Highly active phosphine-free carbene ruthenium catalyst for cross-metathesis of acrylonitrile with functionalized olefins

Article abstract of DOI:10.1016/j.tetlet.2005.08.062

The carbene ruthenium complex [1,3-bis(2,6-dimethylphenyl)-4,5- dihydroimidazol-2-ylidene](C₅H₅N)₂(Cl) ₂RuCHPh (8) was prepared by the reaction of [1,3-bis (2,6-dimethylphenyl)-4,5-dihydroimidazol-2-ylidene](PPh₃)(Cl) ₂RuCHPh (7) with pyridine and used as a highly effective catalyst for the cross-metathesis of acrylonitrile with various functionalized olefins.

Full text of DOI:10.1016/j.tetlet.2005.08.062

Tetrahedron
Letters
Tetrahedron Letters46 (2005) 7225–7228
Highly active phosphine-free carbene ruthenium catalyst for
cross-metathesis of acrylonitrile with functionalized olefins
Chen-Xi Bai,a Wen-Zhen Zhang,a Ren He,a,* Xiao-Bing Lua and Zhi-Qiang Zhanga,b
aState Key Laboratory of Fine Chemicals, Dalian University of Technology, No. 158 Zhongshan Road, Dalian 116012, PR China
bCollege of Chemical Engineering, Anshan University of Science and Technology, Anshan 114044, PR China
Received 25 May 2005; revised 11 August 2005; accepted 15 August 2005
Available online 2 September 2005
Abstract—The carbene ruthenium complex [1,3-bis(2,6-dimethylphenyl)-4,5-dihydroimidazol-2-ylidene](C5H5N)2(Cl)2Ru@CHPh
(8) wasprepared by the reaction of [1,3-bis(2,6-dimethylphenyl)-4,5-dihydroimidazol-2-ylidene](PPh 3)(Cl)2Ru@CHPh (7) with pyr-
idine and used as a highly effective catalyst for the cross-metathesis of acrylonitrile with various functionalized olefins.
Ó 2005 Elsevier Ltd. All rights reserved.
In the last decade, olefin metathesis has emerged as a
powerful tool for C–C bond formation.1 The commer-
cial availability of well-defined transition metal catalysts
(Fig. 1), such as molybdenum alkoxyimido alkylidene
1,2 ruthenium benzylidene catalysts 2, 33 and ether-teth-
ered ruthenium alkylidene derivative catalyst 4,4 have
made olefin metathesis practical for application to syn-
thetic organic chemistry. However, cross-metathesis
(CM), a method for the intermolecular formation of
carbon–carbon double bonds, has been underutilized
in comparison with other metathesis reactions. This is
primarily due to the lack of reaction selectivity and
olefin stereoselectivity.5 The discovery of the highly
active and stable ruthenium-based Ôsecond generationÕ
GrubbsÕ catalyst 3, (H2IMes) (PCy3)(Cl)2Ru@CHPh
remained a synthetic challenge.7 Several examplesof
selective Mo- and Ru-catalyzed acrylonitrile CM have
appeared in the literature.8
However, molybdenum alkoxyimido alkylidene 1 isvery
air- and moisture-sensitive and shows a restricted toler-
ance of several heteroatom functionalities. The presence
of acids, reactive carbonyl groups, and alcohols signifi-
9
cantly leadsto the catalyts inactive.
Most of phos-
phine-ligated ruthenium catalysts have given poor
results for this transformation.10 Recently, a new mem-
ber of the family of catalysts, (H2IMes)(3-bromopyri-
dine)2(Cl)2Ru@CHPh, wasfound to initiate more
rapidly than 3.11 In thisletter, we have developed an
inexpensive and highly efficient ruthenium complex 8
to perform acrylonitrile CM with different functional-
ized olefins.
6
(H2IMes= 1,3-dimesityl-4,5-dihydroimi-dazol-2-ylidene),
hasdramatically advanced the utility of CM.
