Synthesis of polysubstituted pyrroles via Pd-catalyzed oxidative alkene C-H bond arylation and amination

Article abstract of DOI:10.1021/jo502414w

A novel Pd(II)-catalyzed oxidative approach to construct polysubstituted pyrroles from N-homoallylicamines and arylboronic acids was developed. This transformation is supposed to proceed through cascade formation of C-C and C-N bonds via oxidative arylation of unactive alkenes, followed by intramolecular aza-Wacker cyclization.

Full text of DOI:10.1021/jo502414w

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Note
Synthesis of Polysubstituted Pyrroles via Pd-Catalyzed
Oxidative Alkene C–H Bond Arylation and Amination
Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 23 Dec 2014
Downloaded from http://pubs.acs.org on December 24, 2014
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Synthesis of Polysubstituted Pyrroles via Pd-Catalyzed
Oxidative Alkene C–H Bond Arylation and Amination
Journal: The Journal of Organic Chemistry
Manuscript ID: jo-2014-02414w.R1
Manuscript Type: Note
Date Submitted by the Author: 16-Dec-2014
Complete List of Authors: Zheng, Jia; South China University of Technology, School of Chemistry &
Chemical Engineering
Huang, Liangbin; South China University of Technology, School of
Chemistry and Chemical Engineering
Huang, Chuyu; South China University of Technology, School of Chemistry
& Chemical Engineering
Wu, Wanqing; South China University of Technology, School of Chemistry
& Chemical Engineering
Jiang, Huanfeng; South China University of Technology, School of
Chemistry & Chemical Engineering
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Synthesis of Polysubstituted Pyrroles via PdꢀCatalyzed Oxidative
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Alkene C–H Bond Arylation and Amination
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Jia Zheng, Liangbin Huang, Chuyu Huang, Wanqing Wu and Huanfeng Jiang*
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*
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China
jianghf@scut.edu.cn
R3
PdCl2 (10 mol %)
R3
H
Cu(OAc)2 (3 equiv)
R2
N
Ar
ArB(OH)2
N
Et3N (2 equiv)
R2
CH3CN, 80 o
C
R1
R1
24 examples
up to 88% yield
Abstract: A novel Pd(II)ꢀcatalyzed oxidative approach to construct polysubstituted
pyrroles from Nꢀhomoallylicamines and arylboronic acids was developed. This
transformation is supposed to proceed through cascade formation of C–C and C–N
bonds via oxidative arylation of unactive alkenes, followed by intramolecular
azaꢀWacker cyclization.
Transition metalꢀcatalyzed oxidative coupling reactions have emerged as one of the
most powerful tools for the efficient construction of C–
C and Cꢀheteroatom bonds.1, 2
Among them, the Pdꢀcatalyzed oxidative Heck reactions have drawn increasing
attention of synthetic chemists due to the easy accessibility of starting materials such
as arylboronic acids, alkenes and the utility of various products.2 In 1975, Richard F.
Heck reported the first example of oxidative Heck reaction of organoboron reagents
with alkenes bearing an electronꢀwithdrawing group.3 Subsequently, the groups of
Larhed, Gaunt, Sigman, Hou et al. reported various carbon nucleophile−metal species
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can undergo oxidative coupling with activated alkenes, such as styrenes, 1,3ꢀdienes,
strained cyclic olefins.4ꢀ6 However, there are only limited examples about the
oxidative Heck reactions with corresponding nonactivated olefins.7, 8, 9 Two strategies
are usually employed to increase the propensity of coordination of nonactivated
olefins to Pd center and induce reactivity, thus removing the requirement of activated
olefins for oxidative Heck reactions. One pathway is utilizing ligands to adjust the
steric and electronic property of metal catalysts.8 The other pathway is incorporating a
functional group to nonactivated olefin, such as OH, NHBoc etc., which can
coordinate to the Pd center (Scheme 1).9 Lei and Sigman recently reported
respectively an oxidative Heck reaction between arylboronic acids and allylic alcohols
to afford aryl ketones and aldehydes through selective βꢀH elimination.9a, 9b In 2011,
Zhu et al. found that arylated homoallylic alcohols were obtained via a hydroxyl
group assisted Pdꢀcatalyzed oxidative Heck reactions of boronic acids with
homoallylic alcohols.9c A corresponding oxidative arylation of protectedꢀallylamines
was reported by Xu and coꢀworkers in 2013.9d The group of Larhed reported a
Heck/Suzuki domino diarylation reaction by using chelating vinyl ethers.9e Herein, we
report an oxidative cascade reaction which was initiated by the Pdꢀcatalyzed oxidative
Heck reactions with homoallylic amines and phenylboronic acids, followed by the
oxidative amination processes.
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Scheme 1. Pdꢀcatalyzed oxidative coupling between Nꢀhomoallylic amines and
aromatic boronic acids
Pyrrole skeleton frequently occurs in naturally and synthetically bioactive
products as well as topꢀsold marketing medicines.10 For examples, COXꢀ2 isoenzyme
inhibitors, Zomepirac and Fludioxonil are used extensively in pharmaceuticals (Figure
1). Therefore, the development of efficient methods to access these privileged
molecules is of significant importance.11 As our persistent attention on Pdꢀcatalyzed
oxidative functionalization of electronically unbiased alkyl olefins,12 various
polysubstituted pyrroles were synthesized in good to excellent yields from easily
prepared homoallylic amines and commercially available arylboronic acids in oneꢀpot
transformations, using Pd(II) catalyst system.
Figure 1. Examples of bioactive pyrroles
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Initially, using PdCl2 as the catalyst, Nꢀ(butꢀ3ꢀenꢀ1ꢀyl)ꢀ4ꢀmethylaniline (1a) and
phenylboronic acid (2a) were selected as model substrates to optimize the reaction
conditions. As show in Table 1, decomposition was observed when CuCl2, DDQ or
BQ were used, only Cu(OAc)2 gave 33% yield (Table 1, entries 1ꢀ4). As for the
selection of solvent, no desired product was detected when DMSO, DMF was selected
as the solvent. Toluene and 1,4ꢀdioxane gave relatively lower yields than that of
CH3CN (Table 1, entries 5ꢀ8). Further investigation showed that Et3N was the best
additives in comparison with tꢀBuOLi, PivOH, HOAc, DABCO and DBU (Table 1,
entries 9ꢀ17). Compared with Pd(OAc)2 and Pd(TFA)2, PdCl2 exhibited better
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o
reactivity (Table 1, entries 18ꢀ19). When this reaction proceeded at 50 C, only 42%
of product was obtained (Table 1, entry 20). Thus, the standard conditions were
obtained as PdCl2 (10 mol %), Cu(OAc)2 (3 equiv), Et3N (2 equiv), in CH3CN at
80 °C.
Table 1. Optimization of reaction conditionsa
entry
1
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7
8
catalyst
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
oxidant
Cu(OAc)2
CuCl2
additive
solvent
CH3CN
CH3CN
CH3CN
CH3CN
DMSO
yield (%)b
33
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
N.D.
N.D.
N.D.
N.D.
18
12
21
44
39
DDQ
BQ
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
DMF
toluene
1,4ꢀdioxane
CH3CN
CH3CN
CH3CN
ꢀ
9
10
11
tꢀBuOLi
PivOH
HOAc
N.D.
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PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Et3N
DBU
Pyridine
DABCO
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
80 (76) c
N.D.
N.D.
72
Cu(OAc)2 NꢀMethylm
N.D.
orpholine
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PdCl2
Pd(OAc)2 Cu(OAc)2
Pd(TFA)2 Cu(OAc)2
Cu(OAc)2
Bu3N
Et3N
Et3N
Et3N
CH3CN
CH3CN
CH3CN
CH3CN
69
67
44
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19
20d
PdCl2
Cu(OAc)2
a Reaction conditions: 1a (0.1 mmol), 2a (0.15 mmol), catalyst (10 mol %), oxidant (3 equiv) and
additive (2 equiv) in 1 mL of solvent under at 80 oC for 12 h. b Determined by GC. c Isolated yield.
d at 50 oC.
