Regioselective allylic alkylation and etherification catalyzed by in situ generated N-heterocyclic carbene ruthenium complexes

Article abstract of DOI:10.1016/j.tetlet.2005.11.051

Benzimidazolium halides are used for the first time as ligand precursors in ruthenium-catalyzed substitution of allylic carbonates and chlorides by carbon nucleophiles and phenols, respectively. After generation of diaminocarbene species upon deprotonatio

Full text of DOI:10.1016/j.tetlet.2005.11.051

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 535–538
Regioselective allylic alkylation and etherification catalyzed
by in situ generated N-heterocyclic carbene ruthenium complexes
a
a,
b,
c,
*
*
*
¨
Nevin Gurbuz, Ismail Ozdemir, Bekir C¸ etinkaya, Jean-Luc Renaud,
¨
¨
Bernard Demersemanc and Christian Bruneauc,*
aIno€nu€ University, Faculty Science and Arts, Department of Chemistry, 44280 Malatya, Turkey
bDepartment of Chemistry, Ege University, Bornova, 35100 Izmir, Turkey
cInstitut de Chimie, UMR 6509, Organome´talliques et Catalyse: Chimie et Electrochimie Mole´culaires, Universite´ de Rennes 1,
Campus de Beaulieu, 35042 Rennes Cedex, France
Received 11 October 2005; accepted 9 November 2005
Available online 28 November 2005
Abstract—Benzimidazolium halides are used for the first time as ligand precursors in ruthenium-catalyzed substitution of allylic car-
bonates and chlorides by carbon nucleophiles and phenols, respectively. After generation of diaminocarbene species upon deproto-
nation by tBuOK, their association with [Cp*Ru(MeCN)3]PF6 induces a very high regioselectivity in favor of the branched isomers
when cinnamyl derivatives are used as starting substrates. They also provide good regioselectivities for the allylation of phenols by
unsymmetrical aliphatic allylic substrates such as 3-chloro-4-phenylbut-1-ene, and thus provide a straightforward access to new
allylic phenyl ethers.
Ó 2005 Elsevier Ltd. All rights reserved.
Metal-catalyzed allylic substitution is recognized as a
useful process in organic synthesis for C–C and C-het-
eroatom bond forming reaction.1 In this context, the
control of the regioselectivity is of crucial importance
when unsymmetrical allylic derivatives are used as
substrates.
[Cp*(MeCN)3Ru][PF6] bearing labile ligands was
recently shown to be appropriate for the synthesis of
aryl allyl ethers starting from allylic halides and
phenols.3 Remarkably, Cp*(bipy)Ru precursors have
revealed a catalytic activity allowing the direct involve-
ment of neutral undeprotonated soft carbon pronucleo-
philes.4,5 On the other hand, N-heterocyclic carbenes
(NHC) have attracted considerable attention, not only
as isolable species,6,7 but also as ligands for transition-
metal catalysts.8 They have offered very active systems
for catalytic hydrogenation,9 C–C coupling,10 olefin
metathesis,11 amination of aryl halides,12 cyclopropana-
tion,13 and cycloisomerization reactions,14 but only
Mori and co-workers have involved NHC ligands in pal-
ladium complexes to achieve allylic substitution.15
Nu
NuH
R
Nu
+
R
R
X
Catalyst
Branched
Linear
X= Cl, O2COEt
For this type of nucleophilic substitution, pentamethyl-
cyclopentadienyl ruthenium catalysts have already
disclosed promising properties with respect to
regioselectivity in favor of the branched isomer.2 Thus,
We report herein that a combination of a Cp*Ru moiety
and NHC ligand allows the achievement and improve-
ment of both catalytic activity and regioselectivity as
compared to (i), Cp*(bipy)Ru precursors toward soft
carbon nucleophiles and (ii), [Cp*(MeCN)3Ru][PF6]
toward aryl oxide anions.
