t-BuOK promoted stereoselective isomerization of allyl aryl ethers

Article abstract of DOI:10.1016/j.tetlet.2020.152278

The t-BuOK promoted stereoselective isomerization of allyl aryl ethers has been developed. The reactions proceeded well in methyl tert-butyl ether (MTBE), providing the corresponding products in good to excellent yields (83–96percent). Most of the substra

Full text of DOI:10.1016/j.tetlet.2020.152278

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t-BuOK promoted stereoselective isomerization of allyl aryl ethers
Mingqi Shi, Liang Wang, Qun Chen, Mingyang He, Minggui Shen, Zhi-hui
Zhang
PII:
S0040-4039(20)30745-0
DOI:
Reference:
https://doi.org/10.1016/j.tetlet.2020.152278
TETL 152278
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Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
10 June 2020
15 July 2020
21 July 2020
Please cite this article as: Shi, M., Wang, L., Chen, Q., He, M., Shen, M., Zhang, Z-h., t-BuOK promoted
stereoselective isomerization of allyl aryl ethers, Tetrahedron Letters (2020), doi: https://doi.org/10.1016/j.tetlet.
2020.152278
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Graphical Abstract
t-BuOK promoted stereoselective
Leave this area blank for abstract info.
isomerization of allyl aryl ethers
Mingqi Shi,a Liang Wang,a,b,* Qun Chen,a Mingyang He,a Minggui Shen,a,c and Zhi-hui Zhanga,*

1
Tetrahedron Letters
journal homepage: www.elsevier.com
t-BuOK promoted stereoselective isomerization of allyl aryl ethers
Mingqi Shi,a Liang Wang,a,b,* Qun Chen,a Mingyang He,a Minggui Shen,a,c and Zhi-hui Zhanga,*
a School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, Changzhou University, Changzhou 213164,
China
b School of Chemical and Pharmaceutical Engineering, Changzhou Vocational Institute of Engineering, Changzhou 213164, China
c Institute of Chemical Industry of Forest Products, National Engineering Laboratory for Biomass Chemical Utilization, Key and Open Laboratory on Forest
Chemical Engineering, Key Laboratory of Biomass Energy and Material, Jiangsu Province, Nanjing 210037 , China
*Corresponding author. E-mail: lwcczu@126.com and zhangzh@cczu.edu.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The t-BuOK promoted stereoselective isomerization of allyl aryl ethers has been developed.
The reactions proceeded well in methyl tert-butyl ether (MTBE), providing the
corresponding products in good to excellent yields (83–96%). Most of the substrates were
isomerized predominantly to the Z isomers with excellent stereoselectivities. Gram-scale
synthesis was also achieved on a 10 mmol scale. Moreover, the cascade Cannizzaro and
isomerization reactions, and the one-pot isomerization and styryl sulfide formation reactions,
were also realized, affording a potential synthetic route to access interesting compounds.
Available online
Keywords:
Allyl aryl ethers
Isomerization
Base-promoted
Stereoselective synthesis
2009 Elsevier Ltd. All rights reserved.
Vinyl ethers are useful synthetic intermediates in various
organic transformations such as cycloaddition,1-3 cyclization,4
and the aldol reaction.5 They are also utilized as monomers to
produce functional polymers.6,7 Generally, vinyl ethers can be
efficiently prepared via the isomerization of allyl ethers in the
presence of bases (Scheme 1, a)8 or transition metal catalysts
(Scheme 1, b).9
yields, unsatisfactory stereoselectivities, and harsh reaction
conditions.
Inspired by the above-mentioned pioneering works, herein,
we report the t-BuOK-promoted stereoselective isomerization
of allyl aryl ethers in MTBE. The yields and stereoselectivities
are excellent and a series of substrates are compatible with the
reaction conditions (Scheme 1, c).
Among the reported procedures, transition metal catalysts
are used more often than bases. For example, ruthenium10-12
and iridium9a complexes efficiently catalyze the isomerization
of allyl ethers. However, some isomerization reactions did not
proceed well when allyl aryl ethers were used due to the strong
coordinating effect between the catalyst and the substrate.13
Moreover, the high cost of these metal catalysts is a concern
for large-scale reactions. It is also worth noting that usually E-
configuration products are thermodynamically generated as the
dominant products. Thus, the development of stereoselective
isomerization processes for this reaction is still a significant
challenge. On the contrary, the base-promoted isomerization of
allyl ethers has achieved varying degrees of success. Although
these procedures are not catalytic, the bases are much cheaper
and can be readily removed after the reaction. Bases such as t-
BuOK,9d,14,15 butyllithium16 and lithium diisopropylamide17
have been employed for this transformation. However, the
reported methods still suffer from drawbacks such as low
Scheme 1. Synthetic routes for the isomerization of allyl aryl ethers.
Initially, (allyloxy)benzene 1a and t-BuOK were chosen as
the model substrate and base to optimize the reaction
conditions (Table 1). The solvent significantly affected the
reaction. No reaction was observed when the reaction was
conducted either in 1-octane, 1,2-dichlorethane (DCE), CH2Cl2,
acetonitrile, DMF or hexafluoroisopropanol (HFIP) (Entries 1-
o
6) at 100 C for 6 h. DMSO was reported to be a suitable

