[Pd(μ-Br)(PtBu3)]2 as a highly active isomerization catalyst: Synthesis of enol esters from allylic esters

Article abstract of DOI:10.1021/ol301563g

The dimeric Pd(I)-complex [Pd(μ-Br)(P^tBu₃)] ₂ was found to be highly active for catalyzing double-bond migration in various substrates such as unsaturated ethers, alcohols, amides, and arenes, under mild conditions. It efficiently mediates the conversion of allylic esters into enol esters, rather than inserting into the allylic C-O bond. The broad applicability of this reaction was demonstrated with the synthesis of 22 functionalized enol esters.

Full text of DOI:10.1021/ol301563g

ORGANIC
LETTERS
[Pd(μ-Br)(PtBu3)]2 as a Highly Active
Isomerization Catalyst: Synthesis
of Enol Esters from Allylic Esters
2012
Vol. 14, No. 14
3716–3719
€
Patrizia Mamone, Matthias F. Grunberg, Andreas Fromm, Bilal A. Khan, and
Lukas J. Gooßen*
€
FB Chemie À Organische Chemie, TU Kaiserslautern, Erwin-Schrodinger-Str. Geb. 54,
67663 Kaiserslautern, Germany
goossen@chemie.uni-kl.de
Received June 6, 2012
ABSTRACT
The dimeric Pd(I)-complex [Pd(μ-Br)(PtBu3)]2 was found to be highly active for catalyzing double-bond migration in various substrates such as
unsaturated ethers, alcohols, amides, and arenes, under mild conditions. It efficiently mediates the conversion of allylic esters into enol esters,
rather than inserting into the allylic CÀO bond. The broad applicability of this reaction was demonstrated with the synthesis of 22 functionalized
enol esters.
Enol esters are important precursors in a variety of
organic transformations such as aldol- and Mannich type
reactions,1 asymmetric hydrogenations,2 cycloadditions,3
or other cyclization reactions to afford, e.g., heterocycles
or chromones.4 They are employed as auxiliary reagents in
the desymmetrization of alcohols,5 as well as in the synthe-
sis of vinylic amino alcohols and diols.6
O-acylation of enolates.7 However, these require stoichio-
metric amounts of bases, acids, or toxic mercury salts.
Modern, catalytic syntheses of enol esters include the
Zr-catalyzed methylalumination of alkynes,8 the Cu-
catalyzed oxidative esterification of aldehydes with
β-dicarbonyl compounds,9 the Au-catalyzed intramolecu-
lar rearrangements of propargylic esters and alcohols,10
the Fe-catalyzed asymmetric coupling of ketenes with
aldehydes,11 and the addition of carboxylic acids to al-
kynes catalyzed by Ru,12 RuÀRe,13 or Rh complexes.14
Classical approaches to their synthesis involve transes-
terification between alkyl esters and enol acetates, or
(1) (a) Yanagisawa, A.; Matsumoto, Y.; Asakawa, K.; Yamamoto,
H. J. Am. Chem. Soc. 1999, 121, 892. (b) Isambert, N.; Cruz, M.;
(7) Smith, M. B.; March, J. Advanced Organic Chemistry, 5th ed.; John
Wiley & Sons, New York, 2001; p 486.
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A. J.; Feringa, B. L.; Lefort, L.; De Vries, J. G. Acc. Chem. Res. 2007, 40,
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2008, 130, 7828.
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Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2750. (d) Angew. Chem.
2007, 119, 2806. (c) Peng, Y.; Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem.
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Linder, C.; Zimmermann, B. Pure Appl. Chem. 2008, 80, 1725. (b)
Dragutan, V.; Dragutan, I.; Delaude, L.; Demonceau, A. Coord. Chem.
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Chem. Soc. 2005, 127, 15756. (b)Lombardo, M.; Morganti, S.; Trombini,
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r
10.1021/ol301563g
Published on Web 07/02/2012
2012 American Chemical Society

alkenyl alcohols,26 allylic amines and amides.27 However,
none of these systems permitted to convert our test sub-
strate, oleic acid, into an equilibrium mixture of isomers
within a few hours at catalyst loadings below 1%.19
In our search for new lead structures for highly active
isomerization catalysts, reports by Mingos/Vilar and
Hartwig on the dimeric palladium complex [Pd(μ-Br)-
(PtBu3)]2 caught our attention.28 They discovered that this
unusual, dimeric PdI species, which has found applica-
tions in catalytic cross-coupling reactions,29 can be
converted into hydridopalladium(II) complexes under
remarkably mild conditions. We reasoned that a metal
complex with such strong tendency to form PdÀH species,
which are known to add across CÀC double-bonds,22,30
should also be an excellent catalyst for alkene isomeriza-
tion. Indeed, oleic acid was converted to an equilibrium
mixture of double-bond isomers with only 0.5 mol % of
[Pd(μ-Br)(PtBu3)]2 within less than an hour.31
The high activity of this one-component system led us to
evaluate the catalytic activity of the PdI dimer as the
catalyst for double-bond migrations in a range of standard
test substrates. As a reference system, we used a mixture
of Pd(dba)2, isobutyryl chloride, and tri(tert-butyl)-
phosphine. This catalyst has been shown by Lindhardt
and Skrydstrup to set new standards with regard to
catalytic activity and functional group tolerance for sin-
gle-carbon migrations of various double bonds.32 The
examples in Scheme 2 demonstrate that the PdI dimer is
an effective catalyst for double-bond migrations in allylic
arenes (5), amides (7), ethers (9), and alcohols (11 and 13).