Although the advances have been significant, the cross-
metathesis (CM) between functionalized olefins has
Indeed, the original synthetic route of complex 3 and 4,
suitable for small scale laboratory syntheses, was not
PCy3
Cl
Mes
Mes
Cl
Mes N N Mes
N N
Ru
Cl
N
Ru
Ru
(CF3)2MeCO
Ph
Cl
Mo
Cl
Ph
Ph
Cl
O
4
PCy3
3
PCy3
(CF3)2MeCO
2
1
Figure 1. Olefin metathesis catalysts. Mes = 2,4,6-trimethylphenyl.
Keywords: Acrylonitrile; Ruthenium; Metathesis.
*
Corresponding author. Tel.: +86 411 8899 3861; fax: +86 411 8363 3080; e-mail: dlengima@yahoo.com.cn
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.08.062

7226
C.-X. Bai et al. / Tetrahedron Letters 46 (2005) 7225–7228
practical for large scale operations, because it was heav-
ily relied on column chromatography purification steps
and the use of expensive PCy3. For example, the synthe-
sis of 4 was considerably less efficient and more time
consuming, especially because chromatography was re-
quired for purification and not all reagentswere com-
mercially available.4 And expensive and sensitive PCy3
was used for the synthesis of 3.11
treatment of complex 6 and 5 with potassium tert-butox-
ide in toluene followed by stirring for 30 min at 70 °C
(Scheme 1). The resulting clear dark-brown solution
wastransferred into cold ( À10 °C) hexane to give the de-
sired complex 7 asa precipitate.
Complex 7 waspurified by several washeswith hexane
as a brown microcrystalline solid in 77% yield (Scheme
1). A bispyridine ruthenium complex 8 wasprepared
by adding excess pyridine to 7. These reactions were
completed within minutes, in the absence of any solvent.
Product 8 was isolated in 91% yield simply by precipita-
tion in hexane and without further purification.14 The
resulted complex 8 not only retained air and moisture
insensitivity characteristic, but also showed better cata-
lytic characteristic than Grubbs catalyst 3 for acrylo-
We were thusencouraged to develop a straightforward
and convenient method ideal for preparing thisligand
efficiently on a large scale, replacing PCy3 with PPh3.
The compounds(PPh 3)2Cl2Ru@CHPh (6)12 and 1,3-
bis-(2,6-dimethylphenyl)-4,5-dihydroimidazolinium chlo-
ride (5)13 were prepared according to the literature
procedures. The ruthenium complex 7 wasprepared by
N
N
N
N
Cl
RuCl2(=CHPh)(PPh3)2
C H N
10 equiv
5
4
6
Cl
Cl
Cl
N
N
Ru
N
KOBut
-PPh3
Ru
PPh3
Ph
Cl
N
H
Ph
5
7
8
Scheme 1. Synthesis of bispyridine complex 8.
Table 1. Result of the CM with acrylonitrile and catalyst 8
CN
CN
R
Bu, COH,
R=CN,
CHO,
R
8
+
+
COOH
CO Me,
2
R
R
CH2Cl2 (0.05M)
C
B
A
Entry
Substrate A
Products B
Yield [%]a
(Z/E)b
RCH@CHR C Yield [%]c
CN
1
2
12d
36e
3:1
3:1
—
—
CN
CN
Bu
9
CN
CN
CN
3
4
37d
51e
3:1
3:1
7
5
Bu
10
OH
56d
68e
3:1
3:1
5
3
OH
5
6
11
7
8
60d
71e
4:1
4:1
0
0
CO2Me
CO2Me
CHO
12
13
CN
CN
9
10
61d
77e
4:1
4:1
0
0
CHO
11
12
35d
55e
3:1
3:1
11
7
CO2H
CO2H
14
Reaction: CH2Cl2 (c = 0.05 M), 2 equiv acrylonitrile, 45 °C, 12 h.
a Isolated yield.
b Ratiosdetermined by meansof 1H NMR spectroscopy.
c Determined by GC.
d Catalyst 8 = 2 mol %.
e Catalyst 8 = 10 mol %.

