Palladium-catalysed alkene chain-running isomerization

Article abstract of DOI:10.1039/c7cc04953f

We report a method for palladium-catalysed chain-running isomerization of terminal and internal alkenes. Using an air-stable 2,9-dimethylphenanthroline-palladium catalyst in combination with NaBAr₄ promoter, olefins are converted to the most stable double bond isomer at -30 to 20 °C. Silyl enol ethers are readily formed from silylated allylic alcohols. Fluorinated substituents are compatible with the reaction conditions, allowing the synthesis of fluoroenolates. Catalyst loading as low as 0.05% can be employed on a gram scale.

Full text of DOI:10.1039/c7cc04953f

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Palladium-catalysed alkene chain-running
isomerization†
Cite this:DOI: 10.1039/c7cc04953f
Andrew L. Kocen, Maurice Brookhart* and Olafs Daugulis
*
Received 26th June 2017,
Accepted 15th August 2017
DOI: 10.1039/c7cc04953f
rsc.li/chemcomm
We report a method for palladium-catalysed chain-running isomeri-
zation of terminal and internal alkenes. Using an air-stable 2,9-dimethyl-
phenanthroline-palladium catalyst in combination with NaBAr4
promoter, olefins are converted to the most stable double bond
isomer at À30 to 20 8C. Silyl enol ethers are readily formed from
silylated allylic alcohols. Fluorinated substituents are compatible with
the reaction conditions, allowing the synthesis of fluoroenolates.
Catalyst loading as low as 0.05% can be employed on a gram scale.
Alkenes are key intermediates in the synthesis of complex
organic molecules; consequently, their synthesis and reactivity
have been extensively investigated.1,2 Less available but more
desirable alkenes can often be accessed by isomerization of
readily available olefins. Such transition metal-catalysed trans-
formations have been extensively studied and recent investigations
have achieved regio- and diastereoselective control.3,4
Scheme 1 Chain running isomerization to silyl enol ethers.
Alkene isomerization can be coupled with a second trans-
formation that allows trapping of the double bond at a specific
position.5 Isomerization alone can afford either a kinetic or a here that an air-stable 2,9-dimethylphenanthroline-palladium
thermodynamic product of double bond migration.3,4 In the case methyl chloride precatalyst in combination with NaBAr4 as
of kinetic control, linear terminal alkenes are often selectively activator isomerizes a range of substrate olefins to the thermo-
converted to 2-olefins.4 Long-distance chain-running double bond dynamically favoured products.
isomerization has been achieved using palladium or nickel
A 1997 mechanistic study showed that phenanthroline-
catalysis, but it often takes advantage of a thermodynamic driving palladium alkyl cations undergo series of b-hydride eliminations/
force to convert the alkene selectively to another functionality reinsertions that constitute the fundamental mechanistic steps
such as ketone or aldehyde.5a,e–g A few examples describe efficient involved in olefin isomerization.7 Consequently, a phenanthroline-
long-distance chain-running isomerization that conserves the palladium catalyst system should be capable of efficient alkene
valuable alkene functionality (Scheme 1).6 In 2000, Mori reported isomerization. A short optimization study showed that 2,9-dimethyl-
that a ruthenium hydride catalyst at 5 mol% loading performs phenanthroline palladium methyl chloride complex 3 affords the
functionalized, deconjugative alkene isomerization forming silyl best combination of reactivity and stability when activated with
enol ethers in refluxing toluene.6a In a further advance, Grotjahn NaB[C6H3(CF3)2]4.8 As described below, high efficiency and generality
has described a catalyst capable of efficient long-distance olefin of alkene isomerization is observed, allowing catalytic synthesis of
isomerization yielding a silyl enol ether. However, branched synthetically valuable silyl enol ethers, including fluoroenolates.
substrates did not afford silyl enol ether products.6b We report Simple olefins can be rapidly and efficiently converted to the
thermodynamically most stable isomer as well. Disubstituted
alkenes are reactive, and efficient chain-running isomerization is
Department of Chemistry, University of Houston, Houston, TX, 77204-5003, USA.
possible. More substituted substrates typically require longer
E-mail: olafs@uh.edu
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c7cc04953f reaction times.
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Table 1 Isomerization of simple alkenesa
Table 2 Isomerization of silyl allyl ethersa
Entry
1
Alkene
Product
Yield, %
Entry
1b
Alkene
Product
Yield, %
86 (1.4/1 E/Z)
87
90 (2.7/1 E/Z)
2
2
94 (1.1 : 1 E/Z)
3c
4c
60 (4.4 : 1 E/Z)
77 (4.1 : 1 E/Z)
3b
4
90 (450 : 1 E/Z)
99 (23 : 1 E/Z)
80 (2.5 : 1)
5d,e
87 (1.6 : 1 E/Z)
93 (2.0 : 1 E/Z)
5c
6f
6d
84
7c
62 (1.3 : 1 E/Z)
51 (4.7 : 1 E/Z)
a
Reaction conditions: alkene (0.2 mmol),
3
(0.002 mmol),
NaB[C6H3(CF3)2]4 (0.008 mmol), CDCl3 (0.1 mL), 0 1C, 16 h. Yields were
determined by 1H NMR with an internal standard. Please see ESI for
8g
b
c
d
details. Reaction time: 2 h. Reaction time: 1 h. Reaction time: 3 h.
20 (5.6 : 1 E/Z)
The isomerization of simple alkenes was investigated using
1% loading of 3 in combination with 4% of NaB[C6H4(CF3)2]4
activator at 0 1C (Table 1). Allyl phenyl ether was isomerized to
the alkenyl ether in 90% yield giving 2.7/1 product E/Z selectivity
(entry 1). An aromatic bromide substituent is also tolerated
