ZnI2-Catalyzed Aminotrifluoromethylation Cyclization of Alkenes Using PhICF3Cl

Article abstract of DOI:10.1021/acs.joc.0c02637

We report here an alternatively catalytic aminotrifluoromethylation of alkenes using PhICF3Cl as a bifunctional reagent along with ZnI2 as a dual catalyst. A combined catalytic strategy was established for the intramolecular aminotrifluoromethylation of 4-pentenamines. As a result, a set of 2-trifluoroethyl-pyrrolidines was obtained in a high selectivity. Mechanism studies revealed that the reaction included an iodine anion-catalyzed radical chlorotrifluoromethylation of alkenes and a sequential Lewis acid-promoted aminocyclization of the resulting chlorotrifluoromethylated intermediates.

Full text of DOI:10.1021/acs.joc.0c02637

pubs.acs.org/joc
Note
ZnI2‑Catalyzed Aminotrifluoromethylation Cyclization of Alkenes
Using PhICF3Cl
Wanqiao Huang, Cong Xu,* Jianxin Yu, and Mang Wang*
Cite This: J. Org. Chem. 2021, 86, 1987−1999
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: We report here an alternatively catalytic aminotrifluorome-
thylation of alkenes using PhICF3Cl as a bifunctional reagent along with ZnI2
as a dual catalyst. A combined catalytic strategy was established for the
intramolecular aminotrifluoromethylation of 4-pentenamines. As a result, a
set of 2-trifluoroethyl-pyrrolidines was obtained in a high selectivity.
Mechanism studies revealed that the reaction included an iodine anion-catalyzed radical chlorotrifluoromethylation of alkenes
and a sequential Lewis acid-promoted aminocyclization of the resulting chlorotrifluoromethylated intermediates.
SET oxidation of an alkyl radical at first, leading to the
rifluoromethylative bifunctionalizations of alkenes are
Tcommonly used strategies to introduce two useful carbocation that is followed by a nucleophilic amination
(Scheme 1A, c).4d,5 We report here an alternatively catalytic
aminotrifluoromethylation of alkenes (Scheme 1B), which
involves a cascade generation and the amination of the
chlorotrifluoromethylated intermediate. By using ZnI2 as the
catalyst and λ3-chloro(phenyl)trifluoromethyliodane
(PhICF3Cl) as the bifunctional reagent, a combined catalytic
strategy was performed for the intramolecular aminotrifluor-
omethylation of 4-pentenamines 1. As a result, a set of 2-
trifluoroethyl-pyrrolidine derivatives 2 was efficiently obtained.
During our ongoing explorations in the field of trifluor-
omethylation,7−9 PhICF3Cl was prepared by us for the first
time8 and successfully used as a bifunctional reagent in the
chlorotrifluoromethylation of alkenes.9a On the basis of
previous work, we envisioned that such a smooth chlorotri-
fluoromethylation might be extended for an alternative
aminotrifluoromethyaltion via further amine substitution.
With these thoughts in mind, we started to use N-tosyl-2,2-
dimethyl-4-phenyl-4-penten-1-amine (1a) as the model
substrate to test its aminotrifluoromethyaltion cyclization.
Regarding the unique CF3 transfer ability of PhICF3Cl, we
initially carried out the reaction at 60 °C without any
activator.9 The desired transformation indeed worked, and a
mixture resulted after reacting for 12 h in which the
aminotrifluoromethyaltion cyclization product 2a, the chloro-
trifluoromethylated product 3a, and the vinyl-CF3 product 4a
could be detected (Table S1). By comparison, DCM proved to
be a better solvent for the formation of 2a (Table 1, entry 1).
functional groups to organic molecules simultaneously,1 and
aminotrifluoromethylation provides an effective route to
important β-trifluoromethylated amines.2−6 For all the
trifluoromethyl radical addition-triggered aminotrifluorome-
thylations,3−5 the resulting radical adduct would be aminated
in three pathways. Besides direct C−N coupling (Scheme 1A,
a),3 the oxidative addition of a radical intermediate to Cu(I),
followed by reductive elimination, provides a transition-metal-
catalyzed method for achieving aminotrifluoromethylated
products (Scheme 1A, b).4 Another pathway includes the
Scheme 1. Aminotrifluoromethylation of Alkenes Initiated
by CF3 Radical Addition
Received: November 5, 2020
Published: December 30, 2020
https://dx.doi.org/10.1021/acs.joc.0c02637
© 2020 American Chemical Society
J. Org. Chem. 2021, 86, 1987−1999
1987

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
a
reaction temperature was optimized. When the reaction was
carried out at 70 °C, it gave 2a in a slightly higher yield (entry
6). Interestingly, there was no significant decrease in the yield
of 2a even at lower temperature (entries 7 and 8), for example,
the reaction still gave 2a in a 81% yield at room temperature.
According to our previous work,9 PhICF3Cl could efficiently
transfer CF3 to the target alkene substrates at 60 °C in the
absence of the activator. Lower temperatures led to a sluggish
transformation. By comparison, the reaction of 1a with
PhICF3Cl smoothly occurred at 25 °C, indicating that ZnI2
may play two roles as both the activator for PhICF3Cl and the
Lewis acid catalyst for nucleophilic amination. Further control
experiments with no catalyst or either ZnCl2 or ZnBr2 in DCM
at 25 °C supported that the iodine ion was indeed key to
achieve an efficient transformation from 1a to 2a (entry 8 vs
entries 9−11). It should be noted that cyclic product 5a,
resulting from the Lewis acid-mediated electrophilic cycliza-
tion11 of 1a, was formed in a considerable yield in some
cases.10d This background reaction could be selectively avoided
when using ZnI2 as the catalyst (entry 8). It is likely due to the
efficient generation of a reactive CF3 species in the presence of
the iodine ion, which benefits the desired trifluoromethylative
addition to the olefinic double bond. Corresponding N-benzyl
and tert-butoxycarbonyl 4-pentenamines were also tested
toward the optimized reaction conditions, but their amino-
trifluoromethyaltion cyclizations proved to be inefficient
(Table S3).
Table 1. Optimization of Reaction Conditions
b
entry
cat.
T (°C)
2a/3a/4a/5a
1
2
3
4
5
6
7
8
60
60
60
60
60
70
40
25
25
25
25
35:44:5:0
56:0:5:35
59:0:5:23
69:0:5:20
88:0:7:0
90:0:7:0
87:0:7:0
81:0:7:0
Zn(OTf)2
ZnCl2
ZnBr2
ZnI2
ZnI2
ZnI2
ZnI2
9
10
11
trace:trace:0:0
54:0:trace:20
57:0:5:21
ZnCl2
ZnBr2
a
Reaction conditions are as follows: 1a (0.1 mmol), PhICF3Cl (0.2
b
mmol), catalyst (10 mol %), DCM (1.0 mL), N2, and 12 h. 19F NMR
yield using benzotrifluoride as an internal standard.
With the optimal conditions in hand (Table 1, entry 7), we
next investigated the generality of this reaction. As described in
Table 2, a series of 4-pentenamines with various aryl
substituents was first surveyed (2b−p). Generally, a back-
ground reaction could be observed, especially for those
electron-rich substrates 1. For example, 1 bearing alkyl and
alkoxyl groups (2b−f and 2n) usually gave moderate yields
because of the formations of the directly electrophilic
cyclization product 5. In the cases of 1 with electron-
withdrawing aromatic substituents, cyclic aminotrifluorome-
thylation products 2g−k were isolated in relatively higher
To our delight, the yield of 2a was 56% (entry 2) when 10 mol
% Zn(OTf)2 was used as a Lewis acid catalyst to promote the
amination10. Zinc halides were also tested for the trans-
formation, among which ZnI2 presented a super catalysis that
led to 2a in a 88% yield (entries 3−5). The reactions with
other Lewis acid catalysts, including FeCl3, AlCl3, and
Sc(OTf)3 in DCM under 60 °C, worked but were less efficient
than those with zinc salts, while SnCl4 made the reaction
system sluggish (Table S2). Further solvent screening showed
that DCM was the most suitable solvent for the amino-
trifluoromethyaltion cyclization of 1a (Table S1). Next, the
a b
,
Table 2. Substrate Scope of Aminotrifluoromethylation of Alkenes
a
Reaction conditions (the standard reaction conditions) are as follows: 1 (0.1 mmol), PhICF3Cl (0.2 mmol), ZnI2 (10 mol %), anhydrous DCM
b
c
(1.0 mL), 40 °C, N2, and 12 h. Isolated yields based on 1. Under 70 °C.
1988
https://dx.doi.org/10.1021/acs.joc.0c02637
J. Org. Chem. 2021, 86, 1987−1999

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
yields. Moreover, biphenyl and naphthalene were also tolerated
under this condition and could provide the expected products
2l and 2m in 65 and 68% yields, respectively. The steric effect
seemed to be significant for the cyclization and 1b with o-R1 on
the phenyl ring, affording 2b in only a 40% yield. In addition,
the reactions of 4-pentenamines with a cyclic R′ were also
compatible with the reaction, leading to 2o and 2p in good
yields, while the nonbranched substrate 1q gave 2q in a
moderate yield.
Then, a set of sulfonyl groups was arranged as the N-
protecting group toward the aminotrifluoromethylation cycli-
zations of 1. On one hand, the reactions of various N-aryl
sulfonyl-containing substrates could deliver 2r−ab in good to
high yields. On the other hand, N-aliphatic sulfonyl-protected
4-pentenamines, including alkylsulfonyl, benzylsulfonyl, and
styrylsulfonyl substrates, also showed a nice compatibility,
furnishing 2ac−af in 66−85% yields. Furthermore, unactivated
alkenes were tested and proved to be suitable for this reaction.
Cyclic products 2ag and 2ah could be obtained smoothly with
a slightly increased temperature under the optimized
condition.
3 were not stable enough to be isolated. Then, we stirred a
solution of 3a in DCM in the presence of 10 mol % ZnI2 at 40
°C. After reacting for 12 h, 2a was obtained in a 90% yield
(Scheme 2C). This result was in line with the observation of
the conversion of 1 to 2 under TLC monitoring. In addition,
the vinyl-CF3 product 4a was also synthesized separately and
treated by 10 mol % ZnI2 in DCM at 40 °C (Scheme 2C). No
2a was detected, excluding the formation of 2a via the Lewis
acid-promoted electrophilic cyclization of 4a.
Different from Togni’s work in which zinc salt acted as the
activator for Togni’s reagent in the O-trifluoromethyaltion of
alcohols,12 zinc salt was used as the Lewis acid catalyst to
promote the aminocyclization in the present work. The
plausible catalytic mechanism of the catalytic process is
proposed as described in Scheme 3. At low temperatures, it
Scheme 3. A Plausible Catalytic Mechanism
As presented above, a novel catalytic intramolecular
aminotrifluoromethylation of 4-pentenamines 1 has been
developed in which ZnI2 showed efficient catalysis. Next, a
set of control experiments were designed to clarify the reaction
mechanism. At first, a radical trapping experiment with the
addition of 2,2,6,6-tetramethylpiperidine-1-oxide (TEMPO) to
the model reaction (Scheme S1) suggested that a radical
process was involved. Radical clock experiments were
conducted next to verify this point of view. Both (1-
cyclopropylvinyl)benzene and N,N-diallyl-4-methylbenzenesul-
fonamide were prepared toward the standard reaction
conditions (Scheme S2 and Scheme 2A); the ring-opening
Scheme 2. Control Experiments
is necessary to reduce PhICF3Cl using an iodine anion to
release a CF3 radical for addition to alkenes 1, leading to
intermediate I. Then, a SET oxidation of radical I by iodine
rapidly occurs and results in carbocation II. At this time, two
competitive nucleophilic trappings of II exist, including
intramolecular amination and intermolecular chlorination,
delivering the trifluoromethylative cyclization products 2 and
chlorotrifluoromethylation intermediates 3, respectively. The
experimental results that the reaction gave 2 in lower yields
under the catalysis of KI (Scheme 2B) indicates that zinc salt is
indeed required for the complete conversion of 1 to 2 in our
work. Thus, cation II is regenerated from 3 in the presence of
Zn2+ for the final intramolecular amine substitution. Other
Lewis acids, such as Zn(OTf)2 or FeCl3, have also been proven
to be efficient for amine substitution (Scheme 2B). Attempts at
intermolecularly trapping intermediate II using MeOH or H2O
failed. Thus, other mechanisms cannot be ruled out at this
time.
In summary, we developed a catalytic aminotrifluoromethy-
lation of alkenes. By the use of PhICF3Cl as a CF3 source and
ZnI2 as a dual catalyst, the intramolecular aminotrifluorome-
thylation of 4-pentenamines affords 2-trifluoroethyl-pyrroli-
dines in good yields and selectivities. The reaction has been
proven to undergo a cascade I−-catalyzed chlorotrifluorome-
thylation of alkenes and Zn2+-catalyzed amine substitution of
the resulting chlorotrifluoromethylated intermediates. Inves-
tigating the applications of this synthetic method in the
intermolecular trifluoromethyaltive bifunctionalizations of
alkenes is in progress in our group.
product and cyclization product 6 were gained, respectively,
which could be strong proof of a radical mechanism. To gain
insight into the catalytic roles of ZnI2, I−-catalyzed reactions of
1a with or without a Lewis acid catalyst were tested under the
identified conditions (Scheme 2B). It was found that 2a was
obtained in only a 36% yield in the absence of a Lewis acid but
in 80% and 84% yields with Zn(OTf)2 and FeCl3, respectively.
These experimental results indicated that the reaction required
a reductive activator for PhICF3Cl at low temperatures and a
Lewis acid catalyst for the final amination cyclization.
Furthermore, we tried to isolate 3a under controlled reaction
conditions with the aim of understanding the transformation of
3 to 2; however, most chlorotrifluoromethylated intermediates
1989
https://dx.doi.org/10.1021/acs.joc.0c02637
J. Org. Chem. 2021, 86, 1987−1999

