS7 and TS8 of 1,2-silyl migration
and 1,3-dipolar cycloelimination from the methoxy group-
substituted POZ vi show that the energy barrier of TS7 is 8.9
kcal·mol−1 higher than that of TS8 (Scheme 2), providing
formaldehyde oxide (viii) and silacarboxylic acid ester ix as the
primary products.18,19
Scheme 2. Rearrangement of the POZ of α-Alkoxy
Silylalkene
a
Relative zero-point vibrational energies from vi (from TS8 in
parentheses) in kcal·mol−1.
On the basis of these calculation results, we envision that the
ozone oxidation of α-alkoxysilylalkenes A followed by the
reduction of the resulting SOZ will be applicable to the
synthesis of silacarboxylic acids B (Scheme 3),20 and we were
especially interested in the synthesis of enantioenriched B
having an asymmetric silicon atom and its ester derivatives
B′,21 which are the silicon congeners of chiral carbon
carboxylic acid C and its ester derivatives C′.
Figure 2. Optimized geometries of TS2−TS6 with relative zero-point
vibrational energies from ii in kcal·mol−1.
by the CBS-Q method. The results show that the energy
barrier of 1,3-dipolar cycloelimination TS3−TS6 (relative
energy barriers from POZ ii: 11.5−14.7 kcal·mol−1) is higher
than that of 1,2-silyl migration TS2 (7.3 kcal·mol−1).
Figure 3. Reaction surface over the entire reaction pathway of the addition-type ozone oxidation with relative zero-point vibrational energies from i
(from ii in parentheses) in kcal·mol−1.
C
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Scheme 3. New Synthetic Approach for Enantioenriched
Chiral Silacarboxylic Acid and Its Ester Derivatives with
Ozone Oxidation
yields (Scheme 4) (83−90%), and no silylperoxy ester 2f was
observed.
Scheme 4. Ozone Oxidation of α-Alkoxysilylalkenes
There is no need to say that C and C′ are the important
components of bioactive compounds, asymmetric reagents,
and functional materials. Interestingly, B, B′ and C, C′ show
considerably different physical and chemical properties. For
example, C is easily convertible to C′ under acidic conditions
by nucleophilic acyl substitution (eq 8). However, B shows
However, the conversion of 10a−d to the corresponding
silacarboxylic acids is difficult under acidic and basic conditions
owing to the electrophilicity of the silicon atom (vide supra).
To overcome this problem, we designed a siloxy group-
substituted silylalkene as the substrate, which would provide an
easily hydrolyzable silyl silacarboxylic acid ester by ozone
oxidation. After several attempts, we found that the ozone
oxidation of trimethylsiloxysilylalkene 1gd successfully af-
forded silacarboxylic acid 11d in 77% yield,25 with the removal
of the TMS group by hydrolysis with silica gel treatment (eq
11). It is worth noting that the ozone oxidation of optically
higher electrophilicity at the silicon atom than the acyl group;
thus, the reaction with a nucleophile, for example, ROH,
mainly proceeds with substitution at the silicon atom along
with decarbonylation to provide D (eq 9).21−23 Therefore,
active (S)-1ge (>99% ee) produced silacarboxylic acid (S)-11e
(>99% ee) without the loss of enantiopurity (eq 12), as we
further understanding of the characteristics and development
of synthetic approaches for chiral silacarboxylic acids B and its
ester derivatives B′ are required for their application as a new
class of bioactive compounds, asymmetric reagents, and
functional materials.24 However, only one synthetic approach
for B has been developed from sterically labile enantioenriched
chiral silyl lithium E and carbon dioxide so far.21
Synthetic Applications of Ozone Oxidation for
Silacarboxylic Acid and Its Ester Derivatives. At the
outset, we attempted the ozone oxidation of silylalkenes with
an aliphatic alkoxy group. α-n-Butoxysilylalkenes 1fa−fd were
prepared from vinyllithium 12 and commercially available
chlorosilanes 13a−d in good-to-excellent yields (eq 10) (61−
96%).
