Bifunctional Amine-Squaramide Catalyzed Friedel–Crafts Alkylation Based on ortho-Quinone Methides in Oil-Water Phases: Enantioselective Synthesis of Triarylmethanes

Article abstract of DOI:10.1002/adsc.201600814

An efficient enantioselective Friedel–Crafts alkylation reaction of electron-rich β-naphthol with in situ generated ortho-quinone methides catalyzed by chiral bifunctional amine-squaramide catalysts has been developed. The chiral triarylmethane derivative

Full text of DOI:10.1002/adsc.201600814

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DOI: 10.1002/adsc.201600814
Bifunctional Amine-Squaramide Catalyzed Friedel–Crafts
Alkylation Based on ortho-Quinone Methides in Oil-Water
Phases: Enantioselective Synthesis of Triarylmethanes
Yifeng Wang,a Cheng Zhang,a Haojiang Wang,a Yidong Jiang,a Xiaohua Du,a
and Danqian Xua,*
a
State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Key Laboratory of Green Pesticides and
Cleaner Production Technology of Zhejiang Province. Zhejiang University of Technology, Hangzhou 310014, Peopleꢀs
Republic of China
E-mail: chrc@zjut.edu.cn
Received: July 26, 2016; Revised: November 1, 2016; Published online: && &&, 0000
Supporting information for this article can be found under: http://dx.doi.org/10.1002/adsc.201600814.
Abstract: An efficient enantioselective Friedel–
Crafts alkylation reaction of electron-rich b-naph-
thol with in situ generated ortho-quinone methides
catalyzed by chiral bifunctional amine-squaramide
catalysts has been developed. The chiral triarylme-
thane derivatives were obtained in good to high
yields (up to 97% yield) with high enantioselectivi-
ties (up to 97% ee) for most substrates under mild
conditions. This study also revealed that the oil-
water biphase could significantly improve the effi-
ciency of this catalytic system.
and diarylindolylmethanes in the presence of chiral
phosphoric acids with high enantioselectivities, start-
ing from the readily available ortho-hydroxybenzhydr-
yl alcohol.[6] Zhang and Han synthesized special aryl-
diindolylmethanes by asymmetric Friedel–Crafts alky-
lation of electron-rich indoles with 3-indolylphenyl-
methanol catalyzed by a chiral phosphoric acid.[7] Fur-
thermore, the groups of Jarvo,[8] Watson,[9] and
Crudden[10] constructed the target triarylmethanes
with excellent enantioselectivities via stereospecific
Ni- or Pd- catalyzed cross-coupling technology.
ortho-Quinone methides (o-QMs) were introduced
by Fries, and Amouri disclosed the first crystal struc-
ture by X-ray crystallography.[11] o-QMs are powerful
synthetic intermediates for the construction of com-
plex compounds in organic synthesis, drug chemistry
and material chemistry because of their high reactivi-
ty.[12] Generally, o-QMs have been mainly applied in
conjugate additions, hetero Diels–Alder reactions,
Keywords: asymmetric catalysis; Friedel–Crafts re-
action; oil-water phases; ortho-quinone methides;
triarylmethane derivatives
Triarylmethanes have been regarded as an important and 6p-electrocyclizations.[13] For example, Rueping
class of organic compounds due to their remarkable developed a chiral BINOL-based N-triflylphosphor-
significance in materials science, natural products, and
ACHTUNGTRENaNUGN mide-catalyzed, enantioselective synthesis of special
medicinal chemistry especially.[1] For instance, they chromanes via [4+2] hetero-Diels–Alder reactions be-
can be used as potential drug candidates for the treat- tween unactivated alkenes and in situ generated o-
ment of cancer and tubercular diseases.[2] Heteroaryl- QMs.[14] Li synthesized chiral benzyl thiols via the
substituted triarylmethanes have been identified as enantioselective conjugated addition of trityl thiol to
powerful pharmaceuticals and bioactive molecules in situ generated o-QMs, catalyzed by a bifunctional
like letrozole, clotrimazole and vorozole.[3] Recently, squaramide organocatalyst.[15] Hayashi constructed
triarylmethanes as a new class of Connexin50 inhibi- the target triarylmethanes in highly optically enriched
tors were reported by Srinivas.[4] Therefore, substan- form through ortho-quinone methide intermediates
tial attention has been given to novel asymmetric syn- which undergo Rh-catalyzed asymmetric 1,4-addition
thetic methods to access triarylmethanes and related of the arylboron reagents.[16] Recently, a highly enan-
compounds.
