Modular Synthesis of α-Substituted Alkenyl Acetals by a Palladium-Catalyzed Suzuki Reaction of α-Haloalkenyl Acetals with Organoboranes

Article abstract of DOI:10.1055/a-1322-3916

A modular and straightforward synthetic strategy for the preparation of α-substituted alkenyl acetals has been developed. α-Haloalkenyl acetals react smoothly with (het)aryl boronic acids, aryl boronates, or B-Alkyl-9-borabicyclo[3.3.1]nonanes through Pd-catalyzed Suzuki cross-coupling under mild conditions with good to high yields. This protocol features a broad substrate scope and good functional-group compatibility, and is easily scaled up.

Full text of DOI:10.1055/a-1322-3916

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2020, 31, 723–727
letter
723
en
L. Zhang
Letter
Synlett
Modular Synthesis of -Substituted Alkenyl Acetals by a
Palladium-Catalyzed Suzuki Reaction of -Haloalkenyl Acetals
with Organoboranes
Li Zhang*
Pd(OAc)2 (2 mol%)
XPhos (4 mol%)
R2
X
R1
R2 B(OH)2
R1
+
CH(OEt)2
X = Br, Cl
CH(OEt)2
70–93% yield
Cs2CO3 (2.5 equiv)
1,4-dioxane or THF
40–90 °C
School of Fundamental Science, Zhejiang
Pharmaceutical College, No. 666 Siming
Road, Ningbo 315500, P. R. of China
zhangl@zjpu.edu.cn
Modular synthesis
Gram scale-up
Broad substrate scope
Mild reaction conditions
LSeicMhZaohiCoalonlzrohgrfaeFnsupgnlo@dnzadjmipnueg.neAtdauult.hScconirence, Zhejiang Pharmaceutical College, No. 666 Siming Road, Ningbo 315500, P. R. of China
Received: 04.11.2020
Accepted after revision: 25.11.2020
Published online: 25.11.2020
of 3,3-diethoxy-1-arylprop-1-yne with aryl or vinyl halides
or triflates (Scheme 1.3).8 Alternatively, Kang and co-work-
ers reported that palladium(0)-catalyzed coupling and cy-
clization of allenyl alcohols with hypervalent iodonium
salts affords cyclized acetals (Scheme 1.4);9 however, the
reactions of nonsymmetrical biaryl iodonium salts with al-
lenyl alcohols always produce mixtures of acetals. In 2012,
the Zhou group reported that -aryl vinyl acetals are readily
prepared by selective -arylation of acrolein diethyl acetal
under Heck conditions with Pd[(dba)2]/dppf as the catalyst,
although a dramatic effect of steric hindrance is observed
(Scheme 1.5).10 Although -substituted alkenyl acetals can
be synthesized by the methods mentioned above, a modu-
lar and general protocol is still highly desirable. Inspired by
our recent work on introducing an aryl group at the -posi-
tion of various Michael acceptors through C–C cross-cou-
pling reactions,11 a straightforward synthesis of -substi-
DOI: 10.1055/a-1322-3916; Art ID: st-2020-u0585-l
Abstract A modular and straightforward synthetic strategy for the
preparation of -substituted alkenyl acetals has been developed. -
Haloalkenyl acetals react smoothly with (het)aryl boronic acids, aryl bo-
ronates, or B-alkyl-9-borabicyclo[3.3.1]nonanes through Pd-catalyzed
Suzuki cross-coupling under mild conditions with good to high yields.
This protocol features a broad substrate scope and good functional-
group compatibility, and is easily scaled up.
Key words alkenyl acetals, palladium catalysis, Suzuki reaction, cross-
coupling, arylboronic acids, arylation
The past forty years have witnessed tremendous prog-
ress in Suzuki cross-coupling reactions.1,2 A diversity of
Suzuki coupling reactions have been developed by taking
advantage of the broad range of readily available coupling
partners and catalysts.3 Because of its mild conditions and
excellent functional-group compatibility, the Suzuki cou-
pling reaction has become a reliable tool for late-stage func-
tionalization of complex chemicals.4 Among the numerous
efforts devoting to the Suzuki reaction, preparations of
high-added-value molecules based on C–C cross-coupling
reactions are always in demand.
