Gold-Catalyzed Oxidative Cross-Coupling Reactions among Two Distinct Arenes and One Gold Carbene with Phosphoric Acids as Cocatalysts

Article abstract of DOI:10.1002/adsc.202000879

Gold-catalyzed oxidative cross-coupling reactions of two distinct arenes with one gold carbene furnish triarylmethane products. Notably, competitive homo-coupling reactions are efficiently suppressed with a phosphoric acid as co-catalyst (10 mol%) in THF. These cross-coupling reactions have a wide scope of applicable substrates, with respect to indoles, arylamines, and α-aryl diazo cyanides or esters. Our mechanistic analysis indicates that the basicity of the arylanilines greatly affects the cross-coupling efficiency. (Figure presented.).

Full text of DOI:10.1002/adsc.202000879

Title: Gold-catalyzed Oxidative Cross-coupling Reactions Among Two
Distinct Arenes and One Gold Carbene with Phosphoric Acids as
Cocatalysts
Authors: Rai-Shung Liu, Manoj D. Patil, and Balaji Sopanrao Kale
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000879
Link to VoR: https://doi.org/10.1002/adsc.202000879

10.1002/adsc.202000879
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.202((will be filled in by the editorial staff))
Gold-Catalyzed Oxidative Cross-coupling Reactions among
Two Distinct Arenes and One Gold Carbene with Phosphoric
Acids as Cocatalysts
Manoj D. Patil,a Balaji S. Kale,a and Rai-Shung Liua*
a
Frontier Research Center for Matter Science and Technology, Department of Chemistry, National Tsing-Hua
University, Hsinchu, Taiwan, ROC
Email: rsliu@mx.nthu.edu.tw
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract: Gold-catalyzed oxidative cross-coupling
reactions of two distinct arenes with one gold carbene
furnish triarylmethane products. Notably, competitive
homo-coupling reactions are efficiently suppressed with a
phosphoric acid as co-catalyst (10 mol%) in THF. These
cross-coupling reactions have a wide scope of applicable
substrates, with respect to indoles, arylamines, and α-aryl
diazo cyanides or esters. Our mechanistic analysis indicates
that the basicity of the arylanilines greatly affects the cross-
coupling efficiency.
Keywords: gold catalysis; oxidative cross coupling; gold
carbenes; α-aryl diazo compounds; indoles; anilines.
Introduction
Metal carbenes are versatile species to react with
various nucleophiles to form new C–Y bonds (Y = C,
O, N).[1-2] In the presence of phenols, arylamines and
electron-rich arenes or heteroarenes, metal carbenes
typically afford Y–H insertion products (Y = C, O or
N) over various catalysts including Rh, Au, Ag, Ru, Pd
or Cu (Equation 1).[3-6] In seeking new carbene
reactivity, we developed gold-catalyzed oxidative
couplings of two indoles with one α-cyano gold
carbene
to
form
2-substituted
2,2-
di(indolyl)acetonitriles efficiently (Equation 2).[7]
Particularly notable are the dication synthons[8] of gold
carbenes to allow a double attack of indole
nucleophiles. However, products of this type could be
alternatively obtained from Lewis-acid catalyzed
condensations of aldehydes with two indoles
(Equation 2), thus rendering these oxidative couplings
less appealing.
Oxidative cross-coupling of two distinct aryl C–H
bonds to form unsymmetric biaryl species is an
inspiring topic in metal catalysis.[9] We sought a new
strategy to enable a cross-coupling reaction of two
distinct arenes with one gold carbene. This task is
challenging because competitive homo-coupling
reactions must be suppressed efficiently with building
a new strategy. With our efforts, this work describes
the first success of catalytic cross-coupling reactions
involving one indole, one arylamine and one gold
carbene (Equation 3). Our new strategy employs
phosphoric acid (10 mol%) in THF to suppress the two
homo-coupling reactions as depicted in Equation 3.
Notably, our experimental data exclude the
1
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10.1002/adsc.202000879
Advanced Synthesis & Catalysis
intermediacy of α-cyano aryl ketones that were proved
to be inactive under the running conditions (vide infra). in THF (entry 8). We also tested diphenylphosphinic
acid A-2 (pKa 2.30) and diphenylphosphoric acid A-3
(pKa 1.12),[10] which delivered the same product in 62
and 72% yield, respectively (entries 9 and 10). To
Result and Discussion
clarify the effect of the acidity, we employed highly
acidic CF3CO2H (pKa = 0.0) to afford the desired
product 4a in a decreased yield ca. 59% (entry 11).
Brønsted acid such as A-3 with a moderate acidity
(pKa = 1.12) is more appropriate for this cross-
coupling reaction.
Table 1 shows the conditions and catalysts to optimize
the efficiency of cross-coupling reactions among
indole 1a, N,N-dimethyl aniline 3a and α-phenyldiazo
cyanide 2a in dichloromethane (DCM), aiming at our
target 4a. Among the three phosphine gold catalysts,
L’AuCl/AgOTf (L’= P(t-Bu)2(o-biphenyl), PPh3 and
P(OPh)3, entries 1-3), triphenyl phosphite was better
than the other two phosphine ligands to afford
compound 4a in 26% yield; this was encouraging
because the formation of two homo-coupling products
4’ and 4” was greatly suppressed. We thus increased
the loading of AgOTf to 50 mol%, further improving
the yield of compound 4a slightly to 31% (entry 4).
The chemoselectivity was greatly improved on
changing the solvent from DCM to MeCN, giving
compound 4a in 49% yield (entry 6). We thus sought
a suitable Brønsted acid as a co-catalyst because a
protodeauration step was presumably involved in the
We tested these cross-coupling reactions on various
indole derivatives 1b–k to assess the generality of the
reactions (Table 2). For various N-phenyl substituents
as in species 1b–e (X = Me, OMe, Cl and Br), the
cross-coupling reactions gave product yields up to 81-
86%, for those bearing electron-donating groups such
as X = Me (4b) and OMe (4c), but the yields decreased
to 74-78% for X = Cl (4d) and Br (4e). This trend
correlates well with the nucleophilicity of the indoles.
The molecular structure of compound 4b was
confirmed by X-ray diffraction.[11] For N-meta or -
ortho substituted methoxy indoles 1f and 1g their
resulting products 4f and 4g were obtained in 68 and
75% yield (entries 5 and 6). This reaction also worked
well with unsubstituted indole 1h and N-alkyl indole
1i (R = n-Pr), which delivered coupling products 4h
and 4i in lower yields (41 and 57%, entries 7 and 8).
These oxidative coupling reactions were also
applicable to 2- or 3-thienyl-containing indoles 1j and
1k, rendering compounds 4j and 4k in 73 and 82%
yield, respectively (entries 9 and 10).
Table 1. Cross-coupling reactions under various conditions
Entr
y
Catalyst (mol%)
Additive
Solven
t
Time
(h)
Yield[b]
4'
(10 mol%)
Table 2. Oxidative coupling reactions with various indoles
4a
17
4''
--
1[c]
2
LAuCl/AgOTf (10/10)
PPh3AuCl/AgOTf (10/10)
(PhO)3PAuCl/AgOTf (10/10)
(PhO)3PAuCl/AgOTf (10/50)
AgOTf (50)
--
--
DCM
DCM
DCM
DCM
DCM
MeCN
MeCN
THF
10
40
10
12
20
15
10
08
09
06
06
24
26
15
09
11
--
21
26
31
--
--
3
--
--
4
--
--
5[d]
--
--
6
(PhO)3PAuCl/AgOTf (10/50)
(PhO)3PAuCl/AgOTf (10/50)
(PhO)3PAuCl/AgOTf (10/50)
(PhO)3PAuCl/AgOTf (10/50)
(PhO)3PAuCl/AgOTf (10/50)
(PhO)3PAuCl/AgOTf (10/50)
--
--
49
58
69
62
72
59
--
08
--
11
10
06
10
08
17
--
7
A-1
A-1
A-2
A-3
A-4
A-4
8
--
9
THF
--
10
11
12[e]
THF
--
THF
--
THF
--
[a] 1c = 0.26 M.
reaction mechanism. As shown in entry 6, the presence
of phosphoric acid A-1 (10 mol%, pKa 1.14) improved
the yield of species 4a to 58% in MeCN (entry 7), and
further to 69% yield
[b] Product yields are obtained after purification from a silica
column.
[a] 1a = 0.2 M, 2a = 1.5 equiv., 3a = 1.5 equiv.
[b] Product yields are obtained after purification from a silica
column.
Table 3 depicts the applicability of these cross-
coupling reactions to various α-diazo species including
cyanides, esters and ketones. For α-phenyldiazo
cyanides 2b-2e bearing para-substituents (X = Me, Cl,
Br and CF3), their resulting products 5a-5d were
obtained in 72-84% yields (entries 1-4). For meta-
methoxyphenyl analogue 2f, its corresponding product
[c] L = P(t-Bu)2(o-biphenyl).
