Rh-catalyzed oxidizing group-directed ortho C-H vinylation of arenes by vinylstannanes

Article abstract of DOI:10.1039/c5cc04211a

An efficient method for the synthesis of functionalized vinyl arenes from the reaction of N-methoxybenzamides or N-phenoxyacetamides with vinylstannanes via rhodium(III)-catalyzed C-H activation is described. The application of the methodology for the synthesis of a natural product thalactamine and a 7-membered ring oxepine are also demonstrated.

Full text of DOI:10.1039/c5cc04211a

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: S. Prakash, K.
Muralirajan and C. H. Cheng, Chem. Commun., 2015, DOI: 10.1039/C5CC04211A.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/chemcomm

Page 1 of 4
ChemComm
View Article Online
DOI: 10.1039/C5CC04211A
Journal Name
RSCPublishing
COMMUNICATION
Rh-Catalyzed Oxidizing Group-Directed ortho C−H
Vinylation of Arenes by Vinylstannanes
Cite this: DOI: 10.1039/x0xx00000x
Sekar Prakash, Krishnamoorthy Muralirajan and ChienꢀHong Cheng*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
methoxybenzamides.8a,8b Even though the reactions were performed
An efficient method for the synthesis of functionalized vinyl
arenes from the reaction of -methoxybenzamides or
phenoxyacetamides with vinylstannanes via a rhodium(III)-
catalyzed C H activation is described. The application of
the methodology for the synthesis of a natural product
thalactamine and 7-membered ring oxepine is also
demonstrated.
in the presence of an oxidizing directing group, the reactions still
require metal oxidants to complete the reaction. Our continuing
interest in the development of new transmetallation reactions has
prompted us to use vinylstannanes as a cross coupling reagent in the
Rh(III)ꢀcatalyzed C−H activation. Herein, we report a new and mild
Rhꢀcatalyzed C−H activation for the synthesis of 2ꢀvinylbenzamides
and 2ꢀvinylphenols via the vinylation of Nꢀmethoxybenzamides and
Nꢀphenoxyacetamides with vinylstannanes. These interesting
reactions proceed with the advantages of no external metal oxidant
N
N-
−
Highly functionalized vinyl arenes are important organic
substrates for the formation of various C−C and C−hetero bonds, and no halides.
particularly, a broad range of styrene derivatives were used in
We started the vinylation reaction using Nꢀmethoxybenzamide 1a
olefination and hydrogenation reactions.1,2 The transitionꢀmetalꢀ
catalyzed coupling reactions such as Stille, Kumada, Negishi and
Hiyama were known for the synthesis of vinyl arenes.3 In particular,
vinylstannanes have been widely used in the synthesis of styrenes.4aꢀ
and vinylstannane 2a as the substrates and [RhCp*Cl2]2 (2 mol %) as
catalyst. The reaction proceeded in the presence of CsOAc (1.1
mmol) in MeOH at 30 °C for 8 h to afford 2ꢀvinylbenzamide (3a) in
95% yield (See S.I, Table 1, entry 7). In the absence of rhodium
complex no product 3a was observed. To understand the nature of
this reaction, different additives and solvents were employed (See
S.I, Table 1). It is important to note that MeOH gave the best result
and afforded 3a in 95% yield (90% isolated yield), whereas DMF, tꢀ
BuOH, DCE, EtOH, THF and H2O gave moderate to less yields of
3a (S.I, Table 1, entries 1ꢀ6). Further, CsOAc gave 3a in 95% yield,
but NaOAc, KOAc and Cu(OAc)2 gave only moderate yields. No 3a
was obtained with AgOAc as an additive. Despite that the product
yield decreases with decreasing amount of acetate source (S.I, Table
1, entry 8). Remarkably, [IrCp*Cl2]2 and [RuCl2(pꢀcymene)]2 were
also suitable catalysts for this transmetallation reaction affording
vinyl product 3a in 78 and 64% yield, respectively. We also
conducted the reactions of 1a with other vinyl metallic reagents
including vinyl magnesium bromide and vinyl zinc chloride in the
presence of [RhCp*Cl2]2, CsOAc in THF, but we did not get any
related products.
