Tandem michael addition/aldol reaction of allenic ketones with alkyl vinyl ketones: Versatile synthesis of 2-alkynyl 1,5-diketones, 4-alkynyl-3- hydroxycyclohexanones and 4-alkynylcyclohexenones

Article abstract of DOI:10.1002/ejoc.201001161

The reactivity of alkynylenolate was investigated in the reactions of allenic ketones and vinyl ketones. We found that different products could be obtained under different conditions. The tetrabutylammonium fluoride (TBAF)-mediated Michael addition of all

Full text of DOI:10.1002/ejoc.201001161

FULL PAPER
DOI: 10.1002/ejoc.201001161
Tandem Michael Addition/Aldol Reaction of Allenic Ketones with Alkyl Vinyl
Ketones: Versatile Synthesis of 2-Alkynyl 1,5-Diketones, 4-Alkynyl-
3-hydroxycyclohexanones and 4-Alkynylcyclohexenones
Deepika Malhotra,[a] Le-Ping Liu,*[a] and Gerald B. Hammond*[a]
Keywords: Michael addition / Aldol reactions / Allenic ketones / Vinyl ketones / Alkynes
The reactivity of alkynylenolate was investigated in the reac-
tions of allenic ketones and vinyl ketones. We found that dif-
ferent products could be obtained under different conditions.
The tetrabutylammonium fluoride (TBAF)-mediated Michael
addition of allenic ketones to vinyl ketones gave 2-alkynyl
1,5-diketones as the product. Under stronger basic condi-
tions, a tandem Michael addition/aldol reaction of the two
starting materials occurred in one pot, and 4-alkynyl-3-hy-
droxycyclohexanone could be isolated at low temperature,
whereas 4-alkynylcyclohexenones was obtained at room
temperature. It should be noted that only one diastereoiso-
mer of 4-alkynyl-3-hydroxycyclohexanone was isolated from
the reaction even when ethyl vinyl ketone was used as the
Michael acceptor, as determined by 1H and 13C NMR spec-
troscopy. The configurations of the diastereoisomers were
confirmed by NOESY spectroscopy.
Introduction
Michael additions and aldol reactions are important
tools for the synthesis of complex organic molecules; their
enolate chemistry continue to enrich the arsenal of organic
synthetic chemistry.[1,2] Recently, we became interested in
studying the reactivity of alkynylenolates – an alkynyl-sub-
stituted enolate generated from allenoates or propargylic es-
ters under basic conditions – as potential nucleophile in re-
actions such as aldol condensation, Michael addition, alk-
ylation and halogenation (Scheme 1).[3]
To probe further the reactivity of the alkynylenolate, we
speculated that the Michael addition of allenic ketones to
vinyl ketones could yield 2-alkynyl 1,5-diketones, triggering
an intramolecular aldol reaction leading to hydroxycy-
clohexanones or cyclohexenones in tandem fashion.[4]
Herein, we wish to report the tandem Michael addition/
aldol reaction of allenic ketones with alkyl vinyl ketones
and the versatile synthesis of 2-alkynyl 1,5-diketones, 4-alk-
ynyl-3-hydroxycyclohexanones and 4-alkynylcyclohex-
enones. Although 1,5-diketones, hydroxycyclohexanones
and cyclohexenones have often been employed in organic
synthesis and found as substructures in bioactive molecules
or natural products,[5] the synthetically more interesting 2-
alkynyl-substituted analogs have been rarely reported in the
literature.[6]
Scheme 1. Reactivity of alkynylenolates generated from allenoates
or propargylic esters.
Results and Discussion
Using 2-methyl-1,4-diphenylbuta-2,3-dien-1-one (1a) and
methyl vinyl ketone (2a, MVK) as model substrates, we in-
vestigated the formation of the products 3a–5a; the results
are outlined in Table 1. As expected, 2-alkynyl 1,5-diketone
3a was obtained in good yield when tetrabutylammonium
fluoride (TBAF) was used as the base, no product 4a or 5a
was found (Table 1, entry 1).[7] When potassium carbonate
was employed as the base, only trace amounts of 3a was
found, with most of the starting material remaining
(Table 1, entry 1). Phase-transfer catalysis helped the reac-
[a] Department of Chemistry, University of Louisville,
Louisville, Kentucky 40292, USA
Fax: +1-502-852-3899
E-mail: leping.liu@louisville.edu
gb.hammond@louisville.edu
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001161.
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Table 1. Base-mediated reactions of allenic ketone 1a with methyl vinyl ketone.[a]
[a] General reaction conditions: allenic ketone 1a (0.4 mmol), methyl vinyl ketone 2a (0.6 mmol), strong base (2 equiv.), potassium carbon-
ate (5 equiv.), additive (5 mol-%), solvent (2.0 mL), reaction was quenched in 4 h. For entry 1, 0.2 equiv. of TBAF was used. [b] Isolated
yields. [c] Reaction time was prolonged to 24 h.
tion, as shown by the fact that 3a was obtained in moderate obtained (Table 1, entry 12). Product 5a was thought to
yield when tetrabutylammonium bromide (TBAB) was em- arise from the dehydration of 4a, prompting us to postulate
ployed (Table 1, entry 3).[8] Also, under this weakly basic that the dehydration would not take place at low tempera-
conditions, the tandem Michael addition/aldol condensa- ture. Indeed, 4a was isolated as the major product in good
tion product 5a could be isolated at higher temperature yield when the reaction was conducted at –40 °C (Table 1,
(Table 1, entry 4). When a strong base such as potassium entry 13). Other phase-transfer catalysts such as benzyltri-
hydroxide, lithium hydroxide, sodium hydroxide or cesium ethylammonium chloride and tetrabutylammonium hydro-
hydroxide was used in the reaction, compound 5a was ob- gen sulfate were also investigated in the reaction, and sim-
tained as the only product in most cases (Table 1, entries ilar results were obtained (Table 1, entries 14–15). The sol-
5–9). Calcium hydroxide could not promote the reaction, vent effect was also studied, toluene being the best solvent
possibly because of its poor solubility (Table 1, entry 10). for the generation of product 5a (Table 1, entries 12 and
Although potassium hydroxide could promote the reaction, 16–21).
its high hydrophilicity and lack of dispersion caused the
Control reactions were performed under the optimized
reaction mixture to become dark quickly. Fortunately, when conditions to demonstrate the transformations between 3a,
potassium carbonate was used as a co-promoter, the reac- 4a and 5a; the results are shown in Scheme 2. It was found
tion became more gentle and higher yield of product 5a was that 3a could transform into 4a under basic conditions at
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Tandem Michael Addition/Aldol Reaction of Allenic Ketones
low temperature, and both compounds could transform be noted that only one diastereoisomer of the product was
into 5a under the same conditions at room temperature. obtained, even when ethyl vinyl ketone was used as the
1
With the optimum conditions in hand, we proceeded to Michael acceptor, as determined by the H and 13C NMR
study the scope and limitations of these reactions. First, we spectroscopy.
