Palladium(II)-catalyzed SN2′ reactions of α-allenic acetates. Stereoconvergent synthesis of (Z,E)-2-bromo-1,3-dienes

Article abstract of DOI:10.1021/jo015950x

The reaction of acetylated α-allenic alcohols with LiBr in the presence of 1.5 mol % of Pd(OAc)₂ provides easy access to substituted (Z,E)-2-bromo-1,3-dienes in good yields with excellent diaste-reoselectivity. Both secondary and tertiary acetates as well as terminal and nonterminal allenes were studied to investigate the scope and the limitations of the reaction. A mechanism is proposed to clarify how a diastereomeric mixture of the starting compound is transformed into a single diastereomer of the product.

Full text of DOI:10.1021/jo015950x

8120
J . Org. Chem. 2001, 66, 8120-8126
P a lla d iu m (II)-Ca ta lyzed SN2′ Rea ction s of r-Allen ic Aceta tes.
Ster eocon ver gen t Syn th esis of (Z,E)-2-Br om o-1,3-d ien es
Attila Horva´th and J an-E. Ba¨ckvall*
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University,
SE-106 91, Stockholm, Sweden
J eb@organ.su.se
Received J uly 19, 2001
The reaction of acetylated R-allenic alcohols with LiBr in the presence of 1.5 mol % of Pd(OAc)2
provides easy access to substituted (Z,E)-2-bromo-1,3-dienes in good yields with excellent diaste-
reoselectivity. Both secondary and tertiary acetates as well as terminal and nonterminal allenes
were studied to investigate the scope and the limitations of the reaction. A mechanism is proposed
to clarify how a diastereomeric mixture of the starting compound is transformed into a single
diastereomer of the product.
Sch em e 1. Ver sa tile Utiliza tion of th e Br om o
In tr od u ction
Su bstitu ted (π-Allyl)p a lla d iu m Com p lex
Palladium-catalyzed reactions of allenes represent a
large and dynamically growing field of organometallic
chemistry.1,2 Most of these reactions are known to pro-
ceed via a (π-allyl)palladium intermediate. We are par-
ticularly interested in the chemistry of 2-bromo-substi-
tuted (π-allyl)palladium complexes. These complexes can
be formed via the reaction of an allene, bromide ion, and
palladium(II) (Scheme 1), and in certain cases they are
stable enough to be isolated.3 Depending on the substitu-
tion pattern of the allene in the presence of p-benzo-
quinone (BQ), the (π-allyl)palladium complex can react
to give either dibrominated4 or heterocyclic products.3
During the work on 1,2-oxidations of allenes, we observed
that R-acetoxy allenes (A, X ) OAc, Scheme 1) react
without benzoquinone to give substituted 2-bromo-1,3-
dienes as elimination products. In this paper we report
on a highly stereoselective synthesis of 2-bromo-1,3-
dienes from R-acetoxy allenes and lithium bromide via a
palladium(II)-catalyzed SN2′ reaction.
1,3-dienes to give optically active allenes was also
reported recently.12
Most previous syntheses of 2-bromo-1,3-dienes have
involved coupling reactions.13-15 Roush et al. reported a
synthesis of (Z,E)-2-bromo-1,3-dienes13 based on a pal-
ladium(0)-catalyzed cross-coupling of 1,1-dibromo olefins
and vinylboronic acid derivatives under basic conditions.
Dibromo olefins having an allylic alkoxy group afforded
the coupling products selectively and in good yields, but
olefins lacking the allylic alkoxy group gave the desired
products only in moderate (43-61%) yields. Other cross-
coupling reactions such as Stille14 and Negishi15 couplings
were also applied to the synthesis of 2-bromo-1,3-dienes.
These reactions, however, proceeded with poor diaste-
reoselectivity or were applied only to the synthesis of
dienes with one terminal double bond.
2-Bromo-1,3-dienes are useful compounds in organic
synthesis. For example, they are viable coupling reagents
for introducing a diene moiety into more complex mol-
ecules,5,6 and they have been used in Diels-Alder reac-
tions where the bromide acts as a sterically directing
group that can be easily removed or replaced after the
reaction.7-11 A palladium(0)-catalyzed reaction of 2-bromo-
(1) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2000, 39, 3590.
(2) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem.
Rev. (Washington, D.C.) 2000, 100, 3067.
(3) J onasson, C.; Horva´th, A.; Ba¨ckvall, J .-E. J . Am. Chem. Soc.
2000, 122, 9600.
(4) Ba¨ckvall, J .-E.; J onasson, C. Tetrahedron Lett. 1997, 38, 291.
(5) J ohnson, W. S.; Telfer, S. J .; Cheng, S.; Schubert, U. J . Am.
Chem. Soc. 1987, 109, 2517.
(6) Schreiber, S. L.; Kiessling, L. L. J . Am. Chem. Soc. 1988, 110,
631.
Tsirk et al. prepared tertiary amines containing the
(Z,E)-2-bromo-1,3-diene moiety via an amine-induced
(7) Abe, H.; Aoyagi, S.; Kibayashi, C. J . Am. Chem. Soc. 2000, 122,
4583.
(8) Roush, W. R.; Koyama, K.; Curtin, M. L.; Moriarty, K. J . J . Am.
Chem. Soc. 1996, 118, 7502.
(9) Roush, W. R.; Riva, R. J . Org. Chem. 1988, 53, 710.
(10) Parker, K. A.; Iqbal, T. J . Org. Chem. 1987, 52, 4369.
(11) Tsirk, A.; Gronowitz, S.; Hornfeldt, A. B. Tetrahedron 1998,
54, 9529.
(12) Ogasawara, M.; Ikeda, H.; Nagano, T.; Hayashi, T. J . Am.
Chem. Soc. 2001, 123, 2089.
(13) Roush, W. R.; Moriarty, K. J .; Brown, B. B. Tetrahedron Lett.
1990, 31, 6509.
(14) Shen, W.; Wang, L. J . Org. Chem. 1999, 64, 8873.
(15) Ogasawara, M.; Ikeda, H.; Hayashi, T. Angew. Chem., Int. Ed.
2000, 39, 1042.
