Synthesis of novel bifunctional Michael acceptors

Article abstract of DOI:10.1002/ejoc.200400419

The conjugated dienones 1a, 1c-e, and 1g were synthesized by aldol reaction of cyclohex-2-enones 3 with aldehydes or ketones and subsequent elimination. Whereas the acetone adducts could be converted into the desired products 1a/g by treatment with CeCl₃·7H₂O/Nal, the dienones 1c-e were obtained by Appel bromination and dehydrobromination with triethylamine. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400419

FULL PAPER
Synthesis of Novel Bifunctional Michael Acceptors
Laura Mediavilla Urbaneja[a] and Norbert Krause*[a]
Keywords: Aldol addition / Appel bromination / Dienones / Eliminations / Michael additions
The conjugated dienones 1a, 1c−e, and 1g were synthesized
by aldol reaction of cyclohex-2-enones 3 with aldehydes or
ketones and subsequent elimination. Whereas the acetone
adducts could be converted into the desired products 1a/g
by treatment with CeCl3·7H2O/NaI, the dienones 1c−e were
obtained by Appel bromination and dehydrobromination
with triethylamine.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
carefully controlled conditions for the elimination of aldol
addition products.
The Michael addition belongs to the classical tools for
the formation of carbonϪcarbon and carbonϪheteroatom
bonds. The recent development of various efficient proto-
cols for catalytic enantioselective Michael additions has
broadened the scope of this transformation considerably.[1]
These methods, however, are usually applied to simple, un-
substituted substrates like cyclohex-2-enone and only scar-
cely to more elaborate Michael acceptors.[2] In this respect,
conjugated dienones of type 1 are particularly interesting
since sequential 1,4-addition reactions of two nucleophiles
to the endocyclic and exocyclic acceptor system of these
bifunctional Michael acceptors might give rise to the for-
mation of richly functionalized cyclohexanones 2 with up
to three stereogenic centers (Scheme 1).
Results and Discussion
The aldol addition of the lithium enolate of cyclohex-2-
enone (3a) to acetone was reported by Marcantoni et al.[6]
to proceed smoothly if the latter is activated by anhydrous
cerium trichloride. We have found that this method can be
expanded to various cyclic and acyclic ketones, as well as
to isobutyraldehyde, to furnish the desired aldols 4aϪf with
chemical yields ranging from 70 to 90% (Scheme 2). Simi-
larly, 2-methylcyclohex-2-enone (3b) was converted into the
adduct 4g with 79% yield.
Scheme 1. Sequential Michael additions of two nucleophiles to di-
enones 1
So far, only isolated reports on the synthesis of Michael
acceptors 1 have appeared. These were synthesized by se-
lenoxide elimination,[3] photochemical isomerization,[4] or
aldol reactions.[5] The lack of general methods may be due
to the tendency of the exocyclic CϪC double bond to iso-
merize to a thermodynamically more favorable position. In
this communication, we describe an efficient general
method for the synthesis of dienones 1 which relies upon
Scheme 2. CeCl3-mediated aldol reaction of cyclohexenones 3
[a]
Organic Chemistry II, University of Dortmund,
44221 Dortmund, Germany
For the dehydration of the aldol adducts 4 to the desired
conjugated dienones of type 1, we initially employed the
Fax: ϩ49 231/755-3884
E-mail: norbert.krause@uni-dortmund.de
Eur. J. Org. Chem. 2004, 4467Ϫ4470
DOI: 10.1002/ejoc.200400419
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4467

L. Mediavilla Urbaneja, N. Krause
FULL PAPER
conditions used by Marcantoni et al.[6] for the preparation
2-alkylidenecycloalkanes, i.e., heating with CeCl3·7H2O and
sodium iodide in acetonitrile. Indeed, the acetone adducts
4a and 4g produced the desired dienones 1a and 1g, respec-
tively, with good chemical yield (Scheme 3). No traces of
non-conjugated or aromatic isomers could be found. In
contrast to this, the aldols 4c and 4d furnished phenols 5
under these conditions, whereas cyclohexanone adduct 4f
gave only the non-conjugated dienone 6. In the case of the
aldols 4b and 4e, mixtures of regioisomers of type 1 and 6
were obtained which could not be separated.