[d] 3a was recovered in 69% yield in entry 5.
[e]
The amount of 1a and 3a recovered was 67 and 75%,
respectively.
2
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10.1002/adsc.202000879
Advanced Synthesis & Catalysis
Table 4. Cross-coupling reactions with various anilines
5e was produced in 71% yield (entry 5). We performed
the reactions on α-diazo ester 2g and ketone 2h which
afforded cross-coupling products 5f and 5g in 76 and
70% yield, respectively (entries 6 and 7).
Table 3. Cross-coupling reactions with α-diazo species
[a] 1c = 0.18 M.
[b] Product yields are obtained after purification from a silica
column.
[a] 1c = 0.18 M.
[b]
Product yields are obtained after purification from a
silica column.
We also achieved catalytic cross-coupling reactions
between two distinct indoles and one carbene
(Equation 5). Under the standard conditions (molar
ratio: 1c/1l/2a = 1/1.5/1.5), we obtained desired
product 4l from a cross-coupling reaction, in addition
to compound 4c’ in a minor proportion. We also
managed to achieve the cross-coupling reactions
among two distinct anilines and one carbene; the result
is depicted in Equation 6. Under the conditions 3a/3g
/2a = 1/2.0/1.5, we obtained the resulting cross-
coupling products 7b in 63% yields. This good yield
was attributed to a large loading (2 equiv) of anilines
3g, that has moderate nucleophilicity.
[c] Reactions were carried out at 50 °C.
In Table 4, we prepared various N-substituted anilines
3b-3i to assess the effects of amine functionalities. We
first performed the reactions on N-phenyl substituted
anilines 3b (R = H) and 3c (R = Me), yielding the
cross-coupling products 6a and 6b in 80 and 85% yield,
respectively (entries 1 and 2). For electron-rich N-
butyl-derived anilines 3d and 3e, their resulting
products 6c and 6d were obtained in 74 and 82% yield,
respectively (entries 3 and 4). Again, for anilines 3f
and 3g bearing a N-(2-methoxyethyl) substituent, we
obtained a yield for N- methyl product 6f (R = Me,
86%), better than that (70%) of compound 6e (R = H
entries 5 and 6). For anilines 3h and 3i bearing less
basic N-bis(2-methoxyethyl) and morpholine, their
corresponding products 6g and 6h were obtained in 82
and 64% yield, respectively (entries 7 and 8). With
these results, we observed efficiency for R = Me as in
entries 2,4,6 greater than for their unsubstituted
anilines R = H (entries 1, 3, 5). A basic aniline is
expected to diminish the activity of the gold catalyst
when gold is coordinated with aniline; this positive
effect might arise from an increased nucleophilicity of
a basic aniline. According to our subsequent study, a
deprotonation of a basic aniline seems to be more
important to enhance this cross-coupling efficiency
(vide infra).
3
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10.1002/adsc.202000879
Advanced Synthesis & Catalysis
indole 1c is superior to aniline 3a as a nucleophile; this
assessment is evident also with preferable formation of
homo-coupling indole product 4’ in Table 1. Notably,
when aniline 1c was present in the indole/diazo
mixture, formation of these four major products
4c’/1c-H and 4a”/3a-H in Equations 5 and 6 became
so seriously suppressed such that cross-coupling
product 4c was obtained up to 64% yield (Equation 9).
When phosphoric acid A-3 (10 mol%) was present,
this 1c/2a/3a mixture generated desired 4c up to 82%
yield, further to 86% with acid A-3 at a 20 mol%
loading (Equation 10).
Scheme 1. Chemical functionalizations of cross-coupling
products
We performed chemical transformations of one
cross-coupling
product
4m
into
other
indole/arene/carbene species that could not be
obtained in this catalysis. We prepared N-benzyl
derivative 4m in 65% yield according to our protocol
(Scheme 1). Reductive debenzylation of species 4m
with Pd/C/H2 in MeOH yielded compound 4n in 88%
yield.[12] Treatment of species 4n with p-TSA/NaNO2
yielded a diazonium salt that reacted with KI to form
4-iodophenyl product 4o in 92% yield.[13a] With this
diazonium species, compound 4n was further
transformed into an unsubstituted phenyl derivative 4p
and 4-bromophenyl product 4q in 57 and 80% yield,
respectively.[13b]
Accordingly,
various
indole/arene/carbene coupling products can be derived
from chemical functionalization of their aniline
derivative 4m, further expanding the scope of
applications.
To clarify the role of α-cyano ketones as viable
intermediates, we prepared an authentic ketone 2i that
turned out to be robust under the operating conditions,
with a large recovery of all starting materials
(Equation 11). In fact, α-cyano diazo 2a could not be
converted into acyl cyanide 2i with Au(I) and Ag(I) in
wet THF solution (Equation 12). Accordingly,
addition of arenes at gold carbenes is confirmed to be
an initial step. We performed two new experiments
that show that hydroarylation products 1c-H and 3c-H
are inactive species in this cross-coupling process. The
reactions of 1c-H with 3a and 3a-H with 1c failed to
give the desired cross-coupling product 4c (Equations
13 and 14).
Our next task was to clarify the basicity of anilines
in the cross-coupling reaction. As shown in Scheme 2,
we examined the reactions with less basic anilines 3j
(R1 = R2 = H) and 3k (R1 = H, R2 = Ac), which showed
no catalytic activity for either cross- or homo-coupling
reactions (entries 1 and 2). We next tested the reaction
of N, N-dimethyl 2,6-dimethylaniline 3l that turned out
to be an ineffective substrate, but we isolated homo-
coupling bis(indole) product 4c’ (entry 3). Aniline 3l
is highly hindered for a deprotonation reaction, but not
for a para-arylation; the high reactivity of a basic
aniline in the cross coupling is likely to be associated
with a deprotonation.
We performed two control experiments (Equations
7 and 8) to examine the relative rates of reaction of
indole 1c versus aniline 3a toward gold carbenes.
Under the same conditions, an equimolar mixture of
1c/2a and 3a/2a gave rise to homo-coupling and
hydroarylation products 4c’/1c-H and 4a”/3a-H; their
respective yields were 36 and 31% for species 4c’ and
1c-H, and 31 and 26% for species 4a” and 3a-H.
According to the duration (5.5 h versus 8 h) of reaction,
4
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10.1002/adsc.202000879
Advanced Synthesis & Catalysis
[a] 1c = 0.18 M
[b] Product yield are obtained after purification from a silica
column.
Scheme 2. The role of anilines in cross-coupling reactions
According to our product analysis in Scheme 2,
cross-coupling reactions are operable only with those
anilines bearing sufficient basicity to enable a
deprotonation. Concurrently, phosphoric acid A-3 also
enhanced the efficiency of cross coupling, but its
absence still yielded desired product 4c in 64% yield
(Equation 9). We postulate a mechanism involving
phosphoric acid A-3, as depicted in conditions A
(Scheme 3). N-aryl indoles 2 are obviously more active
than those N-alkyl anilines to attack gold carbenes to
form gold-containing iminium A, of which the acidic
proton was deprotonated with aniline 2a to form gold-
containing indole B. Intermediate B is further oxidized
by Ag(I) to form radical cation C, in which the cationic
center induces a dissociation of LAu+ to generate the
indolium species D and LAu(0); the latter is quickly
oxidized by Ag(I) or other oxidant to regenerate LAu+.
After this transformation C→D, the phosphoric acid
reacts further with PhNMe2 to form a complex pair.
This acid-base pair bears a basic P=O oxygen which
can be tightly bound to an iminium salt D through an
electrostatic interaction to facilitate the cross-coupling
reaction. According to our results in Equation 7, in the
absence of PhNMe2 (conditions B), triflate ion
abstracts the acidic proton of A to form gold-
containing indole B and triflic acid. Intermediate B can
further be oxidized by excessive Ag(I) to form
indolium D which is attacked by another molecule of
indole to get homo-coupling product 4’.
Protodeauration of B can also occur with triflic acid to
produce the hydroarylation product 1c-H.
Scheme 3. A postulated mechanism
Conclusion
Before this work, electron-rich arenes were well
known to undergo hydroarylations with gold, rhodium
and other carbenes.[2,3] To seek new carbene chemistry,
we have developed oxidative cross-coupling reactions
between two distinct arenes with one gold carbene
over a wide scope of substrates. Our mechanistic
analysis indicates that relatively basic arylamines and
an additional phosphoric acid are crucial to enhance
these cross-coupling reactions, thus providing
mechanistic insight into the reactions.
