Catalytic asymmetric synthesis of sterically hindered tertiary α-aryl ketones

Article abstract of DOI:10.1021/jo5014806

The catalytic asymmetric synthesis of a series of tertiary α-aryl cyclopentanones and cyclohexanones has been accomplished via a Pd-catalyzed decarboxylative protonation of the corresponding α-aryl-β-keto allyl esters. Enantioselectivities of up to 92% ee and 74% ee were achieved for cyclopentanone and cyclohexanone substrates, respectively. The route described gives access to these important structural motifs in moderate to high levels of enantioselectivity. In particular, this is only the second direct approach for the preparation of tertiary α-aryl cyclopentanones. The synthetic approach allows for simple modification of the aryl group. Significantly, substrates containing sterically hindered aryl groups gave the highest levels of enantioselectivity, and these aryl groups were readily installed by a Pb-mediated arylation of a β-keto allyl ester.

Full text of DOI:10.1021/jo5014806

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Article
Catalytic Asymmetric Synthesis of Sterically
Hindered Tertiary alpha-Aryl Ketones
Robert Doran, and Patrick Jerome Guiry
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo5014806 • Publication Date (Web): 03 Sep 2014
Downloaded from http://pubs.acs.org on September 15, 2014
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Catalytic Asymmetric Synthesis of Sterically Hindered Tertiary αꢀAryl Ketones
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Robert Doran and Patrick J. Guiry*
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Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University
College Dublin, Belfield, Dublin 4, Ireland.
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*Eꢀmail: patrick.guiry@ucd.ie.
Abstract
The catalytic asymmetric synthesis of a series of tertiary αꢀaryl cyclopentanones and cyclohexanones
has been accomplished via a Pdꢀcatalyzed decarboxylative protonation of the corresponding αꢀarylꢀβꢀ
keto allyl esters. Enantioselectivities of up to 92 % ee and 74 % ee were achieved for cyclopentanone
and cyclohexanone substrates, respectively. The route described gives access to these important
structural motifs in moderate to high levels of enantioselectivity. In particular, this is only the second
direct approach for the preparation of tertiary αꢀaryl cyclopentanones. The synthetic approach allows
for simple modification of the aryl group and, significantly, substrates containing sterically hindered
aryl groups gave the highest levels of enantioselectivity and these aryl groups were readily installed
by a Pbꢀmediated arylation of a βꢀketo allyl ester.
Introduction
Enantioenriched tertiary αꢀaryl carbonyls represent an important class of organic compounds. They
are prevalent structural motifs in many biologically active molecules and pharmaceuticals such as
naproxen and clopidogrel.1 They are also important intermediates in the synthesis of many
medicinally important molecules. As a result the asymmetric synthesis of compounds possessing this
structural motif has received a great deal of attention, particularly in the last decade.
A number of approaches have been developed for the catalytic asymmetric synthesis of quaternary αꢀ
aryl carbonyl containing compounds. However, the basic conditions employed in the vast majority of
the reports to date necessitate the use of basic conditions. Therefore, these methods are unsuitable for
the synthesis of tertiary αꢀaryl carbonyls due to the acidity of a tertiary αꢀaryl carbonyl proton.
Excellent progress has been made in recent years in the realization of a catalytic asymmetric synthesis
of tertiary αꢀaryl carbonyls. Jørgensen developed an organocatalytic enantioselective αꢀarylation of
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aldehydes with quinones.2 Fu reported Niꢀcatalyzed Kumada and Negishi coupling reactions using
bisoxazoline ligands to generate αꢀaryl ketones.3 MacMillan described enantioselective αꢀarylations of
aldehydes with diaryliodonium salts in the presence of an organocatalyst.4 Also, MacMillan and
Gaunt independently reported the enantioselective Cuꢀcatalyzed αꢀarylation of silylꢀNꢀ
acyloxazolidinones with diaryliodonium salts using bisoxazoline ligands.5 Zhou reported the Pdꢀ
catalyzed αꢀarylation of silyl ketene acetals to form tertiary αꢀaryl esters6 and more recently the
arylation of Snꢀ or Liꢀenolates to access αꢀaryl ketones7 or lactones.8
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All of the above methods introduce the aryl group during the enantiodetermining step. An alternative
strategy would be to already have the aryl group in place and to generate the tertiary stereocentre via
an asymmetric protonation of an enolate complex. This was first realized by the pioneering work of
Yamamoto in this area with the use of Lewis acid assisted chiral Brønsted acid (LBA) catalysts in the
enantioselective synthesis of αꢀaryl cyclohexanones. Initially developed with the use of stoichiometric
quantities of a BINOLꢀSnCl4 catalyst for the asymmetric protonation of silyl enol ethers,9 the
extensive development of this reaction has resulted in a catalytic variant with an achiral proton
donor10 and expansion of the scope to include tertiary αꢀaryl carboxylic acids.11 Further improvement
was made with the development of a metal free Nꢀtriflyl thiophosphoramide BINOL derived proton
source12 and more recently a Lewis baseꢀtolerant chiral LBA.13
A number of other asymmetric enolate protonation reactions have been described using chiral proton
sources in the synthesis of αꢀaryl cyclohexanones. These include the stoichiometric use of chiral
diols14 and αꢀsulfinyl alcohols.15 Other catalytic approaches involve the use of a BINAPꢀAgF complex
with MeOH as the achiral proton source,16 a chiral sulfonamide/achiral sulfonic acid system17 and a
cationic BINAPꢀAu complex which also was extended to acyclic tertiary αꢀaryl ketones.18
Enantioenriched 2ꢀarylꢀcyclohexanones have also been accessed by oxidative kinetic resolution of
secondary alcohols, kinetic resolution of racemic 2ꢀarylcyclohexanones via an asymmetric Bayerꢀ
Villiger oxidation19 and by arylation with diaryliodonium salts and desymmetrisation with a chiral Liꢀ
base.20
Despite the number of reports of the asymmetric synthesis of tertiary αꢀaryl cyclohexanones, there
have only been three reports which describe the asymmetric synthesis of tertiary αꢀaryl
cyclopentanones. The first of these was reported by Shi via asymmetric epoxidation of benzylidene
cyclobutanes and epoxide rearrangement in a subsequent step.21 Bäckvall used a dynamic kinetic
resolution of allylic alcoholsꢀallylic substitutionꢀoxidative cleavage sequence to access 2ꢀ
phenylcyclopentanone.22 The first direct catalytic asymmetric synthesis of tertiary αꢀaryl ketones was
recently described by Kingsbury using a series of Scꢀcatalyzed diazoalkaneꢀcarbonyl homologations
with bis/tris oxazoline ligands.23
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The Pdꢀcatalyzed asymmetric decarboxylative protonation reaction was developed by Stoltz to
generate tertiary αꢀalkyl/benzyl ketones. The first report used formic acid, in the presence of
molecular sieves, as the proton source to intercept the intermediate generated from a decarboxylative
allylation reaction and form a tertiary stereocentre in the αꢀposition with ee’s with up to 94 %.24
Subsequently homogeneous conditions were developed by Stoltz using Meldrum’s acid as the proton
source.25 Recently we exploited this methodology for the first catalytic asymmetric synthesis of
isoflavanones, a class of tertiary αꢀaryl ketones, via Pbꢀmediated arylation to generate 1 followed by
an asymmetric palladiumꢀcatalyzed decarboxylative asymmetric protonation to generate the chiral
centre in 2 (Scheme 1) using modified conditions.26
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Scheme 1. Catalytic asymmetric synthesis of isoflavanones.
Having applied this methodology to the construction of several nonꢀnatural isoflavanones, we
achieved the first asymmetric synthesis of naturally occurring isoflavanones sativanone and 3ꢀoꢀ
methylviolanone, which feature oxygenation at the 7ꢀposition.27 During the course of this work we
observed an interesting switch in enantioselectivity when the achiral proton source was changed.
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Scheme 2. Enantiodivergence observed with different H+ sources. A: Pd2dba3.CHCl3, (S)ꢀ(CF3)3ꢀtꢀ
BuPHOX, Meldrum's acid, THF, 7 °C, 0.5 h. B: Pd(OAc)2, (S)ꢀ(CF3)3ꢀtꢀBuPHOX, formic acid, 4 Å
mol. sieves, 1,4ꢀdioxane, 40 °C, 10 h.
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We now wish to expand the scope of this work to the catalytic asymmetric synthesis of tertiary αꢀaryl
cyclohexanones and, in particular, cyclopentanones given the dearth of reported methods for their
direct asymmetric synthesis to date. These substrates are readily accessible and would enable us to
develop general catalytic conditions which could be applied to more complex systems in future, in
particular those containing orthoꢀsubstituted aryls.
Results and Discussion
The synthesis of a series of αꢀarylꢀβꢀketo allyl esters was accomplished by first preparing
cyclopentanone and cyclohexanone βꢀketo allyl esters 7 and 8 (Scheme 3). This was achieved via
Dieckmann condensation of commercially available diallyl adipate using NaH as the base to generate
cyclopentanone βꢀketo allyl ester 7 in 73 % yield. Similarly, diallyl pimelate, prepared by
transesterification of pimelic acid with allyl alcohol, was cyclized in the same manner to yield
cyclohexanone βꢀketo allyl ester 8 in 74 % yield over 2 steps using a previously reported method.28
Scheme 3. Synthesis of cyclopentanone βꢀketo allyl ester.
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The next step was to generate a series of αꢀarylꢀβꢀketo allyl esters from the cyclopentanone and
cyclohexanone βꢀketo allyl esters. This could be achieved by the use of aryllead triacetates under
relatively mild conditions of 40 °C in the presence of pyridine. These reagents have shown a
remarkable ability for the αꢀarylation of βꢀketo esters, particularly impressive is their ability to
introduce sterically bulky aryl groups generating a quaternary centre in very high yields.26,29
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A total of 11 aryllead triacetates were prepared according to previously reported methods.26 We chose
a number of sterically demanding, electronꢀrich aryl groups as we knew from our previous report that
this was important to achieve reasonable levels of enantioinduction.26 These were successfully used in
the arylation of the cyclopentanone and cyclohexanone βꢀketo allyl esters in moderate to excellent
yields, with the exception of the 2,6ꢀdimethylphenyl group. The aryl groups utilized and the yields for
the various αꢀarylation reactions are summarized in Table 1.
Table 1. Synthesis of αꢀarylꢀβꢀketo allyl esters.
Yield (%) Yield (%)
Substrate
Ar
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10
2,4,6ꢀ(MeO)3C6H2
2,4ꢀ(MeO)2C6H3
2,6ꢀ(MeO)2C6H3
2,3,4ꢀ(MeO)3C6H2
2,3,6ꢀ(MeO)3C6H2
4ꢀMeOC6H4
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60
a
b
c
d
e
f
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84
91
91
61
62
89
67
90
36
90
61
94
85
92
2ꢀMeOC10H6
89
g
h
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3,4
−(OCH O)−C H
86
2
6
3
2ꢀBnOC10H6
79
j
2ꢀMeOꢀ4,6ꢀMe2C6H2
2,6ꢀMe2C6H3
90
n.d.a
k
a n.d. = not determined; due to poor yield for arylation
and moderate ee for the same aryl group in the
cyclopentanone series.
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We chose the cyclopentanone αꢀarylꢀβꢀketo allyl ester (9a) bearing a 2,4,6ꢀtrimethoxyphenyl group as
the model substrate to assess the viability of our previously optimized conditions for the Pdꢀcatalyzed
decarboxylative asymmetric protonation protocol on these types of substrates (Table 2). Thus, we
attempted the reaction using Pd2dba3.CHCl3, (S)ꢀ(CF3)3ꢀtꢀBuPHOX as the chiral P,Nꢀligand, and
Meldrum’s acid as the proton source at 7 °C in THF (Table 2, entry 1). Promisingly, the reaction went
with full conversion although the level of enantioselectivity was poor at 28 % ee. We then lowered the
temperature to −20 °C and surprisingly this led to formation of the opposite enantiomer (R) of tertiary
αꢀaryl cyclopentanone 11a, albeit with low enantioselectivity and conversion (Table 2, entries 2 and
3). Carrying out the reaction at 23 °C increased the ee slightly to 36 % of the Sꢀenantiomer (Table 2,
entry 4). A number of solvents were then screened with 1,4ꢀdioxane leading to an increase in
enantioselectivity up to 51 % ee (Table 2, entry 5). Encouraged by this we decided to increase the
temperature to 40 °C as we had seen a slight increase going from 7 °C to 23 °C. This resulted in
further increase in enantioinduction up to 75 % ee (Table 2, entry 9). We then reꢀexamined THF at
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Table 2. Optimization of conditions for the decarboxylative asymmetric protonation.
Conv.(%)a
100
ee (%)b
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Entry
Solvent
T (°C)
1
2
THF
THF
7
−20
−20
23
23
23
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23
40
40
30
50
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18
20 (R)
10 (R)
36
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toluene
THF
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4
100(61)
100(69)
100(61)
100
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1,4ꢀdioxane
2ꢀMeꢀTHF
toluene
Et2O
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26
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100
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9
1,4ꢀdioxane
THF
100
75
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14c
100(91)
100
82 (1.5 h)
82 (19 h)
73
THF
THF
100
2:1 THF/benzene
THF
100
58
100
62
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15d
16e
17f
18g
19h
20i
21j
22k
THF
THF
THF
THF
THF
THF
THF
THF
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100
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Reactions carried out with 5 mol % Pd2dba3.CHCl3 and 12.5 mol % ligand in 0.20 M
a
substrate concentration unless otherwise stated. % conversion determined by chiral
HPLC analysis. Yields in parentheses. b % ee values determined by chiral SFC analysis.
c Using commercial Pd2dba3. d 1.0 equiv. Meldrum’s acid. e 5.0 equiv. Meldrum’s acid. f
g
h
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0.025 M THF. 0.10 M THF. Meldrum’s acid added during complex formation.
