Catalytic Enantioselective Synthesis of N-C Axially Chiral Sulfonamides through Chiral Palladium-Catalyzed N-Allylation

Article abstract of DOI:10.1021/acs.joc.9b00989

In the presence of (S,S)-Trost ligand and (allyl-Pd-Cl)₂ catalyst, the reaction of allyl acetate with the anionic species prepared from various N-(2-tert-butylphenyl)sulfonamides and NaH proceeded in an enantioselective manner (up to 95% ee) to give optically active N-allylated sulfonamide derivatives possessing an N-C axially chiral structure in high yields.

Full text of DOI:10.1021/acs.joc.9b00989

Article
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Cite This: J. Org. Chem. XXXX, XXX, XXX−XXX
Catalytic Enantioselective Synthesis of N−C Axially Chiral
Sulfonamides through Chiral Palladium-Catalyzed N‑Allylation
Yuki Kikuchi, Chisato Nakamura, Mizuki Matsuoka, Rina Asami, and Osamu Kitagawa*
Department of Applied Chemistry (QOL Improvement and Life Science Consortium), Shibaura Institute of Technology, 3-7-5
Toyosu, Kohto-ku, Tokyo 135-8548, Japan
S
* Supporting Information
ABSTRACT: In the presence of (S,S)-Trost ligand and (allyl-Pd-Cl)2 catalyst,
the reaction of allyl acetate with the anionic species prepared from various N-(2-
tert-butylphenyl)sulfonamides and NaH proceeded in an enantioselective
manner (up to 95% ee) to give optically active N-allylated sulfonamide
derivatives possessing an N−C axially chiral structure in high yields.
proceed in a highly enantioselective manner, have been
reported by many groups, with most of the compounds
being carboxamide derivatives such as anilides, lactams, imides,
carbamates, and ureas.7 On the other hand, although N−C
axially chiral sulfonamides have also been reported (Figure 2),8
INTRODUCTION
■
Recently, N−C axially chiral compounds have attracted
considerable attention as a new type of nonbiaryl atropiso-
meric molecule.1 In 2002, we reported the synthesis of
optically active N−C axially chiral anilides II through chiral
Pd-catalyzed N-allylation of achiral ortho-tert-butylanilides I
(Figure 1).2 Although the present reaction is the first catalytic
Figure 2. Several N−C axially chiral sulfonamides.
there has been no indication of their catalytic asymmetric
synthesis. Some of these sulfonamides are pharmaceutically
attractive compounds, and their catalytic asymmetric synthesis
is meaningful from the viewpoint of medicinal chemistry as
well as synthetic organic chemistry.7a,b In this paper, we report
the catalytic enantioselective syntheses of N−C axially chiral
sulfonamides (Figure 2) through chiral Pd-catalyzed N-
allylation. Furthermore, the determination of the absolute
stereochemistry of the N-allylation product and the origin of
the enantioselectivity are also described.
Figure 1. Catalytic enantioselective synthesis of N−C axially chiral
anilides developed by our group.
enantioselective synthesis of N−C axially chiral compounds,
the enantioselectivity was by no means satisfactory.2,3 In N-
allylation with a chiral π-allyl Pd catalyst, highly asymmetric
induction at the anilide moiety by a chiral ligand may be
difficult because the anilide anion attacks the π-allyl carbon on
the opposite site of the Pd atom.4 In 2005, we succeeded in the
first highly enantioselective synthesis of N−C axially chiral
anilides III through chiral Pd-catalyzed Buchwald−Hartwig
amination (Figure 1).5 In this reaction, since the N−Ar bond
formation (the construction of the N−C chiral axis) via
reductive elimination occurs around the chiral ligand,6 high
enantioselectivity should be achieved.
RESULTS AND DISCUSSION
■
We predicted that similar to ortho-tert-butylcarboxanilides II
and III, N-(2-tert-butylphenyl)sulfonamides (Figure 2) would
also possess a rotationally stable structure and investigated
their catalytic enantioselective syntheses in detail. Initially,
although the Buchwald−Hartwig amination was attempted,
which gave an excellent result in the synthesis of
carboxanilides, the N-arylation of an achiral sulfonamide 1
did not proceed under the conditions for the synthesis of
Since the publication of our results, catalytic asymmetric
syntheses of various N−C axially chiral compounds, which
Received: April 10, 2019
Published: May 22, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.9b00989
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
carboxanilides III. This may be due to the lower nucleophil-
icity of a sulfonamide anion in comparison to that of a
carboxamide anion. In addition, the Buchwald−Hartwig
amination shown in Figure 1 requires heating at 80 °C,
while N-substituted-N-(2-tert-butylphenyl)sulfonamide was
found to racemize easily at 80 °C (vide infra). Therefore, its
synthesis through Pd-catalyzed N-allylation, which proceeds
under milder conditions, was explored.
To further improve the enantioselectivity, although a wide
selection of allylic reagents (cinnamyl acetate and prenyl
acetate), bases (t-BuOK, t-BuONa, Cs2CO3) and solvents
(CH2Cl2, DMF, CH3CN, toluene) was examined, no better
result was obtained than entry 10 in Table 1.
Table 2 shows the application of the present reaction to
various sulfonamide substrates 1 and 3 under the optimized
The reaction of allyl acetate (1.5 equiv) with the anion
species prepared from achiral 4-tosyl amide 1a and NaH (1.0
equiv) was conducted in the presence of (allyl-Pd-Cl)2 catalyst
(2.2 mol %) and various chiral ligands (4.4 mol %) in THF
(Table 1). In most cases, the reaction completed within 2 h at
Table 2. Application to Various Sulfonamide Substrates
Table 1. Ligand Screening in Catalytic Enantioselective N-
Allylation of Sulfonamide 1a
a
b
entry 1 or 3
R1
R2
2 or 4 yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1a
1b
1c
1d
1e
1f
1g
1h
1i
3a
3b
3c
3d
3e
3f
4-MeC6H4
C6H5
H
H
H
H
H
H
H
H
2a
2b
2c
2d
2e
2f
2g
2h
2i
4a
4b
4c
4d
4e
4f
quant
quant
93
92
86
77
92
86
quant
90
81
quant
95
84
73
73
72
74
70
86
91
88
49
66
78
78
77
74
89
95
91
59
4-NO2C6H4
4-MeOC6H4
2-MeC6H4
2,4,6-Me3C6H2
naphth-1-yl
Me
cyclohexyl
4-MeC6H4
C6H5
4-NO2C6H4
4-MeOC6H4
2-MeC6H4
2,4,6-Me3C6H2
naphth-1-yl
Me
a
b
entry
ligand
(R)-MOP
(R)-BINAP
(S)-DM-BINAP
(R)-SEGPHOS
(R)-DTBM-SEGPHOS
(R)-DIFLUOROPHOS
(S,S)-CHIRAPHOS
(S)-Phox P,N-ligand
(S,S)-Trost ligand A
(S,S)-Trost ligand A
(S,S)-Trost ligand B
(S,S)-Trost ligand C
yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
35
95
89
86
quant
93
quant
quant
95
quant
91
81
0
0
4
10
10
4
H
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
3
11
59
71
53
49
16
3g
3h
4g
4h
quant
94
c
10
11
12
c
a
b
Isolated yield. The ee was determined by HPLC analysis using a
c
chiral column.
c
13
(S,S)-Trost ligand D
32
a
b
Isolated yield. The ee was determined by HPLC analysis using a
c
conditions established in Table 1. In the reactions of Table 2, 3
equiv of allyl acetate was used because the use of 1.5 equiv
brought about a considerable decrease in the chemical yield
with several sulfonamide substrates. By the use of 3 equiv of
allyl acetate, all reactions in Table 2 completed within 3 h at
−20 °C to give products 2 and 4 in good yields.
chiral column. The reaction was conducted at −20 °C.
Similar to 4-tosyl amide 1a, the reaction with benzenesulfo-
namide 1b, 4-nitrobenzenesulfonamide 1c, and 4-methoxy-
benzenesulfonamide 1d gave the allylation products 2b−d with
moderate enantioselectivity (70−74% ee, entries 2−4). These
results indicate that the electron density on the phenyl group
does not significantly influence the enantioselectivity. Mean-
while, it was found that the steric bulkiness of the substrates
led to a remarkable increase in the enantioselectivity. That is,
the reaction of 2-tosyl amide 1e proceeded with a higher
enantioselectivity (86% ee) than that (73% ee) of 4-tosyl
amide 1a (entries 1 and 5). With bulkier sulfonamides 1f and
1g bearing mesityl and naphth-1-yl groups, a further increase in
the enantioselectivity was observed; in these cases, the
products 2f and 2g were obtained with 91 and 88% ee,
respectively (entries 6 and 7). In contrast, the reaction with
less bulky mesyl amide 1h yielded a remarkable decrease in the
enantioselectivity (49% ee, entry 8). The reaction of cyclohexyl
sulfonamide 1i proceeded with a higher enantioselectivity
(66% ee, entry 9) than 1h, showing the contribution of the
steric factor to the enantioselectivity.
rt or −20 °C to afford N-allylated axially chiral product 2a in
excellent yields (entries 2−12), while enantioselectivity was
poor or not observed (entries 1−8, 13). Among the
investigated chiral ligands, Trost ligands A−C9 gave a relatively
good result (entries 9−12); in the reaction with Trost ligand
A, 2a was obtained with 59% ee (entry 9). Furthermore, when
the reaction temperature was lowered to −20 °C from rt, the
ee increased to 71 from 59% (entry 10).
B
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When N-(2,5-di-tert-butylphenyl)sulfonamides 3a−h (R2 =
t-Bu) were used instead of the corresponding mono-tert-butyl
substrates 1a−h (R2 = H), in all reactions, an increase in the
enantioselectivity was observed (entries 10−17). Such increase
in the enantioselectivity by the use of 2,5-di-tert-butyl
substrates is also observed in the Buchwald−Hartwig
amination of carboxamides in Figure 1.5 Also in the cases of
2,5-di-tert-butyl substrates 3, the reaction with sulfonamides
3e−3g, bearing bulky substituents, proceeded in a highly
enantioselective manner (89−95% ee, entries 14−16).