Experimental Section
Synthesis of 2-(4-(dimethylamino) phenyl)-2-phenyl-2-
(1-phenyl-1H-indol-3-yl)acetonitrile phenylacetonitrile
(4a):
A
reaction
tube
was
charged
with
(chlorotriphenoxyphosphoranyl)gold(I) (28 mg, 0.052
mmol), diphenyl hydrogen phosphate A-3 (13 mg, 0.052
mmol) and silver(I) trifluoromethanesulfonate (AgOTf) (66
mg, 0.22 mmol). To the above mixture was added a dry THF
(1.0 mL), and the mixture was stirred at room temperature
under a nitrogen atmosphere for 5 min. To this solution was
added a dry THF solution (2 mL) of N-phenyl Indole 1a
(100 mg, 0.52 mmol), 2-diazo-2-phenylacetonitrile 2a (88
mg, 0.77 mmol) and N, N-dimethyl aniline 3a (94 mg, 0.77
mmol) with syringe in a period of 25 minute. The mixture
was kept stirring at 25 °C for 6 h before it was filtered over
a short celite bed. The solvent was concentrated, and the
crude product was chromatographed through a silica gel
column using ethyl acetate/hexane (10:90) as the eluent to
afford compound 4a (159 mg, 0.37 mmol, 72% yield) as
light yellow semi-solid.
This mechanism rationalizes well the importance of
the basicity of anilines to affect the cross-coupling
reaction; basic anilines form a tight complex with
phosphoric acid in addition to their strong
nucleophilicity. For various BrØnsted acids (Table 1,
entries 8-11), CF3CO2H (pKa 0.0) is inferior to
phosphoric acid A-3 (pKa 1.12) in this cross coupling
-
because the less basic CF3CO2 anion is not tightly
2-phenyl-2,2-bis(1-phenyl-1H-indol-3-yl)acetonitrile
(4’):
bound to an iminium species C.
1
colorless liquid, H NMR (600 MHz, CDCl3): δ 7.62 -7.58
(m, 2 H), 7.53 (d, J = 8.2 Hz, 2 H), 7.46-7.43 (m, 4 H), 7.40
-7.36 (m, 5 H), 7.33 -7.28 (m, 6 H), 7.22 -7.21 (m, 2 H), 7.11
(td, J = 8.0, 0.9 Hz, 2 H), 6.58 (s, 2 H); 13C NMR (150 MHz,
CDCl3): δ 139.1, 136.9, 131.1, 129.5, 129.3, 128.6, 128.1,
5
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10.1002/adsc.202000879
Advanced Synthesis & Catalysis
127.8, 126.8, 124.5, 123.0, 121.4, 121.0, 120.8, 116.7, 116.2, 2-(4-(dimethylamino)phenyl)-2-(1-(4-methoxyphenyl)-
110.8, 44.8; HRMS-ESI+ calcd for C36H25N3Na (M+H):
522.1946, found: 522.1931.
1H-indol-3-yl)-2-phenylacetonitrile (4c):
1
yellow semi-solid, 176.2 mg, 86%; H NMR (400 MHz,
2,2-bis(4-(dimethylamino)phenyl)-2-phenylacetonitrile
(4’’):
CDCl3): δ 7.43-7.37 (m, 3 H), 7.35-7.28 (m, 5 H), 7.22- 7.19
(m, 3 H), 7.05 (t, J = 7.9 Hz, 1 H), 6.96 (d, J = 8.9 Hz, 2 H),
6.65 (d, J = 8.9 Hz, 2 H), 6.53 (s, 1 H), 3.83 (s, 3 H), 2.93
(s, 6 H); 13C NMR (150 MHz, CDCl3): δ 158.6, 149.9, 140.5,
137.7, 132.3, 129.3, 129.0, 128.5, 128.2, 127.7, 126.4, 126.2,
122.8, 122.7, 121.1, 120.5, 117.4, 114.8, 112.2, 110.6, 55.6,
40.3; ESI-MS calcd. for C31H27N3NaO (M+Na): 480.2052;
Found: 480.2038.
yellow solid; 1H NMR (600 MHz, CDCl3): δ 7.31-7.26 (m,
3 H), 7.24-7.23 (m, 2 H), 7.03 (d, J = 8.6 Hz, 4 H), 6.63 (d,
J = 8.8 Hz, 4 H), 2.93 (s, 12 H); 13C NMR (150 MHz,
CDCl3): δ 149.8, 141.6, 129.4, 128.7, 128.3, 128.3, 127.5,
124.2, 111.9, 55.8, 40.3; ESI-MS calcd. for C24H25N3Na
(M+Na): 378.1946; Found: 378.1947.
2-(1-(4-chlorophenyl)-1H-indol-3-yl)-2-(4-
(dimethylamino)phenyl)-2-phenylacetonitrile (4d):
2-(4-(dimethylamino)phenyl)-2-phenylacetonitrile (3a-
H):
yellow solid, 158.2 mg, 78%; 1H NMR (600 MHz, CDCl3):
δ 7.45 (d, J = 8.0 Hz, 1 H), 7.43-7.40 (m, 3 H), 7.37 (d, J =
8.0 Hz, 1 H), 7.34-7.29 (m, 5 H), 7.23-7.18 (m, 4 H), 7.08
(t, J = 8.0 Hz, 1 H), 6.65 (d, J = 8.8 Hz, 2 H), 6.56 (s, 1 H),
2.93 (s, 6 H); 13C NMR (150 MHz, CDCl3): δ 149.8, 140.1,
137.7, 136.9, 132.4, 129.8, 129.7, 128.9, 128.6, 128.5, 128.1,
127.8, 126.7, 125.7, 125.5, 123.2, 122.5, 121.3, 121.0, 120.1,
118.5, 112.0, 110.4, 50.3, 40.3; ESI-MS calcd. for
C30H25ClN3 (M+H): 462.1737; Found: 462.1735.
colorless liquid, 50.44 mg, 26%; 1H NMR (600 MHz,
CDCl3): δ 7.33-7.26 (m, 5 H), 7.15 (d, J = 8.5 Hz, 2 H), 6.66
(d, J = 8.7 Hz, 2 H), 5.03 (s, 1 H), 2.92 (s, 6 H); 13C NMR
(150 MHz, CDCl3): δ 150.2, 136.7, 129.0, 128.4, 127.8,
127.5, 123.2, 120.2, 112.6, 41.7, 40.3; EI-MS calcd. for
C16H16N2 (M+): 236.1313; Found: 236.1308.
2-(1-(4-methoxyphenyl)-1H-indol-3-yl)-2-
phenylacetonitrile (1c-H):
2-(1-(4-bromophenyl)-1H-indol-3-yl)-2-(4-
(dimethylamino)phenyl)-2-phenylacetonitrile (4e):
colorless liquid, 31.8 mg, 21%; 1H NMR (400 MHz,
CDCl3): δ 7.50-7.47 (m, 3 H), 7.41 (d, J = 8.2 Hz, 2 H),
7.39-7.30 (m, 4 H), 7.23-7.19 (m, 2 H), 7.12 (t, J = 7.9 Hz,
1 H), 7.01 (dd, J = 6.8, 2.1 Hz, 2 H), 5.42 (s, 1 H), 3.85 (s,
3 H); 13C NMR (100 MHz, CDCl3): δ 158.6, 137.1, 135.3,
132.0, 129.1, 128.2, 127.7, 127.6, 127.2, 126.1, 123.0, 120.6,
119.7, 119.0, 114.8, 111.2, 110.8, 55.6, 34.4; EI-MS calcd.
for C23H18N2O (M+): 338.1419; Found: 338.1416.
yellow solid, 137.7 mg, 74%; 1H NMR (700 MHz, CDCl3):
δ 7.45 (d, J = 8.3 Hz, 1 H), 7.43-7.40 (m, 4 H), 7.37 (d, J =
8.0 Hz, 1 H), 7.34-7.20 (m, 5 H), 7.24-7.19 (m, 3 H), 7.08
(t, J = 7.4 Hz, 1 H), 6.65 (d, J = 8.3 Hz, 2 H), 6.56 (s, 1 H),
2.93 (s, 6 H); 13C NMR (175 MHz, CDCl3): δ 149.9, 140.1,
137.6, 136.9, 132.3, 129.7, 128.9, 128.6, 128.5, 128.1, 127.8,
126.7, 126.6, 125.7, 123.2, 122.5, 121.3, 121.0, 118.4, 112.0,
110.4, 50.3, 40.3; ESI-MS calcd. for C30H24BrN3Na
(M+Na): 528.1051; Found: 528.1057.
