Further study of axial chirality due to an acyclic imide N-Ar bond: Control of rotational barrier by electronic effects of acyl groups

Article abstract of DOI:10.1016/S0040-4020(01)00295-2

Studies on stability to racemization in a series of optically active N-aroyl-N-(2-t-butylphenyl)acetamides 2a-g (X=NMe₂, OMe, Me, H, F, Cl, CF₃), depending on the electronic effect of their aroyl groups, are described. It has been revealed that the stability of 2 bearing stronger electron-withdrawing groups on the aroyl benzene ring was enhanced, with linear correlation between the ΔG^? and Hammett's σ_p para-substituent constant of 2a-g. Furthermore, the absolute configuration of optically active imides 2a-g has been determined by comparison with the CD spectrum of (S)-N-(2-t-butylphenyl)-N-(4-trifluoromethylbenzoyl)propionamide (5b) derived from (R_a,2S)-N-(2-t-butylphenyl)-N-(4-trifluoromethylbenzoyl)-2- acetoxypropionamide (4b), whose absolute configuration was determined by X-ray analysis.

Full text of DOI:10.1016/S0040-4020(01)00295-2

TETRAHEDRON
Pergamon
Tetrahedron 57 +2001) 4115±4122
Further study of axial chirality due to an acyclic imide
N±Ar bond: control of rotational barrier by electronic effects of
acyl groups
Kazuhiro Kondo,a Takeko Iida,a Hiroko Fujita,a Tomoko Suzuki,a Ryoko Wakabayashi,a
Kentaro Yamaguchib and Yasuoki Murakamia,p
aSchool of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
bChemical Analysis Center, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Received 15 February 2001; accepted 9 March 2001
AbstractÐStudies on stability to racemization in a series of optically active N-aroyl-N-+2-t-butylphenyl)acetamides 2a±g +XˆNMe2, OMe,
Me, H, F,Cl, CF3), depending on the electronic effect of their aroyl groups, are described. It has been revealed that the stability of 2 bearing
stronger electron-withdrawing groups on the aroyl benzene ring was enhanced, with linear correlation between the DG and Hammett's sp
³
para-substituent constant of 2a±g. Furthermore, the absolute con®guration of optically active imides 2a±g has been determined by
comparison with the CD spectrum of +S)-N-+2-t-butylphenyl)-N-+4-tri¯uoromethylbenzoyl)propionamide +5b) derived from +Ra,2S)-N-+2-
t-butylphenyl)-N-+4-tri¯uoromethylbenzoyl)-2-acetoxypropionamide +4b), whose absolute con®guration was determined by X-ray analysis.
q 2001Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Recently, optically active non-biaryl compounds, which
possess axial chirality based on an anilide N±Ar bond,
have been utilized for stereoselective syntheses.1,2 The key
issue is considered to be the relationship between the rota-
tion barrier around the N±Ar bonds and the disposition of
substituents. However, few fundamental studies of these
rotation barriers have been reported.3 Quite recently, we
have reported the ®rst example of optically active imides
1 which possess axial chirality based on an acyclic imide
N±Ar bond rotation.4 Furthermore, in relation to the steric
effects of acyl groups, we have revealed that 1 bearing a
bulky acyl group rather than a relatively small one race-
mized more easily.4 As part of our research program in
relation to optically active N±Ar axially chiral compounds,
we undertook investigation of the relationship between the
stability to racemization and the electronic effects of acyl
groups. In this paper, we describe our study on the stability
to racemization in a series of optically active N-aroyl-N-+2-
t-butylphenyl)acetamides 2a±g bearing various para-
substituents +XˆNMe2, OMe, Me, H, F, Cl, CF3) on the
aroyl benzene ring.5
In order to effect a control system for N±Ar rotation
barriers, namely, stability to racemization, based on
electronic effects of acyl groups, optically active imides
2a±g were selected as the test substrates +Fig. 1). At ®rst,
the stability to racemization in benzene at 408C +sealed-tube
experiments) was investigated with optically active imides
2a±g, which were prepared by the aroylation of 2-t-butyl-
phenylacetamide, and the subsequent optical resolution of
racemic imides +^)-2a±g using semipreparative HPLC
+Daicel Chiralcel OD, eluent: i-PrOH-hexane). The use of
other solvents such as DMF and MeCN in place of benzene
led to the decomposition of 2. The rate constants k for their
racemization are shown in Table 1. The stability to racemi-
zation was delicately controlled by the electronic effect of
X
2a: X=NMe2
O
R
O
2b: X=OMe
2c: X=Me
2d: X=H
Me
N
*
O
t-Bu
Me
N
O
t-Bu
*
2e: X=F
2
1: R=alkyl
2f: X=Cl
Keywords: N±C axial chirality; electronic effect; acyclic imide; rotational
barrier; Hammett's sp para-substituent constant.
Corresponding author. Tel: 181-47-472-1585; fax 181-47-472-1595;
2g: X=CF3
p
Figure 1.
e-mail: murakami@phar.toho-u.ac.jp
0040±4020/01/$ - see front matter q 2001Elsevier Science Ltd. All rights reserved.
PII: S0040-4020+01)00295-2

4116
K. Kondo et al. / Tetrahedron 57 32001) 4115±4122
³
Table 1. Con®gurational stability to racemization with optically active
imides 2a±g in benzene at 408C
value of DS for 2a +29.4), 2c +27.0) and 2e +28.4) relative
to 2g +4.8) would be indicative of a more highly ordered
transition state +relative to the ground state) for the former.
Ar
O
O
Ar
³
The free energies of activation DG were changed by
1.4 kcal/mol from 2a to 2g. As shown in Fig. 2, linear
O
N
Me
Me
N
O
t-Bu
³
correlation between the DG and Hammett's sp para-
t-Bu
substituent constant7 of 2a±g was observed.
