Cyclodimerization of alkynes with phosphine-free ruthenium carbene complexes: Carbene consumption by a shunted alkyne oligomerization

Article abstract of DOI:10.1021/ja0705689

A new cyclodimerization of ruthenium carbenes and alkynes is reported. The cyclodimerization produces substituted cyclopentadienes and consumes the carbene complex. Cyclodimerization of alkynes is predominant at low alkene concentrations and was found to

Full text of DOI:10.1021/ja0705689

Published on Web 04/18/2007
Cyclodimerization of Alkynes with Phosphine-Free Ruthenium Carbene
Complexes: Carbene Consumption by a Shunted Alkyne Oligomerization
Steven T. Diver,* Amol A. Kulkarni, Daniel A. Clark, and Brian P. Peppers
Department of Chemistry, UniVersity at Buffalo, the State UniVersity of New York, Buffalo, New York 14260-3000
Received January 25, 2007; E-mail: diver@buffalo.edu
Scheme 1. Cyclopentadiene Formation
Metathesis promoted by the Grubbs carbenes has become an
important method for the synthesis of alkenes and dienes.1 Despite
this fact, there have been comparatively few studies on the
decomposition of metathesis-active ruthenium carbene complexes.2
Decomposition of metal carbenes is of fundamental interest, and
an improved understanding of the decomposition processes of these
important catalysts will ultimately lead to more efficient catalysts.
In this Communication, we report a new ruthenium carbene-
mediated reaction pathway found to be operating under catalytic
enyne metathesis conditions. The new pathway results in the
formation of cyclopentadienes by two successive alkyne insertions
into the metal carbene (Scheme 1). Since the cyclodimerization
occurs off the alkyne oligomerization pathway, we refer to this
reaction as a shunted oligomerization.
Scheme 2. Enyne Metathesis versus Alkyne Polymerization and
the Shunted Alkyne Polymerization (path b)
Decomposition through cyclodimerization depends on two
partitioning steps of ruthenium vinyl carbenes. Mechanistic inquiry
in enyne metathesis has asked which reacts first, the alkyne or the
alkene. This same question can be applied to the catalytic
intermediate A, a vinyl carbene. The vinyl carbene intermediate
lies at a nexus, as it can bind and react with alkenes or alkynes,3
leading to either enyne metathesis or alkyne oligomerization,4
respectively. Normally, enyne metathesis occurs on the top fork of
Scheme 2 since excess alkene is present; mechanistic studies support
that higher alkene concentration promotes catalytic turnover.3a-c
When alkene concentration is low, alkyne oligomerization may take
place via the bottom fork of Scheme 2. In this case, terminal alkyne
binding and insertion leads to a second vinyl carbene B with a
new branchpoint. Here additional alkyne insertion may occur giving
the oligomer (path a), or a cyclization process may occur giving
the cyclopentadiene (path b). In the cyclodimerization (path b), the
metal fragment is lost, resulting in carbene consumption (details
below). The observed cyclodimerization is significant because this
unique reactivity profile to form cyclopentadiene C provides direct
evidence of a competing process for enyne metathesis. Second, the
cyclodimerization suggests a new metal carbene decomposition
pathway, which has implications for catalysis and the way enyne
metatheses should be conducted.
Cyclodimerization was observed using phosphine-free carbene
complexes with coordinating ethers. The cyclopentadiene product
was observed under catalytic conditions during an attempted cross
enyne metathesis between alkyne 5 and excess methyl vinyl ketone
(MVK). The cross metathesis failed, and the cyclopentadiene 6A
was isolated instead (eq 1 in Scheme 1 and Table 1). Leaving the
alkene out completely gave a 49% yield of the cyclopentadiene
6A (entry 2). Similarly, the Grela complex 1B produced the
corresponding cyclopentadiene in comparable yield (entry 3).