Scheme 4. Elimination of aldol adducts 4cϪe under Appel con-
ditions
Conclusion
The conjugated dienones 1a, 1cϪe, and 1g, which are of
interest as bifunctional Michael acceptors, were synthesized
by aldol reaction of cyclohexenones 3 with aldehydes or
ketones and subsequent regioselective elimination. Whereas
the acetone adducts could be converted into the desired
products 1a/g by treatment with cerium() chloride hepta-
hydrate/sodium iodide, the dienones 1cϪe were obtained in
a one-pot reaction by Appel bromination and dehydrobro-
mination with triethylamine.
Experimental Section
General Remarks: All reactions were carried out under an argon
atmosphere using oven-dried glassware. THF was distilled from so-
dium benzophenone ketyl, toluene was distilled from sodium, di-
chloromethane, triethylamine, and diisopropylamine were distilled
from CaH2, and acetone was distilled from P2O5. All solvents were
used immediately or stored under an argon atmosphere. Solvents
for flash chromatography (pentane, cyclohexane, and ethyl acetate)
were distilled before use. Cyclohex-2-enone, pentan-3-one, isobu-
tyraldehyde, cyclohexanone, and cyclopentanone were distilled
prior to use. 2-Methylcyclohex-2-enone was prepared according to
ref.[8] All other commercially available starting materials were used
without further purification. Column chromatography was carried
out with MachereyϪNagel silica gel 60 (230Ϫ400 mesh). 1H and
13C NMR spectra were recorded with a Bruker DRX-400 or DRX-
500 spectrometer at room temperature in CDCl3 or C6D6 as sol-
vent. Chemicals shifts were determined relative to the residual sol-
vent peaks (CHCl3: δ ϭ 7.26 for protons, δ ϭ 77.0 for carbon
atoms. C6H6: δ ϭ 7.16 for protons, δ ϭ 128.0 for carbon atoms).
The polarization in DEPT experiments is designated with ϩ (CH,
CH3), Ϫ (CH2), or ϫ (Cquat.). IR spectra were obtained with a
Bruker IFS66 FT-IR spectrometer using thin films between NaCl
plates. Mass spectra, high-resolution mass spectra (HRMS), and
fast atom bombardment mass spectra (FAB) were measured with
a Jeol SX102A spectrometer.
Scheme 3. Dehydration of aldol adducts 4 with CeCl3·7H2O/NaI
The latter findings seem to indicate a high tendency
towards double bond isomerization even under very mild
acidic conditions. Consequently, we turned our attention
towards basic elimination conditions which required the
transformation of the hydroxy group of aldols 4 into a good
leaving group. Since the mesylation of tertiary alcohols is
rather difficult, we decided to use Appel’s conditions[7] for
the conversion into the corresponding bromides. Thus,
treatment of adduct 4c with equimolar amounts of carbon
tetrabromide and triphenylphosphane resulted in a clean
conversion into the bromide which was subjected without
isolation to the dehydrobromination with triethylamine
(Scheme 4). Much to our delight, the desired conjugated
dienone 1c was obtained with 63% yield, and no traces of
non-conjugated or aromatic isomerization products were
found. In a similar fashion, the ketone adducts 4d and 4e
were converted into the dienones 1d/e with yields of 40 and
54%, respectively. Only the substrates 4b and 4f again af-
forded mixtures of conjugated and non-conjugated prod-
ucts under the basic elimination conditions. With various
dienones 1 at hand, we are now in the process of examining
their use as bifunctional Michael acceptors according to
Scheme 1.
General Procedure for the Synthesis of Aldol Adducts 4: CeCl3·7H2O
was dried at 140 °C/0.1 mbar for 2 h and was then suspended in
dry THF at 0 °C (ice-water bath) under vigorous stirring. The white
suspension was allowed to stir overnight at room temperature.
