A highly enantioselective [4+2] cycloaddition involving aldehydes and β,γ-unsaturated-α-keto esters

Article abstract of DOI:10.1016/j.tetasy.2017.09.019

A stereoselective inverse electron demand oxo-Diels-Alder reaction involving electron poor dienes (γ-aryl-β,γ-unsaturated-α-keto ester) and electron rich dienophiles has been studied. These cycloaddition reactions are extremely useful for the construction of O-, N-, S-centered heterocyclic compounds, which are routinely used in both synthetic organic and medicinal chemistry. The [4+2] hetero cycloaddition reactions involving various aldehydes and β,γ-unsaturated-α-keto esters were carried out in which three different types of substituted proline catalysts were examined. For these reactions, high selectivities (enantiomeric excess 93–98%) were obtained using catalyst 3. Due to the bulkiness of catalyst 3, compared to the other catalysts tested, it is more efficient at catalyzing these type reactions.

Full text of DOI:10.1016/j.tetasy.2017.09.019

Tetrahedron: Asymmetry xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
A highly enantioselective [4+2] cycloaddition involving aldehydes
and b,c-unsaturated-a-keto esters
⇑
Nanda Kumar Katakam, Yejin Kim, Allan D. Headley
Department of Chemistry, Texas A&M University-Commerce, Commerce, TX 75429-3011, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A stereoselective inverse electron demand oxo-Diels-Alder reaction involving electron poor dienes (c-
aryl-b,c-unsaturated-a-keto ester) and electron rich dienophiles has been studied. These cycloaddition
reactions are extremely useful for the construction of O-, N-, S-centered heterocyclic compounds, which
are routinely used in both synthetic organic and medicinal chemistry. The [4+2] hetero cycloaddition
Received 24 July 2017
Revised 17 September 2017
Accepted 26 September 2017
Available online xxxx
reactions involving various aldehydes and b,c-unsaturated-a-keto esters were carried out in which three
different types of substituted proline catalysts were examined. For these reactions, high selectivities
(enantiomeric excess 93–98%) were obtained using catalyst 3. Due to the bulkiness of catalyst 3, com-
pared to the other catalysts tested, it is more efficient at catalyzing these type reactions.
Ó 2017 Elsevier Ltd. All rights reserved.
1. Introduction
is that the catalysts are typically not recyclable.9 In contrast, the
use of organocatalysts for asymmetric hetero Diels-Alder has many
Ever since the discovery of the Diels-Alder reaction,1 it has
become a cornerstone reaction in organic chemistry for the synthe-
sis of carbon–carbon bonds. Researchers over the years have been
inspired to develop different catalysts to effectively catalyze these
reactions.2 Catalytic asymmetric Diels-Alder reactions have
emerged as a powerful methodology for the stereoselective con-
struction of functionalized six membered rings with control of
regio-, diastereo-, and enantioselectivity.3 The inverse-electron
demand hetero Diels-Alder reactions, which involve the incorpora-
tion of heteroatoms, such as oxygen or nitrogen, have given rise to
the construction of heterocyclic compounds that are of extreme
advantages, such as mild reaction conditions, tolerance of a diverse
range of functional groups, and the easy construction of carbon–
heteroatom bonds. A major advantage is the facile stereospecific
introduction of functionalized ring systems with up to four stereo-
centers in the products.10 Herein, the effectiveness of a series of
proline derived organocatalysts in promoting the enantioselective
outcomes of the hetero Diels-Alder reactions of aldehydes with
electron-deficient enones are analyzed.
2. Results and discussion
importance in medicinal chemistry.4
A number of different
Amines, including proline and different proline derivatives,
have emerged as very effective organocatalysts for various reac-
tions, including aldol, Mannich, and Michael reactions.11 Hayashi
research et al. have successfully utilized diarylprolinol silyl ether
salts to catalyze an asymmetric Diels-Alder reaction.12 Figure 1
shows the organocatalysts that were considered herein.
List et al. and Hayashi et al. developed catalyst 1 and indepen-
dently reported its success in catalyzing the asymmetric Michael
addition involving acetaldehyde.13 Catalyst 2 was synthesized in
our lab and tested owing to possible hydrogen bond donor capabil-
ity of the hydroxyl hydrogen. In 2009, our research group reported
the design, synthesis and application of a new type of highly active
di(N,N-dimethylbenzylamine)prolinol silyl ether organocatalyst
(catalyst 3 in Fig. 1). This organocatalyst was shown to be a highly
water-soluble organocatalyst for the asymmetric Michael addition
Lewis-acid catalysts and chiral Lewis acid complexes5 have been
used to catalyze asymmetric hetero Diels-Alder reactions.6 It was
discovered that chiral Brønsted acids could be used to promote a
highly enantioselective hetero Diels-Alder reaction via hydrogen-
bonding interactions.7 According to frontier orbital theory,8 most
of these catalysts employ a LUMO-activation strategy to activate
electron-deficient dienophiles, and there have been only a few chi-
ral catalysts that take advantage of an alternative strategy that
activates the HOMO. A large percentage of the studies that involve
catalytic asymmetric hetero Diels-Alder reactions are carried out
using organometallic catalysts, which normally require harsh reac-
tion conditions. As a result, a major disadvantage of this approach
⇑
Corresponding author.