2
Tetrahedron Letters
reaction medium for such reactions. With this solvent, a 37%
Table 2. Isomerization of various allyl aryl ethers.a
yield of 2a (95% Z isomer) was obtained (Entry 7).
Tetrahydrofuran (THF) and 1,4-dioxane were also trialled,
however, lower yields and stereoselectivities were obtained
(Entries 8 and 9). Pleasingly, the isomerization of 1a in MTBE
provided the desired Z isomer in 94% yield (Entry 10). Other
bases were then examined (Entries 11-14). Among them, t-
BuONa, NaH, KN(SiMe3)2 and NaN(SiMe3)2 did not promote
the reaction at all. Only trace amounts of 2a were observed
when the reactions were performed in the presence of KOH
and NaOH (Entries 15 and 16). In addition, either elevating or
reducing the reaction temperature led to decreased yields while
the E/Z ratios were not affected (Entries 17 and 18). Finally,
the amount of t-BuOK was evaluated which clearly indicated
that 3 equivalents of t-BuOK was optimum. Moreover, the
reaction performed under air led to a lower yield of 2a due to
the formation of by-products (Entry 19).
Yield
(%)b
Entry
1
Substrate
Main product
Z:E c
94
95
99:1
1a
2a
2b
2
3
98:2
1b
Table 1. Optimization of the reaction conditions.a
86
>99:1
2c
1c
1d
1e
1f
Temp.
(oC)
Yield 2a
4
5
6
83
87
91
87:13
>99:1
>99:1
Entry
Base
Solvent
1-octane
DCE
Z:Ec
(%)b
2d
2e
1
2
3
4
5
6
7
8
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
100
100
100
100
100
100
100
100
0
0
‒
‒
‒
CH2Cl2
MeCN
DMF
0
0
‒
0
‒
2f
2g
2h
HFIP
0
‒
DMSO
THF
37
19
95:5
88:12
7
8
93
96
97:3
1g
1h
1,4-
dioxane
9
t-BuOK
100
12
85:15
>99:1
10
11
12
13
14
15
16
17
18
t-BuOK
t-BuONa
NaH
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
100
100
100
100
100
100
100
120
80
94
0
99:1
‒
9
93
95
92
>99:1
97:3
0
‒
2i
2j
1i
1j
KN(SiMe3)2
NaN(SiMe3)2
KOH
0
‒
10
11
0
‒
trace
trace
75
41
‒
94:6
NaOH
‒
1k
1l
2k
2l
t-BuOK
t-BuOK
99:1
99:1
12
13
83
85
98:2
81d, 90e,
83f
19
t-BuOK
MTBE
100
99:1
aReagents and conditions: 1a (0.2 mmol, 1 equiv.), base (0.6 mmol, 3
equiv.), solvent (2 mL), 6 h, N2. bGC yield based on 1a. cCalculated by 1H
NMR spectroscopy. dt-BuOK (2 equiv.). et-BuOK (4 equiv.). fUnder air.
>99:1
With the optimized reaction conditions in hand, a series of
allyl aryl ethers were then evaluated to probe the scope and
generality of the protocol.18 The results are summarized in
Table 2.
2m
1m