C.-X. Bai et al. / Tetrahedron Letters 46 (2005) 7225–7228
7227
Chang, S. Tetrahedron 1998, 54, 4413–4450; (d) Arm-
strong, S. J. Chem. Soc., Perkin Trans. 1 1998, 317–388; (e)
nitrile CM. Complex 8 wasused for the CM reactions
of acrylonitrile with a variety of functionalized olefins.
All cross-metathesis reactions were performed under
N2 in CH2Cl2 at reflux in the presence of 2 or
10 mol % of catalyst 8, 1 equiv of the acrylonitrile, and
Furstner, A. Top. Organomet. Chem. 1998, 1, 37–72; (f)
¨
Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. 1997, 36,
2036–2056.
2. (a) Schrock, R. R.; Murdzek, J. S.; Bazan, G. C.; Robbins,
J.; Dimane, M.; OÕRegan, M. B. J. Am. Chem. Soc. 1990,
112, 3875–3886; (b) Bazan, G. C.; Khosravi, E.; Schrock,
R. R.; Feast, W. J.; Gibson, V. C.; OÕRegan, M. B.;
Thomas, J. K.; Davis, W. M. J. Am. Chem. Soc. 1990, 112,
8378–8387; (c) Bazan, G. C.; Oskan, J. H.; Cho, H. N.;
Park, Y.; Schrock, R. R. J. Am. Chem. Soc. 1991, 113,
6899–6907.
3. (a) Schwab, P.; France, M. B.; Ziller, J. M.; Grubbs, R. H.
Angew. Chem., Int. Ed. Engl. 1995, 34, 2039; (b) Belder-
rain, T. R.; Grubbs, R. H. Organometallics 1997, 16,
4001–4003.
4. Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A.
H. J. Am. Chem. Soc. 2000, 122, 8168–8179.
5. (a) Connon, S. J.; Blechert, S. Angew. Chem., Int. Ed.
2003, 42, 1900; (b) Grubbs, R. H. J. Am. Chem. Soc. 2000,
122, 58–71; (c) Crowe, W. E.; Zhang, Z. J. J. Am. Chem.
Soc. 1993, 115, 10998–10999.
2 equiv of variousolefinsof type
A to produce
compoundsof type B. The results are shown in Table
1.15 Notably, the fair Z-selectivity was observed from
the CM of acrylonitrile with variousfunctionalized
olefins. As in previous cross-metathesis reactions with
acrylonitrile, the Z-stereoselectivity must be kinetically
controlled or related to the presence of the electron-
withdrawing properties of the cyano substituent.8
No metathesis product was observed spectroscopically
(1H and 13C NMR) at catalyst loadings of less than
2 mol %, employment of higher catalyst concentrations
did promote the metathesis, and we observed a maxi-
mum 36% conversion of acrylonitrile to 1,4-dicyano-2-
butene product with 10 mol % catalyst loading. Though
the yield was not high, it was the best result at present.
Thiswasdue to the moderately strong coordinating of
cyano group with the ruthenium center, thusdeactivat-
ing the catalyst for olefin metathesis.
6. (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org.
Lett. 1999, 1, 953–956; (b) Sanford, M. S.; Love, J. A.;
Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 6543–6554.
7. Trnka, T. M.; Day, M. W.; Grubbs, R. H. Angew. Chem.,
Int. Ed. 2001, 113, 3549–3552.
On the other hand, the highly active ruthenium carbene
complex 8 wasfound to efficiently catalyze the selective
CM of 1-hexene and acrylonitrile. Productswere
obtained in moderate to high yieldsupon hexene and
2 equiv of acrylonitrile with 10 mol % of catalyst 8 in
dry CH2Cl2 (0.05 M) for 12 h. The relatively high load-
ing of catalyst was required to ensure a high yield. The
yield dropped from 51% to 37% when 2 mol % catalyst
wasused (entries3 and 4). Reactionsbetween acryloni-
trile with various functionalized olefins, such as allyl
alcohol, acrolein, ester, and crylic acid, were performed
in good yields(entries5–12). For example, when allyl
alcohol wasutilized, product wasobtained in 68% yield
with 10 mol % catalyst loading (entry 6), however, when
crylic acid was selected as the substrate, the yield
decreased to around 55% (entry 12).