Meldrum’s acid/substrate solution added dropwise. j 0.10 M THF, 1 equiv. Meldrum’s
acid. k Using (S)ꢀtꢀBuPHOX.
this higher temperature and this further increased the ee to 82 % with an yield of 91 % (Table 2, entry
10). For completeness we carried out the reaction at 30 °C and achieved the same level of
enantioselectivity albeit with a longer reaction time (Table 2, entry 11). At 50 °C the ee drops to 73
%, possibly due to the instability of the catalyst at this elevated temperature (Table 2, entry 12).
Further attempts were made to improve the level of enantioselectivity. Surprisingly, using only 1.0
equivalent of Meldrum’s acid did not result in the formation of the competitive allylation product and
had no effect on the enantioselectivity (Table 2, entry 14). Increasing this to 5.0 equivalents had a
detrimental effect on the enantioselectivity (Table 2, entry 15). To ensure complete protonation for
both the cyclopentanone and cyclohexanone motifs with the various aryl groups we chose to use 2.5
equivalents of Meldrum’s acid in the optimized conditions. Forming the complex in the presence of
Meldrum’s acid also had a negative effect on enantioselectivity (Table 2, entry 19) as did the slow
addition of the solution of Meldrum’s acid/substrate solution (Table 2, entry 20). Also, decreasing the
concentration of THF lowered the ee whereas increasing the concentration did not have a significant
effect (Table 2, entries 17 and 18, respectively). The optimum conditions chosen were in THF (1.5
mL for 0.15 mmol) at 40 °C with a oneꢀportion addition of the substrate and Meldrum’s acid (2.5
equiv.).
It is worth noting during the course of optimization of the reaction conditions we found the ee values
would slowly increase over time when the reaction was carried out at 23 °C and 7 °C despite complete
reaction of all of the starting material upon initial sampling of the reaction. The level of increase in ee
observed was significantly greater than 10 % suggesting the intermediate is not a monomeric Pdꢀ
bound species. A previous report by Stoltz and coꢀworkers suggested the reaction proceeded via a
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ligandꢀbound Pdꢀenolate complex.25 For example in Table 2, entry 19 the ee after 30 min was 30 %
with no starting material remaining. When this was sampled after 2 h the ee had increased to 70 %
and was unchanged thereafter. Previous work carried out during the development of conditions for the
catalytic asymmetric synthesis of isoflavanones showed a similar trend.30 During the course of that
study we showed that the process was not dynamic, i.e. the protonated product was not been
deprotonated under the reaction conditions. This led us to the conclusion that a longꢀlived
intermediate was being slowly protonated over time. We believed when the reaction was sampled for
chromatographic analysis this intermediate was been quenched on silica. In order to prove this we
carried out the reaction where we replaced Meldrum’s acid with silica gel and this resulted in
formation of the racemic protonated product in 78 % yield. Unfortunately we have been unable to
establish a potential structure for this postulated intermediate.
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This observed increase in ee over time might explain why in the case of the cyclopentanone substrate
the level of enantioselectivity increased as the temperature was increased. At temperatures lower than
30 °C the intermediate may not have enough reactivity to be asymmetrically protonated by Meldrum’s
acid and hence the lower ee value could be more truly viewed as a lower conversion. It should also be
noted that this process is difficult to observe when the THF used for the reaction is of high purity with
the asymmetrically protonated product formed in as little as 30 min. The use of dry, degassed and
peroxideꢀfree THF is crucial to obtaining good, reproducible levels of enantioselectivity in this
reaction.
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Scheme 4. Proposed mechanism for the formation of lactone 12c.
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An example of the importance of the solvent purity was the formation of an unexpected impurity
during the first few attempts at this reaction. The formation of lactone 12c, albeit in low yields is
likely to have resulted from oxygen insertion (Scheme 4).31 The only reasonable source of this is
dissolved oxygen in the solvent THF or peroxides. It should be noted that this impurity was generated
when a Na/benzophenone still was used. The still however, was freshly setꢀup and had not been
refluxed for a sufficient time to allow complete degassing of the solvent, evident by the deep blue
color which indicates the THF is relatively dry however, a deep purple color indicates the solvent is
also degassed. Perhaps the most significant observation in the formation of this impurity is the
unsaturation of the lactone. This is potentially as a result of βꢀhydride elimination from a
carbopalladated species. Against this argument would be the lack of a detectable quantity of
cyclopentanone 13c in any of the reactions carried out. It is perhaps plausible that there may be
equilibrium between a carbopalladated species and a Pdꢀenolate which may account for the observed
product distribution (Scheme 5). In order to investigate this further we synthesized a cyclopentanone
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substrate which contained a gemꢀdimethyl substituent in the βꢀposition (Scheme 6).
An alkene
product, as observed in the formation of 13c, is not possible with this substrate due to the absence of a
βꢀhydrogen. We have previously exploited this approach in our use of 2,2ꢀdimethylꢀ2,3ꢀdihydrofuran
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as a substrate in intermolecular asymmetric Heck reactions to afford one regioisomeric product.33 We
did not observe the formation of a lactone byꢀproduct with this substrate. We subsequently concluded
that degassed and peroxide free THF prevented the formation of lactone 12c.
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Scheme 5. βꢀgemꢀDimethyl substituted cyclopentanone analogue.
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Another minor byꢀproduct was also during this study due to a side reaction between
dibenzylideneacetone, a ligand from the Pd0 precursor, and Meldrum’s acid in the presence of (S)ꢀ
(CF3)3ꢀtꢀBuPHOX (Scheme 6). The double Michael addition of Meldrum’s acid to dba formed
spirocyclic compound 17, which is a known reaction, but has not been reported as a byꢀproduct from
Pd2dba3.34
Scheme 6. Formation of byꢀproduct of Pd2dba3 and Meldrum’s acid.
O
O
Pd2dba3.CHCl3
O
O
O
O
Ph
Ph
(S)-(CF3)3-t-BuPHOX
O
O
58 %
16
O
17
We then subjected the collection of cyclopentanone and cyclohexanone substrates to the optimized
reaction conditions and the enantioselectivities obtained are summarized in Scheme 7. The highest
level of enantioselectivity was observed for the bulky 2ꢀbenzyloxynapththyl substituted
cyclopentanone substrate (11i, 92 % ee). This high ee was unfortunately not transferred to the
cyclohexanone substrate (18i) which had a more moderate ee of 60 %. In most cases the
cyclopentanone substrates resulted in a higher level of enantioinduction compared to their
cyclohexanone counterpart. The best ee achieved in the cyclohexanone series was 74 % for both the
2,3,4ꢀtrimethoxyphenyl and the 2ꢀmethoxynapththyl substituents, 18d and 18g, respectively. The
tertiary αꢀaryl ketones were obtained in moderate to excellent yields, particularly given the scale of
the reactions. In line with our previous report the presence of substitution in the ortho position of the
aryl group is crucial to achieve reasonable levels of stereoselectivity. For example, the 4ꢀ
methoxyphenyl group gave low ee values of 29 and 38 % for the cyclopentanone and cyclohexanone
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substrates, 11f and 18f, respectively. It should also be noted the importance of the presence of an
oxygenꢀcontaining substituent as evidenced by the drop in enantioselectivity for the 2,6ꢀ
dimethylphenyl substituted cyclopentanone (11k) to 47 % ee. Comparatively, the 2ꢀmethoxyꢀ4,6ꢀ
dimethylphenyl group (11j) gave a much higher ee of 77 % on the cyclopentanone substrate. This is
likely due to an interaction between the oxygen of the methoxy group and the palladium centre. The
presence of steric bulk in the β position had little effect on the level of enantioselectivity as observed
with the βꢀgemꢀdimethyl substituted cyclopentanone analogue (15a, Scheme 5). With a 2,4,6ꢀ
trimethoxypheny group an ee of 77 % was observed compared with 82 % in the absence of
substitution in the βꢀposition.
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Scheme 7. Scope and enantioselectivity of tertiary αꢀaryl cyclopentanones and cyclohexanones.
As noted earlier, a switch in enantioselectivity was observed for isoflavanone substrate 2 when the
proton source was switched to formic acid. The heterogeneous reaction conditions, also developed by
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9
Stoltz,24 were applied to the cyclopentanone and cyclohexanone substrates to ascertain if we would
observe a similar switch in enantioselectivity with these substrates (Scheme 8). The results obtained
showed that only two of the cyclopentanone substrates demonstrated a switch in the sense of
enantioinduction with ee’s of 55 and 26 % (R) for the 2,4,6ꢀtrimethoxyphenyl and 2,4ꢀ
dimethoxyphenyl substrates 11a and 11b, respectively. Both the 2ꢀmethoxyꢀ4,6ꢀdimethylphenyl and
2ꢀbenzyloxynaphthyl substrates, 11h and 11j, formed only racemic products. The products resulting
from the three cyclohexanone substrates screened (11a, 11b and 11i) were formed in moderate to
good enantioselectivities, however, preferentially forming the same enantiomer as when Meldrum’s
acid was used. This goes to underlie the apparent mechanistic differences when using an oxoꢀacid,
formic acid, compared to a carbon acid, Meldrum’s acid. It also shows how subtle the interactions are
between the substrate, catalyst and proton source given the large changes in selectivity observed.
Attempts to understand the differences between these two mechanisms are currently under
investigation and any significant results will be reported in due course.
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Scheme 8. Scope of the switch in enantioselectivity using formic acid.
Conclusion
In conclusion, we have described the catalytic asymmetric synthesis of a series of tertiary αꢀaryl
cyclopentanones and cyclohexanones. This offers a new route to access these important structural
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motifs with moderate to good levels of enantioselectivity. This is only the second report of the direct
catalytic asymmetric synthesis of tertiary αꢀaryl cyclopentanones. A major advantage of this
methodology is the ability to insert a number of different aryl groups prior to the enantiodetermining
step by Pbꢀmediated arylation of a βꢀketo allyl ester. In particular this allows the insertion of bulky
aryl groups where the new stereocentre is generated. Furthermore, the conditions developed for the
decarboxylative asymmetric protonation reaction achieved good levels of enantioselectivity for monoꢀ
and diꢀortho substituted aryl groups.
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Experimental Section
Materials and Methods
Unless otherwise noted, reactions were performed with rigorous exclusion of air and moisture, under
an inert atmosphere of nitrogen in flameꢀdried glassware with magnetic stirring. N2ꢀflushed stainless
steel cannulas or plastic syringes were used to transfer airꢀ and moistureꢀsensitive reagents. All
reagents were obtained from commercial sources and used without further purification unless
otherwise stated. Anhydrous tetrahydrofuran (THF) and dichloromethane were obtained from a dry
solvent dispenser with activated alumina columns. All other anhydrous solvents were obtained from
commercial sources and used as received. For stated reactions THF was freshly distilled under N2
from sodium/benzophenone ketyl. Anhydrous 1,4ꢀdioxane was purchased from Sigma Aldrich and
dried over molecular sieves (3Å beads, 20 g/100 mL for 3 d). Pd(OAc)2 was purchased from Strem.
Powdered activated 4Å molecular sieves were purchased from Sigma Aldrich and were stored in a
desiccator. Tris(dibenzylideneacetone)dipalladium(0) chloroform adduct was prepared via the method
of Zalesskiy et al.35 In vacuo refers to the evaporation of solvent under reduced pressure on a rotary
evaporator. Thinꢀlayer chromatography (TLC) was performed on aluminium plates preꢀcoated with
silica gel F254. They were visualised with UVꢀlight (254 nm) fluorescence quenching, or by charring
with an acidic vanillin solution (vanillin, H2SO4 in ethanol). Flash column chromatography was
carried out using 40ꢀ63 ꢁm, 230ꢀ400 mesh silica gel.
Instrumentation
1H NMR spectra were recorded on a 300, 400, 500 or 600 MHz spectrometer. 13C NMR spectra were
recorded on a 400, 500 or 600 MHz spectrometer at 101, 126 or 151 MHz, respectively. Chemical
shifts (δ) are reported in parts per million (ppm) downfield from tetramethylsilane and are referenced
to residual proton in the NMR solvent (CDCl3 = δ 7.26 ppm, (CD3)2CO = δ 2.05 ppm). 13CꢀNMR are
referenced to the residual solvent peak (CDCl3 = δ 77.16 ppm, (CD3)2CO = δ 206.26 ppm). All 13C
1
spectra are H decoupled. NMR data are represented as follows: chemical shift (δ ppm), multiplicity
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(s = singlet, d = doublet, t = triplet, q = quartet, dd = double doublet, m = multiplet, app. dd, =
apparent doublet of doublets, app. t, = apparent triplet), coupling constant (J) in Hertz (Hz),
integration. High resolution mass spectra [electrospray ionisation (ESIꢀTOF)] (HRMS) were
measured on a timeꢀofꢀflight mass spectrometer with leucine enkephalin (TyrꢀGlyꢀPheꢀLeu) as an
internal lock mass. Infrared spectra were recorded on a FTꢀIR spectrometer and are reported in terms
wavenumbers (νmax) with units of reciprocal centimetres (cmꢀ1). Optical rotation (α) values were
measured at room temperature and specific rotation ([α]D20) values are given in degrees (°). Melting
points were determined in open capillary tubes. Supercritical fluid chromatography (SFC) was
performed using a ChiralcelꢀIA3, IB3, IC3 or ID3 column.
