Aminocarbonyl group containing Hoveyda - Grubbs-type complexes: Synthesis and activity in olefin metathesis transformations

Article abstract of DOI:10.1021/jo800203d

(Chemical Equation Presented) Three novel "boomerang" precatalysts bearing different aminocarbonyl functions are reported. Comparative kinetic studies show that this functional group allows for a control of the catalytic activity in metathesis transformat

Full text of DOI:10.1021/jo800203d

charges.4 Remarkable progress was achieved when Hoveyda
reported the “boomerang” precatalyst 2a5 based on a release/
return concept of the benzylidene ether fragment. Further
developments by Blechert (2b),6 Grela (2c),7 and Zhan (2d)8
have led to more easily activated catalysts enabling a decrease
in the “boomerang” precatalyst loading (down to 1 mol %). In
the course of developing more environmentally friendly me-
tathesis catalysts,9 we recently reported a pyridinium-containing
precatalyst 2e.10 Unfortunately, the remarkable activity enhance-
ment observed with 2e was counter-balanced by its poor
recyclability combined with an important Ru-contamination of
the products. We concluded that a faster acting precatalyst is
not always desired but improved control of the catalyst activity
should be targeted.
Aminocarbonyl Group Containing
Hoveyda-Grubbs-Type Complexes: Synthesis
and Activity in Olefin Metathesis
Transformations
Diane Rix,† Fre´deric Caijo,† Isabelle Laurent,†
Fabien Boeda,‡ Herve´ Clavier,*,‡ Steven P. Nolan,*,‡ and
Marc Mauduit*,†
“Sciences Chimiques de Rennes” UMR 6226 CNRS-Equipe
Chimie Organique et Supramole´culaire-Ecole Nationale
Supe´rieure de Chimie de Rennes, AV. du Ge´ne´ral Leclerc,
35700 Rennes, France, and Institute of Chemical
Research of Catalonia (ICIQ), AV. Pa¨ısos Catalans, 16.
43007 Tarragona, Spain
hclaVier@iciq.es; snolan@iciq.es;
marc.mauduit@ensc-rennes.fr
ReceiVed January 26, 2008
FIGURE 1. Ruthenium-based olefin metathesis precatalysts.
Aiming our synthetic efforts in this direction, we designed
an improved version of complex 2f (Figure 1) bearing a
methylene spacer and reached the forementioned goal where
excellent activity and recyclability can be combined with
generation of low levels of ruthenium-waste.11 We decided to
Three novel “boomerang” precatalysts bearing different
aminocarbonyl functions are reported. Comparative kinetic
studies show that this functional group allows for a control
of the catalytic activity in metathesis transformations. The
scope of the more active catalyst is investigated and shows
a good tolerance to various substrates in ring-closing
metathesis, enyne metathesis, and cross metathesis. ICP-MS
analyses illustrate the good affinity of this catalyst for silica
gel, as levels of Ru contamination lower than 6 ppm are
detected in the final products.
(2) For selected reviews on olefin metathesis, see: (a) Trnka, T. M.; Grubbs,
R. H. Acc. Chem. Res. 2001, 34, 18–29. (b) Handbook of Metathesis; Grubbs,
R. H., Ed.; Wiley-VCH: Weinheim, Germany, 2003. (c) Connon, S. J.; Blechert,
S. Angew. Chem., Int. Ed. 2003, 42, 1900–1923. (d) Nicolaou, K. C.; Bulger,
P. C.; Sarlah, D. Angew. Chem., Int. Ed. 2005, 44, 4490–4527. (e) Beligny, S.;
Blechert, S. In N-Heterocyclic Carbenes in Synthesis; Nolan, S. P., Ed.; Wiley-
VCH: Weinheim, Germany, 2006; pp 1-25.
(3) (a) Scholl, M.; Trnka, T. M.; Morgan, J. P.; Grubbs, R. H. Tetrahedron
Lett. 1999, 40, 2247–2250. (b) Gessler, S.; Randl, S.; Blechert, S. Tetrahedron
Lett. 2000, 41, 9973–9976. (c) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H.
Org. Lett. 1999, 1, 953–956.
(4) Clavier, H.; Grela, K.; Kirschning, A.; Mauduit, M.; Nolan, S. P. Angew.
Chem., Int. Ed. 2007, 46, 6786–6801.
Since the discovery of the well-defined ruthenium-based
catalystCl2(PCy3)2RudCHPh1 that possesses a fairly broad
reaction scope, high tolerance to functional groups, olefin
metathesis has become a mainstream synthetic tool.2 Despite
developments focusing on new precatalysts, such as 1,3 olefin
metathesis still suffers from the required use of high catalytic
(5) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.; Hoveyda, A. H.
