Unsaturated aldehydes as alkene equivalents in the Diels-Alder reaction

Article abstract of DOI:10.1002/chem.200800003

A one-pot procedure is described for using α,β-unsaturated aldehydes as olefin equivalents in the Diels-Alder reaction. The method combines the normal electron demand cycloaddition with aldehyde dienophiles and the rhodium-catalyzed decarbonylation of aldehydes to afford cyclohexenes with no electron-with-drawing substituents. In this way, the aldehyde group serves as a traceless control element to direct the cycloaddition reaction. The Diels-Alder reactions are performed in a diglyme solution in the presence of a catalytic amount of boron trifluoride etherate. Subsequent quenching of the Lewis acid, addition of 0.3% of [Rh(dppp)₂Cl] and heating to reflux achieves the ensuing decarbonylation to afford the product cyclohexenes. Under these conditions, acrolein, crotonaldehyde and cinnamaldehyde have been reacted with a variety of 1,3-dienes to afford cyclohexenes in overall yields between 53 and 88%. In these transformations, the three aldehydes serve as equivalents of ethylene, propylene and styrene, respectively.

Full text of DOI:10.1002/chem.200800003

DOI: 10.1002/chem.200800003
Unsaturated Aldehydes as Alkene Equivalents in the Diels–Alder Reaction
Esben Taarning and Robert Madsen*[a]
Abstract: A one-pot procedure is de-
scribed for using a,b-unsaturated alde-
hydes as olefin equivalents in the
Diels–Alder reaction. The method
combines the normal electron demand
cycloaddition with aldehyde dieno-
philes and the rhodium-catalyzed de-
carbonylation of aldehydes to afford
cyclohexenes with no electron-with-
drawing substituents. In this way, the
aldehyde group serves as a traceless
control element to direct the cycloaddi-
tion reaction. The Diels–Alder reac-
tions are performed in a diglyme solu-
tion in the presence of a catalytic
amount of boron trifluoride etherate.
Subsequent quenching of the Lewis
acid, addition of 0.3% of [Rh-
ACHTRE(UNG dppp)2Cl]and heating to reflux ach-
ieves the ensuing decarbonylation to
afford the product cyclohexenes.
Under these conditions, acrolein, croto-
naldehyde and cinnamaldehyde have
been reacted with a variety of 1,3-
dienes to afford cyclohexenes in overall
yields between 53 and 88%. In these
transformations, the three aldehydes
serve as equivalents of ethylene, pro-
pylene and styrene, respectively.
Keywords: aldehydes
·
cyclo-
AHCTREaUGN lkenes · decarbonylation · Diels–
Alder reaction · homoCAHTREgUNG eneous cat-
alysis
Introduction
developed by using electron-withdrawing groups on the di-
enophile that can be removed in a subsequent reduction.
The most popular group is the phenylsulfonyl group,[7,8] but
ethylthio,[9] nitro[10] and dichloroboryl[11] groups have also
been employed. In all four cases, the Diels–Alder reaction is
achieved under thermal conditions while the subsequent re-
moval of the electron-withdrawing group is accomplished in
the presence of either sodium amalgam (for PhSO2),[7]
Raney-Nickel (for EtS),[9] Bu3SnH/AIBN (for NO2),[10] or by
The Diels–Alder reaction is one of the most powerful meth-
ods in organic chemistry for synthesis of six-membered car-
bocyclic compounds.[1,2] The [4 +2]cycloaddition between a
1,3-diene and a dienophile gives rise functionalized cyclo-
hexenes with good control of both regio-, enantio-, and dia-
stereoselectivity.[2,3] The reaction has found widespread ap-
plication in the synthesis of natural products and other bio-
logically active molecules.[4,5] In the normal Diels–Alder re-
action the reactivity is governed by the energy difference
between the HOMO of the diene and the LUMO of the di-
enophile. The energy of the latter is lowered by electron-
withdrawing substituents and the most common dienophiles
contain carbonyl, cyano, sulfonyl or nitro groups. The effect
is enhanced by coordination to Lewis acids which are
known to accelerate Diels–Alder reactions substantially. For
the same reason, the cycloaddition with simple olefins as di-
enophiles is a poor reaction which requires high tempera-
ture and pressure.[6] Instead, olefin equivalents have been
a
three-step sequence (for BCl2) involving oxidation
(NaOH/H2O2), mesylation (MsCl/pyridine) and reduction
(LiEt3BH).[11] However, the use of stoichiometric reducing
agents for the removal of these groups diminishes the atom
economy of the overall transformation. Hence, we envi-
sioned to use a,b-unsaturated aldehydes for the Diels–Alder
reaction followed by removal of the aldehyde group by a
metal-catalyzed decarbonylation in the same pot. This
tandem Diels–Alder decarbonylation sequence would offer
a more expedient procedure for the cycloaddition with
olefin equivalents and at the same time be able to maintain
the regio- and stereoselectivity that characterizes the normal
Diels–Alder reaction.