After cooling to Ϫ80 °C, a THF solution of the carbonyl com-
pound was added, and the suspension was stirred at Ϫ80 °C for
1 h. In a separate flask, a solution of LDA in THF was prepared
by adding nBuLi to diisopropylamine in THF at 0 °C. After stirring
for 20 min at this temperature, it was cooled to Ϫ80 °C, and the
4468
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4467Ϫ4470

Novel Bifunctional Michael Acceptors
FULL PAPER
enone 3 in THF was added. The mixture was stirred at Ϫ80 °C for
30 min and then added via cannula to the white suspension. The
resulting orange-red suspension was stirred at Ϫ80 °C until TLC
(400 MHz, C6D6): δ ϭ 6.20 (m, 1 H, 3-H), 5.83 (td, J ϭ 2.0, 9.8 Hz,
1 H, 2-H), 3.82 (s, 1 H, OH), 2.20 (dd, J ϭ 4.5, 13.5 Hz, 1 H),
2.04Ϫ1.78 (m, 4 H), 1.72Ϫ1.38 (m, 7 H), 1.34Ϫ1.22 (m, 1 H) ppm.
control showed full consumption of starting material (approx. 13C NMR (100 MHz, C6D6): δ ϭ 202.7 (ϫ, C-1), 149.6 (ϩ, C-3),
1Ϫ2 h.). The reaction mixture was then hydrolyzed with a satd.
NH4Cl solution. The organic layer was separated and concentrated
in vacuo. The aqueous layer was washed three times with diethyl
ether, and the combined organic layers were washed with water and
brine, dried with MgSO4, and the solvent was evaporated. Flash
column chromatography on silica gel (cyclohexane/ethyl acetate,
6:4) afforded the aldol adduct 4.
130.5 (ϩ, C-2), 82.5 (ϫ, C-1Ј), 55.0 (ϩ, C-6), 39.2, 36.7 (Ϫ, C-2Ј),
26.2, 25.5, 24.6, 24.2 (Ϫ, C-4, C-5, C-3Ј) ppm. IR: ν˜ ϭ 3480, 3032,
2957, 1663 cmϪ1. EI-MS: m/z (%) ϭ 180 (10) [Mϩ], 162 (13), 138
(27), 123 (22), 96 (100), 55 (32). HR-EI-MS: calcd. for C11H16O2:
180.1150; found 180.1153.
6-(1-Hydroxycyclohexyl)cyclohex-2-enone (4f): From CeCl3 (10.8 g,
43.8 mmol) in THF (100 mL), cyclohexanone (3.38 g, 34.4 mmol)
in THF (5 mL), diisopropylamine (3.48 g, 34.4 mmol) in THF
(50 mL), nBuLi (14.0 mL, 34.4 mmol, 2.45  solution in hexane),
and cyclohex-2-enone (3a, 3.02 g, 31.4 mmol) in THF (5 mL);
yield: 4.26 g (70%) of 4f as a colorless oil. 1H NMR (400 MHz,
CDCl3): δ ϭ 6.95 (m, 1 H, 3-H), 5.95 (ddd, J ϭ 1.0, 2.5, 9.8 Hz, 1
H, 2-H), 4.50 (s, 1 H, OH), 2.45Ϫ2.30 (m, 3 H), 2.10 (m, 1 H),
1.80Ϫ1.58 (m, 5 H), 1.54Ϫ1.40 (m, 4 H), 1.30 (dt, J ϭ 4.0, 13.0,
Hz, 1 H), 1.08 (qt, J ϭ 3.5, 13.0 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 204.0 (ϫ, C-1), 150.8 (ϩ, C-3), 130.7 (ϩ,
C-2), 73.1 (ϫ, C-1Ј), 55.9 (ϩ, C-6), 35.4, 31.8 (Ϫ, C-2Ј), 26.4, 25.8,
24.6, 21.2, 21.1 (Ϫ, C-4, C-5, C-3Ј, C-4Ј) ppm. IR: ν˜ ϭ 3469, 2930,
1657 cmϪ1. EI-MS: m/z (%) ϭ 194 (3) [Mϩ], 176 (9), 138 (6), 96
(100), 55 (23), 41 (16). HR-EI-MS: calcd. for C12H18O2: 194.1307;
found 194.1304.
