Trimethylchlorosilane and silicon tetrachloride in two novel methodologies for the efficient and mild aldol addition of β-keto esters and malonates to aldehydes

Article abstract of DOI:10.1002/adsc.201000573

Efficient and mild aldol additions of β-keto esters and malonates to aldehydes are described using two novel protocols in the presence of silicon tetrachloride and trimethylchlorosilane, respectively. Scope and limitations of the methods have been discuss

Full text of DOI:10.1002/adsc.201000573

FULL PAPERS
DOI: 10.1002/adsc.201000573
Trimethylchlorosilane and Silicon Tetrachloride in Two Novel
Methodologies for the Efficient and Mild Aldol Addition of
b-Keto Esters and Malonates to Aldehydes
Antonio Massa,a,* Ada Roscigno,b Paolo De Caprariis,b Rosanna Filosa,b
and Antonia Di Molab
a
Dipartimento di Chimica, Universitꢀ di Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy
Fax : (+39)-089-969-603; phone: (+39)-089-969-565; e-mail: amassa@unisa.it
Dipartimento di Scienze Farmaceutiche, Universitꢀ di Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy
b
Received: July 21, 2010; Published online: December 3, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000573.
Abstract: Efficient and mild aldol additions of b- as well as the role of both silicon tetrachloride and
keto esters and malonates to aldehydes are described trimethylchlorosilane in attaining the final products
using two novel protocols in the presence of silicon have been analyzed.
tetrachloride and trimethylchlorosilane, respectively.
Scope and limitations of the methods have been dis-
cussed. Moreover the stability of the obtained prod- Keywords: aldol addition; b-keto esters; malonates;
ucts, trimethylsilyl protection of the hydroxy group, silicon tetrachloride; trimethylchlorosilane
Introduction
and aldol adducts have been observed.[8,9] For exam-
ple, in the presence of the trimethylsilyl enol ether of
The aldol addition of readily enolizable 1,3-dicarbonyl 1,3-pentanedione and without any catalysts, benzalde-
compounds, such as b-keto esters and malonates, to hyde gave the aldol adduct in 40% yield, while other
aldehydes, is very difficult to achieve even though the aldehydes failed.[9a] The reaction of p-nitrobenzalde-
products are valuable intermediates in the total syn- hyde with 2-oxocyclopentanecarboxylic acid esters
thesis of natural products.[1,2] Standard methodologies has been reported in the presence of catalytic
failed because of a retro-aldol process or a dehydra- amounts of KOH or amines to yield complicated mix-
tion reaction to yield the alkylidene compounds. tures of regioisomeric aldol adducts and condensation
However, the aldol addition of 1,3-dicarbonyl com- products.[9c] Recently, the aldol reaction of 2-oxocyclo-
pounds to formaldehyde is a well-establish reaction pentanecarboxylic ester with protected glyceralde-
for hydroxymethylation.[3–7] Aldol addition of metal hydes in the presence of LDA has been described to
enolates of malonates has been successfully achieved give a mixture of diastereomers in low yield.[9f]
with a-alkoxy aldehydes in the presence of ZnCl2.[1]
This disappointing situation points out the lack of a
Very recently Mahrwald described a catalyst-free general access to these aldol adducts. For that reason,
aldol addition of several 1,3-dicarbonyl compounds to several other synthetic methods have been used to
activated aldehydes like ethyl glyoxylate in good to isolate these products.[10–13] The common motif of
high yields.[8] Even if this can be considered the most these methodologies is the in situ trapping of the
effective procedure ever reported, aromatic aldehydes aldol adducts as O-protected compounds. This allows
were completely unreactive while inactivated aliphatic one to avoid both the retro-aldol and dehydration
aldehydes were not tested.[8]
processes. In particular b-keto esters and 2,4-dike-
In the past years several methods have been tried tones have been successfully used as nucleophiles in
but even under very mild conditions (i.e., in the pres- the addition to acetals in the presence of Lewis acids
ence of weak base or weak acid or in a mixture of to yield protected O-alkyl aldol adducts.[11] Recently
both, in proline-organocatalyzed conditions, etc.), var- Sodeoka reported the first enantioselective addition
iable mixtures of regioisomers, dehydration products of b-keto esters to allylic acetals in the presence of
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Adv. Synth. Catal. 2010, 352, 3348 – 3354

Trimethylchlorosilane and Silicon Tetrachloride in Two Novel Methodologies
chiral palladium catalyst to give again protected O- one-pot aldol addition/protection reaction of active
alkyl compounds in good yields and ees.[12] Chiral O- methylene compounds with aldehydes in the presence
protected b-hydroxymalonates have been also ob- of Me3SiCl and i-Pr2EtN.