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Allyl 2ꢀoxocyclopentanecarboxylate (7).28 NaH (793 mg, 19.84 mmol, 60 % dispersion in mineral
oil) was suspended in anhydrous THF (15 mL) in a flame dried Schlenk flask. Diallyl adipate (1) (4.0
mL, 18.04 mmol) in THF (3 mL) was added dropwise to the stirred suspension and the reaction
mixture was stirred at 40 °C for 16 h. The reaction mixture was allowed to cool to room temperature,
quenched by the slow addition of 1 M HCl (20 mL) and extracted with EtOAc (3 × 30 mL). The
combined organic layers were washed with brine (100 mL) and dried over anhydrous Na2SO4. The
solvent was removed in vacuo and the resulting oil was purified by silica gel column chromatography
(20 % EtOAc in pentane) to yield the product as a pale pink oil (2.21 g, 73 %). 1H NMR (300 MHz,
CDCl3, mixture of keto and enol tautomers; 90 % keto): δ 10.34 (s, 0.1H, enol), 5.92 (ddt, J = 17.2,
10.4, 5.6 Hz, 1H), 5.34 (dq, J = 17.2, 1.5 Hz, 1H), 5.24 (dq, J = 10.4, 1.5 Hz, 1H), 4.71 – 4.58 (m,
2H), 3.19 (t, J = 9.2 Hz, 1H), 2.58 – 2.48 (m, 0.3H), 2.37 – 2.25 (m, 4H), 2.22 – 2.08 (m, 1H), 1.97 –
1.80 (m, 1H). All other physical data was identical to those previously reported.36
Allyl 2,2ꢀdimethylꢀ5ꢀoxocyclopentanecarboxylate (21).37 βꢀKeto methyl ester (20) (500 mg, 2.94
mmol), which was synthesized according to a previously reported method,38 was suspended in toluene
(5 mL) and 3 Å molecular sieves (500 mg). Allyl alcohol (0.60 mL, 8.81 mmol) and DMAP (538 mg,
4.41 mmol) were successively added and the reaction mixture was heated to reflux and stirred for 14
h. The reaction mixture was allowed to cool to room temperature, quenched by the slow addition of 1
M HCl (5 mL) and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed
with brine (40 mL) and dried over anhydrous Na2SO4. The solvent was removed in vacuo and the
resulting oil was purified by silica gel column chromatography (20 % EtOAc in pentane) to yield the
product as a colourless oil (311 mg, 54 %). Rf = 0.38 (40 % Et2O in pentane); IR (thin film) νmax 2963,
1
1735, 1726 cmꢀ1; H NMR (400 MHz, CDCl3, mixture of keto and enol tautomers, keto ≈85 %): δ
10.70 (s, 0.15H), 5.98 – 5.82 (m, 1H), 5.36 – 5.27 (m, 1H), 5.25 – 5.19 (m, 1H), 4.65 – 4.55 (m, 2H),
2.90 (s, 1H), 2.52 – 2.33 (m, 2H), 2.04 – 1.94 (m, 1H), 1.80 – 1.71 (m, 1H), 1.19 (s, 3H), 1.08 (s, 3H);
13C{1H} NMR (101 MHz, CDCl3): δ 212.9, 168.5, 131.9, 118.9, 65.8, 65.6, 41.0, 36.8, 36.1, 29.1,
24.1
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General Procedure for the Preparation of αꢀArylꢀβꢀketo Allyl Esters (9 and 10). Aryllead
triacetate (1.2 equiv.) and βꢀketo allyl ester (1.0 equiv., X) were dissolved in anhydrous CHCl3 (10X)
in a flameꢀdried Schlenk flask. Anhydrous pyridine (3.6 equiv.) was added dropwise and the reaction
mixture was stirred at 40 °C for 18 h. The reaction mixture was then filtered through Celite to remove
Pb(OAc)2 precipitate and washed with CHCl3 (30X). The filtrate was transferred to a separatory
funnel and washed twice with 3 M H2SO4 (40X) with vigorous shaking to quench unreacted aryllead
triacetate. The aqueous layers were reꢀextracted with CHCl3 (40X) and the combined organic layers
were washed with water (60X), dried over anhydrous Na2SO4 and filtered. The solvent was removed
in vacuo and the resulting oil was purified by silica gel column chromatography (pentane/Et2O or
EtOAc).
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Allyl 2,2ꢀdimethylꢀ5ꢀoxoꢀ1ꢀ(2,4,6ꢀtrimethoxyphenyl)cyclopentanecarboxylate (14a). The title
compound was prepared according to the general procedure using βꢀketo allyl ester (21) (291 mg,
1.48 mmol) and 2,4,6ꢀtrimethoxyphenyllead triacetate (979 mg, 1.78 mmol) to yield the product as a
white solid (439 mg, 82 %). Rf = 0.22 (40 % Et2O in pentane); IR (thin solid film) νmax 2940, 1748,
1
1715, 1608 cmꢀ1; M.P. = 92ꢀ93 °C; H NMR (400 MHz, CDCl3): δ 6.10 (s, 2H), 5.82 (ddt, J = 17.2,
10.5, 5.8 Hz, 1H), 5.22 – 5.15 (m, 1H), 5.15 – 5.07 (m, 1H), 4.56 (ddt, J = 13.2, 5.8, 1.4 Hz, 1H), 4.45
(ddt, J = 13.2, 5.9, 1.4 Hz, 1H), 3.78 (s, 3H), 3.65 (s, 6H), 2.71 (ddd, J = 20.0, 14.8, 9.3 Hz, 1H), 2.45
– 2.34 (m, 2H), 1.72 – 1.63 (m, 1H), 1.41 (s, 3H), 0.83 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ
211.9, 169.1, 160.4, 159.5, 158.3, 132.6, 117.8, 109.8, 92.0, 91.9, 68.6, 65.8, 55.6, 55.4, 55.2, 45.9,
37.4, 35.3, 27.1, 25.2; HRMS: (ESIꢀTOF) calculated for C20H26O6Na [M + Na+] 385.1627, found
385.1614.
Allyl 2ꢀoxoꢀ1ꢀ(2,4,6ꢀtrimethoxyphenyl)cyclopentanecarboxylate (9a). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (7) (600 mg, 3.57 mmol) and
2,4,6ꢀtrimethoxyphenyllead triacetate (2.361 g) to yield the product as a white solid (951 mg, 80 %).
Rf = 0.15 (40 % Et2O in pentane); IR (thin solid film) νmax 2942, 1748, 1722, 1608, 1588 cmꢀ1; M.P. =
74ꢀ75 °C; 1H NMR (400 MHz, CDCl3): δ 6.10 (s, 2H), 5.93 – 5.80 (m, 1H), 5.28 – 5.20 (m, 1H), 5.16
– 5.11 (m, 1H), 4.67 – 4.54 (m, 2H), 3.77 (s, 3H), 3.67 (s, 6H), 2.98 – 2.87 (m, 1H), 2.61 – 2.50 (m,
1H), 2.33 – 2.21 (m, 1H), 2.10 – 1.92 (m, 2H), 1.91 – 1.79 (m, 1H); 13C{1H} NMR (101 MHz,
CDCl3): δ 212.8, 170.7, 160.5, 158.1, 132.5, 117.9, 112.1, 92.2, 66.1, 61.4, 55.9, 55.5, 38.7, 36.0,
20.4; HRMS: (ESIꢀTOF) calculated for C18H22O6Na [M + Na+] 357.1314, found 357.1326.
Allyl 1ꢀ(2,4ꢀdimethoxyphenyl)ꢀ2ꢀoxocyclopentanecarboxylate (9b). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (7) (250 mg, 1.49 mmol) and 2,4ꢀ
dimethoxyphenyllead triacetate (932 mg, 1.79 mmol) to yield the product as a white solid (349 mg, 77
%). Rf = 0.30 (40 % Et2O in pentane); IR (thin solid film) νmax 2958, 1751, 1724, 1613 cmꢀ1; M.P. =
74ꢀ76 °C; 1H NMR (400 MHz, CDCl3): δ 6.85 (d, J = 8.5 Hz, 1H), 6.46 (d, J = 2.5 Hz, 1H), 6.41 (dd,
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J = 8.5, 2.5 Hz, 1H), 5.91 – 5.79 (m, 1H), 5.24 (dd, J = 17.2, 1.6 Hz, 1H), 5.17 (dd, J = 10.5, 1.3 Hz,
1H), 4.71 – 4.56 (m, 2H), 3.78 (s, 3H), 3.73 (s, 3H), 2.91 (dt, J = 13.5, 6.8 Hz, 1H), 2.46 (t, J = 7.5
Hz, 2H), 2.29 (dt, J = 13.4, 6.8 Hz, 1H), 2.06 – 1.94 (m, 1H), 1.90 – 1.78 (m, 1H); 13C{1H} NMR
(101 MHz, CDCl3): δ 214.1, 170.4, 160.4, 157.8, 132.1, 128. 1, 121.1, 118.3, 104.0, 99.9, 66.2, 64.3,
55.5, 55.5, 38.7, 35.4, 19.9; HRMS: (ESIꢀTOF) calculated for C17H20O5Na [M + Na+] 327.1208,
found 327.1197.
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Allyl 1ꢀ(2,6ꢀdimethoxyphenyl)ꢀ2ꢀoxocyclopentanecarboxylate (9c). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (7) (320 mg, 1.90 mmol) and 2,6ꢀ
dimethoxyphenyllead triacetate (932 mg, 1.79 mmol) to yield the product as a white solid (511 mg, 88
%). Rf = 0.32 (40 % Et2O in pentane); IR (thin solid film) νmax 2957, 1750, 1723, 1613 cmꢀ1; M.P. =
1
74ꢀ75 °C; H NMR (400 MHz, CDCl3): δ 7.18 (t, J = 8.3 Hz, 1H), 6.54 (d, J = 8.3 Hz, 1H), 5.93 –
5.80 (m, 1H), 5.23 (dd, J = 17.2, 1.4 Hz, 1H), 5.14 (dd, J = 10.5, 1.4 Hz, 1H), 4.67 – 4.56 (m, 2H),
3.70 (s, 6H), 2.97 (ddd, J = 13.3, 8.4, 6.8 Hz, 1H), 2.65 – 2.54 (m, 1H), 2.35 – 2.23 (m, 1H), 2.14 –
1.95 (m, 2H), 1.94 – 1.81 (m, 1H); 13C{1H} NMR (101 MHz, CDCl3): δ 212. 6, 170.5, 157.5, 132.5,
128.7, 119.6, 117.9, 105.6, 66.2, 61.6, 55.9, 38.7, 35.9, 20.5; HRMS: (ESIꢀTOF) calculated for
C17H20O5Na [M + Na+] 327.1208, found 327.1201.
Allyl 2ꢀoxoꢀ1ꢀ(2,3,4ꢀtrimethoxyphenyl)cyclopentanecarboxylate (9d). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (7) (250 mg, 1.49 mmol) and
2,3,4ꢀtrimethoxyphenyllead triacetate (986 mg, 1.79 mmol) to yield the product as a white solid (453
mg, 91 %). Rf = 0.27 (40 % Et2O in pentane); IR (thin solid film) νmax 2947, 1753, 1724 cmꢀ1; M.P. =
1
50ꢀ52 °C; H NMR (400 MHz, CDCl3): δ 6.62 (d, J = 8.7 Hz, 1H), 6.53 (d, J = 8.7 Hz, 1H), 5.93 –
5.79 (m, 1H), 5.25 (dq, J = 17.2, 1.5 Hz, 1H), 5.17 (dq, J = 10.4, 1.5 Hz, 1H), 4.70 – 4.57 (m, 2H),
3.80 (s, 6H), 3.78 (s, 3H), 2.92 – 2.82 (m, 1H), 2.48 – 2.39 (m, 2H), 2.23 (ddd, J = 13.0, 8.2, 6.9 Hz,
1H), 2.03 – 1.83 (m, 2H); 13C{1H} NMR (101 MHz, CDCl3): δ 213.3, 170.0, 153.5, 151.2, 142.2,
131.8, 126.0, 122.0, 118.5, 106.3, 66.2, 64.5, 60.5, 60.0, 56.0, 38.2, 36.2, 19.8; HRMS: (ESIꢀTOF)
calculated for C18H22O6Na [M + Na+] 357.1314, found 357.1310.