J. Am. Chem. Soc. 1999, 121, 791–799.
(6) (a) Wakamatsu, H.; Blechert, S. Angew. Chem., Int. Ed. 2002, 41, 794–
796. (b) Wakamatsu, H.; Blechert, S. Angew. Chem., Int. Ed. 2002, 41, 2403–
2405.
(7) (a) Grela, K.; Harutyunyan, S.; Michrowska, A. Angew. Chem., Int. Ed.
2002, 41, 4038–4040. (b) Michrowska, A.; Bujok, R.; Harutyunyan, S.; Sashuk,
V.; Dolgonos, G.; Grela, K. J. Am. Chem. Soc. 2004, 126, 9318–9325.
(8) Zhan, Z.-Y. J. WO Patent 2007003135, 2007.
† “Sciences Chimiques de Rennes” UMR 6226 CNRS-Equipe Chimie
Organique et Supramole´culaire-Ecole Nationale Supe´rieure de Chimie de Rennes.
‡ Institute of Chemical Research of Catalonia.
(1) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 2039–2041.
(9) (a) Audic, N.; Clavier, H.; Guillemin, J.-C.; Mauduit, M. J. Am. Chem.
Soc. 2003, 125, 9248–9249. (b) Clavier, H.; Audic, N.; Guillemin, J.-C.; Mauduit,
M. Chem. Commun. 2004, 1224–1225. (c) Clavier, H.; Audic, N.; Guillemin,
J.-C.; Mauduit, M. J. Organomet. Chem. 2005, 690, 3585-3599. Zhan, Z.-Y.
PCT int. appl. WO 2007003135, 2007.
10.1021/jo800203d CCC: $40.75
Published on Web 05/07/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 4225–4228 4225

SCHEME 1. Synthesis of Amide-Grafted Precatalysts 2g-i
FIGURE 2. Ball-and-stick representation of precatalysts 2g-i. Selected
bond lengths (Å) and angles (deg): 2g, Ru(1)-C(1) 1.8408(9),
Ru(1)-C(22) 1.9779(8), Ru(1)-O(1) 2.2221(6), C(1)-Ru(1)-C(22)
103.38(3), C(1)-Ru(1)-O(1) 80.13(3); 2h, Ru(1)-C(1) 1.8338(9),
Ru(1)-C(22) 1.9852(8), Ru(1)-O(1) 2.2383(7), C(1)-Ru(1)-C(22)
103.42(4), C(1)-Ru(1)-O(1) 79.98(3); 2i, Ru(1)-C(1) 1.823(3),
Ru(1)-C(22) 1.975(3), Ru(1)-O(1) 2.257(2), C(1)-Ru(1)-C(22)
102.32(11), C(1)-Ru(1)-O(1) 79.19(10).
investigate more tunable chemical functions dedicated not only
to improve the activity of a “boomerang”-type complex, but
also to facilitate the anchoring of such catalysts onto various
supports. In view of its high structural modularity and its tunable
electronics via various substituents, the aminocarbonyl function
caught our attention and is the focus of this report.
We initially introduced different aminocarbonyl functions such
as amides (2g and 2h) and carbamates (2i) onto the Hoveyda-type
“boomerang” styrenyl ether fragment. The required aminocarbonyl-
containing ligands 4g-i were synthesized in one step from the
previously reported functionalized aniline 310 (Scheme 1). Reaction
of ligands 4 with the second generation Ru-indenylidene complex
5
12 in the presence of CuCl5 led to a family of air- and moisture-
stable green microcrystalline solids 2g-i.
The structures and atom connectivities of precatalysts were
unambiguously confirmed by single-crystal diffraction studies.
The molecular structures show oxygen coordination to the
ruthenium center (Figure 2). The bond lengths and angles were
found in the same range as those reported for similar com-
plexes,13 except for the Ru(1)-O(1) bond, which is significantly
shorter than in 2b, in particular for complex 2g. Of note, the
C(1)-Ru(1)-C(22) angle was found significantly more acute
than in 2b, indicating a tilt of the N-heterocyclic carbene.
