Asymmetric Michael addition reactions of aldehydes to β-nitrostyrenes catalyzed by (S)–N-(D-prolyl-L-prolyl)-1 -triflicamido-3 -phenylpropan-2-amine

Article abstract of DOI:10.1016/j.tet.2021.132095

In an attempt to improve the catalytic ability of (S)–N-(D-prolyl)-1-triflicamido-3-phenylpropan-2-amine, a catalyst previously reported by us for the asymmetric Michael addition of aldehydes to β-nitrostyrenes, 4 new molecules were designed and synthesiz

Full text of DOI:10.1016/j.tet.2021.132095

Tetrahedron 87 (2021) 132095
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Asymmetric Michael addition reactions of aldehydes to b-
nitrostyrenes catalyzed by (S)eN-(D-prolyl-L-prolyl)-1 -triflicamido-3
-phenylpropan-2-amine
, b, *
Amol B. Gorde a, Anas Ansari a, Ramesh Ramapanicker a
a Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh, 208016, India
b Centre for Environmental Science and Engineering, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh, 208016, India
a r t i c l e i n f o
a b s t r a c t
Article history:
In an attempt to improve the catalytic ability of (S)eN-(D-prolyl)-1-triflicamido-3-phenylpropan-2-
Received 3 February 2021
Received in revised form
15 March 2021
Accepted 18 March 2021
Available online 26 March 2021
amine, a catalyst previously reported by us for the asymmetric Michael addition of aldehydes to
b-
nitrostyrenes, 4 new molecules were designed and synthesized by increasing the distance between the
triflicamide group and the secondary amino group in the catalyst. Under the optimized reaction con-
ditions (S)eN-(D-prolyl-L-prolyl)-1-triflicamido-3-phenylpropan-2-amine exhibited high and improved
catalytic activity and stereoselectivity at a lower catalyst loading (3 mol%). In the studies done with a
large number of aldehydes and b-nitrostyrenes, the Michael adducts were obtained in high yields (up to
94%) and with excellent enantioselectivities (up to 98% ee) and with good to excellent diaster-
eoselectivities (up to 98:2 dr).
Keywords:
Michael addition
Nitroolefins
Organocatalysis
Triflicamide
© 2021 Elsevier Ltd. All rights reserved.
Enantioselectivity
1. Introduction
bond donor, the catalytic activity is improved at room temperature
[12]. Encouraged by these results, and wanting to explore the utility
Proline is used extensively for asymmetric aldol [1] and Man-
nich reactions [2] and the products are obtained with high selec-
tivity. However, Michael addition reactions catalyzed by proline is
not a useful reaction as the stereoselectivity is poor [3]. This has
resulted in the development of a number of catalysts for the
asymmetric Michael addition reaction of carbonyl compounds [4].
Of particular interest has been the reaction between aldehydes and
nitroalkenes. Starting with the triflicamide catalyst reported by
Wang et al. [5], a number of very useful catalysts have been pre-
pared [6]. Lately, attention has been given largely to peptide-based
catalysts containing a prolinamide unit [7,8]. The works of Wen-
nemers [9], Lecouvey [10] and Martín [11] have received great
attention and has made this otherwise difficult asymmetric trans-
formation a synthetic possibility. Recently, we developed a series of
compounds based on Wang’s catalyst and established that if a
suitable linker is introduced between the secondary amino group of
proline and the NHTf (triflicamide) group that acts as the hydrogen
of triflicamides derived from proline, we developed a new catalyst
viz. (S)eN-(D-prolyl)-1-triflicamido-3-phenylpropan-2-amine (1)
[13] Catalyst 1 (Fig. 1) can be considered as a combination of the
triflicamide catalysts of Miura [14] and the dipeptide catalyst
developed by Tsogoeva [15]. Catalyst 1 was fairly good in terms of
enantioselectivity and in terms of the yield of products formed. It
was also able to catalyze the reactions of hindered aldehydes.
However, the reactions required at least 24 h to complete and
10 mol% of the catalyst was required [13]. Our earlier report has
indicated that an optimal length between the secondary amino
group and the hydrogen bond donor in the catalyst is very impor-
tant for the successful catalysis of asymmetric Michael addition
reaction of aldehydes and nitroalkenes by proline-derived mole-
cules [12]. Therefore, it was assumed that a straight forward way to
improve the catalytic ability of 1 is to increase the distance between
the secondary amino group and the -NHTf group. Accordingly, four
molecules 2, 3, 4 and 5 were designed (Fig. 1). Molecule 2 has an
extended alkyl chain in comparison with catalyst 1, while mole-
cules 3, 4 and 5 have an additional proline residue incorporated.
The last three molecules are designed by varying the stereochem-
istry of the two proline residues. These molecules were studied for
* Corresponding author. Department of Chemistry, Indian Institute of Technology
Kanpur, Kanpur, Uttar Pradesh, 208016, India.
E-mail address: rameshr@iitk.ac.in (R. Ramapanicker).
https://doi.org/10.1016/j.tet.2021.132095
0040-4020/© 2021 Elsevier Ltd. All rights reserved.

A.B. Gorde, A. Ansari and R. Ramapanicker
Tetrahedron 87 (2021) 132095
2. Results and discussion
The synthesis of molecule 2 started from the amine 2a, which
was synthesized from commercially available N-Boc-L-phenyl-
alaninal, as reported by Liu [16]. The primary amine 2a was treated
with triflic anhydride to get the compound 2b and the N-Boc group
was removed using TFA in dry dichloromethane to get the amine 2c
(Scheme 1). Coupling of 2c and Boc-D-proline under standard
peptide coupling conditions using EDC$HCl in the presence of HOBt
and DIPEA (DCM, 0 ꢀC - rt) and subsequent removal of the N-Boc
group yielded 2 as its TFA salt (Scheme 1).
Compounds 3, 4 and 5 were prepared as their TFA salts by
coupling (S)-1-triflicamido-3-phenylpropan-2-amine (6) with the
dipeptide derivatives 3a, 3b, and 3c, respectively and subsequently
removing the N-Boc groups (Scheme 2). The amine 6 was synthe-
sized from L-phenylalaninol using the procedure reported by Miura
[13].
Fig. 1. Catalyst 1 and its variations 2, 3, 4 and 5.
The studies were initiated by carrying out the reaction of
propanal with b-nitrostyrene at room temperature in the presence
of 10 mol% of catalysts 2, 3, 4 and 5 in various solvents (Table 1). The
reactions were monitored through TLC and after the complete
disappearance of
b-nitrostyrene the products were isolated
through column chromatography, the diastereomeric ratio was
calculated from 1H NMR spectra of the crude reaction mixture and
the enantiomeric excess was estimated through chiral HPLC. The
chromatograms were compared with that of a racemic mixture of
7a and ent-7a, which were prepared by carrying out the reaction in
the presence of DL-proline.
As expected, on using catalysts 2 and 5, the major enantiomer
formed was 7a and on using catalysts 3 and 4, the major enan-
tiomer formed was ent-7a. The stereochemistry of the products
depends on the stereochemistry of the pyrrolidine ring involved in
the formation of the enamine with propanal and the results were
consistent with those reported earlier [11,12]. A comparison be-
tween the activity of these catalysts in aliphatic (entries 1e5) and
aromatic solvents (entries 6, 7 and 8) reveals that the catalysts
exhibited better activity in aromatic solvents, both in terms of
yields and stereoselectivity. Reactions done in a 1:1 mixture of
isopropyl alcohol and chloroform (entry 1) produced the poorest
results. Comparing these results with those of the reactions in
chloroform (entry5) indicates that isopropyl alcohol has a negative
Scheme 1. Synthesis of 2.
the ability to catalyze the Michael addition reaction of aldehydes
b-nitrostyrenes at rt. The molecule 5 was found to be the best
catalyst and here we report those results.
with
Scheme 2. Synthesis of compounds 3, 4 and 5.
2

A.B. Gorde, A. Ansari and R. Ramapanicker
Tetrahedron 87 (2021) 132095
Table 1
Screening of catalysts and Solvents.
entry
solvent
(yield %)a and eeb of the major products formed with each catalyst
catalyst 2e,h
syn:antic
catalyst 3d
syn:antic
catalyst 4d
syn:antic
catalyst 5e
syn:antic
1
2
3
4
5
6
7
8
IPA: CHCl3 (1:1)
THF
DCM
ACN
CHCl3
benzene
toluene
xylene
xylene
xylene
(85) 49
(55) 74
(68) 76
(72) 33
(75) 86
(80) 89
(78) 90
(81) 91
(65) 91
(54) 91
80:20
83:17
81:19
75:25
76:24
85:15
82:18
78:22
80:20
76:24
(89) 60
(78) 86
(82) 85
(80) 77
(84) 88
(86) 92
(82) 92
(88) 93
(85) 93
(81) 92
82:18
71:29
80:20
81:19
78:22
82:18
80:20
86:14
87:13
85:15
(94) 44
(86) 70
(90) 80
(92) 52
(89) 85
(89) 92
(88) 94
(90) 93
(88) 93
(84) 93
72:28
76:24
73:27
71:29
75:25
78:22
80:20
80:20
76:24
78:22
(95) 41
(84) 80
(88) 86
(93) 80
(90) 87
(88) 94
(85) 94
(90) 95
(85) 95
(82) 95
65:35
80:20
78:22
89:11
75:25
83:17
82:18
86:14
83:17
81:19
9f
10g
a
Isolated yield after column chromatography.
b
c
ee as determined by chiral HPLC analysis using a Chiralpak IC- Column.
diastereomeric ratio is calculated from 1H NMR spectra of the crude reaction mixture.
major product is ent-7a.
d
e
f
major product is 7a.
5 mol% of catalyst with 3 equiv. of propanal were used and reaction time 15 h.
