Palladium-Catalyzed Aerobic Anti-Markovnikov Oxidation of Aliphatic Alkenes to Terminal Acetals

Article abstract of DOI:10.1021/acs.joc.8b02919

Terminal acetals were selectively synthesized from various unbiased aliphatic terminal alkenes and 1,2-, 1,3-, or 1,4-diols using a PdCl₂(MeCN)₂/CuCl catalyst system in the presence of p-toluquinone under 1 atm of O₂ and mild reaction conditions. The slow addition of terminal alkenes suppressed the isomerization to internal alkenes successfully. Electron-deficient cyclic alkenes, such as p-toluquinone, were key additives to enhance the catalytic activity and the anti-Markovnikov selectivity. The halogen groups in the alkenes were found to operate as directing groups, suppressing isomerization and increasing the selectivity efficiently.

Full text of DOI:10.1021/acs.joc.8b02919

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Article
Palladium-catalyzed Aerobic anti-Markovnikov
Oxidation of Aliphatic Alkenes to Terminal Acetals
Saki Komori, Yoshiko Yamaguchi, Yasutaka Kataoka, and Yasuyuki Ura
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02919 • Publication Date (Web): 21 Jan 2019
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Palladium-catalyzed Aerobic anti-Markovnikov Oxidation of Ali-
phatic Alkenes to Terminal Acetals
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Saki Komori, Yoshiko Yamaguchi, Yasutaka Kataoka, and Yasuyuki Ura*
Department of Chemistry, Biology, and Environmental Science, Faculty of Science, Nara Women’s University, Kitauoyani-
shi-machi, Nara 630-8506, Japan
ABSTRACT: Terminal acetals were selectively synthesized from various unbiased aliphatic terminal alkenes and 1,2-, 1,3-, or 1,4-
diols using a PdCl2(MeCN)2/CuCl catalyst system in the presence of p-toluquinone under 1 atm of O2 and mild reaction conditions.
The slow addition of terminal alkenes suppressed the isomerization to internal alkenes successfully. Electron-deficient cyclic alkenes,
such as p-toluquinone, were key additives to enhance the catalytic activity and the anti-Markovnikov selectivity. The halogen groups
in the alkenes were found to operate as directing groups, suppressing isomerization and increasing the selectivity efficiently.
Scheme 1. Markovnikov and anti-Markovnikov Oxidation
of Aliphatic Terminal Alkenes
INTRODUCTION
Realization of anti-Markovnikov selectivity in the oxidation of
terminal alkenes is challenging.1-3 Although ketones are typi-
cally obtained in palladium-catalyzed Wacker-type oxidation
(Scheme 1a), aldehydes can be formed preferentially from ter-
minal alkenes with oxygen or nitrogen directing groups1,4-8 and
vinylarenes.1-3,9-12 In the case of vinylarenes, iron-13,14 and ru-
thenium15,16-catalyzed reactions affording aldehydes have been
reported; these reactions proceed via a tandem epoxidation–
isomerization pathway. On the other hand, unbiased aliphatic
terminal alkenes (other than ethylene) are known to be difficult
to convert into aldehydes selectively.17-19 Grubbs et al. reported
anti-Markovnikov Wacker-type oxidation of the unbiased ali-
phatic alkenes using nitrite salts as co-catalysts under aerobic
conditions.20 Che et al. achieved iron porphyrin-catalyzed anti-
Markovnikov oxidation in the presence of iodosylbenzene as an
oxidant.14
The situation is similar in the formation of acetals, which are
protected compounds of aldehydes or ketones, from terminal al-
kenes. Alkenes with electron-deficient groups,21-25 alkenes with
oxygen, nitrogen, or sulfur directing groups,26-28 1,5-dienes,28
and vinylarenes21,28-32 are known to afford terminal acetals pref-
erentially by reactions with alcohols or diols, depending on the
reaction conditions; however, unbiased aliphatic alkenes nor-
mally afford Markovnikov products (internal acetals33-36 or ke-
tones19,21,30,34,37) and remain challenging substrates for anti-Mar-
kovnikov oxidation (Scheme 1a). Here we report the palladium-
catalyzed aerobic anti-Markovnikov oxidation of aliphatic al-
kenes to terminal acetals under mild reaction conditions
(Scheme 1b). The key features of this reaction include: 1) the
slow addition of alkenes, which can suppress the isomerization
of terminal alkenes into internal alkenes, 2) addition of electron-
deficient cyclic alkenes as auxiliary ligands, which enhance the
catalytic activity and anti-Markovnikov selectivity,9,29 and 3)
halogen groups in alkenes, which act as directing groups despite
their weakly coordinating ability, affording high anti-Markov-
nikov selectivity.
catalytic amounts of PdCl2(MeCN)2 (10 mol%) and CuCl (20
mol%) in t-BuOH at 40 °C under 1 atm of O2 (Table 1). Under
these conditions, terminal acetal 3aa was formed in only 8%
yield along with the formation of 2- and 3-octanones (entry 1).