Allyl 2ꢀoxoꢀ1ꢀ(2,3,6ꢀtrimethoxyphenyl)cyclopentanecarboxylate (9e). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (7) (250 mg, 1.49 mmol) and
2,3,6ꢀtrimethoxyphenyllead triacetate (986 mg, 1.79 mmol) to yield the product as a colourless oil
(454 mg, 91 %). Rf = 0.23 (40 % Et2O in pentane); IR (thin film) νmax 2944, 1746, 1724 cmꢀ1; 1H NMR
(500 MHz, CDCl3): δ 6.78 (d, J = 8.9 Hz, 1H), 6.56 (d, J = 8.9 Hz, 1H), 5.88 (ddt, J = 17.2, 10.5, 5.5
Hz, 1H), 5.25 (dq, J = 17.2, 1.5 Hz, 1H), 5.15 (dq, J = 10.5, 1.5 Hz, 1H), 4.71 – 4.57 (m, 2H), 3.81 (s,
3H), 3.68 (s, 3H), 3.65 (s, 3H), 2.93 (ddd, J = 13.0, 9.6, 6.5 Hz, 1H), 2.62 (dddd, J = 18.1, 8.5, 4.87,
1.8 Hz, 1H), 2.26 (dt, J = 18.1, 8.5 Hz, 1H), 2.13 (dddd, J = 13.0, 6.5, 4.7, 1.8 Hz, 1H), 2.02 – 1.93
(m, 1H), 1.90 – 1.78 (m, 1H); 13C{1H} NMR (126 MHz, CDCl3): δ 211.6, 170.3, 151.0, 147.0, 147.0,
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132.4, 125.2, 117.5, 111.3, 110.0, 106.4, 66.0, 62.1, 59.9, 56.1, 55.8, 38.5, 36.0, 20.1; HRMS: (ESIꢀ
TOF) calculated for C18H22O6Na [M + Na+] 357.1314, found 357.1305.
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Allyl 1ꢀ(4ꢀmethoxyphenyl)ꢀ2ꢀoxocyclopentanecarboxylate (9f). The title compound was prepared
according to the general procedure using βꢀketo allyl ester (7) (250 mg, 1.49 mmol) and 4ꢀ
methoxyphenyllead triacetate (879 mg, 1.79 mmol) to yield the product as a colourless oil (247 mg,
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61 %). Rf = 0.41 (40 % Et2O in pentane); IR (thin film) νmax 2957, 1749, 1730 cmꢀ1; H NMR (500
MHz, CDCl3): δ 7.36 – 7.32 (m, 2H), 6.90 – 6.86 (m, 2H), 5.88 – 5.78 (m, 1H), 5.22 (dq, J = 17.2, 1.4
Hz, 1H), 5.18 (dq, J = 10.5, 1.4 Hz, 1H), 4.60 (dt, J = 5.5, 1.4 Hz, 2H), 3.78 (s, 3H), 2.89 – 2.80 (m,
1H), 2.58 – 2.43 (m, 2H), 2.38 – 2.30 (m, 1H), 2.06 – 1.87 (m, 2H); 13C{1H} NMR (126 MHz,
CDCl3): δ 212.0, 170.6, 159.1, 131.5, 128.6, 127.6, 118.3, 113.9, 66.1, 64.2, 55.2, 37.6, 34.7, 19.3;
HRMS: (ESIꢀTOF) calculated for C16H18O4Na [M + Na+] 297.1103, found 297.1100.
Allyl 1ꢀ(2ꢀmethoxynaphthalenꢀ1ꢀyl)ꢀ2ꢀoxocyclopentanecarboxylate (9g). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (7) (250 mg, 1.49 mmol) and 2ꢀ
methoxynaphthyllead triacetate (968 mg, 1.79 mmol) to yield the product as a white solid (303 mg, 62
%). Rf = 0.32 (40 % Et2O in pentane); IR (thin solid film) νmax 2948, 1744, 1716 cmꢀ1; M.P. = 83ꢀ85
°C; 1H NMR (400 MHz, CDCl3): δ 7.81 – 7.74 (m, 2H), 7.54 (d, J = 8.7 Hz, 1H), 7.45 – 7.36 (m, 1H),
7.39 – 7.30 (m, 1H), 7.22 (d, J = 9.0 Hz, 1H), 5.66 (ddt, J = 17.3, 10.0, 5.6 Hz, 1H), 5.08 – 4.97 (m,
2H), 4.63 – 4.51 (m, 2H), 3.76 (s, 3H), 3.19 (ddd, J = 13.0, 11.2, 6.7 Hz, 1H), 2.73 (dddd, J = 18.0,
8.4, 3.3, 2.1 Hz, 1H), 2.48 – 2.31 (m, 2H), 2.12 – 2.02 (m, 1H), 1.94 – 1.79 (m, 1H); 13C{1H} NMR
(101 MHz, CDCl3): δ 211.8, 172.4, 154.0, 132.6, 131.8, 130.9, 130.2, 129.1, 126.7, 124.0, 123.9,
123.8, 118.1, 116.0, 66.5, 63.9, 57.3, 57.3, 39.0, 36.7, 20.5; HRMS: (ESIꢀTOF) calculated for
C20H20O4Na [M + Na+] 347.1259, found 347.1265.
Allyl 1ꢀ(benzo[d][1,3]dioxolꢀ5ꢀyl)ꢀ2ꢀoxocyclopentanecarboxylate (9h).39 The title compound was
prepared according to the general procedure using βꢀketo allyl ester (7) (250 mg, 1.49 mmol) and 3,4ꢀ
methylenedioxyphenyllead triacetate (902 mg, 1.79 mmol) to yield the product as a colourless oil
(382 mg, 89 %). Rf = 0.45 (40 % Et2O in pentane); IR (thin film) νmax 2890, 1751, 1730 cmꢀ1; 1H NMR
(500 MHz, CDCl3): δ 6.94 (d, J = 1.9 Hz, 1H), 6.84 (dd, J = 8.2, 1.9 Hz, 1H), 6.76 (d, J = 8.2 Hz,
1H), 5.92 (q, J = 1.5 Hz, 2H), 5.83 (ddt, J = 17.2, 10.5, 5.5 Hz, 1H), 5.23 (dq, J = 17.2, 1.5 Hz, 1H),
5.18 (dq, J = 10.5, 1.5 Hz, 1H), 4.59 (dt, J = 5.5, 1.5 Hz, 2H), 2.86 – 2.78 (m, 1H), 2.52 – 2.42 (m,
2H), 2.38 – 2.28 (m, 1H), 2.03 – 1.87 (m, 2H); 13C{1H} NMR (126 MHz, CDCl3): δ 211.6, 170.4,
147.1, 147.1, 131.5, 129.4, 120.7, 118.4, 108.3, 108.1, 101.2, 66.2, 64.4, 37.6, 34.9, 19.2; HRMS:
(ESIꢀTOF) calculated for C16H16O5Na [M + Na+] 311.0895, found 311.0903.
Allyl 1ꢀ(2ꢀ(benzyloxy)naphthalenꢀ1ꢀyl)ꢀ2ꢀoxocyclopentanecarboxylate (9i). The title compound
was prepared according to the general procedure using βꢀketo allyl ester (7) (250 mg, 1.49 mmol) and
2ꢀbenzyloxynaphthyllead triacetate (1.104 g, 1.79 mmol) to yield the product as a white solid (399
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mg, 67 %). Rf = 0.56 (40 % Et2O in pentane); IR (thin solid film) νmax 2948, 1743, 1715 cmꢀ1; M.P. =
121ꢀ123 °C; 1H NMR (400 MHz, CDCl3): δ 7.79 (dd, J = 8.0, 1.5 Hz, 1H), 7.75 (d, J = 8.9 Hz, 1H),
7.57 (dd, J = 8.6, 1.0 Hz, 1H), 7.50 – 7.45 (m, 2H), 7.45 – 7.33 (m, 5H), 7.27 (d, J = 8.9 Hz, 1H), 5.68
(dddt, J = 16.5, 10.9, 8.6, 5.6 Hz, 1H), 5.11 – 4.97 (m, 4H), 4.67 – 4.52 (m, 2H), 3.20 (ddd, J = 12.7,
10.9, 6.7 Hz, 1H), 2.44 (dddd, J = 12.7, 5.9, 3.4, 2.0 Hz, 1H), 2.34 (dddd, J = 18.0, 8.2, 3.4, 2.0 Hz,
1H), 2.19 (ddd, J = 18.0, 9.9, 8.2 Hz, 1H), 2.06 – 1.96 (m, 1H), 1.92 – 1.79 (m, 1H); 13C{1H} NMR
(101 MHz, CDCl3): δ 211.9, 172.3, 153.3, 136.4, 132.7, 131.8, 130.8, 130.1, 129.1, 128.7, 128.3,
128.3, 126.7, 124.1, 123.9, 123.9, 118.1, 116.7, 72.8, 66.5, 64.1, 39.0, 36.7, 20.5; HRMS: (ESIꢀTOF)
calculated for C26H24O4Na [M + Na+] 423.1572, found 423.1567.
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Allyl 1ꢀ(2ꢀmethoxyꢀ4,6ꢀdimethylphenyl)ꢀ2ꢀoxocyclopentanecarboxylate (9j). The title compound
was prepared according to the general procedure using βꢀketo allyl ester (7) (250 mg, 1.49 mmol) and
2ꢀmethoxyꢀ4,6ꢀdimethylphenyllead triacetate (929 mg, 1.79 mmol) to yield the product as a colourless
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oil (404 mg, 90 %). Rf = 0.43 (40 % Et2O in pentane); IR (thin film) νmax 2971, 1748, 1720 cmꢀ1; H
NMR (500 MHz, CDCl3): δ 6.63 (s, 1H), 6.56 (s, 1H), 5.94 – 5.83 (m, 1H), 5.27 (dt, J = 17.2, 1.4 Hz,
1H), 5.18 (dt, J = 10.5, 1.4 Hz, 1H), 4.71 – 4.58 (m, 2H), 3.65 (s, 3H), 3.06 – 2.99 (m, 1H), 2.68 –
2.58 (m, 1H), 2.35 – 2.24 (m, 4H), 2.14 – 1.99 (m, 5H), 1.94 – 1.84 (m, 1H); 13C{1H} NMR (126
MHz, CDCl3): δ 211.9, 171.2, 156.4, 137.8, 137.7, 131.9, 127.3, 126.1, 118.6, 111.9, 66.5, 64.0, 55.9,
38.7, 36.4, 21.2, 20.7, 20.4; HRMS: (ESIꢀTOF) calculated for C18H22O4Na [M + Na+] 325.1416,
found 325.1420.
Allyl 1ꢀ(2,6ꢀdimethylphenyl)ꢀ2ꢀoxocyclopentanecarboxylate (9k). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (7) (250 mg, 1.49 mmol) and 2,6ꢀ
dimethylphenyllead triacetate (875 mg, 1.79 mmol) to yield the product as a colourless oil (146 mg,
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36 %). Rf = 0.63 (40 % Et2O in pentane); IR (thin film) νmax 2969, 1748, 1716 cmꢀ1; H NMR (400
MHz, CDCl3): δ 7.04 (dd, J = 8.5, 6.4 Hz, 1H), 6.99 – 6.94 (m, 2H), 5.85 (ddt, J = 17.2, 10.4, 5.7 Hz,
1H), 5.25 (dq, J = 17.2, 1.4 Hz, 1H), 5.18 (dq, J = 10.4, 1.4 Hz, 1H), 4.70 – 4.55 (m, 2H), 3.24 – 3.14
(m, 1H), 2.78 – 2.67 (m, 1H), 2.56 – 2.46 (m, 1H), 2.33 – 2.14 (m, 8H), 2.09 – 1.97 (m, 1H); 13C{1H}
NMR (101 MHz, CDCl3): δ 214.0, 170.8, 139.3, 136.4, 131.4, 130.1, 126.9, 118.9, 67.9, 66.8, 39.1,
36.4, 23.1, 19.8; HRMS: (ESIꢀTOF) calculated for C17H20O3Na [M + Na+] 295.1310, found 295.1323.
Allyl 2ꢀoxoꢀ1ꢀ(2,4,6ꢀtrimethoxyphenyl)cyclohexanecarboxylate (10a). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (8) (450 mg, 2.47 mmol) and
2,4,6ꢀtrimethoxyphenyllead triacetate (1.635 g, 2.96 mmol) to yield the product as a colourless oil
(518 mg, 60 %). Rf = 0.10 (40 % Et2O in pentane); IR (thin film) νmax 2940, 1729, 1718, 1607 cmꢀ1; 1H
NMR (500 MHz, CDCl3): δ 6.13 (s, 2H), 5.91 – 5.81 (m, 1H), 4.66 (dd, J = 13.7, 5.4 Hz, 1H), 4.56
(dd, J = 13.7, 5.4 Hz, 1H), 3.78 (s, 3H), 3.68 (s, 6H), 2.66 – 2.51 (m, 2H), 2.48 – 2.40 (m, 1H), 2.37 –
2.29 (m, 1H), 1.89 – 1.74 (m, 3H), 1.66 – 1.57 (m, 1H); 13C{1H} NMR (126 MHz, CDCl3): δ 205.6,
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(ESIꢀTOF) calculated for C19H24O6Na [M + Na+] 371.1471, found 371.1480.
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Allyl 1ꢀ(2,4ꢀdimethoxyphenyl)ꢀ2ꢀoxocyclohexanecarboxylate (10b). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (8) (250 mg, 1.37 mmol) and 2,4ꢀ
dimethoxyphenyllead triacetate (857 mg, 1.64 mmol) to yield the product as a colourless oil (394 mg,
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90 %). Rf = 0.23 (40 % Et2O in pentane); IR (thin film) νmax 2940, 1732, 1715, 1612 cmꢀ1; H NMR
(500 MHz, CDCl3): δ 7.08 – 7.00 (m, 1H), 6.52 – 6.46 (m, 2H), 5.84 (ddt, J = 17.1, 10.7, 5.5 Hz, 1H),
5.22 – 5.13 (m, 2H), 4.68 – 4.55 (m, 2H), 3.80 (s, 3H), 3.71 (s, 3H), 2.65 – 2.43 (m, 4H), 1.95 – 1.79
(m, 2H), 1.78 – 1.63 (m, 2H); 13C{1H} NMR (126 MHz, CDCl3): δ 206.74, 171.52, 160.45, 158.70,
132.00, 127.98, 120.18, 117.97, 104.68, 99.96, 65.70, 64.26, 55.69, 55.41, 40.50, 35.44, 27.80, 21.86;
HRMS: (ESIꢀTOF) calculated for C18H22O5Na [M + Na+] 341.1365, found 341.1375.
