Auto Tandem Catalysis: Asymmetric Vinylogous Cycloaddition/Kinetic Resolution Sequence for the Enantioselective Synthesis of Spiro-Dihydropyranone from Benzylidene Meldrum's Acid

Article abstract of DOI:10.1002/adsc.202100559

A catalytic enantioselective vinylogous domino reaction has been achieved from ketone-derived benzylidene Meldrum's acid and α-ketolactones to provide spirolactone dihydropyranones with more than 99% ee. An Auto Tandem Catalysis (ATC) process resulting fr

Full text of DOI:10.1002/adsc.202100559

Title: Auto Tandem Catalysis: Asymmetric Vinylogous Cycloaddition /
Kinetic Resolution Sequence for the Enantioselective Synthesis
of Spiro-Dihydropyranone from Benzylidene Meldrum’s Acid
Authors: martial TOFFANO, Régis Guillot, Chloee BOURNAUD, jean-
François Brière, and Giang Vo-Thanh
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.202100559
Link to VoR: https://doi.org/10.1002/adsc.202100559

10.1002/adsc.202100559
Advanced Synthesis & Catalysis
UPDATE
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Auto Tandem Catalysis: Asymmetric Vinylogous Cycloaddition /
Kinetic Resolution Sequence for the Enantioselective Synthesis
of Spiro-Dihydropyranone from Benzylidene Meldrum’s Acid.
Martial Toffano*,a Régis Guillot,a Chloée Bournaud,a Jean-François Brièreb and Giang
Vo-Thanha
Dedicated to Prof. Jean-Claude Fiaud on the occasion of his 77th birthday
Received: ((will be filled in by the editorial staff))
a
Dr. M. Toffano, Dr. C. Bournaud, Dr. R. Guillot and Prof. G. Vo-Thanh
Institut de Chimie Moléculaire et des Matériaux d’Orsay. CNRS UMR 8182, Université Paris Saclay
91405 Orsay Cedex, France.
E-mail: martial.toffano@universite-paris-saclay.fr
b
Dr. J.-F. Brière
Normandie Univ, UNIROUEN, INSA Rouen, CNRS, COBRA, 76000 Rouen, France.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
a Brønsted base is highly desirable to expand its
Abstract: A catalytic enantioselective vinylogous domino
reaction has been achieved from ketone-derived benzylidene practice in organic synthesis.[4o]
Meldrum’s acid and -ketolactones to provide spirolactone
dihydropyranones with more than 99% ee. An Auto Tandem
Catalysis (ATC) process resulting from dual and
complementary role of (DHQ)2PHAL organocatalyst
resulted in a sequence involving an asymmetric vinylogous
formal (4+2) cycloaddition of benzylidene and the
subsequent kinetic resolution operating through a 1,3-
prototropic shift leading to good yields (> 50%) and the high
Figure 1. Schematic representation of ATC.
selectivity.
Keywords: Auto Tandem Catalysis; Asymmetric Catalysis;
Kinetic Resolution; Organocatalysis; Meldrum’s acid; 1,3
prototropic shift
Chiral enantioenriched 5,6-dihydropyran-2-ones is
an important heterocyclic structure found in numerous
bioactive compounds. Many synthetic strategies have
been developed to obtain this motif.[6] Among them,
the enantioselective vinylogous reaction is a very
important and simple way to construct such a structure
bearing a quaternary stereocenter.[7] As such, the
development of new reagents to obtain novel chiral
5,6-dihydropyran-2-ones is still of high interest. In the
Accessing chiral enantioenriched molecules is still
a major challenge in organic chemistry. Producing
highly complex structures while preserving energy,
resources and time as well as minimizing waste is even
more difficult. Over the years, great attention has been
given to domino, tandem, one-pot, multi-components
and multi-catalyzed reactions in the synthesis of
natural products as well as biologically active
compounds.[1] Among these, the enantioselective Auto
Tandem Catalysis (ATC) offers a powerful tool owing
to the same chiral catalyst promotes at least two
different chemical transformations in a single pot,
while ensuring the asymmetric induction (Figure 1).