8. (a) Crowe, W. E.; Goldberg, D. R. J. Am. Chem. Soc.
1995, 117, 5162–5163; (b) Stefan, R.; Simon, G.; Hideaki,
W.; Siegfried, B. Synlett 2001, 3, 430–432; (c) Love, J. A.;
Morgan, J. P.; Trnka, T. M.; Grubbs, R. H. Angew.
Chem., Int. Ed. 2002, 41, 4035–4037; (d) Michrowska, A.
B.; Bujok, R.; Harutyunyan, S.; Sashuk, V.; Dolgonos, G.;
Grela, K. J. Am. Chem. Soc. 2004, 126, 9318–9325.
9. (a) Ho¨lder, S.; Blechert, S. Synlett 1996, 505–506; (b)
Schneider, M. F.; Lucas, N.; Velder, J.; Blechert, S.
Angew. Chem., Int. Ed. 1997, 36, 257–259; (c) Chatterjee,
A. K.; Morgan, J. P.; Scholl, M.; Grubbs, R. H. J. Am.
Chem. Soc. 2000, 122, 3783–3784.
10. (a) Cossy, J.; BouzBouz, S.; Hoveyda, A. H. J. Organo-
met. Chem. 2001, 634, 216–221; (b) Wright, D. L.; Usher,
L. C.; Estrella-Jimenez, M. Org. Lett. 2001, 3, 4275–4277.
11. (a) Slugovc, C.; Demel, S.; Stelzer, F. Chem. Commun.
2002, 2572–2573; (b) Love, J. A.; Sanford, M. S.; Day, M.
W.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 10103–
10109; (c) Sanford, M. S.; Love, J. A.; Grubbs, R. H.
Organometallic 2001, 20, 5314–5318.
In conclusion, we have demonstrated that phosphine-
free carbene ruthenium complex 8 can efficiently cata-
lyze the cross-metathesis of acrylonitrile with various
functionalized olefins. The cross-metathesis can be per-
formed in good yieldsand fair Z-selectivity. Further
development of ruthenium metathesis complex having
activity in the field of CM isin progressin our
laboratory.
12. Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc.
1996, 118, 100–110.
13. Delaude, L.; Szypa, M.; Demonceau, A.; Noels, A. F. Adv.
Synth. Catal. 2002, 344, 749–756.
14. Spectroscopic data of the new ruthenium carbene complex
1
7 and 8: 7: H NMR (399.9 MHz, CDCl3): d = 19.25 (s,
1H, Ru–CH), 7.69–6.56 (multiple peaks, 24H, PPh3, para
CH, meta CH, and 2,6-dimethylphenyl aromatic CH),
7.68–7.66 (d, 2H, ortho CH, J = 7.2 Hz), 4.14–4.10 (t, 2H,
CH2CH2, J = 7.2 Hz), 3.98–3.94 (t, 2H, CH2CH2,
J = 7.2 Hz), 2.64 (s, 12H, ortho CH3). 13C NMR
(100 MHz, CDCl3): d = 292.3 (d, Ru@CHPh), 219.7,
152.6, 139.7, 138.3, 137.4, 134.2, 132.2, 130.5, 129.4, 129.2,
128.7, 128.6, 128.4, 127.8, 127.6, 125.5, 51.9, 50.2, 21.6,
18.9. 31P NMR (161.9 MHz, CDCl3): d = 37.29 (s). Q-
TOFMS: calcd: 767.1896 [MÀCl]+, found: 767.1916
[MÀCl]+; 8: 1H NMR (399.9 MHz, CDCl3): d = 19.10
(s, 1H, CHPh), 8.63 (br s, 4H, pyridine), 7.80 (br s, 4H,
pyridine), 7.64–7.62 (d, 2H, ortho CH, J = 7.2 Hz), 7.46–
7.42 (t, 1H, para CH, J = 7.8 Hz), 7.28–7.24 (t, 2H,
meta CH, J = 7.8 Hz), 7.17–6.93 (br multiple peaks, 8H,
Acknowledgments
This research was supported by a grant from the China
National Petroleum Corporation (CNPC).