investigated the TBAF-mediated Michael addition of all-
Table 3. Tandem Michael addition/aldol reaction of allenic ketones
enic ketones 1 with vinyl ketones 2 to obtain 2-alkynyl 1,5-
1 with vinyl ketones 2 at low temperature.[a]
diketones 3 (Table 2). These reactions proceeded smoothly
for both aromatic and aliphatic substrates, furnishing 3 in
moderate to good yields. Next, we carried out the tandem
Michael addition/aldol reaction of allenic ketones 1 with
vinyl ketones 2 at low temperature (–40 °C), with the corre-
sponding products 4 obtained in moderate to good yields
(Table 3). This reaction is slow under the conditions uti-
lized, and prolonged reaction times were needed; higher
yields were obtained for aromatic substrates, which may be
due to the higher stability of the aromatic system. It should
Scheme 2. Control transformations between compounds 3a, 4a and
[a] General reaction conditions: allenic ketones 1 (0.4 mmol), vinyl
5a.
ketones 2 (0.6 mmol), KOH (2 equiv.), K2CO3 (5 equiv.), TBAB
(5 mol-%), toluene (2.0 mL). [b] Isolated yields.
Table 2. TBAF-mediated Michael addition of allenic ketones 1 to
vinyl ketones 2.[a]
The configuration of 4 was deduced by conformational
analysis of the transition states and confirmed by NOESY
studies of compounds 4h and 4i (Scheme 3 and Scheme 4).
When methyl vinyl ketone was used in the reaction, transi-
tion state TS-1 is kinetically more favorable than TS-2 be-
[a] General reaction conditions: allenic ketones 1 (0.4 mmol), vinyl
ketones 2 (0.6 mmol), TBAF (0.2 equiv.), THF (2.0 mL). [b] Iso-
lated yields.
Scheme 3. Conformational analysis of transition states and
NOESY effect of compound 4h.
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cause there is a 1,3-diaxial interaction between the methyl TS-3 is also less sterically hindered than the E-enolate in
group and the axial proton in TS-2, whereas the interaction TS-4. Thus, TS-3 is more favorable than TS-4, and cis,trans-
is diminished in TS-1, where the alkynyl moiety is axial. 4i was hence obtained from the reaction instead of
Thus, trans-4h was obtained as product through TS-1 in- trans,trans-4i. The configuration of 4i was also confirmed
stead of cis-4h through TS-2. This configuration was also by its NOESY effect, where spatial proximity exists between
supported by NOESY experiment on the product. Likewise, the two axial protons, between the methyl(a) group and the
when ethyl vinyl ketone was used as the Michael acceptor hydroxy group, and between the proton(a) and the phenyl
in the reaction, the more favorable transition state is also group.
the one in which the alkynyl group is axial and the methyl(b)
The tandem Michael addition/aldol condensation of all-
group is equatorial. On the other hand, the Z-enolate in enic ketones 1 with vinyl ketones 2 at room temperature
was also performed and 4-alkynylcyclohexenones 5 were
obtained as the products in moderate to good yields
(Table 4). These reactions also proceeded smoothly and bet-
ter results were obtained with aromatic substrates.
Conclusions
Using allenic ketones and vinyl ketones as substrates, we
investigated the reactivity of alkynylenolate, and various
alkynyl-substituted molecules were obtained. We found that
TBAF could mediate the Michael addition furnishing 2-
alkynyl 1,5-diketones. Under stronger basic conditions, a
tandem Michael addition/aldol reaction of the two starting
materials was developed, and 4-alkynyl-3-hydroxycy-
clohexanones were isolated at low temperature, whereas 4-
alkynylcyclohexenones were obtained at room temperature.
By analyzing the conformations of the reaction transition
Scheme 4. Conformational analysis of transition states and
NOESY effect of compound 4i.
states, an explanation was provided for the formation of a
single diastereoisomer of 4.
Table 4. Tandem Michael addition/aldol condensation of allenic
ketones 1 with vinyl ketones 2 at room temperature.[a]
Experimental Section
General Procedure for the Synthesis of 2-Alkynyl 1,5-Diketones: To
a solution of allenic ketone 1a (119 mg, 0.50 mmol) in THF
(2.0 mL) was added methyl vinyl ketone (MVK) (44 mg,
0.60 mmol) and TBAF (0.1 mL, 1 m in THF, 0.10 mmol). The mix-
ture was stirred for 4 h at room temperature; afterwards the reac-
tion mixture was quenched with water and extracted with diethyl
ether. The solvent of the organic layer was removed under reduced
pressure and the residue was subjected to
a flash column
chromatography (eluent: ethyl acetate/n-hexane = 1:10) to give
product 3a (111 mg, 73%) as a colorless oil.
General Procedure for the Synthesis of 4-Alkynyl-3-hydroxycy-
clohexanones: To
a solution of allenic ketone 1a (119 mg,
0.50 mmol) in toluene (2.0 mL) was added methyl vinyl ketone
(MVK) (44 mg, 0.60 mmol) and TBAB (8 mg, 5 mol-%). The mix-
ture was cooled to –40 °C followed by the addition of potassium
carbonate (345 mg, 2.5 mmol) and potassium hydroxide (56 mg,
1 mmol). The mixture was stirred at –40 °C for 24 h; afterwards the
reaction mixture was quenched with water and extracted with di-
ethyl ether. The solvent of the organic layer was removed under
reduced pressure and the residue was subjected to a flash column
chromatography (eluent: ethyl acetate/n-hexane = 1:10) to give
product 4a (126 mg, 83%) as a colorless oil.
General Procedure for the Synthesis of 4-Alkynylcyclohexenones: To
a solution of allenic ketone 1a (119 mg, 0.50 mmol) in toluene
(2.0 mL) was added methyl vinyl ketone (MVK) (44 mg,
0.60 mmol), TBAB (8 mg, 5 mol-%), potassium carbonate (345 mg,
2.5 mmol) and potassium hydroxide (56 mg, 1 mmol). The mixture
[a] General reaction conditions: allenic ketones 1 (0.4 mmol), vinyl
ketones 2 (0.6 mmol), KOH (2 equiv.), K2CO3 (5 equiv.), TBAB
(5 mol-%), toluene (2.0 mL). [b] Isolated yields.
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Tandem Michael Addition/Aldol Reaction of Allenic Ketones
was stirred at room temperature for 4 h; afterwards the reaction
mixture was quenched with water and extracted with diethyl ether.
The solvent of the organic layer was removed under reduced pres-
sure and the residue was subjected to a flash column chromatog-
raphy (eluent: ethyl acetate/n-hexane = 1:10) to give product 5a
(101 mg, 71%) as a colorless oil.
