Diastereoselective reaction of [1-(2,4,6-triisopropylphenylsulfinyl)-2-naphthyl]methanimines via diastereomeric rotamers

Article abstract of DOI:10.1016/S0957-4166(02)00379-8

The reactions of various (1-sulfinyl-2-naphthyl)methanimines with alkyllithium reagents were examined. Naphthylmethanimines bearing a 2,4,6-triisopropylphenylsulfinyl group gave the (R_S*,S*)-products as a single diastereomer, possibly derived f

Full text of DOI:10.1016/S0957-4166(02)00379-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 1509–1518
Diastereoselective reaction of
[1-(2,4,6-triisopropylphenylsulfinyl)-2-naphthyl]methanimines via
diastereomeric rotamers
Shuichi Nakamura, Hiroki Yasuda and Takeshi Toru*
Department of Applied Chemistry, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan
Received 13 June 2002; accepted 5 July 2002
Abstract—The reactions of various (1-sulfinyl-2-naphthyl)methanimines with alkyllithium reagents were examined. Naphthyl-
methanimines bearing a 2,4,6-triisopropylphenylsulfinyl group gave the (R*,S*)-products as a single diastereomer, possibly
derived from the predominant rotamer around the CꢀS bond axis. The reactSion of chiral [1-(2,4,6-triisopropylphenylsulfinyl)-2-
naphthyl]methanimine with MeLi and subsequent elimination of the sulfinyl group afforded optically active 1-(2-naph-
thyl)ethylamine. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Recently, high stereoselectivities have been achieved in
asymmetric reactions of non-biaryl axially chiral com-
pounds with high rotational barrier around the CꢀN1,2
and CꢀC bond axes.3 However, resolution of these
compounds is always necessary prior to undertaking
these reactions.2c,e,g,h,4 We have reported diastereoselec-
tive nucleophilic reactions of 1-[(2,4,6-triisopropyl-
Scheme 1 summarizes the preparation of various
racemic [1-(arylsulfinyl)-2-naphthyl]methanimines 2a–h
from 1-(arylsulfinyl)-2-naphthaldehydes5 1a–c. Treat-
ment of 1-(p-tolylsulfinyl)-, 1-(2,4,6-trimethylphenyl-
sulfinyl)-, and 1-(2,4,6-triisopropylphenylsulfinyl)-2-
naphthaldehydes5 1a–c with various amines in the pres-
,
ence of 3 A molecular sieves in refluxing benzene
phenyl)sulfinyl]-2-naphthaldehydes
with
Grignard
gave the corresponding [1-(arylsulfinyl)-2-naphthyl]-
reagents or with silyl enol ethers as well as the stereose-
lective reduction of 1-[(2,4,6-triisopropylphenyl)-
sulfinyl]-2-naphthyl ketones. High stereoselectivities
have been achieved in these reactions without prior
resolution of axially chiral sulfinylnaphthalenes, and it
has been demonstrated that the stereochemical outcome
can be ascribed to the high population of a single
diastereomer around the CnaphthꢀS bond axis, where one
of the isopropyl groups efficiently blocks one face of
the carbonyl group from nucleophilic attack.5 In order
to extend the scope and limitations of this new stereose-
lective reaction, we examined the nucleophilic reaction
of (1-sulfinyl-2-naphthyl)methanimine with nucleo-
philes. We herein report on highly stereoselective reac-
tions of [1-(arylsulfinyl)-2-naphthyl]methanimines with
organolithium reagents.
* Corresponding author. Tel./fax: (+)81-52-735-5217; e-mail: toru@
ach.nitech.ac.jp
Scheme 1.
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00379-8

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S. Nakamura et al. / Tetrahedron: Asymmetry 13 (2002) 1509–1518
methanimines, 2a–g in high yields.6 The N-methylimine
2h was prepared on heating with methylamine under
reflux in ethanol instead of benzene and in the absence
of molecular sieves.7
cleavage of the sulfinyl group caused by nucleophilic
attack of MeLi on the sulfur center. On the other hand,
the reaction of [1-(2,4,6-triisopropylphenylsulfinyl)-2-
naphthyl]methanimine 2c with MeLi gave the (R*,S*)-
(sulfinylnaphthyl)alkylamine 3 in high yield as a Ssingle
diastereomer (entry 3). These results show that the
sterically encumbered 2,4,6-triisopropylphenylsulfinyl
group blocks the nucleophilic attack by MeLi on the
sulfur center. The reaction of 2d–f having various N-
substituents with MeLi afforded the addition products
4–6 with diastereomeric ratio of >98:2 (entries 4–6),
whereas similar treatment of the N-methyl and N-ben-
zylimines 2g,h with MeLi did not afford the desired
products (entries 7 and 8). The highest yield was
obtained in the reaction of the N-p-chlorophenylimine
2f (entry 6). The reaction of 2f with vinyllithium or
phenyllithium also gave the products 7 and 8 with high
stereoselectivity (entries 9 and 10).9 In contrast to the
highly stereoselective reaction of [1-(2,4,6-triisopropyl-
[1-(tert-Butylsulfinyl)-2-naphthyl]methanimine 2i was
prepared in 78% yield by treatment of (tert-butylsulfi-
nyl)naphthaldehyde5 1d (Scheme 2) with p-chloroani-
line in the presence of 0.6 equiv. of TiCl4 in benzene at
0°C.8 Heating the mixture in refluxing benzene in the
,
presence of 3 A molecular sieves failed to afford 2i
because of its thermal instability.
phenylsulfinyl)-2-naphthyl]methanimines
2c–f,
the
Scheme 2.
naphthylmethanimine 2i bearing a bulky tert-butylsulfi-
nyl group gave the product 9 in a ratio of 61:39 (entry
11), showing that high stereoselectivity is not always
obtained in the reaction of the naphthylmethanimines
Alkylation of the sulfinylimines 2 was first examined
with Grignard reagents. However, alkylmagnesium
halides such as methylmagnesium iodide failed to react,
whereas alkyllithium reagents were found to afford the
desired alkylated products. Thus, 1-sulfinylnaphthalen-
2-imines 2a–i were reacted with 1.1 equiv. of the appro-
priate organolithium reagent in THF at −78°C. The
results are shown in Table 1.
1
bearing a bulky sulfinyl group. The H NMR spectrum
of 2i measured at −78°C in THF-d8 showed three sets
of two signals at 1.25 (major) and 1.26 (minor) ppm
due to the tert-butyl protons, at 8.52 (major) and 9.65
(minor) ppm due to the peri-H(8) proton and at 9.26
(minor) and 10.3 (major) ppm due to the methanylyli-
dene proton, which were obviously derived from the
restricted rotation about the CnaphthꢀS bond. Thus, 2i
exists as two conformers, either having the sulfinyl
oxygen close to the imino group (A) or close to the
peri-H(8) of the naphthalene (B) as shown in Fig. 1.
The reaction of 1-(p-tolylsulfinyl)- and 1-(2,4,6-
trimethylphenylsulfinyl)-2-naphthylmethanimines 2a,b
with MeLi resulted in the formation of a number of
unidentified products and the desired products could
not be isolated (entries 1 and 2). This is probably due to
Table 1. Stereoselective reaction of (1-sulfinyl-2-naphthyl)methanimines 2a–i with organolithium reagents
Entry
Substrate
R2
R3M
Product
Yield (%)
Diastereomer ratioa (R*,S*):(R*,R*)
S S
R1
b
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
2g
2h
2f
Tol
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
o-MeOC6H4
Ph
p-ClC6H4
CH2Ph
Me
MeLi
MeLi
MeLi
MeLi
MeLi
MeLi
MeLi
MeLi
CH2ꢁCHLi
PhLi
–
–
–
–
b
Mes
Tip
Tip
Tip
Tip
Tip
Tip
Tip
Tip
tBu
3
4
5
6
72
79
89
\98:2
\98:2
\98:2
\98:2
–
98
N.R.c
b
–
–
9
10
11
p-ClC6H4
p-ClC6H4
p-ClC6H4
7
8
9
85
96
85
\98:2
\98:2
61:39
2f
2i
MeLi
a Determined by 1H NMR analysis.
b A number of unidentified products were obtained.
c 2g was recovered.