3 mol% of catalyst with 3 equiv. of propanal were used and reaction time is 24 h.
reaction time is 12 h.
g
h
effect on the catalysis. It was interesting to note that reactions using
catalyst 3 and 5 were comparable in terms of selectivity in aliphatic
solvents. Reactions in THF and chloroform favored the use of
catalyst 3 (entries 2 and 5), while those in dichloromethane and
acetonitrile favored catalyst 5 (entries 3 and 4). However, these
differences were not substantial. All of the catalysts gave consis-
tently good selectivity in the three aromatic solvents studied. The
yields for reactions using catalyst 2 were noticeably lower. Among
all the conditions and catalysts studied, the reaction using 5 in
xylene was found to be the best, which yielded 7a in 90% yield as a
diastereomeric mixture with 86% syn and 14% anti isomers and
with 95% ee (entry 8). The reactions using catalysts 3, 4 and 5 were
complete in 6 h, which is a substantial improvement over that of
catalyst 1, reported earlier. Catalyst 2 was the slowest to react under
these reaction conditions and the reactions took 12 h for comple-
tion. In an effort to reduce the amount of catalysts used and the
number of equivalents of propanal, all the reactions were per-
formed with 5 and 3 mol% of catalysts and with 3 equiv. of propanal
(entries 9 and 10). It was found that the reaction times increased
from 6 h to 15 h and 24 h with 5 and 3 mol% of the catalysts,
respectively. While there was a sequential, but marginal, reduction
in the yields of the products formed, the enantioselectivities were
not affected. It was very clear that compound 5 is best among all the
catalysts studied. Based on these results, it was decided to continue
the studies with 3 mol% of catalyst 5 in xylene.
The addition of an acid to the reaction mixture is expected to
improve the catalysis by protonation of the aldehyde leading to a
faster generation of the enamines. Accordingly, the reactions were
carried out in the presence of 3 mol% of compound 5 and 3
equivalents of propanal in xylene along with 3 mol% of an organic
acid (Table 2). It was found that all acids studied, except p-TSA and
citric acid had a positive effect on the reactivity and selectivity. The
addition of benzoic acid, p-nitrobenzoic acid and 3,4-
dimethoxyphenylacetic acid gave the best results (entries 1, 2 and
6). In the presence of these acids, the enantioselectivity improved
from 95% ee to 97% ee, the reactions were slightly faster and there
was a noticeable improvement in the yields. Based on these results,
an attempt was made to increase the amount of the acid used in
anticipation of better results. On using 5 and 10 mol% of benzoic
acid as the additive (entries 9 and 10, respectively), the yields
improved to 94%, without much improvement in the reaction times
and enantioselectivity. The reactions with 5 and 10 mol% of benzoic
acid were identical. Therefore, it was decided to continue the
studies with 5 mol% of benzoic acid as the additive for the reactions
done in the presence of catalyst 5.
The scope of catalyst 5 was examined by carrying out the re-
action of several aldehydes with various nitroalkenes at the opti-
mized conditions (3 mol% of 5, 5 mol% of benzoic acid, rt, xylene)
with 3 equivalents of the aldehydes (Table 3). Initial studies were
directed at the reaction of straight chain aldehydes with b-nitro-
styrene to understand the effect of increasing chain length on the
reactivity (entries 1e6). The reactions proceeded in high yields
(85e94%) and with good diastereoselectivity (up to 98:2 dr) and
good to excellent enantioselectivity (92e97% ee). The reaction of
propanal is the most effective and an increase in the chain length
decreases the reactivity and selectivity. Subsequently, reaction of
propanal with various b-nitrostyrene derivatives were performed
(entries 7e11 and 1). All of these reactions consistently gave good
enantioselectivity, while the diastereoselectivity remained mod-
erate in most cases. The reactions were repeated with butanal
(entries 12e16) and pentanal (entries 17e20) and all the products
showed very good ee and were isolated in good yields, but were
obtained with moderate diastereoselectivity. The highest selec-
tivity was obtained for the reactions of propanal with 4-fluoro-
nitrostyrene and 2-chloro- -nitrostyrene (entries 7 and 9) and the
lowest selectivity was obtained for the reaction between pentanal
and 4-methoxy- -nitrostyrene (entry 20).
b-
b
b
In comparison with catalyst 1 that we reported earlier, com-
pound 5 showcases a substantial improvement. The catalyst
loading could be brought down from 10 mol% to 3 mol% and the
number of equivalents of aldehydes required was reduced to 3. The
reactions catalyzed by 5 are faster and the selectivity is comparable
if not better. Catalyst 5 is a very good catalyst, especially for the
reactions of long chain aliphatic aldehydes.
3

A.B. Gorde, A. Ansari and R. Ramapanicker
Tetrahedron 87 (2021) 132095
Table 2
Influences of additives on Michael addition of propanal and b-nitrostyrenes.
entry
Additive
time (h)
yield (%)a
syn:antib
ee (syn)c
1
2
3
4
5
6
7
8
benzoic acid
4-nitrobenzoic acid
acetic acid
4-nitrophenol
tartaric acid
3,4-dimethoxyphenylacetic acid
citric acid
p-TSA
benzoic acid
benzoic acid
20
20
24
20
28
20
48
48
20
20
90
88
82
88
82
87
(>10)
(>10)
94
84:16
81:19
86:14
78:22
80:20
87:13
nd
nd
82:18
82:18
97
97
96
95
96
97
nd
nd
97
97
9d
10e
94
a
Isolated yield after column chromatography.
b
c
diastereomeric ratio is calculated from 1H NMR spectra of the crude reaction mixture.
ee as determined by chiral HPLC analysis using a Chiralpak IC- Column.
5 mol% of benzoic acid was used.
d
e
10 mol% of benzoic acid was used.
3. Conclusion
to 0 ꢀC and triethylamine (2.5 mL,17.98 mmol, 2.5 equiv) and DMAP
(0.26 g, 2.15 mmol, 0.3 equiv) were added to this cold solution. This
was followed by a slow addition of trifluoromethanesulfonic an-
hydride (1.45 mL, 8.62 mmol, 1.2 equiv) over a period of 15 min and
the mixture was stirred for 3 h at 0 ꢀC. Reaction was quenched with
saturated NaHCO3 solution (10 mL) and was extracted with DCM
(2 ꢁ 30 mL). Combined organic layers were washed with brine
(20 mL), dried over Na2SO4 and was filtered. Solvents were
removed under reduced pressure and the product was purified by
column chromatography to get the compound 2b.
In conclusion, a new peptide-based triflicamide organocatalyst
(S)eN-(D-prolyl-L-prolyl)-1
-triflicamido-3
-phenylpropan-2
eamine (5) was identified, from a group of four different catalysts,
which were designed by modifying compound 1, a catalyst that we
reported earlier for the Michael addition reaction of aldehydes to
nitroalkenes. Catalyst 5 resulted in formation of the Michael ad-
ducts with very high yields (up to 94%), moderate to good dia-
stereoselectivity (up to 98:2 dr) and excellent enantioselectivity
(up to 98% ee). Catalyst 5 is definitely a substantial improvement
over the two different catalysts that were previously reported from
our group. With catalyst 5, the catalyst loading could be brought
down to 3 mol% from 10 mol% that was required for our previous
catalysts and the equivalents of aldehyde required could be brought
down to 3 from 4. A relatively poor diastereoselectivity remains as a
possible area for improvement while using 5 for such reactions.
tert-butyl (R)-(1-phenyl-5-((trifluoromethyl)sulfonamido)
pentan-2-yl)carbamate (2b): Column chromatography (80:20
25
petroleum ether/EtOAc); White wax (2.0 g, 71%); [
a
]
D
¼ þ2.00 (c
0.50, MeOH); 1H NMR (400 MHz, CDCl3)
d
7.30e7.19 (m, 3H), 7.14 (d,
J ¼ 7.1 Hz, 2H), 6.58 (s, 1H), 4.53e4.36 (m, 1H), 3.91e3.72 (m, 1H),
3.42e3.15 (m, 2H), 2.73 (d, J ¼ 5.8 Hz, 2H),1.66e1.52 (m, 3H),1.37 (s,
9H) ppm; 13C NMR (100 MHz, CDCl3)
d 156.2, 137.5, 129.3, 128.6,
126.6, 119.7 (q, J ¼ 321.0 Hz), 80.0, 50.8, 44.0, 41.6, 31.9, 28.3,
26.3 ppm; FTIR (thin film): ῡ ¼ 3403, 3321, 29305, 1685, 1552,
1445,1368, 1230, 1189, cmꢂ1. HRMS (ESI-TOF) m/z: [Mþ Na]þcalcd
for C17H25F3N2NaO4S 433.1385, found 433.1388.
4. Experimental section
4.1. General information
All the chemicals were purchased from commercial sources.
Anhydrous solvents were used for the reactions. Column chroma-
tography was done with silica gel (particle size 60e120 and
100e200 mesh) purchased from Merck. The absolute configuration
of the reaction products was confirmed by HPLC, by comparison
with reported data. The enantiomeric ratios were estimated by
chiral HPLC analysis and diastereomeric ratios were determined
from1H NMR analysis. High performance liquid chromatography
(HPLC) was performed on an Agilent Technologies chromatograph
(1100 Series), using the specified Daicel chiral column and guard
columns with a mixture of hexane and 2-propanol as eluents at
4.3. Procedure for the N-Boc deprotection of 2c
To a stirred solution of N-Boc-compound 2b (1.5 g, 3.65 mmol)
in dry DCM (10 mL), TFA (10 mL) was added at 0 ꢀC and the solution
was stirred at rt for 6 h. Reaction was monitored through TLC and
after the complete disappearance of N-Boc-derivatives, the reaction
mixture was concentrated under reduced pressure and 2 N NaOH
solution was added to get a solution of pH 12. This mixture was
extracted with ethyl acetate (3 ꢁ 30 mL) and dried over Na2SO4 and
filtered. Solvents were removed under reduced pressure to get the
amine 2c.
