Z -selective homodimerization of terminal olefins with a ruthenium metathesis catalyst

Article abstract of DOI:10.1021/ja203488e

The cross-metathesis of terminal olefins using a novel ruthenium catalyst results in excellent selectivity for the Z-olefin homodimer. The reaction was found to tolerate a large number of functional groups, solvents, and temperatures while maintaining excellent Z-selectivity, even at high reaction conversions.

Full text of DOI:10.1021/ja203488e

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pubs.acs.org/JACS
Z-Selective Homodimerization of Terminal Olefins with a Ruthenium
Metathesis Catalyst
Benjamin K. Keitz, Koji Endo, Myles B. Herbert, and Robert H. Grubbs*
Arnold and Mabel Beckman Laboratories of Chemical Synthesis, Division of Chemistry and Chemical Engineering,
California Institute of Technology, Pasadena, California 91125, United States
S Supporting Information
b
ABSTRACT: The cross-metathesis of terminal olefins
using a novel ruthenium catalyst results in excellent selec-
tivity for the Z-olefin homodimer. The reaction was found to
tolerate a large number of functional groups, solvents, and
temperatures while maintaining excellent Z-selectivity, even
Figure 1. Previously reported CÀH activated catalyst 1.
at high reaction conversions.
fairly high temperatures in order to initiate (ca. 70 °C).11 Unfortu-
nately, cross-metathesis reactions performed at this temperature and
lefin metathesis using a variety of transition metals has
gained widespread popularity as a robust method for the
low olefin concentration gave relatively low conversion and showed
significant amounts of catalyst decomposition. We suspected that the
poor performance of 1 under these conditions was a result of the
ethylene generated as a byproduct of the reaction, and indeed,
exposure of 1 to an atmosphere of ethylene at room temperature
resulted in complete decomposition within minutes.
O
formation of carbonÀcarbon bonds.1 Ruthenium-based cata-
lysts, in particular, have been used in a wide variety of applications
including biochemistry,2 materials chemistry,3 and synthetic
organic chemistry.4 However, despite its widespread appeal,
olefin metathesis is an equilibrium reaction; therefore, metathesis
applications which require the formation of kinetic products are
generally difficult if not altogether prohibited.1,5 Nevertheless, an
increasingly sophisticated understanding of catalyst selectivity
(with both ruthenium6 and Group VI metals7) has permitted the
development of new catalysts that are capable of selectively
forming kinetic products. Despite this progress, the cross-
metathesis of terminal olefins to selectively form the Z-olefin pro-
duct remained an elusive goal until the recent work of Hoveyda,
Schrock, and co-workers.8 The HoveydaÀSchrock systems showed
excellent selectivities and good turnover numbers (TONs).
However, the researchers concluded that obtaining similar selec-
tivities using ruthenium-based catalysts would be challenging.
Herein, we show that the cross-metathesis homocoupling of
terminal olefins to selectively form Z-olefins is not only possible
with ruthenium but a viable alternative to the use of catalysts
based on Group VI metals.
While the decomposition of 1 in the presence of ethylene was
disappointing, it is not uncommon among metathesis catalysts
and can be mitigated by efficient removal of the gas from
solution.12 Therefore, a series of cross-metathesis reactions were
run under static vacuum, and under these conditions, 1 per-
formed admirably (Table 1). For instance, 1 was stable at 70 °C
in both THF and MeCN as long as oxygen was rigorously
excluded, and it gave high conversions and Z-selectivity for a
variety of terminal olefin substrates. Some substrates showed a
slight decrease in selectivity with increasing conversion, a result
which is most likely caused by decomposition products of 1.13
In contrast to the Group VI metal systems, olefin migration
instead of metathesis was observed in some substrates (10, see
Figure S1).14 Attempts to prevent olefin migration via the use of
additives such as benzoquinone or mild acid met only with
catalyst decomposition.13 This type of reactivity, although
usually undesirable, can be valuable in certain situations.15
Regardless, olefin migration can be eliminated via careful
optimization of reaction conditions (vide infra). Finally, sub-
strates with even a small amount of substitution (11) were
We recently reported on the synthesis of a CÀH activated
ruthenium metathesis catalyst wherein the N-heterocyclic carbene
(NHC) is chelated to the metal center through a RuÀC bond
(Figure 1).9 Surprisingly, this catalyst represented the first example
of a metathesis active complex which had undergone CÀH
activation.1e,10 Furthermore, despite 1’s relatively poor activity in
ring-opening metathesis polymerization (ROMP) and ring-closing
metathesis (RCM) reactions, it displayed remarkable Z-selectivity
for the cross-metathesis product of allylbenzene (2) and cis-1,4-
diacetoxy-2-butene (3) (Scheme 1). With this result in hand, we
reasoned that 1 would excel in a catalytically less complex reaction,
such as the homocoupling of terminal olefins (Scheme 2).
