Michael addition of stannyl ketone enolate to α,β-unsaturated esters catalyzed by tetrabutylammonium bromide and an ab initio theoretical study of the reaction course

Article abstract of DOI:10.1021/ja028853+

Michael addition of stannyl ketone enolates to α,β-unsaturated esters was accomplished in the presence of a catalytic amount of tetrabutylammonium bromide (Bu₄NBr). Other typical systems using lithium enolate or silyl enolate with catalysts (TiCl₄ or Bu₄NF) failed to give the desired products. The bromide anion from Bu₄NBr coordinates to the tin center in enolate to accelerate the conjugate addition where a five-coordinated tin species was generated. The coordination of the bromide anion significantly raises the HOMO level of tin enolate and enhances its nucleophilicity. The conjugate addition provides the intermediate Michael adduct, which has an ester enolate moiety, and the adduct immediately transforms to α-stannyl γ-ketoester by keto - enol tautomerization. This step contributes to the stabilization of the product system and leads to a thermodynamically favorable reaction course. An ab initio calculation reveals that the activation energy in the reaction using the bromide anion is lower than that of the reaction without using it. The transition state in either reaction course has a linear structure, not a cyclic one. This system can be applied to a variety of tin enolates and α,β-unsaturated carbonyls involving enoates, enones, and unsaturated amides.

Full text of DOI:10.1021/ja028853+

Published on Web 05/23/2003
Michael Addition of Stannyl Ketone Enolate to
r,â-Unsaturated Esters Catalyzed by Tetrabutylammonium
Bromide and an ab Initio Theoretical Study of the Reaction
Course
Makoto Yasuda,†,§ Kouji Chiba,‡,§ Noriyuki Ohigashi,† Yasuhiro Katoh,† and
Akio Baba*,†,§
Contribution from the Department of Molecular Chemistry and Handai Frontier Research
Center, Graduate School of Engineering, Osaka UniVersity, 2-1 Yamadaoka, Suita,
Osaka 565-0871, Japan, and Science and Technology System DiVision, Ryoka Systems Inc.,
1-5-2 Irifune, Urayasu, Chiba 279-0012, Japan
Received October 8, 2002; E-mail: baba@chem.eng.osaka-u.ac.jp
Abstract: Michael addition of stannyl ketone enolates to R,â-unsaturated esters was accomplished in the
presence of a catalytic amount of tetrabutylammonium bromide (Bu4NBr). Other typical systems using lithium
enolate or silyl enolate with catalysts (TiCl4 or Bu4NF) failed to give the desired products. The bromide
anion from Bu4NBr coordinates to the tin center in enolate to accelerate the conjugate addition where a
five-coordinated tin species was generated. The coordination of the bromide anion significantly raises the
HOMO level of tin enolate and enhances its nucleophilicity. The conjugate addition provides the intermediate
Michael adduct, which has an ester enolate moiety, and the adduct immediately transforms to R-stannyl
γ-ketoester by keto-enol tautomerization. This step contributes to the stabilization of the product system
and leads to a thermodynamically favorable reaction course. An ab initio calculation reveals that the activation
energy in the reaction using the bromide anion is lower than that of the reaction without using it. The
transition state in either reaction course has a linear structure, not a cyclic one. This system can be applied
to a variety of tin enolates and R,â-unsaturated carbonyls involving enoates, enones, and unsaturated
amides.
Scheme 1. Reaction Patterns between Enolates and
R,â-Unsaturated Carbonyls (Energy Values Calculated when R )
R′ ) Me)
Introduction
Michael addition of metal enolates to R,â-unsaturated car-
bonyls has been widely studied and provides an important
method for preparation of δ-dicarbonyl compounds under neutral
and mild conditions.1 Metal enolates derived from ketones and
esters are typical as Michael donors, and R,â-unsaturated ketones
and esters are often used as Michael acceptors. Therefore, there
are four types of combinations between the donors and the
acceptors as shown in reaction types A-D (Scheme 1).
Although those reactions seem to be similar and often are
considered to be in the same class of reaction, there is a
significant difference among them. While thermal or catalytic
reactions in types A-C have been much studied and reported,2
the reaction of type D under thermal or catalytic conditions has
hardly been reported except for a few examples.3,4 We carried
† Department of Molecular Chemistry, Osaka University.
‡ Ryoka Systems Inc.
§ Handai FRC, Osaka University.
(1) ComprehensiVe Organic Syntheses; Trost, B. M., Ed.; Pergamon Press:
Oxford, U.K., 1991; Vol. 4.
(2) Simple examples using lithium enolate under thermal conditions for types
A-C: (a) Oare, D. A.; Heathcock, C. H. J. Org. Chem. 1990, 55, 157-
172. (b) Yamaguchi, M.; Tsukamoto, M.; Hirao, I. Chem. Lett. 1984, 375-
376.
(3) The classical example using a strong base for the addition of cycloalkanone
enolate to enoates. House, H. O.; Roelofs, W. L.; Trost, B. M. J. Org.
Chem. 1966, 31, 646-655.
out a theoretical calculation of the energy difference ∆E between
the product and the starting systems in types A-D and found
that reaction type D is the most disfavorable (Scheme 1).5 When
9
10.1021/ja028853+ CCC: $25.00 © 2003 American Chemical Society
J. AM. CHEM. SOC. 2003, 125, 7291-7300
7291

A R T I C L E S
Yasuda et al.
Table 1. Addition of Ketone Enolate to R,â-Unsaturated Estera
Scheme 2
entry
M
additive (mmol)
conditions
yield/%
1
2
3
4
5
6
7
Li
THF, -78 °C, 48 h
CH2Cl2, -78 °C, 15 min
CH2Cl2, -78 °C, 2 h
THF, 0 °C, 0.5 h
THF, 63 °C, 6 h
THF, 63 °C, 12 h
THF, 25 °C, 12 h
0
81
SiMe3
SiMe3
SiMe3
SiMe3
SnBu3
SnBu3
TiCl4 (1.0)
TiCl4 (0.1)
Bu4NF (0.1)
CeF (0.1)
<10b
19c
<5
0
Table 2. Addition of Ketone Enolate to R,â-Unsaturated Ketonea
Bu4NBr (0.1)
64
a Metal enolate 1 (3.0 equiv), methyl acrylate 2a (1.0 equiv). b Less than
10% yield under conditions of either -78 °C, 15 min; 25 °C, 6 h; or 40
°C, 12 h. c Less than 20% yield under conditions of either -78 °C, 15 min;
25 °C, 6 h; or 63 °C, 6 h.
entry
M
additive (mmol)
conditions
yield/%
1
2
3
4
Li
THF, -78 °C, 48 h
CH2Cl2, -78 °C, 2 h
THF, -78 °C, 12 h
THF, 63 °C, 12 h
80
87
88
93
SiMe3
SiMe3
SnBu3
TiCl4 (0.1)
Bu4NF (0.1)
Bu4NBr (0.1)
one considers the entropic factor, it is understood why only the
reaction of type D could not proceed in thermal or catalytic
conditions. Because ester enolates are generally more labile than
ketone enolates, reaction type D including transformation from
ketone enolate into ester enolate is not preferred in the
thermodynamic point of view.6 To complete the reaction, more
than an equimolar amount of additives is generally required due
to stabilization of the product system.7 A few examples reported
for the catalytic reaction of type D are ascribed to the fluorine-
stabilized effect or stabilized by further transformation of the
product system.4,8 To design a catalytic or thermal system of
type D, a number of groups have developed chemical synthons
such ortho esters,9 thioesters,10 or a cationic species11 as
unsaturated ester equivalents, and â-lithiated enamines12 as
ketone enolate equivalents in place of the direct use of R,â-
unsaturated esters and ketone enolates.
a Metal enolate 1 (3.0 equiv), enone 2b (1.0 equiv).
in 81% yield (Mukaiyama Michael addition).7 However, a
catalytic amount of Lewis acid or fluoride ion gave low yields
of the product (entries 3-5). Surprisingly, when tin enolate (1,
M ) SnBu3) was used as a metal enolate in the presence of a
catalytic amount of tetrabutylammonium bromide, the desired
product was obtained in 64% yield (entry 7). The reaction
without a catalyst did not proceed even at high temperature
(entry 6).