25 ꢀC. Optical rotations were measured using a 5.0 mL cell with a
(R)-N-(4-amino-5-phenylpentyl)-1,1,1-
25
10 dm path length and are reported as [
solvent).
a
]
(c in g per 100 mL
D
trifluoromethanesulfonamide (2c): White wax, (1.04 g, 92%);
25
[
a
]
D
¼ ꢂ3.33 (c 0.60, MeOH); 1H NMR (400 MHz, CDCl3)
d 7.56 (s,
2H), 7.31e7.23 (m, 3H), 7.15 (d, J ¼ 7.0 Hz, 2H), 6.61 (d, J ¼ 15.6 Hz,
4.2. Procedure for the preparation of compound 2b
1H), 3.59e3.57 (m, 1H), 3.30e3.02 (m, 2H), 3.02e2.79 (m, 2H),
1.95e1.53 (m, 4H) ppm; 13C NMR (100 MHz, CDCl3)
d
134.8, 129.3,
To a solution of 2a (2.0 g, 7.19 mmol) in DCM (20 mL) was cooled
129.1, 127.8, 119.6 (q, J ¼ 321.0 Hz), 53.6, 43.3, 39.0, 28.7, 25.4 ppm;
4

A.B. Gorde, A. Ansari and R. Ramapanicker
Tetrahedron 87 (2021) 132095
Table 3
Asymmetric Michael additions of aldehydes to b-nitrostyrenes catalyzed by 5.
entry
1
Product
time (h)
yield (%)a
94
syn:antib
82:18
ee (syn)c (%)
97
20
2
3
24
36
92
88
92:8
97
96
90:10
4
5
48
36
85
86
98:2
96:4
95
94
6
48
85
95:5
92
7
8
20
20
94
88
83:17
84:16
98
97
9
20
20
90
93
82:18
82:18
98
97
10
(continued on next page)
5

A.B. Gorde, A. Ansari and R. Ramapanicker
Tetrahedron 87 (2021) 132095
Table 3 (continued)
entry
11
Product
time (h)
20
yield (%)a
87
syn:antib
81:19
ee (syn)c (%)
96
12
13
24
24
90
87
90:10
93:7
97
96
14
24
85
92:8
96
15
16
24
24
87
85
89:11
91:9
97
95
17
18
36
36
88
85
95:5
94:6
95
94
19
20
36
36
87
84
88:12
86:14
94
90
a
Isolated yield after column chromatography.
b
c
diastereomeric ratio is calculated from 1H NMR spectra of the crude reaction mixture.
ee as determine by chiral HPLC analysis using a Chiralpak IC-Column.
FTIR (thin film):
ῡ
¼
3420, 3033, 1674, 1522, 1497, 1455,
4.4. Procedure for the preparation of compound 3b
1370,1229,1144, cmꢂ1. HRMS (ESI-TOF) m/z: [MþH]þcalcd for
C
12H18F3N2O2S 311.1041, found 311.1048.
To a stirred solution of compound N-Boc-D-proline methyl ester
(1.0 g, 4.36 mmol, 1 equiv) in dry DCM (20 mL), TFA (10 mL) was
6

A.B. Gorde, A. Ansari and R. Ramapanicker
Tetrahedron 87 (2021) 132095
added at 0 ꢀC and the solution was stirred at rt for 5 h. Reaction was
monitored through TLC and after the complete disappearance of
Boc-2): Column chromatography (70:30 petroleum ether/EtOAc);
25
White wax (1.06 g, 80%); [
a
d
]
¼ þ15.0 (c 0.40, MeOH); (rotamers)
D
compound N-Boc-D-proline methyl ester, the reaction mixture was
1H NMR (400 MHz, CDCl3)
7.31e7.20 (m, 3H), 7.15 (d, J ¼ 6.9 Hz,
concentrated under reduced pressure to get the corresponding
amine, which was forwarded for the next step. A solution of the
2H), 6.22 (d, J ¼ 3.0 Hz, 1H), 4.31e3.98 (m, 2H), 3.68e3.06 (m, 4H),
2.93e2.57 (m, 2H), 2.03e1.54 (m, 8H), 1.41 (s, 9H) ppm; 13C NMR
Boc-
L-proline (0.98 g, 4.41 mmol, 1.0 equiv) in DCM (20 mL) was
(100 MHz, CDCl3) d 172.6, 172.6, 155.4, 155.3, 137.7, 137.7, 129.2,
cooled to 0 ꢀC. To this solution, EDC$HCl (1.26 g, 6.61 mmol, 1.5
equiv), HOBt (0.9 g, 6.61 mmol, 1.5 equiv) and DIPEA (1.96 mL,
11.02 mmol, 2.5 equiv) were added and was stirred for 15 min. To
the cold mixture, the secondary amine (1.06 g, 4.41 mmol, 1.0
equiv) was added as a solution in DCM (5 mL) and the solution was
stirred at rt for 16 h. Reaction was monitored through TLC and after
the complete disappearance of the amine, the reaction mixture was
diluted with DCM (30 mL) and was washed with saturated NaHCO3
solution (10 mL) and then with 1 N KHSO4 solution (10 mL). Crude
solution of the prolinamide was washed with brine (30 mL), dried
over Na2SO4 and was filtered. Solvents were removed under
reduced pressure and the product was purified by column chro-
matography (50:50 petroleum ether/EtOAc) to get the N-Boc ester
compound, clear oil (1.15 g, 81% Yield) which was forwarded for the
ester hydrolysis.
128.6,128.5,126.6,119.6 (q, J ¼ 320.5 Hz), 80.66, 80.64, 60.39, 60.34,
49.8, 49.7, 47.2, 44.1, 41.7, 41.5, 32.0, 31.5, 29.7, 29.4, 29.2, 28.45,
28.40, 25.5, 24.5, 22.7 ppm; FTIR (thin film): ῡ ¼ 3301, 3087, 2977,
1670,1539, 1478, 1412, 1369, 1229, 1178, 1151, cmꢂ1. HRMS (ESI-TOF)
m/z: [MþH]þcalcd for C22H33F3N3O5S 508.2093, found 508.2091.
tert-butyl
(S)-2-((S)-2-(((S)-1-phenyl-3-((trifluoromethyl)
sulfonamido)propan-2-yl)carbamoyl)pyrrolidine-1-carbonyl)
pyrrolidine-1-carboxylate (N-Boc-3): Column chromatography
25
(100% EtOAc); White wax (0.91 g, 83%); [
a
]
¼ ꢂ25.84 (c 0.41,
D
MeOH); 1H NMR (500 MHz, CDCl3)
d
7.62 (d, J ¼ 8.3 Hz, 1H), 7.27
(dd, J ¼ 13.8, 6.4 Hz, 2H), 7.21 (d, J ¼ 7.0 Hz, 1H), 7.20e7.15 (m, 3H),
4.41e4.34 (m, 1H), 4.27e4.10 (m, 2H), 3.61e3.55 (m, 2H), 3.46e3.22
(m, 4H), 2.96e2.83 (m, 2H), 2.15e1.79 (m, 7H), 1.57 (dd, J ¼ 13.5,
7.2 Hz, 1H), 1.49 (s, 9H) ppm; 13C NMR (125 MHz, CDCl3)
d 172.9,
171.8, 155.2, 137.6, 129.1, 128.5, 126.7, 119.5 (q, J ¼ 321.8 Hz), 80.3,
61.0, 57.7, 51.6, 47.7, 47.6, 47.3, 37.2, 29.5, 29.2, 28.7, 24.9, 23.8 ppm;
FTIR (thin film): ῡ ¼ 3317,3087, 2975, 2925, 1659, 1539, 1455, 1412,
1376, 1333, 1229, 1189, cmꢂ1. HRMS (ESI-TOF) m/z: [MꢂH]ꢂcalcd for
To
a stirred solution of N-Boc ester compound (1.15 g,
3.52 mmol, 1.0 equiv) in methanol:water (20 mL) was added
lithium hydroxide (0.42 g, 17.63 mmol, 5 equiv). The reaction
mixture was stirred at rt for 1 h. After the complete disappearance
of N-Boc ester compound on TLC, the reaction mixture was
concentrated under reduced pressure to evaporate solvent and
neutralized with saturated KHSO4 solution (25 mL) and extracted
with ethyl acetate (2 ꢁ 30 mL). Combined organic layers were
washed with brine (20 mL), dried over Na2SO4, and filtered. The
solvent were removed under reduced pressure and acid 3b was
purified by column chromatography (90:10 petroleum ether/
EtOAc) white wax (0.96 g, 87% Yield).