2,2-bis(1-(4-methoxyphenyl)-1H-indol-3-yl)-2-
phenylacetonitrile (4c’):
2-(4-(dimethylamino)phenyl)-2-(1-(2-methoxyphenyl)-
1H-indol-3-yl)-2-phenylacetonitrile (4f):
1
colorless semi-solid, 90.2 mg, 36%; H NMR (600 MHz,
CDCl3): δ 7.63 (dd, J = 8.5, 1.3 Hz, 2 H), 7.59 (dd, J = 7.2,
0.9 Hz, 2 H), 7.36-7.29 (m, 7 H), 7.19-7.14 (m, 4 H), 7.07
(td, J = 8.0, 1.2 Hz, 2 H), 7.02-6.99 (m, 4 H), 6.81 (s, 2 H),
3.68 (s, 6 H); 13C NMR (150 MHz, CDCl3): δ 154.4, 139.5,
137.9, 130.2, 128.7, 128.4, 128.0, 128.0, 127.8, 127.6, 125.8,
122.3, 120.7, 120.1, 115.2, 112.3, 111.0, 55.6, 44.9; ESI-
MS calcd. for C38H29N3NaO2 (M+Na): 582.2157; Found:
582.2150.
yellow solid, 139.4 mg, 68%; 1H NMR (600 MHz, CDCl3):
δ 7.43 (d, J = 7.2 Hz, 2 H), 7.37 (d, J = 8.0 Hz, 1 H), 7.34-
7.28 (m, 4 H), 7.23 (d, J = 8.5 Hz, 2 H), 7.15 (d, J = 4.0 Hz,
2 H), 7.05-7.00 (m, 4 H), 6.65 (d, J = 8.9 Hz, 2 H) 6.52 (s,
1 H), 3.72 (s, 3 H), 2.92 (s, 6 H); 13C NMR (150 MHz,
CDCl3): δ154.3, 149.8, 140.5, 137.9, 130.4, 128.9, 128.8,
128.4, 128.2, 128.1, 127.6, 127.6, 127.1, 125.9, 122.8, 122.4,
120.7, 120.7, 120.2, 116.7, 112.3, 112.0, 111.1, 55.6, 50.3,
40.3; ESI-MS calcd. for C31H27N3NaO (M+Na): 476.1713;
Found: 476.1724.
2-(4-(dimethylamino)phenyl)-2-phenyl-2-(1-phenyl-1H-
indol-3-yl)acetonitrile (4a):
1
yellow semi-sold, 159.2 mg, 72%; H NMR (400 MHz,
2-(4-(dimethylamino)phenyl)-2-(1-(3-methoxyphenyl)-
1H-indol-3-yl)-2-phenylacetonitrile (4f):
CDCl3): δ 7.52 (d, J = 8.2 Hz, 1 H), 7.47 (d, J = 8.2 Hz, 2
H), 7.41-7.37 (m, 6 H), 7.35-7.28 (m, 4 H), 7.24-7.22 (m, 2
H), 7.09 (t, J = 7.3 Hz, 1 H), 6.65 (d, J = 8.8 Hz, 2 H), 6.60
(s, 1 H), 2.94 (s, 6 H); 13C NMR (100 MHz, CDCl3): δ 149.9,
140.3, 139.2, 137.0, 129.6, 128.9, 128.5, 128.1, 127.8, 126.9,
126.8, 126.6, 124.5, 123.9, 123.0, 122.7, 121.2, 120.7, 117.9,
112.0, 112.0, 110.7, 50.3, 40.3; HRMS-ESI+ calcd for
C30H25N3Na (M+Na): 450.1946, found: 450.1935.
yellow solid, 153.7 mg, 75%; 1H NMR (600 MHz, CDCl3):
δ 7.54 (d, J = 8.4 Hz, 1 H), 7.42 (d, J = 7.0 Hz, 2 H), 7.38-
7.29 (m, 5 H), 7.22-7.20 (m, 3 H), 7.08 (t, J = 7.4 Hz, 1 H),
6.98 (dd, J = 6.0, 1.2 Hz, 1 H), 6.94 (t, J = 2.1 Hz, 1 H), 6.86
(dd, J = 8.0, 2.3 Hz, 1 H), 6.65 (dd, J = 6.9, 2.2 Hz, 2 H),
6.60 (s, 1 H), 3.82 (s, 3 H), 2.93 (s, 6 H); 13C NMR (150
MHz, CDCl3): δ 160.4, 149.8, 140.2, 140.2, 136.127.8, 9,
130.3, 128.9, 128.5, 128.1, 126.8, 126.6, 123.0, 122.6, 121.2,
120.7, 117.9, 116.7, 112.1, 112.0, 110.8, 110.5, 55.5, 50.3,
40.3; ESI-MS calcd. for C31H27N3NaO (M+Na): 476.1713;
Found: 476.1715.
2-(4-(dimethylamino)phenyl)-2-phenyl-2-(1-(p-tolyl)-
1H-indol-3-yl)acetonitrile (4b):
yellow solid, 172.6 mg, 81%; 1H NMR (600 MHz, CDCl3):
δ 7.47 (d, J = 8.5 Hz, 1 H), 7.42 (d, J = 7.5 Hz, 2 H), 7.37
(d, J = 8.1 Hz, 1 H), 7.33 (t, J = 7.7 Hz, 2 H), 7.30-7.28 (m,
2 H), 7.27-7.23 (m, 3 H), 7.22 (d, J = 9.0 Hz, 2 H), 7.19 (t,
J = 6.9 Hz, 1 H), 7.06 (t, J = 6.9 Hz, 1 H), 6.65 (d, J = 8.5
Hz, 2 H) 6.57 (s, 1 H), 2.93 (s, 6 H), 2.38 (s, 3 H); 13C NMR
(150 MHz, CDCl3): δ 149.8, 140.3, 137.1, 136.7, 136.6,
130.1, 129.1, 128.9, 128.5, 128.1, 127.7, 126.9, 126.4, 124.5,
122.8, 122.7,, 121.1, 120.5, 117.5, 112.0, 111.7, 50.3, 40.3,
21.0; HRMS-ESI+ calcd for C31H27N3Na (M+Na):
464.2103, found: 464.2118.
2-(4-(dimethylamino)phenyl)-2-(1H-indol-3-yl)-2-
phenylacetonitrile (4h):
1
colorless semi-solid, 122.9 mg, 41%; H NMR (400 MHz,
CDCl3): δ 8.09 (bs, 1 H), 7.38-7.32 (m, 3 H), 7.31-7.26 (m,
3 H), 7.21-7.15 (m, 3 H), 7.06-7.00 (m, 2 H), 6.64 (d, J =
8.5 Hz, 2 H), 6.48 (d, J = 2.5 Hz, 1 H), 2.93 (s, 6 H); 13C
NMR (150 MHz, CDCl3): δ 149.8, 140.4, 136.8, 129.1,
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000879
Advanced Synthesis & Catalysis
128.9, 128.7, 128.4, 128.1, 127.7, 127.0, 125.4, 122.7, 122.6, 2-(4-chlorophenyl)-2-(4-(dimethylamino)phenyl)-2-(1-
120.7, 120.2, 117.0, 111.9, 111.2, 50.2, 40.3; EI-MS calcd.
for C24H21N3 (M+): 351.1735; Found: 351.1738.
(4-methoxyphenyl)-1H-indol-3-yl)acetonitrile (5b):
colorless solid, 158.6 mg, 72%; 1H NMR (600 MHz,
CDCl3): δ 7.40 (d, J = 8.1 Hz, 1 H), 7.36-7.35 (m, 3 H),
7.31-7.29 (m, 5 H), 7.21-7.19 (m, 2 H), 7.07 (t, J = 7.1 Hz,
1 H), 6.97 (d, J = 8.8 Hz, 2 H), 6.65 (d, J = 8.6 Hz, 2 H),
6.54 (s, 1H), 3.83 (s, 3 H), 2.93 (s, 6 H); 13C NMR (150 MHz,
CDCl3): δ 158.5, 149.9, 139.0, 137.5, 133.8, 131.9, 129.5,
129.2, 128.8, 128.6, 126.1, 126.0, 122.9, 122.3, 120.9, 120.6,
116.7, 114.8, 114.7, 112.0, 110.7, 55.5, 49.9, 40.3; ESI-MS
calcd. for C31H27ClN3O (M+H): 492.1843; Found: 492.1842.
2-(4-(dimethylamino)phenyl)-2-phenyl-2-(1-propyl-1H-
indol-3-yl)acetonitrile (4i):
1
yellow semi-solid, 140.8 mg, 57%; H NMR (600 MHz,
CDCl3): δ 7.37-7.35 (m, 2 H), 7.32-7.28 (m, 5 H), 7.20-7.15
(m, 3 H), 6.99 (t, J = 7.9 Hz, 1 H), 6.64 (d, J = 8.9 Hz, 2 H),
6.38 (s, 1 H), 3.96 (t, J = 7.1 Hz, 3 H), 2.93 (s, 6 H), 1.81-
1.75 (m, 2 H), 0.86 (t, J = 7.3 Hz, 3 H); 13C NMR (150 MHz,
CDCl3): δ 149.8, 140.7, 137.1, 128.9, 128.4, 128.1, 127.6,
127.4, 126.0, 122.9, 122.0, 120.9, 119.6, 115.1, 112.0, 109.6, 2-(4-bromophenyl)-2-(4-(dimethylamino)phenyl)-2-(1-
50.3, 48.1, 40.3, 23.4, 11.4; ESI-MS calcd. for C27H27N3Na
(M+Na): 416.2103; Found: 416.2119.