We have been recently developing a bromide anion-
coordinated tin enolate, which is characterized by spectroscopic
study. High coordination of tin enolate generated by using an
equimolar amount of ligands shows a unique nucleophilic
character for selective reactions (Scheme 2).15 This conjugate
addition also requires the ligand (bromide anion), and, interest-
ingly, a catalytic amount was enough to complete the reaction.
On the contrary, the reaction of the R,â-unsaturated ketone
2b with even ketone enolates 1 other than tin enolates took place
to give the product 3ab (Table 2, entries 1-3). The difference
can be explained by the thermodynamically favorable reaction
course of 1 with unsaturated ketone (type B). The tin enolate-
catalytic Bu4NBr system also proceeded smoothly to give the
product in 93% yield (entry 4). It is noted that the reaction
system using tin enolate with Bu4NBr provides a new catalytic
pathway for both unsaturated esters and ketones.
We then explored the generality of the Michael addition by
varying tin enolates 1 and unsaturated carbonyls 2. Table 3
summarizes these results. The reaction of 1a with 2a was carried
out in THF reflux conditions to increase the yield of 3aa from
64% (Table 1, entry 7) to >99% (Table 3, entry 1). The
substituents in the alkoxy moiety on the enoates did not affect
the reaction (entries 1-3). The heteroaromatic enolate 1b gave
the desired adduct 3ba in high yield (entry 4). The reaction of
tin enolate 1c derived from cyclohexanone proceeded even at
room temperature to give the product 3ca quantitatively (entry
In this paper, we report the first example of the catalytic
Michael addition of ketone enolate to R,â-unsaturated ester by
using tin enolate with a catalytic amount of tetrabutylammonium
bromide.13,14
Results and Discussion
Reaction of Ketone Enolate to r,â-Unsaturated Carbonyls.
The reaction of metal enolates 1 derived from acetophenone
with methyl acrylate 2a was chosen as a model system of type
D to investigate the reaction methods and conditions (Table 1).
With the use of lithium enolate (1, M ) Li), no reaction was
observed (entry 1) as expected from the discussion in Scheme
1. In entry 2, the use of silyl enolate (1, M ) SiMe3) with an
equimolar amount of Lewis acid gave the Michael adduct 3aa
(4) The subsequent step such as cyclization after Michael addition contributes
to the stabilization of the product system. (a) Miller, J. J.; de Benneville,
P. L. J. Org. Chem. 1957, 22, 1268-1269. (b) Lee, R. A. Tetrahedron
Lett. 1973, 3333-3336.
(5) Hashimoto, Y.; Machida, S.; Saigo, K.; Inoue, J.; Hasegawa, M. Chem.
Lett. 1989, 943-946.
(6) As expected from this assumption, reaction type A including transformation
from ester enolate to ketone enolate shows the largest stabilization.
(7) (a) Narasaka, K.; Soai, K.; Mukaiyama, T. Chem. Lett. 1974, 1223-1224.
(b) Narasaka, K.; Soai, K.; Aikawa, Y.; Mukaiyama, T. Bull. Chem. Soc.
Jpn. 1976, 49, 779-783.
(8) (a) Yamazaki, T.; Haga, J.; Kitazume, T.; Nakamura, S. Chem. Lett. 1991,
2175-2178. (b) Yamazaki, T.; Hiraoka, S.; Kitazume, T. J. Org. Chem.
1994, 59, 5100-5103.
(9) Kobayashi, S.; Mukaiyama, T. Chem. Lett. 1987, 1183-1186.
(10) Kobayashi, S.; Tamura, M.; Mukaiyama, T. Chem. Lett. 1988, 91-94.
(11) Hashimoto, Y.; Mukaiyama, T. Chem. Lett. 1986, 755-758.
(12) (a) Duhamel, L.; Duhamel, P.; Enders, D.; Karl, W.; Leger, F.; Poirier, J.
M.; Raabe, G. Synthesis 1991, 649-654. (b) Enders, D.; Karl, W. Synlett
1992, 895-897 and references therein.
(13) A part of this work has been reported in a communication. Yasuda, M.;
Ohigashi, N.; Shibata, I.; Baba, A. J. Org. Chem. 1999, 64, 2180-2181.
(14) Yasuda, M.; Ohigashi, N.; Baba, A. Chem. Lett. 2000, 1266-1267.
(15) (a) Yasuda, M.; Chiba, K.; Baba, A. J. Am. Chem. Soc. 2000, 122, 7549-
7555. (b) Yasuda, M.; Hayashi, K.; Katoh, Y.; Shibata, I.; Baba, A. J. Am.
Chem. Soc. 1998, 120, 715-721. (c) Yasuda, M.; Morimoto, J.; Shibata,
I.; Baba, A. Tetrahedron Lett. 1997, 38, 3265-3266. (d) Yasuda, M.; Katoh,
Y.; Shibata, I.; Baba, A.; Matsuda, H.; Sonoda, N. J. Org. Chem. 1994,
59, 4386-4392. (e) Yasuda, M.; Oh-hata, T.; Shibata, I.; Baba, A.; Matsuda,
H. J. Chem. Soc., Perkin Trans. 1 1993, 859-865. (f) Baba, A.; Yasuda,
M.; Yano, K.; Shibata, I.; Matsuda, H. J. Chem. Soc., Perkin Trans. 1 1990,
3205-3207. (g) Yasuda, M.; Baba, A. J. Synth. Org. Chem., Jpn. 2001,
59, 697-706.
9
7292 J. AM. CHEM. SOC. VOL. 125, NO. 24, 2003

Michael Addition of Stannyl Ketone Enolate
A R T I C L E S
Table 3. Michael Addition of Tin Enolate 1 to R,â-Unsaturated Carbonyls 2 Catalyzed by Bu4NBra
a The reactions were performed using tin enolate 1 (3.0 mmol), unsaturated carbonyl 2 (1.0 mmol), and Bu4NBr (0.1 mmol) in THF (10 mL) while
refluxing. b The reaction was performed at 25 °C. c Bu4NBr (1.8 mmol). d 2j (0.7 mmol).
5). The enolates 1d and 1e also afforded the corresponding
Michael adducts in high yields (entries 6 and 7). On the contrary,
tin enolate 1f gave a low yield of 3fc (entry 8). Organotin
enolates exist as an equilibrium of keto- and/or enol-forms, and
the ratio is dependent on the structure of the enolate.16 Enol-
forms generally show higher reactivity than keto-forms.17 The
fact that 1c exists only in enol-form and 1f in keto-form
reasonably explains the difference in their reactivity. Loading
9
J. AM. CHEM. SOC. VOL. 125, NO. 24, 2003 7293

A R T I C L E S
Yasuda et al.
