Palladium-Catalyzed 1,4-Acetoxy-Trifluoroacetoxylation and 1,4-Alkoxy-Trifluoroacetoxylation of Cyclic 1,3-Dienes. Scope and Mechanism

Article abstract of DOI:10.1021/jo971738a

Palladium-catalyzed unsymmetrical 1,4-functionalizations of cyclic 1,3-dienes are described. Trifluoroacetate in combination with acetate or alcohols is utilized to obtain 1-acetoxy-4-(trifluoroacetoxy)-2-cycloalkenes and 1-alkoxy-4-(trifluoroacetoxy)-2-c

Full text of DOI:10.1021/jo971738a

J . Org. Chem. 1998, 63, 2523-2529
2523
P a lla d iu m -Ca ta lyzed 1,4-Acetoxy-Tr iflu or oa cetoxyla tion a n d
1,4-Alk oxy-Tr iflu or oa cetoxyla tion of Cyclic 1,3-Dien es. Scop e a n d
Mech a n ism
Attila Aranyos, Ka´lma´n J . Szabo´,† and J an-E. Ba¨ckvall*,†
Department of Organic Chemistry, Uppsala University Box 531 S-751 21 Uppsala, Sweden
Received September 16, 1997
Palladium-catalyzed unsymmetrical 1,4-functionalizations of cyclic 1,3-dienes are described.
Trifluoroacetate in combination with acetate or alcohols is utilized to obtain 1-acetoxy-4-
(trifluoroacetoxy)-2-cycloalkenes and 1-alkoxy-4-(trifluoroacetoxy)-2-cycloalkenes, respectively, with
good regio- and stereoselectivities. The chemoselectivity of these reactions relies on the different
kinetic stability of the intermediate 4-(trifluoroacetoxy)-, 4-acetoxy-, and 4-methoxy-[η3-(1,2,3)-
cycloalkenyl]palladium complexes. Under the acidic reaction conditions employed, the 4-trifluo-
roacetoxy π-allyl intermediate is the least stable of the three. Certain mechanistic aspects of the
reactions are discussed in the light of DFT calculations.
In tr od u ction
added to the diene leading to unsymmetrical products 1
(X * Y, eq 1). Examples of such reactions are the
palladium-catalyzed 1,4-chloroacetoxylation10 and the
1,4-acetoxy-trifuoroacetoxylation.11 The success of these
unsymmetrical additions relies on the fact that one of
the two nucleophiles employed forms a kinetically un-
stable 4-substituted (π-allyl)palladium intermediate. The
kinetic stability of the (π-allyl)palladium intermediate
depends on the polarity of the C4-X(Y) bond. In the case
of a polar C4-X(Y) bond the functionality at the 4-posi-
tion can be readily exchanged to another group in a
palladium-assisted process.10,12
Electrophilic addition to conjugated dienes have found
limited use in organic synthesis, mainly due to problems
with regio- and stereoselectivity.1 Until recently, the
major use of conjugated dienes has been in cycloadditions
of different types.2 During the last two decades, however,
metal-mediated additions to conjugated dienes have
attracted considerable interest,3,4 and in particular,
transition metal-catalyzed reactions via π-allyl complexes
have evolved as viable processes.4,5 These reactions often
offer useful levels of regio- and stereocontrol.
We have previously reported on several different
palladium(II)-catalyzed 1,4-oxidations of conjugated
dienes.6 These reactions, which proceed via (π-allyl)-
palladium intermediates, are highly regio- and stereo-
selective and can be performed with a number of different
hetero7 and carbon nucleophiles8 under mild conditions.
The synthetic utility of these processes has been success-
fully demonstrated in natural product synthesis.9 An
intriguing feature of these reactions is that under the
appropriate conditions two different nucleophiles can be
This exchange involves an anchimeric assistance by
palladium via a (π-diene)palladium complex and proceeds
with retention of configuration.
Unsymmetrical bis-allylic compounds 1 are useful
building blocks in organic synthesis4-6,10,13 since they can
be selectively functionalized at either allylic position. In
† Present address: Department of Organic Chemistry, Arrhenius
Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
(1) (a) Block, E.; Schwan, A. L. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, U.K., 1991; Vol. 4
(Vol. Ed. Semmelhack, M. F.) p 329. (b) Pattenden, G. In Comprehen-
sive Organic Chemistry; Barton, D., Ollis, W. D., Eds.; Pergamon
Press: Elmsford, NY, 1979; Vol 1, p 171.
(2) (a) Sauer, J .; Sustmann, R. Angew. Chem. 1980, 92, 773; Angew.