S. Nakamura et al. / Tetrahedron: Asymmetry 13 (2002) 1509–1518
1511
The structure determined from the NMR data is in
good accord with that obtained by X-ray crystallogra-
phy; the sulfoxide oxygen is placed away from the
peri-H(8), the imino group almost on the plane of the
naphthalene ring, and the nitrogen away from the
sulfoxide (Fig. 3). In this structure, one of the faces of
the imino group is hindered by the 2,4,6-triisopropyl-
phenyl group. Thus, the reaction with RLi would pro-
ceed through a non-chelated transition state, and the
nucleophile approaches from the less hindered side to
give (R*,S*)-3 (Fig. 3).15 It should be noted that the
non-cheSlated mechanism of the [1-(2,4,6-triisopropyl-
phenylsulfinyl)-2-naphthyl]methanimine is in contrast
to that reported by Clayden and co-workers, in which
the reaction of the 2-imino-1-naphthamide with RLi
proceeds through a chelated transition state.3c,h
Figure 1. The diastereomeric ratio in THF-d8 at −78°C and
the rotational barrier in DMSO-d6 of 2i determined by the H
NMR spectral analysis.
1
The minor conformer was assigned to be the rotamer B
on the basis of the downfield shift10 of the peri-H(8)
proton due to the anisotropy of the sulfinyl group. By
1H NMR analysis, the ratio of the major and the minor
isomers was estimated to be 63:37, which was essen-
tially the same as the diastereomeric ratio of the prod-
ucts.11 The rate constant for the rotation was found to
be k=17 s−1 at 58°C in DMSO-d6 by line shape analysis
of the broadened tert-butyl proton signal in the region
of coalescence. From the rate constant, k, the activation
energy (DG‡) of rotation was calculated using Eyring’s
equation12 to be 17.6 kcal/mol.13
Furthermore, the reaction of [2-(2,4,6-triisopropyl-
phenylsulfinyl)benzyl]methanimine 10 (which appar-
ently has a lower barrier to rotation than the naphthyl-
methanimines 2c–f) with MeLi gave the product 11
with much lower stereoselectivity than that seen in the
reactions of 2c–f (Scheme 3). These results suggest that
the stereochemical outcome in the reactions of 2c–f is
strongly related to the rotational barrier about the
CnaphthꢀS bond, pointing to the significant role of the
peri-H(8) proton.
On the other hand, each signal due to the peri-H(8)
proton and the imino carbon of 2c–f appeared as one
conformer, and the rotamers of the sulfoxides 2c–f
originated from the rotational barrier around the CꢀS
bond axis could not be detected in the 1H NMR
spectra. Since the reaction of 2c–f shows high
diastereoselectivity (Table 1), it can be reasonably
assumed that the reaction of these imines with a nucleo-
phile proceeds faster than the rotation process between
1
rotamers. In the H and 13C NMR spectra of 2c in
CDCl3, the peri-H(8) proton and the imino carbon
appeared at 8.24 and 160.3 ppm, respectively, which are
similar to the chemical shifts of the corresponding
protons in the major rotamer (A) of 2i (Fig. 2). These
spectral data and the chemical behavior of 2c–f and 2i
are quite similar to those of 1-sulfinyl-2-naphthalde-
hydes previously reported.5,14
Scheme 3.
1
Figure 2. Significant H and 13C NMR chemical shifts for the (sulfinylnaphthyl)methanimines 2i and 2f in CDCl3.

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S. Nakamura et al. / Tetrahedron: Asymmetry 13 (2002) 1509–1518
Figure 3. Chem 3D structure derived from the X-ray crystallography of 2c and (R*,S*)-3.
S
Having established the high diastereoselectivity in the
reaction of 2c, we next applied this reaction to the
preparation of an optically active 2-naphthylalkylamine
derivative starting from the chiral [1-(2,4,6-triisopropyl-
phenylsulfinyl)-2-naphthyl]methanimine (R)-2c. When
the sulfinylnaphthaldehyde (R)-1c5b was treated with
diastereomeric rotamers. We have demonstrated that
the high diastereoselectivity is due to the restricted
rotation about the CnaphthꢀS bond having the bulky
2,4,6-triisopropylphenylsulfinyl group. In addition,
removal of the sulfinyl group from the products would
provide a convenient and efficient method for the
preparation of the optically active 2-naphthylalkyl-
amine derivatives.
,
p-methoxyaniline in the presence of 3 A molecular
sieves in refluxing benzene, racemization occurred, giv-
ing the imine 2c with low enantiomeric purity. The
optically active sulfoxide (R)-2c was obtained when
(R)-1c was reacted with p-methoxyaniline in the pres-
ence of TiCl4 at 0°C. The chiral (R)-2c was then reacted
with MeLi at −78°C to give the product 3 in a
diastereomer ratio of >98:2. Cleavage of the sulfinyl
group with n-BuLi and HMPA gave the optically active
amine 12 (Scheme 4),16 which can be transformed to the
amine by the oxidative cleavage of the 4-methoxy-
phenyl N-protecting group.17
4. Experimental
4.1. N-(p-Methoxyphenyl)-[1-(p-tolylsulfinyl)-2-
naphthyl]methanimine, 2a
A mixture of (p-tolylsulfinyl)-2-naphthaldehyde 1a (150
mg, 0.486 mmol), p-methoxyaniline (90 mg, 0.729
,
mmol) and 3 A molecular sieves in benzene (5.0 mL)
was heated under reflux for 12 h. The mixture was
filtered through Celite® and the filtrate was concen-
trated under reduced pressure to leave a residue, which
was purified by column chromatography (silica gel 25 g,
hexane/ethyl acetate=80:20) to afford 2a (206 mg,
99%): mp 39.1–40.0°C; Rf=0.64 (hexane/ethyl ace-
3. Conclusion
The highly enantioselective reaction of naphthylmetha-
nimines bearing the bulky 2,4,6-triisopropylphenylsulfi-
nyl group was achieved without isolation of the
1
tate=50:50); H NMR: l 2.30 (s, 3H, CH3), 3.84 (s,
Scheme 4.

S. Nakamura et al. / Tetrahedron: Asymmetry 13 (2002) 1509–1518
1513
3H, OCH3), 6.94 (d, 2H, J=8.9 Hz, Ar), 7.18 (d, 2H,
J=8.0 Hz, Ar), 7.29 (d, 2H, J=8.9 Hz, Ar), 7.42 (d,
2H, J=8.0 Hz, Ar), 7.45–7.56 (m, 2H, Ar), 7.86–7.91
(m, 1H, Ar), 8.00–8.04 (m, 1H, Ar), 8.39–8.43 (m, 1H,
Ar), 8.75–8.80 (m, 1H, Ar), 9.61 (s, 1H, CHꢁ); 13C
NMR: l 21.2, 55.5, 114.4, 122.8, 124.3, 124.4, 124.9,
127.7, 127.9, 128.9, 129.9, 130.9, 132.6, 135.1, 136.7,
139.5, 140.3, 141.5, 144.2, 153.9, 159.0; IR (KBr): 2960,
1610, 1500, 1460, 1290, 1250, 1080, 1040, 850, 750
cm−1; EIMS m/z (rel. intensity): 400 (M+, 1.2), 383 (48),
382 (100), 213 (33). Anal. calcd for C25H21NO2S: C,
75.16; H, 5.30; N, 3.51. Found: C, 75.11; H, 5.36; N,
3.50%.
