Palladium-Catalyzed Aerobic Synthesis of Terminal Acetals from Vinylarenes Assisted by π-Acceptor Ligands

Article abstract of DOI:10.1002/cctc.201601517

Terminal acetals were synthesized from various vinylarenes and 1,2- or 1,3-diols using a simple PdCl₂(MeCN)₂/methoxy-p-benzoquinone (MeOBQ)/CuCl catalyst system and 1 atm of O₂ under mild reaction conditions by the anti-Markovnikov nucleophilic attack of an oxygen nucleophile on the coordinated vinylarenes. Cyclic α,β-unsaturated carbonyl compounds such as MeOBQ and N-phenylmaleimide were especially effective as additives to afford higher yields of the desired terminal acetals. Kinetic experiments indicated that MeOBQ operates as a π-acceptor ligand for Pd to accelerate the reaction and that the dissociation of a chloride ion from Pd precedes the rate-determining step.

Full text of DOI:10.1002/cctc.201601517

Accepted Article
Title: Palladium-catalyzed Aerobic Synthesis of Terminal Acetals from
Vinylarenes Assisted by π-Acceptor Ligands
Authors: Satoko Matsumura, Ruriko Sato, Sonoe Nakaoka, Wakana
Yokotani, Yuka Murakami, Yasutaka Kataoka, and Yasuyuki
Ura
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemCatChem 10.1002/cctc.201601517
Link to VoR: http://dx.doi.org/10.1002/cctc.201601517
A Journal of
www.chemcatchem.org

10.1002/cctc.201601517
ChemCatChem
FULL PAPER
Palladium-catalyzed Aerobic Synthesis of Terminal Acetals from
Vinylarenes Assisted by -Acceptor Ligands
Satoko Matsumura,[a] Ruriko Sato,[a] Sonoe Nakaoka,[a] Wakana Yokotani,[a] Yuka Murakami,[a]
Yasutaka Kataoka,[a] and Yasuyuki Ura*[a]
Abstract: Terminal acetals were synthesized from various
vinylarenes and 1,2- or 1,3-diols using simple
Recently, we have developed a maleimide-assisted aerobic
anti-Markovnikov Wacker-type oxidation of vinylarenes to
arylacetaldehydes.[29] In this reaction, a bulky alcohol, i.e. t-
AmylOH used as a solvent is responsible for the regioselectivity,
and electron-deficient alkenes such as maleimide used as an
additive would operate as a -acceptor ligand to enhance the
catalytic activity and stabilize Pd(0) intermediates. We expected
that this approach can also be applicable to the related reaction,
i.e. acetalization, and thus developed a Pd-catalyzed aerobic
synthesis of terminal acetals from various vinylarenes and diols,
under milder reaction conditions than those for previously
reported Pd/Cu-catalyzed acetalization (Scheme 1).[20] Kinetic
experiments indicated that an electron-deficient alkene (methoxy-
p-benzoquinone, MeOBQ) operates as a ligand to accelerate the
reaction efficiently.
a
PdCl2(MeCN)2/methoxy-p-benzoquinone (MeOBQ)/CuCl catalyst
system and 1 atm of O2 under mild reaction conditions, via anti-
Markovnikov nucleophilic attack of an oxygen nucleophile to the
coordinated vinylarenes. Cyclic ,-unsaturated carbonyl compounds
such as MeOBQ and N-phenylmaleimide were especially effective as
additives to afford the higher yields of desired terminal acetals. Kinetic
experiments indicated that the added MeOBQ operates as a -
acceptor ligand for palladium to accelerate the reaction, and that
dissociation of a chloride ion from palladium precedes the rate
determining step.
Introduction
Direct synthesis of acetals from alkenes and alcohols is a useful
method which formally involves two steps, i.e. oxidation of
alkenes to aldehydes or ketones and their protection.[1] Although
Markovnikov selectivity is mainly observed in the Pd-catalyzed
intramolecular acetalization and hemiacetalization of alkenols,[2-
12]
intermolecular acetalization of alkenes having an electron-
withdrawing group[13-15] or a directing group[16,
proceeds
17]
selectively in an anti-Markovnikov manner to give terminal acetals.
As for vinylarenes, internal acetals are formed by using a
PdCl2(sparteine)/CuCl2 catalyst system under O2,[18] while
19,
terminal acetals are obtained by other Pd[13,
20], Fe[21], and
iodine[22] catalyst systems (Scheme 1). However, a drawback of
most of the latter reactions is that they require stoichiometric
amount of oxidants other than O2 such as CuCl (combined with
O2),[13] p-benzoquinone (BQ),[19] PhI(OAc)2,[21] and oxone.[22]
Although an aerobic anti-Markovnikov acetalization of styrene
using a PdCl2(MeCN)2/CuCl catalyst system has also been
reported, only one example (with 1,3-propanediol) was shown in
the literature.[20] Considering that the formation of
Scheme 1. Catalytic Markovnikov and anti-Markovnikov acetalization of
vinylarenes.
Results and Discussion
arylacetaldehydes from vinylarenes (such as anti-Markovnikov
Styrene (1a) and pinacol (2a) were used as initial substrates.