The scope of this reaction was explored as the optimized conditions identified. A
range of substituted phenylboronic acids were initially surveyed (Table 2). Both
electronꢀdonating and ꢀwithdrawing groups were tolerated in this cascade reaction. A
variety of paraꢀsubstituted functional groups, such as alkyl, phenyl, halogen and ester
were compatible to obtain desired pyrroles 3ab−3ag in moderate to good yields. The
metaꢀ and paraꢀsubstituted substrates led to good yields of the corresponding products
(3ah, 3ai). The naphthylboronic acid also proceeded smoothly with 1a to afford 88%
yield of product 3aj. In addition, disubstituted phenylboronic acid could be employed
as substrate to give moderate yield of the corresponding product (3ak). Unfortunately,
orthoꢀhalogen phenylboronic acids gave no desired product in this transformation
(3al).
Table 2. Substrate scope of phenylboronic acids a,b
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a
Reaction conditions: 1a (0.1 mmol), 2 (0.15 mmol), PdCl2 (10 mol %), Et3N (2 equiv) and
Cu(OAc)2 (3 equiv) in 1 mL CH3CN at 80 C for 12 h. b Isolated yield. c The reaction was stirred
o
for 24 h
.
In view of the forementioned results, we turned our attention to the scope of
substituted homoallylic amines. Overall, the desired products were generated in
moderate to good yields for various substituted homoallylic amines. When R1 equaled
to H, 67% yield of product 3ba was obtained. Functional groups such as OMe, F, Cl
and Br on the aryl ring were also tolerated in this transformation and gave pyrrole
derivatives in 59−79% yields (3ca−3fa). Yield remained good when R1 switched from
paraꢀposition to metaꢀposition (3ga). However, when R1 was orthoꢀsubstituent, only
trace of desired product could be detected (3ha). For the component with
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disubstitutents on the aryl ring, the reactions proceeded well to generate 3ia in 80%
yield. To our delight, substrates bearing different R2, including alkyl, alkyl ester,
phenyl, naphthyl, all allowed the formation of corresponding products (3ja−3na). In
addition, a slightly lower yield was observed when R3 was phenyl group (3oa). When
4ꢀmethylꢀNꢀ(4ꢀmethylpentꢀ4ꢀenꢀ2ꢀyl)aniline (1p) was used as the substrate, no
reaction occurred. Only trace amount of product was obtained when Nꢀphenyl was
changed to Nꢀbenzyl group (3qa), which suggested that Nꢀphenyl was crucial to this
transformation.
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Table 3. Substrate scope of Nꢀhomoallyliamines.a,b
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R4
Ph
R1
R3
PdCl2 (10 mol %)
R3
H
Cu(OAc)2 (3 equiv)
R2
N
PhB(OH)2
N
Et3N (2 equiv)
CH3CN, 80 o
R2 R4
C
R1
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2a
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N
N
N
N
F
Cl
O
3da,e
60%
3ea e
3ba e
3ca
,
62%
N
, 79%
,
67%
N
N
N
Br
3ia,c
3ga d
3fa e
80%
3ha
, trace
,
77%
,
59%
Cl
COOMe
N
N
N
N
3ka c
3la,
75%
3ma
, 78%
,
60%
3ja
, 81%
N
N
N
N
3oa c
3qa
, trace
3pa,
N.R.
3na
, 69%
,
53%
a
Reaction conditions: 1a (0.1 mmol), 2 (0.15 mmol), PdCl2 (10 mol %), Et3N (2 equiv) and
Cu(OAc)2 (3 equiv) in 1 mL CH3CN at 80 C for 12 h. b Isolated yield. c The reaction was stirred
o
for 24 h. d The reaction was stirred for 36 h. e The reaction was stirred for 48 h.
Both oxidative arylation and aminopalladation start with palladium(II) catalyst,
which means they might be competitive in one process. To gain further insight into
the mechanistic information, we carried out several experiments under the standard
conditions. The transformation still proceeded well to construct pyrroles when we
only used homoallylic amines as the substrates. As show in Scheme 2, 4a and 4b were
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obtained in 75% and 64% yields, respectively (Eq 1). In addition, no desired product
was afforded between 4a and phenylboronic acid under the standard conditions (Eq 2).
Then we shorten the time of the reaction between 1g and 2a from 36 h to 12 h and
successfully isolated intermediate 5 (Eq 3), which indicated that the oxidative Heck
reaction occurred first, followed by the intramolecular aminopalladation.
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Scheme 2. Control experiments
On the basis of the above information and previous reports9, a putative reaction
pathway for this transformation is shown in Scheme 3. Arylpalladium(II) species was
first formed by transmetalation of arylboronic acid, followed by migratory insertion of
the olefin and βꢀhydride elimination to produce intermediate B. Then, intramolecular
aminopalladation gave palladium(II)ꢀalkyl complex C, and subsequently a second
βꢀhydride elimination generated intermediate 5. Finally, oxidative dehydrogenation
afforded the desired product 3. The Pd(0) species obtained in two βꢀhydride
elimination process was oxidized by Cu(OAc)2 to regenerate the Pd(II) species.
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Ar1
HN
R2
R1
PdII
Ar2
R2
R2
R1
R1
PdII
Ar1
Ar2
Ar2
R1
R1
Ar1
N
Ar2
H
R2
NH
N
Ar1
C
N
Ar1
5
R2
1
6
B
A
7
8
Ar2PdII
Pd0
[O]
9
3
PdII
Pd0
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[O]
Ar2B(OH)2
PdII
2
[O]
Scheme 3. Proposed mechanism
In summary, we have elaborated the Pd(II)ꢀcatalyzed oxidative arylative
cyclization of Nꢀhomoallylic amines. Four hydrogen atoms were removed to forge
C–N and C–C bonds in this protocol via sequential unreactive alkene oxidative
arylation and intramolecular azaꢀWackerꢀtype cyclization. The present reaction
allowed simple conversion of accessible starting materials to various polysubstituted
pyrroles.
Experimental Section
General method. H and 13C NMR spectra were recorded on a 400 MHz spectrometer using
1
CDCl3 as solvent and TMS as an internal standard. Mass spectra were obtained with gas
chromatography mass spectrometer. IR spectra were obtained either as potassium bromide pellets
or as liquid films between two potassium bromide pellets with a spectrometer. GCꢀMS was
obtained using electron ionization. HRMS was obtained with a LCMSꢀITꢀTOF mass spectrometer.
General procedure for synthesis of homoallylic amines 1aꢀ1i 13a
Arylamine (1.2 mmol) and K2CO3 (2 mmol) were added to 3 mL DMF. The mixture was slowly
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added allyl bromide (1 mmol) and stirred at 80 C overnight. After that, water was added and the
mixture was extracted with ethyl acetate. The combined organic layer was dried over Na2SO4,
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filtered, concentrated and eventually purified by column chromatography on a silica gel to give
1aꢀ1i with petroleum ether/ethyl acetate as the eluent.
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General procedure for synthesis of homoallylic amines 1j, 1k, 1o, 1p 13b
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A suspension of indium (2 mmol) and allyl bromide (3 mmol) in THF (2 mL) was stirred at room
temperature under N2 for 1 h. Then the reaction mixture was added aniline (1 mmol) and ethyl
vinyl ether (2 mmol) and stirried for another 2 h. The solution was quenched by saturated aqueous
NH4Cl (5 mL) and extracted with ethyl acetate. The organic layer was washed with water, dried
over Na2SO4, filtered and concentrated. The residue was separated by column chromatography on
a silica gel to afford the corresponding homoallylic amines with petroleum ether/ethyl acetate as
the eluent.