In each case, the catalyst loading was reduced to the
minimum effective level, in order to differentiate between
the systems. For all substrate classes, the PdI dimer com-
pared favorably even to the state-of-the-art Pd-catalyst for
single-carbon migration of the double-bond. It is also able
to move the bond over longer alkyl chains. Thus, hexanal
(14) was obtained from 5-hexen-1-ol (13) in high yield and
selectivity.
Scheme 1. Synthesis of Enol Esters via Catalytic Isomerization
The catalytic isomerization of allylic esters to enol esters
would be anattractivealternative tothe aboveapproaches,
because the starting materials are easily accessible by
esterification of carboxylic acids (Scheme 1). However,
because of the weak thermodynamic driving force for the
double-bond migration and the tendency of many metal
catalysts to insert into the C(allyl)ÀO bond with formation
of stable carboxylate complexes,15 this reaction is beyond
the performance limit of most isomerization catalysts.
Even for unsubstituted allyl esters, only two reports of
double-bond migrations exist. Iranpoor et al. found that
stoichiometric amounts of Fe3(CO)12 promote this reaction
when irradiated with UV light.16 Krompiec et al. achieved
up to eight catalytic turnovers for the double-bond
migration, along with C(allyl)ÀO bond cleavage, using
the ruthenium hydride complex RuClH(CO)(PPh3)3.17
Mechanistic studies by Tokunaga et al. confirmed the
low catalytic activity of Ru complexes for this type of
substrate.18
In the context of our research on isomerizing functio-
nalizations of fatty acids,19 we had thoroughly investi-
gated the activity of various isomerization methods
involving acid20 or base mediators,21 as well as metal
catalysts reported for the isomerization of alkenes,22
allylic benzenes,23 allylic ethers,15,24 allylic silyl ethers,25
(13) Ye, S.; Leong, W. K. J. Organomet. Chem. 2006, 691, 1216.
(14) Lumbroso, A.; Koschker, P.; Vautravers, N. R.; Breit, B. J. Am.
Chem. Soc. 2011, 133, 2386.
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(15) Kuznik, N.; Krompiec, S. Coord. Chem. Rev. 2007, 251, 222.
(16) (a) Iranpoor, N.; Imanieh, H.; Iran, S.; Forbes, E. J. Synth.
Commun. 1989, 19, 2955. (b) Iranpoor, N.; Mottaghinejad, E.
J. Organomet. Chem. 1992, 423, 399.
(17) Krompiec, S.; Kuznik, N.; Krompiec, M.; Penczek, R.;
Mrzigod, J.; Torz, A. J. Mol. Catal. A: Chem. 2006, 253, 132.
(18) Four days at 80 °C were required to achieve 92% conversion of
allyl benzoate: Nakamura, A.; Hamasaki, A.; Goto, S.; Utsunomiya,
M.; Tokunaga, M. Adv. Synth. Catal. 2011, 353, 973.
(19) Ohlmann, D. M.; Gooßen, L. J.; Dierker, M. Chem.;Eur. J.
2011, 17, 9508.
(20) Lee, P. H.; Kang, D.; Choi, S.; Kim, S. Org. Lett. 2011, 13, 3470.
(21) For examples, see: (a) Sagoet, O.; Monteux, D.; Langlois, Y.;
Riche, C.; Chiaroni, A. Tetrahedron Lett. 1996, 37, 7019. (b) Su, C.;
Williard, P. G. Org. Lett. 2010, 12, 5378.
(22) For examples, see: (a) Harrod, J. F.; Chalk, A. J. J. Am. Chem.
Soc. 1966, 88, 3491. (b) Casey, C. P.; Cyr, C. R. J. Am. Chem. Soc. 1973,
95, 2248. (c) Grotjahn, D. B.; Larsen, C. R.; Gustafson, J. L.; Nair, R.;
Sharma, A. J. Am. Chem. Soc. 2007, 129, 9592.