6-(1-Hydroxy-1-methylethyl)cyclohex-2-enone (4a):[6] From CeCl3
(13.9 g, 56.4 mmol) in THF (200 mL), acetone (3.20 g, 55.1 mmol)
in THF (5 mL), diisopropylamine (5.06 g, 50.0 mmol) in THF
(50 mL), nBuLi (20.4 mL, 50.0 mmol, 2.45  solution in hexane),
and cyclohex-2-enone (3a, 4.00 g, 41.6 mmol) in THF (5 mL);
yield: 5.10 g (79%) of 4a as a colorless oil.
6-(1-Hydroxy-1-ethylpropyl)cyclohex-2-enone (4b): From CeCl3
(10.3 g, 41.8 mmol) in THF (150 mL), pentan-3-one (3.57 g,
41.5 mmol) in THF (5 mL), diisopropylamine (3.79 g, 37.5 mmol)
in THF (50 mL), nBuLi (15.3 mL, 37.5 mmol, 2.45  solution in
hexane), and cyclohex-2-enone (3a, 3.00 g, 31.2 mmol) in THF
(5 mL); yield: 4.50 g (79%) of 4b as a colorless oil. 1H NMR
(400 MHz, C6D6): δ ϭ 6.27 (m, 1 H, 3-H), 5.81 (dd, J ϭ 1.5,
10.0 Hz, 1 H, 2-H), 4.96 (d, J ϭ 1.8 Hz, 1 H, OH), 2.35 (dd, J ϭ
4.5, 13.8 Hz, 1 H, 6-H), 1.68Ϫ1.60 (m, 4 H), 1.42Ϫ1.35 (m, 1 H),
1.29Ϫ1.17 (m, 2 H), 1.20Ϫ1.10 (m, 1 H), 0.96 (t, J ϭ 7.3 Hz, 3 H,
3Ј-H), 0.93 (t, J ϭ 7.3 Hz, 3 H, 3Ј-H) ppm. 13C NMR (100 MHz,
C6D6): δ ϭ 204.5 (ϫ, C-1), 150.2 (ϩ, C-3), 130.9 (ϩ, C-2), 75.9 (ϫ,
C-1Ј), 51.8 (ϩ, C-6), 29.7, 28.9, 26.1, 24.6 (Ϫ, C-4, C-5, C-2Ј), 8.0,
7.7 (ϩ, C-3Ј) ppm. IR: ν˜ ϭ 3460, 3026, 2966, 1654 cmϪ1. EI-MS:
m/z (%) ϭ 182 (0.4) [Mϩ], 153 (93), 135 (9), 96 (100), 57 (99), 29
(19). HR-FAB-MS: calcd. for C10H18NaO2 [M ϩ Na]: 205.1204;
found 205.1200.
6-(1-Hydroxy-1-methylethyl)-2-methylcyclohex-2-enone (4g): From
CeCl3 (9.00 g, 36.5 mmol) in THF (100 mL), acetone (2.10 g,
36.2 mmol) in THF (5 mL), diisopropylamine (3.29 g, 32.5 mmol)
in THF (50 mL), nBuLi (13.3 mL, 37.5 mmol, 2.45  solution in
hexane), and 2-methylcyclohex-2-enone (3b, 3.00 g, 27.2 mmol) in
1
THF (5 mL); yield: 3.60 g (79%) of 4g as a colorless oil. H NMR
(400 MHz, C6D6): δ ϭ 6.06 (m, 1 H, 3-H), 5.15 (s, 1 H, OH), 2.13
(dd, J ϭ 4.4, 14.2 Hz, 1 H), 1.70Ϫ1.63 (m, 5 H), 1.56Ϫ1.49 (m, 1
H), 1.31Ϫ1.23 (m, 1 H), 1.23 (s, 3 H), 1.18 (s, 3 H) ppm. 13C NMR
(100 MHz, C6D6): δ ϭ 203.6 (ϫ, C-1), 145.5 (ϩ, C-3), 136.2 (ϫ,
C-2), 72.2 (ϫ, C-1Ј), 56.4 (ϩ, C-6), 28.6, 25.1 (Ϫ, C-4, C-5), 25.9
6-(1-Hydroxy-2-methylpropyl)cyclohex-2-enone (4c):[9] From CeCl3
(20.6 g, 83.6 mmol) in THF (300 mL), isobutyraldehyde (5.86 g,
81.3 mmol) in THF (5 mL), diisopropylamine (7.59 g, 75.0 mmol)
in THF (100 mL), nBuLi (30.6 mL, 75.0 mmol, 2.45  solution in
hexane), and cyclohex-2-enone (3a, 6.00 g, 62.4 mmol) in THF
(5 mL); yield: 9.50 g (90%) of 4c as a colorless oil.