C
25H34F3N4O6S 575.2151, found 575.2152.
tert-butyl
(S)-2-((R)-2-(((S)-1-phenyl-3-((trifluoromethyl)
sulfonamido)propan-2-yl)carbamoyl)pyrrolidine-1-carbonyl)
pyrrolidine-1-carboxylate (N-Boc-4): Column chromatography
25
(100% EtOAc); White wax (0.98 g, 89%); [
a
]
D
¼ þ18.96 (c 0.58,
MeOH); 1H NMR (400 MHz, CDCl3)
d
7.36 (s, 1H), 7.28e7.16 (m, 5H),
7.14 (s, 1H), 4.54 (dd, J ¼ 7.3, 2.3 Hz,1H), 4.35 (dd, J ¼ 7.8, 5.7 Hz,1H),
4.13e4.04 (m,1H), 3.87e3.75 (m,1H), 3.59e3.53 (m,1H), 3.46e3.24
(m, 4H), 2.98 (dd, J ¼ 13.8, 7.9 Hz, 1H), 2.73 (dd, J ¼ 13.9, 7.1 Hz, 1H),
2.39e2.29 (m, 1H), 2.16e1.85 (m, 8H), 1.42 (s, 9H) ppm; 13C NMR
(100 MHz, CDCl3) d d 172.8, 171.5, 155.0, 137.3, 129.0, 128.6, 126.7,
119.8 (q, J ¼ 321.5 Hz), 80.5, 60.7, 57.9, 52.1, 47.3, 47.1, 46.0, 37.9,
29.3, 28.5, 27.5, 24.7, 24.4 ppm; FTIR (thin film): ῡ ¼ 3312,3088,
(tert-butoxycarbonyl)-L-prolyl-D-proline (3b): white solid,
25
mp188ꢂ190 ꢀC (0.98 g, 72% Yield); [
a]
¼ þ29.26 (c 0.41, MeOH);
D
(rotamers) 1H NMR (400 MHz, CDCl3)
d 8.04 (bs, 1H), 4.70e4.31 (m,
2H), 3.80e3.27 (m, 4H), 2.45e1.85 (m, 8H), 1.44e1.34 (m, 9H) ppm;
13C NMR (100 MHz, CDCl3)
d
175.5, 174.3, 172.3, 171.9, 155.0, 153.5,
2975, 2931, 1698, 1534, 1497, 1453, 1367, 1335, 1229, 1189, cmꢂ1
.
80.7, 80.5, 60.5, 58.0, 57.8, 47.5, 46.9, 46.7, 30.3, 29.2, 28.5, 28.4, 28.2,
28.1, 27.2, 24.9, 24.7, 23.8 ppm; FTIR (thin film): ῡ ¼ 3452, 2975,
2882, 1734, 1650, 1478, 1408,1366, 1331, 1248, 1126 cm-1. HRMS
(ESI-TOF) m/z: [MþH]þcalcd for C15H25N2O5313.1763, found
313.1769.
HRMS (ESI-TOF) m/z: [MꢂH]ꢂcalcd for C25H34F3N4O6S 575.2151,
found 575.2154.
tert-butyl
(R)-2-((S)-2-(((S)-1-phenyl-3-((trifluoromethyl)
sulfonamido)propan-2-yl)carbamoyl)pyrrolidine-1-carbonyl)
pyrrolidine-1-carboxylate (N-Boc-5): Column chromatography
25
(100% EtOAc); White wax (0.95 g, 87%); [
a
]
¼ ꢂ19.0 (c 0.66,
D
4.5. General procedure for the preparation of N-Boc derivatives 2, 3,
4 and 5
MeOH); 1H NMR (400 MHz, CDCl3)
d 7.34 (s, 1H), 7.30e7.16 (m, 5H),
6.85 (d, J ¼ 8.7 Hz, 1H), 4.46 (dd, J ¼ 8.0, 3.1 Hz, 1H), 4.37e4.26 (m,
2H), 3.81e3.76 (m, 1H), 3.55e3.34 (m, 4H), 3.22e3.13 (m, 1H),
2.93e2.79 (m, 2H), 2.15e1.71 (m, 7H), 1.49 (s, 9H) ppm; 13C NMR
A solution of compound 3a or 3b or 3c (0.6 g, 1.91 mmol, 1.0
equiv) or N-Boc-
D-proline (0.56 g, 2.60 mmol, 1.0 equiv) in DCM
(100 MHz, CDCl3) d 172.9,171.8,155.2,137.6,129.1,128.5,126.7,119.9
(20 mL) was cooled to 0 ꢀC. To this solution, EDC$HCl (0.75 g,
3.94 mmol, 1.5 equiv), HOBt (0.53 g, 3.94 mmol, 1.5 equiv) and
DIPEA (1.14 mL, 6.59 mmol, 2.5 equiv) were added and was stirred
for 15 min. To the cold mixture, the primary amine 2c (0.81 g,
2.60 mmol, 1.0 equiv) or 6 (0.54 g, 1.91 mmol, 1.0 equiv) and was
added as a solution in DCM (20 mL) and the solution was stirred at
rt for 16 h. Reaction was monitored through TLC and after the
complete disappearance of the amine, the reaction mixture was
diluted with DCM (40 mL) and was washed with saturated NaHCO3
solution (20 mL) and then with 1 N KHSO4 solution (10 mL). Crude
solution of the peptide was washed with brine (40 mL), dried over
Na2SO4 and was filtered. Solvents were removed under reduced
pressure and the products were purified by column chromatog-
raphy to get the N-Boc derivatives of 2 to 5.
(q, J ¼ 321.6 Hz), 80.3, 61.0, 57.7, 51.6, 47.6, 47.6, 47.3, 37.2, 29.5, 29.2,
28.7, 24.9, 23.9 ppm; FTIR (thin film): ῡ ¼ 3325,3070, 2970, 29551,
1659, 1547, 1478, 1455, 1410, 1365, 1331, 1227, 1156, cmꢂ1. HRMS
(ESI-TOF) m/z: [M eH]ꢂcalcd for C25H34F3N4O6S 575.2151, found
575.2158.
5. General procedure for the N-Boc deprotection of N-Boc-
compound 2 to 5
To a stirred solution of N-Boc-derivatives of 2 (1 g, 1.96 mmol) or
3 or 4 or 5 (1 g, 1.73 mmol) in dry DCM (10 mL), TFA (10 mL) was
added at 0 ꢀC and the solution was stirred at rt for 6 h. Reaction was
monitored through TLC and after the complete disappearance of N-
Boc-derivatives, the reaction mixture was concentrated under
reduced pressure and 2 N NaOH solution was added to get a solu-
tion of pH 12. This mixture was extracted with ethyl acetate
tert-butyl (R)-2-(((R)-1-phenyl-5-((trifluoromethyl)sulfona-
mido)pentan-2-yl)carbamoyl)pyrrolidine-1-carboxylate
(N-
7

A.B. Gorde, A. Ansari and R. Ramapanicker
Tetrahedron 87 (2021) 132095
(3 ꢁ 20 mL) and dried over Na2SO4 and filtered. Solvents were
removed under reduced pressure to get the peptide catalyst (2 to 5).
(R)-N-((R)-1-phenyl-5-((trifluoromethyl)sulfonamido)pen-
Racemic mixtures of the
g
-nitro aldehydes were prepared as
references for HPLC analysis by carrying out each of the reactions
listed in Table 3 in the presence of 20 mol% of DL-proline as the
catalyst.
(2S,3R)-2-methyl-4-nitro-3-phenylbutanal
chromatography (90:10 petroleum ether/EtOAc); Pale yellow oil
(0.097 g, 94% Yield); 1H NMR (400 MHz, CDCl3)
tan-2-yl)pyrrolidine-2-carboxamide (2): White wax, (0.69 g,
25
86%); [
d
a]
¼ þ17.50 (c 0.40, MeOH); 1H NMR (400 MHz, CDCl3)
(7a):
Column
D
10.45 (d, J ¼ 3.1 Hz,1H), 7.78 (s,1H), 7.60 (s,1H), 7.54e7.33 (m, 1H),
7.27e7.20 (m, 2H), 7.15 (t, J ¼ 6.7 Hz, 2H), 4.56e4.04 (m, 3H), 3.21
(d, J ¼ 30.8 Hz, 3H), 2.87 (dd, J ¼ 13.4, 4.0 Hz, 1H), 2.61 (dd, J ¼ 12.8,
10.1 Hz, 1H), 2.23e2.06 (m, 1H), 1.93e1.75 (m, 1H), 1.61-1-40 (m,
d
9.70 (d, J ¼ 1.7 Hz,
1H), 7.32 (dd, J ¼ 9.9, 4.1 Hz, 3H), 7.18e7.14 (m, 2H), 4.78 (dd, J ¼ 6.9,
4.2 Hz, 1H), 4.67 (dd, J ¼ 12.6, 9.4 Hz, 1H), 3.80 (dd, J ¼ 9.1, 3.5 Hz,
1H), 2.81e2.74 (m, 1H), 0.99 (d, J ¼ 7.3 Hz, 3H) ppm; 13C NMR
6H) ppm; 13C NMR (100 MHz, CDCl3)
d 168.6, 137.8, 129.2, 128.4,
126.6, 119.7 (q, J ¼ 320.9 Hz), 59.6, 51.5, 46.6, 43.9, 41.4, 31.4, 30.3,
26.42, 24.3 ppm; FTIR (thin film): ῡ ¼ 3310, 3087, 2925, 1671, 1565,
1454, 1371, 1229, 1190 cmꢂ1. HRMS (ESI-TOF) m/z: [MþH]þcalcd for
(100 MHz, CDCl3) d 202.3, 136.6, 129.1, 128.2, 128.1, 78.1, 48.5, 44.1,
12.2 ppm; HRMS (ESI-TOF) m/z: [MꢂH]ꢂcalcd for C11H12NO3
206.0817, found 206.0827; HPLC (Chiralpak-IC column, Hexane:2-
C
17H25F3N3O3S 408.1569, found 408.1561.