Data for 3g: A colorless oil. IR (neat): ν = 2979, 2936, 1716, 1682,
˜
1596, 1446, 1178, 966, 716 cm–1. 1H NMR (CDCl3, 500 MHz): δ
= 1.52–1.54 (d, J = 9.0 Hz, 3 H), 1.82–1.83 (d, J = 9.0 Hz, 3 H),
1.88–2.15 (m, 1 H), 2.15–2.17 (d, J = 8.5 Hz, 3 H), 2.30–2.38 (m,
1 H), 2.51–2.59 (m, 1 H), 2.63–2.2.71 (m, 1 H), 7.40–7.43 (q, J =
8.0 Hz, 2 H), 7.50–7.53 (t, J = 8.0 Hz, 1 H), 8.24–8.27 (t, J =
8.0 Hz, 2 H) ppm. 13C NMR (CDCl3, 126 MHz): δ = 3.7, 26.7,
29.9, 33.7, 39.8, 45.3, 81.2, 82.5, 127.9, 129.7, 132.5, 135.4, 199.5,
208.2 ppm. C16H18O2 (242.13): calcd. C 79.31, H 7.49, found C
78.85, H 7.59.
Data for 3a: A colorless oil. IR (neat): ν = 2982, 1716, 1682, 1596,
˜
1490, 1363, 1168, 965 cm–1. 1H NMR (CDCl3, 500 MHz): δ = 1.58
(s, 3 H), 1.95–2.01 (m, 1 H), 2.08 (s, 3 H), 2.34–2.43 (m, 1 H), 2.52–
2.58 (m, 1 H), 2.63–2.69 (m, 1 H), 7.18–7.27 (m, 5 H), 7.35–7.38
(t, J = 7.5 Hz, 2 H), 7.45–7.48 (t, J = 7.5 Hz, 1 H), 8.23–8.25 (d, J
= 8.0 Hz, 2 H) ppm. 13C NMR (CDCl3, 126 MHz): δ = 26.6, 30.0,
33.6, 39.7, 45.9, 86.7, 91.5, 122.8, 128.0, 128.3, 129.7, 131.3, 132.7,
135.3, 198.8, 208.0 ppm. C21H20O2 (304.14): calcd. C 82.86, H 6.62,
found C 82.75, H 6.62.
Data for 3h: A colorless oil. IR (neat): ν = 2982, 2938, 1714, 1682,
˜
1597, 1449, 1243, 1175, 967, 702 cm–1. 1H NMR (CDCl3,
500 MHz): δ = 1.60 (s, 3 H), 1.96–2.02 (m, 1 H), 2.14 (s, 3 H),
2.37–2.43 (m, 1 H), 2.54–2.61 (m, 1 H), 2.67–2.74 (m, 1 H), 3.63
(s, 2 H), 7.23–7.26 (m, 5 H), 7.37–7.40 (m, 2 H), 7.51–7.54 (m, 1
H), 8.24–8.26 (m, 2 H) ppm. 13C NMR (CDCl3, 126 MHz): δ =
25.2, 26.7, 29.9, 33.7, 39.7, 45.4, 84.3, 84.5, 126.5, 127.8, 127.9,
128.4, 129.7, 132.5, 135.3, 136.4, 199.3, 208.1 ppm. HRMS (ESI):
Calcd. for C22H23O2 [M + H+] calcd. 319.1693, found 319.1694.
Data for 3b: Colorless oil. IR (neat): ν = 2959, 2933, 1716, 1681,
˜
1606, 1509, 1446, 1289, 1172, 1031, 966, 690 cm–1. 1H NMR
(CDCl3, 500 MHz): δ = 1.65 (s, 3 H), 2.02–2.08 (m, 1 H), 2.17 (s,
3 H), 2.44–2.49 (m, 1 H), 2.61–2.66 (m, 1 H), 2.66–2.78 (m, 1 H),
3.79 (s, 3 H), 6.81–6.84 (m, 2 H), 7.27–7.30 (m, 2 H), 7.43–7.46 (m,
2 H), 7.52–7.55 (m, 1 H), 8.32–8.33 (m, 2 H) ppm. 13C NMR
(CDCl3, 126 MHz): δ = 26.9, 30.3, 33.9, 40.0, 46.1, 55.5, 86.8, 90.2,
114.2, 115.2, 128.3, 130.0, 132.9, 133.0, 135.6, 159.8, 199.3, 208.3
ppm.
Data for 3i: A colorless oil. IR (neat): ν = 2951, 2867, 1717, 1682,
˜
1
1447, 1241, 1176, 965, 715 cm–1. H NMR (CDCl3, 500 MHz): δ
= 1.16–1.22 (m, 2 H), 1.47–1.58 (m, 7 H), 1.67–1.72 (m, 2 H), 1.74–
2.01 (m, 2 H), 2.14 (s, 3 H), 2.17–2.19 (d, J = 6.5 Hz, 2 H), 2.31–
2.36 (m, 1 H), 2.52–2.58 (m, 1 H), 2.64–2.71 (m, 1 H), 7.39–7.42
(t, J = 7.5 Hz, 2 H), 7.49–7.52 (t, J = 7.5 Hz, 1 H), 8.25–8.27 (d, J
= 7.5 Hz, 2 H) ppm. 13C NMR (CDCl3, 126 MHz): δ = 24.6, 25.2,
26.8, 29.9, 31.9, 33.7, 38.9, 39.7, 45.3, 82.1, 86.6, 127.8, 129.7,
132.4, 135.3, 199.5, 208.1 ppm.
Data for 3c: A colorless oil. IR (neat): ν = 2932, 2870, 1717, 1683,
˜
1489, 1239, 1090, 966, 715 cm–1. 1H NMR (CDCl3, 500 MHz): δ
= 1.64 (s, 3 H), 2.01–2.09 (m, 1 H), 2.08 (s, 3 H), 2.42–2.49 (m, 1
H), 2.54–2.61 (m, 1 H), 2.67–2.71 (m, 1 H), 7.24–7.25 (d, J =
2.8 Hz, 4 H), 7.43–7.45 (t, J = 6.8 Hz, 2 H), 7.51–7.55 (t, J =
Data for 3j:[9] A colorless oil. IR (neat): ν = 2976, 2937, 1714, 1682,
˜
6.5 Hz, 1 H), 8.25–8.28 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR 1596, 1445, 1237, 1112, 972, 757, 691 cm–1. 1H NMR (CDCl3,
(CDCl3, 126 MHz): δ = 26.5, 30.0, 33.6, 39.7, 45.9, 85.6, 92.5,
121.3, 128.1, 128.7, 129.6, 132.5, 132.8, 134.4, 135.2, 198.6, 207.9
ppm. C21H19ClO2 (338.10): calcd. C 74.44, H 5.65, found C 74.36,
H 5.68.