tioselective conjugate addition of 1,3-dicarbonyl com-
However, to the best of our knowledge, only a few pounds to in situ generated o-QMs catalyzed by chiral
enantioselective synthetic routes to triarylmethanes bifunctional amine-squaramide catalysts has been de-
have been reported, compared to the plethora of rac- veloped by Bernardi.[17]
emic routes.[5] Schneider synthesized triarylmethanes
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Figure 1. Screened organocatalysts.
Table 1. Catalyst screening for the enantioselective Friedel–
Crafts alkylation reaction of 6-methoxy-2-[phenyl(tosyl)me-
thyl]phenol 1a with b-naphthol 2a.[a]
Organocatalytic asymmetric synthesis has been re-
garded as an essential part of our groupꢀs work.[18]
Therefore, a new asymmetric bifunctional amine-
squaramide catalyzed process for an enantioselective
synthesis of desired triarylmethanes by using o-QMs
as reactive intermediates was developed in our lab.
We initiated our studies by performing the reaction
of
6-methoxy-2-[phenyl(tosyl)methyl]phenol
1a
(1.0 equiv.) and b-naphthol 2a (1.2 equiv.) at room
temperature in the presence of bifunctional amine-
squaramides (10 mol%) (Figure 1), using K2CO3
(2.5 equiv.) as the base and a mixture of CH2Cl2 and
H2O as the solvent, respectively. We envisaged that
the reactive intermediate o-QM of (E)-6-benzylidene-
2-methoxycyclohexa-2,4-dienone could be generated
in situ through sulfinic acid elimination under the
basic condition, and the introduction of an oil-water
biphasic system might realize the spatial separation of
sulfinic acid from the organic phase to ensure mild
conditions in the regeneration of the catalyst. To our
delight, as shown in Table 1, triarylmethane 3a was
isolated with good yield and enantioselectivity using
Entry
Catalyst
Time [h]
Yield[b] [%]
ee[c] [%]
1
2
3
4
5
6
7
8
9
I
II
6
6
6
6
6
6
6
6
6
87
68
79
51
56
82
79
82
59
À83
À85
78
III
IV
Va
Vb
Vc
Vd
VI
squaramide
I
in the biphasic reaction system
À72
(entry 1). Subsequently, the catalytic potentials of all
kinds of bifunctional amine-squaramide catalysts were
examined. Squaramide II exhibited slightly better
enantioselectivity than the squaramide I, but the yield
of product was slightly lower (entry 2). No improve-
ment in terms of reaction yields and enantioselectivi-
ties was observed by using quinine-derived squar-
81
83
91
92
66
[a]
All reactions were conducted with 1a (0.1 mmol), b-
naphthol 2a (1.2 equiv., 0.12 mmol), and catalyst
(0.01 mmol, 10 mol%), K2CO3 (2.5 equiv.) in 1 mL of
CH2Cl2 and 1 mL of H2O at room temperature.
Yield of the isolated product after chromatography on
silica gel.
ACHTUNGTRENNUNGamide III and quinidine-derived squaramide IV (en-
tries 3 and 4). Pleasingly, cinchonidine-derived squar-
amide Vd with a 3,5-bis(trifluoromethyl)benzene sub-
stituent exhibited promising catalytic activity, which
led to an ee value of 92% (entry 8), while the squar-
[b]
[c]
Determined by chiral HPLC analysis (Daicel Chiralpak
IC-H, hexane/i-PrOH=99/1).
ACHTUNGTRENNUNGamide VI gave the lowest enantioselectivity (entry 9).
