A facile iron-catalyzed dual C-C bond cleavage: An approach towards triarylmethanes

Article abstract of DOI:10.1039/c9nj00149b

A facile iron-catalyzed dual C-C bond cleaving reaction involving 1,3-dicarbonyl units along with electron-rich and sterically bulky arenes as efficient carbon-based leaving groups has been developed. The scope of the dual C-C bond breaking reaction was s

Full text of DOI:10.1039/c9nj00149b

View Article Online
View Journal
NJC
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: D. Paul, S. Khatua
and P. N. Chatterjee, New J. Chem., 2019, DOI: 10.1039/C9NJ00149B.
This is an Accepted Manuscript, which has been through the
Volume 40 Number
1 January 2016 Pages 1–846
Royal Society of Chemistry peer review process and has been
accepted for publication.
NJC
Accepted Manuscripts are published online shortly after
New Journal of Chemistry
www.rsc.org/njc
A journal for new directions in chemistry
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
rsc.li/njc

Page 1 of 20
New Journal of Chemistry
1
2
View Article Online
3
1
4
A Facile Iron-Catalyzed Dual C-C Bond Cleavage: An ApproachDtOoI:w10.a10r39d/Cs9NJ00149B
5
6
2
Triaryl Methanes
3
Dipankar Paul,a Snehadrinarayan Khatuab and Paresh Nath Chatterjeea,*
7
8
9
10
4
5
a Department of Chemistry, National Institute of Technology Meghalaya, Bijni Complex,
Laitumkhrah, Shillong 793003, Meghalaya, INDIA
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6
7
b Centre for Advanced Studies, Department of Chemistry, North Eastern Hill University,
Shillong 793022, Meghalaya, INDIA
8
9
*Corresponding author:
Email: paresh.chatterjee@nitm.ac.in
Abstract
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
A facile iron-catalyzed dual C-C bond cleaving reaction involving 1,3-dicarbonyl unit along
with electron-rich and sterically bulky arene as efficient carbon-based leaving groups has
been developed. The scope of the dual C-C bond breaking reaction was studied in detail using
a range of nucleophiles to produce symmetrical triaryl methanes in good to excellent yields.
We found success in isolating the intermediate of the reaction, formed via the initial Csp3-Csp3
bond cleavage, and subsequently converted the intermediate to the final product via the Csp3-
Csp2 bond cleavage. A notable difference in the leaving aptitudes of the two carbon-based
leaving groups perceived during the study enabled us to develop an application of the dual C-
C bond breaking reaction for the synthesis of unsymmetrical triaryl methanes in a stepwise
manner. To improve the synthetic utility, we have also fashioned a one-pot procedure to
generate unsymmetrical triaryl methanes via sequential C-C bond breaking reactions. In
addition to studying a novel dual C-C bond breaking reaction and providing a hint to the
mechanistic pathway, the application molded from the study for the synthesis of symmetrical
and especially unsymmetrical triaryl methanes may render value to the present work.
25
Keywords
26
27
Arene leaving group, 1,3-dicarbonyl leaving group, dual C-C bond cleavage, FeCl3 catalyzed,
triaryl methanes.
1

New Journal of Chemistry
Page 2 of 20
1
2
3
4
View Article Online
DOI: 10.1039/C9NJ00149B
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
Introduction
5
6
7
8
The utilization of carbon-based leaving groups that operates through C-C bond cleavage still
lacks popularity in the realm of organic synthesis. The high bond dissociation energy of the
C-C bonds, kinetic inaccessibility, and poor selectivity are among the major challenges to
encounter before developing an efficient carbon-based leaving group.1,2 Over the past years,
several reports involving C-C bond cleavages have been published.3-10 However, adapting the
cleavage of a C-C bond to develop an efficient carbon-based leaving group has proved to be a
significant challenge. In recent times, researchers have shown immense interest in developing
new strategies that apply C-C bond cleavage in organic synthesis. In this regard, carbon-
based leaving groups such as meldrum’s acid,11,12 dimedone,13-15 barbituric acid,16 and
others,17,18 have been developed. Li et al. also developed and popularized the use of 1,3-
dicarbonyl compounds as efficient carbon-based leaving groups from diarylmethyl
substituted 1,3-dicarbonyl derivatives 1 (Figure 1a).19,20 High selectivity can be achieved
when employing 1,3-dicarbonyl unit as a leaving group in a C-C bond cleaving variant of the
classical Friedel-Crafts reaction.19 Apart from 1,3-dicarbonyl moieties, relevant literature
reveals that electron-rich and sterically bulky arenes also shows promise for use as a viable
leaving group. Such arenes were observed on several occasions to leave through C-C bond
cleavage causing unwanted side reactions thereby giving an account of their untapped
potential as leaving groups.21-25 Roy et al. in 2011 established the use of such electron-rich
and sterically bulky arene as a leaving group from diaryl methanamines in presence of Lewis
acidic heterobimetallic IrIII-SnCl3 catalyst.26 However, commercial unavailability and toxicity
of the catalyst in addition to lack of mechanistic insight into the reaction have largely
restrained the reported protocol. In this respect, we have recently developed FeCl3 as a
readily available catalyst for tandem Csp3-N and Csp3-Csp2 bond cleaving reaction in diaryl
methanamines involving electron-rich and sterically bulky arenes (such as 1,3,5-
trimethoxybenzene and 3,5-dimethoxytoluene) as leaving groups (Figure 1b).27 We have
demonstrated that 1,3,5-trimethoxybenzene which is an electron-rich and sterically bulky
arene perform exceedingly well as a leaving group in mild reaction conditions. It may be
pointed out that while the leaving 1,3-dicarbonyl moiety results in the cleavage of a Csp3-Csp3
bond, the leaving electron-rich, and sterically bulky arene causes the cleavage of a Csp3-Csp2
bond. Herein, we have directed our efforts towards integrating the two unusual yet efficient
carbon-based leaving groups (i.e. 1,3-dicarbonyl unit along with electron-rich and sterically
bulky arene) in one substrate and successfully developed a novel method involving dual C-C
2
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60

