A Versatile Route to 2-Substituted Cyclic 1,3-Dienes via a Copper(I)-Catalyzed Cross-Coupling Reaction of Dienyl Triflates with Grignard Reagents

Article abstract of DOI:10.1021/jo971737i

A general synthesis of 2-substituted cyclic 1,3-dienes in two steps from α,β-unsaturated ketones has been developed. Formation of a dien-2-yl triflate followed by a copper(I)-catalyzed cross-coupling reaction with a Grignard reagent gives 2-substituted dienes in fair to excellent yields. Alkyl, aryl, and allyl Grignard reagents can be used.

Full text of DOI:10.1021/jo971737i

J . Org. Chem. 1998, 63, 2517-2522
2517
A Ver sa tile Rou te to 2-Su bstitu ted Cyclic 1,3-Dien es via a
Cop p er (I)-Ca ta lyzed Cr oss-Cou p lin g Rea ction of Dien yl Tr ifla tes
w ith Gr ign a r d Rea gen ts
A. Sofia E. Karlstro¨m, Magnus Ro¨nn, Atli Thorarensen,† and J an-E. Ba¨ckvall*,‡
Department of Organic Chemistry, University of Uppsala, Box 531, SE-751 21 Uppsala, Sweden
Received September 16, 1997
A general synthesis of 2-substituted cyclic 1,3-dienes in two steps from R,â-unsaturated ketones
has been developed. Formation of a dien-2-yl triflate followed by a copper(I)-catalyzed cross-coupling
reaction with a Grignard reagent gives 2-substituted dienes in fair to excellent yields. Alkyl, aryl,
and allyl Grignard reagents can be used.
In tr od u ction
requires lengthy procedures,2,10,11 and more efficient and
general methods for their preparation are highly desir-
able.
Conjugated dienes are versatile starting materials in
organic synthesis1 and selective methods for their prepa-
ration are of continuous interest.2 The most common use
of conjugated dienes has been in Diels-Alder reactions3
and related cycloadditions,4 together with some limited
use in electrophilic addition reactions.5 More recently,
however, there has been an increasing interest in the use
of conjugated dienes in metal-mediated reactions.6,7
Coupling reactions of vinyl triflates with organome-
tallic reagents are useful for the synthesis of substituted
alkenes from ketones.12 In particular, the vinyl triflate
coupling with diorganocuprates was developed into a
viable procedure for the stereoselective synthesis of
trisubstituted alkenes (eq 1).13 This method has been
extensively used in, for example, natural product
syntheses.12b
In our laboratory, we have developed synthetic meth-
odology based on palladium catalysis for the 1,4-func-
tionalization of conjugated dienes.8 Application of this
methodology requires access to cyclic 1,3-dienes substi-
tuted at the double bonds. For this reason, we previously
developed a general and practical procedure for the
synthesis of 1-substituted cyclic 1,3-dienes.9 The syn-
thesis of 2-substituted cyclic 1,3-dienes, however, often
† Present address: Pharmacia and Upjohn, Discovery Chemistry,
301 Henrietta Street, Kalamazoo, MI 49007-4940.
‡ Present address: Department of Organic Chemistry, Arrhenius
Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
(1) Pattenden, G. In Comprehensive Organic Chemistry; Barton, D.,
Ollis, W. D., Eds.; Pergamon: Elmsford, N.Y., 1979; Vol. 1, Chapter
2, pp 171-213.
(2) Mehta, G.; Rao, H. S. P. Synthesis of conjugated dienes and
polyenes. In The Chemistry of Functional Groups: The Chemistry of
Polyenes and Dienes; Patai, S., Rappoport, Z., Eds.; Wiley: Chichester,
1997; Vol. 1 (Rappoport, Z., Vol. Ed.), Chapter 9, pp 359-480.
(3) Sauer, J .; Sustmann, R. Angew. Chem. 1980, 92, 773; Angew.
Chem., Int. Ed. Engl. 1980, 19, 779.
The corresponding reaction of a dienyl triflate would
be a potential route for a general synthesis of 2-substi-
tuted dienes from R,â-unsaturated ketones (eq 2). To our
knowledge, only a few isolated examples of this reaction
are present in the literature. In their investigation of
couplings between vinyl triflates and allylic cyanocu-
prates, Lipshutz and Elworthy14 reported one example
of a coupling with a dien-2-yl triflate. In a related study,
Dieter et al.15a reported one example of coupling between
a dien-2-yl triflate and an R-aminoalkyl cyanocuprate.
