Zinc(II) oxide: an efficient catalyst for selective transesterification of β-ketoesters

Article abstract of DOI:10.1016/j.tet.2008.07.034

A facile and selective transesterification of β-ketoesters using zinc(II) oxide as catalyst is described. The emphasis has been placed on the reaction of methyl 3-(3,4-dimethoxyphenyl)-3-oxopropanoate with a series of alcohols of different structures, lea

Full text of DOI:10.1016/j.tet.2008.07.034

Tetrahedron 64 (2008) 9258–9263
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Zinc(II) oxide: an efficient catalyst for selective transesterification of b-ketoesters
`
*
Alex Pericas, Alexandr Shafir, Adelina Vallribera
Department of Chemistry, Universitat Auto`noma de Barcelona, 08193 Cerdanyola, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 May 2008
Received in revised form 10 July 2008
Accepted 10 July 2008
Available online 16 July 2008
A facile and selective transesterification of b-ketoesters using zinc(II) oxide as catalyst is described. The
emphasis has been placed on the reaction of methyl 3-(3,4-dimethoxyphenyl)-3-oxopropanoate with
a series of alcohols of different structures, leading in all cases good to excellent yields.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
During our work on the synthesis of biologically active com-
pounds one of the steps required preparation of a series of analogs of
b
-Ketoesters are some of the most important building blocks in
3-(3,4-dimethoxyphenyl)-3-oxopropanoate, 1, varying only the al-
cohol part of the ester group. We, therefore, needed to identify an
efficient protocol for the transesterification of 1 that would be suit-
able for a wide range of alcohols. Preliminary experiments were
carried out using a catalytic amount of Zn dust19a in refluxing toluene
and only moderate reaction yields were obtained (3f (52%) and 5f
(56%)). After some experimentation, we found that this reaction
couldbeefficientlymediatedbycatalyticamountsofZnO(Scheme1).
organic synthesis. The reactivityof this class of compoundsallowsfor
their rapid elaboration into more complex molecular structures. A
key factor in the chemistry of b-ketoesters is their ability to serve as
both nucleophilic and an electrophilic reagents. Our group in par-
ticular has dedicated a considerable effort to the study of the nu-
cleophilic reactions of these substrates at the intercarbonylic
position.1 Thus, we have described diastereoselective alkylation
of chiral derivatives of different acetoacetic acids and their
transformation to enantiomerically pure 4,4-disubstituted 2-pyr-
O
O
O
O
azolin-5-ones2 and to the synthesis of quaternary -amino acids.3
a
ZnO (cat)
Moreover, we demonstrated that Ni(salicylaldehydate)2,4 Cu(5-tert-
butylsalicylaldehydate)2,5 tributylphosphine,6 and Eu-containing
organic gels7 are effective catalysts forconjugate additions, with high
OCH3
OR
ROH
+
toluene, Δ
- CH3OH
H3CO
H3CO
1
2
3
OCH3
OCH3
enantioselectivities obtained in Michael additions of cyclic
b-
ketoestersin the presence of lanthanum triflates and (S,S)-ip-pybox.8
Scheme 1. Synthesis of
b-ketoester derivatives via transesterification of 1.
A classic method for the preparation of
b-ketoesters is the
reaction of diketene with alcohols.9 In 1995, we demonstrated that
2,2,6-trimethyl-4H-1,3-dioxin-4-one (diketene acetone adduct) is
a superior alternative to the use of diketone.10 However, for the
2. Results and discussion
In order to establish the efficacy of ZnO as a catalyst, we in-
vestigated the transesterification of methyl 3-(3,4-dimethoxy-
phenyl)-3-oxopropanoate, 1, using a range of alcohols in the
presence of 20% ZnO in refluxing toluene. As can be seen in Table 1,
smooth transesterification of 1 took place with a variety of alcohols,
preparation of structurally general b-ketoesters acylation of Mel-
drum’s acid and subsequent reactionwith alcohols should be used.11
Transesterification reaction represents the electrophilic facet of
the reactivity of
b-ketoesters. Most of the methods of trans-
esterification are equilibrium driven reactions where the excess of
one of the reactants is required to achieve good yields. This equi-
librium process can be catalyzed by a wide range of catalysts,
including the recently described catalysis by zeolites12 and natural
clays,13 Mg-Al-hydrotalcites-like anionic clays,14 montmorillonite
K-10,15 Nb2O5,16 polyaniline salts,17 B2O3/ZrO2,18 Zn,19 NH2SO3H/
[C3MIm]Cl.20
affording
b-ketoester products 3a–j in good to excellent yields.
With the exception of entries 2 and 5, all reactions were carried out
in 24 h or less. Results were particularly good in the case of primary
(entry 1) and secondary (entries 2–4) alcohols, with the reaction
reaching completion in as little as 1–6 h. Interestingly, the longest
reaction time, 48 h, was required for the transesterification of 1
with isopropanol, the most volatile of series (entry 2). A likely ex-
planation for this phenomenon is the lower concentration of the
volatile alcohols in solution. The trend seems to hold true for ter-
tiary alcohols, with the yield varying according to the boiling point.
* Corresponding author. Tel.: þ34 935813045; fax: þ34 935811265.
E-mail address: adelina.vallribera@uab.es (A. Vallribera).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.07.034

`
A. Pericas et al. / Tetrahedron 64 (2008) 9258–9263
9259
Table 1
Transesterification of b
-ketoesters catalyzed by ZnOa
Entry
b-Ketoester
Alcohol
Product
Product number
Time (h)
Yieldb (%)
O
O
O
O
CH3
HO
2a
O
O
1
3a
5
93
H3CO
H3CO
1
OCH3
OCH3
O
O
O
2
3
4
1
3b
3c
3d
48
93
99
96
HO
H3CO
2b
OCH3
O
O
O
O
O
1
1
6
HO
HO
H3CO
2c
OCH3
O
1
H3CO
H3CO
H3CO
H3CO
2d
OCH3
O
O
O
5
6
7
1
1
1
3e
3f
72
24
2
62
87c
82
HO
2e
OCH3
O
O
O
HO
HO
2f
OCH3
O
O
O
3g
2g
OCH3
O
O
O
HO
HO
8
9
1
1
3h
3i
3.5
90
81
2h
H3CO
H3CO
OCH3
O
O
O
O
O
5
2i
OCH3
O
10
1
3j
1
99 (92)d
HO
2j
H3CO
OCH3
O
O
O
O
11
12
2c
2f
5c
5f
2
5
98
83
O
CH3
O
4
O
O
4
O
(continued on next page)

`
A. Pericas et al. / Tetrahedron 64 (2008) 9258–9263
9260
Table 1 (continued )
Entry
b
-Ketoester
Alcohol
Product
Product number
Time (h)
24
Yieldb (%)
O
O
O
O
CH3
13
2d
2d
7d
de
O
O
6
Br
Br
14
9d
24
de
O
CH3
O
H3C
H3C
8
O
O
a
Reaction conducted using 10 equiv of ROH and 20% ZnO in toluene at reflux.