Similar to the N-allylation of carboxamides shown in Figure
1, in the present reaction, the sulfonamide anion should
approach π-allyl carbon on the opposite face of the Pd atom.
Nevertheless, the Trost ligand effectively controls the
enantioselective construction of the N−C chiral axis, which
locates at a remote position.10
Figure 4. Absolute stereochemistry of 4f (95% ee).
Under the conditions in Table 2, we examined the N-
allylation of ortho-tert-butylbenzanilide 5b; however, no
allylation product 6b was obtained (Figure 3). When the
Figure 5. Origin of the enantioselectivity.
phosphorus atom, hence the reaction would proceed via TS-A
or TS-B. Furthermore, TS-A may be more favorable than TS-
B, due to the steric repulsion between the sulfonyl group and
Ph (wall) group, giving the N-allylation products possessing
the (P)-configuration as the major enantiomer. An increase in
the steric bulkiness of the sulfonyl substituent (R1) causes
further destabilization of TS-B, which gives the (M)-
enantiomer, leading to the increase in (P)-selectivity.
Figure 3. N-Allylation of carboxamide 5b in the presence of Trost
ligand-Pd catalyst.
reaction was conducted for 24 h at rt, 6b was obtained with a
poor yield (11%) and enantioselectivity (4% ee). This result,
which is in remarkable contrast to the reaction of the
corresponding sulfonamides 1b, may be due to the basicity
of the amide anion (conjugated base). Namely, the anion
species prepared from carboxamide 5b and NaH may abstract
the amide hydrogen of the Trost ligand, resulting in the
formation of an inactive amide−Pd complex (Figure 3). On
the other hand, with the sulfonamide anions, since the
abstraction of the amide hydrogen of the ligand scarcely
occurs because of the lower basicity of the sulfonamide anion
than that of carboxamide anion, the reaction would proceed
smoothly and enantioselectively.
The absolute stereochemistry of the major enantiomer in N-
allylation product 4f (95% ee) was determined to be (P)-
configuration on the basis of X-ray crystal structural analysis
(Figure 4).11
The (P)-selectivity can be rationally explained on the basis
of a working model proposed by Trost (Figure 5).12 That is,
among four possible transition states in the reaction with (S,S)-
Trost ligand, the transition states TS-A and TS-D give the (P)-
products, while reactions via TS-B and TS-C afford (M)-
products. The transition states TS-C and TS-D should be
significantly destabilized because of the strong steric repulsion
between the bulky tert-butyl group and Ph (wall) group on
The increase in the enantioselectivity, which was observed in
the reaction with 2,5-di-tert-butyl derivatives 3, may also be
explained on the basis of Trost model (Figure 5). That is, tert-
butyl group (R2) at C5 (meta) position would give rise to the
steric repulsion with Ph (wall) group of front side to
destabilize TS-B. As a result, the proportion of the reaction
via TS-A increases to give the products 4 with higher ee.
Sulfonamide products 2 and 4 are rotationally stable in the
solid state, and no decrease in the ee was observed even after
standing for several weeks at rt. On the other hand, the ee’s of
2 and 4 in the solution were found to decrease gradually at rt.
For example, the ee’s of mesitylenesulfonamide 4f (88% ee)
and methanesulfonamide 4h (60% ee) lowered to 72% ee and
41% ee, respectively, after standing for 25 h at 25 °C in CCl4
(Figure 6).13 Since the ee’s of carboxamide derivatives II and
III were not changed after standing for several days at rt in the
solution, the rotational stabilities of sulfonamides 2 and 4
would be considerably lower in comparison to those of
carboxamide derivatives. Indeed, the ΔG‡ values of 4f and 4h
at 25 °C were evaluated to be 25.6 and 25.2 kcal/mol,
respectively, and these values were 2−4 kcal/mol lower than
those of caboxamides II and III.
C
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Article
30.9; MS (m/z) 312 (MNa+); HRMS. Calcd for C16H19NNaO2S
(MNa+) 312.1034. Found: 312.1006.
N-(2-(tert-Butyl)phenyl)-4-nitrobenzenesulfonamide (1c). 1c was
prepared from 4-nitrobenzenesulfonyl chloride (731 mg, 3.3 mmol)
and 2-tert-butylaniline (448 mg, 3.0 mmol) in accordance with the
procedure for the synthesis of 1a. Purification of the residue by
column chromatography (hexane/AcOEt = 20 and 3) gave 1c (922
mg, 92%). 1c: white solid; mp 163−165 °C; IR (neat) 3252, 1346,
1157 cm−1; 1H NMR (400 MHz, CDCl3) δ: 8.31 (2H, td, J = 1.8, 8.7
Hz), 8.01 (2H, td, J = 1.8, 8.7 Hz), 7.39 (1H, dd, J = 1.8, 7.8 Hz),
7.34 (1H, dd, J = 2.3, 7.8 Hz), 7.11−7.19 (2H, m), 6.75 (1H, brs),
1.30 (9H, s); 13C{1H} NMR (100 MHz, CDCl3) δ: 150.1, 145.6,
141.0, 134.0, 128.6, 127.5, 127.3, 126.2, 124.3, 123.1, 34.4, 31.0; MS
(m/z) 357 (MNa+); HRMS. Calcd for C16H18N2NaO4S (MNa+)
357.0885. Found: 357.0880.
N-(2-(tert-Butyl)phenyl)-4-methoxybenzenesulfonamide (1d). 1d
was prepared from 4-methoxybenzenesulfonyl chloride (682 mg, 3.3
mmol) and 2-tert-butylaniline (448 mg, 3.0 mmol) in accordance with
the procedure for the synthesis of 1a. Purification of the residue by
column chromatography (hexane/AcOEt = 20 and 3) gave 1d (958
mg, quant). 1d: white solid; mp 95−97 °C; IR (neat) 3254, 1319,
1150 cm−1; 1H NMR (400 MHz, CDCl3) δ: 7.77 (2H, td, J = 2.8, 9.2
Hz), 7.45 (1H, dd, J = 1.4, 7.8 Hz), 7.30 (1H, dd, J = 1.4, 7.8 Hz),
7.13 (1H, dt, J = 1.4, 7.3 Hz), 7.05 (1H, dt, J = 1.8, 7.3 Hz), 6.91 (2H,
td, J = 2.8, 9.2 Hz), 6.66 (1H, brs), 3.83 (3H, s), 1.30 (9H, s);
13C{1H} NMR (100 MHz, CDCl3) δ: 163.1, 139.9, 135.2, 131.5,
Figure 6. Ee change of 4f and 4h at 25 °C in CCl4.
CONCLUSIONS
■
We succeeded in the catalytic enantioselective synthesis of N-
(2-tert-butylphenyl)sulfonamides through (S,S)-Trost ligand-
Pd-catalyzed N-allylation. The enantioselectivity was signifi-
cantly influenced by the steric character of substrates, and the
reaction with bulky sulfonamides proceeded in a highly
enantioselective manner (up to 95% ee). The present reaction
is the first catalytic asymmetric synthesis of N−C axially chiral
sulfonamide derivatives. Furthermore, the absolute config-
uration of the major enantiomer was definitely determined by
X-ray crystal structural analysis and the origin of the
enantioselectivity was also revealed.
129.5, 127.0, 125.0, 122.1, 114.1, 55.6, 34.2, 30.9; MS (m/z) 342
(MNa+); HRMS. Calcd for C17H21NNaO3S (MNa+) 342.1140.
Found: 342.1112.
EXPERIMENTAL SECTION
■
N-(2-(tert-Butyl)phenyl)-2-methylbenzenesulfonamide (1e). 1e
was prepared from 2-methylbenzenesulfonyl chloride (315 mg, 1.65
mmol) and 2-tert-butylaniline (224 mg, 1.5 mmol) in accordance with
the procedure for the synthesis of 1a. Purification of the residue by
column chromatography (hexane/AcOEt = 20) gave 1e (264 mg,
58%). 1e: white solid; mp 95−98 °C; IR (neat) 3308, 1321, 1153
cm−1; 1H NMR (400 MHz, CDCl3) δ: 8.05 (1H, d, J = 6.9 Hz), 7.49
(1H, dt, J = 1.4, 7.8 Hz), 7.34−7.38 (3H, m), 7.00−7.08 (2H, m),
6.89 (1H, dd, J = 1.4, 7.3 Hz), 6.63 (1H, brs), 2.69 (3H, s), 1.47 (9H,
s); 13C{1H} NMR (100 MHz, CDCl3) δ: 140.6, 139.6, 137.1, 135.2,
133.0, 132.7, 129.2, 127.2, 126.9, 126.5, 125.1, 122.5, 34.5, 31.0, 20.5;
MS (m/z) 326 (MNa+); HRMS. Calcd for C17H21NNaO2S (MNa+)
326.1191. Found: 326.1184.
Melting points were uncorrected. 1H and 13C NMR spectra were
recorded on a 400 MHz spectrometer. In H and 13C NMR spectra,
1
chemical shifts were expressed in δ (ppm) downfield from CHCl3
(7.26 ppm) and CDCl3 (77.0 ppm), respectively. HRMS images were
recorded on a double-focusing magnetic sector mass spectrometer
using electron impact ionization. Column chromatography was
performed on silica gel (75−150 μm). Medium-pressure liquid
chromatography (MPLC) was performed on a 25 × 4 cm i.d.
prepacked column (silica gel, 10 μm) with a UV detector. High-
performance liquid chromatography (HPLC) was performed on a 25
× 0.4 cm i.d. chiral column with a UV detector.
Synthesis of Sulfonamide Substrates 1 and 3 (General
Procedure). Under N2 atmosphere, to aniline (448 mg, 3.0 mmol)
and pyridine (0.3 mL, 4.5 mmol) in CH2Cl2 (5.0 mL) was added 4-
methylbenzenesulfonyl chloride (629 mg, 3.3 mmol) at 0 °C, and the
reaction mixture was stirred for 18 h from 0 °C to rt. The mixture was
poured into H2O and extracted with AcOEt. The AcOEt extracts were
washed with brine, dried over MgSO4, and evaporated to dryness.