(a) Noncatalytic methods
O
Me-PPh3Br–
Ar
CH(OEt)2
Ar
CH(OEt)2
(1)
(2)
t-BuOK, Et2O, rt
NaOH, EtOH
reflux
Cl
Cl
Ar
CH(OEt)2
Ar
-Substituted alkenyl acetals are useful building blocks
in organic transformations.5,6 Furthermore, the acetals can
be hydrolyzed to give -arylacroleins, which are unstable at
room temperature. Several methods for the preparation of
-substituted alkenyl acetals have been reported (Scheme
1). A Wittig reaction provides access to -ketal derivatives
of vinylarenes by the reaction of 2,2-diethoxy-1-aryletha-
nones with ylides generated from methyl(triphenyl)phos-
phonium bromide (Scheme 1.1).6 The conversion of gem-di-
halocyclopropanes into ,-unsaturated acetals is also a
general method (Scheme 1.2).7 In addition to the above
noncatalytic methods, several protocols based on palladium
catalysis have also been developed for the preparation of -
substituted alkenyl acetals. In 1997, Cacchi and co-workers
synthesized a series of -aryl alkenyl acetals in moderate
yields by Pd-catalyzed hydroarylation and hydrovinylation
(b) Previous Pd-catalyzed reactions
CH(OEt)2
R2
R2-I or R2-OTf
CH(OEt)2
(3)
Pd(OAc)2, HCO2K
DMF, 40 °C
OR1
OR1
O
Pd(PPh3)4 (5 mol%)
K2CO3 (2.5 equiv)
BF4
I
n
n
O
O
n
+
O
HO
+
(4)
(5)
Ar1
Ar2
OH
MeCN, 60 °C
n = 1, 2
Ar1
Ar2
Pd(dba)2 (2–5 mol%)
dppf (4–10 mol%)
Ar
+
ArOTf
CH(OEt)2
CH(OEt)2
DMA, Li2CO3, 80 °C
(c) Pd-catalyzed Suzuki reactions (this work)
Br
R2
Pd(OAc)2/Ligand (cat.)
C–C cross-coupling
(6)
R2-BY2
+
CH(OR1)2
CH(OR1)2
Scheme 1 Synthetic approaches to -substituted alkenyl acetals
© 2020. Thieme. All rights reserved. Synlett 2021, 32, 723–727
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

724
L. Zhang
Letter
Synlett
tuted alkenyl acetals was envisioned to be feasible through
a Pd-catalyzed Suzuki arylation or alkylation of vinylic ha-
lides (Scheme 1.6). Here is presented an efficient cross-cou-
pling reaction of -haloalkenyl acetals with organoboranes
under Pd-catalyzed Suzuki conditions.
Table 1 Optimization of the Reaction Conditions
Pd(OAc)2 (2 mol%)
XPhos (4 mol%)
B(OH)2
Br
+
CH(OEt)2
Cs2CO3 (2.5 equiv)
CH(OEt)2
3a
1,4-dioxane, 40 °C, 3 h
1a
2a
-Bromoacrolein acetal (1a; 2-bromo-3,3-diethoxy-
prop-1-ene) and phenylboronic acid (2a) were selected as
the model substrates for optimizing the reaction (Table 1).