Yields correspond to the isolated product.
Using 1.3 equiv of ROH.
Using 1.5 equiv of menthol.
No reaction took place.
b
c
d
e
O
O
O
Thus, while a moderate 62% yield was achieved for tert-butanol
(bp¼83 ꢀC) after 72 h (3e, entry 5), the less volatile 1-adamantanol
(sublimes at >200 ꢀC) afforded 87% of the transesterification
product 3f (entry 6) after just 24 h. As demonstrated in entries 7–9,
the protocol was not limited to the regular aliphatic alcohols, and
gave good yields even with the less nucleophilic benzylic, allylic,
and propargylic alcohols. It should be noted that the resulting allyl
and propargylic esters can be difficult to prepare as they readily
undergo the Carroll rearrangement (successive decarboxylation
and rearrangement) to give unsaturated ketones.21
O
O
O
EtO
OEt
O
ZnO (cat)
10
OH
EtO
O
toluene, Δ
- EtOH
+
11
O
O
Ha
Cb
HMBC
cross-correlation
O
EtO
Hc
Menthol, a chiral sterically hindered secondary alcohol, un-
derwent transesterification giving the desired 3j in a 99% yield
(entry 10). While 10 equiv of menthol was used to assure complete
conversion, the reaction was shown to take place even with
1.5 equiv of the alcohol, leading to yields only slightly inferior to
those with 10 equiv. The protocol, therefore, should be suitable
even for cases where the use of a large excess of the alcohol is
undesirable due to the high price of this reagent.
It should be noted that while this work focused mainly on the
synthesis of derivatives of 1, the method is applicable to the trans-
esterification of other b-ketoesters. Some examples include the syn-
thesis of cyclic derivatives, where products 5c and 5f (entries 11 and
12)were obtained in98 and 83% yield, respectively (entries 11 and 12).
It is important to mention that the reaction appears to be spe-
Scheme 2. Selective transesterification of substrate 10 and summary of the results of
the HMBC spectrum of product 11.
3. Experimental section
3.1. General comments
All solvents were dried by standard methods. For 1H and 13C
NMR spectra the deuterated solvents indicated were used. For
preparative scale chromatography, silica gel (60–200 mesh) was
used. Melting points are uncorrected.
3.1.1. Methyl 3-(3,4-dimethoxyphenyl)-3-oxopropanoate (1)
cific for the transesterification of
b
-ketoesters. Other ester de-
The preparation of b-diketone 1 was adapted from a procedure
rivatives, such as -ketoesters as well as normal esters failed to
a
reported by Morrison.22 To a 250 mL round-bottom flask containing
dimethyl carbonate (7.0 mL, 83 mmol), NaH (2.23 g, 55.8 mmol, 60%
suspension in Nujol) and THF (50 mL) was added dropwise a solution
of 3,4-dimethoxyacetophenone (5.00 g, 27.8 mmol) in THF (40 mL).
The reaction mixture was heated to reflux for 5 h, at which point TLC
showed complete consumption of the starting ketone. The contents
of the flask were poured into water, the pH adjusted to 9, and the
mixturewasextracted withCH2Cl2. The organicphasewas dried with
anhydrous Na2SO4 and the solvent was removed. The resulting crude
product was purified bycolumn chromatographyon silica gel, eluting
with hexane/ethyl acetate (5:1) mixture, giving 6.40 g of awhite solid
identified as 1 (26.9 mmol, 97%). Rf (2:1 hexane/ethyl acetate)¼0.46.
1H NMR (CDCl3, 360 MHz): keto (95%)–enol(5%), 3.67 (s, 2.85H, OCO–
CH3), 3.70 (s, enol, 0.15H, OCO–CH3), 3.89 (s, 3H, OCH3), 3.91 (s, 3H,
OCH3), 3.93 (s, 1.90H, CO–CH2), 5.56 (s, enol, 0.05H, C]CH), 6.85 (d,
J¼8.5 Hz, enol, 0.05H, Haromatic), 6.86 (d, J¼8.3 Hz, 0.95H, Haromatic),
7.35 (dd, J¼2.1, 8.5 Hz, enol, 0.05H, Haromatic), 7.48 (d, J¼2.1 Hz, 0.95H,
Haromatic), 7.51 (dd, J¼2.1, 8.3 Hz, 0.95H, Haromatic),12.54 (s, enol, 0.05H,
OH). 13C NMR (CDCl3, 90 MHz): 45.6 (CO–CH2), 51.6 (enol, OCO–CH3),
52.7 (OCO–CH3), 56.2 (OCH3), 56.3 (OCH3), 56.5 (enol, OCH3), 56.6
(enol, OCH3), 85.9 (enol, C]CH),109.0 (enol, Caromatic),110.3 (Caromatic),
110.5 (Caromatic), 110.9 (enol, Caromatic), 119.8 (enol, Caromatic), 123.8
(Caromatic), 126.1 (enol, Caromatic), 129.4 (Caromatic), 149.4 (Caromatic),
undergo the reaction (entries 13 and 14). This difference in re-
activity offered the possibility to perform the transesterification in
a chemoselective fashion. This was demonstrated using substrate
10 that contains both a
b-ketoester and an isolated ethyl ester
groups. Indeed, submitting 10 to the reaction in the presence of ZnO
and a large excess of 2,4-dimethylpentan-3-ol resulted in the for-
mation of the singly-substituted product 11 in 92% yield (Scheme
2). The chemoselectivity of the reaction was established un-
equivocally by obtaining a two-dimensional HMBC NMR spectrum
of 11. Based on the presence of cross-peaks between the 13C reso-
nance of carbonyl Cb (167 ppm) and the 1H resonances of both the
methine Ha (4.59 ppm) and the intercarbonylic Hb (3.44 ppm), it
was confirmed that the substitution took place selectively at the
dicarbonyl moiety.
b-
In summary, we report a new and highly efficient procedure for
the transesterification of -ketoesters using ZnO as catalyst with
b
several kinds of alcohols leading good to excellent yields. The
advantages of the catalyst are its easy and simple operation in the
workup, its selectivity, its generality, and its lower cost of acqui-
sition. We believe that this will present a better and more eco-
nomical alternative to the existing methodologies and will find
widespread application in industries as well as in organic
synthesis.
154.1 (Caromatic), 168.4 (O–C]O),191.1 (C]O). IR (ATR, n
cmꢁ1): 3068

`
A. Pericas et al. / Tetrahedron 64 (2008) 9258–9263
9261
(ArC–Hst), 2980(C–Hst), 2949(C–Hst),2839(C–Hst),1732(C]Ost),
1667 (C]O st),1583 (ArC–C),1510 (ArC–C),1419 (CH3 d as.),1256 (C–
O–C st as), 1243 (C–O–C st as), 1146 (C–O–C st as), 1018 (C–O–C st as).
