Intramolecular palladium(II)-catalyzed 1,2-addition to allenes

Article abstract of DOI:10.1021/ja001748k

Palladium(II)-catalyzed intramolecular 1,2-additions to allenes substituted with an internal nucleophile have been developed. Carboxylic acids, alcohols, N-substituted amides, and carbamates were used as internal nucleophiles in the palladium-catalyzed re

Full text of DOI:10.1021/ja001748k

9600
J. Am. Chem. Soc. 2000, 122, 9600-9609
Intramolecular Palladium(II)-Catalyzed 1,2-Addition to Allenes
Catrin Jonasson, Attila Horva´th, and Jan-E. Ba1ckvall*
Contribution from the Department of Organic Chemistry, Arrhenius Laboratory, Stockholm UniVersity,
SE-106 91 Stockholm, Sweden
ReceiVed May 19, 2000
Abstract: Palladium(II)-catalyzed intramolecular 1,2-additions to allenes substituted with an internal nucleophile
have been developed. Carboxylic acids, alcohols, N-substituted amides, and carbamates were used as internal
nucleophiles in the palladium-catalyzed reaction, which afforded lactones, tetrahydropyrans, tetrahydrofurans,
pyrrolidines, and oxazolidinones in good isolated yields. The reactions were performed in the presence of
LiBr with Pd(OAc)2 as the catalyst. Two different reoxidants, p-benzoquinone or Cu(OAc)2, were used, the
choice of oxidant being dependent on the substrate. The reaction proceeds through an external nucleophilic
attack (Br-) on a (π-allene)palladium complex to produce a (π-allyl)palladium intermediate. Subsequent
intramolecular attack by the second internal nucleophile gives the product. The intermediate (π-allyl)palladium
complexes were isolated and characterized. The scope and limitation of the reaction were studied together
with its mechanism and selectivity, under different reaction conditions.
Introduction
years we have developed several different palladium(II)-
catalyzed 1,4-oxidations of conjugated dienes.,12,13,14 In contrast
to 1,3-dienes, the corresponding 1,2-dienes (allenes) have found
Nucleophilic additions to unsaturated hydrocarbons coordi-
nated to transition metals are important in organic synthesis.1
In particular, palladium-catalyzed reactions involving nucleo-
philic attack on (π-olefin)- and (π-allyl)palladium complexes
have been extensively studied, since they are often associated
with high stereo- and regioselectivity.2 Palladium-catalyzed
processes employing allenes as substrates have been somewhat
neglected compared with alkenes, alkynes, and 1,3-dienes. In
recent years, however, palladium-catalyzed reactions of allenes
have attracted considerable interest, and today many examples
of palladium(0)-catalyzed carbopalladations,3,4 hydropallada-
tions,5 and carbonylations6 of allenes exist together with a variety
of palladium(0)-catalyzed intramolecular variants.7,8,9,10,11
Our research group has been particularly engaged in the
investigation of palladium-catalyzed oxidations, and in recent
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Z.; Yu, Z. J. Org. Chem. 1998, 63, 6387.
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10.1021/ja001748k CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/22/2000

Intramolecular Pd(II)-Catalyzed 1,2-Addition to Allenes
J. Am. Chem. Soc., Vol. 122, No. 40, 2000 9601
Scheme 1
Scheme 2a
limited use in palladium(II)-catalyzed oxidations.15-18 Prior to
our work,17,18 palladium(II)-catalyzed 1,2-functionalization of
allenes had been reported only for carbonylation reactions.16
We recently reported on a mild palladium-catalyzed 1,2-
oxidation of allenes in which two nucleophiles are added
across the double bond.17 These 1,2-additions were recently
extended to intramolecular lactonization and amidation reactions
(Scheme 1).18
We now give a full account of these palladium-catalyzed
intramolecular 1,2-oxidations, report new results on the use of
additional oxygen and nitrogen nucleophiles, and discuss the
reaction mechanism and the scope and limitation of the reaction.
This new methodology provides access to heterocyclic com-
pounds that are useful synthetic intermediates.
a Reagents and conditions: (a) (EtO)3CCH3, EtCOOH (cat.), 78-
79%; (b) LiAlH4, Et2O, 87-95%; (c) TsCl, pyridine, 78-89%; (d)
NaCN, DMSO, 95%; (e) NaOH, EtOH/H2O, 81-95%.
Scheme 3
Results and Discussion
A. Preparation of Starting Materials. A number of methods
are reported for the preparation of allenes,19 and all of the
starting allenes were prepared through the application of known
or slightly modified procedures. The synthesis of the γ-allenic
acids 6a and 6b and γ-allenic alcohol 7 are outlined in Scheme
2.20 The synthesis starts with an ortho-Claisen rearrangement,
which was carried out by heating the propargylic alcohols 1a
and 1b with excess triethyl orthoacetate in the presence of a
small amount of propionic acid. The resulting â-allenic esters
(12) (a) Ba¨ckvall, J.-E.; Bystro¨m,S. E.; Nordberg, R. E. J. Org. Chem.
1984, 49, 4619. (b) Ba¨ckvall, J.-E.; Nystro¨m, J. E.; Nordberg, R. E. J. Am.
Chem. Soc. 1985, 107, 3676. (c) Ba¨ckvall J.-E.; Vågberg, J. O. J. Org.
Chem. 1988, 53, 5695. (d) Ba¨ckvall, J.-E. Pure Appl. Chem. 1992, 64, 42.
(13) (a) Ba¨ckvall, J.-E. Pure Appl. Chem. 1996, 68, 535. (b) Ba¨ckvall,
J.-E.; Andersson, P. G. J. Am. Chem. Soc. 1990, 112, 3683. (c) Ba¨ckvall,
J.-E.; Andersson, P. G. J. Am. Chem. Soc. 1992, 114, 6374. (d) Ba¨ckvall,
J.-E.; Granberg, K. L.; Andersson, P. G.; Gatti, R.; Gogoll, A. J. Org. Chem.
1993, 58, 5445. (e) Andersson, P. G.; Ba¨ckvall, J.-E. Synthesis of
Heterocyclic Natural Products via Regio- and Stereocontrolled Palladium-
Catalyzed Reactions. Review in AdVances in Natural Product Synthesis;
Pearson, W., Ed.; JAI Press: Greenwich, CT, 1996; pp 179-215.
(14) (a) Castan˜o A. M.; Persson, B. A.; Ba¨ckvall, J.-E. Chem. Eur. J.
1997, 3, 481. (b) Itami, K.; Palmgren, A.; Thorarensen, A.; Ba¨ckvall, J.-E.
J. Org. Chem. 1998, 63, 6466. (c) Andersson, P. G.; Nilsson Y. I. M.;
Ba¨ckvall, J.-E. Tetrahedron 1994, 50, 559. (d) Aranyos, A.; Szabo´, K. J.;
Ba¨ckvall, J.-E. J. Org. Chem. 1998, 63, 2529.
2a and 2b were then reduced with LiAlH4,20b tosylated, and
reacted with NaCN in DMSO to form the allenic nitriles 5a
and 5b. Subsequent alkaline hydrolysis with NaOH in EtOH/
H2O afforded the allenic acids 6a and 6b. The allenic alcohol
7 was in turn obtained after reduction with LiAlH4.
The monosubstituted allenic acids were prepared via a
copper(I)-mediated SN2′ displacement of the propargylic tosy-
lates 11a-d21 (Scheme 3). Treatment of the appropriate iodide
8a-d22 with activated zinc (1,2-dibromoethane and TMSCl) in
(15) (a) Hegedus, L. S.; Kambe, N.; Ishii, Y.; Mori, A. J. Org. Chem.
1985, 50, 2240. (b) Ogawa, A.; Kawakami, J.; Sonosa, N.; Hirao, T. J.
Org. Chem. 1996, 6, 4161.
(16) (a) Alper. H.; Hartstock, F. W.; Despeyroux, B. J. Chem. Soc., Chem
Commun. 1984, 905. (b) Lathbury, D.; Vernon, P.; Gallagher, T. Tetrahe-
dron Lett. 1986, 27, 6009. (c) Gallagher, T.; Davies, I. W.; Jones, S. W.;
Lathbury, D.; Mahon, M. F.; Molloy, K. C.; Shaw, R. W.; Vernon, P. J.
Chem. Soc., Perkin Trans. 1 1992, 433. (d) Fox, D. N. A.; Gallagher, T.
Tetrahedron 1990, 46, 4697. (e) Walkup, R. G.; Park, G. Tetrahedron Lett.
1987, 28, 1023. (f) Walkup, R. D.; Mosher, M. Tetrahedron 1993, 49, 9285.
(g) Kimura, M.; Saeki, N.; Uchida, S.; Harayama, H.; Tanaka, S.; Fugami,
K.; Tamaru, Y. Tetrahedron Lett. 1993, 34, 7611.