3
aReagents and conditions: 1 (0.2 mmol, 1 equiv.), t-BuOK (0.6 mmol, 3
equiv.), MTBE (2 mL), 100 oC, 6 h, N2. bGC yields. cCalculated by 1H
NMR spectroscopy.
5
6
3,5-di-tert-butyl
33
29
>99:1
>99:1
4e
4f
5-Cl
aReagents and conditions: 3 (0.2 mmol), t-BuOK (0.8 mmol), MTBE (2
mL), 100 oC, N2, 24 h. bIsolated yields based on 0.1 mmol of 3. cCalculated
by 1H NMR spectroscopy.
Generally, the investigated allyl aryl ethers gave the
corresponding products in good to excellent yields (83–96%).
Functional groups including alkyl, methoxyl, nitro and halogen
were all well tolerated. The effect of steric hindrance was
negligible. Both the ortho-and meta-substituted substrates
provided the desired products in excellent yields. The C–Br
and C–I bonds in 2g and 2h were not affected, enabling further
manipulation of the initial products. Substrates 1k-m were also
examined, and all the reactions proceeded well. It is worth
noting that nearly all the substrates were isomerized
predominantly to the Z isomers. The nitro-substituted allyl aryl
ether 1d, however, gave lower stereoselectivity (Z/E = 87:13).
In addition, substrates with bulkier groups at the ortho-
positions (1n), allyl heteroaryl ether (1o), allyl aryl sulfide (1p),
and N-allylimidazole (1q) were evaluated (Scheme 2). It was
observed that the reaction of 1n led to trace amounts of the
desired product. No reaction occurred when substrate 1o was
utilized. The S-allyl compound 1p and N-allyl compound 1q,
however, were isomerized to the desired products in good
yields. It was also worth noting that E isomers were observed
as the major products in these reactions.
We also examined the one-pot condensation and
isomerization reaction of substrate 3 in the presence of DMSO
(Scheme 3). The expected product 5 was observed as the minor
product. Compound 6 was formed as the major product.
Notably, the C=C bonds of the styryl sulfide are predominantly
trans, while those of the vinyl ether are cis.
Scheme 3. One-pot isomerization and styryl sulfide formation reactions.
With regard to the mechanism, He and co-workers
previously observed the synthesis of styryl sulfides from
benzyl alcohols and DMSO in the presence of Ag/C.19 Li and
co-workers also reported the synthesis of styryl sulfides from
the direct C–C coupling of benzyl alcohols and DMSO under
the assistance of cobalt modified N-doped carbon nanotubes.20
In their studies, benzyl alcohols were oxidized to aldehydes
under basic conditions and meanwhile H2 was generated. The
vinyl sulfoxides were then reduced to form styryl sulfides. It
should also be pointed out that styryl sulfides could also be
directly generated from vinyl sulfoxides under strong basic
reaction conditions.21 However, the exact mechanism currently
remains unclear. Efforts are underway to elucidate the
mechanistic details of this reaction and the results will be
reported in due course.
Scheme 2. Other substrates examined for the isomerization reaction.
The gram-scale synthesis of 2a was also performed. Product
2a was obtained in 81% yield on a 10 mmol scale after 12 h
(Scheme 3).
Scheme 3. Gram-scale synthesis of 2a.
In summary,
a
t-BuOK promoted stereoselective
Next,
we
evaluated
the
reactivity
of
2-
isomerization of allyl aryl ethers has been developed. The
desired products were obtained in good to excellent yields
and excellent stereoselectivities. The gram-scale synthesis
was also achieved on a 10 mmol scale. Moreover, the cascade
Cannizzaro and isomerization reactions, and the one-pot
isomerization and styryl sulfide formation reactions, were also
realized, affording a potential synthetic route to access
interesting compounds.
(allyloxy)benzaldehyde derivatives 3. Interestingly, the formyl
group did not survive under the standard reaction conditions.
Further studies showed that both Cannizzaro and isomerization
reactions occurred in the presence of 4 equivalents of t-BuOK
for 24 h (Table 3). Product 4a-f were obtained with excellent
stereoselectivities, although a lower stereoselectivity was
observed for 4c.
Table 3. t-BuOK promoted Cannizzaro and isomerization reactions.a
Acknowledgments
We gratefully acknowledge financial support from China
Postdoctoral Science Foundation (2018M632289), the Priority
Academic Program Development of Jiangsu Higher Education
Institutions (PAPD), Jiangsu Key Laboratory of Advanced
Catalytic Materials and Technology (BM2012110) and Jiangsu
Key Laboratory of Biomass Energy and Material
(JSBEM201806 and JSBEM201919).
Entry
1
R
H
Product
Yield (%)b
40
Z:Ec
4a
>99:1
2
3
4
4-CH3
4-OMe
5-CH3
4b
4c
4d
43
39
36
>99:1
89:11
>99:1