By using PdCl2(MeCN)2 (10 mol%) and CuCl (20 mol%) as
catalysts and t-AmylOH as a solvent, the reaction proceeded at
40 °C under 1 atm of O2 to form the desired terminal acetal 3aa
in 42% yield (Table 1, entry 1). Effects of a catalytic amount (10
mol%) of additives were then examined. As mentioned above,
electron-deficient, -acidic compounds were mainly tested. BQ
afforded a higher yield of the product (entry 2). Among other
substituted p-quinones, mono-substituted p-quinones, i.e. MeBQ
and MeOBQ gave better yields of 3aa (65% and 69% yields,
respectively, entries 3 and 9). On the other hand, relatively bulky,
31]
Wacker-type oxidation[23-29] and Fe[30,
or Ru[32, 33]-catalyzed
epoxidation-isomerization) is still rare, the accessible aerobic
synthesis of the corresponding terminal acetals can be an
attractive alternative.[34]
[a]
Department of Chemistry, Faculty of Science
Nara Women’s University
Kitauoyanishi-machi, Nara 630-8506, Japan
E-mail: ura@cc.nara-wu.ac.jp
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601517
ChemCatChem
FULL PAPER
observed, i.e. benzaldehyde acetal (4aa), phenylacetaldehyde
(5a), and benzaldehyde (6a), in 10–20% total yield in general.[35]
The formation of 5a can occur via the hydrolysis of 3aa or alkenyl
ether intermediates (vide infra) by in-situ generated H2O. Further
aerobic oxidation of 5a would afford 6a,[29] which reacts with 2a to
give 4aa.
Table 1. Effects of additives on the synthesis of terminal acetals from
vinylarenes using O2.[a]
The optimized reaction conditions were then applied to
various vinylarenes (Table 2). In some cases, prior to isolation,
the reaction mixture was treated with aqueous HCl to
Entry
Additive
Conv. of 1a
Yield of 3aa
(%)[b]
(%)[b]
Table 2. Scope of vinylarenes for the synthesis of terminal acetals from
vinylarenes using O2.[a]
1
2
none
BQ[c]
95
98
92
97
90
82
94
87
100
97
92
97
95
100
100
100
98
93
99
97
19
0
42
54
65
57
41
39
45
39
69
84
78
31
33
55
57
63
69
48
48
35
10
0
3
MeBQ
4
2,5-Me2BQ
2,6-Me2BQ
Me4BQ
tBuBQ
2,6- tBu2BQ
5
6
7
Entry
Product
Time (h)
Yield of
3 (%)[b]
8
9
MeOBQ
1
2
3aa
3ba
24
24
84 (72)
62 (55)
10[d]
11[e]
12
13
14
15
16
17
18
19
20
21
22
23
24
MeOBQ
MeOBQ
2,5-(MeO)2BQ
2,5-Ph2BQ
maleic anhydride
maleimide
N-methylmaleimide
N-phenylmaleimide
methyl acrylate
methyl vinyl ketone
dimethyl maleate
P(OPh)3
3
3ca
30
67 (59)
4
5
3da
3ea
30
24
70 (56)
62 (61)
PPh3
6
3fa
33
67 (31)
NEt3
0
0
pyridine
92
35
[a] Reaction conditions: 1a (0.50 mmol), 2a (1.50 mmol), PdCl2(MeCN)2
(0.050 mmol), additive (0.050 mmol), CuCl (0.10 mmol), t-AmylOH (2.0 mL),
40 °C, O2 (1 atm), 24 h. [b] Determined by 1H NMR. [c] BQ = p-benzoquinone.
[d] 10 mol% of CuCl (0.050 mmol) was used. [e] 5 mol% of CuCl (0.025 mmol)
was used.
7
8
3ga
3ha
27
27
72 (57)
65 (54)
di- and tetra-substituted p-quinones were ineffective (entries 5–8)
or decreased the yield (entries 12 and 13) except for 2,5-Me2BQ
(entry 4). Maleic anhydride and maleimides, which were most
effective for the aerobic anti-Markovnikov Wacker-type oxidation
of vinylarenes to arylacetaldehydes,[29] were also appropriate for
the present acetalization (entries 14–17). Among them, N-
phenylmaleimide gave a result comparable to MeOBQ (entry 17).
Other ,-unsaturated carbonyl compounds were inefficient
(entries 18–20). Although phosphorus and nitrogen ligands were
also examined, the results were poor in all cases (entries 21–24).
The effect of the amount of CuCl was also examined using
MeOBQ as an additive (entries 9–11), and 10 mol% was found to
be the best (84% yield, entry 10). In these reactions shown in
Table 1, small amounts of three other byproducts were also
9
3ia
32
80 (61)
10
11
3ja
24
24
63 (51)
67 (40)
3ka
[a] Reaction conditions: 1 (1.0 mmol), 2a (3.0 mmol), PdCl2(MeCN)2 (0.10
mmol), MeOBQ (0.10 mmol), CuCl (0.10 mmol), t-AmylOH (4.0 mL), 40 °C,
O2 (1 atm), 24–36 h. [b] Determined by 1H NMR. Isolated yields are shown
in parentheses.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601517
ChemCatChem
FULL PAPER
preferentially deprotect small amounts of the byproducts, i.e.
benzaldehyde acetals 4, for better separation by column
chromatography.[35] Most styrenes with an electron-withdrawing
or donating group afforded good yields of corresponding terminal
acetals 3. Somewhat longer reaction times were required for 2-
substituted styrenes (entries 3, 6, and 9). Although 2- and 4-
methoxystyrenes were also examined, less than 5% yields of
corresponding terminal acetals were observed along with the
formation of 2- or 4-methoxyphenylacetaldehyde (13%, 10%) and
2- or 4-methoxybenzaldehyde (16%, 11%), in spite of relatively
high conversions of the substrates (76% after 96 h for 2-
methoxystyrene and 74% after 32 h for 4-methoxystyrene). In the
case of 2-vinylnaphthalene, although 79% of the substrate was
converted after 24 h, only 10% of the desired acetal was obtained,
with 16% of 2-naphthalenecarboxaldehyde.