expected. This new approach is potentially useful for the
synthesis of more functionalized silacarboxylic acids and their
derivatives, including chiral enantioenriched systems with an
asymmetric silicon atom.26
CONCLUSIONS
■
In summary, we have described the chemistry of ozone
oxidation of silylalkenes from the viewpoints of synthetic study
of oxygen-functionalized compounds and the mechanistic
study using computational investigation, which reveals that
the addition-type reaction providing α-silylperoxy carbonyl
As we expected, ozone oxidations of α-n-butoxysilylalkenes
1fa−fd in AcOEt at −78 °C with a reductive workup using
PPh3 produced silacarboxylic acid esters 10a−d in excellent
D
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δ 166.5, 95.6, 65.7, 31.4, 19.7, 18.7, 14.0, 10.7. IR (neat, cm−1): 2867,
1580, 1465, 1207, 1019, 884, 822, 680. HRMS (EI, positive): exact
mass calcd for C15H32OSi [M]+, required m/z: 256.2222; found m/z:
256.2221.
compounds proceeds via the [1,2]-Brook rearrangement-type
silyl migration of POZ following the 1,3-dipolar cycloaddition
with ozone. The possibility of the cleavage-type ozone
oxidation of α-alkoxysilylalkene was estimated in the computa-
tional study, which realized a new approach to silacarboxylic
acids and their esters. Further studies on the synthetic
applications of these two types of ozone oxidation of
silylalkenes are now underway by our group.
1-Butoxy-1-methyldiphenylsilylethylene (1fc). The reaction
of diphenylmethylsilyl chloride (83.9 μL, 0.400 mmol) and (1-
butoxyvinyl)lithium (0.82 M in pentane/THF, 1.5 mL, 1.2 mmol)
according to the general procedure afforded 112 mg (95%) of 1fc as a
1
colorless oil. H NMR (300 MHz, CDCl3): δ 7.61−7.58 (m, 4H),
7.43−7.33 (m, 6H), 4.82 (d, J = 1.8 Hz, 1H), 4.37 (d, J = 1.8 Hz,
1H), 3.74 (t, J = 6.3 Hz, 2H), 1.66 (tt, J = 6.3, 6.3 Hz, 2H), 1.39 (tq, J
= 7.5, 6.3 Hz, 2H), 0.91 (t, J = 7.5 Hz, 3H), 0.68 (s, 3H). 13C NMR
(75 MHz, CDCl3): δ 166.7, 135.5, 135.2, 129.5, 127.8, 97.7, 66.7,
31.1, 19.5, 13.9, −4.5. IR (neat, cm−1): 2959, 1582, 1429, 1214, 1113,
1029, 793, 698. HRMS (EI, positive): exact mass calcd for C19H24OSi
[M]+, required m/z: 296.1596; found m/z: 296.1596.
EXPERIMENTAL SECTION
■
General Methods. All reactions were carried out in heat gun-
dried glassware under an argon atmosphere unless otherwise noted.
Dry tetrahydrofuran (THF) and AcOEt were purchased from Kanto
1
Chemical Co., Inc. and used without further purification. H nuclear
magnetic resonance (NMR) and 13C NMR spectra were recorded on
a Varian Mercury (1H: 300 MHz, 13C: 75 MHz) at ambient
temperature using CDCl3 as solvents. Chemical shifts (δ) in parts per
million were referenced to the solvent residual peak as an internal
1-Butoxy-1-t-butyldiphenylsilylethylene (1fd). The reaction
of t-butyldiphenylsilyl chloride (93.5 μL, 0.360 mmol) and (1-
butoxyvinyl)lithium (0.82 M in pentane/THF, 1.3 mL, 0.72 mmol)
according to the general procedure afforded 81.2 mg (66%) of 1fd as
1
standard: CHCl3 for H NMR (δ 7.26) and CDCl3 for 13C NMR (δ
1
a colorless oil. H NMR (300 MHz, CDCl3): δ 7.74−7.61 (m, 4H),
77.1). The peak multiplicities were given as follows: s, singlet; d,
doublet; q, quartet; quin, quintet; m, multiplet; br, broad. Infrared
spectra were recorded on a Fourier-transform infrared spectropho-
tometer (PerkinElmer SpectrumOne) as a neat liquid on NaCl plates.