E-mail address: allan.headley@tamuc.edu (A.D. Headley).
https://doi.org/10.1016/j.tetasy.2017.09.019
0957-4166/Ó 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Katakam, N. K.; et al. Tetrahedron: Asymmetry (2017), https://doi.org/10.1016/j.tetasy.2017.09.019

2
N. K. Katakam et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
Ph
Br
Ph
Br
N
N
N
N
N
N
OTMS
N
H
OH
OTMS
OTMS
N
H
N
H
N
H
Catalyst 3
4
Catalyst
2
Catalyst
Catalyst 1
Figure 1. Organocatalysts screened for the oxo-Diels-Alder reaction.
of aldehydes to nitroolefins in which high diastereo- and enantios-
electivities were obtained.14
the intermediate B, which after hydrolysis gives the hemiacetal
product. The hemiacetal is then oxidized further to give the prod-
ucts shown in Table 2. Similar hetero Diels-Alder reactions involv-
Recently, our research efforts have focused on the development
of water-soluble organocatalysts that are effective in aqueous
media. In addition to the obvious advantages of carrying out reac-
tions in aqueous media, including ease of product isolation, water
has the unique advantage of being an environmentally benign eco-
nomical solvent. As a result, it is a desirable medium to carry out
asymmetric organocatalysis.15 Catalyst 4, which was developed
in our research group, was found to be very effective for the asym-
metric Michael reactions in aqueous media. Its effectiveness is pri-
marily due to the presence of the ionic ammonium functionality,
which when combined with the presence of the bulky OTMS group,
serves as an effective organocatalyst for asymmetric reactions.16
These bulky groups serve to selectively block one side of the reac-
tant so that a stereoselective reaction can take place from the less
sterically hindered side to afford the stereoselective products. The
development of water-compatible asymmetric organocatalysts is a
growing area of research and many have been developed and
applied to a wide range of organic transformations, in which asym-
metric products are obtained with high stereoselectivities.17,18 In
the use of these catalysts, bulky tags and effective hydrogen bond-
ing capabilities selectively serve to give enantiospecific products.
For the reaction studied herein, the electron rich dienophile
intermediate A is generated in situ from the aldehyde with either
organocatalyst 1, 2, 3 or 4 as shown in the general catalytic cycle
in Scheme 1.19 The electron-rich alkene then undergoes the
stereoselective hetero Diels-Alder reactions with the enone to give
ing b,c-unsaturated-a c-unsaturated-a-
-keto-esters20 and b,
ketophosphonates21 have been studied and are shown to have a
similar reaction cycle.
The reaction involving valeraldehyde and Ƴ-phenyl-b,Ƴ-unsat-
urated-a-keto methyl ester served as a model to gain the opti-
mized set of reaction conditions (catalyst, catalyst loading,
temperature, and solvent) and the results are shown in Table 1.
As mentioned earlier, the initially obtained hemiacetal product
was converted to the more stable lactone product by oxidation
with pyridinium chlorochromate. The percentage yield and enan-
tiomeric excess were determined from the oxidized product.
First, catalyst 4 was considered since it is ionic and was success-
fully used as a recyclable catalyst in aqueous solvents for aldol
reactions that were previously studied in our laboratory.16 Unfor-
tunately, it was not successful. As shown in Table 1, (entries 1, 2
and 3), the reaction was tested in three different solvents, includ-
ing water, but no product was isolated. Next, catalyst 1 was tested
since it was shown to be an effective catalyst for the asymmetric
synthesis of various compounds.22 As shown in Table 1, it was
not effective in catalyzing the reaction in water (entry 6), probably
due to its low solubility, but was most effective in CH2Cl2 (entries 4
and 5). As a result, different ratios of reactants were tested in CH2-
Cl2. For this catalyst, these changes did not have a significant effect
on the reaction. Due to the polar property of catalyst 2 brought
about by the introduction of the dimethylamino groups and the
presence of the hydroxyl group, it was tested for this reaction in
CH2Cl2. As shown in Table 1, this catalyst performed much better,
compared to the previously tried catalysts, even though the yields
were relatively low. In addition, these results showed that silica gel
was needed for this reaction (entries 10 and 11). Silica gel is neces-
sary for the substrates to be converted into the final products and
to achieve catalytic turnover.