(4-methoxyphenyl)-1H-indol-3-yl)acetonitrile (5c):
colorless solid, 180.2 mg, 75%; 1H NMR (600 MHz,
CDCl3): δ 7.45 (d, J = 8.6 Hz, 2 H), 7.40 (d, J = 8.2 Hz, 1
H), 7.35 (d, J = 8.0 Hz, 1 H), 7.31-7.28 (m, 4 H), 7.20-7.17
(m, 2 H), 7.07 (t, J = 7.4 Hz, 1 H), 6.97 (d, J = 8.9 Hz, 2 H),
6.65 (d, J = 8.9 Hz, 2 H), 6.53 (s, 1H), 3.83 (s, 3 H), 2.94 (s,
6 H); 13C NMR (150 MHz, CDCl3): δ 158.5, 149.9, 139.5,
137.5, 131.9, 131.6, 129.9, 129.2, 128.8, 126.1, 126.0, 122.9,
122.2, 121.9, 120.8, 120.6, 116.6, 114.6, 112.0, 111.9, 110.7,
55.5, 49.9, 40.2; ESI-MS calcd. for C31H27BrN3O (M+H):
536.1338; Found: 536.1342.
2-(4-(dimethylamino)phenyl)-2-phenyl-2-(1-(thiophen-
2-yl)-1H-indol-3-yl)acetonitrile (4j):
yellow semisolid, 158.8 mg, 73%; 1H NMR (600 MHz,
CDCl3): δ 7.51 (d, J = 8.2 Hz, 1 H), 7.42-7.41 (m, 2 H), 7.39
(dd, J = 5.2, 1.9 Hz, 1 H), 7.36 (d, J = 8.2 Hz, 2 H), 7.34-
7.30 (m, 3 H), 7.23-7.20 (m, 4 H), 7.08 (td, J = 8.0, 0.8 Hz,
1 H), 6.65 (d, J = 9.0 Hz, 2 H), 6.58 (s, 1 H), 2.94 (s, 6 H);
13C NMR (150 MHz, CDCl3): δ 149.9, 140.2, 137.7, 137.2,
129.0, 128.9, 125.5, 128.1, 127.8, 126.8, 126.3, 126.1, 123.8,
123.1, 122.6, 121.1, 120.8, 117.7, 115.6, 112.0, 111.8, 50.3,
40.3; ESI-MS calcd. for C28H24N3S (M+H): 434.1691;
Found: 434.1690.
2-(4-(dimethylamino)phenyl)-2-(1-(4-methoxyphenyl)-
1H-indol-3-yl)-2-(4-(trifluoromethyl)phenyl)acetonitrile
(5d):
2-(4-(dimethylamino)phenyl)-2-phenyl-2-(1-(thiophen-
3-yl)-1H-indol-3-yl)acetonitrile (4k):
colorless solid, 197.7 mg, 84%; 1H NMR (600 MHz,
CDCl3): δ 7.57 (m, 3 H), 7.42-7.29 (m, 3 H), 7.23-7.18 (m,
5 H), 7.07 (t, J = 8.0 Hz, 1 H), 6.97 (d, J = 8.8 Hz, 2 H), 6.65
(d, J = 8.9 Hz, 2 H), 6.53 (s, 1H), 3.83 (s, 3 H), 2.94 (s, 6
H); 13C NMR (150 MHz, CDCl3): δ 158.5, 150.4 (JC-F = 7.5
Hz), 150.0, 144.4, 137.5, 131.9, 129.8, 129.5 (JC-F = 31.4,
6.3 Hz), 129.2, 128.8, 128.5, 126.2, 125.9, 125.5, 123.0,
122.0, 120.8, 120.7, 120.1 (JC-F = 4.6 Hz), 116.3, 114.7,
112.0, 110.7, 55.8, 50.3, 40.2; ESI-MS calcd. for
C32H27F3N3O (M+H): 526.2106; Found: 526.2116.
1
yellow semisolid, 178.3 mg, 82%; H NMR (700 MHz,
CDCl3): δ 7.52 (d, J = 8.2 Hz, 1 H), 7.42 (d, J = 7.5 Hz, 2
H), 7.41-7.36 (m, 2 H), 7.35-7.29 (m, 5 H), 7.24-7.21 (m, 2
H), 7.19 (d, J = 4.8 Hz, 1 H), 7.08 (t, J = 7.5 Hz, 1 H), 6.66
(d, J = 8.8 Hz, 2 H), 6.59 (s, 1 H), 2.94 (s, 6 H); 13C NMR
(175 MHz, CDCl3): δ 151.3, 141.6, 139.2, 138.7, 132.5,
130.8, 130.3, 129.9, 129.5, 129.2, 128.2, 127.7, 127.6, 125.2,
124.5, 122.6, 122.2, 119.1, 117.1, 113.4, 112.2, 51.7, 47.7
ESI-MS calcd. for C28H23N3NaS (M+Na): 457.1510;
Found: 457.1574.
2-(4-(dimethylamino)phenyl)-2-(3-methoxyphenyl)-2-
(1-(4-methoxyphenyl)-1H-indol-3-yl)acetonitrile (5e):
2-(4-(dimethylamino)phenyl)-2-phenyl-2-(1-(thiophen-
3-yl)-1H-indol-3-yl)acetonitrile (4k):
colorless solid, 155.1 mg, 71%; 1H NMR (600 MHz,
CDCl3): δ 7.38 (d, J = 8.1 Hz, 2 H), 7.30 (d, J = 8.8 Hz, 2
H), 7.25-7.21 (m, 2 H), 7.18 (t, J = 8.1 Hz, 1 H), 7.05 (t, J =
7.8 Hz, 1 H), 7.00-6.96 (m, 5 H), 6.83 (dd, J = 7.7, 2.3 Hz,
1 H), 6.64 (d, J = 8.9 Hz, 2 H), 6.56 (s, 1H), 3.83 (s, 3 H),
3.73 (s, 3 H), 2.93 (s, 6 H); 13C NMR (150 MHz, CDCl3): δ
159.6, 158.4, 149.8, 141.9, 137.4, 132.1, 129.4, 129.2, 128.8,
126.8, 126.2, 126.1, 122.7, 122.6, 121.0, 120.6, 120.4, 117.1,
114.6, 114.3, 112.8, 112.0, 110.5, 55.5, 55.2, 50.3, 40.3;
ESI-MS calcd. for C32H29N3NaO2 (M+Na): 510.2157;
Found: 510.2134.
1
yellow semisolid, 152.9 mg, 67%; H NMR (600 MHz,
CDCl3): δ 7.55 (d, J = 8.4 Hz, 2 H), 7.51 (d, J = 7.9 Hz, 1
H), 7.42 (d, J = 8.3 Hz, 1 H), 7.35-7.31 (m, 4 H), 7.29 (dd,
J = 6.6, 2.1 Hz, 2 H), 7.19 (t, J = 8.2 Hz, 2 H), 7.06 (td, J =
7.9, 0.9 Hz, 1 H), 7.02 (t, J = 7.2 Hz, 1 H), 6.95 (dd, J = 6.7,
2.2 Hz, 2 H), 6.72 (s, 1 H), 6.64 (s, 1 H), 4.02-3.99 (m, 2 H),
3.82 (s, 3 H), 1.75-1.70 (m, 2 H), 1.28-1.24 (m, 2 H), 0.88
(t, J = 7.3 Hz, 3 H); 13C NMR (150 MHz, CDCl3): δ 158.4,
139.5, 137.4, 136.9, 132.1, 128.7, 128.5, 127.8, 126.2, 126.1,
125.8, 122.7, 121.9, 121.7, 121.0, 120.8, 120.3, 119.6, 116.1, ethyl
2-(4-(dimethylamino)phenyl)-2-(1-(4-
methoxyphenyl)-1H-indol-3-yl)-2-phenylacetate (5f):
114.6, 113.5, 110.6, 109.5, 55.5, 46.2, 44.8, 32.2, 20.0, 13.6;
ESI-MS calcd. for C35H31N3NaO (M+Na): 532.2365;
Found: 532.2378.
colorless solid, 171.7 mg, 76%; 1H NMR (400 MHz,
CDCl3): δ 7.40-7.32 (m, 4 H), 7.26-7.21 (m, 5 H), 7.10 (t, J
= 8.1 Hz, 3 H), 6.97-6.19 (m, 3 H), 6.76 (s, 1 H), 6.62 (d, J
= 8.9 Hz, 2 H), 4.27 (q, J = 14.1, 7.0 Hz, 2 H), 3.83 (s, 3 H),
3.73 (s, 3 H), 2.91 (s, 6 H), 1.18 (t, J = 7.0 Hz, 3 H); 13C
NMR (150 MHz, CDCl3): δ 174.0, 158.0, 149.1, 143.2,
137.1, 132.6, 131.1, 130.3, 129.6, 129.4, 128.3, 127.5, 126.5,
126.0, 122.9, 121.8, 120.1, 119.4, 114.5, 111.6, 110.1, 61.4,
55.5, 40.4, 14.0; ESI-MS calcd. for C33H32N2NaO3 (M+Na):
527.2311; Found: 527.2303.