(17) (a) Ba¨ckvall, J.-E.; Jonasson, C. Tetrahedron Lett. 1997, 38, 291.
(18) (a) Jonasson, C.; Ba¨ckvall, J.-E. Tetrahedron Lett. 1998, 39, 3601.
(b) Jonasson, C.; Karstens, W. F. J.; Hiemstra, H.; Ba¨ckvall, J.-E.
Tetrahedron Lett. 2000, 41, 1619.
(20) (a) Mori, K.; Nukada, T.; Ebata, T. Tetrahedron 1981, 37, 1343.
(b) Gallagher, T.; Jones, S. W.; Mahon, M. F.; Molloy, K. C. J. Chem.
Soc., Perkin Trans 1 1991, 2193.
(21) (a) Gooding, O. W.; Beard, C. C.; Jackson, D. Y.; Wren, D. L.;
Cooper, G. F. J. Org. Chem. 1991, 56, 1083. (b) Dunn, M. J.; Jackson R.
F. W.; Pietruszka, J.; Turner, D. J. Org. Chem. 1995, 60, 2210.
(22) 8a-d were prepared from the corresponding bromide (Aldrich,
Lancaster) by treatment with sodium iodide in refluxing acetone. Finkelstein,
H. Chem. Ber. 1910, 43, 1528.
(19) (a) Landor, S. The chemistry of the allenes; Academic Press:
London, 1982. (b) Schuster, H. F.; Coppola, G. M. Allenes in organic
synthesis; John Wiley & Sons: New York, 1984.

9602 J. Am. Chem. Soc., Vol. 122, No. 40, 2000
Jonasson et al.
Scheme 4
Scheme 6
Scheme 5a
ether,34a and the allenic carbamate 47 was obtained from 33
after treatment with benzyl chloroformate in THF.26 N-Benzy-
lamine 48 was prepared by treatment of 33 with benzaldehyde
in ethanol followed by reduction of the resulting imine with
NaBH4.16c
The carbamates 51 and 52 and its one-carbon-higher homo-
logue 53 were prepared from the R-allenic alcohols 49 and 50
and â-allenic alcohol 3a, respectively, by treatment with a small
excess of TsNCO27 (Scheme 6). The R-allenic alcohols 49 and
50 were obtained according to known literature procedures.28
B. Palladium(II)-Catalyzed Intramolecular Bromolacton-
ization. Reaction of γ-allenic acid 22 in the presence of 5 mol
% of Pd(OAc)2, 5 equiv of LiBr, 2.5 equiv of p-benzoquinone
(BQ), and 2.5 equiv of LiOAc in acetic acid at 40 °C afforded
the γ-lactone product 54 in 84% yield, of mainly (Z)-configu-
ration (Z/E ) 92/8) (Table 1). The substrate had to be added
slowly (16-18 h) with a syringe pump in order to prevent side
reactions. The LiOAc was added in an attempt to speed up the
reaction, which proved successful, and the reaction times could
be reduced to 24 h in most cases. The stereochemical assignment
was made by means of NOE measurements. For example,
irradiation of the olefinic proton in 54 resulted in NOE to the
allylic CH-O proton in the (Z)-isomer. The corresponding
irradiation for the (E)-isomer of 54 gave no detectable NOE to
the allylic CH-O protons. A few other γ-allenic acids 23, 24,
6a, and 6b were also shown to undergo the palladium-catalyzed
bromolactonization reaction (Table 1). The size of the allenic
substituent seems to have an effect on the stereochemical
outcome. Thus, increasing the size of the allenic substituent from
a pentyl group (Table 1, entry 1) to an isopropyl group (Table
1, entry 4) reduced the selectivity from Z/E ) 92:8 to Z/E )
76:24.
a Reagents and conditions: (a) LiAlH4, ether, -20 °C, 78-92%;
(b) TsCl, pyridine, 0 °C 55-88%; (c) BnNCO, ether, 63-75%; (d)
BnOCOCl, THF, 64%; (e) (i) benzaldehyde, ethanol; (ii) NaBH4, 59%.
THF at 35 °C followed by transmetalation with CuCN‚2LiCl
generated the organocopper species 10a-d,23 which in turn were
reacted with the propargylic tosylates 11a-d24 to afford the
γ-allenic esters 12-14, δ-allenic esters 15 and 16, ꢀ-allenic ester
17, and γ-allenic nitriles 18-21 in good isolated yields.
The resulting allenic esters 12-17 were either hydrolyzed
by NaOH in EtOH/H2O to allenic acids 22-27 or reduced with
LiAlH4 in diethyl ether to allenic alcohols 28-32 (Scheme 4).
These compounds constitute starting materials for intramolecular
palladium-catalyzed 1,2-oxidation reactions.
The starting materials for the intramolecular amidation
reaction were prepared by first converting the allenic nitriles
5a,b and 18-21 to the corresponding primary amines 33-38
(Scheme 5). The required N-tosyl amides 39-44 were then
obtained by reaction with tosyl chloride in pyridine.25 The allenic
ureas 45 and 46 were synthesized from the primary amines 33
and 34, respectively, via addition of benzyl isocyanate in
(26) Amman, H.; Dupuis, G. Can. J. Chem. 1988, 66, 1651.
(27) Friesen, R. W.; Kolaczewska, A. E. J. Org. Chem. 1991, 56, 4888.
(28) (a) Cowie, J. S.; Landor, P. D.; Landor, S. R. J. Chem. Soc., Perkin
Trans. 1 1973, 720. (b) Duke, R. D.; Rickards, R. J. Org. Chem. 1984, 49,
1898.
(29) Walkup, R. D.; Guan, L.; Kim, S. W.; Kim, Y. S. Tetrahedron Lett.
1992, 33, 3969.
(30) (a) Davies, I. W.; Shaw, R. W.; Wisedale, R.; Gallagher, T. J. Chem.
Soc., Perkin Trans. 1 1994, 3557. (b) Shaw, R. W.; Gallagher, T. J. Chem.
Soc., Perkin Trans. 1 1994, 3549.
(31) (a) Friesen, R. W. Tetrahedron Lett. 1990, 31, 4249. (b) Friesen,
R. W.; Giroux, A.; Cook, K. L. Tetrahedron Lett. 1993, 34, 5983.
(32) Kind gift from Prof. Norbert Krause, University of Bonn, Germany.
(33) Reversible ring-opening of the strained vinylic oxetane, once formed,
by palladium may be another, however, less likely explanation: Larock,
R. C.; Stolz-Dunn, S. K. Tetrahedron Lett. 1989, 30, 3487.
(34) For studies on palladium(II)-catalyzed nucleophilic attack by amides
and carbamates on alkenes and dienes, see (a) Tamaru, Y.; Hojo, M.;
Higashimura, H.; Yoshida, Z.-I. J. Am. Chem. Soc. 1988, 110, 3994. (b)
Tamaru, Y.; Hojo, M.; Yoshida, Z.-I. J. Org. Chem. 1988, 53, 5731. (c)
Ba¨ckvall, J.-E.; Andersson, P. G. J. Am. Chem. Soc. 1990, 112, 3683. (d)
Harayama, H.; Abe, A.; Sakado, T.; Kimura, M.; Fugami, K.; Tanaka, S.;
Tamaru, Y. J. Org. Chem. 1997, 62, 2113. (d) Kimura, M.; Saeki, N.;
Uchida, S.; Harayama, H.; Tanaka, S.; Fugami, K.; Tamaru, Y. Tetrahedron
Lett. 1993, 34, 7611.
(23) (a) Yeh, M. C. P.; Knochel, P. Tetrahedron Lett. 1988, 29, 2395.
(b) Yeh, M.-C. P.; Sheu, B.-A.; Fu, H.-W.; Tau, S.-I.; Chuang, L.-W. J.
Am. Chem. Soc. 1993, 115, 5941. (c) Knochel, P.; Yeh, M. C. P.; Berk, S.
C.; Talbert, J. J. Org. Chem. 1988, 53, 2392.
(24) 11a-d were prepared from the corresponding alcohol by treatment
with tosyl chloride and powdered KOH in ether at -50 °C. Westmuze, H.;
Vermeer, P. Synthesis 1979, 390.
(25) Shaw, R. W.; Gallagher, T. J. Chem. Soc., Perkin Trans. 1 1994,
3549.

Intramolecular Pd(II)-Catalyzed 1,2-Addition to Allenes
J. Am. Chem. Soc., Vol. 122, No. 40, 2000 9603
Table 1. Palladium-Catalyzed Intramolecular Bromolactonization
of Allenic Acids
Scheme 7
slow to be synthetically useful. On the other hand with
palladium-catalysis conditions, utilizing Cu(II) as the reoxidant,
allenic acid 25 was smoothly converted to the six-membered
lactone 59 in 83% yield (Z/E ) 90:10) after 1 h. Similarly,
subjecting δ-allenic acid 26 to the latter reaction conditions
afforded lactone 60 in good yield (82%) with a Z/E ratio of
88:12.