Chem., Int. Ed. Engl. 1980, 19, 779. (b) Balci, M. Chem. Rev. 1981,
81, 91. (c) Weinreb, S. M.; Staib, R. R. Tetrahedron 1982, 38, 3087. (d)
Boger, D. L.; Weinreb, S. M. In Hetero Diels-Alder Methodology in
Organic Synthesis; Academic Press: New York, 1987.
(3) (a) Pearson, A. J . In Advances in Metal-Organic Chemistry;
Liebeskind, L. S., Ed.; J AI Press: Greenwich, CT, 1989; Vol 1, pp 3-25.
(b) Pearson, A. J .; Kole, S. L. J . Am. Chem. Soc. 1984, 106, 6060. (c)
Kolb, H. C.; van Nieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994,
94, 2483.
(4) (a) Ba¨ckvall, J . E. In Advances in Metal-Organic Chemistry;
Liebeskind, L. S., Ed.; J AI Press: Greenwich, CT, 1989; Vol 1, pp 135-
175.
(6) (a) Ba¨ckvall, J . E. Palladium-Catalyzed Oxidation of Dienes.
Review in The Chemistry of Functional Groups: Polyenes and Dienes;
Patai, S., Rappoport, Z., Eds.; Wiley: 1997; pp 653-681. (b) Ba¨ckvall
J . E. Palladium-Catalyzed 1,4-Additions to Conjugated Dienes. Review
in Metal-catalyzed Cross Coupling Reactions; Stang, P., Diederich, F.,
Eds.; VCH: Weinheim, 1998; pp 333-385.
(7) (a) Ba¨ckvall, J . E.; Granberg, K. L.; Andersson, P. G.; Gatti R.;
Gogoll, A. J . Org. Chem. 1993, 58, 5445. (b) Ba¨ckvall, J . E. Pure and
Appl. Chem. 1992, 64, 429. (c) Ba¨ckvall, J . E.; Granberg, K. L.; Hopkins,
R. B. Acta Chem. Scand. 1990, 44, 492.
(8) (a) Castan˜o, A. M.; Persson, B. A.; Ba¨ckvall, J . E. Chem Eur. J .
1997, 3, 482. (b) Ba¨ckvall, J . E.; Nilsson, Y. I. M.; Andersson, P. G.;
Gatti, R. G. P.; Wu, J . Tetrahedron Lett. 1994, 35, 5713. (c) Ro¨nn, M.;
Andersson, P. G.; Ba¨ckvall, J . E. Tetrahedron Lett., in press.
(9) (a) Nilsson, Y. I. M.; Aranyos, A.; Andersson, P. G.; Ba¨ckvall, J .
E.; Parrain, J . L.; Ploteau, C.; Quintard, J . P. J . Org. Chem. 1996, 61,
1825. (b) Andersson, P. G.; Ba¨ckvall, J . E. Synthesis of Heterocyclic
Natural Products via Regio- and Stereocontrolled Palladium-Catalyzed
Reactions. Review for Advances in Natural Product Synthesis; Pearson,
W. Ed.; J AI Press: Greenwich, CT, 1996; pp 179-215.
(5) (a) Tsuji, J . Palladium Reagents and Catalysts: Innovations in
Organic Synthesis; Wiley: Chichester, 1995. (b) Harrington, P. J . In
Comprehensive Organometallic Chemistry II; Eds. Abel, E. W., Stone,
G. A., Wilkinson, G. Eds.; Pergamon: New York, 1995; Vol. 12 (Vol.
Ed. Hegedus, L. S.), pp 797-904.
S0022-3263(97)01738-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/01/1998

2524 J . Org. Chem., Vol. 63, No. 8, 1998
Ta ble 1. P a lla d iu m (II)-Ca ta lyzed 1,4-Acetoxy-Tr iflu or oa cetoxyla tion
Aranyos and Szabo´
a
b
Isolated yields. Not determined. c Determined by 1H NMR spectroscopy.
particular when X and Y are leaving groups of different
reactivity, sequential nucleophilic substitution (either
SN2 or metal-mediated) offers unique opportunities for
regioselective functionalizations. In view of the synthetic
versatility of these unsymmetrical compounds, further
studies on the palladium-catalyzed 1,4-oxidation of 1,3-
dienes leading to their formation were desirable.
system manganese dioxide with catalytic amounts of
p-benzoquinone (BQ) was employed.15
In this paper we report on the use of trifluoroacetate
as an exchangeable nucleophile and the application to
1,4-acetoxy-trifluoroacetoxylation14 and 1,4-alkoxy-tri-
fluoroacetoxylation of cyclic 1,3-dienes. An important
observation is that the stereoselectivity of the 1,4-acetoxy-
trifluoroacetoxylation reaction can be reversed by addition
of acetonitrile. The mechanism of the reactions is
discussed in the light of density functional calculations.