Propanol ¼ 90:10, flow rate: 0.7 mL/min,
l
¼ 254 nm), tR
(S)-1-(L-prolyl)-N-((S)-1-phenyl-3-((trifluoromethyl)sulfona-
major ¼ 31.24, tR minor ¼ 36.42, 97% ee and dr 82:18.
mido)propan-2-yl)pyrrolidine-2-carboxamide (3): White solid
(2S,3R)-2-ethyl-4-nitro-3-phenylbutanal (7b): Column chro-
matography (90:10 petroleum ether/EtOAc); Pale yellow oil (0.10 g,
(0.74 g, 90%); [
a
]
¼ ꢂ39.02 (c 0.41, MeOH); 1H NMR (400 MHz,
25
D
CD3OD)
d
7.36e7.12 (m, 5H), 4.44 (dd, J ¼ 20.4, 5.8 Hz, 1H),
92% Yield); 1H NMR (400 MHz, CDCl3)
d
9.71 (d, J ¼ 2.6 Hz, 1H),
4.25e4.07 (m, 1H), 3.68e3.49 (m, 2H), 3.43e3.18 (m, 5H),
2.94e2.73 (m, 2H), 2.54e2.36 (m, 1H), 2.23e1.76 (m, 7H) ppm; 13
NMR (100 MHz, METHANOL-D3) 172.5, 171.7, 167.3, 167.2, 138.1,
7.35e7.28 (m, 3H), 7.17 (dd, J ¼ 5.3, 3.0 Hz, 2H), 4.71 (dd, J ¼ 12.8,
5.0 Hz, 1H), 4.62 (dd, J ¼ 12.7, 9.7 Hz, 1H), 3.81e3.75 (m, 1H),
2.68e2.65 (m, 1H), 1.52e1.46 (m, 2H), 0.82 (t, J ¼ 7.5 Hz, 3H) ppm;
C
d
137.54,128.9,128.2,126.37,126.32,120.1 (q, J ¼ 321.5 Hz), 60.6, 59.9,
58.9, 51.4, 47.1, 46.2, 46.0, 37.1, 37.0, 31.9, 29.3, 28.2, 24.5, 23.9,
21.6 ppm; FTIR (thin film): ῡ ¼ 3287,3089, 2957, 2931, 1659, 1544,
1497, 1476, 1455, 1377, 1331, 1229, 1162, 1151, cmꢂ1. HRMS (ESI-TOF)
m/z: [MþH]þcalcd for C20H28F3N4O4S 477.1783, found 477.1778.
(R)-1-(L-prolyl)-N-((S)-1-phenyl-3-((trifluoromethyl)sulfo-
13C NMR (100 MHz, CDCl3)
d 203.2, 136.8, 129.2, 128.2, 128.0, 78.6,
55.0, 42.7, 20.4, 10.7 ppm; HRMS (ESI-TOF) m/z: [MꢂH]ꢂcalcd for
C
12H14NO3 220.0974, found 220.0977; HPLC (Chiralpak-IC column,
Hexane:2-Propanol ¼ 90:10, flow rate: 0.7 mL/min,
l
¼ 254 nm), tR
major ¼ 21.83, tR minor ¼ 24.59, 97% ee and dr 92:8.
(S)-2-((R)-2-nitro-1-phenylethyl)pentanal (7c): Column chro-
namido)propan-2-yl)pyrrolidine-2-carboxamide (4): White solid
matography (90:10 petroleum ether/EtOAc); Pale yellow oil
25
(0.71 g, 87%); [
a
]
¼ þ7.87 (c 0.33, MeOH); 1H NMR (400 MHz,
(0.103 g, 88% Yield); 1H NMR (400 MHz, CDCl3)
d
9.69 (d, J ¼ 3.0 Hz,
D
CD3OD)
d
7.39e7.03 (m, 5H), 4.45e4.26 (m, 1H), 4.23e4.00 (m, 1H),
1H), 7.34e7.28 (m, 3H), 7.16 (dd, J ¼ 6.9, 1.6 Hz, 2H), 4.70e4.62 (m,
2H), 3.80e3.73 (m, 1H), 2.72e2.66 (m, 1H), 1.41e1.29 (m, 4H), 0.79
3.63 (dt, J ¼ 10.1, 7.2 Hz, 1H), 3.49e3.42 (m, 1H), 3.34e317 (m, 4H),
3.15e3.03 (m, 1H), 2.98e2.85 (m, 1H), 2.70e2.61 (m, 1H), 2.41e2.28
(m, 1H), 2.21e1.69 (m, 6H), 1.65e1.53 (m, 1H) ppm; 13C NMR
(t, J ¼ 7.1 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3)
d 203.3, 136.8,
129.2, 128.2, 128.0, 78.4, 53.8, 43.2, 29.5, 19.8, 14.0 ppm; HRMS (ESI-
TOF) m/z: [MꢂH]ꢂcalcd for C13H16NO3 234.1130, found 234.1134;
HPLC (Chiralpak-IC column, Hexane:2-Propanol ¼ 90:10, flow rate:
(100 MHz, METHANOL-D4)
d 172.3, 172.0, 169.7, 169.6, 137.9, 129.0,
128.0, 126.1, 120.7 (q, J ¼ 323.0 Hz), 60.8, 60.3, 58.9, 58.7, 51.8, 51.4,
47.0, 46.9, 46.5, 46.3, 37.8, 37.5, 29.3, 29.1, 28.5, 24.5, 24.0 ppm; FTIR
(thin film): ῡ ¼ 3285,3088, 2957, 2925, 1650, 1549, 1476, 1478, 1457,
0.8 mL/min,
l
¼ 254 nm), tR major ¼ 26.95, tR minor ¼ 31.18, 96% ee
and dr 90:10.
1417, 1374, 1280, 1165, 1156, cmꢂ1
.
HRMS (ESI-TOF) m/z:
(2S,3R)-2-isopropyl-4-nitro-3-phenylbutanal (7d): Column
chromatography (90:10 petroleum ether/EtOAc); Pale yellow oil
[MþH]þcalcd for C20H28F3N4O4S 477.1783, found 477.1771.
(S)-1-(D-prolyl)-N-((S)-1-phenyl-3-((trifluoromethyl)sulfo-
(0.10 g, 85% Yield); 1H NMR (400 MHz, CDCl3)
d
9.92 (d, J ¼ 2.4 Hz,
namido)propan-2-yl)pyrrolidine-2-carboxamide (5): White solid
1H), 7.36e7.27 (m, 3H), 7.20e7.16 (m, 2H), 4.66 (dd, J ¼ 12.4, 4.4 Hz,
1H), 4.56 (dd, J ¼ 12.4, 10.0 Hz, 1H), 3.89 (td, J ¼ 10.3, 4.4 Hz, 1H),
2.76 (ddd, J ¼ 10.6, 4.1, 2.5 Hz, 1H), 1.75e1.67 (m, 1H), 1.09 (d,
J ¼ 7.2 Hz, 3H), 0.87 (d, J ¼ 6.9 Hz, 3H) ppm; 13C NMR (100 MHz,
25
(0.70 g, 85%); [
CD3OD)
(m, 1H), 3.69e3.56 (m, 1H), 3.51e3.45 (m, 1H), 3.39e3.12 (m, 5H),
2.95e2.66 (m, 2H), 2.47e2.30 (m, 1H), 2.25e1.61 (m, 7H) ppm; 13
NMR (100 MHz, METHANOL-D3) 172.5, 172.3, 169.7, 169.5, 137.9,
a
]
¼ ꢂ12.72 (c 0.33, MeOH); H NMR (400 MHz,
D
d
7.32e7.11 (m, 5H), 4.32 (dd, J ¼ 11.2, 8.4 Hz, 1H), 4.27e4.11
C
CDCl3) d 204.4, 137.1, 129.2, 128.1, 128.0, 79.0, 58.8, 42.0, 28.0, 21.7,
d
17.0 ppm; HRMS (ESI-TOF) m/z: [MꢂH]ꢂcalcd for C13H16NO3
129.1, 128.9, 128.2, 128.0, 126.3, 121.3 (q, J ¼ 323.7 Hz), 61.6, 60.1,
59.0, 52.4, 51.6, 47.0, 46.8, 46.5, 46.1, 37.9, 37.2, 29.3, 28.4, 25.2, 24.4,
23.8 ppm; FTIR (thin film): ῡ ¼ 3290,3072, 2965, 2931, 1667, 1534,
1497, 1466, 1417, 1377, 1329, 1266, 1152 cmꢂ1. HRMS (ESI-TOF) m/z:
[MꢂH]ꢂcalcd for C20H26F3N4O4S 475.1627, found 475.1625.
234.1130, found 234.11177; HPLC (Chiralpak-IC column, Hexane:2-
Propanol ¼ 90:10, flow rate: 0.5 mL/min,
l
¼ 254 nm), tR
major ¼ 27.07, tR minor ¼ 30.72, 95% ee and dr 98:2.
(S)-2-((R)-2-nitro-1-phenylethyl)hexanal (7e): Column chro-
matography (90:10 petroleum ether/EtOAc); Pale yellow oil (0.10 g,
86% Yield); 1H NMR (400 MHz, CDCl3)
d
9.69 (d, J ¼ 2.7 Hz, 1H),
6. General procedure for the Michael addition of aldehydes to
nitroalkenes
7.37e7.28 (m, 3H), 7.16 (d, J ¼ 6.9 Hz, 2H), 4.72e4.60 (m, 2H),
3.79e3.73 (m, 1H), 2.72e2.64 (m, 1H), 1.49e1.39 (m, 2H), 1.23e1.12
(m, 4H), 0.77 (t, J ¼ 6.7 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3)
To a solution of the aldehyde (1.5 mmol, 3.0 equiv) in 2 mL of the
xylene, the nitroalkene (0.5 mmol, 1.0 equiv) and the catalyst 5
(0.007 g, 0.015 mmol, 0.03 equiv) were added and stirred at rt. The
reaction was continued until the complete disappearance of
nitroalkenes on TLC. The solvent was removed under reduced
pressure and Michael adduct were purified by column chroma-
tography. 1H NMR of crude reaction mixtures were taken to
determine the diastereomeric ratios, wherever applicable. Purified
compounds were subjected to HPLC analysis for the determination
of enantiomeric ratios.
d 203.3, 136.8, 129.1, 128.2, 128.0, 78.5, 53.9, 43.2, 28.6, 27.1, 22.5,
13.7 ppm; HRMS (ESI-TOF) m/z: [MꢂH]ꢂcalcd for C14H18NO3
248.1287, found 248.1285; HPLC (Chiralpak-IC column, Hexane:2-
Propanol ¼ 90:10, flow rate: 0.7 mL/min,
l
¼ 254 nm), tR
major ¼ 22.91, tR minor ¼ 26.63, 94% ee and dr 96:4.