(CDCl3, 360 MHz)
d
: keto (94%)–enol (6%), 0.83 (t, J¼7.5 Hz, 5.64H,
CH2CH3), 0.91 (t, J¼7.5 Hz, 0.36H, enol, CH2CH3), 1.50–1.58 (m,
3.76H, CH2CH3),1.59–1.64 (m, 0.24H, enol, CH2CH3), 3.91 (s, 2H, CO–
CH2), 3.92 (d, J¼7.6 Hz, 6H, OCH3), 4.80 (quint, J¼6.6 Hz, 0.94H,
OCHCH2), 4.88 (quint, J¼6.5 Hz, 0.06H, enol, OCHCH2), 5.58 (s,
0.06H, enol, C]CH), 6.87 (d, J¼8.3 Hz, 1H, Haromatic), 7.29 (d,
J¼2.4 Hz, 0.06H, enol, Haromatic), 7.39 (dd, J¼8.5, 2.0 Hz, 0.06H, enol,
Haromatic), 7.52–7.56 (m, 1.88H, Haromatic), 12.74 (s, 0.06H, enol, OH).
3.1.2. General procedure for the transesterification process:
preparation of isobutyl 3-(3,4-dimethoxyphenyl)-3-
oxopropanoate (3a)
Around-bottomflaskwaschargedwith3-(3,4-dimethoxyphenyl)-
3-oxopropanoate
1
(2.00 g, 8.39 mmol), 2-methylpropan-1-ol
13C NMR (CDCl3, 90 MHz)
d: 9.8 (CH2CH3), 10.0 (enol, CH2CH3), 26.6
(7.75 mL, 83 mmol), ZnO (0.136 g, 1.67 mmol) and 10 mL of toluene.
The flask was fitted with a short-path distillation head and heated,
distillingthe methanolformed duringthereaction. After 5 htheTLCof
the reaction mixture showed complete consumption of the
(CH2CH3), 26.9 (enol, CH2CH3), 46.4 (CO–CH2), 56.3 (OCH3), 56.4
(OCH3), 78.4 (CO–CH2), 86.6 (enol, C]CH), 109.0 (enol, CHaromatic),
110.34 (CHaromatic), 110.6 (CHaromatic), 123.8 (CHaromatic), 129.7
(CHaromatic), 149.5 (Caromatic), 154.0 (Caromatic), 167.9 (O–C]O), 191.5
b-ketoester. The reaction mixture was filtered through a plug of Celite
(C]O). IR (ATR,
st), 2878 (C–H st), 2839 (C–H st), 1729 (C]O st), 1673 (C]O st),
1585 (ArC–C), 1513 (ArC–C), 1417 (CH3 as.), 1317 (C–O–C st as),
n
cmꢁ1): 3080 (ArC–H st), 2967 (C–H st), 2936 (C–H
to remove the catalyst. The filtrate was concentrated under reduced
pressure and the crude residue was purified by column chromato-
graphy on silica gel, eluting with a mixture of n-hexane/ethyl acetate
(3:1), affording 2.29 g (93%) of the product as colorless oil. Rf (2:1
d
1255 (C–O–C st as), 1148 (C–O–C st as), 1130 (C–O–C st as), 1020 (C–
O–C st). Anal. Calcd for C16H22O5: C, 65.29; H, 7.53. Found: C, 65.39;
H, 7.73.
hexane/ethyl acetate)¼0.53. 1H NMR (CDCl3, 360 MHz)
d: keto (94%)–
enol (6%), 0.86 (d, J¼6.8 Hz, 5.64H, CHCH3), 0.96 (d, J¼6.8 Hz, 0.36H,
enol, CHCH3), 1.90 (sept, J¼6.6 Hz, 1H, CHCH3), 3.90 (d, J¼6.6 Hz, 2H,
OCHCH), 3.91 (s, 3H, OCH3), 3.93 (s, 3H, OCH3), 3.94 (s, 2H, CO–CH2),
5.59 (s, 0.06H, enol, C]CH), 6.88 (d, J¼8.1 Hz, 1H, Haromatic), 7.29 (d,
J¼2.4 Hz, 0.06H, enol, Haromatic), 7.39 (dd, J¼8.2, 2.4 Hz, 0.06H, enol,
3.1.5. 2,4-Dimethylpentan-3-yl 3-(3,4-dimethoxyphenyl)-3-
oxopropanoate (3d)
Following the general procedure,
b-ketoester 1 (1.00 g,
4.19 mmol) was allowed to react with 2,4-dimethylpentan-3-ol
(5.88 mL, 41.9 mmol, 10 equiv) in the presence of ZnO (0.07 g,
0.84 mmol, 20 mol %) and 5 mL of toluene for 1 h. Column chro-
matography: silica gel, hexane/ethyl acetate (4:1). Rf (2:1 hexane/
ethyl acetate)¼0.6. Colorless oil; yield: 1.32 g (4.09 mmol, 96%). 1H
Haromatic), 7.51–7.55 (m, 1.88H, Haromatic),12.71 (s, 0.06H, enol, OH). 13
C
NMR (CDCl3, 90 MHz) d: 19.2 (CHCH3), 19.4 (enol, CHCH3), 27.2
(CHCH3), 46.0 (CO–CH2), 56.3(OCH3), 56.4(OCH3), 70.3 (enol, OCHCH),
71.8 (OCHCH), 86.2 (enol, C]CH), 110.3 (CHaromatic), 110.7 (CHaromatic),
111.0 (enol, CHaromatic), 123.8 (CHaromatic), 129.6 (CHaromatic), 149.5
(Caromatic), 154.1 (Caromatic), 168.0 (O–C]O), 191.3 (C]O). IR (ATR,
NMR (CDCl3, 360 MHz)
d
: keto (94%)–enol (6%), 0.81 (d, J¼6.7 Hz,
5.64H, CHCH3), 0.84 (d, J¼6.7 Hz, 5.64H, CHCH3), 0.90 (d, J¼3.8 Hz,
0.36H, enol, CHCH3), 0.91 (d, J¼3.8 Hz, 0.36H, enol, CHCH3), 1.86
(oct, J¼6.5 Hz, 1.88H, CHCH3), 1.91–1.99 (m, 0.12H, enol, CHCH3),
3.92 (s, 3H, OCH3), 3.94 (s, 3H, OCH3), 3.97 (s, 1.94H, CO–CH2), 4.62
(t, J¼6.1 Hz, 1.94H, CHCH), 4.71 (t, J¼6.2 Hz, 0.06H, enol, CHCH),
5.60 (s, 0.06H, enol, C]CH), 6.88 (d, J¼8.5 Hz, 1H, Haromatic), 7.30 (d,
J¼2.1 Hz, 0.06H, enol, Haromatic), 7.41 (dd, J¼8.5, 2.0 Hz, 0.06H, enol,
Haromatic), 7.53 (d, J¼2.1 Hz, 0.94H, Haromatic), 7.57 (dd, J¼8.5, 2.0 Hz,
0.94H, Haromatic), 12.76 (s, 0.06H, enol, OH). 13C NMR (CDCl3,
n
cmꢁ1):2959 (C–H st), 2874 (C–H st), 2839 (C–H st), 1733 (C]O st),
1673 (C]O st), 1584 (ArC–C), 1513 (ArC–C), 1417 (CH3 d as.), 1256 (C–
O–C st as),1147 (C–O–C st as),1103 (C–O–C st as),1019 (C–O–C st sim).
