Isocyanide-based MCRs: Diastereoselective cascade synthesis of perfluoroalkylated pyrano[3,4-c]pyrrole derivatives

Article abstract of DOI:10.1016/j.jfluchem.2021.109723

The highly diastereoselective synthesis of perfluoroalkyl-containing pyrano[3,4-c]pyrroles has been accomplished via a cascade process involving Michael addition, Passerini-type reaction, Mumm rearrangement and an oxo-Diels–Alder reaction. This domino tra

Full text of DOI:10.1016/j.jfluchem.2021.109723

Journal of Fluorine Chemistry 243 (2021) 109723
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Isocyanide-based MCRs: Diastereoselective cascade synthesis of
perfluoroalkylated pyrano[3,4-c]pyrrole derivatives
,
,
Shanxue Yanga 1, Lan Yaob 1, Zhenhua Fana, Jing Hana, Jie Chena, Weimin Hea,
Hongmei Dengc, Min Shaoc, Hui Zhanga c,*, Weiguo Caoa
*
,
,d,
a Department of Chemistry, Innovative Drug Research Center, Shanghai University, Shanghai, 200444, PR China
b Inspection Department, Shanghai Blood Center, Shanghai, 200051, PR China
c Laboratory for Microstructures, Instrumental Analysis and Research Center of Shanghai University, Shanghai, 200444, PR China
d Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, PR China
A R T I C L E I N F O
A B S T R A C T
Keywords:
The highly diastereoselective synthesis of perfluoroalkyl-containing pyrano[3,4-c]pyrroles has been accom-
plished via a cascade process involving Michael addition, Passerini-type reaction, Mumm rearrangement and an
oxo-Diels–Alder reaction. This domino transformation of isocyanides, methyl perfluoroalk-2-ynoates and 3-aroyl
(or heteroyl) acrylic acids proceeded smoothly at room temperature and led to the formation of the highly
diastereoselective target compounds with high functional-group compatibility in good to excellent yields.
Cascade reaction
Diastereoselective synthesis
Isocyanide-based MCRs
Pyrano[3,4-c]pyrrole
Perfluoroalkylated
1. Introduction
In addition, owing to their economical and stereocontrolled nature,
intramolecular hetero-Diels–Alder (IMHDA) reactions have been widely
As is well known, incorporation of fluorine atoms or perfluoroalkyl
moieties into bioactive organic molecules normally makes the resultant
compounds improve their pharmacokinetic properties such as
bioavailability, metabolic stability, and hydrolytic stability, etc [1]. For
this reason, the development of methods for the construction of orga-
nofluorine compounds is of great importance.
used in organic synthesis [6], thus providing a means for the diaster-
eoselective construction of pyranopyrroles.
As a part of our ongoing research in the development of novel
isocyanide-based MCRs for the synthesis of valuable perfluoroalkylated
heterocyclic systems [7], we herein report a new diastereoselective
route for the synthesis of perfluoroalkylated pyrano[3,4-c]-pyrrole de-
rivatives based on the tandem Michael addition, Passerini-type reaction,
Mumm rearrangement and an oxo-Diels–Alder reaction.
Pyrano[3,4-c]-pyrrole moiety is found to exist in many biologically
important natural products and some pharmaceuticals [2]. Recently,
pyrano[3,4-c]-pyrrole derivatives are also found to be promising in
organocatalytic field [3].
2. Results and discussion
However, though a series of articles have been published to report
the preparation of pyrano[3,4-c]-pyrrole derivatives [4], to our best
knowledge, there is no literature available on the synthesis of per-
fluoroalkylated pyrano[3,4-c]-pyrroles. Therefore, the development of
the methods for the construction of such organofluorine compounds is
highly desirable.
Utilizing the isocyanide-based MCRs involved dimethyl acetylene-
dicarboxylate (DMAD), Jiang’s group has accomplished the synthesis of
densely functionalized pyrano[3,4-c]pyrroles at 80 ◦C in MeCN for 6 h
[4]. Inspired by their work, we conducted a model reaction using
(E)-4-oxo-4-phenylbut-2-enoic acid 1a, tert-butyl isocyanide 2a and
methyl 4,4,4-trifluorobut-2-ynoate 3a as model substrates under Jiang’s
conditions. To our delight, the desired product 4a was obtained as a
major diastereoisomer with moderate yield (Table 1, entry 1). The X-ray
diffraction analysis shows unambiguously that 4a is an exo adduct from
IMHDA and its configuration is similar with those of the compounds
Isocyanide-based multicomponent reactions (MCRs) take advantage
of the unique properties of the isocyanide functional group and have
become a versatile tool for the synthesis of structurally diverse hetero-
cycles accompanied by many benefits such as facile execution, high
atom-efficiency, regio-, chemo-, and stereoselectivity, etc [5].
* Corresponding authors at: Department of Chemistry, Innovative Drug Research Center, Shanghai University, Shanghai, 200444, PR China.
E-mail addresses: yehao7171@shu.edu.cn (H. Zhang), wgcao@shu.edu.cn (W. Cao).
1
Contribute equally
https://doi.org/10.1016/j.jfluchem.2021.109723
Received 26 November 2020; Received in revised form 6 January 2021; Accepted 7 January 2021
Available online 13 January 2021
0022-1139/© 2021 Elsevier B.V. All rights reserved.

S. Yang et al.
Journal of Fluorine Chemistry 243 (2021) 109723
the reaction and almost no adverse influence on diastereoselectivity
(Table 2, entry 7 vs entries 13, 15 and 17).
Table 1
Optimization of the reaction conditionsa.
The scope of the isocyanides was also examined. Different sub-
stituents R2 on the nitrogen atom of 2 were proved to be compatible with
the reaction, providing the products in moderate to excellent yields with
high diastereoselectivity (32 ꢀ 98 %; >92:1 dr) (Table 2, entries 19–22).
It should be mentioned that electron-withdrawing groups as 4-nitro-
phenyl somewhat retarded the annulation, and 2c gives only a 32 %
yield of 4 t [11].
Entry
Temperature [oC]
4Time [h]
Molar ratio [1a:2a:3a]
Yield [%]b
Encouraged by the above-mentioned results and to show the syn-
thetic potential of the protocol, (E)-2-(1-oxo-1,3-dihydro-2H-inden-2-
ylidene)acetic acid 1 m and (E)-2-(1-oxo-3,4-dihydronaphthalen-2(1H)-
ylidene)acetic acid 1n were applied to the reaction and the corre-
sponding adduct 4 w and 4x were obtained in good yield (71 %, 79 %)
and (>99:1 dr) diastereoselectivity, respectively (Scheme 1).