d
However, these reported transmetallation reactions required
prefunctionalized arenes, metal oxidants, ligands and strong
activating reagents.4
Scheme 1. Synthetic strategies for vinyl arenes
Rh(III)ꢀcatalyzed C−H olefination of arenes offers great
opportunities for the synthesis of substituted alkene molecules from
halideꢀfree materials.5 The reaction mechanisms were usually via
C−H activation, alkene insertion and βꢀhydride elimination.6 In this
context, a few examples of metalꢀcatalyzed C−H vinylation reactions
were studied,7 but most of the reactions used ethylene gas as
precursor.7a,7b,7d To the best of our knowledge, Rh(III)ꢀcatalyzed
C−H vinylation of aryl rings via transmetallation was not reported.
During the preparation of this manuscript, Ellman reported a Rh(III)ꢀ
catalyzed synthesis of styrenes using vinyl acetate as the vinylating
reagent.7e Recently, Rh(III)ꢀcatalyzed C−H activation followed by
transmetallation was useful for the synthesis of highly functionalized
heterocycles.8 We had developed a Rhꢀcatalyzed [4+2] cyclization
product using aryl boronic acids or aryltrialkoxysilanes with Nꢀ
With the optimized reaction conditions in hand, we explored the
scope of the present reaction. Nꢀmethoxybenzamides with various
functional groups at para position (1bꢀk) provided the
corresponding products (3b-3k) in 70 to 92% yields (Table 1).
Similarly, functional groups at different positions of the aryl rings
were also compatible in the present catalytic reaction (Table 1.
compounds 3l to 3t). However, mꢀMeOꢀ, mꢀClꢀ and mꢀBrꢀNꢀ
methoxybenzamides gave two regioisomeric products (3p, 3s and 3t)
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 1

ChemComm
Page 2 of 4
VJieowuArrtnicalelONnlainme e
COMMUNICATION
DOI: 10.1039/C5CC04211A
as shown in Table 1. Notably, the vinylation of substrate 1r with a phenoxyacetamides (5b and 5c) with vinylstannane (2a) gave the
methylenedioxyl group at meta and para positions of the arene ring corresponding vinylated products 6b and 6c in 78 and 63% yield,
occurred at the more congested ortho position, while products 3s and respectively. Similarly, 4ꢀfluro and 3ꢀchloro Nꢀphenoxyacetamides
3t gave seperable regioisomers with moderate selectivity. The reacted with 2a to afford halogenated vinyl phenols 6d-e in good
present vinylation reaction proceeds smoothly with most of the yields.
functionalized arenes. In addition, hetero arenes such as Nꢀ
methoxyfuranꢀ2ꢀcarboxamide (1u) and Nꢀmethoxythiopheneꢀ2ꢀ
carboxamide (1v) were also successfully employed to afford the 3ꢀ
vinylated products.
Table 1. Synthesis of 2ꢀvinylbenzamides from Nꢀmethoxybenzamidesa,b
Scheme 4. Kinetic isotope effects
Several deuterium experiments were carried out to know the
nature of the present catalytic reaction mechanism (Scheme 4).
Treatment of [D5]ꢀ1a under the standard reaction conditions but
without vinylstannane (2a) gave 89% of D/H exchange at ortho
position indicating that the C−H activation is highly reversible (A).
However, in the presence of 2a, the reaction afforded [D4]ꢀ3a in
82% yield without incorporation of H in the product (B). These
observations clearly suggest that the vinylation by 2a proceeds more
rapidly than the protonation process. Finally, we conducted two
deuterium kinetic isotopic competition experiments to further
understand the nature of the catalytic reaction mechanism. As shown
in Scheme 4, the competition reaction between [D5]ꢀ1a and 1a for
vinylation gave an intermolecular KIE (kH/kD) of 2.33. On the other
hand, an intramolecular competition reaction of oꢀ[D1]ꢀ1a for
vinylation afforded a KIE (kH/kD) of 3.34. The observed interꢀ and
a Unless otherwise mentioned, all reactions were carried out using 1 (1.00
intramolecular isotopic effects of 1a suggested that the C–H bond
cleavage step is plausibly involved in the rateꢀdetermining step.
mmol), 2a (1.50 mmol), [RhCp*Cl2]2 (2 mol %), CsOAc (1.10 mmol) and
MeOH (2.0 mL) at 30 °C for 8 h. b Isolated yield.
