Ruthenium-catalyzed tandem enyne metathesis/hydrovinylation

Article abstract of DOI:10.1039/c0cc00008f

In situ modification of Grubbs' first-generation metathesis catalyst allows for a tandem enyne metathesis/hydrovinylation that is complementary to the regioselectivity of known ruthenium-catalyzed hydrovinylations.

Full text of DOI:10.1039/c0cc00008f

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Ruthenium-catalyzed tandem enyne metathesis/hydrovinylationw
Jason Gavenonis, Ruben V. Arroyo and Marc L. Snapper*
Received 17th February 2010, Accepted 8th June 2010
DOI: 10.1039/c0cc00008f
In situ modification of Grubbs’ first-generation metathesis
catalyst allows for a tandem enyne metathesis/hydrovinylation
that is complementary to the regioselectivity of known
ruthenium-catalyzed hydrovinylations.
appropriate in situ modification of the ruthenium complex, as
illustrated in eqn (3).
Olefin metathesis is a versatile carbon–carbon double bond-
forming reaction that has been used widely in the preparation
of complex organic compounds.1 Tandem, concurrent,
domino, or cascade processes that convert the alkene created
through metathesis into other useful functionalities can
provide even greater increases in molecular complexity
with minimal added cost or waste.2 While there are several
examples of ruthenium-catalyzed tandem processes involving
an olefin metathesis followed by hydrogenation,3 isomerization,4
or oxidation,5 there are relatively few cases in which the
subsequent metal-catalyzed reaction creates additional carbon–
carbon bonds. Two examples include a tandem ring-closing
olefin metathesis/Kharasch addition6 and an enyne metathesis/
cyclopropanation.7 Both processes generate new carbon–
carbon bonds through unique ruthenium-catalyzed mechanisms
in a single reaction vessel. Considering the importance of
streamlining synthetic sequences, we report herein a new
tandem process that combines ruthenium-catalyzed enyne
ring-closing metathesis with ruthenium-catalyzed 1,3-diene
hydrovinylation.8
ð3Þ
Initial studies towards realizing this tandem process focused
on developing the hydrovinylation step. Unfortunately,
control reactions with diene 6 showed poor selectivity using
Yi’s conditions.9 Catalyst 2 in the presence of HBF4ꢀOMe2 led
to the formation of multiple products, including the expected
1,2-hydrovinylation product 7 and both olefin isomers of the
1,4-hydrovinylation product 8. In retrospect, this was not
surprising, since Yi had reported similar results for dienes
not conjugated with another p-system.9 On the other hand,
when diene 6 and ethylene were warmed in the presence of
alkylidene 4 that had been treated with NaOMe in MeOH/
Yi and coworkers published several examples of hydro-
vinylations of 1,3-dienes using ruthenium hydride 2 as an
effective catalyst (eqn (1)).9
toluene, the 1,4-hydrovinylation product
8 was formed
exclusively as a single olefin isomer (eqn (4)).12 Not only
did this observation bode well for developing a ‘‘single-
flask’’ olefin metathesis/hydrovinylation sequence, the unique
regioselectivity complemented existing ruthenium-catalyzed
hydrovinylations.8
ð1Þ
Considering that hydride
2
can be generated from
Grubbs’ olefin metathesis catalyst 4 (eqn (2)),10 it should be
ð2Þ
ð4Þ
possible toeffect an enyne metathesis11 with Grubbs’ catalyst 4,
followed by a hydrovinylation of the resulting 1,3-diene 1 upon
The results for the tandem enyne metathesis/hydrovinylation
sequence are summarized in Table 1. Readily accessible acyclic
enynes that were known to undergo facile ring-closing
metatheses were employed in this study.11 Entry 1 illustrates
the conversion of enyne 9 to 1,4-diene 8. The overall efficiency
and selectivity of the tandem sequence is comparable to the
hydrovinylation reaction described in eqn (4).
Department of Chemistry, Merkert Chemistry Center, Boston College,
Chestnut Hill, MA 02467, USA. E-mail: marc.snapper@bc.edu;
Fax: +1 617 552 1442
w Electronic supplementary information (ESI) available: Experimental
procedure for enyne metathesis–hydrovinylation and characterization
data for 8, 11, 13, 15, 16, 17, and 19. See DOI: 10.1039/c0cc00008f
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Table 1 Tandem, enyne metathesis/1,4-hydrovinylation
Entry
Enynea
Product
Yield13
56%b
(1)
(2)
(3)
(4)
57%c
64%d
71%e
Scheme 1 Mechanism for 1,2- and 1,4-selective hydrovinylations.
by Yi and coworkers (Scheme 1).9 The E-stereoselectivity
could be established by initial coordination of ruthenium
to the s-cis-diene (20), a conformation more favorable in
substrates 12, 14, 16, and 18. Insertion of the terminal olefin
into the ruthenium-hydride bond (2) could then provide
s-allyl species 21 that, upon coordination of ethylene, can
form s-allyl complex 22, which leads to the 1,2-hydrovinylation
product 3. Alternatively, complex 21 can isomerize to s-allyl
complex 24 via p-allyl 23, which then leads to the 1,4-hydro-