Page 3 of 20
New Journal of Chemistry
1
2
3
View Article Online
62
bond cleavage in 1,3-dicarbonyl derivatives with diarylmethyl substituents at the active
DOI: 10.1039/C9NJ00149B
4
5
6
7
8
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
methylene position, 1, to synthesize triaryl methanes (TRAMs) (Figure 1c). We have
examined the effect of various substitutions made in substrate 1 of Figure 1c as well as
studied the effect of a range of nucleophiles to test the scope of the reaction. We have also
isolated the intermediate formed via Csp3-Csp3 bond cleavage and then subsequently converted
the intermediate to the final product via Csp3-Csp2 bond cleavage. Exploiting the different
leaving aptitudes of the 1,3-dicarbonyl group and such arene in substrate 1, we have
successfully synthesized unsymmetrical TRAMs by selectively breaking the Csp3-Csp3 bond
and Csp3-Csp2 bond one after another in a stepwise manner. In a bid to further improve the
synthetic utility of the C-C bond breaking reaction, we were able to fashion a one-pot
procedure to synthesize unsymmetrical TRAMs in good yields. One may note that the
TRAMs are an important class of organic compounds, present in several natural products,
pharmaceuticals, dyes etc.28-30 Several strategies are reported in recent times for the synthesis
of symmetrical and unsymmetrical TRAMs.31-39 However, synthesis of unsymmetrical
TRAMs is commonly considered a challenging task40-44 and as per our knowledge, this is the
first ever method of synthesizing unsymmetrical TRAMs through dual C-C bond cleavage. In
addition to studying a novel dual C-C bond breaking reaction and providing a hint to the
mechanistic pathway, the application bloomed out of the study for the synthesis of
symmetrical and especially unsymmetrical TRAMs may render value to the present work.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3

New Journal of Chemistry
Page 4 of 20
1
2
3
4
5
6
7
8
9
View Article Online
DOI: 10.1039/C9NJ00149B
(a) Li et al. (2011 & 2013)
O
O
Nu
O
O
FeCl3 (5 mol%)
Ph
R
+
+ Nu-H
Ar
Ar'
Ph
Resulted via
Csp3-Csp3 bond
cleavage
R
DCE, rt
Ar
Ar'
1
(b) Chatterjee et al. (2018)
EWG
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
OMe
NH
OMe
Nu
FeCl3 (10 mol%)
MeNO2, 80 °C
+
+ 2 Nu-H
R
Ar
Ar
Nu
MeO
R
MeO
R = Me, OMe
Resulted via
Csp3-Csp2
bond cleavage
O
O
(c) This work
R2
Leaving group
R1
R2
O
R1
O
Nu
OMe
FeCl3 (10 mol%)
MeCN, 80 °C
+
2 Nu-H
Ar
Ar
OMe
Nu
2
3
MeO
R
1
R = Me, OMe
Leaving group
MeO
R
81
82
Figure 1: A correlation of the present work with the literature
Results and Discussion
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
At the outset we considered 1,3-diphenyl-2-(phenyl(2,4,6-trimethoxyphenyl)methyl)propane-
1,3-dione 1a and indole 2a as our model substrates to optimize the reaction conditions (Table
1). In this regard, we tested several reaction conditions and analyzed the results based on the
isolated yield of the desired bis-indolyl methane 3aa (formed via dual C-C bond cleavage)
and the unsymmetrical TRAM 4a (formed via Csp3-Csp3 bond cleavage only). As previous
studies have suggested that FeCl3 is a potent catalyst for breaking Csp3-Csp3 bonds in
diarylmethyl substituted 1,3-dicarbonyl derivatives19 as well as Csp3-Csp2 bonds in N-
protected diaryl methanamines,27 we considered FeCl3 as the catalyst for screening various
solvents. While MeNO2, DCE and toluene as solvents performed reasonably well for the
cleavage of both the Csp3-Csp3 and Csp3-Csp2 bonds, DMF and THF did not show any
promising results (Table 1, entries 1-5). Among all the screened solvents, we found that
MeCN serves as the best medium for the model reaction producing 88% yield of the desired
product 3aa in 1 h (Table 1, entry 6). Other inexpensive and readily available Lewis acids
that were studied for catalyzing the model reaction could not outclass the catalytic efficiency
of FeCl3 (Table 1, entries 6-10). It is worth pointing out that ZnCl2 as a catalyst could only
catalyze the cleavage of Csp3-Csp3 bond in 1a giving rise to 58% of the unsymmetrical TRAM
4

Page 5 of 20
New Journal of Chemistry
1
2
3
4
5
6
7
8
9
View Article Online
100
4a (Table 1, entry 7). TsOH, which is a Brønsted acid, was also successful in caDtaOlI:y1z0.i1n03g9/tCh9eNJ00149B
dual C-C bond cleaving reaction producing a good yield of the desired product 3aa (Table 1,
entry 11). The reaction does not proceed in the absence of any catalyst (Table 1, entry 12).
We have found that temperature plays a crucial role in the progress of the reaction as
lowering the temperature from 80 °C to 50 °C proves detrimental to the yield of the desired
product (Table 1, entry 13). Further lowering of the temperature from 50 °C to room
temperature resulted in no reaction as starting materials were isolated quantitatively after 6
hours (Table 1, entry 14). As indicated in Table 1, 10 mol% loading of FeCl3 catalyst was
found to be optimum for the dual C-C bond cleaving reaction (entries 6, 15-16). It needs to be
pointed out that the leaving 1,3-diphenylpropan-1,3-dione and 1,3,5-trimethoxybenzene were
isolated in 96% and 91% yield, respectively, after the synthesis of 3aa in our optimized
reaction conditions.
101
102
103
104
105
106
107
108
109
110
111
112
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1: Optimization of reaction conditionsa
NH
HN
Ph
O
OMe
Catalyst
Ph
O
OMe
+
+
Solvent
Temperature
N
Ph
Ph
H
Ph
2a
NH
OMe
MeO
4a
3aa
MeO
1a
OMe
113
Yield of
3aa (%)b
72
Yield of
4a (%)b
10
15
18
–
Entry Catalyst
Solvent
Time (h)
1
2
4
3
5c
6
7
8
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
ZnCl2
SnCl2.2H2O
CoCl2.6H2O
BiCl3
TsOH
No catalyst
FeCl3
FeCl3
FeCl3
MeNO2
DCE
Toluene
DMF
1
1
1
6
1
1
1
1
1
1
1
1
1
6
1
1
75
70
–
THF
12
88
trace
73
20
42
78
–
trace
9
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
58
14
trace
15
14
–
36
–
10
9
10
11
12
13d
14e
15f
16g
44
–
85
FeCl3
70
12
aReaction conditions: 1a (1.0 mmol), 2a (2.2 mmol), Catalyst (10 mol%),
5