The main advantages of this strategy consist both in
the multiple role of a single catalyst and the
challenging compatibility between reagents to achieve
an economical domino process.[2,3] However, despite
considerable efforts in this area,[4] examples of ATC
process with high enantioselectivity are limited.[5]
Moreover, an auto-tandem catalysis in the presence of
course
of
our
development
of
efficient
enantioselective transformations, we have recently
discovered an unprecedented route to 3,6-
dihydropyran-2-one
3
as spiro-[4,5] decane
derivatives with up to 98% ee, from a novel platform
in vinylogous series i.e. ketone-derived benzylidene
Meldrum’s acids 1.[8],[9] The reaction proceeded
[10]
through a formal (4+2) cycloaddition.
Herein, we
report a highly enantioselective ATC including a
formal (4+2) cycloaddition followed by a kinetic
resolution of the intermediate to give access to
spiro(bis-lactone) 5,6-dihydropyran-2-ones 4 with
excellent enantiomeric excesses (Scheme 1). The
access to enantioenriched compounds
4
from
1
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10.1002/adsc.202100559
Advanced Synthesis & Catalysis
benzylidene Meldrum’s acids has never been
described so far.
4
5
(DHQD)2Pyr
(DHQD)2PHAL
(DHQ)2PHAL
(DHQ)2PHAL
(DHQ)2PHAL
(DHQ)2PHAL
94
97
99
97
99
97
21/79
25/75
13/87
14/86
15/85
14/86
7,5/69
20/74
11/86
13/82
13/80
11/81
86-(S)
89-(S)
75-(R)
12-(S)
66-(R)
51-(R)
89-(R)
92-(R)
98-(S)
99-(S)
94-(S)
99-(S)
6
7[b]
8[c]
9[d]
[a] Reaction conditions: 1a (0.15 mmol), 2 (0.15 mmol),
catalyst (20 mol%) in DCM (0.5 M) at 25 °C otherwise
noted. Percentage of isolated yields after separation of 3a
and 4a by column chromatography. The conversion and
ratio of isomers (3a/4a) were determined by 1H NMR on the
crude product. Enantiomeric excess (ee) was determined by
chiral HPLC. The absolute configuration of 3a and 4a were
determined by X-Ray analysis of pure crystal [b] Performed
at 10°C. [c] Performed at 40°C. [d] Performed with 10
mol% catalyst at [C]=1.0 M.
Scheme 1. Benzylidene Meldrum’s acid 1 as an original
vinylogous platform.
In our previous work, concerning the vinylogous
addition reaction of benzylidene 1 to ketones, we
observed that triethylamine could isomerize the
obtained product 3 into the conjugated product 4 for
longer reaction. We therefore envisaged that a basic
chiral catalyst could deliver directly the
enantioenriched ,-unsaturated lactone 4, through an
economical domino-sequence. Initial investigations
examined the base-catalyzed reaction of benzylidene
1a with dihydro-4,4-dimethyl-2,3-furandione 2 in the
presence of Cinchona-derived catalysts (Scheme 2 and
Table 1).
Reaction with -ICD as catalyst proceeded
smoothly to give the non-conjugated product 3a as the
major product with low enantioselectivity (Table 1,
entry 2). This result is in agreement with our previous
work (entry 1), which showed that many catalysts with
an inadequate basicity led to the kinetic product 3a,
without subsequent conversion into the conjugated
compound 4a.[8] Dimeric alkaloid catalysts afforded 4a
as the major product with better selectivity than -ICD
and in excellent conversion. Thus (DHQD)2AQN gave
an excellent ratio (3a/4a: 3/97) with 71% ee for 4a
(Table 1, entry 3). (DHQD)2Pyr and (DHQD)2PHAL
provided the conjugated product 4a with lower 3a/4a
selectivity with (21/79) and (25/75) respectively.
Compounds 3a and 4a were isolated in satisfactory
yields, but with
a
significant difference of
enantiomeric excesses of (86%ee3a / 89%ee4a) and
(89%ee3a / 92%ee4a) respectively (Table1, entries 4
and 5). This observation was confirmed when using
(DHQ)2PHAL as catalyst. In this case, a 13/87 ratio of
3a/4a with 75% ee for (R)-3a and excellent 98% ee for
(S)-4a were obtained (Table 1, entry 6). At lower
temperature (10°C), the conjugated spiro(bis-lactone)
(S)-4a was isolated in good yield of 82% and very high
enantiomeric excess of 99%, whereas only 13% of the
non-conjugated compound (S)-3a was obtained with a
low enantiomeric excess of 12% (Table1, entry 7).
