Nonmetathetic activity of ruthenium alkylidene complexes: 1,4-hydrovinylative cyclization of multiynes with ethylene

Article abstract of DOI:10.1021/ja304255h

An efficient 1,4-hydrovinylative cyclization reaction of triynes and tetraynes catalyzed by ruthenium alkylidene complexes under ethylene is described. The regioselectivity of vinyl group incorporation can be controlled by the nature of the substituent on

Full text of DOI:10.1021/ja304255h

Communication
pubs.acs.org/JACS
Nonmetathetic Activity of Ruthenium Alkylidene Complexes: 1,4-
Hydrovinylative Cyclization of Multiynes with Ethylene
Sang Young Yun,† Kung-Pern Wang,† Mansuk Kim,‡ and Daesung Lee*
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607-7061, United States
S
* Supporting Information
Scheme 1. Influence of Temperature and Alkene Structure
on Metathesis versus 1,4-Hydrovinylative Cyclization
ABSTRACT: An efficient 1,4-hydrovinylative cyclization
reaction of triynes and tetraynes catalyzed by ruthenium
alkylidene complexes under ethylene is described. The
regioselectivity of vinyl group incorporation can be
controlled by the nature of the substituent on the alkyne,
and the Grubbs second-generation catalyst is the most
effective among typical ruthenium alkylidene complexes.
rubbs catalysts and their variants, including 1−3, are
G
widely recognized as powerful initiators for olefin
metathesis reactions.1,2 These Ru-based alkylidene complexes
have been used in both academic and industrial research for the
preparation of natural products, pharmaceuticals, and novel
polymeric materials.3
formation of 1,4-hydrovinylative cyclization12 product 5a
involved ethylene, presumably formed by homometathesis of
1-octene. This was confirmed by exposing 4a to ethylene under
otherwise identical reaction conditions, which afforded 5a as
the only product in 74% yield. We surmised that bicycle 6 was
derived from a thermal 6π-electrocyclization13 of the CM
product 7. Indeed, when the reaction was run at 40 °C, 7 was
formed exclusively and then slowly rearranged to 6. It is quite
remarkable that the same catalyst promotes fundamentally
different modes of reaction from a common substrate
depending on the nature of the alkene and the reaction
temperature. Herein we report a highly efficient 1,4-hydro-
vinylative cyclization reaction of triynes and tetraynes under
ethylene with no additives other than a catalytic amount of a
Grubbs-type Ru complex.
First, we briefly screened the catalytic activity of ruthenium
alkylidene complexes 1−3 at two different temperatures to
define their relative effectiveness for the 1,4-hydrovinylative
cyclization (Table 1). Clearly, Grubbs second-generation
catalyst 21d was found to be far more effective than the other
two at 40 °C. When substrate 4b was treated with 5 mol % 1 in
CH2Cl2 at 40 °C for 6 h, product 5b (Figure 1) was obtained in
64% yield (entry 1). Under otherwise identical conditions, the
reaction with 2 provided a quantitative yield of 5b (>98%;
entry 2). On the other hand, Hoveyda−Grubbs catalyst 32a
showed no catalytic activity at this temperature, providing only
recovered starting material (entry 3). However, at 80 °C, all
three complexes provided 5b in yields of 95% with 1 (entry 4),
>98% with 2 (entry 5), and 72% with 3 (entry 6).
During the past decade, the chemistry of Ru complexes 1−3
and their congeners has witnessed explosive growth in diene
and enyne metathesis.3e−g However the nonmetathetic
reactivity4 of these complexes has gained less attention, and
its utility has not been widely demonstrated. This is mainly due
to the fact that nonmetathetic processes have been observed as
side reactions and are believed to be a consequence of the
decomposed ruthenium alkylidene complexes.4 However, the
catalytically active species involved in these nonmetathetic
reactions have yet to be identified. Several examples of the
nonmetathetic reactivity of Grubbs complexes and their
derivatives include Kharasch addition,5 olefin isomerization,6
hydrosilylation,7 hydrogenation,8 and cycloaddition9 reactions.
The discovery of new nonmetathetic reactivity of ruthenium
alkylidene complexes should significantly broaden the scope of
the chemistry mediated by Grubbs-type Ru complexes.