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
MHz, CDCl3): δ 146.2, 143.3, 143.1, 138.2, 136.9, 129.6, 128.4,
128.2, 127.1, 126.9, 123.5, 117.4, 52.8, 44.9, 35.2, 25.7, 21.52, 21.48.
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H27NNaO2S
380.1655; found 380.1659.
EXPERIMENTAL SECTION
■
General Information. All reactions were carried out under a
nitrogen atmosphere in a glovebox. Reagents were purchased from
commercial sources and used without further purification unless
otherwise stated. ZnI2 (Adamas-Beta) was purchased from Tansoole.
Anhydrous DCM (dichloromethane) was distilled over CaH2 before
use. The products were purified by column chromatography over
silica gel (particle size 300−400 mesh ASTM, purchased from
Taizhou, China). Visualization on TLC was achieved using UV light
(254 nm). 1H NMR and 13C NMR spectra were recorded at 25 °C on
Bruker 600 or 500 MHz and 150 or 125 MHz spectrometers,
respectively, in CDCl3 using TMS as an internal standard. 19F NMR
spectra were recorded at 25 °C on a Bruker 470 MHz or Varian 470
MHz spectrometer in CDCl3 using (trifluoromethyl)benzene (δ
−63.2 ppm) as an external standard. 1H, 13C, and 19F NMR data were
recorded as follows: chemical shift (δ, ppm), multiplicity (s = singlet,
d = doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of
doublets, dq = doublet of quartets, td = triplet of doublets), coupling
constant (Hz), integration. High-resolution mass spectra (HRMS)
were obtained using a Bruker micro TOF II focus spectrometer (ESI-
TOF).
General Procedure for Substrates 1. All the substrates 1 were
obtained through a protection of the amino group of 4-arylpent-4-en-
1-amines, which were reducted from the cyano group of different
types of 4-arylpent-4-enenitriles.4a To a suspension of 4-arylpent-4-en-
1-amine (1.0 mmol, 1.0 equiv) in DCM (2.0 mL) at 0 °C was added
sulfonyl chloride (1.1 mmol, 1.1 equiv) in portions. After being stirred
at 0 °C for 5 min, pyridine (2.0 mmol, 2.0 equiv) was added slowly by
a syringe. Then, the mixture was warmed to room temperature for an
additional 12 h. After complete conversion (monitored by TLC), the
reaction was quenched with satured aq NaHCO3, and the reaction
mixture was extracted with DCM (3 × 10 mL). The combined
organic layers were dried over MgSO4 and concentrated in vacuo. The
residue was purified by silica gel column chromatography (the eluent
was petroleum ether/EtOAc 15:1−3:1) to give the corresponding
pure substrates 1a.
N-(2,2-Dimethyl-4-(p-tolyl)pent-4-en-1-yl)-4-methylbenzenesul-
fonamide (1d). Synthesized using 2,2-dimethyl-4-(p-tolyl)pent-4-en-
1-amine and p-toluenesulfonyl chloride. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 5:1) as a
white solid (97% yield, 347 mg). mp 70−71 °C. 1H NMR (600 MHz,
CDCl3): δ 7.51 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 7.8 Hz, 2H), 7.19 (d,
J = 8.4 Hz, 2H), 7.10 (d, J = 7.8 Hz, 2H), 5.18 (d, J = 1.8 Hz, 1H),
4.97 (d, J = 1.8 Hz, 1H), 4.32 (t, J = 7.2 Hz, 1H), 2.49 (d, J = 7.2 Hz,
2H), 2.43 (s, 2H), 2.41 (s, 3H), 2.35 (s, 3H), 0.79 (s, 6H). 13C{1H}
NMR (150 MHz, CDCl3): δ 145.9, 143.1, 140.4, 137.1, 137.0, 129.5,
129.2, 126.9, 126.3, 116.9, 52.8, 44.9, 35.2, 25.7, 21.5, 21.1. HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C21H27NNaO2S 380.1655;
found 380.1662.
N-(4-(4-(tert-Butyl)phenyl)-2,2-dimethylpent-4-en-1-yl)-4-meth-
ylbenzenesulfonamide (1e). Synthesized using 4-(4-(tert-butyl)-
phenyl)-2,2-dimethylpent-4-en-1-amine and p-toluenesulfonyl chlor-
ide. Purified by silica gel column chromatography (the eluent was
petroleum ether/EtOAc 4:1) as a white solid (98% yield, 392 mg).
mp 106−107 °C. 1H NMR (600 MHz, CDCl3): δ 7.65 (d, J = 8.0 Hz,
2H), 7.28 (d, J = 8.2 Hz, 2H), 7.25−7.21 (m, 4H), 5.23 (t, J = 6.8 Hz,
1H), 5.19 (d, J = 1.8 Hz, 1H), 4.97 (d, J = 1.8 Hz, 1H), 2.56 (d, J =
7.0 Hz, 2H), 2.46 (s, 2H), 2.35 (s, 3H), 1.29 (s, 9H), 0.77 (s, 6H).
13C{1H} NMR (150 MHz, CDCl3): δ 150.2, 145.8, 143.0, 140.2,
137.3, 129.7, 127.1, 126.1, 125.3, 116.8, 53.3, 44.6, 35.2, 34.5, 31.4,
25.6, 21.6. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C24H33NNaO2S 422.2124; found 422.2134.
N-(4-(4-Methoxyphenyl)-2,2-dimethylpent-4-en-1-yl)-4-methyl-
benzenesulfonamide (1f). Synthesized using 4-(4-methoxyphenyl)-
2,2-dimethylpent-4-en-1-amine and p-toluenesulfonyl chloride. Puri-
fied by silica gel column chromatography (the eluent was petroleum
ether/EtOAc 3:1) as a white solid (93% yield, 348 mg). mp 72−73
°C. 1H NMR (600 MHz, CDCl3): δ 7.54 (d, J = 8.3 Hz, 2H), 7.25−
7.22 (m, 4H), 6.81 (d, J = 8.7 Hz, 2H), 5.14 (d, J = 1.8 Hz, 1H), 4.93
(d, J = 1.8 Hz, 1H), 4.47 (t, J = 7.1 Hz, 1H), 3.81 (s, 3H), 2.50 (d, J =
7.1 Hz, 2H), 2.41 (s, 5H), 0.79 (s, 6H). 13C{1H} NMR (150 MHz,
CDCl3): δ 159.0, 145.4, 143.1, 136.9, 135.6, 129.6, 127.5, 126.9,
116.2, 113.8, 55.3, 53.0, 45.0, 35.2, 25.7, 21.5. HRMS (ESI-TOF) m/
z: [M + Na]+ Calcd for C21H27NNaO3S 396.1604; found 396.1589.
N-(4-(3-Methoxyphenyl)-2,2-dimethylpent-4-en-1-yl)-4-methyl-
benzenesulfonamide (1g). Synthesized using 4-(3-methoxyphenyl)-
2,2-dimethylpent-4-en-1-amine and p-toluenesulfonyl chloride. Puri-
fied by silica gel column chromatography (the eluent was petroleum
ether/EtOAc 4:1) as a white solid (95% yield, 355 mg). mp 73−74
°C. 1H NMR (500 MHz, CDCl3): δ 7.50 (d, J = 8.3 Hz, 2H), 7.25−
7.21 (m, 3H), 6.90 (d, J = 7.8 Hz, 1H), 6.83−6.81 (m, 2H), 5.22 (d, J
= 1.7 Hz, 1H), 5.01 (d, J = 1.8 Hz, 1H), 4.19 (t, J = 7.2 Hz, 1H), 3.80
(s, 3H), 2.49 (d, J = 7.3 Hz, 2H), 2.43 (s, 2H), 2.42 (s, 3H), 0.81 (s,
6H). 13C{1H} NMR (125 MHz, CDCl3): δ 159.7, 145.9, 144.9, 143.1,
136.8, 129.6, 126.9, 118.7, 117.7, 112.9, 112.2, 55.2, 52.7, 44.9, 35.2,
25.7, 21.5. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C21H27NNaO3S 396.1604; found 396.1595.
N-(2,2-Dimethyl-4-phenylpent-4-en-1-yl)-4-methylbenzenesulfo-
namide (1a). Synthesized using 2,2-dimethyl-4-phenylpent-4-en-1-
amine and p-toluenesulfonyl chloride. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 5:1) as a
white solid (98% yield, 337 mg). mp 81−82 °C. 1H NMR (600 MHz,
CDCl3): δ 7.53 (d, J = 8.2 Hz, 2H), 7.29 (d, J = 4.6 Hz, 4H), 7.27−
7.24 (m, 3H), 5.21 (d, J = 1.7 Hz, 1H), 5.02 (d, J = 1.9 Hz, 1H), 4.37
(t, J = 7.2 Hz, 1H), 2.50 (d, J = 7.2 Hz, 2H), 2.45 (s, 2H), 2.41 (s,
3H), 0.78 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ 146.1,
143.3, 143.1, 136.9, 129.6, 128.5, 127.4, 127.0, 126.4, 117.6, 52.9,
44.9, 35.2, 25.6, 21.5. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C20H25NNaO2S 366.1498; found 366.1491.
N-(2,2-Dimethyl-4-(o-tolyl)pent-4-en-1-yl)-4-methylbenzenesul-
fonamide (1b). Synthesized using 2,2-dimethyl-4-(o-tolyl)pent-4-en-
1-amine and p-toluenesulfonyl chloride. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 4:1) as a
1
white solid (96% yield, 343 mg). mp 99−100 °C. H NMR (500
MHz, CDCl3): δ 7.58 (d, J = 8.3 Hz, 2H), 7.23 (d, J = 8.1 Hz, 2H),
7.11−7.10 (m, 2H), 7.06−7.05 (m, 2H), 5.18 (d, J = 2.1 Hz, 1H),
4.96 (d, J = 2.2 Hz, 1H), 4.77 (t, J = 7.1 Hz, 1H), 2.50 (d, J = 7.1 Hz,
2H), 2.38 (s, 3H), 2.37 (s, 2H), 2.26 (s, 3H), 0.79 (s, 6H). 13C{1H}
NMR (125 MHz, CDCl3): δ 146.1, 143.4, 143.1, 137.0, 134.5, 130.8,
129.6, 128.3, 127.1, 127.0, 125.7, 119.5, 53.1, 47.3, 35.4, 25.5, 21.6,
20.4. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H27NNaO2S
380.1655; found 380.1659.
N-(4-(4-Fluorophenyl)-2,2-dimethylpent-4-en-1-yl)-4-methyl-
benzenesulfonamide (1h). Synthesized using 4-(4-fluorophenyl)-2,2-
dimethylpent-4-en-1-amine and p-toluenesulfonyl chloride. Purified
by silica gel column chromatography (the eluent was petroleum
ether/EtOAc 6:1) as a white solid (98% yield, 355 mg). mp 77−78
°C. 1H NMR (600 MHz, CDCl3): δ 7.58 (d, J = 8.2 Hz, 2H), 7.27−
7.24 (m, 4H), 6.95 (t, J = 8.6 Hz, 2H), 5.17 (d, J = 1.6 Hz, 1H), 5.01
(d, J = 1.7 Hz, 1H), 4.46 (t, J = 7.3 Hz, 1H), 2.51 (d, J = 7.1 Hz, 2H),
2.42 (s, 5H), 0.77 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ
N-(2,2-Dimethyl-4-(m-tolyl)pent-4-en-1-yl)-4-methylbenzenesul-
fonamide (1c). Synthesized using 2,2-dimethyl-4-(m-tolyl)pent-4-en-
1-amine and p-toluenesulfonyl chloride. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 5:1) as a
white solid (95% yield, 340 mg). mp 71−72 °C. 1H NMR (500 MHz,
CDCl3): δ 7.50 (d, J = 8.3 Hz, 2H), 7.23 (d, J = 7.9 Hz, 2H), 7.20−
7.17 (m, 1H), 7.10−7.06 (m, 3H), 5.19 (d, J = 1.9 Hz, 1H), 4.99 (d, J
= 1.8 Hz, 1H), 4.36 (t, J = 7.2 Hz, 1H), 2.47 (d, J = 7.2 Hz, 2H), 2.43
(s, 2H), 2.41 (s, 3H), 2.32 (s, 3H), 0.80 (s, 6H). 13C{1H} NMR (125
4
162.2 (d,1JC−F = 244.8 Hz), 145.0, 143.3, 139.3 (d, JC−F = 3.2 Hz),
136.8, 129.6, 127.9 (d, 3JC−F = 8.0 Hz), 126.9, 117.6, 115.2 (d, 2JC−F
=
21.3 Hz), 53.2, 45.1, 35.2, 25.5, 21.5. 19F NMR (470 MHz, CDCl3): δ
−115.21 to −115.28) (m, 1F). HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C20H24FNNaO2S 384.1404; found 384.1401.
1990
https://dx.doi.org/10.1021/acs.joc.0c02637
J. Org. Chem. 2021, 86, 1987−1999

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
N-(4-(4-Chlorophenyl)-2,2-dimethylpent-4-en-1-yl)-4-methyl-
benzenesulfonamide (1i). Synthesized using 4-(4-chlorophenyl)-2,2-
dimethylpent-4-en-1-amine and p-toluenesulfonyl chloride. Purified
by silica gel column chromatography (the eluent was petroleum
ether/EtOAc 6:1) as a white solid (98% yield, 371 mg). mp 75−76
°C. 1H NMR (600 MHz, CDCl3): δ 7.56 (d, J = 8.3 Hz, 2H), 7.28 (d,
J = 8.0 Hz, 2H), 7.25−7.21 (m, 4H), 5.21 (d, J = 1.6 Hz, 1H), 5.04
(d, J = 1.5 Hz, 1H), 4.30 (t, J = 7.2 Hz, 1H), 2.51 (d, J = 7.2 Hz, 2H),
2.43 (s, 5H), 0.78 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ
144.9, 143.3, 141.7, 136.8, 133.2, 129.6, 128.6, 127.7, 126.9, 118.1,
53.1, 44.9, 35.2, 25.5, 21.5. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C20H24ClNNaO2S 400.1108; found 400.1099.
N-(4-(Benzo[d][1,3]dioxol-5-yl)-2,2-dimethylpent-4-en-1-yl)-4-
methylbenzenesulfonamide (1n). Synthesized using 4-(benzo[d]-
[1,3]dioxol-5-yl)-2,2-dimethylpent-4-en-1-amine and p-toluenesulfon-
yl chloride. Purified by silica gel column chromatography (the eluent
was petroleum ether/EtOAc 3:1) as a white solid (93% yield, 361
mg). mp 88−89 °C. 1H NMR (600 MHz, CDCl3): δ 7.59 (d, J = 8.3
Hz, 2H), 7.27 (d, J = 7.9 Hz, 2H), 6.77 (d, J = 6.4 Hz, 2H), 6.72 (d, J
= 8.5 Hz, 1H), 5.95 (s, 2H), 5.13 (d, J = 1.7 Hz, 1H), 4.93 (d, J = 1.7
Hz, 1H), 4.43 (t, J = 7.2 Hz, 1H), 2.53 (d, J = 7.1 Hz, 2H), 2.42 (s,
3H), 2.38 (s, 2H), 0.79 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3):
δ 147.7, 146.9, 145.5, 143.2, 137.5, 136.9, 129.6, 126.9, 119.7, 116.7,
108.2, 107.1, 101.1, 53.0, 45.1, 35.2, 25.6, 21.5. HRMS (ESI-TOF)
m/z: [M + Na]+ Calcd for C21H25NNaO4S 410.1396; found
410.1392.
4-Methyl-N-((1-(2-phenylallyl)cyclopentyl)methyl)-
benzenesulfonamide (1o). Synthesized using (1-(2-phenylallyl)-
cyclopentyl)methanamine and p-toluenesulfonyl chloride. Purified
by silica gel column chromatography (the eluent was petroleum
ether/EtOAc 5:1) as a white solid (97% yield, 359 mg). mp 80−81
°C. 1H NMR (600 MHz, CDCl3): δ 7.47 (d, J = 8.2 Hz, 2H), 7.31−
7.27 (m, 5H), 7.24 (d, J = 8.0 Hz, 2H), 5.15 (d, J = 1.7 Hz, 1H), 5.05
(d, J = 1.6 Hz, 1H), 4.19 (t, J = 7.1 Hz, 1H), 2.55 (s, 2H), 2.52 (d, J =
7.1 Hz, 2H), 2.42 (s, 3H), 1.57−1.46 (m, 4H), 1.36−1.30 (m, 4H).
13C{1H} NMR (150 MHz, CDCl3): δ 147.0, 143.2, 143.1, 136.8,
129.5, 128.6, 127.5, 126.9, 126.4, 117.3, 49.3, 47.1, 42.8, 35.5, 24.0,
21.5. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H27NNaO2S
392.1655; found 392.1645.
4-Methyl-N-((1-(2-phenylallyl)cyclohexyl)methyl)-
benzenesulfonamide (1p). Synthesized using (1-(2-phenylallyl)-
cyclohexyl)methanamine and p-toluenesulfonyl chloride. Purified by
silica gel column chromatography (the eluent was petroleum ether/
EtOAc 5:1) as a white solid (97% yield, 373 mg). mp 104−105 °C.
1H NMR (600 MHz, CDCl3): δ 7.39 (d, J = 8.2 Hz, 2H), 7.32−7.27
(m, 5H), 7.22 (d, J = 8.0 Hz, 2H), 5.17 (d, J = 1.7 Hz, 1H), 5.03 (d, J
= 1.7 Hz, 1H), 3.98 (t, J = 7.3 Hz, 1H), 2.51 (d, J = 7.3 Hz, 2H), 2.48
(s, 2H), 2.41 (s, 3H), 1.44−1.37 (m, 3H), 1.35−1.31 (m, 3H), 1.30−
1.27 (m, 2H), 1.25 (m, 2H). 13C{1H} NMR (150 MHz, CDCl3): δ
145.9, 143.6, 143.0, 136.8, 129.5, 128.8, 127.6, 126.9, 126.3, 117.8,
37.5, 33.8, 26.0, 21.5, 21.4. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C23H29NNaO2S 406.1811; found 406.1828.
4-methyl-N-(4-phenylpent-4-en-1-yl)benzenesulfonamide (1q).
Synthesized using 4-phenylpent-4-en-1-amine and p-toluenesulfonyl
chloride. Purified by silica gel column chromatography (the eluent
was petroleum ether/EtOAc 5:1) as a white solid (93% yield, 294
mg). mp 49−50 °C. 1H NMR (500 MHz, CDCl3): δ 7.71 (d, J = 8.0
Hz, 2H), 7.31−7.26 (m, 7H), 5.25 (d, J = 1.5 Hz, 1H), 5.00 (d, J =
1.5 Hz, 1H), 4.49 (t, J = 7.0 Hz, 1H), 2.95 (q, J = 6.8 Hz, 2H), 2.50
(t, J = 7.5 Hz, 2H), 2.42 (s, 3H), 1.59 (p, J = 7.2 Hz, 2H). 13C{1H}
NMR (150 MHz, CDCl3): δ 147.1, 143.3, 140.6, 137.0, 129.7, 128.4,
127.6, 127.1, 126.1, 113.1, 42.7, 32.3, 28.0, 21.5. HRMS (ESI-TOF)
m/z: [M + Na]+ Calcd for C18H21NNaO2S 338.1185; found
338.1177.
N-(2,2-Dimethyl-4-(4-(trifluoromethyl)phenyl)pent-4-en-1-yl)-4-
methylbenzenesulfonamide (1j). Synthesized using 2,2-dimethyl-4-
(4-(trifluoromethyl)phenyl)pent-4-en-1-amine and p-toluenesulfonyl
chloride. Purified by silica gel column chromatography (the eluent
was petroleum ether/EtOAc 5:1) as a white solid (92% yield, 379
mg). mp 98−99 °C. 1H NMR (600 MHz, CDCl3): δ 7.58 (d, J = 8.2
Hz, 2H), 7.54 (d, J = 8.1 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.26 (d, J
= 7.8 Hz, 2H), 5.30 (d, J = 1.5 Hz, 1H), 5.14 (d, J = 1.4 Hz, 1H), 4.29
(t, J = 7.1 Hz, 1H), 2.55 (d, J = 7.2 Hz, 2H), 2.49 (s, 2H), 2.42 (s,
3H), 0.76 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ 146.9,
2
145.0, 143.4, 136.9, 129.7, 129.4 (q, JC−F = 31.8 Hz), 126.9, 126.7,
3
1
125.4 (q, JC−F = 3.8 Hz), 124.2 (q, JC−F = 270.2 Hz), 119.4, 53.2,
44.7, 35.3, 25.4, 21.5. 19F NMR (470 MHz, CDCl3): δ −62.41 (s,
3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H24F3NNaO2S
434.1372; found 434.1366.
N-(2,2-Dimethyl-4-(4-(trifluoromethoxy)phenyl)pent-4-en-1-yl)-
4-methylbenzenesulfonamide (1k). Synthesized using 2,2-dimethyl-
4-(4-(trifluoromethoxy)phenyl)pent-4-en-1-amine and p-toluenesul-
fonyl chloride. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 6:1) as a white solid (95% yield,
407 mg). mp 88−89 °C. 1H NMR (600 MHz, CDCl3): δ 7.59 (d, J =
8.0 Hz, 2H), 7.31 (d, J = 8.5 Hz, 2H), 7.27 (d, J = 9.9 Hz, 3H), 7.12
(d, J = 8.3 Hz, 2H), 5.23 (d, J = 1.8 Hz, 1H), 5.06 (d, J = 1.8 Hz, 1H),
4.29 (t, J = 7.1 Hz, 1H), 2.55 (d, J = 7.2 Hz, 2H), 2.45 (s, 2H), 2.43
(s, 3H), 0.77 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ 148.4,
1
144.8, 143.3, 141.9, 136.9, 129.6, 127.7, 126.9, 120.7, 120.5 (q, JC−F
= 255.5 Hz), 118.4, 53.2, 44.8, 35.2, 25.5, 21.5. 19F NMR (470 MHz,
CDCl3): δ −57.82 (s, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C21H24F3NNaO3S 450.1321; found 450.1324.
N-(4-([1,1′-Biphenyl]-4-yl)-2,2-dimethylpent-4-en-1-yl)-4-meth-
ylbenzenesulfonamide (1l). Synthesized using 4-([1,1′-biphenyl]-4-
yl)-2,2-dimethylpent-4-en-1-amine and p-toluenesulfonyl chloride.
Purified by silica gel column chromatography (the eluent was
petroleum ether/EtOAc 5:1) as a white solid (96% yield, 403 mg).
mp 113−114 °C. 1H NMR (600 MHz, CDCl3): δ 7.60 (d, J = 7.1 Hz,
2H), 7.52 (d, J = 6.5 Hz, 4H), 7.45 (t, J = 7.7 Hz, 2H), 7.38−7.34 (m,
3H), 7.12 (d, J = 8.0 Hz, 2H), 5.27 (d, J = 1.7 Hz, 1H), 5.05 (d, J =
1.6 Hz, 1H), 4.49 (t, J = 5.9 Hz, 1H), 2.52 (d, J = 7.2 Hz, 2H), 2.48
(s, 2H), 2.32 (s, 3H), 0.82 (s, 6H). 13C{1H} NMR (150 MHz,
CDCl3): δ 145.6, 143.1, 142.2, 140.4, 140.1, 136.9, 129.6, 128.9,
127.5, 127.1, 126.89, 126.88, 126.8, 117.6, 53.0, 44.8, 35.3, 25.7, 21.5.
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C26H29NNaO2S
442.1811; found 442.1803.
4-Acetyl-N-(2,2-dimethyl-4-phenylpent-4-en-1-yl)-
benzenesulfonamide (1r). Synthesized using 2,2-dimethyl-4-phenyl-
pent-4-en-1-amine and 4-acetylbenzenesulfonyl chloride. Purified by
silica gel column chromatography (the eluent was petroleum ether/
1
N-(2,2-dimethyl-4-(naphthalen-2-yl)pent-4-en-1-yl)-4-methyl-
benzenesulfonamide (1m). Synthesized using 2,2-dimethyl-4-(naph-
thalen-2-yl)pent-4-en-1-amine and p-toluenesulfonyl chloride. Puri-
fied by silica gel column chromatography (the eluent was petroleum
ether/EtOAc 4:1) as a white solid (96% yield, 378 mg). mp 100−101
EtOAc 3:1) as a white solid (90% yield, 335 mg). mp 85−86 °C. H
NMR (600 MHz, CDCl3): δ 8.00 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.4
Hz, 2H), 7.30−7.27 (m, 5H), 5.22 (d, J = 1.8 Hz, 1H), 5.03 (d, J =
1.7 Hz, 1H), 4.57 (t, J = 7.0 Hz, 1H), 2.65 (s, 3H), 2.52 (d, J = 7.1
Hz, 2H), 2.46 (s, 2H), 0.81 (s, 6H). 13C{1H} NMR (150 MHz,
CDCl3): δ 196.8, 145.9, 143.7, 143.2, 139.8, 128.9, 128.6, 127.5,
127.2, 126.4, 117.8, 52.9, 44.9, 35.3, 26.9, 25.6. HRMS (ESI-TOF)
m/z: [M + Na]+ Calcd for C21H25NNaO3S 372.1628; found
372.1617.
1
°C. H NMR (600 MHz, CDCl3): δ 7.83−7.82 (m, 1H), 7.79−7.76
(m, 2H), 7.72 (s, 1H), 7.51−7.47 (m, 2H), 7.45 (dd, J = 8.5, 1.8 Hz,
1H), 7.29 (d, J = 8.2 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 5.34 (d, J =
1.7 Hz, 1H), 5.12 (d, J = 1.6 Hz, 1H), 4.39 (t, J = 7.2 Hz, 1H), 2.56
(s, 2H), 2.47 (d, J = 7.2 Hz, 2H), 2.31 (s, 3H), 0.83 (s, 6H). 13C{1H}
NMR (150 MHz, CDCl3): δ 145.9, 142.9, 140.6, 136.6, 133.4, 132.8,
129.4, 128.2, 128.1, 127.6, 126.7, 126.4, 126.0, 124.89, 124.86, 118.3,
52.9, 45.0, 35.3, 25.7, 21.5. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C24H27NNaO2S 416.1655; found 416.1662.
N-(2,2-Dimethyl-4-phenylpent-4-en-1-yl)-4-(trifluoromethyl)-
benzenesulfonamide (1s). Synthesized using 2,2-dimethyl-4-phenyl-
pent-4-en-1-amine and 4-(trifluoromethyl)benzenesulfonyl chloride.
Purified by silica gel column chromatography (the eluent was
petroleum ether/EtOAc 5:1) as a white solid (94% yield, 374 mg).
1991
https://dx.doi.org/10.1021/acs.joc.0c02637
J. Org. Chem. 2021, 86, 1987−1999