Walkup et al.29 developed, a few years ago, cyclizations of
γ-silyloxy allenes to form (iodovinyl)tetrahydrofurans in the
presence of N-iodosuccinimide and Gallagher et al.30 and Friesen
et al.31 have developed I2-mediated cyclization of N-substituted
allenic amines and carbamates, respectively, to form medium
ring nitrogen heterocycles. Inspired by these reports, we decided
to study the equivalent cyclization of allenic acids 22, 23, and
25, in the presence of N-bromosuccinimide and compare the
results to our newly developed palladium-catalyzed reaction.
Treatment of γ-allenic acids 22 and 23 with 1.2 equiv of NBS
in THF/CH2Cl2 (1:4) furnished the bromolactones 54 and 55
after 2 h (Table 1, entries 3 and 6). Yields and selectivity were
in the same range as for the palladium-catalyzed reaction, which
utilizes BQ as the reoxidant. The reaction of the δ-allenic acid
25 was, on the contrary, very slow with NBS and after reaction
for 24 h lactone 59 was isolated in only 35% yield together
with unreacted starting material and a mixture of side products
(Table 1, entry 12). This should be compared with the
palladium-catalyzed reaction (entry 11), which afforded 59 in
83% yield after 1 h.
a Method A: In a typical procedure the substrate was added slowly
over 16-18 h to a solution of 5 mol % of Pd(OAc)2, 5 equiv of LiBr,
2.5 equiv of LiOAc, and 2.5 equiv of BQ in acetic acid (0.27 M) at 40
°C. The reaction times varied from 24 to 48 h. Method B: The reactions
were carried out at room temperature in acetonitrile (0.15 M) employing
10 mol % of Pd(OAc)2, 5 equiv of LiBr, 2.1 equiv of Cu(OAc)2‚H2O,
and 1.2 equiv of K2CO3 under an atmospheric pressure of O2. The
reaction times varied from 0.5 to 1 h. Method C: The reactions were
carried out in CH2Cl2/THF 4:1 in the presence of 1.2 equiv of NBS.
The reaction times varied from 2 to 24 h. b Isolated yield after flash
chromatography. c Determined by means of NOE measurements and
Thus, the palladium-catalyzed intramolecular reactions with
carboxylic acids as the internal nucleophile work well to give
five- and six-membered lactones.
Attempts to prepare four- or seven-membered rings containing
oxygen proved difficult. â-Alcohol 6732 has previously been
subjected to the palladium-catalyzed conditions employing
p-benzoquinone as the oxidant which resulted in no 1,2-
oxidation products (Scheme 7).18a Subjecting ꢀ-allenic acid 27
to either the Pd-BQ or the Pd-Cu(II) conditions gave only
recovered starting material together with a complex mixture of
byproducts. Apparently, the rate of cyclization to give four- and
seven-membered rings was not high enough to promote the
reaction.33
C. Palladium-Catalyzed Intramolecular Oxybromination
of Allenic Alcohols. During the course of this study, we
considered the possibility of extending the intramolecular
reactions to include alcohols as internal nucleophiles. Thus the
γ-allenic alcohol 28 was slowly added (14 h) to a solution of 5
mol % Pd(OAc)2, 5 equiv of LiBr, and 2.5 equiv of BQ in acetic
acid at 40 °C. After 8 h tetrahydrofuran 61 was isolated in 75%
yield with mainly (Z)-stereochemistry (Z/E ) 94:6) (Table 2).
The cyclization of the alcohols was found to proceed faster than
that of the corresponding acid derivatives, and no addition of
LiOAc was necessary. For example, the reaction of γ-allenic
alcohol 28 was complete after 8 h, whereas the cyclization of
the corresponding γ-allenic acid 22, to form lactone 54, took
24 h. (Table 1, entry 1). To demonstrate the generality of the
1
the Z/E ratio was determined by H NMR.
The reaction was also carried out under the conditions
(method B) developed for the intramolecular amidation reaction.18b
Treatment of γ-allenic acid 22 and 23 with 10 mol % of
Pd(OAc)2, 5 equiv of LiBr, 2.1 equiv of Cu(OAc)2‚H2O, and
1.1 equiv of K2CO3 in acetonitrile under an atmosphere of
oxygen afforded lactone 54 and 55 in high yield (90%) after
only 30 min. These variations of the reaction conditions had a
dramatic effect on the stereochemical outcome of the reaction,
and lactone 54 (Table 1, entry 2) was isolated as a nearly equal
mixture of (Z)- and (E)-isomers (54:46) whereas 55 had the
reversed stereochemistry (Z/E ) 37:63) compared to that
obtained with Pd/BQ.
To study if the bromolactonization reactions could be applied
to allenic acids having one more carbon in the tether between
the allene and the nucleophile, the one-carbon-higher homo-
logues 25 and 26 were prepared (Schemes 3 and 4). However,
subjecting δ-allenic acid 25 to the cyclization conditions, using
benzoquinone as the oxidant, resulted in only trace amounts of
the pyranone 59 after 48 h. The reaction was apparently too

9604 J. Am. Chem. Soc., Vol. 122, No. 40, 2000
Jonasson et al.
Table 2. Palladium-Catalyzed Intramolecular Oxybromination of
Allenic Alcohols
Table 3. Palladium-Catalyzed Intramolecular Bromoamidation of
N-Tosyl Allenic Amides
a Method B: Unless otherwise noted, the reactions were carried out
at room temperature in acetonitrile (0.15 M) employing 10 mol % of
Pd(OAc)2, 5 equiv of LiBr, 2.1 equiv of Cu(OAc)2‚H2O, and 1.2 equiv
of K2CO3 under an atmospheric pressure of O2. The reaction times
varied from 2 to 5 h. Method C: The reactions were carried out in
CH2Cl2/THF 4:1 in the presence of 1.2 equiv of NBS. The reaction
times varied from 2 to 12 h. b Isolated yield after flash chromatography.
c Determined by means of NOE measurements and the Z/E ratio was
determined by 1H NMR. d CuCl2 was used instead of Cu(OAc)2.
e Cu(OTf)2 was used instead of Cu(OAc)2 and no K2CO3 was added.
a Method A: In a typical procedure the substrate was added slowly
over 14 h to a solution of 5 mol % of Pd(OAc)2, 5 equiv of LiBr, and
2.5 equiv of BQ in acetic acid (0.27 M) at 40 °C. The reaction times
were 8 h. Method B: The reactions were carried out at room
temperature in acetonitrile (0.15 M) employing 10 mol % of Pd(OAc)2,
5 equiv of LiBr, 2.1 equiv of Cu(OAc)2‚H2O, and 1.2 equiv of K2CO3
under an atmospheric pressure of O2. The substrate was added over 2
h. Reaction times varied from 0.5 to 2 h. Method C: The reactions
were carried out in CH2Cl2/THF 4:1 in the presence of 1.2 equiv of
NBS. The reaction time was 2 h. b Isolated yield after flash chroma-
tography. c Determined by means of NOE measurements and the Z/E
result was obtained when δ-allenic alcohol 32 was subjected to
the Pd/Cu(II) conditions affording tetrahydropyran 66 in good
yield (70%) and high selectivity (Z/E ) 94:6). When NBS was
used as the electrophilic mediator in the cyclization of δ-allenic
alcohol 31, the reaction was finished after 2 h. The tetrahydro-
pyran 65 could, however, only be isolated in 31% yield together
with a complicated mixture of byproducts (Table 2, entry 9).
1
ratio was determined by H NMR.
overall process and to study the effect of the R substituent on
the stereoselectivity, the palladium-catalyzed reaction was also
applied to three other γ-allenic alcohols 29, 30, and 7 (Table
2). The stereoselectivity was in accordance with that of the
bromolactonization reaction, and a similar trend for decreased
stereoselectivity with higher steric hindrance on the allenic
substituent was observed.
Thus, the palladium-catalyzed intramolecular reactions with
alcohols as the internal nucleophile work well to give tetrahy-
drofurans and tetrahydropyrans in good isolated yields.
γ-Allenic alcohol 28 was also applied to the two other
cyclization conditions (Table 2, entries 2 and 3). Treatment of
28 with NBS in CH2Cl2/THF gave tetrahydrofuran 61 in 64%
yield, with a Z/E ratio of 94/6. The selectivity was in the same
range as for the Pd/BQ cyclization, but the yield was slightly
reduced. Cyclization of the γ-allenic alcohol 28 (Table 2, entry
2) under the Pd/Cu(II) conditions proved more difficult, giving
tetrahydrofuran 61 in only 46% yield, together with a compli-
cated mixture of side-products. The stereoselectivity was lower
(Z/E ) 84/16) than that of the corresponding Pd/BQ reaction
(Z/E ) 94/6) but much improved in comparison with the
selectivity of the corresponding lactonization reaction with
γ-allenic acid 22 (cf. Table 1, entry 2, Z/E ) 54/46).
