Straightforward synthesis of nonconjugated cyclohex-3-enone and conjugated 4-methylenecyclohex-2-enone derivatives

Article abstract of DOI:10.1055/s-0031-1289752

The synthesis of nonconjugated cyclohex-3-enones via the regiodivergent cobalt-catalysed Diels-Alder reactions of 2-(trimethylsilyloxy)buta-1,3-diene with alkynes and hydrolysis of the dihydroaromatic intermediates is described. The application of bidentate phosphine ligands versus pyridine-imine ligands led to the regioselective formation of one out of the two possible regioisomeric products when terminal or unsymmetrically substituted alkynes were applied. The cyclohex-3-enone products were isolated mostly in good yields without isomerisation of the carbon-carbon double bond into conjugation based on the mild reaction conditions. The use of acetoxymethyl-substituted alkynes led to the conjugated 4-methylenecyclohex-2-enones after deprotection of the silyl enol ether. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1289752

FEATURE ARTICLE
1293
Straightforward Synthesis of Nonconjugated Cyclohex-3-enone and
Conjugated 4-Methylenecyclohex-2-enone Derivatives
C
yclohex-
u
3-enones and
l
Conju
i
gated
4
-Methylen
n
ecyclohex-2-enone
R
s
. Kuttner, Svenja Warratz, Gerhard Hilt*
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße, 35043 Marburg, Germany
Fax +49(6421)2825677; E-mail: Hilt@chemie.uni-marburg.de
Received 16 January 2012
We envisaged that a cobalt-catalysed Diels–Alder reac-
tion combined with appropriate workup conditions of
suitable intermediates could be utilised for the synthesis
of structures such as 1 and 3. At best, the synthesis of 1
Abstract: The synthesis of nonconjugated cyclohex-3-enones via
the regiodivergent cobalt-catalysed Diels–Alder reactions of 2-(tri-
methylsilyloxy)buta-1,3-diene with alkynes and hydrolysis of the
dihydroaromatic intermediates is described. The application of bi-
dentate phosphine ligands versus pyridine–imine ligands led to the and 3 should be accomplished from readily available start-
regioselective formation of one out of the two possible regioisomer-
ic products when terminal or unsymmetrically substituted alkynes
were applied. The cyclohex-3-enone products were isolated mostly
ing materials in as few chemical steps as possible.
For this purpose, we investigated the regiodiverse cobalt-
catalysed Diels–Alder reactions of 2-(trimethylsilyl-
oxy)buta-1,3-diene (5) with alkynes 6 for the selective
synthesis of either the cyclohex-3-enone derivative 7 or
in good yields without isomerisation of the carbon–carbon double
bond into conjugation based on the mild reaction conditions. The
use of acetoxymethyl-substituted alkynes led to the conjugated 4-
methylenecyclohex-2-enones after deprotection of the silyl enol
ether.
the regioisomeric cyclohex-3-enone derivative
8
(Scheme 2).5 The elegance and simplicity of this approach
is that both regioisomers 7 and 8 are addressable from the
same starting materials by utilising two different ligands6
in the cobalt catalyst systems.
Key words: alkynes, catalysis, cobalt, Diels–Alder reaction,
dienes, nonconjugation
The silyl enol ether intermediates are directly converted
into the much less oxidation-sensitive ketones 7/8, realis-
ing the desired one-pot approach for the synthesis of these
derivatives.
For a wide variety of functionalisation reactions, the cy-
clohex-2-enone skeleton is a versatile playground and a
huge number of applications of the cyclohex-2-enone
scaffold have been described thus far. Nevertheless, the
chemistry of nonconjugated cyclohex-3-enones such as 11
is far less explored than the transformations associated
with cyclohex-2-enone derivatives such as 2 (Scheme 1).
Even less explored than the chemistry of materials of type
1 are 4-methylenecyclohex-2-enone derivatives such as
3.2
catalyst A
R1
R2
R1
R2
CoBr2(dppe)
TBAF
(aq)
Zn, ZnI2
Me3SiO
O
R1
R2
7
8
+
Me3SiO
5
6
catalyst B
R2
R1
R2
R1
O
O
O
OH
CoBr2(py-imine)
TBAF
(aq)
Zn, ZnI2
isomerisation
isomerisation
Me3SiO
O
1
2
3
4
dppe =
py-imine =
Ph2P
PPh2
N
N
Scheme 1 Isomeric cyclohexenones and their interconversions
This is mostly due to the small number of efficient ap-
proaches for the selective synthesis of various derivatives
of 1 and 3.3 In addition, basically any harsh reaction con-
ditions will cause double-bond migration in 1 to generate
the corresponding conjugated derivatives of type 2. Inter-
mediates of type 3 are sensitive as well, generating phenol
derivatives such as 4 upon double-bond migration and
keto–enol tautomerisation.4
Scheme 2 Regiodiverse synthesis of the cyclohex-3-enone deriv-
atives 7 or 8
The synthesis of nonconjugated cyclohex-3-enone deriv-
atives was first tested utilising symmetrical internal
alkynes (R1 = R2). At first, the two complementary cobalt
catalyst systems were tested with hex-3-yne as substrate.
Catalyst system A, comprising CoBr2(dppe), zinc powder
and zinc iodide, furnished the desired product 7a in 67%
yield, while catalyst system B, comprising CoBr2(py-imine),
zinc powder and zinc iodide, gave 7a in 76% yield.7
Accordingly, entries 1 and 3 (Table 1) were tested using
SYNTHESIS 2012, 44, 1293–1303
x
x
.
x
x
.2
0
1
2
Advanced online publication: 27.03.2012
DOI: 10.1055/s-0031-1289752; Art ID: Z005112SS
© Georg Thieme Verlag Stuttgart · New York

1294
J. R. Kuttner et al.
FEATURE ARTICLE
catalyst B and good overall yields for the two-step proce- dinated to the cobalt centre.5e Also in this series of
dure were obtained. Although in these cases no discrimi- experiments good to excellent regiodiversity was ob-
nation between 7 and 8 is possible, the general approach tained with these two catalyst systems. Most importantly,
leads to products with synthetic potential. The investiga- the mild reaction conditions of the cobalt-catalysed Diels–
tion was then expanded toward terminal alkynes 6 Alder reaction and the direct silyl enol ether cleavage util-
(R2 = H) which led predominantly to the formation of the ising a buffered aqueous potassium fluoride solution led
4-substituted cyclohex-3-enones 7 when catalyst system to the exclusive formation of the desired nonconjugated
A was used. Complementary to these reactions, the trans- cyclohex-3-enones 7 or 8 without isomerisation to the cor-
formations of terminal alkynes 6 utilising the alternative responding cyclohex-2-enone derivatives of type 2. The
CoBr2(py-imine) catalyst precursor (catalyst B) generated improved hydrolysis conditions applying a buffered aque-
the regioisomeric 3-substituted cyclohex-3-enone prod- ous potassium fluoride solution is preferable over the hy-
ucts of type 8. The results of this investigation utilising drolysis with Brønsted acids as we reported earlier,8
symmetrical internal alkynes as well as terminal alkynes because isomerisation toward the conjugated cyclohex-2-
for the cobalt-catalysed Diels–Alder reactions with diene enone derivatives is not observed even upon stirring for a
5 are summarised in Table 1.
prolonged reaction time.
The high degree of regiodiversity when utilising the two The high functional group tolerance of the cobalt-cataly-
different cobalt catalyst systems has been demonstrated in sed Diels–Alder reaction found in previous investigations
a number of applications and is merely based on steric in- was also observed in the present reactions; alkyl, ether,
teractions of the ligands with the starting materials coor- aryl, alkenyl and ester functionalities are well accepted.
Biographical Sketches
Julian Kuttner was born University in Marburg, ob- in the group of Prof. G.
in Bad Arolsen (Germany) taining his diploma in Hilt on cobalt(I)-catalysed
in 1985. He studied chem- 2010. He is currently reactions and their applica-
istry at the Philipps- working as a Ph.D. student tion in organic synthesis.