Isomerization of 1a to 2-octenes was also observed during the
reaction (39%). The formation of 3-octanone would occur by
the Wacker-type oxidation of 2-octenes. Because the isomeri-
zation would be catalyzed by in situ formed Pd-H species, we
expected that, by maintaining the concentration of 1a at a low
level, the isomerization may be suppressed efficiently. When
slow addition of 1a to the reaction mixture by a syringe pump
(7 h) was performed, the formation of 2-octenes was suppressed
significantly (19%), and the yield of 3aa and anti-Markovnikov
selectivity were both increased (entry 2). The effect of electron-
deficient cyclic alkenes as additives was then examined (entries
3–15). We previously found that these alkenes can operate as
ligands to enhance the catalytic activity of the
RESULTS AND DISCUSSION
1-Octene (1a) and pinacol (2a, 3.0 equiv) were treated with
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Table 1. Optimization of Reaction Conditionsa Table 2. Scope of Aliphatic Alkenesa
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Yield of
Yield of
Selectiv-
ity (%)c
Entry
Additive
3aa (%)b
4a (%)b
Yield of 3 Yield of 4 Selectivity
Entry
1
Product
(%)b,c
(%)b
(%)d
1d
2
none
none
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25e
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33
18
70
53
60
33
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34
15
53
13
13
24
55
75
59
60
73
23
41
29
54
67
59
61
69
32
78
28
34
50
44
49
49
21
37
25
38
32
51
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25
47
5
3aa 53(37)
32
62
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3
maleic anhydride
maleimide
N-methylmaleimide
N-phenylmaleimide
BQf
4
2
3ba 55(47)
3ca 73(46)
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12
75
86
5
6
7
3e
8
ClBQ
9
2,6-Cl2BQ
Cl4BQ
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14
15h
16i
4
5f
6g
7f
3da 74(61)
3ea 77(60)
3fa 84(76)
3ga 86(75)
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8
75
91
97
92
MeOBQ
PhBQ
MeBQ
MeBQg
MeBQ
3
MeBQ
17i,j
MeBQ
7
a
Reaction conditions: 1a (0.50 mmol), 2a (1.50 mmol),
PdCl2(MeCN)2 (0.050 mmol), CuCl (0.10 mmol), additive (0.50
mmol), t-BuOH (2.0 mL), 40 °C, O2 (1 atm). 1a was added over
7 h by a syringe pump, and the reaction mixture was stirred for
an additional 1 h (8 h in total). b Determined by 1H NMR. c Se-
8
3ha 77(63)
3ia 40(33)
3ja 60(49)
3ka 56(52)
21
4
79
91
74
67
d
lectivity = 3aa/(3aa+4a). 1a was added at a time (without a
9g
syringe pump). e Total yield of 4a (11%) and 3-octanone (14%).
f BQ = p-benzoquinone. g 10 mol% of MeBQ (0.050 mmol) was
used. h t-AmylOH was used as a solvent. i Under Ar. j Without
CuCl.
10f
11e
21
27
anti-Markovnikov oxidation of vinylarenes to aldehydes9 and
terminal acetals29 under aerobic conditions. Maleic anhydride
and maleimides were found to increase both the yield of 3aa
and the selectivity (entries 3–6). p-Benzoquinone (BQ), which
is often used as an oxidant in Pd-catalyzed reactions, gave low
selectivity for the product (entry 7). Halogen substituted BQs
and MeOBQ were also inefficient (entries 8–11). On the other
hand, PhBQ and MeBQ gave higher yields of 3aa along with
moderate selectivity (entries 12 and 13). Reducing the loading
of MeBQ to 10 mol% was ineffective (entry 14). The use of t-
amylOH instead of t-BuOH as a solvent lowered the yield of
3aa and the selectivity (entry 15). Although the reaction pro-
ceeded even under an argon atmosphere (entry 16), the absence
of both O2 and CuCl resulted in low yield of 3aa (entry 17).
Thus, MeBQ also functioned as an oxidant, especially in the
presence of CuCl. Indeed, in entries 13 and 16, 30% and 58%
of MeBQ were converted into methyl-p-hydroquinone (MeHQ),
respectively, according to 1H NMR analysis.
12e,h
3la 66(60)
3ma 68(51)
18
12
79
85
13e,h
a
Reaction conditions:
1 (2.0 mmol), 2a (6.0 mmol),
PdCl2(MeCN)2 (0.20 mmol), CuCl (0.40 mmol), MeBQ (2.0
mmol), t-BuOH (8.0 mL), 40 °C, O2 (1 atm). 1 was added over 7
h by a syringe pump, and the reaction mixture was stirred for an
additional 1 h (8 h in total). b Determined by 1H NMR. c The val-
d
e
ues in parentheses are isolated yields. Selectivity = 3/(3+4).