Higher temperature or higher concentration in the
presence of lower catalyst loading do not improve the
results (Table1, entries 8 and 9). These results are in
contradiction with a simple chemical isomerization
process of the carbon-carbon double bond of the β, γ-
unsaturated lactone 3a to the conjugated lactone 4a. At
this stage, we supposed a possible ATC process
including an enantioselective formal cycloaddition
following by a kinetic resolution (KR) of 3a to 4a.
Surprisingly, this KR would proceed through a 1,3-
proton shift.
Scheme 2. Catalysts.
Table 1. Asymmetric catalysis with benzylidene 1a and
dihydro-4,4-dimethyl-2,3-furandione 2 in the presence of
alkaloid catalysts. [a]
Yields
[%]
3a/4a
Conv.
[%]
ee3a
[%]
ee4a
[%]
Entry
Cat
3a/4a
1
2
3
(R, R)-TUC
-ICD
81
78
91
99/1
96/4
3/97
76/nd
76/nd
nd/71
92-(R)
35-(R)
nd
nd
nd
To prove the existence of KR, we first verified that
3a is thermodynamically stable in the reaction
conditions without the catalyst. Further investigations
(DHQD)2AQN
71-(R)
2
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10.1002/adsc.202100559
Advanced Synthesis & Catalysis
were conducted into the isomerization of a racemic
mixture of 3a to 4a in the presence of (DHQ)2PHAL
at room temperature in order to determine the ratio
3a/4a as well as the enantiomeric excesses of 3a and
4a and the conversion (Scheme 3). [11] To our delight,
a clear kinetic resolution of racemic 3a was observed
with high efficiency in the presence of (DHQ)2PHAL
(Figure 2).
of the KR process with an enantioselectivity factor E
>100.[12] Subsequently, to demonstrate the role of the
ATC process during the reaction, a kinetic study was
undertaken. Several parameters were investigated such
as conversion, 3a/4a ratio and enantiomeric excesses
of 3a and 4a during the reaction between 1a and 2
catalyzed by (DHQ)2PHAL (Table 2).
Table 2. Auto Tandem Catalysis with benzylidene 1a and
dihydro-4,4-dimethyl-2,3-furandione 2 in the presence of
(DHQ)2PHAL catalyst.[a]
ee3a
[%]
ee4a
[%]
Entry
Time [h]
Conv.[%]
3a/4a
1
2
3
4
5
6
7
8
2
4
51
75
86
90
92
92
96
97
95/5
91-(S)
88-(S)
83-(S)
76-(S)
67-(S)
55-(S)
27-(R)
64-(R)
>99-(S)
99-(S)
Scheme 3. Thermodynamic stability and kinetic resolution
of racemic 3a.[a]
89/11
75/25
64/36
51/49
39/61
13/87
11/89
6
>99-(S)
>99-(S)
>99-(S)
>99-(S)
99-(S)
8
10
12
27
33
[CELLRANG[CEE]LLRANGE][CELLR[ACNEGLLER][CAENLG[LCERE]AL[NCLGREAELLN] RG[ACENE] GLLER]ANGE]
EE
[…
h
h
h
h
h
h
h
h
100
90
80
70
60
50
40
30
20
10
0
99-(S)
[a] Reaction conditions: 1a (0.15 mmol), 2 (0.15 mmol),
catalyst (20 mol%) in DCM (0.5 M) at 21 °C Conversion
and ratio of isomers (3a/4a) were determined by H NMR
on the crude product after filtration on a pad of silica gel.
Enantiomeric excess (ee) determined by chiral HPLC
analysis.
1
Half conversion was observed after 2 hours (Table
2, entry 1). The ratio of 95/5 confirms the preliminary
formation of the non-conjugated compound 3a. The
good selectivity of 91% ee for (S)-3a, reflects probably
the high selectivity when creating the spiro stereogenic
center during the first step of the process. At this stage,
the enantiomeric excess of 4a was determined to (S)-
99% ee. During the progress of reaction, we observed
a loss of the enantiomeric excess of (S)-3a correlating
with the variation of 3a/4a ratio (entries 2-5). The
equivalent quantity of 3a and 4a was obtained around
10 hours of reaction (entry 5). The variation of 3a/4a
ratio in favor of 4a isomer in the course of reaction is
related to the decrease of enantiomeric excess of 3a in
reserving the high enantiomeric excess (99%ee) of 4a,
confirming the predominant action of the KR. This
proceeded until the change of the major enantiomer of
CONV.
0
10
20
30
40
50
60
70
Figure 2. Kinetic resolution of 3a in the presence of
(DHQ)2PHAL. [a] Enantiomeric excesses were determined
by HPLC. Conversion and ratio 3a/4a were determined by
1H NMR (see SI for experimental data).