1
2
3
4
80
6
1.0:1.2:1.2
1.0:1.2:1.2
1.0:1.1:1.1
1.0:1.1:1.1
64
68
65
82c
r.t.
r.t.
r.t.
6
6
12
a
Reaction conditions: (E)-4-oxo-4-phenylbut-2-enoic acid 1a (1.0 mmol), tert-
butyl isocyanide 2a, methyl 4,4,4-trifluorobut-2-ynoate 3a, MeCN (5.0 mL) at
the confined temperature for the specified time.
Based on the experimental results and the previous reports [4,6,7,9],
a mechanistic pathway is proposed (Scheme 2). Initially, Michael
addition of 2 to perfluoroalkylated alkyne 3 gives zwitterion I which is
immediately protonized by acrylic acid 1 to yield aminium II and
carboxyl anion III. The intermediates II and III undergo Passerini-type
reaction [10] to provide isoimide IV, followed by subsequent Mumm
rearrangement [11] to deliver two conformers V and V’ generated from
single bond rotation (RFCC(=O)-N). The final intramolecular oxo--
Diels-Alder reaction affords exo adduct 4 as the major diastereoisomer;
meanwhile, the unfavorable secondary orbital interaction and steric
hindrance between R1 group and CO2Me group in conformer V’ lead to
the formation of endo isomer 4’ as the minor product [9].
b
Isolated yields.
c
The dr value was confirmed to be 59:1 by 19F NMR.
reported by Jiang and his co-workers (Fig. 1) [8]. Considering the
volatility and low boiling point of 3a, we lowered the reaction tem-
perature to improve the yield but failed (Table 1, entry 2). Furthermore,
when the reaction was conducted in
a 1.0:1.1:1.1 instead of
1.0:1.2:1.2 M ratio, the yield did not be altered either. However, when
prolonging the reaction time from 6 h to 12 h, there was an increase in
the yield (Table 1, entry 4).
Having established the optimum reaction conditions (Table 1, entry
4), various R1-substituted acrylic acids were first investigated to explore
the applicability of the reaction. As shown in Table 2, moderate to
excellent yields and high diastereoselectivities (4a–4 r, most cases
>59:1 dr) were obtained with substrates containing various aryl or
heteroaryl groups at the terminal position of acrylic acids. Generally, the
electronic nature of substituents on the phenyl ring of 1 had a similar
impact as reported by Jiang et al. on the yields of the desired products 4.
That is, electron-donating substituent on the phenyl ring of acrylic acid 1
afforded the desired products generally with lower yields compared to
electron-withdrawing group at the same position (Table 2, entry 4 vs
entries 5 and 6; entry 8 vs entry 9). For steric ortho-substituent, 4 j was
delivered in somewhat lower yield 81 % but still with high diaster-
eoselectivity (>99:1 dr) (Table 2, entry 10).
3. Conclusions
We have developed a general and straightforward protocol for the
synthesis of perfluoroalkylated pyrano[3,4-c]-pyrroles. This protocol, as
a cascade process, involves domino Michael addition, Passerini-type
reaction, Mumm rearrangement and an oxo-Diels–Alder reaction for
various 3-aroyl (or heteroyl) acrylic acids, methyl perfluoroalk-2-
ynoates and isocyanides. Advantages of this synthesis include mild re-
action conditions, good to excellent yields, broad substrate scope and
generally high diastereoselectivities. This protocol supplies an unprec-
edented avenue for an array of perfluoroalkylated pyranopyrroles which
are interesting target compounds for screening biological activity.
4. Experimental
In addition to the CF3 group, other perfluoalky groups in the side
chain of alkyne 3 were tested in the reaction (Table 2, entries 13–18).
The substrates with CF2H, C2F5, and n-C3F7 converted to the desired
pyranopyrroles smoothly. Moreover, the increased steric hindrance of
perfluoroalkyl group has only a little detrimental effect on the yields of
4.1. General information
Reagents and solvents were purchased from commercially sources
Fig. 1. X-ray crystal structure of compound 4a.
2

S. Yang et al.
Journal of Fluorine Chemistry 243 (2021) 109723
and used without further purification. Methyl perfluoroalk-2-ynoates 3
[12], (E)-acrylic acids 1a-L [13] and 1 m–n [14] were prepared ac-
cording to the known literatures. Melting points were recorded on a
152.6, 166.9, 169.9, 174.0 ppm. 19F NMR (470 MHz, CDCl3) δ: -71.4 (s,
CF3) ppm. IR (KBr): v 2984, 1741, 1709, 1653, 1451, 1342, 1274, 1186,
1171, 1088, 985 cmꢀ 1. MS (EI) m/z (%): 411 [M]+. HRMS (ESI) calcd.
For C20H20F3NO5 [(M+H)]+: 412.1373; found: 412.1371.
1
WRS-1 instrument and are uncorrected. H, 19F and 13C NMR spectra
were recorded on a Bruker DRX- 500 MHz spectrometer. All chemical
shifts are reported in parts per million downfield (positive) of the
standard: C6F6 for 19F, TMS for 1H and 13C NMR spectra. IR spectra were
obtained on an AVATAR370 FTIR spectrometer. LR-MS (lower resolu-
tion mass spectra) and HR-MS (high resolution mass spectra) were ob-
tained on Agilent 6230, Thermo Fisher Scientific LTO FT Ultra and
HP-5989 instruments, respectively. X-ray analysis was performed on a
Bruker Smart Apex2 CCD spectrometer. Yields reported in this publi-
cation refer to isolated ones of compounds and their purity was deter-
mined by 1H NMR.
4.2.2. Methyl 2-(tert-butyl)-6-(4-methoxyphenyl)-1,3-dioxo-3a-
(trifluoromethyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4b)
Yellow solid; m.p.: 111.1–112.4 ◦C; 1H NMR (500 MHz, CDCl3) δ:
1.60 (s, 9 H), 3.46 (d, J =3.5 Hz, 1 H), 3.65 (s, 3 H), 3.82 (s, 3 H), 5.40 (s,
1 H), 5.76 (d, J =3.5 Hz, 1 H), 6.88–6.89 (m, 2 H), 7.53–7.55 (m, 2 H)
ppm. 13C NMR (125 MHz, CDCl3) δ: 27.8, 38.5, 52.6 (q, 2JC-F =25.7 Hz,
CF3), 53.2, 55.4, 59.5, 72.9, 92.3, 113.9, 124.6 (q, 1JC-F =281.2 Hz, CF3),
125.8, 127.1, 152.6, 160.8, 167.0, 170.0, 174.3 ppm. 19F NMR
(470 MHz, CDCl3) δ: -71.4 (s, CF3) ppm. IR (KBr): v 2958, 1749, 1714,
1654, 1463, 1345, 1273, 1171, 1077, 984 cmꢀ 1. MS (EI) m/z (%): 441
[M]+. HRMS (ESI) calcd. For C21H22F3NO6 [(M+H)]+: 442.1478; found:
442.1473.
