Ruthenium-catalyzed C6-propenylation reactions of substituted pyridine derivatives: Directed and direct C-H activation

Article abstract of DOI:10.1002/chem.201202379

One stone, two birds: Aryl pyridine derivatives in the presence of allyl bromide and a catalytic amount of [{Ru(p-cymene)Cl₂}₂] undergo an unexpected direct C6-propenylation reaction of the pyridine moiety. A one-pot one-catalyst three-component reaction involving sequential and selective direct and directed C-H activation reactions was also developed (see scheme).

Full text of DOI:10.1002/chem.201202379

COMMUNICATION
DOI: 10.1002/chem.201202379
Ruthenium-Catalyzed C6-Propenylation Reactions of Substituted Pyridine
ꢀ
Derivatives: Directed and Direct C H Activation
Yogesh Goriya and Chepuri V. Ramana*[a]
Dedicated to Professor Gautam R. Desiraju on the occasion of his 60th birthday
ꢀ
C C Bond formation through transition-metal catalyzed
2-aryl pyridine derivatives. The possibility of a directed pro-
penylation reaction under the arylation conditions reported
by the research group of Ackermann was explored in this
regard (Scheme 1).[7] The propenylation reaction was carried
ꢀ
functionalization of aryl/heteroaryl C H bonds has recently
attracted attention because these reactions provide more de-
sirable step- and atom economy than those reactions where
prefunctionalization of aryl/heteroaryl rings is required.[1,2]
Pyridine derivatives are interesting in this regard. On one
hand, the pyridine moiety is one of the conventional func-
tional groups employed as a ligand for directed catalytic
2
ꢀ
functionalizations of aryl C H bonds. On the other hand,
ꢀ
catalytic C H activation reactions that lead to functionaliza-
tion of the pyridine moiety are important because the pyri-
dine moiety is a privileged substructure of biologically
active small molecules, functional organic materials, and li-
gands.[3] Generally, the direct C alkylation of pyridine moiet-
ies require the nitrogen atom to be electron deficient to in-
ꢀ
crease the acidity of C H bond at the C2 position; this re-
quirement can be achieved by using N-oxides, N-iminopyri-
dinium ylides, and pyridine compounds in the presence of
Lewis acids.[4,5] Conversely, in the case of directed alkyla-
tions, the pyridine moiety needs to be electron rich because
the catalytic cycle involves the coordination of the nitrogen
atom with a metal complex.[2] Therefore, the direct function-
Scheme 1. Previous work on the propenylation/allylation of pyridine de-
rivatives.
out using allyl bromide, K2CO3 (2.0 equiv), adamantane-1-
ꢀ
alization of pyridine moieties and pyridine-directed C H ac-
carboxylic acid (AdCO2H, 0.3 equiv), and [{RuACHTUNGTRENNUNG(p-cyme-
tivation reactions have, in general, been approached sepa-
rately by using various transition-metal complexes, which
are usually complexes of palladium, rhodium, ruthenium,
and nickel.[1] Herein, we describe an unexpected direct pro-
penylation of pyridine rings using ruthenium catalysts that
ne)Cl2}2] (A; 2.5 mol%) in either toluene or NMP (N-
methyl-2-pyrrolidone) at 1208C in a screw-capped sealed
tube and gave product 2a, which was isolated in 67% and
63% yield, respectively (Scheme 2). The spectral data of 2a
suggested the presence of an E-configured 2-propenyl group
next to the nitrogen atom of the pyridine moiety. This result
was in contrast to earlier reports on the Ru-catalyzed prope-
ꢀ
are generally employed for directed C H activation reac-
tions. Building on this unexpected reaction, the feasibility of
a one-pot one-catalyst directed ortho-arylation reaction, as
well as a direct C6-propenylation reaction of 2-phenylpyri-
dine was also investigated.
ꢀ
nylation of 1a, reactions that involved C H activation at the
ortho position of the phenyl ring.[6]
The use of other allyl halides in the C6-propenylation re-
action of 1a was examined. The reaction was sluggish with
allyl chloride and there was no reaction with crotyl bromide.