New Journal of Chemistry
Page 6 of 20
1
2
3
4
5
6
7
8
View Article Online
DOI: 10.1039/C9NJ00149B
Solvent (5 mL), Temperature 80 °C; bIsolated Yield; cTemperature 60 °C;
dTemperature 50 °C; eTemperature 25 °C; fFeCl3 (20 mol%);
gFeCl3 (5 mol%).
114
9
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
After optimization of the reaction conditions, we evaluated the generality of the FeCl3
catalyzed dual C-C bond cleaving reaction (Table 2). Initially, we decided to study the effect
of different substituents present in the 1,3-dicarbonyl moiety of substrate 1 by varying R1 and
R2 groups (Table 2, entries 1-6). Firstly, we fixed R1 as -Ph and substituted R2 with various
substituents such as -Ph, -tBu and -Me to study the effect on the yield of the product 3aa
(Table 2, entries 1-3). We noted that the variations in yields of the product 3aa were
dependent on the affinity of the various 1,3-dicarbonyl moiety to complex with the Lewis
acidic FeCl3, which in turn depended on the combination of the steric and electronic
influence of the substituents present at R1 and R2 of the 1,3-dicarbonyl moiety. The
observations were found to be in good agreement with previously published results by Li et
al.19 When both R1 and R2 were substituted with -Me groups, the yield of 3aa dropped to
41% (Table 2, entry 4). The yield of the desired product 3aa plummets further when an -OEt
group was present in the 1,3-dicarbonyl unit of substrate 1 (Table 2, entries 5-6). Since the
1,3-dicarbonyl group present in 1a, i.e. R1=R2=Ph, gives the highest yield of the product 3aa,
we have chosen this 1,3-dicarbonyl moiety for further studies. Subsequently, we set out to
test the substrate scope of the dual C-C bond breaking reaction by varying the aromatic group
(-Ar) present in substrate 1 in Table 2. We also evaluated various nucleophiles 2 (Figure 2)
based on their performance in the dual C-C bond breaking reaction. Initially, we varied the -
Ar group by installing several electron-donating groups (EDG) and electron-withdrawing
groups (EWG) at varying positions of the aromatic ring in substrate 1 and studied their
effects on the reaction. We found that there is no significant change in the yield of the
product 3 depending on the position of the EWG in the aromatic ring (Table 2, entries 7-9). It
is apparent from the data presented in Table 2 that EDG at the aromatic ring produces a
slightly lower yield of product 3 when compared with EWG (Table 2, entries 7-13). The
reaction performed well when -Ar group was taken as a polycyclic aromatic entity viz. 1-
naphthyl in 1n giving 82% of the product 3na (Table 2, entry 14). Heteroaromatic substituent
viz. 2-thienyl in substrate 1o also gave the desired reaction yielding 76% of the
corresponding product 3oa (Table 2, entry 15). We have then evaluated the performance of a
list of nucleophiles 2 in the dual C-C bond breaking reaction. In this regard we have tested
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6

Page 7 of 20
New Journal of Chemistry
1
2
3
View Article Online
144
indoles (2a-g), furans (2h-i), 1,3-dimethoxybenzene 2j and 4-methoxythiophenol 2k as
DOI: 10.1039/C9NJ00149B
4
5
6
7
8
145
146
147
148
149
150
151
nucleophiles and observed that the desired product 3 was formed via the cleavage of two C-C
bonds (Table 2, entries 16-25). In presence of indole derivatives 2b-g, the symmetrical bis-
indolyl methanes 3 were isolated in good yields via the dual C-C bond cleavage (Table 2,
entries 16-21). Furans (2h-i) and 1,3-dimethoxybenzene 2j also reacted smoothly with 1a to
generate the respective products 3 (Table 2, entries 22-24). Interestingly, two C-S bonds were
formed at the cost of two C-C bonds when 4-methoxythiophenol 2k was employed as the
nucleophile in the reaction with 1a (Table 2, entry 25).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
OMe
Br
NO2
N
N
N
N
N
N
N
H
H
H
H
2d
H
2c
2e
2f
2b
2g
2a
2h
Bn
MeO
OMe
S
OMe
Br
Si
O
O
S
MeO
2n
2i
2j
2k
2l
2m
152
153
Figure 2: List of nucleophiles 2
154
Table 2: Substrate scope of the dual C-C bond breaking reactiona
R2
O
R1
O
OMe
Nu
FeCl3 (10 mol%)
+
Nu-H
MeCN
80 °C
Ar
Ar
Nu
2
3
MeO
OMe
1
155
Yield of 3
(%)b
Entry Ar, R1, R2; 1
Nu-H, 2 Time (h)
1
2
3
4
5
6
7
8
Ph, Ph, Ph; 1a
Ph, Ph, tBu; 1b
Ph, Ph, Me; 1c
Ph, Me, Me; 1d
Ph, Ph, OEt; 1e
Ph, Me, OEt; 1f
4-ClC6H4, Ph, Ph; 1g
3-ClC6H4, Ph, Ph; 1h
2-ClC6H4, Ph, Ph; 1i
4-BrC6H4, Ph, Ph; 1j
4-NO2C6H4, Ph, Ph; 1k
4-CH3C6H4, Ph, Ph; 1l
4-CH3OC6H4, Ph, Ph; 1m
1-Naphthyl, Ph, Ph; 1n
2-Thienyl, Ph, Ph; 1o
1a
1a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
1
6
6
6
6
6
1
1
1
1
1
1
1
1
1
1
1
3aa (88)
3aa (65)
3aa (58)
3aa (41)
3aa (23)
3aa (15)
3ga (84)
3ha (85)
3ia (85)
3ja (83)
3ka (72)
3la (72)
3ma (70)
3na (82)
3oa (76)
3ab (78)
3ac (87)
9
10
11
12
13
14
15
16
17
7