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Table 2. Optimization of the reaction conditions.[a]
common solvents such as ClCH2CH2Cl, toluene, and
ethyl acetate were found to be inferior as compared
to CH2Cl2, reducing the enantioselectivities and yields
(entries 6 and 8–10). Racemic products were obtained
in THF and CH3CN, since these solvents are miscible
with water, which could not provide an oil-water bi-
phasic reaction system (entries 11 and 12). Moreover,
when reducing the amount of K2CO3 to 1.5 equiv., the
enantioselectivity was maintained but a slightly lower
yield was observed (entry 13). No significant changes
in both yields and enantioselectivities were observed
on increasing the amount of K2CO3 to 3.5 equiv. and
4.5 equiv. (entries 14 and 15).
To clarify the role of water in the reaction, control
experiments were performed. When using CH2Cl2 as
the organic solvent and K2CO3 as the base, it was
found that the enantioselectivity of the corresponding
product get worse with the reduction of the amount
of catalyst Vd (Table 3, entries 1–4). However, in the
CH2Cl2-water biphasic system, it always maintains ex-
Entry Base
Organic solvent Yield[b] [%] ee[c] [%]
1[d]
2
none
KOH
Na2HPO4
NaHCO3
CH3COONa CH2Cl2
K2CO3
CsCO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
nr[e]
92
45
48
nr[e]
82
79
81
89
68
88
87
70
83
80
nd[f]
16
91
89
nd[f]
92
91
92
90
36
0
3[d]
4[d]
5[d]
6
CH2Cl2
CH2Cl2
7
8
9
10
11
12
13[g]
14[h]
15[i]
ClCH2CH2Cl
toluene
ethyl acetate
THF
CH3CN
CH2Cl2
CH2Cl2
0
91
92
92
CH2Cl2
[a]
Unless otherwise specified, all reactions were conducted
with 1a (0.1 mmol), b-naphthol 2a (1.2 equiv.,
0.12 mmol), and the catalyst Vd (0.01 mmol, 10 mol%),
inorganic base (2.5 equiv.), in 1 mL of the specified or- cellent catalytic efficiency in spite of the change in
ganic solvent and 1 mL of H2O at room temperature for
6 h.
Yield of the isolated product after chromatography on
silica gel.
Determined by chiral HPLC analysis (Daicel Chiralpak
IC-H, hexane/i-PrOH=99/1).
Reaction time: 12 h.
nr means no reaction.
nd means not determined.
K2CO3 (1.5 equiv.) was used.
K2CO3 (3.5 equiv.) was used.
K2CO3 (4.5 equiv.) was used.
the amount of catalyst Vd, whereby 5 mol% is regard-
ed as the proper catalyst loading, affording the prod-
uct 3a in 92% yield with 96% ee (entries 8–10). On
the other hand, the enantioselectivity of 3a gradually
declined with the amount of K2CO3 increasing from
[b]
[c]
[d]
[e]
[f]
Table 3. Control experiments for verifying the essential role
of water.[a]
[g]
[h]
[i]
En- Solvent
Cat. loading Yield[b] ee[c]
try
(mL)
[mol%]
[%]
[%]
1
2
3
4
CH2Cl2 (1.0)
CH2Cl2 (1.0)
CH2Cl2 (1.0)
CH2Cl2 (1.0)
CH2Cl2 (1.0)
CH2Cl2 (1.0)
CH2Cl2 (1.0)
CH2Cl2/H2O (1.0/1.0)
CH2Cl2/H2O (1.0/1.0)
CH2Cl2/H2O (1.0/1.0)
CH2Cl2/H2O (1.0/0.5)
CH2Cl2/H2O (1.0/2.0)
CH2Cl2/H2O (0.5/0.5)
CH2Cl2/H2O (2.0/2.0)
2
5
76
79
84
82
79
82
77
87
92
82
82
88
81
83
44
45
75
80
80
65
33
92
96
92
94
93
92
94
In short, systematic screening of the catalysts revealed
that catalyst Vd gave the best enantioselectivity,
which delivered the Friedel–Crafts alkylation product
3a with 82% yield and 92% ee (Table 1, entry 8).
10
15
10
10
10
2
5
10
5
5[d]
6[e]
7[f]
8
With the best organocatalyst in hand, we then in-
vestigated other parameters such as base and solvent.