We then investigated reactivity profiles of these aminocar-
bonyl-grafted precatalysts and examined if these different
functions would be reflected on chemical reactivity. A model
ring-closing metathesis (RCM) reaction involving 2-allyl-2-
methallylmalonate 6 was chosen for the present comparative
investigation, using 1 mol % catalyst at 30 °C in CD2Cl2 (Figure
3). Remarkably, significant differences between initiation rates
were observed and three different classes of complexes can be
identified: the weakly enhanced precatalyst 2g, the moderately
activated carbamate 2i, and the highly improved precatalyst 2h
bearing the trifluoroacetamide function. These differences in
reactivity can be linked to the switchable electronic properties
of the aminocarbonyl group itself (EDG or EWG).14 Conse-
quently, by a judicious choice of the group directly anchored
FIGURE 3. Kinetic studies of RCM of trisubstitued olefin 6 (0.1 M)
with precatalysts 2g-i (1 mol %) in CD2Cl2 at 30 °C; (2g, 2), (2h,
9), (2i, b). Conversions are given by NMR measurement.
to the aminocarbonyl-function, a tuning of the precatalyst
activity can be achieved.
To further examine this aminocarbonyl effect, the reaction
profile of a more activated complex, e.g., trifluoroacetamide
precatalyst 2h, was compared to the RCM reaction involving
diallyltosylamine 8 at 0 °C (Figure 4). As evidence of the
beneficial role of the trifluoroacetamide group, its activity was
found significantly improved compared to commercially avail-
able precatalysts 1 and more particularly 2a, but slightly lower
than the highly efficient 2c7 and 2d.8
These promising results led us to investigate the scope of
the activity of 2h by using selected benchmark substrates for
RCM and enyne metathesis (EM) (Table 1). RCM of various
amide-, ester-, and ether-containing substrates were carried out
at rt in less than 1 h with 1 mol % of 2h. The formation of 5-
and 6-membered rings was also achieved easily; RCM leading
(10) Rix, D.; Clavier, H.; Coutard, Y.; Gulajski, L.; Grela, K.; Mauduit, M.
J. Organomet. Chem. 2006, 691, 5397–5405.
(11) Rix, D.; Ca¨ıjo, F.; Laurent, I.; Gulajski, L.; Grela, K.; Mauduit, M. Chem.
Commun. 2007, 3771–3773.
(12) Clavier, H.; Nolan, S. P. Chem. Eur. J. 2007, 13, 8029–8035.
(13) (a) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am.
Chem. Soc. 2000, 122, 8168–8179. (b) Krause, J. O.; Nuyken, O.; Wurst, K.;
Buchmeiser, M. R. Chem. Eur. J. 2004, 10, 777–784. (c) Weigl, K.; Ksˇhler, K.;
Dechert, S.; Meyer, F. Organometallics 2005, 24, 4049–4056. (d) Fu¨rstner, A.;
Davies, P. W.; Lehmann, C. W. Organometallics 2005, 24, 4065–4071. (e)
Vehlow, K.; Maechling, S.; Blechert, S. Organometallics 2006, 25, 25–28.
(14) The use of EDG or EWG to modify the chemical activity of Ru
complexes has recently been reported by Grela, see: Gulajski, L.; Michrowska,
A.; Bujok, R.; Grela, K. J. Mol. Catal. A 2006, 254, 118–123.
4226 J. Org. Chem. Vol. 73, No. 11, 2008

TABLE 1. Scope of 2h for RCM Transformationsa
FIGURE 4. Kinetic studies of RCM of disubstitued olefin 8 (0.02 M)
with commercially available precatalysts and 2h (1 mol %) in CD2Cl2
at 0 °C: (1, +), (2a, (), (2c, b), (2d, 2), (2h, 9). Conversion determined
by NMR spectroscopy.
to 7-membered-ring translated into a substantial increase in the
required reaction time (entries 5 and 8). Various degrees of diene
substitution are well tolerated, even tetrasubstituted tosylamide
18 required only 2 mol % of 2h and 24 h of heating at 40 °C
to produce 80% of 19 (entry 6). For several dienes, the enhanced
activity of 2h allowed us to decrease the catalyst loading to 0.3
mol %, without any detrimental effect on reaction times (entries
1-3, and 7). We extended the reaction scope of 2h to two
enynes (entries 9 and 10). Although cyclization of enyne 24
required a slight thermal activation, 25 was isolated in good
yields after 6 h. On the other hand, 27 was isolated quantitatively
after 30 min when 0.3 mol % of 2h was used (entry 10). More
interestingly, the contamination in ruthenium waste of 7 and
13 was determined by ICP-MS analyses. With use of 1 mol %
of catalyst loading, respectively only 1.8 ansd 5.5 ppm of Ru
were observed in the products after silica gel chromatography.