When allyl iodide was employed, although complete con-
sumption of 1a was observed, the product 2a was isolated in
poor yield (Scheme 2). Interestingly, the reaction with allyl
acetate led to the isolation of a mixture of products resulting
from mono- and diallylation of the phenyl ring, together
with propenylation products derived from migration of the
double bond of the allyl group in these initial products. The
identity and distribution of the mono- and diallylation prod-
ucts was established by subjecting the crude mixture to
We have been interested in developing a one-pot sequen-
tial Ru-catalyzed directed propenylation[6] and arylation of
[a] Y. Goriya, Dr. C. V. Ramana
Division of Organic Chemistry
CSIR-National Chemical Laboratory
Dr. Homi Bhabha Road
Pune 411 008 (India)
Fax : (+91)20-25902629
E-mail: vr.chepuri@ncl.res.in
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201202379.
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
1
&
ÞÞ
These are not the final page numbers!

currently underway to understand the detailed mechanism
(see the Supporting Information, Scheme SI.1 for a tentative
proposal).
The scope of the present reaction was investigated
(Table 1). Diverse 2-aryl pyridine derivatives, as well as 2-
and 3-alkyl pyridine derivatives gave the corresponding 2-
substituted-6-(1E-prop-1-enyl)-pyridine derivatives in good
to excellent yields. The propenylation of 2-aryl pyridine de-
rivatives (aryl=4-MeC6H4 1b, 4-AcC6H4 1c, and 3,4-
(MeO)2C6H3 1d) proceeded smoothly and afforded the
products (2b–2d) in 60–70% yields. The reaction of 2-(3,4-
dichlorophenyl)pyridine (1e) needs special mention. For
ꢀ
this case, the double Csp2 H activation product (2e) was ob-
tained exclusively in 61% yield (Table 1, entry 5). Surpris-
ingly, the reaction of 2-(2,3-dimethoxyphenyl)pyridine under
the above reaction conditions gave the ortho-O-desmethyl
compound 4 as the major product (isolated in 63% yield)
and 2 f was obtained in less than 5% yield.[8] However, the
same reaction in the absence of Ad-CO2H gave the product
2 f in 62% yield (Table 1, entry 7).
Scheme 2. Reactivity of various allyl halides and allyl acetate.
Simple alkyl pyridine derivatives such as 2-picoline (1g),
2-ethyl pyridine (1h), and 3-picoline (1j) are also good sub-
ꢀ
olefin hydrogenation and subsequently characterizing the
separable mono- and dialkylation products, 3b and 3c, re-
spectively.
strates for the reaction, thus giving exclusively the Csp2 H
propenylation products 2g, 2h, and 2j, respectively, with
complete regio- and stereoselectivity (Table 1, entries 8, 9,
and 11).[9] However, pyridine 1i, which has a 2-benzylox-
yethyl group gave the required corresponding product 2i in
poor yield (Table 1, entry 10). The reactions of disubstituted
pyridine derivatives having either nitro or methoxy groups
gave poor results (Table 1, entries 12 and 14). For example,
when subjected to the standard reaction conditions, 3-nitro-
2-methoxypyridine (1k) and 2-methoxy-4-methylpyridine
(1l) only the starting compounds were isolated. Whereas 3-
nitro-2-phenypyridine (1m) did not react under these reac-
tion conditions, the formation of small amounts of directed-
propenylation product 2n was observed when using 5-nitro-
2-phenylpyridine (1n; see the Supporting Information for a
1H NMR spectrum). Next, we examined the possibility of
direct propenylation of quinoline and 1-methyl-isoquinoline.
Surprisingly, quinoline (1o) decomposed under the standard
reaction conditions and 1-methyl-isoquinoline (1p) gave the
required product in low yields (Table 1, entry 16).