General procedure for synthesis of homoallylic amines 1lꢀ1n, 1q13c
A suspension of allylmagnesium bromide (1.0 M in THF, 1.0 mL, 1.3 mmol) and ZnCl2 (0.1 mmol)
was stirred at room temperature under N2 for 1 h. Then, The mixture was added imine (1 mmol)
and stirred at room temperature for 2 h. The solution was quenched by saturated aqueous NH4Cl
(5 mL) and extracted with ethyl acetate. The organic layer was washed with water, dried over
Na2SO4, filtered and concentrated. The residue was further purified by column chromatography on
a silica gel to give corresponding compounds with petroleum ether/ethyl acetate as the eluent.
General procedure for synthesis of pyrrole derivatives: Homoallylic amine (0.1 mmol),
arylboronic acid (0.15 mmol), PdCl2 (10 mol %), Cu(OAc)2 (3 equiv) and Et3N (2 equiv) were
o
added to 1 mL CH3CN. The mixture was stirred under air at 80 C for the desired reaction time.
After that, water was added and extracted with ethyl acetate twice. The combined organic phase
was dried over Na2SO4 and concentrated. The residue was eventually purified by flash column
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chromatography on a silica gel to afford the product with petroleum ether/ethyl acetate as the
eluent.
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Nꢀ(Butꢀ3ꢀenꢀ1ꢀyl)ꢀ4ꢀmethylaniline (1a)
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1H NMR (400 MHz, CDCl3) δ = 7.05 (d, J = 7.9 Hz, 2H), 6.60 (d, J = 7.9 Hz, 2H), 5.97 – 5.78 (m, 1H),
5.18 (t, J = 14.0 Hz, 2H), 3.84(s, 1H), 3.22 (t, J = 6.6 Hz, 2H), 2.43 (dd, J = 13.4, 6.7 Hz, 2H), 2.30 (s,
3H). 13C NMR (101 MHz, CDCl3) δ = 146.1, 135.9, 129.8, 126.6, 117.0, 113.2, 43.3, 33.7, 20.4 ppm.
MS (EI, 70 eV) m/z: 91, 120, 261. HRMS (ESI) m/z: calcd for C11H16N [M+H]+, 162.1277; found,
162.1278. IR (KBr): 3407, 2919, 2861, 1616, 1519, 1479, 1323, 808 cmꢀ1.
Nꢀ(Butꢀ3ꢀenꢀ1ꢀyl)aniline (1b)
1H NMR (400 MHz, CDCl3) δ = 7.22 (t, J = 7.2 Hz, 2H), 6.75 (t, J = 7.3 Hz, 1H), 6.66 (d, J = 7.8 Hz,
2H), 5.88 (td, J = 16.5, 7.3 Hz, 1H), 5.18 (t, J = 14.3 Hz, 2H), 3.70 (s, 1H), 3.23 (t, J = 6.6 Hz, 2H),
2.43 (q, J = 6.5 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ = 148.3, 135.8, 129.2, 117.4, 117.1, 112.9,
42.9, 33.7 ppm. MS (EI, 70 eV) m/z: 77, 106, 147. HRMS (ESI) m/z: calcd for C10H14N [M+H]+,
148.1121; found, 148.1121. IR (KBr): 3411, 3079, 2926, 2833, 1732, 1600, 1510, 1434, 1321, 918
cmꢀ1.
Nꢀ(Butꢀ3ꢀenꢀ1ꢀyl)ꢀ4ꢀmethoxyaniline (1c)
1H NMR (400 MHz, CDCl3) δ = 6.77 (d, J = 7.9 Hz, 2H), 6.58 (d, J = 7.7 Hz, 2H), 5.99 – 5.66 (m, 1H),
5.11 (t, J = 13.6 Hz, 2H), 3.71 (d, J = 15.8 Hz, 3H), 3.15 (dd, J = 19.2, 12.6 Hz, 2H), 2.36 (q, J = 6.5
Hz, 2H). 13C NMR (101 MHz, CDCl3) δ = 152.2, 142.7, 135.9, 117.0, 114.9, 114.3, 55.8, 43.9, 33.7
ppm. MS (EI, 70 eV) m/z: 108, 121, 136, 177. HRMS (ESI) m/z: calcd for C11H16NO [M+H]+,
178.1226; found, 178.1226. IR (KBr): 3392, 2929, 2830, 1513, 1468, 1237, 819 cmꢀ1.
Nꢀ(Butꢀ3ꢀenꢀ1ꢀyl)ꢀ4ꢀfluoroaniline (1d)
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1H NMR (400 MHz, CDCl3) δ = 6.93 (t, J = 8.0 Hz, 2H), 6.58 (dd, J = 6.9, 4.4 Hz, 2H), 5.97 – 5.78 (m,
1H), 5.18 (t, J = 12.4 Hz, 2H), 3.49 (s, 1H), 3.18 (t, J = 6.5 Hz, 2H), 2.41 (q, J = 6.5 Hz, 2H). 13C NMR
(101 MHz, CDCl3) δ = 155.9 (d, J = 233.0 Hz), 144.7, 135.7, 117.2, 115.6 (d, J = 18.0 Hz), 113.73 (d,
J = 7.4 Hz, 15H), 43.5, 33.6. ppm. MS (EI, 70 eV) m/z: 75, 95, 124, 165. HRMS (ESI) m/z: calcd for
C10H13FN [M+H]+, 166.1027; found, 166.1025. IR (KBr): 3409, 3079, 2928, 2852, 1612, 1514, 1317,
1219, 820 cmꢀ1.
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Nꢀ(Butꢀ3ꢀenꢀ1ꢀyl)ꢀ4ꢀchloroaniline (1e)
1H NMR (400 MHz, CDCl3) δ = 7.15 (d, J = 8.2 Hz, 2H), 6.56 (d, J = 7.8 Hz, 2H), 5.85 (td, J = 16.8,
7.1 Hz, 1H), 5.24 – 5.07 (m, 2H), 3.69 (s, 1H), 3.18 (t, J = 6.5 Hz, 2H), 2.41 (q, J = 6.5 Hz, 2H). 13C
NMR (101 MHz, CDCl3) δ = 146.8, 135.5, 129.0, 121.9, 117.3, 113.9, 42.9, 33.5 ppm. MS (EI, 70 eV)
m/z: 77, 105, 140, 181. HRMS (ESI) m/z: calcd for C10H13ClN [M+H]+, 182.0731; found, 182.0729. IR
(KBr): 3412, 3078, 2925, 2851, 1601, 1503, 1318, 815 cmꢀ1.
4ꢀBromoꢀNꢀ(butꢀ3ꢀenꢀ1ꢀyl)aniline (1f)
1H NMR (400 MHz, CDCl3) δ = 7.28 (d, J = 7.7 Hz, 2H), 6.51 (d, J = 7.8 Hz, 2H), 5.85 (td, J = 16.8,
7.2 Hz, 1H), 5.26 – 5.09 (m, 2H), 3.69 (s, 1H), 3.18 (t, J = 6.5 Hz, 2H), 2.41 (q, J = 6.6 Hz, 2H). 13C
NMR (101 MHz, CDCl3) δ = 147.3, 135.5, 131.9, 117.3, 114.4, 108.9, 42.8, 33.5 ppm. MS (EI, 70 eV)
m/z: 91, 118, 132, 160, 192, 233. HRMS (ESI) m/z: calcd for C10H13BrN [M+H]+, 226.0226; found,
226.0226. IR (KBr): 3411, 3076, 2925, 2849, 1595, 1502, 1320, 812 cmꢀ1.
Nꢀ(Butꢀ3ꢀenꢀ1ꢀyl)ꢀ3ꢀmethylaniline (1g)
1H NMR (400 MHz, CDCl3) δ = 7.15 (t, J = 7.3 Hz, 1H), 6.62 (d, J = 7.0 Hz, 1H), 6.51 (d, J = 7.7 Hz,
2H), 5.91 (td, J = 16.2, 7.3 Hz, 1H), 5.21 (t, J = 14.5 Hz, 2H), 3.61 (s, 1H), 3.25 (t, J = 6.6 Hz, 2H),
2.44 (dd, J = 13.6, 7.7 Hz, 2H), 2.35 (d, J = 14.7 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ =148.4,
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139.0, 135.9, 129.2, 118.4, 117.0, 113.8, 110.1, 42.9, 33.7, 21.7 ppm. MS (EI, 70 eV) m/z: 91, 120, 261.