10.1021/jo015950x CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/02/2001

Pd-Catalyzed SN2′ Reactions of R-Allenic Acetates
J . Org. Chem., Vol. 66, No. 24, 2001 8121
Sch em e 2a
highly diastereoselective formation of the corresponding
product (entry 8, Table 1). The isolated 2-bromo-1,3-
dienes could be stored for a couple of days at room
temperature, but they polymerized slowly. In a control
experiment it was shown that without palladium(II)
catalyst there was no conversion of acetoxy allenes 1b-
6b to bromo-dienes. For example, when allene 2b was
stirred with lithium bromide in acetic acid at 40 °C, no
conversion could be detected after 4 days.
a
Reagents: (a) 1. 3,4-dihydro-2H-pyran; 2. n-BuLi, R′COH; 3.
Allenes without an acetoxy group in the R-position are
known to undergo oxidative dibromination under similar
condition if p-benzoquinone is present (Scheme 1).4
Without benzoquinone and in the presence of a potential
leaving group in the allylic position, however, 2-bromo-
1,3-dienes are formed (Table 1). To investigate the
possibility of dibromination of our substrates, allene 1b
was reacted with lithium bromide in the presence of
p-benzoquinone and palladium(II) acetate (Scheme 4).
LiAlH4; (b) Ac2O, pyridine.
Sch em e 3a
a
Reagents: (a) 1. Paraformaldehyde, diisopropylamine, CuBr;
(b) Ac2O, pyridine, DMAP.
The major product was diene 8 together with its
oxidized Diels-Alder adduct with p-benzoquinone (14),
but 12% of the product from the dibromination reaction
(15a ) was also observed. We found that the dibromination
is regio- and stereoselective giving rise to a single
diastereomer of dibromide 15. To verify this observation
the other, unobserved diastereomer (15b) also had to be
synthesized. The nonselective reaction of allene 1b with
CuBr2 afforded both syn- and anti-15 that could be
separated by preparative HPLC. According to the pro-
posed mechanism (Figure 3), the observed diastereomer
15a should be the anti isomer, but we were unable to
make the stereochemical assignment of compounds 15a
and 15b.
ring opening of 3-bromo-2,5-dialkylthiophene-1,1-dioxide
with either ω-unsaturated acyclic amines (28-35% yield)
or cyclic amino alcohols (89-91% yield).11
Even though several methods exist for the synthesis
of substituted 2-bromo-1,3-dienes, as described above,
they are either applicable only to a specific group of
compounds or give low diastereoselectivity. In this paper
we report a more general, simple, and efficient palladium-
(II)-catalyzed reaction for the stereoselective synthesis
of substituted (Z,E)-2-bromo-1,3-dienes.
Resu lts a n d Discu ssion
Dienes 12 and 13 were too volatile to be conveniently
isolated. Acetoxy allenes 5b and 6b were therefore
reacted in deuterated solvents, and yields were deter-
mined by 1H NMR spectroscopy. During these reactions,
we noticed that the reaction times in deuterated solvents
(acetic acid-d4:acetone-d6 ) 1:1 or neat acetic acid-d4)
were about twice as long, indicating a considerable
solvent isotope effect. The products could be further
reacted in a one-pot Diels-Alder reaction and isolated
as their tetracyanoethylene adduct (Scheme 5).
Syn th esis of Sta r tin g Ma ter ia ls. R-Allenic acetates
1b-5b (Scheme 2) were prepared from the corresponding
alcohols 1a -5a . The alcohols were synthesized according
to a slightly modified procedure reported by Landor et
al.16 (Scheme 2).
Terminal allenes 6b and 7b were conveniently pre-
pared via homologation of the corresponding propargyl
alcohol according to the procedure reported by Crabbe´
et al.,17 followed by acetylation of the R-allenic alcohols
(Scheme 3). All the R-acetoxy allenes were stable at room
temperature and could be stored for several months
without any detectable decomposition.
P a lla d iu m -Ca ta lyzed SN2′ Rea ction s. Acetoxy al-
lene 1b was added to a solution of lithium bromide and
catalytic amount of palladium acetate in a 1:1 mixture
of acetic acid and acetone at 40 °C. The initially orange
solution of the in situ-formed palladium(II) bromide turns
pale yellow after the addition of the allene in a few
minutes. When all the allene has reacted, the color
changes back to orange due to the reformed palladium-
(II) bromide. After workup the bromo-diene 8 was iso-
lated in 85% yield with excellent diastereoselectivity
(Table 1, entry 1). Terminal allenes 2b and 6b also
reacted smoothly and afforded the corresponding dienes
9 and 13, respectively, in good yields. To determine what
steric requirements R and R′ groups have to fulfill,
several other acetoxy allenes (3b-5b) were synthesized
and reacted with lithium bromide (Table 1, entries 4-11).
Apparently, a methyl group is big enough to induce
Changing the solvent from a mixture of acetone and
acetic acid to neat acetic acid led to a faster but less
diastereoselective reaction (method B, Table 1). From the
four possible diastereomers, however, only the two shown
in Figure 1 are formed. Because the double bond closer
to R′ has the E stereochemistry in both of the products
obtained, the only diastereomer obtained from terminal
allenes (R ) H) are the E-dienes (entries 3, 12, and 13,
Table 1). The stereochemistry of the products were
assigned on the basis of the coupling constants between
protons Ha and Hb (3J ) 14.5-14.7 Hz) clearly indicating
a trans relationship and by the NOE measurements
(Figure 1). In the case of nonterminal dienes 8 and 10-
12 the signals of protons Ha and Hb did not separate in
deuterated chloroform; therefore, benzene-d6 was used
to determine the coupling constants and the NOE (Figure
1).
Allenes bearing a tertiary acetoxy group also reacted
with lithium halides in an SN2′ fashion (Scheme 6). In
contrast to the secondary acetoxy compounds these
reactions also worked without the palladium catalyst,
and only when bromide was used as nucleophile could a
4-fold acceleration with Pd(OAc)2 be detected. The mod-
(16) Cowie, J . S.; Landor, P. D.; Landor, S. R. J . Chem. Soc., Perkin
Trans. 1973, 720.
