Synthesis of polycyclic substituted vinylarenes via a one-pot intramolecular aryl alkylation-N-tosylhydrazone insertion reaction

Article abstract of DOI:10.1039/c4cc00809j

A novel method of a palladium-catalyzed/norbornene-mediated intramolecular C-H activation/N-tosylhydrazones insertion reaction is developed. In this process, various bicyclic or tricyclic substituted vinylarenes are obtained with high efficiency under mild conditions. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc00809j

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COMMUNICATION
Synthesis of polycyclic substituted vinylarenes
via a one-pot intramolecular aryl alkylation–
N-tosylhydrazone insertion reaction†
Cite this: Chem. Commun., 2014,
50, 3882
Received 30th January 2014,
Accepted 14th February 2014
Xin-Xing Wu, Ping-Xin Zhou, Li-Jing Wang, Peng-Fei Xu* and Yong-Min Liang*
DOI: 10.1039/c4cc00809j
www.rsc.org/chemcomm
A novel method of a palladium-catalyzed/norbornene-mediated
intramolecular C–H activation/N-tosylhydrazones insertion reac-
tion is developed. In this process, various bicyclic or tricyclic
substituted vinylarenes are obtained with high efficiency under
mild conditions.
Scheme 1 One pot Pd-catalyzed coupling of N-tosylhydrazones and aryl
halides with tethered alkyl halides for the synthesis of polycyclic substituted
vinylarenes. X, Y = I, Br. n = 1, 2, 3.
Palladium-catalyzed cascades involving direct C–H bond activa-
tion have emerged as powerful tools for rapid access to complex
highly functionalized structures.1 The Catellani reaction2 offers
a unique approach to activate the ortho C–H bonds of aryl Pd-catalyzed cross-coupling with aryl halides affording the desired
halides and to provide dual functionalizations at both the ipso- alkene products.12 However, to our knowledge, applying diazo
and ortho-positions.3 In the past years, many Catellani-type compounds to the palladium-catalyzed Catellani reaction has not
reactions have been reported. Seminal work by Catellani utilizing been explored in the literature to date. In this context, we report a
terminal alkynes4 or olefins5 as the coupling partners to trap the coupling of N-tosylhydrazones and aryl halides with tethered alkyl
aryl–Pd complex provided various phenanthrenes and vinylbiphenyl halides. This strategy allows rapid assembly of oxygen or nitrogen
compounds. After Catellani’s work, some terminal reagents such as containing heterocyclic systems from alkyl halides under
arylboronic acids,6 reductants7 were reported. In 2006, a palladium- palladium and norbornene-mediated conditions, which then
catalyzed tandem intramolecular ortho alkylation–cyanation react with N-tosylhydrazones through an efficient sequence of
reaction for the synthesis of annulated heterocycles using CN Pd carbene migratory insertion and b-H elimination leading to
anions in the termination step was further developed by the formation of two separate C–C bonds (Scheme 1).
Lautens and co-workers.8 But almost all of these transforma-
After optimizing the reaction conditions, we employed aryl
tions involved the types of terminal couplings that are limited iodide (1a) (1.0 equiv.), N-tosylhydrazone (2a) (2.0 equiv.), Pd(OAc)2
to Heck, Suzuki, Cassar–Sonogashira or hydrogenolysis reac- (10 mol%), PPh3 (20 mol%), Cs2CO3 (5.0 equiv.), H2O (5.0 equiv.),
tions. Therefore, among the various new developments in and norbornene (1.0 equiv.) in dioxane (0.1 M) at 80 1C (for details,
modified Catellani cross-coupling reactions, the expansion of see the ESI†).
cross-coupling partners is particularly desirable.
We examined the scope of the reaction with a number of
On the other hand, numerous examples of palladium- N-tosylhydrazones with different substitution patterns (Scheme 2).
catalyzed multiple insertion of diazo compounds have been The reaction system displayed good tolerance toward a range of
reported.9,10 In 2001, Van Vranken reported the catalytic cross- functional groups. Aromatic groups bearing electron-donating
coupling using (trimethylsilyl)diazomethane as the coupling (products 3c, 3e, 3h, 3j) or electron-withdrawing substituents
partner in Pd-catalyzed reactions.11 Barluenga and co-workers (products 3b, 3d, 3f, 3g, 3i, 3k) were all tolerated. Steric
demonstrated the application of N-tosylhydrazones in the hindrance had little effect on this transformation, both ortho-
and meta-substituted N-tosylhydrazones exhibited good reactivity.
State Key Laboratory of Applied Organic Chemistry, Lanzhou University,
1,2-Diphenylethanyl and 1-(naphthalen-2-yl)ethanyl substituted
N-tosylhydrazones were good substrates for this transforma-
tion, which smoothly afforded the desired products 3l and 3m
Lanzhou 730000, China. E-mail: liangym@lzu.edu.cn, xupf@lzu.edu.cn;
Fax: +86-931-8912582; Tel: +86-931-8912582