The use of other ruthenium complexes in this reaction
was examined under similar reactions conditions but the re-
sults were not encouraging (for details, see the Supporting
Information and Table S1). Control experiments revealed
that the presence of the base leads to better yields. When
the reaction was carried out in the absence of ruthenium
complex A under otherwise similar reaction conditions, the
formation of 2a was negligible (see the Supporting Informa-
tion and Table S1). This result indicated that ruthenium
complex A is essential for the reaction. The proposal of a
comprehensive mechanism is, at this stage, difficult. Howev-
er, the different reactivity of allyl bromide and allyl acetate
suggests that the reaction might be proceeding through the
N allylation of pyridine in the case of allyl bromide, a trans-
ꢀ
formation that would increase the acidity of the C H bond
at the C2 position. The results obtained from a control ex-
periment using the allyl bromide salt of 1a (Scheme 3) as a
substrate supports this argument. Further investigations are
Next, considering that compound 2g has the complete
carbon framework of dihydropinidine,[10] exhaustive hydro-
genolysis of compound 2g was carried out using a catalytic
amount of PtO2 in HClaq/EtOH at 50 bar H2 pressure and
(ꢁ)-dihydropinidine (5g) was obtained in quantitative yield
(Scheme 4) with complete selectivity for the 1,6-cis-disubsti-
tuted product.[11] Similarly, the hydrogenation of compounds
2h and 2a afforded fully reduced products 5h and 5a, re-
spectively (Scheme 4).
We next investigated whether we could effect sequential
ꢀ
ꢀ
direct C H propenylation and directed C H arylation reac-
tions of 2-aryl pyridine derivatives in one pot.[12] Our initial
experiments using 1a as a substrate revealed that the suc-
cess of the reactions depends upon the order of addition of
reactants, that is, whether arylation or propenylation comes
Scheme 3. Control experiments using N-allylpyridinium salt.
&
2
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Ruthenium-Catalyzed Propenylation
COMMUNICATION
Table 1. The scope of the Ru-catalyzed propenylation reaction of substituted pyridine derivatives.
Entry
Substrate
Product
Yield [%][a]
Entry
Substrate
Product
Yield [%][a]
65
1
67
9
2
3
63
66
10
11
22
54
4
62
12
no reaction
no reaction
–
5
6
61
63
13
14
–
<20
7
8
62[b]
15
16
starting material decomposed
–
67
42
[a] Yield of isolated product. [b] Reactions without Ad-CO2H.
ꢀ
dative addition across the Ar X bond. Another possibility
might be the steric hindrance around the pyridine nitrogen
atom (in 2a, the pyridine moiety is 2,6-disubstituted), a
characteristic that may prevent the pyridine nitrogen atom
from acting as a directing group. The scope of the one-pot
ꢀ
protocol involving two sequential C H bond activation reac-
tions was explored by employing various 2-aryl pyridine de-
rivatives and aryl halides (Scheme 5). The reaction of sub-
strates 1b, 1c, and 1d gave the diarylation and propenyla-
tion products 7ba–7da in 60–70% yields. When 4-methyl-io-
dobenzene (6b) was employed, the reaction was slow and,
even after 40 hours, was incomplete; the reaction gave
mono- and diarylation products 8ab (49%) and 7ab (36%),
respectively. The reactions with 4-acetylchlorobenzene (6c)
with the substrates 1a, 1b, and 1c proceeded smoothly and
gave products 7ac–7cc in 70–80% yields.
Scheme 4. The synthesis of (ꢁ)-dihydropinidine and related compounds.
first. Carrying out the arylation of the phenyl ring first
under the established reactions conditions (1208C) followed
by addition of allyl bromide and heating the reaction mix-
ture at 1208C for an additional 16 hours gave compound
7aa in 89% yield (Scheme 5). Surprisingly, when the reac-
tion sequence was changed, that is, when propenylation is
followed by arylation, the propenylation product 2a was ob-
tained exclusively in 69% yield. Even the direct arylation of
2a under these reaction conditions was found to be unsuc-
cessful. This result might be due to the formation of either a
stable N-coordinated ruthenacycle[13] or a related p complex,
To conclude, we have shown that the complex, [{RuACHTUNGTRENNUNG(p-
ꢀ
cymene)Cl2}2], which is known to effect the directed C H
activation of 2-aryl pyridine derivatives, can also be used to
effect direct C6 propenylation of pyridine derivatives.