New Journal of Chemistry
Page 8 of 20
1
2
3
4
5
6
7
8
9
View Article Online
18
19
20
21
22
23
24
25
1a
1a
1a
1a
1a
1a
1a
1a
2d
2e
2f
2g
2h
2i
1
1
1
1
1
1
6
1
3ad (79) DOI: 10.1039/C9NJ00149B
3ae (72)
3af (75)
3ag (70)
3ah (83)
3ai (82)
3aj (70)
3ak (82)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2j
2k
aReaction conditions: 1 (1.0 mmol), 2 (2.2 mmol), FeCl3 (10 mol%), MeCN (5
mL), Temperature 80 °C; bIsolated yield.
156
157
158
159
160
161
However, in the case of nucleophiles 2l-n, the reaction only causes the exclusive Csp3-Csp3
bond cleavage generating corresponding products 4b-d even after prolonged reaction times
and a large excess of the nucleophiles (Scheme 1). These results indicate that the Csp3-Csp3
bond is easier to cleave in comparison to Csp3-Csp2 bond in substrate 1a during the dual C-C
bond breaking reaction which is a reflection of the differences in their bond strengths.45
Ph
O
Nu
OMe
Ph
O
FeCl3 (10 mol%)
OMe
+
Nu-H
2
Ph
MeO
MeCN (5 mL)
80 °C, 6 h
Ph
(4.0 mmol)
OMe
4
MeO
1a
OMe
(1.0 mmol)
OMe
Br
S
OMe
OMe
OMe
Ph
Ph
Ph
MeO
4d (68%)
OMe
MeO
4b (64%)
OMe
MeO
4c (65%)
OMe
162
163
Scheme 1: Instances of Csp3-Csp3 bond cleavage
164
165
166
167
168
169
170
Above results encouraged us to track the intermediate formed during the dual C-C bond
cleaving reaction. In this regard, we treated 1a with 1.0 equivalent of the nucleophile 2a in
slightly milder reaction conditions anticipating the formation of 4a through the Csp3-Csp3 bond
cleavage (Scheme 2). The reaction proceeded as anticipated to give 4a as the major product
(62%) while 15% of 3aa was also isolated along with a small amount of the unreacted
substrate 1a. When the isolated intermediate 4a was treated with 1.0 equivalent more of 2a
under the optimized reaction conditions, we noticed the formation of 3aa in excellent yield
8

Page 9 of 20
New Journal of Chemistry
1
2
3
View Article Online
171
(93%). This observation not only establishes the intermediate formed during the DreOaI:c10ti.1o0n39/bCu9NtJ00149B
4
5
6
7
172
173
also affirms the difference in leaving aptitudes of 1,3-diphenyl-1,3-propanedione and 1,3,5-
trimethoxybenzene leaving groups.
8
OMe
9
Ph
O
Ph
O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NH
NH
Ph
O
MeO
OMe
Ph
O
OMe
OMe
+
Ph
Ph
2a (1.0 equiv.)
FeCl3 (5 mol%)
MeCN
N
Ph
H
FeCl3 (10 mol%)
MeCN
2a
(1.0 equiv.)
50 °C
MeO
4a (62%)
OMe
MeO
1a (1.0 equiv.)
OMe
NH
3aa (93%)
80 °C
174
175
Scheme 2: Isolation of intermediate 4a and its conversion to 3aa.
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
We also wanted to study the effect of substitutions made at the sterically bulky and electron-
rich aromatic leaving group (-Ar′) present in substrate 1 (Table 3). In this regard, we took
several substrates 1 with varying -Ar′ group and reacted with indole 2a under the optimized
reaction conditions. We found that 2,4,6-trimethoxyphenyl group as the sterically bulky and
electron-rich aromatic substituent in 1a produced an excellent yield of the product 3aa
through the dual C-C bond cleavage while a minor amount of the intermediate 4a was also
observed (Table 3, entry 1). Lowering the electron richness of the aromatic substituent (-Ar′)
by replacing one of the -OMe groups with a -Me group in substrate 1p resulted in lower yield
of 3aa even after longer reaction times (Table 3, entry 2).27 We observed that the
intermediate 4e formed in a minor quantity (16%) while a significant amount of the starting
substrates remained unreacted (Table 3, entry 2). It is worth pointing out that the steric
bulkiness at the benzylic reaction center is not changing when the substrate is changed from
1a to 1p. This significant decrease in the leaving aptitude may have been caused by the
diminished electron-richness of the aromatic leaving group (-Ar′). When the electron-richness
of -Ar′ was lowered further, the reaction ceased to produce any isolable amount of 3aa (Table
3, entries 3-4). In these cases, the starting substrates (1q and 2a; 1r and 2a) were isolated
almost quantitatively after 6 h of reaction in the optimized conditions.
Table 3: Effect of electron richness on the aromatic leaving groupa
HN
HN
O
Ph
Ar'
FeCl3 (10 mol%)
+
Ph
O
+
MeCN
80 °C
Ph
N
Ph
Ph
Ar'
H
NH
4
3aa
1
2a
194
Yield of
Entry
Substrate, 1
Time (h)
Intermediate 4 (%)b
3aa (%)b
9

New Journal of Chemistry
Page 10 of 20
1
2
3
4
5
6
7
8
9
View Article Online
DOI: 10.1039/C9NJ00149B
O
Ph
Ph
O
OMe
1
2
1
6
4a, 9%
88
Ph
MeO
Ph
OMe
, 1a
H
N
O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ph
O
OMe
OMe
45
Ph
Ph
MeO
Ph
, 1p
MeO
,4e, 16%
O
Ph
O
3
4
6
6
–
–
–
–
Ph
O
MeO
Ph
, 1q
Ph
O
Ph
, 1r
aReaction conditions: 1 (1.0 mmol), 2a (2.2 mmol), FeCl3 (10 mol%), MeCN (5 mL),
Temperature 80 °C; bIsolated yield.
195
196
Based on the above experimental observations and the knowledge of relevant literature, we
propose the plausible mechanism for the FeCl3 catalyzed dual C-C bond cleaving reaction in
Scheme 3. The reaction could be initiated by the coordination of the FeCl3 catalyst with the
1,3-dicarbonyl moiety of 1a which may lead to the formation of an ion pair A.19,46 The
carbocation is then trapped by the nucleophile 2a to generate 4a and successively release 1,3-
diphenylpropan-1,3-dione. TRAMs such as 4a are known to be activated by Lewis acids by
interacting with the ipso position to yield species B.21,47 Electron donating assistance from the
indolyl group of species B may be an important factor that promotes the formation of ion pair
C. This explains why less electron-rich groups in substrate 4 fail to cause the Csp3-Csp2 bond
cleavage (Scheme 1). A second molecule of the nucleophilic indole 2a then reacts with the
electrophilic center involved in C to yield the desired product 3aa and consequently release
the 1,3,5-trimethoxybenzene leaving group.
197
198
199
200
201
202
203
204
205
206
207
10