As shown in Table 2, the reaction performed without
inorganic base gave no product (entry 1), which dem-
onstrated that the base played a crucial role in realiz-
ing the regeneration of the tertiary amine-squaramide
catalyst and conducting the subsequent addition with
the electron-rich b-naphthol. Strong base like KOH
gave a product with good yield, but poor enatioselec-
tivity (entry 2). Using Na2HPO4 and NaHCO3 as the
base, respectively, the reaction proceeded with low re-
activity, affording the product in slightly lower yield,
albeit the enantioselectivity was excellent (entries 3
and 4), while weaker base like CH3COONa were not
effective (entry 5). However, bases like Cs2CO3 and
K2CO3 gave the good yields and excellent enantiose-
lectivities, whereby K2CO3 gave the most promising
result (entries 6 and 7). Subsequently, the organic sol-
vent effect on this reaction was investigated. Several
9
10
11
12
13
14
5
5
5
[a]
Unless otherwise specified, all reactions were conducted
with 1a (0.1 mmol), b-naphthol 2a (1.2 equiv.,
0.12 mmol), and the different loading of catalyst Vd,
K2CO3 (2.5 equiv.), in CH2Cl2 or in an oil-water biphasic
system of CH2Cl2 and H2O at room temperature for 6 h.
Yield of the isolated product after chromatography on
silica gel.
Determined by chiral HPLC analysis (Daicel Chiralpak
IC-H, hexane/i-PrOH=99/1).
K2CO3 (1.5 equiv.) was used.
[b]
[c]
[d]
[e]
[f]
K2CO3 (3.5 equiv,) was used.
K2CO3 (4.5 equiv.) was used.
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1.5 equiv. to 4.5 equiv. in the CH2Cl2 reaction system, acted with b-naphthol 2 under the optimized reaction
while the enantioselectivity was always excellent with conditions and the results are summarized in Table 4.
the growth of the amount of K2CO3 in the CH2Cl2- Various 2-[phenyl(tosyl)methyl]phenols underwent
water biphase system (Table 3, entries 3, 5–7 vs. the reaction smoothly and the reactions were typically
Table 2, entries 6, 13–15). This result demonstrated completed within 4–6 h at room temperature. 2-[Phe-
that the water phase is also necessary to spatially sep- nyl(tosyl)methyl]phenols with no substitution at the 6
arate the inorganic base from the reaction mixture to position gave the triarylmethane derivatives 3b–e, 3i
avoid background reaction, apart from ensuring mild in good yields and moderate enantioselectivities (en-
conditions in the regeneration of the catalyst. More- tries 2–5 and 9). When introducing substitution (OMe,
over, 1:1 is the optimum proportion of solvents by in- F) at the 6 position, the Friedel–Crafts reactions af-
vestigating the different solvent ratios (entries 9, 11 forded the corresponding products 3a, 3f–h with
and12). Finally, we investigated the impact of reactant higher enantioselectivities (entries 1 and 6–8). These
concentrations. When the solvent was the mixture of results demonstrated that the presence of an H-bond-
1 mL of CH2Cl2 and 1 mL of H2O, it delivered the ing acceptor (OMe, F) at the 6 position is crucial for
product 3a with the most excellent result, in terms of a satisfactory stereochemical outcome. Based on the
both yield and enantioselectivity (92% yield and 96% competent substrate 6-methoxy-2-[phenyl(tosyl)me-
ee) (entries 9, 13 and 14).