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
1
mp 89−90 °C. H NMR (600 MHz, CDCl3): δ 7.73 (d, J = 8.5 Hz,
N-(4-(4-(tert-Butyl)phenyl)-2,2-dimethylpent-4-en-1-yl)-4-chloro-
benzenesulfonamide (1y). Synthesized using 4-(4-(tert-butyl)-
phenyl)-2,2-dimethylpent-4-en-1-amine and 4-chlorobenzenesulfonyl
chloride. Purified by silica gel column chromatography (the eluent
was petroleum ether/EtOAc 5:1) as a white solid (93% yield, 391
mg). mp 90−91 °C. 1H NMR (600 MHz, CDCl3): δ 7.53 (d, J = 8.6
Hz, 2H), 7.41 (d, J = 8.6 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.25 (d, J
= 7.2 Hz, 2H), 5.22 (d, J = 1.8 Hz, 1H), 4.99 (d, J = 1.7 Hz, 1H), 4.20
(t, J = 7.1 Hz, 1H), 2.50 (d, J = 7.1 Hz, 2H), 2.44 (s, 2H), 1.33 (s,
9H), 0.82 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ 150.6,
145.6, 140.1, 138.9, 138.5, 129.3, 128.4, 126.0, 125.5, 117.1, 52.8,
44.7, 35.3, 34.5, 31.4, 25.7. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C23H30ClNNaO2S 442.1578; found 442.1576.
2H), 7.70 (d, J = 8.5 Hz, 2H), 7.29−7.25 (m, 5H), 5.22 (d, J = 1.5
Hz, 1H), 5.03 (d, J = 1.7 Hz, 1H), 4.50 (t, J = 6.7 Hz, 1H), 2.51 (d, J
= 7.1 Hz, 2H), 2.46 (s, 2H), 0.83 (s, 6H). 13C{1H} NMR (150 MHz,
2
CDCl3): δ 145.8, 143.4, 143.2, 134.1 (q, JC−F = 32.9 Hz), 128.6,
127.5, 127.4, 126.4, 126.1 (3JC−F, J = 3.7 Hz), 123.3 (q, 1JC−F = 271.1
Hz), 117.8, 52.8, 45.0, 35.3, 25.6. 19F NMR (470 MHz, CDCl3): δ
−63.22 (s, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C20H22F3NNaO2S 420.1216; found 420.1213.
4-Chloro-N-(2,2-dimethyl-4-phenylpent-4-en-1-yl)-
benzenesulfonamide (1t). Synthesized using 2,2-dimethyl-4-phenyl-
pent-4-en-1-amine and 4-chlorobenzenesulfonyl chloride. Purified by
silica gel column chromatography (the eluent was petroleum ether/
1
N-(4-(4-(tert-Butyl)phenyl)-2,2-dimethylpent-4-en-1-yl)-4-
(trifluoromethyl)benzenesulfonamide (1z). Synthesized using 4-(4-
(tert-butyl)phenyl)-2,2-dimethylpent-4-en-1-amine and 4-
(trifluoromethyl)benzenesulfonyl chloride. Purified by silica gel
column chromatography (the eluent was petroleum ether/EtOAc
EtOAc 5:1) as a white solid (92% yield, 335 mg). mp 91−92 °C. H
NMR (600 MHz, CDCl3): δ 7.53 (d, J = 8.6 Hz, 2H), 7.41 (d, J = 8.5
Hz, 2H), 7.32−7.27 (m, 5H), 5.22 (d, J = 1.7 Hz, 1H), 5.03 (d, J =
1.8 Hz, 1H), 4.27 (t, J = 7.2 Hz, 1H), 2.48 (d, J = 7.1 Hz, 2H), 2.45
(s, 2H), 0.81 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ 145.9,
143.3, 138.9, 138.3, 129.2, 128.6, 128.4, 127.5, 126.4, 117.8, 52.8,
45.0, 35.2, 25.6. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H22ClNNaO2S 386.0952; found 386.0934.
1
5:1) as a white solid (92% yield, 418 mg). mp 86−87 °C. H NMR
(600 MHz, CDCl3): δ 7.73 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 9.0 Hz,
2H), 7.34 (d, J = 8.1 Hz, 2H), 7.25 (d, J = 8.1 Hz, 2H), 5.22 (d, J =
1.8 Hz, 1H), 4.99 (d, J = 1.8 Hz, 1H), 4.34 (t, J = 7.2 Hz, 1H), 2.55
(d, J = 7.0 Hz, 2H), 2.45 (s, 2H), 1.32 (s, 9H), 0.82 (s, 6H). 13C{1H}
NMR (150 MHz, CDCl3): δ 150.7, 145.5, 143.7, 140.1, 134.1 (q,
2JC−F = 32.9 Hz), 127.4, 126.1 (q, 3JC−F = 3.7 Hz), 126.0, 125.5, 123.2
4-Cyano-N-(2,2-dimethyl-4-phenylpent-4-en-1-yl)-
benzenesulfonamide (1u). Synthesized using 2,2-dimethyl-4-phenyl-
pent-4-en-1-amine and 4-cyanobenzenesulfonyl chloride. Purified by
silica gel column chromatography (the eluent was petroleum ether/
EtOAc 7:1) as a white solid (95% yield, 337 mg). mp 129−130 °C.
1H NMR (600 MHz, CDCl3): δ 7.74 (d, J = 8.5 Hz, 2H), 7.69 (d, J =
7.5 Hz, 2H), 7.32−7.28 (m, 5H), 5.23 (d, J = 1.2 Hz, 1H), 5.04 (d, J
= 1.2 Hz, 1H), 4.49 (t, J = 6.6 Hz, 1H), 2.50 (d, J = 7.0 Hz, 2H), 2.46
(s, 2H), 0.82 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ 145.7,
144.1, 143.2, 132.8, 128.7, 127.6, 127.5, 126.4, 118.0, 117.4, 116.1,
52.8, 45.0, 35.3, 25.6. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C20H22N2NaO2S 355.1475; found 355.1471.
1
(q, JC−F = 271.0 Hz), 117.1, 52.8, 44.7, 35.3, 34.5, 31.3, 25.7. 19F
NMR (470 MHz, CDCl3): δ −63.09 (s, 3F). HRMS (ESI-TOF) m/z:
[M + Na]+ Calcd for C24H30F3NNaO2S 476.1842; found 476.1819.
4-Chloro-N-(4-(4-fluorophenyl)-2,2-dimethylpent-4-en-1-yl)-
benzenesulfonamide (1aa). Synthesized using 4-(4-fluorophenyl)-
2,2-dimethylpent-4-en-1-amine and 4-chlorobenzenesulfonyl chloride.
Purified by silica gel column chromatography (the eluent was
petroleum ether/EtOAc 5:1) as a white solid (98% yield, 375 mg).
1
mp 90−91 °C. H NMR (600 MHz, CDCl3): δ 7.63 (d, J = 7.3 Hz,
N-(2,2-Dimethyl-4-phenylpent-4-en-1-yl)-4-nitrobenzenesulfo-
namide (1v). Synthesized using 2,2-dimethyl-4-phenylpent-4-en-1-
amine and 4-nitrobenzenesulfonyl chloride. Purified by silica gel
column chromatography (the eluent was petroleum ether/EtOAc 3:1)
2H), 7.45 (d, J = 7.4 Hz, 2H), 7.26−7.24 (m, 2H), 6.96 (t, J = 8.0 Hz,
2H), 5.18 (d, J = 1.8 Hz, 1H), 5.01 (d, J = 1.8 Hz, 1H), 4.58 (t, J = 7.2
Hz, 1H), 2.52 (d, J = 6.8 Hz, 2H), 2.43 (s, 2H), 0.78 (s, 6H).
1
13C{1H} NMR (150 MHz, CDCl3): δ 162.2 (d, JC−F = 245.1 Hz),
1
as a white solid (96% yield, 360 mg). mp 92−93 °C. H NMR (600
MHz, CDCl3): δ 8.28 (d, J = 8.7 Hz, 2H), 7.75 (d, J = 8.6 Hz, 2H),
7.32−7.29 (m, 5H), 5.24 (d, J = 1.2 Hz, 1H), 5.05 (d, J = 1.2 Hz,
1H), 4.47 (s, 1H), 2.51 (s, 2H), 2.46 (s, 2H), 0.84 (s, 6H). 13C{1H}
NMR (150 MHz, CDCl3): δ 149.9, 145.6, 145.6, 143.3, 128.7, 128.1,
127.6, 126.4, 124.3, 118.0, 52.8, 45.0, 35.3, 25.6. HRMS (ESI-TOF)
m/z: [M + Na]+ Calcd for C19H22F3N2NaO4S 397.1192; found
397.1187.
144.9, 139.2 (d, 4JC−F = 3.3 Hz), 139.0, 138.3, 129.3, 128.3, 128.0 (d,
2
3JC−F = 7.7 Hz), 117.7, 115.3 (d, JC−F = 21.0 Hz), 53.1, 45.1, 35.2,
25.5. 19F NMR (470 MHz, CDCl3): δ −114.73 to −114.79 (m, 1F).
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C19H21ClFNNaO2S
404.0858; found 404.0857.
N-(4-(4-Fluorophenyl)-2,2-dimethylpent-4-en-1-yl)-4-
(trifluoromethyl)benzenesulfonamide (1ab). Synthesized using 4-
(4-fluorophenyl)-2,2-dimethylpent-4-en-1-amine and 4-
(trifluoromethyl)benzenesulfonyl chloride. Purified by silica gel
column chromatography (the eluent was petroleum ether/EtOAc
5:1) as a white solid (98% yield, 408 mg). mp 99−100 °C. 1H NMR
(600 MHz, CDCl3): δ 7.81 (d, J = 7.9 Hz, 2H), 7.75 (d, J = 8.2 Hz,
2H), 7.26−7.24 (m, 2H), 6.95 (t, J = 8.4 Hz, 2H), 5.18 (d, J = 1.8 Hz,
1H), 5.02 (d, J = 1.8 Hz, 1H), 4.32 (t, J = 7.2 Hz, 1H), 2.54 (d, J = 6.9
Hz, 2H), 2.43 (s, 2H), 0.80 (s, 6H). 13C{1H} NMR (150 MHz,
N-(2,2-Dimethyl-4-phenylpent-4-en-1-yl)-4-(trifluoromethoxy)-
benzenesulfonamide (1w). Synthesized using 2,2-dimethyl-4-phenyl-
pent-4-en-1-amine and 4-(trifluoromethoxy)benzenesulfonyl chloride.
Purified by silica gel column chromatography (the eluent was
petroleum ether/EtOAc 5:1) as a white solid (96% yield, 397 mg).
1
mp 69−70 °C. H NMR (600 MHz, CDCl3): δ 7.64 (d, J = 8.8 Hz,
2H), 7.29 (d, J = 4.3 Hz, 4H), 7.28−7.25 (m, 3H), 5.22 (d, J = 1.7
Hz, 1H), 5.03 (d, J = 1.6 Hz, 1H), 4.24 (t, J = 7.1 Hz, 1H), 2.50 (d, J
= 7.1 Hz, 2H), 2.46 (s, 2H), 0.83 (s, 6H). 13C{1H} NMR (125 MHz,
CDCl3): δ 151.9, 146.0, 143.3, 138.3, 129.1, 128.5, 127.4, 126.4,
CDCl3): δ 162.2 (d, 1JC−F = 245.3 Hz), 144.8, 143.3, 139.2 (d, 4JC−F
3.5 Hz), 134.3 (q, 2JC−F = 32.9 Hz), 127.9 (d, 3JC−F = 7.8 Hz), 127.4,
=
120.9, 120.3 (q, JC−F = 275.5 Hz), 117.6, 53.1, 45.0, 35.2, 25.5. 19F
1
3
1
126.2 (q, JC−F = 3.7 Hz), 123.2 (q, JC−F = 271.2 Hz), 117.8, 115.3
(d, JC−F = 21.3 Hz), 53.1, 45.1, 35.2, 25.5. 19F NMR (470 MHz,
2
NMR (470 MHz, CDCl3): δ −57.68 (s, 3F). HRMS (ESI-TOF) m/z:
[M + Na]+ Calcd for C20H22F3NNaO3S 436.1165; found 436.1133.
N-(2,2-Dimethyl-4-phenylpent-4-en-1-yl)-2,4,6-trimethylbenze-
nesulfonamide (1x). Synthesized using 2,2-dimethyl-4-phenylpent-4-
en-1-amine and 2,4,6-trimethylbenzenesulfonyl chloride. Purified by
silica gel column chromatography (the eluent was petroleum ether/
CDCl3): δ −63.13 (s, 3F), −114.56 to −114.61 (m, 1F). HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C20H21F4NNaO2S 416.1302;
found 416.1302.
N-(2,2-Dimethyl-4-phenylpent-4-en-1-yl)methanesulfonamide
(1ac). Synthesized using 2,2-dimethyl-4-phenylpent-4-en-1-amine and
methanesulfonyl chloride. Purified by silica gel column chromatog-
raphy (the eluent was petroleum ether/EtOAc 7:1) as a light yellow
1
EtOAc 5:1) as a white solid (91% yield, 339 mg). mp 91−92 °C. H
NMR (600 MHz, CDCl3): δ 7.29 (d, J = 3.7 Hz, 4H), 7.26 (s, 1H),
6.92 (s, 2H), 5.21 (d, J = 1.8 Hz, 1H), 5.00 (d, J = 1.8 Hz, 1H), 4.35
(t, J = 7.2 Hz, 1H), 2.52 (s, 6H), 2.48 (d, J = 7.2 Hz, 2H), 2.44 (s,
2H), 2.29 (s, 3H), 0.74 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3):
δ 146.2, 143.1, 142.0, 138.9, 135.6, 131.9, 128.5, 127.5, 126.3, 117.5,
52.3, 44.9, 35.2, 25.7, 22.9, 20.9. HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C22H29NNaO2S 394.1811; found 394.1814.
1
solid (91% yield, 244 mg). mp 53−54 °C. H NMR (600 MHz,
CDCl3): δ 7.37 (d, J = 7.2 Hz, 2H), 7.31 (t, J = 7.6 Hz, 2H), 7.25 (t, J
= 7.3 Hz, 1H), 5.27 (d, J = 1.7 Hz, 1H), 5.08 (d, J = 1.8 Hz, 1H), 4.66
(t, J = 6.9 Hz, 1H), 2.75 (d, J = 7.2 Hz, 2H), 2.72 (s, 3H), 2.50 (s,
2H), 0.82 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ 146.1,
143.4, 128.5, 127.4, 126.5, 117.6, 53.1, 44.7, 39.4, 35.2, 25.6. HRMS
1992
https://dx.doi.org/10.1021/acs.joc.0c02637
J. Org. Chem. 2021, 86, 1987−1999