Allyl 1ꢀ(2,6ꢀdimethoxyphenyl)ꢀ2ꢀoxocyclohexanecarboxylate (10c). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (8) (250 mg, 1.37 mmol) and 2,4ꢀ
dimethoxyphenyllead triacetate (857 mg, 1.64 mmol) to yield the product as a colourless oil (268 mg,
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61 %). Rf = 0.19 (40 % Et2O in pentane); IR (thin film) νmax 2940, 1719, 1736, 1587 cmꢀ1; H NMR
(500 MHz, CDCl3): δ 7.19 (t, J = 8.3 Hz, 1H), 6.56 (d, J = 8.3 Hz, 2H), 5.86 (ddt, J = 17.2, 10.5, 5.5
Hz, 1H), 5.20 (dq, J = 17.2, 1.5 Hz, 1H), 5.13 (dq, J = 10.5, 1.5 Hz, 1H), 4.67 (ddt, J = 13.5, 5.5, 1.5
Hz, 1H), 4.56 (ddt, J = 13.5, 5.5, 1.5 Hz, 1H), 3.69 (s, 6H), 2.69 – 2.58 (m, 1H), 2.55 – 2.43 (m, 2H),
2.39 – 2.30 (m, 1H), 1.90 – 1.77 (m, 3H), 1.68 – 1.57 (m, 1H); 13C{1H} NMR (126 MHz, CDCl3): δ
205.2, 170.6, 157.8, 132.3, 128.8, 119.0, 117.7, 106.0, 65.8, 62.7, 56.0, 40.6, 34.7, 25.2, 21.9; HRMS:
(ESIꢀTOF) calculated for C18H22O5Na [M + Na+] 341.1365, found 341.1353.
Allyl 2ꢀoxoꢀ1ꢀ(2,3,4ꢀtrimethoxyphenyl)cyclohexanecarboxylate (10d). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (8) (250 mg, 1.37 mmol) and
2,3,4ꢀtrimethoxyphenyllead triacetate (907 mg, 1.64 mmol) to yield the product as a colourless oil
(447 mg, 94 %). Rf = 0.24 (40 % Et2O in pentane); IR (thin film) νmax 2945, 1733, 1712 cmꢀ1; 1H NMR
(500 MHz, CDCl3): δ 6.83 (d, J = 8.8 Hz, 1H), 6.64 (d, J = 8.8 Hz, 1H), 5.84 (ddt, J = 17.1, 10.4, 5.6
Hz, 1H), 5.23 – 5.11 (m, 2H), 4.67 – 4.56 (m, 2H), 3.85 (s, 3H), 3.83 (s, 3H), 3.77 (s, 3H), 2.60 – 2.52
(m, 3H), 2.50 – 2.42 (m, 1H), 1.89 – 1.81 (m, 2H), 1.70 – 1.63 (m, 2H); 13C{1H} NMR (126 MHz,
CDCl3): δ 206.5, 171.4, 153.6, 152.4, 142.4, 132.0, 125.0, 121.4, 118.3, 106.8, 65.9, 64.4, 60.6, 56.0,
56.0, 40.6, 35.7, 28.0, 21.7; HRMS: (ESIꢀTOF) calculated for C19H24O6Na [M + Na+] 371.1471,
found 371.1480.
Allyl 2ꢀoxoꢀ1ꢀ(2,3,6ꢀtrimethoxyphenyl)cyclohexanecarboxylate (10e). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (8) (250 mg, 1.37 mmol) and
2,3,6ꢀtrimethoxyphenyllead triacetate (907 mg, 1.64 mmol) to yield the product as a white solid (405
mg, 85 %). Rf = 0.21 (40 % Et2O in pentane); IR (thin solid film) νmax 2942, 1736, 1731 cmꢀ1; M.P. =
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74ꢀ75 °C; 1H NMR (500 MHz, CDCl3): δ 6.82 (d, J = 9.0 Hz, 1H), 6.61 (d, J = 9.0 Hz, 1H), 5.88 (ddt,
J = 17.2, 10.5, 5.5 Hz, 1H), 5.22 (dq, J = 17.2, 1.5 Hz, 1H), 5.14 (dq, J = 10.5, 1.5 Hz, 1H), 4.71 (ddt,
J = 13.4, 5.5, 1.5 Hz, 1H), 4.57 (ddt, J = 13.4, 5.5, 1.5 Hz, 1H), 3.82 (s, 3H), 3.68 (s, 3H), 3.64 (s,
3H), 2.74 – 2.63 (m, 2H), 2.47 (ddd, J = 13.9, 7.9, 3.7 Hz, 1H), 2.43 – 2.34 (m, 1H), 1.88 – 1.72 (m,
3H), 1.63 – 1.54 (m, 1H); 13C{1H} NMR (126 MHz, CDCl3): δ 204.9, 170.6, 151.6, 147.8, 147.5,
132.3, 124.6, 117.7, 111.8, 107.3, 66.0, 63.4, 60.8, 56.2, 56.2, 40.8, 34.7, 25.4, 21.8; HRMS: (ESIꢀ
TOF) calculated for C19H24O6Na [M + Na+] 371.1471, found 371.1472.
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Allyl 1ꢀ(4ꢀmethoxyphenyl)ꢀ2ꢀoxocyclohexanecarboxylate (10f). The title compound was prepared
according to the general procedure using βꢀketo allyl ester (8) (250 mg, 1.37 mmol) and 4ꢀ
methoxyphenyllead triacetate (808 mg, 1.64 mmol) to yield the product as a colourless oil (362 mg,
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92 %). Rf = 0.41 (40 % Et2O in pentane); IR (thin film) νmax 2941, 1735, 1713 cmꢀ1; H NMR (500
MHz, CDCl3): δ 7.18 – 7.13 (m, 2H), 6.91 – 6.86 (m, 2H), 5.85 (ddt, J = 17.0, 10.2, 5.6 Hz, 1H), 5.25
– 5.15 (m, 2H), 4.67 – 4.58 (m, 2H), 3.78 (s, 3H), 2.80 – 2.71 (m, 1H), 2.54 (app. t, J = 6.6 Hz, 2H),
2.41 – 2.33 (m, 1H), 2.02 – 1.90 (m, 1H), 1.88 – 1.71 (m, 3H); 13C{1H} NMR (126 MHz, CDCl3): δ
206.8, 171.2, 159.0, 131.6, 129.0, 128.5, 118.5, 113.9, 66.0, 66.0, 55.2, 40.6, 35.1, 27.8, 22.1; HRMS:
(ESIꢀTOF) calculated for C17H20O4Na [M + Na+] 311.1259, found 311.1264.
Allyl 1ꢀ(2ꢀmethoxynaphthalenꢀ1ꢀyl)ꢀ2ꢀoxocyclohexanecarboxylate (10g). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (8) (250 mg, 1.37 mmol) and 2ꢀ
methoxynaphthyllead triacetate (890 mg, 1.64 mmol) to yield the product as a colourless oil (412 mg,
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89 %). Rf = 0.29 (40 % Et2O in pentane); IR (thin film) νmax 2940, 1734, 1710 cmꢀ1; H NMR (500
MHz, CDCl3): δ 7.79 (d, J = 8.8 Hz, 2H), 7.56 (dd, J = 8.8, 1.2 Hz, 1H), 7.42 – 7.33 (m, 1H), 7.36 –
7.30 (m, 1H), 7.23 (d, J = 9.0 Hz, 1H), 5.79 (ddt, J = 17.2, 10.4, 5.6 Hz, 1H), 5.19 – 5.06 (m, 2H),
4.73 (ddt, J = 13.4, 5.6, 1.4 Hz, 1H), 4.58 (ddt, J = 13.4, 5.6, 1.5 Hz, 1H), 3.78 (s, 3H), 2.87 – 2.73
(m, 2H), 2.73 – 2.64 (m, 1H), 2.55 (ddd, J = 14.9, 8.4, 5.9 Hz, 1H), 1.99 – 1.78 (m, 3H), 1.50 – 1.38
(m, 1H); 13C{1H} NMR (126 MHz, CDCl3): δ 205.8, 171.9, 154.7, 132.0, 131.9, 130.8, 130.4, 129.2,
126.0, 124.4, 123.6, 123.2, 118.1, 115.9, 77.4, 77.2, 76.9, 66.2, 64.6, 57.5, 40.7, 35.3, 25.0, 21.3;
HRMS: (ESIꢀTOF) calculated for C21H22O4Na [M + Na+] 361.1416, found 361.1416.
Allyl 1ꢀ(benzo[d][1,3]dioxolꢀ5ꢀyl)ꢀ2ꢀoxocyclohexanecarboxylate (10h). The title compound was
prepared according to the general procedure using βꢀketo allyl ester (8) (250 mg, 1.37 mmol) and 3,4ꢀ
methylenedioxyphenyllead triacetate (828 mg, 1.64 mmol) to yield the product as a white solid (356
mg, 86 %). Rf = 0.47 (40 % Et2O in pentane); IR (thin solid film) νmax 2944, 1733, 1713 cmꢀ1; M.P. =
76ꢀ78 °C; 1H NMR (500 MHz, CDCl3): δ 6.79 (d, J = 8.2 Hz, 1H), 6.75 (d, J = 1.9 Hz, 1H), 6.70 (dd,
J = 8.2, 1.9 Hz, 1H), 5.95 (s, 2H), 5.87 (ddt, J = 17.3, 10.4, 5.6 Hz, 1H), 5.29 – 5.18 (m, 2H), 4.68 –
4.59 (m, 2H), 2.79 – 2.69 (m, 1H), 2.55 (app. t, J = 6.6 Hz, 2H), 2.37 – 2.28 (m, 1H), 2.01 – 1.91 (m,
1H), 1.88 – 1.68 (m, 3H); 13C{1H} NMR (126 MHz, CDCl3): δ 206.7, 171.1, 147.9, 147.1, 131.6,
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calculated for C17H18O5Na [M + Na+] 325.1052, found 325.1046.
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was prepared according to the general procedure using βꢀketo allyl ester (8) (250 mg, 1.37 mmol) and
2ꢀbenzyloxynaphthyllead triacetate (1.015 g, 1.64 mmol) to yield the product as a white solid (448
mg, 79 %). Rf = 0.52 (40 % Et2O in pentane); IR (thin solid film) νmax 2942, 1732, 1718 cmꢀ1; M.P. =
84ꢀ87 °C; 1H NMR (500 MHz, CDCl3): δ 7.77 (dd, J = 8.1, 1.5 Hz, 1H), 7.74 (d, J = 8.9 Hz, 1H), 7.58
(d, J = 8.6 Hz, 1H), 7.45 – 7.40 (m, 2H), 7.40 – 7.35 (m, 3H), 7.35 – 7.29 (m, 2H), 7.23 (d, J = 8.9
Hz, 1H), 5.75 (ddt, J = 17.2, 10.4, 5.6 Hz, 1H), 5.15 – 5.05 (m, 2H), 5.02 (s, 2H), 4.65 (ddt, J = 13.3,
5.6, 1.4 Hz, 1H), 4.46 (ddt, J = 13.3, 5.6, 1.4 Hz, 1H), 2.82 – 2.74 (m, 1H), 2.74 – 2.66 (m, 1H), 2.62
(dt, J = 15.4, 6.0 Hz, 1H), 2.46 – 2.36 (m, 1H), 1.87 – 1.70 (m, 3H), 1.47 – 1.37 (m, 1H); 13C{1H}
NMR (126 MHz, CDCl3): δ 205.7, 171.9, 154.1, 136.6, 132.1, 131.9, 130.9, 130.3, 129.2, 128.6,
128.2, 128.1, 126.1, 124.4, 123.8, 123.7, 118.3, 117.3, 73.3, 66.3, 64.8, 40.9, 35.4, 24.7, 21.3; HRMS:
(ESIꢀTOF) calculated for C27H26O4Na [M + Na+] 437.1729, found 437.1707.
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Allyl 1ꢀ(2ꢀ(methoxy)ꢀ4,6ꢀdimethylphenyl)ꢀ2ꢀoxocyclohexanecarboxylate (10j). The title compound
was prepared according to the general procedure using βꢀketo allyl ester (8) (250 mg, 1.37 mmol) and
2ꢀmethoxyꢀ4,6ꢀdimethylphenyllead triacetate (854 mg, 1.64 mmol) to yield the product as a colourless
oil (390 mg, 90 %). Rf = 0.37 (40 % Et2O in pentane); IR (thin film) νmax 2935, 1721, 1711, 1612 cmꢀ1;
1H NMR (500 MHz, CDCl3): δ 6.60 (s, 1H), 6.58 (s, 1H), 5.84 (ddt, J = 17.2, 10.6, 5.5 Hz, 1H), 5.20
(dq, J = 17.2, 1.6 Hz, 1H), 5.13 (dq, J = 10.6, 1.4 Hz, 1H), 4.69 (ddt, J = 13.5, 5.5, 1.4 Hz, 1H), 4.55
(ddt, J = 13.5, 5.5, 1.4 Hz, 1H), 3.66 (s, 3H), 2.68 – 2.57 (m, 1H), 2.51 – 2.40 (m, 2H), 2.40 – 2.30
(m, 1H), 2.26 (s, 3H), 2.16 (s, 3H), 1.91 – 1.81 (m, 3H), 1.66 – 1.56 (m, 1H); 13C{1H} NMR (126
MHz, CDCl3): δ 205.4, 171.0, 157.1, 137.3, 137.3, 117.9, 111.9, 65.9, 64.7, 55.9, 40.4, 35.5, 25.9,
22.2, 21.7, 21.1, 14.1; HRMS: (ESIꢀTOF) calculated for C19H24O4Na [M + Na+] 339.1572, found
339.1576.