The scope of diols was also examined (Table 3).[35] Ethylene
glycol regioselectively afforded a low yield of 3ab (entry 1). This
regioselectivity contrasts to the reaction of styrene with ethylene
glycol using a PdCl2(MeCN)2/BQ/DMF system that afforded a
mixture of terminal and internal acetals in an almost 1:1 ratio.[19]
1,3-Propanediol gave a better yield of 3ac (entry 2). 2,2-Dimethyl-
1,3-propanediol was also applicable (entry 3).
Table 3. Scope of diols for the synthesis of terminal acetals from vinylarenes
using O2.[a]
Figure 1. The effects of initial concentrations of (a) 1a, (b) 2a, (c) PdCl2(MeCN)2,
(d) n-Bu4NCl, and (e) MeOBQ, on the initial rates (v0) for the formation of 3aa.
Reaction conditions: 1a (52–320 mM for a; 100 mM for b–e), 2a (310 mM for a,
c–e; 110–460 mM for b), PdCl2(MeCN)2 (26 mM for a–b, d–e; 10–26 mM for c),
MeOBQ (21 mM for a–d; 0–60 mM for e), CuCl (21 mM for a–c, e), n-Bu4NCl
(2.4–9.4 mM for d), t-AmylOH (0.15 mL for a, d–e; 0.35 mL for b–c), CDCl3 (0.95
mL for a, d–e; 0.75 mL for b–c), 40 °C, O2 (1 atm).
Entry
Product
Time (h)
Yield of
3 (%)[b]
[MeOBQ]0 was equal to or higher than [PdCl2(MeCN)2]0 (Figure
1e). This result indicates that one molecule of MeOBQ would
operate as a ligand for Pd to accelerate the reaction, and that an
excess amount of MeOBQ does not interfere.
1
2
3ab
3ac
28
80
48 (24)
86 (49)
Based on the results of kinetic experiments, a possible
mechanism is proposed in Scheme 2. The LPdCl2 species (L =
MeOBQ) is formed from PdCl2(MeCN)2 by ligand exchange.
Dissociation of Cl- and coordination of 1a afford [LPdCl(4-1a)]+.
The coordination of 1a to [LPdCl]+ would be in pre-equilibrium,
which can explain the result shown in Figure 1a.[36] Anti-
Markovnikov nucleophilic attack of t-AmylOH to the coordinated
1a and deprotonation forms a -benzyl intermediate. If diols 2
attack the coordinated 1a instead of t-AmylOH, the formation of
internal acetals would also be expected when primary diols such
as ethylene glycol, 1,3-propanediol, and 2,2-dimethyl-1,3-
propanediol are used, due to less steric hindrance between the
phenyl group in 1a and the diols, according to our previous
study.[19] However, even these cases, only the terminal acetals
were observed and no internal acetals were detected as shown in
Table 3. These results can be rationalized by the regioselective
nucleophilic attack of the bulky t-AmylOH onto the terminal carbon
of the coordinated 1a rather than the attack of the diols. After
isomerization from the -benzyl intermediate to a -benzyl
intermediate, -hydrogen elimination results in alkenyl ethers and
a LPdHCl species. The alkenyl ethers are converted to 3aa in the
3
3ad
72
73 (42)
[a] Reaction conditions: 1a (1.0 mmol), 2 (3.0 mmol), PdCl2(MeCN)2 (0.10
mmol), MeOBQ (0.10 mmol), CuCl (0.10 mmol), t-AmylOH (4.0 mL), 40 °C,
O2 (1 atm), 28–80 h. [b] Determined by 1H NMR. Isolated yields are shown
in parentheses.
To shed light on the reaction mechanism, kinetic
experiments were performed. Initial rates (v0) for the formation of
3aa were measured by 1H NMR under various initial
concentrations of 1a, 2a, PdCl2(MeCN)2, n-Bu4NCl (used as a Cl-
source), and MeOBQ (Figure 1a–e). The changes in [1a]0
appeared to slightly affect v0 at higher concentrations (52–320
mM) than [PdCl2(MeCN)2]0 (26 mM) (Figure 1a), and the changes
in [2a]0 hardly influenced v0 (Figure 1b). On the other hand, the
changes in [PdCl2(MeCN)2]0 and [n-Bu4NCl]0 influenced the rates
distinctly (Figure 1c and 1d), and the reaction orders were
estimated to be 1 and -1, respectively. In the case of MeOBQ, v0
increased in proportion to [MeOBQ]0 when [MeOBQ]0 was below
[PdCl2(MeCN)2]0 (26 mM), and became almost constant when
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601517
ChemCatChem
FULL PAPER
presence of H+ and 2a. HCl dissociates from LPdHCl to give Conclusions
LPd(0), which is reoxidized by CuCl2 to reproduce LPdCl2.