Scheme 3. Plausible Reaction Mechanism
Scheme 4. Tautomerization of Stannyl Enolate
Scheme 5. The Reaction between 7 and 2a with or without
Ligand
of more than an equimolar amount of tetrabutylammonium
bromide was required for the reaction with the â-substituted
enoate 2e (entries 9 and 10). The trifluoromethyl-substituted
enoate was applied to the catalytic system because of the
stabilization effect of the CF3 group (entry 11).8 The amino and
hydroxy groups in the substrates 2g and 2i tolerated the reaction
conditions (entries 12 and 14). The substrate 2j bearing a dual
accepting moiety gave the product 3aj, which was attacked at
both sides (entry 15). This system was applied to R,â-
unsaturated amide 2k to give δ-ketoamides 3ak, 3ck, and 3dk
(entries 16, 19, and 20). Unsaturated ketones smoothly converted
to δ-diketones 3ab, 3al, and 3em (entries 17, 18, and 21).
Investigation of the Reaction Mechanism. (a) Catalytic
Cycle. Because the type D reaction is thermodynamically
disfavored as already described, the present tin enolate-catalytic
Bu4NBr system should require a further step for stabilization
of the product system. Hence, we propose a plausible reaction
course as illustrated in Scheme 3. The tin enolate 1 exists in
keto- and/or enol-forms, and the bromide anion coordinates to
only the enol-form to give 4.15d The high coordination enhances
the nucleophilicity of enolate and adds to unsaturated ester 2.
After conjugate addition, the resulting Michael adduct 5 includes
a stannyl ester enolate (enol-form; O-stannylated form). The
ester enolate 5 readily tautomerized to ester-form 6 (C-
stannylated form) in which the product system is thermody-
namically stabilized. This step takes place with dissociation of
the bromide anion because the tin center bearing only carbons
is reluctant to accept a bromide ligand.15d The product 3 is
obtained after workup.
7 and 8 is 0.10 kcal/mol. A larger difference (5.28 kcal/mol)
between enol-form 9 and ester-form 10 is calculated in ester
enolate, and the equilibrium largely lies on the side of the ester-
form. This thermodynamic factor in ester enolate significantly
affects the step from 5 to 6 in Scheme 3. The unique character
of stannyl enolates in tautomerization allows the general
synthetic route of the type D reaction, while the reaction with
other typical metal enolates failed.
(c) Reaction Step from 4 to 5. Next, the C-C bond
formation step from 4 to 5, which is a rate-determining step,
was investigated by theoretical calculation. We assume that the
effect of the bromide anion catalyst serves as an accelerator of
the Michael addition as shown in Scheme 3. The reaction of
four- or five-coordinated tin enolate (7 or 7-Br) with R,â-
unsaturated ester 2a was chosen as a model reaction system
(Scheme 5). The calculation was performed for the reactions
from the starting materials to the Michael adducts which have
the enol-form at the ester moiety.
The calculated potential energy profiles for the uncatalyzed
and catalyzed reactions corresponding to Scheme 5a and b are
shown in Figures 1 and 2, respectively. The optimized geom-
etries for their pathways and the structures in the reaction courses
are illustrated in Figures 3 and 4 and Scheme 6.
The activation energy in the reaction using the bromide anion
is lower than that of the reaction without using it (18 vs 11
kcal/mol) as shown in Figures 1 and 2. The transition state A
or D in either reaction course has a linear structure, not a cyclic
one, with long distances between Sn and O (A, 3.808 Å; D,
5.576 Å) as shown in Figures 3 and 4. The local minimum
corresponding to the intermediate E was found in the catalyzed-
reaction course from C to G, while the uncatalyzed reaction
directly gave the Michael adduct B from the starting materials
7 + 2a. The structure E has a Sn-O bond still at the enol site.
The ligand which coordinates to the tin center would decrease
(b) Reaction Step from 5 to 6. The ready tautomerization
of the stannyl ester enolate from the enol-form to ester-form
(R-stannyl ester) is reported, and ester enolates of tin are usually
isolated as only the ester-form, not the enol-form.18,19 As
compared to the ester enolate, stannyl ketone enolates are often
isolated as a mixture of keto- and enol-forms.16 The theoretical
calculation shows reasonable results as illustrated in Scheme
4. For the stannyl ketone enolate, the energy difference between
(16) Pereyre, M.; Bellegarde, B.; Mendelsohn, J.; Valade, J. J. Organomet. Chem.
1968, 11, 97-110.
(17) Kobayashi, K.; Kawanisi, M.; Hitomi, T.; Kozima, S. Chem. Lett. 1983,
851-854.
(18) Zapata, A.; Acuna, C. Synth. Commun. 1984, 14, 27-32.
(19) Shimada, E.; Inomata, K.; Mukaiyama, T. Chem. Lett. 1974, 689-690.
9
7294 J. AM. CHEM. SOC. VOL. 125, NO. 24, 2003

Michael Addition of Stannyl Ketone Enolate
A R T I C L E S
Figure 1. Potential energy profile for the reaction between 7 and 2a without
ligand.
Figure 2. Potential energy profile for the reaction between 7 and 2a with
ligand.
Figure 3. Structures along the reaction between 7 and 2a (distances in Å).
the Lewis acidity of tin and interfere with a ready transfer of
the stannyl group from the enolate oxygen to the ester carbonyl
oxygen. The structure of the transition state F shows little
interaction of the tin center with either oxygen. When the
reaction goes forward to G, the interaction of Sn with oxygen
in the ester enolate moiety becomes stronger and contributes to
the stabilization of the potential energy. The Michael adduct G
Figure 4. Structures along the reaction between 7-Br and 2a (distances in
Å).
9
J. AM. CHEM. SOC. VOL. 125, NO. 24, 2003 7295

A R T I C L E S
Yasuda et al.
Scheme 6
that forms via migration of the stannyl group is thermodynami-
cally stable and finally leads to the more stabilized ester-form.20
The coordination of the bromide anion to tin enolate causes
a significant change in the structure and reactivity.15a The
structures and HOMOs of four-coordinated enolate 7 and five-
coordinated enolate 7-Br are illustrated in Figure 5. The highly
coordinated tin enolate 7-Br shows longer distance in the O-Sn
(1.983-2.150 Å) and vinylic bonds (1.350-1.362 Å) and
shorter distance in the C-O bond (1.348-1.317 Å) as compared
to four-coordinated species 7. A four-coordinated tin enolate
has partially double bond character in O-Sn by pπ-dπ
interaction, which has conjugation with the vinylic moiety such
as diene. The coordination of the anionic ligand to the tin center
decreases the interaction of the O-Sn bond to generate partially
double bond character in the C-O bond. We also show the
energies and shapes of the HOMOs of 7 and 7-Br. The
coordination of the bromide anion to the tin center leads to an
increment of the HOMO lobe at the vinylic moiety. The energy
level of HOMO is increased from -132.3 to -55.4 kcal/mol.
These results indicate the significant enhancement of nucleo-
philicity of tin enolates by coordination of the bromide anion
to the tin center.
Figure 5. Structures of tin enolate 7 and coordinated tin enolate 7-Br
(distances in Å) and HOMOs for each species (ꢀ values in parentheses are
the energies).
Conclusions
We have demonstrated that Michael addition of metal ketone
enolate to R,â-unsaturated esters successfully proceeds using
tin enolate combined with Bu4NBr-catalyst. An ab initio
calculation for this reaction system clarified the details of the
reaction course. This system has three mechanistically important
points: (1) The coordination of the bromide anion catalyst
contributes to the enhancement of the reaction rate to enoates
due to an increase of its HOMO level. The activation energy is
lowered by the ligand-coordinated system. (2) The product
(20) The potential energy profile around the transition state between E and G
is too flat and includes several local energy maximums, whose levels are
lower than that of D. The structure F has the highest energy level among
them between E and G. The difference between the uncatalyzed and
catalyzed reactions can be discussed by comparing A and D.