High-performance liquid chromatography was performed on JASCO
CD-2095 and MD-2018 detectors equipped with a JASCO PU-2089
using Daicel CHIRALPAK IC column (0.46 cm × 25 cm),
CHIRALCEL OJ-RH column (0.46 cm × 25 cm), and CHIRALPAK
IC column (2.0 cm × 25 cm). Analytical thin-layer chromatography
was carried out on silica gel 60 F254 (Merck 5715) plates, and the
developed plates were visualized under UV light (254 nm) and by
heating on a hot plate after staining with a 4% solution of
phosphomolybdic acid in ethanol or a 2.5% solution of p-anisaldehyde
in ethanol. Column chromatography was performed using Fuji Silysia
silica gel FL100D (neutral). High-resolution mass spectrometry
(HRMS) analyses were performed at the Analytical Center in IMCE,
Kyushu University.
Preparation of (1-Butoxyvinyl)lithium (0.82 M in Pentane/
THF). To a solution of 1-butyl vinyl ether (800 μL, 6.20 mmol) in
THF (1.7 mL) was added t-BuLi (1.64 M in pentane, 2.50 mL, 4.10
mmol) at −78 °C and stirred at that temperature for 1 h. The reaction
mixture was allowed to warm to 0 °C. The thus obtained (1-
butoxyvinyl)lithium (0.82 M in pentane/THF) was stored in a
refrigerator and used in a week.
7.48−7.33 (m, 6H), 4.87 (d, J = 1.8 Hz, 1H), 4.19 (d, J = 1.8 Hz,
1H), 3.79 (t, J = 6.6 Hz, 2H), 1.75 (tt, J = 8.1, 6.6 Hz, 2H), 1.49 (tq, J
= 8.1, 6.9 Hz, 2H), 0.97 (t, J = 6.9 Hz, 3H). 13C NMR (75 MHz,
CDCl3): δ 166.8, 136.4, 134.2, 129.3, 127.6, 99.8, 66.6, 31.4, 28.3,
19.7, 18.2, 13.9. IR (neat, cm−1): 2960, 1581, 1428, 1211, 1108, 822,
700. HRMS (EI, positive): exact mass calcd for C22H30OSi [M]+,
required m/z: 338.2066; found m/z: 338.2065.
n-Butyl Triphenylsilanecarboxylate (10a): General Proce-
dure for Ozonolysis of α-Alkoxysilylalkene. A stream of ozone
(1.2 v/v % in oxygen, 150 mL/min) was bubbled through a solution
of 1fa (35.9 mg, 0.100 mmol) in AcOEt (5 mL) at −78 °C. After
stirring for 40 min at that temperature, the solution turned pale blue,
indicating the completion of oxidation. The dissolved ozone was
removed by bubbling argon through the solution for 10 min, and then
triphenylphosphine (132 mg, 0.500 mmol) was added to the reaction
mixture followed by allowing the temperature to rise to ambient
temperature. After the solvent was removed under reduced pressure,
the residue was purified by silica gel chromatography (hexane/Et2O =
1
50/1) to afford 32.3 mg (90%) of 10a as a colorless oil. H NMR
(300 MHz, CDCl3): δ 7.68−7.56 (m, 6H), 7.50−7.34 (m, 9H), 4.22
(t, J = 6.6 Hz, 2H), 1.60 (tt, J = 7.8, 6.6 Hz, 2H), 1.32 (tq, J = 7.8, 7.5
Hz, 2H), 1.19 (s, 9H), 0.88 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz,
CDCl3): δ 183.6, 136.2, 130.9, 130.5, 128.1, 62.6, 30.9, 19.3, 13.7. IR
(neat, cm−1): 2959, 1678, 1429, 1114, 740, 698. HRMS (FAB, matrix;
3-nitrobenzyl alcohol, positive): exact mass calcd for C23H25O2Si [M
+ H]+, required m/z: 361.1624; found m/z: 361.1621.