For 12 h (slow addition 7 h + additional 5 h). f No slow addition,
for 3 h. g No slow addition, for 1 h. h Maleic anhydride was used
instead of MeBQ.
The optimized reaction conditions using MeBQ as an addi-
tive were then applied to various aliphatic terminal alkenes (Ta-
ble 2). By increasing the steric hindrance at the substituents, the
anti-Markovnikov selectivity increased (entries 2 and 3). 4-
Phenyl-1-butene also gave a good product yield with good se-
lectivity (entry 4). We found that linear alkenes with a chloro or
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bromo group at the terminal carbon afforded high yields of ter-
fluorine substituents, unlike the present reaction.38 Other al-
kenes with oxygen functional groups such as ethers (entries 10
and 11), carboxy groups (entry 12), and ester groups (entry 13)
also afforded moderate yields of the corresponding terminal ac-
etals with good to high selectivity.
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4
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minal acetals with high selectivity (entries 5–8). The carbon–
halogen bonds remained intact in these products. 4-Iodo-1-bu-
tene also gave the terminal acetal in high selectivity, albeit the
yield was low (entry 9). The low conversion of 4-iodo-1-butene
(47%) indicates that a side reaction such as carbon–iodine bond
cleavage occurred, deactivating the catalyst. In entries 5–7 and
9, the slow addition of alkenes was not necessary because the
isomerization of alkenes did not compete. As a control experi-
ment, 1-bromobutane (1.0 equiv) was used as another additive
for the reaction of 1-octene with pinacol to examine whether the
bromo group in haloalkane is also effective. However, almost
no improvement in the product yields (3aa: 53%, 4a: 29%) and
the selectivity (65%) was observed compared to those shown in
entry 1, Table 2. These results indicate that the halogen substit-
uents in the alkenes act as directing groups, even though they
are regarded as weakly coordinating ligands in general. We also
attempted terminal acetal formation from 4-bromo-1-butene
and pinacol (10 equiv) using a PdCl2(MeCN)2 (10 mol%)/BQ
(2.0 equiv, as an oxidant in this case)/DMF system (60 °C, 6 h),
which has been used for vinylarenes, allyl ethers, and 1,5-
dienes28; however, only 8% of 3fa and 2% of 4f were formed
(89% conversion). Thus, because there are only weakly coordi-
nating compounds in the present system (t-BuOH and pinacol
would not be so favorable as ligands due to steric repulsion
against other ligands on palladium), even halogen substituents,
which are small and have weak coordination ability, may be
able to coordinate to palladium. Related to the above results for
haloalkenes, allylic fluorides are known to afford -fluorinated
aldehydes in a PdCl2(PhCN)2/CuCl2/AgNO2 catalyst system,
although mechanistic investigations suggest that the anti-Mar-
kovnikov selectivity is attributed to the inductive effect of
By using 4-bromo-1-butene as a terminal alkene, the scope of
diols was then examined (Table 3). In the case of the primary
diol 2,2-dimethyl-1,3-propanediol, internal acetal 5fb was also
formed as a by-product in addition to terminal acetal 3fb and 4f,
resulting in decreased selectivity (entry 1). The relatively less
bulky primary diol can also operate as a nucleophile, resulting
in internal nucleophilic attack on the coordinated alkene (vide
infra). On the other hand, the tertiary diols afforded high prod-
uct yields with high selectivity (entries 2 and 3).
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The reaction of 4-bromo-1-butene with pinacol was moni-
tored by 1H NMR spectroscopy (Figure 1). CDCl3 was used as
a co-solvent (t-BuOH/CDCl3 = 1:1). We found that 3-bromobu-
tanal, 6f, an anti-Markovnikov Wacker-type oxidation product,
was formed as the main oxidized compound in the early stages,
and 6f appeared to be gradually converted into 3fa by reaction
with pinacol catalyzed by an in situ generated acid. Because no
induction period was observed in the formation of 3fa, an alter-
native direct conversion from 1f and pinacol to 3fa (which does
not go through 6f) seems to be a competing reaction.
