Ready access to alkylidenecyclopentenones by Nazarov cyclization/β- elimination of 2-hydroxyalkyl-1,4-dien-3-ones

Article abstract of DOI:10.1002/ejoc.201301537

Cross-conjugated dienones bearing α-hydroxyalkyl substituents readily undergo Nazarov cyclization followed by deprotonation of the resulting cyclopentenyl cation, and β-elimination of the exocyclic hydroxy group to form alkylidenecyclopentenones in moderate yield. The deprotonation step occurs with complete regioselectivity opposite to the hydroxyalkyl substituent, with preferential introduction of an endocyclic olefin. The transformation is tolerant of a variety of substituents and occurs under relatively mild conditions. Alkylidenecyclopentenones are readily accessed in moderate yields from α-hydroxy-substituted dienones by Nazarov cyclization followed by β-hydroxy elimination. The regioselectivity of the initial deprotonation of the Nazarov intermediate is remarkably high and leads to an endocyclic alkene opposite to the hydroxy subsitutent. Copyright

Full text of DOI:10.1002/ejoc.201301537

FULL PAPER
DOI: 10.1002/ejoc.201301537
Ready Access to Alkylidenecyclopentenones by Nazarov Cyclization/β-
Elimination of 2-Hydroxyalkyl-1,4-dien-3-ones
Owen Scadeng[a] and F. G. West*[a]
Keywords: Cyclization / Elimination / Carbocycles / Enones / Domino reactions
Cross-conjugated dienones bearing α-hydroxyalkyl substitu-
ents readily undergo Nazarov cyclization followed by depro-
tonation of the resulting cyclopentenyl cation, and β-elimi-
nation of the exocyclic hydroxy group to form alkylidene-
cyclopentenones in moderate yield. The deprotonation step
occurs with complete regioselectivity opposite to the hy-
droxyalkyl substituent, with preferential introduction of an
endocyclic olefin. The transformation is tolerant of a variety
of substituents and occurs under relatively mild conditions.
trocyclization and semipinacol rearrangement[11] would
lead to 1,3-diketone products in which the initially formed
stereocenters are preserved, and a new quaternary center is
formed between the two carbonyl groups. In this paper, we
describe the results of these studies, including an unexpec-
ted preference for a dehydrative double elimination pathway
leading to alkylidenecyclopentenones.
Introduction
The Nazarov cyclization enjoys a well-deserved reputa-
tion as an efficient way to produce cyclopentanoid prod-
ucts.[1] Recent advances in Nazarov cyclization chemistry
have focused on the development of catalytic activation
methods,[2] the development of processes to induce asym-
metry,[3] the use of unconventional substrates,[4] and the en-
hanced build-up of molecular complexity by interception
of the cyclopentenyl cation intermediate.[5] Trapping of the
oxyallyl cation intermediate can proceed by cycloaddition
processes,[6] but nucleophilic capture at only one end of the
allyl system can also be accomplished, leading to a variety
of highly substituted cyclopentanone products. For exam-
ple, we have recently demonstrated that siloxyalkenes,[7]
electron-rich aromatics,[8] and organoaluminum reagents[9]
react readily with the cyclopentenyl cation intermediate in
an umpolung fashion to form α-functionalized cyclopenta-
nones.
The Frontier group has described an innovative strategy
for the intramolecular delivery of substituents to the remote
terminus of a polarized Nazarov-derived oxyallyl cation.[10]
This approach relies on sequential 1,2-Wagner–Meerwein
rearrangements of adjacent groups on the former C-1 and
C-5 termini of carboxy-substituted dienones 1, with con-
comitant formation of a conjugated enone (Scheme 1). We
set out to explore a related process, involving substrates 2,
in which the migrating group is initially bonded to an oxy-
genated carbon atom exocyclic to the newly formed cyclo-
pentanoid. We envisioned that a sequential Nazarov elec-
Scheme 1. Cationic 1,2-shifts of the Nazarov intermediate.
Results and Discussion
A series of 2-hydroxyalkyl-1,4-dien-3-ones 2a–2i was pre-
pared, using the method of Lee and co-workers[12] (Table 1).