*
Corresponding authors. Tel.: +33 (0) 2232 36283; fax: +33 (0)
¨
2232 36939 (J.-L.R., C.B.); fax: +90 4223 410212 (I.O); fax: +90
For this study, the catalysts were prepared starting from
[Cp*(MeCN)3Ru][PF6] 1 that contains very labile aceto-
nitrile ligands, and 1,3-dialkylbenzimidazolium salts
2323 881036 (B.C¸ ); e-mail addresses: iozdemir@inonu.edu.tr;
bekircetinkaya@hotmail.com; jean-luc.renaud@univ-rennes1.fr; christian.
bruneau@univ-rennes1.fr
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.11.051

536
N. Gu¨rbu¨z et al. / Tetrahedron Letters 47 (2006) 535–538
Table 1. Ruthenium-catalyzed allylic alkylation of cinnamyl carbonate
3a
N(C2H5)2
OCH3
OCH3
N
N
+)
N
+
)
Cl-
Cl-
L :
Entry NHC precursor Nucleophile Product Ratiob B/L
N
OCH3
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2a
2b
2c
2d
2a
4
4
4
4
5
5
5
5
6
7
7
7
7
8
8
8
8
9
85/15
88/12
82/18
71/29
74/26
75/25
60/40
62/38
46/54
2a
2b
N
N
+) Br-
+) Br-
N
N
OCH3
2d
2c
Scheme 1.
a Conditions: 0.6 mmol of pronucleophile 4–6, 0.5 mmol of cinnamyl
carbonate 3, 0.015 mmol (based on ruthenium) of (2a–d)-based cat-
alyst in 4 mL of CH3CN at room temperature for 16 h.
2a–d (Scheme 1). These salts quantitatively result from
1
b As determined by H NMR spectroscopy, complete conversion of 3.
quaternization of 1-alkylbenzimidazolines in DMF.16,17
Under basic conditions 2a–d generated the correspond-
ing NHC species that were reacted in situ with 1. As
bipyridine ligands, N-heterocyclic carbenes are strong
r-donors and poor p-acceptors. Whereas bipyridine
ligands act as robust chelates, coordination of only
one NHC might be expected on the basis of previous
works.18 An additional stabilization of the metal center
may be gained through the presence of weakly coordi-
nating oxygen or nitrogen atoms located in the side arms
of the NHC arising from 2a–c (Scheme 1). For each
experiment, the catalytic material was prepared as
follows: the appropriate amount of 2a–d (2 mol per
Ru atom) was treated with a stoichiometric amount
of t-BuOK in THF (5 mL) at 50 °C for 2 h.
[Cp*Ru(CH3CN)3][PF6] was then added and the mix-
ture was heated at 50 °C for 2 h. THF was subsequently
removed under vacuum to leave a solid that was imme-
diately involved as catalytic material. Even if we were
not able to fully characterize the organometallic com-
plex, it is assumed that [Ru-carbene] species are
formed.18,19 Then, the reaction of carbonate 3 with di-
methylmalonate 4 was investigated by successively adding
carbonate 3 (0.5 mmol) and malonate 4 (0.6 mmol) to
the catalytic material (0.015 mmol based on ruthenium)
dissolved in acetonitrile (4 mL). The resulting solution
was stirred overnight at room temperature, concentrated
and using the 2a-based catalyst, the linear product 9L
and the branched isomer 9B were isolated in an almost
1:1 ratio (Table 1, entry 9). Finally, these results empha-
size the potential of Cp*Ru–NHC catalysts for the
regioselective nucleophilic substitution of allylic carbon-
ates. It is also worth noting that the regioselectivity
is opposite to that obtained in the palladium–NHC-
catalyzed reaction that produces the linear isomer as
the major product.15
Nu
R[u] Cat. (3 mol%)
+
NuH
Ph
OCO2Et
Ph
Nu
+
Ph
MeCN, r.t.
7B-9B
7L-9L
4 : H2C(CO2Me)2
5 : H2C(COPh)2
6 : H2C(COMe)2
3
ð1Þ
In order to evaluate the scope of this catalytic system,
the range of nucleophiles was extended to phenol
derivatives. Using experimental conditions very similar
to those reported when 1 was used as a catalyst,3 reac-
tion of phenol with cinnamyl chloride in the presence
of the 2a-catalyst and potassium carbonate in aceto-
nitrile (Eq. 2) led to the formation of the allyl phenyl
ether 11 in a 94:6 branched to linear ratio (Table 2, entry
1). In this case, the blank experiment showed the forma-
tion of the sole linear derivative but in a very low yield.