H2O
X
CO2R3
X
O
O
OR
N
R2
X
Encouraged by the results using catalyst 2 and that the
dimethylamino group played an important role in the reaction,
we envisioned that a catalyst containing the bulky OTMS group
should be an improvement over catalyst 2. As a result, the next cat-
alyst tested was catalyst 3; this catalyst definitely showed an
improvement with shorter reaction times and improved enantios-
electivities. These results also indicate that the best results were
obtained when there was a slightly higher aldehyde concentration
compared to the enone (entries 13 and 14). The reaction was also
carried out using different catalyst concentrations as shown in
entries 17 and 18. These results confirm that a catalyst concentra-
tion of 10 mol % provides the optimum results for this reaction. In
order to ensure that CH2Cl2 was the best solvent for this reaction,
the reaction was carried out in other solvents as shown in Table 1
(entries 19–23). Although a good amount of substrate conversion
R1
A
R1
X
X
X
OR
N
H
OR
N
1, 2, 3
4
or
catalyst
R1
R2
O
OH
O
R1
R2
CO2R3
B
CO2R3
H2O
hemiacetal
Scheme 1. Catalytic cycle for the hetero Diels-Alder reaction, where X and R are
shown in Figure 1 and R1 and R2 are shown in Table 2.
Please cite this article in press as: Katakam, N. K.; et al. Tetrahedron: Asymmetry (2017), https://doi.org/10.1016/j.tetasy.2017.09.019

N. K. Katakam et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
3
Table 1
Optimization of reaction conditions for the hetero Diels-Alder reaction involving valeraldehyde and
c
-phenyl-b,
c-unsaturated-a-keto methyl ester carried out at 23 °C
O
CO2Me
CO2Me
O
CO2Me
HO
O
O
O
+
PCC
DCM
catalyst
Ph
Ph
Ph
Entry
Enone (mmol)
RCHO (mmol)
Cat (mol %)
Solvent
Time
(h)
% Yielde
% eef
d
1
2
3
4
5
6
7
8
0.5
0.5
0.5
1.0
0.5
1.0
0.5
0.5
1.0
1.0
1.0
0.25
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.5
1.5
1.5
1.0
1.5
0.5
3.0
1.5
0.5
1.0
0.5
1.0
1.0
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
4 (10)
4 (10)
4 (10)
1 (10)
1 (10)
1 (10)
2 (10)
2 (10)
2 (10)
2 (30)
2 (10)
3 (20)
3 (10)
3 (10)
3 (10)
3 (10)
3 (5)
CH2Cl2
i-PrOH
H2O
DCM
DCM
96
96
96
20
26
168
34
34
10
32
32
18
20
19
24
96
20
36
20
32
24
96
96
Trace
Trace
Trace
65
64
nd
26
21
24
Trace
Trace
68
76
78
44
29
61
44
nd
nd
nd
96
95
nd
85
82
84
nd
nd
96
95
98
80
88
91
87
98
84
nd
nd
nd
H2O
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
MeCN
DMF
9
10a
11a
12
13
14
15b
16c
17
18
19
20
21
22
23
3 (20)
3 (10)
3 (10)
3 (10)
3 (10)
3 (10)
34
46
Trace
Trace
Trace
THF
i-PrOH
a
b
c
d
e
f
Reaction carried out without using silica.
Reaction carried out at 35 °C.
Reaction carried out at 0 °C.
Time to form cycloadduct.
Determined for oxidized derivative; and nd = not determined.
Determined for oxidized derivative; and nd = not determined.
Table 2
Reaction scope for the oxo-Diels-Alder reaction involving various
c
-aryl-b,
c
-unsaturated-
a
-keto esters and substituted aldehydes
O
CO2Me
CO2Me
O
HO
R1
CO2Me
O
O
O
+
catalyst
PCC
R1
R1
DCM
R2
R2
R2
Entry
R1
R2
Time (h)
% Yield
% ee
1
2
3
4
5
6
7
8
CH3CH2CH2
CH3
(CH3)2CH
C6H5
C6H5
C6H5
C6H5
C6H5
19
15
26
12
16
15
13
14
20
21
12
78
51
64
86
80
76
94
77
76
74
85
98
93
98
98
98
97
98
98
98
98
95
CH3(CH2)3CH2
CH3(CH2)3CH2
CH3(CH2)3CH2
CH3(CH2)3CH2
CH3(CH2)3CH2
CH3(CH2)3CH2
CH3(CH2)3CH2
C6H5CH2
4-MeC6H4
3-MeOC6H4
4-MeOC6H4
4-BrC6H4
4-FC6H4
9
10
11
C6H5
to product was observed in acetonitrile (yield 46%), the ee value
was only 84% (entry 20). The low yields observed in THF and iso-
propanol are probably due to the partial solubility of the enone
in these solvents. The reaction was carried out at different temper-
atures; at a higher temperature (35 °C, entry 15), it is observed that
even though the reaction time was reduced, the yield and enan-
tioselectivity were lower than those obtained at 23 °C. At a lower
temperature of 0 °C, it was observed that the reaction time was
greatly increased, and with no real improvement in % yield or %
ee (entry 16). These results show that the optimum set of reaction
conditions are those shown in entry 14 and were used to carry out
a study of the reaction scope; the results are shown in Table 2.