4.2. General procedure for the synthesis of perfluoroalkylated pyrano
[3,4-c]pyrrole derivatives 4
(E)-3-substituted acrylic acid 1 (1.0 mmol), isonitrile derivative 2
(1.1 mmol) and methyl perfluoroalk-2-ynoate 3 (1.1 mmol) were
sequentially added to MeCN (5.0 mL). The resulted system was stirred
for 12 h at room temperature. The solvent was evaporated under
reduced pressure and the residue was purified by a short column chro-
matography on silica gel (eluent: petroleum ether:ethyl acetate = 20:1
to 5:1) to afford the purified product 4.
4.2.3. Methyl 2-(tert-butyl)-1,3-dioxo-6-(p-tolyl)-3a-(trifluoromethyl)-
1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-carboxylate (4c)
Yellow solid; m.p.: 132.8-134.1 ◦C; 1H NMR (500 MHz, CDCl3) δ:
1.60 (s, 9 H), 2.36 (s, 3 H), 3.47 (d, J =3.5 Hz, 1 H), 3.65 (s, 3 H), 5.40 (s,
1 H), 5.84 (d, J =3.5 Hz, 1 H), 7.17 (d, J =8.0 Hz, 2 H), 7.49 (d, J
=8.0 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3) δ: 21.4, 27.8, 38.5, 52.6
2
1
(q, JC-F =25.9 Hz, CF3), 53.2, 59.5, 72.9, 93.3, 124.6 (q, JC-F
=281.1 Hz, CF3), 125.5, 129.2, 129.4, 130.4, 139.8, 152.7, 167.0,
170.0, 174.2 ppm. 19F NMR (470 MHz, CDCl3) δ: -71.4 (s, CF3) ppm. IR
(KBr): v 2976, 1740, 1711, 1654, 1457, 1341, 1276, 1184, 1165, 1086,
982 cmꢀ 1. MS (EI) m/z (%): 425 [M]+. HRMS (ESI) calcd. For
4.2.1. Methyl 2-(tert-butyl)-1,3-dioxo-6-phenyl-3a-(trifluoromethyl)-
1,2,3,3a,4,7a-hexahydropyrano [3,4-c]pyrrole-4-carboxylate (4a)
White solid; m.p.: 102.7-104.1 ◦C; 1H NMR (500 MHz, CDCl3) δ: 1.61
(s, 9 H), 3.49 (d, J =3.5 Hz, 1 H), 3.66 (s, 3 H), 5.42 (s, 1 H), 5.91 (d, J
=3.5 Hz, 1 H), 7.36–7.38 (m, 3 H), 7.60–7.61 (m, 2 H) ppm. 13C NMR
(125 MHz, CDCl3) δ: 27.8, 38.5, 52.5 (q, 2JC-F =25.9 Hz, CF3), 53.2, 59.6,
72.9, 94.2, 124.6 (q, 1JC-F =281.1 Hz, CF3), 125.5, 128.5, 129.6, 133.2,
C
21H22F3NO5 [(M+H)]+: 426.1529; found: 426.1525.
Table 2
Synthesis of perfluoroalkylated pyrano[3,4-c]-pyrroles 4a.
Entry
R1
R2
RF
Products
Yield [%]b
drc
1
C6H5 (1a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
t-Butyl (2a)
Cyclohexyl (2b)
4-NO2C6H4 (2c)
4-MeOC6H4(2d)
2,6-dimethylC6H4 (2e)
CF3 (3a)
CF3 (3a)
CF3 (3a)
CF3 (3a)
CF3 (3a)
CF3 (3a)
CF3 (3a)
CF3 (3a)
CF3 (3a)
CF3 (3a)
CF3 (3a)
CF3 (3a)
CF2H (3b)
CF2H (3b)
C2F5 (3c)
C2F5 (3c)
n-C3F7 (3d)
n-C3F7 (3d)
CF3 (3a)
CF3 (3a)
CF3 (3a)
CF3 (3a)
4a
4b
4c
83
69
87
95
93
90
97
85
94
81
90
96
92
85
93
64
89
45
68
32
69
98
59:1
2
4-MeOC6H4 (1b)
4-MeC6H4 (1c)
4-FC6H4 (1d)
>99:1
>99:1
>99:1
65:1
3
4
4d
4e
4f
5
4-ClC6H4 (1e)
4-BrC6H4 (1f)
4-NO2C6H4 (1 g)
3-MeC6H4 (1 h)
3-CF3C6H4 (1i)
2-BrC6H4 (1 j)
2-Thienyl (1k)
2-Furyl (1 L)
6
78:1
7
4 g
4 h
4i
>99:1
85:1
8
9
>99:1
>99:1
75:1
10
11
12
13
14
15
16
17
18
19
20
21
22
4 j
4k
4 L
4 m
4n
4o
4p
4q
4 r
4 s
4 t
4 u
4v
>99:1
>99:1
>99:1
>99:1
>99:1
85:1
4-NO2C6H4 (1 g)
4-ClC6H4 (1e)
4-NO2C6H4 (1 g)
C6H5 (1a)
4-NO2C6H4 (1 g)
C6H5 (1a)
80:1
4-NO2C6H4 (1 g)
4-NO2C6H4 (1 g)
4-NO2C6H4 (1 g)
4-NO2C6H4 (1 g)
>99:1
>99:1
>99:1
92:1
a
Reaction conditions: (E)-4-oxobut-2-enoic acid derivative 1 (1.0 mmol), isocyanide derivative 2 (1.1 mmol), perfluoroalkylated alkyne 3 (1.1 mmol), MeCN
(5.0 mL), room temperature, 12 h.
b
c
Total isolated yield of two diastereoisomer.
The dr value was confirmed by 19F NMR.
3

S. Yang et al.
Journal of Fluorine Chemistry 243 (2021) 109723
Scheme 1. Substrate extension.