HRMS (ESI) m/z: calcd for C11H16N [M+H]+, 162.1277; found, 162.1278. IR (KBr): 3410, 3043, 2919,
2847, 1609, 1514, 1424, 1328, 769 cmꢀ1.
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N-(Butꢀ3ꢀenꢀ1ꢀyl)ꢀ2ꢀmethylaniline (1h)
1H NMR (400 MHz, CDCl3) δ = 7.23 (t, J = 7.6 Hz, 1H), 7.14 (d, J = 7.2 Hz, 1H), 6.74 (dd, J = 19.0,
7.7 Hz, 2H), 5.95 (td, J = 16.8, 7.1 Hz, 1H), 5.24 (t, J = 14.9 Hz, 2H), 3.61 (s, 1H), 3.32 (t, J = 6.6 Hz,
2H), 2.53 (q, J = 6.5 Hz, 2H), 2.21 (s, 3H). 13C NMR (101 MHz, CDCl3) δ = 146.2, 136.0, 130.1, 127.2,
122.0, 117.1, 116.9, 109.9, 42.7, 33.7, 17.39 ppm. MS (EI, 70 eV) m/z: 91, 120, 261. HRMS (ESI) m/z:
calcd for C11H16N [M+H]+, 162.1277; found, 162.1278. IR (KBr): 3421, 3076, 2920, 2851, 1607, 1512,
1443, 1316, 745 cmꢀ1.
N-(Butꢀ3ꢀenꢀ1ꢀyl)ꢀ3,5ꢀdimethylaniline (1i)
1H NMR (400 MHz, CDCl3) δ = 6.44 (s, 1H), 6.33 (s, 2H), 5.89 (tt, J = 8.8, 7.1 Hz, 1H), 5.19 (t, J =
14.9 Hz, 2H), 3.56 (s, 1H), 3.23 (t, J = 6.4 Hz, 2H), 2.44 (dd, J = 13.0, 6.4 Hz, 2H), 2.33 (d, J = 14.9
Hz, 6H). 13C NMR (101 MHz, CDCl3) δ = 148.4, 138.9 135.9, 119.5, 117.0, 110.9, 42.9, 33.7, 21.5
ppm. MS (EI, 70 eV) m/z: 77, 134, 175. HRMS (ESI) m/z: calcd for C12H18N [M+H]+, 176.1434; found,
176.1434. IR (KBr): 3408, 2916, 2853, 1603, 1513, 1472, 1302, 1178, 821 cmꢀ1.
4ꢀMethylꢀNꢀ(pentꢀ4ꢀenꢀ2ꢀyl)aniline (1j)
1H NMR (400 MHz, CDCl3) δ = 6.97 (d, J = 7.9 Hz, 2H), 6.51 (d, J = 7.9 Hz, 2H), 5.82 (dt, J = 16.6,
7.3 Hz, 1H), 5.15 – 4.97 (m, 2H), 3.51 (dd, J = 12.3, 6.1 Hz, 1H), 2.38 – 2.29 (m, 1H), 2.28 – 2.13 (m,
4H), 1.17 (d, J = 6.3 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ = 145.1, 135.1, 129.8, 126.4, 117.5,
113.7, 48.4, 40.9, 20.5, 20.4 ppm. MS (EI, 70 eV) m/z: 91, 119, 134, 175. HRMS (ESI) m/z: calcd for
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C12H18N [M+H]+, 176.1434; found, 176.1434. IR (KBr): 3404, 2970, 2922, 2865, 1617, 1518, 1302,
807 cmꢀ1.
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Methyl 3ꢀ(pꢀtolylamino)hexꢀ5ꢀenoate (1k)
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1H NMR (400 MHz, CDCl3) δ = 6.99 (d, J = 7.6 Hz, 2H), 6.57 (d, J = 7.6 Hz, 2H), 5.81 (dt, J = 16.0,
7.5 Hz, 1H), 5.11 (d, J = 13.0 Hz, 2H), 3.92 – 3.83 (m, 1H), 3.66 (s, 3H), 2.54 (ddd, J = 32.9, 15.3, 6.1
Hz, 2H), 2.44 – 2.31 (m, 2H), 2.23 (s, 3H). 13C NMR (101 MHz, CDCl3) δ = 172.3, 134.1, 129.9, 127.2,
118.3, 114.1, 51.6, 50.4, 38.5, 38.4, 20.4 ppm. MS (EI, 70 eV) m/z: 91, 118, 160, 192, 233. HRMS
(ESI) m/z: calcd for C14H20NO2 [M+H]+, 234.1489; found, 234.1491. IR (KBr): 3414, 3018, 2918,
2862, 1616, 1518, 1484, 1300, 1089, 919, 809 cmꢀ1.
Nꢀ(1ꢀ(4ꢀChlorophenyl)butꢀ3ꢀenꢀ1ꢀyl)ꢀ4ꢀmethylaniline (1l)
1H NMR (400 MHz, CDCl3) δ = 7.40 (d, J = 2.2 Hz, 4H), 7.03 (d, J = 4.7 Hz, 2H), 6.63 – 6.49 (m, 2H),
5.96 – 5.69 (m, 1H), 5.38 – 5.13 (m, 2H), 4.55 – 4.33 (m, 1H), 4.11 (s, 1H), 2.81 – 2.45 (m, 2H), 2.32
(d, J = 2.6 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ = 144.9, 142.5, 134.4, 132.6, 129.7, 128.8, 127.9,
126.9, 118.7, 113.8, 57.0, 43.3, 20.5 ppm. MS (EI, 70 eV) m/z: 91, 118, 230, 271. HRMS (ESI) m/z:
calcd for C17H19ClN [M+H]+, 272.1201; found, 272.1200. IR (KBr): 3403, 2919, 2862, 1735, 1617,
1519, 1437, 1297, 1202, 810 cmꢀ1.
4ꢀMethylꢀNꢀ(1ꢀphenylbutꢀ3ꢀenꢀ1ꢀyl)aniline (1m)
1H NMR (400 MHz, CDCl3) δ = 7.57 – 7.31 (m, 5H), 7.03 (s, 2H), 6.57 (s, 2H), 6.00 – 5.83 (m, 1H),
5.29 (t, J = 14.2 Hz, 2H), 4.55 – 4.40 (m, 1H), 3.99 (s, 1H), 2.67 (dd, J = 38.2, 5.1 Hz, 2H), 2.32 (d, J =
3.0 Hz, 3H) 13C NMR (101 MHz, CDCl3) δ = 145.2, 143.9, 134.9, 129.7, 128.7, 127.0, 126.6, 126.4,
118.3, 113.7, 57.5, 43.4, 20.5 ppm. MS (EI, 70 eV) m/z: 90, 118, 196, 237. HRMS (ESI) m/z: calcd for
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C17H20N [M+H]+, 238.1590; found, 238.1592. IR (KBr): 3413, 3024, 2919, 2860, 1616, 1518, 1301,
807 cmꢀ1.