4.4. N-(o-Methoxyphenyl)-[1-(2,4,6-triisopropylphenyl-
sulfinyl)-2-naphthyl]methanimine, 2d
The reaction was carried out as described above, using
1c (204 mg, 0.503 mmol) and o-methoxyaniline (124
mg, 1.01 mmol). Usual work-up gave the crude product
which was purified by column chromatography (silica
gel 4 g, hexane/ethyl acetate/Et3N=95:3:2) to afford 2d
(223 mg, 96%): mp 54.2–54.9°C; Rf=0.26 (hexane/ethyl
1
acetate=80:20); H NMR: l 0.81 (d, 6H, J=6.9 Hz,
CH3×2), 1.18 (d, 6H, J=6.9 Hz, CH3×2), 1.29 (d, 6H,
J=6.8 Hz, CH3×2), 2.82 (sept., 1H, J=6.9 Hz,
CHMe2), 3.92 (s, 3H, OCH3), 4.10 (sept., 2H, J=6.8
Hz, CHMe2×2), 6.89–6.96 (m, 2H, Ar), 7.01 (s, 2H,
Tip), 7.13–7.52 (m, 4H, Ar), 7.80–8.09 (m, 3H, Ar),
8.36 (d, 1H, J=8.7 Hz, Ar), 9.99 (s, 1H, CHꢁ); 13C
NMR: l 23.4, 24.7, 29.0, 34.2, 55.8, 111.2, 120.5, 121.2,
123.2, 123.9, 126.5, 126.7, 126.9, 127.0, 128.7, 129.1,
130.4, 134.2, 136.9, 137.8, 140.0, 142.3, 150.0, 152.5,
153.4, 159.8; IR (KBr): 2940, 1600, 1490, 1460, 1250,
1120, 1050, 1030, 740 cm−1; EIMS m/z (rel. intensity):
511 (M+, 4.8), 495 (33), 495 (46), 494 (74), 453 (34), 452
(100). Anal. calcd for C33H37NO2S: C, 77.46; H, 7.29;
N, 2.74. Found: C, 77.33; H, 7.46 N, 2.71%.
4.2. N-(p-Methoxyphenyl)-[1-(2,4,6-trimethylphenyl-
sulfinyl)-2-naphthyl]methanimine, 2b
The reaction was carried out as described above except
using 1b (157 mg, 0.486 mmol) and p-methoxyaniline
(90 mg, 0.729 mmol). Standard work-up gave the crude
product which was purified by column chromatography
(silica gel 25 g, hexane/ethyl acetate=80:10) to afford
2b (206 mg, 99%): mp 54.5–55.0°C; Rf=0.36 (hexane/
1
ethyl acetate=80:20); H NMR: l 2.18 (s, 3H, CH3),
4.5. N-Phenyl-[1-(2,4,6-triisopropylphenylsulfinyl)-2-
naphthyl]methanimine, 2e
2.42 (s, 6H, CH3×2), 3.82 (s, 3H, OCH3), 6.77 (s, 2H,
Mes), 6.92 (d, 2H, J=6.6 Hz, Ar), 7.31 (d, 2H, J=6.6
Hz, Ar), 7.39–7.52 (m, 2H, Ar), 7.81–7.86 (m, 1H, Ar),
7.93–7.97 (m, 1H, Ar), 8.12–8.16 (m, 1H, Ar), 8.26–8.30
(m, 1H, Ar), 9.89 (s, 1H, CHꢁ); 13C NMR: l 19.9, 20.9,
55.4, 114.2, 122.8, 123.6, 125.7, 127.0, 127.1, 128.8,
129.5, 131.1, 131.3, 134.2, 137.2, 138.2, 138.3, 138.5,
141.8, 145.0, 156.7, 158.5; IR (KBr): 2860, 1610, 1510,
1440, 1290, 1250, 1150, 1060, 1030, 850, 740 cm−1;
EIMS m/z (rel. intensity): 428 (M+, 3), 411 (66), 410
(100), 241 (31). Anal. calcd for C27H25NO2S: C, 75.85;
H, 5.89; N, 3.28. Found: C, 75.85; H, 6.02; N, 3.23%.
The reaction was carried out as described above except
using 1c (202 mg, 0.497 mmol) and aniline (0.068 mL,
0.746 mmol). Standard work-up gave the crude product
which was purified by column chromatography (silica
gel 20 g, hexane/ethyl acetate/Et3N=95:3:2) to afford
2e (228 mg, 95%): mp 54–55°C; Rf=0.46 (hexane/ethyl
1
acetate=80:20); H NMR: l 0.81 (d, 6H, J=6.7 Hz,
CH3×2), 1.18 (d, 6H, J=6.9 Hz, CH3×2), 1.28 (d, 6H,
J=6.7 Hz, CH3×2), 2.81 (sept., 1H, J=6.9 Hz,
CHMe2), 4.09 (sept., 2H, J=6.7 Hz, CHMe2×2), 7.01
(s, 2H, Tip), 7.18–7.50 (m, 7H, Ar), 7.80–8.10 (m, 3H,
Ar), 8.28 (d, 1H, J=8.6 Hz, Ar), 9.99 (s, 1H, CHꢁ); 13
C
4.3. N-(p-Methoxyphenyl)-[1-(2,4,6-triisopropylphenyl-
sulfinyl)-2-naphthyl]methanimine, 2c
NMR: l 23.3, 23.5, 24.7, 29.0, 34.1, 121.3, 123.2, 123.8,
125.9, 126.5, 126.9, 128.7, 129.0, 130.4, 134.1, 136.7,
137.7, 140.0, 149.9, 152.4, 153.4, 159.5; IR (KBr): 2960,
1610, 1590, 1460, 1150, 1030, 820, 740, 700 cm−1; EIMS
m/z (rel. intensity): 481 (M+, 21), 466 (66), 465 (99), 423
(100), 421 (46), 420 (37), 295 (36), 278 (41), 262 (38),
247 (87), 187 (45). Anal. calcd for C32H35NOS: C,
79.79; H, 7.32; N, 2.91. Found: C, 79.72; H, 7.46; N,
2.84%.
The reaction was carried out as described above except
using 1c (108 mg, 0.266 mmol) and p-methoxyaniline
(66 mg, 0.532 mmol). Standard work-up gave the crude
product which was purified by column chromatography
(silica gel 15 g, hexane/Et3N=90:10) to afford 2c (132
mg, 97%): mp 147.0–148.0°C; Rf=0.31 (hexane/ethyl
1
acetate=80:20); H NMR: l 0.82 (d, 6H, J=6.9 Hz,
CH3×2), 1.18 (d, 6H, J=6.9 Hz, CH3×2), 1.28 (d, 6H,
J=6.8 Hz, CH3×2), 2.82 (sept., 1H, J=6.9 Hz,
CHMe2), 3.83 (s, 3H, OCH3), 4.10 (sept., 2H, J=6.8
Hz, CHMe2×2), 6.89–6.96 (m, 2H, Ar), 7.01 (s, 2H,
Tip), 7.29–7.49 (m, 4H, Ar), 7.80–8.09 (m, 3H, Ar),
8.31 (d, 1H, J=8.6 Hz, Ar), 10.1 (s, 1H, CHꢁ); 13C
NMR: l 25.0, 26.3, 30.6, 35.8, 57.0, 115.8, 124.3, 124.9,
125.4, 128.0, 128.1, 128.4, 130.3, 130.8, 132.0, 135.7,
138.7, 139.3, 141.2, 147.1, 151.5, 155.0, 158.9, 159.9; IR
(KBr): 2960, 1620, 1590, 1510, 1480, 1290, 1250, 1150,
1030, 830, 740 cm−1; EIMS m/z (rel. intensity): 511
(M+, 4), 452 (82), 292 (63), 122 (54), 28 (100). Anal.
calcd for C33H37NO2S: C, 77.46; H, 7.29; N, 2.74;
Found: C, 77.35; H, 7.45; N, 2.69%.