(S)-2-((R)-2-nitro-1-phenylethyl)heptanal (7f): Column chro-
matography (92:8 petroleum ether/EtOAc); Pale yellow oil (0.11 g,
85% Yield); 1H NMR (400 MHz, CDCl3)
d
9.69 (d, J ¼ 2.9 Hz, 1H),
7.35e7.26 (m, 3H), 7.17e7.15 (m, 2H), 4.69 (dd, J ¼ 12.8, 5.3 Hz, 1H),
4.62 (dd, J ¼ 12.7, 9.5 Hz, 1H), 3.76 (td, J ¼ 9.6, 5.2 Hz,1H), 2.73e2.65
8

A.B. Gorde, A. Ansari and R. Ramapanicker
Tetrahedron 87 (2021) 132095
(m, 1H), 1.52e1.37 (m, 3H), 1.19e1.07 (m, 5H), 0.79 (t, J ¼ 6.9 Hz, 3H)
ppm; 13C NMR (100 MHz, CDCl3) 203.3, 136.8, 129.1, 128.2, 128.0,
78.5, 53.9, 43.2, 31.6, 27.3, 26.1, 22.3, 13.9 ppm; HRMS (ESI-TOF) m/
z: [MꢂH]ꢂcalcd for C14H18NO3 262.1443, found 262.1441; HPLC
(2S,3R)-2-ethyl-3-(4-fluorophenyl)-4-nitrobutanal (7l): Col-
umn chromatography (90:10 petroleum ether/EtOAc); Pale yellow
oil (0.107 g, 90% Yield); 1H NMR (400 MHz, CDCl3)
d 9.70 (d,
J ¼ 2.4 Hz, 1H), 7.17e7.13 (m, 2H), 7.05e7.00 (m, 2H), 4.72e4.68 (m,
1H), 4.59 (t, J ¼ 6.3 Hz, 1H), 3.81e3.75 (m, 1H), 2.68e2.62 (m, 1H),
1.53e1.45 (m, 2H), 0.82 (t, J ¼ 7.6 Hz, 3H) ppm; 13C NMR (100 MHz,
(Chiralpak-IC column, Hexane:2-Propanol
¼
92:8, flow rate:
0.6 mL/min,
and dr 95:5.
l
¼ 254 nm), tR major ¼ 22.92, tR minor ¼ 26.36, 92% ee
CDCl3)
d
202.9, 162.3, (d, J ¼ 250 Hz), 132.6 (d, J ¼ 3.1 Hz), 129.7 (d,
(2S,3R)-3-(4-fluorophenyl)-2-methyl-4-nitrobutanal
(7g):
J ¼ 8.0 Hz), 116.2, (d, J ¼ 22 Hz), 78.6, 54.9, 42.0, 20.4, 10.6 ppm;
HRMS (ESI-TOF) m/z: [MꢂH]ꢂcalcd for C12H13FNO3 238.0879, found
238.0888; HPLC (Chiralpak-IC column, Hexane:2-Propanol ¼ 90:10,
Column chromatography (90:10 petroleum ether/EtOAc); Pale
yellow oil (0.105 g, 94% Yield); 1H NMR (400 MHz, CDCl3)
d
9.69 (d,
J ¼ 1.4 Hz, 1H), 7.16e7.12 (m, 2H), 7.05e7.00 (m, 2H), 4.78 (dd,
J ¼ 12.7, 5.4 Hz, 1H), 4.66e4.61 (m, 1H), 3.83e3.76 (m, 1H),
2.80e2.71 (m, 1H), 0.99 (d, J ¼ 7.3 Hz, 3H) ppm; 13C NMR (100 MHz,
flow rate: 0.7 mL/min,
l
¼ 254 nm), tR major ¼ 20.79, tR
minor ¼ 23.29, 97% ee and dr 90:10.
(2S,3R)-2-ethyl-4-nitro-3-(p-tolyl)butanal (7m): Column
chromatography (90:10 petroleum ether/EtOAc); Pale yellow oil
CDCl3)
d
202.0, 162.4 (d, J ¼ 247.5Hz), 132.4 (d, J ¼ 3.0 Hz), 129.7 (d,
J ¼ 8.0 Hz), 116.1 (d, J ¼ 21.5 Hz), 78.2, 48.4, 43.4, 12.2 ppm; HRMS
(ESI-TOF) m/z: [MꢂH]ꢂcalcd for C11H11FNO3 224.0723, found
224.0723; HPLC (Chiralpak-IC column, Hexane:2-Propanol ¼ 90:10,
(0.102 g, 87% Yield); 1H NMR (400 MHz, CDCl3)
d
9.70 (d, J ¼ 2.9 Hz,
1H), 7.13 (d, J ¼ 7.9 Hz, 2H), 7.04 (d, J ¼ 8.0 Hz, 2H), 4.72e4.64 (m,
1H), 4.59 (dd, J ¼ 12.5, 9.7 Hz, 1H), 3.73 (td, J ¼ 9.8, 5.0 Hz, 1H),
2.66e2.60 (m, 1H), 2.31 (s, 3H), 1.53e1.47 (m, 2H), 0.82 (t, J ¼ 7.4 Hz,
flow rate: 0.8 mL/min,
l
¼ 254 nm), tR major ¼ 39.74, tR
minor ¼ 44.92, 98% ee and dr 83:17.
3H). ppm; 13C NMR (100 MHz, CDCl3)
d 203.4, 137.9, 133.6, 129.8,
(2S,3R)-2-methyl-4-nitro-3-(p-tolyl)butanal (7h): Column
chromatography (90:10 petroleum ether/EtOAc); Pale yellow oil
127.9, 78.7, 55.1, 42.4, 21.1, 20.4, 10.7 ppm; HRMS (ESI-TOF) m/z:
[MꢂH]ꢂcalcd for C13H16NO3 234.1130, found 234.1134; HPLC
(Chiralpak-IC column, Hexane:2-Propanol ¼ 90:10, flow rate:
(0.097 g, 88% Yield); 1H NMR (400 MHz, CDCl3)
d
9.70 (d, J ¼ 1.8 Hz,
1H), 7.13 (d, J ¼ 7.9 Hz, 2H), 7.03 (d, J ¼ 8.1 Hz, 2H), 4.78e4.74 (m,
1H), 4.67e4.62 (m, 1H), 3.79e3.74 (m, 1H), 2.77e2.71 (m, 1H), 2.31
(s, 3H), 0.99 (d, J ¼ 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3)
0.8 mL/min,
and dr 93:7.
l
¼ 254 nm), tR major ¼ 24.04, tR minor ¼ 27.75, 96% ee
(2S,3R)-3-(2-chlorophenyl)-2-ethyl-4-nitrobutanal (7n): Col-
d
202.4, 137.9, 133.4, 129.8, 127.9, 78.3, 48.5, 43.7, 21.1, 12.1 ppm;
umn chromatography (90:10 petroleum ether/EtOAc); Pale yellow
HRMS (ESI-TOF) m/z: [MꢂH]ꢂcalcd for C12H14NO3 220.0974, found
220.0987; HPLC (Chiralpak-IC column, Hexane:2-Propanol ¼ 90:10,
oil (0.108 g, 85% Yield); 1H NMR (400 MHz, CDCl3)
d 9.72 (d,
J ¼ 2.4 Hz, 1H), 7.42e7.38 (m, 1H), 7.26e7.19 (m, 3H), 4.85 (dd,
J ¼ 12.9, 9.1 Hz, 1H), 4.67 (dd, J ¼ 13.0, 4.7 Hz, 1H), 4.37e4.31 (m,
1H), 2.96e2.91 (m, 1H), 1.60e1.51 (m, 2H), 0.85 (t, J ¼ 7.5 Hz, 3H)
flow rate: 0.6 mL/min,
l
¼ 254 nm), tR major ¼ 34.58, tR
minor ¼ 40.61, 97% ee and dr 84:16.
(2S,3R)-3-(2-chlorophenyl)-2-methyl-4-nitrobutanal
(7i):
ppm; 13C NMR (100 MHz, CDCl3)
d 202.9, 134.5, 134.4, 130.6, 129.3,
Column chromatography (90:10 petroleum ether/EtOAc); Pale
127.5, 76.8, 54.0, 39.2, 20.4, 10.7 ppm; HRMS (ESI-TOF) m/z:
[MꢂH]ꢂcalcd for C12H13ClNO3 254.0584, found 254.0585; HPLC
(Chiralpak-IC column, Hexane:2-Propanol ¼ 90:10, flow rate:
yellow oil (0.0.108 g, 90% Yield); 1H NMR (400 MHz, CDCl3)
d
9.73
(d, J ¼ 1.5 Hz, 1H), 7.40 (dd, J ¼ 7.3, 2.0 Hz, 1H), 7.26e7.23 (m, 2H),
7.21e7.18 (m, 1H), 4.86 (dd, J ¼ 13.1, 9.1 Hz, 1H), 4.80e4.75 (m, 1H),
4.32 (td, J ¼ 9.3, 5.0 Hz, 1H), 3.04e2.94 (m, 1H), 1.02 (d, J ¼ 7.4 Hz,
0.7 mL/min,
l
¼ 254 nm), tR major ¼ 23.68, tR minor ¼ 25.78, 96% ee
and dr 92:8.