Ru´veda et al. coupled a dienyl triflate of a â-keto lactone
with lithium dimethylcuprate.15b It is noteworthy that
these examples, and other cross-couplings between vinyl
(4) (a) Balci, M. Chem. Rev. 1981, 81, 91. (b) Weinreb, S. M.; Staib,
R. R. Tetrahedron 1982, 38, 3087.
(5) (a) Block, E.; Schwan, A. L. In Comprehensive Organic Synthesis;
Trost, B. M., Flemming, I., Eds.; Pergamon: Oxford, U.K., 1991; Vol.
4 (Semmelhack, M. F., Vol. Ed.), Chapter 1, pp 329-362. (b) Vignes,
R. P.; Hamer, J . J . Org. Chem. 1974, 39, 849. (c) Heasley, G. E.;
Heasley, V. L.; Manatt, S. L.; Day, H. A.; Hodges, R. V.; Kroon, P. A.;
Redfield, D. A.; Rold, T. L.; Williamson, D. E. J . Org. Chem. 1973, 38,
4109.
(6) Harrington, P. J . In Comprehensive Organometallic Chemistry
II; Abel, E. W., Stone, G. A.; Wilkinson, G., Eds.; Pergamon: Oxford,
1995; Vol. 12 (Hegedus, L. S., Vol. Ed.), pp 797-904.
(7) (a) Ba¨ckvall, J .-E. In Advances in Metal-Organic Chemistry;
Liebeskind, L. S., Ed.; J AI press: Greenwich, 1989; Vol. 1, pp 135-
175. (b) Ba¨ckvall, J .-E. Palladium-Catalyzed Oxidation of Dienes. In
The Chemistry of Functional Groups: The Chemistry of Polyenes and
Dienes; Patai, S., Rappoport, Z., Eds.; Wiley: Chichester, 1997; Vol. 1
(Rappoport, Z., Vol. Ed.), Chapter 14, pp 653-681.
(8) (a) Ba¨ckvall, J .-E. Palladium-Catalyzed 1,4-Additions to Conju-
gated Dienes. In Metal-catalyzed Cross Coupling Reactions; Stang, P.,
Diederich, F., Eds.; VCH: Weinheim 1998; pp 339-385. (b) Ba¨ckvall,
J .-E. Pure Appl. Chem. 1996, 68, 535.
(9) Selle´n, M.; Ba¨ckvall, J .-E.; Helquist, P. J . Org. Chem. 1991, 56,
835.
(10) Reich, H. J .; Wollowitz, S. J . Am. Chem. Soc. 1982, 104, 7051.
(11) (a) Tanner, D.; Selle´n, M.; Ba¨ckvall, J .-E. J . Org. Chem. 1989,
54, 3374. (b) Koroleva, E. B.; Ba¨ckvall, J .-E.; Andersson P. G.
Tetrahedron Lett. 1995, 36, 5397. (c) Ba¨ckvall, J .-E.; Andersson, P. G.
J . Am. Chem. Soc. 1992, 114, 6374.
(12) For reviews on the reactions of vinyl triflates with organome-
tallic reagents see: (a) Scott, W. J .; McMurry, J . E. Acc. Chem. Res.
1988, 21, 47. (b) Ritter, K. Synthesis 1993, 735. (c) For palladium-
catalyzed couplings see: Farina, V.; Krishnamurthy, V.; Scott, W. J .
Org. React. 1997, 50, 1-652.
(13) McMurry, J . E.; Scott, W. J . Tetrahedron Lett. 1980, 21, 4313.
(14) Lipshutz, B. H.; Elworthy, T. R. J . Org. Chem. 1990, 55, 1695.
(15) (a) Dieter, R. K.; Dieter, J . W.; Alexander, C. W.; Bhinderwala,
N. S. J . Org. Chem. 1996, 61, 2930. (b) Bacigaluppo, J . A.; Colombo,
M. I.; Zinczuk, J .; Ru´veda, E. A. Synth. Comm. 1992, 22, 1973.
S0022-3263(97)01737-4 CCC: $15.00 © 1998 American Chemical Society
Published on Web 03/24/1998

2518 J . Org. Chem., Vol. 63, No. 8, 1998
Karlstro¨m et al.
