Scandium(III) Trifluoromethanesulfonate Catalyzed Selective Reactions of Donor–Acceptor Cyclopropanes with 1,1-Diphenylethanols: An Approach to Polysubstituted Olefins

Article abstract of DOI:10.1002/ejoc.201700221

An unexpected synthetic approach to polysubstituted olefins through the scandium(III) trifluoromethanesulfonate catalyzed ring-opening reaction of donor–acceptor cyclopropanes with 1,1-diphenylethanols was developed. The reactions, which are experimentally easy to handle, feature tolerance of various functional groups and mild reaction conditions. On the basis of experimental evidence, a plausible mechanism was also proposed.

Full text of DOI:10.1002/ejoc.201700221

A Journal of
Accepted Article
Title: Sc(OTf)3-Catalyzed Selective Reactions of Donor-Acceptor
Cyclopropanes with 1,1-diphenylethanols: A New Approach to
Polysubstituted Olefins
Authors: Xiaoyan Zhu, Gang Hong, Chen Hu, Shengying Wu, and
Limin Wang
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: Eur. J. Org. Chem. 10.1002/ejoc.201700221
Link to VoR: http://dx.doi.org/10.1002/ejoc.201700221
Supported by

10.1002/ejoc.201700221
European Journal of Organic Chemistry
COMMUNICATION
Sc(OTf)3-Catalyzed Selective Reactions of Donor-Acceptor
Cyclopropanes with 1,1-diphenylethanols: A New Approach to
Polysubstituted Olefins
Xiaoyan Zhu,[a] Gang Hong,[a] Chen Hu,[a] Shengying Wu,[a] and Limin Wang*[a]
Dedication ((optional))
Abstract: An unexpected synthetic approach to
a
library of
investigating the ring opening and intramolecular Micheal
addition cascade reaction of D-A cyclopropanes with m-N,N-
dimethylaminophenyl-α ， β-unsaturated carbonyl compounds.
Our group also has been interested in the use of D-A
cyclopropanes to react with N-benzylic sulfonamides in the
presence of Lewis acid (Scheme 1a).
polysubstituted olefins via Sc(OTf)3 catalyzed ring-opening reaction
of D-A cyclopropanes with 1,1-diphenylethanols is herein described.
The reactions, which are experimentally easy to handle, feature
tolerance of various functional groups, mild reaction conditions.
Based on experimental evidence, a plausible mechanism is also
proposed.
Introduction
Donor-Acceptor cyclopropanes (D-A cyclopropanes) have
recently become versatile building blocks in synthetic
methodologies in the presence of activating agent.[1] Owing to
their versatility and special reactivity, they have been widely
used in the synthesis of various acyclic and cyclic compounds.
In the presence of Lewis acid, D-A cyclopropanes are easily
went though ring opening to form 1,3-dipolar, and widely
deployed in [3+2] or [3+3] cycloaddition with dienes,
dipolarophiles, or 1,3-dipoles to build functionalized five-, six-
membered compounds.[2] Moreover, D-A cyclopropanes can
also act as sources of 1,2- and 1,4-dipoles[3] under Lewis acid
conditions. Recently, our group[4] has revealed that D-A
cyclopropane can undergo reaction as the less developed 1,2-
dipole in a formal [2+3] annulations reaction.
Compared with abundant reports about the cycloaddition of D-A
cyclopropanes, nucleophilic attack to afford acyclic compounds
is less developed in organic synthesis. Due to the ring strain, D-
A cyclopropanes can undergo ring opening via C-C bond
cleavage under Lewis acid, providing access to the nucleophiles,
which is one of the rapid developing methods to 1,3-
bifunctionalized products.
Scheme 1. Examples of reaction of D-A cyclopropanes and proposed reaction
For example, the ring opening reactions[5] of D-A cyclopropanes
with nucleophiles such as amines, alcohols, thiols and carboxylic
acids were demonstrated by Feng and co-workers.
Subsequently, Yb(OTf)3 catalyzed ring opening reactions of
cyclopropanes with indolines, and Mn(OAc)3 catalyzed
cycloaddition of the N-alkyl indulines, were recently uncovered
by Michael.[6] Moreover, D-A cyclopropanes were undergone
nucleophilic ring opening by N,N-dimethylaniline, and the group
of Kim[7] further advanced the ring opening strategy by
Inspired by above researches, we demonstrated the Lewis acid
catalyzed reactions of D-A cyclopropanes with 1,1-
diphenylethanols to generate dimethyl2-(2,4,4-triphenylbut-3-en-
1-yl)malonates. Though there are some reports about the
preparation of the analogue of dimethyl2-(2,4,4-triphenylbut-3-
en-1-yl)malonates using D-A cyclopropanes[8] (Scheme 1b, 1c).