We believe these results are a consequence of a beneficial
affinity of the ruthenium catalyst or/and its derivatives (degrada-
tion species) for silica.15
We also examined the CM reactions of terminal alkenes and
R,ꢀ-unsaturated olefins (Table 2). Excellent yields were obtained
in short reaction times with use of only 1 mol % of 2h. However,
in the case of more problematic substrates such as acrylonitrile or
allyltosylamine (entries 3 and 4), the cross metathesis reactions
performed with the ester 28 were incomplete, yielding only 40%
and 60% of the desired products 32 and 33, respectively, even when
2 mol % of 2h was used at 40 °C over 24 h.
In summary, we have synthesized in a straightforward manner
three novel Ru-based olefin precatalysts. The use of the
aminocarbonyl function led to a simple and efficient control
(enhancement) of the catalytic activity of these “boomerang”
catalysts. The scope of the best precatalyst 2h was evaluated
for several metathesis transformations with use of as low as
a Reaction condition: 1 mol % of 2h, CH2Cl2, 0.1 M, rt. b Isolated
yield. c 0.3 mol % of 2h was used. d Reaction performed at 40 °C with
2 mol % of 2h. e Reaction performed at 40 °C.
0.3 mol % of catalyst without the need for long reaction times.
Moreover, extremely low levels of residual ruthenium contami-
nation were detected in the final products (below 6 ppm). In
view of the modular aspect of the aminocarbonyl function,
further advances through elaboration of the function appear
promising for the purpose of immobilization onto supports. Such
investigations are currently underway in our laboratories and
will be disclosed shortly.
(15) (a) Several recent complexes have shown a strong affinity for silica
allowing for low contamination in residual ruthenium after a single chromatog-
raphy pass (below 100 ppm). Conrad, J. C.; Parnas, H. H.; Snelgrove, J. L.;
Fogg, D. E. J. Am. Chem. Soc. 2005, 127, 11882-11883. (b) Grela, K.; Kim,
M. Eur. J. Org. Chem. 2003, 963–966. (c) Michrowska, A.; Gulajski, L.; Grela,
K. Chem. Commun. 2006, 841–843. (d) Gawin, R.; Makal, A.; Wozniak, K.;
Mauduit, M.; Grela, K. Angew. Chem., Int. Ed. 2007, 46, 7206–7209.
Experimental Section
General Procedure for Catalyst Formation. To a solution of
catalyst 5 and copper chloride (1.1 equiv) in dry DCM (1 mL for
0.02 mmol of Ru-indenylidene complex) was added 4g-i (1 equiv)
in DCM solution (1 mL for 0.05 mmol of ligand). The resulting
J. Org. Chem. Vol. 73, No. 11, 2008 4227

TABLE 2. Scope of 2h in Cross Metathesisa
the title product (243 mg, 90% yield). 1H NMR (400 MHz, acetone-
3
d6, 25 °C, TMS): δ (ppm) 16.44 (s, 1H), 7.79 (dd, J(H,H) ) 8.8
Hz, 4J(H,H) ) 2.5 Hz, 1H), 7.61 (d, 4J(H,H) ) 2.6 Hz, 1H),
3
7.08-7.06 (m, 5H), 4.97 (sept, J(H,H) ) 6.1 Hz, 1H), 4.28 (s,
3
4H), 2.47 (s, 12H), 2.43 (s, 6H), 1.26 (d, J(H,H) ) 6.1 Hz, 6H).
13C NMR (100 MHz, acetone-d6, 25 °C, TMS): δ (ppm) 291.3 (d,
J(C,Ru) ) 12.3 Hz), 209.9, 149.5, 145.0, 138.7, 131.3, 129.1, 121.1,
121.0, 116.0 (q, J(C,F) ) 286.7 Hz), 114.2, 114.1, 113.2, 75.3,
51.4, 20.6, 20.3. 19F NMR (376 MHz, acetone-d6, 25 °C, TMS): δ
(ppm) -76.2 (s). HRMS (ESI): m/z calcd for C33H38Cl2F3N3O2Ru
- Cl + CH3CN 743.1914 [M+ - Cl + CH3CN], found 743.1926.