4.2.4. Methyl 2-(tert-butyl)-6-(4-fluorophenyl)-1,3-dioxo-3a-
(trifluoromethyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4d)
CF3), 127.5, 127.6, 129.4, 151.8, 163.7 (d, 1JC-F =248.0 Hz, ArF), 166.8,
169.8, 174.0 ppm. 19F NMR (470 MHz, CDCl3) δ: -71.4 (s, CF3), -111.3
(s, ArF) ppm. IR (KBr): v 2952, 1754, 1703, 1654, 1512, 1459, 1339,
1275, 1208, 1178, 1103, 1080, 985 cmꢀ 1. MS (EI) m/z (%): 429 [M]+.
HRMS (ESI) calcd. For C20H19F4NO5 [(M+H)]+: 430.1278; found:
430.1274.
Yellow solid; m.p.: 89.9-91.2 ◦C; 1H NMR (500 MHz, CDCl3) δ: 1.60
(s, 9 H), 3.47 (d, J =3.5 Hz, 1 H), 3.66 (s, 3 H), 5.41 (s, 1 H), 5.84 (d, J
=3.5 Hz, 1 H), 7.04–7.07 (m, 2 H), 7.57–7.60 (m, 2 H) ppm. 13C NMR
(125 MHz, CDCl3) δ: 27.8, 38.5, 52.5 (q, 2JC-F =25.8 Hz, CF3), 53.3, 59.7,
2
1
72.9, 94.0, 115.6 (d, JC-F =21.8 Hz, ArF), 124.6 (q, JC-F =281.2 Hz,
Scheme 2. Proposed mechanism for the synthesis of compound 4.
4

S. Yang et al.
Journal of Fluorine Chemistry 243 (2021) 109723
4.2.5. Methyl 2-(tert-butyl)-6-(4-chlorophenyl)-1,3-dioxo-3a-
(trifluoromethyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4e)
4.2.10. Methyl 6-(2-bromophenyl)-2-(tert-butyl)-1,3-dioxo-3a-
(trifluoromethyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4 j)
Yellow solid; m.p.: 121.7-123.0◦C; 1H NMR (500 MHz, CDCl3) δ:
1.60 (s, 9 H), 3.47 (d, J =3.5 Hz, 1 H), 3.65 (s, 3 H), 5.41 (s, 1 H), 5.90 (d,
J =3.5 Hz, 1 H), 7.33–7.35 (m, 2 H), 7.53–7.55 (m, 2 H) ppm. 13C NMR
(125 MHz, CDCl3) δ: 27.8, 38.5, 52.5 (q, 2JC-F =25.8 Hz, CF3), 53.3, 59.7,
72.9, 94.8, 124.6 (q, 1JC-F =281.2 Hz, CF3), 126.8, 128.8, 131.6, 135.6,
151.6, 166.8, 169.7, 173.8 ppm. 19F NMR (470 MHz, CDCl3) δ: -71.4 (s,
CF3) ppm. IR (KBr): v 2984, 1739 1710, 1654, 1496, 1344, 1274, 1183,
1167, 1092, 981 cmꢀ 1. MS (EI) m/z (%): 445 [M]+. HRMS (ESI) calcd.
For C20H19ClF3NO5 [(M+H)]+: 446.0983; found: 446.0984.
Yellow solid; m.p.: 74.1-75.4 ◦C; 1H NMR (500 MHz, CDCl3) δ: 1.60
(s, 9 H), 3.55 (d, J =4.0 Hz, 1 H), 3.76 (s, 3 H), 5.33 (s, 1 H), 5.75 (d, J
=4.0 Hz, 1 H), 7.20–7.23 (m, 1 H), 7.30–7.33 (m, 1 H), 7.37–7.39 (m,
1 H),7.59–7.61 (m, 1 H) ppm. 13C NMR (125 MHz, CDCl3) δ: 27.7, 38.4,
51.9 (q, 2JC-F =26.0 Hz, CF3), 53.2, 59.6, 72.4, 99.3, 122.0, 124.4 (q, 1JC-
=281.3 Hz, CF3), 127.4, 130.7, 130.8, 133.6, 134.9, 151.5, 166.6,
F
169.7, 173.5 ppm. 19F NMR (470 MHz, CDCl3) δ: -71.4 (s, CF3) ppm. IR
(KBr): v 2975, 1748, 1714, 1439, 1335, 1274, 1185, 1166, 1078,
977 cmꢀ 1. MS (EI) m/z (%): 489 [M]+. HRMS (ESI) calcd. For
C
20H19BrF3NO5 [(M+H)]+: 490.0478; found: 490.0475.
4.2.6. Methyl 6-(4-bromophenyl)-2-(tert-butyl)-1,3-dioxo-3a-
(trifluoromethyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4f)
4.2.11. Methyl 2-(tert-butyl)-1,3-dioxo-6-(thiophen-2-yl)-3a-
(trifluoromethyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4k)
White solid; m.p.: 140.7-142.1 ◦C; 1H NMR (500 MHz, CDCl3) δ: 1.60
(s, 9 H), 3.46 (d, J =4.0 Hz, 1 H), 3.65 (s, 3 H), 5.41 (s, 1 H), 5.91 (d, J
=4.0 Hz, 1 H), 7.46–7.51 (m, 4 H) ppm. 13C NMR (125 MHz, CDCl3) δ:
27.8, 38.5, 52.4 (q, 2JC-F =25.8 Hz, CF3), 53.3, 59.7, 72.9, 94.9, 123.9,
White solid; m.p.: 149.1-150.4 ◦C; 1H NMR (500 MHz, CDCl3) δ: 1.60
(s, 9 H), 3.46 (d, J =4.0 Hz, 1 H), 3.67 (s, 3 H), 5.38 (s, 1 H), 5.79 (d, J
=4.0 Hz, 1 H), 7.01–7.03 (m, 1 H), 7.29–7.32 (m, 2 H) ppm. 13C NMR
(125 MHz, CDCl3) δ: 27.8, 38.3, 52.5 (q, 2JC-F =25.8 Hz, CF3), 53.3, 59.7,
72.9, 93.4, 124.5 (q, 1JC-F =281.3 Hz, CF3), 125.5, 127.0, 127.6, 136.9,
148.2, 166.8, 169.7, 173.9 ppm. 19F NMR (470 MHz, CDCl3) δ: -71.4 (s,
CF3) ppm. IR (KBr): v 2984, 1743, 1709, 1652, 1435, 1313, 1266, 1185,
1162, 1073, 986 cmꢀ 1. MS (EI) m/z (%): 417 [M]+. HRMS (ESI) calcd.
For C18H18F3NO5S [(M+H)]+: 418.0937; found: 418.0933.