400 MHz): δ = 1.01–1.04 (t, J = 7.6 Hz, 3 H), 1.64 (s, 3 H), 2.02–
2.09 (m, 1 H), 2.40–2.51 (m, 3 H), 2.54–2.62 (m, 1 H), 2.66–2.73
(m, 1 H), 7.24–7.33 (m, 5 H), 7.40–7.44 (t, J = 7.6 Hz, 2 H), 7.50–
7.54 (t, J = 7.2 Hz, 1 H), 8.29–8.31 (d, J = 7.2 Hz, 2 H) ppm. 13C
NMR (CDCl3, 101 MHz): δ = 7.8, 26.6, 33.7, 36.0, 38.3, 45.9, 86.7,
91.5, 122.8, 128.1, 128.3, 129.7, 131.3, 132.7, 135.3, 198.9, 210.6
ppm. HRMS (ESI): Calcd. for C22H22O2Na [M + Na+] calcd.
341.1512, found 341.1513.
Data for 3d: Colorless oil. IR (neat): ν = 2931, 2858, 1717, 1681,
˜
1441, 1240, 1176, 967, 714 cm–1. 1H NMR (CDCl3, 500 MHz): δ
= 0.86–0.89 (t, J = 7.0 Hz, 3 H), 1.26–1.47 (m, 9 H), 1.54 (s, 3 H),
1.91–1.95 (m, 1 H), 2.16–2.20 (m, 4 H), 2.31–2.37 (m, 1 H), 2.51–
2.58 (m, 1 H), 2.65–2.72 (m, 1 H), 7.41–7.44 (t, J = 7.5 Hz, 2 H),
7.52–7.54 (t, J = 7.0 Hz, 1 H), 8.27–8.28 (d, J = 7.5 Hz, 2 H) ppm.
13C NMR (CDCl3, 126 MHz): δ = 14.2, 19.1, 22.8, 27.1, 28.7, 30.2,
31.5, 34.0, 40.1, 45.6, 65.2, 82.4, 87.4, 128.1, 130.1, 132.7, 135.6,
200.1, 208.5 ppm.
Data for 3k:[9] A colorless oil. IR (neat): ν = 2975, 2936, 1714, 1683,
˜
1606, 1510, 1457, 1249, 1109, 973, 716 cm–1. 1H NMR (CDCl3,
400 MHz): δ = 0.93–0.97 (t, J = 7.2 Hz, 3 H), 1.55 (s, 3 H), 1.92–
1.99 (m, 1 H), 2.34–2.46 (m, 3 H), 2.46–2.54 (m, 1 H), 2.58–2.67
(m, 1 H), 3.694 (s, 3 H), 6.71–6.73 (d, J = 8.8 Hz, 2 H), 7.17–7.20
(d, J = 8.8 Hz, 2 H), 7.33–7.37 (t, J = 7.2 Hz, 2 H), 7.42–7.46 (t, J
= 7.2 Hz, 1 H), 8.22–8.24 (d, J = 7.2 Hz, 2 H) ppm. 13C NMR
(CDCl3, 101 MHz): δ = 7.8, 26.6, 33.7, 36.0, 38.4, 45.9, 55.2, 86.5,
90.0, 113.9, 114.9, 128.0, 129.7, 132.6, 132.7, 135.4, 159.6, 199.1,
210.7 ppm. HRMS (ESI): Calcd. for C23H24O3Na [M + Na+]
371.1618, found 371.1624.
Data for 3e: Colorless oil. IR (neat): ν = 2929, 2871, 1715, 1651,
˜
1555, 1279, 1178, 965, 763, 694 cm–1. 1H NMR (CDCl3, 500 MHz):
δ = 1.11–1.12 (d, J = 7.0 Hz, 6 H), 1.52 (s, 3 H), 1.69–1.93 (m, 1
H), 2.16 (s, 3 H), 2.20–2.35 (m, 1 H), 2.51–2.56 (m, 2 H), 2.62–2.69
(m, 1 H), 7.34–7.43 (t, J = 8.0 Hz, 2 H), 7.50–7.51 (m, 1 H), 8.26–
8.28 (dd, J = 7.5, 1.5 Hz, 2 H) ppm. 13C NMR (CDCl3, 126 MHz):
δ = 20.6, 22.7, 26.7, 29.9, 33.6, 39.7, 45.2, 81.5, 92.4, 127.7, 129.8,
Data for 3l:[9] A colorless oil. IR (neat): ν = 2976, 2836, 1715, 1684,
˜
132.4, 135.4, 199.6, 208.2 ppm. C18H22O2 (270.16): calcd. C 79.96, 1490, 1237, 1091, 972, 715 cm–1. 1H NMR (CDCl3, 500 MHz): δ
H 8.20, found C 79.69, H 8.20.
= 0.98–1.04 (t, J = 7.6 Hz, 3 H), 1.62 (s, 3 H), 2.00–2.07 (m, 1 H),
2.38–2.50 (m, 3 H), 2.53–2.57 (m, 1 H), 2.62–2.67 (m, 1 H), 7.22
(s, 4 H), 7.39–7.43 (t, J = 7.6 Hz, 2 H), 7.49–7.53 (t, J = 7.2 Hz, 1
H), 8.24–8.25 (d, J = 7.6 Hz, 2 H) ppm. 13C NMR (CDCl3,
126 MHz): δ = 7.8, 26.4, 33.6, 36.0, 38.3, 45.9, 85.5, 92.6, 121.3,
128.1, 128.6, 129.6, 132.5, 132.8, 134.3, 135.3, 198.6, 210.5 ppm.
HRMS (ESI): Calcd. for C22H21ClO2Na [M + Na+] 375.1122,
found 375.1126.
Data for 3f: Colorless oil. IR (neat): ν = 2967, 2931, 1717, 1683,
˜
1596, 1456, 1172, 966, 715 cm–1. 1H NMR (CDCl3, 500 MHz): δ
= 1.16 (s, 9 H), 1.51 (s, 3 H), 1.86–1.92 (m, 1 H), 2.15 (s, 3 H),
2.29–2.35 (m, 1 H), 2.47–2.55 (m, 1 H), 2.62–2.68 (m, 1 H), 7.39–
7.42 (t, J = 7.5 Hz, 2 H), 7.49–7.52 (t, J = 7.5 Hz, 1 H), 8.26–8.27
(d, J = 7.5 Hz, 2 H) ppm. 13C NMR (CDCl3, 126 MHz): δ = 26.8,
27.5, 29.9, 30.7, 33.6, 39.7, 45.1, 80.8, 95.2, 127.7, 129.8, 132.4,
135.4, 199.7, 208.2 ppm. C19H24O2 (284.17): calcd. C 80.24, H 8.51,
found C 79.95, H 8.41.
