Formation of δ-Lactones by Cerium-Catalyzed, Baeyer-Villiger-Type Coupling of β-Oxoesters, Enol Acetates, and Dioxygen

Article abstract of DOI:10.1021/acs.joc.6b01441

Formation of δ-lactones is observed when cyclopentanone-2-carboxylates are converted in a cerium-catalyzed reaction with α-aryl vinyl acetates under oxidative conditions. The products of this transformation possess a 1,4-dicarbonyl constitution together with a quaternary carbon center. Atmospheric oxygen is the oxidant in this process, which can be regarded as ideal from economic and ecological points of view. Further advantages of this new C-C coupling and oxidation reaction are its operational simplicity and the application of nontoxic and inexpensive CeCl₃·7 H₂O as precatalyst. This so far unprecedented reaction is proposed to proceed via 1,2-dioxane derivatives, which decompose under formation of an oxycarbenium cation in a Baeyer-Villiger-type pathway. This mechanistic picture is supported by the observation that electron-rich (donor substituted or heteroaromatic) enol esters give higher yields than electron deficient congeners. Apart from 1,4-diketones and α-hydroxylated β-oxoesters formed as byproducts, the yields of δ-lactones range from moderate to good (up to 74%).

Full text of DOI:10.1021/acs.joc.6b01441

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Article
Formation of delta-Lactones by Cerium-Catalyzed, Baeyer-Villiger-
Type Coupling of beta-Oxoesters, Enol Acetates and Dioxygen
Irina Geibel, Anna Dierks, Marc Schmidtmann, and Jens Christoffers
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01441 • Publication Date (Web): 05 Aug 2016
Downloaded from http://pubs.acs.org on August 7, 2016
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Formation of δꢀLactones by CeriumꢀCatalyzed, BaeyerꢀVilligerꢀType
Coupling of βꢀOxoesters, Enol Acetates and Dioxygen
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Irina Geibel, Anna Dierks, Marc Schmidtmann, Jens Christoffers*
Institut für Chemie, Carl von Ossietzky Universität Oldenburg, 26111 Oldenburg,
Germany
ABSTRACT: Formation of δꢀLactones is observed when cyclopentanoneꢀ2ꢀ
carboxylates are converted in a ceriumꢀcatalyzed reaction with αꢀaryl vinyl acetates
under oxidative conditions. The products of this transformation possess a 1,4ꢀ
dicarbonyl constitution together with a quaternary carbon center. Atmospheric oxygen
is the oxidant in this process, which can be regarded as ideal from economic and
ecological points of view. Further advantages of this new CꢀC coupling and oxidation
reaction are its operational simplicity and the application of nontoxic and inexpensive
CeCl3 ꢁ 7 H2O as precatalyst. This so far unprecedented reaction is proposed to
proceed via 1,2ꢀdioxane derivatives, which decompose under formation of an
oxycarbenium cation in a BaeyerꢀVilligerꢀtype pathway. This mechanistic picture is
supported by the observation, that electronꢀrich (donor substituted or heteroaromatic)
enol esters give higher yields than electron deficient congeners. Apart from 1,4ꢀ
diketones and αꢀhydroxylated βꢀoxoesters formed as byproducts, the yields of δꢀ
lactones range from moderate to good (up to 74%).
OAc
O
Ph
O
O
+ O2 (air)
Ph
CO Bu
2i
O
CO Bu
2i
1 mol% CeCl3 — 7 H2O
F3CCH2OH, 30°C, 1 d
64%
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INTRODUCTION
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The δꢀlactone unit is a widely spread structural motif in natural products and pharmaꢀ
ceutically active compounds. Four prominent examples are warfarin (1),1 an anticoꢀ
agulant, the topoisomerase I inhibitor irinotecan (2),2 a camptothecin derivative,3 the
antimalarial artemisinin (3),4 and ochratoxin A (4),5 a toxin from Aspergillus species
(Figure 1). There are several strategies in the literature to prepare lactones6 with an
αꢀquaternary carbon center.7 However, the most powerful method to access δꢀ
lactone derivatives is the BaeyerꢀVilliger oxidation of a cyclopentanone derivative,8
which is classically achieved by peroxycarboxylic acids,9 although several enzymatic
methods were also reported in recent years.10
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O
O
N
Et
N
N
O
O
OH
Me
O
N
O
O
1
O
Me
O
2
H
O
HO
Et
O
OH
Cl
O
OH
O
Me
O
O
N
H
O
H
O
Me
Me
3
4
Figure 1. Examples for biologically active δꢀlactone derivatives.
A couple of years ago we have reported on the preparation of 1,4ꢀdiketones 7 from βꢀ
oxoesters 5, styrene and molecular oxygen via 1,2ꢀdioxane derivatives 6 (Scheme 1,
top).11 While the use of nontoxic and inexpensive CeCl3 ꢁ 7 H2O as precatalyst and
air as oxidant could classify the first step of this sequence as a contribution to the
field of sustainable chemistry, this view is spoiled by the necessity of using stoichioꢀ
metric amounts of pyridine and acetyl chloride in the second step, which is required
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for the fragmentation of the endoperoxide 6 to the final product 7. We have recently
introduced a preparative simplification by the use of enol acetates instead of styrene
(Scheme 1, bottom).12 With two acetal functions in the intermediate peroxide 9, this
material is simply hydrolyzed whilst acidic workup and purification. During our optiꢀ
mization of the latter process we have actually observed the formation of a small
amount of a byproduct with m/z 290 (by GCMS), which actually differs from product
7aa (m/z 274) by the incorporation of one oxygen atom. We wish to report herein on
the isolation of this compound, its structure elucidation and the optimization of the
reaction procedure in order to turn this oxidized compound to the major product of the
transformation.
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Previous twoꢀstep procedure:
O
Ph
O
Ph
O
O
O
+ AcCl
Ph
HO
CO2Et
+ pyridine
O2 (air)
CO2Et
CO2Et
cat. CeCl3 — 7 H2O
5a
6
7aa
Recent procedure:
OAc
Ph
OAc
Ph
O
Ph
O
O
cat. H+
O
O
8a
HO
CO2Et
SiO2/H2O
O2 (air)
CO2Et
CO2Et
cat. CeCl3 — 7 H2O
5a
9
7aa
Scheme 1. Ceriumꢀcatalyzed oxidative procedures for the preparation of 1,4ꢀdikeꢀ
tones 7 from βꢀoxoesters 5. The older protocol required stoichiometric
amounts of AcCl and pyridine for the fragmentation of the endoperoxide
6 (top). In the newer variant the two acetal functions within the intermeꢀ
diate product 9 are cleaved during the aqueousꢀacidic workup (bottom).
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RESULTS AND DISCUSSION
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An initial attempt of oxidative coupling of enol ester 8a with oxoester 5a (Scheme 2
and Table 1, entry 1) furnished the αꢀhydroxylated compound 10a (43% yield of
isolated material) as the major product13 and the C–C coupling product 7aa as the
main byproduct (39% isolated). Another unexpected byproduct could be identified as
compound 11aa (11% after chromatography); with m/z 290 (GCMS) it is formally the
oxidation product of compound 7aa (m/z 274). After elucidation of the δꢀlactone
constitution (vide infra) we considered it to be a valuable target for optimization of
reaction parameters. In the following screening program we investigated the
influence of the reaction temperature (varied in the range of 20°C to 70°C) and the
relative amount of precatalyst CeCl3 ꢁ 7 H2O (10, 5, 2.5, 1, 0.5, 0.3 and 0 mol%,
resp.) on the yield of compound 11aa. The choice of the solvent turned out to be
essential, as was already investigated in the preceding work on formation of 1,4ꢀ
diketones 7.12 Only the solvents showing significant conversions towards 1,4ꢀ
diketones 7 also gave the derived lactones 11, as were the following: iPrOH, hexaꢀ
fluoroisopropanol (HFIP) and 2,2,2ꢀtrifluoroethanol (TFE). Interestingly, the beneficial
effects of fluorinated solvents in catalysis as well as in oxidation reactions with
peroxidic intermediates are well known.14 In general, the screening was performed on
a GCꢀscale, but in selected cases products were isolated by column chromatography
to obtain a value for the yield of isolated material (see footnotes a and b of Table 1).
Some representative results of the optimization program are listed in Table 1: First of
all, with a small increase of the reaction temperature, the 1,4ꢀdiketone 7aa became
the major product of the conversion (entry 2, 61% by GC). The change of solvent to
HFIP turned the selectivity towards the lactone 11aa (entry 4, 42% isolated). Finally,
the optimal results for the formation of compound 11aa (59% isolated) were obtained
by lowering the amount of precatalyst (1 mol%, entry 8). In this case no αꢀ
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hydroxylated product 10a was formed and the 1,4ꢀdiketone 7aa was the only
byproduct (21% yield after chromatography). Further lowering of the amount of
precatalyst did not improve the yield of the target compound 11aa (entry 9). Without
cerium salt in the reaction mixture, no conversion was observed (entry 10). The
crucial role of the Ce(III)/Ce(IV) redox system for the αꢀoxidation of βꢀoxoesters15 as
well as the formation of the 1,2ꢀdioxane derivatives was discussed by us before.11d It
is however clear, that Ce3+ could also act as a Lewis acid under reaction conditions.16
Some nickel, cobalt, copper and manganese salts, which are known to catalyze the
αꢀhydroxylation reaction of βꢀoxoesters,17 have also been investigated as
precatalysts. The respective results were always significantly inferior to those
obtained with cerium chloride (see Supporting Information for details).
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OAc
O
Ph
O
Ph
Ph
O
O
O
O
8a (1.5 equiv.)
OH
CO2Et
+
+
O
CO2Et
CO2Et
CO2Et
O2 (air), 1 d
cat. CeCl3 — 7 H2O
5a
7aa
10a
11aa
Scheme 2. Isolated products from the ceriumꢀcatalyzed conversion of oxoester 5a
with enol acetate 8a; for conditions and yields see Table 1.
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Table 1.