1
124.6 (q, JC-F =281.2 Hz, CF3), 127.0, 131.8, 132.1, 151.7, 166.8,
169.7, 173.8 ppm. 19F NMR (470 MHz, CDCl3) δ: -71.4 (s, CF3) ppm. IR
(KBr): v 2983, 1737, 1709, 1654, 1493, 1343, 1273, 1185, 1167, 1087,
981 cmꢀ 1. MS (EI) m/z (%): 489 [M]+. HRMS (ESI) calcd. For
C20H19BrF3NO5 [(M+H)]+: 490.0478; found: 490.0465.
4.2.7. Methyl 2-(tert-butyl)-6-(4-nitrophenyl)-1,3-dioxo-3a-
(trifluoromethyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4 g)
4.2.12. Methyl 2-(tert-butyl)-6-(furan-2-yl)-1,3-dioxo-3a-
(trifluoromethyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4 L)
Yellow solid; m.p.: 135.8-137.2 ◦C; 1H NMR (500 MHz, CDCl3) δ:
1.61 (s, 9 H), 3.53 (d, J =4.0 Hz, 1 H), 3.66 (s, 3 H), 5.47 (s, 1 H), 6.13 (d,
J =4.0 Hz, 1 H), 7.77–7.79 (m, 2 H), 8.23–8.24 (m, 2 H) ppm. 13C NMR
(125 MHz, CDCl3) δ: 27.7, 38.6, 52.3 (q, 2JC-F =26.0 Hz, CF3), 53.5, 59.9,
72.9, 98.3, 123.9, 124.5 (q, 1JC-F =281.2 Hz, CF3), 126.1, 138.9, 148.4,
150.4, 166.5, 169.4, 173.3 ppm. 19F NMR (470 MHz, CDCl3) δ: -71.4 (s,
CF3) ppm. IR (KBr): v 2979, 1748, 1710, 1653, 1525, 1351, 1271, 1191,
1167, 1078, 988 cmꢀ 1. MS (EI) m/z (%): 456 [M]+. HRMS (ESI) calcd.
For C20H19F3N2O7 [(M+H)]+: 457.1223; found: 457.1212.
White solid; m.p.: 124.8-125.9 ◦C; 1H NMR (500 MHz, CDCl3) δ: 1.59
(s, 9 H), 3.49 (d, J =4.0 Hz, 1 H), 3.66 (s, 3 H), 5.33 (s, 1 H), 5.88 (d, J
=4.0 Hz, 1 H), 6.41–6.42 (m, 1 H), 6.55–6.56 (m, 1 H), 7.40–7.41 (m,
1 H) ppm. 13C NMR (125 MHz, CDCl3) δ: 27.8, 37.8, 52.4 (q, JC-F
2
1
=25.9 Hz, CF3), 53.3, 59.6, 72.5, 93.1, 108.9, 111.5, 124.5 (q, JC-F
=281.2 Hz, CF3), 143.6, 144.7, 147.7, 166.7, 169.8, 173.7 ppm. 19F
NMR (470 MHz, CDCl3) δ: -71.5 (s, CF3) ppm. IR (KBr): v 2991, 1745,
1710, 1668, 1437, 1320, 1281, 1217, 1189, 1167, 1096, 879 cmꢀ 1. MS
(EI) m/z (%): 401 [M]+. HRMS (ESI) calcd. For C18H18F3NO6 [(M+H)]+:
402.1165; found: 402.1159.
4.2.8. Methyl 2-(tert-butyl)-1,3-dioxo-6-(m-tolyl)-3a-(trifluoromethyl)-
1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-carboxylate (4 h)
White solid; m.p.: 95.2-96.5 ◦C; 1H NMR (500 MHz, CDCl3) δ: 1.61 (s,
9 H), 2.37 (s, 3 H), 3.48 (d, J =4.0 Hz, 1 H), 3.66 (s, 3 H), 5.41 (s, 1 H),
5.88 (d, J =4.0 Hz, 1 H), 7.17–7.18 (m, 1 H), 7.24–7.27 (m, 1 H),
7.40–7.42 (m, 2 H) ppm. 13C NMR (125 MHz, CDCl3) δ: 21.5, 27.8, 38.6,
52.5 (q, 2JC-F =25.8 Hz, CF3), 53.2, 59.6, 72.8, 94.1, 122.7, 124.6 (q, 1JC-
4.2.13. Methyl 2-(tert-butyl)-3a-(difluoromethyl)-6-(4-nitrophenyl)-1,3-
dioxo-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-carboxylate (4 m)
Yellow solid; m.p.: 54.3-55.9 ◦C; 1H NMR (500 MHz, CDCl3) δ: 1.54
(s, 9 H), 3.75 (d, JH-H =5.0 Hz, 1 H), 3.91 (s, 3 H), 4.69 (s, 1 H), 6.04 (d,
JH-H =5.0 Hz, 1 H), 6.51 (t, JH-F =55.5 Hz, 1 H), 7.77–7.79 (d, JH-H
=8.0 Hz, 2 H), 8.21–8.23 (d, JH-H =8.0 Hz, 2 H) ppm. 13C NMR
=281.3 Hz, CF3), 126.1, 128.5 130.4, 133.2, 138.2, 152.7, 166.9,
F
169.9, 174.1 ppm. 19F NMR (470 MHz, CDCl3) δ: -71.4 (s, CF3) ppm. IR
(KBr): v 2983, 1745, 1709, 1653, 1437, 1356, 1276, 1181, 1106, 1086,
990 cmꢀ 1. MS (EI) m/z (%): 425 [M]+. HRMS (ESI) calcd. For
(125 MHz, CDCl3) δ: 28.0, 38.5, 53.3, 55.2 (t, JC-F =20.6 Hz, CF2H),
2
60.0, 73.5, 99.3, 114.4 (t, 1JC-F =246.5 Hz, CF2H), 123.9, 125.9, 138.6,
148.3, 151.6, 167.1, 172.6, 174.4 ppm. 19F NMR (470 MHz, CDCl3) δ:
ꢀ 129.3 to ꢀ 127.6 (m, CF2H) ppm. IR (KBr): v 2959, 1745, 1710, 1524,
1439, 1348, 1268, 1190, 1129, 1067, 861 cmꢀ 1. MS (EI) m/z (%): 438
[M]+. HRMS (ESI) calcd. For C20H20F2N2O7 [(M+H)]+: 439.1318;
found: 439.1347.
C
21H22F3NO5 [(M+H)]+: 426.1529; found: 426.1526.