Svenja Warratz was born Heriot-Watt University in Hilt. Svenja is currently
in Marburg (Germany) in Edinburgh. She obtained planning her Ph.D. thesis
1987. She studied chemis- her bachelors degree in in organic chemistry.
try at the Philipps-Univer- 2009 and her masters de-
sity in Marburg and the gree in 2011 with Prof. G.
Gerhard Hilt was born in metric
organometallic ciate professor in organic
Andernach (Germany) in chemistry and from 1998 chemistry. His research in-
1968. He studied chemis- to 1999 in the group of terests are electron-trans-
try in Bonn, where he ob- Prof. R. Noyori (Nagoya, fer-activated
transition-
tained his diploma in 1992 Japan) on mechanistic in- metal complexes of cobalt
and his Ph.D. in 1996 with vestigations in asymmetric and iron and their applica-
Prof. E. Steckhan on indi- catalysis. From late 1999 tion as catalysts in atom-
rect electrochemical regen- to 2002 he was at the Lud- economic organic transfor-
eration
of
enzymatic wig-Maximilians-Univer-
mations. Another aspect of
cofactors in asymmetric sity (Munich, Germany) his research is the quantifi-
biosynthesis. From 1996 to for his habilitation, associ- cation of Lewis acidities
1998 he worked as a post- ated with the group of Prof. and the relation to reaction
doctoral fellow with Prof. P. Knochel. In 2002 he rates of Lewis acid cataly-
M. F. Semmelhack (Prince- moved to Marburg to his sed organic transforma-
ton, U.S.A.) on stoichio- current position as an asso- tions.
Synthesis 2012, 44, 1293–1303
© Thieme Stuttgart · New York

FEATURE ARTICLE
Cyclohex-3-enones and Conjugated 4-Methylenecyclohex-2-enones
1295
The use of a nonconjugated ester functionality (Table 1, hindrance of the internal alkyne would reduce the reactiv-
entry 10) results in the formation of product 8h. Under the ity and in combination with the trimethylsilyloxy group of
present reaction conditions, the carbon–carbon double the diene 5 overcrowding might occur. Also, the regiodif-
bond did not isomerise to yield the corresponding a,b-un- ferentiation might be reduced when the steric bulkiness of
saturated ester with an exocyclic double bond nor the a,b- the two substituents R1 and R2 in alkyne 6 (Scheme 2) be-
unsaturated ketone with an endocyclic double bond.
comes similar. Therefore, we focused our attention in this
series of experiments mostly on aryl–alkyl-substituted
alkynes. The results of the transformation of unsymmetri-
cal internal alkynes with diene 5 are summarised in
Table 2.
Next, we investigated the application of unsymmetrical
internal alkynes (R2  H) in the regiodivergent cobalt-
catalysed Diels–Alder reaction. We expected that the steric
Table 1 Synthesis of Nonconjugated Cyclohex-3-enone Derivatives from Symmetrical Internal Alkynes and Terminal Alkynes via a Cobalt-
Catalysed Diels–Alder Reaction
Entry
1
Catalyst
Alkyne 6
Main product 7 or 8
Ratio 7/8
Yield (%)
CH2Me
A
B
67
76
–
O
CH2Me
7a
CH2CH2Me
2
3
A
–
–
68
O
CH2CH2Me
CH2OMe
7b
OMe
A
B
61
83
OMe
O
CH2OMe
(CH2)3Me
7c
4
5
A
B
>20:1
1:3.5
60
43
O
7d
(CH2)3Me
O
8d
Ph
6
7
8
A
B
B
>20:1
1:>20
1:>20
83
65
53
O
7e
Ph
O
8e
O
8f
9
A
B
>20:1
1:15
95
42
O
7g
CH2CO2Me
10
CO2Me
O
8h
© Thieme Stuttgart · New York
Synthesis 2012, 44, 1293–1303

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J. R. Kuttner et al.
FEATURE ARTICLE
Table 2 Synthesis of Nonconjugated Cyclohex-3-enone Derivatives from Unsymmetrical Internal Alkynes via a Regiodivergent Cobalt-
Catalysed Diels–Alder Reaction
Entry
1
Catalyst
Alkyne 6
Main product 7 or 8
Ratio 7/8
Yield (%)
92
Ph
Ph
A
5.5:1
O
7i
Ph
Ph
2
3
B
A
1:>20
5.8:1
81
58
O
Ph
Ph
8i
O
7j
Ph
O
4.0:1
13
O
7k
Ph
Ph
4
5
B
A
1:>20
4.0:1
77
93
O
Ph
Ph
8j
O
7l
Ph
6
7
B
A
1:>20
>20:1
82
62
O
Ph
8l
O
(CH2)3Me
7m
8
9
B
A
1:>20
>20:1
30
70
O
(CH2)3Me
SiMe3
8m
SiMe3
O
7n
Synthesis 2012, 44, 1293–1303
© Thieme Stuttgart · New York

FEATURE ARTICLE
Cyclohex-3-enones and Conjugated 4-Methylenecyclohex-2-enones
1297
Table 2 Synthesis of Nonconjugated Cyclohex-3-enone Derivatives from Unsymmetrical Internal Alkynes via a Regiodivergent Cobalt-
Catalysed Diels–Alder Reaction (continued)
Entry
10
Catalyst
Alkyne 6
Main product 7 or 8
Ratio 7/8
Yield (%)
OMe
OMe
O
O
O
A
9.0:1
99
O
O
O
O
7o
OMe
O
O
33
O
11
B
1:>20
75a
O
O
O
OMe
O
8o
a Yield based on recovered starting material.
The regioselectivity for the two complementary catalyst
systems was good to excellent in most cases. While cata-
lyst system A generated the desired products of type 7, the
alternatively used catalyst system B furnished products of
type 8. The yields for the products of types 7 and 8 were
also good; it was only when sterically hindered alkynes
were applied that catalyst B gave reduced yields (Table 2,
entries 8 and 11). When the CoBr2(py-imine) catalyst sys-
tem B was used, even a terminal double bond in the non-
conjugated enyne was accepted (Table 2, entry 4). In
contrast, when the CoBr2(dppe) catalyst precursor was
used in this case (Table 2, entry 3), a 1,4-hydrovinylation
of the terminal double bond was also obtained and the
product 7k was isolated in 13% yield as an interesting side
product.9 The pyridine–imine-type catalysts applied in en-
try 4 are unreactive in 1,4-hydrovinylation reactions
CH2OAc
CoBr2(dppe)
Zn, ZnI2
OAc
+
9
Me3SiO
5
Me3SiO
R1
R1
10
HCl (aq)
O
R1
11
Scheme 3 Synthesis of 4-methylenecyclohex-2-enone derivatives
11
The results of the cobalt-catalysed Diels–Alder reaction/
hydrolysis sequence for the synthesis of 4-methylenecy-
clohex-2-enone derivatives 11 are summarised in Table 3.
which led to product 8j without the formation of such a The desired products could be obtained in all cases; how-
side product. On the other hand, when the substrate with a ever, the yields for most of the transformations were only
1,1-disubstituted double bond was applied (Table 2, en- moderate. The yields for the unsubstituted derivative 11a
tries 5 and 6) neither of the two catalyst systems led to a and for the aryl-substituted products 11d–g, particularly
1,4-hydrovinylation or isomerisation of this subunit. In for the thienyl-substituted product 11e, were in an accept-
many cases the regioselectivity was good to excellent so able range (Table 3, entries 1 and 4–7). Nevertheless, in
that the products can be applied in follow-up transforma- this work we were able to show that the desired 4-methyl-
tions without further purification. In this investigation the enecyclohex-2-enone derivatives of type 11 can be ob-
oxidation of the dihydroaromatic intermediates such as 10 tained. The critical step is the hydrolysis and elimination
(see Scheme 3) to the corresponding phenol derivatives from 10 to 11 and we have not yet been able to identify
was not taken into account but represents an alternative milder conditions that lead to lower yields of side prod-
follow-up reaction for the formation of 3,4-disubstituted ucts.
phenol derivatives.