(R)-2
(S)-2
The structural distinction between the most unstable imide
+^)-2a bearing an NMe2 group and the most stable imide
+^)-2g bearing a CF3 group4b was con®rmed by X-ray crys-
tallographic analysis. The representative ORTEP drawing
of 2a is shown in Fig. 3. The 2-t-butylphenyl group and
the imide plane of both 2a and 2g were approximately
orthogonal, and their imide geometry was the exo±endo
arrangement8 with acetyl carbonyl trans and aroyl carbonyl
cis to the 2-t-butylphenyl group. The nature of imide
Entry
Compound +X)
k [1026+S21)]
1
2
3
4
5
6
7
2a +NMe2)
2b +OMe)
2c +Me)
2d +H)
2e +F)
2f +Cl)
2g +CF3)
9.08^0.02
4.26^0.37
2.93^0.02
2.74^0.09
2.23^0.05
1.79^0.03
1.33^0.27
Table 2. Transition-state functions of optically active imides 2a±g
³
DG at 278C +kcal/mol)
Entry
Compound +Xˆ)
DH³a +kcal/mol)
DS³a +cal/K´mol)
1
2
3
4
5
6
7
2a +NMe2)
2b +OMe)
2c +Me)
2d +H)
2e +F)
2f +Cl)
2g +CF3)
22.6
25.1
24.1
25.0
23.8
26.0
28.2
29.4
22.8
27.0
24.126.2
28.4
22.0
4.8
25.4
25.9
26.2
26.3
26.6
26.8
a
The transition-state functions were calculated according to the Eyring's equation.
the para-substituent on the aroyl benzene ring. As a result, it
was found that the stability of 2 bearing stronger electron-
withdrawing groups on the aroyl benzene ring was
enhanced.
nitrogen can be represented in terms of two angle para-
meters, the summation of the three valence angles around
the nitrogen u, and the twist angle9 t of the amide bond
calculated by the average of v1 +C3C2NC5) and v2
+O2C2NC1), its range10 being between 0 and 908 +the highest
t value11 reported for imide is 83.28). The parameters of 2a
and 2g are shown in Table 3. The essentially sp2 nature of
the imide nitrogen in 2g was con®rmed: uˆ359.88 +the
Next, measurement of the rate constants k for the racemiza-
tion was performed with optically active imides 2a±g in
benzene at three other temperatures. By using these data,
the transition-state functions for racemization were
obtained from the Eyring equation as shown in Table 2.6
³
The enthalpies of activation DH of 2a±g were 22.6, 25.1,
24.1, 25.0, 23.8, 26.0 and 28.2 kcal/mol, respectively. The
³
small value of the DH for 2a +22.6) relative to 2g +28.2)
would be mainly due to the destabilization in the ground
state. The entropies of activation DS for racemization of
2a±g were from 29.4 to 4.8 cal/K.mol. The much smaller
³
³
Figure 2. Plot of DG vs. sp for 2a±g.
Figure 3. The ORTEP drawing of +^)-2a

K. Kondo et al. / Tetrahedron 57 32001) 4115±4122
Table 3. Angle around N, twist angle, and selected bond lengths of 2a and 2g
4117
1
C ±N A
1
1
2
C ±N A
2
2
5
Ê
Twist anglea t of aroyl bond +8)
C ˆO A
C ˆO A
N±C A
Ê
Ê
Ê
Ê
Entry
Compound +Xˆ)
Angle around N u +8)
1
2
2a +NMe2)
2g +CF3)
352.8
359.8
31.6
18.5
1.422+6)
1.432+10)
1.200+5)
1.199+9)
1.435+6)
1.374+10)
1.207+5)
1.213+9)
1.455+5)
1.477+9)
a
The twist angle t was calculated by the average of v1+C3C2NC5) and v2+O2C2NC1).
angle u of the ideal sp2 planar nitrogen atom is 3608). On the
other hand, the angle u of 2a indicated a small pyramidali-
zation of the imide nitrogen: 352.88 +the angle u of the ideal
sp3 nitrogen atom is 328.48). The twist angle t of 2a was
larger than that of 2g +2a: 31 .68, 2g: 1 8.58). The aroyl C+O)±N
double bond character of 2a, compared with 2g, causes a
decrease of the steric repulsion between the aroyl carbonyl
and the 2-t-butyl group in 2-A, facilitating the N±Ar bond
rotation of 2a. Additionally, due to the nitrogen pyramid-
alization and the imide twist in 2a, 2a is more destabilized in
the ground state than 2g. And so the activation energy of 2a
for racemization is smaller than that of 2g. Thus, the
racemization of 2a is more facile than that of 2g. The pos-
sibility that the change in the N±Ar rotational barrier
originates in the double bond character of the N±Ar single
bond was also considered. However, from the X-ray
Ê
bond of 2a +1.435 +6) A was elongated as compared with
Ê
that of 2g +1.374 +10) A, although no marked change in the
length of other acetyl C+O)±N, CˆO and N±Ar bonds was
observed.12 Taking all the experimental results into con-
sideration, one possible mechanism for the more facile
racemization of 2a compared with 2g, would be as follows.
A possible transition state for the racemization is considered
to be two modes +Fig. 4), which are the transition state 2-A
wherein the aroyl carbonyl group is close to the t-butyl
group and the transition state 2-B wherein the acetyl methyl
group is, but molecular modeling studies suggested that the
transition state 2-A seemed to be more favored than the
transition state 2-B. Therefore, the weaker aroyl C+O)±N
O
COCl
H2N
NH
OAc
AcO
t-Bu
t-Bu
pyridine
3 (91%)
Ar
O
O
Ar
OAc
O
N
Me
t-Bu
Me
N
O
t-Bu
O
CF3
O
N
t-Bu
CF3
COCl
(S)-2
Ar
(R)-2
Ar
-
O
O
4a (63%, 99% ee)
3
+
OAc
O
Me
N
O
pyridine, 70 °C
Me
N
O
t-Bu
t-Bu
CF3
O
N
>
Favored
Unfavored
t-Bu
2-A
2-B
Figure 4.
4b (33%, 91% ee)
CF3
SmI2
O
4a
N
O
THF, -44 °C
t-Bu
5a (95%, 97% ee)
CF3
O
SmI2
4b
O
N
THF, -44 °C
t-Bu
5b (81%, 90% ee)
Figure 5. The ORTEP drawing of 4b.
Scheme 1.

4118
K. Kondo et al. / Tetrahedron 57 32001) 4115±4122
active imides 2a±g was established by comparison with the
CD spectrum of 5b derived from 4a,13,14 whose absolute
con®guration was determined by X-ray analysis +Fig. 5).
The preparation of 4a and 4b is shown in Scheme 1.
Acylation of 2-t-butylaniline with +S)-2-acetoxypropionyl
chloride in pyridine and further aroylation +4-tri¯uoro-
methylbenzoyl chloride in pyridine) afforded the separable
diastereomers 4a with 99% ee and 4b with 91% ee as a ca.
2:1mixture. Treatment of the separated diastereomers 4a
and 4b with SmI2 in THF at 2448C afforded 5a and 5b with
97 and 90% ee, respectively.15 The representative CD
spectra of 5a,b and 2f are shown in Fig. 6. Thus, the absolute
con®gurations of 2a,b with positive values of the speci®c
rotation and 2c±g with negative values of the speci®c
rotation, were determined to be S as shown in Fig. 7.
