Palladium-Catalyzed [5+1] Annulation of 2-(1-Arylvinyl) Anilines and α-Diazocarbonyl Compounds toward Multi-functionalized Quinolines

Article abstract of DOI:10.1002/adsc.201701069

A palladium-catalyzed [5+1] annulation of 2-(1-arylvinyl) anilines and α-diazocarbonyl compounds has been developed, affording a series of multi-functionalized quinolines in moderate to good yields. This procedure proceeded with the sequential insertion o

Full text of DOI:10.1002/adsc.201701069

Title: Palladium-Catalyzed [5+1] Annulation of 2-(1-Arylvinyl) Anilines
and α-Diazocarbonyl Compounds toward Multi-functionalized
Quinolines
Authors: Jiawei Zhu, Weiming Hu, Song Sun, Jin-Tao Yu, and Jiang
Cheng
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201701069
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10.1002/adsc.201701069
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial sttaff))
Palladium-Catalyzed [5+1] Annulation of 2-(1-Arylvinyl)
Anilines and α-Diazocarbonyl Compounds toward Multi-
functionalized Quinolines
Jiawei Zhu, Weiming Hu, Song Sun, Jin-Tao Yu and Jiang Cheng*
School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, Jiangsu
Province Key Laboratory of Fine Petrochemical Engineering, Changzhou University, Changzhou, 213164, P. R. China.
Fax: (+86)519-8633-0257; E-mail: jiangcheng@cczu.edu.cn
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))
activities and potential pharmaceutical applications.[6]
Abstract: A palladium-catalyzed [5+1] annulation of 2-
(1-arylvinyl) anilines and α-diazocarbonyl compounds has Besides the traditional methods to access such
been developed, affording a series of multi-functionalized
frameworks,[7]
the
development
of
new
quinolines in moderate to good yields. This procedure
proceeded with the sequential insertion of N-H bond to the
palladium carbene, intramolecular Heck reaction and
decarboxylation steps. In this reaction, alkyl 2-
diazophenylacetates served as C1 building block, which
represents a key compliment to diazo chemistry.
transformation starting from new reaction partners
remains an active research area.
Scheme 1. Some Typical Reactions Involving α-
Diazocarbonyl Compounds.
keywords:
palladium-catalyzed;
annulation;
α-
diazocarbonyl compounds; 2,4-aryl quinolines
α-Diazocarbonyl compounds have been
extensively considered as metal carbene
precursors in [n+2] cyclizative annulation toward
heterocyclic compounds, where they served as C2
subunits (Scheme 1, eq 1).[1] Meanwhile, α-
diazocarbonyl compounds were widely applicable
in the insertion reaction to X-H (X = OR, SR,
NHR, SiH2R) bonds (Scheme 1, eq 3).[2] We
believe the further transformation of metal species
after the insertion of metal carbenes to X-H bonds
would be beneficial to construct the final products
with diversities (Scheme 1, eq 4).[3]
Initially, we test the reaction of 2-(1-
phenylvinyl)aniline 1a (0.2 mmol), ethyl 2-diazo-2-
phenylacetate 2a (0.4 mmol) in the presence of PdCl2
(10 mol%), DTBP or K2S2O8 (0.4 mmol) and K2CO3
With this regard, herein, we wish to report a [5+1]
procedure proceeding with the sequential insertion of
N-H bonds to the palladium carbenes derived from α-
diazocarbonyl compounds,[4] intramolecular Heck
reaction and decarboxylation steps toward multi-
functionalized quinolones (Scheme 1, eq 2). Notably,
o
(0.6 mmol) in diglyme under N2 at 150 C. However,
only trace of the desired product was detected (Table
1, entries 1 and 2). Screening other oxidants revealed
that O2 gave the best result (35%, Table 1, entry 3).
Replacing diglyme with DMSO or DMF increased the
yield to 62% and 65%, respectively (Table 1, entries 4
and 5).To our delight, the reaction efficiency
increased to 68% by using DMAc as the solvent
during
this
transformation,
α-diazocarbonyl
compounds served as C1 subunits in the cyclization
rather than C2 building blocks, which represents a
key compliment to diazo chemistry.[5] The annulated
product 2,4-disubstituted quinoline is one of the
ubiquitous structural motifs with important biological
1
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10.1002/adsc.201701069
Advanced Synthesis & Catalysis
(Table 1, entry 6). Other palladium salts such as reactivity with those analogues possessing electron-
Pd(OAc)2 (48%) and Pd2(dba)3 (43%) were inferior to withdrawing groups (3o and 3m, 52% and 54%).