Based on these experimental results, a proposed mechanism
for the formation of terminal acetals and ketones is shown in
Scheme 2. To the LPdCl2 species, terminal alkene 1 and MeBQ
coordinate to afford 7. Then, t-BuOH attacks the coordinated
alkene preferentially at the terminal carbon to afford alkyl pal-
ladate 8. Although electronic factors favor internal nucleophilic
attack, the steric repulsion between R and t-Bu groups facili-
tates terminal nucleophilic attack. Subsequent elimination of
HCl and -H elimination result in the formation of alkenyl t-
butyl ether 9, which is converted into terminal acetal 3 via alde-
hyde 6 or directly, catalyzed by an acid. If t-BuOH attacks the
internal carbon of the coordinated alkene in 7, ketone 4 is
formed via similar steps to those for the formation of 6. The
formed Pd-H species isomerizes the terminal alkene 1 into in-
ternal alkenes. The reduction of Pd(II) to Pd(0) with release of
HCl and the reoxidation of the Pd(0) species by CuCl2 repro-
duces the PdCl2 species, and the reduced CuCl is reoxidized to
CuCl2 by O2 and HCl. The Pd(0) species can be also reoxidized
to Pd(II) by MeBQ and HCl, especially in the presence of CuCl,
as observed in entry 16, Table 1. In the case of 4-bromo-1-bu-
tene, chelate coordination occurs and, thus, terminal nucleo-
philic attack is more favorable than internal nucleophilic attack
because of the formation of a stable five-membered ring after
the attack. The suppression of isomerization from the terminal
alkene into internal alkenes by Pd-H species can be also ration-
alized by chelate coordination (Scheme 3). Other haloalkenes
would also have similar chelate coordination effects. We pro-
pose that the electron-deficient cyclic alkenes such as MeBQ
coordinate to Pd to facilitate the nucleophilic attack and the re-
duction of Pd(II) to Pd(0), as well as the stabilization of Pd(0)
species, suppressing its deactivation to Pd black.9,29 As another
possibility, the catalytically active species may be Pd-Cu het-
erobimetallic complexes17,39-42 and the electron-deficient cyclic
alkenes may control the reactivity of the bimetallic complexes
through the coordination to Cu.
Table 3. Scope of Diolsa
Yield of 3 Yield of 5 Yield of 4f Selectivity
Entry
1
Product
(%)b,c
(%)b,c
(%)b
(%)d
59
28f
3fb
11
60
(46)e
(22)e
2g
3fc 90(66)
3fd 80(65)
0
0
0
2
>99
98
3h
a
Reaction conditions: 1f (2.0 mmol),
2 (6.0 mmol),
PdCl2(MeCN)2 (0.20 mmol), CuCl (0.40 mmol), MeBQ (2.0
mmol), t-BuOH (8.0 mL), 40 °C, O2 (1 atm), 8 h. b Determined
by 1H NMR. c The values in parentheses are isolated yields. d Se-
e
f
lectivity = 3/(3+5+4f). Isolated as a mixture of 3fb and 5fb.
The value was calculated from the NMR yield of 3fb and the ratio
of 3fb to 5fb in the isolated mixture. g For 28 h. h For 3 h.
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electron-deficient cyclic alkenes such as MeBQ enhanced the
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2
3
4
5
6
catalytic activity and the selectivity. Halogen groups at appro-
priate positions in the alkenes were found to operate as directing
groups to afford the corresponding terminal acetals in high yield
and selectivity. We believe that these findings would be helpful
for the further development of anti-Markovnikov Wacker-type
oxidation and related reactions of aliphatic terminal alkenes.
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EXPERIMENTAL SECTION
General Information. Unless otherwise indicated, all reac-
tions were performed under an oxygen atmosphere (1 atm).
PdCl2(MeCN)2,43 4-iodo-1-butene,44 5-hexenyl benzyl ether,45
9-decenyl benzyl ether45 and 5-hexenoic acid benzyl ester46
were prepared as described in the literature. t-BuOH was pur-
chased from Nacalai tesque Co. Ltd. and was purified by distil-
lation. Other chemicals were also commercially available and
were used without further purification. Flash column chroma-
tography was performed using silica gel SILICYCLE SiliaFlash
F60 (40–63 m, 230–400 mesh). NMR spectra were recorded
on a Bruker AV-300N (300 MHz (1H), 75 MHz (13C)) spec-
trometer or a JEOL JNM AL-400 (400 MHz (1H), 100 MHz
(13C)) spectrometer. Chemical shift values (σ) were expressed
relative to SiMe4. Infrared spectra were measured on a JASCO
FT/IR-6100 spectrophotometer. High-resolution mass spectra
were recorded on a JEOL JMS-T100LC spectrometer (ESI-
TOF MS) with positive ionization mode.
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Figure 1. Time course of the conversion of 1f into 3fa, 6f, and 4f.
Scheme 2. Proposed Mechanism
Synthesis of Terminal Acetals 3.