General Procedure for the Racemic Decarboxylative Protonation Reaction (11 and 18).
Pd(OAc)2 (3.4 mg, 0.015 mmol) and dppe (7.5 mg, 0.019 mmol) were added to a flame dried Schlenk
flask (10 mL) and 1,4ꢀdioxane (1.5 mL) was added. The suspension was stirred at 40 °C for 90 min
and formic acid (34 ꢁL, 0.90 mmol) was added followed immediately by αꢀarylꢀβꢀketo allyl ester
(0.15 mmol) in 1,4ꢀdioxane (1.5 mL) from a flame dried round bottom flask (10 mL, 2ꢀneck). The
reaction mixture was stirred at 40 °C for 10 h, cooled to room temperature and filtered through a plug
of Celite and washed with Et2O. The solvent was removed in vacuo and the resulting residue was
purified by silica gel column chromatography (pentane/Et2O).
3,3ꢀDimethylꢀ2ꢀ(2,4,6ꢀtrimethoxyphenyl)cyclopentanone (racꢀ15a). The title compound was
prepared according to the general procedure using αꢀarylꢀβꢀketo allyl ester (14a) to yield the product
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as an pale yellow oil (14.5 mg, 35 %). Rf = 0.15 (40 % Et2O in pentane); IR (thin film) νmax 2953,
1739, 1608 cmꢀ1; M.P. = 87ꢀ89 °C; 1H NMR (400 MHz, CDCl3): δ 6.11 (d, J = 2.3 Hz, 1H), 6.08 (d, J
= 2.3 Hz, 1H), 3.77 (s, 3H), 3.73 (s, 3H), 3.64 (s, 3H), 3.50 (d, J = 1.4 Hz, 1H), 2.55 – 2.43 (m, 1H),
2.35 (dddd, J = 18.1, 8.4, 5.0, 1.4 Hz, 1H), 1.90 (ddd, J = 12.4, 8.4, 5.0 Hz, 1H), 1.77 – 1.66 (m, 1H),
1.13 (s, 3H), 0.79 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ 220.4, 160.4, 159.9, 158.5, 107.7,
91.4, 91.1, 55.8, 55.7, 55.5, 55.4, 55.4, 41.7, 37.7, 37.0, 30.9, 24.1; HRMS: (ESIꢀTOF) calculated for
C16H22O4Na [M + Na+] 301.1416, found 301.1405.
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2ꢀ(2,4,6ꢀTrimethoxyphenyl)cyclopentanone (racꢀ11a). The title compound was prepared according
to the general procedure using αꢀarylꢀβꢀketo allyl ester (9a) to yield the product as an offꢀwhite solid
(24 mg, 64 %). Rf = 0.15 (40 % Et2O in pentane); IR (thin solid film) νmax 2960, 1738, 1609 cmꢀ1;
M.P. = 87ꢀ89 °C; 1H NMR (400 MHz, CDCl3): δ 6.12 (s, 2H), 3.78 (s, 3H), 3.73 (s, 6H), 3.71 – 3.64
(m, 1H), 2.44 – 2.31 (m, 2H), 2.28 – 2.18 (m, 1H), 2.17 – 2.00 (m, 2H), 1.90 – 1.77 (m, 1H); 13C{1H}
NMR (101 MHz, CDCl3): δ 220.8, 160.4, 158.7, 109.5, 91.3, 55.7, 55.5, 45.2, 38.2, 30.0, 21.9;
HRMS: (ESIꢀTOF) calculated for C14H18O4Na [M + Na+] 273.1103, found 273.1111.
2ꢀ(2,4ꢀDimethoxyphenyl)cyclopentanone (racꢀ11b). The title compound was prepared according to
the general procedure using αꢀarylꢀβꢀketo allyl ester (9b) to yield the product as a pale yellow oil (24
mg, 67 %). Rf = 0.26 (40 % Et2O in pentane); IR (thin film) νmax 2960, 1739, 1614 cmꢀ1; 1H NMR (500
MHz, CDCl3): δ 6.97 (d, J = 7.9 Hz, 1H), 6.47 – 6.42 (m, 2H), 3.78 (s, 3H), 3.74 (s, 3H), 3.30 (dd, J =
10.9, 9.0 Hz, 1H), 2.45 – 2.28 (m, 3H), 2.17 – 2.04 (m, 2H), 1.92 – 1.80 (m, 1H); 13C{1H} NMR (126
MHz, CDCl3): δ 219.8, 160.2, 157.9, 130.9, 120.8, 104.6, 99.4, 55.5, 55.4, 52.0, 38.3, 31.3, 21.5;
HRMS: (ESIꢀTOF) calculated for C13H16O3Na [M + Na+] 243.0997, found 243.0990.
2ꢀ(2,6ꢀDimethoxyphenyl)cyclopentanone (racꢀ11c). The title compound was prepared according to
the general procedure using αꢀarylꢀβꢀketo allyl ester (9c) to yield the product as an offꢀwhite solid (28
mg, 78 %). Rf = 0.29 (40 % Et2O in pentane); IR (thin solid film) νmax 2961, 1739, 1594 cmꢀ1; M.P. =
1
52ꢀ54 °C; H NMR (500 MHz, CDCl3): δ 7.16 (t, J = 8.3 Hz, 1H), 6.54 (d, J = 8.3 Hz, 2H), 3.84 –
3.70 (m, 7H), 2.49 – 2.31 (m, 2H), 2.30 – 2.21 (m, 1H), 2.19 – 2.06 (m, 2H), 1.92 – 1.81 (m, 1H);
13C{1H} NMR (126 MHz, CDCl3): δ 220.4, 158.1, 128.2, 117.0, 104.5, 55.8, 45.4, 38.2, 29.9, 22.1;
HRMS: (ESIꢀTOF) calculated for C13H16O3Na [M + Na+] 243.0997, found 243.0997.
2ꢀ(2,3,4ꢀTrimethoxyphenyl)cyclopentanone (racꢀ11d). The title compound was prepared according
to the general procedure using αꢀarylꢀβꢀketo allyl ester (9d) to yield the product as a pale yellow oil
(32 mg, 85 %). Rf = 0.24 (40 % Et2O in pentane); IR (thin film) νmax 2960, 1739, 1602 cmꢀ1; 1H NMR
(400 MHz, CDCl3): δ 6.74 (d, J = 8.5 Hz, 1H), 6.59 (d, J = 8.5 Hz, 1H), 3.84 (s, 3H), 3.82 (s, 3H),
3.81 (s, 3H), 3.32 – 3.23 (m, 1H), 2.47 – 2.29 (m, 3H), 2.17 – 2.00 (m, 2H), 1.93 – 1.79 (m, 1H);
13C{1H} NMR (101 MHz, CDCl3): δ 219.7, 153.2, 151.5, 142.3, 126.2, 124.4, 107.2, 60.7, 60.2, 56.1,
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52.2, 38.3, 32.3, 21.4; HRMS: (ESIꢀTOF) calculated for C14H18O4Na [M + Na+] 273.1103, found
273.1104.
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2ꢀ(2,3,6ꢀTrimethoxyphenyl)cyclopentanone (racꢀ11e). The title compound was prepared according
to the general procedure using αꢀarylꢀβꢀketo allyl ester (9e) to yield the product as a pale yellow oil
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(32 mg, 86 %). Rf = 0.24 (40 % Et2O in pentane); IR (thin film) νmax 2959, 1739 cmꢀ1; H NMR (500
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MHz, CDCl3): δ 6.75 (d, J = 8.9 Hz, 1H), 6.54 (d, J = 8.9 Hz, 1H), 3.80 (s, 3H), 3.77 (s, 3H), 3.74 –
3.67 (m, 1H), 3.70 (s, 3H), 2.48 – 2.33 (m, 2H), 2.32 – 2.22 (m, 1H), 2.19 – 2.07 (m, 2H), 1.94 – 1.80
(m, 1H); 13C{1H} NMR (126 MHz, CDCl3): δ 220.2, 151.7, 147.2, 125.6, 123.6, 111.4, 106.1, 56.3,
56.0, 46.2, 38.2, 30.7, 22.0. HRMS: (ESIꢀTOF) calculated for C14H18O4Na [M + Na+] 273.1103,
found 273.1104.
2ꢀ(4ꢀMethoxyphenyl)cyclopentanone (racꢀ11f).21 The title compound was prepared according to the
general procedure using αꢀarylꢀβꢀketo allyl ester (9f) to yield the product as a pale yellow oil (22 mg,
1
77 %). Rf = 0.37 (40 % Et2O in pentane); IR (thin film) νmax 2927, 1706, 1668, 1601, 1511 cmꢀ1; H
NMR (400 MHz, CDCl3): δ 7.15 – 7.08 (m, 2H), 6.90 – 6.85 (m, 2H), 3.79 (s, 3H), 3.31 – 3.22 (m,
1H), 2.52 – 2.41 (m, 2H), 2.34 – 2.22 (m, 1H), 2.16 – 2.02 (m, 2H), 1.99 – 1.87 (m, 1H); 13C{1H}
NMR (101 MHz, CDCl3): δ 218.5, 158.6, 130.6, 129.2, 114.2, 55.4, 54.7, 38.4, 31.9, 20.9; HRMS:
(ESIꢀTOF) calculated for C12H14O2Na [M + Na+] 213.0891, found 213.0901.
2ꢀ(2ꢀMethoxynaphthalenꢀ1ꢀyl)cyclopentanone (racꢀ11g). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (9g) to yield the product as an offꢀ
white solid (24 mg, 65 %). Rf = 0.26 (40 % Et2O in pentane); IR (thin solid film) νmax 2962, 1740 cmꢀ
1; M.P. = 115ꢀ118 °C; 1H NMR (500 MHz, CDCl3): δ 7.84 (br s, 1H), 7.81 – 7.74 (m, 2H), 7.49 – 7.43
(m, 1H), 7.35 – 7.31 (m, 1H), 7.25 (d, J = 9.0 Hz, 1H), 3.92 (br s, 1H), 3.84 (s, 3H), 2.66 – 2.52 (m,
1H), 2.52 – 2.37 (m, 2H), 2.29 – 2.15 (m, 2H), 2.05 – 1.90 (m, 1H); 13C{1H} NMR (126 MHz,
CDCl3): δ 219.9, 129.7, 129.1, 128.8, 126.8, 123.6, 122.6, 114.2, 56.2, 47.9, 38.3, 30.9, 22.2; HRMS:
(ESIꢀTOF) calculated for C16H16O2Na [M + Na+] 263.1048, found 263.1058.
2ꢀ(Benzo[d][1,3]dioxolꢀ5ꢀyl)cyclopentanone (racꢀ11h).39 The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (9h) to yield the product as a pale
yellow oil (29 mg, 95 %). Rf = 0.14 (40 % Et2O in pentane); IR (thin film) νmax 2922, 1733, 1674 cmꢀ1;
1H NMR (500 MHz, CDCl3): δ 6.77 (d, J = 8.0 Hz, 1H), 6.70 – 6.66 (m, 1H), 6.66 – 6.62 (m, 1H),
5.93 (s, 2H), 3.30 – 3.17 (m, 1H), 2.53 – 2.38 (m, 2H), 2.33 – 2.21 (m, 1H), 2.20 – 2.10 (m, 1H), 2.10
– 1.99 (m, 1H), 1.97 – 1.85 (m, 1H); 13C{1H} NMR (126 MHz, CDCl3): δ 218.2, 148.0, 146.6, 132.2,
132.2, 121.4, 108.7, 108.5, 101.1, 55.2, 38.4, 32.0, 20.8; HRMS: (ESIꢀTOF) calculated for C12H13O3
[M + H+] 205.0865, found 205.0867.
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2ꢀ(2ꢀ(Benzyloxy)naphthalenꢀ1ꢀyl)cyclopentanone (racꢀ11i). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (9i) to yield the product as an offꢀ
white solid (44 mg, 93 %). Rf = 0.41 (40 % Et2O in pentane); IR (thin solid film) νmax 2958, 1739,
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1593 cmꢀ1; M.P. = 114ꢀ116 °C; H NMR (500 MHz, CDCl3): δ 7.86 (br s, 1H), 7.78 (d, J = 8.2 Hz,
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1H), 7.75 (d, J = 8.2 Hz, 1H), 7.50 – 7.25 (m, 8H), 5.12 (d, J = 11.0 Hz, 1H), 5.04 (d, J = 11.0 Hz,
1H), 3.90 (br s, 1H), 2.43 – 2.30 (m, 1H), 2.29 – 2.15 (m, 2H), 2.11 – 1.94 (m, 2H), 1.92 – 1.78 (m,
1H); 13C{1H} NMR (101 MHz, CDCl3): δ 219.8, 153.1, 136.6, 133.7, 129.7, 129.0, 128.8, 128.7,
128.4, 128.3, 126.8, 123.6, 122.6, 114.6, 71.4, 48.1, 38.2, 30.7, 22.0; HRMS: (ESIꢀTOF) calculated
for C22H20O2Na [M + Na+] 339.1361, found 339.1356.