(17) Crabbe, P.; Fillion, H.; Andre, D.; Luche, J . L. J . Chem. Soc.,
Chem. Commun. 1979, 859.

8122 J . Org. Chem., Vol. 66, No. 24, 2001
Ta ble 1. P a lla d iu m -Ca ta lyzed SN2′ Rea ction of r-Allen ic Aceta tes
Horva´th and Ba¨ckvall
a
b
Only the major diastereomer is shown. The reaction was carried out in the presence of 1.5% Pd(OAc)2 and 2.5 equiv of LiBr at
40 °C in acetic acid/acetone 1:1 mixture (method A) or in acetic acid (method B). c Isolated yield unless otherwise noted; n.d. ) not
determined. Determined by 1H NMR. e Reactions were carried out in deuterated solvents.
d
Sch em e 4a
F igu r e 1. Stereochemical assignments of the products.
a
Reagents and condition: (a) 2.5 equiv of LiBr, 2.5 equiv of
p-benzoquinone, 5% Pd(OAc)2 in acetic acid at 40 °C; yields were
determined by HPLC using naphthalene as internal standard.
Sch em e 5a
a
Reagents: (a) 1. 2.5 equiv of LiBr, 1.5% Pd(OAc)2 in acetic
F igu r e 2. Proposed mechanism for the palladium-catalyzed
SN2′ reaction.
acid at 40 °C; 2. 2 equiv of tetracyanoethylene; numbers in
brackets refer to isolated yields.
Sch em e 6a
carbon. A σ-allyl complex is initially formed, which
rapidly equilibrates to the π-allyl complex. Finally, an
acid-catalyzed elimination of the acetoxy group and
palladium(II) gives the 2-bromo-1,3-diene derivative. To
account for the strongly preferred formation of only one
diastereomer several possibilities has to be considered.
It was shown that under certain conditions palladium
catalyzes the cis-trans isomerization of alkenes.19-21 In
our case the simplest explanation of the observed high
diastereoselectivity would be the isomerization of the
products to the thermodynamically most stable (Z,E)-
diene. To investigate this possibility (E,E)-4-bromo-2,4-
decadiene (22), the minor product from the reaction of
a
Reagents: (a) 2.5 equiv of lithium halide in acetic acid at
40 °C; numbers in brackets refer to reaction times and isolated
yields.
erate yield with chloride as nucleophile is due to the
competing acid-catalyzed rearrangement reaction to form
diene 21.18
Mech a n ism a n d Ster eoch em istr y. The palladium-
(II)-catalyzed reactions of allenes with bromide proceed
via a 2-bromo-(π-allyl)palladium complex (Figure 2).
First, palladium coordinates to either of the two double
bonds and then the bromide attacks the middle allene
(18) Olsson, L. I.; Claesson, A.; Bogentoft, C. Acta Chem. Scand.
1973, 27, 1629.
(19) Schwarz, I.; Braun, M. Chem. Eur. J . 1999, 5, 2300.
(20) Henry, P. M. J . Am. Chem. Soc. 1971, 93, 3547.
(21) Cramer, R.; Lindsey, R. V., J r. J . Am. Chem. Soc. 1966, 88,
3534.

Pd-Catalyzed SN2′ Reactions of R-Allenic Acetates
J . Org. Chem., Vol. 66, No. 24, 2001 8123
F igu r e 3. Proposed mechanism for the stereoselective formation of (Z,E)-2-bromo-1,3-dienes. The coordinated palladium is omitted
from the structures of the allenes, and only the enantiomers with (R) central chirality are indicated for clarity. In each case
palladium is coordinated to the opposite face of the double bond that is attacked by the bromide.
allene 4b, was isolated and stirred in acetic acid in the
presence of lithium bromide and palladium acetate at
40 °C. No isomerization could be detected after 2 days.
Furthermore, when the least diastereoselective reaction
of allene 5b was over (entry 11, Table 1) acetone-d6 was
added to the solution. A slight enhancement of the
diastereoselectivity was expected because reactions in
mixture of acetone and acetic acid show higher preference
to the (Z,E)-diene. No isomerization of the product
occurred after 2 days. The possibility of product isomer-
ization was therefore excluded.
As a consequence, the proposed mechanism requires
that the two diastereomers of the allene are in equilib-
rium during the reaction. To show that this equilibrium
exists, the pure diastereomers of R-acetoxy allene 1b were
isolated and reacted separately with lithium bromide
according to method B (Table 1). Both diastereomers (1b′
and 1b′′) isomerized during the reaction and formed
about 8% of the other diastereomer.
This result clearly shows that the formation of the
(π-allyl)palladium complex from allene, bromide ion, and
palladium(II) is reversible. Furthermore we found that
one diastereomer (1b′) reacted slower than the other
diastereomer (1b′:1b′′ ) 0.6:1). When starting from the
faster reacting diastereomer 1b′′ after 96% conversion,
we observed that the reaction mixture contained more
1b′ than 1b′′, which resulted in a decreased reaction rate
toward the end of the reaction. These observations are
in good agreement with the different reaction rates and
the isomerization of the starting allene.
Knowing about the possibility of starting material
isomerization an alternative route would be that the
slower reacting diastereomer 1b′ isomerizes to 1b′′ and
the product is only formed from 1b′′. In this case,
however, an induction period would be expected in one
of the reactions, but this was not observed. Both diaster-
eomers of the starting allene can therefore form the
product without the need for a preceding isomerization.
If both routes b and c are possible, then routes a and d
(Figure 3) cannot be excluded either because they rep-
resent attack of the nucleophile from the same direction
as b and c, respectively, but on the other diastereomer.
This means that during the reaction a certain amount
of catalyst is in the nonreactive syn,syn form 23e. It has
to reform the allene before it can be transformed to the
product. If terminal allenes are used (R ) H, Figure 3)
they do not contain axial chirality and the mechanism is
more simple. All the intermediate (π-allyl)palladium
complexes can form the (E)-diene either directly or after
an η3-η1-η3-rearrangement. This results in a faster reac-
tion for terminal allenes (entries 3 and 12, Table 1).