Data for 4a: A colorless oil. IR (neat): ν = 3423, 2960, 2934, 1716,
˜
1685, 1491, 1217, 1060, 758, 715 cm–1. 1H NMR (CDCl3,
Eur. J. Org. Chem. 2010, 6855–6862
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6859

D. Malhotra, L.-P. Liu, G. B. Hammond
FULL PAPER
500 MHz): δ = 1.19 (s, 3 H), 2.04–2.10 (m, 1 H), 2.38–2.51 (m, 3
H), 2.55–2.56 (d, J = 1.6 Hz, 1 H), 2.94–3.02 (m, 1 H), 3.80–3.83
(d, J = 14.0 Hz, 1 H), 7.31–7.34 (m, 4 H), 7.36–7.41 (m, 4 H), 7.63–
Data for 4h: A colorless oil. IR (neat): ν = 3372, 2974, 2936, 1715,
˜
1558, 1338, 1069, 970, 766, 703 cm–1. 1H NMR (CDCl3, 400 MHz):
δ = 0.97 (s, 3 H), 1.76 (s, 3 H), 1.81–1.85 (m, 1 H), 2.23–2.31 (m,
7.64 (d, J = 7.5 Hz, 2 H) ppm. 13C NMR (CDCl3, 126 MHz): δ = 3 H), 2.41 (s, 1 H), 2.46–2.85 (m, 1 H), 3.63–3.66 (d, J = 14.4 Hz,
22.3, 35.9, 39.0, 41.3, 52.2, 80.3, 84.4, 93.2, 123.1, 126.5, 127.6,
128.2, 128.4, 131.4, 143.2, 210.6 ppm. HRMS (ESI): Calcd. for
C21H20O2Na [M + Na+] 327.1356, found 327.1360.
1 H), 7.18–7.29 (m, 3 H), 7.46–7.49 (d, J = 8.0 Hz, 2 H) ppm. 13C
NMR (CDCl3, 101 MHz): δ = 3.5, 22.5, 36.1, 39.0, 40.6, 52.2, 79.7,
80.2, 82.7, 126.5, 127.4, 127.5, 143.4, 211.1 ppm. HRMS (ESI):
Calcd. for C16H18O2Na [M + Na+] 265.1199, found 265.1202.
Data for 4b: A colorless oil. IR (neat): ν = 3460, 2960, 2936, 1708,
˜
1606, 1509, 1248, 1165, 1032, 732, 701 cm–1. 1H NMR (CDCl3,
500 MHz): δ = 1.18 (s, 3 H), 1.65–1.66 (m, 1 H), 2.07–2.09 (m, 1
H), 2.39–2.50 (m, 3 H), 2.97–3.03 (m, 1 H), 3.83 (s, 3 H), 3.83–3.85
(d, J = 11.0 Hz, 1 H), 6.84–6.85 (d, J = 9.0 Hz, 2 H), 7.31–7.39 (m,
5 H), 7.62–7.63 (m, 2 H) ppm. 13C NMR (CDCl3, 126 MHz): δ =
22.4, 36.0, 39.1, 41.2, 52.3, 55.3, 80.4, 84.3, 91.6, 114.0, 115.2,
126.5, 127.6, 132.8, 143.2, 159.5, 210.4 ppm. HRMS (ESI): Calcd.
for C22H23O3 [M + H+] 335.1642, found 335.1646.
Data for 4i: A colorless oil. IR (neat): ν = 3501, 2976, 2937, 1711,
˜
1489, 1262, 1099, 994, 757, 692 cm–1. 1H NMR (CDCl3, 400 MHz):
δ = 0.73–0.75 (d, J = 6.8 Hz, 3 H), 1.05 (s, 3 H), 1.97–2.03 (m, 2
H), 2.33–2.46 (m, 2 H), 2.95–3.03 (td, J = 14, 6.0 Hz, 1 H), 3.67–
3.73 (q, J = 6.8 Hz, 1 H), 7.17–7.35 (m, 7 H), 7.45–7.55 (m, 2 H)
ppm. 13C NMR (CDCl3, 101 MHz): δ = 8.3, 23.0, 36.1, 39.1, 42.3,
50.2, 83.6, 84.7, 93.6, 123.2, 127.3, 128.1, 128.3, 131.4, 141.6, 211.2
ppm. HRMS (ESI): Calcd. for C22H23O2 [M + H+] 319.1693, found
319.1695.
Data for 4c: A colorless oil. IR (neat): ν = 3428, 2958, 2934, 1707,
˜
1
1489, 1091, 909, 828, 701 cm–1. H NMR (CDCl3, 500 MHz): δ =
Data for 4j: A colorless oil. IR (neat): ν = 3502, 2972, 2936, 1715,
˜
1.20 (s, 3 H), 2.06–2.09 (m, 1 H), 2.41–2.51 (m, 3 H), 2.60–2.66 (m,
1 H), 2.92–2.98 (m, 1 H), 3.77–3.81 (d, J = 14.5 Hz, 1 H), 7.28–
7.41 (m, 7 H), 7.61–7.63 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR
(CDCl3, 126 MHz): δ = 22.6, 36.2, 39.2, 41.6, 52.4, 80.4, 83.7, 94.5,
121.8, 126.7, 127.8, 127.9, 128.9, 132.9, 134.5, 143.3, 210.7 ppm.
HRMS (ESI): Calcd. for C21H19ClO2Na [M + Na+] 361.0966,
found 361.0968.
1653, 1606, 1457, 1247, 1031, 832, 737, 702 cm–1. 1H NMR
(CDCl3, 400 MHz): δ = 0.72–0.74 (d, J = 6.8 Hz, 3 H), 1.03 (s, 3
H), 1.96–2.00 (m, 1 H), 2.05 (s, 1 H), 2.31–2.46 (m, 2 H), 2.95–3.03
(td, J = 13.6, 6.4 Hz, 1 H), 3.67–3.71 (q, J = 6.8 Hz, 1 H), 3.74 (s,
3 H), 6.77–6.79 (d, J = 8.4 Hz, 2 H), 7.18–7.30 (m, 5 H), 7.49–7.55
(m, 2 H) ppm. 13C NMR (CDCl3, 101 Hz): δ = 8.3, 23.1, 36.2,
39.2, 42.3, 50.1, 55.3, 83.7, 84.5, 92.0, 114.0, 115.3, 127.2, 132.8,
141.7, 159.5, 211.3 ppm. HRMS (ESI): Calcd. for C23H25O3 [M +
H+] 349.1798, found 349.1801.