Page 11 of 20
New Journal of Chemistry
1
2
3
4
5
View Article Online
DOI: 10.1039/C9NJ00149B
FeCl3
FeCl3
O
O
O
O
O
O
NH
FeCl3
OMe
N
H
2a
Ph
Ph
OMe
Ph
Ph
OMe
Ph
Ph
OMe
6
FeCl3
7
8
9
Ph
Ph
Ph
Ph
MeO
OMe
MeO
1a
OMe
NH
MeO
4a
OMe
MeO
OMe
Ph
O
A
10
11
12
13
14
15
16
17
18
Ph
O
H
FeCl3
+
N
FeCl3
FeCl3
H
NH
2a
N
FeCl3
OMe
FeCl3
+
MeO
OMe
Ph
Ph
MeO
MeO
OMe
Ph
H
NH
3aa
OMe
B
OMe
C
19
20
OMe
208
21
22
23
209
Scheme 3: Plausible mechanism of the FeCl3 catalyzed dual C-C bond cleaving reaction
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
We sought to develop an application of the method for the synthesis of unsymmetrical
TRAMs (Table 4). As the previous observations showed that the 1,3-dicarbonyl group has
different leaving aptitude with respect to the electron-rich and sterically bulky aromatic
group, we directed our efforts towards developing reaction conditions that selectively
activates one of the leaving groups while keeping the other leaving group dormant. Crafting
such control would enable us to use two different nucleophiles to selectively substitute the
two carbon-based leaving groups sequentially. In this regard, we realized that ZnCl2 as a
catalyst exclusively generated product 4a (Table 1, entry 7) through Csp3-Csp3 bond cleavage
although the yield was low. We revised the reaction conditions to improve the yield without
compromising on the selectivity of substituting the 1,3-dicarbonyl group exclusively by
nucleophile Nu1-H as depicted in Table 4. Once the substitution of the 1,3-dicarbonyl group
by Nu1-H was complete, we isolated the product 4 and treated it with another nucleophile
Nu2-H to substitute the electron-rich and sterically bulky aromatic leaving group in presence
of the proven FeCl3 catalyst. The reaction progressed effectively to generate unsymmetrical
TRAMs comprising of both the nucleophiles Nu1-H and Nu2-H (Table 4). We have also
confirmed that the nucleophile plays a very inconsequential role in determining the selectivity
of the Csp3-Csp3 and Csp3-Csp2 bond cleaving reaction (Table 4, entries 2-3). Irrespective of the
nucleophile (Nu1-H or Nu2-H), the presence of ZnCl2 catalyst exclusively caused the
cleavage of Csp3-Csp3 bond (product 4 formed after Step 1) while the addition of FeCl3
ensured the subsequent activation of the electron-rich and sterically bulky aromatic leaving
group. Furthermore, to demonstrate the generality of the method, we have successfully tested
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
11

New Journal of Chemistry
Page 12 of 20
1
2
3
4
5
6
7
8
9
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
several pairs of nucleophiles to produce unsymmetrical TRAMs in good yields (TabVleiew4Ar,ticle Online
DOI: 10.1039/C9NJ00149B
entries 1-5, 7-9). The sequential cleavage of Csp3-Csp3 and Csp3-Csp2 bond can also be achieved
by nucleophile 4-methoxythiophenol 2k (Nu1-H) and 5-bromoindole 2f (Nu2-H) under
standard reaction conditions to generate 5e (Table 4, entry 6). Substitutions made in the
parent substrate 1 were well-tolerated in the reaction medium as evident from the yields of
the corresponding products (Table 4, entries 7-9). In our attempt to boost the synthetic utility
of the dual C-C bond breaking method, we were able to fashion a one-pot procedure for the
generation of unsymmetrical TRAMs 5. In this respect, we have treated substrate 1 with
nucleophile Nu1-H in the presence of ZnCl2 and monitored the progress of the reaction. After
complete consumption of Nu1-H, we have added Nu2-H and FeCl3 in the same reaction vessel
and allowed the reaction to proceed (See the experimental section for details). We were
pleased to obtain comparable yields of the unsymmetrical TRAMs using the one-pot protocol
in all the cases as mentioned in Table 4. The one-pot method presented here offers an
expedient route for the generation of unsymmetrical TRAMs in mild reaction conditions.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 4: Sequential cleavage of Csp3-Csp3 and Csp3-Csp2 bonda,b
Step 2
Ph
Step 1
O
Nu2-H 2 (1.0 equiv.)
FeCl3 (10 mol%)
MeCN
80 °C
OMe
Nu1 OMe
Nu1
Nu2
O
OMe
Ph
ZnCl2 (10 mol%)
Nu1-H
2
(1.0 equiv.)
+
Ar
MeCN
80 °C
Ar
5
Ar
MeO
4
MeO
OMe
1
One-pot
i) ZnCl2 (10 mol%), Nu1-H
ii) FeCl3 (10 mol%), Nu2-H
MeCN
80 °C
247
Yield of 4
Yield of 5
Entry Substrate, 1 Nu1-H, 2
Nu2-H, 2
(%)c
(%)c [%]d
NH
NH
OMe
1a
Ph
1
2
2a
2b
2d
Ph
N
MeO
OMe
Bn
4a (86%)
5a (82%) [79%]
N
N
OMe
1a
2c
Ph
Ph
N
H
MeO
OMe
4f (91%)
5b (85%) [78%]
12

Page 13 of 20
New Journal of Chemistry
1
2
3
4
5
6
7
View Article Online
DOI: 10.1039/C9NJ00149B
N
NH
OMe
1a
3
2c
2b
Ph
Ph
8
9
N
H
MeO
OMe
4g (89%)
5b (84%) [80%]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NO2
O
O
OMe
1a
1a
4
5
2h
2h
2g
2f
Ph
MeO
Ph
NH
OMe
4h (86%)e
5c (92%) [82%]
Br
O
O
OMe
Ph
MeO
Ph
NH
OMe
4h (86%)e
5d (91%) [80%]
O
O
Br
S
OMe
S
1a
1a
6
7
2f
Ph
Ph
NH
MeO
OMe
5e (84%) [75%]
4i (88%)
N
N
Br
OMe
2b
2f
2f
Ph
Ph
MeO
N
OMe
H
4f (91%)
5f (82%) [81%]
N
N
Br
OMe
8
9
1g
1l
2b
2b
NH
Cl
MeO
OMe
Cl
4j (92%)
5g (83%) [78%]
N
N
Br
OMe
NH
MeO
OMe
5h (81%) [77%]
4k (90%)
aReaction conditions for stepwise procedure: Step 1:- 1 (1.0 mmol), Nu1-H 2 (1.0 mmol),
ZnCl2 (10 mol%), MeCN (5 mL), Temperature 80 °C, Time 12 h; Step 2:- 4 (0.5 mmol),
Nu2-H 2 (0.5 mmol), FeCl3 (10 mol%), MeCN (3 mL), Temperature 80 °C, Time 1 h;
13