Optimization of the reaction parameters (representative examples).
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Entry
CeCl3 ꢁ 7 H2O Solvent
T
Yield (10a) Yield (7aa) Yield (11aa)
7
8
9
1
2
3
4
5
6
7
8
9
10
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
5 mol%
1 mol%
1 mol%
0.5 mol%
0 mol%
iPrOH
iPrOH
HFIP
HFIP
TFE
23°C
30°C
30°C
30°C
30°C
50°C
30°C
30°C
30°C
30°C
43%a
39%a
61%b
19%b
12%a
49%b
52%b
29%b
21%a
15%b
0%b
11%a
7%b
b
–
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b
–
41%b
42%a
36%b
30%b
59%b
59%a
46%b
0%b
22%a
b
–
b
TFE
–
b
TFE
–
TFE
0%a
b
TFE
–
b
TFE
–
aYields of isolated products after chromatographic purification.
bYields determined by GC with mesitylene as internal standard; the amount of αꢀ
hydroxylated compound 10a could not be determined with certainty because of
lacking baseline resolution with enol ester 8a.
1
The constitution of lactone 11aa was already indicated by H NMR spectroscopy by
the characteristic signals of the two diastereotopic OCH2ꢀprotons (δ = 4.56 and 4.70
ppm). In order to obtain crystalline materials, the para-bromo substituted enol acetate
8b (for its preparation see below) was converted with oxoester 5a to give the proꢀ
ducts 7ab and 11ab both as solid materials, which contained suitable single crystals
for Xꢀray analysis;18 ORTEPꢀrepresentations of their structures in the solid state are
given in Figures 2 and 3. As indicated initially by the difference in molar mass (∆m/z
16), both compounds only differ in the replacement of the cyclopentanone ring by a
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δꢀlactone unit.
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Figure 2.
ORTEPꢀrepresentation of the molecular structure of 1,4ꢀdiketone 7ab in
the solid state, ellipsoids of hetero atoms at the 50% probability level, H
atoms omitted for clarity.
Figure 3.
ORTEPꢀrepresentation of the molecular structure of δꢀlactone 11ab in
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the solid state, ellipsoids of hetero atoms at the 50% probability level, H
atoms omitted for clarity.
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As a mechanistic rationale for the formation of a δꢀlactone from endoperoxidic interꢀ
mediate 9 we propose the loss of an acetate ion under formation of an oxycarbenium
ion 12. One might speculate, whether this elimination could either be facilitated by the
relatively high acidity of the solvent14 or even with the aid of Ce3+ as a Lewis acid.16
Anyhow, cationic species 12 could actually decompose in analogy to a Baeyerꢀ
Villiger reaction pathway with migration of the primary carbon atom under ring
expansion. The migrating carbon atom is in antiperiplanar conformation to the leaving
oxygen atom within the 1,2ꢀdioxane ring, which is a perfect prerequisite for this
rearrangement reaction. An alternative pathway might actually be the migration of the
quaternary carbon center, which would be slightly disfavored due to the electron
withdrawing effect of the ester moiety. A similar regioselectivity was at least once
reported before for an αꢀmethoxycarbonylꢀαꢀmethylcyclopentanone derivative.19 In
order to support this mechanistic picture we suggested introducing electron donating
or withdrawing groups X at the paraꢀposition of the phenyl ring in order to either
stabilize or destabilize the benzylic cation 12. The results (see Scheme 4 and Table
2) clearly indicated that a cationic intermediate such as compound 12 is highly
probable. Furthermore, if isopropenyl acetate is used as enol ester, no formation of
lactone byproduct is observed, which is another indication for the requirement of
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benzylic stabilization of a cationic intermediate 12.
X
O
Ph
OAc
Ph
O
O
O
O
O
HO
HO
ꢀ OAc
ꢀ H
O
CO2Et
CO2Et
CO2Et
12 (X = H)
9
11aa
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Scheme 3. Mechanistic proposal for the formation of δꢀlactone 11aa from endoperꢀ
oxide 9 via oxycarbenium ion 12.
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9
The scope of the lactone formation was investigated by variation of the ring size and
the alkyl groups of the βꢀoxoesters 5x. Furthermore, we have broadly varied the aroꢀ
matic residue Ar of the enol acetate 8y in order to support the mechanistic picture
drawn in Scheme 3. All reactions were performed under the optimized conditions
(Scheme 4). First of all, the aromatic residues of the enol acetates 8y were varied in
order to get insight into the mechanistic proposal given in Scheme 3. Entry 1 of Table
2 is the repetition of the result from Table 1. The reaction of paraꢀbromo derivative 8b
was performed in order to get crystalline products 11ab (44%) and 7ab (19%, entry
2) suitable for single Xꢀray crystal structure analysis (see above); a relatively large
amount of the αꢀhydroxylated compound 10a (35%) was formed in this case. The reꢀ
sults of the next four experiments supported the mechanistic picture drawn in Scheꢀ
me 3: Introduction of the electron donating paraꢀmethoxy substituent enlarged the
yield of the lactone 11ac (66%, entry 3), whereas it got lower when electron withdraꢀ
wing fluorine substituents are introduced (11ad, 47% and 11ae, 38%; entries 4 and
5). With a paraꢀnitro substitution the yields completely collapsed (11af, 7%; entry 6).
The reaction also tolerated electronꢀrich, heteroaromatic residues within the enol
esters, as results in entries 7–9 show: With thiophene and furane derivatives 8g and
8h, the yield of lactones is reasonable (55% in both cases). Interestingly, no αꢀhyꢀ
droxylated product 10a was formed in these cases. With an Nꢀtosyl pyrrole moiety,
the yield decreased (product 11ai, 36%, entry 9). We then took a brief look to other
alkyl residues at the oxoester and found that the isobutyl ester 5b gave an improveꢀ
ment of yields (products 11ba, 64% and 11bc, 74%; entries 10 and 11). With other
ring sizes at the oxoester starting material (six and seven membered ring 5c and 5d,
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respectively), the conversion gave almost no lactone product; the 1,4ꢀdiketones 7ca
(41%) and 7da (45%, entries 12 and 13) are the major products in these cases. Conꢀ
version of a αꢀacetylcyclopentanone (5e) as a βꢀdiketone gave no lactone 11ea unꢀ
der standard conditions. It was however obtained in insignificant amounts (14% toꢀ
gether with 24% 1,4ꢀdiketone 7ea) when the reaction temperature and time were enꢀ
hanced (entry 14).
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OAc
O
Ar
O
Ar
O
Ar
O
O
O
8y (1.1ꢀ2.0 equiv.)
OH
O
COR
+
+
COR
COR
COR
O2 (air), TFE, 30°C, 1 d
n
n
n
n
1 mol% CeCl3 — 7 H2O
5x
7xy
10x
11xy
Scheme 4. Conversion of βꢀoxoesters 5x with enolacetates 8y giving αꢀhydroxy
compounds 10x, 1,4ꢀdiketones 7xy or lactones 11xy; for x, y, n, R, Ar
and yields see Table 2.
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Table 2.
Results for different oxoesters 5x and enol acetates 8y.
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Entry 5x (n, R)
8y (Ar)
yieldsa
7
8
9
1
5a (1, OEt)
5a (1, OEt)
5a (1, OEt)
5a (1, OEt)
5a (1, OEt)
5a (1, OEt)
5a (1, OEt)
5a (1, OEt)
5a (1, OEt)
8a (Ph)
59% (11aa), 21% (7aa),
0% (10a)
2
8b (4ꢀBrC6H4)
8c (4ꢀMeOC6H4)
44% (11ab), 19% (7ab), 35% (10a)
66% (11ac), 15% (7ac), 7% (10a)
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3
4
8d [3,5ꢀ(CF3)2C6H3] 47% (11ad), 21% (7ad) 19% (10a)
5
8e (2,4ꢀF2C6H3)
8f (4ꢀNO2C6H4)
8g (2ꢀthienyl)
8h (2ꢀfuryl)
38% (11ae), 22% (7ae), 32% (10a)
7% (11af), 2% (7af), 36% (10a)
6
7
55% (11ag), 18% (7ag)
55% (11ah), 20% (7ah)
0% (10a)
0% (10a)
8
9
8i (NꢀTosꢀ2ꢀpyrrolyl) 36% (11ai),
16% (7ai), 24% (10a)
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13
14b
5b (1, OiBu) 8a (Ph)
64% (11ba), 29% (7ba),
7% (10b)
2% (10b)
9% (10c)
4% (10d)
0% (10e)
5b (1, OiBu) 8c (4ꢀMeOC6H4)
74% (11bc), 21% (7bc),
9% (11ca), 41% (7ca),
0% (11da), 45% (7da),
14% (11ea), 24% (7ea),
5c (2, OEt)
5d (3, OMe) 8a (Ph)
5e (1, Me) 8a (Ph)
8a (Ph)
aYields of isolated products after chromatographic purification.
bDifferent reaction conditions: 1 mol% CeCl3 ꢁ 7 H2O, TFE, 50°C, 3 d
Enol acetates were prepared following two literature protocols as is exemplified with
procedures for the two new compounds 8e and 8i in the experimental section: The
respective acetophenone derivative was deprotonated with LiHMDS at –78°C in THF
solution and the respective lithium enolate trapped with AcCl at the same temperaꢀ
ture.20 This method was applied for the preparation of compounds 8d and 8e. Alterꢀ
natively, the acetophenone derivative was equilibrated with catalytic amounts of
either H2SO4 or pTosOH in an excess of isopropenylacetate as acetyl donor and the
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mixture separated by fractional distillation or column chromatography.21 This protocol
was actually preferred due to its operational simplicity and applied for the preparation
of compounds 8a, 8b, 8c, 8f (with H2SO4) and 8g, 8h, 8i (with pTosOH).