3. Conclusion
We have demonstrated that the stability to racemization of 2
bearing stronger electron-withdrawing groups on the aroyl
benzene ring is enhanced, with linear correlation between
³
the DG and Hammett's sp para-substituent constant of
2a±g. Furthermore, the absolute con®gurations of 2a,b
with positive values of the speci®c rotation and 2c±g with
negative values of the speci®c rotation were determined to
be S. Further studies along this line are in progress.
4. Experimental
4.1. General
All melting points +mp) were determined on a Yanagimoto
melting point apparatus and are uncorrected. IR spectra
were measured on a JASCO FT/IR-230 diffraction grating
IR spectrophotometer. 1H and 13C NMR spectra were
measured on a JEOL AL-400 or EX-400 NMR spectro-
meter, operating at 400 MHz for 1H NMR and at
1
100 MHz at 13C NMR. H and 13C NMR spectra were
Figure 6. The representative CD and UV spectra of 5a, 5b, +1)-2f and +2)-
2f in CH3CN.
reported in d units, parts per million +ppm) down®eld
from tetramethylsilane +dˆ0). EI MS spectra were
measured on a JEOL JMS-DX-303 instrument. Speci®c
rotations +in deg cm3 g21 L21) were determined on a
JASCO DIP-1000 digital polarimeter. UV spectra were
measured on a Shimadzu UV-265 instrument. Circular
dichroisms +CD) were measured on a JASCO J-720 W spec-
tropolarimeter. Enantiomeric excesses were determined by
HPLC analysis +Daicel Chiralcel OD).
analyses of 2a and 2g +Table 3), there was no marked
change in the length of the N±Ar single bond.
The assignment of the absolute con®gurations of optically
X
N-+2-t-butylphenyl)acetamide, +RS)-N-benzoyl-N-+2-t-butyl-
phenyl)acetamide [+^)-2d] and +RS)-N-+2-t-butylphenyl)-N-
+4-tri¯uoromethylbenzoyl)acetamide [+^)-2g] were prepared
according to our published procedure.4b All reagents were
available from commercial sources and used without further
puri®cation. In general, all reactions were performed in dry
solvents under an argon atmosphere. All racemization experi-
ments were performed on Taitec Thermo Minder SM-05 or
Toyo Lab Thermo LH-1000. Benzene was distilled under an
argon atmosphere from Na. Pyridine was distilled under an
argon atmosphere from CaH2. THF was distilled under an
argon atmosphere from Na/benzophenone ketyl. Silica gel
(+)-2a: X=NMe2
O
(+)-2b: X=OMe
Me
N
O
t-Bu
(-)-2c: X=Me
(-)-2d: X=H
(-)-2e: X=F
(-)-2f: X=Cl
(-)-2g: X=CF3
S
2
Figure 7. The absolute con®gurations of +1)-2a,b and +2)-2c±g.

K. Kondo et al. / Tetrahedron 57 32001) 4115±4122
4119
column chromatography was performed on Kanto Chemical
Silica gel 60 +spherical, 100±210 mm).
+M1), 266, 226, 173, 83 +bp). Anal. Calcd for C20H23NO3: C,
73.82; H, 7.12; N, 4.30. Found: C, 73.73; H, 7.22; N, 4.31.
4.2.3. ,RS)-N-,2-t-Butylphenyl)-N-,4-tolyl)acetamide [,^)-
2c]. Method B was used with N-+2-tert-butylphenyl)aceta-
mide +100 mg, 0.523 mmol). Puri®cation by silica gel
column +benzene:hexaneˆ2:1, the silica gel was pretreated
with 1% Et3N in hexane) afforded the analytically pure +^)-
2c +120 mg, 74%) as a colorless solid. Further puri®cation
of +^)-2c by recrystallization +benzene) afforded colorless
prisms of mp 115±1178C. Rf valueˆ0.52 +EtOAc:hexane
ˆ1:2). UV +MeCN): lmax 253 +emax 11572), 248 +emax
4.2. General procedure for preparation of N-aroyl-N-,2-
t-butylphenyl)acetamides 2a±c, 2e and 2f
Method A: To a stirred solution of N-+2-t-butylphenyl)-
acetamide in pyridine +0.3 M solution of the starting
material) was added aroyl chloride +2.0 equiv) at 08C. The
reaction mixture was stirred at 258C for 13 h, quenched by
the addition of H2O at 08C and extracted with EtOAc. The
organic extracts were washed with saturated aq. NaHCO3
and brine, dried +Na2SO4) and concentrated. Puri®cation by
silica gel column afforded the analytically pure imide 2.
Recrystallization was performed with benzene±hexane as
a solvent unless otherwise stated.
11943), 243 +emax 12005) nm. IR +nujol): nˆ1683 cm21
.
1H NMR +C6D6): dˆ1.32 +s, 9H), 1.92 +s, 3H), 1.95 +s,
1
3H), 6.83 +dd, Jˆ7.8, 1.5 Hz, H), 6.87 +d, Jˆ7.8 Hz, 2H),
1
6.91+ddd, Jˆ7.8, 7.8, 1.5 Hz, H), 7.03 +ddd, Jˆ7.8, 7.8,
1.5 Hz, 1H), 7.29 +dd, Jˆ7.8, 1.5 Hz, 1H), 7.71+d,
Jˆ7.8 Hz, 2H). 13C NMR +C6D6): dˆ21.48, 26.41, 31.58,
35.90, 126.87, 128.47, 128.58, 128.77, 129.15, 131.90,
132.77, 136.94, 141.89, 146.49, 172.52, 173.69. EI MS:
m/z ˆ309 +M1), 267, 174, 84 +bp). Anal. Calcd for
C20H23NO2: C, 77.64; H, 7.49; N, 4.53 Found: C, 77.54;
H, 7.70; N, 4.43.
Method B: To a stirred solution of ArCO2H +2.0 equiv) in
CH2Cl2 +0.3 M solution of the starting material) were added
CCl4 +12 equiv) and PPh3 +3 equiv) at 08C. The mixture was
stirred at 258C for 2.5 h. To this mixture were then added
pyridine +10 equiv) and N-+2-t-butylphenyl)acetamide at
08C. The whole mixture was stirred at 258C for 12 h. The
work-up was performed in the same manner as for
Method A.
4.2.4. ,RS)-N-Benzoyl-N-,2-t-butylphenyl)acetamide [,^)-
2d]. The physical data shown below were identical with
those of our report.4b Colorless prisms, mp 83±848C. UV
4.2.1.