3H) ppm; 13C NMR (100 MHz, CDCl3)
d
201.9, 134.56, 134.51, 130.6,
(2S,3R)-3-(3-chlorophenyl)-2-ethyl-4-nitrobutanal (7o): Col-
129.3, 127.5, 75.5, 47.8, 40.7, 12.3 ppm; HRMS (ESI-TOF) m/z:
[MꢂH]ꢂcalcd for C11H11ClNO3 240.0427, found 240.0423; HPLC
(Chiralpak-IC column, Hexane:2-Propanol ¼ 90:10, flow rate:
umn chromatography (90:10 petroleum ether/EtOAc); Pale yellow
oil (0.110 g, 87% Yield); 1H NMR (400 MHz, CDCl3)
d 9.70 (d,
J ¼ 2.3 Hz, 1H), 7.27 (dd, J ¼ 5.6, 2.0 Hz, 2H), 7.17 (s, 1H), 7.09e7.05
(m, 1H), 4.71 (dd, J ¼ 12.9, 4.7 Hz, 1H), 4.60 (dd, J ¼ 13.0, 9.9 Hz, 1H),
3.80e3.73 (m, 1H), 2.69e2.63 (m, 1H), 1.55e1.46 (m, 2H), 0.84 (t,
0.6 mL/min,
and dr 82:18.
(2S,3R)-3-(3-chlorophenyl)-2-methyl-4-nitrobutanal
Column chromatography (90:10 petroleum ether/EtOAc); Pale
yellow oil (0.112 g, 93% Yield); 1H NMR (400 MHz, CDCl3)
9.68 (d,
l
¼ 254 nm), tR major ¼ 20.71, tR minor ¼ 21.96, 98% ee
(7j):
J ¼ 7.5 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3)
d 202.7,139.0,135.0,
130.4, 128.5, 128.2, 126.3, 78.2, 54.7, 42.3, 20.7, 10.6 ppm; HRMS
(ESI-TOF) m/z: [MꢂH]ꢂcalcd for C12H13ClNO3 254.0584, found
254.0586; HPLC (Chiralpak-IC column, Hexane:2-Propanol ¼ 90:10,
d
J ¼ 1.6 Hz, 1H), 7.29e7.26 (m, 2H), 7.16 (s, 1H), 7.08e7.04 (m, 1H),
4.78 (dd, J ¼ 12.8, 5.2 Hz, 1H), 4.64 (dd, J ¼ 12.9, 9.4 Hz, 1H),
3.81e3.74 (m, 1H), 2.80e2.72 (m, 1H), 1.00 (d, J ¼ 7.3 Hz, 3H) ppm;
flow rate: 0.8 mL/min,
minor ¼ 22.43, 97% ee and dr 89:11.
l
¼ 254 nm), tR major ¼ 19.73, tR
13C NMR (100 MHz, CDCl3)
d
201.8, 138.8, 135.0, 130.4, 128.5, 128.3,
(2S,3R)-2-ethyl-3-(4-methoxyphenyl)-4-nitrobutanal
(7p):
126.4, 77.8, 48.2, 43.7, 12.3 ppm; HRMS (ESI-TOF) m/z: [MꢂH]ꢂcalcd
for C11H11ClNO3 240.0427, found 240.0426; HPLC (Chiralpak-IC
column, Hexane:2-Propanol ¼ 90:10, flow rate: 0.8 mL/min,
Column chromatography (90:10 petroleum ether/EtOAc); Pale
yellow oil (0.106 g, 85% Yield); 1H NMR (400 MHz, CDCl3)
d
9.69 (d,
J ¼ 2.5 Hz, 1H), 7.08 (d, J ¼ 8.6 Hz, 2H), 6.85 (d, J ¼ 8.6 Hz, 2H),
4.70e4.65 (m, 1H), 4.56 (dd, J ¼ 12.4, 9.8 Hz, 1H), 3.77 (s, 3H),
3.77e3.59 (m, 1H), 2.65e2.58 (m, 1H), 1.51e1.45 (m, 2H), 0.81 (t,
l
¼ 254 nm), tR major ¼ 38.22, tR minor ¼ 42.89, 97% ee and dr
82:18.
(2S,3R)-3-(4-methoxyphenyl)-2-methyl-4-nitrobutanal (7k):
Column chromatography (90:10 petroleum ether/EtOAc); Pale
yellow oil (0.103 g, 87% Yield); 1H NMR (400 MHz, CDCl3)
9.69 (d,
J ¼ 7.6 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3)
d 203.4, 159.3,129.1,
128.6, 114.5, 78.8, 55.3, 55.2, 42.1, 20.4, 10.7 ppm; HRMS (ESI-TOF)
m/z: [MꢂH]ꢂcalcd for C16H16NO4 250.1079, found 250.1080; HPLC
(Chiralpak-IC column, Hexane:2-Propanol ¼ 90:10, flow rate:
d
J ¼ 1.7 Hz, 1H), 7.07 (d, J ¼ 8.7 Hz, 2H), 6.85 (d, J ¼ 8.7 Hz, 2H),
4.77e4.72 (m, 1H), 4.65e4.60 (m, 1H), 3.77 (s, 3H), 2.75e2.69 (m,
0.7 mL/min,
and dr 91:9.
l
¼ 254 nm), tR major ¼ 31.27, tR minor ¼ 35.09, 95% ee
1H), 0.99 (d, J ¼ 7.3 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3)
d 202.5,
159.3, 129.1, 128.3, 114.5, 78.4, 55.3, 48.6, 43.4, 12.1 ppm; HRMS
(ESI-TOF) m/z: [MꢂH]ꢂcalcd for C12H14NO4 236.0923, found
236.0920; HPLC (Chiralpak-IC column, Hexane:2-Propanol ¼ 90:10,
(S)-2-((R)-1-(4-fluorophenyl)-2-nitroethyl)pentanal (7q): Col-
umn chromatography (90:10 petroleum ether/EtOAc); Pale yellow
oil (0.11 g, 88% Yield); 1H NMR (400 MHz, CDCl3)
d 9.69 (d,
flow rate: 0.5 mL/min,
l
¼ 254 nm), tR major ¼ 47.03, tR
J ¼ 2.7 Hz, 1H), 7.16e7.12 (m, 2H), 7.03 (t, J ¼ 8.6 Hz, 2H), 4.68 (dd,
minor ¼ 53.59, 96% ee and dr 81:19.
J ¼ 12.7, 5.0 Hz, 1H), 4.59 (dd, J ¼ 12.8, 9.8 Hz, 1H), 3.79e3.73 (m,
9

A.B. Gorde, A. Ansari and R. Ramapanicker
Tetrahedron 87 (2021) 132095
(b) B. List, P. Pojarliev, C. Castello, Org. Lett. 3 (2001) 573e575;
(c) D. Pidathala, L. Hoang, N. Vignola, B. List, Angew. Chem. Int. Ed. 42 (2003)
2785e2788;
1H), 2.70e2.63 (m, 1H), 1.47e1.32 (m, 4H), 0.80 (t, J ¼ 7.0 Hz, 3H)
ppm; 13C NMR (100 MHz, CDCl3)
d
203.0, 162.4 (d, J ¼ 246 Hz), 132.6
(d, J ¼ 3.4 Hz),129.7 (d, J ¼ 8.2 Hz),116.2 (d, J ¼ 22 Hz),116.34,116.12,
78.5, 53.8, 42.4, 29.5, 19.7, 14.0 ppm; HRMS (ESI-TOF) m/z:
[MꢂH]ꢂcalcd for C13H15FNO3 252.1036, found 252.1035; HPLC
(Chiralpak-IC column, Hexane:2-Propanol ¼ 90:10, flow rate:
(d) K. Sakthivel, W. Notz, T. Bui, C.F. Barbas III., J. Am. Chem. Soc. 123 (2001)
5260e5267;
(e) R. Thayumanavan, F. Tanaka, C.F. Barbas III., Org. Lett. 6 (2004) 3541e3544.
[2] (a) B. List, J. Am. Chem. Soc. 122 (2000) 9336e9337;
(b) S. Mukherjee, J.W. Yang, S. Hoffmann, B. List, Chem. Rev. 107 (2007)
5471e5569;
0.7 mL/min,
and dr 95:5.
l
¼ 254 nm), tR major ¼ 19.64, tR minor ¼ 22.46, 95% ee
(c) J.W. Yang, M. Stadler, B. List, Angew. Chem. Int. Ed. Engl. 46 (2007)
609e611;
(d) D. Enders, M. Vrettou, Synthesis (2006) 2155e2158;
(e) N.S. Chowdari, D.B. Ramachary, C.F. Barbas III, Synlett 35 (2003)
1906e1909.
(S)-2-((R)-2-nitro-1-(p-tolyl)ethyl)pentanal (7r): Column
chromatography (90:10 petroleum ether/EtOAc); Pale yellow oil
(0.105 g, 85% Yield); 1H NMR (400 MHz, CDCl3)
d
9.68 (d, J ¼ 3.0 Hz,
[3] (a) B. List, P. Pojarliev, H. Martin, J. Org. Lett. 3 (2001) 2423e2425;
(b) J.M. Betancort, C.F. Barbas III, Org. Lett. 3 (2001) 3737e3740;
(c) N. Mase, K. Watanabe, H. Yoda, K. Takabe, F. Tanaka, C.F. Barbas III, J. Am.
Chem. Soc. 128 (2006) 4966e4967;
1H), 7.13 (d, J ¼ 8.0 Hz, 2H), 7.03 (d, J ¼ 8.0 Hz, 2H), 4.68e4.58 (m,
2H), 3.72 (td, J ¼ 9.5, 5.3 Hz, 1H), 2.69e2.63 (m, 1H), 2.31 (s, 3H),
1.46e1.28 (m, 4H), 0.79 (t, J ¼ 7.1 Hz, 3H) ppm; 13C NMR (100 MHz,
(d) H. Yang, M.W. Wong, Org. Biomol. Chem. 10 (2012) 3229e3235.