Purification of the residue by column chromatography (hexane/
AcOEt = 20 and 3) gave 1a (814 mg, 89%).
N-(2-(tert-Butyl)phenyl)-2,4,6-tri-methylbenzenesulfonamide
(1f). 1f was prepared from 2,4,6-tri-methylbenzenesulfonyl chloride
(722 mg, 3.3 mmol) and 2-tert-butylaniline (448 mg, 3.0 mmol) in
accordance with the procedure for the synthesis of 1a. Purification of
the residue by column chromatography (hexane/AcOEt = 20) and
subsequent MPLC (hexane/AcOEt = 20) gave 1f (726 mg, 73%). 1f:
1
white solid; mp 114−116 °C; IR (neat) 3273, 1314, 1159 cm−1; H
NMR (400 MHz, CDCl3) δ: 7.38 (1H, dd, J = 1.8, 8.2 Hz), 6.99−
7.08 (4H, m), 6.63 (1H, dd, J = 1.4, 7.8 Hz), 6.60 (1H, brs), 2.66
(6H, s), 2.34 (3H, s), 1.49 (9H, s); 13C{1H} NMR (100 MHz,
CDCl3) δ: 142.6, 141.4, 138.7, 136.0, 135.6, 132.2, 127.2, 126.9,
125.2, 122.8, 34.5, 31.0, 23.0, 21.0; MS (m/z) 354 (MNa+); HRMS.
Calcd for C19H25NNaO2S (MNa+) 354.1504. Found: 354.1480.
N-(2-(tert-Butyl)phenyl)naphthalene-1-sulfonamide (1g). 1g was
prepared from nephthalen-1-sulfonyl chloride (748 mg, 3.3 mmol)
and 2-tert-butylaniline (448 mg, 3.0 mmol) in accordance with the
procedure for the synthesis of 1a. Purification of the residue by
column chromatography (hexane/AcOEt = 20 and 3) gave 1g (917
mg, 90%). 1g: white solid; mp 153−155 °C; IR (neat) 3254, 1308,
1159 cm−1; 1H NMR (400 MHz, CDCl3) δ: 8.68 (1H, d, J = 8.7 Hz),
8.34 (1H, dd, J = 1.4, 7.8 Hz), 8.10 (1H, d, J = 8.2 Hz), 7.96 (1H, d, J
= 8.7 Hz), 7.55−7.68 (3H, m), 7.32 (1H, dd, J = 1.8, 7.8 Hz), 6.97−
7.05 (2H, m), 6.93 (1H, dd, J = 1.8, 7.8 Hz), 6.80 (1H, brs), 1.42
(9H, s); 13C{1H} NMR (100 MHz, CDCl3) δ: 140.9, 136.1, 135.1,
134.6, 134.3, 129.7, 129.1, 128.4, 128.0, 127.1, 127.0, 126.8, 125.3,
124.5, 124.2, 122.8, 34.5, 31.0; MS (m/z) 362 (MNa+); HRMS.
Calcd for C20H21NNaO2S (MNa+) 362.1191. Found: 362.1179.
N-(2-(tert-Butyl)phenyl)-4-methylbenzenesulfonamide (1a). 1a:
1
white solid; mp 101−103 °C; IR (neat) 3246, 1325, 1155 cm−1; H
NMR (400 MHz, CDCl3) δ: 7.72 (2H, d, J = 8.2 Hz), 7.42 (1H, dd, J
= 1.4, 7.8 Hz), 7.30 (1H, dd, J = 1.8, 8.2 Hz), 7.24 (2H, d, J = 8.2
Hz), 7.13 (1H, dt, J = 1.8, 7.8 Hz), 7.05 (1H, dt, J = 1.8, 7.8 Hz), 6.66
(1H, brs), 2.39 (3H, s), 1.32 (9H, s); 13C{1H} NMR (100 MHz,
CDCl3) δ: 143.9, 140.0, 137.0, 135.1, 129.6, 127.3, 127.0, 125.0,
122.2, 34.2, 30.9, 21.5; MS (m/z) 326 (MNa+); HRMS. Calcd for
C17H21NNaO2S (MNa+) 326.1191. Found: 326.1181.
N-(2-(tert-Butyl)phenyl)benzenesulfonamide (1b). 1b was pre-
pared from benzenesulfonyl chloride (583 mg, 3.3 mmol) and 2-tert-
butylaniline (448 mg, 3.0 mmol) in accordance with the procedure for
the synthesis of 1a. Purification of the residue by column
chromatography (hexane/AcOEt = 20 and 3) gave 1b (764 mg,
88%). 1b: white solid; mp 113−115 °C; IR (neat) 3248, 1323, 1151
cm−1; 1H NMR (400 MHz, CDCl3) δ: 7.84 (2H, dd, J = 1.4, 7.8 Hz),
7.55 (1H, m), 7.42−7.47 (3H, m), 7.30 (1H, dd, J = 1.4, 7.8 Hz), 7.14
(1H, dt, J = 1.8, 7.3 Hz), 7.07 (1H, dt, J = 1.8, 7.8 Hz), 6.66 (1H,
brs), 1.31 (9H, s); 13C{1H} NMR (100 MHz, CDCl3) δ: 140.3,
140.0, 134.9, 133.0, 129.0, 127.3, 127.1, 127.0, 125.3, 122.6, 34.3,
D
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N-(2-(tert-Butyl)phenyl)methanesulfonamide (1h). 1h was pre-
pared from methanesulfonyl chloride (378 mg, 3.3 mmol) and 2-tert-
butylaniline (448 mg, 3.0 mmol) in accordance with the procedure for
the synthesis of 1a. Purification of the residue by column
chromatography (hexane/AcOEt = 20 and 3) gave 1h (573 mg,
84%). 1h: white solid; mp 114−116 °C; IR (neat) 3345, 1316, 1146
cm−1; 1H NMR (400 MHz, CDCl3) δ: 7.58 (1H, dd, J = 1.4, 8.2 Hz),
7.41 (1H, dd, J = 1.8, 8.2 Hz), 7.24 (1H, dt, J = 1.4, 7.8 Hz), 7.13
(1H, dt, J = 1.4, 7.8 Hz), 6.52 (1H, brs), 3.07 (3H, s), 1.42 (9H, s);
13C{1H} NMR (100 MHz, CDCl3) δ: 139.4, 135.2, 127.5, 127.3,
125.1, 121.3, 40.1, 34.3, 30.8; MS (m/z) 250 (MNa+); HRMS. Calcd
for C11H17NNaO2S (MNa+) 250.0878. Found: 250.0905.
N-(2,5-(Di-tert-butyl)phenyl)-4-methoxybenzenesulfonamide
(3d). 3d was prepared from 4-methoxybenzenesulfonyl chloride (682
mg, 3.3 mmol) and 2,5-di-tert-butylaniline (616 mg, 3.0 mmol) in
accordance with the procedure for the synthesis of 1a. Purification of
the residue by column chromatography (hexane/AcOEt = 30 and 3)
gave 3d (1.04 g, 92%). 3d: white solid; mp 188−190 °C; IR (neat)
3248, 1319, 1148 cm−1; 1H NMR (400 MHz, CDCl3) δ: 7.79 (2H, td,
J = 2.8, 9.2 Hz), 7.37 (1H, d, J = 2.3 Hz), 7.22 (1H, d, J = 8.2 Hz),
7.05 (1H, dd, J = 2.3, 8.2 Hz), 6.91 (2H, td, J = 2.8, 9.2 Hz), 6.61
(1H, brs), 3.09 (3H, s), 1.34 (9H, s), 1.22 (9H, s); 13C{1H} NMR
(100 MHz, CDCl3) δ: 163.1, 149.8, 137.3, 134.7, 131.6, 129.7, 126.7,
121.8, 119.7, 114.1, 55.6, 34.2, 33.9, 31.1, 31.0; MS (m/z) 398
(MNa+); HRMS. Calcd for C21H29NNaO3S (MNa+) 398.1766.
Found: 398.1746.
N-(2-(tert-Butyl)phenyl)cyclohexanesulfonamide (1i). Under N2
atmosphere, to 2-tert-butylaniline (224 mg, 1.5 mmol) and triethyl-
amine (2.5 mL, 18.0 mmol) in CH2Cl2 (0.8 mL) was added
cyclohexanesulfonyl chloride (301 mg, 1.65 mmol) at 0 °C, and the
reaction mixture was stirred for 48 h at rt. The mixture was poured
into 2 N HCl and extracted with AcOEt. The AcOEt extracts were
washed with brine, dried over MgSO4, and evaporated to dryness.
Purification of the residue by column chromatography (hexane/
AcOEt = 20) gave 1i (226 mg, 51%). 1i: white solid; mp 91−93 °C;
N-(2,5-(Di-tert-butyl)phenyl)-2-methylbenzenesulfonamide (3e).
3e was prepared from 2-methylbenzenesulfonyl chloride (315 mg,
1.65 mmol) and 2,5-di-tert-butylaniline (308 mg, 1.5 mmol) in
accordance with the procedure for the synthesis of 1a. Purification of
the residue by column chromatography (hexane/AcOEt = 30) and
subsequent MPLC (hexane/AcOEt = 40) gave 3e (626 mg, 58%). 3e:
1
white solid; mp 125−128 °C; IR (neat) 3337, 1314, 1161 cm−1; H
NMR (400 MHz, CDCl3) δ: 8.10 (1H, dd, J = 1.4, 7.3 Hz), 7.51 (1H,
t, J = 7.3 Hz), 7.35−7.39 (2H, m), 7.28 (1H, d, J = 8.7 Hz), 7.07 (1H,
dd, J = 1.8, 8.2 Hz), 6.78 (1H, d, J = 1.8 Hz), 6.57 (1H, brs), 2.71
(3H, s), 1.47 (9H, s), 1.07 (9H, s); 13C{1H} NMR (100 MHz,
CDCl3) δ: 149.7, 139.6, 138.4, 137.1, 134.5, 133.0, 132.7, 129.8,
126.9, 126.4, 122.3, 120.6, 34.2, 34.0, 31.1, 30.9, 20.4; MS (m/z) 382
(MNa+); HRMS. Calcd for C21H29NNaO2S (MNa+) 382.1817.