PdCl2 (Table 1, entries 7 and 8). Among the bases Moreover, the steric hindrance did not hamper the
tested, such as KOtBu (< 5%), DBU (10%), and Et3N reaction, as 3n and 3p were isolated in 72% and 52%
(< 5%) were all inferior to K2CO3 (Table 1, entries 9- yields,
respectively.
Notably,
2-(1-
11). The reaction efficiency decreased under lower methylethenyl)aniline took part in the reaction,
temperature (Table 1, entry 12). Finally, the blank providing 3t in 48% yield. Moreover, this procedure
reaction revealed that the reaction did not work was not limited to terminal alkene, and 2-[(1E)-1-
without PdCl2, O2 or K2CO3 (Table 1, entry 8, 11-12). phenyl-1-propen-1-yl]benzenamine took part in this
transformation,
providing
3-methyl-2,4-
Table 1. Screening the optimized reaction condition.[a]
diphenylquinoline 3r in 78% yield.
Table 2. Scope of 2-(1-Arylvinyl) Anilines.[a]
Entry
Pd
Oxidant
DTBP
Base
Solvent
diglyme
diglyme
Yield(%)[a]
< 5
1
2
PdCl2
PdCl2
K2CO3
K2CO3
K2S2O8
< 5
3
4
PdCl2
PdCl2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
KOtBu
DBU
diglyme
DMSO
DMF
35
62
5
PdCl2
65
6
PdCl2
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
68
7
Pd(OAc)2
Pd2dba3
PdCl2
48
8
43
9
< 5
10
11
12
13
PdCl2
10
PdCl2
Et3N
< 5
PdCl2
K2CO3
K2CO3
58[c], 65[d]
0[e]
PdCl2
[a] Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), [Pd]
(10 mol%), base (0.6 mmol), solvent (3.0 mL), O2 (1 atm),
at 150 oC for 24 h [b] Isolated yield. [c] 120 oC. [d] 140 oC. [e]
In the absence of either PdCl2, O2, or K2CO3. DMSO =
dimethylsulfoxide. DMF = N,N-dimethylforamide. DMAc
=
dimethylacetamide.
DBU
=
1,8-
diazabicyclo[5.4.0]undec-7-ene.
With the optimized reaction conditions in hand,
the scope and limitation of 2-(1-arylvinyl) anilines
were studied (Table 2). First, substrates with
substitutions on the aniline moiety were tested.
Generally, the reaction efficiency was not sensitive to
the electronic property of the groups on the anilines as
substrates bearing both electron-donating (3b-3d, 63-
73%) and electron-withdrawing groups (3e-3f, 62%-
68%) all worked well to deliver the desired products
in moderate to good yields. The substrates possessing
substitutents at ortho- and meta- positions also
worked well, leading to corresponding 2,4-
diarylquinoline derivatives in 53% (3g) and 64% (3h)
yields. To our delight, 2-(1-phenylvinyl)naphthalen-1-
amine also ran smoothly under the standard
conditions to afford the desired products 3s in 62%
yield. Secondly, substrates with substituted aryl on
the alkene moiety were also tested. Substrates with
electron-donating groups on the aryl attached in the
vinyl (3k, 3l, 3n and 3o, 48-72%) showed similar
[a] Reaction conditions: 1a (0.2 mmol), 2 (0.4 mmol), PdCl2
(0.02 mmol, 3.4 mg), K2CO3 (0.6 mmol, 82.9 mg), DMAc
o
(3.0 mL), O2 (1 atm), at 150 C for 24 h, in a sealed
Schlenk tube.
Next, the scope and limitation of α-diazocarbonyl
compounds were also investigated. As shown in
Scheme 2, the substrates bearing both electron-
donating and electron-withdrawing groups all worked
well to deliver the desired products in moderate to
good yields (3u-3x, 61%-68%). Notably, the
hindrance in aryl in α-diazocarbonl compounds had
almost no effect on the reaction efficiency (3x, 58%).