Ta ble 1. Cop p er (I)-P r om oted Cr oss-Cou p lin g of 1 w ith
Stoich iom etr ic Am ou n ts of Cu p r a tes
Ta ble 2. Cop p er -Ca ta lyzed Cr oss-Cou p lin g of 1 w ith
n -Bu MgBr
entry
CuX
CuBr
CuX (%) solvent T (°C) yield of 2a (%)
1
2
3
4
5
6
7
8
9
10
11
12d
13
14
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
Et2O
Et2O
-20
-20
-20
-20
-20
-20
-20
-20
-20
-20
-60
0
<3b
31b
34b
58b
61
66
67-73
72
10
10
10
10
10
10
5
2
1
10
10
10
10
CuCN
CuBr‚SMe2
entry
RMa
CuI:RMa Tb (°C) product yieldc (%)
CuCl
CuCl‚2LiClc
CuI
1
2
3
4
5
6
7
8
n-BuLi
n-BuLi
PhLi
MeLi
n-BuMgBr
n-BuMgBr
n-BuMgI
n-BuMgBr
1:1
1:2
1:2
1:2
1:1
1:2
1:2
1:2
0
-20
0
2
2
3
4
2
2
2
2
15 (40)a
53
92
CuI
CuI
69
69
0
87
CuCl‚2LiClc
CuI
-20
-20
-20
0
23e
55
<2b
65b
41b,e
<5b
CuI
40
63
CuCl‚2LiClb
CuI
-20
-20
aM ) Li or MgX. bThe cuprate was preformed at -20 °C. GLC
yield, decane as internal standard. Reactions complete within 15
min unless stated otherwise. d15% yield after 20 min, 40% after 5
h. Unreacted 1 recovered, reaction not complete even after several
hours.
c
aGLC yield, decane as internal standard. bUnreacted 1 recov-
c
ered after reaction. CuCl‚2LiCl was prepared as a solution in THF
according to the literature.9 dReaction mixture becomes black
e
e
within a few min. After 2.5 h.
triflates and copper reagents, employ a stoichiometric
amount of a lithium cuprate.
The aim of the present study was to develop a general
synthesis of 2-substituted dienes via the organocopper
approach and, more importantly, to develop a catalytic
version16 of the reaction.
In this paper, we report on a synthetically useful
procedure for the transformation of an R,â-unsaturated
ketone into a 2-substituted 1,3-diene in two simple steps
via a copper(I)-catalyzed cross-coupling of dienyl triflates
with Grignard reagents. We have also studied the
corresponding reaction with stoichiometric amounts of
alkyl- and arylcuprates.
The reaction could also be performed with stoichio-
metric amounts of a Grignard-derived copper reagent (1.2
equiv) with equal or better results. Here also, the
influence of the copper salt on the yield of 2 was
negligible. Furthermore, the stoichiometry of the cuprate
had a significant role. Thus, a 2:1 ratio of Grignard
reagent to copper salt (Bu2Cu(I)(MgBr)2) was necessary
to achieve good yields and a fast reaction (complete
within minutes) (Table 1, entries 6 and 8). A 1:1 ratio
resulted in incomplete conversion and a low yield of 2
even after several hours (Table 1, entry 5). The choice
of halide in the Grignard reagent influenced the yield of
2, and better results were obtained with n-BuMgBr than
with n-BuMgI (Table 1, entries 6 and 7).
Resu lts a n d Discu ssion
Ca ta lytic Rea ction . The use of catalytic amounts of
copper in the cross-coupling reaction between dienyl
triflates and organolithium or Grignard reagents was
next investigated. Lithium reagents, however, were
found to be totally unreactive, whereas Grignard reagents
showed excellent reactivity, leading to fast and clean
reactions in the presence of catalytic amounts of a copper-
(I) salt. The choice of copper catalyst, temperature, and
solvent had a large effect on the yield of the coupling
product 2 when 1 was reacted with n-BuMgBr (Table 2).
Stoich iom etr ic Rea ction . Cyclic dienyl triflates
were prepared according to the method of Scott and
McMurry.17 These triflates were then subjected to reac-
tions with cuprates. In the reaction of dienyl triflate 1
with an excess (2 equiv) of preformed lithium organocu-
prate, n-Bu2CuLi, the desired coupling product 2 was
indeed obtained (eq 3).
A control reaction in the absence of copper salt did not
result in any formation of the desired product (Table 2,
entry 1). The use of CuBr and CuCN afforded 2 in
modest yields (Table 2, entries 2 and 3), whereas CuCl‚2
LiCl18 and CuI gave the best results (Table 2, entries 6
and 7). Variation of the amount of CuI or CuCl‚2 LiCl
between 10 and 1 mol % had no significant effect on the
yield of 2 (Table 2, entries 8-10).
The influence of the copper salt, solvent, and temper-
ature was examined. n-Bu2CuLi, derived from CuI,
CuBr, or CuCN and 2 equiv of n-BuLi, in reaction with
1 at -78 °C in THF or Et2O gave 2 in 45-55% yield.