Found: 382.1813.
1
IR (neat) 3439, 1327, 1144 cm−1; H NMR (400 MHz, CDCl3) δ:
7.44 (1H, dd, J = 1.4, 8.2 Hz), 7.38 (1H, dd, J = 1.4, 7.8 Hz), 7.19
(1H, dt, J = 1.8, 7.8 Hz), 7.07 (1H, dt, J = 1.4, 7.8 Hz), 6.35 (1H,
brs), 3.22 (1H, tt, J = 3.7, 11.9 Hz), 2.20−2.24 (2H, m), 1.88−1.92
(2H, m), 1.59−1.72 (3H, m), 1.46 (9H, s), 1.18−1.34 (3H, m);
13C{1H} NMR (100 MHz, CDCl3) δ: 138.4, 135.6, 127.02, 126.96,
124.0, 120.3, 61.7, 34.1, 30.6, 26.1, 24.9, 24.8; MS (m/z) 318
(MNa+); HRMS. Calcd for C16H25NNaO2S (MNa+) 318.1504.
Found: 318.1520.
N-(2,5-Di-(tert-butyl)phenyl)-2,4,6-tri-methylbenzenesulfona-
mide (3f). 3f was prepared from 2,4,6-tri-methylbenzenesulfonyl
chloride (722 mg, 3.3 mmol) and 2,5-di-tert-butylaniline (616 mg, 3.0
mmol) in accordance with the procedure for the synthesis of 1a.
Purification of the residue by column chromatography (hexane/
AcOEt = 30) and subsequent MPLC (hexane/AcOEt = 30) gave 3f
(814 mg, 70%). 3f: white solid; mp 125−129 °C; IR (neat) 3437,
N-(2,5-(Di-tert-butyl)phenyl)-4-methylbenzenesulfonamide (3a).
3a was prepared from 4-methylbenzenesulfonyl chloride (629 mg, 3.3
mmol) and 2,5-di-tert-butylaniline (616 mg, 3.0 mmol) in accordance
with the procedure for the synthesis of 1a. Purification of the residue
by column chromatography (hexane/AcOEt = 30 and 3) gave 3a
(917 mg, 85%). 3a: white solid; mp 163−166 °C; IR (neat) 3246,
1
1329, 1148 cm−1; H NMR (400 MHz, CDCl3) δ: 7.30 (1H, d, J =
1
1325, 1155 cm−1; H NMR (400 MHz, CDCl3) δ: 7.75 (2H, d, J =
8.2 Hz), 7.07 (1H, dd, J = 1.8, 8.2 Hz), 7.02 (2H, s), 6.53 (1H, d, J =
2.3 Hz), 6.52 (1H, s), 2.65 (6H, s), 2.33 (3H, s), 1.48 (9H, s), 1.04
(9H, s); 13C{1H} NMR (100 MHz, CDCl3) δ: 149.7, 142.5, 139.2,
138.8, 136.1, 134.9, 132.2, 127.0, 122.5, 120.7, 34.3, 33.9, 31.2, 30.8,
23.0, 21.0; MS (m/z) 410 (MNa+); HRMS. Calcd for
C23H33NNaO2S (MNa+) 410.2130. Found: 410.2157.
N-(2,5-Di-(tert-butyl)phenyl)naphthalene-1-sulfonamide (3g).
3g was prepared from nephthalen-1-sulfonyl chloride (748 mg, 3.3
mmol) and 2-tert-butylaniline (616 mg, 3.0 mmol) in accordance with
the procedure for the synthesis of 1a. Purification of the residue by
column chromatography (hexane/AcOEt = 20 and 3) gave 3g (961
mg, 81%). 3g: white solid; mp 172−175 °C; IR (neat) 3271, 1314,
1161 cm−1; 1H NMR (400 MHz, CDCl3) δ: 8.69 (1H, d, J = 9.2 Hz),
8.37 (1H, dd, J = 0.9, 7.3 Hz), 8.11 (1H, d, J = 8.2 Hz), 7.97 (1H, d, J
= 7.3 Hz), 7.55−7.69 (3H, m), 7.23 (1H, d, J = 8.7 Hz), 7.02 (1H,
dd, J = 2.3, 8.7 Hz), 6.77 (1H, d, J = 2.3 Hz), 6.71 (1H, brs), 1.43
(9H, s), 1.01 (9H, s); 13C{1H} NMR (100 MHz, CDCl3) δ: 149.6,
138.8, 136.1, 134.6, 134.4, 134.3, 130.3, 129.2, 128.4, 128.1, 127.0,
126.9, 124.4, 124.2, 122.5, 120.8, 34.2, 34.0, 31.2, 30.9; MS (m/z)
418 (MNa+); HRMS. Calcd for C24H29NNaO2S (MNa+) 418.1817.
Found: 418.1803.
N-(2,5-(Di-tert-butyl)phenyl)methanesulfonamide (3h). 3h was
prepared from methanesulfonyl chloride (378 mg, 3.3 mmol) and 2,5-
di-tert-butylaniline (616 mg, 3.0 mmol) in accordance with the
procedure for the synthesis of 1a. Purification of the residue by
column chromatography (hexane/AcOEt = 20 and 3) gave 3h (740
mg, 87%). 3h: white solid; mp 150−153 °C; IR (neat) 3314, 1316,
1146 cm−1; 1H NMR (400 MHz, CDCl3) δ: 7.62 (1H, d, J = 2.3 Hz),
7.32 (1H, d, J = 8.3 Hz), 7.14 (1H, dd, J = 2.3, 8.3 Hz), 6.48 (1H,
brs), 3.04 (3H, s), 1.44 (9H, s), 1.31 (9H, s); 13C{1H} NMR (100
MHz, CDCl3) δ: 150.6, 136.5, 134.8, 126.9, 122.0, 118.8, 39.8, 34.4,
33.9, 31.1, 30,9; MS (m/z) 306 (MNa+); HRMS. Calcd for
C15H25NNaO2S (MNa+) 306.1504. Found: 306.1533.
8.2 Hz), 7.33 (1H, d, J = 2.3 Hz), 7.21−7.26 (3H, m), 7.05 (1H, dd, J
= 2.3, 8.2 Hz), 6.61 (1H, brs), 2.39 (3H, s), 1.34 (9H, s), 1.20 (9H,
s); 13C{1H} NMR (100 MHz, CDCl3) δ: 149.8, 143.8, 137.5, 137.2,
134.5, 129.5, 127.6, 126.7, 121.9, 119.9, 34.2, 34.0, 31.01, 31.00, 21.5;
MS (m/z) 382 (MNa+); HRMS. Calcd for C21H29NNaO2S (MNa+)
382.1817. Found: 382.1835.
N-(2,5-(Di-tert-butyl)phenyl)benzenesulfonamide (3b). 3b was
prepared from benzenesulfonyl chloride (583 mg, 3.3 mmol) and 2,5-
di-tert-butylaniline (616 mg, 3.0 mmol) in accordance with the
procedure for the synthesis of 1a. Purification of the residue by
column chromatography (hexane/AcOEt = 30 and 3) gave 3b (974
mg, 94%). 3b: white solid; mp 139−141 °C; IR (neat) 3244, 1325,
1159 cm−1; 1H NMR (400 MHz, CDCl3) δ: 7.86−7.89 (2H, m), 7.56
(1H, tt, J = 0.9, 7.3 Hz), 7.45−7.7.50 (2H, m), 7.28 (1H, d, J = 2.3
Hz), 7.23 (1H, d, J = 8.3 Hz), 7.06 (1H, dd, J = 2.3, 8.2 Hz), 6.61
(1H, brs), 1.34 (9H, s), 1.12 (9H, s); 13C{1H} NMR (100 MHz,
CDCl3) δ: 149.9, 140.3, 137.9, 134.4, 133.0, 129.0, 127.5, 126.8,
122.2, 120.3, 34.2, 34.0, 31.0; MS (m/z) 368 (MNa+); HRMS. Calcd
for C20H27NNaO2S (MNa+) 368.1660. Found: 368.1671.
N-(2,5-(Di-tert-butyl)phenyl)-4-nitrobenzenesulfonamide (3c).
3c was prepared from 4-nitrobenzenesulfonyl chloride (731 mg, 3.3
mmol) and 2,5-di-tert-butylaniline (616 mg, 3.0 mmol) in accordance
with the procedure for the synthesis of 1a. Purification of the residue
by column chromatography (hexane/AcOEt = 30 and 3) gave 3c
(1.13 g, 96%). 3c: white solid; mp 171−173 °C; IR (neat) 3268,
1
1348, 1163 cm−1; H NMR (400 MHz, CDCl3) δ: 8.31 (2H, td, J =
2.3, 9.2 Hz), 8.01 (2H, td, J = 2.3, 9.2 Hz), 7.33 (1H, d, J = 2.3 Hz),
7.26 (1H, d, J = 8.2 Hz), 7.13 (1H, dd, J = 1.8, 8.2 Hz), 6.70 (1H,
brs), 1.31 (9H, s), 1.22 (9H, s); 13C{1H} NMR (100 MHz, CDCl3)
δ: 150.2, 150.1, 145.8, 138.3, 133.5, 128.7, 127.2, 124.2, 123.1, 120.6,
34.3, 34.1, 31.1, 31.0; MS (m/z) 413 (MNa+); HRMS. Calcd for
C20H26N2NaO4S (MNa+) 413.1511. Found: 413.1532.