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CONCLUSION
We have introduced a so far unprecedented transformation of cyclopentanoneꢀ2ꢀcarꢀ
boxylates 5a and 5b with αꢀaryl vinyl acetates 8a–8f furnishing eleven new δꢀlacꢀ
tones 11 as products, which hold a 1,4ꢀdicarbonyl constitution and have a quaternary
carbon center in their 2ꢀposition. As byproducts, 1,4ꢀdiketones 7 and αꢀhydroxylated
products 10a and 10b were formed, which could be separated by column chromatoꢀ
graphy. The yields of lactones ranged from 74% with a donor substituted aromatic reꢀ
sidue (4ꢀMeOC6H4) at enol ester 8c (product 11bc) to 38% with an electron deficient
enol ester 8e (difluorophenylꢀsubstitution, product 11ae); with an nitrophenylꢀring, the
yields broke down (7% of product 11af). With this reactivity profile, the mechanistic
picture, which proposes the decomposition of an intermediate 1,2ꢀdioxane derivative
9 under formation of an arylꢀsubstituted oxycarbenium ion 12, was supported. Among
the enol acetates used, also three heteroaromatic examples were investigated, which
gave 55% (thiophene and furane derivatives) and 36% (Nꢀtosylpyrrole) yield of lacꢀ
tones. Despite the frugality of the starting materials, the constitution of the products is
highly interesting. Further advantages of this new CꢀC coupling and oxidation reacꢀ
tion are its operational simplicity and the application of nontoxic and inexpensive
CeCl3 ꢁ 7 H2O as precatalyst and atmospheric oxygen as the oxidant, which can be
regarded as ideal from economic and ecological points of view.
EXPERIMENTAL SECTION
General: Preparative column chromatography was carried out using Merck SiO2 (35–
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70 ꢁm, type 60 A) with hexanes, tertꢀbutyl methyl ether (MTBE), and ethyl acetate
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(EtOAc) as eluents. TLC was performed on aluminum plates coated with SiO2 F254
.
1Hꢀ, 19Fꢀ and 13CꢀNMR spectra were recorded on 500 MHz and 300 MHz
instruments. Multiplicities of carbon signals were determined with DEPT experiments.
HRMS spectra were obtained with an ESI spectrometer (pos. mode) with QꢀTOF
analyzer. IR spectra were recorded on a spectrometer equipped with a diamond ATR
unit. The starting materials 5a, 5c, 5d, 5e and 2,4ꢀdifluoroacetophenone were
commercially available. The following compounds were literature known and
prepared according to published procedures: 5b,22 8a,12 8b,21, 23 8c,12 8d,20, 24 8f,12
8g,25 8h,26 and 2ꢀacetylꢀNꢀtosylpyrrole.27
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1ꢀ(2,4ꢀDifluorophenyl)vinyl acetate (8e). The procedure was performed according
to a literature procedure.20 Under exclusion of air and moisture (nitrogen atmosphere)
and at –78°C, a solution of 2,4ꢀdifluoroacetophenone (2.00 g, 12.8 mmol) in abs.
THF (10 mL) was dropwise added within 30 min to a solution of LiHMDS (14.1 mL of
a 1.0 mol/L solution THF, 14.1 mmol; diluted with 40 mL abs. THF). After stirring the
mixture for further 15 min at –78°C, a solution of AcCl (1.11 g, 14.1 mmol) in abs.
THF (10 mL) was added and the resulting mixture allowed for warming to ambient
temperature within 1 h. Ethyl acetate (50 mL) was added and the mixture filtered
through (SiO2, washing with 50 mL EtOAc). The filtrate was evaporated and the resiꢀ
due chromatographed (SiO2, hexanes/MTBE 3:1, Rf = 0.54) to furnish enolester 8e
(729 mg, 3.68 mmol, 29%) as an orange oil. 1H NMR (500 MHz, CDCl3): δ = 2.23 (s,
3H), 5.20−5.21 (m, 1H), 5.47−5.48 (m, 1H), 6.81−6.88 (m, 2H), 7.35 (td, J = 8.8 Hz, J
= 6.4 Hz, 1H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 20.8 (CH3), 104.7 (t, 2JC,F
=
4
2
4
26.1 Hz, CH), 107.3 (d, JC,F = 8.2 Hz, CH2), 111.4 (dd, JC,F = 21.5 Hz, JC,F = 3.8
Hz, CH), 119.1 (dd, 2JC,F = 11.7 Hz, 4JC,F = 4.1 Hz, C), 129.2 (dd, 3JC,F = 9.8 Hz, 3JC,F
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= 4.1 Hz, CH), 147.1 (d, JC,F = 3.3 Hz, C), 160.1 (dd, JC,F = 254.2 Hz, JC,F = 11.3
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1
3
Hz, CF), 162.8 (dd, JC,F = 252.1 Hz, JC,F = 12.7 Hz, CF), 168.8 (C) ppm. 19F{1H}
NMR (470 MHz, CDCl3): δ = −108.8 (d, J = 9.2 Hz, 1F), −109.0 (d, J = 9.2 Hz, 1F)
ppm. IR (ATR): λ–1 = 2938 (w), 1740 (m), 1676 (m), 1610 (vs), 1498 (s), 1423 (s),
1370 (m), 1268 (s), 1234 (s), 1201 (m), 1141 (s), 1099 (s), 1076 (m), 1013 (m), 968
(vs), 848 (vs), 816 (s), 734 (m), 613 (s) cm–1. HRMS (ESI): calcd. 221.0385 (for
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C10H8F2NaO2 ); found 221.0389 [M + Na+]. C10H8F2O2 (198.17).
+
2ꢀ(1ꢀAcetoxyvinyl)ꢀ1ꢀ(4ꢀmethylphenylsulfonyl)pyrrole (8i). The procedure was
performed according to a literature procedure.25 A mixture of 2ꢀacetylꢀ1ꢀtosylpyrrole
(1.00 g, 3.80 mmol), isopropenyl acetate (1.90 g, 19.0 mmol) and pTosOH ꢁ H2O (51
mg, 0.27 mmol) was stirred for 16 h at 100°C. Subsequently, all volatiles were reꢀ
moved in vacuum and the residue was chromatographed (SiO2, hexanes/MTBE 3:2,
1
Rf = 0.32) to yield the enol ester 8i (600 mg, 1.96 mmol, 52%) as a brown oil. H
NMR (500 MHz, CDCl3): δ = 2.02 (s, 3H), 2.39 (s, 3H), 5.08 (d, J = 1.5 Hz, 1H), 5.20
(d, J = 1.5 Hz, 1H), 6.22 (t, J = 3.4 Hz, 1H), 6.40 (dd, J = 3.4 Hz, J = 1.8 Hz, 1H),
7.26–7.27 (m, 2H), 7.32 (dd, J = 3.4 Hz, J = 1.8 Hz, 1H), 7.68–7.71 (m, 2H) ppm.
13C{1H} NMR (125 MHz, CDCl3): δ = 21.1 (CH3), 21.6 (CH3), 108.8 (CH2), 111.9 (CH),
118.6 (CH), 124.9 (CH), 127.2 (2 CH), 129.5 (C), 129.6 (2 CH), 135.8 (C), 144.2 (C),
145.0 (C), 168.6 (C) ppm. IR (ATR): λ–1 = 3149 (w), 3135 (w), 2930 (w), 1758 (m),
1710 (w), 1679 (w), 1596 (w), 1437 (w), 1365 (s), 1204 (m), 1172 (vs), 1144 (vs),
1084 (s), 1048 (m), 1018 (m), 956 (w), 935 (w), 889 (w), 813 (m), 734 (m), 703 (w),
671 (vs) cm–1. HRMS (ESI): calcd. 328.0614 (for C15H15NNaO4S+); found 328.0627
[M + Na+]. C15H15NO4S (305.35).
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Ethyl 3ꢀ(2ꢀoxoꢀ2ꢀphenylethyl)tetrahydropyranꢀ2ꢀoneꢀ3ꢀcarboxylate (11aa). CeCl3
— 7 H2O (6 mg, 15 ꢁmol) was added to a mixture of βꢀoxoester 5a (240 mg, 1.54
mmol) and enol ester 8a (378 mg, 2.33 mmol, 1.5 equiv.) in TFE (1 mL), and the
reaction mixture was stirred at 30°C for 24 h under an atmosphere of air. Subseꢀ
quently, all volatile materials were removed in vacuum and the residue was purified
by column chromatography (SiO2, hexanes/MTBE 3:1 → 1:1) to yield 1,4ꢀdiketone
7aa [89 mg, 0.32 mmol, 21%, Rf = 0.40 (hexanes/MTBE 1:1)] as a colorless oil.
Secondly, the title compound 11aa [261 mg, 0.90 mmol, 59%, Rf = 0.19
(hexanes/MTBE = 1:1)] was eluted as a colorless oil.