The reaction for the one-carbon-higher homologue δ-allenic
alcohol 31 (Table 2, entry 8) worked best with the Pd/Cu(II)
system, in analogy with the δ-allenic acids 25 and 26, and the
corresponding tetrahydropyran 65 was isolated in 65% yield.
The yield was further improved by adding the substrate slowly
over a period of 2 h. The tetrahydrofuran 65 was then isolated
in 78% yield with good selectivity (Table 2, entry 8). A similar
D. Palladium-Catalyzed Oxidations Involving Nitrogen
Nucleophiles. N-tosylated γ-allenic amines 39-44 were smoothly
cyclized to pyrrolidines 68-73 in the presence of catalytic
amounts of Pd(OAc)2, LiBr (5 equiv), Cu(II) salt (2.1 equiv),
and K2CO3 (1.2 equiv) in acetonitrile under an atmosphere of
oxygen (Table 3).34 The reaction times for these cyclizations
were short (<2 h). Preliminary attempts to cyclize 39 with Pd-
(OAc)2 using p-benzoquinone as a reoxidant for palladium
failed. The amide nitrogen can apparently not act as a nucleo-
phile under the slightly acidic conditions employed here. This
contrast to previous results obtained and reported by our group,
where nitrogen nucleophiles were used in an intramolecular 1,4-
oxidation of 1,3-dienes.13c
During the optimization of the allenic oxidation reactions, it
was shown that CuCl2, which is the most common Cu(II)
oxidant for Pd(0),2a gave 4-5% of a byproduct, in which a
chloride from CuCl2 had attacked the middle allene carbon
instead of the bromide. To suppress this side reaction, other
Cu(II) salts were screened, of which Cu(OAc)2 turned out to

Intramolecular Pd(II)-Catalyzed 1,2-Addition to Allenes
J. Am. Chem. Soc., Vol. 122, No. 40, 2000 9605
Table 4. Palladium-Catalyzed Intramolecular Bromoamidation of
Various N-Substituted Allenic Amides Employing Cu(II)/O2 as an
Oxidanta
Table 5. Palladium-Catalyzed Intramolecular Cyclizations of
Carbamatesa
a Unless otherwise noted, the reactions were carried out at room
temperature in acetonitrile (0.15M) employing 10 mol % of Pd(OAc)2,
5 equiv of LiBr, 2.1 equiv of Cu(OAc)2‚H2O, and 1.2 equiv of K2CO3
under an atmospheric pressure of O2. Reaction times varied from 1 to
3 h. b Isolated yield after flash chromatography. c Determined by means
of NOE measurements and the Z/E ratio was determined by 1H NMR.
a Unless otherwise noted in the experimental part the reactions were
carried out at room temperature in acetonitrile (0.15 M) employing 10
mol % of Pd(OAc)2, 5 equiv of LiBr, 2.1 equiv of Cu(OAc)2‚H2O,
and 1.2 equiv of K2CO3 under an atmospheric pressure of O2. The
reaction times varied from 1 to 24 h. b Isolated yield after flash
chromatography. c Determined by means of NOE measurements and
1
the Z/E ratio was determined by H NMR.
Scheme 8
be best. For the 6,6-disubstituted allenes 42 and 43, CuCl2 gave
the most efficient reaction, and pyrrolidines 71 and 72 were
obtained in 68% and 71% yield, respectively. The terminally
unsubstituted allenic amide 44 worked better in the presence
of Cu(OTf)2 as an oxidant.
It was also of interest to compare these results with the NBS-
promoted cyclizations. Thus, reaction of 39, 40, and 43 in the
presence of NBS in CH2Cl2/THF afforded the corresponding
pyrrolidines 68, 69, and 72. The yields and selectivity of these
compounds were in the same range as for the products obtained
from the palladium-catalyzed version.
Figure 1.
The intramolecular amidation reaction also worked well with
benzyl ureas and carbamates (Table 4). The ureas 45 and 46
cyclized rapidly in 1 and 4 h, respectively, to give compounds
74 and 75 in 78% and 69% yield, respectively. Interestingly,
the stereoselectivity for the isopropyl-substituted pyrrolidine was
higher (Z/E ) 89:11) than that of the pentyl-substituted
pyrrolidine (Z/E ) 76:24). This is in contrast to all other reported
examples. The reaction of the carbamate 47 also performed well,
and the product 76 was isolated in 80% yield after 24 h. The
reaction of benzylamine 48 on the other hand was more sluggish,
and pyrrolidine 77 could only be isolated in 28% yield. This
observation can be rationalized by a strong coordination of the
amine to palladium retarding the cyclization.35
to extend this methodology to include N-tosyl allenic carbam-
ates. Thus carbamate 51 was prepared according to Scheme 6
and subjected to the Pd/Cu(II) conditions, which afforded
oxazolidinone 79 after 2 h in 68% yield (Table 5). Similarly,
treatment of carbamate 52 under the latter conditions afforded
80 in equally good yield (70%). Interestingly, the stereoselec-
tivity in these reactions was low, giving (E)- and (Z)-isomers
in nearly equal amounts, as was the case when γ-allenic acids
were treated under the Pd/Cu(II) conditions (Table 1, method
B). The one-carbon-higher homologue 53 was also cyclized to
give the six-membered oxazolidinone 81, albeit in low yield
(22%).
Dienic amides 78,36 with a carbonyl carbon located within
the tether, did not give the desired lactam product but produced
lactone 55, which was isolated in 70% yield (Scheme 8).
Apparently, the keto function in 78 acts as the nucleophile, and
the resulting iminoester is hydrolyzed under the reaction
conditions to afford the lactone 55 as the sole product.
Encouraged by the results obtained for the palladium-
catalyzed cyclizations of N-substituted allenic amides we tried
D. Mechanism. A likely mechanism for the palladium-
catalyzed 1,2-oxidation is given in Figure 1. This mechanism
is reminiscent of that of the corresponding 1,4-oxidation of
conjugated dienes12,13 and involves a (π-allyl)palladium inter-
mediate. Nucleophilic attack on the initially formed (allene)-
palladium complex produces a σ-allylpalladium intermediate,
which rapidly equilibrates to the corresponding (π-allyl)-
palladium intermediate. Attack by halides on allenes coordinated

9606 J. Am. Chem. Soc., Vol. 122, No. 40, 2000
Jonasson et al.
Scheme 9
Scheme 10
to palladium to give (π-allyl)palladium complexes is well
precedented in the literature.37 Coordination of p-benzoquinone
to palladium in this π-allyl complex induces an intramolecular
nucleophilic attack to give the tetrahydrofuran product.38 In this
process a Pd(0)-benzoquinone complex is formed,39 which
immediately undergoes an intramolecular redox reaction in the
presence of acid to give Pd(II) and hydroquinone.40
The mechanism for the intramolecular lactonization reaction
starting from allenic acids involves a similar catalytic cycle.
An intermediate (π-allyl)palladium complex for the lactonization
reaction has previously been isolated as a chloro dimer.18a The
γ-allenic acid 22 was then reacted with a stoichiometric amount
of Pd(PhCN)2Cl2 in benzene, which afforded (π-allyl)palladium
complex 82. Complex 82 was isolated and characterized and
The mechanism for the reaction with Cu(II) as the reoxidant
is probably similar to that shown for the catalytic cycle in Figure
1. The use of CuCl2/O2 as the oxidant has previously been used
in palladium-catalyzed intramolecular 1,4-oxidations of conju-
gated dienes, even though the reaction was less stereoselective
than the corresponding reaction with p-benzoquinone.12b,13c,14a,42
E. Stereoselectivity. The stereoselectivity of the reaction
seems to be related mainly to the relative abundance of the two
anti- and syn-intermediate (π-allyl)palladium complexes 85 and
86 (Scheme 10). The anti complex 85 is predicted to be the
kinetic intermediate, since the bromide will preferentially add
to the sterically less hindered face (anti to R) of the allenic
double bond closest to the tether. The anti complex 85 can then
isomerize to the corresponding syn-complex 86 via a η3-η1-η3-
rearrangement.43 The thermodynamic stability of a π-allyl
complex is partly dependent on the steric interaction between
the Pd atom and the substituent in the anti position, and 1,3-
disubstituted (π-allyl)palladium complexes are known to be
more stable in a syn,syn configuration.43b,44 However, when the
central position of the π-allyl is substituted, substantial amounts
of the anti conformer have been observed.45,3a,b,e,10c,e It is the
relative stability of these two complexes, the syn and the anti,
as well as their reactivity and rate of isomerization that will
determine the stereochemistry of the resulting products. Several
factors, such as steric effects in the (π-allyl)palladium inter-
mediates exerted by substituents at the allene group, the number
of atoms located between the internal nucleophile and the π-allyl
moiety, the nature of the nucleophile, and the choice of reoxidant
(BQ or Cu(II)) will influence the ratio of the syn and anti
complexes in the catalytic reaction.
subsequently treated with p-benzoquinone, LiBr, and LiOAc
in acetic acid, which resulted in a fast intramolecular cyclization
to give the chloro-analogue of lactone 54 (Table 1).