E
DOI: 10.1021/acs.joc.9b00989
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Catalytic Enantioselective N-Allylation of Sulfonamides
(General Procedure). Under N2 atmosphere, to sulfonamide 3a
(360 mg, 1.0 mmol) in THF (5.0 mL) was added NaH (60% assay
40.2 mg, 1.0 mmol) at 0 °C, and the reaction mixture was stirred for
20 min at −20 °C. The mixture of (allyl-Pd-Cl)2 (8.1 mg, 0.022
mmol), (S,S)-Trost ligand (35 mg, 0.044 mmol), and allyl acetate
(325 μL, 3.0 mmol) in THF (2.0 mL) was added to the reaction
mixture at −20 °C, and the mixture was stirred for 3 h at −20 °C. The
mixture was poured into 1 N HCl and extracted with AcOEt. The
AcOEt extracts were washed with brine, dried over MgSO4, and
evaporated to dryness. Purification of the residue by column
chromatography (hexane/AcOEt = 15) gave 4a (360 mg, 90%).
The ee (78% ee) of 4a was determined by HPLC using Chiralpak AS-
H column [25 cm × 0.46 cm i.d.; 5% i-PrOH in hexane; flow rate, 0.8
mL/min; (+)-4a (major); tR = 8.3 min, (−)-4a (minor); tR = 12.8
min].
N-Allyl-N-(2,5-(di-tert-butyl)phenyl)-4-methylbenzenesulfona-
mide (4a). 4a: white solid; mp 68−72 °C (78% ee), 78−81 °C
(racemate); [α]D25 = +22.3 (77% ee, c 0.74, CHCl3); IR (neat) 1346,
1165 cm−1; 1H NMR (400 MHz, CDCl3) δ: 7.64 (2H, d, J = 8.2 Hz),
7.48 (1H, d, J = 8.2 Hz), 7.30 (2H, d, J = 8.2 Hz), 7.25 (1H, m), 6.34
(1H, d, J = 2.3 Hz), 5.77 (1H, tdd, J = 6.9, 10.1, 17.4 Hz), 4.99−5.05
(2H, m), 4.15 (1H, dd, J = 6.9, 14.2 Hz), 4.07 (1H, dd, J = 6.9, 14.2
Hz), 2.46 (3H, s), 1.53 (9H, s), 1.09 (9H, s); 13C{1H} NMR (100
MHz, CDCl3) δ: 148.4, 146.9, 143.4, 136.7, 136.0, 132.3, 130.0,
129.4, 128.8, 126.7, 125.3, 119.6, 56.0, 36.3, 33.9, 32.9, 30.8, 21.5; MS
(m/z) 422 (MNa+); HRMS. Calcd for C24H33NNaO2S (MNa+)
422.2130. Found: 422.2122.
using Chiralpak AS-H column [25 cm × 0.46 cm i.d.; 15% i-PrOH in
hexane; flow rate, 0.8 mL/min; (+)-2c (major); tR = 9.8 min, (−)-2c
(minor); tR = 20.8 min]. 2c: white solid; mp 103−106 °C (70% ee),
118−121 °C (racemate); [α]D25 = +55.7 (70% ee, c 0.97, CHCl3); IR
1
(neat) 1346, 1163 cm−1; H NMR (400 MHz, CDCl3) δ: 8.36 (2H,
td, J = 2.3, 9.2 Hz), 7.92 (2H, td, J = 2.3, 9.2 Hz), 7.63 (1H, dd, J =
1.4, 7.8 Hz), 7.31 (1H, dt, J = 1.4, 7.3 Hz), 6.99 (1H, dt, J = 1.4, 7.8
Hz), 6.30 (1H, dd, J = 1.8, 8.2 Hz), 5.74 (1H, tdd, J = 6.9, 10.1, 17.0
Hz), 5.12 (1H, d, J = 17.0 Hz), 5.11 (1H, d, J = 10.1 Hz), 4.13−4.23
(2H, m), 1.48 (9H, s); 13C{1H} NMR (100 MHz, CDCl3) δ: 150.3,
150.0, 144.6, 136.1, 131.2, 131.0, 130.0, 129.3, 128.9, 126.0, 123.9,
120.7, 56.3, 36.9, 32.9; MS (m/z) 397 (MNa+); HRMS. Calcd for
C19H22N2NaO4S (MNa+) 397.1198. Found: 397.1189.
N-Allyl-N-(2-(tert-butyl)phenyl)-4-methoxybenzenesulfonamide
(2d). 2d was prepared from sulfonamide 1d (96 mg, 0.3 mmol) in
accordance with the procedure for the synthesis of 4a. Purification of
the residue by column chromatography (hexane/AcOEt = 10) gave
2d (99 mg, 92%). The ee (70% ee) of 2d was determined by HPLC
using Chiralpak AS-H column [25 cm × 0.46 cm i.d.; 15% i-PrOH in
hexane; flow rate, 0.8 mL/min; (+)-2d (major); tR = 11.0 min,
(−)-2d (minor); tR = 18.1 min]. 2d: white solid; mp 78−82 °C (70%
ee), 72.5−76 °C (racemate); [α]D25 = +62.5 (70% ee, c 0.90, CHCl3);
1
IR (neat) 1339, 1155 cm−1; H NMR (400 MHz, CDCl3) δ: 7.67
(2H, td, J = 2.3, 9.2 Hz), 7.58 (1H, dd, J = 1.4, 8.2 Hz), 7.25 (1H, m),
6.99 (1H, m), 6.98 (2H, dd, J = 2.3, 9.2 Hz), 6.44 (1H, dd, J = 1.4, 8.2
Hz), 5.79 (1H, tdd, J = 6.9, 10.0, 16.5 Hz), 5.04 (1H, d, J = 10.0 Hz),
5.03 (1H, d, J = 16.5 Hz), 4.17 (1H, dd, J = 6.9, 14.2 Hz), 3.99 (1H,
dd, J = 6.9, 14.2 Hz), 3.90 (3H, s), 1.54 (9H, s); 13C{1H} NMR (100
MHz, CDCl3) δ: 162.9, 150.3, 137.5, 132.2, 130.9, 130.4, 130.2,
129.4, 128.3, 125.8, 119.6, 113.8, 55.9, 55.6, 36.8, 33.0; MS (m/z)
382 (MNa+); HRMS. Calcd for C20H25NNaO3S (MNa+) 382.1453.
Found: 382.1443.
N-Allyl-N-(2-(tert-butyl)phenyl)-2-methylbenzenesulfonamide
(2e). 2e was prepared from sulfonamide 1e (91 mg, 0.3 mmol) in
accordance with the procedure for the synthesis of 4a. Purification of
the residue by column chromatography (hexane/AcOEt = 10) gave
2e (89 mg, 86%). The ee (86% ee) of 2e was determined by HPLC
using Chiralpak AS-H column [25 cm × 0.46 cm i.d.; 15% i-PrOH in
hexane; flow rate, 0.8 mL/min; (−)-2e (major); tR = 5.7 min, (+)-2e
(minor); tR = 7.0 min]. 2e: white solid; mp 67−70 °C (86% ee), 53−
56 °C (racemate); [α]D25 = −12.7 (86% ee, c 0.87, CHCl3); IR (neat)
1341, 1165 cm−1; 1H NMR (400 MHz, CDCl3) δ: 7.86 (1H, dd, J =
1.4, 7.8 Hz), 7.58 (1H, dd, J = 1.8, 8.2 Hz), 7.47 (1H, dt, J = 1.4, 7.3
Hz), 7.35 (1H, t, J = 7.3 Hz), 7.23−7.27 (2H, m), 6.91 (1H, dt, J =
1.8, 7.3 Hz), 6.32 (1H, dd, J = 1.4, 8.2 Hz), 5.79 (1H, m), 5.05 (1H,
d, J = 11.0 Hz), 5.04 (1H, d, J = 16.5 Hz), 4.31 (1H, dd, J = 6.9, 14.2
Hz), 4.04 (1H, dd, J = 7.3, 14.2 Hz), 2.14 (3H, s), 1.54 (9H, s);
13C{1H} NMR (100 MHz, CDCl3) δ: 150.5, 138.8, 136.8, 136.3,
N-Allyl-N-(2-(tert-butyl)phenyl)-4-methylbenzenesulfonamide
(2a). 2a was prepared from sulfonamide 1a (91 mg, 0.3 mmol) in
accordance with the procedure for the synthesis of 4a. Purification of
the residue by column chromatography (hexane/AcOEt = 15) gave
2a (103 mg, quant). The ee (73% ee) of 2a was determined by HPLC
using Chiralpak AS-H column [25 cm × 0.46 cm i.d.; 15% i-PrOH in
hexane; flow rate; 0.8 mL/min, (+)-2a (major); tR = 7.3 min, (−)-2a
(minor); tR = 11.1 min]. 2a: white solid; mp 100−102 °C (73% ee),
99−102 °C (racemate); [α]D25 = +47.7 (70% ee, c 1.00, CHCl3); IR
1
(neat) 1339, 1157 cm−1; H NMR (400 MHz, CDCl3) δ: 7.62 (2H,
d, J = 8.2 Hz), 7.58 (1H, dd, J = 1.4, 7.8 Hz), 7.31 (2H, d, J = 8.2 Hz),
7.26 (1H, dd, J = 1.8, 8.6 Hz), 6.98 (1H, td, J = 1.3, 7.8 Hz), 6.41
(1H, dd, J = 1.4, 8.2 Hz), 5.78 (1H, m), 5.04 (1H, d, J = 10.5 Hz),
5.03 (1H, d, J = 17.0 Hz), 4.18 (1H, dd, J = 6.9, 14.2 Hz), 4.00 (1H,
dd, J = 6.9, 14.2 Hz), 2.46 (3H, s), 1.54 (9H, s); 13C{1H} NMR (100
MHz, CDCl3) δ: 150.3, 143.5, 137.3, 135.6, 132.1, 130.5, 129.5,
129.3, 128.8, 128.3, 125.8, 119.6, 55.9, 36.8, 33.0, 21.6; MS (m/z)
366 (MNa+); HRMS. Calcd for C20H25NNaO2S (MNa+) 366.1504.
Found: 366.1504.