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Lactone 11aa: H NMR (500 MHz, CDCl3): δ = 1.30 (t, J = 7.1 Hz, 3H), 1.84–1.89
(m, 1H), 2.09–2.25 (m, 3H), 3.62 (d, J = 18.6 Hz, 1H), 4.03 (d, J = 18.6 Hz, 1H),
4.19–4.31 (m, 2H), 4.54–4.57 (m, 1H), 4.67–4.73 (m, 1H), 7.44–7.47 (m, 2H), 7.55–
7.58 (m, 1H), 7.95–7.96 (m, 2H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 14.0
(CH3), 21.0 (CH2), 30.3 (CH2), 45.7 (CH2), 51.0 (C), 62.3 (CH2), 70.0 (CH2), 128.0 (2
CH), 128.6 (2 CH) 133.6 (CH), 136.0 (C), 169.8 (C), 171.4 (C), 196.7 (C) ppm. IR
(ATR): λ–1 = 2978 (w), 2934 (w), 1718 (vs), 1689 (vs), 1597 (w), 1580 (w), 1449 (m),
1405 (m), 1353 (m), 1297 (m), 1282 (m), 1251 (m), 1197 (s), 1166 (m), 1138 (w),
1117 (m), 1099 (m), 1068 (m), 1022 (m), 1002 (m), 985 (s), 939 (w), 857 (m), 753 (s),
+
690 (s), 639 (m), 584 (m) cm–1. HRMS (ESI): calcd. 313.1047 (for C16H18NaO5 );
found 313.1046 [M + Na+]. C16H18O5 (290.32)
1
Ethyl 2ꢀ(2ꢀoxoꢀ2ꢀphenylethyl)cyclopentanoneꢀ2ꢀcarboxylate (7aa): H NMR (500
MHz, CDCl3): δ = 1.22 (t, J = 7.1 Hz, 3H), 2.04–2.20 (m, 3H), 2.47–2.53 (m, 1H),
2.57–2.67 (m, 2H), 3.46 (d, J = 18.5 Hz, 1H), 3.84 (d, J = 18.5 Hz, 1H), 4.16 (q, J =
7.1 Hz, 2H), 7.42–7.45 (m, 2H), 7.54–7.57 (m, 1H), 7.92–7.94 (m, 2H) ppm. The data
were in accordance with literature values.12
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Ethyl
3ꢀ[2ꢀoxoꢀ2ꢀ(4ꢀbromophenyl)ethyl]tetrahydropyranꢀ2ꢀoneꢀ3ꢀcarboxylate
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(11ab): CeCl3 — 7 H2O (3 mg, 8 ꢁmol) was added to a mixture of βꢀoxoester 5a (127
mg, 0.82 mmol) and enol ester 8b (298 mg, 1.23 mmol, 1.5 equiv.) in TFE (0.5 mL),
and the reaction mixture was stirred at 30°C for 24 h under an atmosphere of air.
Subsequently, all volatile materials were removed in vacuum and the residue was
purified by column chromatography (SiO2, hexanes/MTBE 3:1 → 1:1) to yield 1,4ꢀdiꢀ
ketone 7ab [54 mg, 0.15 mmol, 19%, Rf = 0.44 (hexanes/MTBE 1:1)] as a yellow soꢀ
lid (m.p. 103°C). Secondly, the αꢀhydroxylated compound 10a [49 mmol, 0.28 mmol,
35%, Rf = 0.33 (hexanes/MTBE 1:1)]) was obtained as a colorless oil. As a third fracꢀ
tion the title compound 11ab [134 mg, 0.36 mmol, 44%, Rf = 0.18 (hexanes/MTBE
1:1)] was eluted as a colorless solid (m.p. 78°C).
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Lactone 11ab: H NMR (500 MHz, CDCl3): δ = 1.31 (t, J = 7.1 Hz, 3H), 1.84–1.90
(m, 1H), 2.10–2.27 (m, 3H), 3.56 (d, J = 18.6 Hz, 1H), 4.00 (d, J = 18.5 Hz, 1H),
4.20–4.32 (m, 2H), 4.55–4.58 (m, 1H), 4.66–4.71 (m, 1H), 7.59–7.62 (m, 2H), 7.81–
7.84 (m, 2H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 14.0 (CH3), 21.1 (CH2), 30.3
(CH2), 45.7 (CH2), 51.1 (C), 62.4 (CH2), 70.0 (CH2), 128.9 (C), 129.6 (2 CH), 132.0 (2
CH), 134.8 (C), 169.8 (C), 171.4 (C), 195.8 (C) ppm. IR (ATR): λ–1 = 3004 (m), 2979
(m), 2938 (m), 2870 (w), 1726 (s), 1712 (vs), 1686 (s), 1583 (s), 1567 (m), 1470 (m),
1455 (m), 1441 (m), 1396 (s), 1346 (m), 1281 (m), 1247 (s), 1210 (w), 1194 (s), 1166
(s), 1141 (m), 1098 (m), 1068 (s), 1020 (m), 999 (s), 985 (m), 968 (m), 903 (m), 858
(s), 838 (m), 813 (s), 761 (w), 716 (m), 637 (s) cm–1. HRMS (ESI): calcd. 391.0152
+
(for C16H1779BrNaO5 ); found 391.0146 [M + Na+]. C16H17BrO5 (369.21).
1
Ethyl 2ꢀ[2ꢀoxoꢀ2ꢀ(4ꢀbromophenyl)ethyl]cyclopentanoneꢀ2ꢀcarboxylate (7ab): H
NMR (500 MHz, CDCl3): δ = 1.23 (t, J = 7.1 Hz, 3H), 2.04–2.22 (m, 3H), 2.49–2.67
(m, 3H), 3.41 (d, J = 18.5 Hz, 1H), 3.79 (d, J = 18.6 Hz, 1H), 4.16 (q, J = 7.1 Hz, 2H),
7.58–7.61 (m, 2H), 7.78–7.81 (m, 2H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 14.0
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(CH3), 19.8 (CH2), 33.4 (CH2), 37.7 (CH2), 43.3 (CH2), 57.4 (C), 61.7 (CH2), 128.7
(C), 129.5 (2 CH), 131.9 (2 CH), 135.0 (C), 170.6 (C), 195.8 (C), 214.9 (C) ppm. IR
(ATR): λ–1 = 2983 (m), 2960 (m), 2928 (m), 1762 (m), 1740 (vs), 1720 (vs), 1688 (vs),
1651 (m), 1583 (s), 1568 (m), 1486 (m), 1467 (m), 1443 (m), 1396 (s), 1368 (m),
1327 (m), 1259 (m), 1202 (s), 1155 (vs), 1091 (m), 1066 (m), 1044 (m), 1007 (s), 990
(s), 962 (m), 862 (m), 844 (m), 815 (s), 712 (w) cm–1. HRMS (ESI): calcd. 375.0208
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+
(for C16H1779BrNaO4 ); found 375.0216 [M + Na+]. C16H17BrO4 (353.21).
1
Ethyl 2ꢀhydroxycyclopentanoneꢀ2ꢀcarboxylate (10a): H NMR (500 MHz, CDCl3):
δ = 1.29 (t, J = 7.1 Hz, 3H), 2.08–2.14 (m, 3H), 2.43–2.53 (m, 3H), 3.63 (s, 1H),
4.23–4.28 (m, 2H) ppm. The data were in accordance with literature values.13b
Ethyl 3ꢀ[2ꢀoxoꢀ2ꢀ(4ꢀmethoxyphenyl)ethyl]tetrahydropyranꢀ2ꢀoneꢀ3ꢀcarboxylate
(11ac): CeCl3 — 7 H2O (6 mg, 15 ꢁmol) was added to a mixture of βꢀoxoester 5a (237
mg, 1.51 mmol) and enol ester 8c (444 mg, 2.31 mmol, 1.5 equiv.) in TFE (1 mL),
and the reaction mixture was stirred at 30°C for 24 h under an atmosphere of air.
Subsequently, all volatile materials were removed in vacuum and the residue was
purified by column chromatography (SiO2, hexanes/MTBE 2:1 → 1:1) to yield 1,4ꢀ
diketone 7ac [67 mg, 0.22 mmol, 15%, Rf = 0.34 (hexanes/MTBE 1:1)] as a colorless
oil. Secondly, the αꢀhydroxylated compound 10a [18 mg, 0.10 mmol, 7%, Rf = 0.31
(hexanes/MTBE 1:1)]) was obtained as a colorless oil. As a third fraction the title
compound 11ac [320 mg, 0.99 mmol, 66%, Rf = 0.10 (hexanes/MTBE 1:1)] was
eluted as a colorless oil.
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Lactone 11ac: H NMR (500 MHz, CDCl3): δ = 1.30 (t, J = 7.1 Hz, 3H), 1.83–1.88
(m, 1H), 2.09–2.24 (m, 3H), 3.57 (d, J = 18.4 Hz, 1H), 3.86 (s, 3H), 3.99 (d, J = 18.3
Hz, 1H), 4.19–4.31 (m, 2H), 4.52–4.56 (m, 1H), 4.67–4.72 (m, 1H), 6.90–6.93 (m,
2H), 7.92–7.95 (m, 2H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 14.0 (CH3), 21.1
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(CH2), 30.3 (CH2), 45.4 (CH2), 51.1 (C), 55.4 (CH3), 62.2 (CH2), 69.9 (CH2), 113.7 (2
CH), 129.3 (C), 130.3 (2 CH), 163.8 (C), 169.8 (C), 171.6 (C), 195.1 (C) ppm. IR
(ATR): λ–1 = 2958 (w), 2924 (m), 2853 (w), 1721 (vs), 1673 (s), 1600 (vs), 1575 (w),
1511 (w), 1457 (m), 1421 (w), 1407 (w), 1353 (m), 1282 (w), 1251 (s), 1198 (m),
1167 (vs), 1115 (m), 1026 (m), 997 (m), 987 (m), 831 (m), 640 (w) cm–1. HRMS
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(ESI): calcd. 343.1152 (for C17H20NaO6 ); found 343.1159 [M + Na+]. C17H20O6
+
(320.35).
Ethyl 2ꢀ[2ꢀoxoꢀ2ꢀ(4ꢀmethoxyphenyl)ethyl]cyclopentanoneꢀ2ꢀcarboxylate (7ac):
1H NMR (500 MHz, CDCl3): δ = 1.22 (t, J = 7.1 Hz, 3H), 2.04–2.19 (m, 3H), 2.42–
2.53 (m, 1H), 2.57–2.65 (m, 2H), 3.43 (d, J = 18.3 Hz, 1H), 3.78 (d, J = 18.3 Hz, 1H),
3.85 (s, 3H), 4.15 (q, J = 7.1 Hz, 2H), 6.89–6.92 (m, 2H), 7.89–7.92 (m, 2H) ppm.