4.6. N-(p-Chlorophenyl)-[1-(2,4,6-triisopropylphenyl-
sulfinyl)-2-naphthyl]methanimine, 2f
The reaction was carried out as described above except
using 1c (314 mg, 0.773 mmol) and p-chloroaniline (198
mg, 1.55 mmol). Standard work-up gave the crude
product which was purified by column chromatography
(silica gel 18 g, hexane/ethyl acetate/Et3N=95:3:2) to
afford 2f (132 mg, 99%): mp 170.0–170.5°C; Rf=0.53
1
(hexane/ethyl acetate=80:20); H NMR: l 0.81 (d, 6H,
J=6.9 Hz, CH3×2), 1.18 (d, 6H, J=6.9 Hz, CH3×2),
1.29 (d, 6H, J=6.8 Hz, CH3×2), 2.82 (sept., 1H, J=6.9
Hz, CHMe2), 4.07 (sept., 2H, J=6.8 Hz, CHMe2×2),
7.01 (s, 2H, Tip), 7.23–7.51 (m, 6H, Ar), 7.82–7.84 (m,

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S. Nakamura et al. / Tetrahedron: Asymmetry 13 (2002) 1509–1518
1H, Ar), 7.94 (d, 2H, J=8.5 Hz, Ar), 8.24 (d, 1H,
J=8.5 Hz, Ar), 10.0 (s, 1H, CHꢁ); 13C NMR: l 23.4,
24.8, 29.0, 34.2, 122.7, 123.3, 123.8, 126.6, 127.1,
127.8, 128.8, 128.9, 129.1, 130.5, 131.4, 134.2, 136.7,
137.6, 140.3, 150.0, 150.9, 153.6, 160.3; IR (KBr):
2960, 1610, 1490, 1480, 1050, 840, 740 cm−1; EIMS
m/z (rel. intensity): 515 (M+, 0.1), 497 (39), 453 (100),
293 (55), 184 (47), 112 (39). Anal. calcd for
C32H34ClNOS: C, 74.47; H, 6.64; N, 2.71. Found: C,
74.35; H, 6.72; N, 2.76%.
was added TiCl4 (1.41 mol L−1 in CH2Cl2, 0.60 mL,
0.84 mmol) at 0°C. After stirred for 30 min, the mix-
ture was filtered through Celite® and the filtrate was
concentrated under reduced pressure to leave a residue
which was purified by column chromatography (silica
gel 50 g, hexane/ethyl acetate/Et3N=80:18:2) to afford
2i (402 mg, 78%). The atropisomer ratio was deter-
mined to be 63:37 by the 1H NMR analysis of the
product in THF-d8 at −78°C: Rf=0.66 (hexane/ethyl
1
t
acetate=50:50); H NMR: l 1.25 (s, 5.7H, Bu, major
t
isomer), 1.26 (s, 3.3H, Bu, minor isomer), 7.18–7.43
4.7. N-Benzyl-[1-(2,4,6-triisopropylphenylsulfinyl)-2-
(m, 2H, Ar), 7.56–7.64 (m, 3H, Ar), 7.86–7.94 (m, 5H,
Ar), 8.01 (d, 2H, J=8.8 Hz, Ar), 8.28 (d, 2H, J=8.8
Hz, Ar), 8.41–8.44 (m, 1H, Ar), 8.52 (d, 1.3H, J=8.8
Hz, Ar, major isomer), 9.26 (s, 0.7H, CHꢁ, minor
isomer), 9.63–9.69 (m, 0.7H, Ar, minor isomer), 10.3
(s, 1.3H, CHꢁ, major isomer); 13C NMR: l 24.3, 25.0,
60.4, 61.2, 122.2, 122.7, 123.4, 124.7, 125.0, 127.0,
127.3, 127.5, 127.9, 128.4, 128.6, 129.1, 129.4, 131.3,
131.8, 132.3, 132.6, 133.2, 133.8, 134.9, 135.2, 136.7,
138.5, 149.8, 150.0, 156.8, 158.8; IR (KBr): 2960, 1610,
1480, 1200, 1160, 1100, 1050, 840 cm−1; EIMS m/z
(rel. intensity): 369 (M+, 2), 297 (42), 296 (38), 295
(100), 294 (38). Anal. calcd for C21H20ClNOS: C,
68.19; H, 5.45; N, 3.79; Found: C, 68.18; H, 5.51; N,
3.74%.
naphthyl]methanimine, 2g
The reaction was carried out as described above
except using 1c (517 mg, 1.27 mmol) and benzylamine
(205 mg, 1.91 mmol). Standard work-up gave the
crude product which was purified by recrystallization
to afford 2g (573 mg, 91%): mp 58–59°C; Rf=0.42
(hexane/ethyl acetate=80:20); 1H NMR: l 0.79 (d,
6H, J=6.7 Hz, CH3×2), 1.18 (d, 6H, J=6.9 Hz, CH3×
2), 1.28 (d, 6H, J=6.7 Hz, CH3×2), 2.82 (sept., 1H,
J=6.9 Hz, CHMe2), 4.07 (sept., 2H, J=6.7 Hz,
CHMe2×2), 4.84 (s, 2H, CH2Ph), 7.01 (s, 2H, Tip),
7.25–7.49 (m, 6H, Ar), 7.78–7.89 (m, 2H, Ar), 7.98–
8.02 (m, 2H, Ar), 8.10–8.17 (m, 1H, Ar), 9.84 (s, 1H,
CHꢁ); 13C NMR: l 23.5, 24.7, 29.0, 34.2, 65.5, 123.2,
123.9, 126.4, 126.7, 126.9, 127.1, 128.2, 128.4, 128.7,
129.1, 130.3, 134.1, 136.5, 137.8, 139.4, 149.9, 153.3,
160.7; IR (KBr): 2960, 1640, 1600, 1460, 1040, 820,
770, 730, 700 cm−1; EIMS m/z (rel. intensity): 495
(M+, 9.8), 479 (46), 478 (100), 261 (40). Anal. calcd for
C33H37NOS: C, 79.96; H, 7.52; N, 2.83. Found: C,
79.84; H, 7.68; N, 2.79%.
4.10. Reaction of (1-sulfinyl-2-naphthyl)methanimines
with alkyllithium. (R*,S*)-N-(p-Methoxyphenyl)-1-[1-
S
(2,4,6-triisopropylphenylsulfinyl)-2-naphthyl]ethylamine,
(R*,S*)-3
S
To a solution of 2c (102 mg, 0.220 mmol) in THF (2.2
mL) was added MeLi (1.14 mol L−1 THF solution,
0.29 mL, 0.33 mmol) at −78°C and the mixture was
stirred for 15 min. Saturated aq. NH4Cl was added
and the mixture was extracted with CH2Cl2. The com-
bined organic extracts were washed with brine, dried
over Na2SO4, and concentrated under reduced pres-
sure to leave a residue which was purified by column
chromatography (silica gel 12 g, hexane/ethyl ace-
4.8. N-Methyl-[1-(2,4,6-triisopropylphenylsulfinyl)-2-
naphthyl]methanimine, 2h
A solution of 1c (517 mg, 1.27 mmol) and methyl-
amine (200 mg, 40% aqueous solution, 2.58 mmol) in
EtOH (10 mL) was stirred under reflux for 12 h. The
mixture was purified by recrystallization to afford 2h
(470 mg, 87%): mp 54–55°C; Rf=0.35 (hexane/ethyl
tate=90:10) to afford (R*,S*)-3 (84 mg, 73%). The
S
1
acetate=80:20); H NMR: l 0.81 (d, 6H, J=6.7 Hz,
diastereomer ratio was determined to be >98:2 by the
1H NMR analysis of the crude product: mp 76.1–
76.9°C; Rf=0.15 (hexane/ethyl acetate=80:20); 1H
NMR: l 0.65 (d, 3H, J=6.4 Hz, CH3), 0.74 (d, 6H,
J=6.9 Hz, CH3×2), 1.15 (d, 6H, J=6.8 Hz, CH3×2),
1.21 (d, 6H, J=6.9 Hz, CH3×2), 2.83 (sept., 1H, J=
6.9 Hz, CHMe2), 3.65 (s, 3H, OCH3), 3.70–3.98 (br,
1H, NH), 4.20 (sept., 2H, J=6.8 Hz, CHMe2×2), 4.81
(q, 1H, J=6.4 Hz, CH), 6.38–6.42 (m, 2H, Ar), 6.60–
6.64 (m, 2H, Ar), 7.06 (s, 2H, Tip), 7.26–7.60 (m, 3H,
Ar), 7.73–7.81 (m, 2H, Ar), 9.84 (d, 1H, J=8.0 Hz,
Ar); 13C NMR: l 22.4, 23.7, 24.4, 29.1, 34.3, 48.5,
55.6, 114.3, 114.8, 122.8, 123.3, 123.8, 125.8, 126.6,
126.7, 127.5, 128.4, 131.9, 133.2, 133.7, 134.6, 138.7,
140.6, 142.5, 150.0, 152.1, 153.3; IR (KBr): 3360, 2960,
1600, 1510, 1460, 1240, 1040, 820, 760 cm−1; EIMS
m/z (rel. intensity): 527 (M+, 0.1), 509 (72), 304 (69),
121 (48), 28 (100). Anal. calcd for C34H41NO2S: C,
77.38; H, 7.83; N, 2.65; Found: C, 77.34; H, 7.75; N,
2.87%.