tained in diastereoselective oxy-Michael reactions of
Thus, the development of this idea together with a
new application of SiCl4 in the aldol addition of b-
alkylidene malonates using enantiopure alkoxides.[13]
During our studies about the use of SiCl4 in aldol- keto esters are discussed in the present article.
type reactions,[14] we found that malonates are effi-
ciently added to a series of representative aromatic,
heteroaromatic and unsaturated aldehydes.[15] Even if Results and Discussion
the resulting b-hydroxymalonates were obtained in
quantitative conversion in almost all the cases, they One-Pot Aldol Addition of Malonates and b-Keto
were not stable during the standard purification on Esters in the Presence Me3SiCl and i-Pr2EtN
silica gel chromatography and even on TLC plates.
For this reason a protection reaction performed on Preliminary experiments performed on benzaldehyde
the crude product with trimethylchlorosilane was nec- in the presence of 2 equivalents of trimethylchlorosi-
essary and the aldol adducts were isolated as trime- lane and i-Pr2EtN, emphasized the importance of the
thylsilyl ethers in good to high yields (Scheme 1). In tert-butyl ester group of malonates in attaining high
this study it was demonstrated that the concomitant yields of the protected aldol 4 (Scheme 2, Table 1, en-
use of both SiCl4 and i-Pr2EtN was necessary, respec- tries 1–3). However, no substrate control of the ste-
tively, for the activation of the aldehydes and the in reoselectivity was detected. When chiral di(À)-menth-
situ generation of the active nucleophiles by reversi- yl malonate was used a diastereomeric ratio of about
ble deprotonation of malonates. It was also estab- 1/1 was observed (Table 1, entry 4).
lished that the trapping of the hydroxy group of the
Control experiments demonstrated that without the
À
aldol product by SiCl4 as OSiCl3 species is funda- concomitant use of both trimethylchlorosilane and i-
mental to avoid the undesired side-reactions. Finally Pr2EtN, the starting materials were recovered com-
these species, after aqueous NaHCO3 work-up, afford- pletely unreacted. Different reaction conditions
ed the crude free aldol product that was submitted to showed a lower reproducibility. Higher reaction tem-
the protection reaction.
peratures led to variable mixtures of silylated and
Since the success of this difficult aldol addition is free aldol adducts. Lower amounts of trimethylchloro-
reasonably related to the in situ trapping of the aldol silane (ꢀ1 equivalent) gave no reaction.
adduct, we think that it is possible to obtain directly
Then, in the optimized conditions, we were pleased
the trimethylsilyl-protected aldol product in a mild to observe that all the tested aromatic, heteroaromat-
ic, unsaturated and even enolizable aliphatic alde-
hydes gave high yields (Scheme 2, Table 2). The re-
sults of the enolizable aliphatic aldehydes are particu-
larly interesting because only the new products 4h
Scheme 2.
Table 1. One-pot aldol addition/protection reaction of malo-
nates with benzaldehyde in the presence of Me3SiCl and i-
Pr2EtN.
Entry Compound R1
Time [h] Yield of 4 [%][a]
1
2
3
4
4a
4b
4c
4d
Me
Et
t-Bu
(À)-menthyl 24
24
24
18
20
51
87
52
[a]
Scheme 1.
Yields refer to chromatographically pure compounds
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Table 2. One-pot aldol addition/protection reaction of malo-
nates with aldehydes in the presence of Me3SiCl and i-
Pr2EtN.
two inseparable diastereomers in 31% yield (Table 3,
entry 4). However, high regioselectivity was detected:
the attack of the p-nitrobenzaldehyde was observed
at the methylene group only. Higher reaction temper-
ature showed no reaction for benzaldehyde and a
mixture of starting materials, silylated and free aldol
adduct for p-nitrobenzaldehyde in similar conversion
(Table 3, cf. entries 1 and 2 with entries 4 and 5). The
reaction of the enantiopure (À)-menthyl acetoacetate
led to complex mixture of diastereomers in rather low
yield (Table 3, entry 5).