N-Allyl-N-(2-(tert-butyl)phenyl)benzenesulfonamide (2b). 2b was
prepared from sulfonamide 1b (87 mg, 0.3 mmol) in accordance with
the procedure for the synthesis of 4a. Purification of the residue by
column chromatography (hexane/AcOEt = 15) gave 2b (99 mg,
quant). The ee (72% ee) of 2b was determined by HPLC using
Chiralpak AS-H column [25 cm × 0.46 cm i.d.; 15% i-PrOH in
hexane; flow rate, 0.8 mL/min; (+)-2b (major); tR = 6.8 min, (−)-2b
(minor); tR = 9.6 min]. 2b: white solid; mp 68−71 °C (72% ee),
colorless oil (racemate); [α]D25 = +27.8 (72% ee, c 0.49, CHCl3); IR
132.8, 132.7, 132.1, 130.7, 130.6, 129.7, 128.2, 126.2, 125.6, 119.8,
56.0, 36.9, 33.0, 21.6; MS (m/z) 366 (MNa+); HRMS. Calcd for
C20H25NNaO2S (MNa+) 366.1504. Found: 366.1510.
N-Allyl-N-(2-(tert-butyl)phenyl)-2,4,6-trimethylbenzenesulfona-
mide (2f). 2f was prepared from sulfonamide 1f (99 mg, 0.3 mmol) in
accordance with the procedure for the synthesis of 4a. Purification of
the residue by column chromatography (hexane/AcOEt = 30) gave 2f
(86 mg, 77%). The ee (91% ee) of 2f was determined by HPLC using
Chiralpak AS-H column [25 cm × 0.46 cm i.d.; 3% i-PrOH in hexane;
flow rate, 0.8 mL/min; (+)-2f (major); tR = 5.1 min, (−)-2f (minor);
tR = 6.8 min]. 2f: white solid; mp 141−145 °C (90% ee), 140−143
1
(neat) 1343, 1161 cm−1; H NMR (400 MHz, CDCl3) δ: 7.74−7.77
(2H, m), 7.57−7.65 (2H, m), 7.50−7.54 (2H, m), 7.26 (1H, dt, J =
1.4, 7.8 Hz), 6.97 (1H, dt, J = 1.4, 7.8 Hz), 6.38 (1H, dd, J = 1.4, 7.8
Hz), 5.77 (1H, m), 5.05 (1H, d, J = 11.0 Hz), 5.04 (1H, d, J = 16.0
Hz), 4.20 (1H, dd, J = 6.9, 14.2 Hz), 4.04 (1H, dd, J = 6.9, 14.2 Hz),
1.55 (9H, s); 13C{1H} NMR (100 MHz, CDCl3) δ: 150.3, 138.5,
137.1, 132.8, 132.0, 130.6, 129.5, 128.8, 128.7, 128.4, 125.8, 119.8,
56.0, 36.8, 33.0; MS (m/z) 352 (MNa+); HRMS. Calcd for
C19H23NNaO2S (MNa+) 352.1347. Found: 352.1366.
25
°C (racemate); [α]D = +27.2 (90% ee, c 0.67, CHCl3); IR (neat)
1339, 1157 cm−1; 1H NMR (400 MHz, CDCl3) δ: 7.55 (1H, dd, J =
1.4, 8.2 Hz), 7.23 (1H, m), 6.89−6.93 (3H, m), 6.49 (1H, dd, J = 1.4,
8.2 Hz), 5.80 (1H, tdd, J = 7.0, 10.0, 17.0 Hz), 5.04 (1H, d, J = 10.0
Hz), 5.01 (1H, d, J = 17.0 Hz), 4.38 (1H, dd, J = 7.3 13.7 Hz), 4.20
(1H, dd, J = 6.9, 13.7 Hz), 2.30 (3H, s), 2.26 (6H, s), 1.49 (9H, s);
13C{1H} NMR (100 MHz, CDCl3) δ: 150.5, 142.0, 140.0, 135.9,
133.3, 132.6, 132.3, 131.1, 130.7, 128.1, 125.5, 119.8, 55.8, 37.0, 33.0,
24.1, 20.9; MS (m/z) 394 (MNa+); HRMS. Calcd for
C22H29NNaO2S (MNa+) 394.1817. Found: 394.1828.
N-Allyl-N-(2-(tert-butyl)phenyl)-4-nitrobenzenesulfonamide (2c).
2c was prepared from sulfonamide 1c (100 mg, 0.3 mmol) in
accordance with the procedure for the synthesis of 4a. Purification of
the residue by column chromatography (hexane/AcOEt = 15) gave
2c (104 mg, 93%). The ee (74% ee) of 2c was determined by HPLC
F
DOI: 10.1021/acs.joc.9b00989
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
N-Allyl-N-(2-(tert-butyl)phenyl)naphthalene-1-sulfonamide (2g).
2g was prepared from sulfonamide 1g (102 mg, 0.3 mmol) in
accordance with the procedure for the synthesis of 4a. Purification of
the residue by column chromatography (hexane/AcOEt = 15) gave
2g (105 mg, 92%). The ee (88% ee) of 2g was determined by HPLC
using Chiralpak AS-H column [25 cm × 0.46 cm i.d.; 5% i-PrOH in
hexane; flow rate, 0.8 mL/min; (−)-2g (major); tR = 10.2 min, (+)-2g
(minor); tR = 11.2 min]. 2g: white solid; mp 141.5−144 °C (88% ee),
138−140 °C (racemate); [α]D25 = −33.8 (88% ee, c 0.45, CHCl3); IR
(1H, dd, J = 6.9, 14.2 Hz), 4.10 (1H, dd, J = 6.9, 14.2 Hz), 1.53 (9H,
s), 1.08 (9H, s); 13C{1H} NMR (100 MHz, CDCl3) δ: 148.4, 146.9,
139.0, 136.5, 132.6, 132.1, 130.1, 128.8, 126.6, 125.4, 119.7, 56.1,
36.3, 33.9, 32.9, 30.9; MS (m/z) 408 (MNa+); HRMS. Calcd for
C23H31NNaO2S (MNa+) 408.1973. Found: 408.1971.
N-Allyl-N-(2,5-(di-tert-butyl)phenyl)-4-nitrobenzenesulfonamide
(4c). 4c was prepared from sulfonamide 3c (117 mg, 0.3 mmol) in
accordance with the procedure for the synthesis of 4a. Purification of
the residue by column chromatography (hexane/AcOEt = 15) gave
4c (130 mg, quant). The ee (77% ee) of 4c was determined by HPLC
using Chiralpak AS-H column [25 cm × 0.46 cm i.d.; 5% i-PrOH in
hexane; flow rate, 0.8 mL/min; (+)-4c (major); tR = 8.8 min, (−)-4c
(minor); tR = 12.8 min]. 4c: white solid; mp 87−90 °C (racemate),
1
(neat) 1335, 1159 cm−1; H NMR (400 MHz, CDCl3) δ: 8.50 (1H,
d, J = 8.2 Hz), 8.14 (1H, dd, J = 0.9, 7.3 Hz), 8.10 (1H, d, J = 8.2 Hz),
7.91 (1H, d, J = 7.8 Hz), 7.52−7.60 (3H, m), 7.42 (1H, m), 7.20 (1H,
m), 6.68 (1H, td, J = 1.4, 7.8 Hz), 6.11 (1H, dd J = 1.4, 7.8 Hz), 5.66
(1H, tdd, J = 6.9, 10.5, 17.0 Hz), 4.96 (1H, d, J = 10.5 Hz), 4.95 (1H,
d, J = 17.0 Hz), 4.32 (1H, dd, J = 6.9, 14.2 Hz), 4.10 (1H, dd, J = 6.9,
14.2 Hz), 1.58 (9H, s); 13C{1H} NMR (100 MHz, CDCl3) δ: 150.6,
136.1, 134.6, 134.4, 134.3, 132.1, 131.4, 130.9, 130.5, 129.4, 128.5,
128.3, 127.6, 126.7, 126.4, 125.4, 124.1, 119.8, 55.7, 36.9, 33.1; MS
(m/z) 402 (MNa+); HRMS. Calcd for C23H25NNaO2S (MNa+)
402.1504. Found: 402.1496.
25
colorless oil (77% ee); [α]D = +22.7 (78% ee, c 0.45, CHCl3); IR
1
(neat) 1344, 1161 cm−1; H NMR (400 MHz, CDCl3) δ: 8.35 (2H,
td, J = 2.3, 9.2 Hz), 7.95 (2H, td, J = 2.3, 9.2 Hz), 7.53 (1H, d, J = 8.2
Hz), 7.30 (1H, dd, J = 2.3, 8.2 Hz), 6.27 (1H, d, J = 2.3 Hz), 5.73
(1H, tdd, J = 6.9, 10.1, 17.0 Hz), 5.08−5.14 (2H, m), 4.26 (1H, dd, J
= 7.3, 14.7 Hz), 4.14 (1H, dd, J = 6.9, 14.7 Hz), 1.53 (9H, s), 1.09
(9H, s); 13C{1H} NMR (100 MHz, CDCl3) δ: 149.9, 148.7, 146.9,
145.2, 135.6, 131.1, 130.7, 130.0, 126.6, 125.9, 123.9, 120.7, 56.3,
36.4, 34.0, 32.8, 30.8; MS (m/z) 453 (MNa+); HRMS. Calcd for
C23H30N2NaO4S (MNa+) 453.1824. Found: 453.1832.
N-Allyl-N-(2,5-(di-tert-butyl)phenyl)-4-methoxybenzenesulfona-
mide (4d). 4d was prepared from sulfonamide 3d (113 mg, 0.3
mmol) in accordance with the procedure for the synthesis of 4a.