The π-allyl intermediates from the oxybromination reaction
and the intramolecular amidation reaction have now also been
isolated as the more relevant intermediates. Thus, complexes
83 and 84 were obtained as yellow crystalline compounds from
the reaction of allenes 7 and 42, with PdBr2(PhCN)237(Scheme
9). They were fully characterized by spectroscopic methods.
When complex 83 was subjected to the conditions of the
catalytic reaction employing benzoquinone as the oxidant,
tetrahydrofuran 64 was obtained in 72% yield after 12 h.41
Similarly, when compound 84 was allowed to react under the
catalytic conditions, but with CuCl2 as the oxidant, pyrrolidine
71 was produced in 88% yield after 1 h.
When R is a medium-sized group, e.g., a primary alkyl, the
(Z)-isomer is the predominantly formed isomer, via the syn-
intermediate 86. On the other hand if R is a larger group, the
E/Z ratio increases, which indicates a slightly higher amount
of the anti-intermediate 85 in the catalytic reaction. An
explanation for these observations is that the rate of isomer-
ization of the kinetically favored anti complex 85 to the syn
(35) (a) Tamaru, Y.; Hojo, M.; Higashimura, H.; Yoshida, Z.-I. J. Am.
Chem. Soc. 1988, 110, 3994 (b) Hegedus, L. S.; McKearin, J. M. J. Am.
Chem. Soc. 1982, 104, 2444.
(36) The allenic amide 78 was prepared from the corresponding allenic
ester 13 by a cyanide-catalyzed aminolysis. Ho¨gberg, T.; Stro¨m, P.; Ebner,
M.; Ra¨msby, S. J. Org. Chem. 1987, 52, 5020.
(37) (a) Schultz, R. G. Tetrahedron 1964, 20, 2809. (b) Lupin, M. S.;
Shaw, B. L. Tetrahedron Lett. 1964, 883. (c) Lupin, M. S.; Powell, J.; Shaw,
B. L. J. Chem. Soc. 1966, 1687.
(38) Ba¨ckvall, J.-E.; Gogoll, A. Tetrahedron Lett. 1988, 29, 2243.
(39) Minematsu, H.; Takahashi, S.; Hagihara, N. J. Chem. Soc., Chem.
Commun. 1975, 466.
(40) Grennberg, H.; Gogoll, A.; Ba¨ckvall, J.-E. Organometallics 1993,
12, 1790.
(41) This makes the alternative mechanism of the 1,2-oxidation via
oxypalladation or aminopalladationsto give a vinylpalladium speciess
followed by reductive elimination to form the vinyl bromide bond, less
likely.
(42) 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.
(d) Andersson, P. G.; Ba¨ckvall, J.-E. J. Am. Chem. Soc. 1992, 114, 8696.
(43) Corradini, P.; Maglio, A.; Musco, A.; Paiaro, G. J. Chem. Soc.,
Chem. Commun. 1966, 618. (b) Faller, J. W.; Thomsen, M. E.; Mattina,
M. J. J. Am. Soc. Chem. 1971, 93, 2642. (c) Faller, J. W.; Tully, M. T. J.
Am. Soc. Chem. 1972, 94, 2676.
(44) (a) Trost, B.; Strege, P. E.; Weber, L.; Fullerton, T.; Dietsche, T. J,
J. Am. Chem. Soc. 1978, 100, 3407. (b) Mackenzie, P. B.; Whelan, J.;
Bosnich, B. J. Am. Chem. Soc. 1985, 107, 2046.
(45) Lukas, J.; Ramakers-Blom, J. E.; Hewitt, T. G.; De Boer, J. J. J.
Organomet. Chem. 1972, 46, 167.

Intramolecular Pd(II)-Catalyzed 1,2-Addition to Allenes
J. Am. Chem. Soc., Vol. 122, No. 40, 2000 9607
complex 86 decreases with the size of the R group.45 This
explains the observed results in the lactonization and oxybro-
mination reaction when BQ was used as the oxidant. When R
is a pentyl group, (22 (Table 1, entry 1) and 28 (Table 2, entry
1)), the stereoselectivity is high (Z/E ) 92:8 and 94:6) due to
an almost total isomerization to the syn-complex 86, which
produces the (Z)-isomer. However, when R is an isopropyl group
(23 (Table 1, entry 4) and 29 (Table 2, entry 4)), the syn-anti
isomerization is slower, which results in decreased selectivity
(Z/E ) 76:24 and 88:12).
Figure 2.
Scheme 11
Interestingly, the choice of reaction conditions had a dramatic
effect on the stereoselectivity in the lactonization reaction. A
change of reoxidant from BQ to Cu(OAc)2 in the cyclization
of γ-allenic acid 22 (Table 1, entry 2) resulted in total loss of
alkene stereochemistry, and an almost equal mixture of (E)-
and (Z)-isomers (Z/E ) 54:46) was observed. The same effect
on the Z/E ratio, by the change of oxidant, was observed also
for the γ-allenic acid 23 (Table 1, entry 5), and here even a
reversed selectivity (Z/E ) 37:63) was observed with Cu(II).
These observations can be rationalized, if one assumes that
reaction under the Cu(II) conditions leads to a much faster
intramolecular attack on the intermediate π-allyl complexes, with
less time for the anti-complex 85 to isomerize to the more stable
syn-complex 86, than for reactions under the BQ conditions.
This is a reasonable assumption since BQ is known to be a
rather slow oxidant for the π-allyl complexes in these reac-
tions.46 Furthermore, the experiment on stoichiometric com-
plexes (Scheme 9) showed that the internal nucleophile reacted
more slowly (12 h) in the presence of BQ than with Cu(OAc)2
(1 h).
The observation that γ-allenic acid 23 gave the reversed
stereochemistry also supports the theory that the anti-complex
is the kinetically observed intermediate. This reaction was also
performed in the absence of K2CO3 (Table 1, method B) in an
attempt to slow the nucleophilic attack on the π-allyl intermedi-
ate and allow more time for isomerization of the anti- to the
syn-isomer. The observed increase of the relative amount of
the (Z)-isomer from Z/E ) 37:62 to Z/E ) 52:48 in this case
supports the mechanism in Scheme 10.
The number of carbon atoms between the nucleophilic group
and the π-allyl system and the nature of the nucleophile also
influenced the selectivity. In contrast to the poor selectivity
observed, when γ-allenic acids 22 and 23 (Table 1, entries 2
and 5) were cyclized under the Pd/Cu(II) conditions, the one-
carbon-higher homologue δ-allenic acids 25 and 26 (Table 1,
entries 11 and 13) and the N-tosyl-substituted allenic amides
39-44 (Table 3) worked excellently, with high stereoselectivity.
Evidently, cyclization to furnish six-membered rings was slower
than the analogous five-membered ring cyclization, and the
intramolecular nucleophilic attack by N-tosyl allenic amines was
slower compared to nucleophilic attack by carboxylic groups.
The slower intramolecular attack favors formation of the syn-
complex 86 (Table 3 and Table 1, entries 11 and 13). In one of
the cyclizations we observed a higher Z-selectivity for R )
isopropyl than for R ) pentyl (46 f 75 and 45 f 74,
respectively, Table 4). In this case the nucleophile is a urea,
and coordination of the terminal nitrogen to palladium
would also allow π-olefin complex formation with the double
bond further away from the tether (Figure 2). In this case the
syn/anti selectivity will be different from that discussed in
Scheme 10.
Scheme 12
iodocyclizations of trichloroacetimidate derivatives of primary
R-allenic alcohols. The mechanism involves an intramolecular
attack of the nucleophilic group on a rapidly equilibrating
mixture of the bromonium species 87 and 88 (Scheme 11). The
steric interaction between the attacking nucleophile and the R
group on the olefin will disfavor transition-state 88, which leads
to the E isomer. This explanation fits well with our observations.
Treating γ-allenic acid 22 with NBS gave lactone 54 with a
Z/E ratio of 88/12.
F. Synthetic Applications. The present palladium-catalyzed
method allows a mild preparation of various five- and six-
membered heterocycles. The products obtained from the in-
tramolecular palladium-catalyzed 1,2-addition to allenes should
be useful synthetic intermediates for further selective function-
alization. The vinyl bromides obtained can undergo a number
of transformations, such as metal-catalyzed carbonylation,47
palladium-catalyzed coupling reactions,48 or coupling with a
cuprate.49 To demonstrate the synthetic utility of the reaction a
Heck-coupling with methyl acrylate was carried out. Subjecting
69 to the Heck-coupling conditions afforded product 89 in 72%
yield (Scheme 12).