Variation of the copper salt or solvent did not result in
any significant change of the yield. Increasing the
temperature up to 0 °C had no negative effect on the yield
as long as the dibutyl cuprate was preformed at a lower
temperature (-20 °C). The use of equal amounts of CuX
and n-BuLi (n-BuCu(X)Li) gave a much slower reaction
and a lower yield of 2 (Table 1, entry 1) compared to the
use of CuX and n-BuLi in a 1:2 ratio. Different 2-sub-
stituted 1,3-cyclohexadienes were obtained in fair to high
yields in THF from 1 and lithium organocuprates (Table
1, entries 2-4).
The choice of temperature was crucial. At -60 °C no
reaction at all was observed (Table 2, entry 11). Appar-
ently, this temperature is too low to allow formation of a
reactive cuprate species. The yields were roughly equal
at -20 and 0 °C (Table 2, entries 7 and 12). At 0 °C,
however, the reaction did not go to completion, due to
thermal decomposition of the cuprate.19 The reaction
(18) Giner, J .-L.; Margot, C.; Djerassi, C. J . Org. Chem. 1989, 54,
2117.
(19) Posner, G. H. Org. React. 1975, 22, 253-400.
(16) Lipshutz, B. H. Acc. Chem. Res. 1997, 30, 277.
(17) McMurry, J . E.; Scott, W. J . Tetrahedron Lett. 1983, 24, 979.

Reaction of Dienyl Triflates with Grignard Reagents
J . Org. Chem., Vol. 63, No. 8, 1998 2519
Ta ble 3. Syn th esis of 2-Su bstitu ted 1,3-Dien es Em p loyin g Ca ta lytic Am ou n ts of Cu I
mixture turned black within a few minutes. The mode
of addition (1 and n-BuMgBr) can be varied between slow
addition (30 min) of the Grignard reagent to 1 and CuI
in THF, slow addition of 1 to the Grignard reagent and
CuI in THF, or fast addition of both reagents to CuI in
THF, without any significant change of the yield of 2.
(Table 3, entry 8) is a key intermediate20 in a total
synthesis of the natural product paeonilactone A.21 The
malonate functionality in 6 did not interfere with the
cross-coupling reaction with MeMgBr; however, 3 equiv
of the Grignard reagent had to be used due to deproto-
nation of the malonate during the reaction.
Aryl Grignard reagents generally gave high yields in
the cross-coupling reaction (Table 4), but the aryl-
substituted cyclohexadiene products are rather unstable
compounds and special precautions have to be taken
during their isolation.22
Dienyl phosphates such as 20a and 20b are attractive
as alternative substrates to dienyl triflates. Cross cou-
plings of related vinyl phosphates with organocuprates
The scope of the reaction was explored utilizing a
catalytic amount of CuI and 1.5 equiv of RMgBr in THF.
The desired 2-substituted 1,3-dienes were formed in good
to excellent yields when different alkyl or allyl Grignard
reagents were employed (Table 3). Longer alkyl chains
(Table 3, entries 1-3), give yields comparable to the GLC
yields obtained for the coupling of 1 with n-BuMgBr.
Introduction of a methyl substituent can be done in
almost quantitative yields (Table 3, entries 6 and 8). It
is noteworthy that also a secondary alkyl Grignard
reagent can be used (Table 3, entries 4 and 5). In
comparison, the cuprate derived from s-BuLi and CuI was
totally unreactive in an attempted stoichiometric cross
coupling. An allyl group can also be introduced in nearly
quantitative yield (Table 3, entry 7). Compound 14
(20) Ro¨nn, M.; J onasson, C.; Ba¨ckvall, J .-E. Manuscript in prepara-
tion.
(21) (a) Hayashi, T.; Shinbo, T.; Shimiuzu, M.; Arisawa, M.; Morita,
N.; Kimura, M.; Matsuda, S.; Kikushi, T. Tetrahedron Lett. 1985, 26,
3699. (b) Ro¨nn, M.; Andersson, P. G.; Ba¨ckvall, J .-E. Acta Chem.
Scand., in press.
(22) Grisdale, P. J .; Regan, T. H.; Doty, J . C.; Figueras, J .; Williams,
J . L. R. J . Org. Chem. 1968, 33, 1116.

2520 J . Org. Chem., Vol. 63, No. 8, 1998
Karlstro¨m et al.