Syn th etic Utility. The (Z,E)-2-bromo-1,3-dienes ob-
tained should be useful for the synthesis of stereodefined
products via Diels-Alder and coupling reactions. After
All nonterminal allenes (i.e. 1b and 3b-5b) used as
starting materials were mixtures of diastereomers (I and
II, Figure 3). After coordination of palladium to either
double bond the middle allenic carbon could be attacked
by bromide from four directions. These directions are
perpendicular to the plane of the double bond which
palladium is coordinated to. Two of these attacks are cis
to one of the allylic carbons and therefore kinetically
unfavored. The other two possibilities are (1) attack on
the double bond closer to the acetoxy group from the
direction trans to the R group (routes a and b, Figure 3)
and (2) attack on the other double bond from the direction
trans to the C(OAc)R′ group (routes c and d, Figure 3).
The formed π-allyl complexes 23a -d (Figure 3) then
isomerize to the thermodynamically more stable syn,syn
complexes (23e and 23f) via an η3-η1-η3-rearrangement.
This isomerization is faster than the product formation
because only small amount of (E,E)-diene is formed in
the reaction. The next step is elimination of the acetoxy
group and palladium(II) which is only possible if they are
in anti position. Only three of the (π-allyl)palladium
complexes fulfill this requirement, two of them (23c and
23f) form the product, the third (23a ) leads to the
observed byproduct. The elimination is acid-catalyzed,
i.e., the rate is slower in acetic acid-acetone mixture
than in pure acetic acid. This was used to inhibit the
formation of the nondesired diastereomer. If the
final elimination step is slow, then the initially formed
(π-allyl)palladium complex (23a ) has enough time to
isomerize to the more stable syn,syn complexes (23e and
23f) and the product is formed with a higher diastereo-
meric ratio (method A and B, Table 1).

8124 J . Org. Chem., Vol. 66, No. 24, 2001
Horva´th and Ba¨ckvall
(pentane/ethyl acetate 7:1) afforded 4a (0.708 g, 4.59 mmol)
in 59% yield, pale yellow oil. Pure samples of the diastereomers
were obtained by preparative HPLC (pentane/ethyl acetate
2:1). IR (neat, cm-1) 3327, 1963. 4a ′: 1H NMR (CDCl3, 400
MHz) δ 5.27 (m, 2H), 4.31 (br s, 1H), 2.02 (m, 2H), 1.67 (s,
1H), 1.41 (m, 2H), 1.30 (m, 4H), 1.29 (d, J ) 6.4 Hz, 3H), 0.88
(t, J ) 7.1 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 201.6, 96.9,
94.6, 65.9, 91.3, 28.8, 28.7, 23.4, 22.4, 14.0. 4a ′′: 1H NMR
(CDCl3, 300 MHz) δ 5.27 (m, 2H), 4.32 (app pentet d, J ) 6.1,
2.5 Hz, 1H), 2.01 (m, 2H), 1.69 (s, 1H), 1.40 (m, 2H), 1.30 (m,
4H), 1.29 (d, J ) 6.3 Hz, 3H), 0.88 (t, J ) 7.1 Hz, 3H); 13C
NMR (CDCl3, 75 MHz) δ 201.7, 96.9, 94.4, 66.2, 31.3, 28.75,
28.66, 23.4, 22.4, 14.0.
Gen er a l P r oced u r e for th e P r ep a r a tion of Acetyla ted
r-Allen ic Alcoh ols 1b-5b. 1-Meth yl-2,3-n on a d ien yl Ace-
ta te (4b). Allenic alcohol 4a (0.650 g, 4.21 mmol), acetic
anhydride (0.79 mL, 8.42 mmol), and pyridine (0.32 mL, 3.91
mmol) were stirred overnight. Column chromatography (pen-
tane/diethyl ether 9:1) of the crude reaction mixture afforded
4b (0.779 g, 3.97 mmol) in 94% yield as colorless oil. Pure
samples of the diastereomers were obtained by preparative
HPLC (pentane/diethyl ether 98:2). IR (neat, cm-1) 1956, 1741,
1370, 1238, 1044. 4b′: 1H NMR (CDCl3, 400 MHz) δ 5.33 (qdd,
J ) 6.4, 5.7, 2.3 Hz, 1H), 5.26 (qd, J ) 6.5, 2.3 Hz, 1H), 5.23
(app pentet d, J ) 3.1, 5.7 Hz, 1H), 2.02 (s, 3H), 1.99 (ddd, J
) 7.7, 6.7, 3.1 Hz, 2H), 1.39 (m, 2H), 1.31 (d, J ) 6.4 Hz, 3H),
1.28 (m, 4H), 0.87 (m, 3H); 13C NMR (CDCl3, 100 MHz) δ 203.7,
170.3, 94.1, 92.6, 68.6, 31.3, 28.6, 28.4, 22.4, 21.3, 19.6, 14.0.
4b′′: 1H NMR (CDCl3, 400 MHz) δ 5.33 (qdd, J ) 6.4, 2.3, 0.5,
Hz, 1H), 5.28 (qd, J ) 6.4, 2.3 Hz, 1H), 5.22 (app heptet, J )
3.0 Hz, 1H), 2.03 (s, 3H), 1.99 (ddd, J ) 7.8, 6.7, 3.0 Hz, 2H),
1.39 (m, 2H), 1.31 (d, J ) 6.4 Hz, 3H), 1.30 (m, 4H), 0.88 (m,
3H); 13C NMR (CDCl3, 100 MHz) δ 203.5, 170.4, 94.1, 92.7,
68.7, 31.2, 28.7, 28.4, 22.4, 21.3, 19.8, 14.0. Anal. Calcd for
a Diels-Alder cycloaddition the vinylic bromide can be
further functionalized via metal-catalyzed cross-coupling
reactions. The recent observation that 2-bromo-1,3-dienes
can be transformed into optically active allenes also opens
up a useful desymmetrization of allenes starting from
R-acetoxy allenes.
Con clu sion s
An efficient palladium(II)-catalyzed synthesis of sub-
stituted (Z,E)-2-bromo-1,3-dienes has been developed.