thyl]phenol, various b-aryl substituents of o-QMs
To evaluate the scope of this process, various 2- were further investigated (entries 10–21), the corre-
[phenyl(tosyl)methyl]phenols 1 were subsequently re- sponding products 3j–u were obtained in high enan-
Table 4. Substrate scope.[a]
Entry
R1
R2
R3
Product 3
Yield[b] [%]
ee[c] [%]
1
2
3
4
5
6
7
8
6-OMe
H
4-Me
5-OMe
4-Cl
6-F
4-Br-6-OMe
4-I-6-OMe
H
6-OMe
6-OMe
6-OMe
6-OMe
6-OMe
6-OMe
6-OMe
6-OMe
6-OMe
6-OMe
6-OMe
6-OMe
6-OMe
6-OMe
6-OMe
6-OMe
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
92
68
60
83
84
84
84
92
92
95
86
86
88
58
92
77
78
87
87
64
97
93
85
82
76
96
55
42
65
52
78
97
97
72
91
94
91
92
91
95
95
92
94
94
88
91
89
94
93
68
9
4-MeOC6H4
4-MeC6H4
3-MeC6H4
3-MeOC6H4
4-MeOC6H4
2-MeOC6H4
4-FC6H4
4-ClC6H4
4-CF3C6H4
3,5-(CF3)2C6H3
3,4-(-OCH2O-)C6H3
1-naphthyl
2-furyl
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
H
H
H
H
3s
3t
3u
3v
3w
3x
3y
H
Ph
Ph
Ph
Et
3-Br
6-Br
7-Br
H
[a]
All reactions were carried out with 0.1 mmol (1 equiv,) of 1, 0.12 mmol (1.2 equiv,) of naphthol 2 using 5 mol% of catalyst
Vd, K2CO3 (2.5 equiv,) in 1 mL of CH2Cl2 and 1 mL of H2O at room temperature for 4–6 h.
Yield of the isolated product after chromatography on silica gel.
[b]
[c]
Determined by chiral HPLC analysis (Daicel Chiralpak IC-H, AS-H or AD-H).
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Figure 2. Proposed reaction pathway for the chiral bifunctional amine-squaramide catalyzed Friedel–Crafts alkylation reac-
tion of o-QMs with b-naphthol in the oil-water phases.
tioselectivities. Further substitution within the 2-naph- alizes the spatial separation of the inorganic base
thol ring also delivered the products 3v–x in compara- from the organic phase to suppress the racemic back-
bly high yields and enantioselectivities (entries 22– ground reaction,[15] resulting an excellent activity and
24). Moreover, o-QM with a b-alkyl (e.g., Et) sub- enantioselectivity. In addition, in the absence of an H-
stituent gave the corresponding product 3y in good bonding acceptor (OMe) at the 6 position of the o-
yield and moderate enantioselectivity (entry 25).
QM fragment, there may exist two coordination
The proposed reaction pathway for this new bifunc- modes, which led to poor enantioselectivities. Howev-
tional amine-squaramide-catalyzed asymmetric reac- er, there may exist only one coordination mode in the
tion is depicted in Figure 2. The o-QM is generated in presence of the H-bonding acceptor (OMe) at the 6
the organic phase with the production of TsH, which position of the o-QM fragment, which led to good
can protonate the basic nitrogen of the catalyst, and enantioselectivities.[19]
the resulting salt reacts with K2CO3, thereby regener-
In conclusion, a highly efficient chiral bifunctional
ating the catalyst. On the other hand, the use of water amine-squaramide-catalyzed Friedel–Crafts alkylation
as a second phase not only ensures mild conditions in reaction of electron-rich b-naphthol with in situ gener-
the regeneration of the catalyst but also effectively re- ated o-QM has been developed, which constructed
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c) T. Inamoto, S. Papineni, S. Chintharlapalli, S.-D.
Cho, S. Safe, A. M. Kamat, Mol. Cancer. Ther. 2008, 7,
3825–3833; d) P. M. Wood, L. L. Woo, J.-R. Labrosse,
M. N. Trusselle, S. Abbate, G. Longhi, E. Castiglioni, F.
Lebon, A. Purohit, M. J. Reed, J. Med. Chem. 2008, 51,
4226–4238; e) S. D. Cho, S.-O. Lee, S. Chintharlapalli,
M. Abdelrahim, S. Khan, K. Yoon, A. M. Kamat, S.
Safe, Mol. Pharmacol. 2010, 77, 396–404; f) P. M.
Wood, L. Woo, M. P. Thomas, M. F. Mahon, A. Purohit,
B. V. Potter, ChemMedChem 2011, 6, 1423–1438; g) K.
Takahashi, G. Yamagishi, T. Hiramatsu, A. Hosoya, K.
