LDA-Promoted Synthesis of 3-Amino Furans by Selective Lithiation of Enaminones

Article abstract of DOI:10.1021/acs.joc.5b02211

An efficient cascade β-metalation/addition/cyclization reaction promoted by LDA is described in which 3-amino furans were constructed from enaminones and aldehydes. A broad range of substituents on the starting compounds was tolerated, and the polysubstit

Full text of DOI:10.1021/acs.joc.5b02211

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Note
The LDA Promoted Synthesis of 3-Amino
Furans by Selective Lithiation of Enaminones
Lingkai Kong, Yushang Shao, Yanli Li, Yuanyuan Liu, and Yanzhong Li
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b02211 • Publication Date (Web): 18 Nov 2015
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The LDA Promoted Synthesis of 3-Amino Furans by
Selective Lithiation of Enaminones
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Lingkai Kong, Yushang Shao, Yanli Li, Yuanyuan Liu*, Yanzhong Li*
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry
and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai,
200241, China
ABSTRACT: An efficient cascade βꢀmetalation/addition/cyclization reaction promoted by LDA is
described, in which 3ꢀamino furans were constructed from enaminones and aldehydes. A broad
range of substituents on the starting compounds were tolerated, and the polysubstituted furans
were gained with moderate to excellent yields within 2 hours.
Highly functionalized furans play a significant role in organic chemistry, since they as
fundamental heterocyclic motifs are widely found in biologically active natural products,
pharmaceuticals, and materials.1 Moreover, they have also frequently been used as basic building
blocks in synthetic chemistry.2 Thus, substantial interest has been attracted to develop efficient
methods for the preparation of multiply substituted furans.3 The traditional approaches for the
synthesis of furans include Feist−Bénary cyclocondensation4 from 1,3ꢀdicarbonyl compounds and
haloketones (Scheme 1, a), Paal−Knorr cyclocondensation5 from 1,4ꢀdicarbonyl compounds
(Scheme 1, b) and so on. Transitionꢀmetalꢀcatalyzed methods have also been developed for the
assembly of various multisubstituted furans, such as the cyclization of allenyl ketones (Scheme 1,
c),6 Auꢀcatalyzed cyclization reaction of (Z)ꢀenynols (Scheme 1, d),7 and Pdꢀcatalyzed arylation of
furans via C−H activation8 (Scheme 1, e).
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Scheme 1. Synthesis of Highly Substituted Furan
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Another process to construct polysubstituted furan derivatives is ring transformation.9
Functionalization at the 2ꢀ and 5ꢀpositions of furans is ready permitted in chemical transformations,
but similar operations at the 3ꢀ or 4ꢀpositions are difficult to achieve. Electronꢀrich furan derivatives
like 3ꢀaminofurans are easy to modify by FriedelꢀCrafts acylation and exceptionally useful dienes
for use in DielsꢀAlder reactions, while the synthesis of substituted 3ꢀamino funans only has a few
reports.10
The functionalization of aromatic molecules and heterocyclic compounds has often been
achieved by metalation using various bases.11 However, the deprotonation of functionalized
nonꢀaromatic and olefinic systems is more difficult and sensitive compared with aromatic and
heteroaromatic systems.12 An excellent work by Knochel group was the magnesiation or zincation
of highly functionalized alkenes and cycloalkenes using 2,2,6,6ꢀtetramethylpiperidyl base (Scheme
2).12a During the course of our continued work on the preparation of heterocycles from
enaminones,13 we developed an efficient cascade addition/cyclization reaction to synthesize
3ꢀaminoꢀ2,5ꢀaryl (or alkyl) furans promoted by LDA, from enaminones and aldehydes, inspirited by
the βꢀmetalation of unsaturated olefin by the help of orientation effect on carbonyl group. To our
delight, only the desired products via βꢀmetalation process were obtained and no αꢀmetalation
products were observed in this system.