The regioselectivities observed in acetonitrile, THF and
methanol (Table 2, entries 1–3) were quite similar (94:6,
93:7, 89:11, respectively). This observation indicated
a slight effect of the solvent and is in sharp contrast
with the results obtained with 1 as catalyst: in the same
solvents, the regioselectivities are 98:2, 86:14 and
60:40, respectively.20 Quite good regioselectivities were
retained when (2b–d)-catalysts were involved (Table 2,
entries 4–6). These catalytic systems based on (2a–d)
tolerate the presence of an electron-donating group
(such as a methoxy group) or an electron-withdrawing
group (such as an halide) as para-substituent on the
phenyl ring. Thus, good regioselectivities were obtained
1
under vacuum and then filtered on silica gel. H NMR
spectroscopic analysis of the crude product indicated
completion of the reaction affording the desired product
7 (Eq. 1), and a high (7B/7L) branched to linear ratio
(Table 1). A blank experiment, carried out according
to the same procedure but without any ruthenium
source, led to no conversion of the starting substrates.
Indeed, the regioselectivities were fairly good (ranging
between 71:29 with ligand 2d and 88:12 with ligand 2b,
Table 1, entries 1–4). Since 1 is unable to catalyze allylic
alkylation without prior formation of the stabilized
carbonucleophiles via deprotonation of malonate,3 these
results provide a clear evidence of the crucial role of the
carbene ligand in the new catalytic system, wherein a
preliminary preparation of sodiodimethylmalonate is
avoided. The extension of this reaction to the stabilized
carbon pronucleophiles 5 (Eq. 1) also led to good results
as the branched isomer 8B was the major compound
(Table 1, entries 5–8). However, with penta-2,4-dione 6

N. Gu¨rbu¨z et al. / Tetrahedron Letters 47 (2006) 535–538
537
Table 2. Ruthenium-catalyzed allylic etherification of cinnamyl chlo-
ride by aryl oxide anionsa
Table 3. Ruthenium-catalyzed allylic etherification of 15 by aryl oxide
anionsa
Entry NHC precursor Ar
Product Ratiob B/L
Entry NHC precursor Ar
Product Ratiob B/L
1
2a
2a
2a
2b
2c
2d
2a
2b
2c
2d
2a
2b
2c
2d
2a
2b
2c
2d
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-Cl–C6H4
4-Cl–C6H4
4-Cl–C6H4
4-Cl–C6H4
4-MeO–C6H4 13
4-MeO–C6H4 13
4-MeO–C6H4 13
4-MeO–C6H4 13
2-Cl–C6H4
2-Cl–C6H4
2-Cl–C6H4
2-Cl–C6H4
11
11
11
11
11
11
12
12
12
12
94/6
93/7
89/11
92/8
90/10
88/12
89/11
89/11
88/12
87/13
94/6
93/7
93/7
92/8
32/68
64/36
49/51
60/40
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2a
2b
2c
2d
2a
2b
2c
2d
C6H5
C6H5
C6H5
C6H5
4-Cl–C6H4
4-Cl–C6H4
4-Cl–C6H4
4-Cl–C6H4
4-MeO–C6H4 18
4-MeO–C6H4 18
4-MeO–C6H4 18
4-MeO–C6H4 18
16
16
16
16
17
17
17
17
83/17
64/36
78/22
67/33
67/33
83/17
86/14
87/13
69/31
80/20
74/26
77/23
2c
3d
4
5
6
7
8
9
9
10
11
12
13
14
15
16
17
18
10
11
12
a Conditions: 1.2 mmol of ArOH, 1.2 mmol of K2CO3, 1 mmol of
allylic chloride 15, 0.03 mmol (based on ruthenium) of (2a–d)-based
catalyst in 6 mL of MeCN at room temperature for 16 h.
14
14
14
14
b As determined by 1H NMR spectroscopy, complete conversion of 15.
a Conditions: 1.2 mmol of ArOH, 1.2 mmol of K2CO3, 1 mmol of
cinnamyl chloride 10, 0.03 mmol (based on ruthenium) of (2a–d)-
based catalyst in 6 mL of MeCN, room temperature, 16 h.
b As determined by 1H NMR spectroscopy, complete conversion of 10.
c THF as solvent.