Onoe, H. Doi, H. Nagata, Y. Wada, H. Onoe, Y. Wata-
nabe, Bioorg. Med. Chem. 2011, 19, 1464–1470; h) K.
Yoon, S.-O. Lee, S.-D. Cho, K. Kim, S. Khan, S. Safe,
Carcinogenesis 2011, 32, 836–842.
a range of useful triarylmethanes with excellent yields
and enantioselectivities. In addition, this study also
verified that the oil-water biphase could significantly
improve the efficiency of this catalytic system. This
study further underlines a new route for highly enan-
tioselective syntheses of triarylmethanes involving o-
QMs, and also proves the significance of the oil-water
biphase for the chiral bifunctional amine-squaramide
catalysts.
Experimental Section
Catalytic Enantioselective Friedel–Crafts Alkylation
Reaction based on ortho-Quinone Methides
[4] S. B. Bodendiek, C. Rubinos, M. P. Trelles, N. Coleman,
D. P. Jenkins, H. Wulff, M. Srinivas, Front. Pharma-
col.2012, 3, 106.
To
a test tube were added catalyst Vd (0.005 mmol,
5 mol%), K2CO3 (2.5 equiv., 0.25 mmol), the substituted 2-
[phenyl(tosyl)methyl]phenol 1 (0.1 mmol) and b-naphthol 2
(1.2 equiv., 0.12 mmol), 1.0 mL CH2Cl2 and 1.0 mL H2O
were then added through a syringe. The resulting mixture
was stirred at room temperature for 4–6 h until the reaction
was completed (monitored by TLC). Then the mixture was
extracted with CH2Cl2, and the organic layer was dried over
anhydrous Na2SO4, filtered and concentrated under reduced
pressure. The crude product was purified by flash chroma-
tography to afford the product 3. The enantiomeric excess
was determined by HPLC using a Chiralpak IC-H, AS-H or
AD-H column.
[5] a) V. Nair, K. Abhilash, N. Vidya, Org. Lett. 2005, 7,
5857–5859; b) T. Niwa, H. Yorimitsu, K. Oshima, Org.
Lett. 2007, 9, 2373–2375; c) J.-Y. Yu, R. Kuwano, Org.
Lett. 2008, 10, 973–976; d) G. I. McGrew, J. Temaismi-
thi, P. J. Carroll, P. J. Walsh, Angew. Chem. 2010, 122,
5673–5676; Angew. Chem. Int. Ed. 2010, 49, 5541–5544;
e) J. Zhang, A. Bellomo, A. D. Creamer, S. D. Dreher,
P. J. Walsh, J. Am. Chem. Soc. 2012, 134, 13765–13772;
f) S. Tabuchi, K. Hirano, T. Satoh, M. Miura, J. Org.
Chem. 2014, 79, 5401–5411; g) J. Zhang, A. Bellomo, N.
Trongsiriwat, T. Jia, P. J. Carroll, S. D. Dreher, M. T.
Tudge, H. Yin, J. R. Robinson, E. J. Schelter, J. Am.
Chem. Soc. 2014, 136, 6276–6287.
[6] S. Saha, S. K. Alamsetti, C. Schneider, Chem. Commun.
2015, 51, 1461–1464.
Acknowledgements
[7] a) M.-H. Zhuo, Y.-J. Jiang, Y.-S. Fan, Y. Gao, S. Liu, S.
Zhang, Org. Lett. 2014, 16, 1096–1099; b) S. Qi, C.-Y.
Liu, J.-Y. Ding, F.-S. Han, Chem. Commun. 2014, 50,
8605–8608.
[8] a) B. L. Taylor, M. R. Harris, E. R. Jarvo, Angew.
Chem. 2012,124, 7910–7913; Angew. Chem. Int. Ed.
2012, 51, 7790–7793; b) M. R. Harris, L. E. Hanna,
M. A. Greene, C. E. Moore, E. R. Jarvo, J. Am. Chem.
Soc. 2013, 135, 3303–3306.
