Practical radical additions under mild conditions using 2,2′-azobis(2,4-dimethyl-4-methoxyvaleronitrile) [V-70] as an initiator

Article abstract of DOI:10.1021/op970059z

Radical addition reactions of bromomalononitrile to various alkenes using 2,2′-azobis(2,4-dimethyl-4-methoxyvaleronitrile) (V-70) were examined. The advantages of V-70 which is an effective radical initiator at low temperature in contrast to the other azobis compounds are described. Especially V-70L (the low melting point diastereomer) was found to be the best radical initiator.

Full text of DOI:10.1021/op970059z

Organic Process Research & Development 1998, 2, 250−254
Practical Radical Additions under Mild Conditions Using
2
,2′-Azobis(2,4-dimethyl-4-methoxyvaleronitrile) [V-70] as an Initiator
,
†
†
†
†
‡
‡
Yasuyuki Kita,* Kentoku Gotanda, Kenji Murata, Miki Suemura, Atsunori Sano, Takahiro Yamaguchi,
‡
†
Masahisa Oka, and Masato Matsugi
Graduate School of Pharmaceutical Sciences, Osaka UniVersity, 1-6, Yamada-oka, Suita, Osaka 565, Japan, and Tokyo
Research Laboratories, Wako Pure Chemical Industries, Ltd., 1633, Matoba, Kawagoe, Saitama 350-11, Japan
Abstract:
Table 1. Addition of bromomalononitrile 1 to styrene 2a
using various radical initiators
Radical addition reactions of bromomalononitrile to various
alkenes using 2,2′-azobis(2,4-dimethyl-4-methoxyvaleronitrile)
(V-70) were examined. The advantages of V-70 which is an
effective radical initiator at low temperature in contrast to the
other azobis compounds are described. Especially V-70L (the
low melting point diastereomer) was found to be the best radical
initiator.
entry
initiator
time (h)
yield (%) of 3a
1
2
3
4
5
AIBN
BPO
24
24
18
6
no reactiona
no reaction
44
85
79
A formation of carbon-carbon bonds by radical addition
reactions is one of the important tactics in organic synthesis.
In the radical addition reactions, 2,2′-azobisisobutyronitrile
AIBN) is commonly used as a radical initiator. For
1
Et
hν
3
B
b
(
V-70
12
example, addition reactions of alkyl-substituted malononitrile
radicals induced by AIBN to alkenes have been reported.
a
If the reaction mixture was heated to generate the radical species, the dibromo
2
b
adduct 4 was preferentially formed (33% yield). A 400 W high-pressure mercury
lamp was used through a Pyrex filter.
This approach, however, appears to be unsuitable to apply
to heat-sensitive compounds, since AIBN requires generally
3
elevated temperatures in the generation of the radicals. Thus,
At first, radical addition reactions of bromomalononitrile
(1) to styrene (2a) were examined at room temperature in
the presence of various radical initiators, and the results are
summarized in Table 1. The reaction did not proceed at
room temperature using AIBN and a typical peracid radical
initiator such as benzoyl peroxide (BPO) (Table 1, entries 1
addition of iodomalononitriles to oxygen-substituted alkenes
2a
such as ethyl 1-propenyl ether using AIBN was unsuccessful.
On the other hand, photoinduced radical addition reactions
are generally run at ambient temperatures. Additions of
malononitrile radical induced by photoirradiation to alkenes
8
4
are carried out successfully at room temperature, but
photochemical reactions are sometimes accompanied by
difficulties such as practicability for large-scale productions.
To evade these drawbacks, we intended to take advantage
(
5) 2,2′-Azobis(2,4-dimethyl-4-methoxyvaleronitrile) is commercially available
from Wako Pure Chemical Industries Ltd., Japan, and the abbreviation in
