Synthesis of allyl and alkyl vinyl ethers using an in situ prepared air-stable palladium catalyst. Efficient transfer vinylation of primary, secondary, and tertiary alcohols

Article abstract of DOI:10.1021/jo034376h

An air-stable palladium catalyst formed in situ from commercially available components efficiently catalyzed the transfer vinylation between butyl vinyl ether and various allyl and alkyl alcohols to give the corresponding allyl and alkyl vinyl ethers in 61-98% yield in a single step.

Full text of DOI:10.1021/jo034376h

Syn th esis of Allyl a n d Alk yl Vin yl Eth er s Usin g a n in Situ
P r ep a r ed Air -Sta ble P a lla d iu m Ca ta lyst. Efficien t Tr a n sfer
Vin yla tion of P r im a r y, Secon d a r y, a n d Ter tia r y Alcoh ols
Martin Bosch and Marcel Schlaf*
Department of Chemistry and Biochemistry, Guelph-Waterloo Centre for Graduate Work in Chemistry
(GWC)2, University of Guelph, Guelph, Ontario, Canada N1G 2W1
mschlaf@uoguelph.ca
Received March 21, 2003
An air-stable palladium catalyst formed in situ from commercially available components efficiently
catalyzed the transfer vinylation between butyl vinyl ether and various allyl and alkyl alcohols to
give the corresponding allyl and alkyl vinyl ethers in 61-98% yield in a single step.
In tr od u ction
We successfully employed the palladium catalyst (L-
L)Pd(OAc)2; (L-L ) 2,2′-bipyridyl or 1,10-phenanthroline
chelate) for the transfer vinylation of protected sugars.16
The catalyst had originally been described by McKeon
and Fitton.17,18 Prior to our work, its only other reported
applications to vinyl ether synthesis were in the vinyla-
tion of steroids19 and the synthesis of glycidol vinyl ether
in moderate yield.20 The palladium complex accelerates
the equilibration of the reaction shown in eq 1, which
can be driven by an excess of either vinyl ether or alcohol.
Vinyl ethers are a highly valuable class of synthons
with applications in polymer formulations, surfactants,
and drug delivery systems as well as general organic
synthesis.1-3 Arguably even more valuable are allyl vinyl
ethers, as they can undergo Claisen rearrangements,4
which often constitute a key step in the synthesis of
complex natural products or compounds used as flavors
and fragrances.5-7
Simple vinyl ethers are produced on a technical scale
by base-catalyzed addition of alkanols to acetylene,8 while
more complex vinyl ethers have been prepared by mer-
cury-catalyzed transfer vinylations,9 base- or metal-
catalyzed isomerization of allyl ethers, or elimination
reactions.10 â-Oxa-γ,δ-enones, e.g., vinyl acetol, are ac-
cessible by the acid-catalyzed fragmentation of 4-meth-
ylene-1,3-dioxolane.11 Recently Ishii and co-workers re-
ported that [Ir(cod)Cl]2 (cod ) 1,5-cyclooctadiene) is a
highly effective catalyst for the vinylation of alkanols and
phenols using vinyl acetate and Na2CO3 as the stoichio-
metric reagents under inert atmosphere.12 Allyl vinyl
ethers have been prepared from carbonyl precursors
using the Tebbe reagent,13 from silyl enol ethers,14 and
by aldol condensation of R,â-unsaturated esters.15
The reactions are generally slow, e.g., 4-7 days for the
sugar substrates in our previous report, and at such
extended reaction times tend to generate acetals and
ortho esters as side products.16
We now have reevaluated the Pd catalyst for a variety
of primary, secondary, and tertiary alcohols and discov-
ered that the utility of the reaction is greatly improved
simply by changing the counterion ion from acetate to
trifluoro acetate. Most significantly, the catalyst also
effectively vinylates a representative selection of primary
and secondary allyl alcohols leading to the corresponding
allyl vinyl ethers in high yields. To our knowledge, this
is the first direct catalytic route to this class of com-
pounds.
(1) Reyntjens, W. G. S.; Goethals, E. J . Polym. Adv. Technol. 2001,
12, 107-122.
(2) J ong-Mok, K.; Thomson, D. H. J . Dispersion Sci. Technol. 2001,
22, 399-407.
(3) Mu¨ller, H. W. J . Vinyl Ether Polymers, 2nd ed.; Marcel Dekker,
Inc.: New York, 2001.
Resu lts a n d Discu ssion
(4) Ziegler, F. E. Chem. Rev. 1988, 88, 1423-1452.