9
7296 J. AM. CHEM. SOC. VOL. 125, NO. 24, 2003

Michael Addition of Stannyl Ketone Enolate
A R T I C L E S
General Procedure for Synthesis of δ-Dicarbonyl Compounds
(3). To a mixture of a tin enolate 1 (3.0 mmol) and a catalytic amount
of tetrabutylammonium bromide (0.1 mmol) in dry THF (10 mL) was
added an R,â-unsaturated carbonyl 2 (1.0 mmol) under nitrogen. The
reaction mixture was stirred under the conditions noted in Tables 1-3.
Methanol (5 mL) was then added to the solution, and the volatiles were
evaporated. Diethyl ether (30 mL) and aqueous NH4F (15%; 15 mL)
were added, and the precipitated Bu3SnF was filtered off. The filtrate
was washed with water (30 mL × 2), dried (MgSO4), and evaporated.
Column chromatography of the residue on silica gel and distillation or
recrystallization gave pure products.
system has a further stabilization step from the enol-form in
the initial adduct to the ester-form by tautomerization of tin
enolates. This tautomerization is a unique characteristic of the
tin species. (3) The isomerization leads to formation of the keto-
form, which releases the bromide anion, and the catalytic cycle
can be completed. These points lead to the accomplishment of
the first example of the Michael addition type D (ketone enolate
+ unsaturated ester), which has not been completed before under
catalytic conditions. This system can be applied to a variety of
tin enolates and R,â-unsaturated carbonyls involving enoates,
enones, and unsaturated amides.
Product Data. The spectral data of the product 3fc were in excellent
agreement with the purchased sample (Aldrich).
Experimental Section
Methyl 5-Oxo-5-phenylpentanoate (3aa). According to the general
procedure, this compound was prepared from 1a and 2a in dry THF to
give the product as a colorless liquid after chromatography (hexane/
Et2O, 1/1). Further purification was performed by distillation under
General. IR spectra were recorded as thin films on a Hitachi 260-
30 or a HORIBA FT-720 spectrophotometer. 1H and 13C NMR spectra
were obtained with a JEOL JNM-GSX-270 (270 and 67.9 MHz)
spectrometer, respectively, with TMS as internal standard. Mass spectra
were recorded on a JEOL JMS-DS303 or a Shimadzu GCMS-QP2000A
spectrometer. GLC analyses were performed on a Shimadzu GC-8A
with FID using a 2 m × 3 mm column packed with SE-52. Column
chromatography was performed on silica gel (Fuji Silysia BW-200).
Bulb-to-bulb distillation (Kugelrohr) was accomplished in a Sibata
GTO-250RS at the oven temperature and pressure indicated.
Materials. THF was distilled from sodium and benzophenone. Tin
enolates 1a, 1c-f were prepared by known methods from enol acetate
and tributyltin methoxide.16,21 The tin enolate 1b was prepared from
the corresponding enol acetates (1-acetoxy-1-(2-thienyl)ethene and
tributyltin methoxide) in a similar fashion.16,21 1-Acetoxy-1-(2-thienyl)-
ethene was prepared by the reaction of 2-acetylthiophene with ketene.22
The Michael acceptors 2 were commercial products except for 2b. (E)-
1-Phenyl-2-buten-1-one 2b was prepared according to the described
method.23
reduced pressure: bp 120 °C/2 mmHg. IR (neat): 1730, 1690 cm-1
.
1H NMR (270 MHz, CDCl3): 7.98-7.93 (m, 2H, aroma), 7.60-7.42
(m, 3H, aroma), 3.68 (s, 3H, OMe), 3.06 (t, J ) 7.3 Hz, 2H, 4-H2),
2.45 (t, J ) 7.3 Hz, 2H, 2-H2), 2.07 (qn, J ) 7.3 Hz, 2H, 3-H2). 13C
NMR (67.9 MHz, CDCl3): 199.24 (s, C-5), 173.57 (s, C-1), 136.73
(s, ipso), 132.94 (d), 128.48 (d), 127.90 (d), 51.42 (q, OMe), 37.32 (t,
C-4), 33.01 (t, C-2), 19.24 (t, C-3). MS (EI, 70 eV): m/z 206 (M+, 2),
175 (M+ - OMe, 6), 147 (M+ - COOMe, 7), 133 (3), 105 (100), 77
(47). HRMS (EI, 70 eV): calcd for C12H14O3 206.0943, found m/z
206.0943 (M+). Anal. Calcd for C12H14O3: C, 69.89; H, 6.84. Found:
C, 69.59; H, 6.95.
Ethyl 5-Oxo-5-phenylpentanoate (3ac). According to the general
procedure, this compound was prepared from 1a and 2c in dry THF to
give the product as a colorless liquid after chromatography (hexane/
Et2O, 5/1). Further purification was performed by distillation under
reduced pressure: bp 170 °C/2 mmHg. IR (neat): 1736, 1689 cm-1
.
1H NMR (270 MHz, CDCl3): 7.98-7.95 (m, 2H, aroma), 7.59-7.42
(m, 3H, aroma), 4.14 (q, J ) 7.3 Hz, 2H, OCH2), 3.05 (t, J ) 7.3 Hz,
2H, 4-H2), 2.43 (t, J ) 7.3 Hz, 2H, 2-H2), 2.07 (qn, J ) 7.3 Hz, 2H,
3-H2), 1.25 (t, J ) 7.3 Hz, 3H, OCH2CH3). 13C NMR (67.9 MHz,
CDCl3): 199.36 (s, C-5), 173.19 (s, C-1), 136.79 (s, ipso), 132.97 (d),
128.52 (d), 127.93 (d), 60.28 (t, OCH2), 37.40 (t, C-4), 33.35 (t, C-2),
19.35 (t, C-3), 14.15 (q, OCH2CH3). MS (EI, 70 eV): m/z 220 (M+,
11), 175 (M+ - OEt, 25), 147 (M+ - COOEt, 14), 133 (6), 105 (100),
77 (27). HRMS (EI, 70 eV): calcd for C13H16O3 220.1099, found m/z
220.1091, 220.1095, 220.1115 (M+).
Addition of Ketone Enolate to 2a or 2b (Tables 1 and 2). (a) M
) Li.24 A flask was charged with dried THF (2 mL) under nitrogen
and was cooled to -78 °C. A 2.0 M solution of lithium diisopropyl-
amide (from Aldrich) in THF/heptane/ethylbenzene (1.5 mL) was added.
To the mixture was added dropwise acetophenone (3.0 mmol). After
15 min of stirring, 2a or 2b (1.0 mmol) was added under the conditions
found in Table 1 or 2. The reaction was quenched with 20 mL of
aqueous NH4Cl, and the aqueous phase was extracted with Et2O.
(b) M ) Si with TiCl4.7a A solution of TiCl4 (0.5 mmol) in 5 mL
of CH2Cl2 was cooled to -78 °C and stirred under nitrogen. To the
reaction mixture were successively added 2a or 2b (0.5 mmol) and
silyl enolate (1.5 mmol) under the conditions found in Table 1 or 2.
The mixture was quenched with aqueous KHCO3, and the resulted
precipitate was filtered off. The aqueous phase was extracted with Et2O.
The other reactions using silyl enolate were perfomed in the same
manner.