Purification of the residue by column chromatography (hexane/
AcOEt = 10) gave 4d (118 mg, 95%). The ee (74% ee) of 4d was
determined by HPLC using Chiralpak AS-H column [25 cm × 0.46
cm i.d.; 5% i-PrOH in hexane; flow rate, 0.8 mL/min; (+)-4d
(major); tR = 11.2 min, (−)-4d (minor); tR = 19.0 min]. 4d: colorless
oil (74% ee), colorless oil (racemate); [α]D25 = +26.5 (76% ee, c 1.20,
CHCl3); IR (neat) 1341, 1148 cm−1; 1H NMR (400 MHz, CDCl3) δ:
7.69 (2H, td, J = 2.7, 8.7 Hz), 7.49 (1H, d, J = 8.7 Hz), 7.25 (1H, dd,
J = 2.3, 8.7 Hz), 6.98 (2H, td, J = 2.7, 8.7 Hz), 6.39 (1H, d, J = 2.3
Hz), 5.77 (1H, tdd, J = 6.9, 10.0, 17.0 Hz), 5.00−5.05 (2H, m), 4.14
(1H, dd, J = 6.9, 14.2 Hz), 4.06 (1H, dd, J = 7.3, 14.2 Hz), 3.89 (3H,
s), 1.53 (9H, s), 1.11 (9H, s); 13C{1H} NMR (100 MHz, CDCl3) δ:
162.8, 148.4, 146.9, 136.9, 132.3, 130.9, 130.8, 130.0, 126.6, 125.3,
119.5, 113.9, 56.0, 55.6, 36.3, 33.9, 32.9, 30.9; MS (m/z) 438
(MNa+); HRMS. Calcd for C24H33NNaO3S (MNa+) 438.2079.
Found: 438.2058.
N-Allyl-N-(2-(tert-butyl)phenyl)methanesulfonamide (2h). 2h
was prepared from sulfonamide 1h (68 mg, 0.3 mmol) in accordance
with the procedure for the synthesis of 4a. Purification of the residue
by column chromatography (hexane/AcOEt = 5) gave 2h (69 mg,
86%). The ee (49% ee) of 2h was determined by HPLC using
Chiralpak AS-H column [25 cm × 0.46 cm i.d.; 15% i-PrOH in
hexane; flow rate, 0.8 mL/min; (−)-2h (major); tR = 8.8 min, (+)-2h
25
(minor); tR = 10.4 min]. 2h: colorless oil; [α]D = −9.4 (35% ee, c
1
1.08, CHCl3); IR (neat) 1333, 1153 cm−1; H NMR (400 MHz,
CDCl3) δ: 7.59 (1H, dd, J = 1.4, 8.2 Hz), 7.32 (1H, dt, J = 1.8, 7.3
Hz), 7.20 (1H, dt, J = 1.8, 7.8 Hz), 7.14 (1H, dd, J = 1.8, 8.2 Hz),
6.05 (1H, tdd, J = 7.3, 10.1, 17.0 Hz), 5.29 (1H, dd, J = 1.4, 17.0 Hz),
5.27 (1H, d, J = 10.1 Hz), 4.31 (1H, dd, J = 7.8, 14.7 Hz), 4.02 (1H,
dd, J = 6.4, 14.7 Hz), 3.04 (3H, s), 1.49 (9H, s); 13C{1H} NMR (100
MHz, CDCl3) δ: 149.5, 137.5, 131.8, 130.5, 130.1, 128.7, 126.5,
120.8, 56.2, 39.8, 36.4, 32.5; MS (m/z) 290 (MNa+); HRMS. Calcd
for C14H21NNaO2S (MNa+) 290.1191. Found: 290.1194.
N-Allyl-N-(2-(tert-butyl)phenyl)cyclohexanesulfonamide (2i). 2i
was prepared from sulfonamide 1i (87 mg, 0.3 mmol) in accordance
with the procedure for the synthesis of 4a. Purification of the residue
by column chromatography (hexane/AcOEt = 20) gave 2i (101 mg,
quant). The ee (66% ee) of 2i was determined by HPLC using
Chiralcel OD-3 column [25 cm × 0.46 cm i.d.; 1% i-PrOH in hexane;
flow rate, 0.5 mL/min; (−)-2i (minor); tR = 33.7 min, (+)-2i
(major); tR = 33.7 min]. 2i: white solid; mp 83−86 °C (66% ee),
colorless oil (racemate); [α]D25 = +32.6 (35% ee, c 1.91, CHCl3); IR
N-Allyl-N-(2,5-(di-tert-butyl)phenyl)-2-methylbenzenesulfona-
mide (4e). 4e was prepared from sulfonamide 3e (108 mg, 0.3 mmol)
in accordance with the procedure for the synthesis of 4a. Purification
of the residue by column chromatography (hexane/AcOEt = 15) gave
4e (101 mg, 84%). The ee (89% ee) of 4e was determined by HPLC
using Chiralcel OD-3 column [25 cm × 0.46 cm i.d.; 1% i-PrOH in
hexane; flow rate, 0.8 mL/min; (−)-4e (minor); tR = 11.2 min, (+)-4e
(major); tR = 12.8 min]. 4e: white solid; mp 66−69 °C (89% ee), 77−
80 °C (racemate); [α]D25 = +36.4 (90% ee, c 0.59, CHCl3); IR (neat)
1339, 1163 cm−1; 1H NMR (400 MHz, CDCl3) δ: 7.89 (1H, dd, J =
1.4, 7.8 Hz), 7.49 (1H, d, J = 8.2 Hz), 7.46 (1H, dt, J = 1.4, 7.3 Hz),
7.36 (1H, t, J = 7.3 Hz), 7.20−7.25 (2H, m), 6.23 (1H, d, J = 2.3 Hz),
5.79 (1H, m), 5.00−5.05 (2H, m), 4.29 (1H, dd, J = 6.9, 14.2 Hz),
4.10 (1H, dd, J = 6.9, 14.2 Hz), 2.08 (3H, s), 1.53 (9H, s), 1.03 (9H,
s); 13C{1H} NMR (100 MHz, CDCl3) δ: 148.2, 147.1, 138.7, 137.2,
135.6, 133.0, 132.5, 132.3, 130.42, 130.35, 126.6, 126.4, 125.4, 119.7,
56.2, 36.5, 33.8, 33.0, 30.7, 21.9; MS (m/z) 422 (MNa+); HRMS.
Calcd for C24H33NNaO2S (MNa+) 422.2130. Found: 422.2118.
N-Allyl-N-(2,5-(di-tert-butyl)phenyl)-2,4,6-trimethylbenzenesul-
fonamide (4f). 4f was prepared from sulfonamide 3f (116 mg, 0.3
mmol) in accordance with the procedure for the synthesis of 4a.
Purification of the residue by column chromatography (hexane/
AcOEt = 30) gave 4f (94 mg, 73%). The ee (95% ee) of 4f was
determined by HPLC using Chiralcel OD-3 column [25 cm × 0.46
cm i.d.; 1% i-PrOH in hexane; flow rate, 0.8 mL/min; (+)-4f (minor);
tR = 8.5 min, (−)-4f (major); tR = 8.9 min]. 4f: white solid; mp 108−
111 °C (93% ee), 98−100.5 °C (racemate); [α]D25 = −5.91 (93% ee,
1
(neat) 1325, 1138 cm−1; H NMR (400 MHz, CDCl3) δ: 7.59 (1H,
dd, J = 1.8, 8.2 Hz), 7.29 (1H, m), 7.19 (1H, dt, J = 1.8, 7.8 Hz), 7.11
(1H, dd, J = 1.4, 7.8 Hz), 5.92 (1H, tdd, J = 6.9, 10.1, 17.0 Hz), 5.12
(1H, d, J = 10.1 Hz), 5.11 (1H, dd, J = 1.4, 17.0 Hz), 4.32 (1H, dd, J
= 7.3, 14.2 Hz), 4.20 (1H, dd, J = 6.9, 14.2 Hz), 3.17 (1H, tt, J = 3.7,
11.9 Hz), 2.33 (1H, d, J = 12.8 Hz), 2.18 (1H, d, J = 12.8 Hz), 1.85−
1.95 (2H, m), 1.57−1.74 (3H, m), 1.50 (9H, s), 1.24−1.40 (3H, m);
13C{1H} NMR (100 MHz, CDCl3) δ: 150.3, 136.4, 132.8, 131.4,
131.0, 128.4, 126.3, 119.9, 61.6, 56.8, 36.8, 32.6, 27.1, 27.0, 25.4, 25.3,
25.1; MS (m/z) 358 (MNa+); HRMS. Calcd for C19H29NNaO2S
(MNa+) 358.1817. Found: 358.1823.
N-Allyl-N-(2,5-(di-tert-butyl)phenyl)benzenesulfonamide (4b).
4b was prepared from sulfonamide 3b (104 mg, 0.3 mmol) in
accordance with the procedure for the synthesis of 4a. Purification of
the residue by column chromatography (hexane/AcOEt = 15) gave
4b (94 mg, 81%). The ee (78% ee) of 4b was determined by HPLC
using Chiralpak AS-H column [25 cm × 0.46 cm i.d.; 5% i-PrOH in
hexane; flow rate, 0.8 mL/min; (+)-4b (major); tR = 6.9 min, (−)-4b
(minor); tR = 8.8 min]. 4b: white solid; mp 80−82 °C (78% ee), 63−
66 °C (racemate); [α]D25 = +7.1 (71% ee, c 0.98, CHCl3,); IR (neat)
1
1341, 1165 cm−1; H NMR (400 MHz, CDCl3) δ: 7.76 (2H, d, J =
7.3 Hz), 7.62 (1H, t, J = 7.3 Hz), 7.48−7.53 (3H, m), 7.26 (1H, dd, J
= 1.8, 8.7 Hz), 6.31 (1H, d, J = 1.8 Hz), 5.76 (1H, tdd, J = 6.9, 10.0,
17.0 Hz), 5.04 (1H, d, J = 10.0 Hz), 5.03 (1H, d, J = 17.0 Hz), 4.17
1
c 0.46, CHCl3); IR (neat) 1337, 1165 cm−1; H NMR (400 MHz,
G
DOI: 10.1021/acs.joc.9b00989
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
CDCl3) δ: 7.47 (1H, d, J = 8.7 Hz), 7.23 (1H, dd, J = 2.3, 8.2 Hz),
6.90 (2H, s), 6.34 (1H, d, J = 2.3 Hz), 5.77 (1H, tdd, J = 6.8, 10.1,
17.0 Hz), 5.02 (1H, dd, J = 1.3, 10.1 Hz), 4.98 (1H, dd, J = 1.3, 17.0
Hz), 4.37 (1H, dd, J = 7.3 13.7 Hz), 4.22 (1H, dd, J = 6.4, 13.7 Hz),
2.29 (3H, s), 2.25 (6H, s), 1.48 (9H, s), 1.04 (9H, s); 13C{1H} NMR
(100 MHz, CDCl3) δ: 148.0, 147.1, 141.8, 139.8, 135.0, 133.6, 132.8,
132.4, 130.4, 127.8, 125.3, 119.6, 55.9, 36.6, 33.7, 32.9, 30.6, 24.3,
20.8; MS (m/z) 450 (MNa+); HRMS. Calcd for C26H37NNaO2S
(MNa+) 450.2443. Found: 450.2444.