Scheme 2. β-Metalation as Key Step
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We began our investigation with enaminone 1a and 1.4 equiv of LDA (lithium diisopropylamide)
using ꢀ78 oC as lithiation temperature under N2 atmosphere, followed by adding 1.5 equiv of
4ꢀbromobenzaldehyde 2a. 3ꢀAmino furan 3a was obtained with 80% isolated yield efficiently (Table
1, entry 1). To our delight, no αꢀlithiation byproduct was detected. This result encouraged us to take
efforts to optimize the reaction conditions with 1a and 2a as model substrates (Table 1). Firstly,
LDA in situ was tested and almost no difference in the product yields (entries 1ꢀ2). Considering that
LDA is commercially available nowadays, we chose use LDA as organolithium reagent. When
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increasing the lithiation temperature to ꢀ40 C, the yield of desired product 3a decreased to 66%
(entry 3). Fixed the lithiation temperature to ꢀ78 oC, the amounts of LDA and 4ꢀbromobenzaldehyde
2a were screened, revealing that 2.0 equiv of LDA and 2a were essential to this system, with 85%
isolated yield of 3ꢀaminofuran 3a (entries 4ꢀ7).
Table 1. Optimization of Reaction Conditionsa
a
b
Unless otherwise noted, the reactions were carried out under N2 atmosphere in 0.5 mmol scale.
Isolated yield. c LDA in situ.
With the optimized reaction conditions presented in entry 6 of Table 1 in hand, the substrate
scope of the reaction was explored by employing a variety of enaminones 1 and aldehydes 2
(Scheme 3). High chemoselectivities and high efficiency were observed in all cases, a series of
polysubstituted 3ꢀaminofurans were gained in moderate to good yields within 2 hours. The reaction
tolerated aldehydes 2 with aromatic substituents with different electronic properties (2a-d), alkyl
substituents (2eꢀf), or heteroaromatic substituents (2g-h), giving corresponding products 3 in good
to excellent yields (52%ꢀ92%). Among them, 3,4,5ꢀtrimethoxybenzaldehyde (2b), with highly
electronꢀdonating group as substituent R4, gave the best result of 3ꢀaminofuran 3b (92% isolated
yield). And the data also illustrated that benzaldehyde (2d) offered product 3d lower yield (60%
yield), compared with the ones with either electronꢀwithdrawing (2a) or electronꢀdonating groups
(2b) as substituent R4. However, when sterically hindered aldehydes 2c (R4
=
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2ꢀbromoꢀ4ꢀmethylphenyl) with an orthoꢀsubstituent on the benzene ring was employed, the yield of
product 3c dropped dramatically (57% yield). Alkyl aldehydes such as 2e and 2f, yielded
3ꢀaminofurans 3 with good results (3e: 64% yield, 3f: 52% yield). Furthermore, the reaction with
heteroaromatic aldehydes 2g and 2h went also smoothly, resulting the desired products 3g and 3h
in 81% and 67% yields, respectively. In addition, the structure of 3ꢀaminofuran 3c was
characterized by Xꢀray crystallography (see SI, including CIF file).
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Next, we proceeded to extend the reaction scope to different kinds of enaminones 1. The
substituents R1 either with electronꢀwithdrawing (1i, R1 = 4ꢀchlorophenyl) or electronꢀdonating
groups (1j, R1 = 4ꢀmethoxyphenyl) on the benzene rings led the decline of the yields of the
corresponding furan products (3i: 68% yield, 3j: 67% yield), referring to enaminones 1a with phenyl
group as substituents R1 (3a: 85% yield). Notably, the scope of enaminones could be extended to
simple aliphatic enaminones, such as 1k, could afford the corresponding furan 3k in good yield
(80%). Then, efforts were made to examine the Nꢀsubstituents R2, R3, finding that isopropyl is
sterically and electrically fit for this system, other Nꢀsubstituents like phenyl group (1l) and
piperidinꢀ1ꢀyl substituted enaminone (1m) impacted sharply on the yields of the desired products,
resulting in 3l with 41% yield and 3m with 48% yield.