Anal. Calcd for C15H20O5: C, 64.27; H, 7.19. Found: C, 64.37; H, 7.29.
3.1.3. Isopropyl 3-(3,4-dimethoxyphenyl)-3-oxopropanoate (3b)
Following the general procedure,
b-ketoester 1 (10.19 g,
42.7 mmol) was allowed to react with isopropanol (77 mL,
427 mmol, 10 equiv) in the presence of ZnO (0.69 g, 8.55 mmol,
20 mol %) and 10 mL of toluene for 48 h. Column chromatography:
silica gel, hexane/ethyl acetate (3:1). Rf (2:1 hexane/ethyl
acetate)¼0.53. Colorless oil; yield: 10.59 g (39.8 mmol, 93%). 1H
90 MHz) d: 17.4 (CHCH3), 17.5 (enol, CHCH3), 19.8 (CHCH3), 19.9
(enol, CHCH3), 29.7 (CHCH3), 29.8 (enol, CHCH3), 46.2 (CO–CH2),
56.3 (OCH3), 56.4 (OCH3), 82.8 (enol, CO–CH2), 85.0 (CO–CH2), 86.3
(enol, C]CH), 110.4 (CHaromatic), 110.7 (CHaromatic), 120.0 enol
(CHaromatic), 124.0 (CHaromatic), 130.0 (CHaromatic), 149.5 (Caromatic),
NMR (CDCl3, 360 MHz)
d
: keto (94%)–enol (6%), 1.21 (d, J¼6.12 Hz,
5.64H, CHCH3), 1.28 (d, J¼6.1 Hz, 0.36H, enol, CHCH3), 3.89 (s, 1.88H,
CO–CH2), 3.91 (d, J¼7.6 Hz, 6H, OCH3), 5.04 (sept, J¼6.5 Hz, 0.94H,
OCHCH3), 5.13 (m, 0.06H, enol, OCHCH3), 5.54 (s, 0.06H, enol,
C]CH), 6.87 (d, J¼8.2 Hz, 1H, Haromatic), 7.29 (d, J¼2.4 Hz, 0.06H,
enol, Haromatic), 7.37 (dd, J¼8.2, 1.8 Hz, 0.06H, enol, Haromatic), 7.50–
7.54 (m, 1.88H, Haromatic), 12.71 (s, 0.06H, enol, OH). 13C NMR (CDCl3,
154.1 (Caromatic), 168.0 (O–C]O), 191.4 (C]O). IR (ATR, n
cmꢁ1):
3082 (ArC–H st), 2963 (C–H st), 2935 (C–H st), 2839 (C–H st), 1729
(C]O st), 1674 (C]O st), 1585 (ArC–C), 1513 (ArC–C), 1417 (CH3
d
as.),1322 (CH3 d as.),1255 (CH3 d as.),1128 (CH3 d as.),1021 (CH3 d).
Anal. Calcd for C18H26O5: C, 67.06; H, 8.13. Found: C, 67.02; H, 8.43.
90 MHz)
d: 22.3 (CHCH3), 22.6 (enol, CHCH3), 46.7 (CH2), 56.6
3.1.6. tert-Butyl 3-(3,4-dimethoxyphenyl)-3-oxopropanoate (3e)
(OCH3), 56.7 (OCH3), 68.2 (enol, CHCH3), 69.6 (CHCH3), 87.1 (enol,
C]CH), 109.3 (enol, CHaromatic), 110.6 (CHaromatic), 110.9 (CHaromatic),
111.3 (enol, CHaromatic), 120.1 (enol, CHaromatic), 124.1 (CHaromatic),
129.9 (CHaromatic), 149.8 (Caromatic), 154.4 (Caromatic), 167.9 (O–C]O),
Following the general procedure, b-ketoester 1 (2.00 g,
8.39 mmol) was allowed to react with tert-butanol (8 mL, 83 mmol,
10 equiv) in the presence of ZnO (0.14 g, 1.67 mmol, 20 mol %) and
5 mL of toluene for 72 h. Column chromatography: silica gel, hex-
ane/ethyl acetate (3:1). Rf (2:1 hexane/ethyl acetate)¼0.57. Color-
191.8 (C]O). IR (ATR,
(C–H st), 2839 (C–H st),1730 (C]O st),1672 (C]O st),1584 (ArC–C),
1513 (ArC–C), 1417 (CH3 as.), 1256 (C–O–C st as), 1145 (C–O–C st
n
cmꢁ1): 3081 (ArC–H st), 2979 (C–H st), 2936
less oil; yield: 1.45 g (5.2 mmol, 62%). 1H NMR (CDCl3, 360 MHz)
d:
d
keto (94%)–enol (6%), 1.41 (s, 8.46H, CCH3), 1.51 (s, 0.54H, enol,
CCH3), 3.83 (s, 1.88H, CO–CH2), 3.90 (s, 3H, OCH3), 3.92 (s, 3H,
OCH3), 5.48 (s, 0.06H, enol, C]CH), 6.87 (d, J¼8.3 Hz, 1H, Haromatic),
7.30 (d, J¼2.4 Hz, 0.06H, enol, Haromatic), 7.35 (dd, J¼8.4, 2.3 Hz,
0.06H, enol, Haromatic), 7.50–7.53 (m, 1.88H, Haromatic), 12.71 (s,
as), 1103 (C–O–C st as), 1019 (C–O–C st).