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1H NMR (400 MHz, CDCl3) δ = 8.51 (d, J = 5.1 Hz, 1H), 8.25 – 8.16 (m, 1H), 8.01 (dd, J = 16.3, 7.1
Hz, 2H), 7.94 – 7.75 (m, 2H), 7.69 (dd, J = 8.6, 6.3 Hz, 1H), 7.18 (d, J = 4.1 Hz, 2H), 6.74 (s, 2H),
6.29 – 6.00 (m, 1H), 5.53 (dd, J = 16.8, 8.9 Hz, 2H), 4.64 – 4.33 (m, 1H), 3.14 (d, J = 13.4 Hz, 1H),
2.86 (d, J = 7.2 Hz, 1H), 2.50 (d, J = 2.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ = 145.3, 138.7, 135.3,
134.6, 131.1, 129.9, 129.6, 127.8, 126.7, 126.4, 126.1, 125.7, 123.6, 122.7, 118.5, 113.9, 53.6, 41.9,
20.7 ppm. MS (EI, 70 eV) m/z: 91, 118, 246, 287. HRMS (ESI) m/z: calcd for C21H22N [M+H]+,
288.1747; found, 288.1745. IR (KBr): 3416, 3070, 2916, 2861, 1616, 1517, 1302, 1261, 918, 808 cmꢀ1.
4ꢀMethylꢀNꢀ(3ꢀphenylpentꢀ4ꢀenꢀ2ꢀyl)aniline (1o)
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accroding to reference 23b, 1o has enantiomers, dr = 67:33. H NMR (400 MHz, CDCl3) δ =
7.27 – 7.06 (m, 5H), 6.90 (s, 2H), 6.45 (d, J = 6.1 Hz, 2H), 6.18 – 5.99 (m, 1H), 5.18 – 4.99 (m,
2H), 3.71 – 3. 66 (m, 1H), 3.49 – 3.47 (m, 1H), 2.15 (d, 3H), 1.03 (d, 3H), 0.93 (d, 3H). 13C NMR
(101 MHz, CDCl3) δ = 145.0, 144.9, 141.8, 141.0, 139.4, 136.9, 130.0, 129.9, 128.6, 128.4, 128.1,
126.6, 126.5, 117.9, 116.6, 114.2, 113.8, 54.9, 54.4, 52.8, 52.7, 20.5, 18.3, 17.2 ppm. MS (EI, 70
eV) m/z: 91, 134, 251. HRMS (ESI) m/z: calcd for C18H22N [M+H]+, 252.1747; found, 252.1750. IR
(KBr): 3405, 3025, 2971, 2921, 2865, 1616, 1517, 1450, 1299, 807, 701 cmꢀ1.
4ꢀMethylꢀNꢀ(4ꢀmethylpentꢀ4ꢀenꢀ2ꢀyl)aniline (1p)
1H NMR (400 MHz, CDCl3) δ = 7.04 (d, J = 7.9 Hz, 2H), 6.59 (d, J = 7.9 Hz, 2H), 4.85 (d, J = 24.7 Hz,
2H), 3.63 (dd, J = 12.9, 6.4 Hz, 1H), 3.22 (s, 1H), 2.39 (dd, J = 13.8, 6.7 Hz, 1H), 2.29 (s, 3H), 2.16
(dd, J = 13.9, 7.1 Hz, 1H), 1.80 (s, 3H), 1.24 (d, J = 6.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ =
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145.3, 143.1, 129.8, 126.4, 113.5, 112.9, 46.8, 45.6, 22.4, 20.9, 20.4 ppm. MS (EI, 70 eV) m/z: 91, 119,
134, 189. HRMS (ESI) m/z: calcd for C13H20N [M+H]+, 190.1590; found, 190.1591.IR (KBr): 3403,
2968, 2923, 2862, 1650, 1518, 1451, 807 cmꢀ1.
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NꢀBenzylꢀ1ꢀphenylbutꢀ3ꢀenꢀ1ꢀamine (1q)
1H NMR (400 MHz, CDCl3) δ = 7.43 – 7.18 (m, 10H), 5.70 (td, J = 16.9, 8.1 Hz, 1H), 5.04 (t, J = 13.9
Hz, 2H), 3.68 (dd, J = 13.4, 6.2 Hz, 2H), 3.52 (d, J = 13.3 Hz, 1H), 2.40 (d, J = 8.7 Hz, 2H), 1.93 (s,
1H). 13C NMR (101 MHz, CDCl3) δ = 143.8, 140.6, 135.5, 128.5, 128.4, 128.2, 127.4, 127.1, 126.9,
117.6, 61.7, 51.5, 43.1 ppm. MS (EI, 70 eV) m/z: 91, 196, 236. HRMS (ESI) m/z: calcd for C17H20N
[M+H]+, 238.1590; found, 238.1595. IR (KBr): 3324, 3080, 3062, 2927, 2836, 1603, 1493, 1455, 915,
699 cmꢀ1.
2ꢀPhenylꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3aa) 14
(Yellow oil). Yield (17.5 mg, 76%). 1H NMR (400 MHz, CDCl3) δ = 7.17 (ddd, J = 19.2, 12.9, 8.1 Hz,
7H), 7.07 (d, J = 7.7 Hz, 2H), 6.92 (s, 1H), 6.44 (s, 1H), 6.36 (s, 1H), 2.36 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ = 138.1, 136.4, 133.8, 133.1, 129.6, 128.3, 128.0, 126.2, 125.6, 124.4, 110.4, 109.0, 21.0 ppm.
MS (EI, 70 eV) m/z: 115, 129, 233. IR (KBr): 3266, 3073, 2928, 2867, 1598, 1513, 1424, 1325, 1158,
1090 cmꢀ1.
2ꢀ(4ꢀEthylphenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3ab)
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(Yellow oil). Yield (18.3 mg, 70%). H NMR (400 MHz, CDCl3) δ = 7.20–7.01 (m, 8H), 6.91 (s, 1H),
6.41 (s, 1H), 6.36 (s, 1H), 2.62 (q, J = 7.6 Hz, 2H), 2.37 (s, 3H), 1.23 (t, J = 7.6 Hz, 3H). 13C NMR
(100 MHz, CDCl3) δ = 142.2, 138.2, 136.3, 133.9, 130.5, 129.6, 128.2, 127.5, 125.6, 124.1, 110.1,
108.9, 28.5, 21.0, 15.3ppm. MS (EI, 70 eV) m/z: 91, 115, 128, 246, 261. HRMS (ESI) m/z: calcd for
C19H20N [M+H]+, 262.1588; found, 262.1590. IR (KBr): 3309, 3112, 2965, 1705, 1575, 1513, 1460,
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(White solid). Yield (23.2 mg, 75%). mp 127–128 °C. 1H NMR (400 MHz, CDCl3) δ = 7.58 (d, J = 7.7
Hz, 2H), 7.48–7.39 (m, 4H), 7.32 (t, J = 7.3 Hz, 1H), 7.21 (d, J = 7.8 Hz, 2H), 7.13 (q, J = 8.1 Hz, 4H),
6.94 (s, 1H), 6.49 (s, 1H), 6.38 (s, 1H), 2.37 (s, 3H). 13C NMR (100 MHz, CDCl3) δ =140.7, 138.7,
138.1, 136.5, 133.4, 132.1, 129.7, 128.7, 128.5, 127.0, 126.7, 125.6, 124.7, 110.6, 109.1, 21.0 ppm; MS
(EI, 70 eV) m/z: 91, 115, 129, 191, 309. HRMS (ESI) m/z: calcd for C23H20N [M+H]+, 310.1588;
found,310.1590. IR (KBr): 3302, 3114, 2923, 1712, 1579, 1514, 1266, 755 cmꢀ1.
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2ꢀ(4ꢀFluorophenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3ad)
(Yellow oil). Yield (19.8 mg, 79%). 1H NMR (400 MHz, CDCl3) δ 7.17–7.07 (m, 4H), 7.04 (d, J = 8.1
Hz, 2H), 6.90 (t, J = 8.6 Hz, 3H), 6.39–6.38 (m, 1H), 6.34 (t, J = 2.9 Hz, 1H), 2.36 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ =δ 160.5 (d, J = 244 Hz), 136.8, 135.5, 131.8, 128.86 (d, J = 7.9 Hz), 128.6,
128.2 (d, J = 4 Hz), 124.5, 123.3, 113.9 (d, J = 22 Hz), 109.2, 107.9, 20.0ppm; MS (EI, 70 eV) m/z: 91,
115, 133, 251. HRMS (ESI) m/z: calcd for C17H15FN [M+H]+, 252.1177; found,252.1183. IR (KBr):
2200, 2110, 2965, 1720, 1551, 1510, 1462, 1266, 754 cmꢀ1.