Scheme 3. Synthesis of 3-Amino Furans 3a,b
O
R1
R4
O
R4CHO (2) (2.0 equiv)
LDA (2.0 equiv)
ꢀ78 oC, THF, 1 h
R1
NR2R3
ꢀ40 oC, 1 h
NR2R3
1
3
OMe
OMe
Br
Br
Me
O
O
O
Ph
Ph
Ph
Ph
OMe
NiPr2
3a
NiPr2
3b
NiPr2
3c
85% yield
92% yield
57% yield
O
O
O
Ph
Ph
Ph
nBu
NiPr2
NiPr2
3d
NiPr2
3e
64% yield
3f
52% yield
60% yield
O
O
N
O
Ph
Ph
Me
NiPr2
NiPr2
3g
3h
81% yield
67% yield
Cl
Br
MeO
Br
O
O
NiPr2
NiPr2
3j
3i
68% yield
67% yield
Br
Br
Br
O
Ph
O
Ph
O
N
Ph
N
Ph
NiPr2
3k
80% yield
3l
3m
48% yield
41% yield
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a All reactions were carried out under N2 atmosphere in 0.5 mmol scale. b Isolated yield.
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On the basis of the reported work,12a,14 a plausible mechanism for this reaction is proposed as
outlined in Scheme 4. The process began with the βꢀmetalation of enaminone 1 by LDA, with the
help of orientation effect on carbonyl group to form lithium compound A. Then, the attacking of
aldehyde 2 to give intermediate B. The cyclization of B generated 2,5ꢀdihydrofuran ring
intermediate C. After quenched by a saturated solution of ammonium chloride, the desired 3ꢀamino
furan 3 was finally obtained by aromatization.
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Scheme 4. Plausible Mechanisms
In conclusion, we have developed an efficient procedure of the synthesis of 3ꢀamino furans
promoted by LDA, starting with readyꢀinꢀhand reagents. This system tolerated a broad range of
enaminones and aldehydes, achieved with moderate to excellent yields within 2 hours. It provides a
new efficient approach to prepare polysubstituted furans.
EXPERIMENTAL SECTION
General Remarks. Unless otherwise mentioned, all commercial reagents and solvents were used as directly
purchased without further purification. THF was distilled from sodium/benzophenone. Column chromatographic
purification of products was carried out using silica gel (200~300 mesh). NMR spectra were recorded at 400
MHz (1H NMR) and 100 Hz (13C NMR) respectively, referenced to tetramethylsilane (δ = 0.00 ppm) and the
residual solvent peak (δ = 77.00 ppm) in CDCl3 (containing 0.03% TMS) solutions. Jꢀvalues are in Hz.
Highꢀresolution mass spectra were performed on a mass spectrometer with a TOF (for EI or ESI) or FTꢀICR (for
MALDI) analyzer.
General procedure for the preparation of E-enaminone 1.13e To a solution of ynone (5.0 mmol) in toluene
or methanol (5 mL) in Schlenk tube was added secondary amine (6.0 mmol, 1.2 equiv) and stirred at room
temperature until the full conversion of ynone monitored by thinꢀlayer chromatography. The resulting mixture
was concentrated under reduced pressure. Purification by chromatography on silica gel (petroleum ether)
afforded the desired compound 1.16 The data of new compounds 1 were shown as below:
(E)ꢀ1ꢀcyclohexylꢀ3ꢀ(diisopropylamino)propꢀ2ꢀenꢀ1ꢀone: Yellow liquid, obtained in 12 h and purified by
chromatography on silica gel (petroleum ether/ethyl acetate= 4:1); yield: 0.75 g (63%). 1H NMR (400 MHz,
CDCl3) δ 1.10ꢀ1.30 (m, 15H), 1.37ꢀ1.47 (m, 2H), 1.64ꢀ1.68 (m,1H), 1.76ꢀ1.83 (m, 4H), 2.25 (t, J = 11.2 Hz, 1H),
3.73 (br, 2H), 5.23 (d, J = 12.8 Hz, 1H), 7.74 (d, J = 12.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 18.9, 22.9, 25.4,
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25.5, 25.6, 29.2, 47.8, 49.9, 93.1, 146.9, 201.2. HRMS (ESIꢀTOF) m/z: [M+H]+ calcd for C15H28NO: 238.2165;
found: 238.2176.