Cross-conjugated enynones 3a–3d[13] were treated with
Ph2CuLi at low temperature in the presence of acetone, cy-
clopentanone, cyclohexanone, or cyclobutanone to give the
desired substrates in modest to good yields in a single step.
[a] Department of Chemistry, University of Alberta,
E3-43 Gunning–Lemieux Centre, Edmonton, Alberta, T6G
2G2, Canada
E-mail: frederick.west@ualberta.ca
http://www.chem.ualberta.ca/~fgwest/public_html/Home.html
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301537.
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Ready Access to Alkylidenecyclopentenones
Exclusive addition to the β-alkynyl carbon atom was seen case, the majority of the starting material was recovered,
in all cases, and the resulting trisubstituted alkene was along with a small amount of an uncharacterizable mixture
formed with complete selectivity for the (E) geometry.
of products resulting from indiscriminate destruction under
these conditions. Titanium(IV) Lewis acids potentially cap-
able of bidentate complexation were also tested. Ti(OiPr)4
failed to consume 2a, even after extended stirring. The
more reactive TiCl4 did give a new product in modest yield.
However, this proved to be alkylidenecyclopentenone[14] 5a,
resulting from elimination of the tertiary hydroxy group.
The use of Me2AlCl improved the yield of 5a to 51%; under
none of the conditions tested was the desired semipinacol
product (i.e., 4a) observed.
The “double electrophile” structure of 5a is found in a
number of promising anticancer compounds[15] with cyto-
toxic and antiangiogenic[15b] properties. With this in mind,
we examined the other substrates (i.e., 2b–2i) under the con-
ditions of Table 2, Entry 6 to evaluate the generality of this
method for the production of alkylidenecyclopentenones
(Table 3). Acetone adduct 2b gave 5b in only modest yield,
but 2c gave 5c in 62% yield (Table 3, Entries 2 and 3). Sub-
strates 2d–2f, in which the phenyl group at R2 was replaced
with a methyl group, gave similar results (Table 3, En-
tries 4–6). Similar results were also obtained with 2g and
2h, which gave products 5g and 5h, with olefins at the
shared edges of the fused hydrindenone ring systems
(Table 3, Entries 7 and 8).
Table 1. Preparation of dienone substrates 2a–2i.[a]
Entry Enynone R1
R2
R3
R4
Product Yield [%][b]
1
2
3
4
5
6
7
8
9
3a
3a
3a
3b
3b
3b
3c
3c
3d
3d
Me
Me
Me
Me
Me
Me
(CH2)4
(CH2)4
H
Ph
Ph
Ph
Me
Me
Me
H
H
H
H
H
H
H
H
(CH2)4
Me
(CH2)5
(CH2)4
Me
(CH2)5
(CH2)4
Me
2a
2b
2c
2d
2e
2f
2g
2h
2i
68
50
91
35
47
35
55
63
61
76
Ph
Ph
Me (CH2)4
Me (CH2)3
10
H
2j
[a] Standard procedure: A solution of Ph2CuLi (0.24 m in THF;
1.05 equiv.) was cooled to –78 °C. The ketone (1.1 equiv.) was
added, followed immediately by the dropwise addition of enynone
3 (1 equiv.) in THF (0.75 m). After 0.5 h, the reaction was quenched
with aq. HCl, followed by aqueous workup, and the crude product
was purified by flash chromatography. See Supporting Information
for additional details. [b] All yields given are for isolated products
after purification.