Formally, the reaction is an SN2′ substitution; however,
the products are formed with excellent diastereoselec-
tivity even when the substituents on the formed diene
are small. The high diastereomeric purity of these bromo-
dienes makes them attractive for stereoselective organic
syntheses. A mechanism was proposed that account for
the stereoconvergence of the reaction. The following
observations are in good agreement with the proposed
mechanism: (1) isomerization of the starting allene
during the reaction; (2) expected stereochemistry of the
product and byproducts; (3) enhanced reaction rate when
terminal allenes were used; (4) better selectivity and
longer reaction time in less acidic solvent; (5) significant
solvent isotope effect. The reaction of the allene contain-
ing a tertiary acetoxy group proceeds at comparable rate
without catalyst; therefore, it is not expected to be
stereoselective.
Exp er im en ta l Section
C
12H20O2: C, 73.43; H, 10.27. Found: C, 73.63; H, 10.17.
Gen er a l Meth od s. Diethyl ether and THF were distilled
from sodium benzophenone ketyl; dioxane was dried with CaH2
and then with LiAlH4 and distilled from sodium. All other
reagents and solvents were used without further purification.
1H NMR (400 or 300 MHz) and 13C NMR (100 or 75 MHz)
were recorded on a Varian Mercury spectrometer using the
residual peak of chloroform-d (7.26 ppm for 1H and 77 ppm
for 13C) as internal standard. IR spectra were recorded on a
Perkin-Elmer 1600 FT-IR instrument using neat films or KBr
pellets of the samples, and only the strongest or structurally
most important peeks are listed. Mass spectra were recorded
on a ThermoQuest GCQ plus GLC-MS instrument using
electron ionization (EI). Preparative HPLC was performed on
a Bischoff liquid chromatograph using Kromasil 100 SIL 5 µm
(250 × 20 mm) column. Analytical HPLC was performed on a
Waters liquid chromatograph using µ Porasil (300 × 3.9)
column. Elemental analysis was performed by Analitische
Laboratorien, Lindlar, Germany. Melting points are uncor-
rected. Merck silica 60 (240-400 mesh) was used for column
chromatography, and analytical TLC was performed on Merck
precoated silica 60-F254 plates.
Gen er a l P r oced u r e for th e P r ep a r a tion of r-Allen ic
Alcoh ols 1a -5a . 3,4-Deca d ien -2-ol (4a ).22 To a stirred
mixture of 1-octyn-3-ol (0.988 g, 7.83 mmol) and 3,4-dihydro-
2H-pyran (0.659 g, 7.83 mmol) was added a catalytic amount
of HCl gas. The reaction mixture was stirred until it cooled to
room temperature, 11 mL of dry THF was added, and it was
cooled to 0 °C. n-BuLi (7.3 mL, 1.6 M in hexane) was added
dropwise, and the resulting yellow solution was stirred for 1.5
h before acetaldehyde (0.345 g, 7.83 mmol) was slowly added.
The mixture was stirred for 4 h at 0 °C, quenched with water,
and extracted three times with ether. The combined organic
solutions were washed with water and brine and dried over
Na2SO4. Most of the ether was evaporated, and the resulting
5-(tetrahydro-2H-2-pyranyloxy)-3-decyn-2-ol was added drop-
wise to a suspension of LiAlH4 (0.327 g, 8.61 mmol) in diethyl
ether (18 mL). The mixture was refluxed for 4 h, quenched
with the minimum amount of water, and filtered through
Celite. The solid residue was washed four times with ether,
and then the solvent was evaporated. Column chromatography
Gen er a l P r oced u r e for th e P r ep a r a tion of Acetoxy
Allen es 6b a n d 7b. 1-P r op a d ien ylcycloh exyl Aceta te (7b).
Following a slight modification of the procedure of Crabbe et
al.,17 1-ethynylcyclohexanol (2.97 g, 23.9 mmol), paraformal-
dehyde (1.15 g, 38.2 mmol), cuprous bromide (1.72 g, 12.0
mmol), and diisopropylamine (4.05 mL, 28.7 mmol) were
refluxed in dry dioxane (160 mL) overnight. The dioxane was
carefully evaporated, and water was added to the residue.
Extraction with diethyl ether and evaporation of the solvent
gave 1-propadienylcyclohexanol23 (7a ) that was used without
further purification. Acetic anhydride (4.51 mL, 47.8 mmol),
pyridine (1.79 mL, 22.2 mmol), and DMAP (0.292 g, 2.39 mmol)
were added to the alcohol, and the mixture was stirred at 40
°C overnight. Column chromatography (pentane/ether 95:5) of
the crude mixture afforded 7b (3.07 g, 17.0 mmol) in 71%
overall yield, colorless oil: IR (neat, cm-1) 1954, 1735, 1367,
1
1232; H NMR (CDCl3, 400 MHz) δ 5.59 (t, J ) 6.8 Hz, 1H),
4.80 (d, J ) 6.8 Hz, 2H), 2.04 (m, 2H), 1.96 (s, 3H), 1.65 (m,
2H), 1.47 (m, 5H), 1.30 (m, 1H); 13C NMR (CDCl3, 100 MHz)
δ 207.6, 169.8, 95.4, 80.5, 77.5, 35.2 (2H), 25.2 (2H), 22.1, 22.0.
Anal. Calcd for C11H16O2: C, 73.30; H, 8.95. Found: C, 73.12;
H, 8.93.
Gen er a l P r oced u r e for th e P r ep a r a tion of Dien es
8-13 a n d 18-20. (6Z,8E)-7-Br om o-6,8-h exa d eca d ien e (8).
Allene 1b (94.30 mg, 0.336 mmol) was added to a solution of
Pd(OAc)2 (1.13 mg, 0.00504 mmol) and LiBr (72.85 mg, 0.841
mmol) in 3.4 mL of acetic acid/acetone 1:1 mixture (method
A) or in acetic acid (method B). The solution was stirred at 40
°C until it turned to orange (9 h in this case). Water and
pentane were added, and the aqueous phase was extracted
twice with pentane. The combined organic extracts were
washed with water, sat. NaHCO3, and brine and dried over
Na2SO4. Evaporation of the solvent followed by flash chroma-
tography (pentane/ether 9:1) afforded 8 (86.4 mg, 0.287 mmol)
in 85% yield, pale yellow liquid: IR (neat, cm-1) 1647, 1612,
(22) Cherkezishvili, K. I.; Gverdtsimeli, I. M.; Taktakishvili, M. O.