(c) M ) Si with Bu4NF.25 A solution of silyl enolate (1.5 mmol)
and 2a or 2b (0.5 mmol) in 2 mL of THF was kept at the temperatures
described in Table 1 or 2 and stirred under nitrogen. To the reaction
mixture was added Bu4NF (0.05 mmol, 1 M in THF). Workup was
performed according to the literature.25
(d) M ) Si with CsF.26 A solution of CsF (0.05 mmol) in 2 mL of
THF was kept at the temperatures described in Table 1 and stirred under
nitrogen. To the reaction mixture were successively added 2a (0.5
mmol) and silyl enolate (1.5 mmol). Workup was performed according
to the literature.26
tert-Buthyl 5-Oxo-5-phenylpentanoate (3ad). According to the
general procedure, this compound was prepared from 1a and 2d in dry
THF to give the product as a colorless liquid after chromatography
(hexane/Et2O, 10/1). Further purification was performed by distillation
under reduced pressure: bp 160 °C/2 mmHg. IR (neat): 1728, 1689
cm-1. 1H NMR (270 MHz, CDCl3): 7.98-7.95 (m, 2H, aroma), 7.59-
7.43 (m, 3H, aroma), 3.06 (t, J ) 6.8 Hz, 2H, 4-H2), 2.34 (t, J ) 6.8
Hz, 2H, 2-H2), 2.03 (qn, J ) 6.8 Hz, 2H, 3-H2), 1.45 (s, 9H, tBu). 13
C
NMR (67.9 MHz, CDCl3): 199.55 (C-5), 172.56 (C-1), 136.88 (ipso),
132.97, 128.54, 127.99, 80.24 (CMe3), 37.49 (C-4), 34.66 (C-2), 28.09
(CMe3), 19.62 (C-3). MS (EI, 70 eV): m/z 248 (M+, 0.08), 175 (M+
- OtBu, 67), 147 (M+ - COOtBu, 22), 133 (12), 105 (100), 77 (29).
HRMS (EI, 70 eV): calcd for C15H20O3 248.1412, found m/z 248.1440,
248.1425 (M+). Anal. Calcd for C15H20O3: C, 72.55; H, 8.12. Found:
C, 72.38; H, 7.98.
Methyl 5-(2-Thienyl)-5-oxopentanoate (3ba). According to the
general procedure, this compound was prepared from 1b and 2a in dry
THF to give the product as a colorless liquid after chromatography
(hexane/Et2O, 2/1). Further purification was performed by distillation
under reduced pressure: bp 155 °C/2 mmHg. IR (neat): 1682, 1730
cm-1. 1H NMR (270 MHz, CDCl3): 7.74-7.71 (m, 1H, aroma), 7.65-
7.61 (m, 1H, aroma), 7.15-7.11 (m, 1H, aroma), 3.68 (s, 3H, OMe),
2.99 (t, J ) 7.3 Hz, 2H, 4-H2), 2.44 (t, J ) 7.3 Hz, 2H, 2-H2), 2.08
(21) Labadie, S. S.; Stille, J. K. Tetrahedron 1984, 40, 2329-2336.
(22) Gwynn, B. H.; Degering, E. F. J. Am. Chem. Soc. 1942, 64, 2216-2218.
(23) Oare, D. A.; Henderson, M. A.; Sanner, M. A.; Heathcock, C. H. J. Org.
Chem. 1990, 55, 132-157.
(24) Oare, D. A.; Heathcock, C. H. J. Org. Chem. 1990, 55, 157-172.
(25) RajanBabu, T. V. J. Org. Chem. 1984, 49, 2083-2089.
(26) Boyer, J.; Corriu, R. J. P.; Perz, R.; Reye, C. J. Organomet. Chem. 1980,
184, 157-166.
9
J. AM. CHEM. SOC. VOL. 125, NO. 24, 2003 7297

A R T I C L E S
Yasuda et al.
(qn, J ) 7.3 Hz, 2H, 3-H2). 13C NMR (67.9 MHz, CDCl3): 192.32
(C-5), 173.55 (C-1), 144.12, 133.52, 131.86, 128.07, 51.54 (OMe),
38.13 (C-4), 33.01 (C-2), 19.64 (C-3). MS (EI, 70 eV): m/z 212 (M+,
10), 181 (M+ - OMe, 12), 153 (M+ - COOMe, 12), 139 (10), 111
(100), 83 (83). HRMS (EI, 70 eV): calcd for C10H12O3S 212.0507,
found m/z 212.0509 (M+). Anal. Calcd for C10H12O3S: C, 56.59; H,
5.70. Found: C, 56.44; H, 5.89.
Ethyl 3-Trifluoromethyl-5-oxo-5-phenylpentanoate (3af). Ac-
cording to the general procedure, this compound was prepared from
1a and 2f in dry THF to give the product as a colorless liquid after
chromatography (hexane/Et2O, 5/1). Further purification was performed
by distillation under reduced pressure: bp 125 °C/2 mmHg. IR (neat):
1
1736, 1689 cm-1. H NMR (270 MHz, CDCl3): 7.99-7.95 (m, 2H,
aroma), 7.64-7.26 (m, 3H, aroma), 4.14 (q, J ) 7.3 Hz, 2H, OCH2),
3.75-3.45 (m, 1H, 3-H), 3.34 (dd, J ) 18.6, 4.9 Hz, 1H, 4-HA), 3.25
(dd, J ) 18.6, 7.8 Hz, 1H, 4-HB), 2.69 (dd, J ) 16.1, 5.9 Hz, 1H,
2-HA), 2.53 (dd, J ) 16.1, 7.3 Hz, 1H, 2-HB), 1.23 (t, J ) 7.3 Hz, 3H,
Me). 13C NMR (67.9 MHz, CDCl3): 195.62 (C-5), 170.24 (C-1), 136.18
(ipso), 133.52, 128.69, 128.00, 127.40 (q, 1JCF ) 279.2 Hz, CF3), 60.99
Methyl 3-(2-Oxocyclohexyl)propanoate (3ca). According to the
general procedure, this compound was prepared from 1c and 2a in dry
THF to give the product as a colorless liquid after chromatography
(hexane/Et2O, 2/1). Further purification was performed by distillation
under reduced pressure: bp 105 °C/2 mmHg. IR (neat): 1743, 1712
1
cm-1. H NMR (270 MHz, CDCl3): 3.66 (OMe, 3H), 2.50-1.37 (m,
2
3
(OCH2), 36.55 (C-4), 35.76 (q, JCF ) 28 Hz, C-3), 33.15 (t, JCF
)
13H). 13C NMR (67.9 MHz, CDCl3): 212.40 (s, cycloCdO), 173.91
(s, C-1), 51.38 (q, OMe), 49.63 (d, CH), 42.04 (t), 34.06 (t), 31.53 (t),
27.94 (t), 24.96 (t), 24.74 (t). MS (EI, 70 eV): m/z 184 (M+, 24), 153
(M+ - OMe, 41), 152 (100), 125 (M+ - COOMe, 20), 124 (43), 111
(24), 97 (19). HRMS (EI, 70 eV): calcd for C10H16O3 184.1099, found
m/z 184.1095 (M+). Anal. Calcd for C10H16O3: C, 65.19; H, 8.75.
Found: C, 65.47; H, 8.95.
3.1 Hz, C-2), 13.94 (q, Me). MS (EI, 70 eV): m/z 288 (M+, 8), 243
(M+ - OEt, 29), 215 (M+ - COOEt, 18), 105 (100), 77 (27). HRMS
(EI, 70 eV): calcd for C14H15F3O3 288.0973, found m/z 288.0956,
288.0971 (M+). Anal. Calcd for C14H15F3O3: C, 58.33; H, 5.24.
Found: C, 58.10; H, 5.10.
2-(N,N-Dimethylamino)ethyl 5-Oxo-5-phenylpentanoate (3ag).