Notably, in all instances, the initial deprotonative elimi-
nation occurred on the side distal to the hydroxyalkyl moi-
Dienone 2a was used for initial investigations. This sub- ety, permitting the subsequent β-elimination of the exocy-
strate, if it underwent the desired semipinacol process, clic oxygen substituent (see below). Based on these results,
would give spirocyclic product 4a (Table 2). Treatment with we propose that the first equivalent of Lewis acid complexes
BF3·OEt2 at low temperature followed by gradual warming to the hydroxy group, and that the second equivalent is re-
resulted in the consumption of 2a, but gave a complex and quired to activate the dienone carbonyl group
intractable mixture of products (Table 2, Entry 1). Similar (Scheme 2).[16] Electrocyclization then gives a cyclopentenyl
results were seen with Me3SiOTf (Table 2, Entry 2). Possible cation A, which may be polarized, with a more positive
competition for complexation of the Lewis acid by the hy- character at the terminus opposite to the oxygenated side-
droxy group was considered, and so excess Me3SiOTf in chain. Elimination on this side gives an aluminum dienolate
the presence of 1 equiv. amine base was also used, with the B that is poised to eject the Lewis-acid-complexed oxygen
expectation that this would effect in situ silylation of the atom at the exocyclic β-position to provide the alkylidene-
alcohol and so prevent any interference in the activation of cyclopentenone. Alternatively, a cationic chelate C involving
–
the carbonyl group (Table 2, Entry 3). Unfortunately, in this an Me2Al species and an Me2AlCl2 counterion, previously
Table 2. Attempted Nazarov/semipinacol reaction of 2a.
Entry
Conditions
Product
Yield [%][a]
1
2
3
BF3·OEt2 (1.1 equiv.), CH2Cl2, –78 °C Ǟ room temp., 4 h
Me3SiOTf (1.1 equiv.), CH2Cl2, –78 °C Ǟ room temp., 4 h
Me3SiOTf (2.1 equiv.), (iPr)2NEt (1.0 equiv.), CH2Cl2, –78 °C Ǟ room temp., 48 h
Ti(OiPr)4 (1.1 equiv.), CH2Cl2, 0 °C Ǟ room temp., 48 h
TiCl4 (1.1 equiv.), CH2Cl2, –78 Ǟ 0 °C, 2 h
intractable mixture
intractable mixture
minimal conversion
no conversion
5a
–
–
–
–
23
51
4
5
6[b]
Me2AlCl (2.2 equiv.), CH2Cl2, 0 °C Ǟ room temp., 16 h
5a
[a] All yields given are for isolated products after purification. [b] Dienone 2a was only partially consumed when 1.1 equiv. Me2AlCl was
used. An excess of this reagent was required for complete conversion.
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Table 3. Conversion of 2a–2h to alkylidenecyclopentenones.[a]
Entry Dienone
R1
R2
R4
Product Yield [%][b]
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
Me
Me
Me
Me
Me
Me
Ph
Ph
Ph
(CH2)4
Me
(CH2)5
5a
5b
5c
5d
5e
5f
51
36
62
46
43
61
34
58
Me (CH2)4
Me Me
Me (CH2)5
2g
2h
(CH2)4
(CH2)4
(CH2)4
Me
5g
5h
[a] Standard procedure: Dienone 2 was dissolved in CH2Cl2
(0.05 m), and the solution was cooled to 0 °C. A solution of Me2-
AlCl in (1.0 m in hexanes; 2.2 equiv.) was added dropwise. The reac-
tion mixture was stirred at 0 °C for 0.5 h, then it was warmed to
room temp. and stirred for an additional 15.5 h, followed by HCl
(1 n) quench, aqueous workup, and chromatographic purification.
See Supporting Information for additional details. [b] All yields
given are for isolated product after purification.
proposed by Evans and co-workers for nucleophilic ad-
ditions to β-hydroxycarbonyl compounds,[17] may be in-
volved. An alternative sequence involving direct elimination
from B or from the corresponding chelate derived from C
cannot be ruled out. Thus, a conventional Nazarov reaction
to give hydroxyalkylcyclopentenone D (or its aluminum
complex) could occur, followed by elimination in situ to
give 5. However, it should be noted that under no circum-
stances were intermediates such as D obtained in the prod-
uct mixtures from these reactions.
Scheme 2. Proposed double elimination mechanism.
(1)
We next turned our attention to substrates 2i and 2j,
which lack a proton at the preferred site of the depro-
tonative elimination (i.e., R3 = Me instead of H). With the
usual elimination unavailable, we envisioned that the de-
sired semipinacol process might be able to compete with
elimination. Moreover, the absence of a substituent at the
αЈ-position was expected to alter the polarization of the
allyl cation, increasing the positive-charge density adjacent
to the hydroxyalkyl group at the α-position, and so again
favoring the semipinacol pathway.
gone a Nazarov cyclization, but neither contained the
sought-after 1,3-diketone structure, and were instead iden-
tified as 7j and 8j [Equation (2)].