New Journal of Chemistry
Page 14 of 20
1
2
3
4
5
6
7
8
9
View Article Online
DOI: 10.1039/C9NJ00149B
bReaction conditions for the one-pot procedure: (i) 1 (1.0 mmol), Nu1-H 2 (1.0 mmol), ZnCl2
(10 mol%), MeCN (5 mL), Temperature 80 °C, Time 12 h; (ii) Nu2-H 2 (1.0 mmol), FeCl3
(10 mol%), Temperature 80 °C, Time 1 h; cIsolated yield via stepwise procedure. dIsolated
yield via one-pot procedure; eTime 6 h, Temperature 60 °C.
248
249
Conclusion
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
In conclusion, we have developed a facile FeCl3 catalyzed dual C-C bond cleaving reaction
involving 1,3-dicarbonyl units along with electron-rich and sterically bulky arenes as carbon-
based leaving groups. We have tested several 1,3-dicarbonyl units and electron-rich arenes to
select the best performing leaving group of each kind. With the two carbon-based leaving
groups integrated into one substrate, we examined the substrate scope of the dual C-C bond
cleaving reaction. We observed that indoles, furans, 1,3-dimethoxybenzene, 4-
methoxythiophenol were all compatible nucleophiles in the dual C-C bond breaking reaction.
We were also able to isolate the intermediate formed in the reaction through the initial Csp3-
Csp3 bond cleavage and subsequently converted it to the final product through the eventual
Csp3-Csp2 bond cleavage. By varying the reaction conditions, we controlled the leaving
aptitudes of the 1,3-dicarbonyl group and the arene and successfully applied this controlled
activation of the leaving groups to synthesize unsymmetrical TRAMs in a stepwise manner as
well as in one-pot. Furthermore, the 1,3-dicarbonyl compound and the electron-rich arene can
be recovered and reused. Apart from developing a novel dual C-C bond breaking reaction and
giving insight into the mechanistic pathway, the results presented here demonstrate the first
ever synthesis of TRAMs through dual C-C bond cleavage. Further investigation on the
scope, mechanism, and synthetic applications of the dual C-C bond cleaving reaction are on-
going in our laboratory.
268
Experimental
269
270
General remarks
All reagents and solvents are of AR grade and were procured from Sigma Aldrich, Alfa
271
272
273
274
275
276
Aesar, Spectrochem and Sisco Research Laboratories Pvt. Ltd. and used without further
purification. All the reactions were done in oven-dried glass apparatus in an air atmosphere
unless otherwise noted. Reactions were monitored by thin-layer chromatography (TLC) on
silica gel 60 F254 using UV light and p-anisaldehyde stain as visualizing agents. Organic
products were purified by dry column vacuum chromatography48 using silica gel G as the
1
13
stationary phase and petroleum ether 60-80 °C/ethyl acetate as the eluent. H and C NMR
14

Page 15 of 20
New Journal of Chemistry
1
2
3
View Article Online
DOI: 10.1039/C9NJ00149B
277
spectra were measured on a Bruker Avance II (1H NMR: 400 MHz and 13C NMR: 100 MHz)
4
5
6
7
8
278
279
280
281
282
283
284
285
286
287
288
spectrometer. Chemical shifts are reported in ppm from tetramethylsilane, with the solvent
resonance as the internal standard (unless otherwise mentioned, chloroform: δ 7.26 ppm).
Data are reported as follows: chemical shifts, multiplicity (s=singlet, d=doublet, t=triplet,
q=quartet, br=broad, dd=double doublet, m=multiplet), coupling constant (in Hz),
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
integration. C NMR spectra were recorded at 100 MHz with proton decoupling. Chemical
shifts are reported in ppm from tetramethylsilane with the solvent resonance as the internal
standard (unless otherwise mentioned, chloroform: δ 77.0 ppm). Elemental analyses were
carried out using a CHNS Analyzer Perkin Elmer 2400 Series II instrument. The starting
1
substrates 1 were prepared from reported procedures49,50 after minor modifications. The H
13
NMR and C NMR spectra of the synthesized starting substrates 1 were satisfactory and in
good agreement with reported data.
289
290
291
292
293
294
295
296
297
298
299
300
Typical procedure for the synthesis of symmetrical TRAM 3aa
A 25 mL round-bottom flask equipped with a magnetic bar and water condenser were
charged with 1a (1.0 mmol), 2a (2.2 mmol), MeCN (5 mL) and FeCl3 (10 mol%) in an air
atmosphere. The flask was placed in a constant temperature bath at 80 °C and the progress of
the reaction was monitored by TLC. After the completion of the reaction, the solvent was
removed under reduced pressure and the crude product was purified by dry column vacuum
chromatography (silica gel G, petroleum ether 60-80 °C/EtOAc) to obtain the desired product
3aa in 88% yield. White solid. 1H NMR (400 MHz, CDCl3): δ (ppm) = 7.71 (br, 2H), 7.30 (d,
J = 8.0 Hz, 2H), 7.27-7.12 (m, 7H), 7.08 (t, J = 7.6 Hz, 2H), 6.92 (d, J = 7.6 Hz, 2H), 6.50 (d,
13
J = 2.4 Hz, 2H), 5.79 (s, 1H). C NMR (100 MHz, CDCl3): δ (ppm) = 144.0, 136.7, 128.7,
128.2, 127.0, 126.2, 123.7, 121.9, 119.9, 119.6, 119.2, 111.1, 40.2.
Physical and spectral data are in good agreement with the reported literature.21
301
302
303
304
305
306
307
308
Typical procedure for the synthesis of 4a from substrate 1a via ZnCl2 catalyzed Csp3-
Csp3 bond cleavage
A 25 mL round-bottom flask equipped with a magnetic bar and water condenser were
charged with 1a (1.0 mmol), 2a (1.0 mmol), MeCN (5 mL) and ZnCl2 (10 mol%) in air
atmosphere. The flask was placed into a constant temperature bath at 80 °C and the progress
of the reaction was monitored by TLC. After the completion of the reaction, the solvent was
removed under reduced pressure and the crude product was purified by dry column vacuum
chromatography (silica gel G, petroleum ether 60-80 °C/EtOAc) to obtain the desired product
15