Interestingly, the Grubbs complex 2 did not produce any isolable
cyclopentadienes (entry 4).5 The phosphine-free Grubbs pyridine
solvate 3 gave results similar to that found in entry 4. The first
generation Hoveyda complex 1C produced 6A (entry 6), albeit more
slowly (12-20 h, excess alkyne) than with complex 1A. Use of
Table 1. Cyclopentadiene Formation (eq 1, Scheme 1)
complex
entrya
(1 equiv)
alkene
6, yieldb,c
1
2
3
4
5
6
7
8
1A
1A
1B
2
3
1C
MVK, 60 mM
none
none
none
none
none
none
none
6A, 35%d
6A, 49% (53%)e
6B, 39%
<5%
<5%
6A, 37%f
6A, 32%
6A, 31%
1A, Ph3P (1:1)
4
a Conditions: metal complex 1-4 (5 mM), alkyne 5 (20 mM), CH2Cl2,
rt, 1-24 h. Unless otherwise noted, all carbene complex and alkyne were
consumed. b Yield is based on carbene complex. c NMR yield versus internal
standard. d Isolated. e Repurified complex 1A gave 53% 6A. f 18% recovered
1C.
1A with Ph3P or use of the preformed Blechert complex 4 gave a
reduced yield of 6A (entries 7 and 8). From these data, the presence
of coordinating ether on the benzylidene moiety is required to obtain
the cyclized product.
Cyclopentadienes were produced under nominal conditions of
enyne metathesis (Table 2). Cyclopentadiene production is associ-
ated with carbene decomposition and might explain why high
loadings are needed in some cases. Typical enyne cross metatheses
use an excess of alkene.6 Mechanistic studies3a suggest that excess
alkene is needed to turn over the vinyl carbene intermediate. In a
typical enyne metathesis between alkyne and 1-hexene, we observed
the yields of metathesis product and cyclopentadiene. At lower
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10.1021/ja0705689 CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
tion11 to give a cyclopentadiene 14. With regard to catalytic enyne
metatheses, the cyclopentadiene formation step consumes the
carbene complex by a process that has not been previously observed
for the Grubbs’ carbenes. Facile 1,5-hydride shift12 would produce
observed tautomer 6A. The modest yields of cyclopentadienes can
be explained by the many competing reactions, including those
promoted by the ruthenium(II) byproduct. The aryl ether moiety
on the carbene appears to be critical to producing the cyclopenta-
diene by cyclodimerization.
In summary, a new alkyne cyclodimerization has been observed
under conditions of enyne metathesis. The addition of a second
alkyne to a vinyl carbene intermediate suggests partitioning between
enyne metathesis and alkyne oligomerization. From kinetic studies,
we previously found that higher alkene concentration accelerates
the rate of enyne metathesis. Higher alkene concentration improves
catalytic efficiency by accelerating vinyl carbene turnover and by
minimizing carbene decomposition possible through the cyclodimer-
ization process. Further mechanistic studies are in progress.
Table 2. Cyclodimerization Observed under Nominal Metathesis
Conditions
entrya
alkene
6A, yieldb,c
diene yieldb,d
1
2
3
4
5
6
1-hexene, 20 mM
1-hexene, 40 mM
1-hexene, 60 mM
1,5-COD, 20 mM
1,5-COD, 40 mM
1,5-COD, 60 mM
10%
4%
7, 29%
7, 40%
7, 51%
8, 30%
8, 40%
8, 55%
nde
20%
12%
8%
a Conditions: 1A (1 equiv, 5 mM), alkyne 5 (20 mM, 4 equiv), CH2Cl2,
rt, 24 h. All reactions went to complete conversion of alkyne 5. b Average
of two runs. c Determined by 1H NMR; yield is based on carbene complex.
1
d Determined by H NMR; yield is based on the alkyne. e Not detected.
alkene concentrations, evidence of competing reactions was ex-
pected. At 1 equiv of 1-hexene (entry 1), the cyclopentadiene 6A
was detected in 10% yield.7 As the 1-hexene concentration was
increased, the cyclopentadiene yield dropped with a concomitant
increase in the yield of 1,3-diene (entries 2 and 3). Next we probed
whether the cyclodimerization occurred during a more difficult
metathesis. We previously developed conditions for cyclohexadiene
ring synthesis (e.g., 8) by “methylene-free” enyne metathesis using
1,5-cyclooctadiene (COD).8 The success of the methylene-free ring
synthesis was dependent on COD concentration. We hypothesized
that a slow vinyl carbene turnover step could lead to competitive
pathways, including metal carbene decomposition. To test this, we
examined the methylene-free conditions at different concentrations
of alkene (entries 4-6). With 1 equiv of COD, the cyclopentadiene
6A and cyclohexadiene 8 were produced (entry 4). Increased
concentration of COD increased the ratio of the cross metathesis
product 8 to the cyclodimerization product (entries 5 and 6). Under
the appropriate conditions, cyclopentadiene formation, and hence
carbene decomposition, can be effectively suppressed.