High chemoselectivities were obtained in the case of
1,3-cyclohexadiene and 1,3-cycloheptadiene, the 1-ac-
etoxy-4-(trifluoroacetoxy)-2-alkenes being the main prod-
uct.16 Formation of the two symmetric side products
(diacetate and bis-trifluoroacetate) was also observed but
the relative amounts of these can be kept low by carefully
tuned reaction conditions. The influence of some addi-
tives were studied in the oxidation of 1,3-cyclohexadiene,
and the results are summarized in Table 1.
Trifluoroacetic anhydride proved to be an essential
additive (cf. entries 1 and 2). Its role is to trap the water
formed from manganese dioxide in the reaction. The
presence of water would result in substantial hydrolysis
of the trifluoroacetate group in the products under the
strong acidic conditions employed. The optimum amount
of lithium trifluoroacetate is between 1 and 2 equiv. One
equivalent gave slightly better selectivity but lower yield,
while 2 equiv gave slightly higher yield but lower stereo-
Resu lts a n d Discu ssion
1,4-Acet oxy-Tr iflu or oa cet oxyla t ion . Palladium-
catalyzed oxidation of 1,3-dienes was performed in dichlo-
romethane/acetic acid or acetone/acetic acid solvent
mixtures in the presence of lithium trifluoroacetate,
trifluoroacetic acid, and trifluoroacetic anhydride using
palladium acetate as the catalyst (eq 2). The reoxidation
(10) Ba¨ckvall, J . E.; Nystro¨m, J . E.; Nordberg, R. E. J . Am. Chem.
Soc. 1985, 107, 3676.
(11) Ba¨ckvall, J . E.; Vågberg, J . O.; Nordberg, R. E. Tetrahedron
Lett. 1984, 25, 2717.
(12) (a) Szabo´, K. J . J . Am. Chem. Soc. 1996, 118, 7818. (b) Szabo´,
K. J . Chem. Eur. J . 1997, 3, 592. (c) Szabo´, K. J .; Hupe, E.; Larsson,
A. L. Organometallics 1997, 16, 3779.
(13) (a) Geneˆt, J . P.; Piau, F. J . Org. Chem. 1981, 46, 2414. (b)
Ba¨ckvall, J . E.; Nordberg, R. E.; Nystro¨m, J . E. Tetrahedron Lett. 1982,
23, 1617. (c) Tanigawa, Y.; Nishimura, K.; Kawasaki, A.; Murahashi,
S. I. Tetrahedron Lett. 1982, 23, 5549.
(15) The oxidation system MnO2/cat. BQ was developed in our
laboratory in 1983: Ba¨ckvall, J . E. Pure Appl. Chem. 1983, 55, 1669.
Ba¨ckvall, J . E.; Bystro¨m, S. E.; Nordberg, R. E. J . Org. Chem. 1984,
49, 4619.
(14) A correction to the previously published procedure11 is given
in the Experimental Section.
(16) Cyclooctadiene as well as acyclic dienes gave worse chemose-
lectivity and in some of the cases bad regioselectivity.11

Palladium-Catalyzed 1,4-Acetoxy-Trifluoroacetoxylation
J . Org. Chem., Vol. 63, No. 8, 1998 2525
Ta ble 2. P a lla d iu m (II)-Ca ta lyzed
1,4-Alk oxy-Tr iflu or oa cetoxyla tion a
selectivity (cf. entries 1 and 4). Further increase of this
additive led to increase in the bis-trifluoroacetoxy side
product. High trifluoroacetic acid concentration reduces
the relative amount of the diacetates formed, but as a
side effect the stereoselectivity drops as well. Thus, the
use of 5 equiv of trifluoroacetic acid afforded 2 with a
trans:cis ratio of 80:20 (entry 3). With addition of
acetonitrile, and changing the solvent from dichlo-
romethane to acetone-acetic acid (1:1), the stereochem-
istry of the 1,4-addition could be reversed providing
predominantly the cis-product. Accordingly, with the use
of 2 equiv of acetonitrile, compound 3 was obtained with
a cis:trans selectivity of 83:17, however, only in a moder-
ate yield (40%, entry 5).