1-Butoxy-1-triphenylsilylethylene 1fa: General Procedure
for Preparation of α-Alkoxysilylalkene. To a solution of
triphenylsilyl chloride (118 mg, 0.400 mmol) in THF (1 mL) was
added (1-butoxyvinyl)lithium (0.82 M in pentane/THF, 1.5 mL, 1.2
mmol) at 0 °C. After the solution was stirred at ambient temperature
for 24 h, the reaction was quenched with 1 M aq NaOH and extracted
with hexane. The combined organic phase was washed with brine,
dried over Na2SO4, filtered, and the solvent was removed under
reduced pressure. The residue was purified by silica gel chromatog-
raphy (hexane/Et2O = 50:1) to afford 89.7 mg (61%) of 1fa as a
n-Butyl Triisopropylsilanecarboxylate (10b). The ozonolysis
of 1fb (25.7 mg, 0.100 mmol) according to the general procedure
afforded 22.2 mg (83%) of 10b as a colorless oil. 1H NMR (300 MHz,
CDCl3): δ 4.10 (t, J = 6.3 Hz, 2H), 1.61 (tt, J = 6.3, 6.3 Hz, 2H), 1.40
(tq, J = 6.9, 6.3 Hz, 2H), 1.29−1.20 (m, 3H), 1.11 (d, J = 6.9 Hz,
18H), 0.93 (t, J = 6.9 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 185.7,
61.1, 31.1, 19.5, 18.4, 13.8, 10.7. IR (neat, cm−1): 2946, 2869, 1676,
1465, 884, 687. HRMS (EI, positive): exact mass calcd for
C14H30O2Si [M]+, required m/z: 258.2015; found m/z: 258.2015.
n-Butyl Methyldiphenylsilanecarboxylate (10c). The ozonol-
ysis of 1fc (29.7 mg, 0.100 mmol) according to the general procedure
afforded 25.5 mg (86%) of 10c as a colorless oil. 1H NMR (300 MHz,
CDCl3): δ 7.68−7.64 (m, 4H), 7.48−7.36 (m, 6H), 4.16 (t, J = 6.6
Hz, 2H), 1.62 (tt, J = 6.6, 6.6 Hz, 2H), 1.35(tq, J = 7.5, 6.6, Hz, 2H),
0.90 (t, J = 7.5 Hz, 3H), 0.82 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
184.7, 135.0, 132.4, 130.3, 128.1, 62.3, 30.9, 19.3, 13.8, −5.0. IR
(neat, cm−1): 2960, 1677, 1429, 1143, 797, 731, 698. HRMS (FAB,
matrix; 3-nitrobenzyl alcohol, positive): exact mass calcd for
C18H23O2Si [M + H]+, required m/z: 299.1467; found m/z:
299.1468.
1
colorless oil. H NMR (300 MHz, CDCl3): δ 7.62−7.59 (m, 6H),
7.45−7.33 (m, 9H), 4.95 (d, J = 1.8 Hz, 1H), 4.39 (d, J = 1.8 Hz,
1H), 3.80 (t, J = 6.6 Hz, 2H), 1.68 (tt, J = 6.6, 6.3 Hz, 2H), 1.37 (tq, J
= 7.5, 6.3 Hz, 2H), 0.90 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz,
CDCl3): δ 165.6, 136.3, 133.6, 129.7, 127.8, 100.1, 67.0, 31.2, 19.5,
13.9. IR (neat, cm−1): 2959, 1582, 1428, 1214, 1111, 1029, 834, 698.
HRMS (EI, positive): exact mass calcd for C24H26OSi [M]+, required
m/z: 358.1753; found m/z: 358.1751.
1-Butoxy-1-triisopropylsilylethylene (1fb). The reaction of
triisopropylsilyl chloride (84.7 μL, 0.400 mmol) and (1-butoxyvinyl)
lithium (0.82 M in pentane/THF, 1.5 mL, 1.2 mmol) according to
the general procedure afforded 98.2 mg (96%) of 1fb as a colorless
oil. 1H NMR (300 MHz, CDCl3): δ 4.69 (d, J = 1.8 Hz, 1H), 4.25 (d,
J = 1.8 Hz, 1H), 3.61 (t, J = 6.3 Hz, 2H), 1.63 (tt, J = 6.3, 6.3 Hz,
2H), 1.42 (tq, J = 6.9, 6.3 Hz, 2H), 1.22−1.11 (m, 3H), 1.07 (d, J =
5.7 Hz, 18H), 0.93 (t, J = 6.9 Hz, 3H). 13C NMR (75 MHz, CDCl3):
n-Butyl t-Butyldiphenylsilanecarboxylate (10d). The ozonol-
ysis of 1fd (31.0 mg, 91.6 μmol) according to the general procedure
afforded 27.5 mg (88%) of 10d as a colorless oil. 1H NMR (300 MHz,
E
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CDCl3): δ 7.73−7.67 (m, 4H), 7.49−7.33 (m, 6H), 4.21 (t, J = 6.6
Hz, 2H), 1.62 (tt, J = 7.8, 6.6 Hz, 2H), 1.36 (tq, J = 7.8, 7.5 Hz, 2H),
1.19 (s, 9H), 0.91 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ
184.1, 136.2, 131.3, 130.0, 127.9, 62.2, 30.9, 27.5, 19.4, 18.4, 13.8. IR
(neat, cm−1): 2960, 1675, 1472, 1428, 1139, 740, 699. HRMS (FAB,
matrix; 3-nitrobenzyl alcohol, positive): exact mass calcd for
C21H29O2Si [M + H]+, required m/z: 341.1937; found m/z:
341.1939.