The enantioenriched conjugated (S)-4a was
obtained by the preferentially isomerization of (S)-3a
promoted by the basic (DHQ)2PHAL catalyst. While
the reaction rate was relatively rapid at low conversion, 3a from (S) to (R) between 12h and 27h reaction time,
proving the efficient consumption of (S)-3a and
resulting in the enrichment of (R) enantiomer (Table 2,
entries 6 and 7). This was confirmed by the
enantiomeric excess of (R)-3a increasing from 27 to
64% ee for a reaction time from 27 to 33 h (Table 2,
the transformation slowed after 10 hours (41% of
conversion in 10 hours and 48% in 24 hours). To
achieve conversions of 59%, 292 hours of reaction
time was required. This is proof of the real efficiency
3
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10.1002/adsc.202100559
Advanced Synthesis & Catalysis
entries 7 and 8). After 27 h of reaction, 96% of
conversion was obtained with 13/87 ratio in favor of
4a product. (R)-3a was detected with 27% ee whereas
(S)-4a was isolated with an excellent enantiomeric
excess of 99% ee.
Obtaining the ideal conditions of this ATC reaction
through our experiments, our focus turned to the
substrates scope. A series of benzylidene Meldrum’s
acid 1a-p were used in the ATC reaction in the
presence of dihydro-4,4-dimethyl-2,3-furandione 2
leading to the formation of 5,6-dihydropyran-2-ones
4a-p as expected (Table 3).[13]
[a] Reaction conditions: Benzylidene 1 (0.15 mmol), 2
(0.15mmol), catalyst (20 mol%) in DCM (0.5 M) at 10 °C
for 24h otherwise noted. Conversion and ratio of isomers
1
(3a-p/4a-p) were determined by H NMR on the crude
product. Enantiomeric excess (ee) determined by chiral
HPLC. [b] Reaction performed at 25°C. [c] Isolated yields
after column chromatography. [d] Absolute configuration
for 4a, 4b, 4c, 4d, 4g, 4i, 4j, 4k and 4n was determined to
be (S) by X-Ray analysis (see ref [14]). [e] 72h reaction time.
As indicated in Table 3, a better enantioselectivity
was observed at 10 °C with benzylidene Meldrum’s
acids 1a and 1b (entries 1-2 vs 3-4). In all cases,
excellent conversions of substrates 4a-j were obtained
in 24hours. In the most of cases, the ratio 3a-j/4a-j in
favor of conjugated 4a-j product ranging from 25/75
to 8/92 was detected, leading to satisfactory isolated
yields (64 to 87%). Interestingly, all conjugated
products were obtained with very high enantiomeric
excess with the majority greater than 99% ee (entries
3-13). The absolute configuration for compounds 4a,
4b, 4c, 4d, 4g, 4i, 4j, 4k and 4n were determined to
be (S) by X-ray analysis.[14] The high
enantioselectivity of the process seems to be
independent of the electronic nature of the
benzylidene, since the presence of electron-
withdrawing or donating group do not affect the
excellent enantioselectivity of the process. However,
the steric effect and more precisely, the ortho or
meta position of substituent on the aryl group
showed more impact on the ratio 3/4. For example,
substrate 1k led to an equivalent ratio of 52/48
suggesting probably a slower KR rate compared to
other substrates 4a-j. In this case, 3k was isolated
with 74% ee and more than 99% ee for 4k (entry 13).
The steric effect on the KR rate was confirmed with
compounds 1l-p. Despite compound 1l bearing a
meta-methyl group on the aryl offered a good
conversion, compound 4l was obtained as minor
product with only 15% yield and 99% ee (entry 14).
Extending the reaction time to 72 h led to the
inversion of the ratio 3l/4l from 82/18 to 10/90 in
favor of the conjugated product 4l with a limited loss
of the enantiomeric excess to 98% ee (entry 15).