Entry Compound R
Time [h] Yield of 4 [%][a]
1
2
3
4
5
6
7
8
9
4c
4e
4f
4g
4h
4i
4j
4k
4l
Ph
18
87
70
75
80
85
90
90
92
20
4-MeOC6H4 18
4-NO2C6H4 24
PhCH=CH 24
PhCH2CH2
CH3A(CH2)8 24
2-furyl
4-ClC6H4
2-ClC6H4
5
CTHUNGTRENNUNG
18
18
24
Aldol Addition of b-Keto Esters in the Presence of
SiCl4 and i-Pr2EtN
[a]
Yields refer to chromatographically pure compounds
The disappointing results of b-keto esters compared
and 4i were obtained, while the dimerization products to malonates in the one-pot procedure, led us to ex-
derived from a possible self-aldol addition were not amine the reactivity of tert-butyl acetoacetate in the
observed (Table 2, entries 5 and 6).
presence of SiCl4 (Scheme 4, Table 4). In preliminary
However, a low yield was obtained with 2-chloro- experiments performed under the same conditions as
benzaldehyde (Table 2, entry 9). This result is proba- previously used for the addition of malonates to ben-
bly due to the failure of the in situ silylation of the zaldehyde (see Scheme 1),[15] tert-butyl acetoacetate
aldol adduct rather than the aldol addition itself. gave low conversion. A mixture 2/1 of two diastereo-
Therefore, when the aldol adduct 3l, easily prepared
in quantitative conversion according to Scheme 1, was
submitted to the silylation reaction, the product 4l
was similarly obtained in 20% yield, together with the
aldehyde and malonate for the retro-aldol reaction.
Next, we turned our attention to the reactivity of b-
keto esters under similar conditions (Scheme 3,
Table 3). Surprisingly, in the presence of tert-butyl
acetoacetate, benzaldehyde and 3-phenylpropionalde-
hyde did not react at all (Table 3, entries 1–3), while
p-nitrobenzaldehyde gave at À208C a 1/1 mixture of
Scheme 3.
Scheme 4.
Table 3. One-pot aldol addition/protection reaction of b-keto esters to aldehydes in the presence of Me3SiCl and i-Pr2EtN.
Entry
Compound
R
R1
Temperature [8C]
Yield of 6 [%][a]
dr[b]
1
2
3
4
5
6
6a
6a
6b
6c
6c
6d
Ph
Ph
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
(À)-menthyl
À20
r.t.
À20
À20
r.t.
no reaction
no reaction
no reaction
31
complex mixture
35
–
–
–
1/1
–
PhCH2CH2
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
À20
1/2/1
[a]
Yields refer to chromatographically pure compounds
Determined by H NMR analysis of crude 6.
[b]
1
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Trimethylchlorosilane and Silicon Tetrachloride in Two Novel Methodologies
Table 4. Aldol addition of b-keto esters to aldehydes in the presence of SiCl4 and i-Pr2EtN.
Entry
Compound
R
R1
DMF [equiv.]
M [mol/L]
Yield of 6 [%][a]
dr[b]
1
2
3
4
5
6
7
6a
6a
6e
6c
6a
6c
6d
Ph
Ph
Ph
t-Bu
t-Bu
Me
t-Bu
t-Bu
t-Bu
(À)-menthyl
0
0.17
0.17
0.17
0.17
1.0
20
31
15
41
45
65
30
2/1
2/1
2/1
1.5/1
2/1
0.4
0.4
0.4
0.4
0.4
0.4
4-NO2C6H4
Ph
4-NO2C6H4
4-NO2C6H4
1.0
1.0
1.5/1
1/3/1
[a]
Yields refer to chromatographically pure compounds
Determined by H NMR analysis of the crude aldol 7.
[b]
1
Table 5. aldol addition of tert-butyl acetoacetate to aldehydes in the presence of SiCl4 and i-Pr2EtN.
Entry
Compound
R
Yield of 6 [%][a]
Yield of 8 [%][a,b]
dr[c]
1
2
3
4
5
6
7
8
9
6a
6c
6f
7g
6h
6i
6j
6k
6b
Ph
45
65
–
–
5
–
2/1
4-NO2C6H4
4-CNC6H4
2-CNC6H4
4-ClC6H4
2-furyl
PhCH=CH
4-MeOC6H4
PhCH2CH2
1.5/1
1.5/1
1.3/1
1.5/1
1.5/1
–
48
26[e]
38
9
decomp.
decomp.
decomp.
no reaction
39[d]
–
–
–
–
–
[a]
Yields refer to chromatographically pure compounds
Elimination products.
