Nickel-catalyzed efficient and practical Suzuki-Miyaura coupling of alkenyl and aryl carbamates with aryl boroxines

Article abstract of DOI:10.1021/ol9029534

(Figure Presented) Suzuki-Miyaura coupling of unactivated alkenyl carbamates Is described to construct polysubstituted olefins. The developed process is also suitable for heteroaromatic and even electron-rich aromatic carbamates.

Full text of DOI:10.1021/ol9029534

ORGANIC
LETTERS
2010
Vol. 12, No. 4
884-887
Nickel-Catalyzed Efficient and Practical
Suzuki-Miyaura Coupling of Alkenyl
and Aryl Carbamates with Aryl
Boroxines
Li Xu,†,‡ Bi-Jie Li,*,† Zhen-Hua Wu,† Xing-Yu Lu,† Bing-Tao Guan,† Bi-Qin Wang,‡
Ke-Qing Zhao,‡ and Zhang-Jie Shi*,†,§
Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of
Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of
Chemistry and Green Chemistry Center, Peking UniVersity, Department of Chemistry,
Sichuan Normal UniVersity, Chengdu, Sichuan, and State Key Laboratory of
Organometallic Chemistry, Chinese Academy of Sciences, Shanghai, China
zshi@pku.edu.cn; libi@pku.edu.cn
Received December 24, 2009
ABSTRACT
Suzuki-Miyaura coupling of unactivated alkenyl carbamates is described to construct polysubstituted olefins. The developed process is also
suitable for heteroaromatic and even electron-rich aromatic carbamates.
Suzuki-Miyaura coupling has become one of the most
versatile synthetic methods in organic synthesis.1 The easy
availability of boron reagents, broad functional group toler-
ance, and general applicability of the reaction contributed
to its increasing importance in both academic research and
industrial production.2 In the past several decades, significant
efforts have been made in catalyst/ligand development, thus
expanding the coupling partner from aryl iodide/bromide and
triflate to relatively unreactive aryl chloride and tosylate/
mesylate.3 In this context, the identification of a new coupling
partner would have significant impact on Suzuki-Miyaura
coupling.4
Aryl carboxylates, derived from phenols, appeared to be
particularly appealing since they are abundant and easily
available. Recently, Garg’s group and our group have
independently developed the nickel-catalyzed Suzuki-Miyaura
coupling of aryl carboxylates.5 The substrate scope of this
type of Suzuki-Miyaura coupling could be further extended
to activated vinyl acetates.6 Despite these significant ad-
vances, the full potential of this reaction has not been
† Peking University.
‡ Sichuan Normal University.
(2) (a) Buchwald, S. L.; Martin, R. Acc. Chem. Res. 2008, 41, 1461.
(b) Wu¨rtz, S.; Glorius, F. Acc. Chem. Res. 2008, 41, 1523. (c) Molander,
G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275. (d) Molander, G. A.;
Canturk, B. Angew. Chem., Int. Ed. 2009, 48, 9240. (e) Miyaura, N. Top.
Curr. Chem. 2002, 219, 11. (f) Tobisu, M.; Chatani, N. Angew. Chem., Int.
Ed. 2009, 48, 3565.
§ Chinese Academy of Sciences.
(1) (a) Diederich, F.; Stang, P. J., Eds. Metal-catalyzed cross-coupling
reactions; Wiley-VCH: Weinheim, 1998. (b) Miyaura, N.; Suzuki, A. Chem.
ReV. 1995, 95, 2457. (c) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.;
Lemaire, M. Chem. ReV. 2002, 102, 1359.
10.1021/ol9029534  2010 American Chemical Society
Published on Web 01/25/2010