Alternatively, insertion of O2 into the Pd-H bond of LPdHCl or
reaction of LPd(0) with O2 and HCl may proceed to afford a
PdOOH species,[37-42] and subsequent protonolysis by HCl also
gives LPdCl2. These pathways do not require the aid of a Cu salt.
When the reaction of 1a with 2a was performed in the absence of
CuCl (the reaction conditions shown in Table 2 without CuCl),
98% of 1a was converted and 47% of 3aa was formed after 24 h,
indicating that the pathways involving the PdOOH species are
also likely to reproduce LPdCl2. The key roles of the -acceptor
ligands such as MeOBQ, would be acceleration of the steps for
the nucleophilic attack of t-AmylOH to the coordinated 1a and for
the reduction from Pd(II) to Pd(0), as well as stabilization of the
in-situ generated electron-rich Pd(0) species to suppress the
decomposition to Pd black, similar to those in the maleimide-
assisted aerobic anti-Markovnikov Wacker-type oxidation of
vinylarenes.[29] The Eyring plot for the reaction of 1a with 2a
afforded the activation parameters, H‡ = 8.7 ± 0.8 kcal mol-1 and
S‡ = -49 ± 3 cal mol-1 K-1, respectively.[43] The large negative S‡
value indicates that the rate determining step would be the
nucleophilic attack of t-AmylOH to the coordinated 1a, rather than
the other steps such as the reduction from Pd(II) to Pd(0).
Although the coordination of a -acceptor ligand to Pd(II) species
is not as efficient as to Pd(0) species because of the weak -back
donation, there are still several reported examples such as Pd(II)-
maleic anhydride complexes characterized by X-ray analysis.[44,
Palladium-catalyzed synthesis of terminal acetals from
various vinylarenes and 1,2- or 1,3-diols under 1 atm of O2 and
mild reaction conditions has been developed. Cyclic ,-
unsaturated carbonyl compounds such as p-quinones, maleic
anhydride, and maleimides were effective as additives to afford
the higher yields of desired terminal acetals. Among them,
MeOBQ and N-phenylmaleimide were the best. Kinetic
experiments indicated that the added MeOBQ operates as a -
acceptor ligand for palladium to accelerate the reaction, and that
dissociation of a chloride ion from palladium precedes the rate
determining step. The key roles of the -acceptor ligands would
be acceleration of the steps for the nucleophilic attack of t-
AmylOH to the coordinated vinylarenes and for the reduction from
Pd(II) to Pd(0), as well as stabilization of the in-situ generated
electron-rich Pd(0) species to suppress the decomposition to Pd
black. We believe that this catalyst system using cyclic ,-
unsaturated carbonyl compounds as ligands can also be applied
to other reactions related to Wacker-type oxidation to enhance the
catalytic activity.
Experimental Section
General Information
45]
Unless otherwise indicated, all reactions were performed under an oxygen
Evidence of the coordination of BQ to Pd(II) in solution has
[48]
been provided by an NMR study.[46] Moreover, p-quinones have
been known to promote various steps in Pd-catalyzed reactions
such as coordination of alkenes, nucleophilic addition, and
reductive elimination, by coordinating to Pd(II).[47]
atmosphere (1 atm). PdCl2(MeCN)2 was prepared as described in the
literature. t-AmylOH was purchased from Wako Pure Chemical Industries
and Tokyo Chemical Industry Co. Ltd. and was degassed by carrying out
three freeze-pump-thaw cycles. Other chemicals were also commercially
available and were used without further purification. Flash column
chromatography 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), 282 MHz (19F)) spectrometer.
Chemical shift values () were expressed relative to SiMe4 for 1H and 13
NMR. CF3CO2H was used as an external standard for 19F NMR. High-
resolution mass spectra were recorded on JEOL JMS-T100LC
C
a
spectrometer (ESI-TOF MS) with positive ionization mode.
Synthesis of Terminal Acetals 3
2-(Phenylmethyl)-4,4,5,5-tetramethyl-1,3-dioxolane (3aa): To
a
reaction vessel, CuCl (10.0 mg, 0.10 mmol), PdCl2(MeCN)2 (25.9 mg, 0.10
mmol), MeOBQ (13.8 mg, 0.10 mmol), and pinacol (355 mg, 3.0 mmol)
were added, and O2 was purged. To the mixture, t-AmylOH (4 mL) and
styrene (115 L, 1.0 mmol) were added and the reaction mixture was
stirred at 40 °C for 24 h. After cooling to room temperature, the solvent and
volatile materials were evaporated. To the residue, 2.4 M HCl aq. (1.25
mL) and THF (2.5 mL) were added, and the reaction mixture was stirred
at 40 °C for 4 h. The mixture was then neutralized with NaHCO3 aq., and
Et2O was added to extract. The organic layer was dried over MgSO4, and
was filtrated. The filtrate was evaporated, and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate = 20/1 with 1%
triethylamine) to afford 3aa as a colorless oil (159 mg, 0.72 mmol, 72%
yield). The spectral data for 3aa were in accordance with those reported in
the literature.[19]
Scheme 2. A proposed mechanism.