[RhIIICp
*Cl2]2
O
O
CsOAc
NH2
OMe
N
H
CsCl
3a
1a
Rh(III)L3
O
O
Scheme
tributyl(styryl)stannane
2.
Reaction
of
Nꢀmethoxybenzamides
with
(E)ꢀ
N
RhIII
OMe
N
RhIII
OMe
I
IV
Additionally, the introduction of a styryl moiety at the ortho
position of Nꢀmethoxybenzamides using (E)ꢀtributyl(styryl)stannane,
was also tested (Scheme 2). The expected oꢀstyrylbenzamides 4a, 4b
and 4c were successfully prepared in reasonable yields.
AcO
SnBu3
SnBu3
2a
O
O
N
OMe
RhIII
N
RhIII
OMe
III
SnBu3
SnBu3
II
O
O
CsOAc
Scheme 5. A plausible reaction mechanism
Based on our observations and the literature precedence, a
plausible mechanism to account for the present catalytic reaction
using 1a and 2a as the substrates is shown in Scheme 5.9 The
catalytic reaction is probably initiated by the exchange of chloride
ligands in [RhCp*Cl2]2 with CsOAc to give RhCp*(OAc)2. Then,
facile cyclometalation of 1a with RhCp*(OAc)2 affords fiveꢀ
membered intermediate I. Further, πꢀcoordination of the vinyl group
Scheme 3. Synthesis of 2ꢀvinylphenols from Nꢀphenoxyacetamides
We also investigated the reaction of Nꢀphenoxyacetamides with
vinylstannane under the same optimized conditions. In this case, the
C−H activation occurs at the oꢀphenoxy group and the reaction
proceeded smoothly to afford 2ꢀvinylphenol (6a) in 76% yield of 2a to the Rh(III) center (II and III)10 and subsequent
(Scheme 3). The catalytic reaction can be extended to electron
donating groupꢀ and haloꢀsubstituted Nꢀphenoxyacetamides. Thus,
transmetallation of vinylstannane in the presence of excess CsOAc
provides intermediate IV.8a,8b The latter then undergoes reductive
treatment of electronꢀdonating 4ꢀmethylꢀ and 3,5ꢀdiꢀmethyl elimination followed by a concerted redox process to give 2ꢀvinyl
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 3 of 4
Journal Name
ChemComm
View Article Online
COMMUNICATION
DOI: 10.1039/C5CC04211A
benzamide and Rh(III) species. In the catalytic reaction,
stoichiometric amount of acetate source is required for the
transmetallation step (see S.I for mechanistic related experiments).
3
(a) D. Milstein and J. K. Stille, J. Am. Chem. Soc. 1978, 100, 3636;
(b) W. J. Scottt and J. K. Stille, J. Am. Chem
. Soc. 1986, 108, 3033;
(c) T. Chatterjee, R. Dey and B. C. Ranu, New J. Chem., 2011, 35
,
1103; (d) A. Akao, T. Tsuritani, S. Kii, K. Sato, N. Nonoyama, T.
Mase and N. Yasuda, Synlett, 2007, 31; (e) W. Susanto, C.ꢀY. Chu,
W. J. Ang, T.ꢀC. Chou, L.ꢀC. Lo and Y. Lam, J. Org. Chem. 2012,
77, 2729.
Two examples of the synthetic application of vinylation products
3 and 6 are shown in Scheme 6. First, we successfully synthesized
3w in 78% in a gramꢀscale reaction. Then 3w was converted to an
important alkaloid thalactamine (8b) in 71% yield under a PdCl2ꢀ
catalyzed condition,11a followed by Nꢀmethylation. It is noteworthy
that thalactamine was generally isolated from thalictrum minus
(ranunculaceae family)11b plants. Second, we isolated 7ꢀmembered
ring oxepine (8c) in good yield from the reaction of 6d with
diphenylacetylene using a reported method .11c
4
(a) A. F. Littke, L. Schwarz and G. C. Fu, J. Am. Chem. Soc. 2002,
124, 6343; (b) S. P. H. Mee, V. Lee and J. E. Baldwin, Angew. Chem.