Ta ble 4. Syn th esis of 2-Ar yl-Su bstitu ted 1,3-Dien es fr om
Cyclic Dien yl Tr ifla tes a n d Ar MgBr
The formation of octane can partly be explained by
thermal or oxidative decomposition of the cuprate19 or
by decomposition of the Grignard reagent,25 but a control
experiment under the usual reaction conditions, without
dienyl triflate 1, afforded much less octane. The amount
of 21 formed in couplings with stoichiometric lithium
cuprates was shown to be temperature dependent with
larger amounts being formed at lower temperature (up
to 20%). Compound 21 and other side products were not
detected for reactions that give higher yields of the cross-
coupling product. We propose a mechanism involving an
intermediate Cu(III) species obtained by oxidative addi-
tion of the dienyl triflate to a cuprate (Scheme 1). This
oxidative addition most likely proceed via a π-olefin-
copper complex followed by a nucleophilic vinylic substi-
tution.26 The products obtained from the reaction of 1
with n-BuMgBr (2, octane, 1,3-cyclohexadiene, and oc-
tane) can then arise via different reductive eliminations
from the Cu(III) species. A reductive elimination where
one R group couples to the diene gives the cross-coupling
product. An undesired reductive coupling of the R groups
would produce octane when R ) n-Bu and leave a
(cyclohexadien-2-yl)copper complex. The latter may pro-
duce 1,3-cyclohexadiene or react in a second cycle with
RMgBr and dienyl triflate to produce 21.
aReactions were run at 0 °C in THF with 1.5 equiv of ArMgBr
according to the general procedure in the Experimental Section.
bIsolated yield, after bulb to bulb distillation for aryl-substituted
cyclohexadienes and after column chromatography for aryl-
substituted cycloheptadienes.
Sch em e 1
are known.23 Unfortunately, 20 showed low reactivity
in our system. Dienyl phosphate 20a was totally unre-
active toward both organolithium and Grignard reagent-
derived cuprates. However, 20b reacted with n-BuMgBr
under standard catalytic conditions, but the reaction was
slower than for the corresponding triflate 1, and the yield
of 2 was low (34% by GLC after several hours). An
attempted coupling between 20b and PhMgBr failed to
give the cross-coupling product and 20b was recovered.
This shows the remarkable leaving-group ability of the
triflate group.
Con clu sion
In conclusion, we have developed a general method for
the synthesis of 2-substituted cyclic 1,3-dienes. The
availability of various R,â-unsaturated ketones, as well
as the easy access to various Grignard reagents from the
corresponding halides, should make this method widely
applicable in organic synthesis. The use of catalytic
amounts of copper makes product isolation easier, gives
a cleaner reaction, and is of course advantageous in an
economical and environmental sense.16 An investigation
on the use of acyclic dienyl triflates is on its way and
would add to the generality of this method.
Mech a n ism . The modest yields in the case of cou-
plings between 1 and butyl Grignard reagent (and other
alkyl Grignards, except methyl) are explained by the
formation of cyclohexadiene (ca 20%), bicyclohexadienyl
(21) (5-10% for catalytic couplings with n-BuMgBr), and
octane (20-30%). With 7 as substrate the symmetrical
coupling product 22 can be isolated. These side products
are in agreement with those previously observed in
couplings between vinyl halides and copper reagents.24
Exp er im en ta l Section
NMR spectra were recorded for CDCl3 solutions (1H at 400
MHz and 13C at 100.5 MHz) using tetramethylsilane (0.0 ppm)
1
or residual CHCl3 (7.26 ppm) as internal standards in H NMR
(23) (a) Blaszczak, L.; Winkler J .; O’Kuhn S. Tetrahedron Lett. 1976,
4405. (b) Claesson, A.; Quader, A.; Sahlberg, C. Tetrahedron Lett. 1983,
24, 1297.
(24) (a) Normant, F. Pure Appl. Chem. 1978, 50, 709. (b) Corey, E.
J .; Posner, G. H. J . Am. Chem. Soc. 1968, 90, 5615. (c) Whitesides, G.
M.; Fischer, W. F., J r.; San Filippo, J ., J r; Bashe, R. W.; House, H. O.
J . Am. Chem. Soc. 1969, 91, 4871.
(25) Kharasch, M. S.; Reinmuth, O. Grignard Reactions of Nonme-
tallic Substances; Prentice Hall: New York, 1954; Chapter 2.
(26) For a discussion of the mechanism of a related nucleophilic
vinylic substitution see: Maffeo, C. V.; Marchese, G.; Naso, F.; Ronzini,
L. J . Chem. Soc., Perkin Trans. 1 1979, 92.

Reaction of Dienyl Triflates with Grignard Reagents
J . Org. Chem., Vol. 63, No. 8, 1998 2521
and CDCl3 (77.0 ppm) in 13C NMR. Mass spectra were
obtained in GC/MS or direct inlet mode (EI, 70 eV). Ether
and THF were dried over Na-benzophenone prior to use.