Among the different allyl reagents screened, allyl bromide
ꢀ
which can undergo neither C H bond ruthenation nor oxi-
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
3
&
ÞÞ
These are not the final page numbers!

C. V. Ramana and Y. Goriya
action mixture was poured into a mixture of diethyl ether and ice-cold
water. The organic layer was separated and the aqueous layer was ex-
tracted (3ꢁ15 mL) with diethyl ether. The combined organic layers were
dried (Na2SO4) and concentrated under reduced pressure. The crude ma-
terial was purified using column chromatography through silica gel (5!
7% ethyl acetate in petroleum ether) to afford compound 2a (921 mg,
73%) as a yellow liquid.
ꢀ
B) Representative procedure for sequential directed and direct C H acti-
vations: To a suspension of 2-phenylpyridine (1 g, 6.44 mmol), K2CO3
(1.79 g, 12.89 mmol), and 1-AdCO2H (348 mg, 1.93 mmol) in dry toluene
(15 mL), [{RuACHTNUGRTNEUNG(p-cymene)Cl2}2] (94 mg, 0.154 mmol) was added and the
reaction mixture was flushed with argon for 10 min. To this mixture, bro-
mobenzene (1.69 mL, 16.11 mmol) was added and the resulting mixture
was heated at 1208C for 18 h. To this mixture, allyl bromide (1.41 mL,
16.27 mmol) was added and the resulting mixture was heated at 1208C
for an additional 15–18 h. The reaction mixture was diluted with diethyl
ether and water. The organic layer was separated and the aqueous layer
was extracted (3 times) with diethyl ether. The combined organic layers
were dried (Na2SO4) and solvent was removed under reduced pressure.
The crude material was purified using column chromatography through
silica gel (8!9% ethyl acetate in pet ether) to afford compound 7aa
(1.86 g, 83%) as a white solid.
Acknowledgements
CVR thank the Ministry of Science and Technology for funding through
the Department of Science and Technology [Grant numbers: SR/S5/GC-
20/2007 and SR/S5/OBP-66A/2008(G)]. Financial support from the CSIR
(New Delhi) in the form of a research fellowship to YG is gratefully ac-
knowledged. We thank Dr. Yogesh S. Vikhe for conducting some of the
early experiments.
ꢀ
Keywords: alkenylation
heterocycles · pyridine derivatives · ruthenium
·
C H activation
·
nitrogen
Scheme 5. A one-pot sequential arylation and propenylation reaction of
arylpyridine derivatives.
ꢀ
[1] For selected recent reviews on directed C H activation, see:
a) A. E. Shilov, G. B. Shul’pin, Chem. Rev. 1997, 97, 2879–2932;
b) P. Thansandote, M. Lautens, Chem. Eur. J. 2009, 15, 5874–5883;
c) L. Ackermann, R. Vicente, A. R. Kapdi, Angew. Chem. 2009, 121,
9976–10011; Angew. Chem. Int. Ed. 2009, 48, 9792–9826; d) F. Belli-
na, R. Rossi, Tetrahedron 2009, 65, 10269–10310; e) T. Satoh, M.
Miura, Synthesis 2010, 3395–3409; f) D. A. Colby, R. G. Bergman,
J. A. Ellman, Chem. Rev. 2010, 110, 624–655; g) T. W. Lyons, M. S.
Sanford, Chem. Rev. 2010, 110, 1147–1169; h) S. Messaoudi, J.-D.
Brion, M. Alami, Eur. J. Org. Chem. 2010, 6495–6516; i) A. E.
Wendlandt, A. M. Suess, S. S. Stahl, Angew. Chem. 2011, 123,
11256–11283; Angew. Chem. Int. Ed. 2011, 50, 11062–11087; j) S. H.
Cho, J. Y. Kim, J. Kwak, S. Chang, Chem. Soc. Rev. 2011, 40, 5068–
5083; k) L. Ackermann, Chem. Rev. 2011, 111, 1315–1345; l) C.-L.
Sun, B.-J. Li, Z.-J. Shi, Chem. Rev. 2011, 111, 1293–1314; m) T. C.