CH3×2), 1.19 (d, 6H, J=6.9 Hz, CH3×2), 1.30 (d, 6H,
J=6.8 Hz, CH3×2), 2.83 (sept., 1H, J=6.9 Hz,
CHMe2), 3.51 (s, 3H, CH3), 4.05 (sept., 2H, J=6.8
Hz, CHMe2×2), 7.02 (s, 2H, Tip), 7.28–7.49 (m, 2H,
Ar), 7.78–7.79 (m, 2H, Ar), 7.94–8.01 (m, 1H, Ar),
8.11–8.18 (m, 1H, Ar), 9.48 (s, 1H, CHꢁ); 13C NMR:
l 23.4, 24.5, 28.9, 34.1, 48.2, 123.0, 123.8, 126.3,
126.4, 126.6, 128.5, 129.3, 130.3, 133.9, 136.2, 137.7,
138.8, 149.7, 153.1, 160.9; IR (KBr): 2960, 1630, 1600,
1460, 1060, 880, 820, 740 cm−1; EIMS m/z (rel. inten-
sity): 419 (M+, 26), 402 (100), 361 (36), 185 (59). Anal.
calcd for C27H33NOS: C, 77.28; H, 7.93; N, 3.34.
Found: C, 77.18; H, 7.97; N, 3.39%.
4.9. N-(p-Chlorophenyl)-[1-(tert-butylsulfinyl)-2-
naphthyl]methanimine, 2i
To a solution of 1d (366 mg, 1.40 mmol) and p-
chloroaniline (1.79 g, 14.0 mmol) in benzene (14 mL)

S. Nakamura et al. / Tetrahedron: Asymmetry 13 (2002) 1509–1518
1515
4.11. (R*,S*)-N-(o-Methoxyphenyl)-1-[1-(2,4,6-triiso-
the crude product: mp 153–154°C; Rf=0.22 (hexane/ethyl
acetate=80:20); H NMR: l 0.77 (d, 6H, J=6.5 Hz,
propylphSenylsulfinyl)-2-naphthyl]ethylamine, (R*,S*)-4
1
S
CH3×2), 1.19 (d, 6H, J=6.7 Hz, CH3×2), 1.20 (d, 6H,
J=6.9 Hz, CH3×2), 1.27 (d, 3H, J=6.1 Hz, CH3), 2.87
(sept., 1H, J=6.5 Hz, CHMe2), 4.05–4.28 (m, 3H,
CHMe2×2, NH), 4.95 (q, 1H, J=6.1 Hz, CH), 6.31 (d,
2H, J=8.9 Hz, Ar), 6.94 (d, 2H, J=8.9 Hz, Ar), 7.06 (s,
2H, Tip), 7.48–7.61 (m, 3H, Ar), 7.75–7.83 (m, 2H, Ar),
9.63–9.72 (m, 1H, Ar); 13C NMR: l 22.6, 23.7, 24.2, 28.9,
34.2, 47.9, 113.9, 122.0, 122.7, 123.4, 123.7, 125.9, 126.9,
128.4, 129.0, 132.1, 132.8, 133.6, 134.8, 138.0, 142.1,
144.9, 150.0, 153.3; IR (KBr): 3290, 2960, 1600, 1490,
1460, 1320, 1040, 1020, 820, 750 cm−1; EIMS m/z (rel.
intensity): 531 (M+, 100), 515 (32), 405 (69), 347 (69), 312
(53), 205 (73), 128 (58). Anal. calcd for C33H38ClNOS:
C, 74.48; H, 7.20; N, 2.63. Found: C, 74.47; H, 7.36; N,
2.48%.
The reaction was carried out as described above except
using 2d (72.5 mg, 0.142 mmol) and MeLi (1.14 mol L−1,
0.14 mL, 0.160 mmol). Standard work-up gave the crude
product which was purified column chromatography
(silica gel 20 g, hexane/ethyl acetate=95:5) to afford
(R*,S*)-4 (65 mg, 87%). The diastereomeric ratio was
S
1
determined to be >98:2 by the H NMR analysis of the
crude product: mp 39–40°C; Rf=0.48 (hexane/ethyl
acetate=80:20); H NMR: l 0.71 (d, 9H, J=6.5 Hz,
1
(CH6 3)2CH, CH3), 1.14 (d, 6H, J=6.6 Hz, CH3×2), 1.21
(d, 6H, J=7.0 Hz, CH3×2), 2.87 (sept., 1H, J=6.6 Hz,
CHMe2), 3.84 (s, 3H, OCH3), 4.21 (sept., 2H, J=7.0 Hz,
CHMe2×2), 4.52–4.72 (m, 1H, NH), 4.89 (q, 1H, J=6.5
Hz, CH), 6.25–6.35 (m, 1H, Ar), 6.49–6.79 (m, 3H, Ar),
7.07 (s, 2H, Tip), 7.32–7.61 (m, 3H, Ar), 7.69–7.83 (m,
2H, Ar), 9.79–9.84 (m, 1H, Ar); 13C NMR: l 22.4, 23.6,
23.7, 24.4, 29.1, 34.3, 47.5, 55.4, 109.1, 110.7, 116.5, 121.6,
122.8, 123.3, 123.8, 125.8, 126.7, 128.4, 131.9, 133.1,
133.7, 134.5, 136.2, 138.6, 146.3, 150.0, 153.2; IR (KBr):
3360, 2960, 1600, 1510, 1460, 1240, 1040, 820, 760 cm−1;
EIMS m/z (rel. intensity): 514 (M+, 1), 512 (43), 511 (100),
306 (32). Anal. calcd for C34H41NO2S: C, 77.38; H, 7.83;
N, 2.65. Found: C, 77.17; H, 7.94; N, 2.75%.