Diisopropylamine was dried over CaH2 and distilled im-
mediately before use. 2-Cyclohexen-1-one and 4,4-diphenyl-
2-cyclohexen-1-one were purchased from Aldrich. N-Phenylbis-
(trifluoromethanesulfonimide) (Tf2NPh) was obtained from
Lancaster. Grignard reagents were bought from Aldrich
(MeMgBr, PhMgBr, allylMgBr) or prepared by standard
procedures as solutions in ether or THF. Grignard reagents
and organolithium reagents were always standardized before
use.27 2-Cycloheptenone was prepared from cycloheptene via
allylic oxidation,28 followed by hydrolysis and oxidation, or from
cycloheptanone by the method of Trost et al.29 4-(Dicar-
bomethoxymethyl)-2-cyclohexenone20 was prepared in several
steps from 1,3-cyclohexadiene via 1-acetoxy-4-(dicarbo-
methoxymethyl)-2-cyclohexene.30 All copper-mediated reac-
tions were run under an argon atmosphere. Slow addition was
performed by the use of a syringe pump. Merck silica gel 60
(240-400 mesh) was used for flash chromatography.
1,3-Cycloh ep ta d ien -2-yl tr ifla te (14)32 was obtained from
2-cycloheptenone following the above procedure: colorless
liquid; 79% yield after column chromatography (pentane).
Spectral data were consistent with those previously reported.32
Typ ica l P r oced u r e for Cr oss-Cou p lin gs of 1 w ith
P r efor m ed Lith iu m Or ga n o Cu p r a tes (Ta ble 1). To a
slurry of CuX (1 mmol) in THF or ether (10 mL) at -20 °C,
under an argon atmosphere, was added RLi (2 mmol) via
syringe. After 30 min, the temperature was adjusted to the
value indicated in Table 1 and 1 (0.5 mmol) was added via
syringe. The reaction mixture was stirred until completion
as judged by TLC. Aqueous NH4Cl and ether were added to
quench the reaction. n-Decane (0.5 mmol) was added as
internal standard, and a sample was taken for GLC analysis.
The aqueous layer was extracted with pentane/ether (50:50)
twice, and the combined organic layers were subsequently
washed with brine and dried (MgSO4). The diene obtained
was isolated after evaporation of the solvent in vacuo, followed
by column chromatography or bulb-to-bulb distillation.
1,3-Cycloh exa d ien -2-yl Tr ifla te (1).31 Gen er a l P r oce-
Typical P r ocedu r e Em ployin g Stoich iom etr ic Am ou n ts
of a P r efor m ed Ma gn esiu m Dibu tylcu p r a te in th e Rea c-
tion w ith 1 (Ta ble 1). To a slurry of CuX (0.6 mmol) in THF
(10 mL) at -20 °C under an argon atmosphere was added
BuMgY (1.3 mmol) via syringe. After 30 min, the temperature
was adjusted to the value indicated in Table 1, and 1 (0.5
mmol) was added via syringe. The reaction mixture was
stirred until completion (usually within minutes) as judged
by TLC. Aqueous NH4Cl and ether were added to quench the
reaction. n-Decane (0.5 mmol) was added as internal stan-
dard, and a sample was taken for GLC analysis. The aqueous
layer was extracted with pentane/ether (50:50) twice, and the
combined organic layers were subsequently washed with brine
and dried (MgSO4). Crude 2 (as a mixture with n-octane and
20) was obtained by evaporation of the solvent in vacuo.
d u r e for th e Syn th esis of Cyclic Dien yl Tr ifla tes.
A
solution of LDA (14.4 mmol) in THF (20 mL) was prepared
from diisopropylamine (1.89 mL, 14.4 mmol) and n-butyl-
lithium (1.6 M in hexane, 9.0 mL, 14.4 mmol) at 0 °C under
N2. The resulting solution was cooled to -78 °C by means of
a dry ice/acetone bath. 2-Cyclohexenone (1.26 g, 13.1 mmol)
in THF (20 mL) was added dropwise, and the reaction mixture
was stirred for 30 min at -78 °C. A solution of Tf2NPh (5 g,
14.0 mmol) dissolved in THF (20 mL) was then added. After
complete addition, the reaction mixture was warmed to 0 °C
and stirred at this temperature until the reaction was judged
complete according to TLC (1-2 h). The solvent was evapo-
rated, and the crude material was dissolved in ether and
washed with water twice. The organic layer was dried (Na2-
SO4) and concentrated in vacuo. The crude product was
purified by column chromatography (pentane) to yield 2.41 g
(80%) of 1 as a colorless liquid, which had an 1H NMR
spectrum in accordance with a literature spectrum:31 1H NMR
δ 6.01 (dtd, J ) 0.8, 4.3, 10.1 Hz, 1H), 5.82 (dq, J ) 2.2, 10.1
Hz, 1H), 5.68 (ddt, J ) 4.7, 2.2, 0.8 Hz, 1H), 2.43-2.35 (m,
2H), 2.29-2.20 (m, 2H); 13C NMR δ 145.9, 131.5, 120.9, 118.6
(q, J (13C,19F) ) 320 Hz), 114,6, 21.6, 21.4.