(5) Murray, A. W. Org. React. Mech. 2001, 473-603.
(6) Nowicki, J . Molecules 2000, 5, 1033-1050.
(7) Hirsemann, M.; Abraham, L. J . Org. Chem. 2002, 9, 1461-1471.
(8) Kirk, R. E.; Othmer, D. F. Encyclopedia of Chemical Technology,
4th ed.; J ohn Wiley & Sons: New York, Toronto, 1991; Vol. 1.
(9) Watanabe, W. H.; Conlon, L. E. J . Am. Chem. Soc. 1956, 79,
2828-2833.
The results of our study are summarized in Table 1.
All reactions were carried out at 75 °C in air with a 0.5
(14) Maeda, K.; Shinokubo, H.; Oshima, K.; Utimoto, K. J . Org.
Chem. 1996, 61, 2262-2263.
(15) Hiersemann, M. Synthesis 2000, 1279-1290.
(16) Handerson, S.; Schlaf, M. Org. Lett. 2002, 4, 407-409.
(17) McKeon, J . E.; Fitton, P.; Griswold, A. A. Tetrahedron 1972,
28, 227-232.
(18) McKeon, J . E.; Fitton, P. Tetrahedron 1972, 28, 233-238.
(19) Weintraub, P. M.; King, C.-H. J . Org. Chem. 1997, 62, 1560-
1562.
(20) Tachibana, T.; Aihara, T. CAN: 112:138900; J P 01272577 Seimi
Chemical Co., Ltd. J apan: J apan, 1989.
(10) Larock, R. C. Comprehensive Organic Transformations; Wiley-
VCH: New York, 1999.
(11) Mattay, J .; Thuenker, W.; Scharf, H.-D. Lieb. Ann. Chem. 1981,
1105-1117.
(12) Okimoto, Y.; Sakaguchi, S.; Ishii, Y. J . Am. Chem. Soc. 2002,
124, 1590-1591.
(13) Kinney, W. A.; Coghlan, M. J .; Paquette, L. A. J . Am. Chem.
Soc. 1985, 107, 7352-7360.
10.1021/jo034376h CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/22/2003
J . Org. Chem. 2003, 68, 5225-5227
5225

Bosch and Schlaf
TABLE 1. Vin yla tion of Sim p le P r im a r y, Secon d a r y,
Ter tia r y, a n d Allylic Alcoh ols (ROH) w ith n -Bu tyl Vin yl
Eth er (BVE) a s th e Rea gen t a n d Solven t (Mola r Ra tio
ROH/BVE ) 1:20) a n d (DP P )P d X2 (DP P )
-
4,7-Dip h en yl-1,10-p h en a n th r olin e; X ) OAc-, OOCCF 3
a t 0.5 Mol % Ca ta lyst Loa d a n d 75 °C Rea ction
Tem p er a tu r e (i.e., Reflu xin g BVE)
)
% yielda of vinyl ether formed
and time to equilibrium (h)
with counterion X:b
-
entry
alcohol vinylated
OAc-
OOCCF3
primary alcohols
benzyl alcohol
benzyl alcoholc
1,6-hexanediold
4-penten-1-ol
secondary alcohols
cyclopentanol
cyclohexanol
1
2
3
4
84 (23)
not det
98 (5)
88 (4)
98 (20)
98 (2.5)
95 (1)
95 (8)
5
6
7
8
9
92 (24)
86 (33)
77 (24)
82 (55)
not det
not det
92 (3)
86 (4)
79 (6)
83 (13)
86 (6)
86 (32)
1-phenylethanol
menthol
isomenthol
F IGURE 1. Proposed mechanism of the catalytic transfer
vinylation.
10
neomenthol
Table 1 also establish that the exchange of the counterion
has no effect on the equilibrium position itself, as the
achieved yields are the same within the error range of
their determination.
tertiary alcohols
adamantanol
tert-butyl alcohol
allylic alcohols
allyl alcoholf
11
12
42 (.72)e
47(.32)e
61 (48)
72 (32)
13
14
15
16
17
18
19
62 (24)
not det
not det
not det
not det
not det
not det
90 (7)
81 (8)
80 (8)
84 (3)
89 (2.5)
96 (1)
0 (>12)
The proposed mechanism for the transfer vinylation
is shown in Figure 1. In the initial equilibrium, one of
the counterions X- is displaced by η2-coordination of vinyl
ether. The coordinating ability of the counterion is related
to the pKa of the corresponding acid (4.75 for acetic acid
vs 0.50 for trifluoro acetic acid on the aqueous scale).