In the event, 2i was not fully consumed under the condi-
tions successfully used with 2a–2h, even after 48 h in the
presence of 4 equiv. Me2AlCl. On the other hand, treatment
with BF3·OEt2 resulted in the rapid consumption of 2i to
give one main product after 30 min [Equation (1)]. Unfortu-
nately, this product proved to be 6i, resulting from elimi-
(2)
Alkylidenecyclopentanone 7j is presumed to arise from
nation of the tertiary alcohol, with no Nazarov cyclization trapping of oxyallyl cation E with chloride, followed by eli-
of either 2i or 6i having occurred. mination of the hydroxy group (Scheme 3, path a). Notably,
Similarly, 2j was not consumed by treatment with Me2- the chloride adduct was isolated as a single diastereomer
AlCl under the described reaction conditions. After a short (unassigned). Cyclopentenone 8j appears to have been pro-
screening of Lewis acids, we discovered that TiCl4 cleanly duced by a Nazarov cyclization followed by two consecutive
produced two new products upon warming to room tem- 1,2-phenyl migrations, similar to the previously discussed
perature, and in contrast to the pilot studies with 2a, we work of the Frontier group (Scheme 3, path b).[10] Subse-
found that 2.1 equiv. of TiCl4 was required for complete quent elimination of the hydroxy group would then give an
consumption of 2j. Both products appeared to have under- allylic cation that can be trapped by chloride.
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Ready Access to Alkylidenecyclopentenones
at this time, but it may result from a transition state for the
elimination that minimizes the steric clash between the
larger substituent (RL) of the tertiary alcohol and the meth-
ine carbon atom at C-4.
Scheme 3. Proposed mechanism for the formation of 7j and 8j.
The results seen with dienone 2j further support the hy-
pothesis that there is a higher charge density at the α-posi-
tion distal to the hydroxy substituent in the Nazarov inter-
mediate – so much so that even the potential relief of the
ring strain present in the cyclobutyl substituent by semipin-
acol ring-expansion is not favored as a termination event.
Instead, either chloride trapping at that site or consecutive
1,2-shifts of the phenyl groups occurs.
Scheme 4. Stereoselective elimination in unsymmetrically substi-
tuted cases.
Conclusions
The formation of alkylidenecyclopentenones 5a–5h did
not involve any issues concerning alkene geometry, since in
all cases, the R4 substituents on the tertiary alcohol were
identical. We wondered whether substrates derived from un-
symmetrical ketones would show any selectivity in the eli-
mination step. With this in mind, substrates 2k and 2l were
prepared by the standard method (Scheme 4). Treatment
under the conditions used in Table 3 gave alkylidenecyclo-
pentenones 5k and 5l in fair yields, which were formed in
each case as a mixture of alkene geometrical isomers. In the
case of 5k, the two isomers were obtained in a ratio of 2.3:1
and could be separated by preparative TLC for full analysis.
NOE experiments showed clear correlations in each isomer
between the C-4 benzylic methine group and the alkyl
group in a cis relationship to it. Significant chemical shift
differences between the (E) and (Z) isomers of 5k for the
allylic protons cis or trans to the ketone carbonyl group
were seen, and similar differences were also apparent for
the isomers of 5l (formed in a 3.6:1 ratio), which allowed
their assignment by analogy to 5k. The origin of the selec-
Cross-conjugated dienones with hydroxyalkyl substitu-
ents at one of the α-positions undergo a domino Nazarov
cyclization/dehydration process to give highly unsaturated
alkylidenecyclopentenones in modest to good yields, in
preference to an alternative semipinacol pathway that is po-
tentially available. Unsymmetrically substituted hy-
droxyalkyl groups show modest stereoselectivity in the eli-
mination step. Further studies with these substrates and
biological evaluation of the dienone products 5 will be de-
scribed in due course.