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(E)ꢀ3ꢀ(diisopropylamino)ꢀ1ꢀ(4ꢀmethoxyphenyl)propꢀ2ꢀenꢀ1ꢀone: Yellow solid, obtained in 25 min and purified
by chromatography on silica gel (petroleum ether/ethyl acetate= 3:1); yield: 1.27 g (97%); mp: 77ꢀ78 oC. 1H NMR
(400 MHz, CDCl3) δ 1.26ꢀ1.28 (m, 12H), 3.62 (m, 1H), 3.84 (s,3H), 3.40 (m, 1H), 5.89 (d, J = 12.4 Hz, 1H), 6.91
(d, J = 9.2 Hz, 2H), 7.91 (d, J = 8.8 Hz, 2H), 7.97 (d, J = 12.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 19.3, 23.3,
55.1, 91.2, 113.3, 129.5, 133.7, 148.7,162.0, 187.6. HRMS (ESIꢀTOF) m/z: [M+H]+ calcd for
C16H24NO2:262.1802; found: 262.1807.
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General procedure for the preparation of 3-amino furans 3. To a solution of enaminone 1 (0.5 mmol) in
dry THF (5 mL) in Schlenk tube was dropwisely added a 2.0 M solution of LDA in THF (1.0 mmol, 0.5 mL) and
stirred at ꢀ78 oC for one hour under nitrogen. Then, aldehyde 2 (1.0 mmol) was added at ꢀ78oC and the reaction
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mixture was allowed to warm to ꢀ40 C and kept at the temperature until the full conversion of enaminone 1
monitored by thinꢀlayer chromatography. The resulting mixture was quenched with a saturated solution of NH4Cl
and extracted with ethyl acetate (10 mL×3). The combined organic layers were washed with brine and dried over
anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by chromatography on silica
gel (petroleum ether) afforded the desired compound 3.
2ꢀ(4ꢀbromophenyl)ꢀN,Nꢀdiisopropylꢀ5ꢀphenylfuranꢀ3ꢀamine (3a): Colorless liquid, 170 mg (85% yield). 1H
NMR (400 MHz, CDCl3) δ 1.03 (d, J = 6.0 Hz, 12H), 3.37ꢀ3.43 (m, 2H), 6.68 (s, 1H), 7.21ꢀ7.25 (m, 1H), 7.35ꢀ7.39
(m, 2H), 7.46ꢀ7.48 (m, 2H), 7.69ꢀ7.72 (m, 2H), 8.22ꢀ8.25 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 20.6, 20.6, 49.8,
108.8, 120.1, 123.5, 126.3, 127.4, 128.6, 130.5, 130.7, 131.0, 131.9, 147.4, 150.9. HRMS (EIꢀTOF) m/z: M+
calcd for C22H24NOBr: 397.1041; found: 397.1038.
N,Nꢀdiisopropylꢀ5ꢀphenylꢀ2ꢀ(3,4,5ꢀtrimethoxyphenyl)furanꢀ3ꢀamine (3b): Colorless liquid, 188 mg (92% yield).
1H NMR (400 MHz, CDCl3) δ 1.08 (d, J = 6.4 Hz, 12H), 3.41ꢀ3.48 (m, 2H), 3.90 (s, 3H), 3.93 (s, 6H), 6.70 (s, 1H),
7.22ꢀ7.26 (m, 1H), 7.37ꢀ7.41 (m, 2H), 7.71ꢀ7.74 (m, 2H), 7.76 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 20.7, 49.5,
55.8, 55.8, 60.7, 102.0, 108.8, 123.3, 127.0, 127.1, 128.5, 130.6, 130.7, 136.7, 148.0, 150.2, 152.7. HRMS
(EIꢀTOF) m/z: M+ calcd for C25H31NO4: 409.2253; found: 409.2252.