Data for 4d: A colorless oil. IR (neat): ν = 3433, 2955, 2929, 2858,
˜
1
1715, 1447, 701 cm–1. H NMR (CDCl3, 500 MHz): δ = 0.89–0.90
(m, 3 H), 1.07 (s, 3 H), 1.28–1.39 (m, 7 H), 1.50–1.54 (m, 2 H),
1.90–1.96 (m, 1 H), 2.20–2.27 (t, J = 6.5 Hz, 2 H), 2.33–2.40 (m, 3
H), 2.89–2.93 (m, 1 H), 3.74–3.76 (d, J = 14.0 Hz, 1 H), 7.27–7.35
(m, 3 H), 7.57–7.58 (d, J = 7.0 Hz, 2 H) ppm. 13C NMR (CDCl3,
126 MHz): δ = 14.3, 18.9, 22.8, 22.9, 28.9, 29.1, 31.5, 36.5, 39.2,
40.9, 52.5, 80.5, 83.8, 84.8, 126.8, 127.6, 127.7, 143.6, 211.2 ppm.
HRMS (ESI): Calcd. for C21H28O2Na [M + Na+] 335.1982, found
335.1985.
Data for 4k: A colorless oil. IR (neat): ν = 3488, 2932, 2858, 1711,
˜
1652, 1456, 1340, 1159, 936, 701 cm–1. 1H NMR (CDCl3,
400 MHz): δ = 0.70–0.72 (d, J = 7.2 Hz, 3 H), 0.80–0.83 (t, J =
7.2 Hz, 3 H), 0.92 (s, 3 H), 1.15–1.35 (m, 7 H), 1.43–1.50 (m, 2 H),
1.82–1.87 (m, 2 H), 2.14–2.17 (t, J = 7.2 Hz, 2 H), 2.23–2.31 (td, J
= 13.2, 4.0 Hz, 1 H), 2.35–2.40 (m, 1 H), 2.87–2.96 (td, J = 13.6,
6.4 Hz, 1 H), 3.61–3.66 (q, J = 6.8 Hz, 1 H), 7.19–7.28 (m, 3 H),
7.46 (br. s, 2 H) ppm. 13C NMR (CDCl3, 101 MHz): δ = 8.3, 14.0,
18.8, 22.5, 23.3, 28.6, 28.8, 31.3, 36.4, 39.1, 41.7, 50.0, 83.6, 83.9,
84.8, 125.9, 127.1, 127.9, 141.7, 211.6 ppm. HRMS (ESI): Calcd.
for C22H31O2 [M + H+] 327.2319, found 327.2323.
Data for 4e: A colorless oil. IR (neat): ν = 3419, 2967, 2933, 1714,
˜
1
1656, 1321, 967, 701 cm–1. H NMR (CDCl3, 400 MHz): δ = 1.03
(s, 3 H), 1.15–1.17 (t, J = 6.4 Hz, 6 H), 1.87–1.93 (m, 1 H), 2.07–
2.11 (m, 1 H), 2.29–2.39 (m, 3 H), 2.51–2.59 (m, 1 H), 2.51–2.85–
2.93 (m, 1 H), 3.72–3.75 (d, J = 14.0 Hz, 1 H), 7.24–7.34 (m, 3 H),
7.54–7.56 (d, J = 7.2 Hz, 2 H) ppm. 13C NMR (CDCl3, 101 MHz):
δ = 20.5, 22.5, 23.1, 23.2, 36.1, 38.9, 40.4, 52.2, 80.3, 82.9, 89.9,
126.5, 127.3, 127.4, 143.3, 210.8 ppm. HRMS (ESI): Calcd. for
C18H22O2Na [M + Na+] 293.1512, found 293.1516.
Data for 5a: A colorless oil. IR (neat): ν = 3058, 2931, 1714, 1681,
˜
1
1490, 1330, 1265, 1056, 756 cm–1. H NMR (CDCl3, 500 MHz): δ
= 1.44 (s, 3 H), 2.19–2.25 (m, 1 H), 2.38–2.42 (m, 1 H), 2.56–2.61
(m, 1 H), 2.99–3.06 (m, 1 H), 6.06 (s, 1 H), 7.32–7.33 (m, 3 H),
7.38–7.39 (m, 3 H), 7.43–7.45 (m, 2 H), 7.62–7.63 (m, 2 H) ppm.
13C NMR (CDCl3, 126 MHz): δ = 28.1, 35.2, 35.3, 38.9, 83.1, 91.6,
122.9, 127.4, 127.6, 128.2, 128.3, 128.8, 131.6, 138.7, 163.6, 198.8
ppm. HRMS (ESI): Calcd. for C21H19O [M + H+] 287.1430, found
287.1434.
Data for 4f: A colorless oil. IR (neat): ν = 3386, 2963, 2929, 2866,
˜
1703, 1636, 1360, 915, 701 cm–1. 1H NMR (CDCl3, 500 MHz): δ
= 1.04 (s, 3 H), 1.24 (s, 9 H), 1.88–1.92 (m, 1 H), 2.32–2.39 (m, 4
H), 2.86–2.92 (m, 1 H), 3.73–3.76 (d, J = 15.0 Hz, 1 H), 7.29–7.36
(m, 3 H), 7.58–7.60 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR (CDCl3,
101 MHz): δ = 22.5, 27.4, 30.4, 36.2, 38.9, 40.3, 52.2, 80.3, 82.2,
92.7, 126.6, 126.9, 127.3, 127.4, 143.3, 210.9 ppm. HRMS (ESI):
Calcd. for C19H24O2Na [M + Na+] 307.1669, found 307.1671.
Data for 5b: A colorless oil. IR (neat): ν = 2930, 2837, 1673, 1606,
˜
1
1456, 1248, 1172, 1032, 731 cm–1. H NMR (CDCl3, 500 MHz): δ
= 1.43 (s, 3 H), 2.19–2.26 (m, 1 H), 2.38–2.42 (m, 1 H), 2.56–2.60
(m, 1 H), 3.01–3.09 (m, 1 H), 3.82 (s, 3 H), 6.06 (s, 1 H), 6.86–6.87
(d, J = 9.0 Hz, 2 H), 7.38–7.40 (m, 5 H), 7.63–7.64 (d, J = 3.5 Hz,
2 H) ppm. 13C NMR (CDCl3, 126 MHz): δ = 28.4, 35.5, 35.6, 39.3,
55.6, 83.2, 90.3, 114.2, 115.3, 127.7, 127.8, 128.5, 129.1, 133.3,
139.1, 159.9, 164.4, 199.2 ppm. HRMS (ESI): Calcd. for C22H21O2
[M + H+] 317.1536, found 317.1538.