(Table 3, entries 1–4, B/L ratio average: 73/27) were
reached when (2a–d)-based catalysts were used instead
of 1. Thus, a 83/17 ratio was obtained when the NHC
precursor 2a was used. Good regioselectivities were also
obtained when p-chlorophenol (Table 3, entries 5–8,
17B/17L ratio up to 87/13) and p-methoxyphenol (Table
3, entries 9–12, 18B/18L ratio up to 80/20) were
involved as nucleophiles. Compounds 16B–18B are
new compounds, which are conveniently and selectively
prepared by this ruthenium-catalyzed reaction.
d MeOH as solvent.
for p-substituted phenols and changing the electronic
properties of the substituent had little influence on regio-
selectivity (Table 2, entries 7–14). However, chloro-
substitution at the ortho-position had a detrimental
effect on the regioselectivity (Table 2, entries 15–18).
In these reactions, the catalysis may be slowed and the
non-catalyzed reaction may become competitive.
Indeed, under the same reaction conditions but without
any ruthenium complex, 2-chlorophenol reacted with
cinnamyl chloride 10 to produce the sole linear deriva-
tive 14L in 75% yield after 16 h. The same lack of regio-
selectivity was observed with 2-chlorophenol when
[Cp*Ru(CH3CN)3][PF6] was used as catalyst precursor.3
OAr
[Ru] Cat. (3 mol%)
MeCN, K2CO3, r.t.
Ph
Ph
Ph
+
ArOH
OAr
+
Cl
15
16B-18B
16L-18L
ð3Þ
In conclusion, we have disclosed that the coordination
of N-heterocyclic carbenes to a Cp*Ru center generates
useful catalyst precursors for allylic substitution reac-
tions starting from unsymmetrical allylic carbonates or
halides. Among the different precursors 2a–d, it is diffi-
cult to select one for its better efficiency as the observed
regioselectivities are quite similar and slightly depend on
the nature of the nucleophile. This new catalytic system
achieved high regioselectivities with different nucleo-
philes (soft carbon nucleophiles, aryl oxide anions)
and significantly improved regioselectivities when
aliphatic allylic halides were used.
OAr
[Ru] Cat.(3 mol%)
+
ArOH
Ph
Cl
Ph
OAr
+
Ph
11B-14B
solvent, K2CO3, r.t.
11L-14L
10
ð2Þ
Allyl aryl ethers arising from cinnamyl derivatives are
valuable intermediates in organic chemistry,21 but it is
also of interest to develop an efficient access to branched
allylic aryl ethers starting from aliphatic allylic halides
(vs cinnamyl chloride type substrates). For this study,
3-chloro-4-phenylbut-1-ene 15, which offered both con-
veniences of low volatility facilitating experimental work
and easy synthesis,22 was chosen as allylic substrate. The
reaction of phenoxide anion with 15 in the presence of
3 mol % of 1 in acetonitrile at room temperature quan-
titatively afforded the phenyl ethers 16B and 16L (Eq.
3) but a 1.5/1 B/L ratio indicated a rather moderate reg-
ioselectivity.20 Significantly increased regioselectivities
Acknowledgments
This work was supported by CNRS, the Technological
¨
¨
and Scientific Research Council of Turkey TUBITAK
[TBAG-2474 (104T085)], and Inonu University
Research Fund (BAP 2005/42). The authors are grateful
to the European Union COST Program Actions COST
D17/0008/00 and D24/0005/02 for support.

538
N. Gu¨rbu¨z et al. / Tetrahedron Letters 47 (2006) 535–538
Mauduit, M.; Guillemin, J.-C. Chem. Commun. 2004,
References and notes
2282.
12. (a) Stauffer, S. R.; Lee, S.; Stambouli, J. P.; Hanck, S. I.;
Hartwig, J. F. Org. Lett. 2000, 2, 1423; (b) Grasa, G. A.;
Viciu, M. S.; Nolan, S. P. J. Org. Chem. 2001, 66,
7729.
1. Tsuji, J. In Transition Metal Reagents and Catalysts.
Innovations in Organic Synthesis; Wiley: Chichester, 2000;
p 109.
2. (a) Kondo, T.; Ono, H.; Satake, N.; Mitsudo, T.;
Watanabe, Y. Organometallics 1995, 14, 1945; (b) Kondo,
T.; Mitsudo, T. In Ruthenium in Organic Synthesis;
Murahashi, S.-I., Ed.; VCH: Weinheim, 2004; pp 129–151.
3. Mbaye, M. D.; Demerseman, B.; Renaud, J.-L.; Toupet,
L.; Bruneau, C. Adv. Synth. Catal. 2004, 346, 835.