After an extensive search of reaction conditions, it was
pleasing to find that the reaction of 1a (1.0 equiv), 2a (2.0
equiv), Pd(OAc)2 (2 mol%), XPhos (4 mol%), and Cs2CO3 (2.5
equiv) in 1,4-dioxane at 40 °C gave the expected coupling
product 3a in 84% isolated yield (Table 1, entry 1). Switching
the ligand XPhos to other phosphine ligands (DPPP, PCy3, or
PPh3) resulted in a sharp drop in yield (entries 2–4), where-
as SPhos could be used as an ancillary ligand (entry 5).12
Compared with the result with Cs2CO3, other inorganic bas-
es (K3PO4, K2CO3, and Na2CO3) gave inferior yields (entries
6–8). 1,4-Dioxane clearly emerged as the most suitable sol-
vent among those screened (entries 9–12). In addition to
phenylboronic acid (2a), (pinacolboryl)benzene (2aa′) or
5,5-dimethyl-2-phenyl-1,3,2-dioxaborinane (2ab′) can be
used as an alternative reactant for this coupling reaction
(entries 13 and 14). The reaction could also be performed at
room temperature, albeit with a long reaction time (entry
15). Control experiments confirmed that both the ligand
and the base are necessary (entries 16 and 17).
With the optimized reaction conditions in hand, the
scope of the (het)arylboronic acid 2 was next examined,
with 1a as the electrophile (Scheme 2). Generally, the cou-
pling reaction of the vinylic bromide 1a with electron-rich
and electron-deficient arylboronic acids readily gave the
corresponding -arylacrolein acetals 3 in good to high
yields. In addition to the successful coupling reactions of 3-
tolylboronic acid (2b) and 4-tolylboronic acid (2c), sterical-
ly hindered 2-tolylboronic acid (2d) and (2,6-dimethylphe-
nyl)boronic acid (2d) also reacted smoothly to afford the
corresponding products 3d and 3e in yields of 77 and 73%,
respectively. Moreover, arylboronic acids having electron-
donating methoxy or tert-butyl groups on the phenyl ring
participated well in the reaction to deliver products 3f and
3g, respectively, in high yields. This procedure also tolerates
the presence of an alkene (3h) on the phenyl ring at the nu-
cleophilic coupling partner. Halo groups (3i and 3j), which
provide sites for further derivatizations by transition-met-
al-catalyzed cross-coupling reactions, are also compatible
with the reaction. Furthermore, other common functional
groups (trifluoromethyl, cyano, aldehyde, ketone, and ester)
were nicely tolerated (3k–o). Note that for the preparation
of 3l–n, THF was a better solvent than 1,4-dioxane. As far as
the size of aryl group is concerned, 2- and 1-naphthylbo-
ronic acids coupled efficiently with 1a to give the desired
products 3p and 3q, respectively. Notably, cross-couplings
of 1a with several hetarylboronic acids were also success-
ful, giving the expected products 3r–t in yields of 71–90%.
(1.0 equiv)
(2.0 equiv)
PPh2
PCy2
O
O
PCy2
OMe
O
O
B
B
i-Pr
i-Pr
MeO
PPh2
i-Pr
XPhos
DPPP
SPhos
2aa'
2ab'
Entry
Variation from the standard conditionsa
Yield (%)
1
2
none
84
< 5
< 5
< 10
74
DPPP instead of XPhos
Cy3PH·BF4 instead of XPhos
PPh3 instead of XPhos
SPhos instead of XPhos
K3PO4 instead of Cs2CO3
K2CO3 instead of Cs2CO3
Na2CO3 instead of Cs2CO3
THF instead of 1,4-dioxane
EtOH instead of 1,4-dioxane
toluene instead of 1,4-dioxane
DMF instead of 1,4-dioxane
2aa′ instead of 2a
3
4
5
6
56
7
< 10
< 5
64
8
9
10
11
12
13
14
15
16
17
76
< 5
< 5
72
2ab′ instead of 2a
74
r.t., 12 h
63
no Cs2CO3
14
no XPhos
< 5
a Standard conditions: 1a (41.6 mg, 0.2 mmol), 2a (48.8 mg, 0.4
mmol), Cs2CO3 (163 mg, 0.5 mmol), Pd(OAc)2 (0.9 mg, 0.004 mmol),
XPhos (3.8 mg, 0.008 mmol), 1.4-dioxane (1 mL), stirring, 40 °C, 3 h.