Finally, the transformation of the bisfunctionalised start-
Another possibility for an interesting follow-up transfor- ing material 12 led to a regioselective cobalt-catalysed
mation is the acidic workup of the cycloaddition products Diels–Alder reaction and to a 1,4-hydrovinylation of the
bearing an acetate group in the side chain (Scheme 3). Un- terminal double bond with a second equivalent of diene 5
der these reaction conditions, the acidic hydrolysis of in- (Scheme 4). Similar to the reaction sequence outlined in
termediates of type 10 can be used for the formation of Scheme 3, the hydrolysis with aqueous hydrochloric acid
conjugated 4-methylenecyclohex-2-enones 11 in a one- led to the formation of two keto functionalities and to the
pot procedure.
© Thieme Stuttgart · New York
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J. R. Kuttner et al.
FEATURE ARTICLE
CH2OH
Table 3 Synthesis of Conjugated 4-Methylenecyclohex-2-enone
Derivatives via a Cobalt-Catalysed Diels–Alder Reaction/Hydrolysis
Sequence
1. CoBr2(dppe)
Zn, ZnI2
2
+
O
Me3SiO
O
12
5
2. HCl (aq)
25%
13
Entry Catalyst Alkyne 9 Product 11
Yield (%)
OAc
Scheme 4 Synthesis of the 4-methylenecyclohex-2-enone deriv-
ative 13
1
2
A
A
61
O
11a
OAc
In conclusion, we were able to show that the application
of two cobalt catalyst systems with complementary regio-
selectivity can be applied for the facile synthesis of a wide
range of nonconjugated cyclohex-3-enone derivatives.
The simplicity of the synthetic approach and the high
functional group tolerance of the catalysts will allow the
synthesis of such building blocks for the evaluation of
their follow-up chemistry. Furthermore, the application of
acetoxymethyl-functionalised alkynes in the cobalt-catal-
ysed Diels–Alder reaction and acidic hydrolysis led to the
generation of 4-methylenecyclohex-2-enone derivatives.
Although the yields are not very good at this stage, further
research into milder methods for the hydrolysis could fur-
nish a valuable method for the synthesis of such building
blocks. An outline for the possibilities embedded in this
synthetic approach has been demonstrated in the synthesis
of derivative 13, a product with many possibilities for
follow-up transformations.
14
O
11b
OMe
OMe
3
4
A
B
11a
OMe
O
11c
OAc
35
53
32
O
OMe
11d
OMe
OAc
S
5
6
B
B
Column chromatography was performed using silica gel
(Macherey-Nagel, 230–400 mesh size) and TLC was carried out us-
ing silica gel plates (Merck). IR spectra were obtained using a Bruker
Physics IFS 200 Interferometer, a Nicolet Magna IR 750, or a Bruker
Alpha-P spectrophotometer. 1H NMR (300 MHz) and 13C NMR (75
MHz) spectra were recorded using a Bruker Avance-300 instrument
with CDCl3 as the solvent. Low-resolution mass spectra were re-
corded using a Varian MAT CH 7A or a Micromass VG 7070 spec-
trometer for EI measurements, or a Micromass VG Autospec
spectrometer for ESI measurements. HRMS were obtained using a
Finnigan MAT 95S instrument for EI measurements or a Micro-
mass VG Autospec spectrometer for ESI measurements.
O
S
11e
OAc
O
F
11f
F
Preparative Cobalt-Catalysed [4+2] Cycloaddition; Typical
Procedure
OAc
7
8
B
B
43
26
A Schlenk flask was charged with [1,2-bis(diphenylphosphi-
no)ethane]dibromocobalt(II) complex [CoBr2(dppe); 62 mg, 0.1
mmol, 10 mol%] or [2,4,6-trimethyl-N-(pyridin-2-ylmethyl-
ene)aniline]dibromocobalt(II) complex [CoBr2(py-imine); 44 mg,
0.1 mmol, 10 mol%], anhyd ZnI2 (64 mg, 0.2 mmol, 20 mol%) and
zinc powder (13 mg, 0.2 mmol, 20 mol%) under argon atmosphere.
After addition of anhyd CH2Cl2 (1.0 mL), 2-(trimethylsilyloxy)bu-
ta-1,3-diene (5; 1.5 mmol) and the alkyne (1.0 mmol) were added.
The mixture was stirred at r.t. and the conversion was monitored by
GC/MS. After the conversion was complete, the mixture was either
directly subjected to deprotection of the silyl ether or diluted with
pentane to precipitate the metal salts and filtered through a small
plug of silica gel using pentane or Et2O–pentane as eluent to yield
the cyclohexadiene product.
O
Ph
11g
Ph
OAc
O
11h
a In this case, the symmetrical 1,4-dimethoxybut-2-yne was used as
starting material.
elimination reaction to form 13 in 25% yield. Relative to
the functional group density in 13 and the very short ac-
cess route, the yield can be considered acceptable.
Trimethylsilyl Deprotection Using In Situ Generated TBAF;
Typical Procedure
A Schlenk flask was charged with TBAB (150–200 mg) and sat. aq
KF soln (2 mL), which was brought to pH 7.0 by the addition of 1
M AcOH. The above cycloaddition reaction mixture was taken up
Synthesis 2012, 44, 1293–1303
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FEATURE ARTICLE
Cyclohex-3-enones and Conjugated 4-Methylenecyclohex-2-enones
1299
in THF–H2O (5:1, 10 mL) and was added to this suspension. The
mixture was stirred vigorously at r.t. and the conversion was moni-
tored by TLC. After complete conversion, the phases were separat-
ed, and the organic layer was taken up in Et2O (40 mL) and washed
once with H2O (20 mL). The combined aqueous phases were ex-
tracted with Et2O (2  20 mL) and the combined organic phases
were washed once with brine (20 mL), dried (MgSO4) and filtered
through a small plug of silica gel. After the solvent was removed,
the crude product was purified by column chromatography on silica
gel.
IR (neat): 2979, 2927, 2819, 1718, 1449, 1384, 1355, 1296, 1193,
1082, 952, 929, 908 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.00 (s, 2 H), 3.95 (s, 2 H), 3.30
(s, 3 H), 3.29 (s, 3 H), 2.96 (s, 2 H), 2.58–2.53 (m, 2 H), 2.47–2.42
(m, 2 H).
13C NMR (75 MHz, CDCl3): d = 210.0, 133.2, 130.3, 70.68, 70.66,
58.04, 58.00, 41.8, 38.3, 27.5.
MS (EI, 70 eV): m/z (%) = 184 (1) [M]+, 152 (100), 137 (12), 123
(9), 109 (23), 93 (20), 79 (31), 67 (13), 53 (10).
HRMS (ESI): m/z [M + Na]+ calcd for C10H16O3Na: 207.0992;
found: 207.0995.
Hydrolysis; Typical Procedure
The cyclohexadiene (1.0 mmol) was dissolved in THF (2.0 mL) and
aq 1.0 M HCl (2.0 mL) was added. The mixture was stirred at r.t.
and the conversion was monitored by GC/MS. After complete con-
version, the phases were separated, and the organic layer was taken
up in Et2O (30 mL) and washed once with H2O (20 mL). The com-
bined aqueous phases were extracted with Et2O (2 × 20 mL) and the
combined organic phases were washed once with brine (20 mL),
dried (MgSO4) and filtered through a small plug of silica gel. The
solvent was removed under reduced pressure and the crude product
was purified by column chromatography on silica gel.
4-Butylcyclohex-3-enone (7d)
Eluent: pentane–Et2O, 5:1; colourless oil.
Yield: 458 mg (3.01 mmol, 60%).
Rf = 0.25 (pentane–Et2O, 5:1).
IR (neat): 2957, 2929, 2872, 1719, 1466, 1443, 1405, 1379, 1340,
1190, 1019, 973 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.41 (tt, J = 3.6, 1.2 Hz, 1 H), 2.82
(dt, J = 3.5, 1.7 Hz, 2 H), 2.49–2.34 (m, 4 H), 2.11–1.93 (m, 2 H),
1.44–1.22 (m, 4 H), 0.88 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 211.0, 138.9, 117.5, 39.6, 38.6,
36.7, 29.7, 28.5, 22.3, 13.9.