vinylation product 15. Given the higher dilution of our reaction,
the absence of HBF4,15 and the presence of a Lewis-basic
co-solvent (MeOH), it is possible ethylene coordination to
form intermediate 22 could be retarded, allowing for isomer-
ization of the allyl intermediates (i.e., 21 - 23 - 24) prior to
insertion of ethylene into the corresponding ruthenium–
carbon s-bond.
With this in mind, we examined if the conditions required to
convert Grubbs’ alkylidene 4 to complex 2 in situ accounted
for the 1,4-hydrovinylation selectivity observed in our
tandem process. Control reactions using ruthenium hydride
2 at higher dilutions in the presence of MeOH resulted
in an extremely sluggish 1,4-hydrovinylation of diene 1
(2% conversion to 15 after 24 h). Formation of diene 3 was
not observed, indicating that the presence of methanol
may account for the selectivity, but not the reactivity
of this system. Since NMR studies indicated that the
conversion of alkylidene 4 to hydride 2 is incomplete on the
time scale of the tandem sequence (ca. 50% conversion in
10 min.), a mixed catalyst system of 2 and 4 (2.5 mol %
each) in methanol/toluene was then examined. In this
case, the hydrovinylation of diene 1 resulted in complete
consumption of starting material, generating 15 after 1 h
(eqn (5)), matching both the reactivity and selectivity
of the tandem process, even at reduced catalyst loadings.
(5)
67%e
(6)
49%e
under
a
Enyne metatheses were performed with 20 mol%
4
1 atm ethylene in toluene (0.20 M enyne) at 75 1C, followed by
treatment with NaOMe (20 mol%, 0.04 M in MeOH for 10 min
b
prior to hydrovinylation. Hydrovinylation was run for 80 min.
c
d
Hydrovinylation was run for 180 min. Hydrovinylation was run
e
for 5.5 h. Hydrovinylation was run for 90 min.
In general, the highest yields for the tandem process were
obtained for enynes with a quaternary or sp2-hybridized
carbon adjacent to the alkyne. Under these conditions, enyne
12, for example, is transformed to the expected 1,4-hydrovi-
nylation product 13 in 74% isolated yield (64% yield based on
87% purity as indicated by GC analysis, entry 3). Similarly,
aromatic enynes (i.e., 14, 16, and 18) are converted predo-
minantly to 1,4-dienes (15, 17, and 19 respectively) in 49–71%
yields.13 Some of the lower yields in these examples are likely
due to the instability of the products upon work-up.14 Albeit
with elevated catalyst loading, the ‘‘single-flask’’ conversion of
enyne 14 to diene 15 proceeded in higher overall yield than
that reported for the stepwise sequence that leads to diene
3.9,11 While 1,4-adducts have been observed in cobalt-
catalyzed hydrovinylations of 1,3-dienes,12 to the best of our
knowledge, 1,4-hydrovinylation of these type of dienes has not
been reported previously.
It is possible to rationalize the selectivity of the hydro-
vinylation by considering the ruthenium intermediates proposed
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Given these observations, a more complex mechanism than
that outlined in Scheme 1 is likely involved.
3 J. Louie, C. W. Bielawski and R. H. Grubbs, J. Am. Chem. Soc.,
2001, 123, 11312–11313; B. Schmidt and M. Pohler, Org. Biomol.
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J. Am. Chem. Soc., 2002, 124, 13390–13391; B. Schmidt, Eur. J.
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2005, 127, 16329–16332; B. Schmidt and M. Pohler, J. Organomet.
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ð5Þ
In summary, we have developed a single-vessel, ruthenium-
catalyzed, enyne metathesis/hydrovinylation sequence. Unlike
other ruthenium-catalyzed hydrovinylations, this transformation
proceeds stereoselectively with overall 1,4-addition of ethylene
across the 1,3-dienes. Further studies into the selectivity,
scope, and mechanism of this process, as well as applications
to natural product synthesis, are currently underway.
7 B. G. Kim and M. L. Snapper, J. Am. Chem. Soc., 2006, 128,
52–53.
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We thank the National Science Foundation (CHE-0612875/
0911212) for financial support. R.V.A. is grateful to the
Spanish government for a visiting student fellowship. We also
acknowledge Schering-Plough for X-ray facility support and
Materia for the gift of metathesis catalyst.
Notes and references
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13 1,4-Hydrovinylation yields reported are based on isolated yields
corrected for product purity as determined by GC analyses.
14 When multiple attempts using silica gel chromatography were used
to improve product purity, increased levels of minor byproducts
were observed by NMR and recovery of the desired 1,4-hydro-
vinylation products suffered significantly.
15 HBF4 likely promotes the dissociation of PCy3 (see ref. 8).
ꢁc
This journal is The Royal Society of Chemistry 2010
5694 | Chem. Commun., 2010, 46, 5692–5694