Typ ica l P r oced u r e for Rea ction s of Cyclic Dien yl
Tr ifla tes w ith Gr ign a r d Rea gen ts Em p loyin g a Ca ta lytic
Am ou n t of a Cu (I) Sa lt (Ta bles 3 a n d 4). CuI (2 mg, 0.01
mmol) was suspended in THF under an atmosphere of argon,
at the temperature indicated in Table 3 or 4. The dienyl
triflate (1 mmol) was added. The Grignard reagent (1.5 mmol)
was then added via syringe, and the mixture was stirred at
the chosen temperature until judged complete according to
TLC (<15 min.). The reaction was quenched by addition of
aqueous NH4Cl and ether. n-Decane (1 mmol) was added as
internal standard if the mixture was to be analyzed by GLC,
and a sample was taken. Ether and water were added, and
the water phase was extracted with ether twice. The combined
organic layers were washed with brine, dried (MgSO4), and
evaporated in vacuo. The crude product was purified by the
method stated for each compound below.
5,5-Dip h en yl-1,3-cycloh exa d ien -2-yl tr ifla te (5) was
obtained from 4,4-diphenyl-2-cyclohexenone following the
procedure above: viscous oil; 89% yield after column chroma-
tography (pentane/ether 99:1): 1H NMR δ 7.31-7.17 (m, 10H),
6.45 (dd, J ) 0.8, 10.1 Hz, 1H), 5.98 (dd, J ) 2.2, 10.1 Hz,
1H), 5.80 (dtd, J ) 4.8, 2.3, 0.8 Hz, 1H), 3.06 (d, J ) 4.8 Hz,
2H); 13C NMR δ 146.6, 145.3, 139.1, 128.2, 127.2, 126.7, 120.1,
118.5 (q, J (13C,19F) ) 321 Hz), 113.7, 47.7, 36.3; IR (CDCl3)
3062, 1657, 1597, 1492, 1423, 1228, 1137, 1090, 861 cm-1
.
4-Dim eth ylm alon ate-1,3-cycloh exadien -2-yl tr iflate (6)20
was obtained from 4-(dicarbomethoxymethyl)-2-cyclohex-
enone20 following the general procedure above, with the
exception that 2.1 equiv of LDA was used and the reaction
mixture was stirred for 3 h at -78 °C before addition of Tf2-
NPh: clear oil; 55% yield after column chromatography
Da ta for Selected Cr oss-Cou p lin g P r od u cts. 2-n -Bu -
tyl-1,3-cycloh exa d ien e (2) was purified by column chroma-
tography (pentane) followed by bulb-to-bulb distillation: 1H
NMR δ 5.82 (m, 2H), 5.46 (m, 1H), 2.09 (m, 4H), 2.00 (m, 2H),
1.42-1.25 (m, 4H), 0.90 (t, J ) 7.3 Hz, 3H); 13C NMR δ 136.0,
127.3, 126.5, 119.9, 35.3, 30.6, 22.4, 22.35, 22.3, 14.0; IR 3032,
2930, 1466, 1165 cm-1
.
1
(pentane/ether 75:25); H NMR δ 5.98 (dd, J ) 10.2, 4.3 Hz,
2-P h en yl-1,3-cycloh exa d ien e (3)10,33 was purified by fil-
tration through alumina followed by bulb-to-bulb distillation.
Spectral data are consistent with those previously reported.10,33
2-Meth yl-1,3-cycloh exa d ien e (4)34 was purified by distil-
lation. Spectral data are consistent with those previously
reported.34
1H), 5.89 (dt, J ) 10.2, 2.0 Hz, 1H), 5.68 (dt, J ) 2.1, 4.9 Hz,
1H), 3.74 (dd, J ) 5.2, 0.6 Hz, 6H), 3.51 (d, J ) 9.0 Hz, 1H),
3.15 (m, 1H), 2.56 (m, 1H), 2.33 (m, 1H); 13C NMR δ 168.1,
168.0, 145.3, 132.0, 122.0, 118.5 (q, J (13C,19F) ) 319 Hz), 114.0,
53.6, 52.7, 52.6, 32.0, 25.5.