3,4-Diethylcyclohex-3-enone (7a)
Eluent: pentane–Et2O, 5:1; colourless oil.
Catalyst A: yield: 203 mg (1.33 mmol, 67%).
Catalyst B: yield: 230 mg (1.51 mmol, 76%).
Rf = 0.26 (pentane–Et2O, 5:1).
MS (EI, 70 eV): m/z (%) = 152 (6) [M]+, 151 (57), 95 (39), 68 (100).
HRMS: m/z [M]+ calcd for C10H16O: 152.1201; found: 152.1213.
IR (neat): 2966, 2933, 2873, 1721, 1459, 1403, 1375, 1361, 1296,
1244, 1218, 1190, 515 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.78 (s, 2 H), 2.43–2.34 (m, 4 H),
2.07 (q, J = 7.6 Hz, 2 H), 2.02 (q, J = 7.7 Hz, 2 H), 0.96 (t, J = 7.6
Hz, 3 H), 0.93 (t, J = 7.6 Hz, 3 H).
3-Butylcyclohex-3-enone (8d)
Eluent: pentane–Et2O, 5:1; colourless oil.
Yield: 130 mg (0.86 mmol, 43%); 7d/8d = 1:3.5.
Rf = 0.25 (pentane–Et2O, 5:1).
13C NMR (75 MHz, CDCl3): d = 211.7, 132.3, 128.9, 43.0, 38.9,
28.9, 25.40, 25.36, 13.0, 12.8.
IR (neat): 2957, 2927, 2859, 1715, 1458, 1402, 1344, 1289, 1193,
884, 755, 500 cm–1.
MS (EI, 70 eV): m/z (%) = 152 (78) [M]+, 110 (54), 95 (100), 81
(40), 67 (24).
HRMS: m/z [M]+ calcd for C10H16O: 152.1201; found: 152.1202.
1H NMR (300 MHz, CDCl3): d = 5.60–5.59 (m, 1 H), 2.78 (s, 2 H),
2.50–2.38 (m, 4 H), 2.04–1.95 (m, 2 H), 1.45–1.22 (m, 4 H), 0.89 (t,
J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 210.9, 136.3, 120.3, 42.9, 38.5,
36.3, 29.4, 24.9, 22.2, 13.9.
3,4-Dipropylcyclohex-3-enone (7b)
Eluent: pentane–Et2O, 5:1; colourless oil.
MS (EI, 70 eV): m/z (%) = 152 (16) [M]+, 110 (28), 95 (26), 68
Catalyst A: yield: 245 mg (1.36 mmol, 68%).
Rf = 0.29 (pentane–Et2O, 5:1).
(100).
HRMS (ESI): m/z [M + Na]+ calcd for C10H16ONa: 175.1093;
found: 175.1095.
IR (neat): 2960, 2932, 2871, 1720, 1465, 1403, 1378, 1362, 1263,
1214, 1186, 515 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.79 (s, 2 H), 2.43–2.33 (m, 4 H),
2.09–1.98 (m, 4 H), 1.45–1.30 (m, 4 H), 0.89 (t, J = 7.3 Hz, 3 H),
0.88 (t, J = 7.3 Hz, 3 H).
4-Phenylcyclohex-3-enone (7e)
Eluent: pentane–Et2O, 5:1; yellow solid.
Yield: 713 mg (4.15 mmol, 83%).
13C NMR (75 MHz, CDCl3): d = 212.0, 131.6, 128.1, 43.6, 38.9,
Rf = 0.16 (pentane–Et2O, 5:1).
34.6, 34.5, 29.3, 21.5, 21.2, 14.0, 13.9.
IR (KBr): 3036, 2929, 1716, 1493, 1443, 1414, 1394, 1340, 1237,
1197, 985, 756, 696, 473, 444 cm–1.
MS (EI, 70 eV): m/z (%) = 180 (42) [M]+, 109 (100), 95 (37), 81
1H NMR (300 MHz, CDCl3): d = 7.42–7.25 (m, 5 H), 6.10 (tt,
J = 3.9, 1.2 Hz, 1 H), 3.07 (dt, J = 3.8, 1.8 Hz, 2 H), 2.91 (td,
J = 6.9, 1.6 Hz, 2 H), 2.65 (t, J = 6.9 Hz, 2 H).
(33), 67 (24).
HRMS: m/z [M]+ calcd for C12H20O: 180.1514; found: 180.1515.
13C NMR (75 MHz, CDCl3): d = 209.9, 140.7, 137.8, 128.4, 127.4,
125.2, 120.9, 39.9, 38.7, 27.9.
3,4-Bis(methoxymethyl)cyclohex-3-enone (7c)
Eluent: pentane–Et2O, 1:1; yellow oil.
MS (EI, 70 eV): m/z (%) = 172 (71) [M]+, 130 (100), 129 (94), 115
(58).
HRMS: m/z [M]+ calcd for C12H12O: 172.0888; found: 172.0898.
Catalyst A: yield: 223 mg (1.23 mmol, 61%).
Catalyst B: yield: 603 mg (3.31 mmol, 83%).
Rf = 0.14 (pentane–Et2O, 1:1).
© Thieme Stuttgart · New York
Synthesis 2012, 44, 1293–1303

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FEATURE ARTICLE
3-Phenylcyclohex-3-enone (8e)
HRMS: m/z [M]+ calcd for C9H12O3: 168.0786; found: 168.0785.
Eluent: pentane–Et2O, 5:1; yellow solid.
3-Methyl-4-phenylcyclohex-3-enone (7i)
Eluent: pentane–Et2O, 5:1; colourless oil.
Yield: 449 mg (2.61 mmol, 65%).
Rf = 0.16 (pentane–Et2O, 5:1).
Yield: 172 mg (0.92 mmol, 92%); 7i/8i = 5.5:1.
Rf = 0.17 (pentane–Et2O, 5:1).
IR (KBr): 3053, 2911, 1703, 1493, 1444, 1398, 1335, 1247, 1195,
1069, 886, 747, 692, 421, 411 cm–1.
IR (neat): 2909, 2852, 1714, 1492, 1443, 1399, 1357, 1251, 1187,
759, 700, 484 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.38–7.32 (m, 2 H), 7.28–7.23 (m,
1 H), 7.18–7.13 (m, 2 H), 2.96 (s, 2 H), 2.76–2.71 (m, 2 H), 2.62–
2.58 (m, 2 H), 1.65 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 210.5, 142.1, 132.7, 128.2, 128.1,
126.9, 126.6, 45.5, 39.2, 31.7, 20.2.
1H NMR (300 MHz, CDCl3): d = 7.40–7.25 (m, 5 H), 6.34 (tt,
J = 4.2, 1.9 Hz, 1 H), 3.28 (d, J = 1.9 Hz, 2 H), 2.70–2.63 (m, 2 H),
2.58–2.54 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 209.9, 139.7, 134.9, 128.5, 127.5,
125.0, 123.5, 41.9, 37.9, 25.2.
MS (EI, 70 eV): m/z (%) = 172 (68) [M]+, 144 (34), 130 (84), 129
(100), 115 (70).
HRMS: m/z [M]+ calcd for C12H12O: 172.0888; found: 172.0901.
MS (EI, 70 eV): m/z (%) = 186 (40) [M]+, 144 (20), 129 (100), 115
(20).
3-(Cyclohex-1-enyl)cyclohex-3-enone (8f)
HRMS (ESI): m/z [M + H]+ calcd for C13H15O: 187.1117; found:
Eluent: pentane–Et2O, 5:1; colourless solid.
187.1119.
Yield: 186 mg (1.06 mmol, 53%).
4-Methyl-3-phenylcyclohex-3-enone (8i)
Eluent: pentane–Et2O, 5:1; yellow oil.
Rf = 0.26 (pentane–Et2O, 5:1).
