Olefin cross-metathesis with vinyl halides

Article abstract of DOI:10.1039/b801687a

The first successful example of olefin cross-metathesis with chloroalkenes is reported. The Royal Society of Chemistry.

Full text of DOI:10.1039/b801687a

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Olefin cross-metathesis with vinyl halidesw
Volodymyr Sashuk, Cezary Samoj$owicz, Anna Szadkowska and Karol Grela*
Received (in Cambridge, UK) 30th January 2008, Accepted 28th February 2008
First published as an Advance Article on the web 27th March 2008
DOI: 10.1039/b801687a
The first successful example of olefin cross-metathesis with
chloroalkenes is reported.
Functionalised olefins are important building blocks for
organic synthesis. Catalytic olefin cross-metathesis (CM) is a
convenient route to functionalise olefins from simple alkene
precursors.1 One of the most appealing facets of this transfor-
Scheme 2 The fate of chloromethylidene 2 according to Johnson et al.9a
mation is that a carbon–carbon double bond of one or both
cross-metathesis partners can be substituted by a heteroatom-
containing group Z (Scheme 1).1d
With the advent of highly active catalysts2 1a–1c the range
of functionalised olefins that participate in CM now includes
a,b-unsaturated carbonyl-containing olefins,1a–c acrylonitrile,3
vinylphosphonates,4 vinyl phosphine oxides,5 perfluorinated
alkane containing olefins,6 vinyl sulfones,7 vinyl-azulenes8 and
others.
alkenyl chlorides. The Authors observed that complex 2 is
formed initially in CM, but undergoes rapid decomposition
into catalytically inactive 3 and 4 (Scheme 2).9a
In a separate experiment it was shown that 2, generated at
ꢀ70 1C, underwent PCy3 shift to form 4 upon increasing the
temperature to 0–20 1C. The Authors conclude that rapid
decomposition of 2, not the failure to form 2, accounts for the
failure of attempted CM reactions of vinyl chloride using
catalysts such as 1a9a and, therefore, that modified catalysts
for olefin metathesis with vinyl halides are needed.9b Inspired
by this excellent mechanistic study, we decided to investigate
the same reaction using complexes 1b–d.12 We expected that
the phosphine-free catalysts will promote the CM of alkenyl
chlorides, instead of undergoing the PCy3-involving decom-
position pathway, described by Johnson et al.9
The CM reaction of 4-methoxystyrene 5a with (E)-1,2-
dichloroethylene (6a) used as a solvent (100 equiv. relative to
5a) at reflux temperature was chosen as a model trans-
formation.z As expected, use of 5 mol% of 1a2a led to rather
low conversion of 5a; GC analysis revealed that CM product
7a was formed in 15% yield, thus indicating only three turn-
overs (Table 1, entry 1). Importantly, we observed that the
addition of CuCl, which is known to sequester PCy3 into an
Scheme 1 Cross-metathesis of functionalized olefins and selected
Ru-precatalysts.
Therefore, CM complements other C–C coupling methods,
such as Wittig, Horner–Wadsworth–Emmons or Heck reac-
tions.1 However, not all functional groups are compatible with
Ru-based catalysts in CM reactions. In particular, phosphine-
containing catalysts such as 1a have been reported to fail to
mediate CM of vinyl halides.9 This is unfortunate, given that
alkenyl halides are key building blocks in transition-metal-
catalysed syntheses, particularly in various Pd-catalysed cou-
pling reactions.10,11 Johnson et al. studied the fate of complex
2, the product of an initial metathesis cycle in CM of some
Table 1 Comparative screening of catalysts in CM of 5a
Entry
Catalyst (mol%)
Yield (%)a
TON
1
2
3
4
5
6
a
1a (5)
1a (5)b
1b (5)
1c (5)
1c (1)
1d (5)
15
32
24
54
21
24
3
6
5
11
21
5
Institute of Organic Chemistry, Polish Academy of Sciences,
Kasprzaka 44/52, 01-224 Warsaw, Poland. E-mail:
klgrela@gmail.com
w Electronic supplementary information (ESI) available: Experimental
details for the preparation of the reported compounds and copies of
NMR spectra. See DOI: 10.1039/b801687a
b
Yields were determined by GC. With 5% mol of CuCl.