The catalytic decarbonylation of aldehydes can be ach-
ieved with rhodium catalysts at elevated temperatures.[12,13]
The most reactive catalysts are rhodium(I) complexes con-
taining bi- or tridentate phosphine ligands.[13] In a recent
study, 1,3-bis(diphenylphosphino)propane (dppp) was shown
to be the ligand of choice for this transformation among a
[a]E. Taarning, Prof. Dr. R. Madsen
Center for Sustainable and Green Chemistry
Department of Chemistry, Building 201
Technical University of Denmark, 2800 Kgs. Lyngby (Denmark)
Fax : (+45)4593-3968
E-mail: rm@kemi.dtu.dk
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
5638
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 5638 – 5644

FULL PAPER
range of phosphine ligands.[14] The corresponding complex
[Rh(dppp)2Cl]has been used for decarbonylation of a varie-
As a result, it was decided to use Lewis acid catalysis to
increase the rate of the cycloaddition reaction. Several
Lewis acids were selected and the reactions were investigat-
ACHTREUNG
ty of different aldehydes ranging from unprotected carbohy-
drates[15] to aldehydes in natural product syntheses.[16] The
complex can be prepared in two steps from commercially
available RhCl3·3H2O by conversion into [Rh(cycloocte-
ne)2Cl]2 followed by ligand exchange with dppp.[17] Alterna-
tively, the active catalyst can be generated in situ from the
same components if the decarbonylation is performed in a
diglyme solution.[14] Very recently, the mechanism for the
decarbonylation was studied by experimental and theoreti-
cal methods and shown to proceed by an oxidative addition
Table 1. Diels–Alder reaction with acrolein catalyzed by various Lewis
acids.[a]
Entry
Catalyst
Conversion
of diene [%][b]
1
ZnCl2
ZnCl2
AlCl3
BF3·OEt2
FeCl3
0
>99
43
>99
37
À
into the aldehyde C H bond followed by a rate-limiting ex-
2[c]
3
trusion of carbon monoxide and reductive elimination.[18]
Herein, we describe the development of a,b-unsaturated
aldehydes as alkene equivalents in the Diels–Alder reaction.
Acrolein and substituted acroleins are added to various 1,3-
dienes followed by a rhodium-catalyzed decarbonylation in
the same pot to remove the aldehyde group (Scheme 1).
4[d]
5[e]
6
La
A
0
7
8
Sc
Bi
C
66
75
[a]To a solution of 2,3-dimethyl-1,3-butadiene (5 mmol) and acrolein
(7.5 mmol) in diglyme (5 mL) was added the Lewis acid (0.25 mmol) and
the mixture was stirred at room temperature for 60 min. [b]Determined
by GC. [c]Under neat conditions for 40 min. [d]Reaction time 10 min
with 89% isolated yield of 3,4-dimethyl-3-cyclohexene-1-carbaldehyde.
[e]Some by-products are visible by GC analysis.
Scheme 1. One-pot Diels–Alder decarbonylation reaction.
ed under neat conditions as well as in the presence of a sol-
vent (Table 1). In the latter case, diglyme was chosen as the
solvent since it had shown good results in the decarbonyla-
tion reaction.[14,15] Zinc chloride was found to be an excel-
lent catalyst under neat conditions with full conversion in
40 min while no reaction occurred in a diglyme solution (en-
tries 1 and 2). Furthermore, subsequent addition of [Rh-
Results and Discussion
Acrolein as dienophile: The initial experiments were carried
out under thermal conditions in the presence of [Rh-
A
ACHTRE(UNG dppp)2Cl]and heating to 170 8C resulted in complete decar-
bonylation. However, extensive isomerization of the double
bond in the product also occurred, which is most likely
caused by the presence of zinc chloride at elevated tempera-
ture. Thus, it appears necessary to remove or quench the
Lewis acid prior to increasing the temperature in order to
avoid product isomerization. Unfortunately, it was not possi-
ble to quench zinc chloride with reagents like water or eth-
ylenediamine. Instead, a number of other Lewis acids were
investigated (entries 3–8). Aluminum chloride and BF3·OEt2
gave rise to a highly exothermic reaction under neat condi-
tions which led to instantaneous decomposition of the start-
ing materials. In diglyme, however, the reactivity of the two
Lewis acids was lowered significantly and an efficient Diels–
Alder reaction could be achieved with the latter. The cyclo-
addition went to completion in 10 min at room temperature
with 5% of BF3·OEt2 and afforded the product in 89% iso-
lated yield. The conversion with aluminum chloride and
other Lewis acids were slower.
ACHTREUNG
tion between acrolein and simple dienes will occur at tem-
peratures around 1008C[19] while the catalytic decarbonyla-
tion requires a temperature around 1508C.[14–16] Therefore,
we were confident that the Diels–Alder reaction would
occur before the decarbonylation. Indeed, when the auto-
clave was heated to 1708C for 24 h, the reaction mixture
consisted of 66% of 1-methylcyclohexene and 34% of the
Diels–Alder adduct that had not undergone decarbonyla-
tion. Unfortunately, it was not possible to push the decar-
bonylation to completion under these conditions. By com-
parison, the decarbonylation of the same aldehyde in an
open flask at 1708C only required 4 h for full conversion.