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
(ESI-TOF) m/z: [M + Na]+ Calcd for C14H21NNaO2S 290.1185;
found 290.1190.
1H), 5.95 (t, J = 6.6 Hz, 1H), 5.29 (d, J = 1.8 Hz, 1H), 5.10 (s, 1H),
3.17 (d, J = 6.5 Hz, 2H), 2.54 (s, 2H), 0.88 (s, 7H). 13C{1H} NMR
(150 MHz, CDCl3): δ 167.5, 146.5, 143.6, 134.9, 131.3, 128.6, 128.5,
127.5, 126.8, 126.5, 117.4, 48.9, 45.3, 36.3, 26.0. HRMS (ESI-TOF)
m/z: [M + Na]+ Calcd for C20H23NNaO 316.1672; found 316.1661.
tert-Butyl (2,2-Dimethyl-4-phenylpent-4-en-1-yl)carbamate
(1aj). Synthesized using 2,2-dimethyl-4-phenylpent-4-en-1-amine
and di-tert-butyl dicarbonate in tetrahydrofuran. No pyridine or any
other base was needed. Purified by silica gel column chromatography
(the eluent was petroleum ether/EtOAc 15:1) as awhite solid (98%
N-(2,2-Dimethyl-4-phenylpent-4-en-1-yl)ethanesulfonamide
(1ad). Synthesized using 2,2-dimethyl-4-phenylpent-4-en-1-amine
and ethanesulfonyl chloride. Purified by silica gel column chromatog-
raphy (the eluent was petroleum ether/EtOAc 7:1) as a light yellow
solid (90% yield, 254 mg). mp 56−57 °C. 1H NMR (600 MHz,
CDCl3): δ 7.37 (d, J = 7.2 Hz, 2H), 7.32 (t, J = 7.6 Hz, 2H), 7.26 (t, J
= 7.3 Hz, 1H), 5.27 (d, J = 1.8 Hz, 1H), 5.08 (d, J = 1.8 Hz, 1H), 4.35
(t, J = 6.9 Hz, 1H), 2.86 (q, J = 7.4 Hz, 2H), 2.73 (d, J = 7.0 Hz, 2H),
2.50 (s, 2H), 1.20 (t, J = 7.4 Hz, 3H), 0.84 (s, 6H). 13C{1H} NMR
(150 MHz, CDCl3): δ 146.2, 143.4, 128.6, 127.5, 126.5, 117.6, 53.0,
46.4, 44.8, 35.4, 25.6, 8.2. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd
for C15H23NNaO2S 282.1522; found 282.1527.
1
yield, 284 mg). mp 55−56 °C. H NMR (600 MHz, CDCl3): δ 7.36
(d, J = 7.2 Hz, 2H), 7.30 (t, J = 7.2 Hz, 2H), 7.24 (t, J = 7.3 Hz, 1H),
5.25 (d, J = 1.9 Hz, 1H), 5.05 (d, J = 1.8 Hz, 1H), 4.47 (t, J = 6.0 Hz,
1H), 2.87 (d, J = 6.6 Hz, 2H), 2.47 (s, 2H), 1.43 (s, 9H), 0.75 (s,
6H). 13C{1H} NMR (150 MHz, CDCl3): δ 156.2, 146.7, 143.4, 128.3,
127.2, 126.5, 117.1, 78.9, 50.6, 45.1, 35.9, 28.4, 25.5. HRMS (ESI-
TOF) m/z: [M + Na]+ Calcd for C18H27NNaO2 312.1934; found
312.1924.
N-(2,2-Dimethyl-4-phenylpent-4-en-1-yl)-1-phenylmethanesul-
fonamide (1ae). Synthesized using 2,2-dimethyl-4-phenylpent-4-en-
1-amine and phenylmethanesulfonyl chloride. Purified by silica gel
column chromatography (the eluent was petroleum ether/EtOAc 5:1)
1
as a white solid (87% yield, 299 mg). mp 83−84 °C. H NMR (600
General Procedure for the Synthesis of Products 2. An oven-
dried test tube (10.0 mL) equipped with a Teflon-coated magnetic
stir bar was charged with 1 (0.1 mmol, 1.0 equiv), the
trifluoromethylation reagent chloro(phenyl)trifluoromethyliodane
(0.2 mmol, 2.0 equiv),8 and ZnI2 (0.01 mmol, 10 mol %) in
sequence in a glovebox. After anhydrous DCM (1.0 mL) was added,
the tube was sealed with a Teflon screw-cap septum and taken
outside. The reaction mixture was stirred at 40 °C in an oil bath for
12 h, then quenched with H2O (1.0 mL) after being cooled to room
temperature. The aqueous layer was separated and extracted with
DCM (3 × 5.0 mL). The combined organic layers were dried over
MgSO4 and concentrated in vacuo. The residue was purified by silica
gel column chromatography (the eluent was petroleum ether/EtOAc
20:1−3:1) to afford the pure product 2.
MHz, CDCl3): δ 7.34−7.33 (m, 5H), 7.29 (t, J = 7.5 Hz, 2H), 7.27−
7.23 (m, 3H), 5.22 (d, J = 1.8 Hz, 1H), 5.00 (d, J = 1.8 Hz, 1H), 4.33
(t, J = 6.8 Hz, 1H), 4.07 (s, 2H), 2.60 (d, J = 6.9 Hz, 2H), 2.43 (s,
2H), 0.75 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ 146.2,
143.3, 130.6, 129.4, 128.9, 128.7, 128.5, 127.4, 126.5, 117.5, 58.4,
53.5, 44.8, 35.4, 25.5. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C20H25NNaO2S 366.1498; found 366.1489.
(E)-N-(2,2-Dimethyl-4-phenylpent-4-en-1-yl)-2-phenylethene-1-
sulfonamide (1af). Synthesized using 2,2-dimethyl-4-phenylpent-4-
en-1-amine and (E)-2-phenylethene-1-sulfonyl chloride. Purified by
silica gel column chromatography (the eluent was petroleum ether/
1
EtOAc 5:1) as a white solid (85% yield, 303 mg). mp 85−86 °C. H
NMR (600 MHz, CDCl3): δ 7.43−7.42 (m, 2H), 7.41−7.39 (m, 3H),
7.35−7.32 (m, 3H), 7.25 (t, J = 7.6 Hz, 2H), 7.19 (t, J = 7.2 Hz, 1H),
6.54 (d, J = 15.4 Hz, 1H), 5.24 (d, J = 1.8 Hz, 1H), 5.07 (d, J = 1.7
Hz, 1H), 4.59 (t, J = 7.0 Hz, 1H), 2.67 (d, J = 7.0 Hz, 2H), 2.50 (s,
2H), 0.84 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ 146.1,
143.3, 141.4, 132.7, 130.8, 129.1, 128.5, 128.3, 127.4, 126.5, 125.0,
117.6, 52.9, 44.9, 35.2, 25.7. HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C21H25NNaO2S 378.1498; found 378.1492.
4,4-Dimethyl-2-phenyl-1-tosyl-2-(2,2,2-trifluoroethyl)pyrrolidine
(2a). Purified by silica gel column chromatography (the eluent was
petroleum ether/EtOAc 5:1) as a white solid (87% yield, 35.8 mg).
mp 127−128 °C. 1H NMR (600 MHz, CDCl3): δ 7.31 (d, J = 7.2 Hz,
2H), 7.22−7.19 (m, 3H), 7.11 (d, J = 8.1 Hz, 2H), 7.05 (d, J = 8.1
Hz, 2H), 4.04 (dq, J = 16.3, 11.4 Hz, 1H), 3.43 (d, J = 9.3 Hz, 1H),
3.19−3.10 (m, 2H), 2.47 (d, J = 14.3 Hz, 1H), 2.40 (d, J = 14.3 Hz,
1H), 2.36 (s, 3H), 1.25 (s, 3H), 1.11 (s, 3H). 13C{1H} NMR (150
MHz, CDCl3): δ 142.6, 142.1, 136.5, 129.1, 127.9, 127.4, 127.1,
N-(2,2-Dimethylpent-4-en-1-yl)-4-methylbenzenesulfonamide
(1ag). Synthesized using 2,2-dimethylpent-4-en-1-amine and p-
toluenesulfonyl chloride. Purified by silica gel column chromatog-
raphy (the eluent was petroleum ether/EtOAc 10:1) as a white solid
(97% yield, 260 mg). mp 60−61 °C. 1H NMR (600 MHz, CDCl3): δ
7.75 (d, J = 7.9 Hz, 2H), 7.31 (d, J = 7.9 Hz, 2H), 5.72 (td, J = 17.3,
7.5 Hz, 1H), 5.02−4.98 (m, 2H), 4.75 (t, J = 6.9 Hz, 1H), 2.67 (d, J =
6.9 Hz, 2H), 2.43 (s, 3H), 1.96 (d, J = 7.5 Hz, 2H), 0.86 (s, 6H).
13C{1H} NMR (150 MHz, CDCl3): δ 143.3, 137.0, 134.3, 129.7,
1
3
126.9, 125.5 (q, JC−F = 276.8 Hz), 69.5 (q, JC−F = 2.3 Hz), 62.0,
4
2
53.5 (q, JC−F = 1.2 Hz), 43.8 (q, JC−F = 27.0 Hz), 36.7, 28.8, 27.4,
21.4. 19F NMR (470 MHz, CDCl3): δ −56.405 (t, J = 11.3 Hz, 3F).
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H24F3NNaO2S
434.1372; found 434.1378.
Procedure for the Synthesis of Product 2a (1.0 mmol Scale). In a
similar manner to the general procedure for products 2, a solution of
1a (343.5 mg, 1.0 mmol), chloro(phenyl)trifluoromethyliodane
(616.9 mg, 2.0 mmol), and ZnI2 (31.9 mg, 2.83 mmol) in dry
anhydrous DCM (10.0 mL) was stirred at 40 °C under a N2
atmosphere for 12 h to afford 2a (308.9 mg, 75%).
127.1, 117.9, 52.9, 44.0, 34.1, 24.9, 21.5. HRMS (ESI-TOF) m/z: [M
+ Na]+ Calcd for C14H21NNaO2S 290.1185; found 290.1178.
N-(2,2-Dimethylpent-4-en-1-yl)-4-(trifluoromethyl)-
benzenesulfonamide (1ah). Synthesized using 2,2-dimethylpent-4-
en-1-amine and 4-(trifluoromethyl)benzenesulfonyl chloride. Purified
by silica gel column chromatography (the eluent was petroleum
ether/EtOAc 10:1) as a white solid (96% yield, 309 mg). mp 63−64
°C. 1H NMR (600 MHz, CDCl3): δ 8.00 (d, J = 8.1 Hz, 2H), 7.79 (d,
J = 8.2 Hz, 2H), 5.72 (ddt, J = 17.5, 10.2, 7.5 Hz, 1H), 5.05−4.98 (m,
2H), 4.94 (t, J = 6.1 Hz, 1H), 2.73 (d, J = 6.8 Hz, 2H), 1.97 (d, J = 7.4
Hz, 2H), 0.87 (s, 6H). 13C{1H} NMR (150 MHz, CDCl3): δ 143.7,
4,4-Dimethyl-2-(o-tolyl)-1-tosyl-2-(2,2,2-trifluoroethyl)-
pyrrolidine (2b). Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 7:1) as a white solid (40% yield,
17.0 mg). mp 99−100 °C. 1H NMR (600 MHz, CDCl3): δ 7.95 (d, J
= 7.9 Hz, 1H), 7.56 (d, J = 8.3 Hz, 2H), 7.27−7.25 (m, 3H), 7.19 (td,
J = 7.4, 1.3 Hz, 1H), 7.10 (d, J = 7.2 Hz, 1H), 3.81 (dq, J = 17.4, 11.8
Hz, 1H), 3.53 (d, J = 8.9 Hz, 1H), 3.29−3.21 (m, 2H), 2.45 (d, J =
13.2 Hz, 1H), 2.43 (s, 3H), 2.25 (d, J = 13.2 Hz, 1H), 2.25 (s, 3H),
1.08 (s, 3H), 0.92 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ
143.2, 142.6, 136.7, 133.3, 132.9, 129.3, 128.4, 127.5, 127.3, 125.7 (q,
1JC−F = 277.0 Hz), 125.5, 72.5 (q, 3JC−F = 2.0 Hz), 61.5, 50.9 (q, 4JC−F
2
3
134.3 (q, JC−F = 33.0 Hz) 134.0, 127.5, 126.3 (q, JC−F = 3.6 Hz),
1
123.2 (q, JC−F = 272.0 Hz), 118.1, 52.9, 44.0, 34.2, 24.8. 19F NMR
(470 MHz, CDCl3): δ −63.13 (s, 3F). HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C14H18F3NNaO2S 344.0903; found 344.0897.
N-(2,2-Dimethyl-4-phenylpent-4-en-1-yl)benzamide (1ai). Syn-
thesized using 2,2-dimethyl-4-phenylpent-4-en-1-amine and benzoyl
chloride by changing pyridine into Et3N. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 10:1) as
2
= 1.2 Hz), 41.0 (q, JC−F = 26.4 Hz), 36.8, 29.1, 28.1, 21.8, 21.5. 19F
NMR (470 MHz, CDCl3): δ −58.11 (t, J = 11.0 Hz, 3F). HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C22H26F3NNaO2S 448.1529;
found 448.1530.
4,4-Dimethyl-2-(m-tolyl)-1-tosyl-2-(2,2,2-trifluoroethyl)-
pyrrolidine (2c). Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 5:1) as a white solid (84% yield,
1
awhite solid (90% yield, 265 mg). mp 78−79 °C. H NMR (600
MHz, CDCl3): δ 7.61 (d, J = 6.9 Hz, 1H), 7.47 (t, J = 7.4 Hz, 1H),
7.39 (t, J = 7.5 Hz, 4H), 7.33 (t, J = 7.5 Hz, 2H), 7.27 (t, J = 7.2 Hz,
1993
https://dx.doi.org/10.1021/acs.joc.0c02637
J. Org. Chem. 2021, 86, 1987−1999