2ꢀ(2ꢀbromoꢀ4ꢀmethylphenyl)ꢀN,Nꢀdiisopropylꢀ5ꢀphenylfuranꢀ3ꢀamine (3c): White solid, 117 mg (57% yield);
mp: 133ꢀ134 oC. 1H NMR (400 MHz, CDCl3) δ 0.99 (d, J = 6.4 Hz, 12H), 2.32 (s, 3H), 3.30ꢀ3.36 (m, 2H), 6.71 (s,
1H), 7.08ꢀ7.10 (m, 1H), 7.20ꢀ7.24 (m, 1H), 7.34ꢀ7.38 (m, 2H), 7.47ꢀ7.48 (m, 1H), 7.71ꢀ7.75 (m, 3H); 13C NMR
(100 MHz, CDCl3) δ 20.9, 21.0, 49.6, 107.1, 122.4, 123.5, 127.2, 127.4, 128.6, 129.5, 131.1, 131.5, 131.9,
134.0, 139.2, 147.2, 151.0. HRMS (EIꢀTOF) m/z: M+ calcd for C23H26NOBr: 411.1198; found: 411.1201.
N,Nꢀdiisopropylꢀ2,5ꢀdiphenylfuranꢀ3ꢀamine (3d): Colorless liquid, 95 mg (60% yield). 1H NMR (400 MHz,
CDCl3) δ 1.06 (d, J = 6.4 Hz, 12H), 3.40ꢀ3.46 (m, 2H), 6.70 (s, 1H), 7.18ꢀ7.25 (m, 2H), 7.34ꢀ7.40 (m, 4H),
7.72ꢀ7.74 (m, 2H), 8.34ꢀ8.36 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 20.7, 49.8, 108.9, 123.5, 124.8, 126.5,
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127.2, 127.9, 128.6, 131.0, 131.3, 131.7, 148.4, 150.5. HRMS (EIꢀTOF) m/z: M+ calcd for C22H25NO: 319.1936;
found: 319.1932.
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2ꢀcyclohexylꢀN,Nꢀdiisopropylꢀ5ꢀphenylfuranꢀ3ꢀamine (3e): Colorless liquid, 104 mg (64% yield). 1H NMR (400
MHz, CDCl3) δ 0.98 (d, J = 6.4 Hz, 12H), 1.26ꢀ1.38 (m, 4H), 1.62ꢀ1.83 (m, 6H), 2.84ꢀ2.88 (m, 1H), 3.24ꢀ3.31 (m,
2H), 6.49 (s, 1H), 7.14ꢀ7.18 (m, 1H), 7.31ꢀ7.35 (m, 2H), 7.60ꢀ7.63 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 21.2,
26.1, 26.5, 31.5, 34.3, 49.6, 106.9, 123.0, 125.9, 126.4, 128.5, 131.6, 149.3, 157.4. HRMS (EIꢀTOF) m/z: M+
calcd for C22H31NO: 325.2406; found: 325.2410.
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2ꢀbutylꢀN,Nꢀdiisopropylꢀ5ꢀphenylfuranꢀ3ꢀamine (3f): Colorless liquid, 78 mg (52% yield). 1H NMR (400 MHz,
CDCl3) δ 0.95 (t, J = 7.6 Hz, 3H), 0.98 (d, J = 6.4 Hz, 12H), 1.39ꢀ1.44 (m, 2H), 1.64ꢀ1.68 (m, 2H), 2.64 (t, J = 7.6
Hz, 2H), 3.27ꢀ3.30 (m, 2H), 6.51 (s, 1H), 7.17ꢀ7.19 (m, 1H), 7.31ꢀ7.35 (m, 2H), 7.60ꢀ7.63 (m, 2H);13C NMR (100
MHz, CDCl3) δ 14.0, 21.2, 22.8, 25.2, 30.2, 49.8, 107.2, 123.0, 126.4, 127.4, 128.5, 131.6, 149.6, 153.8. HRMS
(EIꢀTOF) m/z: M+ calcd for C20H29NO: 299.2249; found: 299.2247.