Thus, it was apparent that the liberated carbon monoxide
hampered the decarbonylation in the autoclave and it was
therefore decided to pursue the tandem reaction in an open
system. In this case, 2,3-dimethyl-1,3-butadiene (b.p. 688C)
was selected as the diene and reacted with acrolein at
reflux. However, due to the low boiling point of acrolein,
the cycloaddition required 30 h for complete conversion.
More hindered dienes required even longer reaction times
and this procedure was therefore not suitable for general
use.
Again, it was necessary to quench the Lewis acid before
the decarbonylation could be achieved. This could be per-
formed by adding one equivalent of K2HPO4 relative to
BF3·OEt2 together with a small amount of water which did
not interfere with the ensuing decarbonylation reaction. On
the contrary, neutralizing BF3·OEt2 with Na2CO3 or K2CO3
Chem. Eur. J. 2008, 14, 5638 – 5644
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5639

R. Madsen and E. Taarning
caused the decarbonylation to proceed slowly and gave rise
to side products and precipitation of rhodium metal.
To examine the scope and limitations of this new one-pot
protocol, a number of other dienes were also subjected to
the reaction with acrolein (Table 2, entries 2–10). In general,
the Diels–Alder decarbonylation sequence worked very well
for a variety of hydrocarbon dienes where yields around
80% were typically obtained (entries 2–6). It should be
noted that some of the products are highly volatile and thus
difficult to isolate quantitatively. Ether and ester functionali-
ties can also be accommodated in the diene (entries 7–10),
although the 1,4-disubstituted dienes in entries 8–10 reacted
significantly slower than the other dienes. The longer reac-
tion time in the Diels–Alder reaction resulted in a slightly
decreased yield of the product cyclohexenes due to a slow
acid-catalyzed decomposition of the allyl ether and ester
dienes. No sign of a retro Diels–Alder reaction was ob-
served when the intermediate aldehydes were heated to
1628C during the decarbonylation reaction. Several dienes
failed to undergo the cycloaddition in the presence of
BF3·OEt2. Furan underwent polymerization while dienes
with conjugating electron-withdrawing groups such as sorbic
aldehyde and b-ionone did not react with acrolein. In all
cases, except for entry 1, did the Diels–Alder reaction fur-
nish more than one aldehyde (regioisomers and exo/endo
isomers). Particularly, the reaction with the 1,4-disubstituted
dienes led to the formation of all four isomeric aldehydes.
However, after decarbonylation they all gave rise to the
same cyclohexene product which illustrates the benefit of
the one-pot procedure where no work-up of the intermedi-
ate aldehyde is required.
Earlier studies on simple aldehydes had shown that the
decarbonylation could be achieved with an in situ generated
catalyst from RhCl3·3H2O and dppp.[14] Addition of these
two reagents to the Diels–Alder adduct did result in the de-
sired decarbonylation upon heating, but the reaction was ac-
companied by severe double bond isomerization. It was not
possible to add RhCl3·3H2O and dppp before the Diels–
Alder reaction since dppp catalyzes a rapid polymerization
of acrolein. Therefore, it was decided to use [RhCAHTRE(UNG dppp)2Cl]
for the decarbonylation. This complex was prepared by a
new one-step procedure where RhCl3·3H2O was treated
with two equivalents of dppp in an ethanol solution at reflux
for 30 min followed by removal of the solvent in vacuo. This
afforded a crude [RhACHTRE(UGN dppp)2Cl]complex which was equal in
reactivity to the catalyst formed by the previous two-step
procedure.[17] With 0.3% of the crude complex the decar-
bonylation could be achieved in 20 h to afford the desired
1,2-dimethylcyclohexene in 86% isolated yield from the
starting diene (Table 2, entry 1). The progress of the decar-
bonylation could be monitored by measuring the evolution
of carbon monoxide. Diglyme was removed in an aqueous
work-up and the product was isolated by extraction with
pentane and subsequent distillation.
Table 2. Acrolein as ethylene synthon in the Diels–Alder reaction.[a]
Other a,b-unsaturated aldehydes as dienophiles: With the
successful application of acrolein as an ethylene equivalent
the studies were now extended to other unsaturated alde-
hydes. Since the Diels–Alder reaction is also highly sensitive
to substituents in the dienophile it was decided first to ex-
amine the rate of the BF3·OEt2-catalyzed cycloaddition reac-
tion with various aldehydes. As shown above, the reaction
between 2,3-dimethyl-1,3-butadiene and acrolein goes to
completion within 10 min in diglyme with 5% of BF3·OEt2
(Table 1, entry 4). Changing the solvent to diethyl ether had
no influence on the rate of the cycloaddition (Table 3,
entry 1). However, the reactions with substituted acroleins
were slower and it was necessary to use a larger amount of
the Lewis acid. With 10% of BF3·OEt2 the reaction with
methacrolein went to completion in 30 min and proceeded
very cleanly to give the product in high yield (entry 2). The
reactions with crotonaldehyde and cinnamaldehyde were
significantly more sluggish, but full conversion could still be
Entry
1
Diene
Product
Yield [%][b]
86
2
3
4
65
77
75
5
81
6
84
79
7[c]
8
66
53
61
obtained within
a reasonable timeframe (Figure 1 and
Table 3, entries 3 and 4). This, however, was not possible
with 3-methylcrotonaldehyde where only trace amounts of
the cycloaddition product was obtained even with very long
reaction times and up to 30% of BF3·OEt2 (Figure 1). The
use of other Lewis acids such as zinc chloride and bismuth
triflate did not improve the yield of the cycloaddition prod-
uct. In this connection, it should be noted that 3-methylcro-
tonaldehyde is known to give a poor yield in the thermal
9[d]
10[c]
[a]Reactions were carried out on a 5–40 mmol scale in diglyme (1 m solu-
tion) with 6–10% of BF3·OEt2 for the Diels–Alder reaction (10–300 min
at RT) and 0.3% of [RhACHTRE(UNG dppp)2Cl]for the decarbonylation (8–20 h at
reflux). [b]Isolated yield. [c]1% [Rh
ylation took 42 h.