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
35.8 mg). mp 127−128 °C. 1H NMR (500 MHz, CDCl3): δ 7.14 (d, J
= 8.1 Hz, 1H), 7.10 (t, J = 7.6 Hz, 1H), 7.06 (d, J = 8.4 Hz, 2H), 7.03
(d, J = 8.3 Hz, 2H), 7.00 (d, J = 7.2 Hz, 1H), 6.92 (s, 1H), 4.05 (dq, J
= 16.3, 11.5 Hz, 1H), 3.49 (d, J = 9.2 Hz, 1H), 3.19−3.10 (m, 2H),
2.47 (d, J = 14.3 Hz, 1H), 2.37 (d, J = 16.8, 1H), 2.35 (s, 3H), 2.15 (s,
3H), 1.27 (s, 3H), 1.13 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3):
δ 142.5, 142.0, 137.4, 136.4, 128.9, 128.2, 127.9, 127.7, 126.9, 125.6
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H26F3NNaO3S
464.1478; found 464.1467.
2-(4-Fluorophenyl)-4,4-dimethyl-1-tosyl-2-(2,2,2-trifluoroethyl)-
pyrrolidine (2h). Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 7:1) as a white solid (85% yield,
36.5 mg). mp 118−119 °C. 1H NMR (600 MHz, CDCl3): δ 7.30 (d, J
= 8.4 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 7.18 (d, J = 8.0 Hz, 2H), 7.10
(d, J = 8.0 Hz, 2H), 6.86 (t, J = 8.5 Hz, 2H), 4.00 (dq, J = 16.0, 11.3
Hz, 1H), 3.42 (d, J = 9.4 Hz, 1H), 3.17 (d, J = 9.4 Hz, 1H), 3.10 (dq,
J = 16.1, 11.1 Hz, 1H), 2.45 (d, J = 14.4 Hz, 1H), 2.37 (s, 3H), 2.36
(d, J = 14.4 Hz, 1H), 1.23 (s, 3H), 1.10 (s, 3H). 13C{1H} NMR (150
1
3
(q, JC−F = 276.6 Hz), 124.1, 69.2 (q, JC−F = 2.4 Hz), 62.2, 53.6 (q,
4JC−F = 1.0 Hz), 43.9 (q, 2JC−F = 26.9 Hz), 36.7, 28.7, 27.5, 21.5, 21.4.
19F NMR (470 MHz, CDCl3): δ −56.25 (t, J = 11.8 Hz, 3F). HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C22H26F3NNaO2S 448.1529;
found 448.1534.
MHz, CDCl3): δ 162.0 (d, 1JC−F = 245.9 Hz), 143.0, 138.0 (d, 4JC−F
3.3 Hz), 136.5, 129.1, 128.9 (d, 3JC−F = 8.1 Hz), 126.8, 125.4 (q, 1JC−F
=
4,4-Dimethyl-2-(p-tolyl)-1-tosyl-2-(2,2,2-trifluoroethyl)-
pyrrolidine (2d). Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 5:1) as a white solid (73% yield,
31.1 mg). mp 127−128 °C. 1H NMR (600 MHz, CDCl3): δ 7.17 (d, J
= 8.1 Hz, 2H), 7.11 (d, J = 8.1 Hz, 2H), 7.03 (d, J = 8.0 Hz, 2H), 6.96
(d, J = 8.0 Hz, 2H), 4.04 (dq, J = 16.2, 11.4 Hz, 1H), 3.43 (d, J = 9.3
Hz, 1H), 3.17 (d, J = 9.2 Hz, 1H), 3.11 (dq, J = 16.0, 11.2 Hz, 1H),
2.45 (d, J = 14.4 Hz, 1H), 2.38 (d, J = 15.0 Hz, 1H), 2.36 (s, 3H),
2.31 (s, 3H), 1.25 (s, 3H), 1.11 (s, 3H). 13C{1H} NMR (150 MHz,
CDCl3): δ 142.5, 139.1, 137.2, 136.6, 128.9, 128.5, 127.0, 126.9,
2
3
= 276.8 Hz), 114.6 (d, JC−F = 21.3 Hz), 69.0 (q, JC−F = 2.9 Hz),
4
2
61.9, 53.6 (q, JC−F = 1.2 Hz), 43.9 (q, JC−F = 27.0 Hz), 36.6, 28.7,
27.4, 21.4. 19F NMR (470 MHz, CDCl3): δ −56.48 (t, J = 11.0 Hz,
3F), −115.16 to −115.22) (m, 1F). HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C21H23F4NNaO2S 452.1278; found 452.1286.
2-(4-Chlorophenyl)-4,4-dimethyl-1-tosyl-2-(2,2,2-trifluoroethyl)-
pyrrolidine (2i). Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 5:1) as a white solid (85% yield,
38.0 mg). mp 129−130 °C. 1H NMR (600 MHz, CDCl3): δ 7.22 (d, J
= 8.6 Hz, 2H), 7.16 (d, J = 8.2 Hz, 2H), 7.11 (t, J = 8.9 Hz, 4H), 3.99
(dq, J = 16.2, 11.3 Hz, 1H), 3.45 (d, J = 9.3 Hz, 1H), 3.19 (d, J = 9.4
Hz, 1H), 3.10 (dq, J = 16.2, 11.1 Hz, 1H), 2.46 (d, J = 14.4 Hz, 1H),
2.39 (s, 3H), 2.33 (d, J = 14.4 Hz, 1H), 1.24 (s, 3H), 1.11 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3): δ 143.0, 140.7, 136.4, 133.6,
1
3
125.6 (q, JC−F = 276.6 Hz), 69.2 (q, JC−F = 2.9 Hz), 62.0, 53.4 (q,
4JC−F = 1.2 Hz), 43.8 (q, 2JC−F = 26.9 Hz), 36.6, 28.8, 27.4, 21.4, 20.9.
19F NMR (470 MHz, CDCl3): δ −56.38 (t, J = 10.8 Hz). HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C22H26F3NNaO2S 448.1529;
found 448.1519.
129.2, 128.5, 127.9, 126.8, 125.4 (q, 1JC−F = 276.8 Hz), 68.9 (q, 3JC−F
2-(4-(tert-Butyl)phenyl)-4,4-dimethyl-1-tosyl-2-(2,2,2-
trifluoroethyl)pyrrolidine (2e). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 7:1) as a
4
2
= 2.0 Hz), 62.1, 53.4 (q, JC−F = 1.2 Hz), 43.7 (q, JC−F = 27.1 Hz),
36.6, 28.6, 27.4, 21.5. 19F NMR (470 MHz, CDCl3): δ −56.40 (t, J =
11.3 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C21H23ClF3NNaO2S 468.0982; found 468.0983.
1
white solid (60% yield, 28.1 mg). mp 123−124 °C. H NMR (600
MHz, CDCl3): δ 7.17−7.14 (m, 4H), 7.01 (d, J = 8.4 Hz, 2H), 7.00
(d, J = 8.4 Hz, 2H), 4.09 (dq, J = 16.2, 11.5 Hz, 1H), 3.49 (d, J = 9.2
Hz, 1H), 3.18−3.09 (m, 2H), 2.48 (d, J = 14.5 Hz, 1H), 2.38 (d, J =
14.5 Hz, 1H), 2.33 (s, 3H), 1.30 (s, 9H), 1.28 (s, 3H), 1.14 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3): δ 150.3, 142.3, 138.7, 136.5,
4,4-Dimethyl-1-tosyl-2-(2,2,2-trifluoroethyl)-2-(4-
(trifluoromethyl)phenyl)pyrrolidine (2j). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 5:1) as a
1
white solid (60% yield, 28.8 mg). mp 127−128 °C. H NMR (600
MHz, CDCl3): δ 7.41−7.37 (m, 4H), 7.10 (d, J = 8.1 Hz, 2H), 7.04
(d, J = 8.1 Hz, 2H), 4.06 (dq, J = 16.4, 11.3 Hz, 1H), 3.52 (d, J = 9.3
Hz, 1H), 3.24 (d, J = 9.3 Hz, 1H), 3.15 (dq, J = 16.4, 11.1 Hz, 1H),
2.52 (d, J = 14.5 Hz, 1H), 2.36 (d, J = 14.4 Hz, 1H), 2.36 (s, 3H),
1.28 (s, 3H), 1.14 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ
1
3
128.9, 126.9, 126.8, 125.6 (q, JC−F = 276.8 Hz), 68.7 (q, JC−F = 2.7
4
2
Hz), 62.1, 53.6 (q, JC−F = 1.2 Hz), 43.9 (q, JC−F = 26.9 Hz), 36.6,
34.3, 31.4, 28.7, 27.4, 21.4. 19F NMR (470 MHz, CDCl3): δ −56.19
(t, J = 10.6 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C25H32F3NNaO2S 490.2004; found 490.2007.
2
146.0, 143.1, 136.3, 129.7 (q, JC−F = 32.4 Hz), 129.2, 127.4, 126.6,
125.3 (q, 1JC−F = 276.7 Hz), 124.8 (q, 3JC−F = 3.6 Hz), 123.9 (q, 1JC−F
= 270.3 Hz), 68.8 (q, 3JC−F = 2.6 Hz), 62.3, 53.6 (q, 4JC−F = 1.2 Hz),
43.6 (q, 2JC−F = 27.2 Hz), 36.7, 28.6, 27.4, 21.4. 19F NMR (470 MHz,
CDCl3): δ −56.25 (t, J = 10.8 Hz, 3F), −62.68 (s, 3F). HRMS (ESI-
TOF) m/z: [M + Na]+ Calcd for C22H23F6NNaO2S 502.1246; found
502.1227.
2-(4-Methoxyphenyl)-4,4-dimethyl-1-tosyl-2-(2,2,2-
trifluoroethyl)pyrrolidine (2f). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 5:1) as a
1
white solid (48% yield, 21.2 mg). mp 128−129 °C. H NMR (600
MHz, CDCl3): δ 7.21 (d, J = 8.6 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H),
7.05 (d, J = 8.0 Hz, 2H), 6.68 (d, J = 8.9 Hz, 2H), 4.04 (dq, J = 16.1,
11.4 Hz, 1H), 3.79 (s, 3H), 3.42 (d, J = 9.3 Hz, 1H), 3.16 (d, J = 9.3
Hz, 1H), 3.09 (dq, J = 16.2, 11.1 Hz, 1H), 2.44 (d, J = 14.4 Hz, 1H),
2.37 (d, J = 14.4 Hz, 1H), 2.36 (s, 3H), 1.24 (s, 3H), 1.11 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3): δ 158.8, 142.5, 136.6, 133.9,
129.0, 128.3, 126.9, 125.5 (q, 1JC−F = 276.8 Hz), 113.0, 69.0 (q, 3JC−F
4,4-Dimethyl-1-tosyl-2-(2,2,2-trifluoroethyl)-2-(4-
(trifluoromethoxy)phenyl)pyrrolidine (2k). Purified by silica gel
column chromatography (the eluent was petroleum ether/EtOAc
5:1) as a white solid (70% yield, 34.7 mg). mp 107−108 °C. 1H NMR
(600 MHz, CDCl3): δ 7.32 (d, J = 8.8 Hz, 2H), 7.13 (d, J = 8.2 Hz,
2H), 7.08 (d, J = 8.0 Hz, 2H), 7.01 (d, J = 8.5 Hz, 2H), 4.03 (dq, J =
16.3, 11.3 Hz, 1H), 3.48 (d, J = 9.3 Hz, 1H), 3.19 (d, J = 9.4 Hz, 1H),
3.13 (dq, J = 16.2, 11.1 Hz, 1H), 2.49 (d, J = 14.5 Hz, 1H), 2.36 (s,
3H), 2.35 (d, J = 14.4 Hz, 1H), 1.26 (s, 3H), 1.12 (s, 3H). 13C{1H}
NMR (150 MHz, CDCl3): δ 148.4, 143.1, 140.7, 136.4, 129.1, 128.7,
4
2
= 2.9 Hz), 61.9, 55.2, 53.4 (q, JC−F = 1.2 Hz), 43.9 (q, JC−F = 26.8
Hz), 36.6, 28.7, 27.4, 21.4. 19F NMR (470 MHz, CDCl3): δ −56.40
(t, J = 11.3 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C22H26F3NNaO3S 464.1478; found 464.1471.
2-(3-Methoxyphenyl)-4,4-dimethyl-1-tosyl-2-(2,2,2-
trifluoroethyl)pyrrolidine (2g). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 5:1) as a
1
1
126.7, 125.4 (q, JC−F = 276.8 Hz), 120.4 (q, JC−F = 255.9 Hz),
119.9, 68.7 (q, 3JC−F = 2.9 Hz), 62.1, 53.6 (q, 4JC−F = 1.2 Hz), 43.9 (q,
2JC−F = 27.1 Hz), 36.7, 28.6, 27.5, 21.4. 19F NMR (470 MHz,
1
white solid (71% yield, 31.4 mg). mp 124−125 °C. H NMR (600
MHz, CDCl3): δ 7.13 (t, J = 7.0 Hz, 3H), 7.06 (d, J = 7.9 Hz, 2H),
6.93 (d, J = 7.7 Hz, 1H), 6.75 (d, J = 11.6 Hz, 2H), 4.00 (dq, J = 16.3,
11.4 Hz, 1H), 3.67 (s, 3H), 3.45 (d, J = 9.3 Hz, 1H), 3.20−3.09 (m,
2H), 2.46 (d, J = 14.4 Hz, 1H), 2.37 (d, J = 17.3 Hz, 1H), 2.36 (s,
CDCl3): δ −56.37 (t, J = 11.8 Hz, 3F), −57.76 (s, 3F). HRMS (ESI-
TOF) m/z: [M + Na]+ Calcd for C22H23F6NNaO3S 518.1195; found
518.1191.
2-([1,1′-Biphenyl]-4-yl)-4,4-dimethyl-1-tosyl-2-(2,2,2-
trifluoroethyl)pyrrolidine (2l). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 5:1) as a
3H), 1.25 (s, 3H), 1.11 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3):
1
δ 159.1, 143.7, 142.6, 136.4, 129.0, 128.8, 126.9, 125.5 (q, JC−F
=
3
1
276.9 Hz), 119.4, 113.5, 112.7, 69.4 (q, JC−F = 2.6 Hz), 62.1, 55.0,
53.6 (q, JC−F = 1.2 Hz), 43.9 (q, JC−F = 27.0 Hz), 36.6, 28.8, 27.5,
white solid (65% yield, 31.7 mg). mp 103−104 °C. H NMR (600
4
2
MHz, CDCl3): δ 7.54 (d, J = 6.9 Hz, 2H), 7.45 (t, J = 7.7 Hz, 2H),
7.37 (t, J = 7.2 Hz, 1H), 7.36 (d, J = 9.0 Hz, 2H), 7.33 (d, J = 8.5 Hz,
21.4. 19F NMR (470 MHz, CDCl3): δ −56.33 (t, J = 11.1 Hz, 3F).
1994
https://dx.doi.org/10.1021/acs.joc.0c02637
J. Org. Chem. 2021, 86, 1987−1999

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
2H), 7.11 (d, J = 8.2 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 4.13 (dq, J =
16.3, 11.4 Hz, 1H), 3.52 (d, J = 9.3 Hz, 1H), 3.24 (d, J = 9.3 Hz, 1H),
3.16 (dq, J = 16.3, 11.2 Hz, 1H), 2.52 (d, J = 14.4 Hz, 1H), 2.43 (d, J
= 14.5 Hz, 1H), 2.29 (s, 3H), 1.29 (s, 3H), 1.16 (s, 3H). 13C{1H}
NMR (150 MHz, CDCl3): δ 140.9, 140.3, 140.2, 136.5, 129.0, 128.9,
127.6, 127.5, 126.9, 126.9, 126.4, 125.6 (q, 1JC−F = 276.8 Hz), 68.9 (q,
δ −56.37 (t, J = 10.3 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C24H28F3NNaO2S 474.1685; found 474.1667.
2-Phenyl-1-tosyl-2-(2,2,2-trifluoroethyl)pyrrolidine (2q). Purified
by silica gel column chromatography (the eluent was petroleum
ether/EtOAc 10:1) as a white solid (52% yield, 20.0 mg). mp 105−
1
106 °C. H NMR (600 MHz, CDCl3): δ 7.31−7.29 (m, 2H), 7.24−
4
2
3JC−F = 2.7 Hz), 62.2, 53.5 (q, JC−F = 1.2 Hz), 43.8 (q, JC−F = 26.9
7.20 (m, 3H), 7.10 (d, J = 7.8 Hz, 2H), 3.70 (ddd, J = 9.3, 7.7, 6.0 Hz,
1H), 3.54 (ddd, J = 9.2, 7.7, 6.4 Hz, 1H), 3.51−3.37 (m, 2H), 2.49−
2.39 (m, 2H), 2.37 (s, 3H), 2.05 (dq, J = 14.1, 7.1 Hz, 1H), 1.95 (dq,
J = 13.2, 6.8 Hz, 1H). 13C{1H} NMR (150 MHz, CDCl3): δ 142.74,
142.71, 129.1, 128.2, 127.4, 126.9, 126.6, 125.9 (q, 1JC−F = 276.6 Hz),
Hz), 36.7, 28.7, 27.4, 21.4. 19F NMR (470 MHz, CDCl3): δ −56.20
(t, J = 11.5 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C27H28F3NNaO2S 510.1685; found 510.1680.
4,4-Dimethyl-2-(naphthalen-2-yl)-1-tosyl-2-(2,2,2-trifluoroethyl)-
pyrrolidine (2m). Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 3:1) as a white solid (68% yield,
3
2
68.6 (q, JC−F = 2.4 Hz), 49.5, 41.8 (q, JC−F = 26.7 Hz), 40.9, 22.9,
21.4. 19F NMR (470 MHz, CDCl3): δ −58.35 (t, J = 11.0 Hz, 3F).
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C19H20F3NNaO2S
406.1059; found 406.1065.
1
31.4 mg). mp 126−127 °C. H NMR (600 MHz, CDCl3): δ 7.77−
7.71 (m, 3H), 7.52 (d, J = 8.8 Hz, 1H), 7.51−7.46 (m, 2H), 7.24 (dd,
J = 8.8, 2.2 Hz, 1H), 6.97 (d, J = 8.2 Hz, 2H), 6.73 (d, J = 8.0 Hz,
2H), 4.20 (dq, J = 16.4, 11.4 Hz, 1H), 3.56 (d, J = 9.3 Hz, 1H), 3.30
(d, J = 9.3 Hz, 1H), 3.23 (dq, J = 16.4, 11.2 Hz, 1H), 2.56 (d, J = 14.5
Hz, 1H), 2.51 (d, J = 14.5 Hz, 1H), 2.21 (s, 3H), 1.31 (s, 3H), 1.18
(s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 142.5, 139.0, 136.3,
132.5, 132.5, 128.8, 128.6, 127.6, 127.1, 126.6, 126.5, 126.3, 126.2,
1-(4-((4,4-Dimethyl-2-phenyl-2-(2,2,2-trifluoroethyl)pyrrolidin-1-
yl)sulfonyl)phenyl)ethan-1-one (2r). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 3:1) as a
white solid (60% yield, 26.4 mg). mp 93−94 °C. 1H NMR (600 MHz,
CDCl3): δ 7.77 (d, J = 8.4 Hz, 2H), 7.25−7.20 (m, 5H), 7.14 (t, J =
15.6 Hz, 2H), 4.07 (dq, J = 16.4, 11.4 Hz, 1H), 3.54 (d, J = 9.6 Hz,
1H), 3.21 (d, J = 9.3 Hz, 1H), 3.16 (dq, J = 16.2, 11.4 Hz, 1H), 2.61
(s, 3H), 2.52 (d, J = 14.5 Hz, 1H), 2.40 (d, J = 14.5 Hz, 1H), 1.30 (s,
3H), 1.15 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ 196.9,
1
3
125.7 (q, JC−F = 276.9 Hz), 69.2 (q, JC−F = 2.8 Hz), 62.4, 53.4 (q,
4JC−F = 1.0 Hz), 43.8 (q, JC−F = 27.0 Hz), 36.7, 28.8, 27.5, 21.3. 19F
2
NMR (470 MHz, CDCl3): δ −56.16 (t, J = 10.8 Hz, 3F). HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C25H26F3NNaO2S 484.1529;
found 484.1538.
1
142.9, 141.7, 139.1, 128.2, 128.0, 127.7, 127.0, 127.0, 125.4 (q, JC−F
= 277.4 Hz), 69.4 (q, 3JC−F = 2.9 Hz), 62.3, 53.5 (q, 4JC−F = 1.2 Hz),
43.7 (q, 2JC−F = 27.1 Hz), 36.8, 27.7, 27.4, 26.8. 19F NMR (470 MHz,
CDCl3): δ −56.20 (t, J = 11.3 Hz, 3F). HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C22H24F3NNaO3S 462.1321; found 462.1320.
2-(Benzo[d][1,3]dioxol-5-yl)-4,4-dimethyl-1-tosyl-2-(2,2,2-
trifluoroethyl)pyrrolidine (2n). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 4:1) as a
1
white solid (58% yield, 26.5 mg). mp 124−125 °C. H NMR (600
4,4-Dimethyl-2-phenyl-2-(2,2,2-trifluoroethyl)-1-((4-
(trifluoromethyl)phenyl)sulfonyl)-pyrrolidine (2s). Purified by silica
gel column chromatography (the eluent was petroleum ether/EtOAc
6:1) as a white solid (87% yield, 40.5 mg). mp 145−146 °C. 1H NMR
(600 MHz, CDCl3): δ 7.45 (d, J = 8.2 Hz, 2H), 7.22−7.18 (m, 5H),
7.11 (t, J = 7.8 Hz, 2H), 4.11 (dq, J = 16.4, 11.4 Hz, 1H), 3.59 (d, J =
9.2 Hz, 1H), 3.19−3.11 (m, 2H), 2.55 (d, J = 14.6 Hz, 1H), 2.39 (d, J
= 14.6 Hz, 1H), 1.33 (s, 3H), 1.18 (s, 3H). 13C{1H} NMR (150
MHz, CDCl3): δ 7.20 (d, J = 8.1 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H),
6.85 (dd, J = 8.3, 2.1 Hz, 1H), 6.64 (d, J = 8.3 Hz, 1H), 6.61 (d, J =
2.1 Hz, 1H), 5.90 (dd, J = 27.1, 1.5 Hz, 2H), 4.00 (dq, J = 16.3, 11.4
Hz, 1H), 3.47 (d, J = 9.3 Hz, 1H), 3.18 (d, J = 9.3 Hz, 1H), 3.08 (dq,
J = 16.3, 11.1 Hz, 1H), 2.43 (d, J = 14.5 Hz, 1H), 2.37 (s, 3H), 2.32
(d, J = 14.4 Hz, 1H), 1.25 (s, 3H), 1.13 (s, 3H). 13C{1H} NMR (150
MHz, CDCl3): δ 147.4, 146.9, 142.6, 136.6, 135.9, 128.9, 126.9, 125.5
(q, 1JC−F = 276.8 Hz), 120.6, 107.9, 107.0, 101.2, 69.1 (q, 3JC−F = 2.7
2
MHz, CDCl3): δ 142.4, 141.4, 133.4 (q, JC−F = 32.9 Hz), 128.0,
127.8, 127.1, 127.0, 125.5 (3JC−F, J = 3.7 Hz), 125.4 (q, 1JC−F = 277.0
Hz), 123.3 (q, 1JC−F = 271.0 Hz), 69.1 (q, 3JC−F = 2.7 Hz), 62.5, 53.6
4
2
Hz), 62.0, 53.5 (q, JC−F = 1.2 Hz), 44.1 (q, JC−F = 26.7 Hz), 36.5,
28.7, 27.4, 21.4. 19F NMR (470 MHz, CDCl3): δ −56.29 (t, J = 10.8
Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C22H24F3NNaO4S 478.1270; found 478.1274.
4
2
(q, JC−F = 1.2 Hz), 43.7 (q, JC−F = 27.3 Hz), 36.8, 28.6, 27.4. 19F
NMR (470 MHz, CDCl3): δ −56.07 (t, J = 11.5 Hz, 3F), −63.15 (s,
3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H21F6NNaO2S
488.1089; found 488.1069.
3-Phenyl-2-tosyl-3-(2,2,2-trifluoroethyl)-2-azaspiro[4.4]nonane
(2o). Purified by silica gel column chromatography (the eluent was
petroleum ether/EtOAc 7:1) as a white solid (71% yield, 31.1 mg).
mp 122−123 °C. 1H NMR (600 MHz, CDCl3): δ 7.32 (d, J = 7.4 Hz,
2H), 7.21 (t, J = 7.2 Hz, 1H), 7.18 (t, J = 7.5 Hz, 2H), 7.10 (d, J = 8.1
Hz, 2H), 7.05 (d, J = 8.1 Hz, 2H), 3.95 (dq, J = 16.2, 11.4 Hz, 1H),
3.49 (d, J = 9.1 Hz, 1H), 3.23 (d, J = 9.1 Hz, 1H), 3.16 (dq, J = 16.2,
11.2 Hz, 1H), 2.55 (s, 2H), 2.35 (s, 3H), 1.88−1.81 (m, 1H), 1.75−
1.69 (m, 1H), 1.68−1.60 (m, 3H), 1.60−1.57 (m, 2H), 1.49−1.42
(m, 1H). 13C{1H} NMR (150 MHz, CDCl3): δ 142.6, 142.0, 136.7,
129.1, 127.8, 127.4, 127.2, 126.8, 125.5 (q, 1JC−F = 276.9 Hz), 69.1 (q,
1-((4-Chlorophenyl)sulfonyl)-4,4-dimethyl-2-phenyl-2-(2,2,2-
trifluoroethyl)pyrrolidine (2t). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 7:1) as a
1
white solid (80% yield, 34.6 mg). mp 125−126 °C. H NMR (600
MHz, CDCl3): δ 7.24 (t, J = 9.0 Hz, 3H), 7.20−7.17 (m, 4H), 7.05
(d, J = 8.6 Hz, 2H), 4.07 (dq, J = 16.4, 11.3 Hz, 1H), 3.50 (d, J = 9.2
Hz, 1H), 3.17 (d, J = 9.0 Hz, 1H), 3.15 (dq, J = 16.2, 11.4 Hz, 1H),
2.52 (d, J = 14.5 Hz, 1H), 2.40 (d, J = 14.5 Hz, 1H), 1.30 (s, 3H),
1.15 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ 141.7, 138.3,
3JC−F = 2.7 Hz), 60.8, 51.8 (q, 4JC−F = 1.2 Hz), 47.7, 43.2 (q, 2JC−F
=
137.6, 128.6, 128.2, 128.0, 127.7, 127.0, 125.4 (q, JC−F = 276.8 Hz),
1
69.2 (q, 3JC−F = 2.7 Hz), 62.2, 53.5 (q, 4JC−F = 1.2 Hz), 43.7 (q, 2JC−F
= 27.1 Hz), 36.8, 28.7, 27.4. 19F NMR (470 MHz, CDCl3): δ −56.18
(t, J = 11.3 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C20H21ClF3NNaO2S 454.0826; found 454.0770.
26.9 Hz), 38.8, 37.7, 24.6, 24.4, 21.4. 19F NMR (470 MHz, CDCl3): δ
−56.43 (t, J = 11.3 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C23H26F3NNaO2S 460.1529; found 460.1519.
3-Phenyl-2-tosyl-3-(2,2,2-trifluoroethyl)-2-azaspiro[4.5]decane
(2p). Purified by silica gel column chromatography (the eluent was
petroleum ether/EtOAc 7:1) as a white solid (75% yield, 33.9 mg).
mp 123−124 °C. 1H NMR (600 MHz, CDCl3): δ 7.32 (d, J = 7.3 Hz,
2H), 7.22−7.17 (m, 3H), 7.14 (d, J = 8.1 Hz, 2H), 7.05 (d, J = 8.0
Hz, 2H), 4.02 (dq, J = 16.1, 11.3 Hz, 1H), 3.56 (d, J = 9.7 Hz, 1H),
3.14 (d, J = 9.7 Hz, 1H), 3.07 (dq, J = 16.0, 11.1 Hz, 1H), 2.46 (d, J =
14.4 Hz, 1H), 2.39 (d, J = 14.5 Hz, 1H), 2.35 (s, 3H), 1.63−1.58 (m,
1H), 1.54−1.51 (m, 2H), 1.48−1.41 (m, 4H), 1.41−1.33 (m, 3H).
13C{1H} NMR (150 MHz, CDCl3): δ 142.6, 142.1, 136.7, 129.1,
4-((4,4-Dimethyl-2-phenyl-2-(2,2,2-trifluoroethyl)pyrrolidin-1-yl)-
sulfonyl)benzonitrile (2u). Purified by silica gel column chromatog-
raphy (the eluent was petroleum ether/EtOAc 8:1) as a white solid
(79% yield, 33.4 mg). mp 152−153 °C. 1H NMR (600 MHz,
CDCl3): δ 7.47 (d, J = 8.2 Hz, 2H), 7.22 (t, J = 7.2 Hz, 1H), 7.20−
7.12 (m, 6H), 4.09 (dq, J = 16.4, 11.5 Hz, 1H), 3.59 (d, J = 9.2 Hz,
1H), 3.20−3.12 (m, 2H), 2.55 (d, J = 14.6 Hz, 1H), 2.40 (d, J = 14.6
Hz, 1H), 1.33 (s, 3H), 1.19 (s, 3H). 13C{1H} NMR (150 MHz,
CDCl3): δ 143.0, 141.4, 132.2, 128.1, 127.9, 127.2, 127.0, 125.3 (q,
3
1JC−F = 276.9 Hz), 117.4, 115.3, 69.2 (q, JC−F = 2.9 Hz), 62.5, 53.5
127.9, 127.4, 127.1, 126.9, 125.6 (q, 1JC−F = 276.8 Hz), 68.9 (q, 3JC−F
= 2.3 Hz), 59.5, 51.4 (q, JC−F = 1.2 Hz), 44.0 (q, JC−F = 26.8 Hz),
(q, JC−F = 1.2 Hz), 43.6 (q, JC−F = 27.2 Hz), 36.9, 28.5, 27.4. 19F
NMR (470 MHz, CDCl3): δ −56.05 (t, J = 11.3 Hz, 3F). HRMS
4
2
4
2
40.4, 37.4, 36.9, 25.6, 23.6, 23.2, 21.4. 19F NMR (470 MHz, CDCl3):
1995
https://dx.doi.org/10.1021/acs.joc.0c02637
J. Org. Chem. 2021, 86, 1987−1999