Naoto Kokan − Institute for Materials Chemistry and
Engineering, IRCCS, Kyushu University, Kasuga, Fukuoka 816-
8580, Japan
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.9b03350
Notes
t-Butyldiphenylsilanecarboxylic Acid (11d). A stream of
ozone (1.2 v/v % in oxygen, 150 mL/min) was bubbled through
the solution of 1gd (20.5 mg, 57.8 μmol) in AcOEt (5 mL) at −78
°C. After being stirred at that temperature for 25 min, the solution
turned pale blue, indicating the completion of oxidation. The
dissolved ozone was removed by bubbling of argon through the
solution for 10 min, and then triphenylphosphine (76.7 mg, 0.292
mmol) was added to the reaction mixture followed by allowing the
temperature to rise to ambient temperature. After the solvent was
removed under reduced pressure, the residue was dissolved in hexane
(5 mL), and silica gel (FL100D, 300 mg) was added to the reaction
mixture. After being stirred at ambient temperature for 30 min, the
silica gel was filtrated through a pat of Celite, and the solvent was
removed under reduced pressure. The residue was purified by silica
gel chromatography (hexane/Et2O = 10:1) to afford 77% of 11d as
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was supported by JSPS KAKENHI grants
JP17H06235 and JP18H04419 in Middle Molecular Strategy,
Integrated Research Consortium on Chemical Sciences, the
Cooperative Research Program of “Network Joint Research
Center for Materials and Devices,” Ube Industries Foundation,
and Kakihara Science Technology Foundation. The authors
thank N. Mitsuda for technical assistance and T. Nishi and S.
Yano (Kyushu Univ.) for assistance in the HRMS measure-
ments.
1
colorless crystals. The yield was determined by H NMR analysis by
REFERENCES
■
using bromoform as an internal standard. The spectroscopic analysis
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(S)-t-Butyl(methyl)(phenyl)silanecarboxylic Acid [(S)-11e].
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oil. The yield was determined by 1H NMR analysis by using
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obtained 11e showed identical spectra, as reported in the literature.21
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* Supporting Information
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The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.9b03350.
X-ray crystallographic data for compound s2:
CCDC1956315 (CIF)
Synthetic procedures and characterization data for
additional compounds (5a, 1gd, 1ge, and s2−4),
optimized geometries of CBS-Q calculations, and
NMR spectra for the reported products (PDF)
AUTHOR INFORMATION
■
Corresponding Author
̅
Omura, S.; Oguri, H. Design and De Novo Synthesis of 6-Aza-
artemisinins. Org. Lett. 2018, 20, 4667−4671.
Katsuhiko Tomooka − Institute for Materials Chemistry and
Engineering, IRCCS and Department of Molecular and
Material Sciences, Kyushu University, Kasuga, Fukuoka 816-
8580, Japan; orcid.org/0000-0002-0762-5746;
Email: ktomooka@cm.kyushu-u.ac.jp
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Authors
Kazunobu Igawa − Institute for Materials Chemistry and
Engineering, IRCCS and Department of Molecular and
Material Sciences, Kyushu University, Kasuga, Fukuoka 816-
8580, Japan; orcid.org/0000-0002-7354-5162
Yuuya Kawasaki − Institute for Materials Chemistry and
Engineering, IRCCS, Kyushu University, Kasuga, Fukuoka 816-
8580, Japan; orcid.org/0000-0003-3354-1690
Sora Nozaki − Department of Molecular and Material Sciences,
Kyushu University, Kasuga, Fukuoka 816-8580, Japan
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