New Journal of Chemistry
Page 16 of 20
1
2
3
4
5
6
7
8
9
View Article Online
1
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
4a in 86% yield. Light pink solid. H NMR (400 MHz, CDCl3) δ (ppm) = 7.84 (DsO, I1: 1H0.1)0,379/.C299NJ00149B
(d, J = 6.7, 4H), 7.25-7.18 (m, 5H), 6.86 (d, J = 2.6, 1H), 6.28 (s, 1H), 6.15 (s, 2H), 3.79 (s,
3H), 3.57 (s, 6H). 13C NMR (100 MHz, CDCl3): δ (ppm) = 159.7, 159.0, 144.6, 136.0, 128.2,
126.9, 124.9, 121.8, 121.4, 119.1, 118.9, 117.9, 114.3, 110.8, 91.7, 55.7, 55.2, 53.4, 36.3.
Physical and spectral data are in good agreement with the reported literature.51
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Typical procedure for the synthesis of unsymmetrical TRAM 5a from intermediate 4a
via FeCl3 catalyzed Csp3-Csp2 bond cleavage
A 25 mL round-bottom flask equipped with a magnetic bar and water condenser was charged
with 4a (0.5 mmol), 2d (0.5 mmol), MeCN (3 mL) and FeCl3 (10 mol%) in air atmosphere.
The flask was placed into a constant temperature bath at 80 °C and the progress of the
reaction was monitored by TLC. After the completion of the reaction, the solvent was
removed under reduced pressure and the crude product was purified by dry column vacuum
chromatography (silica gel G, petroleum ether 60-80 °C/EtOAc) to obtain the desired product
5a in 82% yield. Light pink solid. 1H NMR (400 MHz, CDCl3) δ (ppm) = 7.89 (s, 1H), 7.43-
7.17 (m, 12H), 7.13 (dd, J = 14.8, 7.9, 2H), 7.04-6.94 (m, 4H), 6.64 (d, J = 4.5, 2H), 5.91 (s,
13
1H), 5.20 (s, 2H). C NMR (100 MHz, CDCl3) δ (ppm) = 144.05, 137.90, 137.01, 136.68,
132.51, 128.74, 128.66, 128.25, 127.95, 127.78, 127.38, 127.20, 127.07, 126.43, 126.13,
123.62, 121.92, 121.69, 120.12, 120.02, 119.80, 119.21, 118.96, 118.72, 111.03, 109.73,
49.92, 40.21. Anal. Cacld (%) for C30H24N2: C 87.35; H 5.86; Found: C 87.31; H 5.90.
329
330
331
332
333
334
335
336
337
338
339
340
Typical procedure for the one-pot synthesis of unsymmetrical TRAM 5a from substrate
1a
A 25 mL round-bottom flask equipped with a magnetic bar and water condenser was charged
with 1a (1.0 mmol), Nu1-H 2a (1.0 mmol), MeCN (5 mL) and ZnCl2 (10 mol%) in air
atmosphere. The flask was placed into a constant temperature bath at 80 °C and the progress
of the reaction was monitored by TLC. After the full consumption of the starting materials,
1.0 mmol of the Nu2-H 2d as well as FeCl3 (10 mol%) were added to the reaction mixture
and the reaction mixture was allowed to stir for 1 h at 80 °C. The progress of the reaction was
monitored by TLC. On completion of the reaction, the solvent was removed under reduced
pressure and the crude product was purified by dry column vacuum chromatography (silica
gel G, petroleum ether 60-80 °C/EtOAc) to obtain the desired product 5a in 79% yield.
16

Page 17 of 20
New Journal of Chemistry
1
2
3
4
5
6
View Article Online
DOI: 10.1039/C9NJ00149B
341
Supporting Information Summary
1
13
342
343
Additional experimental details, characterization data as well as H and C NMR spectra of
7
8
the products 3, 4 and 5 are given in supporting information.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
344
Acknowledgments
345
346
347
348
349
Scientific and Engineering Research Board (SERB) is gratefully acknowledged for financial
support to P.N.C (sanction order no. SB/FT/CS-115/2014; dated 24/08/2015). We thank NIT
Meghalaya (for financial support to D.P.). P. N. C. thanks Dr. S. Pan, IIT Guwahati for useful
discussions and many help. IIT Guwahati and SAIF, NEHU are also acknowledged for
analytical facilities.
350
351
352
Conflict of Interest
The authors declare no conflict of interest.
References
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
1.
2.
3.
B. Rybtchinski and D. Milstein, Angew. Chem. Int. Ed., 1999, 38, 870-883.
M. Tobisu and N. Chatani, Chem. Soc. Rev., 2008, 37, 300-307.
E. Fillion, E. Beaton, Y. Nguyen, A. Wilsily, G. Bondarenko and J. Jacq, Adv. Synth.
Catal., 2016, 358, 3422-3434.
4.
5.
6.
7.
8.
9.
N. Zhang and J. Vozzolo, J. Org. Chem., 2002, 67, 1703-1704.
D. Nečas, M. Turský, I. Tišlerová, and M. Kotora, New J. Chem., 2006, 30, 671-674.
D. Nečas and M. Kotora, Org. Lett., 2008, 10, 5261-5263.
D. Necas, M. Turský, and M. Kotora, J. Am. Chem. Soc., 2004, 126, 10222-10223.
Y. J. Park, J. -W. Park and C. -H. Jun, Acc. Chem. Res., 2008, 41, 222-234.
C. He, S. Guo, L. Huang, and A. Lei, J. Am. Chem. Soc., 2010, 132, 8273-8275.
10. C. Sen and S. C. Ghosh, Adv. Synth. Catal., 2018, 360, 905-910.
11. S. J. Mahoney, T. Lou, G. Bondarenko, and E. Fillion, Org. Lett., 2012, 14, 3474-3477.
12. E. L. Armstrong, H. K. Grover, and M. A. Kerr, J. Org. Chem., 2013, 78, 10534-10540.
13. M. Saha and A. K. Pal, Tetrahedron Lett., 2011, 52, 4872-4877.
14. M. Li, A. Taheri, M. Liu, S. Sun and Y. Gu, Adv. Synth. Catal., 2014, 356, 537-556.
15. M. Li and Y. Gu, Adv. Synth. Catal., 2012, 354, 2484-2494.
16. P. Bhuyan and M. Deb, Synthesis, 2008, 2891-2898.
17