(23) For examples, see: (a) Lastra-Barreira, B.; Francos, J.; Crochet,
P.; Cadierno, V. Green Chem. 2011, 13, 307. (b) Golborn, P.; Scheinmann,
F. J. Chem. Soc., Perkin Trans. 1 1973, 2870. (c) Mayer, M.; Welther, A.;
von Wangelin, A. J. ChemCatChem 2011, 3, 1567.
(24) For examples, see: (a) Yamamoto, Y.; Fujikawa, R.; Miyaura,
N. Synth. Commun. 2000, 30, 2383. (b) Carless, H. A.; Haywood, D. J.
J. Chem. Soc., Chem. Commun. 1980, 980. (c) Crivello, J. V.; Kong, S.
J. Org. Chem. 1998, 63, 6745.
The most striking result obtained in this series of test
reactions was that allyl benzoate (3a) was cleanly con-
verted to the corresponding enol ester 4a. Using only
0.25 mol % of PdI in toluene, near-quantitative conversion
to 1-propenyl benzoate (4a) was achieved within 2 h at
50 °C, with a product (E/Z)-ratio of 1:2. The only other
component detected in the reaction mixture was 2% of the
(27) (a) Krompiec, S.; Krompiec, M.; Penczek, R.; Ignasiak, H.
Coord. Chem. Rev. 2008, 252, 1819. (b) Escoubet, S.; Gastaldi, S.;
Bertrand, M. Eur. J. Org. Chem. 2005, 18, 3855.
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Williams, D. J. J. Organomet. Chem. 2000, 600, 198. (b) Dura-Vila, V.;
Mingos, D. M. P.; Vilar, R.; White, A. J.P.; Williams, D. Chem.
Commun. 2000, 1525. (c) Barrios-Landeros, F.; Carrow, B. P.; Hartwig,
J. F. J. Am. Chem. Soc. 2008, 130, 5842.
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C. C. C.; Colacot, T. J. Angew. Chem., Int. Ed. 2010, 49, 676. Angew.
Chem. 2010, 122, 686. (c) Proutiere, F; Aufiero, M; Schoenebeck, F
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(31) This reactivity has also been exploited in isomerizing olefin
metatheses: Ohlmann, D. M.; Tschauder, N.; Stockis, J.-P.; Gooßen,
K.; Dierker, M.; Gooßen, L. J. submitted for publication (2012).
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Org. Lett., Vol. 14, No. 14, 2012
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Table 1. Isomerization of Allylic Esters to Enol Estersf
Scheme 2. Double-Bond Migration with the PdI Catalyst33
starting material 3a, which did not disappear even after a
prolonged reaction time, indicating that the equilibrium
had been reached. In view of the rich chemistry of allylic
acetate activation by palladium catalysts, it was surprising
that no trace of benzoic acid arising from C(allyl)ÀO bond
cleavage was observed.34,15
Encouraged by the observation thatequilibration occurs
so rapidly and that its position lies so far on the side of the
enol esters, we optimized the catalyst loading and reaction
conditions33 and then explored the scope of the reaction
protocol. As can be seen from the examples in Table 1, the
reaction is broadly applicable with regard both to the
carboxylate and allyl alcohol side of the esters.35
Allylic esters of electron-rich and electron-deficient aro-
matic (4aÀi), heteroaromatic (4j,k), aliphatic (4lÀo), and
cinnamic (4p) carboxylates were successfully converted.
A variety of functionalities including alkoxy (4c,d),
hydroxy (4g), amino (4h), nitro (4i), and keto groups
(4o) were tolerated. Even halogen-containing substrates
reacted smoothly without any indication of competing
Heck-type reactions (4e,f). In all cases, (E:Z)-ratios be-
tween 1:2 and 1:5 were obtained.
The allyl residue can be linear or branched in the
1- and/or 2-positions (4qÀv). Enol esters branched in the
1-position are of considerable interest as substrates for
a [Pd(μ-Br)(PtBu3)]2 (0.50 mol %). b [Pd(μ-Br)(PtBu3)]2 (2.50 mol %).
c Yield and (E/Z)-selectivity was determined by NMR with anisole as
internal standard. d 25 °C, 10% of other isomers. e [Pd(μ-Br)(PtBu3)]2
(1.00 mol %). f Reaction conditions: Allylic esters 1aÀv (1.00 mmol),
[Pd(μ-Br)(PtBu3)]2 (0.25 mol %), 2 mL of toluene, 50 °C, 16 h, isolated
yields. (E/Z)-selectivity was determined by GC.
(33) For details, see the Supporting Information.
(34) Weaver, J. D.; Recio, A., III; Grenning, A. J.; Tunge, J. A. Chem.
Rev. 2011, 111, 1846.