IR (KBr): 2925, 1711, 1426, 1406, 1345, 1284, 1242, 1188, 923,
792, 518, 413 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.94 (t, J = 3.9 Hz, 1 H), 5.71 (t,
J = 3.8 Hz, 1 H), 3.04 (d, J = 1.3 Hz, 2 H), 2.56–2.45 (m, 4 H),
2.23–2.14 (m, 4 H), 1.73–1.54 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 210.9, 135.5, 135.0, 123.5, 120.0,
40.6, 38.4, 25.8, 25.6, 25.2, 22.9, 22.3.
MS (EI, 70 eV): m/z (%) = 176 (100) [M]+, 133 (17), 119 (32), 105
(23), 91 (33), 79 (20).
HRMS: m/z [M]+ calcd for C12H16O: 176.1201; found: 176.1195.
Yield: 753 mg (4.05 mmol, 81%).
Rf = 0.17 (pentane–Et2O, 5:1).
IR (neat): 3055, 2912, 1717, 1493, 1442, 1362, 1247, 1210, 762,
702 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.38–7.32 (m, 2 H), 7.28–7.22 (m,
1 H), 7.16–7.13 (m, 2 H), 3.13 (d, J = 1.7 Hz, 2 H), 2.62–2.52 (m, 4
H), 1.71 (t, J = 2.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 210.5, 141.5, 130.2, 129.6, 128.3,
128.2, 126.7, 45.3, 38.5, 31.5, 20.2.
MS (EI, 70 eV): m/z (%) = 186 (92) [M]+, 144 (68), 129 (100), 115
(22), 43 (22).
4-(Prop-1-en-2-yl)cyclohex-3-enone (7g)
Eluent: pentane–Et2O, 5:1; yellow oil.
HRMS: m/z [M]+ calcd for C13H14O: 186.1045; found: 186.1036.
Yield: 224 mg (1.65 mmol, 95%).
3-Allyl-4-phenylcyclohex-3-enone (7j)
Eluent: pentane–Et2O, 5:1; colourless oil.
Rf = 0.28 (pentane–Et2O, 5:1).
IR (neat): 3093, 2970, 2858, 1724, 1609, 1443, 1399, 1341, 1269,
1195, 890, 819, 412 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.87 (t, J = 4.0 Hz, 1 H), 5.03 (s,
1 H), 4.97 (s, 1 H), 3.00 (d, J = 3.6 Hz, 2 H), 2.69 (t, J = 6.9 Hz, 2
H), 2.53 (t, J = 6.8 Hz, 2 H), 1.94 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 210.3, 142.1, 137.6, 120.8, 111.9,
39.8, 38.5, 25.8, 20.7.
Yield: 122 mg (0.58 mmol, 58%); 7j/8j = 5.8:1.
Rf = 0.21 (pentane–Et2O, 5:1).
IR (neat): 3075, 3021, 2970, 2901, 2846, 1714, 1635, 1491, 1438,
1358, 1293, 1252, 1190, 994, 914, 756, 700, 563, 487 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.38–7.32 (m, 2 H), 7.30–7.24 (m,
1 H), 7.19–7.15 (m, 2 H), 5.71 (ddt, J = 16.9, 10.2, 6.5 Hz, 1 H),
5.07–4.98 (m, 2 H), 2.98 (s, 2 H), 2.78–2.71 (m, 4 H), 2.62–2.58 (m,
2 H).
13C NMR (75 MHz, CDCl3): d = 210.5, 141.8, 135.5, 134.5, 128.7,
128.3, 127.8, 126.8, 116.5, 43.1, 39.0, 38.2, 31.9.
MS (EI, 70 eV): m/z (%) = 212 (28) [M]+, 197 (35), 169 (48), 155
(75), 141 (100), 128 (77), 115 (53), 91 (34), 77 (26).
MS (EI, 70 eV): m/z (%) = 136 (86) [M]+, 94 (28), 93 (50), 79 (100).
HRMS: m/z [M]+ calcd for C9H12O: 136.0888; found: 136.0893.
Methyl 2-(5-Oxocyclohex-1-enyl)acetate (8h)
Eluent: pentane–Et2O, 1:1; yellow oil.
Yield: 352 mg (2.10 mmol, 42%); 7h/8h = 1:15.
Rf = 0.30 (pentane–Et2O, 1:1).
HRMS (ESI): m/z [M + Na]+ calcd for C15H16ONa: 235.1093;
found: 235.1094.
IR (neat): 2954, 2851, 1712, 1436, 1342, 1258, 1195, 1161, 1062,
1007, 970, 889, 846, 754, 705, 498 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.78 (s, 1 H), 3.68 (s, 3 H), 3.05
(s, 2 H), 2.91 (s, 2 H), 2.46 (s, 4 H).
13C NMR (75 MHz, CDCl3): d = 209.3, 171.3, 129.2, 125.5, 51.9,
42.9, 41.9, 37.9, 24.8.
MS (EI, 70 eV): m/z (%) = 168 (68) [M]+, 126 (100), 108 (100), 97
3-[2-(3-Oxobutyl)prop-2-enyl]-4-phenylcyclohex-3-enone (7k)
Eluent: pentane–EtOAc, 3:1; yellow oil.
Yield: 36 mg (0.13 mmol, 13%); 7k/8k = 4:1.
Rf = 0.16 (pentane–EtOAc, 3:1).
IR (neat): 2903, 1710, 1644, 1491, 1437, 1357, 1253, 1189, 1160,
895, 760, 702, 485 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.37–7.31 (m, 2 H), 7.29–7.23 (m,
1 H), 7.18–7.13 (m, 2 H), 4.78–4.77 (m, 2 H), 2.92 (s, 2 H), 2.79–
(34), 79 (92), 67 (38).
Synthesis 2012, 44, 1293–1303
© Thieme Stuttgart · New York

FEATURE ARTICLE
Cyclohex-3-enones and Conjugated 4-Methylenecyclohex-2-enones
1301
2.75 (m, 2 H), 2.70 (s, 2 H), 2.60 (t, J = 6.8 Hz, 2 H), 2.35–2.29 (m,
3-Butyl-4-(2,6-dimethylcyclohex-1-enyl)cyclohex-3-enone (7m)
2 H), 2.15–2.09 (m, 2 H), 2.05 (s, 3 H).
The product was obtained as a 1:1 mixture of axially chiral diaste-
reomers which could not be separated by simple silica gel column
chromatography.
13C NMR (75 MHz, CDCl3): d = 210.5, 207.8, 145.4, 141.8, 135.6,
128.34, 128.26, 127.8, 126.9, 111.5, 43.0, 41.5, 40.3, 38.9, 32.0,
29.8, 29.4.
MS (EI, 70 eV): m/z (%) = 282 (46) [M]+, 264 (19), 239 (18), 224
(100), 211 (90), 193 (39), 181 (72), 167 (90), 155 (93), 141 (64),
128 (76), 115 (52), 91 (41), 77 (19).
Eluent: pentane–Et2O, 6:1; yellow oil.
Yield: 161 mg (0.62 mmol, 62%).
Rf = 0.39 (pentane–Et2O, 5:1).
IR (neat): 2956, 2927, 2869, 1718, 1495, 1456, 1371, 1291, 1182,
1112, 1045, 982, 802 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.96–2.80 (m, 2 H), 2.49–2.41 (m,
3 H), 2.30–1.52 (m, 9 H), 1.49–1.48 (m, 3 H), 1.45–1.16 (m, 5 H),
0.97–0.85 (m, 6 H).
HRMS (ESI): m/z [M + Na]+ calcd for C19H22O2Na: 305.1512;
found: 305.1511.
4-Allyl-3-phenylcyclohex-3-enone (8j)
Eluent: pentane–Et2O, 5:1; yellow oil.