2-(p-Fluorophenylmethyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3ba):
The reaction was performed in a similar manner as 3aa. After cooling to
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601517
ChemCatChem
FULL PAPER
room temperature, the solvent and volatile materials were evaporated. To
the residue, 3 M HCl aq. (1.25 mL) and THF (2.5 mL) were added, and the
reaction mixture was stirred at 40 °C for 4 h. The mixture was then
neutralized with NaHCO3 aq., and Et2O was added to extract. The organic
layer was dried over MgSO4, and was filtrated. The filtrate was evaporated,
and the residue was purified by silica gel column chromatography
(hexane/ethyl acetate = 20/1 with 1% triethylamine) to afford 3ba as a
colorless oil (130 mg, 0.55 mmol, 55% yield). 1H NMR (300 MHz, CDCl3)
 7.23–7.18 (m, 2H), 7.00–6.90 (m, 2H), 5.19 (t, J = 4.8 Hz, 1H), 2.87 (d,
J = 4.8 Hz, 2H), 1.18 (s, 6H), 1.15 (s, 6H). 13C NMR (75 MHz, CDCl3) 
161.9 (1JCF = 244 Hz), 132.3 (4JCF = 3.0 Hz), 131.5 (2JCF = 8.3 Hz), 115.1
(3JCF = 21 Hz), 101.0, 82.1, 42.2, 24.2, 22.2. 19F NMR (282 MHz, CDCl3) 
-117.8. HRMS (ESI): m/z calcd for C14H19FO2Na [M+Na]+ 261.1267, found
261.1284.
= 4.8 Hz, 2H), 1.18 (s, 6H), 1.15 (s, 6H). 13C NMR (75 MHz, CDCl3)  138.9,
133.0, 129.8, 129.6, 128.7, 122.3, 100.6, 82.1, 42.6, 24.1, 22.1. HRMS
(ESI): m/z calcd for C14H19BrO2Na [M+Na]+ 321.0466, found 321.0454.
2-(m-Nitrophenylmethyl)-4,4,5,5-tetramethyl-1,3-dioxolane (3ha): The
reaction was performed in a similar manner as 3aa. After cooling to room
temperature, the solvent and volatile materials were evaporated. The
residue was purified by silica gel column chromatography (hexane/ethyl
acetate = 5/1 with 1% triethylamine) to afford 3ha as a colorless oil (144
mg, 0.54 mmol, 54% yield). The spectral data for 3ha were in accordance
with those reported in the literature.[19]
2-(o-Methylphenylmethyl)-4,4,5,5-tetramethyl-1,3-dioxolane (3ia): The
reaction was performed in a similar manner as 3aa. After cooling to room
temperature, the solvent and volatile materials were evaporated. To the
residue, 3 M HCl aq. (1.25 mL) and THF (2.5 mL) were added, and the
reaction mixture was stirred at 40 °C for 3 h. The mixture was then
neutralized with NaHCO3 aq., and Et2O was added to extract. The organic
layer was dried over MgSO4, and was filtrated. The filtrate was evaporated,
and the residue was purified by silica gel column chromatography
(hexane/ethyl acetate = 20/1 with 1% triethylamine) to afford 3ia as a
colorless oil (144 mg, 0.61 mmol, 61% yield). The spectral data for 3ia
were in accordance with those reported in the literature.[19]
2-(o-Chlorophenylmethyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3ca):
The reaction was performed in a similar manner as 3aa. After cooling to
room temperature, the solvent and volatile materials were evaporated. The
residue was purified by silica gel column chromatography (hexane/ethyl
acetate = 20/1 with 1% triethylamine) to afford 3ca as a colorless oil (151
mg, 0.59 mmol, 59% yield). The spectral data for 3ca were in accordance
with those reported in the literature.[19]
2-(m-Chlorophenylmethyl)-4,4,5,5-tetramethyl-1,3-dioxolane (3da):
The reaction was performed in a similar manner as 3aa. After cooling to
room temperature, the solvent and volatile materials were evaporated. To
the residue, 5 M HCl aq. (1.25 mL) and THF (2.5 mL) were added, and the
reaction mixture was stirred at 40 °C for 5 h. The mixture was then
neutralized with NaHCO3 aq., and Et2O was added to extract. The organic
layer was dried over MgSO4, and was filtrated. The filtrate was evaporated,
and the residue was purified by silica gel column chromatography
(hexane/ethyl acetate = 10/1 with 1% triethylamine) to afford 3da as a
colorless oil (142 mg, 0.56 mmol, 56% yield). 1H NMR (300 MHz, CDCl3)
 7.25–7.13 (m, 4H), 5.20 (t, J = 4.8 Hz, 1H), 2.87 (d, J = 4.8 Hz, 2H), 1.18
(s, 6H), 1.15 (s, 6H). 13C NMR (75 MHz, CDCl3)  138.6, 133.9, 130.1,
129.5, 128.3, 126.7, 100.7, 82.1, 42.7, 24.2, 22.1. HRMS (ESI): m/z calcd
for C14H19ClO2Na [M+Na]+ 277.0971, found 277.0986.