(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(2-iso-
propoxy-5-(isobutylcarbamido)benzylidene)ruthenium(II) Dichlo-
ride (2i). Following the general procedure with ligand 4i afforded
the title product (45 mg, 84% yield). 1H NMR (400 MHz, CD2Cl2
25 °C, TMS): δ (ppm) 16.45 (s, 1H), 7.65 (d, J ) 8.7 Hz, 1H),
7.09 (s, 4H), 6.99 (s broad, 1H), 6.78 (d, J ) 8.7 Hz, 1H), 6.62 (s
broad, 1H), 4.85 (sept, J ) 6.0 Hz, 1H), 4.18 (s, 4H), 3.95 (d, J )
6.6 Hz, 1H), 2.45 (s, 18H), 2.02-1.95 (m, 1H), 1.23 (d, J ) 6.0
Hz, 6H), 0.99 (d, J ) 6.7 Hz, 6H). 13C NMR (125 MHz, CD2Cl2,
25 °C, TMS): δ (ppm) 294.3, 210.4, 153.8, 148.0, 145.0, 139.0,
133.2, 129.2, 119.5, 112.9, 112.5, 75.2, 71.2, 51.1, 29.7, 28.0, 20.8,
18.8. HRMS (ESI): m/z calcd for C36H47Cl2N3O3Ru + Na 764.1936
[M+ + Na], found 764.1939. Elemental analysis calcd (%) for
C36H47Cl2N3O3Ru: C 58.29, H 6.39, N 5.66. Found: C 58.28, H
6.46, N 5.24.
a Reactions conditions: 1 mol % of 2h, CH2Cl2, 0.1 M, rt. b Isolated
yield. c Reaction performed at 40 °C with 2 mol % of 2h.
mixture was stirred at 35 °C for 5 h. Volatiles were removed under
reduced pressure, acetone was added to the residue, and the solution
was filtered through a pad of Celite. The filtrate was concentrated
and purified by chromatography on silica gel (pentane/acetone, 75/
25) to yield to catalysts 2g-i as green microcrystalline solids.
(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(2-iso-
propoxy-5-(adamantanamido)benzylidene)ruthenium(II) Dichlo-
ride (2g). Following the general procedure with ligand 4g afforded
the title product (28 mg, 86% yield). 1H NMR (400 MHz, acetone-
d6, 25 °C, TMS): δ (ppm) 16.39 (s, 1H), 8.42 (s, 1H), 7.64 (dd,
3J(H,H) ) 8.7 Hz, 4J(H,H) ) 2.5 Hz, 1H), 7.61 (d, 4J(H,H) ) 2.5
Hz, 1H), 7.07 (s, 4H), 6.92 (d, 3J(H,H) ) 8.7 Hz, 1H), 4.90 (sept,
3J(H,H) ) 6.1 Hz, 1H), 4.28 (s, 4H), 2.78 (s, 3H), 2.47 (s, 12H),
2.44 (s, 6H), 2.00 (s, 6H), 1.78 (s, 6H), 1.24 (d, 3J(H,H) ) 6.1 Hz,
6H). 13C NMR (100 MHz, acetone-d6, 25 °C, TMS): δ (ppm) 293.3
(d, J(C,Ru) ) 11.9 Hz, CH), 210.9, 175.5, 148.1, 144.9, 138.6,
134.3, 129.4, 129.1, 120.7, 114.4, 112.5, 74.6, 51.3, 41.1, 38.8,
36.3, 28.3, 20.6, 20.3. HRMS (ESI): m/z calcd for C42H53Cl2N3O2Ru
- Cl + CH3CN 908.3135 [M+ - Cl + CH3CN], found 809.3161.
Elemental analysis calcd (%) for C42H53Cl2F3N3O2Ru: C 62.75, H
6.65, N 5.23. Found: C 62.32, H 6.71, N 5.15.
Acknowledgment. D.R., F.C., I.L., and M.M. thank the
CNRS, the Region Bretagne, the ENSCR, and the Bretagne-
valorisation. F.B., H.C., and S.P.N. gratefully thank the ICIQ
Foundation for financial support. S.P.N (research grant) and H.C.
(postdoctoral fellowship) both acknowledge the Ministerio de
Educacio´n y Ciencia (Spain). S.P.N. is an ICREA Research
Professor. Umicore A.G. is gratefully acknowledged for gener-
ous gifts of materials. We also thank Dr. Jordi Benet-Buchholz
and Mr. Eduardo Carmelo-Escudero for X-ray structure
determinations.
Supporting Information Available: Synthetic procedure and
characterization of new compounds, data of kinetic studies and
crystallographic informations files (CIF) of complexes 2g-i.
This material is available free of charge via the Internet at http://
pubs.acs.org. The CIF files have also been deposited with the
CCDC, Nos. CCDC-634625, 666288, and 675653; copies of
the data can be obtained free of charge on applications to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK, fax +44 1223 336
033, http://www.ccdc.cam.ac.uk, e-mail deposit@ccdc.cam.ac.uk.
(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(2-isopro-
poxy-5-(2,2,2-trifluoroacetamido)benzylidene)ruthenium(II) Dichlo-
ride (2h). Following the general procedure with ligand 4h afforded
JO800203D
4228 J. Org. Chem. Vol. 73, No. 11, 2008