Boorman, I. Larrosa, Chem. Soc. Rev. 2011, 40, 1910–1925.
was found to be optimum for the direct propenylation. The
expected directed allylation/propenylation of the phenyl
ring was found to be the predominant pathway with allyl
ꢀ
acetate. The complementary directed and direct C H activa-
tion reactions, which are both catalyzed by [{Ru
A
ne)Cl2}2], have been exploited to develop a novel one-pot
ꢀ
protocol wherein multiple Ru-mediated C C bond forma-
ꢀ
tions occur through sequential C H activation reactions.
This protocol, which we believe to be the first of its kind,
will pave the way for the development of similar reactions
by appropriate substrate and catalyst selection. Further in-
vestigations to understand the mechanism of this reaction
and to extend the scope of this reaction to include other het-
erocyclic substrates are in progress.
ꢀ
[2] For ruthenium-catalyzed pyridine-directed C H activation, see: a) S.
Murai, J. Synth. Org. Chem. Jpn. 1994, 52, 992–1001; b) N. Chatani,
Y. Ie, F. Kakiuchi, S. Murai, J. Org. Chem. 1997, 62, 2604–2610;
c) N. Chatani, Y. Ishii, Y. Ie, F. Kakiuchi, S. Murai, J. Org. Chem.
1998, 63, 5129–5136; d) S. Oi, S. Fukita, N. Hirata, N. Watanuki, S.
Miyano, Y. Inoue, Org. Lett. 2001, 3, 2579–2581; e) L. Ackermann,
A. Althammer, R. Born, Angew. Chem. 2006, 118, 2681–2685;
Angew. Chem. Int. Ed. 2006, 45, 2619–2622; f) L. Ackermann, M.
Experimental Section
A) Representative procedure for direct propenylation: [{RuACTHUNTGRNEUNG(p-cyme-
ne)Cl2}2] (94 mg, 0.154 mmol) was added to a suspension of 2-phenylpyri-
dine (1 g, 6.44 mmol), K2CO3 (1.79 g, 12.89 mmol), 1-AdCO2H (348 mg,
1.93 mmol) in dry toluene (15 mL). The reaction mixture was degassed
with argon for 10 min and allyl bromide (2.79 mL, 32.22 mmol) was
added and the resulting solution was stirred at 1208C for 18–20 h. The re-
ˇ
Mulzer, Org. Lett. 2008, 10, 5043–5045; g) F. Pozgan, P. H. Dixneuf,
Adv. Synth. Catal. 2009, 351, 1737–1743; h) P. B. Arockiam, C.
Fischmeister, C. Bruneau, P. H. Dixneuf, Angew. Chem. 2010, 122,
6779–6782; Angew. Chem. Int. Ed. 2010, 49, 6629–6632; i) H. Pro-
&
4
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Ruthenium-Catalyzed Propenylation
COMMUNICATION
kopcovꢂ, S. D. Bergman, K. Aelvoet, V. Smout, W. Herrebout, B.
Van der Veken, L. Meerpoel, B. U. W. Maes, Chem. Eur. J. 2010, 16,
13063–13067; j) L. Ackermann, R. Vicente, H. K. Potukuchi, V. Pir-
ovano, Org. Lett. 2010, 12, 5032–5035; k) W. Li, P. B. Arockiam, C.
Fischmeister, C. Bruneau, P. H. Dixneuf, Green Chem. 2011, 13,
2315–2319; l) H. Li, W. Wei, Y. Xu, C. Zhang, X. Wan, Chem.
Commun. 2011, 47, 1497–1499; m) E. Ferrer Flegeau, C. Bruneau,
P. H. Dixneuf, A. Jutand, J. Am. Chem. Soc. 2011, 133, 10161–
10170.
[6] a) S. Oi, Y. Tanaka, Y. Inoue, Organometallics 2006, 25, 4773–4778;
b) K. Cheng, B. Yao, J. Zhao, Y. Zhang, Org. Lett. 2008, 10, 5309–
5312.
[7] a) L. Ackermann, P. Novꢂk, R. Vicente, N. Hofmann, Angew. Chem.