(ϩ, C-2Ј), 16.0 (ϩ, 2-CH3) ppm. IR: ν˜ ϭ 3475, 2973, 1652 cmϪ1
.
EI-MS: m/z (%) ϭ 168 (0.4) [Mϩ], 153 (12), 110 (100), 95 (56), 82
(13), 59 (24), 43 (34). HR-FAB-MS: calcd. for C10H17O2 [M ϩ H]:
169.1228; found 169.1230.
6-(1-Methylethylidene)cyclohex-2-enone (1a):[4] A suspension of
CeCl3·7 H2O (19.4 g, 52.1 mmol) and NaI (7.80 g, 52.0 mmol) in
acetonitrile (80 mL) was stirred for 24 h under reflux. The resulting
mixture was cooled to room temperature, and a solution of 4a
(2.50 g, 16.2 mmol) in acetonitrile (10 mL) was added dropwise.
The reaction mixture was refluxed for 2 h; at this point, TLC con-
trol showed complete consumption of the starting material. After
cooling to room temperature, the mixture was diluted with diethyl
ether (200 mL), water (50 mL) was added, and the mixture was
stirred for 5 min. The organic layer was separated, and the aqueous
phase was washed three times with diethyl ether. The combined
organic layers were washed with a satd. Na2S2O3 solution, water
and brine, and dried with Na2SO4. After removal of the solvent,
the crude product was purified by flash column chromatography on
silica gel (pentane/diethyl ether/triethylamine, 8:2:0.02), affording
1.80 g (83%) of 1a as a pale yellow liquid.
6-(1-Hydroxycyclobutyl)cyclohex-2-enone (4d): From CeCl3 (4.50 g,
18.3 mmol) in THF (75 mL), cyclobutanone (1.14 g, 16.3 mmol) in
THF (5 mL), diisopropylamine (1.64 g, 16.2 mmol) in THF
(25 mL), nBuLi (6.6 mL, 16.2 mmol, 2.45  solution in hexane),
and cyclohex-2-enone (3a, 1.30 g, 13.5 mmol) in THF (5 mL);
yield: 2.00 g (89%) of 4d as a colorless oil. 1H NMR (400 MHz,
C6D6): δ ϭ 6.21 (m, 1 H, 3-H), 5.83 (m, 1 H, 2-H), 3.70 (s, 1 H,
OH), 2.30 (m, 1 H), 2.23Ϫ2.10 (m, 3 H), 1.95Ϫ1.84 (m, 2 H),
1.73Ϫ1.54 (m, 4 H), 1.40 (m, 1 H) ppm. 13C NMR (100 MHz,
C6D6): δ ϭ 201.8 (ϫ, C-1), 149.9 (ϩ, C-3), 130.4 (ϩ, C-2), 76.5
(ϫ, C-1Ј), 54.4 (ϩ, C-6), 35.3, 32.9 (Ϫ, C-2Ј), 26.1, 23.9 (Ϫ, C-4,
C-5), 13.8 (Ϫ, C-3Ј) ppm. IR: ν˜ ϭ 3465, 3031, 2937, 1665 cmϪ1
.
EI-MS: m/z (%) ϭ 166 (44) [Mϩ], 96 (68), 68 (36), 58 (60), 43 (100).
HR-FAB-MS: calcd. for C10H15O2 [M ϩ H]: 167.1072; found
167.1056.