4.2.9. Methyl 2-(tert-butyl)-1,3-dioxo-3a-(trifluoromethyl)-6-(3-
(trifluoromethyl)phenyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4i)
Yellow solid; m.p.: 116.3-117.6 ◦C; 1H NMR (500 MHz, CDCl3) δ:
1.61 (s, 9 H), 3.51 (d, J =4.0 Hz, 1 H), 3.66 (s, 3 H), 5.46 (s, 1 H), 6.00 (d,
J =4.0 Hz, 1 H), 7.49–7.52 (m, 1 H), 7.61–7.63 (m, 1 H), 7.77–7.79 (m,
1 H), 7.88 (s, 1 H) ppm. 13C NMR (125 MHz, CDCl3) δ: 27.8, 38.5, 52.4
4.2.14. Methyl 2-(tert-butyl)-6-(4-chlorophenyl)-3a-(difluoromethyl)-1,3-
dioxo-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-carboxylate (4n)
Yellow solid; m.p.: 106.1-107.4 ◦C; 1H NMR (500 MHz, CDCl3) δ:
1.53 (s, 9 H), 3.70 (d, JH-H =5.0 Hz, 1 H), 3.91 (s, 3 H), 4.63 (s, 1 H), 5.80
(d, JH-H =4.5 Hz, 1 H), 6.50 (t, JH-F =55.5 Hz, 1 H), 7.32–7.34 (m, 2 H),
7.52–7.55 (m, 2 H) ppm. 13C NMR (125 MHz, CDCl3) δ: 28.0, 38.5, 53.2,
2
1
(q, JC-F =26.0 Hz, CF3), 53.3, 59.8, 73.0, 96.1, 122.5, 124.0 (q, JC-F
1
=270.7 Hz, ArCF3), 124.6 (q, JC-F =281.2 Hz, CF3), 126.2, 128.6,
2
2
1
129.1, 131.2 (q, JC-F =32.3 Hz, ArCF3), 134.0, 151.3, 166.7, 169.6,
55.5 (t, JC-F =20.6 Hz, CF2H), 59.8, 73.5, 95.7, 114.5 (t, JC-F
=246.3 Hz, CF2H), 126.4, 128.8, 131.3, 135.6, 152.9, 167.4, 172.8,
174.9 ppm. 19F NMR (470 MHz, CDCl3) δ: ꢀ 129.2 to ꢀ 127.7 (m, CF2H)
ppm. IR (KBr): v 2924, 1794, 1715, 1652, 1520, 1346, 1270, 1179,
1165, 1024, 855 cmꢀ 1. MS (ESI) m/z (%): 428 [M]+. HRMS (ESI) calcd.
173.6 ppm. 19F NMR (470 MHz, CDCl3) δ: -62.9 (s, ArCF3), -71.5 (s, CF3)
ppm. IR (KBr): v 2988, 1752, 1716, 1655, 1439, 1351, 1261, 1187,
1169, 1088, 989 cmꢀ 1. MS (EI) m/z (%): 479 [M]+. HRMS (ESI) calcd.
For C21H19F6NO5 [(M+H)]+: 480.1246; found: 480.1247.
5

S. Yang et al.
Journal of Fluorine Chemistry 243 (2021) 109723
For C20H20ClF2NO5 [(M+H)]+: 428.1077; found: 428.1074.
(s, 1 H), 6.15 (d, J =4.0 Hz, 1 H), 7.79 (d, J =9.0 Hz, 2 H), 8.24 (d, J
=9.0 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3) δ: 25.1, 25.8, 28.1, 28.3,
38.5, 52.6 (q, 2JC-F =26.0 Hz, CF3), 53.2, 53.4, 72.8, 98.1, 123.8, 124.4
4.2.15. Methyl 2-(tert-butyl)-6-(4-nitrophenyl)-1,3-dioxo-3a-
(pentafluoroethyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4o)
1
(q, JC-F =281.3 Hz, CF3), 126.1, 138.8, 148.4, 150.6, 166.4, 168.7,
172.4 ppm. 19F NMR (470 MHz, CDCl3) δ: -71.2 (s, CF3) ppm. IR (KBr): v
2942, 1742, 1715, 1654, 1529, 1437, 1350, 1211, 1190, 1083,
859 cmꢀ 1. MS (ESI) m/z (%): 483 [M+H]+. HRMS (ESI) calcd. For
Yellow solid; m.p.: 125.5-127.1 ◦C; 1H NMR (500 MHz, CDCl3) δ:
1.59 (s, 9 H), 3.63 (d, J =4.0 Hz, 1 H), 3.65 (s, 3 H), 5.53 (s, 1 H), 6.16 (d,
J =4.0 Hz, 1 H), 7.74–7.76 (d, J =9.0 Hz, 2 H), 8.22–8.24 (d, J =9.0 Hz,
C
22H21F3N2O7 [(M+H)]+: 483.1380; found: 483.1379.
2 H) ppm. 13C NMR (125 MHz, CDCl3) δ: 27.5, 38.3, 51.3 (t, JC-F
2
=20.2 Hz, CF2), 53.4, 59.7, 72.5, 98.9, 114.0 (tq, 1JC-F =262.4 Hz, 2JC-F
=37.1 Hz, CF2), 118.8 (qt, 1JC-F =286.6 Hz, 2JC-F =36.2 Hz, CF3), 123.8,
125.9, 138.9, 148.3, 149.6, 166.5, 169.4, 173.0 ppm. 19F NMR
(470 MHz, CDCl3) δ: -79.1 (s, CF3), -117.6 – -115.8 (m, CF2) ppm. IR
(KBr): v 2987, 1744, 1714, 1653, 1520, 1348, 1262, 1183, 1124, 1064,
948 cmꢀ 1. MS (EI) m/z (%): 506 [M]+. HRMS (ESI) calcd. For
4.2.20. Methyl 2,6-bis(4-nitrophenyl)-1,3-dioxo-3a-(trifluoromethyl)-
1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-carboxylate (4 t)
Yellow solid; m.p.: 193.8-195.1 ◦C; 1H NMR (500 MHz, CDCl3) δ:
3.70 (s, 3 H), 3.92 (d, J =4.0 Hz, 1 H), 5.65 (s, 1 H), 6.22 (d, J =4.0 Hz,
1 H), 7.64–7.67 (m, 2 H), 7.83–7.85 (m, 2 H), 8.27–8.29 (m, 2 H),
8.37–8.39 (m, 2 H) ppm. 13C NMR (125 MHz, CDCl3) δ: 38.9, 53.3 (q,
2JC-F =26.5 Hz, CF3), 54.0, 73.4, 97.1, 124.0, 124.2 (q, 1JC-F =281.7 Hz,
CF3), 124.7, 126.4, 127.4, 136.8, 138.4, 147.8, 148.7, 151.6, 167.1,
167.4, 170.9 ppm. 19F NMR (470 MHz, CDCl3) δ: -70.6 (s, CF3) ppm. IR
(KBr): v 2926, 1741, 1733, 1654, 1524, 1348, 1277, 1213, 1197, 1171,
1078, 856 cmꢀ 1. MS (ESI) m/z (%): 521 [M]+. HRMS (ESI) calcd. For
C
21H19F5N2O7 [(M+H)]+: 507.1191; found: 507.1171.