2-(p-Methylphenylmethyl)-4,4,5,5-tetramethyl-1,3-dioxolane (3ja): The
reaction was performed in a similar manner as 3aa. After cooling to room
temperature, the solvent and volatile materials were evaporated. To the
residue, 3 M HCl aq. (1.25 mL) and THF (2.5 mL) were added, and the
reaction mixture was stirred at 40 °C for 4 h. The mixture was then
neutralized with NaHCO3 aq., and Et2O was added to extract. The organic
layer was dried over MgSO4, and was filtrated. The filtrate was evaporated,
and the residue was purified by silica gel column chromatography
(hexane/ethyl acetate = 20/1 with 1% triethylamine) to afford 3ja as a
colorless oil (119 mg, 0.51 mmol, 51% yield). The spectral data for 3ja
were in accordance with those reported in the literature.[19]
2-(p-Acetoxyphenylmethyl)-4,4,5,5-tetramethyl-1,3-dioxolane (3ka):
The reaction was performed in a similar manner as 3aa. After cooling to
room temperature, the solvent and volatile materials were evaporated. To
the residue, 1 M HCl aq. (1.25 mL) and THF (2.5 mL) were added, and the
reaction mixture was stirred at 40 °C for 7 h. The mixture was then
neutralized with NaHCO3 aq., and Et2O was added to extract. The organic
layer was dried over MgSO4, and was filtrated. The filtrate was evaporated,
and the residue was purified by silica gel column chromatography
(hexane/ethyl acetate = 5/1 with 1% triethylamine) to afford 3ka as a
colorless oil (111 mg, 0.40 mmol, 40% yield). 1H NMR (300 MHz, CDCl3)
 7.28–7.25 (m, 2H), 7.01–6.98 (m, 2H), 5.21 (t, J = 4.8 Hz, 1H), 2.89 (d,
J = 5.1 Hz, 2H), 2.29 (s, 3H), 1.18 (s, 6H), 1.16 (s, 6H). 13C NMR (75 MHz,
CDCl3)  169.64, 149.35, 134.3, 131.0, 121.3, 100.9, 82.1, 42.5, 24.2, 22.2,
21.2. HRMS (ESI): m/z calcd for C16H22O4Na [M+Na]+ 301.1416, found
301.1425.
2-(p-Chlorophenylmethyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3ea):
The reaction was performed in a similar manner as 3aa. After cooling to
room temperature, the solvent and volatile materials were evaporated. The
residue was purified by silica gel column chromatography (hexane/ethyl
acetate = 20/1 with 1% triethylamine) to afford 3ea as a colorless oil (78
mg, 0.31 mmol, 61% yield). The spectral data for 3ea were in accordance
with those reported in the literature.[19]
2-(o-Bromophenylmethyl)-4,4,5,5-tetramethyl-1,3-dioxolane
(3fa):
The reaction was performed in a similar manner as 3aa. After cooling to
room temperature, the solvent and volatile materials were evaporated. The
residue was purified by silica gel column chromatography (hexane/ethyl
acetate = 10/1 with 1% triethylamine) to afford 3fa as a colorless oil (94
mg, 0.31 mmol, 31% yield). 1H NMR (300 MHz, CDCl3)  7.53 (dd, J = 1.2,
7.8 Hz, 1H), 7.33 (dd, J = 1.8, 7.5 Hz, 1H), 7.25 (dd, J = 1.1, 7.5 Hz, 1H),
7.08 (dt, J = 1.5, 7.7 Hz, 1H), 5.30 (t, J = 5.1 Hz, 1H), 3.10 (d, J = 5.1 Hz,
2H), 1.22 (s, 6H), 1.19 (s, 6H). 13C NMR (75 MHz, CDCl3)  136.3, 132.7,
132.3, 128.3, 127.4, 125.2, 122.3, 99.9, 82.2, 43.0, 24.2, 22.2. HRMS
(ESI): m/z calcd for C14H19BrO2Na [M+Na]+ 321.0466, found 321.0470.
2-(Phenylmethyl)-1,3-dioxolane (3ab): The reaction was performed in a
similar manner as 3aa. After cooling to room temperature, the solvent and
volatile materials were evaporated. The residue was purified by silica gel
column chromatography (hexane/ethyl acetate
=
5/1 with 1%
triethylamine) to afford 3ab as a colorless oil (40 mg, 0.24 mmol, 24%
yield). The spectral data for 3ab were in accordance with those reported
in the literature.[19]
2-(m-Bromophenylmethyl)-4,4,5,5-tetramethyl-1,3-dioxolane (3ga):
The reaction was performed in a similar manner as 3aa. After cooling to
room temperature, the solvent and volatile materials were evaporated. The
residue was purified by silica gel column chromatography (hexane/ethyl
acetate = 20/1 with 1% triethylamine) to afford 3ga as a colorless oil (170
mg, 0.57 mmol, 57% yield). 1H NMR (300 MHz, CDCl3)  7.41 (s, 1H),
7.37–7.33 (m, 1H), 7.21–7.13 (m, 2H), 5.21 (t, J = 4.8 Hz, 1H), 2.86 (d, J
2-(Phenylmethyl)-1,3-dioxane (3ac): The reaction was performed in a
similar manner as 3aa. After cooling to room temperature, the solvent and
volatile materials were evaporated. To the residue, 3 M HCl aq. (1.25 mL)
and THF (2.5 mL) were added, and the reaction mixture was stirred at
40 °C for 1 h. The mixture was then neutralized with NaHCO3 aq., and
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601517
ChemCatChem
FULL PAPER
[9]
N. T. Byrom, R. Grigg, B. Kongkathip, G. Reimer, A. R. Wade, J. Chem.
Soc., Perkin Trans. 1 1984, 1643-1653.