Int. Ed. 2004, 43, 1132; (c) D.ꢀH. Lee, Y. Qian, JꢀH. Park, JꢀS. Lee,
SꢀE. Shim and M.ꢀJ. Jin, Adv. Synth. Catal. 2013, 355, 1729; (d) S. P.
H. Mee, V. Lee and J. E. Baldwin, Chem. Eur. J. 2005, 11, 3294; (e)
S. E. Denmark and C. R. Butler, Chem. Commun, 2009, 20; (f) T.
Korenaga, A. Ko, K. Uotani, Y. Tanaka and T. Sakai, Angew. Chem.
Int. Ed. 2011, 50, 10703; (g) X. Han, B. M. Stoltz and E. J. Corey, J.
Am. Chem. Soc. 1999
5. (a) S. Rakshit, C. Grohmann, T. Besset and F. Glorius, J. Am. Chem.
Soc. 2011, 133, 2350; (b) T. K. Hyster and T. Rovis, Chem. Commun
, 121, 7600.
.
2011, 47, 11846; (c) X. Zhang, D. Chen, M. Zhao, J. Zhao, A. Jia and
X. Li, Adv. Synth. Catal. 2011, 353, 719; (d) B. Li, J. Ma, N. Wang,
H. Feng, S. Xu and B. Wang, Org. Lett. 2012, 14, 736; (e) C.
Kornhaa, J. Li and L. Ackermann, J. Org. Chem. 2012, 77, 9190; (f)
L. Xu, Q. Zhu, G. Huang, B. Cheng and Y. Xia, J. Org. Chem. 2012,
77, 3017; (g) B. Li, H. Feng, S. Xu and B. Wang, Chem. Eur. J.
2011, 17, 12573; (h) Y. Shang, X. Jie, H. Zhao, P. Hu and W. Su,
Org. Lett. 2014, 16, 416.
Scheme 6. Synthetic applications
In conclusion, we have demonstrated for the first time a rhodiumꢀ
catalyzed C−H ortho vinylation of arenes with vinyl stannanes and
its application in natural product synthesis. The C−H activation and
transmetallation reaction has not been studied yet using any
transition metal as the catalyst. The present protocol features mild
reaction condition and good functional group tolerance. Studies on
the development of new catalytic vinylation reactions and
application in natural product synthesis are currently underway.
6
(a) K. Muralirajan, R. Haridharan, S. Prakash, and C.ꢀH. Cheng, Adv.
Synth. Catal. 2015, 357, 761; (b) K. Parthasarathy and C. Bolm,
Chem. Eur. J. 2014, 20, 4896; (c) S. H. Park, J. Y. Kim and S.
Chang, Org. Lett. 2011, 13, 2372; (d) M. V. Pham and N. Cramer,
Angew. Chem. Int. Ed. 2014, 53, 14575; (e) X.ꢀS. Zhang, Q.ꢀL. Zhu,
Y.ꢀF. Zhang, Y.ꢀB. Li, and Z.ꢀJ. Shi, Chem. Eur. J. 2013, 19, 11898;
Acknowledgements
We thank the Ministry of Science and Technology of the
Republic of China (MOSTꢀ103ꢀ2633ꢀMꢀ007ꢀ001) for support
of this research.
(f) T. Iitsuka, K. Hirano, T. Satoh, and M. Miura, J. Org. Chem
2015, 80, 2804.
.
Notes and references
7. (a) H. Horino and N. Inoue, J. Org. Chem. 1981, 46, 4416; (b) F. W.
Patureau and F. Glorius, J. Am. Chem. Soc. 2010, 132, 9982; (c) Y.
Matsuura, M. Tamura, T. Kochi, M. Sato, N. Chatani and F.
Kakiuchi, J. Am. Chem. Soc. 2007, 129, 9858; (d) S. Rakshit, C.