The effect of acetonitrile on the stereoselectivity can
be explained by its coordination to palladium leading to
the displacement of the coordinated trifluoroacetate. In
this way the migration pathway is blocked, and the
external attack is favored. Nitriles are known to coordi-
nate well to Pd(II) and form stable isolable complexes.17
a
The reactions were performed using 5% Pd(OAc)2, 1 equiv of
CF3COOLi, 4 equiv of CF3COOH, 8.2 equiv of ROH, and 1.5 equiv
b
of BQ in 6 mL of CH2Cl2. Isolated yields. c Determined by 1H
NMR spectroscopy.
alcohol, 4 equiv of trifluoroacetic acid, and 1 equiv of
lithium trifluoroacetate gave the best results.
Acetonitrile also increases the polarity of the reaction
medium which is expected to favor the ionic dissociation
of trifluoroacetate from the (π-allyl)palladium trifluoro-
acetate. Even though, the cationic (π-allyl)palladium
intermediate 5b (eq 3) is expected to be more reactive
than the neutral one (5a ), trifluoroacetate is a very weak
nucleophile, and therefore high yields from external
attack are difficult to obtain.
When 1,3-cycloheptadiene was used as substrate,
predominantly the cis-product 4 was formed. This result
is in line with previous studies,6b,11 where it was sug-
gested that the geometry required for the cis-migration
is unfavorable in the case of the seven-membered ring
(entry 6).
1,4-Alk oxy-Tr iflu or oa cetoxyla tion . In the presence
of various alcohols, trifluoroacetic acid, lithium trifluo-
roacetate and a stoichiometric amount of BQ, unsym-
metrical alkoxy-trifluoroacetoxy compounds were ob-
tained in fairly good yields and good stereoselectivities
in a palladium-catalyzed oxidation (eq 4, Table 2).
Both the yields and the selectivities are in the same
range independent of the alcohol employed. The reaction
products can be viewed as dihydroxyl synthons where one
OH group is protected while the other is activated. The
trifluoroacetoxy group can be selectively hydrolyzed or
exchanged with nucleophiles via palladium(0) catalysis.13
In particular, product 10 is a versatile intermediate since
after elaborating the trifluoroacetoxy group the benzyl
group can be easily removed to release the alcohol
function, thereby offering further functionalizations.
Mech a n ism . According to the accepted mechanistic
scheme of the palladium-catalyzed 1,4-oxidation of con-
jugated dienes (Scheme 1),6 this reaction proceeds via
coordination of the diene to the active palladium species,
followed by trans attack of the nucleophile on one of the
double bonds. In the 1,4-acetoxy-trifluoroacetoxylation,
under the acidic reaction conditions employed, the trif-
luoroacetate is the strongest nucleophile available. The
initial formation of the 4-trifluoroacetoxy-[η3-(1,2,3)-allyl]-
palladium complex is also indicated by the presence of a
small amount of the bis-trifluoroacetate product in the
final reaction mixture. However, this 4-trifluoroacetoxy
substituted (π-allyl)palladium intermediate (eq 1) is
kinetically unstable under the reaction conditions (vide
infra), and therefore, the trifluoroacetoxy group can
readily be displaced by another functionality, such as
alkoxy or acetoxy, which forms a more stable C4-O bond
(path A). In the case of the 1,4-alkoxy-trifluoroacetoxy-
lations a direct nucleophilic attack on the palladium-
diene complex is a likely competing pathway (path B).
The kinetically stable (π-allyl)palladium complex can
subsequently react with a second nucleophile. Coordina-
tion of BQ activates the π-allyl intermediate which then
will be attacked by the best nucleophile available. Ad-
dition of lithium trifluoroacetate ensures a high trifluo-
roacetate concentration, and therefore, the second nu-
Palladium acetate and palladium trifluoroacetate were
tested as catalysts, and the former was found to give
cleaner reactions and higher yields. To achieve a maxi-
mum amount of the unsymmetrical product, the relative
amounts of the acid, the alcohol, and the lithium trifluo-
roacetate had to be optimized. Thus, 8.2 equiv of the
(17) Kharasch, M. S.; Seyler, R. C.; Mayo, F. R. J . Am. Chem. Soc.
1938, 60, 882.

2526 J . Org. Chem., Vol. 63, No. 8, 1998
Aranyos and Szabo´
Sch em e 1
cleophilic attack will be performed by trifluoroacetate,
either by cis-migration or external attack. Internal
attack via cis-migration leads to a trans-product (entries
1, 3, and 4 in Tables 1 and 1-5 in Table 2), whereas
external attack by trifluoroacetate furnishes a cis-product
(entries 5 and 6, Table 1). With 1,3-cyclohexadiene as a
substrate, the stereochemistry of the nucleophilic attack
can be reversed from trans to cis (entry 5 in Table 1).