N,Nꢀdiisopropylꢀ5ꢀphenylꢀ2ꢀ(pyridinꢀ4ꢀyl)furanꢀ3ꢀamine (3g): Yellow liquid, 130 mg (81% yield). 1H NMR (400
MHz, CDCl3) δ 1.06 (d, J = 6.4 Hz, 12H), 3.42ꢀ3.48 (m, 2H), 6.74 (s, 1H), 7.27ꢀ7.31 (m, 1H), 7.39ꢀ7.43 (m, 2H),
7.74ꢀ7.76 (m, 2H), 8.17ꢀ8.19 (m, 2H), 8.57ꢀ8.59 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 20.5, 49.8, 109.0, 118.3,
123.7, 127.9, 128.6, 130.1, 135.7, 137.9, 145.7, 149.5, 152.5. HRMS (EIꢀTOF) m/z: M+ calcd for C21H24N2O:
320.1889; found: 320.1890.
N,Nꢀdiisopropylꢀ4'ꢀmethylꢀ5ꢀphenylꢀ[2,2'ꢀbifuran]ꢀ3ꢀamine (3h): Yellow liquid, 109 mg (67% yield). 1H NMR
(400 MHz, CDCl3) δ 1.029 (d, J = 6.0 Hz, 6H), 1.034 (d, J = 6.8 Hz, 6H), 2.37 (s, 3H), 3.36ꢀ3.39 (m, 2H),
6.03ꢀ6.04 (m, 1H), 6.63ꢀ6.64 (m, 1H), 6.85ꢀ6.86 (m, 1H), 7.19ꢀ7.23 (m, 1H), 7.34ꢀ7.38 (m, 2H), 7.71ꢀ7.74 (m,
2H); 13C NMR (100 MHz, CDCl3) δ 13.6, 20.9, 49.8, 107.3, 108.1, 108.6, 123.4, 127.0, 128.6, 129.2, 130.8,
143.4, 144.4, 150.6. HRMS (EIꢀTOF) m/z: M+ calcd for C21H25NO2: 323.1885; found: 323.1891.
2ꢀ(4ꢀbromophenyl)ꢀ5ꢀ(4ꢀchlorophenyl)ꢀN,Nꢀdiisopropylfuranꢀ3ꢀamine (3i): Colorless liquid, 148 mg (68%
yield). 1H NMR (400 MHz, CDCl3) δ 0.95 (d, J = 6.4 Hz, 12H), 3.32ꢀ3.35 (m, 2H), 6.59 (s, 1H), 7.26 (d, J = 8.3 Hz,
2H), 7.38 (d, J=8.3 Hz, 2H), 7.54 (d, J=8.3 Hz, 2H), 8.11 (d, J=8.3 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 20.4,
49.8, 109.6, 120.6, 125.0, 126.6, 129.1, 129.5, 130.6, 131.4, 132.3, 133.3, 148.2, 150.3. HRMS (ESIꢀTOF) m/z:
[M+H]+ calcd for [C22H23BrClNO+H+]: 432.0730; found: 432.0737.
2ꢀ(4ꢀbromophenyl)ꢀN,Nꢀdiisopropylꢀ5ꢀ(4ꢀethoxyphenyl)furanꢀ3ꢀamine (3j): Yellow liquid, 144 mg (67% yield).