Experimental Section
Representative Procedure for Enynone Synthesis. 2-Methyl-1-phen-
ylpent-1-en-4-yn-3-one
(3a):
2-Methyl-N-methoxy-N-methyl-
cinnamamide (5.12 g, 25 mmol) was dissolved in THF (60 mL),
then the flask was flushed with argon, and the mixture cooled to
0 °C. A solution of ethynylmagnesium bromide (0.5 m in THF;
60 mL, 30 mmol, 1.2 equiv.) was added slowly over 2 min. The
tivity in favor of the (Z) isomer in both cases is uncertain solution was then stirred at this temperature until the starting mate-
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1863

O. Scadeng, F. G. West
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rial was consumed (as determined by TLC analysis). The reaction
was then quenched with HCl (1 n aq.; 50 mL), and the mixture was
extracted with Et2O (2ϫ 50 mL). The organic layers were com-
bined, washed with H2O (50 mL) and brine (50 mL), and dried
with MgSO4. After filtration, the solution was concentrated by ro-
tary evaporation, and the product was purified by flash chromatog-
raphy (silica gel; hexanes/EtOAc, 20:1) to give enynone 3a (2.68 g,
(2ϫ), 126.5, 52.5, 33.3, 32.8, 26.5, 25.3, 10.0 ppm. HRMS (EI):
calcd. for C23H22O [M]+ 314.1671; found 314.1670.
Nazarov Reaction of Dienone 2j. Formation of Alkylidenecyclobut-
ane (7j) and Chlorocyclobutane (8j): Dienone 2j (30 mg,
0.094 mmol) was dissolved in CH2Cl2 (3 mL), and the solution was
cooled to –78 °C. TiCl4 (1.0 m in toluene; 200 μL, 2.1 equiv.) was
added dropwise, resulting in a reddish brown color. The mixture
was stirred at this temperature for 30 min, then it was warmed to
room temperature where it remained for 45 min. The reaction was
then quenched with water (5 mL), and the mixture was extracted
with CH2Cl2 (2ϫ 5 mL). The combined organic extracts were
washed with water (2ϫ 5 mL) and brine (5 mL), dried with
MgSO4, and concentrated by rotary evaporation. The products
were then purified by flash chromatography (hexanes/EtOAc, 15:1)
to give 7j (10 mg, 31%) and 8j (10 mg, 31%), both as yellow oils.
63%) as a yellow solid. Rf = 0.43 (hexanes/EtOAc, 8:1). M.p. 58–
1
60 °C. IR (film): ν = 3259, 3049, 2965, 2092, 1629 cm–1. H NMR
˜
(500 MHz, CDCl3): δ = 8.06 (br. s, 1 H), 7.52–7.49 (m, 2 H), 7.47–
7.42 (m, 2 H), 7.41–7.37 (m, 1 H), 3.32 (s, 1 H), 2.13 (d, J = 1.4 Hz,
3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 180.1, 146.7, 137.8,
135.3, 130.2, 129.5, 128.6, 79.9, 79.8, 12.1 ppm. HRMS (EI): calcd.
for C12H10O [M]+ 170.0732; found 170.0729.
Representative Procedure for Dienone Synthesis. 2-(1-Hydroxy-
cyclopentyl)-4-methyl-1,5-diphenylpenta-1,4-dien-3-one (2a): A sus-
pension of CuBr·SMe2 (322 mg, 1.57 mmol, 1.05 equiv.) in THF
(5 mL) was flushed with argon and cooled to 0 °C. A solution of
phenyllithium (1.9 m in dibutyl ether; 1.65 mL, 3.15 mmol,
2.1 equiv.) was added dropwise. The mixture was stirred for 45 min,
during which time the solid slowly dissolved, and the solution
turned dark brown. The solution was then cooled to –78 °C. Cyclo-
pentanone (259 μL, 1.65 mmol, 1.1 equiv.) was added, immediately
followed by the dropwise addition of a solution of enynone 3a
(255 mg, 1.5 mmol) in THF (2 mL). The resulting solution was
stirred at this temperature for 30 min, and the reaction was then
quenched with HCl (1 n aq.; 5 mL). The mixture was extracted
with Et2O (2ϫ 10 mL). The organic layers were combined, washed
with H2O (15 mL) and brine (10 mL), and dried with MgSO4. After
filtration, the solution was concentrated by rotary evaporation, and
the resulting oil was purified by flash chromatography (silica gel;
hexanes/EtOAc, 5:1) to give dienone 2a (339 mg, 68%) as a white
Data for 7j: R = 0.73 (hexanes/EtOAc, 8:1). IR (film): ν = 3060,
˜
f
2959, 1728, 1661 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.36–7.28
(m, 4 H), 7.22–7.18 (m, 5 H), 6.82 (br. s, 1 H), 5.07 (s, 1 H), 4.22
(app quintet, J = 3.0 Hz, 1 H), 3.41–3.32 (m, 1 H), 3.26–3.18 (m,
1 H), 2.42–2.34 (m, 1 H), 2.14–2.00 (m, 3 H), 1.14 (s, 3 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 195.9, 164.9, 141.9, 135.8, 130.0,
128.4, 127.6, 127.2, 127.0, 126.4, 125.4, 72.1, 56.3, 51.1, 35.0, 33.4,
18.5, 16.6 ppm. HRMS (EI): calcd. for C22H2135ClO [M]+
336.1281; found 336.1281.