Moreover, an inversion of the absolute configuration
for the unreactive major enantiomer 3l (-55% ee)
suggests an active KR process. A similar effect was
observed for substrates 1m and 1n which requires a
longer reaction time to give predominantly the
desired conjugated products 4m-n. After 72h, the
ratio value is totally reversed from 99/1 to 7/93 for
3n/4n (entries 18, 19) and from 95/5 to 26/74 for
3m/4m (entries 16, 17). Conjugated compound 1m
was isolated with excellent enantioselectivity over
99% ee and 1n with 97% ee. The limit of the reaction
was observed for substrates 1o and 1p. After 24 h
lower conversions and non-conjugated products 3o
and 3p were obtained as major product with 97/3 and
96/4 ratio respectively along with moderate
enantiomeric excesses (64 and 44% ee, entries 20,
22). Longer reaction time slightly increase the ratio
Table 3. Substrates scope for Auto Tandem Catalysis of 5,6-
dihydropyran-2-ones 4a-p.[a]
Yields
[%] [c]
3/4
ee3a-p
[%]
ee4a-p
Conv
.[%]
Entry
Ar
3/4
[%] [d]
]
1[b]
2[b]
3
4a: Ph
99
99
97
99
96
97
98
98
98
99
93
13/87
14/86
14/86
16/84
8/92
11/86
11/82
13/82
13/64
7/87
75(R)
75
98-(S)
94-(S)
99-(S)
>99-(S)
>99-(S)
>99-(S)
>99
4b: 4-(CN)C6H4
4a: Ph
12(S)
57
4
4b: 4-(CN)C6H4
4c: 4-ClC6H4
5
96
6
4d: 4-(MeO)C6H4
4e:4-(NO2)C6H4
4f: 4-(CH3)C6H4
4g: 4-(CF3)C6H4
4h: 2-naphthyl
4i: 4-(MeO2C)C6H4
20/80
25/75
11/89
10/90
14/86
20/80
11/73
8/65
37
7
33
8
9/86
13
>99
9
8/72
21
>99-(S)
>99
10[b]
11
8/76
62
14/67
2
97-(S)
4j:3,4-(-OCH2O-)
C6H4
12
98
24/76
21/67
67.5
98-(S)
13
14
4k: 3-BrC6H4
4l: 3-(CH3)C6H4
4l:
98
91
99
67
97
85
99
61
93
81
82
52/48
82/18
10/90
95/5
40/44
64/15
9/87
74
89
>99-(S)
99
15[e]
16
- 55
91
98
4m: 4-(ibu)C6H4
4m:
58/nd
22/65
62/nd
6/82
nd
17[e]
18
26/74
99/1
67
>99
nd
4n: 2-furyl
4n:
83
19[e]
20
7/93
- 60
64
97-(S)
nd
4o: 2-ClC6H4
4o:
97/3
57/nd
50/38
64/nd
65/9
21[e]
22
56/44
96/4
23
>99
nd
4p: 1-naphthyl
4p:
44
23[e]
86/14
41
96
4
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10.1002/adsc.202100559
Advanced Synthesis & Catalysis
of conjugated product to only 56/44 for 3o/4o and
86/14 for 3p/4p suggesting the KR rate is particularly
slow for these substrates (entries 21, 23). However, 4o
and 4p were isolated with 99% and 96%ee
respectively. Based on these results, the efficiency of
this process depends both on the enantioselectivity of
the vinylogous cycloaddition (first step), determining
the chemical yield and on the KR (second step)
establishing the enantioselectivity of the general
process. This ATC process is efficient in 1 mmol scale
to produce 4a as enantioenriched compound with 99%
ee (scheme 4). Moreover, all the catalyst is easily
recovered. [15]
occur preferentially at the -position to afford the
product (S)-4a.
Scheme 4. Large scale Auto Tandem Catalysis with
benzylidene 1a and dihydro-4,4-dimethyl-2,3-furandione 2.
The chemical process is summarized in scheme 5. It
is related to the asymmetric formation of the spiro
stereogenic center catalyzed by (DHQ)2PHAL leading
to the non-conjugated lactone 3a as an enantioenriched
mixture (cycle I).[8] The second cycle consists in the
isomerization of (S)-3a to conjugated lactone (S)-4a
via a kinetic resolution process controlled by the same
catalyst (cycle II). This kinetic resolution operates
Scheme 6. Proposed mechanism for the synthesis of spiro
5,6-dihydropyran-2-ones 4a-p by ATC process.