13C NMR (75 MHz, CDCl3): d = 212.02, 211.98, 137.0, 135.7,
134.4, 132.0, 129.9, 129.4, 128.3, 127.8, 42.7, 42.5, 38.9, 38.8,
34.8, 33.3, 32.9, 31.9, 31.3 (4 C), 30.7, 29.8, 29.3, 28.7, 23.2, 22.7,
20.65, 20.63, 20.52, 20.49, 20.13, 20.09, 14.0, 13.9.
MS (EI, 70 eV): m/z (%) = 260 (80) [M]+, 245 (33), 217 (100), 175
(31), 159 (44), 133 (30), 119 (30), 105 (50), 91 (48).
Yield: 326 mg (1.54 mmol, 77%).
Rf = 0.21 (pentane–Et2O, 5:1).
IR (neat): 3077, 3056, 2973, 2902, 2844, 1714, 1635, 1492, 1442,
1361, 1296, 1251, 1196, 992, 913, 755, 700, 476 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.37–7.32 (m, 2 H), 7.29–7.24 (m,
1 H), 7.17–7.14 (m, 2 H), 5.71 (ddt, J = 16.8, 10.4, 6.3 Hz, 1 H),
5.08–5.01 (m, 2 H), 3.16 (s, 2 H), 2.78 (d, J = 6.3 Hz, 2 H), 2.57 (s,
4 H).
13C NMR (75 MHz, CDCl3): d = 210.3, 141.1, 136.0, 132.0, 131.5,
128.4, 127.9, 127.0, 116.1, 45.7, 38.6, 38.1, 28.7.
MS (EI, 70 eV): m/z (%) = 212 (88) [M]+, 197 (30), 169 (70), 155
HRMS: m/z [M]+ calcd for C18H28O: 260.2140; found: 260.2135.
4-Butyl-3-(2,6-dimethylcyclohex-1-enyl)cyclohex-3-enone (8m)
The product was obtained as a 1:1 mixture of axially chiral diaste-
reomers which could not be separated by simple silica gel column
chromatography.
(100), 141 (90), 129 (82), 115 (45), 91 (95), 77 (39).
HRMS: m/z [M]+ calcd for C15H16O: 212.1201; found: 212.1198.
Eluent: pentane–Et2O, 6:1; yellow oil.
Yield: 78 mg (0.30 mmol, 30%).
Rf = 0.39 (pentane–Et2O, 5:1).
3-(2-Methallyl)-4-phenylcyclohex-3-enone (7l)
Eluent: pentane–Et2O, 5:1; colourless oil.
IR (neat): 2956, 2932, 2871, 1716, 1676, 1456, 1377, 1251, 1205,
1035, 841 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.93–2.59 (m, 2 H), 2.50–2.32 (m,
4 H), 2.21–2.12 (m, 1 H), 2.06–1.83 (m, 4 H), 1.78–1.49 (m, 3 H),
1.47 (s, 3 H), 1.41–1.17 (m, 5 H), 0.95–0.84 (m, 6 H).
13C NMR (75 MHz, CDCl3): d = 211.9, 211.7, 135.9, 135.0, 133.5,
133.1, 130.8, 128.9, 128.63, 128.59, 46.0, 43.2, 38.70, 38.66, 34.8,
33.5, 33.1, 31.9, 31.32, 31.31, 31.30, 30.4, 30.0, 29.4, 28.0, 27.7,
23.3, 22.8, 20.5 (2 C), 20.40, 20.37, 20.1, 19.9, 14.0, 13.9.
Yield: 210 mg (0.93 mmol, 93%); 7l/8l = 4:1.
Rf = 0.24 (pentane–Et2O, 5:1).
IR (neat): 2968, 2907, 1714, 1647, 1492, 1441, 1359, 1251, 1189,
890, 757, 700, 484 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.37–7.31 (m, 2 H), 7.29–7.23 (m,
1 H), 7.20–7.15 (m, 2 H), 4.80 (s, 1 H), 4.71 (s, 1 H), 2.95 (s, 2 H),
2.80–2.75 (m, 2 H), 2.69 (s, 2 H), 2.62–2.58 (m, 2 H), 1.60 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 210.7, 142.9, 141.9, 135.2, 128.6,
128.3, 127.8, 126.8, 111.9, 43.0, 41.9, 39.0, 32.0, 22.4.
MS (EI, 70 eV): m/z (%) = 260 (69) [M]+, 245 (32), 217 (100), 187
(29), 159 (61), 133 (30), 119 (34), 105 (52), 91 (50).
MS (EI, 70 eV): m/z (%) = 226 (42) [M]+, 211 (80), 183 (40), 169
HRMS: m/z [M]+ calcd for C18H28O: 260.2140; found: 260.2151.
(100), 155 (97), 141 (96), 128 (85), 115 (65), 91 (50), 77 (34).
3-Methyl-4-(trimethylsilyl)cyclohex-3-enone (7n)
Eluent: pentane–Et2O, 5:1; colourless oil.
HRMS: m/z [M + Na]+ calcd for C16H18ONa: 249.1250; found:
249.1252.
Yield: 253 mg (1.39 mmol, 70%).
4-(2-Methallyl)-3-phenylcyclohex-3-enone (8l)
Eluent: pentane–Et2O, 5:1; colourless oil.
Rf = 0.27 (pentane–Et2O, 5:1).
IR (neat): 1718, 1247, 832, 752, 688, 501 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.84 (s, 2 H), 2.48–2.33 (m, 4 H),
1.82 (s, 3 H), 0.16 (s, 9 H).
Yield: 372 mg (1.64 mmol, 82%).
Rf = 0.24 (pentane–Et2O, 5:1).
IR (neat): 3076, 3022, 2968, 2933, 1718, 1648, 1493, 1443, 1362,
1298, 1251, 1195, 890, 759, 703, 418 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.37–7.32 (m, 2 H), 7.29–7.23 (m,
1 H), 7.19–7.15 (m, 2 H), 4.83 (s, 1 H), 4.72 (s, 1 H), 3.18 (s, 2 H),
2.75 (s, 2 H), 2.61–2.48 (m, 4 H), 1.63 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 210.5, 143.6, 141.1, 132.1 (2 C),
128.3, 127.8, 126.9, 111.5, 45.7, 41.9, 38.7, 28.5, 22.6.
13C NMR (75 MHz, CDCl3): d = 211.6, 141.0, 130.9, 47.4, 38.7,
28.9, 23.1, 0.0.
MS (EI, 70 eV): m/z (%) = 182 (43) [M]+, 167 (74), 151 (12), 75
(32), 73 (100), 59 (16).
HRMS: m/z [M]+ calcd for C10H18OSi: 182.1127; found: 182.1131.
6-(2-[2-(4-Methoxyphenyl)-5-oxocyclohex-1-enyl]ethyl)-2,2-
dimethyl-4H-1,3-dioxin-4-one (7o)
MS (EI, 70 eV): m/z (%) = 226 (60) [M]+, 211 (22), 183 (19), 169
(37), 155 (100), 142 (38), 128 (21), 115 (13), 91 (14), 77 (18).
Eluent: pentane–Et2O, 1:3; colourless solid.
HRMS: m/z [M]+ calcd for C16H18O: 226.1358; found: 226.1349.
Yield: 354 mg (0.99 mmol, 99%); 7o/8o = 9:1.
Rf = 0.16 (pentane–Et2O, 1:3).
© Thieme Stuttgart · New York
Synthesis 2012, 44, 1293–1303

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J. R. Kuttner et al.
FEATURE ARTICLE
IR (neat): 1714, 1633, 1607, 1511, 1390, 1375, 1291, 1251, 1197,
1179, 1041, 1012, 902, 829, 798, 760, 509 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.04 (d, J = 8.5 Hz, 2 H), 6.89 (d,
J = 8.4 Hz, 2 H), 5.09 (s, 1 H), 3.81 (s, 3 H), 2.96 (s, 2 H), 2.70 (t,
J = 6.5 Hz, 2 H), 2.57 (t, J = 6.4 Hz, 2 H), 2.29–2.18 (m, 4 H), 1.59
(s, 6 H).