The data were in accordance with literature values.12
Ethyl 3ꢀ{2ꢀoxoꢀ2ꢀ[3,5ꢀbis(trifluoromethyl)phenyl]ethyl}tetrahydropyranꢀ2ꢀoneꢀ3ꢀ
carboxylate (11ad): CeCl3 — 7 H2O (2 mg, 5 ꢁmol) was added to a mixture of βꢀoxoꢀ
ester 5a (82 mg, 0.53 mmol) and enol ester 8d (204 mg, 0.68 mmol, 1.3 equiv.) in
TFE (0.4 mL), and the reaction mixture was stirred at 30°C for 22 h under an atmoꢀ
sphere of air. Subsequently, all volatile materials were removed in vacuum and the
residue was purified by column chromatography (SiO2, hexanes/MTBE 1:1) to yield
1,4ꢀdiketone 7ad (45 mg, 0.11 mmol, 21%, Rf = 0.55) as a colorless oil. Secondly,
the αꢀhydroxylated compound 10a (18 mg, 0.10 mmol, 19%, Rf = 0.34) was obtained
as a colorless oil. As a third fraction the title compound 11ad (106 mg, 0.25 mmol,
47%, Rf = 0.29) was eluted as a colorless oil.
1
Lactone 11ad: H NMR (500 MHz, CDCl3): δ = 1.32 (t, J = 7.1 Hz, 3H), 1.89–1.95
(m, 1H), 2.16–2.24 (m, 3H), 3.61 (d, J = 18.6 Hz, 1H), 4.04 (d, J = 18.6 Hz, 1H),
4.22–4.34 (m, 2H), 4.56–4.60 (m, 1H), 4.64–4.69 (m, 1H), 8.08 (s, 1H), 8.39 (s, 2H)
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ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 14.0 (CH3), 21.0 (CH2), 30.3 (CH2), 45.7
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(CH2), 51.3 (C), 62.6 (CH2), 70.1 (CH2), 122.8 (q, JCF = 273.1 Hz, 2 CF3), 126.7–
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126.8 (m, CH), 128.1 (q, JCF = 4.0 Hz, 2 CH), 132.5 (q, JCF = 34.1 Hz, 2 C), 137.6
(C), 169.4 (C), 171.1 (C), 194.4 (C) ppm. 19F{1H} NMR (470 MHz, CDCl3): δ = –63.0
(s, 2 CF3) ppm. IR (ATR): λ–1 = 2981 (w), 1726 (m), 1670 (m), 1620 (w), 1453 (w),
1371 (w), 1349 (w), 1276 (s), 1250 (m), 1170 (s), 1126 (s), 1020 (w), 988 (w), 902
(m), 844 (m), 699 (m), 681 (s) cm–1. HRMS (ESI): calcd. 449.0794 (for
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+
C18H16F6NaO5 ); found 449.0801 [M + Na+]. C18H16F6O5 (426.31).
Ethyl 2ꢀ{2ꢀoxoꢀ2ꢀ[3,5ꢀbis(trifluoromethyl)phenyl]ethyl}cyclopentanoneꢀ2ꢀcarboꢀ
xylate (7ad): 1H NMR (500 MHz, CDCl3): δ = 1.24 (t, J = 7.1 Hz, 3H), 2.07–2.15 (m,
2H), 2.18–2.26 (m, 1H), 2.55–2.58 (m, 2H), 2.67–2.72 (m, 1H), 3.43 (d, J = 18.6 Hz,
1H), 3.85 (d, J = 18.6 Hz, 1H), 4.14–4.23 (m, 2H), 8.07 (s, 1H), 8.37 (s, 2H) ppm.
13C{1H} NMR (125 MHz, CDCl3): δ = 14.0 (CH3), 19.8 (CH2), 33.4 (CH2), 37.6 (CH2),
43.3 (CH2), 57.5 (C), 61.9 (CH2), 122.8 (q, 1JCF = 273.2 Hz, 2 CF3), 126.5–126.6 (m,
2
CH), 128.1 (q, 3JCF = 4.1 Hz, 2 CH), 132.5 (q, JCF = 34.0 Hz, 2 C), 137.9 (C), 170.3
19
(C), 194.3 (C), 214.3 (C) ppm. F{1H} NMR (470 MHz, CDCl3): δ = –63.1 (s, 2 CF3)
ppm. IR (ATR): λ–1 = 2986 (w), 1754 (m), 1726 (m), 1704 (m), 1621 (w), 1453 (w),
1388 (w), 1345 (w), 1278 (s), 1174 (s), 1230 (s), 1229 (w), 911 (m), 845 (m), 701 (m),
+
683 (s) cm–1. HRMS (ESI): calcd. 433.0845 (for C18H16F6NaO4 ); found 433.0847 [M
+ Na+]. C18H16F6O4 (410.31).
Ethyl 3ꢀ[2ꢀoxoꢀ2ꢀ(2,4ꢀdifluorophenyl)ethyl]tetrahydropyranꢀ2ꢀoneꢀ3ꢀcarboxylate
(11ae): CeCl3 — 7 H2O (5 mg, 13 ꢁmol) was added to a mixture of βꢀoxoester 5a (240
mg, 1.54 mmol) and enol ester 8e (455 mg, 2.29 mmol, 1.5 equiv.) in TFE (1 mL),
and the reaction mixture was stirred at 30°C for 24 h under an atmosphere of air.
Subsequently, all volatile materials were removed in vacuum and the residue was
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purified by column chromatography (SiO2, hexanes/MTBE 3:1 → 1:1) to yield 1,4ꢀ
diketone 7ae [103 mg, 0.33 mmol, 22%, Rf = 0.50 (hexanes/MTBE 1:1)] as a
colorless oil. Secondly, the αꢀhydroxylated compound 10a [85 mg, 0.49 mmol, 32%,
Rf = 0.32 (hexanes/MTBE 1:1)]) was obtained as a colorless oil. As a third fraction
the title compound 11ae [190 mg, 0.58 mmol, 38%, Rf = 0.25 (hexanes/MTBE 1:1)]
was eluted as a colorless oil.
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Lactone 11ae: H NMR (500 MHz, CDCl3): δ = 1.27 (t, J = 7.1 Hz, 3H), 1.81–1.88
(m, 1H), 2.10–2.18 (m, 3H), 3.52 (dd, J = 19.2 Hz, J = 3.7 Hz, 1H), 3.95 (dd, J = 19.2
Hz, J = 3.4 Hz, 1H), 4.17–4.28 (m, 2H), 4.50–4.54 (m, 1H), 4.60–4.65 (m, 1H), 6.86
(ddd, JHF = 11.1 Hz, JHF = 8.6 Hz, JHH = 2.4 Hz, 1H), 6.91–6.95 (m, 1H), 7.92 (td, JHF
= 8.6 Hz, JHH = 6.5 Hz, 1H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 14.0 (CH3),
4
21.0 (CH2), 30.2 (CH2), 49.9 (d, JCF = 9.1 Hz, CH2), 51.2 (d, 5JCF = 2.0 Hz, C), 62.2
2
2
2
(CH2), 69.9 (CH2), 104.8 (dd, JCF = 27.7 Hz, JCF = 25.5 Hz, CH), 112.3 (dd, JCF
=
21.4 Hz, 4JCF = 3.4 Hz, CH), 121.1 (dd, 3JCF = 12.8 Hz, 4JCF = 3.6 Hz, C), 132.6 (dd,
3
1
3
3JCF = 10.8 Hz, JCF = 3.9 Hz, CH), 162.9 (dd, JCF = 258.7 Hz, JCF = 12.7 Hz, CF),
166.1 (dd, 1JCF = 258.2 Hz, 3JCF = 12.4 Hz, CF), 169.7 (C), 171.1 (C), 193.2 (d, 3JCF
=
4.6 Hz, C) ppm. 19F{1H} NMR (470 MHz, CDCl3): δ = –100.5 (d, J = 12.7 Hz, 1F), –
102.8 (d, J = 12.7 Hz, 1F) ppm. IR (ATR): λ–1 = 2979 (w), 1739 (s), 1720 (s), 1683
(s), 1609 (s), 1497 (m), 1477 (w), 1428 (m), 1403 (m), 1356 (m), 1298 (m), 1286 (m),
1268 (m), 1250 (s), 1231 (s), 1195 (s), 1168 (m), 1141 (m), 1818 (m), 1068 (m), 1024
(m), 1004 (w), 986 (m), 969 (s), 940 (w), 906 (w), 854 (s), 819 (m), 734 (m), 703 (w)
+
cm–1. HRMS (ESI): calcd. 327.1039 (for C16H17F2O5 ); found 327.1056 [M + H+].
C16H16F2O5 (326.30).
Ethyl 2ꢀ[2ꢀoxoꢀ2ꢀ(2,4ꢀdifluorophenyl)ethyl]cyclopentanoneꢀ2ꢀcarboxylate (7ae):
1H NMR (500 MHz, CDCl3): δ = 1.23 (t, J = 7.2 Hz, 3H), 2.02–2.11 (m, 2H), 2.12–
2.21 (m, 1H), 2.47–2.60 (m, 2H), 2.64–2.69 (m, 1H), 3.41 (dd, J = 19.2 Hz, J = 3.4
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Hz, 1H), 3.74 (dd, J = 19.1 Hz, J = 3.5 Hz, 1H), 4.16 (q, J = 7.1 Hz, 2H), 6.87 (ddd,
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J
HF = 11.1 Hz, JHF = 8.6 Hz, JHH = 2.4 Hz, 1H), 6.93–6.96 (m, 1H), 7.90 (td, JHF = 8.7
Hz, JHH = 6.6 Hz, 1H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 14.0 (CH3), 19.8
(CH2), 33.4 (CH2), 37.6 (CH2), 47.8 (d, 4JCF = 8.7 Hz, CH2), 57.7 (d, 5JCF = 1.5 Hz, C),
61.6 (CH2), 104.8 (dd, 2JCF = 27.7 Hz, 2JCF = 25.5 Hz, CH), 112.3 (dd, 2JCF = 21.5 Hz,
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4JCF = 3.3 Hz, CH), 121.5 (dd, JCF = 13.2 Hz, JCF = 3.5 Hz, C), 132.6 (dd, JCF
=
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10.5 Hz, JCF = 4.1 Hz, CH), 162.8 (dd, JCF = 258.8 Hz, JCF = 12.5 Hz, CF), 166.0
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3
3
(dd, JCF = 257.9 Hz, JCF = 12.2 Hz, CF), 170.4 (C), 193.3 (d, JCF = 4.7 Hz, C),
214.5 (C) ppm. 19F{1H} NMR (470 MHz, CDCl3): δ = –101.1 (d, J = 12.4 Hz, 1F), –
103.0 (d, J = 12.5 Hz, 1F) ppm. IR (ATR): λ–1 = 2981 (w), 1753 (s), 1724 (s), 1688
(s), 1611 (s), 1500 (m), 1430 (m), 1404 (w), 1359 (m), 1323 (w), 1269 (s), 1235 (s),
1201 (m), 1144 (s), 1099 (s), 1047 (w), 1034 (w), 996 (m), 972 (s), 927 (w), 854 (s),
+
820 (m), 735 (m) cm–1. HRMS (ESI): calcd. 311.1089 (for C16H17F2O4 ); found
311.1101 [M + H+]. C16H16F2O4 (310.30).