According to the general procedure, this compound was prepared from
1a and 2g in dry THF to give the product as a colorless liquid after
chromatography (Et2O). Further purification was performed by distil-
lation under reduced pressure: bp 180 °C/2 mmHg. IR (neat): 1736,
1689 cm-1. 1H NMR (270 MHz, CDCl3): 7.98-7.94 (m, 2H, aroma),
7.59-7.42 (m, 3H, aroma), 4.18 (t, J ) 5.9 Hz, 2H, OCH2), 3.06 (t, J
) 6.8 Hz, 2H, 4-H2), 2.55 (t, J ) 5.9 Hz, 2H, CH2NMe2), 2.47 (t, J )
6.8 Hz, 2H, 2-H2), 2.28 (s, 6H, NMe2), 2.07 (qn, J ) 6.8 Hz, 2H,
3-H2). 13C NMR (67.9 MHz, CDCl3): 199.27 (C-5), 173.19 (C-1),
136.71 (ipso), 132.92, 128.36, 127.90, 62.04 (OCH2), 57.70 (CH2NMe2),
45.59 (NMe2), 37.32 (C-4), 33.19 (C-2), 19.26 (C-3). MS (EI, 70 eV):
m/z 263 (M+, 0.3), 219 (M+ - NMe2, 0.3), 175 (2), 147 (2), 105 (17),
77 (11), 58 (100). HRMS (EI, 70 eV): calcd for C15H21O3N 263.1521,
found m/z 263.1526, 263.1537 (M+). Anal. Calcd for C15H21O3N: C,
68.42; H, 8.04; N, 5.32. Found: C, 68.36; H, 8.05; N, 5.16.
Methyl 4-Methyl-5-oxo-5-phenylpentanoate (3da). According to
the general procedure, this compound was prepared from 1d and 2a in
dry THF to give the product as a colorless liquid after chromatography
(hexane/Et2O, 5/1). Further purification was performed by distillation
under reduced pressure: bp 155 °C/2 mmHg. IR (neat): 1735, 1681
cm-1. 1H NMR (270 MHz, CDCl3): 7.97-7.95 (m, 2H, aroma), 7.60-
7.40 (m, 3H, aroma), 3.65 (s, 3H, OMe), 3.6-3.5 (m, 1H, 4-H), 2.47-
2.26 (m, 2H, 2-H2), 2.24-2.10 (m, 1H, 3-HA), 1.85-1.71 (m, 1H,
3-HB), 1.21 (d, J ) 6.83 Hz, 3H, 4-Me). 13C NMR (67.9 MHz,
CDCl3): 203.46 (s, C-5), 173.68 (s, C-1), 136.33 (s, ipso), 133.00 (d),
128.65 (d), 128.28 (d), 51.50 (q, OMe), 39.53 (d, C-4), 31.45 (t, C-2),
28.24 (t, C-3), 17.32 (q, 4-Me). MS (EI, 70 eV): m/z 220 (M+, 17),
189 (M+ - OMe, 10), 161 (M+ - COOMe, 5), 147 (3), 105 (100), 77
(24). HRMS (EI, 70 eV): calcd for C13H16O3 220.1099, found m/z
220.1102 (M+). Anal. Calcd for C13H16O3: C, 70.89; H, 7.32. Found:
C, 70.61; H, 7.34.
2-(2-Oxo-2-phenylethyl)succinic Acid Diethyl Ester (3ah). Ac-
cording to the general procedure, this compound was prepared from
1a and 2h in dry THF to give the product as a colorless liquid after
chromatography (hexane/Et2O, 1/1). Further purification was performed
by distillation under reduced pressure: bp 185 °C/2 mmHg. IR (neat):
Ethyl 6,6-Dimethyl-5-oxoheptanoate (3ec). According to the
general procedure, this compound was prepared from 1e and 2c in dry
THF to give the product as a colorless liquid after chromatography
(hexane/Et2O, 5/1). Further purification was performed by distillation
under reduced pressure: bp 80 °C/2 mmHg. IR (neat): 1736, 1705
1
1736, 1689 cm-1. H NMR (270 MHz, CDCl3): 7.99-7.95 (m, 2H,
aroma), 7.61-7.43 (m, 3H, aroma), 4.21-4.10 (m, 4H, 2 × OCH2),
3.58-3.42 (m, 3H, PhCOCHA and 2-H), 3.25 (dd, J ) 16.6, 4.4 Hz,
1H, PhCOCHB), 2.80 (dd, J ) 16.6, 6.3 Hz, 1H, 3-HA), 2.68 (d, J )
16.6, 6.3 Hz 1H, 3-HB), 1.28-1.20 (m, 6H, 2 × Me). 13C NMR (67.9
MHz, CDCl3): 197.42 (PhCO), 173.68, 171.58, 136.47 (ipso), 133.23,
128.55, 127.99, 60.93 (OCH2), 60.62 (OCH2), 39.27 (PhCOCH2), 36.69
(C-2), 35.41 (C-3), 14.09 (Me), 14.00 (Me). MS (EI, 70 eV): m/z 292
(M+, 2), 247 (M+ - OEt, 39), 187 (17), 105 (100), 77 (20). HRMS
(EI, 70 eV): calcd for C16H20O5 292.1311, found m/z 292.1316,
292.1293, 292.1294, 292.1296 (M+). Anal. Calcd for C16H20O5: C,
65.74; H, 6.90. Found: C, 65.58; H, 6.89.
1
cm-1. H NMR (270 MHz, CDCl3): 4.13 (q, J ) 7.3 Hz, 2H, OCH2-
CH3), 2.56 (t, J ) 7.3 Hz, 2H, 4-H2), 2.31 (t, J ) 7.3 Hz, 2H, 2-H2),
1.88 (qn, J ) 7.3 Hz, 2H, 3-H2), 1.25 (t, J ) 7.3 Hz, 3H, OCH2CH3),
1.13 (s, tBu). 13C NMR (67.9 MHz, CDCl3): 215.22 (C-5), 173.32 (C-
1), 60.27 (OCH2CH3), 44.06 (C-6), 35.29, 33.33, 26.35 (CMe3), 19.14
(C-3), 14.22 (OCH2CH3). MS (EI, 70 eV): m/z 200 (M+, 0.14), 155
(M+ - OEt, 23), 143 (100), 127 (4), 115 (71). HRMS (EI, 70 eV):
calcd for C11H20O3 200.1412, found m/z 200.1423, 200.1387 (M+).
Ethyl 3-Phenyl-5-oxo-5-phenylpentanoate (3ae). According to the
general procedure, this compound was prepared from 1a and 2e in dry
THF to give the product as a colorless liquid after chromatography
(hexane/Et2O, 2/1). A solid was obtained after standing for 1 day and
quickly washed by hexane to give the pure product: mp 60 °C. IR
2-Hydroxyethyl 5-Oxo-5-phenylpentanoate (3ai). According to the
general procedure, this compound was prepared from 1a and 2i in dry
THF to give the product as a colorless liquid after chromatography
(Et2O). Further purification was performed by distillation under reduced
pressure: bp 170 °C/2 mmHg. IR (neat): 3479, 1728, 1682 cm-1. 1H
NMR (270 MHz, CDCl3): 7.97-7.94 (m, 2H, aroma), 7.59-7.42 (m,
3H, aroma), 4.22 (t, J ) 4.4 Hz, 2H, COOCH2), 3.82 (t, J ) 4.4 Hz,
2H, CH2OH), 3.06 (t, J ) 6.8 Hz, 2H, 4-H2), 2.69 (brs, 1H, OH), 2.48
(t, J ) 6.8 Hz, 2H, 2-H2), 2.08 (qn, J ) 6.8 Hz, 2H, 3-H2). 13C NMR
(67.9 MHz, CDCl3): 199.61 (C-5), 173.48 (C-1), 136.59 (ipso), 133.09,
128.54, 127.96, 65.95 (COOCH2), 60.91 (CH2OH), 37.29 (C-4), 33.18
1
(KBr): 1728, 1674 cm-1. H NMR (270 MHz, CDCl3): 7.93-7.89
(m, 2H, aroma), 7.57-7.16 (m, 8H, aroma), 4.03 (q, J ) 7.3 Hz, 2H,
OCH2), 3.88 (qn, J ) 7.3 Hz, 1H, 3-H), 3.40 (dd, J ) 16.6, 7.3 Hz,
1H, 4-HA), 3.32 (dd, J ) 16.6, 7.3 Hz, 1H, 4-HB), 2.81 (dd, J ) 15.6,
7.3 Hz, 1H, 2-HA), 2.67 (dd, J ) 15.6, 7.3 Hz, 1H, 2-HB), 1.13 (t, J )
7.3 Hz, 3H, OCH2CH3). 13C NMR (67.9 MHz, CDCl3): 198.09 (C-5),
171.77 (C-1), 143.28, 136.88, 133.01, 128.51, 128.00, 127.33, 126.71,
60.31 (OCH2), 44.55, 40.76, 37.55, 14.03 (Me). MS (EI, 70 eV): m/z
296 (M+, 17), 251 (M+ - OEt, 13), 223 (M+ - COOEt, 5), 209 (42),
177 (5), 105 (100), 77 (27). HRMS (EI, 70 eV): calcd for C19H20O3
296.1413, found m/z 296.1425, 296.1421 (M+). Anal. Calcd for
C19H20O3: C, 77.00; H, 6.80. Found: C, 76.85; H, 6.75.