Department of Chemistry, National Tsing Hua University, Hsinchu
30013, Taiwan. Eꢀmail: chcheng@mx.nthu.edu.tw; Homepage:
http://mx.nthu.edu.tw/%7Echcheng
†
Electronic Supplementary Information (ESI) available: Experimental
Grohmann, T. Besset and F. Glorius, J. Am. Chem. Soc. 2011, 133
2350; (e) K. D. Otley and J. A. Ellman, Org. Lett. 2015 17, 1332. .
,
procedures and characterization for new compounds are provided. See
DOI: 10.1039/c000000x/
,
8
(a) K. Karthikeyan, R. Haridharan and C.ꢀH. Cheng, Angew. Chem.
Int. Ed. 2012, 51, 12343; (b) N. Senthilkumar, K. Parthasarathy, P.
1
(a) J. WencelꢀDelord, T. Droge, F. Liu and F. Glorius, Chem. Soc.
Rev. 2011, 40, 4740; (b) G. Song, F. Wang and X. Li, Chem. Soc.
Rev. 2012, 41, 3651; (c) D. A. Colby, A. S. Tsai, R. G. Bergman and
J. A. Ellman, Acc. Chem. Res. 2012, 45, 814; (e) F. W. Patureau, J.
Gandeepan and C.ꢀH. Cheng, Chem. Asian J. 2013,
Z. Lu, P. Lu, Y.ꢀH. Xu and T.ꢀP. Loh, Org. Lett. 2014, 16, 2614; (d)
K, Chen, H, Li, Y, Li, X.ꢀS, Zhang, Z.ꢀQ, Lei and Z.ꢀJ Shi, Chem.
Sci., 2012, , 16457.
8, 2175; (c) M.ꢀ
.
3
WencelꢀDelord and F. Glorius, Aldrichimica Acta. 2012, 45, 31; (f)
9
(a) A. L. Casado, P. Espinet, A. M. Gallego and J. M. Martinezꢀ
Ilarduya, Chem. Commun. 2001, 339; (b) W. D. Cotter, L. Barbour,
K. L. Namara, R. Hechter and R. J. Lachicotte, J. Am. Chem. Soc.
1998, 120, 11016; (c) M. E. Doster, J. A. Hatnean, T. Jeftic, S. Modi
and S. A. Johnson, J. Am. Chem. Soc. 2010, 132, 11923;. (d) C.
Amatore, A. A. Bahsoun, A. Jutand, G. Meyer, A. N. Ntepe and L.
Ricard, J. Am. Chem. Soc. 2003, 125, 4212.
H. Li, Y. Li, X.ꢀS. Zhang, K. Chen, X. Wang, and Z.ꢀJ. Shi, J. Am.
Chem. Soc. 2011, 133, 1524.
2
(a) F. Kakiuchi and S. Murai, Acc. Chem. Res. 2002, 35, 826; (b) X.
Chen, K. M. Engle, D.ꢀH. Wang and J.ꢀQ. Yu, Angew. Chem., Int.
Ed. 2009, 48, 5094; (c) Y. Wu, J. Wang, F. Mao and F. Y. Kwong,
Chem. Asian J. 2014, 9, 26; (d) L. Ackermann, Chem. Rev. 2011,
111, 1315; (e) T. Satoh and M. Miura, Chem. Eur. J. 2010, 16
11212; (f) D. A. Colby, R. G. Bergman and J. A. Ellman, Chem. Rev
2010, 110, 624.
,
10 P.; Espinet and A. M. Echavarren, Angew. Chem. Int. Ed. 2004, 43
,
.
4704.
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 3

ChemComm
Page 4 of 4
COMMUNICATION
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C5CC04211A
11 (a) T. Izumi. Y. Nishimoto, K. Kohei and A. Kasahara, J.
Hetreocyclic. Chem. 1990, 27, 1419; b) B. D. Krane and M. Shamma,
J. Nat. Prod. 1982, 45, 377; (c) A. Seoane, N. Casanova, N.
Quiñones, J. L. Mascareñas and M. Gulías, J. Am. Chem. Soc. 2014,
136, 834.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012