This should be compared with the corresponding Pd(0)-
catalyzed cyclization/Heck process reaction developed by Gal-
lagher et al.7b Cyclization of N-tosyl-substituted allenic amide
42 using PdCl2 in the presence of methyl acrylate and NEt3 in
DMF at 100 °C afforded the Heck product 90 in only 32% yield
together with a substantial amount of dimeric products.
Conclusion
A palladium(II)-catalyzed intramolecular 1,2-functionalization
of allenes has been developed. The reaction, which is a two-
(47) Reference 2, pp 188-209.
The stereochemical outcome of the NBS-promoted cyclization
can be explained from previous studies by Friesen et al.31b on
(48) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (b)
Miyaura, N.; Maeda, K.; Suginome, H.; Susuki, A. J. Org. Chem. 1982,
47, 2117. (c) Reference 2, pp 209-244.
(46) Ba¨ckvall. J.-E. Acc. Chem. Res. 1983, 16, 335.
(49) McMurry, J. E.; Scott, W. J. Tetrahedron Lett. 1980, 21, 4313.

9608 J. Am. Chem. Soc., Vol. 122, No. 40, 2000
Jonasson et al.
(1.62 g, 42.5 mmol) in diethyl ether (10 mL) under nitrogen at -20
°C was added hexa-4,5-diene nitrile 21 (3.3 g, 35.5 mmol) in ether
(1 mL) over 5 min. After 30 min, the mixture was allowed to warm to
room temperature, and the stirring was continued for 2 h. The mixture
was then diluted with CH2Cl2 and quenched by the dropwise addition
of saturated aqueous NaOH (2 M). The mixture was filtered, and the
solids were washed with CH2Cl2. The combined filtrate and washings
were then evaporated to give hexa-4,5-dienylamine 38 as pale yellow
oil (2.69 g, 78%) which was used without further purification. The 1H
NMR data are in accordance to those previously reported.50
General Procedure for Sulfonamide Preparation (39-43). To an
ice-cold solution of the crude amine 38 (2.69 g, 27 mmol) in pyridine
(33 mL) was added tosyl chloride (6.30 g, 33 mmol). The mixture was
stirred for 2h at 0 °C and then allowed to stand at -15 °C overnight.
The suspension was then diluted with ether and washed with aqueous
HCl (2 M). The aqueous washings were then back-extracted with ether.
The combined organic extracts were washed with brine, dried (Na2-
SO4), and evaporated under reduced pressure. The residue was purified
by flash chromatography (pentane /ether 3:2) to afford compound 44
as a pale yellow oil (4.5 g, 65%). The 1H NMR data are in accordance
to those previously reported.50
electron oxidation reaction, is reminiscent of the corresponding
Pd(II)-catalyzed 1,4-functionalization of 1,3-dienes. As in the
latter reaction, this new reaction proceeds via a π-allyl
intermediate formed from attack by a first nucleophile, followed
by an intramolecular nucleophilic attack on the π-allyl moiety.
The new intramolecular 1,2-oxidation utilizes mild oxidants such
as p-benzoquinone or copper(II) salts and should therefore
tolerate various functionalities. The reaction provides access to
a variety of oxygen- and nitrogen-containing five- and six-
membered heterocycles. Furthermore, these latter compounds
are useful intermediates for further selective functionalizations.
Experimental Section
7-Methyl-octa-4,5-dienoic Acid Ethyl Ester (13). General Pro-
cedure for the Preparation of Allenic Esters 12-17 and Allenic
Nitriles 18-21. A suspension of zinc (3.89 g, 59.4 mmol) in THF (5
mL) containing 1,2-dibromoethane (0.39 g, 2.1 mmol) was heated with
a heat gun for 30 s and allowed to cool to room temperature.
Chlorotrimethylsilane (0.22 mL, 1.8 mmol) was then added, and the
mixture was allowed to stir for 15 min before a THF solution (25 mL)
of the functionalized alkyl iodide, ethyl-3-iodopropionate 8a (13.1 g,
57.4 mmol), was slowly added with a syringe. After the end of the
addition, the reaction was stirred for 12 h at 35 °C. The solution was
then cooled to -10 °C, and a solution of CuCN (3.68 g, 41.4 mmol)
and predried LiCl (3.53 g, 83.0 mmol) in THF (50 mL) was added.
The resulting green-gray solution was stirred at 0 °C for 30 min. The
solution was then cooled to -40 °C, and the corresponding propargylic
tosylate 11b (10 g, 39.7 mmol) was slowly added. The reaction mixture
was allowed to slowly warm to room temperature. After the addition
of water, the reaction mixture was extracted with ether three times.
The combined extracts were washed with water and brine, dried
(MgSO4), and concentrated. The residue was then filtered through silica
to give 13 in 93% yield (8.06 g). 1H NMR (400 MHz, CDCl3): δ 5.18
(m, 1H), 5.14 (m, 1H), 4.10 (q, J ) 7.2 Hz, 2H), 2.39 (m, 2H), 2.32-
2.20 (m, 3H), 1.24 (t, J ) 7.2 Hz, 3H), 0.97 (d, J ) 6.8 Hz, 6H); 13C
NMR (100 MHz, CDCl3): δ 201.8, 172.8, 99.8, 90.8, 60.3, 33.5, 27.9,
2,3-Nonadienyl Tosylcarbamate (51). General Procedure for
Tosylcarbamate Preparation (52 and 53). To a solution of the alcohol
49 (0.8 g, 5.71 mmol) in THF (12 mL) was added p-toluenesulfonyl
isocyanate (1.23 g, 6.28 mmol). The resulting solution was stirred at
room temperature for 30 min. The mixture was then diluted with ether
and washed with water and brine. The organic phase was dried and
concentrated. The residue was purified by silica gel chromatography
(pentane/ether 3:1) to give 51 in 85% yield. 1H NMR (300 MHz,
CDCl3): δ 7.93 (d, J ) 8.4 Hz, 2H), 7.77 (br s, NH), 7.33 (d, J ) 8.4
Hz, 2H), 5.20 (m, 1H), 5.15 (m, 1H), 4.53 (dd, J ) 6.8, 2.3 Hz, 2H),
2.44, (s, 3H), 1.95 (dtd, J ) 7.3, 6.8, 2.9 Hz, 2H), 1.35 (m, 2H), 1.27
(m, 4H), 0.87 (t, J ) 6.7 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ
205.5, 150.0, 144.9, 135.3, 129.5, 128.3, 93.3, 85.8, 65.4, 31.3, 28.6,
28.2, 22.4, 21.7, 14.1. IR (neat): 3242, 1966, 1752, 1349, 1162 cm-1
.
5-(1-Bromo-1-heptenyl)-tetrahydro-2-furanone (54). General Pro-
cedure for Palladium(II)-Catalyzed Cyclization of γ-Allenic Acids
(Method A, Table 1, 54-58). The allenic acid 22 (40 mg, 0.22 mmol)
in acetic acid (0.4 mL, 0.55 M) was added during 18 h with a syringe
pump to a stirred solution of Pd(OAc)2 (2.5 mg, 0.011 mmol), 1,4-
benzoquinone (142 mg, 1.31 mmol), LiOAc‚2H2O (134 mg, 1.31
mmol), and LiBr (114 mg, 1.31 mmol) in acetic acid (2.4 mL, 0.1 M)
at 40 °C. After the reaction was complete (20 h), water and ether were
added. The phases were separated, and the aqueous phase was extracted
two times with ether. The combined organic extracts were washed with
aqueous NaOH (2 M) (until the organic layer was pale yellow), brine
and dried (MgSO4). Evaporation of the solvent and silica gel chroma-
tography using pentane/ether (3:2) afforded 54 (48.2 mg, 84%) as a
mixture of Z- and E-isomers in a ratio of 92:8; colorless oil. Pure
samples of the E and Z isomers were obtained by preparative HPLC
(pentane /EtOAc; 4:1) (Z)-54: 1H NMR (400 MHz, CDCl3): δ 6.12
(t, J ) 7.3 Hz, 1H), 5.01 (dd, J ) 7.1, 6.3 Hz, 1H), 2.68 (ddd, J )
17.8, 10.0, 6.0 Hz, 1H), 2.53 (ddd, J ) 17.8, 9.7, 7.2 Hz, 1H), 2.43
(m, 1H), 2.27 (m, 1H), 2.20 (q, J ) 7.3 Hz, 2H), 1.42 (quintet, J ) 7.3
Hz, 2H), 1.30 (m, 4H), 0.89 (t, J ) 6.9 Hz, 3H); 13C NMR (100 MHz,
CDCl3): δ 176.5, 132.6, 124.6, 82.3, 31.3, 30.7, 27.9, 27.7, 27.2, 22.4,
13.9. (E)-54: 1H NMR (400 MHz, CDCl3): δ 6.13 (t, J ) 8.2 Hz,
1H), 5.39 (dd, J ) 8.0, 6.3 Hz, 1H), 2.75 (ddd, J ) 17.8, 10.3, 5.6 Hz,
1H), 2.54 (ddd, J ) 17.8, 10.3, 8.0 Hz, 1H), 2.32 (m, 2H), 2.16 (m,
1H), 1.42 (m, 2H), 1.30 (m, 4H), 0.90 (t, J ) 6.9 Hz, 3H); 13C NMR
(100 MHz, CDCl3): δ 176.4, 138.1, 123.0, 75.9, 31.1, 29.7, 28.7, 28.2,
26.8, 22.3, 13.9. (Z+E mixture):EIMS m/z 260 [M+ (79Br), 2.8], 262
[M+ (81Br), 3.3], 111 (100). IR (CDCl3): 1795 cm-1. Anal. Calcd for
C11H17BrO2: C, 50.59; H, 6.56; Found: C, 50.73; H, 6.47.