exploited since it suffered from several limitations. First, the
catalyst loading was usually high. Second, specific substrates
such as naphthyl, activated phenyl, and styryl carboxylates
were required to obtain satisfactory results.5 Unactivated
aromatic carboxylate reacted poorly, while vinylic carboxy-
late has not even been reported to undergo successful reaction
by nickel catalysis.5,6 Thus, we set out to address these issues
to make this chemistry more practical. In our continuing
efforts in C-O bond activation, we report here the nickel-
catalyzed Suzuki-Miyaura coupling of both unactivated
alkenyl and phenyl carbamates.7 The use of carbamate as a
protecting group provided further synthetic opportunity due
to its well-known ability in directed ortho metalation (DoM)
pioneered by Snieckus.8
We initially chose the unactivated alkenyl carboxylate as
the substrate, which was readily available and synthetically
useful.1-CyclohexenylacetatewasfirstappliedtoSuzuki-Miyaura
coupling. Unfortunately, the desired C-C formation com-
pletely failed, with most of the cyclohexanone recovered.
Other carboxylates were tested but failed. To our surprise, a
change of the protecting group to carbamate resulted in a
remarkable improvement of efficiency.8b,c N,N-Dimethyl
cyclohexenyl carbamate 1a engaged in the coupling reaction
Scheme 1. Cross-Coupling of Unactivated Vinyl Carbamate
in a good yield. Further systematic studies indicated that the
coupling between carbamate 1a and phenyl boroxine 2a ran
very smoothly in the presence of Ni(PCy3)2Cl2 (5.0 mol %)
and PCy3 (10.0 mol %) as a catalyst, K2CO3 (2.0 equiv) as
a base, and an adequate amount of water as an additive. The
arylated product 3a was isolated in 85% yield (Scheme 1).
This is the first successful example to construct such an
arylated olefin from unactivated alkenyl carbamates.
Table 1. Cross-Coupling between 1 and Phenyl Boroxinesa
(3) (a) Bohm, V. P. W.; Weskamp, T.; Gstottmayr, C. W. K.; Herrmann,
W. A. Angew. Chem., Int. Ed. 2000, 39, 1602. (b) Herrmann, W. A.; Elison,
M.; Fischer, J.; Kocher, C. G.; Artus, R. J. Angew. Chem., Int. Ed. 1995,
34, 2371. (c) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc.
1998, 120, 9722. (d) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 1999,
121, 1473. (e) Fu¨rstner, A.; Leitner, A.; Me´ndez, M.; Krause, H. J. Am.
Chem. Soc. 2002, 124, 13856. (f) Littke, A. F.; Fu, G. C. Angew. Chem.,
Int. Ed. 2002, 41, 4176. (g) Nguyen, H. N.; Huang, X.; Buchwald, S. L.
J. Am. Chem. Soc. 2003, 125, 11818. (h) Tang, Z.-Y.; Hu, Q.-S. J. Am.
Chem. Soc. 2004, 126, 3058. (i) So, C. M.; Lau, C. P.; Kwong, F. Y. Angew.
Chem., Int. Ed. 2008, 47, 8059. (j) Zhang, L.; Wu, J. J. Am. Chem. Soc.
2008, 130, 12250. (k) Ackermann, L.; Althammer, A.; Born, R. Angew.
Chem., Int. Ed. 2006, 45, 2619. (l) Brennfu¨hrer, A.; Neumann, H.; Beller,
M. Angew. Chem., Int. Ed. 2009, 48, 4114. (m) Marion, N.; Nolan, S. P.
Acc. Chem. Res. 2008, 41, 1440.
(4) (a) Wenkert, E.; Michelotti, E. L.; Swindell, C. S. J. Am. Chem.
Soc. 1979, 101, 2246. (b) Dankwardt, J. W. Angew. Chem., Int. Ed. 2004,
43, 2428. (c) Guan, B.; Xiang, S.; Wu, T.; Wang, B.; Zhao, K.; Shi, Z.