,RS)-N-,2-t-Butylphenyl)-N-,4-dimethylamino-
+MeCN): lmax 224 +emax 7383) nm. IR +KBr): nˆ1687 cm21
.
benzoyl)acetamide [,^)-2a]. Method B was used with
N-+2-tert-butylphenyl)acetamide +1.00 g, 5.23 mmol). Puri-
®cation by silica gel column +EtOAc:hexaneˆ1:3, the silica
gel was pretreated with 1% Et3N in hexane) afforded the
analytically pure +^)-2a +666 mg, 38%) as a colorless solid
along with the starting material +278 mg, 28%). Further
puri®cation of +^)-2a by recrystallization +benzene±
hexane) afforded colorless prisms of mp 95±978C. Rf
valueˆ0.32 +EtOAc:hexaneˆ1:2). UV +MeCN): lmax 340
+emax 25113), 235 +10832) nm. IR +nujol): nˆ1702,
1H NMR +C6D6): dˆ1.30 +s, 9H), 1.86 +s, 3H), 6.79 +dd,
1
1
Jˆ7.3, 1.5 Hz, H), 6.90 +ddd, Jˆ7.3, 7.3, 1.5 Hz, H),
1
7.00±7.05 +m, 4H), 7.28 +dd, Jˆ7.3, 1.5 Hz, H), 7.71±
7.74 +m, 2H). 13C NMR +C6D6): dˆ26.15, 31.77, 36.06,
127.2, 128.1, 129.0, 129.2, 129.6, 131.3, 132.8, 136.9,
137.9, 147.3, 173.1, EI MS: m/zˆ295 +M1), 253, 239,
149, 77 +bp).
4.2.5.
,RS)-N-,2-t-Butylphenyl)-N-,4-¯uorobenzoyl)-
1661 cm21
.
1H NMR +C6D6): dˆ1.41 +s, 9H), 2.06 +s,
acetamide [,^)-2e]. Method A was used with N-+2-tert-
butylphenyl)acetamide +510 mg, 2.67 mmol). Puri®cation
by silica gel column +EtOAc:hexaneˆ1:8, the silica gel
was pretreated with 1% Et3N in hexane) afforded the
analytically pure +^)-2e +827 mg, 99%) as a colorless
solid. Further puri®cation of +^)-2e by recrystallization
+benzene±hexane) afforded colorless prisms of mp 117±
1208C. Rf valueˆ0.61+EtOAc:hexane ˆ1:2). UV +MeCN):
3H), 2.30 +s, 6H), 6.29 +d, Jˆ9.0 Hz, 2H), 6.96±7.02 +m,
1
3H), 7.34 +dd, Jˆ8.0, 1.6 Hz, H), 7.34 +d, Jˆ9.0 Hz, 2H).
13C NMR +C6D6): dˆ26.44, 31.69, 36.02, 39.20, 110.52,
122.69, 126.69, 128.27, 129.04, 132.13, 133.05, 138.69,
146.94, 152.40, 171.91, 173.28. EI MS: m/z ˆ338 +M1),
279, 204, 189, 148 +bp). Anal. Calcd for C21H26N2O2: C,
74.52; H, 7.74; N, 8.28. Found: C, 74.69; H, 7.85; N, 8.21.
1
lmax 225 +emax 12221) nm. IR +nujol): nˆ1686 cm21. H
NMR +C6D6): dˆ1.27 +s, 9H), 1.82 +s, 3H), 6.66 +dd,
4.2.2. ,RS)-N-,2-t-Butylphenyl)-N-,4-methoxybenzoyl)-
acetamide [,^)-2b]. Method A was used with N-+2-tert-
butylphenyl)acetamide +498 mg, 2.60 mmol). Puri®cation
by silica gel column +benzene:hexaneˆ2:1, the silica gel
was pretreated with 1% Et3N in hexane) afforded the analy-
tically pure +^)-2b +703 mg, 83%) as a colorless solid.
Further puri®cation of +^)-2b by recrystallization +benzene)
afforded colorless prisms of mp 128±1298C. Rf valueˆ0.75
+EtOAc:hexaneˆ1:2). UV +MeCN): lmax 281+ emax 12138),
215 +22128) nm. IR +nujol): nˆ1698, 1670 cm21. 1H NMR
+C6D6): dˆ1.33 +s, 9H), 1.94 +s, 3H), 3.14 +s, 3H), 6.62 +br d,
1
Jˆ8.5, 8.5 Hz, 2H), 6.74 +dd, Jˆ7.8, 1.5 Hz, H), 6.90
+ddd, Jˆ7.8, 7.8, 1.5 Hz, 1H), 7.03 +ddd, Jˆ7.8, 7.8,
1
1.5 Hz, H), 7.28 +dd, Jˆ7.8, 1.5 Hz,1H), 7.57 +dd, Jˆ8.5,
5.4 Hz, 2H). 13C NMR +C6D6): dˆ26.00, 31.64, 35.94,
114.92 +d, Jˆ23 Hz), 126.95, 128.76, 129.30, 131.38 +d,
Jˆ8.3 Hz), 132.43, 132.51 +d, Jˆ3.3 Hz), 137.47, 146.81,
164.37 +d, Jˆ252 Hz), 171.38, 172.83. EI MS: m/z ˆ313
+M1), 254 +bp), 214, 158, 43. Anal. Calcd for C19H20NO2F:
C, 72.82; H, 6.43; N, 4.47 Found: C, 73.10; H, 6.59; N, 4.51.
1
4.2.6.
,RS)-N-,2-t-Butylphenyl)-N-,4-chlorobenzoyl)-
Jˆ8.8 Hz, 2H), 6.87 +dd, Jˆ7.7, 1.6 Hz, H), 6.93 +ddd,
1
acetamide [,^)-2f]. Method A was used with N-+2-tert-
butylphenyl)acetamide +100 mg, 0.523 mmol). Puri®cation
by silica gel column +benzene:hexaneˆ2:1, the silica gel
was pretreated with 1% Et3N in hexane) afforded the
analytically pure +^)-2f +171 mg, 99%) as a colorless
Jˆ7.7, 7.7, 1.6 Hz, H), 7.04 +ddd, Jˆ8.2, 7.7, 1.6 Hz,
1
1H), 7.31+dd, Jˆ8.2, 1.6 Hz, H), 7.80 +br d, Jˆ8.8 Hz,
2H). 13C NMR +C6D6): dˆ26.23, 31.66, 35.97, 54.65,
113.30, 126.83, 128.44, 128.53, 129.16, 131.64, 132.77,
138.05, 146.86, 162.33, 171.89, 173.09. EI MS: m/z ˆ325

4120
K. Kondo et al. / Tetrahedron 57 32001) 4115±4122
solid. Further puri®cation of +^)-2f by recrystallization
+benzene±hexane) afforded colorless prisms of mp 148±
1498C. Rf valueˆ0.60 +EtOAc:hexaneˆ1:2). UV +MeCN):
hexaneˆ1:150). [a]26 ˆ2288 +c 0.45, benzene). CD
D
+MeCN): lext 275 +De 21.16), 240 +12.33), 223 +22.48) nm.
l
max 232 +emax 13538) nm. IR +nujol): nˆ1719, 1676 cm21
.