(27) (a) Watson, S. C.; Eastman, J . F. J . Organomet. Chem. 1967,
9, 165. (b) Bergbreiter, D. E.; Pendergrass, E. J . Org. Chem. 1981, 46,
219.
(28) Hansson, S.; Heumann, A.; Rein, T.; Åkermark, B. J . Org.
Chem. 1990, 55, 975.
(29) Trost, B. M.; Salzmann, T. N.; Hiroi, K. J . Am. Chem. Soc. 1976,
98, 4887.
(32) (a) Lamparter, E.; Hanack, M. Chem. Ber. 1973, 106, 3216. (b)
Garcia Fraile, A.; Garcia Martinez, A.; Herrera Fernandez A.; Sanches
Garcia, J . M. An. Qu´ım. 1979, 75, 723. (c) Garcia Martinez, A.; Herrera
Fernandez A. An. Quı´m. 1978, 74, 789.
(33) Becker, K. B. Synthesis 1980, 238.
(30) Ba¨ckvall, J .-E.; Vågberg, J . Org. Synth. 1990, 69, 38.
(31) Wulff, W. D.; Peterson, G. A.; Bauta, W. E.; Chan, K.-S.; Faron,
K. L.; Gilbertson, S. R.; Kaesler, R. W.; Yang, D. C.; Murray, C. K. J .
Org. Chem. 1986, 51, 277.
(34) (a) Paquette, L. A.; Bellamy, F.; Wells, G. J .; Bo¨hm, M. C.;
Gleiter, R. J . Am. Chem. Soc. 1981, 103, 7122. (b) Parsons, E. J .;
J ennings, P. W. Organometallics 1988, 7, 1435. (c) Ba¨ckvall, J .-E.;
Bystro¨m, S. E.; Nordberg, R. E. J . Org. Chem. 1984, 49, 4619.

2522 J . Org. Chem., Vol. 63, No. 8, 1998
Karlstro¨m et al.
1
2-[4-(P h en ylm eth oxy)bu tyl]-1,3-cycloh exa d ien e (9)11a
was purified by column chromatography (pentane/ether 99:
1). Spectral data are consistent with those previously
reported.11a
2,2′-Bis(1,3,cycloh ep ta d ien yl) (22): H NMR δ 5.98 (m,
6H), 2.19 (m, 8H), 1.93 (m, 4H); 13C NMR δ 140.4, 133.9, 129.5,
128.3, 31.2, 29.8, 28.7.
Ackn owledgm en t. Financial support from the Swed-
ish Natural Science Research Council is gratefully
acknowledged.
5-(Dica r bom eth oxym eth yl)m a lon a te-2-m eth yl-1,3-cy-
cloh exa d ien e (14)20 was isolated as a clear colorless oil after
column chromatography (pentane/Et2O 75:25): 1H NMR δ 5.85
(app dt, J ) 9.6, 1.5 Hz, 1H), 5.74 (dd, J ) 9.6, 4.5 Hz, 1H),
5.42 (m, 1H), 3.72 (s, 3H), 3.48 (d, J ) 9.6 Hz, 1H), 2.96 (m,
1H), 2.28 (m, 1H), 2.01 (m, 1H), 1.72 (app q, J ) 1.8 Hz, 3H);
13C NMR δ 168.8, 168.7, 131.4, 129.5, 126.6, 119.2, 54.1, 52.4,
52.3, 32.6, 26.5, 20.9; IR 2955, 1732, 1436, 1333, 1252, 1215,
Su p p or tin g In for m a tion Ava ila ble: Experimental and
characterization data for compounds 8, 10-13, and 15-19.
Copies of H and 13C NMR spectra for compounds 2, 5, 6, 8,
1
10, 11, 14-19, and 22 (14 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
1195, 1158 cm-1
.
Sp ectr a l Da ta for Sid e P r od u cts in th e Cr oss-Cou p lin g
Rea ction . 2,2′-Bis(1,3,cycloh exa d ien yl) (21).35 Compound
21 is unstable and could not be isolated in pure form. Any
attempts resulted in polymerization: 1H NMR δ 6.20 (dq, J )
9.9, 1.7 Hz, 2H), 5.95 (dtd, J ) 9.9, 4.3, 0.8 Hz, 2H), 5.88 (m,
2H), 2.23 (m, 4H), 2.12 (m, 4H); 13C NMR δ 133.8, 127.6, 124.1,
120.0, 22.7, 22,1.
J O971737I
(35) Williamson, J . R.; Mallakpour, S. E. Iran. J . Chem. Chem. Eng.
1991, 10, 66; Chem. Abstr. 1992, 117, 251034t. CAS registry no.
provided by the author: 144558-82-7.