13C NMR (75 MHz, CDCl3): d = 209.7, 170.6, 161.0, 158.6, 135.5,
133.6, 128.9, 128.1, 113.9, 106.3, 93.3, 55.2, 42.9, 38.7, 32.2, 32.0,
29.9, 24.9.
1H NMR (300 MHz, CDCl3): d = 6.13 (d, J = 0.8 Hz, 1 H), 5.36–
5.27 (m, 2 H), 4.24 (d, J = 1.4 Hz, 2 H), 3.40 (s, 3 H), 2.78–2.69 (m,
2 H), 2.56–2.47 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 199.2, 153.0, 139.5, 125.7, 114.7,
71.3, 58.8, 37.8, 31.8.
MS (EI, 70 eV): m/z (%) = 152 (21) [M]+, 122 (78), 109 (63), 91
(71), 81 (66), 79 (100), 77 (63).
HRMS (ESI): m/z [M + Na]+ calcd for C9H12O2Na: 175.0730;
found: 175.0731.
MS (EI, 70 eV): m/z (%) = 356 (1) [M]+, 298 (56), 272 (62), 214
(44), 172 (40), 121 (26), 58 (28), 43 (100).
3-(4-Methoxyphenyl)-4-methylenecyclohex-2-enone (11d)
Eluent: pentane–Et2O, 2:1; yellow oil.
HRMS: m/z [M]+ calcd for C21H24O5: 356.1624; found: 356.1621.
Yield: 74 mg (0.35 mmol, 35%).
6-(2-[2-(4-Methoxyphenyl)-4-oxocyclohex-1-enyl]ethyl)-2,2-
dimethyl-4H-1,3-dioxin-4-one (8o)
Eluent: pentane–Et2O, 1:3; yellow solid.
Rf = 0.16 (pentane–Et2O, 2:1).
IR (neat): 3406, 2955, 2839, 1663, 1605, 1576, 1559, 1510, 1443,
1421, 1369, 1295, 1247, 1174, 1033, 840, 533 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.37–7.32 (m, 2 H), 6.95–6.90 (m,
2 H), 6.05 (d, J = 1.1 Hz, 1 H), 5.56–5.51 (m, 1 H), 5.21 (s, 1 H),
3.84 (s, 3 H), 2.89–2.81 (m, 2 H), 2.59 (t, J = 7.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 199.3, 160.8, 158.0, 142.1, 130.5,
130.3, 125.7, 119.7, 113.8, 55.3, 38.2, 32.7.
MS (EI, 70 eV): m/z (%) = 214 (100) [M]+, 186 (31), 171 (76), 158
(49), 155 (31), 128 (28), 115 (43).
HRMS: m/z [M]+ calcd for C14H14O2: 214.0994; found: 214.0984.
Yield: 119 mg (0.33 mmol, 33%).
Rf = 0.16 (pentane–Et2O, 1:3).
IR (thin film, CH2Cl2): 1715, 1631, 1608, 1510, 1389, 1374, 1271,
1245, 1201, 1176, 1032, 1017, 901, 833, 809, 732, 701, 509 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.02 (d, J = 8.8 Hz, 2 H), 6.88 (d,
J = 8.8 Hz, 2 H), 5.10 (s, 1 H), 3.81 (s, 3 H), 3.09 (s, 2 H), 2.56–2.55
(m, 4 H), 2.35–2.23 (m, 4 H), 1.59 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 209.6, 170.8, 161.0, 158.6, 132.9,
132.2, 131.5, 128.9, 114.0, 106.3, 93.2, 55.3, 46.0, 38.4, 32.2, 29.9,
28.6, 24.9.
4-Methylene-3-(2-thienyl)cyclohex-2-enone (11e)
Eluent: pentane–Et2O, 5:1; yellow oil.
MS (EI, 70 eV): m/z (%) = 356 (1) [M]+, 298 (11), 227 (3), 214 (7),
186 (5), 171 (6), 58 (66), 43 (100).
HRMS: m/z [M]+ calcd for C21H24O5: 356.1624; found: 356.1624.
Yield: 101 mg (0.53 mmol, 53%).
Rf = 0.07 (pentane–Et2O, 10:1).
IR (neat): 3473, 3100, 2954, 1662, 1558, 1423, 1367, 1273, 1244,
1176, 922, 854, 709, 527 cm–1.
4-Methylenecyclohex-2-enone (11a)
Eluent: pentane–Et2O, 10:1; yellow oil.
1H NMR (300 MHz, CDCl3): d = 7.46 (dd, J = 5.1, 1.1 Hz, 1 H),
7.33 (dd, J = 3.7, 1.1 Hz, 1 H), 7.11 (dd, J = 5.1, 3.7 Hz, 1 H), 6.21
(d, J = 1.1 Hz, 1 H), 5.62 (s, 1 H), 5.58 (t, J = 1.2 Hz, 1 H), 2.84 (t,
J = 6.7 Hz, 2 H), 2.59 (t, J = 6.7 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 198.6, 150.4, 141.6, 140.1, 129.6,
128.5, 127.9, 125.1, 119.4, 38.4, 32.9.
MS (EI, 70 eV): m/z (%) = 190 (100) [M]+, 161 (33), 147 (30), 134
(38), 129 (14).
HRMS: m/z [M]+ calcd for C11H10OS: 190.0452; found: 190.0456.
Yield: 132 mg (1.22 mmol, 61%).
Rf = 0.12 (pentane–Et2O, 10:1).
1H NMR (300 MHz, CDCl3): d = 7.08 (d, J = 9.9 Hz, 1 H), 5.95 (d,
J = 9.9 Hz, 1 H), 5.33 (s, 1 H), 5.29 (s, 1 H), 2.78–2.71 (m, 2 H),
2.56–2.48 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 198.9, 147.3, 140.5, 128.0, 119.2,
37.1, 29.1.
The analytical data were in accordance with literature data.10
3-Methyl-4-methylenecyclohex-2-enone (11b)
Eluent: pentane–Et2O, 5:1; yellow oil.
3-(4-Fluorophenyl)-4-methylenecyclohex-2-enone (11f)
Eluent: pentane–MTBE, 10:1; yellow oil.
Yield: 17 mg (0.14 mmol, 14%).
Yield: 65 mg (0.32 mmol, 32%).
Rf = 0.08 (pentane–Et2O, 10:1).
Rf = 0.09 (pentane–MTBE, 10:1).
1H NMR (300 MHz, CDCl3): d = 5.90 (s, 1 H), 5.35 (s, 1 H), 5.33
(s, 1 H), 2.74 (t, J = 7.0 Hz, 2 H), 2.72 (t, J = 7.0 Hz, 2 H), 2.05 (s,
3 H).
13C NMR (75 MHz, CDCl3): d = 199.4, 154.3, 142.2, 127.8, 115.4,
37.6, 31.3, 20.0.
IR (neat): 3068, 2954, 2357, 1662, 1595, 1504, 1367, 1226, 1165,
843, 482 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.41–7.32 (m, 2 H), 7.15–7.05 (m,
2 H), 6.03 (d, J = 1.2 Hz, 1 H), 5.56–5.51 (m, 1 H), 5.15 (s, 1 H),
2.92–2.83 (m, 2 H), 2.59 (t, J = 7.1 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 199.0, 163.5 (d, J = 249.6 Hz),
157.2, 141.9, 134.0 (d, J = 3.2 Hz), 130.8 (d, J = 8.4 Hz), 126.7,
120.0, 115.5 (d, J = 21.7 Hz), 38.0, 32.4.
The analytical data were in accordance with literature data.11
3-(Methoxymethyl)-4-methylenecyclohex-2-enone (11c)
Eluent: pentane–Et2O, 2:1; yellow oil.
MS (EI, 70 eV): m/z (%) = 202 (76) [M]+, 187 (18), 173 (40), 159
(72), 146 (100), 133 (26), 120 (25).
Yield: 17 mg (0.11 mmol, 11%).
Rf = 0.13 (pentane–Et2O, 2:1).
HRMS: m/z [M]+ calcd for C13H11OF: 202.0794; found: 202.0799.