4.2.12.
,R)-N-,2-t-Butylphenyl)-N-,4-¯uorobenzoyl)-
1H NMR +C6D6): dˆ1.26 +s, 9H), 1.80 +s, 3H), 6.71 +dd,
Jˆ7.8, 1.5 Hz, 1H), 6.89 +ddd, Jˆ7.8, 7.8, 1.5 Hz, 1H), 7.00
+d, Jˆ8.5 Hz, 2H), 7.02 +ddd, Jˆ7.8, 7.8, 1.5 Hz, 1H), 7.27
+dd, Jˆ7.8, 1.5 Hz, 1H), 7.47 +d, Jˆ8.5 Hz, 2H). 13C
NMR +C6D6): dˆ25.94, 31.65, 35.94, 126.99, 128.13,
128.83, 129.34, 130.18, 132.32, 134.85, 137.23, 137.27,
146.81, 171.48, 172.77. EI MS: m/zˆ331+M 112), 329
+M1), 272, 158, 84 +bp). Anal. Calcd for C19H20NO2Cl:
C, 69.19; H, 6.11; N, 4.25 Found: C, 69.00; H, 5.90;
N, 4.51.
acetamide [,R)-2e]. RTˆ45 min +i-PrOH:hexaneˆ1:100).
[a]23 ˆ1438 +c 0.41, THF). CD +MeCN): lext 272 +De
D
10.56), 240 +20.81), 224 +10.49) nm. +S)-2e. RTˆ
30 min +i-PrOH:hexaneˆ1:100). [a]23 ˆ2458 +c 0.36,
D
THF). CD +MeCN): lext 274 +De 21.21), 240 +12.78),
224 +21.61) nm.
4.2.13.
,R)-N-,2-t-Butylphenyl)-N-,4-chlorobenzoyl)-
acetamide [,R)-2f]. RTˆ30 min +i-PrOH:hexaneˆ1:100).
[a]23 ˆ1298 +c 0.30, THF). CD +MeCN): lext 278 +De
D
11.34), 248 +23.52), 228 +16.10) nm. +S)-2f. RTˆ
22 min +i-PrOH:hexaneˆ1:100). [a]23 ˆ2298 +c 0.32,
4.2.7.
,RS)-N-,2-t-Butylphenyl)-N-,4-tri¯uoromethyl-
D
THF). CD +MeCN): lext 278 +De 21.20), 248 +13.36),
228 +23.74) nm.
benzoyl)acetamide [,^)-2g]. The physical data shown
below were identical with those of our report.4b Colorless
plates, mp 125±1268C. UV +MeCN): lmax 224 +emax 16025)
nm. IR +nujol): nˆ1678, 1722 cm21
.
1H NMR +C6D6):
4.2.14.
,R)-N-,2-t-Butylphenyl)-N-,4-tri¯uoromethyl-
1
benzoyl)acetamide [,R)-2g]. RTˆ26 min +i-PrOH:
dˆ1.26 +s, 9H), 1.73 +s, 3H), 6.70 +dd, Jˆ7.7, 1.5 Hz, H),
hexaneˆ1:100). [a]24 ˆ1558 +c 0.30, THF). CD
1
D
6.91+ddd, Jˆ7.7, 7.7, 1.5 Hz, H), 7.03 +ddd, Jˆ7.7, 7.7,
1.5 Hz, 1H), 7.25±7.29 +m, 3H), 7.53 +d, Jˆ8.1Hz, 2H). 13C
NMR +C6D6): dˆ25.76, 31.65, 35.97, 124.1 +q, Jˆ272 Hz),
124.9 +q, J ˆ3.3 Hz), 127.1, 128.6, 129.0, 129.4, 132.1,
132.1 +q, Jˆ32.5 Hz), 136.9, 140.0, 146.8, 171.4, 172.6.
EI MS: m/zˆ363 +M1), 265, 149, 83 +bp). Optical resolution
of +^)-2a±g.
+MeCN): lext 278 +De 11.85), 238 +23.38), 220 +11.70)
ˆ
nm. +S)-2g. RTˆ16 min +i-PrOH:hexaneˆ1:100). [a]20
D
2558 +c 0.42, THF). CD +MeCN): lext 278 +De 21.58), 238
+13.56), 216 +21.10) nm.
4.3. General procedure for racemization experiment of
optically active imides 2a±g
Optical resolutions of +^)-2a±g were performed by semi-
preparative HPLC using a chiral phase column +Daicel Chir-
alcel OD: 25 cmx1cm i.d.). IR, NMR and MS data of
optically active imides 2a±g were identical with those of
the racemates. All speci®c rotations shown below were
measured with 2a±g in .99% ee.
A solution of optically active imides 2a±g +8.89£1023
mmol) in benzene +3.0 mL) was stirred at each temperature
+sealed-tube experiments). The rate constants shown below
for their racemization were measured in the 15±70% range
of reaction conversion.
26
26
2a: 1 0 k338Cˆ3.69^0.02 s21, 1 0 k408Cˆ9.08^0.02 s21
,
,
,
,
,
,
,
4.2.8.
,S)-N-,2-t-Butylphenyl)-N-,4-dimethylamino-
1026k478Cˆ18.85^0.54 s21, 1 0 k548Cˆ44.46^1.01 s21
26
.
benzoyl)acetamide [,S)-2a]. Retention Time +RT)ˆ37 min
+i-PrOH:hexaneˆ1:10). [a]22 ˆ1378 +c 0.70, THF). CD
D
26
26
2b: 1 0 k338Cˆ1.74^0.02 s21, 1 0 k408Cˆ4.26^0.37 s21
+MeCN): lext 340 +De 10.63), 272 +20.57), 248 +11.71),
222 +23.02) nm. +R)-2a. RTˆ30 min +i-PrOH:hexane
1026k478Cˆ11.75^1.14 s21, 1 0 k548Cˆ25.50^0.73 s21
26
.