3.1.4. Pentan-3-yl 3-(3,4-dimethoxyphenyl)-3-oxopropanoate (3c)
Following the general procedure,
b-ketoester 1 (4.21 g,
17.7 mmol) was allowed to react with 3-pentanol (20 mL,
177 mmol, 10 equiv) in the presence of ZnO (0.27 g, 3.35 mmol,
19 mol %) and 5 mL of toluene for 6 h. Column chromatography:
silica gel, hexane/ethyl acetate (3:1). Rf (2:1 hexane/ethyl
acetate)¼0.56. Colorless oil; yield: 5.14 g (17.4 mmol, 99%). 1H NMR
0.06H, enol, OH). 13C NMR (CDCl3, 90 MHz)
d: 28.2 (CCH3), 28.7
(enol, CCH3), 47.4 (CO–CH2), 56.2 (OCH3), 56.4 (OCH3), 81.3 (enol,
OCCH3), 82.2 (OCCH3), 87.8 (enol, C]CH), 108.9 (enol, CHaromatic),
110.3 (CHaromatic), 110.6 (CHaromatic), 110.9 (enol, CHaromatic), 119.6
(enol, CHaromatic), 123.7 (CHaromatic), 129.8 (CHaromatic), 149.4

`
A. Pericas et al. / Tetrahedron 64 (2008) 9258–9263
9262
(Caromatic), 153.9 (Caromatic), 167.2 (O–C]O), 191.8 (C]O). IR (ATR,
cmꢁ1): 2974 (C–H st), 2935 (C–H st), 2839 (C–H st), 1728 (C]O st),
1673 (C]O st), 1584 (ArC–C), 1513 (ArC–C), 1417 (CH3 as.), 1256
n
CH2CH]CH2), 6.88 (d, J¼8.4 Hz, 1H, Haromatic), 7.28 (d, J¼8.4 Hz,
0.08H, enol, Haromatic), 7.39 (dd, J¼8.4, 2.3 Hz, 0.07H, enol, Haromatic),
7.51–7.54 (m, 1.88H, Haromatic), 12.54 (s, 0.06H, enol, OH). 13C NMR
d
(C–O–C st as), 1129 (C–O–C st as), 1020 (C–O–C st sim). Anal. Calcd
for C15H20O5: C, 64.27; H, 7.19. Found: C, 64.62; H, 7.21.
(CDCl3, 90 MHz) d: 45.8 (CO–CH2), 56.2 (OCH3), 56.4 (OCH3), 65.1
(enol, COCH2CH), 86.0 (enol, C]CH), 110.3 (CHaromatic), 110.5
(CHaromatic), 111.0 (enol, CHaromatic), 118.7 (enol, CH]CH2), 118.9
(CH]CH2), 123.7 (CHaromatic), 129.5 (CHaromatic), 131.9 (CH]CH2),
149.5 (Caromatic), 154.1 (Caromatic), 167.7 (O–C]O), 191.1 (C]O). IR
3.1.7. Adamantyl 3-(3,4-dimethoxyphenyl)-3-oxopropanoate (3f)
Following the general procedure,
b-ketoester 1 (18.9 g,
79.5 mmol) was allowed to react with 1-adamantanol (15.81 g,
103.7 mmol, 1.3 equiv) in the presence of ZnO (1.34 g, 16.6 mmol,
21 mol %) and 200 mL of toluene for 24 h. Column chromatography:
silica gel, hexane/ethyl acetate (3:1). Rf (2:1 hexane/ethyl
acetate)¼0.58. Colorless oil, solidified to a white solid after 2 days
under vacuum; yield: 24.7 g (68.9 mmol, 87%). Mp: 84–85 ꢀC. 1H
(ATR,
(C]O st), 1671 (C]O st), 1584 (ArC–C), 1513 (ArC–C), 1417 (CH3
as.), 1256 (C–O–C st as), 1130 (C–O–C st as), 1019 (C–O–C st sim).
n
cmꢁ1): 3081 (]CH2 st), 2936 (C–H st), 2839 (C–H st), 1736
d
Anal. Calcd for C14H16O5: C, 63.63; H, 6.10. Found: C, 63.55; H, 6.10.
3.1.10. Prop-2-ynyl 3-(3,4-dimethoxyphenyl)-3-oxopropanoate (3i)
NMR (CDCl3, 360 MHz)
d
: keto (96%)–enol (4%), 1.62 (s, 6H,
Following the general procedure, b-ketoester 1 (1.50 g,
CH2CHCH2ada), 2.07 (d, J¼2.9 Hz, 6H, CH2CHCH2ada), 2.13 (s, 3H,
CH2CHCH2ada), 2.18 (s, 0.36H, enol, CH2CHCH2ada), 3.84 (s, 1.92H,
CO–CH2), 3.92 (s, 3H, OCH3), 3.94 (s, 3H, OCH3), 5.49 (s, enol, 0.04H,
C]CH), 6.88 (d, J¼8.3 Hz, 1H, Haromatic), 7.30 (d, J¼2.1 Hz, enol,
0.04H, Haromatic), 7.37 (dd, J¼2.1, 8.5 Hz, enol, 0.04H, Haromatic), 7.51–
7.55 (m, 1.92H, Haromatic), 12.54 (s, 0.04H, enol, OH). 13C NMR (CDCl3,
6.3 mmol) was allowed to react with propargylic alcohol (83.66 mL,
63 mmol, 10 equiv) in the presence of ZnO (0.100 g, 1.26 mmol,
20 mol %) and 10 mL of toluene for 5 h. Column chromatography:
silica gel, hexane/ethyl acetate (2:1). Rf (2:1 hexane/ethyl
acetate)¼0.52. Light-yellow oil; yield: 1.33 g (5.1 mmol, 81%). 1H
NMR (CDCl3, 360 MHz)
d
: keto (92%)–enol (8%), 2.48 (t, J¼2.5 Hz,
90 MHz)
d: 31.1 (enol, CH2CHCH2ada), 31.2 (CH2CHCH2ada), 36.4
0.92H, C^CH), 2.51 (t, J¼2.5 Hz, 0.08H, enol, C^CH), 3.92 (s, 3H,
OCH3), 3.94 (s, 3H, OCH3), 4.01 (s, 1.84H, CO–CH2), 4.74 (d, J¼2.6 Hz,
1.84H, COCH2C^CH), 4.80 (d, J¼2.6 Hz, 0.16H, enol, COCH2C^CH),
5.64 (s, 0.08H, enol, C]CH), 6.88 (d, J¼8.4 Hz, 1H, Haromatic), 7.28 (d,
J¼8.4 Hz, 0.08H, enol, Haromatic), 7.39 (dd, J¼8.4, 2.3 Hz, 0.08H, enol,
Haromatic), 7.50–7.53 (m, 1.84H, Haromatic), 12.55 (s, 0.08H, enol, OH).
(CH2CHCH2ada), 36.5 (enol, CH2CHCH2ada), 41.4 (CH2CHCH2ada),
41.9 (enol, CH2CHCH2ada), 47.6 (COCH2COOR), 56.3 (OCH3), 56.4
(OCH3), 65.1 (enol, COCH2CH), 81.3 (enol, OCCH3), 82.3 (OC(CH2)3),
87.9 (enol, C]CH), 110.3 (CHaromatic), 110.6 (CHaromatic), 111.0 (enol,
CHaromatic), 123.8 (CHaromatic), 129.8 (CHaromatic), 149.4 (Caromatic),
153.9 (Caromatic), 166.9 (O–C]O), 191.8 (C]O). IR (ATR,
n
cmꢁ1):
13C NMR (CDCl3, 90 MHz)
d: 45.6 (CO–CH2), 53.1 (COCH2C^CH),
2908 (C–H st), 2850 (C–H st), 1728 (C]O st), 1673 (C]O st), 1585
(ArC–C), 1514 (ArC–C), 1254 (C–O–C st as), 1147 (C–O–C st as), 1053
(C–O–C st as), 1021 (C–O–C st as).