References and notes
1. For recent reviews, see: (a) Trnka, T. M.; Grubbs, R. H.
Acc. Chem. Res. 2001, 34, 18–29; (b) Furstner, A. Angew.
¨
Chem., Int. Ed. 2000, 39, 3012–3043; (c) Grubbs, R. H.;

7228
C.-X. Bai et al. / Tetrahedron Letters 46 (2005) 7225–7228
pyridine, 2,6-dimethylphenyl aromatic CH), 4.14 (br s,
J = 7Hz, J = 11Hz, 1H, cis), 5.28–5.26 (m, 1H), 2.22–2.20
(m, 1H), 2.15–2.12 (m, 1H), 1.39–1.33 (m, 4H), 0.85–0.80
(m, 3H). Compound 11: 1H NMR (399.9 MHz, CDCl3)
d = 6.81 (dt, J = 3 Hz, J = 17 Hz, 1H, trans), 6.48 (dt, J =
7 Hz, J = 16 Hz, 1H, cis), 5.72–5.69 (m, 1H), 4.34 (dd,
J = 2 Hz, J = 7 Hz, 2H, trans), 4.23 (dd, J = 2 Hz, J =
7 Hz, 2H, cis), 2.11 (s, 1H). Compound 12: 1H NMR
(399.9 MHz, CDCl3) d = 6.75 (dt, J = 7 Hz, J = 17 Hz,
1H, trans), 6.64 (dt, J = 7 Hz, J = 11 Hz, 1H, cis), 6.51 (dt,
J = 2 Hz, J = 17 Hz, 1H, trans), 6.43 (dt, J = 7 Hz,
J = 11 Hz, 2H, cis), 3.84 (s, 3H). Compound 13: 1H
NMR (399.9 MHz, CDCl3) d = 9.70 (d, J = 7Hz, 1H),
6.90 (dt, J = 7 Hz, J = 17 Hz, 1H, trans), 6.71 (dt,
J = 7 Hz, J = 11 Hz, 1H, cis), 6.40 (d, J = 17 Hz, 1H,
trans), 6.37 (d, J = 11 Hz, 1H, cis). Compound 14: 1H
NMR (399.9 MHz, CDCl3) d = 11.0 (d, J = 7 Hz, 1H),
6.68 (dt, J = 7 Hz, J = 17 Hz, 1H, trans), 6.45 (dt,
J = 7 Hz, J = 11 Hz, 1H, cis), 5.39 (d, J = 17 Hz, 1H,
trans), 5.31 (d, J = 7 Hz, 1H, cis).
4H, NCH2CH2N), 2.65 (br s, 6H, ortho CH3), 2.35 (br s,
6H, ortho CH3). 13C NMR (100 MHz, CDCl3): d = 307.3
(m, Ru@CHPh), 220.4 (s, Ru–C(N)2), 152.3, 150.0, 136.7,
136.0, 130.6, 130.3, 129.6, 129.0, 128.4, 128.1, 124.0, 123.8,
77.5, 77.2, 76.9, 48.3, 46.5, 22.8, 18.7. Q-TOFMS: calcd:
663.1828 [MÀCl]+, found: 663.1830 [MÀCl]+.
15. General procedure for CM reactionswith acrylonitrile: To
a mixture of substrate (1.05 mmol) and acrylonitrile
(112 mg, 2.10 mmol) in dichloromethane (20 mL) was
added 8 (70 mg, 10 mol %). The resulting mixture was
stirred at 45 °C for 12 h. The solvent was removed under
reduced pressure. Chromatography (4:1 hexane/EtOAc)
of the crude residue gave products. All compounds gave
satisfactory spectroscopic and analytical data. Selected
data for compounds 9–14 are included. Compound 9:1H
NMR (399.9 MHz, CDCl3) d = 6.18 (s, 1H, cis), 6.27 (s,
1H, trans). Compound 10: 1H NMR (399.9 MHz, CDCl3)
d = 6.66 (dt, J = 7 Hz, J = 17 Hz, 1H, trans), 6.42 (dt,