Remarkably, much stricter reaction conditions were neces-
sary for the reaction of quinolin-8-ylboronic acid to yield
the desired product 3r.
When an alkylboronic acid was used as the nucleophilic
reagent of the reaction, none of the expected product was
obtained, even when the loading of the catalyst and the re-
action temperature were increased. However, -alkylalke-
nyl acetals could be synthesized efficiently by using the ap-
propriate B-alkyl-9-borabicyclo[3.3.1]nonane (alkyl-9-
BBN) as the boron reagent. For example, the -alkylacrolein
acetal 3u was synthesized in 90% yield by Pd-catalyzed
Suzuki alkylation of 1a with [2-(2-naphthyl)ethyl]-9-BBN
(2b), which, in turn, was easily prepared by addition of 2-
ethylnaphthalene to the 9-BBN dimer (Scheme 3).
© 2020. Thieme. All rights reserved. Synlett 2021, 32, 723–727

725
L. Zhang
Letter
Synlett
Next, the scope of the -haloalkenyl acetal was explored
(Table 2). A range of -bromoalkenyl acetals, including the
linear acetal 1 (Table 2, entry1), the cyclic acetal 1c (entry
2), and the nonterminal alkenyl acetal 1d (entry 3), reacted
smoothly with arylboronic acids under the standard condi-
tions, affording the corresponding products 3v–x in yields
of 73–93%. Note that an atom-economical substrate, the -
chloroalkenyl acetal 1e, was also suitable as an electrophile,
affording 3x in 84% yield, despite needing a higher reaction
temperature (entry 4).
Table 2 Scope of the -Haloalkenyl Acetala
R3
Pd(OAc)2 (2 mol%)
XPhos (4 mol%)
B(OH)2
X
R1
+
CH(OR2)2
R3
Cs2CO3 (2.5 equiv)
dioxane, 40 °C, 3 h
R1
1
2
CH(OR2)2
(1.0 equiv)
(2.0 equiv)
3
Entry
Substrate
Product (yieldb)
Br
1
2
CH(OMe)2
1b
CH(OMe)2
3v, 73%
Pd(OAc)2 (2 mol%)
XPhos (4 mol%)
Het
R
B(OH)2
Br
Het
R
+
Br
CH(OEt)2
1a
Cs2CO3 (2.5 equiv)
1,4-dioxane, 40 °C, 3–10 h
CH(OEt)2
O
2
3
O
O
O
1c
Me
OMe
3w, 78%
Me
Me
Me
Me
OMe
CH(OEt)2
CH(OEt)2
CH(OEt)2
CH(OEt)2
3c, 73%
CH(OEt)2
3f, 86%
Br
Ph
3e, 73%
3d, 77%
3b, 78%
3
CH(OEt)2
Ph
1d
CH(OEt)2
3x, 93%
CF3
F
Cl
t-Bu
Cl
4c
3x, 84%
CH(OEt)2
Ph
CH(OEt)2
CH(OEt)2
CH(OEt)2
3g, 81%
CH(OEt)2
3h, 89%
CH(OEt)2
3i, 81%
3j, 70%
3k, 74%
1e
a Reaction conditions: 1 (0.2 mmol), ArB(OH)2 (2; 0.4 mmol), Cs2CO3 (163
mg, 0.5 mmol), Pd(OAc)2 (0.9 mg, 0.004 mmol), XPhos (3.8 mg, 0.008
mmol), 1,4-dioxane (1 mL), stirring, 40 °C, 3 h.
b Isolated yield.
COMe
CN
CO2Me
CHO
c At 90 °C.
CH(OEt)2
3n, 87%a
CH(OEt)2
3l, 92%a
CH(OEt)2
3o, 79%
CH(OEt)2
3m, 73%a
CH(OEt)2
3p, 80%
In addition, the reaction could be easily scaled up to 6
mmol without a significant decrease in the yield of the cou-
pling product (Scheme 4). For example, the reaction of 1a
(1.25 g, 6 mmol) with (4-methoxyphenyl)boronic acid af-
forded 1.20 g of 3f (85% yield; Scheme 4.1). Similarly, the re-
action of 1a and 1-naphthylboronic acid gave 1.21 g of the
desired product 3q in 79% isolated yield (Scheme 4.2).