ˆ1:10). [a]22 ˆ2388 +c 0.58, THF). CD +MeCN): lext
D
26
26
2c: 1 0k338Cˆ1.18^0.02 s21, 1 0k408Cˆ2.93^0.02 s21
338 +De 20.36), 272 +10.94), 248 +21.63), 222 +12.53) nm.
1026k478Cˆ6.67^0.06 s21, 1 0 k548Cˆ16.31^0.22 s21
26
.
4.2.9.
,S)-N-,2-t-Butylphenyl)-N-,4-methoxybenzoyl)-
26
26
2d: 1 0 k338Cˆ1.02^0.02 s21, 1 0 k408Cˆ2.73^0.09 s21
acetamide [,S)-2b]. RTˆ20 min +i-PrOH:hexaneˆ1:15).
1026k548Cˆ10.85^0.23 s21, 1 0 k588Cˆ24.95^0.44 s21
26
.
[a]22 ˆ158 +c 0.33, THF). CD +MeCN): lext 292 +De
D
10.42), 258 +20.59), 234 +10.67) nm. +R)-2b. RTˆ
26
26
2e: 1 0k408Cˆ2.23^0.05 s21, 1 0k478Cˆ5.76^0.05 s21
32 min +i-PrOH:hexaneˆ1:15). [a]23 ˆ268 +c 0.37,
D
1026k548Cˆ11.26^0.32 s21, 1 0 k618Cˆ27.78^0.37 s21
26
.
THF). CD +MeCN): lext 290 +De 20.42), 258 +10.72),
236 +20.54) nm.
26
26
2f: 1 0k408Cˆ1.79^0.03 s21, 1 0k478Cˆ4.51^0.07 s21
1026k548Cˆ10.94^0.17 s21, 1 0 k618Cˆ26.48^0.11 s21
26
.
4.2.10. ,R)-N-,2-t-Butylphenyl)-N-,4-tolyl)acetamide [,R)-
2c]. RTˆ44 min +i-PrOH:hexaneˆ1:100). [a]23 ˆ1268 +c
D
26
26
2g: 1 0 k408Cˆ1.33^0.27 s21, 1 0 k478Cˆ4.10^0.07 s21
0.33, THF). CD +MeCN): lext 278 +De 11.68), 248
+23.12), 228 +12.15) nm. +S)-2c. RTˆ30 min +i-PrOH:
1026k548Cˆ10.95^0.15 s21, 1 0 k618Cˆ24.50^0.55 s21
26
.
hexaneˆ1:100). [a]21 ˆ2238 +c 0.27, THF). CD +MeCN):
D
lext 278 +De 21.57), 248 +13.59), 228 +22.30) nm.
4.4. ,Sa,2S)-N-,2-t-Butylphenyl)-N-,4-tri¯uoromethyl-
benzoyl)-2-acetoxypropionamide ,4a) and ,Ra,2S)-N-,2-
t-butylphenyl)-N-,4-tri¯uoromethylbenzoyl)-2-acetoxy-
propionamide ,4b)
4.2.11. ,R)-N-Benzoyl-N-,2-t-butylphenyl)acetamide [,R)-
2d]. RTˆ40 min +i-PrOH:hexaneˆ1:150). [a]26 ˆ1298 +c
D
1.38, benzene). CD +MeCN): lext 275 +De 11.31), 240
+22.12), 220 +12.97) nm. +S)-2d. RTˆ32 min +i-PrOH:
To a stirred solution of 2-t-butylaniline +0.92 mL, 5.90

K. Kondo et al. / Tetrahedron 57 32001) 4115±4122
4121
mmol) in pyridine +14.7 mL) was added +S)-2-acetoxy-
propionyl chloride +1.5 mL, 11.8 mmol) at 08C. The reac-
tion mixture was stirred at 258C for 3 h, quenched by the
addition of H2O at 08C and extracted with EtOAc. The
organic extracts were washed with saturated aq. NaHCO3
and brine, dried +Na2SO4) and concentrated. Puri®cation by
silica gel column +EtOAc:hexaneˆ1:10, the silica gel was
pretreated with 3% Et3N in hexane) afforded analytically
pure +2S)-N-+2-t-butylphenyl)-2-acetoxypropionamide +3)
+1.42 g, 91%) as a colorless solid. Recrystallization
+benzene±hexane) afforded colorless prisms of mp 115±
added SmI2, 0.1 M solution in THF +1.7 mL, 0.170 mmol)
at 2448C. The reaction mixture was stirred at 2448C for
20 min, and quenched by the addition of hexane and silica
gel at the same temperature. The whole mixture was ®ltered
to remove the silica gel and concentrated. Puri®cation by
silica gel column +EtOAc:hexaneˆ1:10, the silica gel was
pretreated with 3% Et3N in hexane) afforded 5a +20.1mg,
95%, 97% ee) as a colorless solid. Recrystallization
+benzene±hexane) afforded colorless prisms of mp 124.5±
1258C +71% ee). Rf valueˆ0.68 +EtOAc:hexane ˆ1:2). UV
+MeCN): lmax 224 +emax 17569) nm. CD +MeCN): lext 281
115.58C. [a]20 ˆ2318 +c 2.16, CHCl3). Rf valueˆ0.37
+11.18), 239 +22.27), 224 +17.19) nm. [a]20 ˆ1878 +c
D
D
1
+EtOAc:hexaneˆ1:2). IR +KBr): nˆ3321, 1748,
1.08, THF, 71% ee). IR +nujol): nˆ1721, 1678 cm21. H
1642 cm21
.
1H NMR +C6D6): dˆ1.20 +s, 9H), 1.44 +d,
NMR +C6D6): dˆ0.89 +t, Jˆ7.3 Hz, 3H), 1.28 +s, 9H),
1.97±2.05 +m, 2H), 6.73 +dd, Jˆ7.8, 1.7 Hz, 1H), 6.94
+ddd, Jˆ7.8, 7.8, 1.7 Hz, 1H), 7.06 +ddd, Jˆ7.8, 7.8,
1.7 Hz, 1H), 7.28 +d, Jˆ8.1Hz, 2H), 7.31 +dd, Jˆ7.8,
1
Jˆ6.8 Hz. 3H), 1.59 +s, 3H), 5.37 +q, Jˆ6.8 Hz, H), 6.98
+ddd, Jˆ8.1, 8.1, 1.5 Hz 1H), 7.12 +ddd, Jˆ8.1, 8.1, 1.5 Hz,
1H), 7.23 +dd, Jˆ8.1, 1.5 Hz, 1H), 7.91+br s, 1H), 8.30 +br d
Jˆ8.1Hz, 1H). 13C NMR +C6D6): dˆ17.77, 20.35, 30.36,
34.24, 71.21, 125.40, 126.09, 126.25, 126.91, 135.38,
140.39, 167.19, 168.00. EI MS: m/zˆ263 +M1), 206, 132,
88 +bp). Anal. Calcd for C15H21NO3: C, 68.42; H, 8.04; N,
5.32. Found: C, 68.56; H, 8.04; N, 5.25. To a stirred solution
of +2S)-N-+2-t-butylphenyl)-2-acetoxypropionamide +3)
+20.3 mg, 0.08 mmol) in pyridine +0.3 mL) was added
4-tri¯uoromethylbenzoyl chloride +0.07 mL, 0.47 mmol)
at 08C. The reaction mixture was stirred at 258C for 16 h,
quenched by the addition of H2O at 08C and extracted with
EtOAc. The organic extracts were washed with saturated aq.