The preparation of trisubstituted olefins employing D-A
cyclopropanes, to the best of our knowledge, has never been
reported. In addition, active boronic organic compounds[9],
though efficiently taking part in the nucleophilic reaction, are not
easily accessible. Herein, the reaction of D-A cyclopropanes
with 1,1-diphenylethanols was studied as a model reaction.
Formal [2+3] cycloadditions where D-A cyclopropanes act as
1,2-dipoles to offer the five-membered rings was not found in
this work. And the reaction of D-A cyclopropanes reacted with
the carbon nucleophiles instead of the oxygen nuclephiles.
Dramatically, accessible 1,1-diphenylethanol was directly
[a]
Key Laboratory for Advanced Materials and Institute of Fine
Chemicals, East China University of Science and Technology, 130
Meilong Road, Shanghai 200237, P. R. China
E-mail: wanglimin@ecust.edu.cn.
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700221
European Journal of Organic Chemistry
COMMUNICATION
developed to react with D-A cyclopropane, and the sp3 C-C bond
was connected to the electrophilic site of the D-A cyclopropane
rather than the site of tertiary alcohol, which was less
investigated.
[a] Reaction conditions: 1a (0.25 mmol), 2a (0.25 mmol), Lewis acid (x mol %),
and solvent (1 mL), at 80 oC. [b] Isolated yield. [c] 20 mol % of Sc(OTf)3. [d]
Under argon.
With the optimized reaction conditions in hand, we then explored
the substrate scope of D-A cyclopropanes
1 and 1,1-
diphenylethanols (Table 2). First, series of D-A
2
a
cyclopropanes containing electron-donating or electron-
withdrawing substituents were investigated (Table 2, entries 1-
10). Substituents such as Me, OMe, F, Cl and Br on 3-position
or 4-position of the phenyl ring worked well to afford the
corresponding products in 70-89% yields (Table 2, entries 2-8).
Delightedly, the D-A cyclopropane with 2-naphthyl group could
also afford corresponding product in 64% yield (Table 2, entry 9).
However, pyridine-substituted D-A cyclopropanes could not
afford the desired product (Table 2, entry 10).
Results and Discussion
Herein, we reported the reaction of D-A cyclopropanes with 1,1-
diphenylethanols catalyzed by Sc(OTf)3 to give the
corresponding dimethyl2-(2,4,4-triphenylbut-3-en-1-yl)malonates.
Based on above considerations, we studied a model reaction
between D-A cyclopropane 1a and 1,1-diphenylethanol 2a to
optimize the reaction conditions (Table 1). To our delight, the
desired product 3a could be isolated in 32% yield by using 200
mol% AlCl3 as the catalyst in 1,2-DCE at 80 oC for 12 h (Table 1,
entry 1). Inspired by this result, various catalysts including
Cu(OTf)2, FeCl3, and BF3•OEt2 were employed with no
improvement in yield (Table 1, entries 8-10). When rare-earth
triflates were investigated, only Sc(OTf)3 can give 60% yield of
the product (Table 1, entries 2-5). We also applied the rare earth
perfluorooctanoates [Sc(OPF)3] and pentafluorobenzoates
[Sc(Pfb)3] developed by our group to catalyze the reaction.
Disappointingly, these catalysts had a negative effect on the
reaction (Table 1, entries 6 and 7). Efforts to enhance yield by
replacing 1,2-DCE with other solvents such as CH3NO2, Toluene
and EtOH (Table 1, entries 11-14) proved that the yield
gradually decreased, while DCM had positive effect on the
reaction affording the product in 77% yield (Table 1, entry 11).
There was a slight decrease in yield when the reaction was
conducted under argon (Table 1, entry 15). Further screening of
temperature revealed that the reaction was the most efficient
Table 2. Sc(OTf)3 catalyzed reactions of D-A cyclopropanes with 1,1-
diphenylethanols.
Entry[a]
R1
R2
R3
3
Yield
(%)[b]
77
1
Ph
H
H
3a
3b
3c
3d
3e
3f
2
4-MeC6H4
3-MeC6H4
4-OMeC6H4
4-FC6H4
3-FC6H4
4-ClC6H4
4-BrC6H4
2-naphthyl
2-pyridine
Ph
H
H
78
3
H
H
86
4
H
H
70
5
H
H
79
6
H
H
89
7
H
H
3g
3h
3i
76
o
8
H
H
79
when it was proceeded in DCM at 80 C for 12 h under air in
presence of Sc(OTf)3 (5 mol %) (Table 1, entries 16 and 17).