4
Tetrahedron Letters
References and notes
gel column chromatography. Compounds 4 and 6 were
synthesized from compound 3 using the same method.
19 Zhang, Q.; Cai, S.; Li, L.; Chen, Y.; Rong, H.; Niu, Z.;
Liu, J.; He, W.; Li, Y. ACS Catal. 2013, 3, 1681.
20 Li, J.; Liu, G.; Shi, L.; Xing, Q.; Li, F. Green Chem.
2017, 19, 5782.
1
2
3
4
5
6
Krompiec, S.; Bujak, P.; Szczepankiewicz, W.
Tetrahedron Lett. 2008, 49, 6071.
Greene, A. E.; Charbonnier, F. Tetrahedron Lett. 1985,
26, 5525.
Harmata, M.; Lee, D. R.; Barnes, C. L. Org. Lett. 2005,
7, 1881.
Chen, C.; Lai, Y.; Wu, R.; Liu, Y.; Lin, Y.
ChemCatChem 2016, 8, 2193.
Kawano, Y.; Fujisawa, H.; Mukaiyama, T. Chem. Lett.
2005, 34, 614.
Sangermano, M.; Malucelli, G.; Bongiovanni, R.; Pirola,
A.; Annby, U.; Rehnberg, N. Eur. Polym. J. 2002, 38,
655.
21 Shi, M.; Shen, Y. J. Chem. Res (S). 2002, 422.
7
8
Kim, W. G.; Ahn, H. K.; Lee, H. W.; Kim, S. H.;
Crivello, J. V. Opt. Mater. 2002, 21, 343.
(a) Tarbel, D. S.; Lovett, W. E. J. Am. Chem. Soc. 1956,
78, 2259. (b) Price, C. C.; Snyder, W. H. J. Am. Chem.
Soc. 1961, 83, 1773. (c) Price, C. C.; Snyder, W. H. J.
Org. Chem. 1962, 27, 4639. (d) Taskinen, E.; Virtanen, R.
J. Org. Chem. 1977, 42, 1443. (e) Scharf, H. D.; Plum,
H.; Fleischhauer, J.; Schleker, W. Chem. Ber. 1979, 112,
862. (f) Taskinen, E. Tetrahedron 1993, 49, 11389. (g)
Taskinen, E.; Laine, M. Struct. Chem. 1997, 8, 367. (h)
Mereyala, H. B.; Gurrala, S. R.; Mohan, S. K.
Tetrahedron 1999, 55, 11331. (i) Taskinen, E. J. Chem.
Soc. Perkin Trans. 2 2001, 1824.
9
(a) Ohmura, T.; Shirai, Y.; Yamamoto, Y.; Miyaura, N.
Chem. Commun. 1998, 1337. (b) Krompiec, S.; Kuznik,
N.; Urbala, M.; Rzepa, J. J. Mol. Catal. A: Chem. 2006,
248, 198. (c) Carless, H. A.; Haywood, D. J. J. Chem.
Soc., Chem. Commun. 1980, 980. (d) Crivello, J. V.;
Kong, S. J. Org. Chem. 1998, 63, 6745. (e) Mamone, P.;
Grunberg, M. F.; Fromm, A.; Khan, B. A.; Gooßen, L. J.
Org. Lett. 2012, 14, 3716.
10 Larsen, C. R.; Grotjahn, D. B. J. Am. Chem. Soc. 2012,
134, 10357.
11 Grotjahn, D. B.; Larsen, C. R.; Gustafson, J. L.; Nair, R.;
Sharma, A. J. Am. Chem. Soc. 2007, 129, 9592.
12 Donohoe, T. J.; O’Riordan, T. J. C.; Rosa, C. P. Angew.
Chem., Int. Ed. 2009, 48, 1014.
13 Krompiec, S.; Kuz´nik, N.; Krompiec, M.; Penczek, R.;
Mrzigod, J.; Torz, A. J. Mol. Catal. A: Chem. 2006, 253,
132.
14 Evans, D. A.; Kvaerno, L.; Dunn, T. B.; Beauchemin, A.;
Raymer, B.; Mulder, J. A.; Olhava, E. J.; Juhl, M.;
Kagechika, K.; Favor, D. A. J. Am. Chem. Soc. 2008,
130, 16295.
15 Krompiec, S.; Marcol, B.; Zych, D.; Kurpanik, A.;
Danikiewicz, W.; Matussek, M.; Kuznik, N.
ChemistrySelect 2017, 2, 6717.
16 Harmata, M.; Lee, D. R.; Barnes, C. L. Org. Lett. 2005,
7, 1881.
17 Su, C.; Williard, P. G. Org. Lett. 2010, 12, 5378.
18 General procedure for the synthesis of 2: A sealed tube
equipped with a magnetic stirrer bar was charged with
substrate 1 (0.2 mmol, 1 equiv.), t-BuOK (0.6 mmol, 3
equiv.) and MTBE (2 mL) in a glovebox. The reaction
o
mixture was then heated to 100 C and stirred for 6 h.
After reaction completion, water (10 mL) was added to
the reaction mixture and the mixture was extracted with
ether (10 mL × 3). The collected organic extracts were
dried over Na2SO4. The solvent was removed under
reduced pressure and the residue was purified by silica