NaHCO3 and brine, dried +Na2SO4) and concentrated. Puri-
®cation by silica gel column +EtOAc:hexaneˆ1:10, the
silica gel was pretreated with 3% Et3N in hexane) afforded
the analytically pure 4a +21.2 mg, 63%, 99% ee) and 4b
+11.0 mg, 33%, 91% ee) as colorless solids. 4a: Colorless
1
1.7 Hz, H), 7.52 +d, Jˆ8.1Hz, 2H). 13C NMR +C6D6):
dˆ8.85, 31.45, 31.72, 36.07, 124.13 +q, Jˆ272 Hz),
124.92 +q, Jˆ3.3 Hz), 127.12, 128.36, 129.04, 129.51,
132.05 +q, Jˆ32.5 Hz), 132.09, 136.68, 140.30, 147.10,
171.48, 176.22. EI MS: m/zˆ377 +M1), 320, 264, 132
+bp). Anal. Calcd for C21H22NO2F3: C, 66.83; H, 5.88; N,
3.71. Found: C, 67.18; H, 5.98; N, 3.86.
4.4.2.
,S)-N-,2-t-butylphenyl)-N-,4-tri¯uoromethyl-
benzoyl)propionamide ,5b). The same manner for the
synthesis of 5a was used with 4b +91%ee) to afford 5b
+81%, 90% ee). Colorless prisms +benzene±hexane), mp
123±1248C +90% ee). [a]20 ˆ21108 +c 1.06, THF, 90%
D
ee). CD +MeCN): lext 280 +21.01), 238 +12.72), 222
+24.15) nm. Other spectral data of 5b were identical with
those of 5a.
prisms, mp 95±96.58C +hexane, 98% ee). [a]20 ˆ22588 +c
D
2.72, benzene, 98% ee), Rf valueˆ0.61+EtOAc:
Crystal data and re®nement for 2a and 4b.
1
hexaneˆ1:2). IR +nujol): nˆ1738, 1712, 1684 cm21. H
Ê
NMR +C6D6): dˆ1.21 +s, 9H), 1.65 +s, 3H), 1.71 +d,
2a: C21H26N2O2, Mˆ338.45, monoclinic, aˆ19.654+3) A
Jˆ6.6 Hz, 3H), 5.74 +q, Jˆ6.6 Hz, 1H) 6.82±6.89 +m,
bˆ8.307+2) A cˆ12.142+3) A bˆ99.77+2)8, Vˆ1953.7+7)
Ê
Ê
1
Ê 3
2H), 7.03 +d, Jˆ8.3 Hz, 2H), 7.06±7.09 +m, H), 7.46±
A , space group P21/c +# 14), Zˆ4, Dcalcˆ1.151 g cm23
.
7.49 +m, 3H). 13C NMR +CDCl3): dˆ16.58, 20.56, 31.86,
36.11, 71.11, 123.11 +q, Jˆ272 Hz), 124.54 +q, Jˆ3.3 Hz),
126.63, 129.05, 129.20, 129.59, 132.34 +q, Jˆ33 Hz),
132.54, 134.66, 138.14, 147.63, 170.75, 171.23, 175.21.
EI MS: m/zˆ435 +M1), 374, 263, 173 +bp). Anal. Calcd
for C23H24NO4F3: C, 63.44; H, 5.56; N, 3.22. Found: C,
63.72; H, 5.65; N, 3.19. 4b: Colorless prisms, mp 124±
Crystal dimensions 0.40£0.40£0.15 mm, m+CuKa)ˆ
5.86 cm21. Data collection and processing: AFC7S diffract-
Ê
ometer, graphite monochromated MoKa +lˆ1.54178 A)
radiation, 4018 re¯ections measured, giving 2158 with
I.3.00s +I). The structure was solved by direct methods
using SIR9216a and was re®ned by full-matrix least-squares
techniques using DIRDIF94.17 The non-hydrogen atoms
were re®ned anisotropically. The ®nal residuals for re¯ec-
tions with I.3.00s +I) were Rˆ0.088, Rwˆ0.075. Full
details of the crystallographic results have been deposited
with the Cambridge Crystallographic Data Center +no.
CCDC 160500).
1258C +benzene±hexane, 94% ee). [a]24 ˆ2868 +c 1.02,
D
benzene, 94% ee). Rf valueˆ0.56 +EtOAc:hexane ˆ1:2).
1
IR +nujol): nˆ1733, 1673 cm21. H NMR +C6D6): dˆ1.29
+d, Jˆ6.6 Hz, 3H), 1.30 +s, 9H), 1.65 +s, 3H), 5.70 +q,
1
1
Jˆ6.6 Hz, H), 6.88 +ddd, Jˆ7.6, 7.6, 1.7 Hz, H), 6.97±
7.05 +m, 2H), 7.21+d, Jˆ8.3 Hz, 2H), 7.25 +dd, Jˆ7.6,
1.7 Hz, H), 7.51+d, Jˆ8.3 Hz, 2H). 13C NMR +C6D6):
4b: C23H24NO4F3, Mˆ435.44, orthorhombic, aˆ9.021+1)
1
Ê
Ê
Ê
Ê 3
dˆ16.30, 20.13, 32.16, 36.54, 70.16, 123.95 +q,
Jˆ272 Hz), 124.83 +q, Jˆ4.2 Hz), 126.77, 129.33, 130.37,
132.01, 132.19 +q, Jˆ32.5 Hz), 134.87, 139.40, 148.28,
169.17, 171.03, 173.53. EI MS: m/zˆ435 +M1), 291, 248,
134 +bp). Anal. Calcd for C23H24NO4F3: C, 63.44; H, 5.56;
N, 3.22. Found: C, 63.74; H, 5.43; N, 3.16.