IR (neat): 3407, 2928, 2350, 1667, 1448, 1283, 1189, 1091, 910
cm–1.
Synthesis 2012, 44, 1293–1303
© Thieme Stuttgart · New York

FEATURE ARTICLE
Cyclohex-3-enones and Conjugated 4-Methylenecyclohex-2-enones
1303
4-Methylene-3-phenylcyclohex-2-enone (11g)
Eluent: pentane–Et2O, 5:1; yellow oil.
(3) (a) McAndrew, B. A. J. Chem. Soc., Perkin Trans. 1 1979,
1837. (b) Balme, G.; Goré, J. J. Org. Chem. 1983, 48, 3336.
(c) Birch, A. J. J. Proc. R. Soc. N.S.W. 1949, 83, 245.
(d) Jung, M. E.; Rayle, H. L. Synth. Commun. 1994, 24, 197.
(e) Chamakh, A.; Amri, H. Tetrahedron Lett. 1998, 39, 375.
(4) (a) Kim, J. N.; Im, Y. J.; Kim, J. M. Tetrahedron Lett. 2002,
43, 6597. (b) Park, D. Y.; Kim, S. J.; Kim, T. H.; Kim, J. N.
Tetrahedron Lett. 2006, 47, 6315.
(5) (a) Danz, M.; Hilt, G. Adv. Synth. Catal. 2011, 353, 303.
(b) Auvinet, A.-L.; Harrity, J. P. A.; Hilt, G. J. Org. Chem.
2010, 75, 3893. (c) Hilt, G.; Janikowski, J. Org. Lett. 2009,
11, 773. (d) Hilt, G.; Danz, M. Synthesis 2008, 2257.
(e) Mörschel, P.; Janikowski, J.; Hilt, G.; Frenking, G. J. Am.
Chem. Soc. 2008, 130, 8952. (f) Hilt, G.; Janikowski, J.;
Hess, W. Angew. Chem. Int. Ed. 2006, 45, 5204; Angew.
Chem. 2006, 118, 5328. (g) Hilt, G.; Paul, A.; Harms, K.
J. Org. Chem. 2008, 73, 5187. (h) Hilt, G.; Paul, A.; Hengst,
C. Synthesis 2009, 3305. (i) Hilt, G.; Hess, W.; Harms, K.
Synthesis 2008, 75. (j) Treutwein, J.; Hilt, G. Angew. Chem.
Int. Ed. 2008, 47, 6811; Angew. Chem. 2008, 120, 6916.
(k) Hilt, G.; Janikowski, J. Angew. Chem. Int. Ed. 2008, 47,
5243; Angew. Chem. 2008, 120, 5321. For recent reviews
concerning cobalt-catalysed reactions involving
Yield: 80 mg (0.43 mmol, 43%).
Rf = 0.17 (pentane–Et2O, 5:1).
IR (neat): 3048, 2952, 2901, 1661, 1563, 1491, 1441, 1317, 1172,
916, 876, 736, 694, 455 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.44–7.34 (m, 5 H), 6.06 (d,
J = 1.2 Hz, 1 H), 5.55–5.50 (m, 1 H), 5.17 (s, 1 H), 2.93–2.83 (m, 2
H), 2.61 (t, J = 7.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 199.1, 158.3, 141.9, 138.1, 129.4,
129.0, 128.3, 126.7, 120.0, 38.0, 32.5.
MS (EI, 70 eV): m/z (%) = 184 (96) [M]+, 169 (15), 155 (59), 141
(72), 128 (100), 115 (25), 102 (24).
HRMS (ESI): m/z [M + Na]+ calcd for C13H12ONa: 207.0780;
found: 207.0781.
4-Methylene-3-(prop-1-en-2-yl)cyclohex-2-enone (11h)
Eluent: pentane–Et2O, 5:1; yellow oil.
Yield: 38 mg (0.26 mmol, 26%).
Rf = 0.21 (pentane–Et2O, 5:1).
cyclopentadienylcobalt-type catalyst systems, see:
(l) Leboeuf, D.; Gandon, V.; Malacria, M. In Handbook of
Cyclization Reactions, Vol. 1; Ma, S., Ed.; Wiley-VCH:
Weinheim, 2009, 367. (m) Galan, B. R.; Rovis, T. Angew.
Chem. Int. Ed. 2009, 48, 2830. (n) Omae, I. Appl.
Organomet. Chem. 2008, 22, 149. (o) Hess, W.; Treutwein,
J.; Hilt, G. Synthesis 2008, 3537. (p) Omae, I. Appl.
Organomet. Chem. 2007, 21, 318. (q) Kotha, S.;
Brahmachary, E.; Lahiri, K. Eur. J. Org. Chem. 2005, 4741.
(r) Malacria, M.; Aubert, C.; Renaud,
J.-L. In Science of Synthesis, Houben–Weyl Methods of
Molecular Transformations, Vol. 1; Lautens, M., Ed.; Georg
Thieme Verlag: Stuttgart, 2001, 439. (s) Saito, S.;
Yamamoto, Y. Chem. Rev. 2000, 100, 2901.
IR (neat): 3088, 2956, 1662, 1561, 1440, 1368, 1269, 1228, 1178,
1017, 910, 729, 450 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.88 (d, J = 1.1 Hz, 1 H), 5.45–
5.40 (m, 1 H), 5.34 (s, 1 H), 5.28–5.23 (m, 1 H), 5.19–5.15 (m, 1 H),
2.77–2.69 (m, 2 H), 2.52 (t, J = 7.0 Hz, 2 H), 1.95 (dd, J = 1.4, 0.9
Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 199.7, 159.8, 141.9, 140.4, 124.5,
118.8, 118.3, 38.3, 32.6, 22.3.
MS (EI, 70 eV): m/z (%) = 148 (96) [M]+, 133 (35), 120 (74), 105
(97), 92 (32), 91 (100), 79 (29).
HRMS (ESI): m/z [M + H]+ calcd for C10H13O: 149.0961; found:
149.0962.
(6) Ligands: dppe = 1,2-bis(diphenylphosphino)ethane; py-
imine = 2,4,6-trimethyl-N-(pyridin-2-ylmethylene)aniline.
(7) In previous reactions the use of iron powder increased the
chemo- and regioselectivity. In this series of experiments,
the iron powder additive was not necessary and was
therefore not added.
(8) Hilt, G.; Smolko, K. I.; Lotsch, B. V. Synlett 2002, 1081.
(9) The catalysts with phosphine-type ligands show reactivity
for the Diels–Alder reaction as well as for 1,4-hydrovinyl-
ation. In contrast, catalysts with pyridine–imine-type ligands
are unreactive in 1,4-hydrovinylation reactions thus far.
(10) Jung, M. E.; Rayle, H. L. Synth. Commun. 1994, 24, 197.
(11) Thomas, M. T.; Fallis, A. G. J. Am. Chem. Soc. 1976, 98,
1227.
References
(1) (a) Stapleford, K. S. J. Synth. Commun. 1982, 12, 651.
(b) Crowshaw, K.; Newstead, R. C.; Rogers, N. A. J.
Tetrahedron Lett. 1964, 2307.
(2) (a) Irie, H.; Katakawa, J.; Mizuno, Y.; Udaka, S.; Taga, T.;
Osaki, K. J. Chem. Soc., Chem. Commun. 1978, 717.
(b) Nemoto, H.; Hashimoto, M.; Kurobe, H.; Fukumoto, K.
J. Chem. Soc., Perkin Trans. 1 1985, 927. (c) Rickards, R.
W.; Rodwell, J. L.; Schmalzl, K. J. J. Chem. Soc., Chem.
Commun. 1977, 849. (d) Wild, H. J. Org. Chem. 1994, 59,
2748. (e) Wild, H.; Born, L. Angew. Chem., Int. Ed. Engl.
1991, 30, 1685; Angew. Chem. 1991, 103, 1729.
(f) Katsuta, Y.; Aoyama, Y.; Osone, H.; Wada, A.; Ito, M.
J. Chem. Soc., Perkin Trans. 1 1997, 1405.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 1293–1303