Scheme 1. Previously Reported Z-Selectivity of 1
Due to the relatively large adamantane group on 1 and the
associative initiation mechanism of complexes of this type, 1 requires
Received: April 15, 2011
Published: June 08, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/ja203488e J. Am. Chem. Soc. 2011, 133, 9686–9688
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Scheme 2. Homocoupling of Terminal Olefins with 1
Table 2. Cross-MetathesisofTerminal Olefinswith1 at35 °Ca
substrate
time, h
conv,b %
Z,b %
yield,c %
allylbenzene (2)
1
5.5
4
>95
>95
>95
73
92
73
81
>95
62
21
54
79
74
À
methyl undecenoate (5)
allyl acetate (6)
1-hexene (7)d
89
3
69
allyl trimethylsilane (8)
1-octene (9)
3
>95
>95
>95
0
>95
83
4
Table 1. Cross-Metathesis of Terminal Olefins with 1 at
70 °C under Static Vacuuma
allyl pinacol borane (10)
3-methyl-1-hexene (11)
pentenoic acid (12)
4-penten-1-ol (13)
2-(allyloxy)ethanol (14)
N-allylaniline (15)
4
>95
À
À
72
24
24
1
substrate
solvent
time, h
conv,c %
Z,c %
0
À
>95
87
72
73
67
allylbenzene (2)
methyl undecenoate (5)b THF
THF
6 (10)
4 (6)
3 (6)
6 (7.5)
6 (10)
3 (6)
6
>95 (>95)
78 (93)
53 (60)
83 (87)
63 (72)
83 (97)
10
83 (67)
87 (85)
89 (83)
80 (80)
>95 (>95)
80 (68)
>95
1
66
2
70
71
allyl acetate (6)
1-hexene (7)b
THF
THF
THF
THF
a 2 mol % catalyst in THF (3.33 M in substrate) at 35 °C. b Measured by
1H NMR spectroscopy. c Isolated yield. d Run in sealed container.
allyl trimethylsilane (8)
1-octene (9)
allyl pinacol borane (10) THF
Table 3. Solvent Screen for Cross-Metathesis of 5 with 1 at
Room Temperaturea
3-methyl-1-hexene(11)
allylbenzene (2)
THF
12
0
0
MeCN 2.5 (21)
12 (15)
>95 (>95)
substrate
solvent
time, h conv,b %
Z,b %
methyl undecenoate (5)
MeCN 2.5 (21)
7 (11)
>95 (70)
a 2 mol % catalyst in solvent (0.6 M in substrate) at 70 °C under static
MeCN
3 (28) 19 (76)
3 (28) 49 (87)
3 (28) 50 (86)
94 (91)
88 (75)
89 (76)
vacuum. b 4 mol % catalyst. c Measured by 1H NMR spectroscopy.
MeOH
EtOH
C6H6
disappointingly resistant to homodimerization, even at tem-
peratures exceeding 100 °C.