2009, 121, 6161–6164; Angew. Chem. Int. Ed. 2009, 48, 6045–6048;
b) P. Arockiam, V. Poirier, C. Fischmeister, C. Bruneau, P. H. Dix-
neuf, Green Chem. 2009, 11, 1871–1875; c) L. Ackermann, Chem.
Commun. 2010, 46, 4866–4877; d) L. Ackermann, A. V. Lygin, Org.
Lett. 2011, 13, 3332–3335; e) L. Ackermann, N. Hofmann, R. Vice-
nte, Org. Lett. 2011, 13, 1875–1877.
[3] a) B. J. Holliday, C. A. Mirkin, Angew. Chem. 2001, 113, 2076–2097;
Angew. Chem. Int. Ed. 2001, 40, 2022–2043; b) G. Desimoni, G.
Faita, P. Quadrelli, Chem. Rev. 2003, 103, 3119–3154; c) G. D.
Henry, Tetrahedron 2004, 60, 6043–6061; d) D. G. Kurth, M. Higu-
chi, Soft Matter 2006, 2, 915–927; e) V. C. Gibson, C. Redshaw,
G. A. Solan, Chem. Rev. 2007, 107, 1745–1776; f) C. Bianchini, G.
Giambastiani, L. Luconi, A. Meli, Coord. Chem. Rev. 2010, 254,
431–455.
[8] C.-C. Lee, W.-Y. Chu, Y.-H. Liu, S.-M. Peng, S.-T. Liu, Eur. J. Inorg.
Chem. 2011, 4801–4806.
[9] Selected examples of Csp3 H activation of 2-alkyl pyridine deriva-
ꢀ
tives: a) B. M. Trost, D. A. Thaisrivongs, J. Am. Chem. Soc. 2009,
131, 12056–12057; b) B. Qian, S. M. Guo, J. P. Shao, Q. M. Zhu, L.
Yang, C. G. Xia, H. M. Huang, J. Am. Chem. Soc. 2010, 132, 3650–
3651; c) G. Song, Y. Su, X. Gong, K. Han, X. Li, Org. Lett. 2011, 13,
1968–1971; d) B. Qian, P. Xie, Y. J. Xie, H. M. Huang, Org. Lett.
2011, 13, 2580–2583; e) O. Baudoin, Chem. Soc. Rev. 2011, 40,
4902–4911.
ꢀ
[4] For C H activation of the C2 position of pyridine derivatives, see:
a) R. F. Jordan, D. F. Taylor, J. Am. Chem. Soc. 1989, 111, 778–779;
b) E. J. Moore, W. R. Pretzer, T. J. Oconnell, J. Harris, L. Labounty,
L. Chou, S. S. Grimmer, J. Am. Chem. Soc. 1992, 114, 5888–5890;
c) R. Grigg, V. Savic, Tetrahedron Lett. 1997, 38, 5737–5740; d) M.
Murakami, S. Hori, J. Am. Chem. Soc. 2003, 125, 4720–4721; e) K.
Godula, B. Sezen, D. Sames, J. Am. Chem. Soc. 2005, 127, 3648–
3649; f) J. C. Lewis, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc.
2007, 129, 5332–5333; g) A. M. Berman, J. C. Lewis, R. G. Bergman,
J. A. Ellman, J. Am. Chem. Soc. 2008, 130, 14926–14927; h) Y.
Nakao, K. S. Kanyiva, T. Hiyama, J. Am. Chem. Soc. 2008, 130,
2448–2449; i) S. Yotphan, R. G. Bergman, J. A. Ellman, Org. Lett.
2010, 12, 2978–2981. Review: j) Y. Nakao, Synthesis 2011, 3209–
3219; k) B.-T. Guan, Z. Hou, J. Am. Chem. Soc. 2011, 133, 18086–
18089.
[10] For selected total syntheses of dihydropinidine, see: a) Y. Watanabe,
H. Iida, C. Kibayashi, J. Org. Chem. 1989, 54, 4088–4097; b) Z. H.
Lu, W. S. Zhou, J. Chem. Soc. Perkin Trans. 1 1993, 593–596; c) C.