Chem. Commun. 2008, 1437. (d) Ueno, S.; Chatani, N.; Kakiuchi, F. J. Am.
Chem. Soc. 2007, 129, 6098. (e) Blakey, S. B.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2003, 125, 6046. (f) Kakiuchi, F.; Usui, M.; Ueno, S.; Chatani,
N.; Murai, S. J. Am. Chem. Soc. 2004, 126, 2706. (g) Ueno, S.; Mizushima,
E.; Chatani, N.; Kakiuchi, F. J. Am. Chem. Soc. 2006, 128, 16516. (h)
Tobisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem., Int. Ed. 2008, 47,
4866. (i) Shi, Z.; Li, B.; Wan, X.; Cheng, J.; Fang, Z.; Cao, B.; Qin, C.;
Wang, Y. Angew. Chem., Int. Ed. 2007, 46, 5554. (j) Gonza´lez-Bobes, F.;
Fu, G. C. J. Am. Chem. Soc. 2006, 128, 5360. (k) Netherton, M. R.; Fu,
G. C. Angew. Chem., Int. Ed. 2002, 41, 3910.
a All the reactions were carried out on the scale of 0.25 mmol of 1,
0.30 mmol of 2a, 0.0125 mmol of Ni(PCy3)2Cl2, 0.025 mmol of PCy3, 0.50
mmol of K2CO3, and 0.25 mmol of H2O in 5 mL of dioxane at 110 °C for
16 h. b E:Z ) 5:1.
(5) Guan, B.-T.; Wang, Y.; Li, B.-J.; Yu, D.-G.; Shi, Z.-J. J. Am. Chem.
Soc. 2008, 130, 14468. (b) Quasdorf, K. W.; Tian, X.; Garg, N. K. J. Am.
Chem. Soc. 2008, 130, 14422. For a highlight and a computational study,
see: (c) Goossen, L. J.; Goossen, K.; Stanciu, C. Angew. Chem., Int. Ed.
2009, 48, 3569. (d) Li, Z.; Zhang, S.-L.; Fu, Y.; Guo, Q.-X.; Liu, L. J. Am.
Chem. Soc. 2009, 131, 8815. For Negishi and Kumada couplings, see: (e)
Li, B.-J.; Li, Y.-Z.; Lu, X.-Y.; Liu, J.; Guan, B.-T.; Shi, Z.-J. Angew. Chem.,
Int. Ed. 2008, 47, 10124. (f) Li, B.-J.; Xu, L.; Wu, Z.-H.; Guan, B.-T.;
Sun, C.-L.; Wang, B.-Q.; Shi, Z.-J. J. Am. Chem. Soc. 2009, 131, 14656.
(6) (a) Sun, C.-L.; Wang, Y.; Zhou, X.; Wu, Z.-H.; Li, B.-J.; Guan,
B.-T.; Shi, Z.-J. Chem. Eur. J. 2009,accepted. DOI: chem.200902785. For
rhodium-catalyzed reactions of several vinyl acetates, see: (b) Yu, J.-Y.;
Kuwano, R. Angew. Chem., Int. Ed. 2009, 48, 7217.
To explore the substrate scope, we investigated different
alkenyl carbamates. Obviously, starting from activated R,ꢀ-
unsaturated cyclic ketone 1b, the desired cross-coupling
product was afforded in an excellent yield. Both linear and
cyclic R,ꢀ-unsaturated esters 1c and 1d were also suitable
substrates, and the desired arylated products 3c and 3d were
isolated in good to excellent yields (Table 1). Both 1-stilbenyl
carbamate 1e and 1-styryl carbamate 1f were further submit-
ted, and the corresponding cross-coupling also occurred
smoothly. It is important to note that, unlike vinyl acetates,
both carbamates located at the 1- or 2-position of the styrene
(7) During the preparation of this manuscript, contributions from the
groups of Garg and Snieckus appeared: (a) Quasdorf, K. W.; Riener, M.;
Petrova, K. V.; Garg, N. K. J. Am. Chem. Soc. 2009, 131, 17748. (b) Antoft-
Finch, A.; Blackburn, T.; Snieckus, V. J. Am. Chem. Soc. 2009, 131, 17750.
(8) (a) Snieckus, V. Chem. ReV. 1990, 90, 879. (b) Sengupta, S.; Leite,
M.; Raslan, D. S.; Quesnelle, C.; Snieckus, V. J. Org. Chem. 1992, 57,
4066. (c) Yoshikai, N.; Matsuda, H.; Nakamura, E. J. Am. Chem. Soc. 2009,
131, 9590.
Org. Lett., Vol. 12, No. 4, 2010
885