Acknowledgment. The authors thank SUNY Buffalo and the
NSF (CHE-092434) for support of this work. We are also grateful
to Materia and Boehringer Ingelheim Pharmaceuticals for gifts of
ruthenium carbene complexes.
Supporting Information Available: Experimental procedures and
characterization data for 6, 9, and10. This material is available free of
charge via the Internet at http://pubs.acs.org.
References
(1) (a) Grubbs, R. H. Angew. Chem., Int. Ed. 2006, 45, 3760-3765. (b)
Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem., Int. Ed. 2005,
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The substitution pattern on the cyclopentadiene substructure was
established through NOE studies and cycloadduct formation. NOE
studies of 6A established the proximity of the vinylic proton with
both benzoyloxymethylene groups, supporting the 1,3-disposition
of the alkyne substituents.9 The cyclopentadienes were trapped to
give the corresponding cycloadducts 9 and 10. Reaction of 1A with
other 1-alkynes produced cyclopentadienes as tautomeric mixtures.10
(4) This pathway is commonly associated with the Schrock carbenes, though
there is evidence of alkyne polymerization using reactive phosphine-free
ruthenium carbenes: (a) Kraus, J. O.; Zarka, M. T.; Anders, U.;
Weberskirch, R.; Nuyken, O.; Buchmeiser, M. R. Angew. Chem., Int. Ed.
2003, 42, 5965-5969. (b) Schuehler, D. E.; Williams, J. E.; Sponsler,
M. B. Macromolecules 2004, 37, 6255-6257.
(5) In the crude 1H NMR, there was less than 5% (vs internal standard) of
what was tentatively assigned as cyclopentadienes (CH2 resonance at δ
3.6 ppm). Efforts to isolate this from the oligomeric mixture proved
fruitless.
Scheme 3. Proposed Mechanism of Alkyne Cyclodimerization
(6) Stragies, R.; Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997,
36, 2518-2520.
(7) In these entries, the balance of the mass is assumed to be polymer.
(8) Kulkarni, A. A.; Diver, S. T. J. Am. Chem. Soc. 2004, 126, 8110-8111.
(9) See Supporting Information for further details.
(10) In some cases, trisubstituted benzenes were also observed in the crude
1H NMR spectra. Cyclotrimerization of alkynes is an expected competitive
oligomerization process and had been previously observed in a different
context, without carbene decomposition: (a) Peters, J. U.; Blechert, S.
Chem. Commun. 1997, 1983. (b) Das, S. K.; Roy, R. Tetrahedron Lett.
1999, 40, 4015-4018.
(11) Reductive elimination to form cyclopentadienes: (a) Trost, B. M.; Hashmi,
A. S. K. J. Am. Chem. Soc. 1994, 116, 2183-2184. (b) Wulff, W. D.;
Bax, B. M.; Brandvold, T. A.; Chan, K. S.; Gilbert, A. M.; Hsung, R. P.;
Mitchell, J.; Clardy, J. Organometallics 1994, 13, 102-126. (c) Barluenga,
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7050-7054. (d) Datta, S.; Odedra, A.; Liu, R.-S. J. Am. Chem. Soc. 2005,
127, 11606-11607.
The proposed mechanism of the carbene-promoted alkyne
cyclodimerization is illustrated in Scheme 3. Vinyl carbene forma-
tion is followed by alkyne binding with the generation of isomeric
vinyl carbenes 12. Electrocyclization of (2E)-12 would access the
ruthenacyclohexadienes 13, which would suffer reductive elimina-
(12) 1,5-Hydride shift is known to be rapid in cyclopentadienes; see: Corey,
E. J.; Weinshenker, N. M.; Schaaf, T. K.; Huber, W. J. Am. Chem. Soc.
1969, 91, 5675-5677.
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