6-(1-Hydroxycyclopentyl)cyclohex-2-en-1-one (4e): From CeCl3
(9.20 g, 37.3 mmol) in THF (150 mL), cyclopentanone (3.80 g, (E)-6-(2-Methylpropylidene)cyclohex-2-enone (1c): A solution of
45.2 mmol) in THF (5 mL), diisopropylamine (3.79 g, 37.5 mmol) CBr4 (12.8 g, 38.6 mmol) in dry CH2Cl2 (10 mL) was stirred for
in THF (50 mL), nBuLi (15.3 mL, 37.5 mmol, 2.45  solution in 5 min at 0 °C, and a solution of 4c (5.40 g, 32.1 mmol) in dry
hexane), and cyclohex-2-enone (3a, 3.00 g, 31.2 mmol) in THF CH2Cl2 (10 mL) was added. The reaction mixture was stirred for
(5 mL); yield: 4.35 g (77%) of 4e as a colorless oil. 1H NMR 5 min at 0 °C, and then a precooled solution (0 °C) of PPh3 (10.1 g,
Eur. J. Org. Chem. 2004, 4467Ϫ4470
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4469

L. Mediavilla Urbaneja, N. Krause
38.5 mmol) in dry CH2Cl2 (20 mL) was added dropwise. Stirring at 2-Methyl-6-(1-methylethylidene)cyclohex-2-enone (1g): As in the
FULL PAPER
0 °C was continued for 90 min, followed by the dropwise addition
of Et3N (5.06 g, 50.0 mmol). After stirring for another 10 min at 0
°C, the major part of the solvent was removed in vacuo. The residue
was poured slowly with stirring into diethyl ether (50 mL). Fil-
tration through Celite, washing of the residue with diethyl ether,
drying of the filtrate with Na2SO4 and removal of the solvent gave
preparation of 1a, refluxing of 4g (1.50 g, 8.9 mmol) in acetonitrile
(5 mL) with CeCl3·7 H2O (10.7 g, 28.7 mmol) and NaI (4.32 g,
28.8 mmol) in acetonitrile (30 mL) for 12 h afforded 1.02 g (75%)
of 1g as a pale yellow liquid. 1H NMR (400 MHz, C6D6): δ ϭ 6.14
(s, 1 H, 3-H), 2.30 (t, J ϭ 6.0 Hz, 2 H), 2.16 (s, 3 H, 2Ј-H), 1.88
(d, J ϭ 1.2 Hz, 3 H, 2-CH3), 1.86Ϫ1.85 (m, 2 H), 1.50 (s, 3 H, 2Ј-
the crude product. Purification by flash column chromatography H) ppm. 13C NMR (100 MHz, C6D6): δ ϭ 190.9 (ϫ, C-1), 141.9
(SiO2, pentane/diethyl ether/triethylamine, 4:1:0.02) afforded 3.02 g
(63%) of 1c as a pale yellow oil. H NMR (500 MHz, C6D6): δ ϭ
(ϩ, C-3), 141.1, 138.1, 130.2 (ϫ, C-2, C-6, C-1Ј), 28.7, 26.6 (Ϫ, C-
4, C-5), 23.0, 22.1 (ϩ, C-2Ј), 16.8 (ϩ, 2-CH3) ppm. IR: ν˜ ϭ 2922,
1
6.73 (d, J ϭ 9.8 Hz, 1 H, 1Ј-H), 6.27 (td, J ϭ 4.3, 10.0 Hz, 1 H, 3- 1660, 1624 cmϪ1. EI-MS: m/z (%) ϭ 150 (100) [Mϩ], 135 (21),
H), 6.14 (td, J ϭ 1.7, 10.0 Hz, 1 H, 2-H), 2.38Ϫ2.25 (m, 1 H, 2Ј- 107 (61), 91 (26), 79 (19), 39 (18). HR-EI-MS: calcd. for C10H14O:
H), 2.21 (dt, J ϭ 1.5, 6.3 Hz, 2 H), 1.73 (m, 2 H), 0.82 (d, J ϭ 150.1045; found 150.1043.