Zh. Obshch. Khim. 1976, 46, 1297.
(23) For 1H NMR, see: Claesson, A.; Bogentoft, C. Acta Chem.
Scand. 1972, 26, 2540.

Pd-Catalyzed SN2′ Reactions of R-Allenic Acetates
J . Org. Chem., Vol. 66, No. 24, 2001 8125
1
1
1466, 950; H NMR (CDCl3, 400 MHz) δ H NMR (C6D6, 400
MHz) δ 6.23 (dt, J ) 14.6, 7.2 Hz, 1H), 5.97 (d, J ) 14.6 Hz,
1H), 5.64 (t, J ) 7.1 Hz, 1H), 2.28 (app q, J ) 7.1 Hz, 2H),
2.04 (app q, J ) 7.2 Hz, 2H), 1.36-1.17 (m, 16H), 0.89 (t, J )
7.1 Hz, 3H), 0.84 (t, J ) 6.9 Hz, 3H); 13C NMR (CDCl3, 100
MHz) δ 134.8, 132.0, 129.1, 125.4, 32.2, 31.8, 31.44, 31.40, 29.3,
36.4), 327 (70.7), 239 (81Br, 100), 237 (79Br, 83.2). Anal. Calcd
for C22H31BrO2: C, 64.86; H, 7.67. Found: C, 65.02; H, 7.70.
(Z)-3,4-Dibr om o-1-h ep tyl-2-n on en yl Aceta te (15). 15a
obtained as a byproduct from the same reaction as compound
14. 15b was isolated from the reaction of allene 1b with 3 equiv
of CuBr2 in acetonitrile. Pure samples of 15a and 15b were
obtained by preparative HPLC (pentane/diethyl ether 95:5),
pale yellow liquid: IR (neat, cm-1) 1744, 1370, 1233. 15a : 1H
NMR (CDCl3, 400 MHz) δ 6.03 (d, J ) 7.8 Hz, 1H), 5.52 (dt, J
) 6.0, 7.5 Hz, 1H), 4.56 (t, J ) 7.3 Hz, 1H), 2.04 (m, 2H), 2.03
(s, 3H), 1.70 (m, 1H), 1.61 (m, 1H), 1.30 (m, 16H), 0.88 (t, J )
6.9 Hz, 3H), 0.87 (t, J ) 6.9 Hz, 3H); 13C NMR (CDCl3, 100
MHz) δ 170.0, 131.2, 130.4, 73.8, 57.6, 37.8, 33.3, 31.7, 30.9,
29.3, 29.1, 26.9, 24.7, 22.6, 22.3, 21.0, 14.1, 13.9. EIMS m/z
361 (81Br, 48.0), 359 (79Br, 48.3), 319 (81Br, 98.6), 317 (79Br,
100), 301 (81Br, 17.9), 299 (79Br, 16.5), 237 (35.7), 219 (63.2).
15b: 1H NMR (CDCl3, 300 MHz) δ 6.05 (d, J ) 7.9 Hz, 1H),
5.56 (dt, J ) 7.9, 6.5 Hz, 1H), 4.54 (t, J ) 7.4 Hz, 1H), 2.05 (s,
3H), 2.02 (m, 2H), 1.69 (m, 1H), 1.59 (m, 1H), 1.29 (m, 16H),
0.89 (t, J ) 6.7 Hz, 3H), 0.87 (t, J ) 6.7 Hz, 3H); 13C NMR
(CDCl3, 75 MHz) δ 169.7, 130.9, 130.0, 73.6, 57.3, 38.3, 33.7,
31.8, 31.0, 29.4, 29.2, 27.2, 24.8, 22.7, 22.5, 21.2, 14.2, 14.0.
EIMS m/z 361 (81Br, 50.8), 359 (79Br, 51.0), 319 (81Br, 99.3),
317 (79Br, 100), 301 (81Br, 14.8), 299 (79Br, 15.3), 237 (37.8),
219 (57.7). Anal. Calcd for C18H32Br2O2: C, 49.11; H, 7.33.
Found: C, 49.27; H, 7.42.
29.20, 29.16, 28.1, 22.7, 22.5, 14.1, 14.0. Anal. Calcd for C16H29
Br: C, 63.78; H, 9.70. Found: C, 64.01; H, 9.80.
-
(3E)-2-Br om o-1,3-u n d eca d ien e (9). Prepared from allene
2b (101.77 mg, 0.484 mmol) following the general procedure
(method B). After flash chromatography (pentane/ether 9:1),
the title compound was isolated in 79% yield (88.34 mg, 0.382
mmol), colorless liquid: IR (neat, cm-1) 1647, 1587, 1466, 953,
1
872; H NMR (CDCl3, 400 MHz) δ 6.10 (dt, J ) 14.7, 6.7 Hz,
1H), 6.01 (d, J ) 14.7 Hz, 1H), 5.69 (s, 1H), 5.51 (s, 1H), 2.17
(dt, J ) 6.7, 7.0 Hz, 2H), 1.43 (m, 2H), 1.29 (m, 8H), 0.89 (t, J
) 6.9 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 138.8, 130.2,
128.2, 117.5, 32.1, 31.8, 29.2, 29.1, 29.0, 22.6, 14.1.
(3Z,5E)-4-Br om o-3,5-tr id eca d ien e (10). Prepared from
allene 3b (84.24 mg, 0.353 mmol) following the general
procedure (method A). After flash chromatography (pentane/
ether 9:1), the title compound was isolated in 88% yield (80.80
mg, 0.312 mmol), colorless liquid: IR (neat, cm-1) 1648, 1613,
1458, 950; 1H NMR (CDCl3, 400 MHz) δ 6.02 (m, 2H), 5.83 (t,
J ) 7.0 Hz, 1H), 2.30 (app pent., J ) 7.4 Hz, 2H), 2.15 (m,
2H), 1.42 (m, 2H), 1.29(m, 8H), 1.04 (t, J ) 7.6 Hz, 3H), 0.89
(t, J ) 6.9 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 134.9, 133.3,
129.0, 124.8, 32.2, 31.8, 29.3, 29.20, 29.16, 24.9, 22.7, 14.1, 12.9.