4. Mbaye, M. D.; Demerseman, B.; Renaud, J.-L.; Toupet,
L.; Bruneau, C. Angew. Chem., Int. Ed. 2003, 42, 5066.
5. Hubert, C.; Renaud, J.-L.; Demerseman, B.; Fischmeister,
C.; Bruneau, C. J. Mol. Catal. 2005, 237, 161–164.
6. Arduengo, A. J., III. Acc. Chem. Res. 1999, 32, 913.
7. Bourissou, D.; Guerret, O.; Gabba¨ı, F. P.; Bertrand, G.
Chem. Rev. 2000, 100, 39.
¨
13. C¸ etinkaya, B.; Ozdemir, I.; Dixneuf, P. H. J. Organomet.
Chem. 1997, 534, 153.
14. (a) C¸ etinkaya, B.; Demir, S.; Ozdemir, I.; Toupet, L.;
¨
´
Semeril, D.; Bruneau, C.; Dixneuf, P. H. New J. Chem.
¨
2001, 25, 519; (b) C¸ etinkaya, B.; Demir, S.; Ozdemir, I.;
´
Toupet, L.; Semeril, D.; Bruneau, C.; Dixneuf, P. H.
Chem. Eur. J. 2003, 9, 2323.
15. (a) Sato, Y.; Yoshino, T.; Mori, M. Org. Lett. 2003, 5, 31;
(b) Sato, Y.; Yoshino, T.; Mori, M. J. Organomet. Chem.
2005, 690, 5753.
¨
16. For the synthesis of salts 2a,b,d see: Ozdemir, I.; Go¨k, Y.;
Gurbuz, N.; C¸ etinkaya, E.; C¸ etinkaya, B. Heterocycl.
¨
¨
Chem. 2005, 42, 303.
17. For the synthesis of salt 2c see: Ozdemir, I.; Go¨k, Y.;
Gurbuz, N.; Yac¸ar, S.; C¸ etinkaya, E.; C¸ etinkaya, B. Pol.
8. (a) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41,
1290; (b) Herrmann, W. A. In Applied Homogeneous
Catalysis with Organometallic Compounds; Cornils, B.,
Herrmann, W. A., Eds.; VCH: Weinheim, 1996; p 712.
9. (a) Perry, M. C.; Cui, X.; Powell, M. T.; Hou, D.-R.;
Reibenspies, J. H.; Burgess, K. J. Am. Chem. Soc. 2003,
125, 113; (b) Cui, X.; Burgess, K. J. Am. Chem. Soc. 2003,
125, 14212; (c) Fan, Y.; Cui, X.; Burgess, K.; Hall, M. B.
J. Am. Chem. Soc. 2004, 126, 16688.
¨
¨
¨
J. Chem. 2004, 78, 2141.
18. Baratta, W.; Herdtweck, E.; Herrmann, W. A.; Rigo, P.;
Schwarz, J. Organometallics 2002, 21, 2101.
19. Dragutan, V.; Dragutan, I.; Demonceau, A. Platinum
Metals Rev. 2005, 49, 123.
20. Mbaye, M. D. PhD thesis, University of Rennes 1,
2004.
21. (a) Labrosse, J.-R.; Poncet, C.; Lhoste, P.; Sinou, D.
Tetrahedron: Asymmetry 1999, 10, 1069; (b) Trost, B. M.;
Thiel, O. R.; Tsui, A.-C. J. Am. Chem. Soc. 2002, 124,
11616; (c) Trost, B. M.; Tang, W. J. Am. Chem. Soc. 2002,
124, 14542.
10. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457; (b)
¨
Ozdemir, I.; Demir, S.; Yaßsar, S.; C¸ etinkaya, B. Appl.
Organomet. Chem. 2005, 19, 550; (c) Clavier, H.; Cout-
able, L.; Guillemin, J.-C.; Mauduit, M. Tetrahedron:
Asymmetry 2005, 16, 921.
´
11. (a) Semeril, D.; Bruneau, C.; Dixneuf, P. H. Adv. Synth.
22. Julia, M.; Verpeaux, J. N.; Zahneissen, T. Bull. Soc. Chim.
Fr. 1994, 131, 539.
Catal. 2002, 344, 585; (b) Trnka, T. M.; Grubbs, R. Acc.
Chem. Res. 2001, 34, 18; (c) Clavier, H.; Audic, N.;