[b]
[c]
[d]
[e]
1
Evaluated by H NMR analysis of the crude aldol 7.
tert-Butyl (2-furfurylidene)acetoacetate was characterized according to Ref.[18]
Yield refers to product 7g.
mers was observed, even if with high regioselectivity, gave almost a quantitative conversion even if with
for the attack at the methylene group. As observed rather low diastereoselectivity (Table 4, entry 6).
before for compounds 3 in the aldol addition of malo- Then, after the treatment with TMSCl, 6 was isolated
nates (Scheme 1),[15] attempts at purification of crude with a very interesting 65% yield for the two consecu-
product 7 led to decomposition of the aldol adduct tive steps.
and only the starting materials were isolated. There-
Enantiopure (À)-menthyl acetoacetate was not re-
fore the protection of the hydroxy group with trime- active in the presence of benzaldehyde, while with p-
thylchlorosilane was necessary but 6 was still isolated nitrobenzaldehyde it gave a complex mixture of dia-
in low yield (Table 4, entry 1). Better results were ob- stereomers in a rather low yield (Table 4, entry 7).
served when dimethylformamide (DMF) was used for Control experiments performed in the presence of
the activation of SiCl4 (Table 4, entry 2).[16] Under only SiCl4 led to complex mixtures of products and i-
these conditions, the tert-butyl ester was the most ef- Pr2EtN alone was not able to promote the reaction.
fective while methyl acetoacetate was still poorly re-
Then, in the optimized conditions the scope and the
active (Table 4, entry 3). However, in the presence of limitations of the method were analyzed in the pres-
p-nitrobenzaldehyde we observed higher conversion ence of tert-butyl acetoacetate (Table 5). In the case
for 7 and 6 was isolated in 41% yield (Table 4 of 2-furfural and aromatic aldehydes bearing, respec-
1
entry 4), pointing out that this aldehyde can be con- tively, a p-cyano, o-cyano, p-chloro group, H NMR
sidered a better model substrate.
analysis of the crude mixtures revealed very good
A further improvement was observed for both ben- conversions for the aldol 7, but with rather low diaste-
zaldehyde and p-nitrobenzaldehyde when the concen- reoselectivity (Table 5, entries 3–6), However TMS-
tration of the reaction medium increased from 0.17M protections gave variable results because of the low
to 1.0M (Table 4, entries 5–7). In particular, perform- stability of the aldol adducts 7 shown even under the
ing the reaction in the presence of the commercially used mild conditions. In particular, a,b-unsaturated
available 1M dichloromethane solution of SiCl4 only, compounds 8 were isolated after the TMSCl treat-
we were pleased to observe that p-nitrobenzaldehyde ment of crude aldol 7f and 7h because of the elimina-
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Antonio Massa et al.
FULL PAPERS
tion reaction. In this way 6f and 6h were obtained in acted with malonates in high yields to afford directly
yields comparable to that of benzaldehyde (Table 5, the silyl-protected aldol adducts. However, this one-
entry 3). Moreover in the attempt at silylation of pot procedure was less effective for b-keto esters.
aldol 7i only the elimination product and the starting
On the other hand, SiCl4 was very effective for the
materials were isolated (Table 5, entry 6). As ob- aldol addition of both b-keto esters and malonates.
served before (Table 2, entry 9), in the presence of a The resulting free aldol adducts were obtained in
cyano group in the ortho position, we were not able good to high conversions. These compounds showed
to isolate the protected aldol 6g (Table 5, entry 4). low stability during chromatography. For that reason
The chromatography of the crude mixture, gave us the trimethylsilyl protection of the hydroxy group per-
the possibility to isolate a free aldol adduct 7g even if formed on the crude aldols was necessary for the iso-
in low yield (Table 5, entry 4).[17] In this case the start- lation and the characterization of the final products.
ing materials were also isolated because of a retro-
aldol reaction occurring during the chromatography.
Since comparable methods to access of aldol ad-
ducts of malonates and b-keto esters have never been
On the other hand attempts at aldol additions to reported before for this wide range of aldehydes, fur-
cinnamaldehyde and p-methoxybenzaldehyde led to ther studies are currently under way to expand the
complex mixtures of products (Table 5, entries 7 and scope with respect to both the electrophile and active
8) and we did not perform the trimethylsilyl protec- methylene components and to develop asymmetric
tion. Moreover, as usually reported for aliphatic alde- versions of the reactions.
hydes in other SiCl4-mediated transformations,[14,15,16]
3-phenylpropionaldehyde did not react at all.