To demonstrate the utility of the protocol, functional-
group transformations of the coupled product 3a were sur-
veyed (Scheme 5). As an example, atropaldehyde (4) was
O
S
N
CH(OEt)2
CH(OEt)2
3q, 79%
CH(OEt)2
3r, 71%a,b
CH(OEt)2
3s, 90%
3t, 90%a
Scheme 2 Scope of (het)arylboronic acids. Reagents and conditions: 1a
(0.2 mmol), ArB(OH)2 2 (0.4 mmol), Cs2CO3 (163 mg, 0.5 mmol),
Pd(OAc)2 (0.9 mg, 0.004 mmol), XPhos (3.8 mg, 0.008 mmol), 1,4-di-
oxane (1 mL), stirring, 40 °C, 3–10 h. Isolated yields are reported. a
Stirred at 60 °C in THF (1 mL). b Pd(OAc)2 (2.2 mg, 0.01 mmol) and
XPhos (9.5 mg, 0.02 mmol) were used.
CH(OEt)2
Br
MeO
Ar = 4-MeOC6H4
(1)
(2)
CH(OEt)2
3f, 85%, 1.20 g
+ (9-BBN)2
Pd(OAc)2 (2 mol%)
XPhos (4 mol%)
1a
(0.75 equiv)
(1.5 equiv)
1.25 g, 6 mmol
+
CH(OEt)2
THF, rt, 24 h
Cs2CO3 (2.5 equiv)
1,4-dioxane (0.2 M)
40 °C, 5 h
Ar = 1-naphthyl
Pd(OAc)2 (2 mol%)
XPhos (4 mol%)
CH(OEt)2
ArB(OH)2
2
CH(OEt)2
Br
9-BBN
+
12 mmol
Cs2CO3 (2.5 equiv)
1,4-dioxane, 40 °C, 3 h
2b
3q, 79%, 1.21 g
1a
3u, 90%
(1.0 equiv)
(a solution of 2b in THF)
Scheme 4 Gram-scale synthesis of -substituted acrolein acetals 3f
and 3q
Scheme 3 Synthesis of the -alkyl acrolein acetal 3u
© 2020. Thieme. All rights reserved. Synlett 2021, 32, 723–727

726
L. Zhang
Letter
Synlett
easily obtained by formic acid mediated hydrolysis of its di-
ethyl acetal 3a,13 and is an especially useful building blocks
for cycloaddition reactions. Interestingly, with K3PO4 as the
basic additive, 3a underwent efficient reduction by the
diimide generated from 2-nitrobenzenesulfonyl hydrazide
(NBSH) at room temperature14 to give 2-phenylpropional
diethyl acetal 5 in 95% yield. Furthermore, 3a could be
cleaved to give 2,2-diethoxy-1-phenylethanone 6 (61%
yield) by treatment with RuCl3·xH2O catalyst in the pres-
ence of NaIO4 and Bu4NBr under aqueous conditions.15
References and Notes
(1) (a) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979,
3437. (b) Miyaura, N.; Suzuki, A. J. Chem. Soc., Chem. Commun.
1979, 866.
(2) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(3) For selected reviews, see: (a) Campeau, L.-C.; Hazari, N. Organo-
metallics 2019, 38, 3. (b) Lennox, A. J. J.; Lloyd-Jones, G. C. Chem.
Soc. Rev. 2014, 43, 412. (c) Johansson Seechurn, C. C. C.;
Kitching, M. O.; Colacot, T. J.; Snieckus, V. Angew. Chem. Int. Ed.
2012, 51, 5062. (d) So, C. M.; Kwong, F. Y. Chem. Soc. Rev. 2011,
40, 4963.