(entry 2). Allylbenzenes are converted to the conjugated isomers
in excellent yields and E/Z selectivities (entries 3 and 4). The
isomerization of 1-hexene produces a mixture of 2-hexenes and
9g
49 (450 : 1 E/Z)
a
Reaction conditions: alkene (0.2 mmol), catalyst (0.002 mmol),
NaB[C6H3(CF3)2]4 (0.008 mmol), CDCl3 (0.1 mL), 0 1C, 16 h. Yields were
determined by 1H NMR with an internal standard. Please see ESI for
b
c
d
e
f
details. Time: 2 h. Time: 3 h. Time: 22 h. 30 1C. Time: 48 h.
g
Time: 24 h.
3-hexenes in nearly a thermodynamic ratio (entry 5).3l Isomeri- 3-hydroxyhexene gave a mixture of two possible trisubstituted
zation of the disubstituted olefin (entry 6) efficiently produces enolates in 71% combined yield (entry 8). This example shows
the trisubstituted alkene.
that reaction does not stop after a enol silane is formed; the
Next, we investigated base-free synthesis of synthetically double bond can migrate past the silyloxy substituent. The
useful silyl enol ethers.9 While transition metal-catalysed iso- product of entry 9 was obtained by a mono-isomerization
merization of O-silylated unsaturated alcohols has been followed by a Lewis-acid catalysed allylic rearrangement of a
reported previously, only a very limited number of substrates silyloxy group.10
have been investigated.3i,4d,k,6 Most of the literature examples
Targeted transposition of a functional group across many
involve conversion of an unsubstituted allyl moiety to an enol bonds within a molecule presents a useful strategy toward the
silane functionality. synthesis of complex molecules. Long distance chain-running
Using standard conditions, a broad range of silyl allyl ethers isomerization was examined next (Table 3). Both aldehyde
can be isomerized to the corresponding enol silanes (Table 2). and ketone silyl enol ethers can be formed by isomerization
Unsubstituted tert-butyldimethylsilyl allyl ether was converted of monosubstituted alkenes (entries 1 and 2). Disubstituted
to the silyl enol ether of propionaldehyde in an 86% yield (entry 1). double bonds can be subjected to isomerization as well
Disubstituted olefins are reactive as well. Thus, entry 2 shows (entries 3 and 4). Interestingly, a disubstituted enol is obtained
conversion of a methallylic alcohol derivative to the silyl enol in preference to trisubstituted olefin (entry 3). By using a more
ether of isobutyralde in 87% yield (entry 2). Ketone enolate silyl bulky silyl protected group and a different catalyst, Grotjahn
ethers are formed in good yields (entries 3 and 4). The reaction was able to change the preference to a trisubstituted alkene.6b
tolerates aromatic chlorides and protected propiophenone enolate Butenyl benzene was converted to the conjugated product in
was obtained in 87% yield as a 1.6/1 E/Z isomer mixture (entry 5). good yield and selectivity (entry 5). Entry 6 shows the result
Protected butyraldehyde enolate was formed in 93% yield (entry 6). obtained with 0.05 mol% catalyst at room temperature on one
Bis-protected 2-butenediol was converted to 4-hydroxybutyr- gram scale. The isomerization product was isolated in 76%
aldehyde enol silane in 62% yield (entry 7). Silyl protected yield as a 2.6/1 E/Z mixture.
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Table 3 Chain running isomerizationa
In conclusion, we have shown that an air- and moisture
stable, easily prepared 2,9-dimethylphenanthroline palladium
catalyst 3 in combination with NaBAr4 as promoter in chloroform
or dichloromethane converts alkenes to the most stable double
bond isomer at room temperature or below. Silyl enol ethers
are readily formed from silylated allylic alcohols. Long-distance
double bond chain-running can afford enol silanes as well.
Fluorinated substituents are compatible with the reaction
conditions, allowing the synthesis of protected fluoroenolates.
Catalyst loadings as low as 0.05% can be employed in gram
scale reactions and turnover numbers as high as ca. 1520 were
demonstrated.
Entry
1b
Alkene
Product
Yield, %
66 (2.0/1 E/Z)
64 (3.3 : 1 E/Z)
2
3c,d,e
4c
80 (1.3 : 1 E/Z)
We are grateful to the Welch Foundation (Chair E-0044 to O. D.,
Grant E-1893 to M. B.) and NIGMS (Grant No. R01GM077635 to
O. D.) for supporting this work.
80
5b,d
56 (450 : 1)
6c,d,f
76 (2.6 : 1 E/Z)
Conflicts of interest
a
Reaction conditions: alkene (0.2 mmol), catalyst (0.002 mmol),
NaB[C6H3(CF3)2]4 (0.008 mmol), CDCl3 (0.1 mL), 0 1C, 3 h. Yields in
entries 1, 2, 4, and 5 were determined by 1H NMR with an internal
standard. Yields in entries 3 and 6 are isolated yields of pure product.
There are no conflicts to declare.
b
c
d
Please see ESI for details. Time: 48 h. Time: 24 h. Room temperature. Notes and references
e
f
Scale: 2.0 mmol. Alkene (4.6 mmol), catalyst (0.0023 mmol),
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The chain-running isomerization procedure can be used to
synthesize fluorinated silyl enol ethers that are valuable synthetic
precursors but are difficult to access (Scheme 2).11 Isomerization of
alkenyl fluoride 4 resulted in formation of 5 in 78% yield. A silane
activator was necessary in this case, presumably due to weak
coordination of the fluorine-substituted olefin to palladium.4f,7
Furthermore, isomerization of 6 to 7 produces a fluoromethyl-
substituted enol ether in moderate isolated yield.
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dimethylphenanthroline-palladium methyl chloride complex.
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