1H NMR (400 MHz, CDCl3) δ 1.03 (d, J = 6.8 Hz, 12H), 3.39ꢀ3.42 (m, 2H), 3.80 (s, 3H), 6.56 (s, 1H), 6.92 (d, J =
8.8 Hz, 2H), 7.46 (d, J = 8.8 Hz, 2H), 7.65 (d, J = 8.8 Hz, 2H), 8.21 (d, J = 8.8 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 20.6,49.8, 55.2, 107.3, 114.1, 119.7, 123.8, 125.0, 126.1, 130.6, 131.0, 132.0, 146.8, 151.0, 159.1.
HRMS (EIꢀTOF) m/z: M+ calcd for C23H26BrNO2: 427.1147; found: 427.1151.
2ꢀ(4ꢀbromophenyl)ꢀ5ꢀcyclohexylꢀN,Nꢀdiisopropylfuranꢀ3ꢀamine (3k): Colorless liquid, 162 mg (80% yield). 1H
NMR (400 MHz, CDCl3) δ 0.99 (d, J = 6.4 Hz, 12H), 1.23ꢀ1.45 (m, 5H), 1.68ꢀ1.71 (m, 1H), 1.77ꢀ1.80 (m, 2H),
2.04ꢀ2.06 (m, 2H), 2.59ꢀ2.63 (m, 1H), 3.32ꢀ3.38 (m, 2H), 5.96 (s, 1H), 7.39ꢀ7.42 (m, 2H), 8.09ꢀ8.12 (m, 2H); 13
C
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NMR (100 MHz, CDCl3) δ 20.7, 25.9, 26.1, 31.4, 37.4, 49.7, 106.6, 119.2, 125.9, 130.5, 130.9, 131.1, 145.5,
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158.6. HRMS (EIꢀTOF) m/z: M+ calcd for C22H30BrNO: 403.1511; found: 403.1506.
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2ꢀ(4ꢀbromophenyl)ꢀN,N,5ꢀtriphenylfuranꢀ3ꢀamine (3l): Colorless liquid, 96 mg (41% yield). 1H NMR (400 MHz,
CDCl3) δ 6.64 (s, 1H), 6.92ꢀ6.95 (m, 2H), 7.12ꢀ7.14 (m ,4H), 7.18ꢀ7.27 (m, 5H), 7.33ꢀ7.38 (m, 4H), 7.61ꢀ7.63 (m,
2H), 7.66ꢀ7.69 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 108.4, 121.0, 121.1, 122.3, 123.7, 125.5, 127.9, 128.3,
128.7, 129.2, 130.0, 130.6, 131.5, 145.2, 146.1, 152.5. HRMS (EIꢀTOF) m/z: M+ calcd for C28H20BrNO:
465.0728; found: 465.0725.
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1ꢀ(2ꢀ(4ꢀbromophenyl)ꢀ5ꢀphenylfuranꢀ3ꢀyl)piperidine (3m): Colorless liquid, 92 mg (48% yield). 1H NMR (400
MHz, CDCl3) δ 1.53ꢀ1.56 (m, 2H), 1.67ꢀ1.73 (m, 4H), 2.83ꢀ2.86 (m, 4H), 6.71 (s, 1H), 7.20ꢀ7.26 (m, 1H),
7.35ꢀ7.38 (m, 2H), 7.48ꢀ7.50 (m, 2H), 7.66ꢀ7.69 (m, 2H), 7.83ꢀ7.85 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 24.0,
26.2, 53.5, 102.2, 119.3, 123.5, 125.3, 127.4, 128.6, 130.4, 130.6, 131.4, 139.9, 140.4, 151.3. HRMS (EIꢀTOF)
m/z: M+ calcd for C21H20BrNO: 381.0728; found: 381.0724.
ASSOCIATED CONTENT
Supporting Information
Experimental details and characterization data for all new compounds, Xꢀray crystallographic data (CIF
file). This material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: yyliu@chem.ecnu.edu.cn.
*Eꢀmail: yzli@chem.ecnu.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank the National Natural Science Foundation of China (Grant No. 21272074) and Program for
Changjiang Scholars and Innovative Research Team in University (PCSIRT) for financial support.
REFERENCES
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