ACHTRE(UNG dppp)2Cl]was used. [d]Decarbon-
5640
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 5638 – 5644

Diels–Alder Reactions
FULL PAPER
Table 3. BF3·OEt2-catalyzed Diels–Alder reaction with 2,3-dimethyl-1,3-butadiene and a,b-unsaturated alde-
tribranched aldehyde could be
decarbonylated slowly at a tem-
perature around 2158C. How-
ever, under these forcing condi-
tions the reaction was accompa-
nied by small amounts of prod-
uct from double-bond isomeri-
zation which could not be
separated. As a result, it was
decided to abandon methacro-
lein as a propylene synthon.
Instead, crotonaldehyde was
examined and in this case the
decarbonylation proceeded at
1628C without any side reac-
tions. Three different dienes
were subjected to the one-pot
hydes.[a]
Entry
Dienophile
BF3·OEt2
loading [%]
Reaction
time
Product
Yield [%][b]
1[c]
5
10 min
30 min
6 h
87
95
89
2
10
10
3
4
15
24 h
74
Diels–Alder
decarbonylation
sequence in diglyme to afford
the product cyclohexenes in
good yields (Table 4, entries 1–
[a]Reactions were performed with 30 mmol of diene and 45 mmol of dienophile in 30 mL of diglyme. [b]Iso-
lated yield. [c]Diethyl ether was used instead of diglyme.
Scheme 2. Regioselectivity with methacrolein and crotonaldehyde.
3). In the latter two cases very small amounts of the corre-
sponding regioisomers were also obtained according to anal-
ysis by GC-MS.
~
:
Figure 1. Comparison of the cycloaddition rate for crotonaldehyde (
*
10% BF3·OEt2), cinnamaldehyde ( : 15% BF3·OEt2) and 3-methylcroto-
Cinnamaldehyde can serve as a styrene equivalent in the
Diels–Alder reaction when followed by the decarbonylation.
Although, the cycloaddition reaction with cinnamaldehyde
is slower than for crotonaldehyde, the same three dienes
still reacted to completion within 24 h (entries 4–6). Subse-
quent quenching of BF3·OEt2 and heating with the rhodium
catalyst achieved the decarbonylation in a satisfying overall
yield and with excellent regioselectivity for the last two
cases. It should be noted that this procedure with olefin
equivalents gives rise to the opposite regioisomer as com-
pared to the thermal Diels–Alder reaction with substituted
olefins.[20] For example, the thermal reaction between iso-
prene and styrene at 2008C affords the product in entry 5 as
a 2:7 mixture of “meta” and “para” in 31% yield.[21]
&
naldehyde ( : 10% BF3·OEt2) in the reaction with 2,3-dimethyl-1,3-buta-
diene.
Diels–Alder reaction[19] and we are not aware of any suc-
cessful Lewis acid-catalyzed cycloadditions with this dieno-
phile.
With the optimized cycloaddition reaction available the
stage was now set to investigate the one-pot sequence with
the substituted dienophiles. Methacrolein and crotonalde-
hyde can both serve as propylene equivalents, but will give
rise to different regioisomeric products. Methacrolein will
mainly afford the “para” product after decarbonylation
while crotonaldehyde will furnish the corresponding “meta”
product (Scheme 2). Unfortunately, the decarbonylation of
the Diels–Alder adduct from methacrolein did not proceed
at 1628C. This is probably due to the steric bulk in the a-tri-
branched aldehyde (see Table 3, entry 2) and has previously
been observed with a similar hindered aldehyde.[14] The tem-
perature was therefore raised and it turned out that the neat
Conclusion
In summary, we have shown that a,b-unsaturated aldehydes
can serve as olefin equivalents in the BF3·OEt2-catalyzed
Diels–Alder reaction with 1,3-dienes when the cycloaddition
Chem. Eur. J. 2008, 14, 5638 – 5644
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5641

R. Madsen and E. Taarning
Table 4. Diels–Alder decarbonylation protocol with various a,b-unsaturated aldehydes.[a]
30 min. The mixture was then concen-
trated to afford crude [RhACHTREUNG(dppp)2Cl]
as a yellow solid which was dissolved
in diglyme (2 mL). Another flask was
charged with diglyme (40 mL), diene
(39 mmol) and aldehyde (60 mmol)
followed by addition of BF3·OEt2
(0.30–0.74 mL, 2.4–5.9 mmol). The
mixture was stirred at room tempera-
ture until the cycloaddition had gone
to completion according to GC or
TLC. The mixture was quenched with
Entry
Diene
Dienophile
Major
product
Regioisomer
ratio
Yield [%][b]
1[c]
–
86
67
K2HPO4·3H2O
(0.60–1.2 g,
2.4–
5.9 mmol) and water (0.25 mL). The
above catalyst solution was added and
the reaction was degassed and heated
to reflux until the decarbonylation had
gone to completion. The mixture was
cooled to room temperature, diluted
with water (50 mL) and extracted with
pentane (5”50 mL). The combined or-
ganic phases were washed with water
(5”50 mL) and dried with anhydrous
Na2SO4. Pentane was removed by dis-
tillation followed by isolation of the
product cyclohexene by either distilla-
tion or flash chromatography. The de-
carbonylation could be monitored by
measuring the evolution of carbon
monoxide. This was achieved by con-
necting the reaction flask to a burette
filled with water. The bottom of the
burette was further connected to a re-
servoir flask with water. In this way,
carbon monoxide from the reaction
forces water from the burette into the
reservoir flask.