Trifluoroacetate is a weakly coordinated ligand on pal-
ladium(II), and in the presence of acetonitrile in an
acetone/acetic acid solvent mixture it can be displaced,
giving rise to more external attack.
11a -13a ) are involved as a result of the first nucleophilic
attack. Density functional calculations on these com-
plexes show18 (Figure 1) that the C4-O bond in the
trifluoroacetoxy complex 13a is longer (1.542 Å) than the
corresponding distance in the acetoxy (12a , 1.514 Å), or
methoxy complexes (11a , 1.483 Å). Other structural
parameters, such as C3-C4 and Pd-C3 bond lengths,
also suggest a more intensive 4-substituent effect12 in
compound 13a than in 11a or 12a .
Th eor etica l Resu lts. The palladium-assisted ex-
change of the 4-functionality in the [η3-(1,2,3)-allyl]-
palladium intermediates is a mechanistically interesting
process of the 1,4-alkoxy-trifluoroacetoxylation and 1,4-
acetoxy-trifluoroacetoxylation reactions, and it is also
responsible for the chemoselective formation of the
unsymmetrical products. Functional groups in the 4-po-
sition (X or Y in eq 1) of (π-allyl)palladium complexes may
interact with the palladium atom. The intensity of this
4-substituent effect (â-substituent effect) depends on the
conformation of the X(Y) functionality, the polarity of the
C4-X(Y) bond, and the σ-donor π-acceptor property of
the ancillary ligands on palladium.12 Various aspects of
these substituent effects have been discussed in three
recent publications,12 and therefore, in this theoretical
section we discuss only those features, which are of
relevance for the present catalytic reactions.
(for a definition of X, see Figure 1)
In the presence of trifluoroacetic acid the 4-functional-
ity (OMe, OAc, OCOCF3) can be protonated. Protonation
of the O4 atom further increases the polarity of the C4-O
bonds thereby amplifying the 4-substituent effect. We
also attempted to optimize the O-protonated structures,
but these complexes did not represent a minimum on the
potential energy surface, since during the optimization
dissociation of the C4-O bond occurred. Therefore, the
properties of the protonated species could only be studied
by freezing the C4-O bond lengths at various distances,
while optimizing the rest of the geometrical parameters.
In the protonated complexes 11b-13b19 the C4-O
distance is constrained at 1.6 Å, which would be conceiv-
A particularly important consequence of the 4-sub-
stituent effect is the elongation and weakening of the
C4-X(Y) bond in the substituted (π-allyl)palladium
intermediates. It has been shown12 that increase of the
polarity of the C4-X(Y) bond leads to weakening of this
bond and, accordingly, decrease of the kinetic stability
of the complex. In the investigated catalytic 1,4-oxidation
reactions three different π-allyl complexes (Figure 1,
(18) In all these compounds there are two conformations the boat
and the chair, which have about the same energy. As the â-substituent
effect is stronger in the chair conformation than in the boat one, only
the former was considered here. For the different conformers of similar
compounds see ref 12.
(19) In the case of the acetate and trifluoroacetate, protonation at
the carbonyl oxygen is energetically more favorable. However, proto-
nation of O4 allows direct comparison with the methoxy group. See
ref 12c.

Palladium-Catalyzed 1,4-Acetoxy-Trifluoroacetoxylation
J . Org. Chem., Vol. 63, No. 8, 1998 2527
F igu r e 1. B3PW91/LANL2DZ-optimized geometries of 11a ,b-13a ,b.
able for the equilibrium bond length in an O-protonated
C-O(H)-C structure (Figure 1). Comparison of the
geometry of 11a -13a with 11b-13b reveals some typical
structural effects of the enhanced â-substituent effects:
(a) increased difference between the Pd-C1 and Pd-C3
bond lengths; (b) shortening of the C3-C4 bond indicat-
ing the enhanced π-character of the C3-C4 bond.20 The
stability of the protonated complexes was investigated

2528 J . Org. Chem., Vol. 63, No. 8, 1998
Aranyos and Szabo´
on the heavy atoms (LANL2DZ+P)29 leading to a theo-
retical model, which is denoted as B3PW91/LANL2DZ+P/
/B3PW91/LANL2DZ. All calculations were performed on
a Digital Alphastation 500 using Gaussian94 software
package.30
Exp er im en ta l Section
NMR spectra were recorded for CDCl3 solutions (1H at 400
MHz and 13C at 100.5 MHz) using chloroform-d (7.26 ppm,
1H, 77.0 ppm, 13C) as internal standard. Coupling constants
were evaluated using J -doubling31 technique. Mass spectra
were obtained in GC/MS mode (EI, 70 eV). Dichloromethane
was distilled over CaH2. Other solvents were used without
further purification. Pd(OAc)2 was purchased from Fluoro-
chem. All other chemicals were bought from Lancaster or
Aldrich and were used without further purification. Merck
silica gel 60 (240-400 mesh) was used for flash chromatog-
raphy.