The research was supported by National Natural Science
Foundation of China (21402176) and Natural Science Foun-
dation of Zhejiang Province (LY14B020003) and Zhejiang
Key Course of Chemical Engineering and Technology, as
well as Key Laboratory of Green Pesticides and Cleaner Pro-
duction Technology of Zhejiang Province.
[9] Q. Zhou, H. D. Srinivas, S. Dasgupta, M. P. Watson, J.
Am. Chem. Soc. 2013, 135, 3307–3310.
References
[10] a) M. Nambo, C. M. Crudden, Angew. Chem. 2014, 126,
761–765; Angew. Chem. Int. Ed. 2014, 53, 742–746;
b) S. C. Matthew, B. W. Glasspoole, P. Eisenberger,
C. M. Crudden, J. Am. Chem. Soc. 2014, 136, 5828–
5831.
[1] a) D. F. Duxbury, Chem. Rev. 1993, 93, 381–433; b) M.
Shchepinov, V. Korshun, Chem. Soc. Rev. 2003, 32,
170–180; c) Y.-Q. Xu, J.-M. Lu, N.-J. Li, F. Yan, X.-W.
Xia, Q.-F. Xu, Eur. Polym. J. 2008, 44, 2404–2411;
d) S. A. Snyder, S. P. Breazzano, A. G. Ross, Y. Lin,
A. L. Zografos, J. Am. Chem. Soc. 2009, 131, 1753–
1765.
[2] a) A. K. Srivastava, R. Sharma, R. Mishra, A. K. Bala-
pure, P. S. Murthy, G. Panda, Bioorg. Med. Chem. 2006,
14, 1497–1505; b) M. K. Parai, G. Panda, V. Chaturvedi,
Y. Manju, S. Sinha, Bioorg. Med. Chem. Lett. 2008, 18,
289–292; c) R. Palchaudhuri, V. Nesterenko, P. J. Her-
genrother, J. Am. Chem. Soc. 2008, 130, 10274–10281.
[3] a) M. Recanatini, A. Cavalli, P. Valenti, Med. Res. Rev.
2002, 22, 282–304; b) S. D. Cho, K. Yoon, S. Chintharla-
palli, M. Abdelrahim, P. Lei, S. Hamilton, S. Khan,
S. K. Ramaiah, S. Safe, Cancer. Res. 2007, 67, 674–683;
[11] a) K. Fries, K. Kann, Justus Liebigs Ann. Chem. 1907,
353, 335–356; b) H. Amouri, Y. Besace, J. L. Bras, J.
Vaissermann, J. Am. Chem. Soc. 1998, 120, 6171–6172.
[12] For selected examples of using o-QMs as synthetic in-
termediates, see: a) B. B. Snider, Q. Lu, J. Org. Chem.
1996, 61, 2839–2844; b) H. Amouri, J. Le Bras, Acc.
Chem. Res. 2002, 35, 501–510; c) M. A. Marsini, Y.
Huang, C. C. Lindsey, K.-L. Wu, T. R. Pettus, Org. Lett.
2008, 10, 1477–1480; d) S. B. Ferreira, F. d. C. da Silva,
A. C. Pinto, D. T. Gonzaga, V. F. Ferreira, J. Heterocycl.
Chem. 2009, 46, 1080–1097; e) D. Richter, N. Hampel,
T. Singer, A. R. Ofial, H. Mayr, Eur. J. Org. Chem.
2009, 3203–3211; f) A. L. Lawrence, R. M. Adlington,
Adv. Synth. Catal. 0000, 000, 0 – 0
6
ꢁ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
J. E. Baldwin, V. Lee, J. A. Kershaw, A. L. Thompson,
Org. Lett. 2010, 12, 1676–1679.
[15] W. Guo, B. Wu, X. Zhou, P. Chen, X. Wang, Y. G.
Zhou, Y. Liu, C. Li, Angew. Chem. 2015, 127, 4605–
4609; Angew. Chem. Int. Ed. 2015, 54, 4522–4526.
[16] Y. Huang, T. Hayashi, J. Am. Chem. Soc. 2015, 137,
7556–7559.
[17] L. Caruana, M. Mondatori, V. Corti, S. Morales, A.