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
4
2
(ESI-TOF) m/z: [M + Na]+ Calcd for C21H21F3N2NaO2S 445.1168;
found 445.1142.
2.6 Hz), 62.5, 53.6 (q, JC−F = 1.2 Hz), 43.8 (q, JC−F = 27.2 Hz),
36.8, 34.3, 31.3, 28.5, 27.4. 19F NMR (470 MHz, CDCl3): δ −56.04
(t, J = 10.8 Hz, 3F), −63.04 (s, 3F). HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C25H29F6NNaO2S 544.1715; found 544.1720.
1-((4-Chlorophenyl)sulfonyl)-2-(4-fluorophenyl)-4,4-dimethyl-2-
(2,2,2-trifluoroethyl)pyrrolidine (2aa). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 9:1) as a
4,4-Dimethyl-1-((4-nitrophenyl)sulfonyl)-2-phenyl-2-(2,2,2-
trifluoroethyl)pyrrolidine (2v). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 4:1)as a
1
white solid (74% yield, 32.8 mg). mp 126−127 °C. H NMR (600
MHz, CDCl3): δ 8.02 (d, J = 8.8 Hz, 2H), 7.25−7.20 (m, 5H), 7.15−
7.13 (m, 2H), 4.10 (dq, J = 16.2, 11.4 Hz, 1H), 3.61 (d, J = 9.0 Hz,
1H), 3.22−3.14 (m, 2H), 2.57 (d, J = 14.6 Hz, 1H), 2.41 (d, J = 14.6
Hz, 1H), 1.35 (s, 3H), 1.20 (s, 3H). 13C{1H} NMR (150 MHz,
CDCl3): δ 149.3, 144.5, 141.5, 128.1, 128.0, 127.9, 127.0, 125.3 (q,
1JC−F = 276.8 Hz), 69.2 (q, 3JC−F = 2.9 Hz), 62.6, 53.5 (q, 4JC−F = 1.2
1
white solid (90% yield, 40.5 mg). mp 142−143 °C. H NMR (600
MHz, CDCl3): δ 7.27−7.24 (m, 4H), 7.16 (d, J = 8.6 Hz, 2H), 6.88
(t, J = 8.6 Hz, 2H), 4.01 (dq, J = 16.3, 11.3 Hz, 1H), 3.47 (d, J = 9.3
Hz, 1H), 3.17 (d, J = 9.6 Hz, 1H), 3.12 (dq, J = 16.2, 10.8 Hz, 1H),
2.50 (d, J = 14.5 Hz, 1H), 2.36 (d, J = 14.5 Hz, 1H), 1.27 (s, 3H),
1.13 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ 162.0 (d, 1JC−F
=
=
=
Hz), 43.6 (q, 2JC−F = 27.2 Hz), 36.9, 28.6, 27.4. 19F NMR (470 MHz,
CDCl3): δ −56.06 (t, J = 10.8 Hz, 3F). HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C20H21F3N2NaO4S 465.1066; found 465.1070.
4,4-Dimethyl-2-phenyl-2-(2,2,2-trifluoroethyl)-1-((4-
(trifluoromethoxy)phenyl)-sulfonyl)pyrrolidine (2w). Purified by
silica gel column chromatography (the eluent was petroleum ether/
EtOAc 5:1) as a white solid (76% yield, 36.6 mg). mp 111−112 °C.
1H NMR (600 MHz, CDCl3): δ 7.19 (t, J = 7.8 Hz, 3H), 7.14−7.11
4
3
246.9 Hz), 138.7, 137.7, 137.7 (d, JC−F = 3.5 Hz), 128.9 (d, JC−F
1
2
8.1 Hz), 128.8, 128.2, 125.3 (q, JC−F = 276.8 Hz), 114.7 (d, JC−F
21.2 Hz), 69.0 (q, 3JC−F = 2.4 Hz), 62.1, 53.5 (q, 4JC−F = 1.2 Hz), 43.8
(q, 2JC−F = 27.1 Hz), 36.7, 28.6, 27.5. 19F NMR (470 MHz, CDCl3): δ
−56.34 (t, J = 10.8 Hz, 3F), −114.47 to −114.53 (m, 1F). HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C20H20ClF4NNaO2S
472.0732; found 472.0710.
(m, 4H), 7.01 (d, J = 8.4 Hz, 2H), 4.12 (dq, J = 16.3, 11.4 Hz, 1H),
3.58 (d, J = 9.2 Hz, 1H), 3.21 (d, J = 9.6 Hz, 1H), 3.15 (dq, J = 16.8,
11.4 Hz, 1H), 2.54 (d, J = 14.6 Hz, 1H), 2.39 (d, J = 14.5 Hz, 1H),
1.33 (s, 3H), 1.19 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ
151.1, 141.5, 137.5, 128.7, 128.0, 127.7, 127.0, 125.4 (q, 1JC−F = 276.8
2-(4-Fluorophenyl)-4,4-dimethyl-2-(2,2,2-trifluoroethyl)-1-((4-
(trifluoromethyl)phenyl)-sulfonyl)pyrrolidine (2ab). Purified by
silica gel column chromatography (the eluent was petroleum ether/
EtOAc 7:1) as a white solid (86% yield, 41.6 mg). mp 122−123 °C.
1H NMR (600 MHz, CDCl3): δ 7.54 (d, J = 8.2 Hz, 2H), 7.33 (d, J =
8.1 Hz, 2H), 7.21 (d, J = 8.4 Hz, 1H), 7.20 (d, J = 8.4 Hz, 1H), 6.81
(t, J = 8.6 Hz, 2H), 4.04 (dq, J = 16.3, 11.2 Hz, 1H), 3.56 (d, J = 9.3
Hz, 1H), 3.23 (d, J = 9.3 Hz, 1H), 3.14 (dq, J = 16.4, 10.9 Hz, 1H),
2.53 (d, J = 14.6 Hz, 1H), 2.35 (d, J = 14.6 Hz, 1H), 1.30 (s, 3H),
1
3
Hz), 120.4, 120.2 (q, JC−F = 257.3 Hz), 68.9 (q, JC−F = 2.6 Hz),
4
2
62.4, 53.6 (q, JC−F = 1.2 Hz), 43.7 (q, JC−F = 27.1 Hz), 36.8, 28.6,
27.4. 19F NMR (470 MHz, CDCl3): δ −56.06 (t, J = 11.3 Hz, 3F),
−57.73 (s, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C21H21F6NNaO3S 504.1039; found 504.1027.
1.17 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ 162.1 (d, 1JC−F
=
4
2
1-(Mesitylsulfonyl)-4,4-dimethyl-2-phenyl-2-(2,2,2-
trifluoroethyl)pyrrolidine (2x). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 6:1) as a
247.5 Hz), 142.6, 137.5 (d, JC−F = 3.5 Hz), 133.7 (q, JC−F = 32.8
Hz), 128.8 (d, 3JC−F = 8.1 Hz), 127.1, 125.6 (q, 3JC−F = 3.6 Hz), 125.2
(q, 1JC−F = 276.8 Hz), 123.2 (q, 1JC−F = 271.1 Hz), 114.7 (d, 2JC−F
=
1
21.3 Hz), 68.9 (q, 3JC−F = 2.7 Hz), 62.4, 53.5 (q, 4JC−F = 1.2 Hz), 43.8
(q, 2JC−F = 27.2 Hz), 36.8, 28.5, 27.5. 19F NMR (470 MHz, CDCl3): δ
−56.26 (t, J = 10.8 Hz, 3F), −63.17 (s, 3F), −114.25 to −114.30 (m,
1F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H20F7NNaO2S
506.0995; found 506.0992.
white solid (70% yield, 30.8 mg). mp 122−123 °C. H NMR (600
MHz, CDCl3): δ 7.57 (d, J = 7.4 Hz, 2H), 7.30−7.26 (m, 3H), 6.86
(s, 2H), 4.22 (dq, J = 15.6, 11.1 Hz, 1H), 3.11 (dq, J = 15.6, 10.6 Hz,
1H), 3.02 (d, J = 9.8 Hz, 1H), 2.91 (d, J = 9.8 Hz, 1H), 2.70 (d, J =
14.5 Hz, 1H), 2.51 (s, 6H), 2.31 (d, J = 14.5 Hz, 1H), 2.26 (s, 3H),
1.20 (s, 3H), 1.11 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ
4,4-Dimethyl-1-(methylsulfonyl)-2-phenyl-2-(2,2,2-
trifluoroethyl)pyrrolidine (2ac). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 15:1) as a
white solid (85% yield, 28.5 mg). mp 59−60 °C. 1H NMR (600 MHz,
CDCl3): δ 7.54 (d, J = 7.7 Hz, 2H), 7.41 (t, J = 7.8 Hz, 2H), 7.33 (t, J
= 7.3 Hz, 1H), 3.91 (dq, J = 16.3, 11.2 Hz, 1H), 3.38 (d, J = 9.3 Hz,
1H), 3.22 (d, J = 9.3 Hz, 1H), 3.09 (dq, J = 16.3, 11.1 Hz, 1H), 2.57
(d, J = 18.6 Hz, 1H), 2.55 (d, J = 19.2 Hz, 1H), 2.13 (s, 3H), 1.30 (s,
3H), 1.20 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ 141.0,
1
142.8, 139.9, 139.7, 133.9, 132.0, 128.0, 127.9, 127.7, 125.7 (q, JC−F
= 276.8 Hz), 70.7 (q, 3JC−F = 2.5 Hz), 60.2, 52.1 (q, 4JC−F = 1.2 Hz),
43.2 (q, 2JC−F = 26.7 Hz), 35.9, 30.0, 27.6, 22.9, 20.9. 19F NMR (470
MHz, CDCl3): δ −56.71 (t, J = 10.11 Hz, 3F). HRMS (ESI-TOF) m/
z: [M + Na]+ Calcd for C23H28F3NNaO2S 462.1685; found 462.1689.
2-(4-(tert-Butyl)phenyl)-1-((4-chlorophenyl)sulfonyl)-4,4-dimeth-
yl-2-(2,2,2-trifluoroethyl)-pyrrolidine (2y). Purified by silica gel
column chromatography (the eluent was petroleum ether/EtOAc
7:1) as a white solid (79% yield, 38.6 mg). mp 117−118 °C. 1H NMR
(600 MHz, CDCl3): δ 7.15−7.10 (m, 6H), 7.00 (d, J = 8.6 Hz, 2H),
4.10 (dq, J = 16.3, 11.5 Hz, 1H), 3.56 (d, J = 9.2 Hz, 1H), 3.19 (d, J =
9.2 Hz, 1H), 3.12 (dq, J = 16.2, 11.4 Hz, 1H), 2.52 (d, J = 14.5 Hz,
1H), 2.38 (d, J = 14.6 Hz, 1H), 1.32 (s, 3H), 1.31 (s, 9H), 1.18 (s,
3H). 13C{1H} NMR (150 MHz, CDCl3): δ 150.7, 138.3, 138.0, 137.7,
1
3
128.4, 128.1, 126.9, 125.5 (q, JC−F = 276.8 Hz), 69.2 (q, JC−F = 2.7
4
2
Hz), 61.3, 52.5 (q, JC−F = 1.4 Hz), 43.4 (q, JC−F = 26.8 Hz), 37.5,
36.1, 29.3, 27.2. 19F NMR (470 MHz, CDCl3): δ −56.50 (t, J = 11.5
Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C15H20F3NNaO2S 358.1059; found 358.1069.
1-(Ethylsulfonyl)-4,4-dimethyl-2-phenyl-2-(2,2,2-trifluoroethyl)-
pyrrolidine (2ad). Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 15:1) as a white solid (80% yield,
28.0 mg). mp 61−63 °C. 1H NMR (600 MHz, CDCl3): δ 7.56 (d, J =
8.2 Hz, 2H), 7.40−7.38 (m, 2H), 7.32 (t, J = 7.3 Hz, 1H), 3.90 (dq, J
= 16.2, 11.3 Hz, 1H), 3.40 (d, J = 9.5 Hz, 1H), 3.28 (d, J = 9.5 Hz,
1H), 3.07 (dq, J = 16.2, 11.1 Hz, 1H), 2.58 (d, J = 14.4 Hz, 1H), 2.51
(d, J = 14.4 Hz, 1H), 2.46−2.40 (m, 1H), 2.13−2.07 (m, 1H), 1.28
(s, 3H), 1.18 (s, 3H), 1.17 (t, J = 7.5 Hz, 3H). 13C{1H} NMR (150
1
3
128.5, 128.2, 126.7, 125.5 (q, JC−F = 277.0 Hz), 68.6 (q, JC−F = 2.6
4
2
Hz), 62.4, 53.6 (q, JC−F = 1.2 Hz), 43.8 (q, JC−F = 27.1 Hz), 36.7,
34.4, 31.4, 28.6, 27.4. 19F NMR (470 MHz, CDCl3): δ −56.04 (t, J =
10.6 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C24H29F3NNaO2S 510.1452; found 510.1435.
2-(4-(tert-Butyl)phenyl)-4,4-dimethyl-2-(2,2,2-trifluoroethyl)-1-
((4-(trifluoromethyl)phenyl)-sulfonyl)pyrrolidine (2z). Purified by
silica gel column chromatography (the eluent was petroleum ether/
EtOAc 7:1) as a white solid (63% yield, 32.9 mg). mp 124−125 °C.
1H NMR (600 MHz, CDCl3): δ 7.42 (d, J = 8.2 Hz, 2H), 7.17 (d, J =
1
MHz, CDCl3): δ 141.7, 128.3, 128.0, 127.0, 125.6 (q, JC−F = 276.8
3
4
Hz), 69.3 (q, JC−F = 2.6 Hz), 61.8, 52.7 (q, JC−F = 1.4 Hz), 46.2,
43.3 (q, JC−F = 26.7 Hz), 36.1, 29.2, 27.6, 7.8. 19F NMR (470 MHz,
2
8.1 Hz, 2H), 7.12 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.5 Hz, 2H), 4.13
(dq, J = 16.4, 11.4 Hz, 1H), 3.62 (d, J = 9.2 Hz, 1H), 3.21 (d, J = 9.2
Hz, 1H), 3.15 (dq, J = 16.2, 11.4 Hz, 1H), 2.54 (d, J = 14.7 Hz, 1H),
2.38 (d, J = 14.6 Hz, 1H), 1.35 (s, 3H), 1.29 (s, 9H), 1.20 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3): δ 150.8, 142.5, 138.3, 133.3 (q,
2JC−F = 32.7 Hz), 127.2, 126.7, 125.4 (q, 1JC−F = 276.8 Hz), 125.3 (q,
CDCl3): δ −56.57 (t, J = 10.8 Hz, 3F). HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C16H22F3NNaO2S 372.1216; found 372.1210.
1-(Benzylsulfonyl)-4,4-dimethyl-2-phenyl-2-(2,2,2-trifluoroethyl)-
pyrrolidine (2ae). Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 10:1) as a white solid (80% yield,
33.0 mg). mp 86−87 °C. 1H NMR (600 MHz, CDCl3): δ 7.60 (d, J =
1
3
3JC−F = 3.6 Hz), 124.8, 123.3 (q, JC−F = 271.1 Hz), 68.6 (q, JC−F
=
1996
https://dx.doi.org/10.1021/acs.joc.0c02637
J. Org. Chem. 2021, 86, 1987−1999