56.3 (OCH3), 56.5 (OCH3), 75.4 (COCH2C^CH), 77.4 (COCH2C^CH),
86.5 (enol, C]CH), 109.1 (enol, CHaromatic), 110.3 (CHaromatic), 110.5
(CHaromatic), 111.0 (enol, CHaromatic), 120.0 (enol, CHaromatic), 123.8
(CHaromatic), 129.3 (CHaromatic), 149.5 (Caromatic), 154.3 (Caromatic),
3.1.8. Benzyl 3-(3,4-dimethoxyphenyl)-3-oxopropanoate (3g)
167.2 (O–C]O),190.7 (C]O). IR (ATR, n
cmꢁ1): 3261 (^CH st), 2938
Following the general procedure,
b
-ketoester
1
(2.00 g,
(C–H st), 2840 (C–H st), 2129 (C^C st), 1740 (C]O st), 1671 (C]O
st), 1584 (ArC–C), 1513 (ArC–C), 1417 (CH3 d as.), 1256 (C–O–C st as),
1129 (C–O–C st as), 1103 (C–O–C st as), 1017 (C–O–C st sim). Anal.
Calcd for C14H14O5: C, 64.12; H, 5.38. Found: C, 64.15; H, 5.41.
8.39 mmol) was allowed to react with benzylalcohol (8.6 mL,
83 mmol, 10 equiv) in the presence of ZnO (0.136 g, 1.67 mmol,
20 mol %) and 8 mL of toluene for 2 h. Column chromatography:
silica gel, hexane/ethyl acetate (4:1). Rf (2:1 hexane/ethyl
acetate)¼0.54. Colorless oil; yield: 2.7 g (6.9 mmol, 82%). 1H NMR
3.1.11. (1S,2R,5S)-2-Isopropyl-5-methylcyclohexyl 3-(3,4-
dimethoxyphenyl)-3-oxopropanoate (3j)
(CDCl3, 360 MHz)
d
: keto (93%)–enol (7%), 3.99 (s, 1.86H, CO–CH2),
5.17 (s, 1.86H, COCH2Ph), 5.23 (s, 0.14H, enol, COCH2Ph), 5.65 (s,
0.07H, enol, C]CH), 6.84 (d, J¼8.5 Hz, 1H, Haromatic), 7.30 (s, 5H,
COCH2Ph), 7.49–7.52 (m, 1.86H, Haromatic), 12.71 (s, 0.07H, enol, OH).
Following the general procedure, b-ketoester 1 (2.00 g,
8.39 mmol) was allowed to react with (ꢁ)-menthol (13.1 g,
83 mmol, 10 equiv) in the presence of ZnO (0.136 g, 1.67 mmol,
20 mol %) and 15 mL of toluene for 1 h. Column chromatography:
silica gel, hexane/ethyl acetate (2:1). Rf (2:1 hexane/ethyl
acetate)¼0.61. Colorless oil; yield: 3.025 g (8.37 mmol, 99%). 1H
13C NMR (CDCl3, 90 MHz)
d: 46.0 (CO–CH2), 56.2 (OCH3), 56.4
(OCH3), 66.3 (enol, COCH2Ph), 67.4 (COCH2Ph), 86.8 (enol, C]CH),
110.2 (enol, CHaromatic), 110.3 (CHaromatic), 110.6 (CHaromatic), 110.9
(enol, CHaromatic), 123.6 (enol, CHaromatic), 123.8 (CHaromatic), 128.5
(COCH2Ph), 128.6 (COCH2Ph), 128.9 (COCH2Ph), 129.5 (CHaromatic),
135.7 (COCH2Ph), 149.5 (Caromatic), 154.1 (Caromatic), 167.8 (O–C]O),
NMR (CDCl3, 360 MHz)
d
: keto (93%)–enol (7%), 0.66 (d, J¼7.1 Hz,
3H, CH3CHCH3), 0.79 (d, J¼7.1 Hz, 3H, CH3CHCH3), 0.87 (d, J¼6.5 Hz,
3H, CHCH3), 0.77–1.06 (m, 3H), 1.32 (tt, J¼11.2, 3.2 Hz, 1H,
CHCH(CH3)2), 1.38–1.52 (m, 1H, (CH2)2CHCH3), 1.59–1.76 (m, 3H),
1.99 (d apparent, J¼11.2 Hz, 1H, CHCH(CH3)2), 3.91 (s, 3H, OCH3),
3.92 (q, J¼28.8, 14.7 Hz, 2H, CO–CH2), 3.93 (s, 3H, OCH3), 4.70 (dt,
J¼4.2, 10.7 Hz, 0.93H, COCH), 4.70 (dt, J¼4.2, 10.7 Hz, 0.07H, enol,
COCH), 5.56 (s, 0.07H, enol, C]CH), 6.87 (d, J¼8.4 Hz, 1H, Haromatic),
7.28 (d, J¼2.2 Hz, 0.07H, enol, Haromatic), 7.39 (dd, J¼8.4, 2.2 Hz,
0.07H, enol, Haromatic), 7.50–7.55 (m, 1.86H, Haromatic), 12.74 (s,
191.1 (C]O). IR (ATR, n
cmꢁ1): 3003 (aromatic CH st), 2936 (CH st),
2838 (C–H st), 1736 (C]O), 1671 (C]O), 1584 (aromatic C–C), 1511
(aromatic C–C), 1416 (CH3 d as.), 1263 (C–O–C st as), 1131 (C–O–C st
as), 1019 (C–O–C st sim).