24.0, 22.6, 22.5, 14.4. IR (CHCl3): 1960, 1743 cm-1
.
Undeca-4,5-dienoic Acid (22). General Procedure for the Prepa-
ration of Acids 23-27. A mixture of ester 12 (0.94 g, 4.5 mmol) and
NaOH (2.85 g, 71.6 mmol) in ethanol (10 mL) and H2O (3.8 mL) was
stirred and heated under reflux overnight. The mixture was concentrated
in vacuo, and the residue was diluted with water. The aqueous solution
was extracted with ether to remove neutral impurities. The aqueous
layer was then acidified with concentrated HCl to pH 1 and extracted
with ether. The ether solution was washed with water and brine, dried
(MgSO4), and concentrated in vacuo. Purification by flash chromatog-
raphy (pentane/ether 2:1) gave 22 in 81% yield (0.71 g). 1H NMR (400
MHz, CDCl3): δ 10.6 (br s, COOH), 5.16 (m, 2H), 2.48 (distorted t,
J ) 7.4 Hz, 2H), 2.30 (m, 2H), 1.96 (m, 2H), 1.38 (m, 2H), 1.29 (m,
4H), 0.89 (t, J ) 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 203.3,
179.3, 92.8, 89.2, 33.2, 31.5, 28.92, 28.90, 23.6, 22.6, 14.2. IR (neat):
1964, 1712 cm-1. Anal. Calcd for C11H18O2: C, 72.49; H, 9.95;
Found: C,72.31; H, 9.99.
Undeca-4,5-dien-1-ol (28). General Procedure for the Preparation
of Alcohols 29-32. To an ice-cold suspension of LiAlH4 (87.8 mg,
2.3 mmol) in dry ether (2 mL) under argon was added 12 (0.44 g, 2.1
mmol) in ether (2 mL). After 30 min the mixture was allowed to warm
to room temperature, and the reaction mixture was quenched by the
addition of EtOAc and water. The resulting suspension was diluted
with 1 M HCl and extracted with ether. The combined organic phases
were washed with NaHCO3 and brine, dried, and concentrated. The
residue was purified with silica gel chromatography (pentane/ether 3:1)
to give 0.29 g of 28 (83%) as a clear oil. 1H NMR (300 MHz, CDCl3):
δ 5.12 (m, 2H), 3.67 (t, J ) 6.5 Hz, 2H), 2.06 (m, 2H), 1.96 (m, 2H),
1.72 (tt, J ) 7.6, 6.5 Hz, 2H), 1.38 (m, 2H), 1.32 (m, 4H), 0.88 (t, J
) 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 203.6, 91.5, 90.1, 62.5,
32.0, 31.4, 28.99, 28.96, 25.3, 22.6, 14.2. IR (CHCl3): 2326, 1961
6-(1-Bromo-1-heptenyl)-tetrahydro-2H-2-pyranone (59). General
Procedure for Palladium(II)-Catalyzed Cyclization of δ-Allenic
Acids (Method B, Table 1, 59 and 60). A suspension of δ-allenic
acid 25, (108 mg, 0.55 mmol), Pd(OAc)2 (12.3 mg, 0.055 mmol), LiBr
cm-1
.
N-(p-Tolylsulfonyl)-hexa-4,5-dienylamine. (44). General Proce-
dure for the Preparation of Amine 33-37. To a suspension of LiAlH4
(50) Shaw, R. W.; Gallagher, T. J. Chem. Soc., Perkin Trans. 1 1994,
24, 3549.

Intramolecular Pd(II)-Catalyzed 1,2-Addition to Allenes
J. Am. Chem. Soc., Vol. 122, No. 40, 2000 9609
(239 mg, 2.75 mmol), Cu(OAc)2‚H2O (229 mg, 1.15 mmol), and
K2CO3 (83.4 mg, 0.6 mmol) in acetonitrile (3.66 mL) was stirred at
room temperature under an oxygen atmosphere for 1 h. The reaction
was then diluted with brine/H2O, and ether was added. The phases were
separated, and the aqueous phase was extracted three times with ether.
The combined organic extracts were then washed with water, dried
(MgSO4), and evaporated. The residue was purified by silica gel
chromatography (pentane/ether 2:1) to afford 59 in 83% yield (0.13
mg) as a mixture of Z- and E-isomers (90:10). Pure samples of the
Z-isomer was obtained by preparative HPLC (pentane/EtOAc; 4:1). (Z)-
59: 1H NMR (400 MHz, CDCl3): δ 6.09 (dd, J ) 6.9, 0.84 Hz, 1H),
4.83 (dd, J ) 8.9, 3.9 Hz, 1H), 2.60 (ddd, J ) 17.8, 8.8, 6.9 Hz, 1H),
2.50 (ddd, J ) 17.8, 6.6, 5.6 Hz, 1H) 2.20 (app q, J ) 2.7 Hz, 2H)
1.97 (m, 4H), 1.41 (m, 2H), 1.30 (m, 4H), 0.89 (t, J ) 7.0, 3H); 13C
NMR (100 MHz, CDCl3): δ 170.2, 132.4, 124.3, 83.1, 31.4, 30.9, 29.7,
27.8, 27.5, 22.5, 18.1, 14.1. The following NMR data for the E isomer
were taken from the mixture: (E)-59: 1H NMR (400 MHz, CDCl3):
δ 5.16 (dd, J ) 10.3, 3.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ
170.2, 136.9, 124.3, 83.1, 31.2, 30.8, 29.7, 28.8, 27.5, 22.5, 18.7, 14.1.
EIMS m/z 260 [M+ (79Br), 2.8], 262[M+ (81Br), 3.3], 111 (100). IR
(neat): 1739 cm-1. Anal. Calcd for C12H19BrO2: C, 52.38; H, 6.96;
Found: C, 52.28; H, 7.11.
2-(1-Bromo-3-methyl-1-butenyl)-tetrahydrofuran (62). General
Procedure for Palladium(II)-Catalyzed Cyclization of γ-Allenic
Alcohols (Method A, Table 2, 61-64). The allenic alcohol 29 (200
mg, 1.43 mmol) was added during 14 h with a syringe pump to a stirred
solution of Pd(OAc)2 (16.1 mg, 0.07 mmol), 1,4-benzoquinone (386
mg, 3.57 mmol), and LiBr (621 mg, 7.14 mmol) in acetic acid (5.2
mL) at 40 °C. After the reaction was complete (8 h), water and a mixture
of ether/pentane (1:2) was added. The phases were separated, and the
aqueous phase was extracted two times with ether/pentane (1:2). The
combined organic extracts were washed with aqueous NaOH (2M) until
the organic layer was pale yellow and then dried (MgSO4). Evaporation
of the solvent and silica gel chromatography using pentane/ether
(95:5) afforded 62 (217 mg, 70%) as a inseparable mixture of Z- and
E-isomers 88:12; colorless oil. (Z)-62: 1H NMR (400 MHz, CDCl3):
δ 5.81 (dd, J ) 8.9, 1.0 Hz, 1H), 4.41 (ddd, J ) 6.9, 5.9, 1.0 Hz, 1H),
3.99 (m, 1H), 3.85 (m, 1H), 2.74 (d septet, J ) 8.9, 6.7, Hz, 1H), 1.97
(m, 4H), 1.01 (d, J ) 6.7 Hz, 3H), 1.00 (d, J ) 6.7 Hz, 3H); 13C NMR
(100 MHz, CDCl3): δ 135.8, 126.5, 82.6, 69.2, 31.5, 30.5, 25.8, 21.9,
21.8. The following NMR data for the E-isomer were taken from the
mixture: (E)-62: 1H NMR (400 MHz, CDCl3): δ 5.85 (dd, J ) 9.9,
0.5 Hz, 1H), 4.74 (br t, J ) 7.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3): δ 141.9, 126.0, 76.0, 69.2, 31.5, 29.6, 26.7, 23.2, 22.9. EIMS
m/z 218 [M+ (79Br), 2.1], 220 [M+ (81Br), 2.1], 139,(100). Anal. Calcd
for C9H15BrO: C, 49.33; H, 6.90; Found: C,49.46; H, 7.05.