Moreover, methyl- (67%), ethyl- (68%) and benzyl-
2
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10.1002/adsc.201701069
Advanced Synthesis & Catalysis
(67%) 2-diazophenylacetates provided comparable produces the Pd(II) species C. After that, an
yields.
intramolecular Heck reaction takes place leading to
intermediate D. Then the procedure proceeds with β-
H elimination leading to intermediate E, along with
HPdCl species, which enter the catalytic cycle by
sequential reductive elimination to Pd(0) and
oxidation by O2.[8] Third, the hydrolization of E
produces intermediate F, which loses CO2 toward
intermediate G. Finally, the aromatization of E
affords the final product 3.
Scheme 2. Scope of α-diazocarbonyl compounds [a]
[a]
Reaction conditions: 1a (0.2 mmol), 2 (0.4 mmol),
PdCl2 (0.02 mmol, 3.4 mg), K2CO3 (0.6 mmol, 82.9 mg),
DMAc (3.0 mL), O2 (1 atm), at 150 oC for 24 h, in a sealed
Schlenk tube.
The practicability of this transformation was
further increased as 3a was isolated in an acceptable
67% yield in a 1 mmol scale reaction.
Some control experiments were conducted to get
insights into this transformation. The potential
intermediates B and E were detected under the
standard procedure (Scheme 3, eq 1) and all could
transform into the final product in comparable yields
(Scheme 3, eqs 2 and 3). Although the isolation of G
failed, intermediate G was detected by GC-MS too.
Scheme 4. A tentative mechanism.
In conclusion, we have developed a palladium-
catalyzed annulation of 2-(1-arylvinyl) anilines with
commercially available α-diazocarbonyl compounds,
affording a series of multi-functionalized quinolones
in moderate to good yields. This procedure proceeds
with the sequential insertion of N-H bonds to the
palladium carbenes, intramolecular Heck reaction and
decarboxylation steps. α-Diazocarbonyl compounds
served as C1 building blocks for the construction of
multi-functionalized quinolones, representing a key
compliment to the diazo chemistry.
Experimental Section
Experimental Details
Synthesis of Multi-functionalized Quinolines
Under oxygen, a 20 mL Schlenk tube equipped with a stir
bar was charged with 2-(1-substituted vinyl) anilines (0.2
mmol), aryldiazo esters (0.4 mmol), PdCl2 (0.02 mmol),
K2CO3 (0.6 mmol), DMAc (3 mL). The tube was sealed
with a Teflon lined cap. The reaction mixture was stirred at
150 °C for 24 h in oil bath. After the completion of the
reaction, the solvent was concentrated in vacuum and the
residue was purified by flash column chromatography on
silica gel with petroleum ether-EtOAc （V1/V2 = 50:1）
as the eluent to give the desired product.
Scheme 3. Preliminary mechanism study.
Based on these experimental results, a proposed
mechanism was outlined in Scheme 4. First, in the
presence of Pd(II), after the extrusion of N2,
palladium carbene A is formed. Then, the insertion of
N-H to palladium carbene A produces intermediate B,
along with PdCl2. Second, in the presence of base and
PdCl2, after the α-deprotonation of intermediate B
Acknowledgements
3
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10.1002/adsc.201701069
Advanced Synthesis & Catalysis
We thank the National Natural Science Foundation of China (no.
11483-11486. f) I. Aviv and Z. Gross, Chem. Commun.
2006, 4477-4479.
21572025), “Innovation
&
Entrepreneurship Talents”
Introduction Plan of Jiangsu Province, the Key University
Science Research Project of Jiangsu Province (15KJA150001),
Jiangsu Key Laboratory of Advanced Catalytic Materials
&Technology (BM2012110) and Advanced Catalysis and Green
Manufacturing Collaborative Innovation Center for financial
support. Sun thanks the National Natural Science Foundation of
China (no. 21602019) and Young Natural Science Foundation of
Jiangsu Province (BK20150263) for financial support. Yu thanks
the National Natural Science Foundation of China (no.
21672028).
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4
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10.1002/adsc.201701069
Advanced Synthesis & Catalysis
COMMUNICATION
Palladium-Catalyzed [5+1] Annulation of 2-(1-
Arylvinyl)
Compounds
Quinolines
Anilines
toward
and
α-Diazocarbonyl
Multi-functionalized
Adv. Synth. Catal. 2017, XX, Page – Page
Jiawei Zhu, Weiming Hu, Song Sun, Jin-Tao Yu
and Jiang Cheng*
5
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