With this developed efficient method, we further investi-
gated the electron-rich aromatic system, which was more
challenging in Suzuki-Miyaura coupling due to the deac-
tivation by the electron-donating substituents (Table 2). To
our satisfaction, with a carbamate as a leaving group, the
cross-coupling took place smoothly with phenylboroxine as
a nucleophile in good efficiency, regardless of whether a
methoxyl or a N,N-dimethylamino group was equipped under
our developed condition (entries 1 and 2). Undoubtedly,
activated aromatic substrates such as 2-naphthyl carbamate
and phenyl carbamates with electron-withdrawing groups
gave better results (entries 3-6). With the p-resorcinol
derived dicarbamate, double arylation was also observed, and
terphenyl was produced in one step in good yield (entry 7).
Although generally pyridinyl and quinolyl derivatives tend
to deactivate the catalytic reactivity of nickel complexes, our
system was also suitable for such substrates, and the desired
products were produced in good yields (entries 8 and 9).
Scheme 2
.
Cross-Coupling at Lower Catalyst Loading and
Larger Scale
derivatives are suitable substrates.6 Notably, such cross-
coupling took place well in the presence of 1.0 mol % of
catalyst loading without a decrease in the efficiency (Scheme
2). To explore the application of such transformations, this
cross-coupling was scaled up to 5.0 mmol without a decrease
of the efficiency.
Table 2. Ni-Catalyzed Cross-Coupling of Various Aryl
Carbamates 5 with 2aa
Figure 1. Ni-catalyzed coupling products of various boroxines 2.
The reactions of different substituted aryl boroxines with
slightly unreactive alkenyl carbamate 1g were subsequently
investigated (Figure 1). Sterically hindered ortho-methyl
phenyl boroxine did not affect the yield. Electron-withdraw-
ing and electron-donating groups on the phenyl boroxine had
no impact on the efficiencies. Various functional groups such
as methoxy and fluoro groups were compatible with such
mild conditions, which provided an opportunity for further
functionalization of the products with various methods.4,9
a All the reactions were carried out in the scale of 0.25 mmol of 5, 0.30
mmol of 2a, 0.0125 mmol of Ni(PCy3)2Cl2 and 0.025 mmol of PCy3, 0.50
mmol of K2CO3, and 0.25 mmol of H2O in 5 mL of dioxane at 110 °C for
16 h.
In summary, we demonstrated the Suzuki-Miyaura cou-
pling of alkenyl carbamates with aryl boroxines to construct
polysubstituted olefins. Such cross-coupling was also suitable
for even electron-rich aryl carbamates. Lower catalyst
loading, easy scaling-up, and a wide range of substrate scope
(9) (a) Bohm, V. P. W.; Gstottmayr, C. W. K.; Weskamp, T.; Herrmann,
W. A. Angew. Chem., Int. Ed. 2001, 40, 3387. (b) Kim, Y. M.; Yu, S.
J. Am. Chem. Soc. 2003, 125, 1696. (c) Ackermann, L.; Born, R.; Spatz,
J. H.; Meyer, D. Angew. Chem., Int. Ed. 2005, 44, 7216. (d) Yoshikai, N.;
Mashima, H.; Nakamura, E. J. Am. Chem. Soc. 2005, 127, 17978.
886
Org. Lett., Vol. 12, No. 4, 2010

make this process applicable to produce complex molecules.
Further exploration of its synthetic utility and mechanistic
investigation is currently underway.
and Fok Ying Tung Education Foundation is gratefully
acknowledged.
Supporting Information Available: Brief experimental
details and other spectral data for products. This material is
available free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. Support of this work by the grant from
NSFC (No. 20872104, 20832002, 20925207, and 20821062)
andthe“973”programfromMOSTofChina(2009CB825300)
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