9
H
H
64
ND[c]
10
11
12
13
14
15
16
17
18
19
20
21
22
H
H
3j
4-Me
4-OMe
2-OMe
4-tBu
4-F
4-Cl
4-Me
4-F
4-Cl
4-Br
2,6-F,F
4-Me
4-Me
4-OMe
2-OMe
4-tBu
4-F
4-Cl
H
3k
3l
91
Table 1. Optimization of Reaction Conditions.
Ph
86
Ph
3m
3n
3o
3p
3q
3r
70
Ph
96
Ph
49
Ph
32
Ph
85
Ph
H
64
Entry[a]
Catalyst (mol %)
Solvent
Time
(h)
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
6
Yield
(%)[b]
32
Ph
H
3s
42
Ph
H
3t
54
3u[d]
3v
30
1
AlCl3(200)
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
DCM
Ph
H
2
3[c]
Sc(OTf)3(5)
Sc(OTf)3(20)
Y(OTf)3 (5)
60
4-NO2C6H4
4-Me
86
57
[a] The reaction was conducted with 1 (0.25 mmol), 2 (0.25 mmol), Lewis acid
(5 mol %), CH2Cl2 (1 mL), 80 oC and 24 h. [b] Isolated yield. [c] ND = no
product. [c] The configuration of 3u was determined by its NOESY H-H
interactions.
4
28
5
Yb(OTf)3(5)
Sc(OPF)3 (5)
Sc(Pfb)3 (5)
Cu(OTf)2(20)
FeCl3 (20)
39
6
25
7
24
8
41
Then, we studied the scope of 1,1-diphenylethanols. Various
substituted 1,1-diphenylethanol derivatives smoothly reacted
with D-A cyclopropane under Sc(OTf)3 to afford the dimethyl 2-
(2,4,4- triphenylbut-3-en-1-yl)malonates in good yields (Table 2,
entries 11-22). In general, 70-96% results were obtained when
electron-donating groups such as 4-Me, 4-OMe, 2-OMe and 4-
tBu were present on the phenyl of the 1,1-diphenylethanols
(Table 2, entries 11-14). Interestingly, the 1,1-bis(4-(tert-
butyl)phenyl)ethanol afforded 3n in 96% yield. While 1,1-
diphenylethanols with substituents (F, Cl) at the 4-position on
9
23
10
11
12
13
14
15[d]
16
17
BF3•OEt2(20)
Sc(OTf)3 (5)
Sc(OTf)3 (5)
Sc(OTf)3 (5)
Sc(OTf)3 (5)
Sc(OTf)3 (5)
Sc(OTf)3 (5)
Sc(OTf)3 (5)
48
77
CH3NO2
Toluene
EtOH
32
30
none
73
DCM
DCM
53
DCM
24
67
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700221
European Journal of Organic Chemistry
COMMUNICATION
the phenyl R2 and R3, produced the corresponding products 3o
and 3p in 49% and 32%, respectively (Table 2, entries 15, 16).
Subsequently, unsymmetrically substituted 1,1-diphenylethanols
were investigated (Table 2, entries 17-21). It should be noted
that the products with exact (Z)-selectivity were observed when
employing unsymmetrically substituted 1,1-diphenylethanols.
1,1-diphenylethanols with electron-donating (Me) at the 4-
position on the phenyl R2 gave the corresponding products in
higher yields than 1,1-diphenylethanol possessing electron-
withdrawing (F, Cl, Br) at the 4-position on the phenyl R2. 1-(2,6-
difluorophenyl)-1-phenylethanol afforded the corresponding
product in 30% yield (Table 2, entry 21). The olefin geometry
was established unambiguously by differential NOE 1H NMR
experiments (See ESI for details). In addition, 86% yield was
obtained when NO2 substituted D-A cyclopropane reacted with
methyl substituted 1,1-diphenyldiethanol (Table 2, entry 22). The
structure of 3n was unambiguously confirmed by X-ray analysis
(See ESI for details).
formation of the ring-opening products and cycloaddition
products (Scheme 4). First, the activation of 1a using Sc(OTf)3
possibly generate the ring-opening 1,3-dipole intermediate 1b. In
the meantime, 1,1-diphenylethene 2a’ is generated from 2a
catalyzed by Lewis acid[14]. After the formation of the 1,3-dipole
and addition of the unsaturated compound 2a’, intermediate 1c
is formed. Then, for the D-A cyclopropanes with substituents 4-
NO2 and 3,4,5-trimethoxy， the electrophilic center of 1c is
trapped by a malonate anion to undergo 1,5-cyclization forming
cyclopentane 3a’ (pathway 1). For other substituted D-A
cyclopropanes, final product 3a is formed through Sc(OTf)3
catalyzed proton abstraction (pathway 2).