From Table 2, it is obvious that the best set of results in terms of
reaction time, enantioselectivity and yield, is shown in entry 4. It
appears that when the larger iso-propyl group is removed from
the reaction center by a methylene unit, the best yield is obtained.
From entry 3, even though the iso-propyl group is present, it is clo-
ser to the reaction center and results in a lower combination of
Please cite this article in press as: Katakam, N. K.; et al. Tetrahedron: Asymmetry (2017), https://doi.org/10.1016/j.tetasy.2017.09.019

4
N. K. Katakam et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
enantioselectivity, yield and slightly longer time. It also appears
that electron-withdrawing and electron donating substituents on
the phenyl ring do not have a major effect on this reaction. From
entry 10, in which a very effective electron-withdrawing group
on the phenyl ring is used, it can be seen that there is only a slight
improvement of the reaction, compared to reactions with other
substituents.
4.1.2. (S,R)-a-Methyl-b-phenyl-c,d-unsaturated-d-methylester
lactone19
1H NMR (400 MHz, CDCl3): d (ppm) = 7.38–7.30 (m, 3H), 7.18–
7.15 (m, 2H), 6.50 (d, 1H), 3.85 (s, 3H), 3.53 (dd, 1H), 2.77–2.68
(m, 1H), 1.19 (d, 3H). 13C NMR (100 MHz, CDCl3): d (ppm)
= 169.40, 161.0, 141.80, 139.90, 129.40 (2C), 128.20, 127.90 (2C),
119.0, 52.90, 44.90, 40.40, 14.30. Enantiomeric excess ratio was
determined using Diacel OD-H column and UV = 240 nm; tmajor
21.285 min, tminor = 17.750 min.
=
3. Conclusions
4.1.3. (S,R)-
a-Isopropyl-b-phenyl-c,d-unsaturated-d-
Of the four catalysts considered for the stereoselective inverse
electron demand oxo-Diels-Alder reaction, we have shown that
catalysts 3 can be used to effectively carry out this reaction, in
which high enantiomeric excess was obtained. The key step in this
reaction cycle involves the reaction of the bulky catalyst with the
aldehyde to form an enamine intermediate which is a key step in
the formation of the six-membered cyclic adduct. A previously pro-
posed transition state model for similar reactions can be used to
explain the stereochemical outcomes of these reactions.19 The
effectiveness of the catalyst herein is due to the presence of the
bulky OTMS group, combined with the presence of two benzyl
dimethyl amino groups.
methylester lactone
10
1H NMR (400 MHz, CDCl3): d (ppm) = 7.34–7.25 (m, 3H),
7.12–7.09 (m, 2H), 6.54 (dd, 1H), 3.86 (s, 3H), 3.79 (dd, 1H), 2.54
(ddd, 1H), 1.96–1.90 (m, 1H), 1.11 (d, 3H), 1.02 (d, 3H). 13C NMR
(100 MHz, CDCl3):
d (ppm) = 167.23, 160.85, 141.83, 139.66,
129.34 (2C), 127.85, 127.17 (2C), 116.40, 53.50, 52.75, 41.21,
29.12, 20.97, 19.89. Enantiomeric excess ratio was determined
using Diacel OD-H column and tmajor = 11.687 min, tminor = 9.255
min.
4.1.4. (S,R)-a-Pentyl-b-phenyl-c,d-unsaturated-d-methylester
lactone19
1H NMR (400 MHz, CDCl3): d (ppm) = 7.35–7.27 (m, 3H), 7.14–
7.11 (m, 2H), 6.52 (d, 1H), 3.85 (s, 3H), 3.65 (dd, 1H), 2.76–2.71
(m, 1H), 1.68–1.54 (m, 2H), 1.46–1.32 (m, 2H), 1.27–1.18 (m,
4H), 0.83 (t, 3H). 13C NMR (100 MHz, CDCl3): d (ppm) = 168.23,
160.90, 141.49, 139.59, 129.28 (2C), 127.92, 127.38 (2C), 117.34,
52.74, 45.82, 42.97, 31.44, 29.81, 26.41, 22.34, 13.93. Enantiomeric
excess ratio was determined using Diacel OD-H column and tmajor
= 12.027 min, tminor = 9.513 min.