[M+ - 1 (79Br), 40.8], 235 [M+ - 1 (81Br), 33.8], 153 (100). Anal.
Calcd for C10H17BrO: C, 51.52; H, 7.35; Found: C, 51.62; H, 7.51.
N-(p-Tolylsulfonyl)-2-(1-bromo-3-ethyl-hept-1-enyl)-pyrroli-
dine (70). General Procedure for Palladium(II)-Catalyzed Cycliza-
tion of γ-Allenic Amides (Method B, Table 3, 4, and 5, 68-81). A
suspension of γ-allenic tosylamide 41 (150 mg, 0.43 mmol), Pd(OAc)2
(9.6 mg, 0.04 mmol), LiBr (186.9 mg, 2.14 mmol), Cu(OAc)2 (179.6,
0.90 mmol), and K2CO3 (71.0 mg, 0.51 mmol) in acetonitrile (2.86
mL) was stirred at room temperature under an oxygen atmosphere for
2-5 h. The reaction was then diluted with brine/H2O, and ether was
added. The phases were separated, and the aqueous phase was extracted
three times with ether. The combined organic extracts were then washed
with water, dried (MgSO4), and evaporated. The residue was purified
by silica gel chromatography (pentane/ether 3:1) to afford 146 mg (80%)
of 70 as a mixture of Z- and E-isomers (89/11); colorless oil. Pure
samples of the diastereomeric E- and Z-isomers were obtained by
preparative HPLC (pentane /EtOAc 10:1). (Z)-70: 1H NMR (400 MHz,
CDCl3): δ 7.73 (d, J ) 8.4 Hz, 2H), 7.30 (d, J ) 8.4, 2H), 5.79 (dd,
J ) 9.5, 1.1 Hz, 1/2 H), 5.76 (dd, J ) 9.5, 1.1 Hz, 1/2 H), 4.40 (m, 1H),
3.47 (m, 1H), 3.33 (m, 1H), 2.44 (m, 1H), 2.42 (s, 3H), 2.05 (m, 1H),
1.88 (m, 1H), 1.80-1.58 (m, 3H), 1.53-1.17 (m, 7H), 0.93-0.83 (m,
6H); 13C NMR (100 MHz, CDCl3): δ 143.3, (135.6, 135.5), (134.9,
134.8), 129.5 (2C), (127.9, 127.7, 2C), (127.29, 127.28), (66.1, 66.0),
49.4, 42.7, (34.29, 34.27), (32.14, 32.10), (29.45, 29.30), (27.81, 27.78),
(23.9, 23.8), (22.91, 22.88), 21.6, 14.2, (11.8, 11.7). (E)-70: 1H NMR
(400 MHz, CDCl3): δ 7.73 (d, J ) 8.4 Hz, 2H), 7.30 (d, J ) 8.4, 2H),
5.69 (d, J ) 10.6 Hz, /2 H), 5.67 (d, J ) 10.6 Hz, /2 H), 4.75 (m,
1H), 3.60 (m, 1H), 3.39 (m, 1H), 2.44 (m, 1H), 2.42 (s, 3H), 2.05 (m,
1H), 1.88 (m, 1H), 1.80-1.58 (m, 3H), 1.53-1.17 (m, 7H), 0.98 (t, J
) 6.9 Hz, 11/2H), 0.92 (t, J ) 6.9 Hz, 11/2H), 0.87 (t, J ) 6.9 Hz,
11/2H), 0.82 (t, J ) 6.9 Hz, 11/2H); 13C NMR (100 MHz, CDCl3): δ
(143.0, 142.9), (139.6, 139.5) (136.6, 136.5), (129.33, 129,30, 2C),
(127.9, 127.7), (127.2, 127.1, 2C), 59.4, 49.6, (42.1, 41.9) (34.8, 34.1),
(32.8, 32.7), (29.8, 29.4), (28.1, 27.6), 25.27, 23.2, (22.91, 22.88), 21.6,
14.2, (12.0, 11.7). (E/Z-mixture): IR (neat): 1352, 1159 cm-1. Anal.
Calcd for C20H30BrNO2S: C, 56.07; H, 7.06; N, 3.27. Found: C, 56.08;
H, 7.23; N, 3.30.
1
1
2-Bromo-(π-allyl)palladium Complex (83). The complex 83 was
prepared by adding 7 (20 mg, 0.16 mmol) to a red slurry of PdBr2-
(PhCN)2 (63 mg, 0.13 mmol) in benzene (5 mL). After 10 min the
reaction mixture turned yellow, and the benzene was evaporated. The
resulting oil was washed with ether/pentane (1:2) to get rid of
benzonitrile. Evaporation of the solvent afforded 83 as a yellow powder
1
in 94% yield (48.6 mg). H NMR (400 MHz, CDCl3): δ 4.20 (t, J )
6.0 Hz, 1H), 3.75 (t, J ) 6.0 Hz, 1H), 2.12 (m, 1H), 1.98 (m, 3H),
1.72 (s, 3H), 1.63 (br s, OH), 1.39 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 109.1, 91.0, 81.2, 62.5, 31.5, 29.9, 28.3, 25.6.
2-(1-Bromo-3-methyl-1-butenyl)tetrahydro-2H-pyran (66). Gen-
eral Procedure for Palladium(II)-Catalyzed Cyclization of δ-Allenic
Alcohols (Method B, Table 2, 65-66). δ-Allenic alcohol 32, (100 mg,
0.65 mmol) was added over 2 h to a suspension of Pd(OAc)2 (14.6
mg, 0.065 mmol), LiBr, (282.3 mg, 3.24 mmol), Cu(OAc)2‚H2O (271.2,
1.36 mmol), and K2CO3 (107.5 mg, 0.78 mmol) in acetonitrile (4.21
mL) at room temperature under an oxygen atmosphere. The reaction
was allowed to stir for an additional 1h and was then diluted with brine/
H2O and ether. The phases were separated, and the aqueous phase was
extracted three times with ether. The combined organic extracts were
then washed with water, dried (MgSO4), and evaporated. The residue
was purified by silica gel chromatography (pentane/ether 95:5) to afford
106 mg (70%) of 66 as a mixture of Z- and E-isomers (94:6); colorless
oil. A pure sample of the Z-isomer was obtained by preparative HPLC
(pentane /EtOAc 98:2). (Z)-66: 1H NMR (400 MHz, CDCl3): δ 5.82
(dd, J ) 8.7, 0.9 Hz, 1H), 4.08 (m, 1H), 3.80 (ddd, J ) 10.4, 2.1, 0.7
Hz, 1H), 3.51 (m, 1H), 2.75 (d septet, J ) 8.7, 6.8 Hz, 1H), 1.89 (m,
1H), 1.82 (m, 1H), 1.68-1.44 (m, 4H), 1.01 (d, J ) 6.8 Hz, 3H) 1.00
(d, J ) 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 136.1, 125.6,
81.8, 68.7, 31.2, 30.6, 25.7, 23.4, 21.83, 21.82. The following NMR
data for the E-isomer were taken from the mixture: (E)-66: 1H NMR
(400 MHz, CDCl3): 4.14 (m, 1H), 3.52 (m, 1H). EIMS m/z 233
Reaction of 83 under the Catalytic Conditions with BQ as the
Reoxidant. The complex 83 (40 mg, 0.10 mmol) was dissolved in acetic
acid (0.4 mL) and treated with LiBr (44.4 mg, 0.51 mmol) and
benzoquinone (27.5 mg, 0.255 mmol). The reaction was stirred
overnight at 40 °C to give tetrahydrofuran 64 in 72% yield after normal
workup (see general procedure for γ-allenic alcohol cyclizations.)
Acknowledgment. Financial support from the Swedish
Natural Science Research Council and the Swedish Foundation
for Strategic Research is gratefully acknowledged.
Supporting Information Available: Details for the prepara-
tion and spectroscopic data for compounds 2a-6a, 2b-6b, 7,
12, 14-21, 23-27, 29-32, 39-43, 45-50, 52, 53, 55-58, 60,
1
61, 63-65, 68, 69, 71-81, 84, and 89. Copies of H and 13C
NMR spectra for compounds 2b, 6b, 13-20, 23-32, 39, 40, 42,
43, 45, 47-49, 51-53, 56, 63, 72, 77, 78, 83, 84, and 89. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JA001748K