Scheme 4. Possible mechanism
Conclusions
In summary, we have explored the novel reactivity resided in D-
A cyclopropanes. A series of polysubstituted olefins are obtained
in good to excellent yields through this simple synthetic
approach. A plausible mechanism is proposed. Considering the
chameleon features of D-A cyclopropanes, further investigation
toward this substrate is underway.
Scheme 2. The [3+2] cycloaddition reaction of substitutional D-A
cyclopropanes.
To our surprise, the D-A cyclopropanes with substituents 4-NO2
and 3,4,5-trimethoxy[10] failed to give the desired products,
instead [3+2] cycloaddition products were obtained in 36%, 76%
yields, respectively (Scheme 2). The structure of 3w was also
unambiguously assigned by X-ray analysis (See ESI for details).
Experimental Section
General Procedure for Sc(OTf)3-Catalyzed Selective Reactions of
Donor-Acceptor Cyclopropanes with 1,1-diphenylethanols: The
mixture of donor-acceptor cyclopropanes 1a (0.25 mmol), 1,1-
diphenylethanols 2a (0.25 mmol), Sc(OTf)3 (5 mol %) and DCM (1 mL)
were added into a sealed tube. After being stirred vigorously at 80 oC for
12 h, the mixture was evaporated under vacuum. The corresponding
product was isolated by silica gel column chromatography with a
petroleum ether/ethyl acetate mixture (100:4) as eluent.
Scheme 3. Control experiments for investigating mechanism.
Acknowledgements
Next, control experiments were performed to gain insights into
the reaction mechanism (Scheme 3). When 2a was under
standard condition, 1,1-diphenylethene[11] was isolated in 68 %
yield (Scheme 3, eq 1). Subsequently, 1,1-diphenyiethene was
employed to smoothly react with D-A cyclopropane under
standard conditions, and the final product 3a was observed in 69%
yields. The results indicate that 1,1-diphenylethene might be an
intermediate in the present reaction system.
This research was financially supported by the National Nature
Science Foundation of China (21272069, 20672035) and the
Fundamental Research Funds for the Central Universities and
Key Laboratory of Organofluorine Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences.
Keywords: Lewis acid; Ring-opening reaction; D-A
cyclopropanes; Olefins
On the basis of experimental results and previous related
reports[12, 13], we proposed a possible mechanism for the
[1]
a) V. S. Korotkov, O. L. Larionov, A. Hofmeister, J. Magull, A. Meijere, J.
Org. Chem. 2007, 72, 7504-7510; b) H. Xiong, H. Xu, S. H. Liao, Z. W.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700221
European Journal of Organic Chemistry
COMMUNICATION
Xie, Y. Tang, J. Am. Chem. Soc. 2013, 135, 7851-7854; c) S.
Chakrabarty, I. Chatterjee, B. Wibbeling, C. G. Daniliuc, A. Studer,
Angew. Chem. Int. Ed. 2014, 53, 5964-5968; d) H. L. Liu, C. H. Yuan, Y.
Wu, Y. M. Xiao, H. C. Guo, Org. Lett. 2015, 17, 4220-4223.
[2]
a) I. S. Young, M. A. Kerr, Angew. Chem. Int. Ed. 2003, 42, 3023-3026;
b) E. O. Gorbacheva, A. A. Tabolin, R. A. Novikov, Y. V. Nelyubina, S.
L. Ioffe, Org. Lett. 2013, 15, 350-353; c) R. Talukdar, D. P. Tiwari, A.
Saha, M. K. Ghorai, Org. Lett. 2014, 16, 3954-3957; d) R. Talukdar, D.
P. Tiwari, A. Saha, M. K. Ghorai, Org. Lett. 2014, 16, 3954-3957; e) Z.
J. Wang, S. Chen, J. Ren, Z. W. Wang, Org. Lett. 2015, 17, 4184-4187;
f) W. W. Ma, J. Fang, J. Ren, Z.W. Wang, Org. Lett. 2015, 17, 4180-
4183; g) K. S. Halskov, L. Næsborg, F. Tur, K. A. Jørgensen, Org. Lett.