Data for 8j: R = 0.82 (hexanes/EtOAc, 8:1). IR (film): ν = 3059,
˜
f
2955, 1713, 1600 cm–1. H NMR (500 MHz, CDCl3): δ = 7.60 (s,
1
1 H), 7.41–7.36 (m, 2 H), 7.33–7.28 (m, 4 H), 7.24–7.21 (m, 2 H),
6.96–6.92 (m, 2 H), 3.86 (s, 1 H), 3.02–2.95 (m, 2 H), 2.75–2.68 (m,
2 H), 2.37 (app dtt, J =18.0, 9.2, 6.7 Hz, 1 H), 1.97 (app dtt, J =
17.3, 8.7, 6.1 Hz, 1 H), 1.17 (s, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 205.4, 163.5, 145.8, 145.5, 136.2, 130.1, 128.9, 128.4,
127.3, 127.0, 125.9 67.8, 64.9, 49.4, 38.0, 23.5, 16.6 ppm. HRMS
(EI): calcd. for C22H2135ClO [M]+ 336.1281; found 336.1280.
solid. Rf = 0.51 (hexanes/EtOAc, 2:1). M.p. 107–108 °C. IR (film):
1
ν = 3445, 3025, 2961, 1637 cm–1. H NMR (500 MHz, CDCl ): δ
˜
3
Representative Synthesis of Unsymmetrical Alkylidene Cyclopent-
enones. (Z)-5k and (E)-5k: According to the standard procedure for
alkylidenecyclopentenone synthesis (see above), 2k (40 mg,
0.12 mmol) was transformed into a mixture of (Z)-5k and (E)-5k
(24 mg, 64%) in a 2.3:1 ratio (determined by integration of upfield
= 7.37 (br. s, 1 H), 7.30–7.27 (m, 2 H), 7.25–7.21 (m, 3 H), 7.18–
7.16 (m, 1 H), 7.15–7.12 (m, 2 H), 7.08 (br. s, 1 H), 7.07–7.04 (m,
2 H), 2.85 (s, 1 H), 2.02–1.96 (m, 2 H), 1.95 (d, J = 1.3 Hz, 3 H),
1.94–1.86 (m, 4 H), 1.78–1.74 (m, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 204.1, 144.8, 143.3, 137.4, 136.4, 135.8, 129.4 (2ϫ),
128.6 (2ϫ), 128.4, 128.3, 127.8, 83.5, 39.1, 23.1, 12.5 ppm. HRMS
(ESI): calcd. for C23H25O2 [M + H]+ 333.1849; found 333.1852.
1
ethyl triplets in the H NMR spectrum), as a yellow oil after flash
chromatography (silica gel; pentane/EtOAc, 30:1). The isomers
were then separated by preparatory TLC (silica gel; two successive
elutions with hexanes/EtOAc, 30:1 and then hexanes/EtOAc, 15:1)
for analytical purposes.