When the less coordinating trifluoro acetate is used, this
equilibrium lies further to the right. Consequently, at
equal catalyst precursor concentrations, more actually
catalytically active centers are formed resulting in a
faster reaction. At the same time, the use of trifluroac-
etate leads to the formation of acetals as a major
byproduct catalyzed by the formation of the much stron-
ger acid HOC(O)CF3 in the catalytic cycle. Acetal forma-
tion is, however, completely suppressed when the free
acid is scavenged by NEt3 added in 10-15-fold excess
with respect to palladium. No coordinative inhibition of
the catalyst by the auxiliary base or change in product
distributions is observed even at higher base concentra-
tions.
No transfer vinylation was observed when 2,2:6,6-ter-
pyridine was employed as the ligand. Monodentate
ligands such as pyridine also fail to give active cata-
lysts;12,17,18 i.e., a cis chelation is a necessary condition
for catalysis to occur. This suggests an intramolecular
attack of a coordinated alkoxide on the activated double
bond to give the palladium alkyl complex (bottom center
of Figure 1) as the key intermediate.
The fact that the reaction is very sensitive to steric
effects supports this model. Vinyl ethers with substitu-
ents other than hydrogen on the R-carbon of the vinyl
group do not give any transfer vinylation because either
the η2-vinyl alkoxide intermediate cannot be formed at
all or cannot assume the right conformation for the oxy-
palladation to occur. The method is thus limited to simple
ethenyl ethers. Steric bulk on either one but not both of
the two alcohol moieties involved in any given reaction
is however well tolerated. Entries 1 and 2 in Table 1
demonstrate the effect of a bulky vinyl source on the
reaction rate and equilibrium position while entries 11
1-penten-3-ol
(-)-carveolg
2-cyclohexen-1-ol
(S)-(-)-perillyl alcohol
3-methyl-2-buten-1-ol
linalool
a
b
-
By GC. If X- ) OOCCF3 30 mol % of NEt3 were added to
suppress acetal formation; see text. c tert-Butyl vinyl ether was
d
used instead of butyl vinyl ether. Reaction produces primarily
divinyl ether; calculation is based on this product only. e Reaction
abandoned before equilibrium was established. f Using propyl vinyl
g
ether instead of butyl vinyl ether. p-Mentha-6,8-dien-2-ol; mix-
ture of two isomers. One isomer is initially vinylated faster than
the other, but at equilibrium the ratio of vinylated isomers matches
that of the starting alcohol.
mol % catalyst load with respect to alcohol. The catalyst
is formed in situ from PdX2, and the ligand at equimolar
ratios. To drive the equilibrium, a 20-fold molar excess
of commercially available butyl vinyl ether (BVE) was
employed as both the solvent and vinyl source. At the
end of the reaction, unreacted BVE can be recovered by
passing the reaction mixture through activated charcoal
to remove the catalyst followed by distillation. Propyl
vinyl ether (PVE) was used for the vinylation of allyl
alcohol (entry 13) due to separation problems between
the product allyl vinyl ether and BVE. This substitution
had no noticeable effect on the overall reaction. tert-Butyl
vinyl ether (entry 2) was used for a direct comparison of
the steric demands of the vinyl source on the reaction
rate and equilibrium. 4,7-Diphenyl-1,10-phenanthroline
(DPP) was chosen as the ligand in all cases as it resulted
in optimum catalyst solubility in the vinyl ether reaction
medium giving clear yellow reaction solutions. Other 2,2′-
bipyridyl- and phenanthroline-derived ligands are also
effective but were not further investigated.
Entries 1, 3-8, and 11-13 of Table 1 show that the
exchange of acetate for trifluoroacetate substantially
shortens the time until the reaction reaches equilibrium
as indicated by invariant product concentrations beyond
the reaction times listed in Table 1. The same entries in
5226 J . Org. Chem., Vol. 68, No. 13, 2003

Catalytic Synthesis of Allyl and Alkyl Vinyl Ethers
TABLE 2. Com p a r ison of th e P a lla d iu m - a n d
Ir id iu m -Ba sed Vin yla tion Ca ta lysts for Allyl a n d Alk en yl
Alcoh ols a n d P h en ols
counterion) are known to catalyze the enolization of allyl
alcohols,22,23 which can subsequently tautomerize to the
corresponding carbonyl compounds. These are, however,
not observed in the GC traces of the reactions, which
suggests that in the absence of stabilizing ligands the
iridium center is deactivated by an irreversible reaction
with the enol, whose formation competes with the
transfer vinylation. Thus, the transfer vinylation yields
inversely correlate to the ease of formation and stability
of the corresponding enols: e.g., perillyl alcohol, whose
enolization would result in an exocyclic double bond is
vinylated in high yield, while the kinetically and ther-
modynamically more easily enolized linear allyl alcohols
instantly poison the catalyst and therefore give no vinyl
ethers.