(C-2), 19.27 (C-3). MS (EI, 70 eV): m/z 236 (M+, 7), 175 (M+
-
OC2H4OH, 32), 147 (M+ - C3H5O3, 12), 105 (100), 77 (25). HRMS
(EI, 70 eV): calcd for C13H16O4 236.1048, found m/z 236.1066,
9
7298 J. AM. CHEM. SOC. VOL. 125, NO. 24, 2003

Michael Addition of Stannyl Ketone Enolate
A R T I C L E S
reduced pressure: bp 120 °C/2 mmHg. IR (neat): 1705, 1643 cm-1
236.1025, 263.1044, 236.1051 (M+). Anal. Calcd for C13H16O4: C,
66.09; H, 6.83. Found: C, 66.11; H, 6.80.
.
1H NMR (270 Hz, CDCl3): 3.02 (NMeA, 3H), 2.93 (NMeB, 3H), 2.48-
1.39 (m, 13H). 13C NMR (67.9 Hz, CDCl3): 213.48 (s, cycloCO),
172.87 (s, C-1), 49.99 (d, CH), 42.19 (t), 37.17 (q), 35.24 (q), 34.58
(t), 31.02 (t), 28.10 (t), 25.35 (t), 24.96 (t). MS (EI, 70 eV): m/z 197
(M+, 24), 153 (M+ - NMe2, 4), 125 (M+ - CONMe2, 14), 100 (20),
97 (3), 72 (26). HRMS (EI, 70 eV): calcd for C11H19NO2 197.1416,
found m/z 197.1407, 197.1407 (M+). Anal. Calcd for C11H19NO2: C,
66.97; H, 9.71; N, 7.10. Found: C, 64.96; H, 9.67; N, 6.79.
Tetracarbonyl Compound 3aj. According to the general procedure,
this compound was prepared from 1a and 2j in dry THF to give the
product as a colorless liquid after chromatography (hexane/Et2O, 1/1).
Further purification was performed by distillation under reduced
pressure: bp 220 °C/3.8 × 10-2 mmHg. IR (neat): 1732, 1681 cm-1
.
1H NMR (270 MHz, CDCl3): 7.98-7.93 (m, 4H, aroma), 7.59-7.27
(m, 6H, aroma), 4.23 (t, J ) 4.9 Hz, 4H, 2 × COOCH2), 3.68 (t, J )
4.9 Hz, 4H, 2 × COOCH2CH2), 3.06 (t, J ) 7.3 Hz, 4H, 2 ×
PhCOCH2), 2.47 (t, J ) 7.3 Hz, 4H, 2 × CH2COO), 2.07 (t, J ) 7.3
Hz, 2 × PhCOCH2CH2). 13C NMR (67.9 MHz, CDCl3): 199.32 (s,
PhCO), 173.13 (COO), 136.73 (ipso), 133.03, 128.54, 127.96, 68.99
(OCH2), 63.31 (OCH2), 37.35 (PhCOCH2), 33.16 (OCOCH2), 19.24
(PhCOCH2CH2). MS (CI, 70 eV): m/z 455 (M+ + 1, 3), 335 (49), 235
(6), 219 (9), 147 (6), 105 (18). HRMS (CI, 70 eV): calcd for C26H31O7
455.2070, found m/z 455.2048, 455.2052 (M+ + 1). Anal. Calcd for
C26H30O7: C, 68.71; H, 6.65. Found: C, 69.01; H, 6.66.
N,N-Dimethyl 4-Methyl-5-oxo-5-phenylpentanamide (3dk). Ac-
cording to the general procedure, this compound was prepared from
1d and 2k in dry THF to give the product as a colorless liquid after
chromatography (Et2O). Further purification was performed by distil-
lation under reduced pressure: bp 170 °C/2 mmHg. IR (neat): 1682,
1643 cm-1. 1H NMR (270 MHz, CDCl3): 8.02-7.98 (m, 2H, aroma),
7.59-7.44 (m, 3H, aroma), 3.68 (qt, J ) 6.8, 5.9 Hz, 1H, 4-H), 2.93
(s, 3H, NMeA), 2.92 (s, 3H, NMeB), 2.47-2.08 (m, 3H, 2-H2 and 3-HA),
1.91-1.76 (m, 1H, 3-HB), 1.22 (d, J ) 6.8 Hz, 3H, 4-Me). 13C NMR
(67.9 MHz, CDCl3): 204.14 (C-5), 172.44 (C-1), 136.45 (ipso), 132.96,
128.63, 128.36, 39.75 (C-4), 37.14 (NMeA), 35.33 (NMeB), 30.55 (C-
2), 28.59 (C-3), 17.59 (4-Me). MS (EI, 70 eV): m/z 233 (M+, 14),
189 (M+ - NMe2, 4), 161 (M+ - CONMe2, 10), 128 (19), 105 (100),
77 (33), 72 (56). HRMS (EI, 70 eV): calcd for C14H19NO2 233.1416,
found m/z 233.1401, 233.1395 (M+). Anal. Calcd for C14H19NO2: C,
72.07; H, 8.21; N, 6.00. Found: C, 72.15; H, 8.15; N, 6.00.
N,N-Dimethyl-5-oxo-5-phenylpentanamide (3ak). According to the
general procedure, this compound was prepared from 1a and 2k in dry
THF to give the product as a colorless liquid after chromatography
using [Fuji Silysia FL100DX] (hexane/Et2O, 1/1). Further purification
was performed by distillation under reduced pressure: bp 130 °C/1.5
× 10-1 mmHg. IR (neat): 1682, 1643 cm-1
.
1H NMR (270 MHz,
CDCl3): 8.01-7.96 (m, 2H, aroma), 7.59-7.40 (m, 3H, aroma), 3.11
(t, J ) 6.8 Hz, 2H, 4-H2), 3.01 (s, 3H, NMeA), 2.95 (s, 3H, NMeB),
2.44 (t, J ) 6.8 Hz, 2H, 2-H2), 2.09 (qn, J ) 6.8 Hz, 2H, 3-H2). 13C
NMR (67.9 MHz, CDCl3): 200.14 (C-5), 172.45 (C-1), 136.88 (ipso),
132.99, 128.55, 128.08, 37.76 (C-4), 37.18 (NMeA), 35.33 (NMeB),
32.32 (C-2), 19.62 (C-3). MS (EI, 70 eV): m/z 219 (M+, 26), 175
(M+ - NMe2, 12), 147 (M+ - CONMe2, 32), 105 (100), 77 (41).