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
7.4 Hz, 2H), 7.43 (t, J = 7.8 Hz, 2H), 7.35 (t, J = 7.4 Hz, 1H), 7.31−
7.30 (m, 3H), 7.17−7.16 (m, 2H), 3.86 (dq, J = 15.8, 11.3 Hz, 1H),
3.75 (d, J = 13.5 Hz, 1H), 3.32 (d, J = 9.6 Hz, 1H), 3.24 (d, J = 13.5
Hz, 1H), 3.17 (d, J = 9.6 Hz, 1H), 2.72 (dq, J = 16.2, 11.1 Hz, 1H),
2.60 (d, J = 14.2 Hz, 1H), 2.42 (d, J = 14.2 Hz, 1H), 1.24 (s, 3H),
1.08 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ 141.2, 130.8,
128.6, 128.4, 128.2, 127.2, 125.5 (q, 1JC−F = 276.8 Hz), 69.7 (q, 3JC−F
= 2.7 Hz), 61.8, 57.6, 52.4 (q, JC−F = 1.2 Hz), 43.5 (q, JC−F = 26.7
Hz), 36.1, 29.4, 27.6. 19F NMR (470 MHz, CDCl3): δ −56.67 (t, J =
10.8 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C21H24F3NNaO2S 358.1059; found 358.1069.
was petroleum ether/EtOAc 3:1) as a white solid (23% yield, 10.3
mg). mp 108−109 °C. H NMR (600 MHz, CDCl3): δ 7.67 (d, J =
1
7.9 Hz, 2H), 7.51 (d, J = 7.8 Hz, 2H), 7.32−7.27 (m, 5H), 4.59 (t, J =
7.3 Hz, 1H), 2.93 (qt, J = 9.7, 4.9 Hz, 2H), 2.69 (dd, J = 12.9, 6.9 Hz,
1H), 2.47 (dd, J = 13.0, 7.4 Hz, 1H), 2.43 (s, 3H), 2.33−2.23 (m,
2H), 0.71 (s, 3H), 0.71 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3):
δ 143.4, 140.5, 137.0, 129.7, 128.3, 127.9, 127.0, 126.5, 124.6 (q, 1JC−F
= 277.4 Hz), 70.8 (q, 3JC−F = 2.3 Hz), 54.1 (d, 4JC−F = 1.2 Hz), 51.7,
50.8 (q, 2JC−F = 26.7 Hz), 35.9, 26.8, 26.7, 21.5. 19F NMR (470 MHz,
CDCl3): δ −58.55 (t, J = 9.4 Hz, 3F). HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C21H25ClF3NNaO2S 470.1139; found 470.1126.
(Z)-4-Methyl-N-(6,6,6-trifluoro-2,2-dimethyl-4-phenylhex-4-en-
1-yl)benzenesulfonamide ((Z)-4a). Isolated under the conditions of
entry 8 in Table 1. Purified by silica gel column chromatography (the
eluent was petroleum ether/EtOAc 2:1) as a white solid (12% yield,
5.0 mg). mp 96−97 °C. 1H NMR (600 MHz, CDCl3): δ 7.53 (d, J =
8.2 Hz, 2H), 7.33−7.31 (m, 3H), 7.27 (d, J = 8.5 Hz, 2H), 7.21−7.20
(m, 2H), 5.65 (q, J = 8.2 Hz, 1H), 3.92 (t, J = 7.2 Hz, 1H), 2.47 (d, J
= 7.4 Hz, 2H), 2.43 (s, 5H), 0.80 (s, 6H). 13C{1H} NMR (150 MHz,
4
2
(E)-4,4-Dimethyl-2-phenyl-1-(styrylsulfonyl)-2-(2,2,2-
trifluoroethyl)pyrrolidine (2af). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 12:1) as a
white solid (66% yield, 28.0 mg). mp 91−92 °C. 1H NMR (600 MHz,
CDCl3): δ 7.54 (d, J = 7.7 Hz, 2H), 7.40 (t, J = 7.5 Hz, 2H), 7.37−
7.33 (m, 4H), 7.17 (d, J = 6.6 Hz, 2H), 7.09 (d, J = 15.4 Hz, 1H),
5.27 (d, J = 15.4 Hz, 1H), 4.05 (dq, J = 16.3, 11.2 Hz, 1H), 3.33 (d, J
= 9.4 Hz, 1H), 3.16−3.07 (m, 2H), 2.56 (s, 2H), 1.32 (s, 3H), 1.19
(s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ 141.5, 141.4, 132.6,
3
CDCl3): δ 150.4 (q, JC−F = 5.4 Hz), 143.4, 138.9, 136.8, 129.6,
1
1
128.5, 128.4, 127.6, 127.0, 122.3 (q, JC−F = 269.6 Hz), 119.2 (q,
130.6, 128.9, 128.4, 128.2, 128.1, 127.2, 125.5 (q, JC−F = 276.8 Hz),
2JC−F = 33.4 Hz), 52.8, 49.0, 35.5, 25.5, 21.5. 19F NMR (470 MHz,
123.2, 68.8 (q, 3JC−F = 2.7 Hz), 61.1, 52.6 (q, 4JC−F = 1.8 Hz), 43.9 (q,
2JC−F = 26.9 Hz), 36.4, 29.5, 27.1. 19F NMR (470 MHz, CDCl3): δ
−56.23 (t, J = 11.3 Hz, 3F) HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C22H24F3NNaO2S 446.1372; found 446.1358.
CDCl3): δ −55.82 (d, J = 8.5 Hz, 3F). HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C21H24F3NNaO2S 434.1372; found 434.1374.
(E)-N-(6,6,6-Trifluoro-2,2-dimethyl-4-phenylhex-4-en-1-yl)-
benzamide ((E)-4ai). Purified by silica gel column chromatography
(the eluent was petroleum ether/EtOAc 5:1) as a white solid (25%
4,4-Dimethyl-1-tosyl-2-(2,2,2-trifluoroethyl)pyrrolidine (2ag).
Purified by silica gel column chromatography (the eluent was
petroleum ether/EtOAc 20:1) as a white solid (80% yield, 26.9 mg).
mp 118−119 °C. 1H NMR (600 MHz, CDCl3): δ 7.73 (d, J = 8.2 Hz,
2H), 7.35 (d, J = 8.0 Hz, 2H), 3.72−3.67 (m, 1H), 3.43−3.34 (m,
1H), 3.18 (d, J = 10.6 Hz, 1H), 3.06 (d, J = 10.6 Hz, 1H), 2.44 (s,
3H), 2.34−2.25 (m, 1H), 1.86 (dd, J = 13.1, 7.3 Hz, 1H), 1.60 (dd, J
= 13.1, 8.4 Hz, 1H), 1.05 (s, 3H), 0.45 (s, 3H). 13C{1H} NMR (150
1
yield, 9.1 mg). mp 95−96 °C. H NMR (600 MHz, CDCl3): δ 7.69
(d, J = 7.4 Hz, 2H), 7.50 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H),
7.38−7.34 (m, 5H), 6.01 (t, J = 6.7 Hz, 1H), 5.73 (q, J = 8.8 Hz, 1H),
3.17 (d, J = 6.5 Hz, 2H), 2.81 (s, 2H), 0.82 (s, 6H). 13C{1H} NMR
(150 MHz, CDCl3): δ 167.7, 151.8 (q, 3JC−F = 5.4 Hz), 142.6, 134.8,
1
131.4, 128.85, 128.81, 128.6, 126.8, 126.7, 123.2 (q, JC−F = 269.4
Hz), 119.7 (q, 2JC−F = 33.2 Hz), 49.9, 39.7, 36.6, 25.7. 19F NMR (470
MHz, CDCl3): δ −56.30 (d, J = 8.5 Hz). HRMS (ESI-TOF) m/z: [M
+ Na]+ Calcd for C21H22F3NNaO 384.1546; found 384.1536.
2,4,4-Trimethyl-2-phenyl-1-tosylpyrrolidine (5a). Isolated under
the conditions of entry 4 in Table 1. Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 4:1) as a
1
MHz, CDCl3): δ 143.9, 133.7, 129.8, 127.7, 126.0 (q, JC−F = 275.5
3
2
Hz), 61.1, 54.5 (q, JC−F = 3.2 Hz), 46.8, 40.9 (q, JC−F = 26.4 Hz),
37.5, 26.3, 25.5, 21.6. 19F NMR (470 MHz, CDCl3): δ −63.75 (t, J =
11.3 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C15H20F3NNaO2S 358.1059; found 358.1047.
4,4-Dimethyl-2-(2,2,2-trifluoroethyl)-1-((4-(trifluoromethyl)-
phenyl)sulfonyl)pyrrolidine (2ah). Purified by silica gel column
chromatography (the eluent was petroleum ether/EtOAc 20:1) as a
1
white solid (35% yield, 12.1 mg). mp 122−123 °C. H NMR (600
MHz, CDCl3): δ 7.52 (d, J = 8.1 Hz, 2H), 7.40 (d, J = 7.8 Hz, 2H),
7.25 (t, J = 7.6 Hz, 2H), 7.19 (d, J = 7.9 Hz, 3H), 3.39−3.33 (m, 2H),
2.40 (s, 3H), 2.19 (d, J = 13.1 Hz, 1H), 1.97 (d, J = 13.2 Hz, 1H),
1.93 (s, 3H), 1.06 (s, 3H), 0.97 (s, 3H). 13C{1H} NMR (150 MHz,
CDCl3): δ 147.6, 142.6, 137.7, 129.2, 128.0, 127.4, 126.4, 125.9, 70.6,
62.6, 59.8, 36.7, 28.3, 28.1, 27.5, 21.5. HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C20H25NNaO2S 366.1498; found 366.1486.
1
white solid (78% yield, 30.4 mg). mp 126−127 °C. H NMR (600
MHz, CDCl3): δ 7.98 (d, J = 8.0 Hz, 2H), 7.84 (d, J = 8.2 Hz, 2H),
3.77−3.72 (m, 1H), 3.39−3.30 (m, 1H), 3.21 (d, J = 10.6 Hz, 1H),
3.08 (dd, J = 10.6, 1.4 Hz, 1H), 2.37−2.28 (m, 1H), 1.91 (dd, J =
13.2, 7.3 Hz, 1H), 1.64 (dd, J = 13.1, 8.3 Hz, 1H), 1.07 (s, 3H), 0.49
2
(s, 3H). 13C{1H} NMR (150 MHz, CDCl3): δ 140.5, 134.8 (q, JC−F
= 32.9 Hz), 128.1, 126.4 (q, 3JC−F = 3.7 Hz), 125.8 (q, 1JC−F = 275.5
Hz), 123.2 (q, 1JC−F = 271.2 Hz), 61.2, 54.8 (q, 3JC−F = 3.3 Hz), 46.7,
2-(4-Methoxyphenyl)-2,4,4-trimethyl-1-tosylpyrrolidine (5f). Pu-
rified by silica gel column chromatography (the eluent was petroleum
ether/EtOAc 3:1) as a white solid (40% yield, 13.8 mg). mp 93−94
°C. 1H NMR (600 MHz, CDCl3): δ 7.47 (d, J = 8.1 Hz, 2H), 7.29 (d,
J = 8.8 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 6.76 (d, J = 8.8 Hz, 2H),
3.78 (s, 3H), 3.35 (s, 2H), 2.38 (s, 3H), 2.17 (d, J = 13.2 Hz, 1H),
1.95 (d, J = 13.2 Hz, 1H), 1.91 (s, 3H), 1.08 (s, 3H), 1.00 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3): δ 158.1, 142.4, 139.6, 137.7,
2
40.8 (q, JC−F = 26.6 Hz), 37.7, 26.1, 25.4. 19F NMR (470 MHz,
CDCl3): δ −63.11 (s, 3F), −63.75 (t, J = 11.3 Hz). HRMS (ESI-
TOF) m/z: [M + Na]+ Calcd for C15H17F6NNaO2S 412.0776; found
412.0759.
(4,4-Dimethyl-2-phenyl-2-(2,2,2-trifluoroethyl)pyrrolidin-1-yl)-
(phenyl)methanone (2ai). Purified by silica gel column chromatog-
raphy (the eluent was petroleum ether/EtOAc 10:1) as a white solid
(48% yield, 17.4 mg). mp 81−82 °C. 1H NMR (600 MHz, CDCl3): δ
7.43−7.41 (m, 2H), 7.37−7.34 (m, 3H), 7.28−7.24 (m, 4H), 7.16−
7.14 (m, 1H), 3.90 (dq, J = 15.5, 11.5 Hz, 1H), 3.38 (d, J = 10.6 Hz,
1H), 3.26 (d, J = 10.6 Hz, 1H), 2.82 (dq, J = 15.5, 10.7 Hz, 1H), 2.64
(d, J = 13.4 Hz, 1H), 2.10 (d, J = 13.4 Hz, 1H), 0.96 (s, 3H), 0.75 (s,
3H). 13C{1H} NMR (150 MHz, CDCl3): δ 170.5, 144.7, 138.6, 129.3,
128.5, 128.2, 126.7, 126.4 (q, 1JC−F = 277.2 Hz), 126.0, 125.9, 68.0 (q,
129.1, 127.3, 127.1, 113.2, 70.0, 62.6, 59.8, 55.2, 36.6, 28.3, 28.3, 27.6,
21.5. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H27NNaO3S
396.1604; found 396.1593.
2-(Benzo[d][1,3]dioxol-5-yl)-2,4,4-trimethyl-1-tosylpyrrolidine
(5n). Purified by silica gel column chromatography (the eluent was
petroleum ether/EtOAc 3:1) as a white solid (30% yield, 11.7 mg).
mp 105−106 °C. 1H NMR (600 MHz, CDCl3): δ 7.51 (d, J = 8.1 Hz,
2H), 7.20 (d, J = 8.0 Hz, 2H), 6.91 (dd, J = 8.2, 1.9 Hz, 1H), 6.77 (d,
J = 1.9 Hz, 1H), 6.69 (d, J = 8.2 Hz, 1H), 5.92 (dd, J = 11.1, 1.5 Hz,
2H), 3.40−3.30 (m, 2H), 2.40 (s, 3H), 2.15 (d, J = 13.2 Hz, 1H),
1.94 (d, J = 13.2 Hz, 1H), 1.90 (s, 3H), 1.09 (s, 3H), 1.02 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3): δ 147.4, 146.0, 142.5, 141.6,
4
2
3JC−F = 2.1 Hz), 64.5, 52.9 (q, JC−F = 1.7 Hz), 40.2 (q, JC−F = 25.6
Hz), 36.4, 28.1, 27.6. 19F NMR (470 MHz, CDCl3): δ −59.17 (t, J =
11.0 Hz, 3F). HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C21H22F3NNaO 384.1546; found 384.1544.
137.7, 129.1, 127.3, 119.1, 107.4, 107.0, 101.0, 70.2, 62.7, 59.9, 36.6,
28.3, 28.2, 27.7, 21.5. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C21H25NNaO4S 410.1396; found 410.1386.
N-(4-Chloro-6,6,6-trifluoro-2,2-dimethyl-4-phenylhexyl)-4-meth-
ylbenzenesulfonamide (3a). Isolated under the conditions of entry 3
in Table 1. Purified by silica gel column chromatography (the eluent
1997
https://dx.doi.org/10.1021/acs.joc.0c02637
J. Org. Chem. 2021, 86, 1987−1999