Ethyl
3ꢀ[2ꢀoxoꢀ2ꢀ(4ꢀnitrophenyl)ethyl]tetrahydropyraneꢀ2ꢀoneꢀ3ꢀcarboxylate
(11af): CeCl3 — 7 H2O (2 mg, 5 ꢁmol) was added to a mixture of βꢀoxoester 5a (83
mg, 0.51 mmol) and enol ester 8f (150 mg, 0.72 mmol, 1.4 equiv.) in TFE (0.3 mL),
and the reaction mixture was stirred at 30°C for 24 h under an atmosphere of air.
Subsequently, all volatile materials were removed in vacuum and the residue was
purified by column chromatography (SiO2, hexanes/MTBE 1:1) to yield the αꢀhydroxyꢀ
lated compound 10a (31 mg, 0.18 mmol, 36%, Rf = 0.32) was obtained as a colorless
oil. Secondly, the 1,4ꢀdiketone 7af (4 mg, 0.01 mmol, 2%, Rf = 0.30) as a colorless
oil. As a third fraction the title compound 11af (12 mg, 0.04 mmol, 7%, Rf = 0.10) was
eluted as a yellow solid (m.p. 116°C).
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Lactone 11af: 1H NMR (500 MHz, CDCl3): δ = 1.32 (t, J = 7.1 Hz, 3H), 1.89–1.94 (m,
1H), 2.15–2.25 (m, 3H), 3.62 (d, J = 18.6 Hz, 1H), 4.06 (d, J = 18.6 Hz, 1H), 4.22–
4.33 (m, 2H), 4.57–4.61 (m, 1H), 4.66–4.71 (m, 1H), 8.11–8.15 (m, 2H), 8.30–8.33
(m, 2H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 14.0 (CH3), 21.0 (CH2), 30.3
(CH2), 46.1 (CH2), 51.2 (C), 62.6 (CH2), 70.1 (CH2), 123.9 (2 CH), 129.2 (2 CH),
140.4 (C), 150.6 (C), 169.6 (C), 171.1 (C), 195.4 (C) ppm. IR (ATR): λ–1 = 3115 (w),
3053 (w), 2963 (w), 2914 (w), 1739 (vs), 1708 (vs), 1682 (vs), 1600 (m), 1519 (vs),
1474 (w), 1405 (w), 1347 (vs), 1294 (m), 1244 (s), 1227 (vs), 1192 (vs), 1165 (vs),
1135 (m), 1113 (s), 1099 (s), 1063 (m), 1030 (m), 989 (m), 908 (w), 856 (s), 830 (m),
746 (s), 711 (w), 688 (m), 639 (m) cm–1. HRMS (ESI): calcd. 358.0897 (for
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+
C16H17NNaO7 ); found 358.0895 [M + Na+]. C16H17NO7 (335.31).
Ethyl 2ꢀ[2ꢀoxoꢀ2ꢀ(4ꢀnitrophenyl)ethyl]cyclopentanoneꢀ2ꢀcarboxylate (7af): 1H
NMR (500 MHz, CDCl3): δ = 1.23 (t, J = 7.1 Hz, 3H), 2.08–2.15 (m, 2H), 2.19–2.24
(m, 1H), 2.55–2.59 (m, 2H), 2.67–2.70 (m, 1H), 3.45 (d, J = 18.6 Hz, 1H), 3.85 (d, J =
18.6 Hz, 1H), 4.15–4.21 (m, 2H), 8.09–8.12 (m, 2H), 8.30–8.33 (m, 2H) ppm. The
data were in accordance with literature values.12
Ethyl 3ꢀ[2ꢀoxoꢀ2ꢀ(2ꢀthienyl)ethyl]tetrahydropyranꢀ2ꢀoneꢀ3ꢀcarboxylate (11ag):
CeCl3 — 7 H2O (5 mg, 13 ꢁmol) was added to a mixture of βꢀoxoester 5a (200 mg,
1.28 mmol) and enol ester 8g (280 mg, 1.66 mmol, 1.3 equiv.) in TFE (1 mL), and the
reaction mixture was stirred at 30°C for 20 h under an atmosphere of air. Subseꢀ
quently, all volatile materials were removed in vacuum and the residue was purified
by column chromatography (SiO2, hexanes/MTBE 9:1 → 1:1) to yield the 1,4ꢀdikeꢀ
tone 7ag [64 mg, 0.23 mmol, 18%, Rf = 0.41 (hexanes/MTBE 1:1)] as a colorless oil.
Secondly, the title compound 11ag [210 mg, 0.71 mmol, 55%, Rf = 0.18 (hexꢀ
anes/MTBE 1:1)] was eluted as a yellow oil.
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Lactone 11ag: H NMR (500 MHz, CDCl3): δ = 1.28 (t, J = 7.1 Hz, 3H), 1.81–1.88
(m, 1H), 2.11–2.21 (m, 3H), 3.52 (d, J = 18.2 Hz, 1H), 3.95 (d, J = 18.2 Hz, 1H),
4.17–4.28 (m, 2H), 4.49–4.52 (m, 1H), 4.58–4.65 (m, 1H), 7.11 (dd, J = 4.9 Hz, J =
3.9 Hz, 1H), 7.64 (dd, J = 4.9 Hz, J = 0.9 Hz, 1H), 7.74 (dd, J = 3.8 Hz, J = 0.9 Hz,
1H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 13.9 (CH3), 21.0 (CH2), 30.2 (CH2),
45.8 (CH2), 51.0 (C), 62.2 (CH2), 69.9 (CH2), 128.1 (CH), 132.4 (CH), 134.1 (CH),
143.1 (C), 169.5 (C), 171.2 (C), 189.5 (C) ppm. IR (ATR): λ–1 = 3093 (w), 2975 (w),
2934 (w), 1716 (vs), 1657 (s), 1519 (w), 1453 (w), 1414 (s), 1360 (m), 1281 (m),
1252 (m), 1222 (m), 1196 (s), 1166 (m), 1137 (w), 1117 (m), 1068 (w), 1058 (w),
1021 (m), 986 (m), 951 (w), 856 (m), 823 (w), 730 (s), 638 (w) cm–1. HRMS (ESI):
calcd. 319.0611 (for C14H16NaO5S+); found 319.0618 [M + Na+]. C14H16O5S (296.34).
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Ethyl 2ꢀ[2ꢀoxoꢀ2ꢀ(2ꢀthienyl)ethyl]cyclopentanoneꢀ2ꢀcarboxylate (7ag): H NMR
(500 MHz, CDCl3): δ = 1.23 (t, J = 7.1 Hz, 3H), 2.02–2.21 (m, 3H), 2.45–2.68 (m,
3H), 3.42 (d, J = 18.1 Hz, 1H), 3.75 (d, J = 18.2 Hz, 1H), 4.16 (q, J = 7.1 Hz, 2H),
7.12 (dd, J = 5.0 Hz, J = 3.8 Hz, 1H), 7.63 (dd, J = 4.9 Hz, J = 1.1 Hz, 1H), 7.73 (dd,
J = 3.8 Hz, J = 1.2 Hz, 1H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 13.9 (CH3),
19.2 (CH2), 33.3 (CH2), 37.6 (CH2), 43.6 (CH2), 57.4 (C), 61.7 (CH2), 128.2 (CH),
132.3 (CH), 133.9 (CH), 143.4 (C), 170.5 (C), 189.7 (C), 214.8 (C) ppm. IR (ATR): λ–1
= 3106 (w), 3088 (w), 2977 (w), 2963 (w), 2917 (w), 1750 (s), 1722 (vs), 1662 (s),
1519 (w), 1447 (w), 1416 (s), 1360 (w), 1323 (w), 1263 (m), 1228 (s), 1191 (m), 1152
(m), 1103 (w), 1060 (w), 939 (w), 731 (m) cm–1. HRMS (ESI): calcd. 303.0667 (for
C14H16NaO4S+); found 303.0676 [M + Na+]. C14H16O4S (280.34).
Ethyl
3ꢀ[2ꢀoxoꢀ2ꢀ(2ꢀfuryl)ethyl]tetrahydropyranꢀ2ꢀoneꢀ3ꢀcarboxylate
(11ah):
CeCl3 — 7 H2O (5 mg, 13 ꢁmol) was added to a mixture of βꢀoxoester 5a (201 mg,
1.28 mmol) and enol ester 8h (253 mg, 1.66 mmol, 1.3 equiv.) in TFE (1 mL), and the
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reaction mixture was stirred at 30°C for 20 h under an atmosphere of air. Subseꢀ
quently, all volatile materials were removed in vacuum and the residue was purified
by column chromatography (SiO2, hexanes/MTBE 1:1 → 1:2) to yield the 1,4ꢀdikeꢀ
tone 7ah [69 mg, 0.26 mmol, 20%, Rf = 0.29 (hexanes/MTBE 1:1)] as a colorless oil.
Secondly, the title compound 11ah [196 mg, 0.70 mmol, 55%, Rf = 0.08 (hexꢀ
anes/MTBE 1:1)] was eluted as a light yellow oil.