HRMS (EI, 70 eV): calcd for C13H17NO2 219.1259, found m/z 219.1255
(M+).
2,2-Dimethyl-3,7-dioxo-5,7-diphenylheptane (3em). According to
the general procedure, this compound was prepared from 1e and 2m
in dry THF to give the product as a colorless liquid after chromatog-
raphy (hexane/Et2O, 2/1). Further purification was performed by
distillation under reduced pressure: bp 175 °C/4.0 × 10-2 mmHg. IR
(neat): 1689 cm-1. 1H NMR (270 MHz, CDCl3): 8.00-7.90 (m, 2H,
aroma), 7.56-7.13 (m, 8H, aroma), 3.91 (qn, J ) 6.8 Hz, 1H, 5-H),
3.38 (dd, J ) 16.1, 6.8 Hz, 1H, 6-HA), 3.26 (dd, J ) 16.1, 7.3 Hz, 1H,
6-HB), 2.93 (d, J ) 6.8 Hz, 2H, 4-H2), 1.04 (s, 9H, CMe3). 13C NMR
(67.9 MHz, CDCl3): 213.85 (C-3), 198.60 (C-7), 143.97 (ipso), 136.84
(ipso), 132.91, 128.46, 128.40, 128.05, 127.41, 126.46, 44.52, 44.03
(C-2), 42.85, 36.65, 26.06 (CMe3). MS (EI, 70 eV): m/z 308 (M+,
1,5-Diphenyl-3-methyl-1,5-pentanedione (3ab). According to the
general procedure, this compound was prepared from 1a and 2b in dry
THF to give the product as a colorless liquid after chromatography
(hexane/Et2O, 5/1). Further purification was performed by distillation
under reduced pressure: bp 165 °C/3.5 × 10-2 mmHg. IR (neat): 1678
cm-1. 1H NMR (270 MHz, CDCl3): 8.02-7.98 (m, 4H, aroma), 7.60-
7.43 (m, 6H, aroma), 3.23-3.13 (m, 2H, 2-HA and 4-HA), 2.93-2.81
(m, 3H, 2-HB, 4-HB, and 3-H), 1.09 (d, J ) 5.9 Hz, 3H, 3-Me). 13C
NMR (67.9 MHz, CDCl3): 199.64 (s, C-1 and C-5), 137.02 (s, ipso),
133.03 (d), 128.59 (d), 128.17 (d), 45.37 (t, C-2 and C-4), 26.62 (d,
C-3), 20.27 (q, 3-Me). MS (EI, 70 eV): m/z 266 (M+, 0.7), 161 (2),
147 (51), 105 (100), 77 (55). HRMS (EI, 70 eV): calcd for C18H18O2
266.1307, found m/z 266.1302 (M+). Anal. Calcd for C18H18O2: C,
81.17; H, 6.81. Found: C, 80.93; H, 6.96.
3-(2-Oxo-2-phenylethyl)cyclohexanone (3al). According to the
general procedure, this compound was prepared from 1a and 2l in dry
THF to give the product as a colorless liquid after chromatography
(hexane/Et2O, 1/1). Further purification was performed by distillation
under reduced pressure: bp 185 °C/2.8 × 10-2 mmHg. IR (neat): 1710,
1680 cm-1. 1H NMR (270 MHz, CDCl3): 7.95-7.92 (m, 2H, aroma),
7.60-7.40 (m, 3H, aroma), 3.04 (dd, J ) 16.1, 6.8 Hz, 1H, PhCOCHA),
2.94 (dd, J ) 16.1, 5.8 Hz, 1H, PhCOCHB), 2.6-1.4 (m, 9H, ring).
13C NMR (67.9 MHz, CDCl3): 210.62 (s, C-1), 198.38 (s, PhCO),
136.96 (s, ipso), 133.22 (d), 128.66 (d), 128.04 (d), 47.77 (t, PhCOCH2),
44.68 (t, C-2), 41.23 (t, C-6), 34.87 (d, C-3), 31.12 (t, C-4), 24.88 (t,
C-5). MS (EI, 70 eV): m/z 216 (M+, 14), 120 (56), 105 (100), 96
(33), 77 (36). HRMS (EI, 70 eV): calcd for C14H16O2 216.1150, found
m/z 216.1161 (M+). Anal. Calcd for C14H16O2: C, 77.75; H, 7.46.
Found: C, 77.58; H, 7.47.
t
t
36), 251 (M+ - Bu, 63), 209 (M+ - BuCOCH2, 34), 189 (58), 131
(100). HRMS (EI, 70 eV): calcd for C21H24O2 308.1776, found m/z
308.1772, 308.1777 (M+). Anal. Calcd for C21H24O2: C, 81.78; H, 7.84.
Found: C, 81.57; H, 7.79.
1-(2-Thienyl)-ethen-1-ol Acetate. bp 34 °C/2 mmHg. IR (neat):
1766, 1635, 1195 cm-1. 1H NMR (270 MHz, CDCl3): 7.26-7.22 (m,
1H, aroma), 7.12-7.09 (m, 1H, aroma), 6.99-6.95 (m, 1H, aroma),
5.38 (d, J ) 2.4 Hz, 1H, 2-HA), 4.94 (d, J ) 2.4 Hz, 1H, 2-HB), 2.27
(s, 3H, COMe). 13C NMR (67.9 MHz, CDCl3): 168.66 (CO), 147.65
(C-1), 138.13, 127.42, 125.77, 124.64, 101.16 (C-2), 20.82 (Me). MS
(EI, 70 eV): m/z 168 (M+, 26), 125 (M+ - OMe, 100), 109 (M+
-
OCOMe, 6), 83 (C4H3S+, 20), 43 (33). HRMS (EI, 70 eV): calcd for
C8H8O2S 168.0245, found m/z 168.0251 (M+).
Computational Method. We applied the HF/DFT hybrid method
originally proposed by Becke,27 referenced as a B3PW91 three-
parameter hybrid functional. All calculations were performed with
Gaussian 98 revision A.7.28 For basis sets, 6-31+G(d) was employed
for H, C, O, and Br atoms, and LanL2DZ was employed for Sn,
(27) Becke, A. D. J. Chem. Phys. 1993, 98, 5648-5652.
(28) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M.
A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann,
R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin,
K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi,
R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.;
Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.;
Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz,
J. V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.;
Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham,
M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.;
Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.;
Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian
98, revision A.7; Gaussian, Inc.: Pittsburgh, PA, 1998.
N,N-Dimethyl 3-(2-Oxocyclohexyl)propanamide (3ck). According
to the general procedure, this compound was prepared from 1c and 2k
in dry THF to give the product as a colorless liquid after chromatog-
raphy (Et2O). Further purification was performed by distillation under
9
J. AM. CHEM. SOC. VOL. 125, NO. 24, 2003 7299

A R T I C L E S
Yasuda et al.
respectively. All energies were calculated including the zero point
energy correction by the normal-mode analysis for each structure.
Thanks are due to Mr. H. Moriguchi, Faculty of Engineering,
Osaka University, for assistance in obtaining MS spectra.
Supporting Information Available: Listing of absolute ener-
gies and geometries for calculated species (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. We thank Dr. Hirotaka Ikeda (Ryoka
Systems Inc.) for fruitful discussions. This work was supported
by a Grant-in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science, and Technology, Japan.
JA028853+
9
7300 J. AM. CHEM. SOC. VOL. 125, NO. 24, 2003