New Journal of Chemistry
Page 18 of 20
1
2
3
4
View Article Online
DOI: 10.1039/C9NJ00149B
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
17. Y. Yang, F. Ni, W. M. Shu, and A. X. Wu, Chem. Eur. J., 2014, 20, 11776-11782.
5
6
7
8
18. X. Yao and C. -J. Li, J. Org. Chem., 2005, 70, 5752-5755.
19. H. Li, W. Li, W. Liu, Z. He and Z. Li, Angew. Chem. Int. Ed., 2011, 50, 2975-2978.
20. W. Li, X. Zheng, and Z. Li, Adv. Synth. Catal., 2013, 355, 181-190.
21. P. Thirupathi and S. Soo Kim, J. Org. Chem., 2010, 75, 5240-5249.
22. S. Ruengsangtongkul, P. Taprasert, U. Sirion and J. Jaratjaroonphong, Org. Biomol.
Chem., 2016, 14, 8493-8502.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
23. R. Mudududdla, R. Sharma, S. Abbat, P. V. Bharatam, R. A. Vishwakarma and S. B.
Bharate, Chem. Commun., 2014, 50, 12076-12079.
24. T. Shoji, S. Kim, K. Yamamoto, T. Kawai, Y. Okada and K. Chiba, Org. Lett., 2014,
16, 6404-6407.
25. H. Li, J. Yang, Y. Liu and Y. Li, J. Org. Chem., 2009, 74, 6797-6801.
26. P. N. Chatterjee, A. K. Maity, S. S. Mohapatra and S. Roy, Tetrahedron, 2013, 69,
2816-2826.
27. D. Paul, S. Khatua and P. N. Chatterjee, ChemistrySelect, 2018, 3, 11649-11656.
28. M. Shiri, M. A. Zolfigol, H. G. Kruger and Z. Tanbakouchian, Chem. Rev., 2009, 110,
2250-2293.
29. M. Nambo and C. M. Crudden, ACS Catalysis, 2015, 5, 4734-4742.
30. P. J. Praveen, P. Parameswaran, and M. Majik, Synthesis, 2015, 47, 1827-1837.
31. J. Zhang, A. Bellomo, A. D. Creamer, S. D. Dreher and P. J. Walsh, J. Am. Chem. Soc.,
2012, 134, 13765-13772.
32. Y. Xia, L. Chen, P. Qu, G. Ji, S. Feng, Q. Xiao, Y. Zhang and J. Wang, J. Org. Chem.,
2016, 81, 10484-10490.
33. X. Shen, N. Gu, P. Liu, X. Ma, J. Xie, Y. Liu and B. Dai, Chin. J. Chem. 2016, 34,
1033-1038.
34. S. Gao, X. Xu, Z. Yuan, H. Zhou, H. Yao and A. Lin, Eur. J. Org. Chem., 2016, 2016,
3006-3012.
35. H. S. P. Rao and A. V. B. Rao, Beilstein J. Org. Chem., 2016, 12, 496-504.
36. C. Yue, F. Na, X. Fang, Y. Cao and J. C. Antilla, Angew. Chem. Int. Ed., 2018, 57,
11004-11008.
37. Z. Zhang, H. Wang, N. Qiu, Y. Kong, W. Zeng, Y. Zhang and J. Zhao, J. Org. Chem.,
2018, 83, 8710-8715.
18

Page 19 of 20
New Journal of Chemistry
1
2
3
4
5
6
7
8
9
402
38. J. -X. Liu, Z. -Q. Zhu, L. Yu, B. -X. Du, G. -J. Mei and F. Shi, SynthesiDs,OI2: 1001.1083V,9ie/5wC09ANr,tiJc0le0O1n4l9inBe
3436-3444.
403
404
405
406
407
408
409
410
411
39. Y. Li, Y. Zhu, G. Tu, J. Zhang and Y. Zhao, RSC Adv., 2018, 8, 30374-30378.
40. S. K. Das and G. Panda, Tetrahedron Lett., 2005, 46, 3097-3102.
41. A. R. Katritzky and D. Toader, J. Org. Chem., 1997, 62, 4137-4141.
42. S. Lin and X. Lu, J. Org. Chem., 2007, 72, 9757-9760.
43. J. Esquivias, R. Gómez Arrayás and J. C. Carretero, Angew. Chem. Int. Ed. 2006, 45,
629-633.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
44. Z. Li, Z. Duan, J. Kang, H. Wang, L. Yu, and Y. Wu, Tetrahedron, 2008, 64, 1924-
1930.
412
413
414
415
416
417
418
419
420
421
45. Y. -R. Luo and J. Kerr, CRC Handbook of Chemistry and Physics, 2012, 89, 89.
46. S. Biswas, S. Maiti, and U. Jana, Eur. J. Org. Chem., 2010, 2010, 2861-2866.
47. C. B. Castellani, A. Perotti, M. Scrivanti and G. Vidari, Tetrahedron, 2000, 56, 8161-
8166.
48. D. S. Pedersen and C. Rosenbohm, Synthesis, 2001, 2001, 2431-2434.
49. D. Paul and P. N. Chatterjee, ChemistrySelect, 2018, 3, 12150-12154.
50. K. Jette, M. Kristin, M. Dirk, Z. Alexander and B. Matthias, Adv. Synth. Catal., 2007,
349, 865-870.
51. F. L. Sun, X. J. Zheng, Q. Gu, Q. L. He and S. L. You, Eur. J. Org. Chem., 2010, 2010,
47-50.
19

New Journal of Chemistry
Page 20 of 20
1
2
3
4
View Article Online
DOI: 10.1039/C9NJ00149B
Table of contents
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
An efficient iron-catalyzed dual C-C bond cleavage reaction has been developed for the
synthesis of triaryl methanes.