(4) For a review, see: Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew.
Chem. Int. Ed. 2005, 44, 4442.
CHO
HCO2H/H2O (v/v = 3:2)
(5) (a) Ferraboschi, P.; Reza-Elahi, S.; Verza, E.; Santaniello, E. Tetra-
hedron: Asymmetry 1999, 10, 2639. (b) Coates, R. M.; Hobbs, S. J.
J. Org. Chem. 1984, 49, 140. (c) Kagabu, S.; Mizoguchi, S. Synthe-
sis 1996, 372.
0 °C to rt, 40 min
4, 74%
CH(OEt)2
NBSH (2.0 equiv)
K3PO4 (1.0 equiv)
CH(OEt)2
(6) (a) Bailey, W. F.; Reed, D. P.; Clark, D. R.; Kapur, G. N. Org. Lett.
2001, 3, 1865. (b) Zhang, Q.; Zhu, S.-F.; Qiao, X.-C.; Wang, L.-X.;
Zhou, Q.-L. Adv. Synth. Catal. 2008, 350, 1507. (c) Gu, Y.; Wu, F.;
Yang, J. Adv. Synth. Catal. 2018, 360, 2727.
(7) (a) Crossland, I. Org. Synth. 1981, 60, 6. (b) Song, Q.-W.; Yu, B.;
Liu, A.-H.; He, Y.; Yang, Z.-Z.; Diao, Z.-F.; Song, Q.-C.; Li, X.-D.;
He, L.-N. RSC Adv. 2013, 3, 19009.
MeCN (0.15 M)
rt, 12 h
3a
5, 95%
RuCl3 xH2O (5 mol%)
NaIO4 (5.0 equiv)
CH(OEt)2
O
Bu4NBr (0.1 equiv)
H2O (0.1 M), rt, 1 h
6, 61%
(8) Cacchi, S.; Fabrizi, G.; Moro, L.; Pace, P. Synlett 1997, 1367.
(9) Kang, S.-K.; Ha, Y.-H.; Yang, H.-Y. J. Chem. Res., Synop. 2002, 282.
(10) Qin, L.; Ren, X.; Lu, Y.; Li, Y.; Zhou, J. Angew. Chem. Int. Ed. 2012,
51, 5915.
Scheme 5 Further transformations of the coupled product 3a
In summary, a general protocol has been developed for
the synthesis of -substituted alkenyl acetals through Suzuki
coupling of -haloalkenyl acetals with various organobo-
ranes.16 This protocol features a broad substrate scope, ex-
cellent functional-group compatibility, and easy scaleup.
Furthermore, the terminal vinyl acetals can be subjected to
various transformations. This method should contribute to
modular preparations of -substituted alkenyl acetals.
Studies on the application of this method to similar Suzuki
reactions of other Michael acceptors are ongoing.
(11) (a) Zhang, L.; Fang, Y.; Jin, X.; Guo, T.; Li, R.; Li, Y.; Li, X.; Ye, Q.;
Luo, X.; Tian, Z. Org. Chem. Front. 2018, 5, 1457. (b) Zhang, L.;
Fang, Y.; Jin, X.; Xu, H.; Li, R.; Wu, H.; Chen, B.; Zhu, Y.; Yang, Y.;
Tian, Z. Org. Biomol. Chem. 2017, 15, 8985. (c) Fang, Y.; Zhang, L.;
Jin, X.; Li, J.; Yuan, M.; Li, R.; Wang, T.; Wang, T.; Hu, H.; Gu, J.
Eur. J. Org. Chem. 2016, 1577. (d) Fang, Y.; Zhang, L.; Li, J.; Jin, X.;
Yuan, M.; Li, R.; Wu, R.; Fang, J. Org. Lett. 2015, 17, 798. (e) Fang,
Y.; Zhang, L.; Jin, X.; Li, J.; Yuan, M.; Li, R.; Gao, H.; Fang, J.; Liu, Y.