Data for 4g: A colorless oil. IR (neat): ν = 3446, 2951, 2867, 1707,
˜
1447, 1373, 1053, 970, 701 cm–1. 1H NMR (CDCl3, 400 MHz): δ
= 1.06 (s, 3 H), 1.54–1.62 (m, 5 H), 1.76–1.79 (m, 2 H), 1.90–1.96
(m, 1 H), 2.01–2.08 (m, 1 H), 2.14 (s, 1 H), 2.20–2.22 (d, J = 6.0 Hz,
2 H), 2.32–2.42 (m, 3 H), 2.87–2.96 (m, 1 H), 3.73–3.77 (d, J =
14.4 Hz, 1 H), 7.28–7.37 (m, 3 H), 7.56–7.58 (d, J = 8.0 Hz, 2 H)
ppm. 13C NMR (CDCl3, 101 MHz): δ = 22.6, 24.7, 31.5, 32.1, 36.3,
39.0, 39.2, 40.6, 47.6, 52.4, 80.3, 83.6, 84.0, 126.4, 127.0, 127.4,
Data for 5c: A colorless oil. IR (neat): ν = 2955, 2928, 1676, 1597,
˜
1489, 1264, 1091, 828, 766, 701 cm–1. 1H NMR (CDCl3, 500 MHz):
δ = 1.45 (s, 3 H), 2.21–2.27 (m, 1 H), 2.40–2.43 (m, 1 H), 2.58–2.61
127.5, 143.3, 210.7 ppm. HRMS (ESI): Calcd. for C21H26O2Na [M (m, 1 H), 2.97–3.04 (m, 1 H), 6.07 (s, 1 H), 7.30–7.41 (m, 7 H),
+ Na+] 333.1825, found 333.1827. 7.60–7.61 (d, J = 3.5 Hz, 2 H) ppm. 13C NMR (CDCl3, 126 MHz):
6860
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 6855–6862

Tandem Michael Addition/Aldol Reaction of Allenic Ketones
δ = 28.3, 35.4, 35.6, 39.2, 82.3, 92.9, 121.6, 127.6, 128.0, 128.5,
128.9, 129.2, 133.1, 134.6, 138.9, 163.6, 198.9 ppm. HRMS (ESI):
Calcd. for C21H18ClO [M + H+] 321.1041, found 321.1045.
7.33 (t, J = 7.6 Hz, 2 H) ppm. 13C NMR (CDCl3, 101 MHz): δ =
13.4, 28.4, 35.4, 36.8, 37.8, 55.3, 82.5, 90.4, 113.9, 115.3, 127.5,
127.7, 128.0, 131.9, 132.9, 138.6, 158.4, 159.4, 199.1 ppm. HRMS
(ESI): Calcd. for C23H22O2Na [M + Na+] 353.1512, found
353.1515.
Data for 5d: A colorless oil. IR (neat): ν = 2930, 2858, 1683, 1456,
˜
1
1264, 701 cm–1. H NMR (CDCl3, 500 MHz): δ = 0.87–0.89 (t, J
Data for 5k: A colorless oil. IR (neat): ν = 2966, 2928, 1674, 1606,
˜
= 7.0 Hz, 3 H), 1.25–1.32 (m, 7 H), 1.35–1.42 (m, 2 H), 1.49–1.55
(m, 2 H), 2.06–2.13 (m, 1 H), 2.21–2.24 (m, 3 H), 2.47–2.52 (m, 1
H), 2.91–2.98 (m, 1 H), 5.97 (s, 1 H), 7.35–7.37 (m, 3 H), 7.56–7.58
(m, 2 H) ppm. 13C NMR (CDCl3, 126 MHz): δ = 14.0, 18.7, 22.5,
28.4, 28.5, 28.7, 31.2, 34.7, 35.2, 39.3, 82.3, 83.4, 127.2, 127.4,
128.1, 128.7, 138.9, 164.4, 199.2 ppm. HRMS (ESI): Calcd. for
C21H27O [M + H+] 295.2056, found 295.2059.
1456, 1306, 1089, 1013, 828, 762 cm–1. 1H NMR (CDCl3,
400 MHz): δ = 1.20 (s, 3 H), 1.48 (s, 3 H), 2.08–2.16 (td, J = 12.8,
4.0 Hz, 1 H), 2.27–2.33 (dt, J = 13.2, 4.8 Hz, 1 H), 2.53–2.59 (td,
J = 17.2, 4.4 Hz, 1 H), 2.87–2.96 (m, 1 H), 7.12–7.17 (m, 2 H),
7.18–7.23 (m, 4 H), 7.24–7.27 (m, 1 H), 7.30–7.34 (m, 2 H) ppm.
13C NMR (CDCl3, 101 MHz): δ = 13.4, 28.2, 35.2, 36.9, 37.7, 81.7,
93.1, 121.6, 127.6, 128.1, 128.6, 132.2, 132.8, 134.1, 138.4, 157.9,
198.8 ppm. HRMS (ESI): Calcd. for C22H20ClO [M + H+]
335.1197, found 335.1200.
Data for 5e: A colorless oil. IR (neat): ν = 2968, 2930, 2870, 1675,
˜
1
1653, 1558, 1320, 1150, 701 cm–1. H NMR (CDCl3, 400 MHz): δ
= 1.10 (s, 6 H), 1.22 (s, 3 H), 1.98–2.05 (m, 1 H), 2.14–2.16 (m, 1
H), 2.40–2.45 (m, 1 H), 2.51–2.54 (m, 1 H), 2.83–2.90 (m, 1 H),
5.89 (s, 1 H), 7.29 (s, 3 H), 7.50 (s, 2 H) ppm. 13C NMR (CDCl3,
101 MHz): δ = 20.6, 23.0, 28.3, 34.6, 35.2, 39.2, 81.5, 88.8, 127.2,
127.4, 128.1, 128.7, 138.9, 164.6, 199.3 ppm. HRMS (ESI): Calcd.
for C18H21O [M + H+] 253.1587, found 253.1589.
Data for 5l: A colorless oil. IR (neat): ν = 2929, 2858, 1676, 1617,
˜
1456, 1306, 1098, 896, 766 cm–1. 1H NMR (CDCl3, 400 MHz): δ
= 0.79–0.83 (t, J = 6.8 Hz, 3 H), 1.06 (s, 3 H), 1.20–1.32 (m, 6 H),
1.38–1.45 (m, 5 H), 1.97–2.05 (td, J = 12.8, 4.0 Hz, 1 H), 2.10–2.16
(m, 3 H), 2.46–2.52 (dt, J = 16.8, 4.0 Hz, 1 H), 2.84–2.93 (m, 1
H), 7.13 (br. s, 2 H), 7.22–7.32 (m, 3 H) ppm. 13C NMR (CDCl3,
101 MHz): δ = 13.3, 14.0, 18.7, 22.5, 28.5, 28.6, 28.8, 31.3, 35.4,
36.2, 38.2, 82.4, 82.8, 127.3, 127.6, 127.8, 131.4, 138.7, 159.1, 199.4
ppm. HRMS (ESI): Calcd. for C22H29O [M + H+] 309.2213, found
309.2216.