Et2O was added to extract. The organic layer was dried over MgSO4, and
was filtrated. The filtrate was evaporated, and the residue was purified by
silica gel column chromatography (hexane/ethyl acetate = 5/1 with 1%
triethylamine) to afford 3ac as a colorless oil (87 mg, 0.49 mmol, 49%
yield). The spectral data for 3ac were in accordance with those reported in
the literature.[22]
[10] B. Kongkathip, R. Sookkho, N. Kongkathip, Chem. Lett. 1985, 14, 1849-
1850.
[11] T. Hosokawa, Y. Makabe, T. Shinohara, S.-I. Murahashi, Chem. Lett.
1985, 14, 1529-1530.
[12] W. Kroutil, I. Osprian, M. Mischitz, K. Faber, Synthesis 1997, 156-158.
[13] T. Hosokawa, T. Ohta, S. Kanayama, S. Murahashi, J. Org. Chem. 1987,
52, 1758-1764.
2-(Phenylmethyl)-5,5-dimethyl-1,3-dioxane (3ad): The reaction was
performed in a similar manner as 3aa. After cooling to room temperature,
the solvent and volatile materials were evaporated. To the residue, 3 M
HCl aq. (1.5 mL) and THF (2.5 mL) were added, and the reaction mixture
was stirred at 40 °C for 2 h. The mixture was then neutralized with NaHCO3
aq., and Et2O was added to extract. The organic layer was dried over
MgSO4, and was filtrated. The filtrate was evaporated, and the residue was
purified by silica gel column chromatography (hexane/ethyl acetate = 7/1
with 1% triethylamine) to afford 3ad as a colorless oil (86 mg, 0.42 mmol,
[14] T. Hosokawa, T. Yamanaka, S.-I. Murahashi, J. Chem. Soc., Chem.
Commun. 1993, 117-119.
[15] T. Hosokawa, T. Yamanaka, M. Itotani, S.-I. Murahashi, J. Org. Chem.
1995, 60, 6159-6167.
[16] J. Lai, X. Shi, L. Dai, J. Org. Chem. 1992, 57, 3485-3487.
[17] T. Hosokawa, S. Aoki, S.-I. Murahashi, Synthesis 1992, 558-561.
[18] A. M. Balija, K. J. Stowers, M. J. Schultz, M. S. Sigman, Org. Lett. 2006,
8, 1121-1124.
[19] M. Yamamoto, S. Nakaoka, Y. Ura, Y. Kataoka, Chem. Commun. 2012,
48, 1165-1167.
[20] T. Hosokawa, Y. Ataka, S.-I. Murahashi, Bull. Chem. Soc. Jpn. 1990, 63,
166-169.
[21] A. Dutta Chowdhury, G. Kumar Lahiri, Chem. Commun. 2012, 48, 3448-
1
42% yield). H NMR (300 MHz, CDCl3)  7.31–7.19 (m, 5H), 4.60 (t, J =
5.1 Hz, 1H), 3.59 (d, J = 10.8 Hz, 2H), 3.38 (d, J = 10.8 Hz, 2H), 2.94 (d, J
= 5.1 Hz, 2H), 1.19 (s, 3H), 0.69 (s, 3H). 13C NMR (75 MHz, CDCl3)  136.7,
129.6, 128.2, 126.4, 102.6, 77.3, 41.6, 30.1, 23.0, 21.8. HRMS (ESI): m/z
calcd for C13H18O2Na [M+Na]+ 229.1205, found 229.1213.
3450.
[22] M. A. Kumar, P. Swamy, M. Naresh, M. M. Reddy, C. N. Rohitha, S.
Prabhakar, A. V. S. Sarma, J. R. P. Kumar, N. Narender, Chem.
Commun. 2013, 49, 1711-1713.
[23] J. Muzart, Tetrahedron 2007, 63, 7505-7521.
[24] J. Guo, P. Teo, Dalton Trans. 2014, 43, 6952-6964.
[25] J. J. Dong, W. R. Browne, B. L. Feringa, Angew. Chem., Int. Ed. 2015,
54, 734-744.
Kinetic Experiments
[26] J. A. Wright, M. J. Gaunt, J. B. Spencer, Chem. Eur. J. 2006, 12, 949-
All the reactions were performed in sealed J. young NMR tubes (528-LPV-
8). PdCl2(MeCN)2, MeOBQ, CuCl (or n-Bu4NCl), and pinacol were placed
in the NMR tube under argon. The tube was cooled in an ice bath. t-
AmylOH, methyl benzoate (as an internal standard, 15 L, 0.12 mmol),
styrene, and CDCl3 were added to the above mixture at 0 °C, and O2 (10
mL) was passed through the reaction mixture via syringe. The sample was
955.
[27] P. Teo, Z. K. Wickens, G. Dong, R. H. Grubbs, Org. Lett. 2012, 14, 3237-
3239.
[28] S. L. Bourne, S. V. Ley, Adv. Synth. Catal. 2013, 355, 1905-1910.
[29] S. Nakaoka, Y. Murakami, Y. Kataoka, Y. Ura, Chem. Commun. 2016,
52, 335-338.
[30] G.-Q. Chen, Z.-J. Xu, C.-Y. Zhou, C.-M. Che, Chem. Commun. 2011, 47,
°
then introduced into a NMR probe at 25 C, and was warmed to 40 °C
10963-10965.
immediately. The increase of the integration of CH signal (5.23 ppm) for
3aa was followed by 1H NMR spectroscopy. The moment at which the
probe temperature reached to 40 °C was regarded as a starting time. The
initial rates were calculated from the maximum slopes on the graphs
plotted the concentration of 3aa vs. reaction time.