% yield with
Pd catalyst
% yield with
Ir catalystb
entry
alcohol
4-pentenol
1,6-hexanediol
phenol
allyl alcohol
1-penten-3-ol
(-)-carveol
2-cyclohexen-1-ol
(S)-(-)-perillyl alcohol
3-methyl-1-butenol
linalool
1
2
3
4
5
6
7
8
9
95
98
0
90
81
80
84
89
96
0
100
87
98
0
<5
49
33
86
0
10
0
a
GC yields. b Reaction conditions: alcohol/vinyl acetate/Na2CO3/
Ir ) 1.0:2.0:0.6:0.02; toluene, argon, 100 °C for 4 h; for comparison,
some yields were taken from ref 12.
Finally, neither catalyst vinylates 2-propyn-ol, 2-butyn-
1-ol, or other propargyl alcohols tested. Instead, immedi-
ate darkening of the reaction mixtures and formation of
a brown precipitate is observed in both cases.
and 12 and the series of menthols (entries 8-10) il-
lustrate the effect of steric bulk of the incoming alcohols
on the reaction rate. While the yields at equilibrium
under the given conditions are essentially the same for
all three menthols, the vinylation of isomenthol, in which
both alkyl substituents are oriented trans to the reacting
hydroxyl reaches equilibrium in 6 h, while with neo-
menthol, in which the reacting hydroxyl group is oriented
cis to the bulky isopropyl substituent, it requires 32 h to
reach its equilibrium. If both the vinyl source and the
incoming alcohol are sterically demanding, no reaction
occurs. Also the catalyst fails to vinylate the sterically
demanding tertiary allyl alcohol linalool. Other primary
and secondary allyl alcohols are, however, cleanly viny-
lated in good to excellent yields (entries 13-18 in Table
1). Table 2 compares the results obtained with the
iridium and the palladium system with allyl and alkenyl
alcohols, showing their complementarity for different
classes of substrates.
Both catalysts tolerate the presence of double bonds
remote to the hydroxyl function to be vinylated and also
vinylate diols, but the palladium system does not vinylate
phenols, probably due to the lower nucleophilicity of
phenoxide vs alkoxide,21 which prevents the oxypallada-
tion step from occurring. In turn, the iridum system
vinylates phenols but completely fails for linear allyl
alcohols, while for allyl alcohols in which the double bond
is part of a ring system variable yields are obtained.
Cationic iridium complexes of the type [Ir(cod)(L)(L′)]X
(L ) phosphine, L′ ) nitrile, X ) noncoordinating
Con clu sion
The complex (DPP)Pd(OOCCF3)2 (DPP ) 4,7-diphenyl-
1,10-phenanthroline) is an optimized catalyst for the
equilibrium transfer vinylation of various alcohols with
butyl vinyl ether as the reactant and solvent and NEt3
as an auxiliary base. The catalyst system is air-stable,
does not generate acetal byproducts on the time scale of
the reaction, tolerates remote carbon-carbon double
bonds in the alcohol substrates, and vinylates allyl
alcohols but not phenols. It is thus complementary to the
iridium catalyst [Ir(cod)Cl]2 (cod ) 1,5-cyclooctadiene),
which uses vinyl acetate under basic conditions as the
vinyl source and does vinylate phenols, but not allyl
alcohols.
Ack n ow led gm en t. We thank NSERC, the Cana-
dian Foundation for Innovation (CFI), the Ontario
Innovation Trust Fund (OIT), and the University of
Guelph for funding.
Su p p or tin g In for m a tion Ava ila ble: Typical reaction
protocol; extensive GC and GC-MS characterization data for
all vinyl ethers synthesized; and 1H/13C NMR data and spectral
images for new vinyl ethers synthesized. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O034376H
(22) Chin, C. S.; Lee, B.; Kim, S. J . Chem. Soc., Dalton Trans. 1991,
443-447.
(21) Pearson, R. G.; Sobel, H.; Songstad, J . J . Am. Chem. Soc. 1968,
90, 319-326.
(23) Chin, C. S.; Lee, B. J . Chem. Soc., Dalton Trans. 1991, 1323-
1327.
J . Org. Chem, Vol. 68, No. 13, 2003 5227