In conclusion, we describe for the first time an Auto
Tandem Catalysis (ATC) process including an
enantioselective
vinylogous
formal
(4+2)
through
a
1,3-prototropic shift. Despite such
being well-documented in
cycloaddition followed by a kinetic resolution (KR)
leading to enantioenriched-final product. This KR
process proceeds through a 1,3-prototropic shift. The
system leads to a high selectivity for the preparation of
5,6-dihydropyran-2-one as original spiro-[4,5]decanes
4a-p with a quaternary stereocenter. This ATC
sequence capitalizes on the cooperative effect of
transformation
enantioselective catalysis,[16] the present process
ensures the amplification of enantiomeric excess. To
the best of our knowledge, a kinetic resolution that
proceeds through a 1,3-prototropic shift leading to an
enantiomeric excess amplification has never been
reported yet.
(DHQ)2PHAL
organocatalyst
on
the
two
enantiodeterminating steps allowing to overcome the
maximum of 50% yield which could be usually
reached in regular KR-processes.
Experimental Section
General procedure for Auto Tandem Catalysis of 5,6-
dihydropyran-2-ones 4a-p: Meldrum’s acid derivative 1a-p
(0.15 mmol) and dihydro-4,4-dimethyl-2,3-furandione 2
(0.15 mmol, 19.5 mg) were diluted in dry CH2Cl2 (0.3 mL,
0.5 M) and (DHQ)2PHAL (20 mol%, 23.9 mg) was added.
After stirring at the desired temperature for 24 hours under
argon atmosphere, the reaction was filtered on a pad of silica
gel [eluent: Petroleum Ether/EtOAc (6/4)] to remove
catalyst and concentrated in vacuo at 30°C to avoid the
possible non-catalyzed thermodynamic isomerization of 3a
to 4a. Conversion and 3a-p /4a-p ratio were determined by
1H NMR on the crude product. The residue was purified by
column chromatography on silica gel to separate the desired
spirolactones 3a-p and 4a-p. 23.9 mg of clean
(DHQ)2PHAL were isolated by washing the pad of silica
with eluent [CH2Cl2/MeOH (9/1)] and concentrated in
vacuo (100% recovered).
Scheme 5. Proposed enantioselective ATC process for the
synthesis of spiro 5,6-dihydropyran-2-ones 4a-p.
The proposed catalytic sequence is shown in
scheme 6. The inside mechanism of the first cycle is
based on our previous body of work.[8] Based on a
study by Dixon and co-workers,[16d] basic catalyst
deprotonates the weakly acidic α-position of (S)-3a to
form the intermediate (S)-I.
A
regioselective
reprotonation of the extended enolate (S)-I would then
5
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10.1002/adsc.202100559
Advanced Synthesis & Catalysis
Detailed experimental procedures for substrates synthesis,
kinetic resolution of racemic 3a, NMR-, HPLC-spectra and
crystallographic data can be found in the supporting
information.
A. Samim, D. Panja, S. Kundu, Catal. Sci.Technol. 2019,
9, 6002-6006; n) P. T. K. Arachchige, C. S. Yi, Org. Lett.
2019, 21, 3337-3341; o) A. Kondoh, C. Ma, M. Terada,
Chem. Commun. 2020, 56, 10894-10897; p) J. R.
Alexander, V. I. Shchepetkina, K. S. Stankevich, R. J.
Benedict, S. P. Bernhard, R. J. Dreiling, M. J. Cook,
Org. Lett. 2021 23, 559-564.
Acknowledgements
This work was supported by the Centre National de la Recherche
Scientifique (C.N.R.S), funded by the french government. The
author thanks Dr. Amélie Duraud for proof-reading.
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were obtained from basic catalysis to give pure samples
(see SI).
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10.1002/adsc.202100559
Advanced Synthesis & Catalysis
[14] Based on the (S)-absolute configuration and the
levorotation for compounds 4a, 4b, 4c, 4d, 4g, 4i, 4j, 4k
and 4n, we suppose a same (S)-configuration for 4e, 4f
4h, 4l, 4m, 4o and 4p which are levorotary compounds.
CCDC 1992495, 2062725 & 2045183-2045189 contains
the supplementary crystallographic data for this paper.
These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre via
http://www.ccdc.cam.ac.uk/Community/.
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[15] 100% of the catalyst was recovered after reaction (see
experimental section)
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Advanced Synthesis & Catalysis
UPDATE
Auto Tandem Catalysis: Asymmetric Vinylogous
Cycloaddition/Kinetic Resolution Sequence for the
Enantioselective Synthesis of Spiro-
Dihydropyranone from Benzylidene Meldrum’s
Acid.
Adv. Synth. Catal. Year, Volume, Page – Page
Martial Toffano*, Régis Guillot, Chloée Bournaud,
Jean-François Brière and Giang Vo-Thanh
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