3.1.9. Allyl 3-(3,4-dimethoxyphenyl)-3-oxopropanoate (3h)
Following the general procedure,
b-ketoester 1 (1.50 g,
6.3 mmol) was allowed to react with allylalcohol (4.30 mL,
63 mmol, 10 equiv) in the presence of ZnO (0.10 g, 1.26 mmol,
20 mol %) and 8 mL of toluene for 3.5 h. Column chromatography:
silica gel, hexane/ethyl acetate (2:1). Rf (2:1 hexane/ethyl
acetate)¼0.52. Colorless oil; yield: 1.50 g (5.6 mmol, 90%). 1H NMR
0.07H, enol, OH). 13C NMR (CDCl3, 90 MHz)
d: 16.3 (CH3CHCH3), 16.7
(enol, CH3CHCH3), 21.0 (CH3CHCH3), 22.2 (CHCH3), 22.3 (enol,
CHCH3), 23.5 (CHCH2CH2), 23.8 (enol, CHCH2CH2), 26.2
(CHCH(CH3)2), 26.6 (enol, CHCH(CH3)2), 31.7 (CHCH3), 34.4
(CHCH2CH2), 34.5 (enol, CHCH2CH2), 40.9 (CHCH2CH), 41.4 (enol,
CHCH2CH), 46.6 (CO–CH2), 47.1 (CHCH(CH3)2), 47.5 (enol,
CHCH(CH3)2), 56.3 (OCH3), 56.4 (OCH3), 74.3 (enol, COCH), 75.8
(COCH), 86.6 (enol, C]CH), 109.0 (enol, CHaromatic), 110.3
(CHaromatic), 110.6 (CHaromatic), 111.0 (enol, CHaromatic), 119.8 (enol,
CHaromatic), 123.7 (CHaromatic), 129.7 (CHaromatic), 149.5 (Caromatic),
(CDCl3, 360 MHz) d: keto (94%)–enol (6%), 3.91 (s, 3H, OCH3), 3.93
(s, 3H, OCH3), 3.98 (s, 1.88H, CO–CH2), 4.64 (dt, J¼5.7, 1.42 Hz, 1.88H,
COCH2CH), 4.69 (dt, J¼5.7, 1.42 Hz, 0.12H, enol, COCH2CH), 5.21 (dq,
J¼1.3, 10.5 Hz, 1H, C]CHtransH), 5.29 (dq, J¼1.3, 17.2 Hz, 1H,
C]CHHcis), 5.62 (s, 0.06H, enol, C]CH), 5.83–5.93 (m, 1H,

`
A. Pericas et al. / Tetrahedron 64 (2008) 9258–9263
9263
154.0 (Caromatic), 167.5 (O–C]O), 191.4 (C]O). IR (ATR,
2953 (C–H st), 2868 (C–H st), 1729 (C]O st), 1675 (C]O st), 1585
(ArC–C), 1514 (ArC–C), 1417 (CH3 as.), 1256 (C–O–C st as), 1148
(C–O–C st as), 1022 (C–O–C st sim). Anal. Calcd for C21H30O5: C,
69.59; H, 8.34. Found: C, 68.97; H, 8.24.
n
cmꢁ1):
CH2CH3), 1.80–1.92 (m, 4H, CHCH3, CH2CH2CH2), 2.22 (t, J¼7.2 Hz,
0.16H, enol, CH2CH2CH2), 2.30 (t, J¼7.2 Hz, 1.84H, CH2CH2CH2), 2.61
(t, J¼7.2 Hz, 2H, CH2CH2CH2), 3.46 (s, 2H, COCH2CO), 4.08 (q,
J¼7.2 Hz, 2H, CH2CH3), 4.62 (t, J¼6.1 Hz, 1H, CHCH), 5.00 (s, 0.08H,
d
enol, C]CH), 12.15 (s, 0.08H, enol, OH). 13C NMR (CDCl3, 90 MHz)
d:
14.5 (CH2CH3), 17.4 (CHCH3), 18.9 (CH2CH2CH2), 19.7 (CHCH3), 21.6
(enol), 29.6 (CHCH3), 29.7 (enol, CHCH3), 33.3 (CH2CH2CH2), 33.6
(enol, CH2CH2CH2), 34.4 (enol), 42.3 (CH2CH2CH2), 49.5 (COCH2CO),
60.6 (CH2CH3), 82.5 (enol, CO–CH2), 84.4 (COCH), 89.8 (enol, C]CH),
3.1.12. Pentan-3-yl 2-oxocyclopentanecarboxylate (5c)
Following the general procedure,
b-ketoester 4 (5.00 g,
30.4 mmol) was allowed to react with 3-pentanol (32 mL,
304 mmol, 10 equiv) in the presence of ZnO (0.49 g, 6.08 mmol,
20 mol %) and 30 mL of toluene for 2 h. Column chromatography:
silica gel, hexane/ethyl acetate (4:1). Rf (2:1 hexane/ethyl
acetate)¼0.63. Colorless oil; yield: 5.9 g (29.7 mmol, 98%). 1H NMR
167.4 (COOCH), 173.2 (COOEt), 177.6 (enol), 202.4 (C]O). IR (ATR,
n
cmꢁ1): 2965 (C–H st), 2937 (C–H st), 2876 (C–H st), 1731 (C]O st),
1712 (C]O st), 1464 (CH3 d as.), 1311 (C–O–C st as), 1238 (C–O–C st
as), 1175 (C–O–C st as), 1131 (C–O–C st as), 1096 (C–O–C st as).
(CDCl3, 360 MHz)
d
: keto (98%)–enol (2%), 0.84 (t, J¼7.5 Hz, 3H,
CH2CH3), 0.88 (t, J¼7.5 Hz, 3H, CH2CH3), 1.49–1.62 (abs complex, 4H,
CH2CH3), 1.78–1.92 (abs complex, 1H, CH2CH2CH), 2.06–2.16 (abs
complex, 1H, CH2CH2CH), 2.24–2.31 (abs complex, 4H,
CH2CH2CH2CH), 3.12 (t, J¼8.8 Hz, 0.98H, COCHCOOR), 4.77 (quint,
J¼6.2 Hz, 1H, OCH(CH2)2), 10.44 (s, 0.02H, enol, OH). 13C NMR
Acknowledgements
´
Financial support from Ministerio de Educacion y Ciencia (Pro-
jects CTQ2005-04968-C02-01 and Consolider Ingenio 2010
(CSD2007-00006)) and DURSI-Generalitat de Catalunya (SGR
2005-00305) are gratefully acknowledged. A.S. has been supported
(CDCl3, 90 MHz) d: 9.8 (CH2CH3), 9.9 (CH2CH3), 21.3 (CH2CH2CH),
26.8 (CH2CH3), 27.8 (CH2CH2CH), 38.3 (CH2CH2CH2CH), 55.3
(COCHCOOR), 78.2 (OCH (CH2)2), 169.6 (O–C]O), 212.8 (C]O). IR
(ATR,
´
through a Ramon y Cajal contract from the Ministerio de Educacion
y Ciencia of Spain.
n
cmꢁ1): 2967 (C–H st), 2940 (C–H st), 2880 (C–H st), 1752
(C]O st), 1718 (C]O st), 1458 (CH3 d as.), 1252 (C–O–C st as), 1189
References and notes
(C–O–C st as), 1103 (C–O–C st as).
´
˜
´
1. Galvez, N.; Molins, E.; Moreno-Manas, M.; Sebastian, R. M.; Serra, N.; Trepat, E.;
Vallribera, A. J. Heterocycl. Chem. 2000, 37, 895.
3.1.13. Adamantyl 2-oxocyclopentanecarboxylate (5f)
´
2. Moreno-Man˜as, M.; Sebastian, R. M.; Vallribera, A.; Molins, E.; Espinosa, E.
Following the general procedure,
b
-ketoester
4
(2 g,
Tetrahedron: Asymmetry 1997, 8, 1525.