Mazzanti, M. Fochi, L. Bernardi, Chem. Eur. J. 2015,
21, 6037–6041.
[18] a) D. Q. Xu, Y. F. Wang, S. P. Luo, S. Zhang, A. G.
Zhong, H. Chen, Z. Y. Xu, Adv. Synth. Catal. Adv.
Synth. Catal 2008, 350, 2610–2616; b) D. Q. Xu, A. B.
Xia, S. P. Luo, J. Tang, S. Zhang, J. R. Jiang, Z. Y. Xu,
Angew. Chem. 2009, 121, 3879–3882; Angew. Chem.
Int. Ed. 2009, 48, 3821–3824; c) D. Q. Xu, Y. F. Wang,
W. Zhang, S. P. Luo, A. G. Zhong, A. B. Xia, Z. Y. Xu,
Chem. Eur. J. 2010, 16, 4177–4180; d) Y.-F. Wang, R.-X.
Chen, K. Wang, B.-B. Zhang, Z.-B. Li, D.-Q. Xu, Green
Chem. 2012, 14, 893–895; e) A. B. Xia, C. Wu, T. Wang,
Y. P. Zhang, X. H. Du, A. G. Zhong, D. Q. Xu, Z. Y.
Xu, Adv. Synth. Catal. Adv. Synth. Catal 2014, 356,
1753–1760.
[13] For recent selected reviews on ortho-quinone methides,
see: a) R. W. Van De Water, T. R. Pettus, Tetrahedron
2002, 58, 5367–5405; b) N. J. Willis, C. D. Bray, Chem.
Eur. J. 2012, 18, 9160–9173; c) M. S. Singh, A. Nagara-
ju, N. Anand, S. Chowdhury, RSC Adv. 2014, 4, 55924–
55959; d) W.-J. Bai, J. G. David, Z.-G Feng, M. G.
Weaver, K.-L. Wu, T. R. R. Pettus, Acc. Chem. Res.
2014, 47, 3655–3664; e) Z. B. Wang, J. W. Sun, Synthesis
2015, 47, 3629–3644; f) L. Caruana, M. Fochi, L. Ber-
nardi, Molecules 2015, 20, 11733–11764; for recent se-
lected examples on ortho-quinone methides, see:
g) T. P. Pathak, M. S. Sigman, J. Org. Chem. 2011, 76,
9210–9215; h) M.-W. Chen, L.-L. Cao, Z.-S. Ye, G.-F.
Jiang, Y.-G. Zhou, Chem. Commun. 2013, 49, 1660–
1662; i) B. Wu, X. Gao, M.-W. Chen, Y.-G. Zhou, Chin.
J. Chem. 2014, 32, 981–984; j) B. Wu, X. Gao, M.-W.
Chen, Y.-G. Zhou, Tetrahedron Lett. 2015, 56, 1135–
1137; k) B. Wu, X. Gao, Z. Yan, W.-X. Huang, Y.-G.
Zhou, Tetrahedron Lett. 2015, 56, 4334–4338; l) B. Wu,
X. Gao, Z. Yan, M.-W. Chen, Y.-G. Zhou, Org. Lett.
2015, 17, 6134–6137.
[19] M. N. Grayson, K. N. Houk, J. Am. Chem. Soc. 2016,
138, 9041–9044.
[14] C. C. Hsiao, S. Raja, H. H. Liao, I. Atodiresei, M.
Rueping, Angew. Chem. 2015, 127, 5854–5857; Angew.
Chem. Int. Ed. 2015, 54, 5762–5765.
Adv. Synth. Catal. 0000, 000, 0 – 0
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8 Bifunctional Amine-Squaramide Catalyzed Friedel–Crafts
Alkylation Based on ortho-Quinone Methides in Oil-Water
Phases: Enantioselective Synthesis of Triarylmethanes
Adv. Synth. Catal. 2017, 359, 1 – 8
Yifeng Wang, Cheng Zhang, Haojiang Wang, Yidong Jiang,
Xiaohua Du, Danqian Xu*
Adv. Synth. Catal. 0000, 000, 0 – 0
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