F igu r e 2. Calculated relative B3PW91/LAN2DZ+P//B3PW91/
LAN2DZ energies of complexes 11b-13b as a function of
C4-O bond distances.
in two additional points of the potential energy surface.
Freezing the C4-O distance at 1.8 Å led to a sharp
decrease of total energies (Figure 2). When the C4-O
bond was constrained at 2.0 Å, which would be expected
for the transition state of a C-O bond cleavage, a further
decrease of the total energy occurred for all three
complexes. The energy decrease was considerably greater
for the trifluoroacetoxy substituted complex (17.8 kcal/
mol) than the acetoxy (11.7 kcal/mol) or methoxy (5.8
kcal/mol) substituted ones.
The results clearly show the expected trend, namely
that the reactivity order of these groups in the acid-
catalyzed C4-O bond cleavage is the following: CF3COO-
> AcO- > MeO-.21 This means that in any combination
of these nucleophiles, the more reactive22 will form a
kinetically less stable 4-substituted [η3-(1,2,3)-allyl]pal-
ladium intermediate, and under sufficiently acidic reac-
tion conditions, unsymmetrical functionalization is pos-
sible.
tr a n s-1-Acetoxy-4-(tr iflu or oacetoxy)-2-cycloh exen e (2).
Pd(OAc)2 (16.8 mg, 0.075 mmol), lithium trifluoroacetate (180
mg, 1.5 mmol), CF3COOH (230 µL, 3 mmol), (CF3CO)2O (320
µL, 2.25 mmol), MnO2 (157 mg 1.65 mmol), and p-benzo-
quinone (24 mg, 0.225 mmol) were dissolved in a mixture of 5
mL of CH2Cl2 and 2 mL of acetic acid. To this stirred solution
freshly distilled 1,3-cyclohexadiene (147 µL, 1.5 mmol) was
added via a syringe pump during 6-8 h. The reaction mixture
was stirred for another 8 h at room temperature and then
diluted with 50 mL pentane/ether (50/50). The resulting
mixture was extracted with water (2 × 15 mL), brine (2 × 15
mL), saturated aqueous Na2CO3 (3 × 15 mL), and brine. The
organic phase was dried over MgSO4 and concentrated in
vacuo. Rapid flash chromatography using an 85:15 mixture
of pentane and ether as eluent gave 0.278 g (74%) of compound
2 as a colorless oil (93% trans). 1H NMR: δ 6.05 (ddd, 1H, J
) 10.0, 3.4, 1.5 Hz), 5.94 (ddd, 1H, J ) 10.0, 3.7, 1.4 Hz), 5.52-
5.47 (m, 1H), 5.36-5.30 (m, 1H), 2.27-2.11 (m, 2H), 2.06 (s,
3H), 1.92-1.82 (m, 1H), 1.82-1.72 (m, 1H); 13C NMR: δ 170.3,
2
1
157.1 (q J C-F ) 41.9 Hz), 132.5, 127.5, 114.4 (q J C-F ) 286.1
Hz), 72.0, 66.6, 25.1, 25.0, 21.1; IR (in CDCl3 solution): 3048,
2963, 2942, 1779, 1729, 1373, 1225, 1157, 1032, 1010 cm-1
;
Con clu d in g Rem a r k s
MS m/z (%): 252 (M+, <1), 219 (<1), 209 (1) 192 (1), 139 (6),
96 (100), 79 (63), 69 (30). Anal. Calcd: C, 47.62; H 4.39.
Found: C, 47.52; H, 4.32.
In the above study we have described a new method
for preparation of some unsymmetrically substituted
cycloalkenes. These products can be further functional-
ized selectively by for example Pd(0)-catalyzed allylic
substitutions.23 A mechanism for the alkoxy- and ac-
etoxy-trifluoroacetoxylations has been suggested, which
is supported by theoretical calculations performed on the
proposed allylpalladium intermediates.