4. Experimental section
4.1. General procedure for enantioselective hetero Diels-Alder
reactions
The synthesis of the catalysts used are described elsewhere:
catalyst 1;22a catalyst 2 and catalyst 3;23 catalyst 4.16 The syntheses
of the enones are described elsewhere.24 For the hetero Diels-Alder
reactions, the enone (0.5 mmol) was dissolved in 0.5 mL of dichlor-
omethane and kept in an ice bath, then the aldehyde (1.5 mL), cat-
alyst (0.05 mmol), silica (50 mg of silica) were added separately to
the reaction solution, which was allowed to stir until TLC analysis
indicated that the reaction was complete. Spots were visualized
under UV light (k = 254 nm) using TLC silica gel 60 F254 plates
coated with aluminum. The cycloadduct formed was purified by
column chromatography to give the hemiacetal, which is dissolved
in 2 mL of dichloromethane and oxidized adding 1 equiv of pyri-
dinium chlorochromate (PCC). After the oxidation was complete,
the crude product was purified by column chromatography using
4.1.5. (S,R)-a-Heptyl-b-phenyl-c,d-unsaturated-d-methylester
lactone19
1H NMR (400 MHz, CDCl3): d (ppm) = 7.35–7.26 (m, 3H), 7.14–
7.11 (m, 2H), 6.51 (d, 1H), 3.84 (s, 3H), 3.66–3.63 (dd, 1H), 2.76–
2.70 (m, 1H), 1.69–1.54 (m, 2H), 1.47–1.31 (m, 2H), 1.27–1.16
(m, 8H), 0.84 (t, 3H); 13C NMR (100 MHz, CDCl3): d (ppm)
= 168.35, 160.88, 141.46, 139.56, 129.24 (2C), 127.88, 127.34
(2C), 117.15, 52.65, 45.72, 42.87, 31.74, 29.83, 29.29, 28.88,
26.71, 22.64, 14.08. Enantiomeric excess ratio was determined
using Diacel OD-H column and tmajor = 11.337 min, tminor = 8.577
min.
silica gel (porosity 60 Å, particle size 40–63 lm) and 8/2 hexanes
and ethyl acetate. 1H and 13C NMR spectra were obtained using a
Varian 400 MHz instrument with TMS as the internal standard.
Enantiomeric ratios were determined using a Shimadzu LC solution
Chromatography Data System, in which Diacel chiral OD-H or AD-
H columns with hexane/isopropanol (90:10) used as the eluent and
flow rate 1.0 mL/min; UV = 240 nm were used. Racemates were
synthesized using morpholine as an achiral catalyst. Enantiomeric
excess determinations were made based on comparisons with pre-
viously reported literature determinations.19 Similar HPLC condi-
tions were used for the separation of the enantiomers for each
reaction and based on the retention times, NMR and IR data, the
identity of each enantiomer was determined.
4.1.6. (S,R)-
a-Pentyl-b-4-methylphenyl-c,d-unsaturated-d-
methylester lactone19
1H NMR (400 MHz, CDCl3): d (ppm) = 7.13 (d, 2H), 7.01 (d, 2H),
6.50 (d, 1H), 3.84 (s, 3H), 3.62–3.59 (m, 1H), 2.74–2.68 (m, 1H),
2.32 (s, 3H), 1.68–1.53 (m, 2H), 1.46–1.31 (m, 2H), 1.28–1.17 (m,
4H), 0.83 (t, 3H); 13C NMR (100 MHz, CDCl3): d (ppm) = 168.35,
160.88, 141.32, 137.66, 136.57, 129.92 (2C), 127.20 (2C), 117.69,
52.65, 45.86, 42.46, 31.46, 29.70, 26.44, 22.36, 21.14, 13.95. Enan-
tiomeric excess ratio was determined using Diacel OD-H column
and tmajor = 9.408 min, tminor = 7.845 min.