CDCl3)
d 203.4, 137.9, 133.6, 129.8, 127.9, 78.6, 53.9, 42.9, 29.5, 21.1,
ꢀ
[4] (Selected examples:). (b) C. Palomo, S. Vera, A. Mielgo, E. Gomez-Bengoa,
19.8, 14.0 ppm; HRMS (ESI-TOF) m/z: [MꢂH]ꢂcalcd for C14H18NO3
Angew. Chem. 118 (2006) 6130e6133;
(d) M. Keller, A. Perrier, R. Linhardt, L. Travers, S. Wittmann, A.-M. Caminade,
J.-P. Majoral, O. Reiser, A. Ouali, Adv. Synth. Catal. 355 (2013) 1748e1754;
(e) C.A. Wang, Z.K. Zhang, T. Yue, Y.L. Sun, L. Wang, W.D. Wang, Y. Zhang,
C. Liu, W. Wang, Chem. Eur J. 18 (2012) 6718e6723;
(f) Y. Wang, D. Li, J. Lin, K. Wei, RSC Adv. 5 (2015) 5863e5874;
(g) L. TuchmaneShukron, S.J. Miller, M. Portnoy, Chem. Eur J. 18 (2012)
2290e2296;
(h) I. Sagamanova, C. Rodríguez-Escrich, I.G. Molnar, S. Sayalero, R. Gilmour,
M.A. Pericas, ACS Catal. 5 (2015) 6241e6248;
(i) E. Alza, S. Sayalero, P. Kasaplar, D. Almasi, M.A. Pericas, Chem. Eur J. 17
(2011) 11585e11595;
(j) S. Chandrasekhar, C.P. Kumar, T.P. Kumar, K. Haribabu, B. Jagadeesh,
J.K. Lakshmib, P.S. Mainkar, RSC Adv. 4 (2014) 30325e30331;
(k) J. Watts, L. Luu, V. McKee, E. Carey, F. Kelleher, Adv. Synth. Catal. 354
(2012) 1035e1042;
(l) H. Yu, M. Liu, S. Han, Tetrahedron 70 (2014) 8380e8384;
(m) C. He, X. Ren, Y. Feng, Y. Chai, S. Zhang, W. Chen, Tetrahedron Lett. 56
(2015) 4036e4038;
248.1287, found 248.1281; HPLC (Chiralpak-IC column, Hexane:2-
Propanol ¼ 90:10, flow rate: 0.8 mL/min,
l
¼ 254 nm), tR
major ¼ 20.25, tR minor ¼ 23.71, 94% ee and dr 94:6.
(S)-2-((R)-1-(2-chlorophenyl)-2-nitroethyl)pentanal
(7s):
Column chromatography (90:10 petroleum ether/EtOAc); Pale
yellow oil (0.116 g, 87% Yield); 1H NMR (400 MHz, CDCl3)
d
9.71 (d,
J ¼ 2.7 Hz, 1H), 7.42e7.39 (m, 1H), 7.27e7.19 (m, 4H), 4.86 (dd,
J ¼ 13.0, 9.3 Hz, 1H), 4.67 (dd, J ¼ 13.1, 4.6 Hz, 1H), 4.35e4.30 (m,
1H), 2.99e2.92 (m, 1H), 1.40e1.27 (m, 4H), 0.82 (d, J ¼ 7.2 Hz, 3H)
ppm; 13C NMR (100 MHz, CDCl3)
d 202.9, 134.6, 134.4, 130.6, 129.3,
127.5, 76.1, 52.9, 39.6, 29.6, 19.8, 14.0 ppm; HRMS (ESI-TOF) m/z:
[MꢂH]ꢂcalcd for C13H15ClNO3 268.0740, found 268.0742; HPLC
(Chiralpak-IC column, Hexane:2-Propanol ¼ 90:10, flow rate:
0.7 mL/min,
and dr 88:12.
l
¼ 254 nm), tR major ¼ 17.71, tR minor ¼ 19.58, 94% ee
(n) T.C. Nugent, M. Shoaib, A. Shoaib, Org. Biomol. Chem. 9 (2011) 52e56;
(o) P. Garcia-Garcia, A. Ladepeche, R. Halder, B. List, Angew. Chem. 120 (2008)
4797e4799;
(S)-2-((R)-1-(4-methoxyphenyl)-2-nitroethyl)pentanal (7t):
ꢁ
ꢀ
ꢁ
ꢀ
(p) K. Ormandyova, S. Bilka, M. Meciarova, R. Sebesta, Chemistry Select 4
Column chromatography (90:10 petroleum ether/EtOAc); Pale
(2019) 8870e8875;
yellow oil (0.110 g, 84% Yield); 1H NMR (400 MHz, CDCl3)
d 9.68 (d,
ꢁ
ꢀ
ꢀ
(q) P. Cmelova, D. Vargova, R. Sebesta, J. Org. Chem. 86 (2021) 581e592.
[5] (a) W. Wang, J. Wang, H. Li, Angew. Chem. 117 (2005) 1393e1395;
(b) W. Wang, J. Wang, H. Li, Angew. Chem. Int. Ed. 44 (2005) 1369e1371;
(c) J. Wang, H. Li, B. Lou, L. Zu, H. Guo, W. Wang, Chem. Eur J. 12 (2006)
4321e4332.
J ¼ 2.7 Hz, 1H), 7.07 (d, J ¼ 8.6 Hz, 2H), 6.85 (d, J ¼ 8.6 Hz, 2H),
4.66e4.55 (m, 2H), 3.78 (s, 3H), 3.69 (dd, J ¼ 9.5, 5.3 Hz, 1H),
2.67e2.61 (m, 1H), 1.43e1.31 (m, 4H), 0.79 (t, J ¼ 7.0 Hz, 3H) ppm;
13C NMR (100 MHz, CDCl3)
d 203.4, 159.3, 129.1, 128.5, 114.5, 78.7,
[6] (a) R.-S. Luo, J. Weng, H.-B. Ai, G. Lu, A.S.C. Chan, Adv. Synth. Catal. 351 (2009)
2449e2459;
55.3, 54.0, 42.5, 29.5, 19.8, 14.0 ppm; HRMS (ESI-TOF) m/z:
[MꢂH]ꢂcalcd for C14H18NO4 264.1236, found 264.1239; HPLC
(Chiralpak-IC column, Hexane:2-Propanol ¼ 90:10, flow rate:
(b) Y. Li, X.-Y. Liu, G. Zhao, Tetrahedron: Asymmetry 17 (2006) 2034e2039;
(c) Y. Hayashi, H. Gotoh, T. Hayashi, M. Shoji, Angew. Chem. Int. Ed. 44 (2005)
4212e4215;
(d) J. Xiao, F.-X. Xu, Y.-P. Lu, T.-P. Loh, Org. Lett. 12 (2010) 1220e1223;
(e) D. Roca-Lopez, P. Merino, F.J. Sayago, C. Cativiela, R.P. Herrera, Synlett
(2011) 249e253;
0.6 mL/min,
and dr 86:14.
l
¼ 254 nm), tR major ¼ 24.34, tR minor ¼ 28.10, 90% ee
(f) R. Parella, S. Jakkampudi, H. Arman, J.C.-G. Zhao, Adv. Synth. Catal. 361
(2019) 208e213;
(g) C.K. Mahato, S. Mukherjee, M. Kundu, A. Pramanik, J. Org. Chem. 84 (2019)
1053e1063.
Declaration of competing interest
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
[7] (Reviews on peptides as organocatalysts:). (a) H. Wennemers, Chem. Com-
mun. 47 (2011) 12036e12041;
(b) Y. Arakawa, H. Wennemers, ChemSusChem 6 (2013) 242e245;
(c) J.D. Revell, H. Wennemers, Curr. Opin. Chem. Biol. 11 (2007) 269e278;
(d) E.A.C. Davie, S.M. Mennen, Y. Xu, S. Miller, J. Chem. Rev. 107 (2007)
5759e5812.
Acknowledgments
[8] (Examples of short-chain peptides containing proline as organocatalysts). (a)
Z. Tang, Z.-H. Yang, L.-F. Cun, L.-Z. Gong, A.-Q. Mi, Y.-Z. Jiang, Org. Lett. 6 (2004)
2285e2287;
We thank the Science and Engineering Research Board, Depart-
ment of Science and Technology India for funding this project
through EMR/2017/000414. We thank Prof. D. H. Dethe for helping
us with HPLC analysis.
(b) O. Illa, O. PorcareTost, C. Robledillo, C. Elvira, P. Nolis, O. Reiser,
V. Branchadell, R.M. Ortuno, J. Org. Chem. 83 (2018) 350e363;
(c) X. Cao, G. Wang, R. Zhang, Y. Wei, W. Wang, H. Sun, L. Chen, Org. Biomol.
Chem. 9 (2011) 6487e6490.
[9] (a) P. Krattiger, R. Kovasy, J.D. Revell, S. Ivan, H. Wennemers, Org. Lett. 7
(2005) 1101e1103;
Appendix A. Supplementary data
(b) M. Wiesner, J.D. Revell, S. Tonazzi, H. Wennemers, J. Am. Chem. Soc. 130
(2008) 5610e5611;
(c) M. Wiesner, M. Neuburger, H. Wennemers, Chem. Eur J. 15 (2009)
10103e10109;
(d) M. Wiesner, H. Wennemers, Synthesis (2010) 1568e1571;
(e) Y. rakawa, M. Wiesner, H. Wennemers, Adv. Synth. Catal. 353 (2011)
1201e1206;
(f) J. Duschmale, J. Wiest, M. Wiesner, H. Wennemers, Chem. Sci. 4 (2013)
1312e1318;
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2021.132095.
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A.B. Gorde, A. Ansari and R. Ramapanicker
Tetrahedron 87 (2021) 132095
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