(35) Synthesis of 1-propenyl benzoate (4a): Under a nitrogen atmo-
sphere, a 50 mL vessel was charged with di-μ-bromobis(tri-tert-
butylphosphine)dipalladium(I) (27.2 mg, 35.0 μmol), allyl benzoate
(3a) (1.76 g, 10.0 mmol), and toluene (20 mL). The mixture was stirred
at 50 °C for 16 h, diluted with diethyl ether (40 mL), and filtered through
a pad of celite (5 g), and the solvent was removed in vacuo (50 mbar,
40 °C). The crude product was purified by column chromatography
(SiO2, diethyl ether/n-pentane gradient) to give prop-1-enyl benzoate
(4a) (1.65 g, 94% yield, E:Z 1:2) as colorless liquid.
enantioselective hydrogenations, but because of their
limited availability, there are only few reports on such
reactions.2,36 Wewere thus pleased tofind that compounds
4qÀu can be hydrogenated in high yields and enantiomeric
excess (Scheme 3).37 This demonstrates the viability of
(36) (a) Jiang, Q.; Xiao, D.; Zhang, Z.; Cao, P.; Zhang, X. Angew.
Chem., Int. Ed. 1999, 38, 516. Angew. Chem. 1999, 111, 578. (b) Jung,
H. M.; Koh, J. H.; Kim, M.-J.; Park, J. Org. Lett. 2000, 2, 2487. (c) Wu,
S.; Wang, W.; Tang, W.; Lin, M.; Zhang, X. Org. Lett. 2002, 4, 4495.
(37) Reetz, M. T.; Goossen, L. J.; Meiswinkel, A.; Paetzold, J.;
Jensen, J. F. Org. Lett. 2003, 5, 3099.
3718
Org. Lett., Vol. 14, No. 14, 2012

Scheme 3. Rh-Catalyzed Asymmetric Hydrogenation of Enol
Esters
Scheme 4. Proposed Activation of the PdI Dimer
enantioselective syntheses via a double-bond isomerization/
asymmetric hydrogenation sequence.
Starting from 19, a possible mechanism for the isomer-
ization reaction would involve an insertion of the alkene
into the PdÀhydride 19 followed by β-hydride elimination
with formation of the isomerized olefin and regeneration
of the initial PdÀhydride 19. Further mechanistic investi-
gations to elucidate the origin of the high isomerization
activity of [Pd(μ-Br)(PtBu3)]2 are underway.
In order to evaluate how the catalytically active species
may form from the PdI dimer, we calculated the standard
Gibbs free energy (ΔRGQ) for the formation of various
Pd-hydride species using the B3LYP density functional.33
The lowest energy expenditure was calculated for the
formation of Pd hydride 19 along with the monomeric
palladacycle 20 (ΔRGQ = 14.9 kcal/mol) (see Table S3
(Supporting Information) and Scheme 4). Since this reac-
tion proceeds via an endergonic pathway, the driving force
for the formation of 19 is the concomitant dimerization of
20 to the stable palladacycle 21 (ΔRGQ = À18 kcal/mol).
The PdÀH complex 19 likely acts as the catalytically
active species, but because of its high reactivity, we were
not surprised to detect the oxidized dimeric palladacycle 21
as major signal when monitoring the catalytic reaction by
1H and 31P NMR (31P NMR:À8.6 ppm). A minor signal at
À9.0 ppm also appeared, which might originate from an
isomer of 21. It is known that 21 can also form from PdÀH
species 18, with concomitant release of a phosphine and
hydrogen gas.38 Moreover, 21 may result from the decom-
position of 19 after it has achieved the double bond
migration. Another experimental result that supports
19 as the catalytically active species is that upon trapping
with tri-tert-butylphosphine, the more stable bis(tert-
butylphosphino)palladium hydride complex 18 was de-
tected (1H NMR: triplet at À15.6 ppm).28a
In conclusion, the PdI dimer [Pd(μ-Br)(PtBu3)]2 pos-
sesses a new level of reactivity for catalyzing double
bond migrations in a wide range of unsaturated sub-
strate classes. It even catalyzes the isomerization of
allylic esters to the corresponding enol esters, which
are valuable starting materials, e.g., for asymmetric
hydrogenation.
Acknowledgment. We thank D. Halter and Dr. W. Dzik
(TU Kaiserslautern) for technical assistance, NanoKat,
the DFG (SFB-TRR 88 “3MET”), the Landesgraduier-
tenstiftung Rheinland-Pfalz (fellowships to P.M., M.F.G.,
and A.F.) and the HEC Pakistan (fellowship to B.A.K.)
for financial support, and Umicore for the donation of
catalyst metals.
Supporting Information Available. Screening table,
experimental procedures, characterization of all new
compounds, and data of DFT calculations. This material
is available free of charge via the Internet at http://pubs.
acs.org.
(38) Clark, H. C.; Goel, A. B.; Goel, S J. Organomet. Chem. 1979,
166, C29.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 14, 2012
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