4.14. (R*,S*)-N-(p-Chlorophenyl)-1-[1-(2,4,6-triiso-
propylphSenylsulfinyl)-2-naphthyl]prop-2-enylamine,
(R*,S*)-7
S
The reaction was carried out as described above except
using 2f (105 mg, 0.203 mmol) and MeLi (0.74 mol L−1,
0.30 mL, 0.222 mmol). Standard work-up gave the crude
product which was purified column chromatography
(silica gel 20 g, hexane/ethyl acetate=95:5) to afford
4.12. (R*,S*)-N-Phenyl-1-[1-(2,4,6-triisopropylphenyl-
(R*,S*)-7 (94 mg, 85%). The diastereomer ratio was
S
sulfinyl)-S2-naphthyl]ethylamine, (R*,S*)-5
determined to be >98:2 by 1H NMR analysis of the crude
product: mp 200–201°C; Rf=0.42 (hexane/ethyl ace-
tate=80:20); 1H NMR: l 0.76 (d, 6H, J=6.8 Hz, CH3×2),
1.16 (d, 12H, J=6.9 Hz, CH3×4), 2.85 (sept., 1H, J=6.9
Hz, CHMe2), 4.01–4.22 (m, 3H, CHMe2×2, NH), 4.91 (d,
1H, J=10.3Hz, CH2=), 4.98(d, 1H, J=16.1Hz, CH2=),
5.39 (ddd, 1H, J=4.1, 10.3, 16.1 Hz, CHꢁ), 6.15–6.26 (m,
1H, CH), 6.53 (d, 2H, J=8.8 Hz, Ar), 7.03 (s, 2H, Tip),
7.05 (d, 2H, J=8.8 Hz, Ar), 7.40–7.54 (m, 3H, Ar),
7.73–7.88 (m, 2H, Ar), 9.03–9.15 (m, 1H, Ar); 13C NMR:
l 23.6, 24.5, 29.1, 34.2, 52.5, 114.4, 115.0, 122.2, 123.3,
123.6, 124.6, 126.2, 126.7, 128.5, 129.0, 131.6, 133.3,
135.5, 137.2, 138.3, 139.2, 145.1, 149.9, 153.2; IR (KBr):
3320, 2960, 1600, 1500, 1460, 1320, 1040, 1020, 930, 820
cm−1; EIMS m/z (rel. intensity): 543 (M+, 9), 418 (35),
417 (100). Anal. calcd for C34H38ClNOS: C, 75.04; H,
7.04; N, 2.57. Found: C, 74.95; H, 7.12; N, 2.58%.
S
The reaction was carried out as described above except
using 2e (63 mg, 1.30 mmol) and MeLi (1.14 mol L−1,
0.170 mL, 0.194 mmol). Standard work-up gave the crude
product which was purified column chromatography
(silica gel 10 g, hexane/ethyl acetate=95:5) to afford
(R*,S*)-5 (58 mg, 89%). The diastereomer ratio was
S
1
determined to be >98:2 by the H NMR analysis of the
crude product: mp 201–202°C; Rf=0.30 (hexane/ethyl
acetate=80:20); 1H NMR:
l
0.67–0.92 (m, 9H,
(CH6 3)2CH, CH3), 1.15 (d, 6H, J=6.7 Hz, CH3×2), 1.20
(d, 6H, J=6.9 Hz, CH3×2), 2.87 (sept., 1H, J=6.9 Hz,
CHMe2), 4.05–4.35 (m, 3H, CHMe2×2, NH), 4.91 (q, 1H,
J=6.5 Hz, CH), 6.40–6.67 (m, 3H, Ar), 6.95–7.15 (m, 4H,
Tip, Ar), 7.41–7.62 (m, 3H, Ar), 7.69–7.87 (m, 2H, Ar),
9.81 (d, 1H, J=8.5 Hz, Ar); 13C NMR: l 22.5, 23.6, 23.8,
29.1, 34.3, 47.8, 112.9, 117.5, 122.8, 123.4, 123.8, 125.8,
126.8, 128.4, 129.2, 131.9, 133.1, 133.7, 134.6, 138.6,
142.3, 146.4, 150.0, 153.3; IR (KBr): 3340, 2960, 1600,
1500, 1460, 1320, 1170, 1040, 1020, 850, 750, 700 cm−1;
EIMS m/z (rel. intensity): 497 (M+, 100), 405 (36). Anal.
calcd for C33H39NOS: C, 79.63; H, 7.90; N, 2.81. Found:
C, 79.56; H, 8.06; N, 2.71%.
4.15. (R*,S*)-N-(p-Chlorophenyl)-1-phenyl-1-[1-(2,4,6-
S
triisopropylphenylsulfinyl)-2-naphthyl]methylamine,
(R*,S*)-8
S
The reaction was carried out as described above except
using 2f (63 mg, 0.130 mmol) and PhLi (1.14 mol L−1,
0.170 mL, 0.194 mmol). Standard work-up gave the crude
product which was purified column chromatography
(silica gel 10 g, hexane/ethyl acetate=95:5) to afford
4.13. (R*,S*)-N-(p-Chlorophenyl)-1-[1-(2,4,6-triiso-
propylphSenylsulfinyl)-2-naphthyl]ethylamine, (R*,S*)-6
S
(R*,S*)-8 (58 mg, 89%). The diastereomer ratio was
S
1
The reaction was carried out as described above except
using 2f (21 mg, 0.041 mmol) and MeLi (1.14 mol L−1,
0.040 mL, 0.046 mmol). Standard work-up gave the crude
product which was purified column chromatography
(silica gel 4 g, hexane/ethyl acetate/Et3N=95:3:2) to
determined to be >98:2 by the H NMR analysis of the
crude product: mp 177–178°C; Rf=0.32 (hexane/ethyl
acetate=80:20); H NMR: l 0.80 (d, 6H, J=6.8 Hz,
1
CH3×2), 1.13 (d, 6H, J=6.8 Hz, CH3×2), 1.18 (d, 6H,
J=6.9 Hz, CH3×2), 2.81 (sept., 1H, J=6.8 Hz, CHMe2),
3.99–4.18 (m, 3H, CHMe2×2, NH), 4.21–4.29 (br, 1H,
CH), 6.55 (d, 2H, J=8.9 Hz, Ar), 6.98 (s, 2H, Tip), 7.06
afford (R*,S*)-6 (21 mg, 98%). The diastereomer ratio
S
1
was determined to be >98:2 by the H NMR analysis of

1516
S. Nakamura et al. / Tetrahedron: Asymmetry 13 (2002) 1509–1518
(d, 2H, J=8.9 Hz, Ar), 7.19–7.49 (m, 7H, Ar), 7.71–
7.83 (m, 3H, Ar), 8.58–8.62 (m, 1H, Ar); 13C NMR: l
23.6, 24.7, 29.2, 34.2, 53.5, 114.5, 122.2, 123.3, 123.7,
126.2, 126.3, 126.6, 127.0, 127.1, 127.2, 128.5, 129.0,
130.6, 131.8, 132.9, 135.7, 138.0, 141.1, 141.8, 145.4,
149.7, 153.1; IR (KBr): 3360, 2960, 1600, 1500, 1460,
1320, 1040, 1020, 820, 740, 700 cm−1; EIMS m/z (rel.
intensity): 593 (M+, 5), 466 (35), 390 (30), 388 (73), 372
(61), 359 (36), 358 (30), 357 (100), 263 (41), 203 (72).
Anal. calcd for C38H40ClNOS: C, 76.81; H, 6.78; N,
2.36. Found: C, 76.83; H, 6.95; N, 2.16%.
(m, 4H, Ar), 7.07 (s, 2H, Tip), 7.45–7.60 (m, 2H, Ar),
7.72–7.80 (m, 1H, Ar), 8.15–8.24 (m, 1H, Ar), 8.64 (s,
1H, CHꢁ); 13C NMR: l 23.6, 23.8, 24.2, 29.2, 34.4,
55.4, 114.1, 122.5, 123.3, 126.0, 128.3, 130.0, 130.5,
134.3, 135.2, 144.6, 145.6, 150.9, 153.6, 154.2, 158.5; IR
(KBr): 2960, 1620, 1590, 1510, 1460, 1250, 1040, 1020,
840, 770 cm−1; EIMS m/z (rel. intensity): 446 (M+, 16),
446 (53), 444 (100), 402 (90), 401 (43), 291 (92), 242
(48), 149 (32). Anal. calcd for C29H35NO2S: C, 75.30;
H, 7.22; N, 3.14; Found: C, 75.04; H, 7.71; N, 2.91%.
4.18. (R*,S*)- and (R*,R*)-N-(p-Methoxyphenyl)-1-
S
S
4.16. (R*,S*)- and (R*,R*)-N-(p-Chlorophenyl)-1-[1-
S
S
[2-(2,4,6-triisopropylphenylsulfinyl)phenyl]ethylamine,
(R*,S*)- and (R*,R*)-11
(tert-butylsulfinyl)-2-naphthyl)]ethylamine, (R*,S*)- and
S
S
S
(R*,R*)-9
S
The reaction was carried out as described above except
using 10 (101 mg, 0.226 mmol) and MeLi (1.14 mol
L−1, 0.30 mL, 0.339 mmol). Standard work-up gave the
crude product which was purified column chromatogra-
phy (silica gel 12 g, hexane/ethyl acetate=85:15) to
afford a diastereomeric mixture of 11 (105 mg, 97%).