The pathway of the aldol addition of b-keto esters Experimental Section
to aldehydes in the presence of SiCl4 and i-Pr2EtN
can be considered as being similar to the addition of General Remarks
malonates, whose mechanism was previously dis-
All reactions were performed in oven-dried (1408C) or
flame-dried glassware under dry N2. Dichloromethane was
reagent grade and was dried and distilled immediately from
cussed in the introduction section.[15]
The two novel SiCl4- and Me3SiCl-based methodol-
ogies show several common features. In particular, in
both the cases, the in situ formation of the active nu-
cleophilic species can be attributed to i-Pr2EtN for
the reversible deprotonation of the methylene active
compounds. Moreover both SiCl4 and Me3SiCl led to
protected aldol adducts, a requisite to avoid the unde-
sired retro-aldol and elimination reactions. In the case
of SiCl4, the final aldol adducts are reasonably ob-
CaH2 before use. Column chromatographic purification of
products was carried out using silica gel 60 (70–230 mesh,
Merck). The reagents (Aldrich and Fluka) were used with-
out further purification. The NMR spectra were recorded
on Bruker DRX 400, 300, 250 spectrometers (400 MHz,
1
300 MHz, 250 MHz for H; 100 MHz, 75 MHz, 62.5 MHz for
13C). Spectra were referenced to residual CHCl3 (7.26 ppm,
1H, 77.23 ppm, 13C). Coupling constants J are reported in
Hz. Yields are given for isolated products showing one spot
on a TLC plate and no impurities detectable in the NMR
spectrum. Mass spectral analyses were carried out using an
electrospray spectrometer, Waters 4 micro quadrupole. Ele-
mental analyses were performed with FLASHEA 1112
series-Thermo Scientific for CHNS-O apparatus.
À
tained as OSiCl3-protected compounds. As reported
À
in the literature, the OSiCl3 group is not stable and
it can be hydrolyzed under the mild work-up condi-
tions to afford the unprotected hydroxy deriva-
tives.[14b,15,16]
However, the role of Me3SiCl in the one-pot reac-
tion is not fully clarified at the present. We presume
that Me3SiCl can also activate the carbonyl group as a
Lewis acid.[19] As another possibility, intermediate for-
mation of silyl enol ethers and silyl ketene acetals is
expected. In fact these species are reported to form
from simple ketones and esters under not very differ-
ent reaction conditions.[20]
General Procedure for One-Pot Aldol Addition–
Silylation Reaction in the Presence of Me3SiCl and i-
Pr2EtN
In a flame-dried, 2-necked, round-bottom flask, aldehyde
(0.40 mmol) was added to a solution of i-Pr2EtN (2.0 equiv.,
0.80 mmol), malonate diester (1.1 equiv., 0.44 mmol) and
Me3SiCl (2.0 equiv., 0.80 mmol) in dry dichloromethane
(2.0 mL) under nitrogen at À208C. At the end of the reac-
tion, the mixture was quenched with saturated aqueous
NaHCO3 (5 mL), extracted with 15ꢂ3 mL of CH2Cl2 and
dried over anhydrous Na2SO4. After removing the solvent
under reduced pressure, the crude oil was purified by flash
chromatography from hexane to 95/5 hexane/AcOEt mix-
ture to afford the pure products 4.
Conclusions
In this article we have described two efficient proto-
cols for the aldol addition of b-keto esters and malo-
nates to aldehydes based on the use of Me3SiCl and
SiCl4, respectively. In particular, in the presence of
Me3SiCl and i-Pr2EtN, aromatic, heteroaromatic, un-
saturated and even enolizable aliphatic aldehydes re-
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Adv. Synth. Catal. 2010, 352, 3348 – 3354

Trimethylchlorosilane and Silicon Tetrachloride in Two Novel Methodologies
Guzaev, H. LÅnnberg, Synthesis 1997, 1281–1284; f) for
General Procedure for SiCl4-Mediated Aldol
Reaction
hydroxymethylation of a-methyl-substituted acetoace-
tic ethyl ester, see: T. Akeboshi, Y. Ohtsuka, T. Sugai,
H. Ohta, Tetrahedron 1998, 54, 7387–7394; g) for iron-
catalyzed hydroxymethylation, see: C. Ogawa, S. Ko-
bayashi, Chem. Lett. 2007, 36, 56–57.