Anal. Calcd for C13H23Br: C, 60.23; H, 8.94. Found: C, 60.42;
H, 8.93.
(2E,4Z)-4-Br om o-2,4-d eca d ien e (11). Prepared from al-
lene 4b (97.97 mg, 0.499 mmol) following the general proce-
dure (method A). After flash chromatography (pentane/ether
9:1) the title compound was isolated in 84% yield (91.44 mg,
0.421 mmol), colorless liquid: IR (neat, cm-1) 1652, 1614, 1447,
Gen er a l P r oced u r e for th e P r ep a r a tion of Com p ou n d
16 a n d 17. 5-Br om o-3-eth yl-4-cycloh exen e-1,1,2,2-tetr a -
ca r bon itr ile (17). Prepared from allene 6b (89.12 mg, 0.636
mmol) following the general procedure (method B). After the
reaction was over, tetracyanoethylene (162.8 mg, 1.27 mmol)
was added to the orange solution and stirring was continued
overnight. The reaction mixture was extracted with dichlo-
romethane, the combined extracts was washed with sat.
NaHCO3 and brine and dried over Na2SO4, and the solvent
was evaporated. Column chromatography (pentane/ethyl
acetate 2:1) afforded 17 (127.4 mg, 0.441 mmol) in 69% yield,
white crystal: Mp: 136-139 °C; IR (KBr, cm-1) 3082, 2257,
1
948; H NMR (CDCl3, 400 MHz) δ 6.04 (m, 2H), 5.82 (t, J )
7.1 Hz, 1H), 2.28 (app q, J ) 7.1 Hz, 2H), 1.82 (m, 3H), 1.43
(m, 2H), 1.32 (m, 4H), 0.90 (t, J ) 7.0 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) δ 131.8, 130.4, 129.2, 125.0, 31.4, 31.3, 28.2,
22.5, 17.4, 14.0.
1
1657, 1426, 864; H NMR (CDCl3, 300 MHz) δ 6.21 (dd, J )
1.9, 3.7 Hz, 1H), 3.46 (ddd, J ) 18.4, 3.3, 2.1 Hz, 1H), 3.38
(ddd, J ) 18.4, 2.2, 1.6 Hz, 1H), 2.97 (m, 1H), 2.05 (dqd, J )
13.6, 7.4, 4.2 Hz, 1H), 1.76 (ddq, J ) 13.6, 10.5, 7.4 Hz, 1H),
1.24 (t, J ) 7.4 Hz, 3H); 13C NMR (CDCl3, 75 MHz) δ 126.5,
113.6, 110.6, 109.9, 109.6, 108.3, 44.6, 43.1, 39.43, 39.39, 24.6,
11.0. Anal. Calcd for C12H9BrN4: C, 49.85; H, 3.14; N, 19.38.
Found: C, 49.88; H, 3.29; N, 19.28.
(2Z,4E)-3-Br om o-2,4-h exa d ien e (12). Prepared from al-
lene 5b following the general procedure (method B). After
extraction with pentane and drying with Na2SO4, the solvent
was carefully evaporated via a distillation column at normal
pressure. IR (neat, cm-1) 1744, 1448, 948; 1H NMR (CDCl3,
400 MHz) δ 6.04 (m, 2H), 5.88 (q, J ) 6.7 Hz, 1H), 1.85 (br d,
J ) 6.7 Hz, 3H), 1.82 (m, 3H); 13C NMR (CDCl3, 100 MHz) δ
130.3, 129.1, 126.5, 126.1, 17.5, 17.0.
(3E)-2-Br om o-1,3-h exa d ien e (13).24 Prepared from allene
6b following the general procedure (method B). Pure samples
of the title compound were obtained after careful distillation.
IR (neat, cm-1) 1624, 1459, 842; 1H NMR (CDCl3, 300 MHz) δ
6.15 (dt, J ) 14.8, 6.3 Hz, 1H), 6.01 (br d, J ) 14.8 Hz, 1H),
5.70 (br s, 1H), 5.52 (br s, 1H), 2.20 (app br pentet, J ) 7.3
Hz, 2H), 1.06 (t, J ) 7.5 Hz, 3H); 13C NMR (CDCl3, 75 MHz)
δ 140.0, 130.2, 127.4, 117.6, 25.1, 13.2.
6-Br om o-5-h eptyl-8-pen tyl-1,4,5,8-tetr a h yd r o-1,4-n a ph -
th a len ed ion e (14). Obtained as a byproduct from the reaction
of allene 1b (23.50 mg, 0.0838 mmol) with LiBr (18.18 mg,
0.209 mmol) and p-benzoquinone (22.64 mg, 0.209 mmol) in
the presence of Pd(OAc)2 (0.94 mg, 0.0042 mmol) in acetic acid
(0.35 mL) at 40 °C. Pure samples of the title compound was
obtained by preparative HPLC (pentane/diethyl ether 95:5);
yellow liquid: IR (neat, cm-1) 1655, 843; 1H NMR (CDCl3, 400
MHz) δ 6.72 (s, 2H), 6.28 (d, J ) 5.2 Hz, 1H), 3.68 (dt, J )
3.8, 5.0 Hz, 1H), 3.42 (ddt, J ) 9.3, 5.2, 3.8 Hz, 1H), 1.77 (m,
2H), 1.44 (m, 2H), 1.27 (m, 16H), 0.88 (t, J ) 6.8 Hz, 3H), 0.85
(t, J ) 6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 186.2, 186.0,
143.1, 142.1, 136.5, 136.4, 130.1, 123.7, 42.5, 38.1, 36.8, 33.2,
31.8 (2C), 29.5, 29.1, 27.5, 25.9, 22.6, 22.4, 14.1, 14.0. EIMS
m/z 408 (81Br, 25.7), 406 (79Br, 24.2), 338 (81Br, 36.3), 336 (79Br,
syn -4-Br om o-3,6-d im eth yl-4-cycloh exen e-1,1,2,2-tetr a -
ca r bon itr ile (16). Prepared from allene 5b (94.12 mg, 0.671
mmol) following the general procedure. Column chromatog-
raphy (pentane/ethyl acetate 7:1) followed by crystallization
from cyclohexane afforded 16 (133.5 mg, 0.462 mmol) in 69%
yield, white crystal: Mp: 90-91 °C; IR (KBr, cm-1) 3081, 2257,
1
1654, 1449, 867; H NMR (CDCl3, 400 MHz) δ 6.10 (dd, J )
2.7, 1.7 Hz, 1H), 3.37 (qdd, J ) 7.4, 1.2, 1.7 Hz, 1H), 3.26 (qdd,
J ) 7.2, 2.7, 2.1 Hz, 1H), 1.83 (d, J ) 7.4 Hz, 3H), 1.61 (d, J
) 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 128.2, 120.8,
110.9, 110.7, 109.6, 109.2, 43.4, 43.0, 41.5, 38.8, 17.1, 17.0.