The diastereomer ratio a:b was determined to be 77:23
by the 1H NMR analysis of the crude product: Rf=0.17
(hexane/ethyl acetate=80:20); 1H NMR: l 0.60 (d,
0.7H, J=6.3 Hz, CH3, minor isomer), 0.80–1.03 (m,
6H, CH3×2), 1.22 (d, 6H, J=6.6 Hz, CH3×2), 1.25 (d,
1.4H, J=6.6 Hz, CH3×2, minor isomer), 1.27 (d, 4.6H,
J=6.8 Hz, CH3×2, major isomer), 1.52 (d, 2.3H, J=6.6
Hz, CH3, major isomer), 2.89 (sept., 1H, J=6.8 Hz,
CHMe2), 3.47–3.52 (m, 0.2H, NH, minor isomer), 3.60
(s, 2.3H, OCH3, major isomer), 3.69 (s, 0.7H, OCH3,
minor isomer), 3.72–3.81 (m, 0.8H, NH, major), 3.92
(sept., 2H, J=6.6 Hz, CHMe2×2), 4.12 (q, 0.2H, J=6.3
Hz, CH, minor isomer), 4.48 (q, 0.8H, J=6.6 Hz, CH,
major isomer), 5.67 (d, 1.5H, J=9.0 Hz, Ar, major
isomer), 6.37 (d, 1.5H, J=9.0 Hz, Ar, major isomer),
6.44 (d, 0.5H, J=8.9 Hz, Ar, minor isomer), 6.67 (d,
0.5H, J=8.9 Hz, Ar, minor isomer), 7.07 (s, 0.5H, Tip,
minor isomer), 7.13 (s, 1.5H, Tip, major isomer), 7.30–
7.48 (m, 3H, Ar), 7.91–7.98 (m, 0.2H, Ar, minor iso-
mer), 8.01–8.09 (d, 0.8H, Ar, major isomer); 13C NMR:
l 22.5, 23.5, 23.7, 24.4, 24.6, 24.9, 28.3, 28.7, 34.4, 48.9,
49.8, 55.5, 114.0, 114.2, 114.4, 114.7, 123.3, 125.0,
125.3, 125.4, 126.0, 127.1, 127.3, 130.5, 130.6, 133.5,
135.2 140.1, 140.7, 141.2, 141.3, 143.1, 143.2, 151.4,
151.5, 152.0, 153.6; IR (KBr): 3340, 2960, 1600, 1510,
1460, 1240, 1040, 1020, 820, 760 cm−1; EIMS m/z (rel.
intensity): 477 (M+, 17), 462 (95), 461 (100), 256 (77).
Anal. calcd for C30H39NO2S: C, 75.43; H, 8.23; N, 2.93.
Found: C, 75.32; H, 8.30; N, 2.97%.
The reaction was carried out as described above except
using 2i (101 mg, 0.273 mmol) and MeLi (1.14 mol L−1,
0.26 mL, 0.300 mmol). Standard work-up gave the
crude product which was purified column chromatogra-
phy (silica gel 20 g, hexane/ethyl acetate=80:20) to
afford a diastereomeric mixture of 9 (89 mg, 85%). The
diastereomer ratio a:b:c was determined to be 34:27:39
1
by the H NMR analysis of the crude product. Since
the diastereomers a and b were determined to be the
atropisomeric products by variable temperature 1H
NMR; the ratio of (R*,S*)/(R*,R*) turned to be 61:39:
S
Rf=0.40 (hexane/ethyl acetatSe=50:50); 1H NMR: l
t
t
1.26 (s, 2.4H, Bu, b), 1.33 (s, 3.5H, Bu, c), 1.38 (s,
t
3.1H, Bu, a), 1.52 (d, 0.8H, J=6.1 Hz, -CH3, b), 1.62
(d, 1.0H, J=6.3 Hz, -CH3, a), 1.63 (d, 1.2H, J=6.6 Hz,
-CH3, c), 3.52–4.18 (m, 1.3H, NH, CHMe2, b+c), 5.33–
5.53 (m, 0.7H, NH, CHMe2, a), 6.49–6.73 (m, 2H, Ar,
a+b+c), 7.02–7.18 (m, 2H, Ar, a+b+c), 7.45–8.07 (m,
5H, Ar, a+b+c), 8.41–8.46 (m, 0.7H, Ar, a+c), 9.47–
9.51 (m, 0.3H, Ar, b); 13C NMR: l 22.9, 23.7, 24.5,
25.0, 25.6, 26.0, 46.5, 47.7, 50.1, 60.0, 60.1, 60.3, 114.5,
114.6, 114.7, 121.8, 122.2, 122.7, 124.1, 124.6, 126.4,
126.6, 126.7, 127.0, 127.2, 128.2, 128.3, 128.5, 129.2,
132.2, 132.4, 132.6, 133.0, 133.2, 133.4, 133.4, 133.5,
133.6, 144.9, 145.2, 145.5, 145.7, 146.4; IR (KBr): 3290,
2960, 1600, 1500, 1040, 820, 760 cm−1; EIMS m/z (rel.
intensity): 385 (M+, 6), 314 (38), 312 (100). Anal. calcd
for C22H24ClNOS: C, 68.46; H, 6.27; N, 3.63. Found:
C, 68.46; H, 6.35; N, 3.55%.
4.17. N-(p-Methoxyphenyl)-[2-(2,4,6-triisopropylphenyl-
sulfinyl)phenyl]methanimine, 10
A
mixture of 2-(2,4,6-triisopropylphenyl)sulfinyl-
benzaldehyde (601 mg, 1.69 mmol) and p-methoxyani-
line (313 mg, 2.54 mmol) in the presence of 3 A
,
molecular sieves in benzene was heated under reflux for
12 h. The mixture was filtered through Celite® and the
filtrate was concentrated under reduced pressure to
leave a residue which was purified by column chro-
matography (silica gel 40 g, hexane/ethyl acetate/
Et3N=98:2:8) to afford 10 (748 mg, 96%): mp
4.19. Preparation of the chiral sulfoxides. (R)-N-
(p-Methoxyphenyl)-[1-(2,4,6-triisopropylphenylsulfinyl)-
2-naphthyl]methanimine, (R)-2c
The reaction was carried out as described in the prepa-
ration of racemic 2i except using (R)-1c (43 mg, 0.106
mmol), p-methoxyphenylamine (131 mg, 1.06 mmol)
and TiCl4 (1.41 mol L−1, 0.045 mL, 0.064 mmol).
Standard work-up gave the crude product which was
purified by column chromatography (silica gel 50 g,
hexane/Et3N=90:10) to afford (R)-2c (51 mg, 94%).
1
142–143°C; Rf=0.32 (hexane/ethyl acetate=80:20); H
NMR: l 0.97 (d, 6H, J=6.6 Hz, CH3×2), 1.12 (d, 6H,
J=6.7 Hz, CH3×2), 1.25 (d, 6H, J=6.9 Hz, CH3×2),
2.89 (sept., 1H, J=6.7 Hz, CHMe2), 3.71 (sept., 2H,
J=6.9 Hz, CHMe2×2), 3.82 (s, 3H, OCH3), 6.81–6.96

S. Nakamura et al. / Tetrahedron: Asymmetry 13 (2002) 1509–1518
1517
HPLC (Daicel Chiralcel OD-H, hexane/iPrOH=95:5,
flow rate 0.5 mL/min) tR 17.9 (S) and 21.2 min (R);
[h]2D0=−589.5 (c 0.23, CHCl3).
S. Tetrahedron Lett. 1996, 37, 7607–7610; (b) Kitagawa,
O.; Izawa, H.; Taguchi, T.; Shiro, M. Tetrahedron Lett.