In a flame-dried, 2-necked, round-bottom flask, acetoacetate
esters (1.5 equiv., 0.60 mmol) was added to a solution of i-
Pr2EtN (2.0 equiv., 0.80 mmol), SiCl4 (1.1 equiv., 0.44 mL of
1.0M solution in CH2Cl2), DMF (0.10 mmol) and aldehyde
(0.40 mmol) under nitrogen at À208C. At the end of the re-
action, the mixture was quenched with saturated aqueous
NaHCO3 (5 mL), extracted with 15ꢂ3 mL of CH2Cl2 and
dried over anhydrous Na2SO4. After removing the solvent
under reduced pressure, the crude products 7 were analyzed
by 1H NMR and submitted to TMS protection.
[4] For aldol addition of formaldehyde to 1,3-dicarbonyl
compounds used in the total syntheses of natural prod-
ucts, see: a) Y. Tsuda, A. Ishiura, S. Takamura, S.
Hosoi, K. Isobe, K. Mohri, Chem. Pharm. Bull. 1991,
39, 2797–2802; b) T. H. Chan, A. E. Schwerdtfeger, J.
Org. Chem. 1991, 56, 3294–3298.
[5] For aldol addition of formaldehyde to activated ke-
tones: V. Lecomte, C. Bolm, Adv. Synth. Catal. 2005,
347, 1666–1672.
[6] For enantioselective aldol addition of formaldehyde in
the presence of chiral palladium complexes, see: I. Fu-
kuchi, Y. Hamashima, M. Sodeoka, Adv. Synth. Catal.
2007, 349, 509–512.
[7] For an aldol addition of aqueous formaldehyde with a
bicyclic ß-keto ester, see: S. Shirakawa, S. Shimizu,
Synlett 2007, 3160–3164.
General Procedure for Trimethyl Silyl Protection of
Crude Aldols 7
Diisopropylethylamine (2.0 equiv., 0.8 mmol) and trimethyl-
silyl chloride (2.0 equiv., 0.8 mmol) were added to a solution
of the crude product 3 in dry dichloromethane (3.0 mL) at
À208C under nitrogen. At the end of the reaction, the mix-
ture was quenched with saturated aqueous NaHCO3 (5 mL),
extracted with 15ꢂ3 mL of CH2Cl2 and dried over anhy-
drous Na2SO4. After removing the solvent under reduced
pressure, the crude oil was purified by flash chromatography
from hexane to 95/5 hexane/AcOEt mixture to afford the
pure products 6.
[8] K. Rohra, R. Mahrwald, Adv. Synth. Catal. 2008, 350,
2877–2880.
[9] a) L. Birkofer, A. Ritter, H. Vernaleken, Chem. Ber.
1966, 99, 2518–2520; b) B. D. Wilson, J. Org. Chem.
1963, 28, 314–320; c) H. Hellmann, D. Dieterich, Justus
Liebigs Ann. Chem. 1962, 656, 89–96; d) R. Mayer, B.
Gebhardt, Chem. Ber. 1960, 93, 1212–1219; e) W.
Schroth, W. Treibs, Justus Liebigs Ann. Chem. 1961,
639, 214–228; f) W. Chen, B. M. Pinto, Carbohydr. Res.
2007, 342, 2163–2172.
All the compounds 6 are new. For their spectroscopic data
see supporting information.
Supporting Information
Spectroscopic data of the new compounds 4d, 4g, 4h and 6
are reported in the Supporting Information. For all the
other compounds see Ref.[15]
[10] P. Camps, J. M. Drudis, Tetrahedron Lett. 1978, 2597–
2598.
[11] R. Antonioletti, F. Bonadies, A. Scettri, J. Org. Chem.
1988, 53, 5540–5542.
[12] N. Umebayashi, Y. Hamashima, D. Hashizume, M. So-
deoka, Angew. Chem. 2008, 120, 4264–4267; Angew.
Chem. Int. Ed. 2008, 47, 4196–4199.
References
[1] a) For aldol additions of malonates in total synthesis of
epolactaene, see: S. Marumoto, H. Kogen, S. Naruto, J.
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FULL PAPERS
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ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 3348 – 3354