2ꢀ(4ꢀChlorophenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3ae)
(White solid). Yield (22.2 mg, 83%). mp 88–89 °C. 1H NMR (400 MHz, CDCl3) δ = 7.15 (dd, J = 14.0,
8.2 Hz, 4H), 7.05 (t, J = 6.9 Hz, 4H), 6.91 (s, 1H), 6.42 (s, 1H), 6.35 (s, 1H), 2.37 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ = 137.8, 136.7, 132.6, 131.6, 129.7, 129.4, 128.2, 125.6, 124.8, 110.7, 109.1, 21.0
ppm. MS (EI, 70 eV) m/z: 115, 129, 267. HRMS (ESI) m/z: calcd for C17H15ClN [M+H]+, 268.0881;
found, 268.0888. IR (KBr): 3299, 3113, 1711, 1572, 1514, 826, 753 cmꢀ1.
2ꢀ(4ꢀBromophenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3af)
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(White solid). Yield (26.1 mg, 84%). mp 100–101 °C. 1H NMR (400 MHz, CDCl3) δ = 7.32 (d, J = 7.9
Hz, 2H), 7.14 (d, J = 7.8 Hz, 2H), 7.02 (dd, J = 18.4, 7.9 Hz, 4H), 6.92 (s, 1H), 6.43 (m, 1H), 6.35 (s,
1H), 2.37 (s, 3H).13C NMR (100 MHz, CDCl3) δ = 137.8, 136.7, 132.6, 132.0, 131.2, 129.8, 129.7,
125.6, 124.9, 120.2, 110.7, 109.2, 21.0 ppm; MS (EI, 70 eV) m/z: 115, 129, 311. HRMS (ESI) m/z:
calcd for C17H15BrN [M+H]+ ,312.0377; found,312.0382. IR (KBr): 3307, 3038, 2921, 1707, 1575,
1514. 1457, 1266, 823, 753 cmꢀ1.
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Methyl 4ꢀ(1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2ꢀyl)benzoate (3ag)
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(White solid.). Yield (17.4 mg, 60%). mp 86−87 °C. H NMR (400 MHz, CDCl3) δ = 7.86 (d, J = 7.4
Hz, 2H), 7.16 (dd, J = 18.1, 7.6 Hz, 4H), 7.05 (d, J = 7.6 Hz, 2H), 6.94 (s, 1H), 6.53 (s, 1H), 6.36 (s,
1H), 3.88 (s, 3H), 2.36 (s, 3H).13C NMR (100 MHz, CDCl3) δ = 167.0, 137.8, 137.5, 136.9, 132.7,
129.8, 129.4, 127.6, 127.4, 125.8, 125.6, 111.8, 109.4, 52.0, 21.0 ppm; MS (EI, 70 eV) m/z: 91, 115,
130, 232, 260, 291. HRMS (ESI) m/z: calcd for C19H18NO2 [M+H]+, 292.1337; found, 292.1332. IR
(KBr): 3300, 3114, 1719, 1600, 1568, 1515, 1277 cmꢀ1.
2ꢀ(3ꢀChlorophenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3ah)
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(Yellow oil). Yield (21.6 mg, 81%). H NMR (400 MHz, CDCl3) δ = 7.20 (s, 1H), 7.04–7.15 (m, 6H),
6.92 (s, 2H), 6.44 (s, 1H), 6.34 (s, 1H), 2.37 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 137.7, 136.8,
134.9, 133.9, 132.3, 129.7, 129.2, 128.0, 126.3, 126.1, 125.5, 125.1, 111.1, 109.2, 21.0. ppm; MS (EI,
70 eV) m/z: 115, 129, 267. HRMS (ESI) m/z: calcd for C17H15ClN [M+H]+, 268.0889; found, 268.0888.
IR (KBr): 3113, 1713, 1565, 1516, 1266, 751 cmꢀ1.
2ꢀ(mꢀTolyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3ai)
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(Yellow oil). Yield (19.0 mg, 77%). H NMR (400 MHz, CDCl3) δ = 7.15–7.04 (m, 6H), 6.98 (d, J =
7.4 Hz, 1H), 6.91 (s, 1H), 6.87 (d, J = 7.6 Hz, 1H), 6.42 (s, 1H), 6.35 (t, J = 2.7 Hz, 1H), 2.36 (s, 3H),
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2.27 (s, 3H). 13C NMR (100 MHz, CDCl3) = 138.2, 137.6, 136.3, 133.9, 133.0, 129.5, 129.0, 127.8,
127.0, 125.5, 125.4, 124.3, 110.3, 108.9, 21.4, 21.0 ppm; MS (EI, 70 eV) m/z: 91, 115, 129, 247.
HRMS (ESI) m/z: calcd for C18H18N [M+H]+, 248.1429; found,248.1434. IR (KBr): 3035, 2922, 1700,
1599, 1514, 1466, 1334, 822, 775, 709 cmꢀ1.
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2ꢀ(Naphthalenꢀ2ꢀyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3aj)
(Yellow oil). Yield (24.9 mg, 88%). 1H NMR (400 MHz, CDCl3) δ = 7.79–7.75 (m, 1H), 7.72–7.63 (m,
3H), 7.45–7.39 (m, 2H), 7.23 (d, J = 8.5 Hz, 1H), 7.11 (s, 4H), 6.98 (s, 1H), 6.57–6.56 (m, 1H), 6.41 (s,
1H), 2.36 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 138.1, 136.5, 133.8, 133.4, 131.9, 130.7, 129.7,
127.9, 127.6, 127.4, 126.8, 126.6, 126.0, 125.6, 125.5, 124.7, 110.9, 109.2, 21.0 ppm; MS (EI, 70 eV)
m/z: 91, 115, 133, 165, 283. HRMS (ESI) m/z: calcd for C21H18N [M+H]+, 284.1033; found,284.1034.
IR (KBr): 3052, 2928, 1711, 1571, 1513, 1457, 1334, 820, 747, 714 cmꢀ1.
2ꢀ(3ꢀChloroꢀ4ꢀmethylphenyl)ꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3ak)
(Yellow oil). Yield (19.7 mg, 70%). 1H NMR (400 MHz, CDCl3) δ = 7.20 (s, 1H), 7.13 (d, J = 8.0 Hz,
2H), 7.04 (d, J = 7.8 Hz, 2H), 7.01 (d, J = 7.9 Hz, 1H), 6.89 (s, 1H), 6.81 (d, J = 7.9 Hz, 1H), 6.41ꢀ6.40
(m, 1H), 6.33 (s, 1H), 2.36 (s, 3H), 2.31 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 137.8, 136.7, 134.0,
133.7, 132.3, 130.4, 129.7, 128.5, 126.4, 125.6, 124.7, 110.6, 110.1, 109.1, 21.0, 19.7 ppm; MS (EI, 70
eV) m/z: 91, 115, 129, 281. HRMS (ESI) m/z: calcd for C18H17ClN [M+H]+, 282.1044; found,282.1044.
IR (KBr): 3109, 2926, 1713, 1561, 1513, 1460, 1335, 822 cmꢀ1.