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Lactone 11ah: H NMR (500 MHz, CDCl3): δ = 1.29 (t, J = 7.1 Hz, 3H), 1.81–1.87
(m, 1H), 2.12–2.20 (m, 3H), 3.47 (d, J = 18.5 Hz, 1H), 3.86 (d, J = 18.6 Hz, 1H),
4.18–4.29 (m, 2H), 4.50–4.53 (m, 1H), 4.59–4.65 (m, 1H), 6.53 (dd, J = 3.6 Hz, J =
1.7 Hz, 1H), 7.21 (d, J = 3.6 Hz, 1H), 7.57 (d, J = 1.7 Hz, 1H) ppm. 13C{1H} NMR (125
MHz, CDCl3): δ = 14.0 (CH3), 21.0 (CH2), 30.2 (CH2), 45.0 (CH2), 50.8 (C), 62.3
(CH2), 69.9 (CH2), 112.4 (CH), 117.6 (CH), 146.7 (CH), 152.0 (C), 169.6 (C), 171.2
(C), 185.7 (C) ppm. IR (ATR): λ–1 = 3131 (w), 2980 (w), 2938 (w), 1722 (vs), 1674 (s),
1571 (w), 1468 (s), 1399 (m), 1351 (w), 1281 (m), 1241 (m), 1200 (m), 1164 (m),
1120 (w), 1068 (w), 1021 (m), 985 (m), 883 (w), 857 (w), 770 (m), 637 (w) cm–1.
+
HRMS (ESI): calcd. 303.0840 (for C14H16NaO6 ); found 303.0839 [M + Na+].
C14H16O6 (280.28).
Ethyl 2ꢀ[2ꢀoxoꢀ2ꢀ(2ꢀfuryl)ethyl]cyclopentanoneꢀ2ꢀcarboxylate (7ah): 1H NMR
(500 MHz, CDCl3): δ = 1.23 (t, J = 7.1 Hz, 3H), 2.03–2.18 (m, 3H), 2.45–2.63 (m,
3H), 3.33 (d, J = 18.4 Hz, 1H), 3.67 (d, J = 18.4 Hz, 1H), 4.12–4.21 (m, 2H), 6.53 (dd,
J = 3.5 Hz, J = 1.7 Hz, 1H), 7.19 (dd, J = 3.6 Hz, J = 0.7 Hz, 1H), 7.57 (dd, J = 1.7
Hz, J = 0.8 Hz, 1H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 14.0 (CH3), 19.8 (CH2),
33.3 (CH2), 37.6 (CH2), 42.7 (CH2), 57.2 (C), 61.7 (CH2), 112.3 (CH), 117.3 (CH),
146.5 (CH), 152.2 (C), 170.6 (C), 185.8 (C), 214.7 (C) ppm. IR (ATR): λ–1 = 2982 (w),
2909 (w), 1750 (s), 1724 (vs), 1679 (m), 1570 (w), 1469 (m), 1399 (w), 1368 (w),
1323 (w), 1278 (w), 1229 (m), 1158 (m), 1109 (w), 1019 (m), 769 (w), 634 (w) cm–1.
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HRMS (ESI): calcd. 287.0892 (for C14H16NaO5 ); found 287.0902 [M + Na+].
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C14H16O5 (264.28).
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Ethyl 3ꢀ{2ꢀoxoꢀ2ꢀ[1ꢀ(4ꢀmethylphenylsulfonyl)pyrrolꢀ2ꢀyl]ethyl}tetrahydropyranꢀ2ꢀ
oneꢀ3ꢀcarboxylate (11ai): CeCl3 — 7 H2O (5 mg, 13 ꢁmol) was added to a mixture of
βꢀoxoester 5a (200 mg, 1.28 mmol) and enol ester 8i (507 mg, 1.66 mmol, 1.3 equiv.)
in TFE (1 mL), and the reaction mixture was stirred at 30°C for 22 h under an atmoꢀ
sphere of air. Subsequently, all volatile materials were removed in vacuum and the
residue was purified by column chromatography (SiO2, hexanes/MTBE 3:1 → 1:1) to
yield the αꢀhydroxylated compound 10a [53 mg, 0.31 mmol, 24%, Rf = 0.31 (hexꢀ
anes/MTBE 1:1)] as a colorless oil. Secondly, the 1,4ꢀdiketone 7ai [87 mg, 0.21
mmol, 16%, Rf = 0.27 (hexanes/MTBE 1:1)]) was obtained as a colorless oil. As a
third fraction the title compound 11ai [201 mg, 0.46 mmol, 36%, Rf = 0.10 (hexꢀ
anes/MTBE 1:1)] was eluted as a yellow oil.
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Lactone 11ai: 1H NMR (300 MHz, CDCl3): δ = 1.23 (t, J = 7.2 Hz, 3H), 1.75–1.82 (m,
1H), 2.00–2.19 (m, 3H), 2.38 (s, 3H), 3.33 (d, J = 17.9 Hz, 1H), 3.70 (d, J = 17.9 Hz,
1H), 4.09–4.28 (m, 2H), 4.45–4.60 (m, 2H), 6.30 (dd, J = 3.7 Hz, J = 3.2 Hz, 1H),
7.08 (dd, J = 3.8 Hz, J = 1.7 Hz, 1H), 7.25–7.28 (m, 2H), 7.75 (dd, J = 3.2 Hz, J = 1.7
Hz, 1H), 7.82–7.86 (m, 2H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 13.9 (CH3),
21.0 (CH2), 21.6 (CH3), 30.0 (CH2), 45.7 (CH2), 51.0 (C), 62.2 (CH2), 69.8 (CH2),
110.4 (CH), 123.8 (CH), 128.4 (2 CH), 129.3 (2 CH), 130.3 (CH), 132.4 (C), 135.3
(C), 145.0 (C), 169.5 (C), 171.1 (C), 184.8 (C) ppm. IR (ATR): λ–1 = 2984 (w), 2946
(w), 1724 (vs), 1675 (m), 1596 (w), 1439 (w), 1405 (m), 1364 (w), 1304 (w), 1245
(m), 1171 (s), 1143 (m), 1090 (m), 1020 (w), 815 (m), 736 (m), 670 (s) cm–1. HRMS
(ESI): calcd. 456.1088 (for C21H23NNaO7S+); found 456.1087 [M + Na+]. C21H23NO7S
(433.48).
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Ethyl 2ꢀ{2ꢀoxoꢀ2ꢀ[1ꢀ(4ꢀmethylphenylsulfonyl)pyrrolꢀ2ꢀyl]ethyl}cyclopentanoneꢀ2ꢀ
carboxylate (7ai): 1H NMR (300 MHz, CDCl3): δ = 1.12 (t, J = 7.1 Hz, 3H), 1.92–2.16
(m, 3H), 2.36–2.47 (m, 2H), 2.40 (s, 3H), 2.50–2.58 (m, 1H), 3.13 (d, J = 17.7 Hz,
1H), 3.52 (d, J = 17.7 Hz, 1H), 3.98–4.13 (m, 2H), 6.31 (dd, J = 3.7 Hz, J = 3.2 Hz,
1H), 7.06 (dd, J = 3.8 Hz, J = 1.7 Hz, 1H), 7.24–7.31 (m, 2H), 7.76 (dd, J = 3.2 Hz, J
= 1.7 Hz, 1H), 7.81–7.86 (m, 2H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 13.9
(CH3), 19.8 (CH2), 21.6 (CH3), 33.2 (CH2), 37.7 (CH2), 43.5 (CH2), 57.5 (C), 61.6
(CH2), 110.4 (CH), 123.6 (CH), 128.5 (2 CH), 129.2 (2 CH), 130.2 (CH), 132.6 (C),
135.6 (C), 144.9 (C), 170.4 (C), 184.8 (C), 214.6 (C) ppm. IR (ATR): λ–1 = 2977 (w),
2930 (w), 1748 (s), 1721 (vs), 1678 (m), 1596 (w), 1439 (m), 1403 (m), 1365 (m),
1228 (w), 1172 (vs), 1143 (vs), 1091 (m), 1016 (m), 953 (w), 856 (w), 814 (m), 755
(m), 671 (s) cm–1. HRMS (ESI): calcd. 440.1138 (for C21H23NNaO6S+); found
440.1155 [M + Na+]. C21H23NO6S (417.48).
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Isobutyl 3ꢀ(2ꢀoxoꢀ2ꢀphenylethyl)tetrahydropyranꢀ2ꢀoneꢀ3ꢀcarboxylate (11ba):
CeCl3 — 7 H2O (5 mg, 13 ꢁmol) was added to a mixture of βꢀoxoester 5b (221 mg,
1.20 mmol) and enol ester 8a (389 mg, 2.40 mmol, 2.0 equiv.) in TFE (1 mL), and the
reaction mixture was stirred at 30°C for 24 h under an atmosphere of air. Subseꢀ
quently, all volatile materials were removed in vacuum and the residue was purified
by column chromatography (SiO2, hexanes/MTBE 2:1) to yield 1,4ꢀdiketone 7ba (106
mg, 0.35 mmol, 29%, Rf = 0.34) as a colorless oil. Secondly, the αꢀhydroxylated comꢀ
pound 10b (16 mg, 0.08 mmol, 7%, Rf = 0.23) was eluted as a colorless oil. As a third
fraction the title compound 11ba (244 mg, 0.77 mmol, 64%, Rf = 0.14) was eluted as
a colorless oil.
Lactone 11ba: 1H NMR (500 MHz, CDCl3): δ = 0.93 (d, J = 6.8 Hz, 3H), 0.94 (d, J =
6.8 Hz, 3H), 1.84–1.89 (m, 1H), 1.97 (nonet, J = 6.7 Hz, 1H), 2.10–2.24 (m, 3H), 3.62
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(d, J = 18.6 Hz, 1H), 3.93–4.00 (m, 2H), 4.03 (d, J = 18.6 Hz, 1H), 4.52–4.56 (m, 1H),
4.67–4.72 (m, 1H), 7.42–7.45 (m, 2H), 7.54–7.57 (m, 1H), 7.93–7.95 (m, 2H) ppm.