General Procedure for the Synthesis of 3. Method A: To a
reaction vessel, CuCl (39.6 mg, 0.40 mmol), PdCl2(MeCN)2
(51.9 mg, 0.20 mmol), MeBQ (244 mg, 2.0 mmol), and pinacol
(709 mg, 6.0 mmol) were added, and O2 was purged. To the
mixture, t-BuOH (8 mL) was added and the reaction mixture
was stirred at 40 ℃. Immediately, a terminal alkene (2.0 mmol)
was added slowly over 7 h by a syringe pump, and the reaction
mixture was stirred for an additional 1–5 h (8–12 h in total). The
solvent and volatile materials were evaporated under vacuum.
To the residue, dichloromethane (10 mL) and silica gel (2.5 g)
were added, and the solvent was evaporated to adsorb the resi-
due on the silica gel. Purification by silica gel column chroma-
tography (hexane/ethyl acetate = 20/1 with 1% triethylamine)
afforded the product as a pale yellow oil. Method B: This
method is similar to Method A. After the reaction completed,
the solvent and volatile materials were evaporated under vac-
uum. To the residue, a saturated aqueous NaHCO3 solution and
diethyl ether were added to extract. The aqueous layer was fur-
ther extracted with diethyl ether (twice). The combined organic
layer was washed with water and brine, and was dried over an-
hydrous sodium sulfate. After filtration, the solvent was evapo-
rated under vacuum. To the residue, dichloromethane (10 mL)
and silica gel (2.5 g) were added, and the solvent was evapo-
rated to adsorb the residue on the silica gel. Purification by sil-
ica gel column chromatography (hexane/ethyl acetate = 20/1
with 1% triethylamine) afforded the product as a pale yellow oil.
Method C: To a reaction vessel, CuCl (39.6 mg, 0.40 mmol),
PdCl2(MeCN)2 (51.9 mg, 0.20 mmol), MeBQ (244 mg, 2.0
mmol), and pinacol (709 mg, 6.0 mmol) were added, and O2
was purged. To the mixture, t-BuOH (8 mL) and a terminal al-
kene (2.0 mmol) were added and the reaction mixture was
stirred at 40 ℃ for 1–28 h. The solvent and volatile materials
were evaporated under vacuum. To the residue, dichloro-
methane (10 mL) and silica gel (2.5 g) were added, and the sol-
Scheme 3. Suppression of the Isomerization by Chelate Co-
ordination
CONCLUSION
We have developed a Pd-catalyzed aerobic anti-Markovnikov
oxidation of aliphatic alkenes to terminal acetals. The use of a
bulky nucleophile, t-BuOH, resulted in the anti-Markovnikov
selectivity. Slow addition of terminal alkenes efficiently sup-
pressed the isomerization into internal alkenes. The addition of
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vent was evaporated to adsorb the residue on the silica gel. Pu-
12H). 13C{1H} NMR (75 MHz, CDCl3) δ 100.5, 81.7, 35.4, 33.6,
32.7, 24.2, 23.2, 22.0. HRMS (ESI): m/z calcd for C11H20BrO2
[M-H]+ 263.0647, found 263.0637.
1
2
3
4
5
6
7
8
rification by silica gel column chromatography (hexane/ethyl
acetate = 20/1 with 1% triethylamine) afforded the product as a
pale yellow oil. Method D: This method is similar to Method
C. After the reaction completed, the solvent and volatile mate-
rials were evaporated under vacuum. To the residue, a saturated
aqueous NaHCO3 solution and diethyl ether were added to ex-
tract. The aqueous layer was further extracted with diethyl ether
(twice). The combined organic layer was washed with water
and brine, and was dried over anhydrous sodium sulfate. After
filtration, the solvent was evaporated under vacuum. To the res-
idue, dichloromethane (10 mL) and silica gel (2.5 g) were added,
and the solvent was evaporated to adsorb the residue on the sil-
ica gel. Purification by silica gel column chromatography (hex-
ane/ethyl acetate = 20/1 with 1% triethylamine) afforded the
product as a pale yellow oil.
2-(6-Bromohexyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3ha). Method A was applied (366 mg, 1.25 mmol, 63% yield).
1H NMR (300MHz, CDCl3) δ 5.02 (t, J = 5.1 Hz, 1H), 3.39 (t,
J = 6.9 Hz, 2H), 1.90–1.80 (m, 2H), 1.62–1.55 (m, 2H), 1.46–
1.35 (m, 6H), 1.19 (s, 12H). 13C{1H} NMR (75 MHz, CDCl3) δ
100.8, 81.6, 36.3, 33.9, 32.7, 28.7, 28.0, 24.2 (2C), 22.0. HRMS
(ESI): m/z calcd for C13H24BrO2 [M-H]+ 291.0960, found
291.0970.
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2-(3-Iodopropyl)-4,4,5,5-tetramethyl-1,3-dioxolane (3ia).
Method D was applied (196 mg, 0.66 mmol, 33% yield). The
spectral data for 3ia were in accordance with those reported in
the literature.47
2-(5-Benzyloxypentyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3ja). Method D was applied (299 mg, 0.97 mmol, 49% yield).