2016, 18, 2220-2223. h) S. Das, S. Chakrabarty, C. G. Daniliuc, Studer,
Org. Lett. 2016, 18, 2784-2787; i) T. Chidley, N. Vemula, C. A. Carson,
M. A. Kerr, B. L Pagenkopf, Org. Lett. 2016, 18, 2922-2925.
a) R. A. Novikov, D. O. Balakirev, V. P. Timofeev, Y. V. Tomilov,
Organometallics, 2012, 31, 8627-8638; b) R. A. Novikov, A. V.
Tarasova, V. A. Korolev, V. P. Timofeev, Y. V. Tomilov, Angew. Chem.
Int. Ed. 2014, 53, 1-6; c) R. A. Novikov, A. V. Tarasova, V. A. Korolev,
E. V. Shulishov, V. P. Timofeev, Y. V. Tomilov, J. Org. Chem. 2015, 80,
8225-8235.
[3]
[4]
[5]
M. Y. Zhu, J. Q. Liu, J. J. Yu, L. S. Chen, C. M. Zhang, L. M. Wang, Org.
Lett. 2014, 16, 1856-1859.
a) Y. Xia, L. Lin, F. Chang, X. Fu, X. Liu, X. Feng, Angew. Chem.Int. Ed.
2015, 54, 13748; b) Y. Xia, X. Liu, H. Zheng, L. Lin, X. Feng, Angew.
Chem. Int. Ed. 2015, 54, 227; c) R. Karmakar, A. Suneja, V. K. Singh,
Org. Lett. 2016, 18, 2636-2639.
[6]
[7]
[8]
[9]
[10]
J. E. C. Tejeda, B. K. Landschoot, M. A. Kerr, Org. Lett. 2016, 18, 2142-
2145.
a) A. Kim, S. G. Kim, Eur. J. Org. Chem. 2015, 6419-6422; b) A. Kim, S.
G. Kim, Adv. Synth. Catal. 2016, 358, 2701-2706.
a) J. X. Yin, C. J. T. Hyland, J. Org. Chem. 2015, 80, 6529-6536; b) V.
Ortega, A. G. Csꢀkꢁ, J. Org. Chem. 2016, 81, 3917-3923.
A. J. J. Lennox, G. C. Lloyd-Jones, J. Am. Chem. Soc. 2012, 134, 7431-
7441.
Y. A. Volkova, E. M. Budynina, A. E. Kaplun, O. A. Ivanova, A. O.
Chagarovskiy, D. A. Skvortsov, V. B. Rybakov, I. V. Trushkov, M. Y.
Melnikov, Chem. Eur. J. 2013, 19, 6586-6590.
[11] Z. B. Wang, Y. F. Wong, J. W. Sun, Angew. Chem. Int. Ed. 2015, 54,
13711-13714.
[12] Y. P. Han, X. R. Song, Y. F. Qiu, X. H. Hao, J. Wang, X. X. Wu, X. Y.
Liu, Y. M. Liang, J. Org. Chem. 2015, 80, 9200-9207.
[13] T. Kaicharla, T. Roy, M. Thangaraj, R. G. Gonnade, A. T. Biju, Angew.
Chem. Int. Ed. 2016, 55, 1-5.
[14] a) Y. S. Shao, K. Zhu, Z. C. Qin, E. Li, Y. Z. Li, J. Org. Chem. 2013, 78,
5731−5736; b) S. Jana, A. Dey, M. Singsardar, A. K. Bagdi, A. Hajra, J.
Org. Chem. 2016, 81, 9489−9493.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700221
European Journal of Organic Chemistry
COMMUNICATION
COMMUNICATION
D-A cyclopropane *
Xiaoyan Zhu, Gang Hong, Chen Hu,
Shengying Wu, Limin Wang*
Page No. – Page No.
Sc(OTf)3-Catalyzed Selective
Reactions of Donor-Acceptor
Cyclopropanes with 1,1-
diphenylethanols: A New Approach to
Polysubstituted Olefins
Accessible 1,1-diphenylethanol was directly developed to react with D-A
cyclopropane, and the sp3 C-C bond was connected to the electrophilic site of the
D-A cyclopropane to form the trisubstituted olefins products. Dramatically, the D-A
cyclopropanes with substituents 4-NO2 and 3,4,5-trimethoxy offered the
cycloaddition products.
* The sp3 C-C bond of 1,1-diphenylethanol was directly connected to the electrophilic site of the D-A cyclopropane to form the
products
This article is protected by copyright. All rights reserved.