2-(4-(dimethylamino)phenyl)-2-(1-(4-methoxyphenyl)-
1H-indol-3-yl)-2-(p-tolyl)acetonitrile (5a):
1
colorless semi-solid, 162.6 mg, 77%; H NMR (400 MHz,
CDCl3): δ 7.38 (t, J = 6.2 Hz, 2 H), 7.29 (t, J = 7.6 Hz, 4 H),
7.23-7.16 (m, 4 H), 7.12 (d, J = 7.6 Hz, 2 H), 7.05 (t, J = 7.5
Hz, 1 H), 6.96 (d, J = 7.3 Hz, 2 H), 6.65 (d, J = 7.8 Hz, 2 H),
6.54 (s, 1H), 3.83 (s, 3 H), 2.93 (s, 6 H), 2.32 (s, 3 H); 13C
NMR (150 MHz, CDCl3): δ 158.4, 149.8, 137.4, 137.4,
132.1, 129.8. 129.2.129.1, 128.9, 128.0, 127.3, 126.3, 126.1, 1-(4-(dimethylamino)phenyl)-1-(1-(4-methoxyphenyl)-
125.5, 122.8, 122.7, 121.1, 120.4, 117.4, 114.6, 112.0, 110.5, 1H-indol-3-yl)-1-phenylpropan-2-one (5g):
55.5, 50.0, 40.3, 21.0; ESI-MS calcd. for C32H30N3O
colorless solid, 148.8 mg, 70%; 1H NMR (400 MHz,
CDCl3): δ 7.42-7.35 (m, 4 H), 7.34-7.31 (m, 3 H), 7.26-7.22
(M+H): 472.2389; Found: 472.2388.
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000879
Advanced Synthesis & Catalysis
1
(m, 3 H), 7.18-7.10 (m, 4 H), 7.03 (t, J = 6.6 Hz, 3 H), 7.00
(dd, J = 8.8, 2.0 Hz, 2 H), 6.93 (t, J = 7.8 Hz, 1 H), 6.63 (d,
J = 8.9 Hz, 2 H), 3.85 (s, 3 H), 2.91 (s, 6 H), 2.16 (s, 3 H);
13C NMR (175 MHz, CDCl3): δ 207.1, 158.2, 149.0, 142.8,
Yellow semi-solid, 152.8 mg, 70%; H NMR (400 MHz,
CDCl3): δ 7.42-7.37 (m, 3 H), 7.35-7.27 (m, 6 H), 7.21-7.15
(m, 3 H), 7.05 (t, J = 8.8 Hz, 1 H), 6.97 (dd, J = 6.7, 2.2 Hz,
2 H), 6.57 (d, J = 8.7 Hz, 2 H), 6.53 (s, 1H), 3.83 (s, 3 H),
137.0, 132.5, 130.4, 129.7, 129.6, 129.0, 128.1, 127.8, 127.7, 3.59 (bs, 1 H), 3.58 (t, J = 5.3 Hz, 2 H), 3.56 (s, 3 H), 3.25
126.3, 126.0, 122.2, 122.2, 119.8, 118.2, 114.6, 111.8, 110.0, (t, J = 5.0 Hz, 2 H); 13C NMR (100 MHz, CDCl3): δ 158.4,
66.9, 55.5, 40.3; ESI-MS calcd. for C32H31N2O2 (M+H):
475.2386; Found: 475.2373.
147.8 140.3, 137.5, 132.1, 129.8, 129.3, 129.1, 128.9, 128.5,
128.3, 128.1, 127.8, 126.1, 122.8, 121.0, 120.5, 117.2, 114.7,
112.8, 110.6, 58.7, 55.6, 43.3; ESI-MS calcd. for
C32H30N3O2 (M+H): 488.2338; Found: 488.2337.
2-(1-(4-methoxyphenyl)-1H-indol-3-yl)-2-phenyl-2-(4-
(phenylamino)phenyl)acetonitrile (6a):
2-(4-((2-methoxyethyl)(methyl)amino)phenyl)-2-(1-(4-
methoxyphenyl)-1H-indol-3-yl)-2-phenylacetonitrile
(6f):
colorless solid, 181.1 mg, 80%; 1H NMR (700 MHz,
CDCl3): δ 7.44 (d, J = 7.3 Hz, 2 H), 7.41 (d, J = 8.3 Hz, 1
H), 7.38 (d, J = 8.0 Hz, 1 H), 7.35 (t, J = 7.0 Hz, 2 H), ),
6.33-6.31 (m, 3 H), ), 7.29-7.24 (m, 4 H), 7.21 (t, J = 7.3 Hz,
1 H), 7.09-7.06 (m, 3 H), 7.00 (d, J = 8.5 Hz, 2 H), 6.98 (d,
J = 8.8 Hz, 2 H), 6.94 (t, J = 7.2 Hz, 1 H), 6.56 (s, 1 H), 5.77
(bs, 1 H), 3.84 (s, 3 H); 13C NMR (175 MHz, CDCl3): δ
colorless solid, 193.2 mg, 86%; 1H NMR (400 MHz,
CDCl3): δ 7.43-7.38 (m, 3 H), 7.36-7.29 (m, 6 H), 7.20-7.17
(m, 3 H), 7.06 (t, J = 7.9 Hz, 1 H), 6.97 (d, J = 8.9 Hz, 2 H),
6.65 (d, J = 8.9 Hz, 2 H), 6.55 (s, 1H), 3.83 (s, 3 H), 3.54-
158.5, 143.1, 142.1, 139.9, 137.5, 132.0, 131.3, 129.3, 129.2, 3.47 (m, 4 H), 3.33 (s, 3 H), 2.97 (s, 3 H); 13C NMR (100
129.2, 128.6, 128.1, 127.9, 126.1, 122.9, 122.5, 121.6, 120.9, MHz, CDCl3): δ 158.4, 148.7, 140.4, 137.5, 132.1, 129.3,
120.5, 118.6, 116.8, 116.6, 114.7, 110.6, 55.5, 50.5; ESI-
MS calcd. for C35H27N3NaO (M+Na): 528.2052; Found:
528.2046.
129.0, 128.5, 128.1, 127.8, 126.8, 126.3, 126.2, 122.8, 121.1,
120.5, 117.2, 114.7, 111.7, 110.6, 70.1, 59.0, 55.6, 52.3,
50.3, 38.8; ESI-MS calcd. for C33H31N3NaO2 (M+Na):
524.2314; Found: 524.2311.
2-(1-(4-methoxyphenyl)-1H-indol-3-yl)-2-(4-
(methyl(phenyl)amino)phenyl)-2-phenylacetonitrile
(6b):
2-(4-(bis(2-methoxyethyl)amino)phenyl)-2-(1-(4-
methoxyphenyl)-1H-indol-3-yl)-2-phenylacetonitrile
(6g):
colorless solid, 217.8 mg, 85%; 1H NMR (700 MHz,
CDCl3): δ 7.45 (d, J = 7.7 Hz, 2 H), 7.41-7.38 (m, 2 H), 7.35
(t, J = 7.1 Hz, 2 H), ), 6.33-6.29 (m, 5 H), ), 7.25-7.20 (m, 3
H), 7.12 (d, J = 7.6 Hz, 2 H), 7.08 (t, J = 7.2 Hz, 1 H), 7.06
(t, J = 6.8 Hz, 1 H), 6.99 (d, J = 8.8 Hz, 2 H), 6.87 (d, J =
colorless solid, 200.4 mg, 82%; 1H NMR (600 MHz,
CDCl3): δ 7.44-7.37 (m, 4 H), 7.35-7.28 (m, 5 H), 7.21-7.17
(m, 3 H), 7.06 (td, J = 8.2, 0.9 Hz, 1 H), 6.97 (dd, J = 6.7,
2.2 Hz, 2 H), 6.64 (d, J = 9.0 Hz, 2 H), 6.57 (s, 1H), 3.83 (s,
3 H), 3.54-3.52 (m, 8 H), 3.33 (s, 3 H); 13C NMR (150 MHz,
CDCl3): δ 158.4, 147.7, 140.3, 137.5, 132.1, 129.3, 129.1,
8.8 Hz, 2 H), 6.59 (s, 1 H), 3.85 (s, 3 H), 3.31 (s, 3 H);; 13
C
NMR (175 MHz, CDCl3): δ 158.5, 148.5, 148.3, 140.0,
137.5, 132.0, 130.3, 129.3, 129.2, 128.9, 128.5, 128.1, 126.2, 128.5, 128.1, 127.7, 126.7, 126.2, 122.8, 121.0, 120.4, 117.2,
125.8, 125.5, 123.2, 123.1, 122.8, 121.0, 120.5, 117.2, 116.9, 116.1, 114.7, 111.7, 111.4, 110.6, 70.1, 70.0, 58.9, 55.5,
114.7, 114.7, 110.6, 55.5, 50.5, 40.1; ESI-MS calcd. for
C36H29N3NaO (M+Na): 542.2208; Found: 542.2294.