5
Graphical Abstract
t-BuOK promoted stereoselective isomerization of allyl
aryl ethers
Mingqi Shi,a Liang Wang,a,b,* Qun Chen,a Mingyang He,a
Minggui Shen,a,c and Zhi-hui Zhanga,*
a School of Petrochemical Engineering, Jiangsu Key
Laboratory of Advanced Catalytic Materials & Technology,
Changzhou University, Changzhou 213164, China
b School of Chemical and Pharmaceutical Engineering,
Changzhou Vocational Institute of Engineering, Changzhou
213164, China
c Institute of Chemical Industry of Forest Products, National
Engineering Laboratory for Biomass Chemical Utilization,
Key and Open Laboratory on Forest Chemical Engineering,
Key Laboratory of Biomass Energy and Material, Jiangsu
Province, Nanjing 210037, China
E-mail: lwcczu@126.com and zhangzh@cczu.edu.cn
t-BuOK promoted stereoselective isomerization of
allyl aryl ethers has been developed.

6
Tetrahedron Letters
Highlights
 Good to excellent yields and stereoselectivities.
 Good substrate scope;
 Gram-scale synthesis can be achieved.
 Cascade Cannizzaro and isomerization reactions,
and the one-pot isomerization and styryl sulfide
formation reactions can be realized.

7
Conflict of interest statement
The authors declared that they have no
conflicts of interest to this work. We declare that
we do not have any commercial or associative
interest that represents a conflict of interest in
connection with the work submitted.