A, bˆ9.386+1) A, cˆ25.868+4) A, Vˆ2190.2+5) A , space
group P212121 +# 19), Zˆ4, Dcalcˆ1.320 g cm23. Crystal
dimensions 0.50£0.45£0.45 mm, m+MoKa)ˆ1.06 cm21
.
Data collection and processing: CCD diffractometer,
Ê
graphite monochromated MoKa +lˆ0.71069 A) radiation,
12744 re¯ections measured, giving 2735 with I.0.50s +I).
The structure was solved by direct methods using SIR9716b
and was re®ned by full-matrix least-squares techniques
using DIRDIF94.17 The non-hydrogen atoms were re®ned
anisotropically. The ®nal residuals for re¯ections with
4.4.1. ,R)-N-,2-t-butylphenyl)-N-,4-tri¯uoromethyl-
benzoyl)propionamide ,5a). To a stirred solution of 4a
+24.2 mg, 0.056 mmol, 99% ee) in THF +0.2 mL) was

4122
K. Kondo et al. / Tetrahedron 57 32001) 4115±4122
Yamamoto, M.; Yamaguchi, K.; Yamada, K. J. Chem. Soc.,
Perkin Trans. 1 1997, 1233±1239.
I.0.50s +I) were Rˆ0.041, Rwˆ0.044. Full details of the
crystallographic results have been deposited with the
Cambridge Crystallographic Data Center +no. CCDC
160501).
4. +a) Kondo, K.; Fujita, H.; Suzuki, T.; Murakami, Y.
Tetrahedron Lett. 1999, 40, 5577±5580. +b) Kondo, K.; Iida,
T.; Fujita, H.; Suzuki, T.; Yamaguchi, K.; Murakami, Y.
Tetrahedron 2000, 56, 8883±8891.
Acknowledgements
5. For our preliminary communication on the electronic effects
of acyl groups, see: Kondo, K.; Fujita, H.; Suzuki, T.;
Murakami, Y. Enantiomer 2000, 5, 115±118.
We thank the Ministry of Education, Science and Culture,
Japan for support. K. K. was ®nancially supported by the
Mitsubishi Chemical Corporation Fund and the Uehara
Memorial Foundation.
³
³
6. According to Eyring's equation, DH and DS of 2a±g were
calculated. For Eyring's equation, see: Cagle, Jr., F. W.;
Eyring, H. J. Am. Chem. Soc. 1951, 73, 5628±5630.
7. Hammett, L. P. Physical Organic Chemistry, 2nd ed.;
McGraw-Hill: New York, 1970.
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10. Twist angle t is de®ned as follows: tˆ1/2 +v11v2). Accord-
ing to the de®nition, the t value lies in the range between
21808 and 1808. However, the larger the distortion, the nearer
the value lies to 908 or 2908; on the other hand, the smaller the
distortion, the nearer the value lies to 08, 1 808, or 21808.
Therefore, in order to avoid confusion regarding the magni-
tude of t, we represented the twist angle as utu +for
08#utu#908) or 180-utu +for 908#utu), see: Yamada, S.
Angew. Chem. Int. Ed. Engl. 1993, 32, 1083±1085.
11. Yamada, S.; Nunami, N.; Hori, K. Chem. Lett. 1998, 451±452.
12. No marked change in the imide moiety between N-+4-t-butyl-
phenyl)-N-+4-dimethylaminobenzoyl)acetamide and N-+4-t-
butylphenyl)-N-+4-tri¯uoromethylbenzoyl)acetamide
was
observed by X-ray analysis. For a recent report of pyramidal
amide nitrogen, see: Ohwada, T.; Achiwa, T.; Okamoto, I.;
Shudo, K.; Yamaguchi, K. Tetrahedron Lett. 1998, 39, 865±
868.
13. The imide geometry of 5b was considered to be the exo±endo
arrangement with acetyl carbonyl trans and aroyl carbonyl cis
to the 2-t-butylphenyl group, although that of 4b was the
endo±exo arrangement as shown in Fig. 3. In fact, the CD
Cotton effect of 4b was not observed.
14. For the CD exciton chirality method, see: Harada, N.,
Nakanishi, K. Circular Dichroic Spectroscopy±Exciton
Coupling in Organic Chemistry; University Science Books:
Mill Valley, 1983.
2. For recent reports in relation to non-biaryl axial chirality
except an N±Ar axis, see: +a) Kawabata, T.; Yahiro, K.;
Fuji, K. J. Am. Chem. Soc. 1991, 113, 9694±9696. +b)
Dogan, I.; Pustet, N.; Mannschreck, A. J. Chem. Soc., Perkin
Trans. 2 1993, 1557±1560. +c) Ohno, A.; Kunitomo, J.;
Kawai, Y.; Kawamoto, T.; Tomishima, M.; Yoneda, F. J.
Org. Chem. 1996, 61, 9344±9355. +d) Ikeura, Y.; Ishichi,
Y.; Tanaka, T.; Fujishima, A.; Murabayashi, M.; Kawada,
M.; Ishimaru, T.; Kamo, I.; Doi, T.; Natsugari, H. J. Med.
Chem. 1998, 41, 4232±4239. +e) Koide, H.; Uemura, M. Chir-
ality 2000, 12, 352±359.
15. +a) For a pioneering report of deacetoxylation with SmI2, see:
Molander, G.A., Hahn, G. J. Org. Chem. 1986, 51, 1135±
1138. +b) Quite recently, similar asymmetric synthesis of
anilides has been reported by Simpkins et al., see Ref. 1+j).
16. +a) Altomare, A.; Cascarano, M.; Giacovazzo, C.; Guagliardi,
A. J. Appl. Cryst. 1993, 26, 343±350. +b) Altomare, A.; Burla,
M. C.; Camalli, M.; Cascarano, G. L.; Giacovazzo, C.;
Guagliardi, A.; Moliterni, A. G. G.; Polidori, G.; Spagna, R.
J. Appl. Cryst. 1999, 32, 115±119.
17. Beurskens, P. T.; Admiraal, G.; Beurskens, G.; Bosman, W. P.;
de Gelder, R.; Israel, R.; Smits, J. M. M.; the DIRDIF-94
program system, Technical Report of the Crystallography
Laboratory, University of Nijmegen, The Netherlands, 1994.
3. For recent studies in relation to the rotational barrier around a
cyclic imide N±Ar bond, see: +a) Kishikawa, K.; Tsuru, I.;
Kohmoto, S.; Yamamoto, M.; Yamada, K. Chem. Lett. 1994,
1605±1606. +b) Kishikawa, K.; Yoshizaki, K.; Kohmoto, S.;