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2ꢀ(2ꢀMethoxyꢀ4,6ꢀdimethylphenyl)cyclopentanone (racꢀ11j). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (9j) to yield the product as a pale
yellow oil (28 mg, 88 %). Rf = 0.33 (40 % Et2O in pentane); IR (thin film) νmax 2958, 1739, 1612,
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1581 cmꢀ1; H NMR (400 MHz, CDCl3): δ 6.63 (s, 1H), 6.55 (s, 1H), 3.70 (s, 3H), 3.34 (br s, 1H),
2.53 – 2.04 (m, 11H), 1.94 – 1.79 (m, 1H); 13C{1H} NMR (101 MHz, CDCl3): δ 220.2, 156.6, 137.8,
137.5, 124.0, 110.4, 55.3, 49.0, 38.0, 29.9, 22.0, 21.5, 20.1; HRMS: (ESIꢀTOF) calculated for
C14H18O2Na [M + Na+] 241.1204, found 241.1215.
2ꢀ(2,6ꢀDimethylphenyl)cyclopentanone (racꢀ11k). The title compound was prepared according to
the general procedure using αꢀarylꢀβꢀketo allyl ester (9k) to yield the product as a pale yellow oil (26
1
mg, 92 %). Rf = 0.44 (40 % Et2O in pentane); IR (thin film) νmax 2960, 1738 cmꢀ1; H NMR (500
MHz, CDCl3): δ 7.08 – 7.00 (m, 3H), 3.66 – 3.59 (m, 1H), 2.56 – 2.05 (m, 11H), 2.03 – 1.90 (m, 1H);
13C{1H} NMR (126 MHz, CDCl3): δ 218.9, 135.8, 127.0, 52.8, 38.1, 29.6, 21.6, 21.4; HRMS: (ESIꢀ
TOF) calculated for C13H16ONa [M + Na+] 211.1099, found 211.1107.
2ꢀ(2,4,6ꢀTrimethoxyphenyl)cyclohexanone (racꢀ18a).40 The title compound was prepared according
to the general procedure using αꢀarylꢀβꢀketo allyl ester (10a) to yield the product as an offꢀwhite solid
(17 mg, 45 %). Rf = 0.17 (40 % Et2O in pentane); IR (thin solid film) νmax 2939, 1710, 1608 cmꢀ1;
M.P. = 109ꢀ111 °C; 1H NMR (500 MHz, CDCl3): δ 6.14 (s, 2H), 3.89 (dd, J = 12.3, 6.6 Hz, 1H), 3.79
(s, 3H), 3.74 (s, 6H), 2.62 – 2.55 (m, 1H), 2.37 – 2.26 (m, 1H), 2.18 – 2.08 (m, 1H), 2.07 – 2.01 (m,
1H), 2.00 – 1.89 (m, 2H), 1.85 – 1.74 (m, 1H), 1.74 – 1.63 (m, 1H); 13C{1H} NMR (126 MHz,
CDCl3): δ 209.92, 160.12, 158.54, 110.29, 91.35, 55.81, 55.39, 46.19, 41.56, 31.29, 25.40, 25.30;
HRMS: (ESIꢀTOF) calculated for C15H20O4Na [M + Na+] 287.1259, found 287.1266.
2ꢀ(2,4ꢀDimethoxyphenyl)cyclohexanone (racꢀ18b). The title compound was prepared according to
the general procedure using αꢀarylꢀβꢀketo allyl ester (10b) to yield the product as an offꢀwhite solid
(34 mg, 97 %). Rf = 0.30 (40 % Et2O in pentane); IR (thin solid film) νmax 2937, 1712, 1613, 1588 cmꢀ
1; M.P. = 92ꢀ93 °C; 1H NMR (500 MHz, CDCl3): δ 7.00 (d, J = 8.2 Hz, 1H), 6.51 – 6.44 (m, 2H), 3.85
(dd, J = 13.0, 5.4 Hz, 1H), 3.79 (s, 3H), 3.74 (s, 3H), 2.55 – 2.42 (m, 2H), 2.22 – 2.10 (m, 2H), 2.05 –
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1.93 (m, 2H), 1.87 – 1.71 (m, 2H); 13C{1H} NMR (126 MHz, CDCl3): δ 210.4, 159.8, 157.9, 129.1,
120.4, 104.2, 98.7, 55.5, 55.4, 50.6, 42.4, 33.7, 27.7, 25.9; HRMS: (ESIꢀTOF) calculated for
C14H18O3Na [M + Na+] 257.1154, found 257.1162.
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2ꢀ(2,6ꢀDimethoxyphenyl)cyclohexanone (racꢀ18c). The title compound was prepared according to
the general procedure using αꢀarylꢀβꢀketo allyl ester (10c) to yield the product as a pale yellow oil (33
mg, 94 %). Rf = 0.43 (40 % Et2O in pentane); IR (thin film) νmax 2938, 1711, 1594 cmꢀ1; M.P. = 79ꢀ81
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°C; H NMR (500 MHz, CDCl3): δ 7.18 (t, J = 8.3 Hz, 1H), 6.56 (d, J = 8.3 Hz, 2H), 4.00 (dd, J =
11.9, 6.8 Hz, 1H), 3.76 (s, 6H), 2.65 – 2.57 (m, 1H), 2.39 – 2.30 (m, 1H), 2.19 – 2.09 (m, 1H), 2.09 –
1.97 (m, 2H), 1.97 – 1.91 (m, 1H), 1.88 – 1.77 (m, 1H), 1.77 – 1.63 (m, 1H); 13C{1H} NMR (126
MHz, CDCl3): δ 209.7, 157.9, 128.0, 125.6, 117.9, 104.5, 55.8, 46.3, 41.5, 31.0, 25.2, 25.2; HRMS:
(ESIꢀTOF) calculated for C14H18O3Na [M + Na+] 257.1154, found 257.1157.
2ꢀ(2,3,4ꢀTrimethoxyphenyl)cyclohexanone (racꢀ18d).41 The title compound was prepared according
to the general procedure using αꢀarylꢀβꢀketo allyl ester (10d) to yield the product as a pale yellow oil
(39 mg, 98 %). Rf = 0.23 (40 % Et2O in pentane); IR (thin film) νmax 2936, 1711, 1604 cmꢀ1; 1H NMR
(500 MHz, CDCl3): δ 6.78 (d, J = 8.6 Hz, 1H), 6.65 (d, J = 8.6 Hz, 1H), 3.85 (s, 3H), 3.84 (s, 4H),
3.83 – 3.80 (m, 1H), 3.80 (s, 3H), 2.57 – 2.43 (m, 2H), 2.21 – 2.12 (m, 2H), 2.03 – 1.93 (m, 2H), 1.86
– 1.73 (m, 2H); 13C{1H} NMR (126 MHz, CDCl3): δ 210.4, 152.7, 151.6, 142.0, 125.5, 123.4, 107.2,
60.9, 60.7, 56.0, 51.2, 42.3, 34.2, 27.6, 25.8, 15.4; HRMS: (ESIꢀTOF) calculated for C15H20O4Na [M
+ Na+] 287.1259, found 287.1253.
2ꢀ(2,3,6ꢀTrimethoxyphenyl)cyclohexanone (racꢀ18e). The title compound was prepared according
to the general procedure using αꢀarylꢀβꢀketo allyl ester (10e) to yield the product as a pale yellow oil
(37 mg, 93 %). Rf = 0.23 (40 % Et2O in pentane); IR (thin film) νmax 2939, 1709 cmꢀ1; M.P. = 97ꢀ100
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°C; H NMR (500 MHz, CDCl3): δ 6.76 (d, J = 8.9 Hz, 1H), 6.58 (d, J = 8.9 Hz, 1H), 3.93 (dd, J =
12.1, 6.7 Hz, 1H), 3.81 (s, 3H), 3.76 (s, 3H), 3.71 (s, 3H), 2.65 – 2.58 (m, 1H), 2.35 (dddd, J = 16.3,
13.1, 6.2, 1.2 Hz, 1H), 2.22 – 2.09 (m, 1H), 2.10 – 1.98 (m, 2H), 1.98 – 1.90 (m, 1H), 1.88 – 1.76 (m,
1H), 1.75 – 1.65 (m, 1H); 13C{1H} NMR (126 MHz, CDCl3): δ 209.8, 151.6, 147.7, 147.2, 124.2,
111.2, 106.3, 60.7, 56.3, 56.1, 47.3, 41.4, 31.5, 25.2, 25.1; HRMS: (ESIꢀTOF) calculated for
C15H20O4Na [M + Na+] 287.1259, found 287.1255.
2ꢀ(4ꢀMethoxyphenyl)cyclohexanone (racꢀ18f).9 The title compound was prepared according to the
general procedure using αꢀarylꢀβꢀketo allyl ester (10f) to yield the product as an offꢀwhite solid (30
mg, 97 %). Rf = 0.36 (40 % Et2O in pentane); IR (thin solid film) νmax 2926, 1704 cmꢀ1; M.P. = 86ꢀ88
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°C; H NMR (500 MHz, CDCl3): δ 7.06 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 3.79 (s, 3H),
3.56 (dd, J = 12.4, 5.4 Hz, 1H), 2.56 – 2.48 (m, 1H), 2.48 – 2.39 (m, 1H), 2.29 – 2.20 (m, 1H), 2.18 –
2.09 (m, 1H), 2.04 – 1.93 (m, 2H), 1.87 – 1.75 (m, 2H); 13C{1H} NMR (126 MHz, CDCl3): δ 210.8,
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158.5, 131.0, 129.5, 113.9, 56.7, 55.3, 42.3, 35.4, 28.0, 25.5; HRMS: (ESIꢀTOF) calculated for
C13H16O2Na [M + Na+] 227.1048, found 227.1041.
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2ꢀ(2ꢀMethoxynaphthalenꢀ1ꢀyl)cyclohexanone (racꢀ18g). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (10g) to yield the product as an offꢀ
white solid (33 mg, 87 %). Rf = 0.28 (40 % Et2O in pentane); IR (thin solid film) νmax 2937, 1708,
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1596 cmꢀ1; M.P. = 116ꢀ118 °C; H NMR (500 MHz, CDCl3): δ 7.81 – 7.75 (m, 2H), 7.71 (d, J = 8.6
Hz, 1H), 7.45 – 7.40 (m, 1H), 7.33 – 7.29 (m, 1H), 7.27 (d, J = 9.0 Hz, 1H), 4.27 (dd, J = 12.4, 6.6
Hz, 1H), 3.87 (s, 3H), 2.77 – 2.70 (m, 1H), 2.52 – 2.41 (m, 1H), 2.28 – 2.17 (m, 1H), 2.17 – 2.10 (m,
2H), 2.05 – 1.89 (m, 2H), 1.84 – 1.73 (m, 1H); 13C{1H} NMR (126 MHz, CDCl3): δ 209.8, 154.1,
132.4, 129.8, 129.0, 128.9, 126.4, 123.3, 123.1, 114.0, 56.5, 48.4, 41.5, 31.8, 25.2, 25.1; HRMS:
(ESIꢀTOF) calculated for C17H18O2Na [M + Na+] 277.1204, found 277.1196.
2ꢀ(Benzo[d][1,3]dioxolꢀ5ꢀyl)cyclohexanone (racꢀ18h). The title compound was prepared according
to the general procedure using αꢀarylꢀβꢀketo allyl ester (10h) to yield the product as an offꢀwhite solid
(12 mg, 37 %). Rf = 0.37 (40 % Et2O in pentane); IR (thin solid film) νmax 2930, 1710 cmꢀ1; M.P. = 88ꢀ
90 °C; 1H NMR (500 MHz, CDCl3): δ 6.76 (d, J = 8.0 Hz, 1H), 6.64 (d, J = 1.7 Hz, 1H), 6.57 (dd, J =
8.0, 1.7 Hz, 1H), 5.93 (s, 2H), 3.56 – 3.50 (m, 1H), 2.55 – 2.49 (m, 1H), 2.48 – 2.39 (m, 1H), 2.28 –
2.21 (m, 1H), 2.19 – 2.10 (m, 1H), 2.04 – 1.91 (m, 2H), 1.87 – 1.73 (m, 2H); 13C{1H} NMR (126
MHz, CDCl3): δ 210.6, 147.7, 146.6, 132.7, 121.7, 109.1, 108.3, 101.1, 57.3, 42.3, 35.5, 27.9, 25.6;
HRMS: (ESIꢀTOF) calculated for C13H15O3 [M + H+] 219.1021, found 219.1019.