1,2ꢀDiphenylꢀ1Hꢀpyrrole (3ba) 15
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(White solid). Yield (14.7 mg, 67%). mp 88−90 °C. H NMR (400 MHz, CDCl3) δ = 7.30 (m, 3H),
7.17 (td, J = 14.5, 7.2 Hz, 7H), 6.94 (s, 1H), 6.44 (s, 1H), 6.36 (s, 1H). 13C NMR (100 MHz, CDCl3) δ
= 140.6, 133.8, 133.0, 129.0, 128.3, 128.1, 126.6, 126.3, 125.8, 124.4, 110.7, 109.2 ppm; MS (EI, 70
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eV) m/z: 77, 108, 115, 219. IR (KBr): 3055, 2924, 1715, 1591, 1396, 1461, 1329, 759, 697 cmꢀ1.
1ꢀ(4ꢀMethoxyphenyl)ꢀ2ꢀphenylꢀ1Hꢀpyrrole (3ca) 16
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(Yellow oil). Yield (19.7 mg, 79%). 1H NMR (400 MHz, CDCl3) δ = 7.16 (ddd, J = 24.1, 15.4, 7.7 Hz,
7H), 6.89 (s, 1H), 6.85 (d, J = 8.6 Hz, 2H), 6.43 (s, 1H), 6.34 (t, J = 2.6 Hz, 1H), 3.81 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ = 158.2, 133.9, 133.8, 133.1, 128.2, 128.0, 126.9, 126.1, 124.5, 114.1,
110.1, 108.8, 55.4 ppm. MS (EI, 70 eV) m/z: 77, 115, 234, 249. IR (KBr): 3054, 2923, 2845, 1712,
1595, 1511, 1462, 1248, 1034, 755 cmꢀ1.
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1ꢀ(4ꢀFluorophenyl)ꢀ2ꢀphenylꢀ1Hꢀpyrrole (3da)
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(Yellow oil). Yield (14.0 mg, 60%). H NMR (400 MHz, CDCl3) δ = 7.20–7.00 (m, 6H), 6.93 (t, J =
8.5 Hz, 2H), 6.82 (s, 1H), 6.35 (s, 1H), 6.28 (t, J = 2.7 Hz, 1H).13C NMR (100 MHz, CDCl3) δ =
160.1(d, J = 245 Hz), 135.6(d, J = 3 Hz), 132.9, 131.7, 127.2 (d, J = 19 Hz), 126.3 (d, J = 8.4 Hz),
125.3, 123.3, 114.9, 114.7, 109.6, 108.3 ppm; MS (EI, 70 eV) m/z: 95, 115, 133, 237. HRMS (ESI) m/z:
calcd for C16H13FN [M+H]+, 238.1028; found, 238.1027. IR (KBr): 3067, 2926, 1709, 1591, 1509,
1466, 1224, 838, 756 cmꢀ1.
1ꢀ(4ꢀChlorophenyl)ꢀ2ꢀphenylꢀ1Hꢀpyrrole (3ea) 17
(Yellow oil). Yield (15.7 mg, 62%). 1H NMR (400 MHz, CDCl3) δ = 7.29–7.20 (m, 5H), 7.10 (dd, J
= 12.2, 8.2 Hz, 4H), 6.90 (s, 1H), 6.42 (s, 1H), 6.36 ((t, J = 3.1 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ
= 139.1, 133.8, 132.6, 132.2, 129.1, 128.3, 128.2, 126.8, 126.5, 124.2, 111.0, 109.6. ppm; MS (EI, 70
eV) m/z: 95, 108, 115, 217, 253. IR (KBr): 3110, 1709, 1580, 1495, 1334 cmꢀ1.
1ꢀ(4ꢀBromophenyl)ꢀ2ꢀphenylꢀ1Hꢀpyrrole (3fa) 18
(Yellow oil). Yield (17.5 mg, 59%). 1H NMR (400 MHz, CDCl3) δ = 7.43 (d, J = 8.2 Hz, 2H), 7.21 (dd,
J = 12.5, 7.1 Hz, 3H), 7.12 (d, J = 7.6 Hz, 2H), 7.03 (d, J = 8.2 Hz, 2H), 6.90 (s, 1H), 6.42 (s, 1H), 6.36
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(t, J = 2.7 Hz, 1H).13C NMR (100 MHz, CDCl3) δ = 139.6, 133.8, 132.7, 132.1, 128.3, 128.2, 127.1,
126.5, 124.1, 120.1, 111.1, 109.7 ppm; MS (EI, 70 eV) m/z: 115, 143, 224, 299. IR (KBr): 3075, 2924,
1709, 1582, 1491, 1334, 755 cmꢀ1.
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2ꢀPhenylꢀ1ꢀ(mꢀtolyl)ꢀ1Hꢀpyrrole (3ga)
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(Yellow oil). Yield (17.9 mg, 77%). H NMR (400 MHz, CDCl3) δ = 7.24–7.12 (m, 6H), 7.08 (d, J =
7.6 Hz, 1H), 7.04 (s, 1H), 6.93 (d, J = 7.0 Hz, 2H), 6.44 (s, 1H), 6.36 ((t, J = 3.0 Hz, 1H), 2.32 (s,
3H).13C NMR (100 MHz, CDCl3) δ = 140.5, 139.0, 133.8, 133.1, 128.7, 128.2, 128.0, 127.4, 126.3,
126.2, 124.4, 123.0, 110.5, 109.1, 21.3. ppm; MS (EI, 70 eV) m/z: 115, 129, 233. HRMS (ESI) m/z:
calcd for C17H16N [M+H]+, 234.1276; found, 234.1277.IR (KBr): 3106, 1710, 1588, 1493, 1336, 755,
701 cmꢀ1.
1ꢀ(3,5ꢀDimethylphenyl)ꢀ2ꢀphenylꢀ1Hꢀpyrrole (3ia)
(Yellow oil). Yield (19.8 mg, 80%). 1H NMR (400 MHz, CDCl3) δ = 7.22–7.12 (m, 5H), 6.93–6.86 (m,
2H), 6.81–6.74 (m, 2H), 6.42 (m, 1H), 6.33 (s, 1H), 2.24 (s, 6H).13C NMR (100 MHz, CDCl3) δ =
140.4, 138.6, 133.7, 133.1, 128.3, 128.1, 127.9, 126.1, 124.4, 123.5, 110.4, 108.9 , 21.2 ppm; MS (EI,
70 eV) m/z: 77, 115, 129, 247. HRMS (ESI) m/z: calcd for C18H18N [M+H]+, 248.1435; found,
248.1434. IR (KBr): 3108, 1712, 1598, 1475, 1346, 756 cmꢀ1.
2ꢀMethylꢀ5ꢀphenylꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3ja) 19
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(Yellow oil). Yield (20.0 mg, 81%). H NMR (400 MHz, CDCl3) δ = 7.29 (s, 1H), 7.17 (dd, J = 11.2,
7.4 Hz, 4H), 7.09 (dd, J = 13.9, 7.5 Hz, 5H), 6.38 (d, J = 3.1 Hz, 1H), 6.12 (d, J = 2.7 Hz, 1H), 2.41 (s,
3H), 2.16 (s, 3H).13C NMR (100 MHz, CDCl3) δ = 137.2, 136.8, 134.2, 133.7, 131.8, 129.6, 128.2,
127.9, 127.8,125.6, 108.5, 107.3, 21.1, 13.3ppm; MS (EI, 70 eV) m/z: 91, 115, 129, 191, 247. IR (KBr):
3035, 2924, 1714, 1593, 1513, 1450, 1396, 754 cmꢀ1.