1H NMR (300 MHz, CDCl3) δ 7.30–7.17 (m, 5H), 4.96 (t, J =
5.1 Hz, 1H), 4.43 (s, 2H), 3.39 (t, J = 6.6 Hz, 2H), 1.59–1.50
(m, 4H), 1.37–1.32 (m, 4H), 1.13 (s, 12H). 13C{1H} NMR (75
MHz, CDCl3) δ 138.6, 128.3, 127.6, 127.4, 100.8, 81.5, 72.8,
70.3, 36.4, 29.7, 26.2, 24.3, 24.2, 22.0. HRMS (ESI): m/z calcd
for C19H30O3Na [M+Na]+ 329.2093, found 329.2076.
2-Heptyl-4,4,5,5-tetramethyl-1,3-dioxolane (3aa). Method
1
A was applied (0.17 g, 0.74 mmol, 37% yield). H NMR (300
MHz, CDCl3) δ 5.02 (t, J = 5.4 Hz, 1H), 1.61–1.54 (m, 2H),
1.40–1.27 (m, 10H), 1.19 (s, 12H), 0.87 (t, J = 6.9 Hz, 3H).
13C{1H} NMR (75 MHz, CDCl3) δ 101.0, 81.5, 36.5, 31.8, 29.6,
29.2, 24.5, 24.2, 22.6, 22.1, 14.1. HRMS (ESI): m/z calcd for
C14H27O2 [M-H]+ 227.2011, found 227.2019.
2-(3-Methylbutyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3ba). Method A was applied (0.19 g, 0.95 mmol, 47% yield).
1H NMR (300 MHz, CDCl3) δ 5.01 (t, J = 5.1 Hz, 1H), 1.61–
1.51 (m, 3H), 1.31–1.23 (m, 2H), 1.19 (s, 12H), 0.88 (d, J = 6.6
Hz, 6H). 13C{1H} NMR (75 MHz, CDCl3) δ 101.2, 81.5, 34.3,
33.4, 28.0, 24.2, 22.5, 22.1. HRMS (ESI): m/z calcd for
C12H23O2 [M-H]+ 199.1698, found 199.1691.
2-(9-Benzyloxynonyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3ka). Method B was applied (374 mg, 1.03 mmol, 52% yield).
1H NMR (300 MHz, CDCl3) δ 7.27–7.16 (m, 5H), 4.97 (t, J =
5.1 Hz, 1H), 4.43 (s, 2H), 3.39 (t, J = 6.6 Hz, 2H), 1.59–1.49
(m, 4H), 1.34–1.22 (m, 12H), 1.13 (s, 12H). 13C{1H} NMR (75
MHz, CDCl3) δ 138.5, 128.2, 127.4, 127.3, 100.8, 81.3, 72.7,
70.3, 36.3, 29.6, 29.5, 29.3 (3C), 26.0, 24.3, 24.1, 21.9. HRMS
(ESI): m/z calcd for C23H38O3Na [M+Na]+ 385.2719, found
385.2703.
2-(3,3-Dimethylbutyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3ca). Method A was applied (196 mg, 0.91 mmol, 46% yield).
1H NMR (300 MHz, CDCl3) δ 4.99 (t, J = 5.1 Hz, 1H), 1.60–
1.52 (m, 2H), 1.31–1.20 (m, 2H), 1.19 (s, 12H), 0.87 (s, 9H).
13C{1H} NMR (75 MHz, CDCl3) δ 101.7, 81.6, 38.3, 31.7, 30.0,
29.2, 24.2, 22.1. HRMS (ESI): m/z calcd for C13H25O2 [M-H]+
213.1855, found 213.1860.
2-(4-Carboxybutyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3la). Method B was applied. Maleic anhydride was used in-
stead of MeBQ as an additive. Water was used instead of a sat-
urated aqueous NaHCO3 solution for extraction. After filtration
of the drying agent, the solvent was evaporated and volatile ma-
terials were further removed under vacuum at 40 ℃ overnight
to afford 3la as a pale yellow oil (276 mg, 1.20 mmol, 60%
yield). 1H NMR (400 MHz, CDCl3) δ 11.42 (br, 1H), 5.00 (t, J
= 5.2 Hz, 1H), 2.32 (t, J = 7.6 Hz, 2H), 1.68–1.55 (m, 4H), 1.47–
1.38 (m, 2H), 1.16 (s, 12H). 13C{1H} NMR (75 MHz, CDCl3) δ
179.7, 100.5, 81.7, 35.9, 33.9, 24.6, 24.1, 23.9, 21.9. IR (neat)
ν 1710 cm-1 (C=O). HRMS (ESI): m/z calcd for C12H21O4 [M-
H]+ 229.1440, found 229.1431.