Anal. Calcd for C12H9BrN4: C, 49.85; H, 3.14; N, 19.38.
Found: C, 49.95; H, 3.12; N, 19.50.
(1-Ch lor o-2-p r op en ylid en e)cycloh exa n e (18). Prepared
from allene 7b (107.09 mg, 0.594 mmol) following the general
procedure (method B). After flash chromatography (pentane/
ether 9:1), the title compound was isolated in 62% yield (57.9
mg, 0.370 mmol), colorless liquid: IR (neat, cm-1) 1647, 1617,
1448, 878, 843; 1H NMR (CDCl3, 400 MHz) δ 5.64 (app hextett,
J ) 1.3 Hz, 1H), 5.35 (d, J ) 1.1 Hz, 1H), 5.12 (dd, J ) 1.3,
1.1 Hz, 1H), 2.39 (m, 2H), 2.15 (m, 2H), 1.63-1.53 (m, 6H);
13C NMR (CDCl3, 100 MHz) δ 147.0, 136.7, 120.1, 114.3, 37.0,
29.7, 28.3, 27.2, 26.4. Anal. Calcd for C9H13Cl: C, 69.00; H,
8.36. Found: C, 69.21; H, 8.48.
(1-Br om o-2-p r op en ylid en e)cycloh exa n e (19). Prepared
from allene 7b (117.80 mg, 0.654 mmol) following the general
procedure (method B). After flash chromatography (pentane/
ether 9:1), the title compound was isolated in 74% yield (96.9
mg, 0.482 mmol), yellow liquid: IR (neat, cm-1) 1645, 1610,
(24) Grimaldi, J .; Cozzone, A.; Bertrand, M. Bull. Soc. Chim. Fr.
1967, 2723.

8126 J . Org. Chem., Vol. 66, No. 24, 2001
Horva´th and Ba¨ckvall
1447, 884, 843; 1H NMR (CDCl3, 300 MHz) δ 5.74 (m, 1H),
5.59 (dd, J ) 1.4, 0.5 Hz, 1H), 5.51 (app. t, J ) 1.4 Hz, 1H),
2.36 (m, 2H), 2.14 (m, 2H), 1.65-150 (m, 6H); 13C NMR (CDCl3,
75 MHz) δ 146.5, 127.2, 122.3, 118.6, 36.7, 29.6, 28.3, 27.8,
26.4.
chromatography (pentane/ether 9:1), the title compound was
separated from 11 by preparative HPLC (pentane/ether 98:
1
2), colorless liquid. IR (neat, cm-1) 1647, 1447, 947; H NMR
(CDCl3, 400 MHz) δ 6.26 (dm, J ) 14.5 Hz, 1H), 6.13 (ddq, J
) 14.5, 0.4, 6.6 Hz, 1H), 5.92 (tq, J ) 7.8, 0.7 Hz, 1H), 2.19
(app q, J ) 7.5 Hz, 2H), 1.86 (ddd, J ) 6.6, 1.5, 0.7 Hz, 3H),
1.41 (m, 2H), 1.30 (m, 4H), 0.89 (t, J ) 7.0 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) δ 133.4, 132.7, 124.8, 121.2, 31.3, 29.5, 28.9,
22.5, 17.9, 14.0.
(1-Iod o-2-p r op en ylid en e)cycloh exa n e (20). Prepared
from allene 7b (86.21 mg, 0.478 mmol) following the general
procedure. After flash chromatography (pentane/ether 9:1), the
title compound was isolated in 82% yield (97.1 mg, 0.391
mmol), violet liquid: IR (neat, cm-1) 1639, 1606, 1446, 892,
1
843; H NMR (CDCl3, 400 MHz) δ 5.89 (dd, J ) 1.7, 1.2 Hz,
Ackn owledgm en t. Financial support from the Swed-
ish Foundation for Strategic Research and the Swedish
Natural Science Research Council is gratefully acknowl-
edged.
1H), 5.86 (app. t, J ) 1.2 Hz, 1H), 5.83 (m, 1H), 2.32 (m, 2H),
2.11 (m, 2H), 1.60-1.51 (m, 6H); 13C NMR (CDCl3, 100 MHz)
δ 144.8, 127.2, 126.7, 103.4, 36.4, 29.4, 28.3, 27.7, 26.5. EIMS
m/z 248 (1.1), 121 (75.1), 93 (100).
1-(Cycloh exylid en m eth yl)vin yl Aceta te (21). Obtained
as a byproduct from the reaction of allene 7b with LiCl. IR
(neat, cm-1) 1758, 1448, 1370, 1019; The 1H NMR spectra is
in accordance to that previously reported;18 13C NMR (CDCl3,
100 MHz) δ 169.0, 151.7, 147.2, 116.0, 104.5, 37.6, 29.9, 28.4,
27.6, 26.4, 21.0.
Su p p or tin g In for m a tion Ava ila ble: A more detailed
discussion about the mechanism; characterization of com-
pounds 1a -3a , 5a , 1b-3b, 5b, and 6b; 1H NMR and 13C NMR
spectra of compounds 1a , 1b, 3a -5a , 3b-7b, 8-11, 13-22.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(2E,4E)-4-Br om o-2,4-d eca d ien e (22) Prepared from allene
4b following the general procedure (method B). After flash
J O015950X