Eriksson, K. S. Din, F. Schlyterb, H.-E. Hçgberga, Tetrahedron:
Asymmetry 2006, 17, 1074–1080; d) M. Kavala, F. Mathia, J. Kozi-
sek, P. Szolcsanyi, J. Nat. Prod. 2011, 74, 803–808; e) R. C. Simon,
B. Grischek, F. Zepeck, A. Steinreiber, F. Belaj, W. Kroutil, Angew.
Chem. 2012, 124, 6817–6820; Angew. Chem. Int. Ed. 2012, 51, 6713–
6716.
[11] For the hydrogenolysis of pyridine derivatives, see: a) T. S. Hamil-
ton, R. Adams, J. Am. Chem. Soc. 1928, 50, 2260–2263; b) A. Solla-
diꢃ-Cavallo, M. Roje, A. Baram, V. Sunjic, Tetrahedron Lett. 2003,
44, 8501–8503.
[12] For one-pot ruthenium-mediated sequential direct arylation and hy-
drosilylation, see: a) L. Ackermann, R. Born, P. ꢄlvarez-Bercedo,
Angew. Chem. 2007, 119, 6482–6485; Angew. Chem. Int. Ed. 2007,
46, 6364–6367; b) B. Li, C. B. Bheeter, C. Darcel, P. H. Dixneuf,
ACS Catal. 2011, 1, 1221–1224.
[13] a) L. Zhang, L. Dang, T. B. Wen, H. H. Y. Sung, I. D. Williams, Z.
Lin, G. Jia, Organometallics 2007, 26, 2849–2860; b) M. Albrecht,
Chem. Rev. 2010, 110, 576–623.
[5] a) L.-C. Campeau, S. Rousseaux, K. Fagnou, J. Am. Chem. Soc.
2005, 127, 18020–18021; b) K. S. Kanyiva, Y. Nakao, T. Hiyama,
Angew. Chem. 2007, 119, 9028–9030; Angew. Chem. Int. Ed. 2007,
46, 8872–8874; c) A. Larivꢃe, J. J. Mousseau, A. B. Charette, J. Am.
Chem. Soc. 2008, 130, 52–54; d) S. H. Cho, S. J. Hwang, S. Chang, J.
Am. Chem. Soc. 2008, 130, 9254–9256; e) L.-C. Campeau, D. J.
Schipper, K. Fagnou, J. Am. Chem. Soc. 2008, 130, 3266–3267;
f) J. J. Mousseau, A. Lariv’ee, A. e. B. Charette, Org. Lett. 2008, 10,
1641–1643; g) J. J. Mousseau, A. L. Fortier, A. B. Charette, Org.
Lett. 2010, 12, 516–519; h) H.-Y. Sun, S. I. Gorelsky, D. R. Stuart,
L.-C. Campeau, K. Fagnou, J. Org. Chem. 2010, 75, 8180–8189; i) S.
Duric, C. C. Tzschucke, Org. Lett. 2011, 13, 2310–2313; j) W. P. Mai,
J. W. Yuan, Z. C. Li, G. C. Sun, L. B. Qu, Synlett 2012, 145–149.
Received: July 4, 2012
Published online: && &&, 0000
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
5
&
ÞÞ
These are not the final page numbers!

C. V. Ramana and Y. Goriya
One stone, two birds: Aryl pyridine
derivatives in the presence of allyl bro-
ꢀ
C H Activation
mide and a catalytic amount of [{RuACHTUNGTRENNUNG(p-
Y. Goriya, C. V. Ramana* . . &&&& — &&&&
cymene)Cl2}2] undergo an unexpected
direct C6-propenylation reaction of the
pyridine moiety. A one-pot one-cata-
lyst three-component reaction involv-
ing sequential and selective direct and
Ruthenium-Catalyzed C6-Propenyla-
tion Reactions of Substituted Pyridine
ꢀ
Derivatives: Directed and Direct C H
Activation
ꢀ
directed C H activation reactions was
also developed (see scheme).
&
6
&
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!