2[c]
24:1
3[c]
24:1
88
4[d]
–
73
59
5[d]
39:1
6[d]
39:1
75
[a]Reactions were carried out with 10–15% of BF 3·OEt2 for the Diels–Alder reaction and 0.3% of [Rh-
ACHTREUNG(dppp)2Cl]for the decarbonylation (14–30 h). [b]Isolated yield of both isomers. [c]10% of BF 3·OEt2 was used
for 5–6 h. [d]15% of BF 3·OEt2 was used for 24 h.
1,2-Dimethylcyclohexene: b.p. 134–
1368C
(lit.[11]
b.p.
135–1368C);
1H NMR (CDCl3, 300 MHz): d=1.50–
1.60 (m, 4H), 1.61 (s, 6H), 1.86–
1.97 ppm (m, 4H); 13C NMR (CDCl3,
is combined with a rhodium-catalyzed decarbonylation in
the same pot. In this way, the aldehyde group functions as a
traceless control element which directs both reactivity and
regioselectivity in the overall transformation. Acrolein, cro-
tonaldehyde and cinnamaldehyde were shown to act as syn-
thons for ethylene, propylene and styrene, respectively, and
good yields were obtained of the product cyclohexenes. Al-
though, the decarbonylation is performed at 1628C, the re-
action still tolerates a number of functional groups in the
substrates including esters, silyl ethers and isolated olefins.[22]
The two-step procedure generates only a minimum amount
of waste compared to previous methods[7–11] since both reac-
tions are performed with only a catalytic amount of an addi-
tive. Thus, we believe this procedure will be a valuable new
tool for synthesis of certain cyclohexenes from cheap start-
ing materials in an atom-economical fashion.
75 MHz): d=19.14, 23.46, 31.71, 125.60 ppm; MS: m/z: 110 [M]+.
1-Methylcyclohexene: b.p. 107–1108C (lit.[23] b.p. 106–1108C); 1H NMR
(CDCl3, 300 MHz): d=1.49–1.67 (m, 4H), 1.64 (s, 3H), 1.87–2.01 (m,
4H), 5.36–5.42 ppm (tdd, 1H, J=1.5, 3.4, 5.2 Hz); 13C NMR (CDCl3,
75 MHz): d=22.37, 22.99, 23.94, 25.28, 30.02, 121.10, 134.05 ppm; MS: m/
z: 96 [M]+.
1-(4-Methyl-3-pentenyl)cyclohexene: b.p. 100–1028C at 17 mm Hg;
1H NMR (CDCl3, 300 MHz): d=1.48–1.66 (m, 4H), 1.60 (s, 3H), 1.68 (s,
3H), 1.88–2.12 (m, 8H), 5.06–5.15 (m, 1H), 5.37–5.42 ppm (m, 1H);
13C NMR (CDCl3, 75 MHz): d=17.65, 22.57, 23.02, 25.23, 25.69, 26.46,
28.37, 38.09, 120.66, 124.47, 131.23, 137.72 ppm; MS: m/z: 164 [M]+.
NMR data are in accordance with literature values.[7b]
BicycloACHTREUNG
[2.2.2]-2-octene: 1H NMR (CDCl3, 300 MHz): d=1.10–1.19 (m,
4H), 1.36–1.46 (m, 4H), 2.35–2.43 (m, 2H), 6.12–6.19 ppm (m, 2H);
13C NMR (CDCl3, 75 MHz): d=25.75, 29.46, 134.21 ppm; MS: m/z: 108
[M]+. NMR data are in accordance with literature data.[7b]
9,9-Dimethyltricyclo[4,4,0,18,10]-1-undecene: b.p. 115–1208C at 15 mm Hg
(lit.[7b] b.p. 118–1238C at 15 mm Hg); [a]D20 = À29.9 (c=2.2, CH2Cl2);
1H NMR (CDCl3, 300 MHz): d=0.84 (d, 1H, J=9.3 Hz), 0.97 (s, 3H),
1.13–1.23 (m, 1H), 1.25 (s, 3H), 1.40–1.48 (m, 1H), 1.56–1.71 (m, 1H),
1.76–1.90 (m, 2H), 1.94–2.11 (m, 3H), 2.11–2.24 (m, 1H), 2.41 (t, 1H, J=
5.8 Hz), 2.45–2.61 (m, 2H), 5.14 ppm (q, 1H, J=3.3 Hz); 13C NMR
(CDCl3, 75 MHz): d=22.79, 23.57, 24.53, 27.19, 32.56, 33.37, 33.55, 35.59,
39.56, 42.17, 52.22, 116.88, 146.73 ppm; MS: m/z: 176 [M]+.