2-(3-Phenylpropyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3da). Method A was applied (0.30 g, 1.21 mmol, 61% yield).
1H NMR (300 MHz, CDCl3) δ 7.23–7.11 (m, 5H), 5.02 (t, J =
5.1 Hz, 1H), 2.62 (t, J = 7.5 Hz, 2H), 1.76–1.66 (m, 2H), 1.63–
1.57 (m, 2H), 1.16 (s, 12H). 13C{1H} NMR (75 MHz, CDCl3) δ
142.2, 128.4, 128.2, 125.6, 100.7, 81.6, 35.8, 35.7, 26.1, 24.2,
22.1. HRMS (ESI): m/z calcd for C16H23O2 [M-H]+ 247.1698,
found 247.1707.
2-(5-Chloropentyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3ea). Method C was applied (284 mg, 1.20 mmol, 60% yield).
1H NMR (300MHz, CDCl3) δ 5.02 (t, J = 5.4 Hz, 1H), 3.52 (t,
J = 6.9 Hz, 2H), 1.82–1.73 (m, 2H), 1.64–1.56 (m, 2H), 1.52–
1.37 (m, 4H), 1.19 (s, 12H). 13C{1H} NMR (75 MHz, CDCl3) δ
100.7, 81.6, 45.0, 36.2, 32.5, 26.9, 24.2, 23.8, 22.0. HRMS
(ESI): m/z calcd for C12H22ClO2 [M-H]+ 233.1308, found
233.1306.
2-(4-Benzyloxycarbonylbutyl)-4,4,5,5-tetramethyl-1,3-di-
oxolane (3ma). Method B was applied. Maleic anhydride was
used instead of MeBQ as an additive (326 mg, 1.02 mmol, 51%
yield). 1H NMR (300 MHz, CDCl3) δ 7.37–7.31 (m, 5H), 5.11
(s, 2H), 5.01 (t, J = 5.1 Hz, 1H), 2.37 (t, J = 7.5 Hz, 2H), 1.74–
1.56 (m, 4H), 1.48–1.38 (m, 2H), 1.18 (s, 12H). 13C{1H} NMR
(75 MHz, CDCl3) δ 173.4, 136.1, 128.5, 128.1, 100.6, 81.6, 66.1,
36.0, 34.2, 24.9, 24.2, 24.0, 22.0. IR (neat) ν 1738 cm-1 (C=O).
HRMS (ESI): m/z calcd for C19H27O4 [M-H]+ 319.1909, found
319.1922.
2-(3-Bromopropyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3fa). Method C was applied (384 mg, 1.53 mmol, 76% yield).
The spectral data for 3fa were in accordance with those reported
in the literature.47
2-(3-Bromopropyl)-5,5-dimethyl-1,3-dioxane (3fb) and 2-
(2-bromoethyl)-2,5,5-trimethyl-1,3-dioxane (5fb). Method D
was applied. 2,2-Dimethyl-1,3-propanediol was used instead of
pinacol. Purification by silica gel column chromatography af-
forded a mixture of 3fb and 5fb as a pale yellow oil (323 mg,
1.36 mmol, 68% total yield, 3fb:5fb = 2.1:1). 1H NMR for 3fb
2-(4-Bromobutyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3ga). Method C was applied (395 mg, 1.49 mmol, 75% yield).
1H NMR (300MHz , CDCl3) δ 5.03 (t, J = 4.8 Hz, 1H), 3.40 (t,
J = 6.9 Hz, 2H), 1.95–1.85 (m, 2H), 1.64–1.48 (m, 4H), 1.19 (s,
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(300MHz, CDCl3) δ 4.46 (t, J = 4.8 Hz, 1H), 3.61–3.38 (m, 6H),
Markovnikov Oxidation of Allylic Esters. Angew. Chem., Int.
Ed. 2013, 52, 5561-5565.
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Reactions; John Wiley & Sons: Hoboken, 2014; Vol. 84, p
75-413.
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Organometallic Compounds; 2nd ed.; Cornils, B., Herrmann,
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Palladium(II)-Catalysed Oxidation of Alkenes. Synthesis
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2.06–1.97 (m, 2H), 1.81–1.75 (m, 2H), 1.18 (s, 3H), 0.72 (s,
3H). 1H NMR for 5fb (300MHz, CDCl3) δ 3.61–3.38 (m, 6H),
2.28 (t, J = 8.4 Hz, 2H), 1.38 (s, 3H), 1.03 (s, 3H), 0.85 (s, 3H).
13C{1H} NMR for 3fb (75 MHz, CDCl3) δ 101.1, 77.2, 33.7,
33.3, 30.1, 27.2, 22.9, 21.8. 13C{1H} NMR for 5fb (75 MHz,
CDCl3) δ 98.3, 70.4, 42.9, 29.8, 27.2, 22.8, 22.3, 19.9. HRMS
(ESI): m/z calcd for C9H17BrKO2 [M+K]+ 275.0049, found
275.0045.