We recently reported a regioselective tandem enyne cross-
metathesis (CM) and metallotropic 1,3-shift process10 that
delivers diverse patterns of unsaturated molecules, where the
remote substituent serves as a controlling element for the high
mode selectivity.11 In our continued effort to expand the scope
of this tandem metathesis process, we examined the metathesis
behavior of bis-1,3-diyne-containing substrates such as 4a. To
our surprise, under typical metathesis conditions with catalyst 2
and 1-octene (8 equiv, toluene, 80 °C, 6 h), a 2:1 mixture of 5a
and 6 was obtained (Scheme 1). It was obvious that the
Received: May 2, 2012
Published: June 18, 2012
© 2012 American Chemical Society
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Journal of the American Chemical Society
Communication
a
a
Table 1. Screening of Catalysts and Reaction Conditions
Table 2. Scope with Symmetrical Substrates
b
entry
catalyst
T (°C)
time (h)
yield of 5b (%)
1
2
3
4
5
6
1
2
3
1
2
3
40
40
40
80
80
80
6
6
6
1
1
1
54
>98
0
95
>98
72
a
The ruthenium complexes RuCl3, RuCl2(PPh3)3, Ru3(CO)12, and
[RuCp(CH3CN)3]PF6 did not provide any hydrovinylative cyclization
b
product. Isolated yields after SiO2 chromatography.
Figure 1. ORTEP diagram of 5b.
Having established the optimized reaction conditions, we
next explored the generality and scope of the 1,4-hydro-
vinylative cyclization using a variety of tetrayne substrates 4a−o
(Table 2).14 Substrates possessing trialkyl- and triarylsilyl
groups afforded products 5a−f in good yields, regardless of the
nature of the tether. The substrate containing a tert-butyl group
also provided product 5g in 91% yield. Similarly, substrates
with benzyl- and silyl-protected tertiary alcohols furnished
products 5h and 5i in 73 and 84% yield, respectively. However,
5j was not produced from the corresponding substrate 4j
containing the free alcohol, and the starting material was
recovered unchanged. The substrate bearing phenyl groups was
marginally effective, providing a 55% yield of 5l. A substrate
possessing a fluorene-derived tether gave 5m in 95% yield.
Unexpectedly, neither the primary nor secondary alkyl group-
containing substrate gave the corresponding cyclized product
5n or 5o.15 It is noteworthy that, in all cases, no products
derived from the metathesis pathway were detected.
a
Isolated yields after SiO2 chromatography are shown.
containing phenyl and triisopropylsilyl groups both afforded
virtually single regioisomers 9h and 9i (>20:1 ratio) in 85 and
69% yield, respectively (entries 8 and 9).
The current 1,4-hydrovinylative cyclization, which creates
conjugated trienes with connectivities complementary to those
of the metathesis products, should have significant synthetic
utility. For example, the trienes generated from metathesis and
1,4-hydrovinylative cyclization are transformed into cyclic
dienes with different double-bond locations within similar
molecular frameworks. As shown in eqs 1 and 2, selective enyne
To expand the scope of the reaction, we next examined the
reactivity of unsymmetrical triyne-containing substrates 8a−i
(Table 3). For triynes, the unconjugated alkyne moiety may be
reactive enough toward metathesis. Gratifyingly, the delicate
balance between the metathesis and nonmetathetic pathways
still favored the latter, providing vinylated cyclic products in
excellent yields. Under the optimized reaction conditions,
substrates 8a and 8b containing a methyl group afforded
products 9a/9a′ and 9b/9b′ in 82 and 77% yield with 1:1.5 and
1.8:1 ratios, respectively (entries 1 and 2). Upon replacement
of the methyl group with a phenyl group in substrates 8c−f, the
regioselectivity increased progressively depending on the size of
the substituents,16 providing regioisomers 9c−f over 9c′−f′
with ratios of up to 9:1 (entries 3−6). Although substrate 8g
with p-methoxyphenyl and triisopropylsilyl substituents pro-
vided 9g and 9g′ in a 10:1 ratio (entry 7), substrates 8h and 8i
metathesis of 4a and subsequent 6π-electrocyclization of the
triene intermediate provided 6, while 1,4-hydrovinylative
cyclization of 9c followed by electrocyclization gave 10.
Two possible mechanistic pathways for the present 1,4-
hydrovinylative cyclization can be considered (Scheme 2). In
path A, the ruthenium hydride17 derived from decomposition
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Journal of the American Chemical Society
Communication
hydride elimination would deliver the product and regenerate
the catalyst. Alternatively, in path B, formation of a
ruthenacyclopentadiene intermediate12b,18 followed by ethylene
insertion, β-hydride elimination, and reductive elimination
would deliver the product and regenerate the catalyst.