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
General Procedure for Control Experiments. An oven-dried
test tube (10.0 mL) equipped with a Teflon-coated magnetic stir bar
was charged with (1-cyclopropylvinyl)benzene or N,N-diallyl-4-
methylbenzenesulfonamide (0.1 mmol, 1.0 equiv), the trifluorome-
thylation reagent chloro(phenyl)trifluoromethyliodane (0.2 mmol, 2.0
equiv), and ZnI2 (0.01 mmol, 10 mol %) in sequence in a glovebox.
After anhydrous DCM (1.0 mL) was added, the tube was sealed with
a Teflon screw-cap septum and taken outside. The reaction mixture
was stirred at 25 °C in an oil bath for 12 h, then quenched with H2O
(1.0 mL). The aqueous layer was separated and extracted with DCM
(3 × 5.0 mL). The combined organic layers were dried over MgSO4
and concentrated in vacuo. The residue was purified by silica gel
column chromatography to afford the pure products.
and Technology of Jilin Province (nos. 20190103127JH and
20200201067JC), and the Education Department of Jilin
Province (no. JJKH20201166KJ) for the funding support of
this work.
REFERENCES
■
(1) For selected reviews of trifluoromethylative bifunctionalizations
of alkenes, see: (a) Egami, H.; Sodeoka, M. Trifluoromethylation of
Alkenes with Concomitant Introduction of Additional Functional
Groups. Angew. Chem., Int. Ed. 2014, 53, 8294. (b) Merino, E.;
Nevado, C. Addition of CF3 Across Unsaturated Moieties: A Powerful
Functionalization Tool. Chem. Soc. Rev. 2014, 43, 6598. (c) Alonso,
C.; Martínez de Marigorta, E.; Rubiales, G.; Palacios, F. Carbon
Trifluoromethylation Reactions of Hydrocarbon Derivatives and
Heteroarenes. Chem. Rev. 2015, 115, 1847. (d) Koike, T.; Akita, M.
Fine Design of Photoredox Systems for Catalytic Fluoromethylation
of Carbon-Carbon Multiple Bonds. Acc. Chem. Res. 2016, 49, 1937.
(e) Yin, G.; Mu, X.; Liu, G. Palladium(II)-Catalyzed Oxidative
Difunctionalization of Alkenes: Bond Forming at a High-Valent
Palladium Center. Acc. Chem. Res. 2016, 49, 2413. (f) Gu, Q.-S.; Li,
Z.-L.; Liu, X.-Y. Copper(I)-Catalyzed Asymmetric Reactions Involv-
ing Radicals. Acc. Chem. Res. 2020, 53, 170. (g) Li, Z.-L.; Fang, G.-C.;
Gu, Q.-S.; Liu, X.-Y. Recent Advances in Copper-Catalysed Radical-
Involved Asymmetric 1,2-Difunctionalization of Alkenes. Chem. Soc.
Rev. 2020, 49, 32.
3-(Chloromethyl)-1-tosyl-4-(2,2,2-trifluoroethyl)pyrrolidine (6).
Isolated under the standard conditions by changing the substrate to
N,N-diallyl-4-methylbenzenesulfonamide. Purified by silica gel col-
umn chromatography (the eluent was petroleum ether/EtOAc 10:1)
1
as a white solid (43% yield, 15.3 mg). mp 62−63 °C. H NMR (600
MHz, CDCl3): δ 7.73 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H),
3.51 (dd, J = 10.3, 7.0 Hz, 1H), 3.44−3.37 (m, 3H), 3.14−3.10 (m,
2H), 2.58−2.50 (m, 2H), 2.45 (s, 3H), 2.24−2.19 (m, 1H), 1.99−
1.94 (m, 1H). 13C{1H} NMR (150 MHz, CDCl3): δ 143.9, 133.4,
129.8, 127.5, 126.2 (q, 1JC−F = 275.2 Hz), 51.1, 50.3, 43.3, 42.0, 35.0
3
2
(q, JC−F = 2.6 Hz), 31.9 (q, JC−F = 28.9 Hz), 21.6. 19F NMR (470
MHz, CDCl3): δ −64.89 (t, J = 10.5 Hz, 3F). HRMS (ESI-TOF) m/
z: [M + Na]+ Calcd for C14H17ClF3NNaO2S 378.0513; found
378.0507.
(2) For selected reviews of aminotrifluoromethylations of alkenes,
see: (a) Tian, Y.; Chen, S.; Gu, Q.-S.; Lin, J.-S.; Liu, X.-Y. Amino- and
Azidotrifluoromethylation of Alkenes. Tetrahedron Lett. 2018, 59, 203.
(b) Jiang, H.; Studer, A. Intermolecular Radical Carboamination of
Alkenes. Chem. Soc. Rev. 2020, 49, 1790.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02637.
(3) (a) Matcha, K.; Antonchick, A. P. Cascade Multicomponent
Synthesis of Indoles, Pyrazoles, and Pyridazinones by Functionaliza-
tion of Alkenes. Angew. Chem., Int. Ed. 2014, 53, 11960. (b) Yu, X.-L.;
Chen, J.-R.; Chen, D.-Z.; Xiao, W.-J. Visible-Light-Induced Photo-
catalytic Azotrifluoromethylation of Alkenes with Aryldiazonium Salts
and Sodium Triflinate. Chem. Commun. 2016, 52, 8275. (c) Zhu, C.-
L.; Wang, C.; Qin, Q.-X.; Yruegas, S.; Martin, C. D.; Xu, H. Iron(II)-
Catalyzed Azidotrifluoromethylation of Olefins and N-Heterocycles
for Expedient Vicinal Trifluoromethyl Amine Synthesis. ACS Catal.
2018, 8, 5032. (d) Wu, Y.; Zhang, Y.; Yang, Z.; Jiao, J.; Zheng, X.;
Feng, W.; Zhang, M.; Cheng, H.; Tang, L. Dual Roles of tert-Butyl
Nitrite in the Transition Metal- and External Oxidant-Free
Trifluoromethyloximation of Alkenes. ChemSusChem 2019, 12,
3960. (e) Lu, K.; Wei, X.; Li, Q.; Li, Y.; Ji, L.; Hua, E.; Dai, Y.;
Zhao, X. Synthesis of α-Trifluoromethyl Ethanone Oximes via the
Three-Component Reaction of Aryl-Substituted Ethylenes, tert-Butyl
Nitrite, and the Langlois Reagent. Org. Chem. Front. 2019, 6, 3766.
(f) Wang, P.; Zhu, S.; Lu, D.; Gong, Y. Intermolecular
Trifluoromethyl-Hydrazination of Alkenes Enabled by Organic
Photoredox Catalysis. Org. Lett. 2020, 22, 1924.
(4) (a) Lin, J.-S.; Dong, X.-Y.; Li, T.-T.; Jiang, N.-C.; Tan, B.; Liu,
X.-Y. A Dual-Catalytic Strategy To Direct Asymmetric Radical
Aminotrifluoromethylation of Alkenes. J. Am. Chem. Soc. 2016, 138,
9357. (b) Yu, L.-Z.; Wei, Y.; Shi, M. Copper-Catalyzed Cascade
Cyclization of 1,5-Enynes via Consecutive Trifluoromethylazidation/
Diazidation and Click Reaction: Self-Assembly of Triazole Fused
Isoindolines. Chem. Commun. 2016, 52, 13163. (c) Li, X.-F.; Lin, J.-S.;
Liu, X.-Y. Catalytic Radical Intramolecular Aminoperfluoroalkylation
and Aminodifluoromethylation of Unactivated Alkenes with Fluoro-
alkylsulfonyl Chlorides. Synthesis 2017, 49, 4213. (d) Mou, X.-Q.;
Rong, F.-M.; Zhang, H.; Chen, G.; He, G. Copper(I)-Catalyzed
Enantioselective Intramolecular Aminotrifluoromethylation of O-
Homoallyl Benzimidates. Org. Lett. 2019, 21, 4657.
1H, 13C, 19F NMR spectra for compounds 1−6 (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Mang Wang − Jilin Province Key Laboratory of Organic
Functional Molecular Design & Synthesis, College of
Chemistry, Northeast Normal University, Changchun
130024, China; orcid.org/0000-0001-8006-4626;
Email: wangm452@nenu.edu.cn
Cong Xu − Jilin Province Key Laboratory of Organic
Functional Molecular Design & Synthesis, College of
Chemistry, Northeast Normal University, Changchun
130024, China; orcid.org/0000-0001-9817-7186;
Email: xuc348@nenu.edu.cn
Authors
Wanqiao Huang − Jilin Province Key Laboratory of Organic
Functional Molecular Design & Synthesis, College of
Chemistry, Northeast Normal University, Changchun
130024, China; orcid.org/0000-0001-9828-8521
Jianxin Yu − Jilin Province Key Laboratory of Organic
Functional Molecular Design & Synthesis, College of
Chemistry, Northeast Normal University, Changchun
130024, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02637
Notes
The authors declare no competing financial interest.
(5) For selected relative works, see: (a) Valverde, E.; Kawamura, S.;
Sekine, D.; Sodeoka, M. Metal-Free Alkene Oxy- and Amino-
perfluoroalkylations via Carbocation Formation by Using Perfluoro
Acid Anhydrides: Unique Reactivity between Styrenes and Perfluoro
Diacyl Peroxides. Chem. Sci. 2018, 9, 7115. (b) Zhang, L.; Zhang, G.;
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China
(nos. 21672032 and 21802016), the Department of Science
■
1998
https://dx.doi.org/10.1021/acs.joc.0c02637
J. Org. Chem. 2021, 86, 1987−1999

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Wang, P.; Li, Y.; Lei, A. Electrochemical Oxidation with Lewis-Acid
Catalysis Leads to Trifluoromethylative Difunctionalization of
Alkenes Using CF3SO2Na. Org. Lett. 2018, 20, 7396. (c) Huang,
Y.; Hong, H.; Zou, Z.; Liao, C.; Lu, J.; Qin, Y.; Li, Y.; Chen, L.
Electrochemical Vicinal Aminotrifluoromethylation of Alkenes: High
Regioselective Acquisition of β-Trifluoromethylamines. Org. Biomol.
Chem. 2019, 17, 5014. (d) Levitre, G.; Dagousset, G.; Anselmi, E.;
Tuccio, B. a.; Magnier, E.; Masson, G. Four-Component Photoredox-
Mediated Azidoalkoxy-trifluoromethylation of Alkenes. Org. Lett.
2019, 21, 6005 and the references cited therein..
Muns, A.; Gnamm, C.; Commandeur, C.; Commandeur, M.;
́
Reymond, S. b.; Guerinot, A.; Cossy, J. Iron- and Indium-Catalyzed
Reactions toward Nitrogen- and Oxygen-Containing Saturated
Heterocycles. Acc. Chem. Res. 2015, 48, 761. (g) He, X.; Choy, P.
Y.; Leung, M. P.; Yuen, O. Y.; Liu, T.; Shang, Y.; Kwong, F. Y. A ZnI2-
Catalyzed Regioselective Cascade 1,4-Conjugate Addition/5-Exo-Dig
Annulation Pathway for One-Pot Access to Heterobiaryl Frameworks.
Chem. Commun. 2019, 55, 15069.
(11) (a) Larrosa, I.; Romea, P.; Urpí, F. Synthesis of Six-Membered
Oxygenated Heterocycles through Carboneoxygen Bond-Forming
Reactions. Tetrahedron 2008, 64, 2683. (b) Godoi, B.; Schumacher, R.
F.; Zeni, G. Synthesis of Heterocycles via Electrophilic Cyclization of
Alkynes Containing Heteroatom. Chem. Rev. 2011, 111, 2937.
(12) Koller, R.; Stanek, K.; Stolz, D.; Aardoom, R.; Niedermann, K.;
Togni, A. Zinc-Mediated Formation of Trifluoromethyl Ethers from
Alcohols and Hypervalent Iodine Trifluoromethylation Reagents.
Angew. Chem., Int. Ed. 2009, 48, 4332.
(6) For nontrifluoromethyl radical-inatiated aminotrifluoromethyla-
tion reactions, see: (a) Fuchikami, T.; Shibata, Y.; Urata, H.
Transition-Metal Complex Catalyzed Polyfluoroalkylation. A Facile
Synthesis of Fluorine-Containing Oxiranes and Enynes. Chem. Lett.
1987, 16, 521. (b) Egami, H.; Kawamura, S.; Miyazaki, A.; Sodeoka,
M. Trifluoromethylation Reactions for the Synthesis of β-Trifluor-
omethylamines. Angew. Chem., Int. Ed. 2013, 52, 7841. (c) Lin, J.-S.;
Liu, X.-G.; Zhu, X.-L.; Tan, B.; Liu, X.-Y. Copper-Catalyzed
Aminotrifluoromethylation of Unactivated Alkenes with (TMS)CF3:
Construction of Trifluoromethylated Azaheterocycles. J. Org. Chem.
2014, 79, 7084. (d) Kawamura, S.; Egami, H.; Sodeoka, M.
Aminotrifluoromethylation of Olefins via Cyclic Amine Formation:
Mechanistic Study and Application to Synthesis of Trifluoromethy-
lated Pyrrolidines. J. Am. Chem. Soc. 2015, 137, 4865. (e) Chang, B.;
Su, Y.; Huang, D.; Wang, K.-H.; Zhang, W.; Shi, Y.; Zhang, X.; Hu, Y.
Synthesis of Trifluoroethyl Pyrazolines via Trichloroisocyanuric Acid
Promoted Cascade Cyclization/Trifluoromethylation of β,γ-Unsatu-
rated Hydrazones. J. Org. Chem. 2018, 83, 4365. (f) Xiao, H.; Shen,
H.; Zhu, L.; Li, C. Copper-Catalyzed Radical Aminotrifluoromethy-
lation of Alkenes. J. Am. Chem. Soc. 2019, 141, 11440. (g) Qin, S.;
Yao, L.; Luo, Y.; Liu, T.; Xu, J.; Sun, Y.; Wang, N.; Yan, J.; Tang, B.;
Yang, G.; Yang, C. Synthesis of Aziridines with Multiple Chiral
Substitutions by Copper-Catalyzed Diastereoselective Radical Amino-
trifluoromethylation of Alkenes. Org. Chem. Front. 2020, 7, 3132.
(7) (a) Xu, C.; Liu, J.; Ming, W.; Liu, Y.; Liu, J.; Wang, M.; Liu, Q.
In Situ Generation of PhI+CF3 and Transition-Metal-Free Oxidative
sp2 Trifluoromethylation. Chem. - Eur. J. 2013, 19, 9104. (b) Zheng,
G.; Ma, X.; Li, J.; Zhu, D.; Wang, M. Electrophilic N-
Trifluoromethylation of N-H Ketimines. J. Org. Chem. 2015, 80, 8910.
(8) Xu, C.; Song, X.; Guo, J.; Chen, S.; Gao, J.; Jiang, J.; Gao, F.; Li,
Y.; Wang, M. Synthesis of Chloro(phenyl)trifluoromethyliodane and
Catalyst-Free Electrophilic Trifluoromethylations. Org. Lett. 2018, 20,
3933.
(9) (a) Xu, C.; Huang, W.; Zhang, R.; Gao, C.; Li, Y.; Wang, M.
Trifluoromethylations of Alkenes Using PhICF3Cl as Bifunctional
Reagent. J. Org. Chem. 2019, 84, 14209. (b) Guo, J.; Xu, C.; Liu, X.;
Wang, M. Aryltrifluoromethylative Cyclization of Unactivated Alkenes
by the Use of PhICF3Cl Under Catalyst-Free Conditions. Org. Biomol.
Chem. 2019, 17, 2162. (c) Guo, J.; Xu, C.; Wang, L.; Huang, W.;
Wang, M. Catalyst-Free and Selective Trifluoromethylative Cycliza-
tion of Acryloanilides Using PhICF3Cl. Org. Biomol. Chem. 2019, 17,
4593.
(10) For selected Lewis acid-catalyzed amination reactions, see:
(a) Seko, S.; Miyake, K. Zinc-Promoted Direct Amination of
Nitropyridines with Methoxyamine via Vicarious Nucleophilic
Substitution. Chem. Commun. 1998, 1519. (b) Ton, T. M. U.; Tejo,
C.; Tiong, D. L. Y.; Chan, P. W. H. Copper(II) Triflate Catalyzed
Amination and Aziridination of 2-Alkyl Substituted 1,3-Dicarbonyl
Compounds. J. Am. Chem. Soc. 2012, 134, 7344. (c) Yu, J.; Liu, S.-S.;
Cui, J.; Hou, X.-S.; Zhang, C. A Mild and Efficient Direct α-
Amination of β-Dicarbonyl Compounds Using Iodosobenzene and p-
Toluenesulfonamide Catalyzed by Perchlorate Zinc Hexahydrate. Org.
Lett. 2012, 14, 832. (d) Liu, G.-Q.; Li, W.; Wang, Y.-M.; Ding, Z.-Y.;
Li, Y.-M. Ligand Acceleration in ZnI2-Catalyzed Intramolecular
Hydroamination of Unfunctionalized Olefins. Tetrahedron Lett.
2012, 53, 4393. (e) Dadiboyena, S., II; Hamme, A. T. Environ-
mentally Benign Lewis Acid Promoted [2 + 3]-Dipolar Cycloaddition
Reactions of Nitrile Imines with Alkenes in Water. Eur. J. Org. Chem.
2013, 2013, 7567. (f) Cornil, J.; Gonnard, L.; Bensoussan, C. l.; Serra-
1999
https://dx.doi.org/10.1021/acs.joc.0c02637
J. Org. Chem. 2021, 86, 1987−1999