[31] A. D. Chowdhury, R. Ray, G. K. Lahiri, Chem. Commun. 2012, 48, 5497-
5499.
[32] J. Chen, C.-M. Che, Angew. Chem., Int. Ed. 2004, 43, 4950-4954.
[33] G. Jiang, J. Chen, H.-Y. Thu, J.-S. Huang, N. Zhu, C.-M. Che, Angew.
Chem., Int. Ed. 2008, 47, 6638-6642.
[34] Although stoichiometric amounts of the reagents are required, a simple
NBS/AgOTf system also has been reported recently. See: P. V. Balaji, S.
Chandrasekaran, Eur. J. Org. Chem. 2016, 2547-2554.
[35] See Supporting Information for the yields of byproducts.
[36] R. G. Wilkins, in Kinetics and Mechanism of Reactions of Transition Metal
Complexes, 2nd ed., VCH, Weinheim, Germany, 1991, p. 24.
[37] M. C. Denney, N. A. Smythe, K. L. Cetto, R. A. Kemp, K. I. Goldberg, J.
Am. Chem. Soc. 2006, 128, 2508-2509.
Acknowledgements
This study was supported by JSPS KAKENHI Grant Numbers
JP16H01028 in Precisely Designed Catalysts with Customized
Scaffolding and JP25410116.
[38] M. M. Konnick, B. A. Gandhi, I. A. Guzei, S. S. Stahl, Angew. Chem., Int.
Ed. 2006, 45, 2904-2907.
[39] J. M. Keith, R. P. Muller, R. A. Kemp, K. I. Goldberg, W. A. Goddard, J.
Oxgaard, Inorg. Chem. 2006, 45, 9631-9633.
[40] M. M. Konnick, S. S. Stahl, J. Am. Chem. Soc. 2008, 130, 5753-5762.
[41] N. Decharin, B. V. Popp, S. S. Stahl, J. Am. Chem. Soc. 2011, 133,
13268-13271.
Keywords: acetals • electron-deficient compounds • palladium •
synthetic methods • vinylarenes
[42] N. Decharin, S. S. Stahl, J. Am. Chem. Soc. 2011, 133, 5732-5735.
[43] See Supporting Information for details.
[44] C. Fernández-Rivas, D. J. Cárdenas, B. Martín-Matute, Á. Monge, E.
Gutiérrez-Puebla, A. M. Echavarren, Organometallics 2001, 20, 2998-
3006.
[45] V. G. Albano, C. Castellari, M. E. Cucciolito, A. Panunzi, A. Vitagliano,
Organometallics 1990, 9, 1269-1276.
[46] J.-E. Báckvall, A. Gogoll, Tetrahedron Lett. 1988, 29, 2243-2246.
[47] A. Vasseur, J. Muzart, J. Le Bras, Eur. J. Org. Chem. 2015, 4053-4069.
[48] R. A. Michelin, G. Facchin, P. Uguagliati, Inorg. Chem. 1984, 23, 961-
969.
[1]
[2]
[3]
[4]
[5]
[6]
E. M. Beccalli, G. Broggini, M. Martinelli, S. Sottocornola, Chem. Rev.
2007, 107, 5318-5365.
S. Igarashi, Y. Haruta, M. Ozawa, Y. Nishide, H. Kinoshita, K. Inomata,
Chem. Lett. 1989, 18, 737-740.
T. Hosokawa, F. Nakajima, S. Iwasa, S.-I. Murahashi, Chem. Lett. 1990,
19, 1387-1390.
T. M. Meulemans, N. H. Kiers, B. L. Feringa, P. W. N. M. v. Leeuwen,
Tetrahedron Lett. 1994, 35, 455-458.
G. V. M. Sharma, A. S. Chander, K. Krishnudu, P. R. Krishna,
Tetrahedron Lett. 1997, 38, 9051-9054.
J. Nokami, H. Ogawa, S. Miyamoto, T. Mandai, S. Wakabayashi, J. Tsuji,
Tetrahedron Lett. 1988, 29, 5181-5184.
[7]
[8]
J. Lai, X. Shi, Y. Gong, L. Dai, J. Org. Chem. 1993, 58, 4775-4777.
N. T. Byrom, R. Grigg, B. Kongkathip, J. Chem. Soc., Chem. Commun.
1976, 216-217.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601517
ChemCatChem
FULL PAPER
Entry for the Table of Contents
FULL PAPER
Satoko Matsumura, Ruriko Sato, Sonoe
Nakaoka, Wakana Yokotani, Yuka
Murakami, Yasutaka Kataoka, Yasuyuki
Ura*
Page No. – Page No.
Palladium-catalyzed Aerobic
Synthesis of Terminal Acetals from
Vinylarenes Assisted by -Acceptor
Ligands
Terminal acetals were synthesized from various vinylarenes and diols using a
PdCl2(MeCN)2/methoxy-p-benzoquinone (MeOBQ)/CuCl catalyst system and 1
atm of O2 under mild reaction conditions, via anti-Markovnikov nucleophilic attack
of an oxygen nucleophile to the coordinated vinylarenes. MeOBQ operated as a
ligand for palladium to accelerate the reaction.
This article is protected by copyright. All rights reserved.