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Table 2 CM between 6a and alkenes 5
Yield (%)a
41
Time/h
20
Entry
1
Substrate
Catalyst (mol%)
Product
1c (5%)
5b
5b
7b (Z : E = 1.4 : 1)
7b (Z : E = 1.4 : 1)
2
3
1c (10%)b
1c (15%)c
20
20
87
76
5c
5a
7c (Z : E = 1.5 : 1)
7a (Z : E = 5 : 1)
4
5
1d (15%)c
1d (10%)d
6
20
91
85
5d
5e
7d (only Z isomer)
7e (only Z isomer)
6
7
1c (5%)
24
20
35 (66)
32 (34)f
1c (10%)e
5f
7f (only Z isomer)
8
1c (10%)e
20
(52)
5g
7g (Z : E = 2.6 : 1)
a
b
Isolated yields of analytically pure products. In parenthesis are yields determined by GC or 1H NMR. Catalyst added in 4 equal portions over
c
4 h. Catalyst added in 3 equal portions over 3 h. Catalyst added in 6 equal portions over 6 h. Catalyst added in 5 equal portions over
f
5 h. Substrate 5f was consumed completely during the reaction.
d
e
insoluble ill-defined complex,3b positively influenced the reac-
tion, leading to formation of 7a in 32% yield (entry 2). The
phosphine-free Hoveyda–Grubbs complex2b 1b exhibited a
similar level of reactivity (entry 3) without any additive. To
our delight, complex 1c,12a the boosted version of Hoveyda’s
catalysts, led to formation of 7a in remarkable 54% yield
(TON = 11, entry 4) when used in 5 mol%. An even higher
turnover number, TON = 21, was achieved when the same
catalyst was used in 1 mol% (entry 5). The newly developed
complex 1d, although quite reactive in other CM reactions,12b
in this particular case was only moderately active (entry 6).
The CM product, 7a, was formed, irrespective of the
catalyst used, as a mixture of (Z) and (E) isomers in the ratio
5 : 1. Recent computational studies on the CM reaction
pathways of 1a with ethylene, (E)-1,2-difluoroethylene and
(E)-1,2-dichloroethylene demonstrated that the metathesis of
halogenated olefins is a kinetically controlled process.13 This
theoretical result is in good agreement with the observed
preference to form thermodynamically less stable product
(Z)-7a (Table 1). Interestingly, application of (Z)-1,2-dichloro-
ethylene (6b)14 led to a distinctly different outcome—the
reaction of 5a with 6b catalysed by 5 mol% of 1c gave 7a in
much lower stereoselectivity (Z : E = 1.08 : 1) and yield
(32%).
Having optimised conditions,15 we attempted to test the
practicability and scope of this reaction (Table 2).y
Utilizing 5 mol% of 1c, introduced in one portion, it was
possible to obtain product 7b in 41% isolated yield (entry 1).
Much better results were obtained by adding 10 mol% of the
catalyst in four equal portions over four hours (entry 2). This
result suggests that the propagating species formed from 1c are
still relatively short-lived, therefore the portion-wise addition
of the (pre)catalyst is optimal. Catalyst 1d, used in a similar
regime also led to a very good result (entry 4). Unexpectedly,15
vinyl sulfides (5d, 5e) were found to be good CM partners,
leading to formation of the corresponding products with
excellent stereoselectivities (entries 5, 6). Nitrogen-substituted
alkene 5f was also found to produce the expected (Z)-alkenyl
chloride 7f (entry 7), although in lower yield (Scheme 3).16
Reaction of 1a with vinyl bromide, studied by Johnson et al.,
was complicated by halogen exchange among Ru complexes;
nevertheless, no productive CM was observed.9a Similarly,
Weinreb and Chao reported a failure in RCM of a diene
containing a bromo-substituted double bond (the same reaction
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and J. P. A. Harrity, Org. Biomol. Chem., 2004, 2, 1; (c) K. Grela,
A. Michrowska and M. Bieniek, Chem. Rec., 2006, 6, 144.
3 (a) S. Randl, S. Gessler, H. Wakamatsu and S. Blechert, Synlett,
2001, 430, 432; (b) M. Rivard and S. Blechert, Eur. J. Org. Chem.,
2003, 68, 2225.