3. Moreno-Man˜as, M.; Trepat, E.; Sebastia´n, R. M.; Vallribera, A. Tetrahedron:
Asymmetry 1999, 10, 4211.
4. Clariana, J.; Ga´lvez, N.; Marchi, C.; Moreno-Man˜as, M.; Vallribera, A.; Molins, E.
Tetrahedron 1999, 55, 7331.
5. Comelles, J.; Moreno-Man˜as, M.; Pe´rez, E.; Roglans, A.; Sebastia´n, R. M.; Vall-
ribera, A. J. Org. Chem. 2004, 69, 6834.
6. (a) Lumbierres, M.; Marchi, C.; Moreno-Man˜as, M.; Sebastia´n, R. M.; Vallribera,
12.80 mmol) was allowed to react with 1-adamantanol (2.92 g,
38.36 mmol, 3 equiv) in the presence of ZnO (0.20 g, 2.56 mmol,
20 mol %) and 20 mL of toluene for 5 h. Column chromatography:
silica gel, hexane/ethyl acetate (3:1). Rf (3:1 hexane/ethyl
acetate)¼0.60. Colorless oil; yield: 2.78 g (10.62 mmol, 83%). 1H
NMR (CDCl3, 360 MHz) d: keto (99%)–enol (1%),1.64 (s, 6H, CH2ada),
A.; Lago, E.; Molins, E. Eur. J. Org. Chem. 2001, 2321; (b) Gimbert, C.; Lumbierres,
´
M.; Marchi, C.; Moreno-Man˜as, M.; Sebastian, R. M.; Vallribera, A. Tetrahedron
2005, 61, 8598.
1.76–1.89 (abs complex, 1H, CH2CH2CH), 2.04–2.12 (abs complex,
1H, CH2CH2CH), 2.10 (s, 6H, CH2CHCH2ada), 2.14 (s, 3H,
CH2CHCH2ada), 2.20–2.28 (abs complex, 4H, CH2CH2CH2CH), 3.02
(t, J¼8.9 Hz, 0.99H, COCHCOOR), 10.43 (s, 0.01H, enol, OH). 13C NMR
´
´
˜
7. Martınez, S.; Martın, L.; Molins, E.; Moreno-Manas, M.; Roig, A.; Vallribera, A.
Monatsh. Chem. 2006, 137, 627.
8. Comelles, J.; Pericas, A.; Moreno-Man˜as, M.; Vallribera, A.; Drudis-Sole´, G.;
Lledos, A.; Parella, T.; Roglans, A.; Garcı´a-Granda, S.; Roces-Ferna´ndez, L. J. Org.
Chem. 2007, 72, 2077.
(CDCl3, 90 MHz) d: 21.2 (CH2CH2CH), 27.8 (CH2CH2CH2CH), 31.2
(CH2CHCH2ada), 36.4 (CH2CHCH2ada), 38.4 (CH2CH2CH2CH), 41.5
(CH2CHCH2ada), 56.2 (COCHCOOR), 82.0 (OC (CH2)3), 168.7 (O–
9. Clemens, R. J. Chem. Rev. 1986, 241.
10. Ga´lvez, N.; Moreno-Man˜as, M.; Padro´s, I.; Sebastia´n, R. M.; Serra, N.; Vallribera,
C]O), 213.2 (C]O). IR (ATR, n
cmꢁ1): 2909 (C–H st), 2850 (C–H st),
A. Polyhedron 1995, 14, 1397.
11. (a) Oikawa, Y.; Sugano, K.; Yonemitsu, O. J. Org. Chem. 1978, 43, 2087; (b) Marchi,
C.; Trepat, E.; Moreno-Man˜as, M.; Vallribera, A.; Elies, M. Tetrahedron 2002, 58,
5699.
12. Sasidharan, M.; Kumar, R. J. Mol. Catal. A: Chem. 2004, 210, 93.
13. Da Silva, F. C.; Ferreira, V. F.; Rianelli, R. S.; Perreira, W. C. Tetrahedron Lett. 2002,
43, 1165.
1750 (C]O st), 1716 (C]O st), 1454 (CH3 d as.), 1248 (C–O–C st as),
1186 (C–O–C st as), 1102 (C–O–C st as), 1051 (C–O–C st sim). Anal.
Calcd for C16H22O3: C, 73.25; H, 8.45. Found: C, 73.12; H, 8.74. Bp:
175 ꢀC at 0.55 mbar.
14. Bulbule, V. J.; Borate, H. B.; Munot, Y. S.; Deshpande, V. H.; Sawargave, S. P.;
Gaikwad, A. G. J. Mol. Catal. A: Chem. 2007, 276, 158.
15. Jin, T.; Zhang, S.; Li, T. Green Chem. 2002, 4, 32.
16. de Sairre, M. I.; Bronze-Uhle, E. S.; Donate, P. M. Tetrahedron Lett. 2005, 46, 2705.
17. Palaniappan, S.; Shekhar, R. C. Polym. Adv. Technol. 2004, 15, 140.
18. Madje, B. R.; Patil, P. T.; Shindalkar, S. S.; Benjamin, S. B.; Shingare, M. S.;
Dongare, M. K. Catal. Commun. 2004, 5, 353.
19. (a) Bandgar, B. P.; Sadavarte, V. S.; Uppalla, L. S. J. Chem. Res., Synop. 2001, 16; (b)
Chavan, S. P.; Shivasankar, K.; Sivappa, R.; Kale, R. Tetrahedron Lett. 2002, 43,
8583.
3.1.14. 1-(2,4-Dimethylpentan-3-yl) 7-ethyl 3-oxoheptane-
dioate (11)
Following the general procedure,
b-ketoester 10 (1.5 g,
6.51 mmol) was allowed to react with 2,4-dimethylpentan-3-ol
(9.13 mL, 65.1 mmol, 10 equiv) in the presence of ZnO (0.10 g,
1.30 mmol, 20 mol %) and 4 mL of toluene for 2 h. Column chro-
matography: silica gel, hexane/ethyl acetate (4:1). Rf (2:1 hexane/
ethyl acetate)¼0.62. Colorless oil; yield: 1.78 g (5.92 mmol, 92%). 1H
20. Bo, W.; Ming, Y. L.; Shuan, S. J. Tetrahedron Lett. 2003, 44, 5037.
21. (a) Carroll, M. F. J. Chem. Soc. 1940, 704; (b) Kimel, W.; Cope, A. C. J. Am. Chem.
Soc. 1943, 65, 1992.
NMR (CDCl3, 360 MHz)
6H, CHCH3), 0.86 (d, J¼6.8 Hz, 6H, CHCH3), 1.21 (t, J¼7.45 Hz, 3H,
d
: keto (92%)–enol (8%), 0.83 (d, J¼6.8 Hz,
22. Morrison, G. C. European Patent Application, EP 0126651, 1984.