4.1.7. (S,R)-
a-Pentyl-b-3-methoxyphenyl-c,d-unsaturated-d-
methylester lactone19
1H NMR (400 MHz, CDCl3): d (ppm) = 7.26–7.22 (m, 1H), 6.80
(dd, 1H), 6.71 (d, 1H), 6.65 (t, 1H), 6.49 (d, 1H), 3.84 (s, 3H), 3.77
(s, 3H), 3.61 (dd, 1H), 2.73 (dd, 1H), 1.69–1.53 (m, 2H), 1.46–1.31
(m, 2H), 1.27–1.15 (m, 4H), 0.83 (t, 3H); 13C NMR (100 MHz,
CDCl3): d (ppm) = 168.22, 160.90, 160.22, 141.63, 141.22, 130.36,
119.51, 117.20, 113.40, 112.86, 55.32, 52.74, 45.68, 42.83, 31.43,
29.67, 26.41, 22.34, 13.93. Enantiomeric excess ratio was deter-
4.1.1. (S,R)-a-Propyl-b-phenyl-c,d-unsaturated-d-methylester
lactone19
1H NMR (400 MHz, CDCl3): d (ppm) = 7.35–7.27 (m, 3H), 7.15–
7.11 (m, 2H), 6.52 (d, 1H), 3.85 (s, 3H), 3.64 (m, 1H), 2.78–2.72
(m, 1H), 1.70–1.34 (m, 4H), 0.86 (t, 3H); 13C NMR (100 MHz,
CDCl3): d (ppm) = 168.23, 160.90, 141.49, 139.59, 129.28 (2C),
127.92, 127.38 (2C), 117.34, 52.74, 45.55, 42.97, 31.98, 20.04,
13.93. Enantiomeric excess ratio was determined using Diacel
OD-H column and tmajor = 13.617 min, tminor = 10.528 min.
mined using Diacel OD-H column and tmajor = 18.392 min, tminor
13.719 min.
=
Please cite this article in press as: Katakam, N. K.; et al. Tetrahedron: Asymmetry (2017), https://doi.org/10.1016/j.tetasy.2017.09.019

N. K. Katakam et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
5
3. (a) Kobayashi, S.; Kobayashi, S., Jørgensen, K. A., Eds.; Wiley: New York, 2002;
pp 187–209.; (b) Jørgensen, K. A.; Johannsen, M.; Yao, S.; Audrain, H.;
Thorhauge, J. Acc. Chem. Res. 1999, 32, 605.
4.1.8. (S,R)-
a-Pentyl-b-4-methoxyphenyl-c,d-unsaturated-d-
methylester lactone19
1H NMR (400 MHz, CDCl3): d (ppm) = 7.04 (d, 2H), 6.84 (d, 2H),
6.5 (d, 1H), 3.84 (s, 3H), 3.77 (s, 3H), 3.59 (dd, 1H), 2.71–2.65 (m,
1H), 1.67–1.52 (m, 2H), 1.45–1.28 (m, 2H), 1.27–1.15 (m, 4H),
4. Jiang, X.; Wang, R. Chem. Rev. 2013, 113, 5515–5546.
5. (a) Evans, D. A.; Olhava, E. J.; Johnson, J. S.; Janey, J. M. Angew. Chem., Int. Ed.
1998, 37, 3372; (b) Evans, D. A.; Johnson, J. S. J. Am. Chem. Soc. 1998, 120, 4895;
(c) Audrain, H.; Thorhauge, J.; Hazell, R. G.; Jorgensen, K. A. J. Org. Chem. 2000,
65, 4487; (d) Barroso, S.; Blay, G.; Munoz, M. C.; Pedro, J. R. Adv. Synth. Catal.
2009, 351, 107; (e) Zhu, Y.; Chen, X.; Xie, M.; Dong, S.; Qiao, Z.; Lin, L.; Liu, X.;
Feng, X. Chem. Eur. J. 2010, 16, 11963; (f) Johnson, J. S.; Evans, D. A. Acc. Chem.
Res. 2000, 33, 325; (g) Ghosh, A. K.; Mathivanan, P. Tetrahedron: Asymmetry
1998, 9, 1; (h) Kagan, H. B.; Riant, O. Chem. Rev. 1992, 1007, 92.
6. (a) Kagan, H. B.; Riant, O. Chem. Rev. 1992, 92, 1007; (b) Corey, E. J. Angew.
Chem., Int. Ed. 2002, 41, 1650; (c) Reymond, S.; Cossy, J. Chem. Rev. 2008, 108,
5359.
0.83 (t, 3H); 13C NMR (100 MHz, CDCl3):
d (ppm) = 168.48,
160.88, 159.25, 141.32, 131.55, 128.42 (2C), 117.70, 114.57 (2C),
55.36, 52.65, 46.13, 42.06, 31.46, 29.70, 26.44, 22.37, 13.95. Enan-
tiomeric excess ratio was determined using Diacel OD-H column
and tmajor = 13.633 min, tminor = 11.031 min.