4 (a) A. K. Chatterjee, T.-L. Choi and R. H. Grubbs, Synlett, 2001,
1034; (b) M. Lera and C. J. Hayes, Org. Lett., 2001, 3, 2765; (c) D.
S. Stoianova and P. R. Hanson, Org. Lett., 2000, 2, 1769.
5 (a) N. Vinokurov, A. Michrowska, A. Szmigielska, Z. Drzazga, G.
Scheme 3 CM between 5b and 1,2-dibromoethylene (6c).17 (a)
Catalyst added in 5 equal portions over 5 h. (b) Isolated yields of
analytically pure product.
Wojciuk, O. M. Demchuk, K. Grela, K. M. Pietrusiewicz and H.
´
Butenschon, Adv. Synth. Catal., 2006, 348, 931; (b) F. Bisaro and
with a chloro-substituted diene was high-yielding).11d Interest-
ingly, in the reaction between 1,2-dibromoethylene (6c) and 5b
the expected dibromide 7h was formed, albeit in low yield (34%).
Calculations done recently by Fomine et al. show that the Gibbs
free activation energy of the CM reaction of halogen substituted
alkenes is strongly dependent on the volume of halogen sub-
stituents and therefore the steric factor makes the most important
contribution to the outcome of such CM reactions.13
¨
V. Gouverneur, Tetrahedron, 2005, 61, 2395.
6 S. Imhof, S. Randl and S. Blechert, Chem. Commun., 2001,
1692.
7 (a) K. Grela and M. Bieniek, Tetrahedron Lett., 2001, 42, 6425; (b)
K. Grela, A. Michrowska, M. Bieniek, M. Kim and R. Klajn,
Tetrahedron, 2003, 59, 4525; (c) M. Bieniek, D. Ko"oda and K.
Grela, Org. Lett., 2006, 8, 5689.
8 A. Mikus, V. Sashuk, M. Ke˛dziorek, C. Samoj"owicz, S. Ostrowski
and K. Grela, Synlett, 2005, 1142.
To summarize, we have shown that CM of alkenes with (E)-
1,2-dichloroethylene promoted by phosphine-free catalysts
like 1c leads to formation of the expected chloroalkenes in
acceptable yields while the analogous reaction with 1,2-dibro-
moethylene is more challenging. Fortunately, following the
development of active palladium catalysts, even vinyl chlorides
have become valuable substrates for Pd-couplings.10b
Although not all mechanistic details of this transformation
are fully explained, ongoing work is directed toward further
applications of CM as a mild and selective method for the
synthesis of chlorinated molecules.
9 (a) M. L. Macnaughtan, M. J. A. Johnson and J. W. Kampf, J.
Am. Chem. Soc., 2007, 129, 7708; (b) M. L. Macnaughtan, Needed:
Modified Catalysts for Olefin Metathesis with Vinyl Halides, poster
and oral presentation. The 17th International Symposium on
Olefin Metathesis (ISOM 17), Pasadena, USA, 29 July–3 August,
2007; (c) See also: A. K. Chatterjee, J. P. Morgan, M. Scholl and
R. H. Grubbs, J. Am. Chem. Soc., 2000, 122, 3783; (d) Mechan-
istically related enyne cross-metathesis involving vinyl chlorides
has been recently described, see ref. 9a.
10 (a) J. Tsuji, Transition Metal Reagents and Catalysts: Innovations in
Organic Synthesis, Wiley, New York, 2000, p. 27; (b) A recent
example: A. F. Littke and G. C. Fu, Angew. Chem., Int. Ed., 2002,
41, 4176.
11 RCM involving fluoro- and chloro-substituted C–C double bonds
has been achieved; for selected examples, see: (a) M. Marhold, A.
Buer, H. Hiemstra, J. H. van Maarseveen and G. Haufe, Tetra-
hedron Lett., 2004, 45, 57; (b) W. Chao, Y. R. Mahajan and S. M.
Weinreb, Tetrahedron Lett., 2006, 47, 3815; (c) V. De Matteis, F.
L. van Delft, J. Tiebes and F. P. J. T. Rutjes, Eur. J. Org. Chem.,
2006, 71, 1166; (d) W. Chao and S. M. Weinreb, Org. Lett., 2003, 5,
2505.
KG and CS thank the Foundation for Polish Science
(‘‘Mistrz’’ Programme) for financial support.