6.5 Hz, 6 H, 3Ј-H) ppm. 13C NMR (125 MHz, C6D6): δ ϭ 187.3
(ϫ, C-1), 148.0 (ϩ, C-1Ј), 143.7 (ϩ, C-3), 132.7 (ϫ, C-6), 131.3 (ϩ,
Acknowledgments
Generous support of this work by the Deutsche Forschungsgemein-
C-2), 26.9 (ϩ, C-2Ј), 25.6, 25.1 (Ϫ, C-4, C-5), 22.3 (ϩ, C-3Ј) ppm.
IR: ν˜ ϭ 2961, 1674, 1627 cmϪ1. EI-MS: m/z (%) ϭ 150 (100) [Mϩ],
107 (58), 82 (60), 67 (54), 39 (97). HR-EI-MS: calcd. for C10H14O:
150.1045; found 150.1066. The E geometry was assigned by com-
parison of the chemical shift of 1Ј-H with that of related com-
pounds.[10]
schaft, the European Community (COST D24/0003/01) and the
Fonds der Chemischen Industrie is gratefully acknowledged.
[1]
[1a]
Recent reviews:
2001, 171Ϫ196.
N. Krause, A. Hoffmann-Röder, Synthesis
[1b]
A. Alexakis, C. Benhaim, Eur. J. Org.
6-(Cyclobutylidene)cyclohex-2-enone (1d): According to the syn-
thesis of 1c from CBr4 (3.98 g, 12.0 mmol) in CH2Cl2 (5 mL), 4d
(1.66 g, 10.0 mmol) in CH2Cl2 (5 mL), PPh3 (3.15 g, 12.0 mmol) in
CH2Cl2 (10 mL) and Et3N (1.52 g, 15.0 mmol); reaction time: 3 h.
Yield: 600 mg (40%) of 1d as a pale yellow oil. 1H NMR (400 MHz,
CDCl3): δ ϭ 6.75 (td, J ϭ 4.3, 10.0 Hz, 1 H, 3-H), 6.04 (td, J ϭ
1.7, 10.0 Hz, 1 H, 2-H), 3.15 (m, 2 H), 2.80 (m, 2 H), 2.50 (m, 2
H), 2.33 (m, 2 H), 2.85 (pent, J ϭ 7.8 Hz, 2 H, 3Ј-H) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 188.9 (ϫ, C-1), 156.9 (ϫ, C-1Ј),
148.1 (ϩ, C-3), 131.6 (ϩ, C-2), 125.4 (ϫ, C-6), 34.2, 30.8, 25.3,
25.3 (Ϫ, C-4, C-5, C-2Ј), 17.6 (Ϫ, C-3Ј) ppm. IR: ν˜ ϭ 3030, 2950,
1687, 1634 cmϪ1. EI-MS: m/z (%) ϭ 148 (100) [Mϩ], 147 (76), 133
(32), 120 (22), 105 (46), 39 (26). HR-EI-MS: calcd. for C10H12O:
148.0888; found 148.0880
[1c]
Chem. 2002, 3221Ϫ3236.
B. List, Tetrahedron 2002, 58,
[1d]
5573Ϫ5590.
T. Hayashi, K. Yamasaki, Chem. Rev. 2003,
103, 2829Ϫ2844.
[2] [2a]
R. Naasz, L. A. Arnold, A. J. Minnaard, B. L. Feringa,
Angew. Chem. 2001, 113, 953Ϫ956; Angew. Chem. Int. Ed.
[2b]
2001, 40, 927Ϫ930.
L. Mediavilla Urbaneja, A. Alexakis,
N. Krause, Tetrahedron Lett. 2002, 43, 7887Ϫ7890.
[3] [3a]
H. J. Reich, I. L. Reich, J. M. Renga, J. Am. Chem. Soc.
1973, 95, 5813Ϫ5815. [3b] H. J. Reich, J. M. Renga, I. L. Reich,
J. Am. Chem. Soc. 1975, 97, 5434Ϫ5446.
[4]
C. A. N. Catalan, D. J. Merep, M. L. T. De Delfini, J. A. Reta-
mar, Riv. Ital. EPPOS 1981, 63, 209Ϫ215.