Experimental Section
General procedure for Diels–Alder decarbonylation sequence: A solu-
tion of RhCl3·3H2O (29.3 mg, 0.111 mmol) and dppp (95.6 mg,
0.225 mmol) in ethanol (10 mL) was degassed and heated to reflux for
1-Phenylcyclohexene: b.p. 122–1258C at 13 mm Hg (lit.[24] b.p. 1288C at
1
16 mm Hg); Rf =0.45 (EtOAc/hexane 1:99); H NMR (CDCl3, 300 MHz):
5642
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 5638 – 5644

Diels–Alder Reactions
FULL PAPER
d=1.63–1.73 (m, 2H), 1.75–1.84 (m, 2H), 2.18–2.27 (m, 2H), 2.39–2.47
(m, 2H), 5.13–5.19 (m, 1H), 7.19–7.42 ppm (m, 5H); 13C NMR (CDCl3,
75 MHz): d=22.40, 23.31, 26.12, 27.63, 125.00, 125.16, 126.73, 128.40,
136.80, 142.92 ppm; MS: m/z: 130 [MÀC2H4]+.
Acknowledgement
Financial support from the Lundbeck Foundation is gratefully acknowl-
edged. The Center for Sustainable Green Chemistry is funded by the
Danish National Research Foundation.
1-(Butoxymethyl)cyclohexene: b.p. 95–1028C at 15 mm Hg; 1H NMR
(CDCl3, 300 MHz): d=0.90 (t, 3H, J=7.3 Hz), 1.30–1.43 (m, 2H), 1.49–
1.68 (m, 6H), 1.93–2.05 (m, 4H), 3.35 (t, 2H, J=6.6 Hz), 3.78–3.80 (m,
2H), 5.63–5.69 ppm (m, 1H); 13C NMR (CDCl3, 75 MHz): d=13.92,
19.39, 22.42, 22.52, 24.97, 25.86, 31.85, 69.62, 75.56, 124.47, 135.21 ppm;
HRMS: m/z: calcd for C11H20ONa: 191.1412 [M+Na]+; found: 191.1403.
[1]O. Diels, K. Alder, Justus Liebigs Ann. Chem. 1928, 460, 98–122.
[2]F. Fringuelli, A. Taticchi, The Diels–Alder Reaction—Selected Practi-
cal Methods, Wiley, Chichester, 2002.
[3]a) E. J. Corey, Angew. Chem. 2002, 114, 1724–1741; Angew. Chem.
Int. Ed. 2002, 41, 1650–1667; b) Y. Hayashi, in Cycloaddition Reac-
tions in Organic Synthesis (Eds.: S. Kobayashi, K. A. Jørgensen),
Wiley-VCH, Weinheim, 2002, pp. 5–55.
[4]a) K.-i. Takao, R. Munakata, K.-i. Tadano, Chem. Rev. 2005, 105,
4779–4807; b) K. A. Jørgensen, Eur. J. Org. Chem. 2004, 2093–
2102; c) K. C. Nicolaou, S. A. Snyder, T. Montagnon, G. Vassiliko-
giannakis, Angew. Chem. 2002, 114, 1742–1773; Angew. Chem. Int.
Ed. 2002, 41, 1668–1698.
[5]For biosynthetic Diels–Alder reactions, see: E. M. Stocking, R. M.
Williams, Angew. Chem. 2003, 115, 3186–3223; Angew. Chem. Int.
Ed. 2003, 42, 3078–3115.
3-(Butoxymethyl)-6-methylcyclohexene: Rf =0.67 (Et2O/pentane 1:19);
1H NMR (CDCl3, 300 MHz): d=0.87–0.97 (m, 6H), 1.21–1.45 (m, 3H),
1.48–1.72 (m, 5H), 2.09–2.39 (m, 2H), 3.19–3.31 (m, 2H), 3.36–3.46 (m,
2H), 5.52–5.66 ppm (m, 2H); 13C NMR (CDCl3, 75 MHz): d=13.94,
19.37, 21.43, 23.15, 27.95, 29.99, 31.81, 35.26, 70.81, 74.56, 127.25,
134.88 ppm; HRMS: m/z: calcd for C12H22ONa: 205.1568 [M+Na]+;
found: 205.1563.