Data for 5f: A colorless oil. IR (neat): ν = 2967, 2929, 2867, 1677,
˜
1599, 1270, 1150, 701 cm–1. 1H NMR (CDCl3, 500 MHz): δ = 1.24
(s, 9 H), 1.29 (s, 3 H), 2.06–2.13 (td, J = 13.0, 4.0 Hz, 1 H), 2.20–
2.24 (dt, J = 13.0, 4.5 Hz, 1 H), 2.48–2.53 (dt, J = 16.5, 4.0 Hz, 1
H), 2.89–2.96 (m, 1 H), 5.97 (s, 1 H), 7.36–7.38 (t, J = 3.5 Hz, 3
H), 7.57–7.59 (m, 2 H) ppm. 13C NMR (CDCl3, 126 MHz): δ =
27.2, 28.1, 30.7, 34.3, 34.9, 38.9, 80.5, 91.4, 126.8, 127.2, 127.7,
128.4, 138.7, 164.4, 198.9 ppm. HRMS (ESI): Calcd. for C19H23O
[M + H+] 289.1563, found 289.1566.
Supporting Information (see also the footnote on the first page of
this article): Copies of the NMR spetra (1H, 13C and NOESY) of
the new compounds shown in Tables 1, 2, 3, and 4.
Acknowledgments
Data for 5g: A colorless oil. IR (neat): ν = 2949, 2865, 1677, 1558,
˜
1264, 1151, 766, 701 cm–1. 1H NMR (CDCl3, 500 MHz): δ = 1.25–
1.29 (m, 2 H), 1.31 (s, 3 H), 1.54–1.66 (m, 4 H), 1.76–1.82 (m, 2
H), 2.04–2.15 (m, 2 H), 2.23–2.27 (m, 3 H), 2.49–2.54 (m, 1 H),
2.94–3.05 (m, 1 H), 5.99 (s, 1 H), 7.37–7.38 (t, J = 3.5 Hz, 3 H),
7.59–7.61 (m, 2 H) ppm. 13C NMR (CDCl3, 126 MHz): δ = 24.6,
25.3, 28.4, 32.0, 34.7, 35.2, 39.1, 39.4, 82.3, 82.8, 127.2, 127.4,
128.1, 128.7, 138.9, 164.4, 199.2 ppm. HRMS (ESI): Calcd. for
C21H25O [M + H+] 293.1900, found 293.1906.
We are grateful to the National Science Foundation for financial
support (CHE-0809683). We also thank Dr. Neal Stolowich for
helpful discussions on the configurations of compounds 4h and 4i.
[1] a) Modern Aldol Reactions (Ed.: R. Mahrwald), Wiley-VCH,
Weinheim, 2004, vol. 1 and 2; b) B. M. Trost, C. S. Brindle,
Chem. Soc. Rev. 2010, 39, 1600; c) T. Brodmann, M. Lorenz,
R. Schaeckel, S. Simsek, M. Kalesse, Synlett 2009, 174; d) J.
Mlynarski, J. Paradowska, Chem. Soc. Rev. 2008, 37, 1502; e)
B. Schetter, R. Mahrwald, Angew. Chem. 2006, 118, 7668; An-
gew. Chem. Int. Ed. 2006, 45, 7506; f) D. B. Kimball, L. A.
Silks III, Curr. Org. Chem. 2006, 10, 1975.
[2] For selected recent reviews on conjugate addition reactions,
see: a) Conjugate Addition Reactions in Organic Synthesis (Ed.:
P. Perlmutter), Pergamon, Oxford, 1992; b) M. P. Sibi, S. Man-
yem, Tetrahedron 2000, 56, 8033; c) B. L. Feringa, Acc. Chem.
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f) F. Lopez, A. J. Minnaard, B. L. Feringa, Acc. Chem. Res.
2007, 40, 179; g) S. Sulzer-Mosse, A. Alexakis, Chem. Commun.
2007, 3123. Selected recent reviews on allenes, see: h) Modern
Allene Chemistry (Eds.: N. Krause, A. S. K. Hashmi), Wiley-
VCH: Weinheim, Germany, 2004; i) B. J. Cowen, S. J. Miller,
Chem. Soc. Rev. 2009, 38, 3102; j) S. Ma, Acc. Chem. Res. 2009,
42, 1679.
Data for 5h: A colorless oil. IR (neat): ν = 2951, 2922, 1674, 1616,
˜
1558, 1456, 1264, 1151, 766, 701 cm–1. 1H NMR (CDCl3,
500 MHz): δ = 1.29 (s, 3 H), 1.89 (s, 3 H), 2.07–2.13 (m, 1 H),
2.22–2.26 (m, 1 H), 2.48–2.53 (m, 1 H), 2.93–2.99 (m, 1 H), 5.98
(s, 1 H), 7.37–7.39 (m, 3 H), 7.57–7.58 (m, 2 H) ppm. 13C NMR
(CDCl3, 126 MHz): δ = 3.6, 28.3, 34.6, 35.2, 39.2, 78.6, 81.3, 127.2,
127.4, 128.1, 128.7, 138.9, 164.2, 199.1 ppm. HRMS (ESI): Calcd.
for C16H17O [M + H+] 225.1274, found 225.1278.
Data for 5i: A colorless oil. IR (neat): ν = 2928, 2864, 1675, 1597,
˜
1443, 1306, 1013, 892, 756, 704 cm–1. 1H NMR (CDCl3, 400 MHz):
δ = 1.18 (s, 3 H), 1.48 (s, 3 H), 2.07–2.14 (td, J = 13.2, 4.0 Hz, 1
H), 2.26–2.31 (dt, J = 12.8, 4.8 Hz, 1 H), 2.52–2.58 (dt, J = 13.2,
4.4 Hz, 1 H), 2.89–2.98 (m, 1 H), 7.16–7.32 (m, 10 H) ppm. 13C
NMR (CDCl3, 101 MHz): δ = 13.4, 28.3, 35.3, 36.8, 37.8, 82.7,
92.0, 123.2, 127.5, 127.7, 128.0, 128.3, 131.6, 132.1, 138.5, 158.2,
198.9 ppm. HRMS (ESI): Calcd. for C22H21O [M + H+] 301.1587,
found 301.1590.
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Data for 5j: A colorless oil. IR (neat): ν = 2961, 2929, 1674, 1606,
˜
1456, 1291, 1172, 1032, 892, 731 cm–1. 1H NMR (CDCl3,
400 MHz): δ = 1.17 (s, 3 H), 1.48 (s, 3 H), 2.06–2.14 (td, J = 13.2,
4.0 Hz, 1 H), 2.25–2.31 (dt, J = 13.2, 4.8 Hz, 1 H), 2.51–2.57 (dt,
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[9] The 1H NMR spectra of compounds 3j, 3k, and 3l contain
traces of olefinic impurity which might derive from ethyl vinyl
ketone.
Received: August 17, 2010
Published Online: October 21, 2010
6862
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 6855–6862