2ꢀ(2ꢀ(Benzyloxy)naphthalenꢀ1ꢀyl)cyclohexanone (racꢀ18i). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (10i) to yield the product as an offꢀ
white solid (26 mg, 52 %). Rf = 0.40 (40 % Et2O in pentane); IR (thin solid film) νmax 2937, 1707,
1595 cmꢀ1; M.P. = 129ꢀ130 °C; 1H NMR (400 MHz, CDCl3): δ 7.84 – 7.74 (m, 3H), 7.49 – 7.32 (m,
8H), 5.19 (d, J = 11.2 Hz, 1H), 5.11 (d, J = 11.2 Hz, 1H), 4.32 – 4.18 (m, 1H), 2.59 – 2.49 (m, 1H),
2.43 – 2.31 (m, 1H), 2.30 – 2.17 (m, 1H), 2.16 – 2.05 (m, 1H), 2.00 – 1.89 (m, 2H), 1.79 – 1.66 (m,
1H), 1.65 – 1.52 (m, 1H); 13C{1H} NMR (101 MHz, CDCl3): δ 209.7, 153.4, 137.1, 132.6, 129.9,
129.0, 128.9, 128.6, 128.2, 128.2, 126.5, 123.5, 123.4, 123.1, 115.0, 71.5, 48.7, 41.6, 31.6, 25.1, 24.7;
HRMS: (ESIꢀTOF) calculated for C23H23O2 [M + H+] 331.1698, found 331.1693.
2ꢀ(2ꢀMethoxyꢀ4,6ꢀdimethylphenyl)cyclohexanone (racꢀ18j). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (10j) to yield the product as a pale
yellow oil (28 mg, 80 %). Rf = 0.37 (40 % Et2O in pentane); IR (thin film) νmax 2935, 1710, 1580 cmꢀ1;
1H NMR (500 MHz, CDCl3): δ 6.63 (s, 1H), 6.58 (s, 1H), 3.73 (s, 3H), 3.66 – 3.58 (m, 1H), 2.65
(dddd, J = 16.5, 4.6, 2.7, 1.8 Hz, 1H), 2.40 – 2.31 (m, 1H), 2.30 (s, 3H), 2.22 (s, 3H), 2.11 – 1.93 (m,
4H), 1.90 – 1.79 (m, 1H), 1.74 – 1.63 (m, 1H); 13C{1H} NMR (126 MHz, CDCl3): δ 209.9, 156.8,
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137.3, 136.9, 125.6, 124.0, 110.4, 55.5, 49.5, 41.3, 31.1, 25.1, 25.0, 21.5, 20.3; HRMS: (ESIꢀTOF)
calculated for C15H21O2 [M + H+] 233.1542, found 233.1544.
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General Procedure for the Decarboxylative Asymmetric Protonation. Pd2dba3·CHCl3 (7.8 mg,
0.0075 mmol) and (S)ꢀ(CF3)3ꢀtꢀBuPHOX (11.1 mg, 0.0188 mmol) were dissolved in freshly distilled
THF in a flame dried Schlenk flask and stirred at 40 °C for 30 min. αꢀArylꢀβꢀketo allyl ester (0.15
mmol) and Meldrum’s acid (0.375 mmol) were dissolved in THF in a flame dried round bottom flask
(10 mL, 2ꢀneck) and added to the Pdꢀcomplex solution, maintained at 40 °C, in one portion. The
reaction mixture was stirred at 40 °C for 2 h, filtered through a bed of charcoal on a plug of Celite and
washed with EtOAc. The filtrate was concentrated in vacuo and purified by silica gel column
chromatography (pentane/Et2O).
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(S)ꢀ3,3ꢀDimethylꢀ2ꢀ(2,4,6ꢀtrimethoxyphenyl)cyclopentanone ((S)ꢀ15a). The title compound was
prepared according to the general procedure using αꢀarylꢀβꢀketo allyl ester (14a) to yield the product
as a pale yellow oil (38 mg, 92 %, 77 % ee), identical in all respects to the previously prepared
racemic sample, with the exception of [α]D20 = −33.4 (c 1.0, CHCl3); SFC (Chiralcel IAꢀ3, scCO2/2ꢀ
propanol, 99/1 to 70/30 gradient over 5 min, 3 mL/min): Rt = 2.67 (major) and 3.70 min.
(S)ꢀ2ꢀ(2,4,6ꢀTrimethoxyphenyl)cyclopentanone ((S)ꢀ11a). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (9a) to yield the product as an offꢀ
white solid (34 mg, 91 %, 82 % ee), identical in all respects to the previously prepared racemic
sample, with the exception of [α]D20 = −53.3 (c 1.7, CH2Cl2); SFC (Chiralcel ICꢀ3, scCO2/MeOH, 99/1
to 60/40 gradient over 4 min, 3 mL/min): Rt = 2.78 (major) and 2.43 min.
(S)ꢀ2ꢀ(2,4ꢀDimethoxyphenyl)cyclopentanone ((S)ꢀ11b). The title compound was prepared according
to the general procedure using αꢀarylꢀβꢀketo allyl ester (9b) to yield the product as an offꢀwhite solid
(27 mg, 82 %, 60 % ee), identical in all respects to the previously prepared racemic sample, with the
exception of [α]D20 = −51.0 (c 1.0, CHCl3); SFC (Chiralcel ICꢀ3, scCO2/MeOH, 99/1 to 60/40 gradient
over 4 min, 3 mL/min): Rt = 2.56 (major) and 2.44 min.
(S)ꢀ2ꢀ(2,6ꢀDimethoxyphenyl)cyclopentanone ((S)ꢀ11c). The title compound was prepared according
to the general procedure using αꢀarylꢀβꢀketo allyl ester (9c) to yield the product as an offꢀwhite solid
(31 mg, 94 %, 80 % ee), identical in all respects to the previously prepared racemic sample, with the
exception of [α]D20 = −70.0 (c 1.0, CHCl3); SFC (Chiralcel ICꢀ3, scCO2/MeOH, 99/1 to 70/30 gradient
over 5 min, 3 mL/min): Rt = 3.88 (major) and 3.75 min.
(S)ꢀ2ꢀ(2,3,4ꢀTrimethoxyphenyl)cyclopentanone ((S)ꢀ 11d). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (9d) to yield the product as an offꢀ
white solid (30 mg, 80 %, 70 % ee), identical in all respects to the previously prepared racemic
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sample, with the exception of [α]D20 = −60.5 (c 1.0, CHCl3); SFC (Chiralcel ICꢀ3, scCO2/MeCN, 99/1
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to 70/30 gradient over 5 min, 3 mL/min): Rt = 3.92 (major) and 4.51 min.
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(S)ꢀ2ꢀ(2,3,6ꢀTrimethoxyphenyl)cyclopentanone ((S)ꢀ 11e). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (9e) to yield the product as an offꢀ
white solid (32 mg, 85 %, 71 % ee), identical in all respects to the previously prepared racemic
sample, with the exception of [α]D20 = −52.3 (c 1.0, CHCl3); SFC (Chiralcel IBꢀ3, scCO2/MeCN, 99/1
to 70/30 gradient over 5 min, 3 mL/min): Rt = 2.74 (major) and 3.07 min.
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(S)ꢀ2ꢀ(4ꢀMethoxyphenyl)cyclopentanone ((S)ꢀ 11f). The title compound was prepared according to
the general procedure using αꢀarylꢀβꢀketo allyl ester (9f) to yield the product as an offꢀwhite solid (15
mg, 53 %, 29 % ee),42 identical in all respects to the previously prepared racemic sample, with the
exception of SFC (Chiralcel ICꢀ3, scCO2/2ꢀpropanol, 99/1 to 70/30 gradient over 5 min, 3 mL/min):
Rt = 3.25 (major) and 2.88 min.
(S)ꢀ2ꢀ(2ꢀMethoxynaphthalenꢀ1ꢀyl)cyclopentanone ((S)ꢀ 11g). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (9g) to yield the product as an offꢀ
white solid (33 mg, 92 %, 85 % ee), identical in all respects to the previously prepared racemic
sample, with the exception of [α]D20 = −92.2 (c 1.0, CHCl3); SFC (Chiralcel IBꢀ3, scCO2/MeOH, 99/1
to 70/30 gradient over 5 min, 3 mL/min): Rt = 2.86 (major) and 3.17 min.
(S)ꢀ2ꢀ(Benzo[d][1,3]dioxolꢀ5ꢀyl)cyclopentanone ((S)ꢀ 11h). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (9h) to yield the product as an offꢀ
white solid (22 mg, 72 %, 24 % ee), identical in all respects to the previously prepared racemic
sample, with the exception of [α]D20 = −2.2 (c 1.0, CHCl3); SFC (Chiralcel ICꢀ3, scCO2/2ꢀpropanol,
99/1 to 70/30 gradient over 5 min, 3 mL/min): Rt = 2.93 (major) and 2.72 min.
(S)ꢀ2ꢀ(2ꢀ(Benzyloxy)naphthalenꢀ1ꢀyl)cyclopentanone ((S)ꢀ 11i). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (9i) to yield the product as an offꢀ
white solid (45 mg, 95 %, 92 % ee), identical in all respects to the previously prepared racemic
sample, with the exception of [α]D20 = 30.6 (c 1.0, CHCl3); SFC (Chiralcel ICꢀ3, scCO2/MeOH, 99/1
to 70/30 gradient over 5 min, 3 mL/min): Rt = 5.73 (major) and 6.64 min.
(S)ꢀ2ꢀ(2ꢀMethoxyꢀ4,6ꢀdimethylphenyl)cyclopentanone ((S)ꢀ 11j). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (9j) to yield the product as an offꢀ
white solid (30 mg, 92 %, 77 % ee), identical in all respects to the previously prepared racemic
sample, with the exception of [α]D20 = −88.4 (c 1.0, CHCl3); SFC (Chiralcel ICꢀ3, scCO2/MeOH, 99/1
to 70/30 gradient over 5 min, 3 mL/min): Rt = 2.83 (major) and 2.61 min.
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(S)ꢀ2ꢀ(2,6ꢀDimethylphenyl)cyclopentanone ((S)ꢀ11k). The title compound was prepared according
to the general procedure using αꢀarylꢀβꢀketo allyl ester (9k) to yield the product as an offꢀwhite solid
(26 mg, 92 %, 47 % ee), identical in all respects to the previously prepared racemic sample, with the
exception of [α]D20 = −88.4 (c 1.0, CHCl3); SFC (Chiralcel ICꢀ3, scCO2/MeCN, 99/1 to 70/30 gradient
over 5 min, 3 mL/min): Rt = 2.52 (major) and 2.39 min.
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(S)ꢀ2ꢀ(2,4,6ꢀTrimethoxyphenyl)cyclohexanone ((S)ꢀ 18a). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (10a) to yield the product as an offꢀ
white solid (35 mg, 88 %, 60 % ee), identical in all respects to the previously prepared racemic
sample, with the exception of [α]D20 = −19.6 (c 0.5, CHCl3); SFC (Chiralcel ICꢀ3, scCO2/MeOH, 99/1
to 70/30 gradient over 5 min, 3 mL/min): Rt = 3.85 (major) and 3.62 min.
(S)ꢀ2ꢀ(2,4ꢀDimethoxyphenyl)cyclohexanone ((S)ꢀ 18b). The title compound was prepared according
to the general procedure using αꢀarylꢀβꢀketo allyl ester (10b) to yield the product as an offꢀwhite solid
(34 mg, 97 %, 72 % ee), identical in all respects to the previously prepared racemic sample, with the
exception of [α]D20 = −20.9 (c 1.0, CHCl3); SFC (Chiralcel IBꢀ3, scCO2/MeCN, 99/1 to 70/30 gradient
over 5 min, 3 mL/min): Rt = 2.90 (major) and 3.29 min.
(S)ꢀ2ꢀ(2,6ꢀDimethoxyphenyl)cyclohexanone ((S)ꢀ 18c). The title compound was prepared according
to the general procedure using αꢀarylꢀβꢀketo allyl ester (10c) to yield the product as an offꢀwhite solid
(33 mg, 93 %, 70 % ee), identical in all respects to the previously prepared racemic sample, with the
exception of [α]D20 = −21.3 (c 1.0, CHCl3); SFC (Chiralcel IBꢀ3, scCO2/MeCN, 99/1 to 70/30 gradient
over 5 min, 3 mL/min): Rt = 3.64 (major) and 4.10 min.
(S)ꢀ2ꢀ(2,3,4ꢀTrimethoxyphenyl)cyclohexanone ((S)ꢀ 18d). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (10d) to yield the product as an offꢀ
white solid (33 mg, 83 %, 74 % ee), identical in all respects to the previously prepared racemic
sample, with the exception of [α]D20 = −25.1 (c 1.0, CHCl3); SFC (Chiralcel ICꢀ3, scCO2/2ꢀpropanol,
99/1 to 70/30 gradient over 5 min, 3 mL/min): Rt = 2.86 (major) and 3.28 min.
(S)ꢀ2ꢀ(2,3,6ꢀTrimethoxyphenyl)cyclohexanone ((S)ꢀ 18e). The title compound was prepared
according to the general procedure using αꢀarylꢀβꢀketo allyl ester (10e) to yield the product as an offꢀ
white solid (34 mg, 87 %, 67 % ee), identical in all respects to the previously prepared racemic
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sample, with the exception of [α]D = −36.7 (c 0.25, CHCl3); SFC (Chiralcel IBꢀ3, scCO2/MeCN,
99/1 to 70/30 gradient over 5 min, 3 mL/min): Rt = 4.12 (major) and 5.55 min.
(S)ꢀ2ꢀ(4ꢀMethoxyphenyl)cyclohexanone ((S)ꢀ 18f). The title compound was prepared according to
the general procedure using αꢀarylꢀβꢀketo allyl ester (10f) to yield the product as an offꢀwhite solid
(18 mg, 59 %, 38 % ee), identical in all respects to the previously prepared racemic sample, with the
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