(4-Methyl-2-cyclohexenyl)methyl benzoate: Rf =0.55 (EtOAc/heptane
1
1:99); H NMR (CDCl3, 300 MHz): d=1.00 (d, 3H, J=7.1 Hz), 1.30–1.45
(m, 1H), 1.56–1.79 (m, 3H), 2.15–2.27 (m, 1H), 2.50–2.61 (m, 1H), 4.20
(d, 1H, J=1.3 Hz), 4.22 (s, 1H), 5.58–5.76 (m, 2H), 7.40–7.59 (m, 3H),
8.03–8.08 ppm (m, 2H); 13C NMR (CDCl3, 75 MHz): d=21.27, 23.03,
27.73, 29.82, 34.42, 67.90, 125.81, 128.29, 129.51, 130.36, 132.81, 135.95,
166.56 ppm; HRMS: m/z: calcd for C15H18O2Na: 253.1205 [M+Na]+;
found: 253.1206.
[6]P. D. Bartlett, K. E. Schueller, J. Am. Chem. Soc. 1968, 90, 6071–
6077.
[7]a) R. V. C. Carr, L. A. Paquette, J. Am. Chem. Soc. 1980, 102, 853–
855; b) R. V. C. Carr, R. V. Williams, L. A. Paquette, J. Org. Chem.
1983, 48, 4976–4986.
[8]For application of phenyl vinyl sulfone as an ethylene equivalent in
total synthesis, see: a) S. Dalai, V. N. Belov, S. Nizamov, K. Rauch,
D. Finsinger, A. de Meijere, Eur. J. Org. Chem. 2006, 2753–2765;
b) T. Omodani, K. Shishido, J. Chem. Soc. Chem. Commun. 1994,
2781–2782; c) J. R. Bull, K. Bischofberger, J. Chem. Soc. Perkin
Trans. 1 1991, 2859–2865.
[9]K. Wiesner, T. Y. R. Tsai, G. I. Dmitrienko, K. P. Nambiar, Can. J.
Chem. 1976, 54, 3307–3309.
[10]N. Ono, H. Miyake, A. Kamimura, A. Kaji, J. Chem. Soc. Perkin
Trans. 1 1987, 1929–1935.
tert-Butyl((4-methyl-2-cyclohexenyl)methoxy)diphenylsilane:
Rf =0.30
(EtOAc/heptane 1:39); 1H NMR (CDCl3, 300 MHz): d=0.99 (d, 3H, J=
3.7 Hz), 1.11 (s, 9H), 1.22–1.34 (m, 1H), 1.63–1.75 (m, 3H), 2.13–2.42 (m,
2H), 3.50–3.65 (m, 2H), 5.57–5.70 (m, 2H), 7.37–7.49 (m, 6H), 7.70–
7.76 ppm (m, 4H); 13C NMR (CDCl3, 75 MHz): d=19.30, 21.39, 22.72,
26.87, 27.97, 29.99, 37.74, 67.32, 127.28, 127.56, 129.48, 133.98, 134.89,
135.60; HRMS: m/z: calcd for C24H32OSiNa: 387.2120 [M+Na]+; found:
387.2120.
1,2,4-Trimethylcyclohexene: b.p. 150–1548C (lit.[25] b.p. 1548C); 1H NMR
(CDCl3, 300 MHz): d=0.94 (d, 3H, J=2.6 Hz), 1.08–1.23 (m, 1H), 1.24–
1.70 (m, 9H), 1.85–2.11 ppm (m, 3H); 13C NMR (CDCl3, 75 MHz): d=
18.86, 19.10, 21.95, 29.32, 31.73, 31.98, 40.53, 125.14, 125.16 ppm; MS: m/
z: 124 [M]+.
1,5-Dimethylcyclohexene: b.p. 132–1338C (lit.[26] b.p. 127–1298C);
1H NMR (CDCl3, 300 MHz): d=0.93–0.98 (m, 3H), 1.03–1.19 (m, 1H),
1.51–1.73 (m, 6H), 1.87–2.06 (m, 3H), 5.33–5.40 ppm (m, 1H); 13C NMR
(CDCl3, 75 MHz): d=21.97, 23.74, 25.36, 28.89, 30.63, 38.73, 120.64,
133.65 ppm; MS: m/z: 110 [M]+.
[11]M. Zaidlewicz, J. R. Binkul, W. Sokꢁl, J. Organomet. Chem. 1999,
580, 354–362.
[12]K. Ohno, J. Tsuji, J. Am. Chem. Soc. 1968, 90, 99–107.
[13]a) C. M. Beck, S. E. Rathmill, Y. J. Park, J. Chen, R. H. Crabtree,
L. M. Liable-Sands, A. L. Rheingold, Organometallics 1999, 18,
5311–5317; b) D. H. Doughty, L. H. Pignolet, J. Am. Chem. Soc.
1978, 100, 7083–7085.
5-Methyl-1-(4-methyl-3-pentenyl)cyclohexene: b.p. 107–1088C at 12 mm
Hg; 1H NMR (CDCl3, 300 MHz): d=0.96 (d, 3H, J=2.7 Hz), 1.05–1.22
(m, 1H), 1.54–1.75 (m, 9H), 1.87–2.13 (m, 7H), 5.06–5.16 (m, 1H), 5.35–
5.41 ppm (brs, 1H); 13C NMR (CDCl3, 75 MHz): d=17.67, 22.00, 25.33,
25.70, 26.49, 28.92, 30.83, 37.07, 37.91, 120.26, 124.47, 131.22, 137.29 ppm;
MS: m/z: 178 [M]+.