brackets [V-70] is its trade name. This compound is a mixture of
diastereomeric isomers whose melting point are 58 and 107 °C and should
be stored below -10 °C to prevent any decomposition. V-70 is stable in a
refrigerator for a few months, and the pure V-70 can be easily obtained by
the following procedure: V-70 (10 g, ca. 90% content) was added to dry
acetone (20 mL) at -10 °C under stirring. The heterogeneous solution was
stirred for 30 min at -10 °C. Collection of the crystalline precipitates
afforded 6.2 g of pure V-70 (62%, >99% content).
5
of 2,2′-azobis(2,4-dimethyl-4-methoxyvaleronitrile) [V-70]
which is known as an effective initiator in the synthesis of
6
polymers. We expected that it would generate radical
species at room temperature or below, because the half-life
data of this compound indicated a species more unstable than
AIBN.7
(6) (a) Robertson, J. A. U.S. Pat. 2,586,995, 1952; Chem. Abstr. 1952, 46, 9579c.
b) Lim, D. Collect. CzechosloV. Chem. Commun. 1968, 33, 1122. (c)
(
Shinohara, N.; Kudo, M.; Iwabuchi, M. Jpn. Kokai Tokkyo Koho JP 04,-
66,588 [92,66,588] (Cl. C07F7/12), 02 Mar 1992, Appl. 90/172,449, 29
Jun 1990, 4 pp; Chem. Abstr. 1992, 117, 26799b. (d) Satsuka, H.; Takasu,
Y. Jpn. Kokai Tokkyo Koho JP 06,172,232 [94,172,232] (Cl. C07C22/04),
21 Jun 1994, Appl. 92/329,416, 09 Dec 1992, 6 pp; Chem. Abstr. 1994,
121, 230457a. (e) Katsura, T.; Shiratani, H. Eur. Pat. Appl. EP 709,369
(Cl. C07C253/30), 1 May 1996, JP Appl. 94/289,079, 27 Oct 1994, 7 pp;
Chem. Abstr. 1996, 125, 58121f.
†
Osaka University.
Wako Pure Chemical Industries, Ltd.
‡
(
1) For reviews, see: (a) Jaspers, C. P.; Curran, D. P.; Fevig, T. L. Chem. ReV.
1
1
991, 91, 1237. (b) Porter, N. A.; Giese, B.; Curran, D. P. Acc. Chem. Res.
991, 24, 296. (c) Curran, D. P. Synthesis 1988, 417, 489. (d) Ramaiah, M.
Tetrahedron 1987, 43, 3541. (e) Giese, B. Radicals in Organic Synthesis:
Formation of Carbon-Carbon Bonds; Pergamon Press: Oxford, 1986.
2) (a) Curran, D. P.; Thoma, G. J. Am. Chem. Soc. 1992, 114, 4436. (b) Curran,
D. P.; Seong, C. M. Tetrahedron 1992, 48, 2157, 2175.
3) For a review, see: Fossey, J.; Lefort, D.; Sorba, J. In Free Radicals in
Organic Chemistry; John Wiley & Sons: New York, 1995; p 105.
4) (a) Boldt, P.; Schulz, L. Tetrahedron Lett. 1966, 1415. (b) Boldt, P.; Schulz,
L.; Etzemuller, J. Chem. Ber. 1967, 100, 1281. (c) Boldt, P.; Thielecke,
W.; Etzemuller, J. Chem Ber. 1969, 102, 4257. (d) Boldt, P.; Schulz, L.;
Klinsmann, U.; Koster, H.; Thielecke, W. Tetrahedron 1970, 26, 3591. (e)
Bartels, H. M.; Boldt, P. Liebigs Ann. Chem. 1981, 40. (f) Bartels, H. M.;
Boldt, P.; Schomburg, O. Chem. Ber. 1981, 114, 3997.
(
(
(
(7) The temperature at which half of each initiator is decomposed in 10 h in
toluene: AIBN, 65 °C; V-59, 67 °C; V-65, 51 °C; V-70, 30 °C; V-30, 104
2
°C; V-40, 88 °C; V-601, 66 °C. In 10 h in H O: VA-088, 88 °C; VA-086,
86 °C; VA-080, 80 °C; VA-082, 82 °C; V-50, 56 °C. In 10 h in MeOH:
VA-061, 61 °C.
(8) Dichloromethane was used as the solvent in this reaction; however, the use
of other solvents such as benzene or diethyl ether also gave the similar
results. The yields in radical addition reactions of bromomalononitrile 1 to
styrene 2a using V-70 (5 mol %) were 73% (in benzene, rt, 24 h) and 76%
(in diethyl ether, rt, 24 h).
2
50
•
Vol. 2, No. 4, 1998 / Organic Process Research & Development
S1083-6160(97)00059-5 CCC: $15.00 © 1998 American Chemical Society and Royal Society of Chemistry
Published on Web 05/19/1998