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Methyl 2ꢀ(5ꢀphenylꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrolꢀ2ꢀyl)acetate (3ka)
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(Yellow oil). Yield (18.3 mg, 60%). 1H NMR (400 MHz, CDCl3) δ = 7.06 (t, J = 6.7 Hz, 4H), 6.99 (dd,
J = 13.8, 7.7 Hz, 5H), 6.32 (d, J = 2.8 Hz, 1H), 6.19 (d, J = 2.8 Hz, 1H), 3.51 (s, 3H), 3.46 (s, 2H), 2.29
(s, 3H). 13C NMR (100 MHz, CDCl3) δ = 171.1, 137.8, 136.0, 135.2, 133.3, 129.7, 128.5, 128.0, 127.9,
127.8, 125.9, 109.2, 108.9, 52.0, 33.1, 21.1 ppm; MS (EI, 70 eV) m/z: 115, 230, 246, 305. HRMS (ESI)
m/z: calcd for C20H20NO2 [M+H]+, 306.1495; found, 306.1489. IR (KBr): 3069, 2923, 1738, 1572,
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1513, 1447 cmꢀ1.
2ꢀ(4ꢀChlorophenyl)ꢀ5ꢀphenylꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3la)
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(White solid). Yield (25.7 mg, 75%). mp 199−200 °C. H NMR (400 MHz, CDCl3) δ = 7.15 (dd, J =
12.0, 8.1 Hz, 5H), 7.09–7.01 (m, 4H), 6.98 (d, J = 8.3 Hz, 2H), 6.89 (d, J = 7.9 Hz, 2H), 6.45 (s, 2H),
2.33 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 137.3, 136.2, 136.1,134.5, 133.2, 132.0, 131.9, 129.8,
129.6, 128.7, 128.5, 128.1, 127.9, 126.3, 110.0, 109.9, 21.1 ppm; MS (EI, 70 eV) m/z: 91, 145, 191,
205, 343. HRMS (ESI) m/z: calcd for C23H19ClN [M+H]+, 344.1203; found, 344.1201. IR (KBr): 3115,
1712, 1567, 1515, 1482, 826, 754 cmꢀ1.
2,5ꢀDiphenylꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3ma) 20
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(White solid). Yield (24.1 mg, 78%). mp 193−194 °C. H NMR (400 MHz, CDCl3) δ = 7.12–7.04 (m,
6H), 7.00 (d, J = 7.3 Hz, 4H), 6.95 (d, J = 7.7 Hz, 2H), 6.83 (d, J = 7.7 Hz, 2H), 6.39 (s, 2H), 2.24 (s,
3H).13C NMR (100 MHz, CDCl3) δ = 137.0, 136.4, 135.9, 133.4, 129.4, 128.7, 128.6, 127.8, 126.1,
109.8, 21.1 ppm; MS (EI, 70 eV) m/z: 91, 139, 191, 309. IR (KBr): 2991, 2924, 1764,1600, 1513, 1454,
1381, 1242, 1056, 753 cmꢀ1.
2ꢀ(Naphthalenꢀ1ꢀyl)ꢀ5ꢀphenylꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3na)
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(Yellow solid). Yield (24.8 mg, 69%). mp 151−152 °C. H NMR (400 MHz, CDCl3) δ = 7.99 (d, J =
7.5 Hz, 1H), 7.72 (d, J = 6.1 Hz, 1H), 7.64 (d, J = 8.1 Hz, 1H), 7.38–7.32 (m, 2H), 7.23–7.16 (m, 2H),
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7.12–7.06 (m, 6H), 6.72 (s, 3H), 6.51 (m, 1H), 6.40 (m, 1H), 2.09 (s, 3H).13C NMR (100 MHz, CDCl3)
δ = 136.34, 136.3, 134.9, 133.5, 133.4,131.3 129.4, 129.0, 128.4, 128.0, 127.9, 127.6, 126.6, 126.0,
125.9, 125.6, 124.8, 111.7, 109.5, 21.0 ppm; MS (EI, 70 eV) m/z: 91, 165, 207, 239, 359. HRMS (ESI)
m/z: calcd for C27H21NNa [M+Na]+, 382.1558; found, 382.1566. IR (KBr): 2991, 1764, 1595, 1514,
1477, 1377, 1242, 1056, 753 cmꢀ1.
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2ꢀMethylꢀ3,5ꢀdiphenylꢀ1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (3oa) 21
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(Yellow solid). Yield (17.1 mg, 69%). mp 137−139 °C. H NMR (400 MHz, CDCl3) δ = 7.52 (d, J =
7.4 Hz, 2H), 7.41 (t, J = 7.4 Hz, 2H), 7.16 (m, 10H), 6.57 (s, 1H), 2.39 (s, 3H), 2.25 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ = 137.4, 137.0, 136.6, 133.9, 133.3, 129.7, 128.4, 128.1, 128.0, 127.9, 125.8,
125.4, 122.6, 118.9, 116.9, 109.1, 21.2, 12.4 ppm; MS (EI, 70 eV) m/z: 91, 117, 146, 161, 191, 323. IR
(KBr): 3026, 2924, 1732, 1598, 1513, 1452, 1379, 754.698 cmꢀ1.
1ꢀ(pꢀtolyl)ꢀ1Hꢀpyrrole (4a) 22
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(Yellow solid). Yield (12.3 mg, 78%). mp 84–85 °C. H NMR (400 MHz, CDCl3) δ= 7.38–7.22 (m,
5H), 7.09 (s, 2H), 6.36 (s, 2H), 2.40 (s, 3H). 13C NMR (100 MHz, CDCl3) δ = 137.5, 134.3, 129.0,
119.5, 118.4, 109.0, 19.8 ppm; MS (EI, 70 eV) m/z: 115, 129, 157. IR (KBr): 2919, 2851, 1652, 1588,
1467, 1262, 1092, 1022, 801, 753 cmꢀ1.
1ꢀ(4ꢀChlorophenyl)ꢀ1Hꢀpyrrole (4b) 23
(Yellow solid). Yield (11.9 mg, 67%). mp 90 °C. 1H NMR (400 MHz, CDCl3) δ= 7.39 (d, J = 8.7 Hz,
2H), 7.33 (d, J = 8.7 Hz, 2H), 7.05 (s, 2H), 6.36 (s, 2H). 13C NMR (100 MHz, CDCl3) δ = 139.3, 131.1,
129.6, 121.6, 119.3, 110.8 ppm; MS (EI, 70 eV) m/z: 115, 142, 177. IR (KBr): 2921, 2862, 1639, 1506,
1467, 1074, 826, 729 cmꢀ1.
2ꢀPhenylꢀ1ꢀ(mꢀtolyl)ꢀ2,5ꢀdihydroꢀ1Hꢀpyrrole (5)
1
(Yellow oil). Yield (13.4 mg, 57%). H NMR (400 MHz, CDCl3) δ = 7.32–7.26 (m, 4H), 7.22 (d, J =
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6.4 Hz, 1H), 7.02 (t, J = 7.5 Hz, 1H), 6.47 (d, J = 7.3 Hz, 1H), 6.36 (s, 1H), 6.31 (d, J = 8.2 Hz, 1H),
5.96ꢀ5.91 (m, 1H), 5.85 (d, J = 6.0 Hz, 1H), 5.40 (s, 1H), 4.47 (dd, J = 14.0, 5.0 Hz, 1H), 4.25 (d, J =
13.9 Hz, 1H), 2.24 (s, 3H).13C NMR (100 MHz, CDCl3) δ = 146.5, 142.8, 138.8, 132.5, 128.9, 128.8,
127.1, 126.2, 124.2, 117.1, 112.85, 109.5, 69.7, 56.2, 21.8 ppm; MS (EI, 70 eV) m/z: 91, 118, 143, 158,
194, 235. HRMS (ESI) m/z: calcd for C17H18N [M+H]+, 236.1433; found, 236.1434. IR (KBr): 3055,
2925, 1708, 1594, 1494, 1357, 758, 699 cmꢀ1.
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Acknowledgements
We are grateful to the National Basic Research Program of China (973 Program) (2011CB808600), the
National Natural Science Foundation of China (21172076 and 21202046), the Guangdong Natural
Science Foundation (10351064101000000), and the Fundamental Research Funds for the Central
Universities (2014ZP0004 and 2014ZZ0046).
Supporting Information
1H and 13C NMR spectra of all synthesized compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
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