[14]M. Kreis, A. Palmelund, L. Bunch, R. Madsen, Adv. Synth. Catal.
2006, 348, 2148–2154.
[15]R. N. Monrad, R. Madsen, J. Org. Chem. 2007, 72, 9782–9785.
[16]a) G. S. Weatherhead, G. A. Cortez, R. R. Schrock, A. H. Hoveyda,
Proc. Natl. Acad. Sci. USA 2004, 101, 5805–5809; b) M. G. Banwell,
M. J. Coster, A. J. Edwards, O. P. Karunaratne, J. A. Smith, L. L.
Welling, A. C. Willis, Aust. J. Chem. 2003, 56, 585–595; c) S. M.
Allin, S. L. James, M. R. J. Elsegood, W. R. Martin, J. Org. Chem.
2002, 67, 9464–9467; d) R. K. Boeckman, Jr., J. Zhang, M. R.
Reeder, Org. Lett. 2002, 4, 3891–3894.
[17]a) A. van der Ent, A. L. Onderdelinden, Inorg. Synth. 1990, 28, 90–
92; b) B. R. James, D. Mahajan, Can. J. Chem. 1979, 57, 180–187.
[18]P. Fristrup, M. Kreis, A. Palmelund, P.-O. Norrby, R. Madsen, J. Am.
Chem. Soc. 2008, 130, 5206–5215.
1,2-Dimethyl-4-phenylcyclohexene: b.p. 130–1318C at 13 mm Hg (lit.[27]
1
b.p. 128–1308C at 11 mm Hg); H NMR (CDCl3, 300 MHz): d=1.65–1.70
(m, 6H), 1.71–2.29 (m, 6H), 2.73–2.86 (m, 1H), 7.18–7.38 ppm (m, 5H);
13C NMR (CDCl3, 75 MHz): d=18.87, 19.05, 30.29, 32.35, 40.05, 40.91,
125.32, 125.48, 125.85, 126.84, 128.28, 147.32 ppm; MS: m/z: 186 [M]+.
1-Methyl-5-phenylcyclohexene: b.p. 122–1238C at 13 mm Hg; 1H NMR
(CDCl3, 300 MHz): d=1.58–1.74 (m, 1H), 1.68 (s, 3H), 1.83–1.93 (m,
1H), 2.01–2.20 (m, 4H), 2.78–2.90 (m, 1H), 5.42–5.49 (brs, 1H), 7.14–
7.33 ppm (m, 5H); 13C NMR (CDCl3, 75 MHz): d=23.62, 25.82, 29.45,
38.31, 40.54, 120.86, 125.91, 126.86, 128.32, 133.77, 147.30 ppm; MS: m/z:
172 [M]+. 13C NMR data are in accordance with literature data.[28]
[19]H. L. Holmes, Org. React. 1948, 4, 60–173.
[20]J. S. Meek, R. T. Merrow, S. J. Cristol, J. Am. Chem. Soc. 1952, 74,
2667–2668.
5-Phenyl-1-(4-methyl-3-pentenyl)cyclohexene: b.p. 113–1158C at 0.1 mm
Hg; H NMR (CDCl3, 300 MHz): d=1.65 (s, 3H), 1.74 (s, 3H), 1.67–1.80
[21]Yu. A. Titov, A. I. Kuznetsova, Izv. Akad. Nauk SSSR Ser. Khim.
1960, 1297–1298.
1
(m, 1H), 1.90–2.27 (m, 9H), 2.76–2.90 (m, 1H), 5.13–5.21 (m, 1H), 5.53
(brs, 1H), 7.20–7.39 ppm (m, 5H); 13C NMR (CDCl3, 75 MHz): d=17.70,
25.71, 25.83, 26.45, 29.61, 36.81, 37.79, 40.59, 120.47, 124.30, 125.91,
126.86, 128.32, 131.38, 137.45, 147.37 ppm; MS: m/z: 240 [M]+; elemental
analysis (%) calcd for C18H24: C 89.94, H 10.06; found: C 89.58, H 10.12.
[22]For more information on compatible functional groups in the decar-
bonylation, see reference [14]. Aryl bromides are not tolerated due
to a competing oxidative addition to rhodium.
[23]W. A. Nugent, J. Feldman, J. C. Calabrese, J. Am. Chem. Soc. 1995,
117, 8992–8998.
Chem. Eur. J. 2008, 14, 5638 – 5644
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5643

R. Madsen and E. Taarning
[24]A. C. Cope, F. S. Fawcett, G. Mann, J. Am. Chem. Soc. 1950, 72,
[27]K. Alder, H. F. Rickert, Ber. Dtsch. Chem. Ges. 1938, 71, 379–386.
[28]K. Nakagawa, M. Sawai, Y. Ishii, M. Ogawa, Bull. Chem. Soc. Jpn.
1977, 50, 2487–2488.
3399–3404.
[25]J. B. Lambert, D. E. Marko, J. Am. Chem. Soc. 1985, 107, 7978–
7982.
Received: January 2, 2008
[26]J. Meinwald, R. F. Grossman, J. Am. Chem. Soc. 1956, 78, 992–995.
Published online: May 9, 2008
5644
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 5638 – 5644