Table 2. Comparison of azobis-type initiators
initiator
yield %
initiator
yield %
AIBN
V-59
V-65
V-70
V-501
V-30
V-40
no reaction
45
no reaction
95
68
12
V-601
no reaction
VA-088
VA-086
VA-080
VA-082
V-50
61
20
3
8
10
21
no reaction
VA-061
Table 3. Effects of the temperature in the radical addition
reactions of bromomalononitrile 1 to styrene 2a using V-70
(5 mol%)
entry
temp. (°C)
time (h)
yield (%)
1
2
3
4
5
25
10
10
0
12
24
36
24
48
79
71
80
56
89
0
Figure 1. Azo polymerization initiators.
and 2). In the case of Et B, which is known as a useful
radical initiator at low temperature, the yield of the desired
adduct (3a) was low, probably due to the decomposition of
Table 4. Effects of the ratio of V-70 in the radical addition
reactions of bromomalononitrile 1 to styrene 2a
3
9
ratio of V-70
entry
(mol %)
time (h)
yield (%)
71
79
80
1
(Table 1, entry 3). On the other hand, V-70 is quite
effective for inducing the addition of 1 to 2a at 25 °C to
give 3a in a satisfactory yield (Table 1, entry 5). The adduct
1
2
3
4
10.0
5.0
1.0
6
12
48
48
3
a was identical with an authentic sample which was
none
no reaction
4
obtained by the photoirradiation method (Table 1, entry 4).
An important point in this reaction is that the dibromo
derivative 4 is preferentially formed, although the reaction
mixture of 1 and 2a is heated in refluxing benzene or toluene
to generate the radical species in the presence of AIBN.
We then examined the radical addition reactions initiated
by various azobis compounds listed in Figure 1, which are
known as commonly used radical initiators for the synthesis
of polymers. The results are summarized in Table 2. We
found that V-70 was a very effective radical initiator in this
The generality of the additions of 1 to the other alkenes
2b-j) using V-70 was examined next. Consequently, target
(
adducts 3b-j were obtained with high yields under mild
conditions such as room temperature in each case (Table 5).11
It is noteworthy that the malononitrile radical cleanly reacts
with oxygen-substituted alkenes (2f,g) using V-70 at room
temperature (Table 5, entries 6 and 7), meanwhile the
addition of methyl iodomalononitrile to oxygen-substituted
alkenes using AIBN under the heated conditions was
10
case, too, for the addition of 1 to 2a at room temperature
2
1
unsuccessful.
(
25 °C) to give 3a. The yields calculated by H NMR are
In addition, the advantage of using V-70 than AIBN was
observed in the reaction of 1a and an activated oxygen-
substituted styrene derivative 5 followed by alcoholysis
listed in Table 2.
Next, we examined the effect of the temperature when
V-70 was used as the initiator in the reaction above (Table
12
(
Table 6). The use of V-70 predominantly gave the desired
3
). Although the relative reaction rate was somewhat low,
the adduct 3a was also obtained with satisfactory yield of
9% at 0 °C (Table 3, entry 5). Furthermore, as a result of
the examination of the essential amount of V-70, the adduct
a was also obtained with satisfactory yield of 80% even if
a 1 mol % amount of V-70 was used (Table 4, entry 3).
radical adduct 6 via a carbon-carbon bond forming reaction
in good yield, although the use of AIBN predominantly gave
the product 7 generated from the dibromo adduct (RCH-
BrCHBrOMe).
Furthermore, this V-70 is a mixture of diastereomers
which is composed by V-70H (high melting point) and
8
3
(9) For a review, see: Oshima, K.; Utimoto, K. Synth. Org. Chem. 1989, 47,
4
0.
(11) Kita, Y.; Sano, A.; Yamaguchi, T.; Oka, M.; Gotanda, K.; Matsugi, M.
Tetrahedron Lett. 1997, 38, 3549.
(
10) Other azobis compounds used in this paper are commercially available from
Wako.
(12) Miwa, T.; Hitaka, T.; Akimoto, H. J. Org. Chem. 1993, 58, 1696.
Vol. 2, No. 4, 1998 / Organic Process Research & Development
•
251