Representative Procedure for Alkylidenecyclopentenone Synthesis. 5-
Cyclopentylidene-2-methyl-3,4-diphenylcyclopent-2-enone (5a):
A
solution of 2a (50 mg, 0.15 mmol) in CH2Cl2 (3 mL) was flushed
with argon and cooled to 0 °C. A solution of AlMe2Cl (1.0 m in
hexanes; 0.33 mL, 2.2 equiv.) was added dropwise, and the color of
the solution turned dark orange. After 30 min, the cooling bath
was removed, and the reaction mixture was stirred for 16 h. After
the starting material had been consumed (as shown by TLC analy-
sis), HCl (1 n aq.; 1 mL) was added slowly to quench the reaction.
The mixture was then extracted with CH2Cl2 (5 mL). The organic
phase was washed sequentially with water (5 mL) and brine (5 mL),
and then dried with MgSO4. The mixture was then filtered and
concentrated by rotary evaporation, and the residue was purified
by flash chromatography (silica gel; hexanes/EtOAc, 10:1) to give
5a (24 mg, 51%) as a yellow semisolid. Rf = 0.38 (hexanes/EtOAc,
Data for (Z)-5k: R = 0.48 (hexanes/EtOAc, 20:1). IR (film): ν =
˜
f
3026, 2962, 1677, 1621 cm–1. 1H NMR (500 MHz, CDCl3): δ =
7.31–7.24 (m, 3 H), 7.18–7.12 (m, 4 H), 7.09–7.02 (m, 3 H), 4.73
(q, J = 2.0 Hz, 1 H), 2.91 (dq, J = 12.0, 7.5 Hz, 1 H), 2.87 (dq, J
= 12.0, 7.5 Hz, 1 H), 1.95 (d, J = 1.9 Hz, 3 H), 1.66 (s, 3 H), 1.07
(app t, J = 7.8 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
197.0, 162.5, 153.3, 140.9, 139.3, 135.3, 133.9, 128.5, 128.4, 128.2
(2ϫ), 128.1, 126.4, 52.5, 26.7, 21.4, 12.6, 9.8 ppm. HRMS (EI):
calcd. for [M]+ C22H22O 302.1671; found 302.1670.
Data for (E)-5k: R = 0.46 (hexanes/EtOAc, 20:1). IR (film): ν =
˜
f
3026, 2972, 1677, 1621 cm–1. 1H NMR (500 MHz, CDCl3): δ =
7.30–7.24 (m, 3 H), 7.20–7.17 (m, 2 H), 7.16–7.12 (m, 2 H), 7.09–
7.04 (m, 2 H), 4.79 (br. s, 1 H), 2.33 (d, J = 0.8 Hz, 3 H), 2.06 (m,
8:1). IR: ν = 3060, 2929, 1682, 1648 cm–1. 1H NMR (500 MHz,
˜
CDCl3): δ = 7.30–7.26 (m, 2 H), 7.25–7.21 (m, 3 H), 7.17–7.13 (m, 2 H), 1.97 (d, J = 1.9 Hz, 3 H), 0.63 (app t, J = 7.6 Hz, 3 H) ppm.
2 H), 7.10–7.0.5 (m, 3 H), 4.69 (br. s, 1 H), 3.02–2.92 (m, 2 H),
13C NMR (125 MHz, CDCl3): δ = 198.0, 162.2, 152.1, 141.3, 139.5,
2.32–2.26 (m, 2 H), 2.00 (d, J = 1.9 Hz, 3 H), 1.83–1.72 (m, 2 H), 135.2, 133.8, 128.5, 128.4, 128.2 (2ϫ), 128.1, 126.4, 52.1, 30.5, 17.8,
1.62–1.57 (m, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 197.1, 10.7, 9.9 ppm. HRMS (EI): calcd. for C22H22O [M]+ 302.1671;
162.3, 158.7, 140.2, 139.4, 135.3, 131.4, 128.5, 128.4 (2ϫ), 128.2
found 302.1670.
1864
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Eur. J. Org. Chem. 2014, 1860–1865

Ready Access to Alkylidenecyclopentenones
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[11]
Acknowledgments
The authors thank the Natural Sciences and Engineering Research
Council of Canada (NSERC) for generous funding of this project,
and the University of Alberta for a Queen Elizabeth II Graduate
Scholarship (O. S.).
[12]
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Received: October 9, 2013
Published Online: January 15, 2014
Eur. J. Org. Chem. 2014, 1860–1865
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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