Com p u ta tion a l Deta ils. The geometries were opti-
mized employing Density Functional Theory using a
Becke24 type three-parameter model B3PW9125-27 in
connection with the LANL2DZ basis set28 (denoted as
B3PW91/LANL2DZ). For single-point energy calcula-
tions of the protonated species the LANL2DZ basis set
was augmented with one set of d polarization functions
cis-1-Acet oxy-4-(t r iflu or oa cet oxy)-2-cycloh exen e (3).
Pd(OAc)2 (16.8 mg, 0.075 mmol), CF3COOLi (900 mg, 7.5
mmol), CF3COOH (230 µL, 3 mmol), MnO2 (157 mg, 1.65
mmol), p-benzoquinone (35 mg, 0.33 mmol), (CF3CO)2O (420
µL, 3 mmol), and acetonitrile (160 µL, 3 mmol) were dissolved
in 5 mL of acetone/acetic acid (1:1). To this stirred solution
was added 1,3-cyclohexadiene (147 µL, 1.5 mmol) via a syringe
pump during 10 h. The reaction mixture was stirred for
additional 12 h at room temperature, and then it was diluted
with 50 mL of ether/pentane (50:50). The resulting mixture
was worked up the same way as in the case of compound 2,
giving 0.148 g (40%) of colorless oil 2 (83% cis). 1H NMR: δ
6.03 (dm, 1H, J ) 10.1 Hz), 5.93 (dm, 1H, J ) 10.1 Hz), 5.47-
5.37 (m, 1H), 5.29-5.23 (m, 1H), 2.08 (s, 3H), 2.05-1.84 (m,
2
4H). 13C NMR: δ 170.5, 157.1 (q J C-F ) 42.7 Hz), 133.0,
1
127.1, 114.5 (q J C-F ) 285.8 Hz), 71.7, 67.0, 24.5, 24.3, 21.1;
(20) The relationship between the geometrical parameters and the
intensity of the â-substituent effects is discussed in ref 12.
(21) Even if the solvation effects raise an activation barrier to the
C4-O bond cleavage, the intrinsic stabilization by the 4-substituent
effect will lower most effectively the activation energy in case of the
trifluoracetoxy substituted complex 12b.
IR (in CDCl3 solution): 2962, 1780, 1727, 1374, 126, 1161, 1036
cm-1; MS m/z (%): 192 (M+ - 60, 1), 139 (12), 96 (100), 79
(56), 69 (34).
(29) (a) Huzinaga, S.; Andzelm, J .; Klobukowski, M.; Radzio-
Andzelm, E.; Sakai, Y.; Tatewaki, H. Gaussian Basis Sets for Molecular
Calculations; Elsevier: Amsterdam, 1984. (b) Exponents for the d
functions: C, 0.630; O, 1.154; F, 1.496; Pd (diffuse d function), 0.0628.
(30) Gaussian 94, Revision B.3; Frisch, M. J .; Trucks, G. W.;
Schlegel, H. B.; Gill, P. M. W.; J ohnson, B. G.; Robb, M. A.; Cheeseman,
J . R.; Keith, T.; Petersson, G. A.; Montgomery, J . A.; Raghavachari,
K.; Al-Laham, M. A.; Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.;
Peng, C. Y.; Ayala, P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.;
Replogle, E. S.; Gomperts, R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.;
Defrees, D. J .; Baker, J .; Stewart, J . P.; Head-Gordon, M.; Gonzalez,
C.; Pople, J . A.; Gaussian, Inc., Pittsburgh, PA, 1995.
(22) In the sense of the cleavage reaction.
(23) The allylic trifluoroacetate is a highly reactive group in Pd(0)-
catalyzed allylic substitutions: (a) Tsuji, Y.; Funato, M.; Ozawa, M.;
Ogiyama, H.; Kajita, S.; Kawamura, T. J . Org. Chem. 1996, 61, 5779.
Rajanbabu, T. V. J . Org. Chem. 1985, 50, 3642. (c) Ba¨ckvall, J . E.;
Granberg, K. L.; Heumann, A. Israel. J . Chem. 1991, 31, 17.
(24) Becke, A. D. J . Chem. Phys. 1993, 98, 5648.
(25) Kohn, W.; Sham, L. J . Phys. Rev. 1965, 140, 1133.
(26) Becke, A. D. Phys. Rev. A 1988, 38, 3098.
(27) Perdew, J . P.; Wang, Y. Phys. Rev. B 1992, 45, 13244.