2-(3-Bromopropyl)-4,4,6,6-tetramethyl-1,3-dioxane (3fc).
Method D was applied. 2,4-Dimethyl-2,4-pentanediol was used
instead of pinacol (347 mg, 1.31 mmol, 66% yield). 1H NMR
(300MHz , CDCl3) δ 4.91 (t, J = 4.8 Hz, 1H), 3.43 (t, J = 6.9
Hz, 2H), 2.03–1.94 (m, 2H), 1.73–1.66 (m, 2H), 1.58 (d, J =
13.8 Hz, 1H), 1.45 (d, J = 13.8 Hz, 1H), 1.32 (s, 6H), 1.22 (s,
6H). 13C{1H} NMR (75 MHz, CDCl3) δ 89.2, 71.0, 45.5, 34.1,
33.8, 33.3, 27.7, 25.1. HRMS (ESI): m/z calcd for C11H21O2 [M-
Br]+ 185.1542, found 185.1550.
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Maleimide-assisted
anti-Markovnikov
Wacker-type
oxidation of vinylarenes using molecular oxygen as a
terminal oxidant. Chem. Commun. 2016, 52, 335-338.
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Efficient and Highly Aldehyde Selective Wacker Oxidation.
Org. Lett. 2012, 14, 3237-3239.
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Markovnikov regioselectivity in the Wacker reaction of
styrenes. Chem. Eur. J. 2006, 12, 949-955.
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Primary Alcohols from Terminal Olefins: Formal Anti-
Markovnikov Hydration via Triple Relay Catalysis. Science
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2-(3-Bromopropyl)-4,4,7,7-tetramethyl-1,3-dioxepane
(3fd). Method D was applied. 2,5-Dimethyl-2,5-hexanediol was
used instead of pinacol (360 mg, 1.29 mmol, 65% yield). 1H
NMR (300MHz , CDCl3) δ 4.73 (t, J = 5.7 Hz, 1H), 3.40 (t, J =
6.9 Hz, 2H), 1.94–1.84 (m, 2H), 1.79–1.60 (m, 6H), 1.22 (s, 6H),
1.18 (s, 6H). 13C{1H} NMR (75 MHz, CDCl3) δ 90.9, 74.7, 35.5,
35.3, 33.7, 30.0, 28.7, 25.8. HRMS (ESI): m/z calcd for
C12H23O2 [M-Br]+ 199.1698, found 199.1693.
(13) Chowdhury, A. D.; Ray, R.; Lahiri, G. K. An iron
catalyzed regioselective oxidation of terminal alkenes to
aldehydes. Chem. Commun. 2012, 48, 5497-5499.
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Selective oxidation of terminal aryl and aliphatic alkenes to
aldehydes catalyzed by iron(iii) porphyrins with triflate as a
counter anion. Chem. Commun. 2011, 47, 10963-10965.
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Che, C.-M. Ruthenium Porphyrin-Catalyzed Aerobic
Oxidation of Terminal Aryl Alkenes to Aldehydes by a
Tandem Epoxidation–Isomerization Pathway. Angew. Chem.,
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the Highly Selective Conversion of Terminal Alkenes into
Aldehydes through Epoxidation–Isomerization with
Ruthenium(IV)–Porphyrin Catalysts. Angew. Chem., Int. Ed.
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aldehydes. J. Chem. Soc., Chem. Commun. 1986, 909-910.
(18) Wenzel, T. T. Oxidation of olefins to aldehydes using a
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(19) Ogura, T.; Kamimura, R.; Shiga, A.; Hosokawa, T.
Reversal of Regioselectivity in Wacker-Type Oxidation of
Simple Terminal Alkenes and Its Paired Interacting Orbitals
(PIO) Analysis. Bull. Chem. Soc. Jpn. 2005, 78, 1555-1557.
(20) Wickens, Z. K.; Morandi, B.; Grubbs, R. H. Aldehyde-
Selective Wacker-Type Oxidation of Unbiased Alkenes
Enabled by a Nitrite Co-Catalyst. Angew. Chem., Int. Ed.
2013, 52, 11257-11260.
ASSOCIATED CONTENT
The Supporting Information is available free of charge on the ACS
Publications website at DOI: xxx.
1H and 13C NMR spectra for 3 (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail for Y.U.: ura@cc.nara-wu.ac.jp.
ORCID
Yasuyuki Ura: 0000-0003-0484-1299
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This study was supported by JSPS KAKENHI Grant Numbers
JP16H01028 in Precisely Designed Catalysts with Customized
Scaffolding, JP25410116, JP18K05122, and JP18H03914.
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