[5] [5a]
T. Takanami, K. Suda, H. Ohmori, Tetrahedron Lett. 1990,
31, 677Ϫ680. [5b] J.-X. Wang, L. Kang, Y. Hu, B. G. Wie, Synth.
[5c]
Commun. 2002, 32, 1691Ϫ1696.
G. Sabitha, G. S. K. K.
Reddy, K. B. Reddy, J. S. Yadav, Synthesis 2004, 263Ϫ266.
6-(Cyclopentylidene)cyclohex-2-enone (1e): According to the syn-
thesis of 1c from CBr4 (1.58 g, 4.8 mmol) in CH2Cl2 (3 mL), 4e
(650 mg, 3.6 mmol) in CH2Cl2 (3 mL), PPh3 (1.25 g, 4.8 mmol) in
CH2Cl2 (6 mL) and Et3N (0.56 g, 5.5 mmol); reaction time: 3 h.
Yield: 315 mg (54%) of 1e as a pale yellow oil. 1H NMR (400 MHz,
C6D6): δ ϭ 6.24 (td, J ϭ 4.0, 10.0 Hz, 1 H, 3-H), 6.16 (td, J ϭ 1.6,
10.0 Hz, 1 H, 2-H), 3.02 (m, 2 H), 2.26 (t, J ϭ 6.5 Hz, 2 H), 2.00
(t, J ϭ 7.3 Hz, 2 H), 1.80Ϫ1.70 (m, 2 H), 1.49 (pent, J ϭ 7.0 Hz,
2 H), 1.37 (pent, J ϭ 7.0 Hz, 2 H) ppm. 13C NMR (100 MHz,
C6D6): δ ϭ 188.3 (ϫ, C-1), 157.3 (ϫ, C-1Ј), 145.8 (ϩ, C-3), 132.6
(ϩ, C-2), 125.6 (ϫ, C-6). 34.7, 33.0, 28.6, 27.3, 25.6, 25.5 (Ϫ, C-4,
[5d]
G. A. Kraus, J. Kim, Synthesis 2004, 1737Ϫ1738.
[6]
G. Bartoli, M. Bosco, R. Dalpozzo, A. Giuliani, E. Marcan-
toni, T. Mecozzi, L. Sambri, E. Torregiani, J. Org. Chem. 2002,
67, 9111Ϫ9114.
R. Appel, K. Warning, Chem. Ber. 1975, 108, 606Ϫ629. [7b]
[7] [7a]
R. Appel, H. D. Wihler, Chem. Ber. 1976, 109, 3446Ϫ3449.
D. Y. Hua, Y. Chen, H.-S. Sin, M. J. Maroto, P. D. Robinson,
S. W. Newell, E. M. Perchellet, J. B. Ladesich, J. A. Freeman, J.-
P. Perchellet, P. K. Chiang, J. Org. Chem. 1997, 62, 6888Ϫ6896.
S.-P. Hong, H. A. Lindsay, T. Yaramasu, X. Zhang, M. C.
McIntosh, J. Org. Chem. 2002, 67, 2042Ϫ2055.
[8]
[9]
[10] [10a]
[10b]
H. O. Krabbenhoft, J. Org. Chem. 1979, 44, 4050Ϫ4055.
C-5, C-2Ј, C-3Ј) ppm. IR: ν˜ ϭ 3032, 2957, 1660, 1626, 1601 cmϪ1
.
E. Piers, H. E. Morton, J. M. Chong, Can. J. Chem. 1987,
EI-MS: m/z (%) ϭ 162 (100) [Mϩ], 133 (28), 105 (15), 91 (36), 79
(34), 67 (19), 39 (19). HR-EI-MS: calcd. for C11H14O: 162.1045;
found 162.1046.
[10c]
65, 78Ϫ87.
D. L. J. Clive, X. Huang, Tetrahedron 2001,
57, 3845Ϫ3858.
Received June 14, 2004
4470
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4467Ϫ4470