Notes and references
z Comparative CM experiments with diene 5a (refer to Scheme 1): to a
stirred solution of diene 5a (0.2 mmol, 26.8 mg) and durene (used as an
internal standard, 0.1 mmol) in (E)-1,2-dichloroethene (100 equiv., 1.6
mL) placed under argon in a Schlenk tube a catalyst (0.001–0.005
mmol) was added in a single portion at room temperature and the
reaction mixture was refluxed for 20 h. Reaction mixtures were
immediately analysed by GC, using an HP 6890 chromatograph with
an HP 5 column. The responses of the FID detector were calibrated
using 5a–durene and 7a–durene standard solutions. Each CM experi-
ment was repeated at least twice.
y Representative procedure of CM reaction: to a solution of alkene
(0.60 mmol) in (E)-1,2-dichloroethene (100 equiv., 4.6 mL) was added
a Ru-catalyst as a solid by portions (one portion per hour) or in one
portion (0.03–0.09 mmol, 5.0–15.0 mol%). The resulting mixture was
refluxed for 6–24 h. The solvent was removed under reduced pressure.
The crude product was purified by flash or preparative thin layer
chromatography (c-hexane–EtOAc).
12 (a) A. Michrowska, R. Bujok, S. Harutyunyan, V. Sashuk, G.
Dolgonos and K. Grela, J. Am. Chem. Soc., 2004, 126, 9318; (b) M.
Bieniek, R. Bujok, M. Cabaj, N. Lugan, G. Lavigne, D. Arlt and
K. Grela, J. Am. Chem. Soc., 2006, 128, 13652; (c) For the first
successful example of the CM with vinyl chlorides, see: K. Grela,
A. Michrowska, M. Bieniek, V. Sashuk and A. Szadkowska,
Phosphine-Free EWG-activated Ruthenium Olefin Metathesis Cat-
alysts: Design, Preparation and Applications, in New Frontiers in
Metathesis Chemistry: From Nanostructure Design to Sustainable
Technologies for Synthesis of Advanced Materials, NATO ASI
Series, ed. Y. Imamoglu and V. Dragutan, Springer-Verlag, Berlin,
2007, pp. 111–124.
13 For a computational study on metathesis of halogenated olefins,
see: S. Fomine, J. V. Ortega and M. A. Tlenkopatchev, J. Mol.
Catal. A: Chem., 2007, 263, 121.
14 (Z)-1,2-Dichloroethylene used by us contained 15% of the
(E)-isomer.
15 After screening of various conditions it was found that running
CM in neat 6a is optimal. For example, CM of 5a with 10 equiv. of
6a catalyzed by 1c in refluxing dichloromethane lead to 10–20%
lower conversions (compare with Table 1, entry 4). It should be
noted that using 6a as a solvent is justified from the economic point
of view, as it can be fully recovered by distillation after reaction
and reused.
16 For a study on the reactivity of RuQCHER complexes (E = S, N,
O), see: J. Louie and R. H. Grubbs, Organometallics, 2002, 21,
2153, and the references cited herein.
1 For reviews on catalytic cross-metathesis, see: (a) S. Blechert and S.
J. Connon, Angew. Chem., Int. Ed., 2003, 42, 1900; (b) A. J. Vernall
and A. D. Abell, Aldrichimica Acta, 2003, 36, 93; (c) For industrial
applications, see: R. L. Pederson, I. M. Fellows, T. A. Ung, H.
Ishihara and S. P. Hajela, Adv. Synth. Catal., 2002, 344, 728; (d)
For a recent review on metathesis of heteroatom-substituted
olefins, see: P. Van de Weghe, P. Bisseret, N. Blanchard and J.
Eustache, J. Organomet. Chem., 2006, 691, 5078.
2 (a) Handbook of metathesis, ed. R. H. Grubbs, Wiley-VCH,
Weinheim, Germany, 2003; (b) A. H. Hoveyda, D. G. Gillingham,
J. J. Van Veldhuizen, O. Kataoka, S. B. Garber, J. S. Kingsbury
17 1,2-Dibromoethylene was used as commercially available mixture
of isomers, Z : E = 1.8 : 1.
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This journal is The Royal Society of Chemistry 2008
2470 | Chem. Commun., 2008, 2468–2470