3 (21) 13 (77) >95 (84)
Et2O
3 (7)
50 (85)
93 (73)
92 (87)
93 (85)
À
methyl undecenoate (5)
Although 1 is clearly functional at high temperature, the presence
of deleterious side reactions encouraged us to search for conditions
in which 1 would initiate at lower temperatures. Extensive optimiza-
tion revealed that 1 could effect the homodimerization of terminal
olefins at 35 °C with high olefin concentration (ca. 3 M). This result
is not surprising, considering that the initiation of 1 should depend
on olefin concentration. Nevertheless, we did not anticipate that the
activity and selectivity of 1 would be superior at 35 °C. Furthermore,
reactions performed at lower temperature and higher concentration
had the additional advantage of not requiring any special technique
to remove ethylene.16
DMF
3 (21) 44 (77)
3 (21) 35 (81)
CH2Cl2
(CF3)2CHOH 3 (28)
0 (0)
diglyme 3 (28) 31 (81)
95 (80)
a 2 mol % catalyst in solvent (2.25 M in substrate) at 25 °C. b Measured
by 1H NMR spectroscopy.
product, while hexafluoroisopropanol resulted in immediate catalyst
decomposition.17 The fact that high Z-selectivity is maintained in
protic solvents further demonstrates the functional group compat-
ibility of 1. Nevertheless, mildly acidic substrates and solvents appear
to result in catalyst decomposition.
For mostsubstrates, reactions with1at35°C showedselectivity
similar to that of reactions performed at 70 °C but with improved
activity (Table 2). Isolated yields of the homodimerization pro-
ducts were also good. Gratifyingly, in the case of 10, no detectable
amount of olefin migration was observed, and excellent Z-selectivity
was maintained up to very high conversion. Emboldened by this
success, we attempted to dimerize several more advanced substrates
(11À14). Unfortunately, in the case of hindered (11) or acidic
substrates (12), no activity was observed. On the other hand, 1 was
able to dimerize alcoholic substrates (13, 14) with excellent con-
version and good selectivity. This latter result is particularly impor-
tant since it is the first example of Z-selective cross-metathesis with
alcohol substrates.
Given that 1 not only is stable to water and other protic media
but also shows increased activity, we deemed it appropriate to
examine a wide variety of different solvents for the homodimer-
ization of 5 at room temperature (Table 3).9 Several polar and
nonpolar solvents were tested, and the majority were conducive to
the transformation. Coordinating solvents (e.g., MeCN) resulted in
slower reactions but were able to achieve TONs roughly equivalent
to those of reactions run in noncoordinating solvents. Protic
solvents such as MeOH and EtOH yielded highly Z-olefin-enriched
In conclusion, we have demonstrated the first example of
Z-selective homodimerization of terminal olefins using a ruthe-
nium-based catalyst. Optimization of reaction conditions revealed
that 1 was effective for a multitude of substrates at different tem-
peratures and in a variety of solvents. The selectivity and activity
(TONs from 20 to 50) of 1 were comparable to those obtained with
previously reported molybdenum and tungsten catalysts. Notably, 1
was able to dimerize several challenging substrates, including alcohols,
with excellent conversion and good selectivity for the Z-olefin.
However, despite the recent success of ruthenium and Group VI
systems, new catalysts, which undergo more turnovers and function
under practical experimental conditions, are clearly needed to tackle
more advanced olefin substrates and metathesis reactions.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental details and NMR
spectra. This material is available free of charge via the Internet at
http://pubs.acs.org.
b
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’ AUTHOR INFORMATION
2009, 48, 1014. (d) Gauthier, D.; Lindhardt, A. T.; Olsen, E. P. K.;
Overgaard, J.; Skrydstrup, T. J. Am. Chem. Soc. 2010, 132, 7998.
(16) A vent to an inert atmosphere was sufficient. See the Supporting
Information.
Corresponding Author
rhg@caltech.edu
(17) 1 was only sparingly soluble in MeOH.
’ ACKNOWLEDGMENT
This work was financially supported by the NIH (NIH
5R01GM031332-27), the NSF (CHE-1048404), Mitsui Chemi-
cals, Inc. (K.E.), and the NDSEG (fellowship to B.K.K.). Instru-
mentation facilities at which this work was carried out were
supported by NIH RR027690. Materia, Inc. is thanked for its
donation of metathesis catalysts.
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