4.1.9. (S,R)-
a-Pentyl-b-4-bromophenyl-c,d-unsaturated-d-
7. Huang, Y.; Unni, A. K.; Thadani, A. N.; Rawal, V. H. Nature 2003, 424, 146.
8. Sustmann, R. Pure Appl. Chem. 1974, 40, 569.
methylester lactone19
1H NMR (400 MHz, CDCl3): d (ppm) = 7.45 (d, 2H), 7.01 (d, 2H),
6.46 (d, 1H), 3.84 (s, 3H), 3.62 (dd, 1H), 2.68 (dd, 1H), 1.68–1.52 (m,
2H), 1.46–1.30 (m, 2H), 1.28–1.14 (m, 4H), 0.83 (t, 3H); 13C NMR
9. Li, J.-L.; Liu, T.-Y.; Chen, Y.-C. Acc. Chem. Res. 2012, 45, 1491.
10. Sinha, D.; Perera, S.; Zhao, J. C.-G. Chem. Eur. J. 2013, 19, 6976.
11. (a) Qiao, Y.; Headley, A. D. Catalysts 2013, 3, 709; (b) Ghosh, S. K.; Dhungana, K.;
Headley, A. D.; Ni, B. Org. Biomol. Chem. 2012, 10, 8322; (c) Sarkar, D.; Bhattarai,
R.; Headley, A. D.; Ni, B. Synlett 2011, 1993.
12. Hayashi, Y.; Samanta, S.; Gotoh, H.; Ishikawa, H. Angew. Chem. 2008, 120, 6736.
13. (a) Garcia-Garcia, P.; Ladepeche, A.; Halder, R.; List, B. Angew. Chem., Int. Ed.
2008, 47, 4719; (b) Hayashi, Y.; Itoh, T.; Ohkubo, M.; Ishikawa, H. Angew. Chem.,
Int. Ed. 2008, 47, 4722.
14. (a) Zheng, Z.; Perkins, B. L.; Ni, B. J. Am. Chem. Soc. 2010, 132, 50; (b) Ghosh, S.
K.; Zheng, Z.; Ni, B. Adv. Synth. Catal. 2010, 352, 2378; (c) Chintala, P.; Ghosh, S.
K.; Long, E.; Headley, A. D.; Ni, B. Adv. Synth. Catal. 2011, 353, 2905.
15. (a) Li, C. J.; Chan, T. H. Organic Reactions in Aqueous Media; Wiley: New York,
1997; (b) Ten, G.-J.; Brink, I. W.; Arends, C. E.; Sheldon, R. A. Science 2000, 287,
636; (c) Lindstroem, U. M. Chem. Rev. 2002, 102, 2751; (d) Breslow, R. Acc.
Chem. Res. 1991, 24, 159; (e) Kobayashi, S.; Manabe, K. Acc. Chem. Res. 2002, 35,
533; (f) Kobayashi, S.; Manabe, K. Pure Appl. Chem. 2000, 72, 1373; (g) Li, C. J.
Chem. Rev. 2005, 105, 3095; (h) Paradowska, J.; Stodulski, M.; Mlynarski, J.
Angew. Chem., Int. Ed. 2009, 48, 4288; (j) Raj, M.; Singh, V. K. Chem. Commun.
2009, 6687.
(100 MHz, CDCl3):
d (ppm) = 167.94, 160.74, 141.87, 138.61,
132.50 (2C), 129.10 (2C), 121.90, 116.47, 52.78, 45.72, 42.33,
31.46, 29.70, 26.44, 22.37, 13.95. Enantiomeric excess ratio was
determined using Diacel AD-H column and tmajor = 11.748 min,
tminor = 9.092 min.
4.1.10. (S,R)-
a-Pentyl-b-4-trifluoromethylphenyl-c,d-
unsaturated-d-methylester lactone19
1H NMR (400 MHz, CDCl3): d (ppm) = 7.60 (d, 2H), 7.27 (d, 2H),
6.48 (d, 1H), 3.85 (s, 3H), 3.73 (dd, 1H), 2.73 (dd, 1H), 1.69–1.54 (m,
2H), 1.46–1.32 (m, 2H), 1.28–1.15 (m, 4H), 0.83 (t, 3H); 13C NMR
(100 MHz, CDCl3):
d (ppm) = 167.68, 160.63, 143.66, 142.04,
127.79 (2C), 126.29 (2C), 115.98, 52.88, 45.55, 42.70, 31.44,
29.67, 26.41, 22.34, 13.93; 19F NMR (400 MHz, CDCl3): d (ppm)
= À62.70 (s, 3F). Enantiomeric excess ratio was determined using
Diacel AD-H column and tmajor = 9.553 min, tminor = 7.081 min.
16. Ghosh, S. K.; Qiao, Y.; Ni, B.; Headley, A. Org. Biomol. Chem. 2013, 11, 1801–
1804.
17. (a) Brogan, A. P.; Dickerson, T. J.; Janda, K. D. Angew. Chem., Int. Ed. 2006, 45,
8100; (b) Hayashi, Y. Angew. Chem., Int. Ed. 2006, 45, 8103; (c) Gruttadauria, M.;
Giacalone, F.; Noto, R. Adv. Synth. Catal. 2009, 351, 33; (d) Raj, M.; Singh, V. K.