4.2.16. Methyl 2-(tert-butyl)-1,3-dioxo-3a-(pentafluoroethyl)-6-phenyl-
1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-carboxylate (4p)
Yellow solid; m.p.: 101.2-102.3 ◦C; 1H NMR (500 MHz, CDCl3) δ:
1.59 (s, 9 H), 3.59 (d, J =4.0 Hz, 1 H), 3.65 (s, 3 H), 5.50 (s, 1 H), 5.93 (d,
J =4.0 Hz, 1 H), 7.35–7.38 (m, 3 H), 7.57–7.59 (m, 2 H) ppm. 13C NMR
(125 MHz, CDCl3) δ: 27.6, 38.3, 51.6 (t, 2JC-F =20.6 Hz, CF2), 53.2, 59.5,
72.5, 94.8, 114.1 (tq, 1JC-F =262.4 Hz, 2JC-F =37.3 Hz, CF2), 118.8 (qt,
C
22H14F3N3O9 [(M+H)]+: 522.0761; found: 522.0783.
4.2.21. Methyl 2-(4-methoxyphenyl)-6-(4-nitrophenyl)-1,3-dioxo-3a-
(trifluoromethyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4 u)
2
1JC-F =287.0 Hz, JC-F =38.0 Hz, CF3), 125.4, 128.5, 129.6, 133.2,
151.8, 166.8, 169.9, 173.8 ppm. 19F NMR (470 MHz, CDCl3) δ: -79.2 (s,
CF3), -116.7 – -115.9 (m, CF2) ppm. IR (KBr): v 2985, 1747, 1715, 1655,
1459, 1344, 1266, 1212, 1185, 1121, 1072, 945 cmꢀ 1. MS (EI) m/z (%):
461 [M]+. HRMS (ESI) calcd. For C21H20F5N2O5 [(M+H)]+: 462.1341;
found: 462.1336.
Yellow solid; m.p.: 169.5-170.6 ◦C; 1H NMR (500 MHz, CDCl3) δ:
3.69 (s, 3 H), 3.84 (s, 3 H), 3.86 (d, J =4.0 Hz, 1 H), 5.61 (s, 1 H), 6.23 (d,
J =4.0 Hz, 1 H), 7.00–7.02 (m, 2 H), 7.27–7.31 (m, 2 H), 7.82–7.84 (m,
2 H), 8.25–8.27 (m, 2 H) ppm. 13C NMR (125 MHz, CDCl3) δ: 38.8, 53.1
(q, 2JC-F =26.2 Hz, CF3), 53.7, 55.6, 73.1, 97.8, 114.8, 123.9, 124.4 (q,
1JC-F =281.5 Hz, CF3), 126.2. 127.8, 138.7, 148.5, 151.1 160.2, 166.8,
168.2, 171.9 ppm. 19F NMR (470 MHz, CDCl3) δ: -70.8 (s, CF3) ppm. IR
(KBr): v 2961, 1733, 1727, 1652, 1517, 1443, 1350, 1275, 1250, 1189,
1161, 1025, 975 cmꢀ 1. MS (EI) m/z (%): 506 [M]+. HRMS (ESI) calcd.
For C23H17F3N2O8 [(M+H)]+: 507.0993; found: 507.0976.
4.2.17. Methyl 2-(tert-butyl)-6-(4-nitrophenyl)-1,3-dioxo-3a-
(heptafluoropropyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4q)
Yellow solid; m.p.: 125.6-127.1 ◦C; 1H NMR (500 MHz, CDCl3) δ:
1.59 (s, 9 H), 3.65–3.67 (m, 4 H), 5.57 (s, 1 H), 6.16 (d, J =3.5 Hz, 1 H),
7.74–7.77 (m, 2 H), 8.22–8.24 (m, 2 H) ppm. 13C NMR (125 MHz,
CDCl3) δ: 27.5, 38.5, 52.2 (t, 2JC-F =19.1 Hz, CF2), 53.4, 59.8, 72.4, 98.8,
110.1 (tq, 1JC-F =266.9 Hz, 2JC-F =38.1 Hz, CF2), 115.6 (m, CF2), 117.5
(qt, 1JC-F =287.5 Hz, 2JC-F =33.3 Hz, CF3), 123.8, 126.0, 138.9, 148.3,
149.7, 166.5, 169.4, 173.0 ppm. 19F NMR (470 MHz, CDCl3) δ: -80.6 –
-80.3 (m, CF3), -112.6 – -112.5 (m, CF2), -122.5 – -122.4 (m, CF2) ppm.
IR (KBr): v 2987, 1743, 1713, 1653, 1519, 1456, 1349, 1231, 1177,
1131, 1097, 901 cmꢀ 1. MS (EI) m/z (%): 556 [M]+. HRMS (ESI) calcd.
For C22H19F7N2O7 [(M+H)]+: 557.1186; found: 557.1156.
4.2.22. Methyl 2-(2,6-dimethylphenyl)-6-(4-nitrophenyl)-1,3-dioxo-3a-
(trifluoromethyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4v)
Yellow solid; m.p.: 213.0-214.5 ◦C; 1H NMR (500 MHz, CDCl3) δ:
2.13 (s, 3 H), 2.16 (s, 3 H), 3.77 (s, 3 H), 3.97 (d, J =4.0 Hz, 1 H), 5.41 (s,
1 H), 6.27 (d, J =4.0 Hz, 1 H), 7.13–7.15 (m, 2 H), 7.24–7.27 (m, 1 H),
7.80–7.82 (m, 2 H), 8.25–8.27 (m, 2 H) ppm. 13C NMR (125 MHz,
2
CDCl3) δ: 17.9, 18.1, 40.1, 53.5, 54.9 (q, JC-F =25.8 Hz, CF3), 72.9,
98.4, 124.0, 124.4 (q, 1JC-F =282.0 Hz, CF3), 126.0. 128.8. 129.3, 130.1,
135.8, 137.1, 138.5, 148.5, 151.2, 166.1, 167.4, 171.2 ppm. 19F NMR
(470 MHz, CDCl3) δ: -70.4 (s, CF3) ppm. IR (KBr): v 2956, 1770, 1727,
1653, 1514, 1440, 1341, 1248, 1220, 1206, 1116, 966 cmꢀ 1. MS (ESI)
m/z (%): 505 [M+H]+. HRMS (ESI) calcd. For C24H19F3N2O7 [(M+H)]+:
505.1223; found: 505.1222.