(28) (a) Dunning, T. H.; Hay, P. J . Modern Theoretical Chemistry;
Plenum: New York, 1977. (b) Hay, P. J .; Wadt, W. R. J . Chem. Phys.
1985, 82, 270. (c) Hay, P. J .; Wadt, W. R. Ibid. 1985, 82, 299.
(31) Rio-Portilla, F. D.; Blechta, V.; Freeman, R. J . Magn. Reson.
1994, 111, 132.

Palladium-Catalyzed 1,4-Acetoxy-Trifluoroacetoxylation
J . Org. Chem., Vol. 63, No. 8, 1998 2529
cis-1-Acetoxy-4-(tr iflu or oa cetoxy)-2-cycloh ep ten e (4).
Pd(OAc)2 (16.8 mg, 0.075 mmol), CF3COOLi (720 mg, 6 mmol),
CF3COOH (580 µL, 7.5 mmol), p-benzoquinone (162 mg, 1.5
mmol), and MnO2 (130 mg 1.5 mmol) were dissolved in 5 mL
of acetic acid. To this stirred solution was added 1,3-cyclo-
heptadiene (163 µL, 1.5 mmol) via a syringe pump over 6-8
h. The reaction mixture was stirred for further 16 h at room
temperature, and then it was diluted with ether/pentane (50:
50). The resulting mixture was worked up as in the case of
compound 2, resulting in 0.215 g of 4 as a colorless oil (96%
cis).
Cor r ection of th e P r eviou sly P u blish ed P r oced u r e11
for P r ep a r a tion of Com p ou n d 2. To a stirred solution of
Pd(OAc)2 (700 mg, 3.12 mmol), CF3COOH (9.5 mL, 125 mmol),
LiOOCCF3 (3.48 g, 32 mmol), MnO2 (6.5 g, 75 mmol), (CF3-
CO)2O (17.3 mL, 123 mmol), and p-benzoquinone (1.35 g, 12.5
mmol) in acetic acid (200 mL) at room temperature was added
1,3-cyclohexadiene (4.9 g, 61.3 mmol) over a period of 4 h. The
reaction mixture was stirred for another 6 h and thereafter
was poured into pentane/ether (9:1; 1500 mL). The resulting
solution was washed with brine (150 mL), water (2 × 200 mL),
sat. Na2CO3 (2 × 100 mL), 2 M NaOH (100 mL), water (100
mL), and brine (150 mL). The organic phase was dried and
concentrated to give 11.3 g of crude product. Fractional bulb-
to-bulb distillation afforded 10.3 g (67%) of compound 2 (92%
trans) as a colorless oil, which contained traces of the bis-
trifluoroacetate side product.
tr a n s-1-Meth oxy-4-(tr iflu or oacetoxy)-2-cycloh exen e (6).
Pd(OAc)2 (16.8 mg, 0.075 mmol), CF3COOLi (180 mg, 1.5
mmol), CF3COOH (430 µL, 6 mmol), p-benzoquinone (243 mg,
2.25 mmol), and methanol (0.5 mL 12.3 mmol) were dissolved
in 6 mL of CH2Cl2. To this stirred solution was added 1,3-
cyclohexadiene (147 µL, 1.5 mmol) via a syringe pump during
6-8 h. The reaction mixture was stirred for additional 16 h
at room temperature. Then 50 mL of 50:50 mixture of ether
and pentane was added, and the resulting mixture was
extracted with water, brine, 2 M NaOH (2×) and brine. The
organic phase was dried (MgSO4) and then concentrated to
give the crude product. Rapid flash chromatography with
pentane/ether (90:10) as an eluent was used to separate the
excess of the alcohol, and partially the quinone. The fractions
containing the product were combined and concentrated, and
the resulting mixture was subjected to a second flash chro-
matography using pentane/ether ) 97:3 as eluent, which gave
0.230 g (61%) of 4 as a colorless oil (92% trans). The spectral
data of this compound were identical with those previously
reported.32 This procedure is representative for the prepara-
tion of all the other trans-1-alkoxy-4-(trifluoroacetoxy)-2-
cyclohexenes, using 8.2 equiv of the corresponding alcohols.
Ackn owledgm en t. Financial support from the Swed-
ish Natural Science Research Council and the Swedish
Research Council for Engineering Sciences is gratefully
acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Experimental and
characterization data for compounds 4, 7-10. Copies of 1H and
13C NMR spectra for compound 8 (4 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
J O971738A
(32) . Ba¨ckvall, J . E.; Nordberg, R. E.; Wilhelm, D. J . Am. Chem.
Soc. 1985, 107, 6892.