13C{1H} NMR (125 MHz, CDCl3): δ = 18.9 (2 CH3), 21.0 (CH2), 27.6 (CH), 30.23
(CH2), 45.7 (CH2), 51.0 (C), 69.9 (CH2), 72.1 (CH2), 128.0 (2 CH), 128.5 (2 CH) 133.6
(CH), 136.0 (C), 169.7 (C), 171.5 (C), 196.7 (C) ppm. IR (ATR): λ–1 = 2965 (w), 2936
(w), 2878 (w), 1724 (vs), 1686 (s), 1599 (w), 1452 (m), 1407 (m), 1356 (m), 1284 (m),
1252 (s), 1219 (m), 1200 (s), 1170 (m), 1121 (m), 1003 (m), 988 (m), 945 (w), 756
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(m), 692 (m), 642 (w) cm–1. HRMS (ESI): calcd. 319.1540 (for C18H23O5 ); found
319.1558 [M + H+]. C18H22O5 (318.37).
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Isobutyl 2ꢀ(2ꢀoxoꢀ2ꢀphenylethyl)cyclopentanoneꢀ2ꢀcarboxylate (7ba): H NMR
(500 MHz, CDCl3): δ = 0.89 (d, J = 6.8 Hz, 6H), 1.92 (nonet, J = 6.6 Hz, 1H), 2.06–
2.23 (m, 3H), 2.52 (dddd, J = 18.6 Hz, J = 8.5 Hz, J = 3.6 Hz, J = 1.0 Hz, 1H), 2.60–
2.67 (m, 2H), 3.49 (d, J = 18.6 Hz, 1H), 3.85 (d, J = 18.5 Hz, 1H), 3.90 (d, J = 6.5 Hz,
2H), 7.43–7.46 (m, 2H), 7.55–7.58 (m, 1H), 7.93–7.95 (m, 2H) ppm. 13C{1H} NMR
(125 MHz, CDCl3): δ = 19.0 (2 CH3), 19.9 (CH2), 27.7 (CH), 33.4 (CH2), 37.7 (CH2),
43.5 (CH2), 57.4 (C), 71.6 (CH2), 128.0 (2 CH), 128.6 (2 CH), 133.4 (CH), 136.3 (C),
170.8 (C), 196.7 (C), 214.9 (C) ppm. IR (ATR): λ–1 = 2962 (m), 2875 (w), 1751 (s),
1722 (vs), 1689 (vs), 1597 (w), 1470 (w), 1449 (m), 1402 (w), 1354 (m), 1260 (m),
1221 (vs), 1152 (m), 1106 (m), 1027 (w), 991 (m), 922 (w), 753 (s), 690 (m) cm–1.
+
HRMS (ESI): calcd. 303.1591 (for C18H23O4 ); found 303.1588 [M + H+]. C18H22O4
(302.37).
Isobutyl 2ꢀhydroxycyclopentanoneꢀ2ꢀcarboxylate (10b): 1H NMR (500 MHz,
CDCl3): δ = 0.92 (d, J = 6.7 Hz, 6H), 1.96 (nonet, J = 6.7 Hz, 1H), 2.07–2.16 (m, 3H),
2.42–2.54 (m, 3H), 3.67 (s, 1H), 3.95–4.04 (m, 2H) ppm. 13C{1H} NMR (125 MHz,
CDCl3): δ = 18.4 (CH2), 18.9 (2 CH3), 27.7 (CH), 34.8 (CH2), 35.8 (CH2), 72.4 (CH2),
79.8 (C), 171.6 (C), 213.3 (C) ppm. IR (ATR): λ–1 = 3481 (m), 2966 (m), 2878 (w),
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1758 (s), 1731 (vs), 1472 (m), 1373 (m), 1257 (m), 1166 (s), 1100 (m), 1051 (m),
1010 (m), 984 (m), 946 (m), 917 (m), 823 (w), 786 (w) cm–1. GCMS (EI, 70 eV): m/z
(%) 200 (0.5) [M+], 144 (27) [M+ – C4H8), 88 (82) [M+ – C6H8O2], 57 (100) [M+ –
C6H8O4]. C10H16O4 (200.23).
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Isobutyl 3ꢀ[2ꢀoxoꢀ2ꢀ(4ꢀmethoxyphenyl)ethyl]tetrahydropyranꢀ2ꢀoneꢀ3ꢀcarboxylaꢀ
te (11bc): CeCl3 — 7 H2O (5 mg, 13 ꢁmol) was added to a mixture of βꢀoxoester 5b
(220 mg, 1.20 mmol) and enol ester 8c (346 mg, 1.80 mmol, 1.5 equiv.) in TFE (1
mL), and the reaction mixture was stirred at 30°C for 24 h under an atmosphere of
air. Subsequently, all volatile materials were removed in vacuum and the residue was
purified by column chromatography (SiO2, hexanes/MTBE 1:1) to yield 1,4ꢀdiketone
7bc (83 mg, 0.25 mmol, 21%, Rf = 0.42) as a colorless oil. Secondly, the αꢀhydroxyꢀ
lated compound 10b (5 mg, 0.02 mmol, 2%, Rf = 0.36) was eluted as a colorless oil.
As a third fraction the title compound 11bc (309 mg, 0.89 mmol, 74%, Rf = 0.22) was
eluted as a light yellow oil.
Lactone 11bc: 1H NMR (500 MHz, CDCl3): δ = 0.93 (d, J = 6.8 Hz, 3H), 0.94 (d, J =
6.8 Hz, 3H), 1.82–1.87 (m, 1H), 1.97 (nonet, J = 6.7 Hz, 1H), 2.07–2.23 (m, 3H), 3.57
(d, J = 18.3 Hz, 1H), 3.84 (s, 3H), 3.96–4.00 (m, 2H), 3.98 (d, J = 18.4 Hz, 1H), 4.51–
4.56 (m, 1H), 4.66–4.72 (m, 1H), 6.89–6.92 (m, 2H), 7.90–7.93 (m, 2H) ppm. 13C{1H}
NMR (125 MHz, CDCl3): δ = 18.9 (CH3), 19.0 (CH3), 21.1 (CH2), 27.6 (CH), 30.3
(CH2), 45.4 (CH2), 51.0 (C), 55.4 (CH3), 69.9 (CH2), 72.1 (CH2), 113.7 (2 CH), 129.2
(C), 130.3 (2 CH), 163.8 (C), 169.8 (C), 171.6 (C), 195.1 (C) ppm. IR (ATR): λ–1
=
2964 (w), 2936 (w), 2876 (w), 2843 (w), 1739 (s), 1723 (vs), 1673 (m), 1601 (vs),
1575 (w), 1511 (w), 1470 (w), 1407 (w), 1353 (w), 1251 (s), 1223 (m), 1169 (vs),
1118 (m), 1029 (w), 998 (m), 831 (m), 640 (w) cm–1. HRMS (ESI): calcd. 349.1646
+
(for C19H25O6 ); found 349.1644 [M + H+]. C19H24O6 (348.40).
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(7bc): H NMR (500 MHz, CDCl3): δ = 0.89 (d, J = 6.8 Hz, 6H), 1.91 (nonet, J = 6.7
Hz, 1H), 2.05–2.21 (m, 3H), 2.50 (dddd, J = 18.8 Hz, J = 8.8 Hz, J = 3.9 Hz, J = 1.2
Hz, 1H), 2.59–2.67 (m, 2H), 3.46 (d, J = 18.4 Hz, 1H), 3.80 (d, J = 18.4 Hz, 1H), 3.85
(s, 3H), 3.89 (d, J = 6.5 Hz, 2H), 6.90–6.92 (m, 2H), 7.89–7.92 (m, 2H) ppm. 13C{1H}
NMR (125 MHz, CDCl3): δ = 19.0 (2 CH3), 19.8 (CH2), 27.7 (CH), 33.4 (CH2), 37.7
(CH2), 43.2 (CH2), 55.5 (CH3), 57.4 (C), 71.6 (CH2), 113.7 (2 CH), 129.4 (C), 130.3 (2
CH), 164.7 (C), 170.9 (C), 195.2 (C), 215.1 (C) ppm. IR (ATR): λ–1 = 2962 (m), 2876
(w), 1751 (s), 1722 (vs), 1677 (m), 1601 (vs), 1576 (w), 1511 (w), 1468 (w), 1403 (w),
1354 (w), 1259 (s), 1225 (s), 1169 (vs), 1112 (m), 1028 (w), 988 (m), 833 (m) cm–1.
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HRMS (ESI): calcd. 333.1697 (for C19H25O5 ); found 333.1693 [M + H+]. C19H24O5
(332.40).
Ethyl 3ꢀ(2ꢀoxoꢀ2ꢀphenylethyl)oxepanꢀ2ꢀoneꢀ3ꢀcarboxylate (11ca): CeCl3 — 7 H2O
(5 mg, 13 ꢁmol) was added to a mixture of βꢀoxoester 5c (209 mg, 1.23 mmol) and
enol ester 8a (300 mg, 1.85 mmol, 1.5 equiv.) in TFE (1 mL), and the reaction
mixture was stirred at 30°C for 24 h under an atmosphere of air. Subsequently, all
volatile materials were removed in vacuum and the residue was purified by column
chromatography (SiO2, hexanes/MTBE 3:1 → 1:1) to yield the 1,4ꢀdiketone 7ca [147
mg, 0.51 mmol, 41%, Rf = 0.41 (hexanes/MTBE 1:1)] as a colorless solid (m.p.
89°C). Secondly, the αꢀhydroxylated compound 10c [21 mg, 0.11 mmol, 9%, Rf =
0.33 (hexanes/MTBE 1:1)]) was obtained as a colorless oil. As a third fraction the title
compound 11ca [35 mg, 0.12 mmol, 9%, Rf = 0.16 (hexanes/MTBE 1:1)] was eluted
as a colorless solid (m.p. 105°C).
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(m, 4H), 2.06 (ddd, J = 14.6 Hz, J = 12.6 Hz, J = 2.7 Hz, 1H), 2.21–2.25 (m, 1H), 3.35
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