1997, 38, 4447–4450; (c) Kitagawa, O.; Izawa, H.; Sato,
K.; Dobashi, A.; Taguchi, T.; Shiro, M. J. Org. Chem.
1998, 63, 2634–2640; (d) Hughes, A. D.; Simpkins, N. S.
Synlett 1998, 967–968; (e) Hughes, A. D.; Price, D. A.;
Simpkins, N. S. J. Chem. Soc., Perkin Trans. 1 1999,
1295–1304; (f) Fujita, M.; Kitagawa, O.; Izawa, H.;
Dobashi, A.; Fukaya, H.; Taguchi, T. Tetrahedron Lett.
1999, 40, 1949–1952; (g) Kitagawa, O.; Momose, S.;
Fushimi, Y.; Taguchi, T. Tetrahedron Lett. 1999, 40,
8827–8831; (h) Bach, T.; Schro¨der, J.; Harms, K. Tetra-
hedron Lett. 1999, 40, 9003–9004; (i) Curran, D. P.; Liu,
W.; Chen, C. H. J. Am. Chem. Soc. 1999, 121, 11012–
11013; (j) Fujita, M.; Kitagawa, O.; Yamada, Y.; Izawa,
H.; Hasegawa, H; Taguchi, T. J. Org. Chem. 2000, 65,
1108–1114; (k) Kitagawa, O.; Fujita, M.; Kohriyama, M.;
Hasegawa, H.; Taguchi, T. Tetrahedron Lett. 2000, 41,
8539–8544.
4.20. Reaction of (R)-2c with MeLi. (RS,S)-N-
(p-Methoxyphenyl)-1-[1-(2,4,6-triisopropylphenylsulfinyl)-
2-naphthyl]ethylamine, (RS,S)-3
The reaction was carried out as described in the prepa-
ration of racemic 3 except using (R)-2c (49 mg, 0.095
mmol) and MeLi (1.14 mol L−1, 0.095 mL, 0.108
mmol). Standard work-up gave the crude product
which was purified by column chromatography (silica
gel 10 g, hexane/ethyl acetate=90:10) to afford (RS,S)-
3. The diastereomer ratio was determined to be >98:2
1
by the H NMR analysis of the crude product. column
chromatography (silica gel 10 g, hexane/ethyl acetate=
90:10) to afford a mixture of (RS,S)-3. The enantiomer
excess was determined to be 93% ee by the HPLC
analysis. HPLC (Daicel Chiralpak AD, hexane/
iPrOH=80:20, flow rate 0.5 mL/min) tR 19.5 (R) and
26.2 min (S).
3. For the reaction of N,N-diisopropylnaphthamide, see: (a)
Clayden, J.; Westlund, N.; Wilson, F. X.; Tetrahedron
Lett. 1996, 37, 5577–5580; (b) Clayden, J. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 949–951; (c) Clayden, J.; West-
lund, N.; Wilson, F. X. Tetrahedron Lett. 1999, 40,
3329–3330; (d) Bragg, R. A.; Clayden, J. Tetrahedron
Lett. 1999, 40, 8323–8326; (e) Bragg, R. A.; Clayden, J.
Tetrahedron Lett. 1999, 40, 8327–8331; (f) Clayden, J.;
Westlund, N.; Wilson, F. X. Tetrahedron Lett. 1999, 40,
7883–7887; (g) Clayden, J.; Westlund, N.; Beddoes, R. L.;
Helliwell, M. J. Chem. Soc., Perkin Trans. 1 2000, 1351–
1361; (h) Clayden, J.; McCarthy, C.; Westlund, N.;
Frampton, C. S. J. Chem. Soc., Perkin Trans. 1 2000,
1363–1378; (i) Clayden, J.; Westlund, N.; Frampton, C.
S. J. Chem. Soc., Perkin Trans. 1 2000, 1379–1385; (j)
Clayden, J.; McCarthy, C.; Cumming, J. G. Tetrahedron
Lett. 2000, 41, 3279–3283; (k) Clayden, J.; Helliwell, M.;
McCarthy, C.; Westlund, N. J. Chem. Soc., Perkin Trans.
1 2000, 3232–3249; (l) Clayden, J.; Johnson, P.; Pink, J.
H.; Helliwell, M. J. Org. Chem. 2000, 65, 7033–7040; (m)
Dai, W.; Lau, C. W. Tetrahedron Lett. 2001, 42, 2541–
2544.
4.21. Preparation of (S)-N-(4-methoxyphenyl)-1-
(2-naphthyl)ethylamine, (S)-12
To a solution of (RS,S)-3 (18.2 mg, 0.031 mmol) and
HMPA (0.030 mL, 0.172 mmol) in THF (0.3 mL) was
added n-BuLi (0.10 mL, 1.54 mol L−1 in hexane, 0.155
mmol) at −78°C. Then the reaction mixture was
allowed to warm to 0°C and stirred for 60 min. Stan-
dard work-up gave the crude product which was
purified by column chromatography (silica gel 15 g,
hexane/ethyl acetate=95:5) to afforded (S)-12 (4.4 mg,
42%). The enantiomer excess was determined to be 94%
ee by the HPLC analysis: HPLC (Daicel Chiralcel
OD-H, hexane/iPrOH=90:10, flow rate 0.5 mL/min) tR
18.1 (R) and 21.3 (S) min; [h]2D0=+15.6 (c 0.194,
CHCl3, 94% ee).
4. (a) Thayumanavan, S.; Beak, P.; Curran, D. P. Tetra-
hedron Lett. 1996, 37, 2899–2902; (b) Cass, Q. B.; Degani,
A. L. G.; Tiritan, M. E.; Matlin, S. A.; Curran, D. P.;
Balog, A. Chirality 1997, 9, 109–112; (c) Koide, H.;
Uemura, M. Chem. Commun. 1998, 2483–2484; (d) Cur-
ran, D. P.; Hale, G. R.; Geib, S. J.; Balog, A.; Cass, Q.
B.; Degani, A. L. G.; Hernandes, M. Z.; Freitas, L. C. G.
Tetrahedron: Asymmetry 1997, 8, 3955–3975; (e) Clayden,
J.; Lai, L. W. Angew. Chem., Int. Ed. 1999, 38, 2556–
2557; (f) Godfrey, C. R. A.; Simpkins, N. S.; Walker, M.
D. Synlett 2000, 388–390; (g) Hata, T.; Koide, H.;
Uemura, M. Synlett 2000, 1145–1147; (h) Shimizu, K. D.;
Freyer, O. H.; Adams, R. D. Tetrahedron Lett. 2000, 40,
5431–5434; (i) Kondo, K.; Iida, T.; Fujita, H.; Suzuki, T.;
Yamaguchi, K.; Murakami, Y. Tetrahedron 2000, 56,
8883–8891; (j) Hata, T.; Koide, H.; Taniguchi, N.;
Uemura, M. Org. Lett. 2000, 2, 1907–1910; (k) Clayden,
J.; Lai, L. W. Tetrahedron Lett. 2001, 42, 3163–3166; (l)
Clayden, J.; Johnson, P.; Pink, J. H. J. Chem. Soc.,
Perkin Trans. 1 2001, 371–375; (m) Dai, W.; Yeung, K.
K. Y.; Chow, C. W.; Williams, I. D. Tetrahedron: Asym-
metry 2001, 12, 1603–1613; (n) Ates, A.; Curran, D. P. J.
Am. Chem. Soc. 2001, 123, 5130–5131.
Acknowledgements
We thank Dr. Shinya Kusuda, Ono Pharmaceutical
Co., Ltd., for X-ray crystallographic analyses. This
work was partly supported by a Grant-in-Aid for Scien-
tific Research (no. 11650890) from the Ministry of
Education, Science, Sports and Culture of Japan.
References
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1518
S. Nakamura et al. / Tetrahedron: Asymmetry 13 (2002) 1509–1518
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and
2-methyl-substituted,
1-(alkylsulfi-
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isomer having the sulfinyl oxygen close to the peri-H(8)