ACKNOWLEDGMENTS
■
This work was partly supported by JSPS KAKENNHI (C
17K08220).
REFERENCES
■
(1) For reviews, see: (a) Alkorta, I.; Elguero, J.; Roussel, C.;
Vanthuyne, N.; Piras, P. Atropisomerism and Axial Chirality in
Heteroaromatic Compounds. Adv. Heterocycl. Chem. 2012, 105, 1.
(b) Takahashi, I.; Suzuki, Y.; Kitagawa, O. Asymmetric Synthesis of
Atropisomeric Compounds with an N−C Chiral Axis. Org. Prep.
Proced. Int. 2014, 46, 1. (c) Kumarasamy, E.; Raghunathan, R.; Sibi,
M. P.; Sivaguru, J. Nonbiaryl and Heterobiaryl Atropisomers:
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(2) Kitagawa, O.; Kohriyama, M.; Taguchi, T. Catalytic Asymmetric
Synthesis of Optically Active Atropisomeric Anilides through
Enantioselective N-Allylation with Chiral Pd-tol-BINAP Catalyst. J.
Org. Chem. 2002, 67, 8682.
(3) Papers on enantioselective synthesis of N-C axially chiral anilides
through chiral Pd-catalyzed N-allylation by other groups: (a) Terauchi,
J.; Curran, D. P. N-Allylation of anilides with chiral palladium
catalysts: The first catalytic asymmetric synthesis of axially chiral
anilides. Tetrahedron: Asymmetry 2003, 14, 587. (b) Liu, Y.; Feng, X.;
Du, H. Asymmetric synthesis of axially chiral anilides by Pd-catalyzed
allylic substitutions with P/olefin ligands. Org. Biomol. Chem. 2015,
13, 125.
(4) (a) Hayashi, T. Catalytic Asymmetric Synthesis; Ojima, I., Ed.;
VCH Publishers: New York, 1994; pp 325−365. (b) Trost, B. M.;
Van Vranken, D. L. Asymmetric Transition Metal-Catalyzed Allylic
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and Downs of Allylpalladium Complexes in Catalysis. Synlett 1996,
705. (d) Trost, B. M.; Crawley, M. L. Asymmetric transition-metal-
catalyzed allylic alkylations: applications in total synthesis. Chem. Rev.
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(5) (a) Kitagawa, O.; Takahashi, M.; Yoshikawa, M.; Taguchi, T.
Efficient Synthesis of Optically Active Atropisomeric Anilides through
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Takahashi, M.; Dobashi, Y.; Taguchi, T. Highly Enantioselective
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Asymmetric N-Arylation: Conformational Analysis and Application to
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Palladium-catalyzed synthesis of arylamines from aryl halides.
Mechanistic studies lead to coupling in the absence of tin reagents.
Tetrahedron Lett. 1995, 36, 3609.
(7) Typical papers on catalytic enantioselective synthesis of N-C
axially chiral carboxamide derivatives: (a) Brandes, S.; Bella, M.;
Kjoersgaard, A.; Jørgensen, K. A. Chirally Aminated 2-Naphthols-
Organocatalytic Synthesis of Non-Biaryl Atropisomers by Asymmetric
Friedel-Crafts Amination. Angew. Chem., Int. Ed. 2006, 45, 1147.
(b) Tanaka, K.; Takeishi, K.; Noguchi, K. Enantioselective Synthesis
of Axially Chiral Anilides through Rhodium-Catalyzed [2 + 2 + 2]
Cycloaddition of 1,6-Diynes with Trimethylsilylynamides. J. Am.
Chem. Soc. 2006, 128, 4586. (c) Shirakawa, S.; Liu, K.; Maruoka, K.
Catalytic Asymmetric Synthesis of Axially Chiral o-Iodoanilides by
Phase-Transfer Catalyzed Alkylations. J. Am. Chem. Soc. 2012, 134,
916. (d) Zhang, J.-W.; Xu, J.-H.; Cheng, D.-J.; Shi, C.; Liu, X.-Y.; Tan,
B. Discovery and enantiocontrol of axially chiral urazoles via
organocatalytic tyrosine click reaction. Nat. Commun. 2016, 7,
No. 10677. (e) Li, S.; Yang, C.; Wu, Q.; Zheng, H.; Li, X.; Cheng,
J. Atroposelective Catalytic Asymmetric Allylic Alkylation Reaction
for Axially Chiral Anilides with Achiral Morita−Baylis−Hillman
Carbonates. J. Am. Chem. Soc. 2018, 140, 12836.
N-Allyl-N-(2,5-(di-tert-butyl)phenyl)naphthalene-1-sulfonamide
(4g). 4g was prepared from sulfonamide 3g (119 mg, 0.3 mmol) in
accordance with the procedure for the synthesis of 4a. Purification of
the residue by column chromatography (hexane/AcOEt = 15) gave
4g (131 mg, quant). The ee (91% ee) of 4g was determined by HPLC
using Chiralcel OD-3 column [25 cm × 0.46 cm i.d.; 1% i-PrOH in
hexane; flow rate; 0.8 mL/min, (+)-4g (minor); tR = 13.1 min,
(−)-4g (major); tR = 16.9 min]. 4g: white solid; mp 145.5−147 °C
25
(91% ee), 144−147 °C (racemate); [α]D = −96.4 (91% ee, c 0.51,
CHCl3); IR (neat) 1339, 1161 cm−1; 1H NMR (400 MHz, CDCl3) δ:
8.47 (1H, d, J = 8.2 Hz), 8.17 (1H, dd, J = 0.9, 7.3 Hz), 8.09 (1H, d, J
= 8.2 Hz), 7.90 (1H, d, J = 8.2 Hz), 7.49−7.57 (3H, m), 7.40 (1H,
m), 7.18 (1H, dd, J = 2.3, 8.7 Hz), 6.02 (1H, d, J = 2.3 Hz), 5.68 (1H,
tdd, J = 6.9, 10.1, 17.0 Hz), 4.96 (1H, d, J = 10.1 Hz), 4.95 (1H, d, J =
17.0 Hz), 4.33 (1H, dd, J = 7.3, 14.2 Hz), 4.18 (1H, dd, J = 6.9, 14.2
Hz), 1.58 (9H, s), 0.74 (9H, s); 13C{1H} NMR (100 MHz, CDCl3)
δ: 148.0, 147.1, 135.3, 135.0, 134.2, 132.3, 131.1, 130.2, 129.6, 128.5,
127.9, 127.3, 126.6, 126.2, 125.5, 124.2, 119.7, 56.0, 36.5, 33.5, 33.0,
30.4; MS (m/z) 458 (MNa+); HRMS. Calcd for C27H33NNaO2S
(MNa+) 458.2130. Found: 458.2130.
N-Allyl-N-(2,5-(di-tert-butyl)phenyl)methanesulfonamide (4h).
4h was prepared from sulfonamide 3h (85 mg, 0.3 mmol) in
accordance with the procedure for the synthesis of 4a. Purification of
the residue by column chromatography (hexane/AcOEt = 10) gave
4h (91 mg, 94%). The ee (59% ee) of 4h was determined by HPLC
using Chiralpak AS-H column [25 cm × 0.46 cm i.d.; 5% i-PrOH in
hexane; flow rate, 0.8 mL/min; (−)-4h (major); tR = 6.9 min, (+)-4h
(minor); tR = 8.7 min]. 4h: white solid; mp 70−72 °C (58% ee), 91−
93 °C (racemate); [α]D25 = −15.5 (58% ee, c 1.00, CHCl3); IR (neat)
1
1323, 1140 cm−1; H NMR (400 MHz, CDCl3) δ: 7.50 (1H, d, J =
8.2 Hz), 7.32 (1H, dd, J = 2.3, 8.7 Hz), 7.08 (1H, d, J = 2.3 Hz), 6.06
(1H, m), 5.29 (1H, d, J = 11.0 Hz), 5.29 (1H, d, J = 15.6 Hz), 4.36
(1H, dd, J = 7.8, 14.7 Hz), 3.96 (1H, dd, J = 6.9, 14.7 Hz), 3.04 (3H,
s), 1.47 (9H, s), 1.30 (9H, s); 13C{1H} NMR (100 MHz, CDCl3) δ:
149.3, 146.3, 137.0, 132.0, 130.2, 127.3, 125.7, 121.0, 56.3, 40.0, 36.1,
34.1, 32.5, 31.1; MS (m/z) 346 (MNa+); HRMS. Calcd for
C18H29NNaO2S (MNa+) 346.1817. Found: 346.1816.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.9b00989.
Copies of 1H and 13C NMR spectra for all new
compounds 1−4; chiral HPLC chart of compounds 2
and 4; X-ray crystal data of compound 4f; and data for
the evaluation of the rotational barriers in 4f and 4h
(PDF)
Crystallographic data of 4f (CIF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: kitagawa@shibaura-it.ac.jp.
ORCID
Osamu Kitagawa: 0000-0001-7964-1879
Notes
The authors declare no competing financial interest.
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H
DOI: 10.1021/acs.joc.9b00989
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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(13) The complete racemization of 4f (90% ee) was observed after
heating for 1 h at 80 °C in CCl4.
I
DOI: 10.1021/acs.joc.9b00989
J. Org. Chem. XXXX, XXX, XXX−XXX