Table 3. Scope and Selectivity with Unsymmetrical
Substrates
To gain more insights into the mechanism, we treated 4a
with the ruthenium hydride complex [(PCy3)2COClRuH] (11)
(eq 3).19 Although this complex is well-known for its reactivity
in hydrovinylation,17 the expected product 5a was not
produced under these conditions. Also, when 4a was treated
with the ruthenium alkylidene-derived active hydrovinylation
catalyst described by Snapper and co-workers,12c the 1,4-
hydrovinylative cyclization did not occur; instead, 4a was
recovered intact (eq 4). These control experiments indicate
that the hydroruthenation pathway catalyzed by ruthenium
hydride (path A) may not be operating.20
To examine the feasibility of the other reaction manifold in
which the intact ruthenium methylidene is the catalytically
active species, we added diallyl malonate to the reaction
mixture after the hydrovinylation substrate was completely
consumed. When catalyst 2 was employed in this experiment,
the added diallyl malonate remained intact while 1,4-hydro-
vinylation continued to occur when more substrate was added
to the reaction mixture. On the other hand, when 3 was used,
the added diallyl malonate was consumed completely, affording
the corresponding ring-closing metathesis product. The lack of
metathesis activity with 2 in the former experiment results from
the formation of a phosphine-ligated ruthenium methylidene
species,21 which is known to be catalytically inactive toward
metathesis. When 3 was used in the latter experiment, however,
formation of the metathesis-inactive phosphine-ligated ruthe-
nium methylidene was impossible, so the metathesis activity of
3 remained. NMR monitoring of the reaction clearly proved the
formation of an intact ruthenium methylidene species from 2,
and an independently prepared ruthenium methylidene showed
a reaction profile indistinguishable from that of the in situ-
generated catalyst under ethylene.22 In light of all this evidence,
we conclude that the most probable mechanism for the 1,4-
hydrovinylative cyclization involves the ruthenium methylidene
species (path B in Scheme 2), where the catalytically active
species is either the ruthenium methylidene itself or its
tricyclohexylphosphine-dissociated form. This is quite unusual,
as without exception the known examples of nonmetathetic
activity of Grubbs-type alkylidene complexes have been
mediated by ruthenium hydride species such as 11.23
a
b
Isolated yields after SiO2 chromatography. Contaminated with a
product of ethylene CM on the 1,3-diyne moiety.
Scheme 2. Two Plausible Mechanisms
In conclusion, we have shown that the reactivity of multiynes
with Grubbs catalysts can be switched from metathesis to
nonmetathetic mode by changing the nature of the externally
added alkene. Using this new nonmetathetic reactivity of
Grubbs complexes, we have developed an efficient 1,4-
hydrovinylative cyclization of multiynes under ethylene. For
unsymmetrical triyne substrates, high regioselectivity can be
of the ruthenium alkylidene would be a catalytically active
species, by which an initial hydroruthenation followed by
cyclization would occur. Subsequent ethylene insertion and β-
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alkyne and 1,3-diyne moieties. This study adds another new
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Grubbs-type ruthenium alkylidenes, which we believe should
further broaden their utility.
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ASSOCIATED CONTENT
* Supporting Information
■
S
(7) (a) Maifeld, S. V.; Miller, R. L.; Lee, D. Tetrahedron Lett. 2002,
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AUTHOR INFORMATION
Corresponding Author
dsunglee@uic.edu
■
(8) (a) Menozzi, C.; Dalko, P. I.; Cossy, J. Synlett 2005, 2449.
(b) Børsting, P.; Nielsen, P. Chem. Commun. 2002, 2140. (c) Finnegan,
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(b) Young, D. D.; Senaiar, R. S.; Deiters, A. Chem.Eur. J. 2006, 12,
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(12) Mori and co-workers observed a related 1,4-hydrovinylative
cyclization by 2 under ethylene; the reported maximum yield was only
12%. See: (a) Mori, M.; Saito, N.; Tanaka, D.; Takimoto, M.; Sato, Y.
J. Am. Chem. Soc. 2003, 125, 5606. (b) Mori, M.; Tanaka, D.; Saito, N.;
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́
aut, C.; Duboc,
Present Address
‡Samsung Cheil Industries Inc., Gocheon-Dong 332-2, Uiwang-
Si, Gyeonggi-Do 437-711, Korea.
̂
́
Author Contributions
̃
†S.Y.Y and K.-P.W. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the University of Illinois at Chicago for financial
support, Prof. Chae S. Yi for a generous donation of 11, and Dr.
Roger F. Henry for X-ray analysis of 5b.
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