50.9, 50.8, 50.3; ESI-MS calcd. for C35H35N3NaO3 (M+Na):
568.2576; Found: 568.2584.
2-(4-(butylamino)phenyl)-2-(1-(4-methoxyphenyl)-1H-
indol-3-yl)-2-phenylacetonitrile (6c):
2-(1-(4-methoxyphenyl)-1H-indol-3-yl)-2-(4-
morpholinophenyl)-2-phenylacetonitrile (6h):
1
1
colorless semi-solid, 160.9 mg, 74%; H NMR (400 MHz,
yellow semi-solid, 143.2 mg, 64%; H NMR (600 MHz,
CDCl3): δ 7.43-7.36 (m, 4 H), 7.35-7.26 (m, 5 H), 7.19 (t, J
= 8.1 Hz, 1 H), 7.15 (dd, J = 6.7, 1.8 Hz, 1 H), 7.05 (t, J =
7.1 Hz, 1 H), 6.96 (dd, J = 6.7, 2.0 Hz, 2 H), 6.54-6.52 (m,
3H), 3.83 (s, 3 H), 3.65 (bs, 1 H), 3.07 (t, J = 7.1 Hz, 2 H),
1.61-1.54 (m, 2 H), 1.45-1.35 (m, 2 H), 0.93 (t, J = 7.3 Hz,
3 H); 13C NMR (100 MHz, CDCl3): δ 158.4, 148.1, 140.4,
CDCl3): δ 7.41-7.39 (m, 2 H), 7.36-7.23 (m, 3 H), 7.32-7.27
(m, 6 H), 7.19 (t, J = 7.2 Hz, 1 H), 7.06 (t, J = 7.1 Hz, 1 H),
6.97 (d, J = 8.9 Hz, 2 H), 6.85 (d, J = 8.5 Hz, 2 H), 6.52 (s,
1H), 3.84-3.82 (m, 7 H), 3.15 (t, J = 4.4 Hz, 4 H); 13C NMR
(150 MHz, CDCl3): δ 158.4, 139.9, 137.4, 131.9, 130.5,
129.2, 129.0, 128.5, 128.1, 127.9, 126.1, 122.8, 122.4, 120.9,
137.5, 132.1, 129.3, 129.1, 128.5, 128.2, 127.8, 126.3, 126.1, 12.5, 116.8, 115.0, 114.6, 110.6, 67.7, 55.5, 50.4, 48.7; ESI-
122.8, 122.1, 120.5, 117.3, 114.7, 112.3, 110.6, 55.6, 50.4,
43.5, 31.6, 20.2, 13.9; ESI-MS calcd. for C33H32N3O
(M+H): 486.2545; Found: 486.2545.
MS calcd. for C33H30N3O2 (M+H): 500.2338; Found:
500.2345.
2-(4-((4-methoxybenzyl)amino)phenyl)-2-(1-(4-
methoxyphenyl)-1H-indol-3-yl)-2-phenylacetonitrile
(4m):
2-(4-(butyl(methyl)amino)phenyl)-2-(1-(4-
methoxyphenyl)-1H-indol-3-yl)-2-phenylacetonitrile
(6d):
colorless solid, 160.0 mg, 65%; 1H NMR (600 MHz,
CDCl3): δ 7.42-7.40 (m, 2 H), 7.38-7.35 (m, 2 H), 7.33-7.29
(m, 5 H), 7.25 (d, J = 8.5 Hz, 2 H), 7.20-7.15 (m, 3 H), 7.06
(d, J = 7.8 Hz, 1 H), 6.97 (d, J = 8.8 Hz, 2 H), 6.86 (d, J =
8.5 Hz, 2 H), 6.57 (d, J = 8.7 Hz, 2 H), 6.54 (s, 1H), 4.21 (s,
2 H), 4.03 (bs, 1 H) 3.83 (s, 3 H), 3.78 (s, 3 H); 13C NMR
(150 MHz, CDCl3): δ 158.9, 158.4, 147.7, 140.2, 137.5,
132.0, 130.9, 129.2, 129.1, 128.8, 128.5, 128.2, 128.1, 127.8,
1
colorless semi-solid, 183.5 mg, 82%; H NMR (600 MHz,
CDCl3): δ 7.43-7.42 (m, 2 H), 7.40-7.36 (m, 2 H), 7.34-7.27
(m, 6 H), 7.18 (d, J = 8.8 Hz, 2 H), 7.05 (t, J = 7.2 Hz, 1 H),
6.96 (d, J = 8.8 Hz, 2 H), 6.66 (d, J = 8.8 Hz, 2 H), 6.56 (s,
1H), 3.38 (s, 3 H), 3.26 (t, J = 7.6 Hz, 2 H), 2.90 (s, 3 H),
1.54-1.50 (m, 2 H), 1.34-1.28 (m, 2 H), 0.91 (t, J = 7.3 Hz,
3 H); 13C NMR (150 MHz, CDCl3): δ 158.4, 148.7, 140.4,
137.4, 132.1, 129.6, 129.2, 128.9, 128.4, 128.1, 127.7, 126.1, 126.2, 126.1, 122.8, 122.7, 121.0, 120.4, 117.1, 114.6, 114.0,
125.8, 125.4, 122.7, 121.0, 120.4, 117.3, 114.7, 114.6, 111.5, 112.5, 110.6, 55.5, 55.2, 50.4, 47.7; ESI-MS calcd. for
110.5, 55.5, 52.4, 50.3, 38.1, 28.8, 13.9; ESI-MS calcd. for
C34H34N3O (M+H): 500.2702; Found: 500.2701.
C37H31N3NaO2 (M+Na): 572.2314; Found: 572.2394.
2-(4-aminophenyl)-2-(1-(4-methoxyphenyl)-1H-indol-3-
yl)-2-phenylacetonitrile (4n):
2-(4-((2-methoxyethyl)amino)phenyl)-2-(1-(4-
methoxyphenyl)-1H-indol-3-yl)-2-phenylacetonitrile
(6e):
colorless solid, 68.7 mg, 88%; 1H NMR (400 MHz, CDCl3):
δ 7.42-7.39 (m, 3 H), 7.37-7.33 (m, 2 H), 7.31-7.29 (m, 4
H), 7.19 (t, J = 7.2 Hz, 1 H), 7.15 (dd, J = 6.6, 1.9 Hz, 2 H),
8
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10.1002/adsc.202000879
Advanced Synthesis & Catalysis
7.06 (t, J = 7.1 Hz, 1 H), 6.96 (dd, J = 6.8, 2.0 Hz, 2 H), 6.62
(dd, J = 6.6, 1.9 Hz, 2 H), 6.53 (s, 1H), 3.71 (bs, 2 H); 13C
NMR (150 MHz, CDCl3): δ 158.4, 146.0, 140.1, 137.5,
132.0, 129.4, 129.3, 129.2, 128.5, 128.1, 127.8, 126.2, 126.1,
122.8, 122.6, 121.0, 120.5, 117.0, 114.9, .114.6, 110.6, 55.5,
50.4; ESI-MS calcd. for C29H23N3NaO (M+Na): 452.1739;
Found: 452.1747.
McKervy, M. A.; Ye, T. Modern Catalytic Method for
Organic Synthesis with Diazo compounds: From
Cyclopropanes to Ylides; Wiley; New York USA, 1998;
c) H. M. L. Davies, R. E. J. Beckwith, Chem. Rev., 2003,
103, 2861-2904; d) L. Liu, J. Zhang, Chem. Soc. Rev.,
2016, 45, 506-516; e) M. R. Fructos, M. M. Díaz-
Requejo, P. J. Pérez, Chem. Commun. 2016, 52, 7326-
7335.
2-(4-iodophenyl)-2-(1-(4-methoxyphenyl)-1H-indol-3-
yl)-2-phenylacetonitrile (4o):
[2] For gold carbenes derived from diazo precursors, see
selected papers: a) M. R. Fructos, T. R. Belderrain, P. de
Fremont, N. M. Scott, S. P. Nolan, M. M. Requejo, P. J.