4.2.18. Methyl 2-(tert-butyl)-1,3-dioxo-3a-(heptafluoropropyl)-6-phenyl-
1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-carboxylate (4 r)
Yellow solid; m.p.: 71.5-72.7 ◦C; 1H NMR (500 MHz, CDCl3) δ: 1.59
(s, 9 H), 3.62 (d, J =4.0 Hz, 1 H), 3.66 (s, 3 H), 5.53 (s, 1 H), 5.93 (d, J
=4.0 Hz, 1 H), 7.35–7.38 (m, 3 H), 7.57–7.59 (m, 2 H), ppm. 13C NMR
(125 MHz, CDCl3) δ: 27.6, 38.5, 52.5 (t, 2JC-F =20.6 Hz, CF2), 53.2, 59.6,
72.5, 94.8, 110.2 (tq, 1JC-F =266.8 Hz, 2JC-F =37.9 Hz, CF2), 116.0 (m,
4.2.23. Methyl 2-(tert-butyl)-1,3-dioxo-3a-(trifluoromethyl)-
2,3,3a,4,6,10c-hexahydro-1H-indeno[1′,2′:5,6]pyrano[3,4-c]pyrrole-4-
carboxylate (4 w)
1
2
CF2), 117.6 (qt, JC-F =287.7 Hz, JC-F =33.9 Hz, CF3), 125.4, 128.5,
129.6, 133.2, 151.8, 166.8, 169.9, 173.8 ppm. 19F NMR (470 MHz,
CDCl3) δ: -80.6 – -80.4 (m, CF3), -112.7 – -112.6 (m, CF2), -122.5 –
-122.5 (m, CF2) ppm. IR (KBr): v 2979, 1746, 1710, 1654, 1451, 1334,
1227, 1191, 1136, 1050, 900 cmꢀ 1. MS (EI) m/z (%): 511 [M]+. HRMS
(ESI) calcd. For C22H20F7NO5 [(M+H)]+: 512.1308; found: 512.1304.
Yellow solid; m.p.: 155.4-157.2 ◦C; 1H NMR (500 MHz, CDCl3) δ:
1.63 (s, 9 H), 3.46 (d, J = 22 Hz, 1 H), 3.65 (s, 3 H), 3.76 (s, 1 H), 3.93 (d,
J = 22 Hz, 1 H), 5.50 (s, 1 H), 7.28–7.31 (m, 1 H), 7.32–7.35 (m, 1 H),
7.42–7.43 (m, 1 H), 7.47–7.49 (m, 1 H) ppm. 13C NMR (125 MHz,
2
CDCl3) δ: 27.8, 36.0, 39.8, 51.9 (q, JC-F =26.0 Hz, CF3), 53.4, 59.7,
73.4, 73.5, 108.6, 118.2, 124.3, 124.5 (q, 1JC-F =281.2 Hz, CF3), 126.4,
126.6, 137.0, 141.9, 151.3, 166.9, 169.9, 173.5 ppm. 19F NMR
(470 MHz, CDCl3) δ: -71.4 (s, CF3) ppm. IR (KBr): v 2964, 1741, 1709,
1654, 1493, 1364, 1273, 1189, 1124, 1065, 992 cmꢀ 1. MS (ESI) m/z
(%): 424 [M]+. HRMS (ESI) calcd. For C21H20F3NO5 [(M+H)]+:
424.1373; found: 424.1368.
4.2.19. Methyl 2-cyclohexyl-6-(4-nitrophenyl)-1,3-dioxo-3a-
(trifluoromethyl)-1,2,3,3a,4,7a-hexahydropyrano[3,4-c]pyrrole-4-
carboxylate (4 s)
Yellow solid; m.p.: 190.3-191.5 ◦C; 1H NMR (500 MHz, CDCl3) δ:
1.23–1.38 (m, 3 H), 1.66–1.73 (m, 3 H), 1.84–1.87 (m, 2 H), 2.04–2.15
(m, 2 H), 3.60 (d, J =4.0 Hz, 1 H), 3.65 (s, 3 H), 3.98–4.05 (m, 1 H), 5.49
6

S. Yang et al.
Journal of Fluorine Chemistry 243 (2021) 109723
[4] (a) R.J. Madhushaw, C.L. Li, K.H. Shen, C.C. Hu, R.S. Liu, Tungsten-promoted [3+
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ylate (4x)
Yellow solid; m.p.: 128.3-130.1◦C; 1H NMR (500 MHz, CDCl3) δ:
1.61 (s, 9 H), 2.47–2.53 (m, 1 H), 2.79–2.94 (m, 2 H), 3.06–3.13 (m,
1 H), 3.45 (s, 1 H), 3.66 (s, 3 H), 5.35 (s, 1 H), 7.13–7.15 (m, 1 H),
7.21–7.26 (m, 2 H), 7.51–7.52 (m, 1 H) ppm. 13C NMR (125 MHz,
2
CDCl3) δ: 24.8, 27.5, 27.7, 40.6, 52.2 (q, JC-F =25.9 Hz, CF3), 53.1,
59.5, 71.9, 104.9, 121.9, 124.4 (q, 1JC-F =280.1 Hz, CF3), 126.5, 127.3,
128.4, 129.5, 136.1, 145.6, 167.1, 169.6, 173.5 ppm. 19F NMR
(470 MHz, CDCl3) δ: -71.4 (s, CF3) ppm. IR (KBr): v 2981, 1748, 1712,
1669, 1458, 1335, 1281, 1237, 1192, 1157, 1054, 981 cmꢀ 1. MS (EI) m/
z (%): 437 [M]+. HRMS (ESI) calcd. For C22H22F3NO5 [(M+H)]+:
438.1529; found: 438.1524.
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Declaration of Competing Interest
The authors report no declarations of interest.
Acknowledgments
(b) S. Sadjadi, M.M. Heravi, N. Nazari, Isocyanide-based multicomponent
reactions in the synthesis of heterocycles, RSC Adv. 6 (2016) 53203–53272,
https://doi.org/10.1039/C6RA02143C;
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(c) A. Varadi, T.C. Palmer, R.N. Dardashti, S. Majumdar, Isocyanide-based
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The authors are grateful to the National Natural Science Foundation
of China (Grant No. 21672138) for their financial support.
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Appendix A. Supplementary data
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.jfluchem.2021.10
9723.
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8