Chem. Commun. 2009, 6687; (e) Mase, N.; Barbas, C. F., III Org. Biomol. Chem.
ˇ
2010, 8, 4043–4050; (f) Toma, Š.; Šebesta, R.; Meciarová, M. Curr. Org. Chem.
2011, 15, 2257.
4.1.11. (S,R)-
a-Benzyl-b-4-phenyl-c,d-unsaturated-d-methyl-
ester lactone19
18. (a) Hayashi, Y.; Aratake, S.; Okano, T.; Takahashi, J.; Sumiya, T.; Shoji, M. Angew.
Chem., Int. Ed. 2006, 45, 5527; (b) Font, D.; Jimeno, C.; Pericàs, M. A. Org. Lett.
2006, 8, 4653; (c) Wu, Y.; Zhang, Y.; Yu, M.; Zhao, G.; Wang, S. Org. Lett. 2006, 8,
4417; (d) Mase, N.; Nakai, Y.; Ohara, N.; Yoda, H.; Takabe, K.; Tanaka, F.; Barbas,
C. F. J. Am. Chem. Soc. 2006, 128, 734; (e) Cheng, L.; Wu, X.; Lu, Y. Org. Biomol.
Chem. 2007, 1018, 5; (f) Hayashi, Y.; Urushima, T.; Aratake, S.; Okano, T.; Obi, K.
Org. Lett. 2008, 10, 21; (g) Amedjkouh, M.; Brandberg, M. Chem. Commun. 2008,
3043; (h) Singh, V.; Singh, V. K. Org. Lett. 2007, 9, 1117; (i) Mao, Z.; Jia, Y.; Li,
W.; Wang, R. J. Org. Chem. 2010, 75, 7428.
1H NMR (400 MHz, CDCl3): d (ppm) = 7.33–7.17 (m, 6H), 7.14 (d,
2H), 7.01 (d, 2H), 6.51 (d, 1H), 3.87 (s, 3H), 3.59 (t, 1H), 3.12–2.96
(m, 2H), 2.88 (dd, 1H); 13C NMR (100 MHz, CDCl3): d (ppm)
= 167.95, 160.76, 141.63, 139.19, 137.29, 129.30 (2C), 129.18
(2C), 128.73 (2C), 127.98, 127.31 (2C), 127.07, 116.55, 52.84,
47.75, 41.47, 35.71. Enantiomeric excess ratio was determined
using Diacel OD-H column and tmajor = 20.269 min, tminor
31.372 min.
=
19. Karsten, J.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2003, 42, 1498.
20. (a) Eiden, F.; Winkler, W. Arch. Pharm. 1986, 319, 704; (b) Schreiber, S. L.;
Meyers, H. V. J. Am. Chem. Soc. 1988, 110, 5198; (c) Yamamoto, Y.; Momiyama,
N.; Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 5962; (d) Sundén, H.; Ibrahem, I.;
Eriksson, L.; Córdova, A. Angew. Chem., Int. Ed. 2005, 44, 4877.
Acknowledgements
21. (a) Samanta, S.; Kruase, J.; Mandal, T.; Zhao, C.-G. Org. Lett. 2007, 14, 2745; (b)
Weise, C. F.; Lauridesen, V. H.; Rambo, R. S.; Iversen, E. H.; Olsen, M.-L.;
Jorgensen, K. J. Org. Chem. 2014, 79, 3537.
22. (a) Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji, M. Angew. Chem., Int. Ed. 2005, 44,
4212; (b) Hu, Q.-Y.; Zhou, G.; Corey, E. J. J. Am. Chem. Soc. 2004, 126, 13708; (c)
Corey, E. J. Angew. Chem., Int. Ed. 2002, 41, 1650; (d) Ryu, D. H.; Corey, E. J. J. Am.
Chem. Soc. 2004, 126, 8106.
We are grateful to the National Science Foundation United
States for financial support of this research (CHE-1213287) and
the Robert A Welch Foundation (T-0014).
References
23. Qiao, Y.; Chen, Q.; Lin, S.; Ni, B.; Headley, A. D. J. Org. Chem. 2013, 78, 2693.
24. Wu, Y.-C.; Liu, L.; Li, H.-J.; Wang, D.; Chen, Y.-J. J. Org. Chem. 2006, 71, 6592.
1. Diels, O.; Alder, K. Liebigs Ann. 1928, 460, 98.
2. Hashimoto, S.; Komeshima, N.; Koga, K. J. Chem. Soc., Chem. Commun. 1979, 437.
Please cite this article in press as: Katakam, N. K.; et al. Tetrahedron: Asymmetry (2017), https://doi.org/10.1016/j.tetasy.2017.09.019