Perez, Angew. Chem., Int. Ed., 2005, 44, 5284-5288; b)
G. Xu, C. Zhu, W. Gu, J. Li, J. Sun, Angew. Chem., Int.
Ed., 2015, 54, 883-887; c) J. Barluenga, G. Lonzi, M.
Tomas, L. A. Lopez, Chem. Eur. J., 2013, 19, 1573-
1576; d) J. F. Briones, H. M. L. Davies, J. Am. Chem.
Soc., 2012, 134, 1191611919; e) V. V. Pagar, A. M.
Jadhav, R.-S. Liu, J. Am. Chem. Soc., 2011, 133, 20728-
20731; f) A. M. Jadhav, V. V. Pagar, R.-S. Liu, Angew.
Chem., Int. Ed., 2012, 51, 11809-11813; g) V. V. Pagar,
R.-S. Liu, Angew. Chem., Int. Ed., 2015, 54, 4923-4926.
h) L. N. S. Comprido, J. E. M. N. Klein, G. Knizia, J.
Kastner, A. S. K. Hashmi, Angew. Chem. Int. Ed., 2015,
54,10336 –10340. i) L. N. S. Comprido, J. E. M. N.
Klein, G. Knizia, J. Kastner, A. S. K. Hashmi, Chem.
Eur. J., 2016, 22, 2892 –2895.
colorless solid, 115.7 mg, 92%; 1H NMR (400 MHz,
CDCl3): δ 7.67 (dd, J = 6.6, 1.9 Hz, 2 H), 7.41-3.36 (m, 3
H), 7.36-7.32 (m, 3 H), 7.29 (d, J = 8.8 Hz, 2 H), 7.24-7.19
(m, 1 H), 7.15 (dd, J = 6.6, 1.9 Hz, 2 H), 7.08 (td, J = 7.1,
0.9 Hz, 1 H), 6.97 (dd, J = 6.7, 2.3 Hz, 2 H), 6.49 (s, 1H),
3.83 (s, 3 H); 13C NMR (150 MHz, CDCl3): δ 158.6, 139.5,
139.0, 137.8, 137.6, 131.8, 130.1, 129.3, 128.8, 128.6, 128.3,
128.0, 126.2. 125.9, 123.1, 121.8, 120.7, 115.8, 114.7, 110.8,
94.1, 55.6, 50.9; ESI-MS calcd. for C29H21IN2NaO (M+Na):
563.0596; Found: 563.0596.
2-(4-bromophenyl)-2-(1-(4-methoxyphenyl)-1H-indol-3-
yl)-2-phenylacetonitrile (4q):
1
colorless semi-solid, 91.8 mg, 80%; H NMR (600 MHz,
CDCl3): δ 7.67 (d, J = 8.6 Hz, 2 H), 7.42-7.38 (m, 3 H),
7.36-7.32 (m, 4 H), 7.31-7.29 (m, 2 H), 7.20 (t, J = 7.3 Hz,
1 H), 7.16 (d, J = 8.6 Hz, 2 H), 7.08 (t, J = 8.0 Hz, 1 H), 6.97
(m, 2 H), 6.51 (s, 1H), 3.84 (s, 3 H); 13C NMR (150 MHz,
CDCl3): δ 158.6, 139.6, 139.0, 137.8, 137.6, 130.1, 129.3,
128.8, 128.6, 128.3, 128.2, 128.0, 126.2, 125.9, 123.1, 121.8,
120.9, 120.7, 114.7, 110.8, 94.0, 55.5, 50.9; EI-MS calcd.
for C29H21BrN2O (M+): 492.0837; Found: 492.0842.
[3] For Au see: a) Z. Yu, B. Ma, M. Chen, H.-H. Wu, L. Liu,
J. Zhang, J. Am. Chem. Soc., 2014, 136, 6904-6907; b)
Y. Xi, Y. Su, Z. Yu, B. Dong, E. J. McClain, Y. Lan, X.
Shi, Angew. Chem., Int. Ed., 2014, 53, 9817-9821; c) E.
López, G. Lonzi, L. A. López, Organometallics,
2014, 33, 5924-5927; d) I. Rivilla, B. P. Gõmez-
Emeterio, M. R. Fructos, M. M. Díaz-Requejo, P. J.
Pérez, Organometallics, 2011, 30, 2855-2860.
2-(1-(4-methoxyphenyl)-1H-indol-3-yl)-2,2-
diphenylacetonitrile (4p):
colorless liquid, 55.0 mg, 57%; 1H NMR (600 MHz,
CDCl3): δ 7.42-7.39 (m, 5 H), 7.36-7.31 (m, 7 H), 7.29 (dd,
J = 6.6, 2.1 Hz, 2 H), 7.20 (t, J = 8.1 Hz, 1 H), 7.06 (td, J =
8.0, 0.7 Hz, 1 H), 6.97 (dd, J = 6.7, 2.1 Hz, 2 H), 6.50 (s,
1H), 3.83 (s, 3 H); 13C NMR (150 MHz, CDCl3): δ 158.5,
139.6, 137.5, 131.9, 129.3, 128.6, 128.2, 128.0, 126.2, 122.9,
122.3, 120.9, 120.6, 116.5, 114.7, 110.7, 55.5, 51.2; ESI-
MS calcd. for C29H22N2NaO (M+Na): 437.1630; Found:
437.1625.
[4] For Rh, Cu, Ag, Pd: see: a) M. P. Doyle, R.
Duffy, M. Ratnikov,
L.
Zhou, Chem.
Rev., 2010, 110, 704-724; b) H. M. L. Davies, Y.-J.
Lian, Acc. Chem. Res. 2012, 45, 923-935; c) H. M. L.
Davies, D. Mo-rton, Chem. Soc. Rev. 2011, 40, 1857-
1869; d) M. M. Díaz-Requejo, P. J. Pérez, Chem.
Rev. 2008, 108, 3379-3394; e) Z. Liu, J. Wang, J. Org.
Chem. 2013, 78, 10024-10030; f) A. DeAngelis, V. W.
2-(4-(bis(2-methoxyethyl)amino)phenyl)-2-(4-
(dimethylamino)phenyl)-2-phenylacetonitrile (7b):
colorless liquid, 230.6 mg, 63%; 1H NMR (600 MHz,
CDCl3): δ 7.31-7.23 (m, 5 H), 7.03 (dd, J = 6.8, 2.2 Hz, 2
H), 6.98 (dd, J = 6.8, 2.1 Hz, 2 H), 6.63 (dd, J = 6.8, 2.2 Hz,
2 H), 6.61 (dd, J = 6.8, 2.1 Hz, 2 H), 3.53-3.50 (m, 8 H),
3.33 (s, 6 H), 2.93 (s, 6 H); 13C NMR (150 MHz, CDCl3): δ
149.7, 147.2, 141.6, 129.7, 129.4, 128.6, 128.3, 128.2, 127.9,
127.5, 124.2, 111.9, 111.3, 70.0, 58.9, 55.8. 50.8, 40.3; ESI-
MS calcd. for C28H34N3O2 (M+H): 444.2651, found:
444.2655.
Shurtleff, O. Dmitrenko, J. M. Fox, J.
Am.
Chem.Soc. 2011, 133, 1650-1653; g) M. J. Rosenfeld, B.
K. Shankar, H. Shechter, J. Org. Chem. 1988, 53, 2699-
2705; h) D. Yadagiri, P. Anbarasan, Org. Lett. 2014, 16,
2510-2513; i) W.-W. Chan, S.-F. Lo, Z. Zhou, W.-
Y. Yu, J. Am. Chem. Soc. 2012, 134, 13565-13568; j) T.
K. Hyster, K. E. Ruhl, T. Rovis, J. Am. Chem.
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Acknowledgements
[5] For Cu: see: a) T. C. Maier, G. C. Fu, J. Am. Chem.
Soc. 2006, 128, 4594-4595; b) C. Chen, S.-F. Zhu, B.
Liu, L.-X. Wang, Q.-L. Zhou, J. Am. Chem. Soc.
2007, 129, 12616-12617; For Pd see: c) X.-L. Xie, S.-F.
Zhu, J.-X. Guo, Y. Cai, Q.-L. Zhou, Angew. Chem. Int.
Ed., 2014, 53, 2978-2981.
We thank the Ministry of Education (MOE 106N506CE1) and the
Ministry of Science and Technology (MOST 107- 3017-F-007-002),
Taiwan, for financial support of this work.
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10.1002/adsc.202000879
Advanced Synthesis & Catalysis
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10
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Advanced Synthesis & Catalysis
FULL PAPER
Gold-catalyzed Oxidative Cross-coupling Reactions
Among Two Distinct Arenes and One Gold Carbene
with Phosphoric Acids as Cocatalysts
Adv. Synth. Catal. Year, Volume, Page – Page
M. D. Patil, B. S. Kale and R.-S. Liu*
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