† Electronic supplementary information (ESI) available. CCDC 981261 (3o). For
in 92% and 66% yields, respectively. Additionally, the corre-
sponding 3,4-dihydronaphthalenyl substituted N-tosylhydrazone
ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c4cc00809j
3882 | Chem. Commun., 2014, 50, 3882--3884
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Table
1
Synthesis of bicyclic vinylarenes via
a
palladium-catalyzed/
norbornene-mediated tandem reactiona
Entry
1
Substrates
Products
Yieldb (%)
89
61
60
49
2
55
60
3
4
5
Scheme 2 Pd-catalyzed synthesis of five-membered heterocycles. General
reaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), Pd(OAc)2 (10% mmol), PPh3
(20% mmol), Cs2CO3 (5.0 equiv.), norbornene (1.0 equiv.), dioxane (2 ml), H2O
(5.0 equiv.), 80 1C, 16 h.
87
82
was compatible with the reaction conditions and was converted
into 3n in 78% yield. Notably, the synthesis of nitrogen-
containing heterocyclic products also proved to be very
efficient which were obtained in moderate to good yields
(products 3o–s).
76
48
The scope of the aryl halides was investigated next (Table 1).
We also investigated the feasibility of using aryl bromides
under the optimized reaction conditions. To our delight, sub-
strate 1a and 1b were transformed into the five-membered ring
oxacycle 3a in 89% and 61% yields, respectively. Considering
the reaction, maybe 1b is less competitive toward Pd(0) oxida-
tive addition than aryl iodide 1a. Extension to larger ring
systems was also possible under these conditions affording
the desired six- and seven-membered rings in moderate to good
59
38
6
a
Conditions: 1 (0.2 mmol), 2a (0.4 mmol), Pd(OAc)2 (10% mmol), PPh3
(20% mmol), Cs2CO3 (5.0 equiv.), norbornene (1.0 equiv.), dioxane
(2 ml), H2O (5.0 equiv.), 80 1C, 16 h. Yield of the isolated product.
b
To fully demonstrate the applicability of this methodology,
yields. Interestingly, the methyl containing aryl iodides exhi- we attempted using a substrate lacking an ortho substituent 1t,
bited higher reactivity than aryl bromides except in the case tosylhydrazone 2a and alkyl iodide 6a for the multicomponent
of entry 3. However, the methoxy containing aryl iodides reaction. We were able to obtain the product in satisfactory
with tethered alkyl iodide were less reactive than tethered alkyl yield (Scheme 3).
bromide (entries 4–6).
In summary, we have developed a distinct strategy to syn-
Following the success of the formation of the bicyclic sub- thesize polycyclic substituted vinylarenes using a palladium-
strates, we explored the possibility of tricyclic products through catalyzed/norbornene-mediated tandem ortho alkylation–metal
a double ortho-alkylation–carbene migratory insertion and b-H carbene insertion reaction system. This method has been
elimination sequence (Table 2). Gratefully, the 5, 6, 5-ring applied toward the synthesis of a variety of synthetically useful
system product 5a was prepared in 81% yield (entry 1), While bicyclic and tricyclic vinylarenes products. The reaction features
the larger 6, 6, 6- and 7, 6, 7-ring systems were only generated in good yields, excellent functional-group tolerance, and a wide
46% and 42% yields, respectively (entries 2 and 3). In addition, compatibility of structurally and electronically varied substrates,
tricyclic compound 5d was prepared in 79% yield from the making it applicable to structurally complex compounds. In
corresponding p-methoxy N-tosylhydrazone (entry 4).
addition, this modified Catellani-type C–H activation provides
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Table 2 Synthesis of tricyclic vinylarenes via a palladium-catalyzed/
norbornene-mediated tandem reactiona
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Entry
1
Substrates
Products
Yieldb (%)
81
2
3
46
42
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79
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a
Conditions: 4 (0.2 mmol), 2 (0.4 mmol), Pd(OAc)2 (10% mmol), PPh3
(20% mmol), Cs2CO3 (5.0 equiv.), norbornene (2.0 equiv.), dioxane
(4 ml), H2O (5.0 equiv.), 80 1C, 16 h. Yield of the isolated product.
b
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Scheme 3 Three component reaction. Conditions: 1t (0.2 mmol), 2a
(0.4 mmol), 6a (0.6 mmol), Pd(OAc)2 (10% mmol), PPh3 (20% mmol),
Cs2CO3 (5.0 equiv.), norbornene (2.0 equiv.), dioxane (4 ml), H2O (5.0 equiv.),
80 1C, 16 h.
´
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broad implications for developing various dual functionaliza-
tions of aryl halides.
We thank the National Science Foundation (NSF 21072080
and 21272101), National Basic Research Program of China
(973 Program) 2010CB833203 and "111" program of MOE and
PCSIRT: IRT1138 for financial support.
´
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3884 | Chem. Commun., 2014, 50, 3882--3884
This journal is ©The Royal Society of Chemistry 2014