Synlett 2015, 26, 980. (f) Yuan, M.; Fang, Y.; Zhang, L.; Jin, X.;
Tao, M.; Ye, Q.; Li, R.; Li, J.; Zheng, H.; Gu, J. Chin. J. Chem. 2015,
33, 1119. (g) Fang, Y.; Yuan, M.; Zhang, J.; Zhang, L.; Jin, X.; Li, R.;
Li, J. Tetrahedron Lett. 2016, 57, 1460.
(12) Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461.
(13) Jiang, M.; Feng, L.; Feng, J.; Jiao, P. Org. Lett. 2017, 19, 2210.
(14) (a) Myers, A. G.; Zheng, B.; Movassaghi, M. J. Org. Chem. 1997,
62, 7507. (b) Fang, Y.; Yuan, M.; Jin, X.; Zhang, L.; Li, R.; Yang, S.;
Fang, M. Tetrahedron Lett. 2016, 57, 1368.
Funding Information
This work was supported by the Ningbo Natural Science Foundation
of China (No. 2019A610203).
N
a
turalSc
i
e
nc
e
F
o
u
n
d
a
ti
o
n
o
f
N
i
n
g
b
o
(2
0
1
9
A
6
1
0
2
0
3
)
(15) (a) Tabatabaeian, K.; Mamaghani, M.; Mahmoodi, N. O.;
Khorshidi, A. Catal. Commun. 2008, 9, 416. (b) Joarder, D. D.;
Gayen, S.; Sarkar, R.; Bhattacharya, R.; Roy, S.; Maiti, D. K. J. Org.
Chem. 2019, 84, 8468.
(16) (3,3-Diethoxyprop-1-en-2-yl)benzene (3a): Typical Proce-
dure
Acknowledgment
Many thanks to Professor Yewen Fang at the Ningbo University of
Technology for his generous support and valuable suggestions.
A Schlenk tube equipped with a magnetic stirrer bar was
charged with Pd(OAc)2 (0.9 mg, 0.004 mmol, 2 mol%), XPhos
(3.8 mg, 0.008 mmol, 4 mol%), Cs2CO3 (163 mg, 0.5 mmol, 2.5
equiv), and PhB(OH)2 (2a; 48.8 mg, 0.4 mmol, 2 equiv). The tube
was then sealed with a cap and degassed by alternating vacuum
evacuation and N2 backfill. A 0.2 M solution of 2-bromo-3,3-
diethoxyprop-1-ene (1a; 41.6 mg, 0.2 mmol) in 1,4-dioxane (1
mL) was added to the tube under nitrogen, and the mixture was
stirred at 40 °C for 3 h. When the reaction was complete (TLC),
the mixture was cooled to r.t., diluted with EtOAc (2 mL), and
pushed through a plug of silica gel with EtOAc. The filtrate was
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/a-1322-3916.
S
u
p
p
orti
n
gI
n
f
orm
a
ti
o
n
S
u
p
p
orti
n
gI
n
f
orm
a
ti
o
n
© 2020. Thieme. All rights reserved. Synlett 2021, 32, 723–727

727
L. Zhang
Letter
Synlett
concentrated under reduced pressure, and the residue was puri-
fied by chromatography [silica gel (300-400 mesh), EtOAc-
petroleum ether (1:100)] to give a light-yellow oil; yield: 34.6
mg (84%).
3 H), 5.56 (s, 1 H), 5.55 (s, 1 H), 5.25 (s, 1 H), 3.68–3.62 (m, 2 H),
3.58–3.52 (m, 2 H), 1.21 (t, J = 7.1 Hz, 6 H). 13C NMR (125 MHz,
CDCl3):  = 144.9, 138.5, 128.1, 127.6, 126.7, 115.7, 101.8, 61.4,
15.1.
1H NMR (500 MHz, CDCl3):  = 7.53–7.52 (m, 2 H), 7.34–7.28 (m,
© 2020. Thieme. All rights reserved. Synlett 2021, 32, 723–727