Table 5. Additions of bromomalononitrile 1 to various
alkenes 2 using V-70
alkene 2
time
(h)
yield of 3
entry
R1
R2
R3
R4
(%)
1
2
3
4
5
6
7
8
9
a
b
c
d
e
f
g
h
i
Ph
Ph
Me
H
H
Me
Me
H
H
H
H
H
Me
Me
H
H
H
H
Me
H
Me
H
H
12
72
12
12
24
24
24
24
24
24
79
68
81
84
78
76
72
88
90
89
Me
I(CH
OAc
OEt
2 8
)
a
H
b
cyclopentene
cyclohexene
norbornene
c
d
1
0
j
a
1
Calculated by crude H NMR. The molar ratios of the trans- to cis-isomer
b
c
d
were 2.82 , 1.02 , 0.18 .
Figure 2. (A) Structure of V-70L and V-70H. (B) X-ray
crystallography of V-70L.
Table 6. Additions of bromomalononitrile 1 to 5
time
(h)
temp.
(°C)
combined yield
of 6 and 7 (%)
ratioa
6:7
entry
initiator
1
2
V-70
AIBN
2
24
25
25
80
55
55:45
10:90
a
1
Ratio was determined by H NMR of crude products.
V-70L (low melting point). X-ray crystallography showed
that V-70L was racemic and V-70H was meso (Figure 2).
The separation of these epimers is readily possible through
the difference of the solubility in diethyl ether.13
Although the kinetic study of the decomposition of each
isomer of V-70 is reported,14 the difference of activity for
the radical addition reactions has not been apparent. There-
fore, we examined the difference in the activity between
V-70L and V-70H next. As a result, we found that V-70L
is more active as a radical initiator than V-70H (Figure 3).
This remarkable difference in activity was distinctly reflected
in the isolated yields over the same time interval (Table 7).
In conclusion, we clarified that V-70 has the highest
activity as a radical initiator of the readily available azobis
compounds listed in Figure 1 and that V-70 causes radical
Figure 3. Difference in the activity as the initiator between
V-70L and V-70H.
addition reactions at room temperature or below and affords
a high yield of the addition products. By use of V-70,
successful radical addition reactions were achieved which
were did not take place with typical radical initiators such
as AIBN or BPO. Furthermore, it has been apparent that
the low melting point diastereomer V-70L has higher activity
than another diastereomer (V-70H). It may be effectively
applied to the compounds having labile functions which are
sensitive to heat or basic or acidic conditions during the
radical addition reactions. It is expected that some other
useful reactions using the excellent initiator V-70 will be
developed.
(
13) V-70L: mp ca. 58 °C (dec.); 1H NMR (CDCl
s, 12 H), 2.26 (d, 2 H, J ) 11 Hz), 2.42 (d, 2 H, J ) 11 Hz), 3.21 (s, 6 H).
3
) δ 1.29 (s, 12 H), 1.64
(
1
V-70H: mp ca. 100 °C (dec.); H NMR (CDCl
s, 6 H), 1.69 (s, 6 H), 2.19 (d, 2 H, J ) 11 Hz), 2.59 (d, 2 H, J ) 11 Hz),
.19 (s, 6 H).
3
) δ 1.20 (s, 6 H), 1.27
(
3
(
14) The kinetics of the decomposition of each isomer of V-70 were measured
at 30-60 °C in several solvents: Palma, G.; Talamini, G.; Gasparini, P.;
Busetti, V. Chim. Ind. (Milan) 1970, 52 (11), 1116.
252
•
Vol. 2, No. 4, 1998 / Organic Process Research & Development

Table 7. Comparison of the activity between diastereomers
of V-70
2-(2-Bromo-1-methyl-2-phenylethyl)malononitrile (3b):
1
(
3
(
68% yield, as a colorless oil); H NMR (CDCl
H, J ) 6 Hz), 2.50 (m, 1 H), 3.32 (d, 1 H, J ) 9 Hz), 4.87
d, 1 H, J ) 9 Hz), 7.34 (m, 5 H); IR (KBr) cm 2240.
3
) δ 1.10 (d,
-
1
2
-(2-Bromo-1,2-dimethylpropyl)malononitrile (3c): (81%
4
b
yield, as white crystals); mp 40.5-41.9 °C (lit. 41.0-41.5
1
°
3
C); H NMR (CDCl
H), 1.91 (s, 3 H), 2.59 (dq, 1 H, J ) 7, 2 Hz), 4.59 (d, 1
H, J ) 2 Hz).
2-(2-Bromo-1,1,2-trimethylpropyl)malononitrile (3d): (84%
3
) δ 1.43 (d, 3 H, J ) 7 Hz), 1.82 (s,
alkene 2
temp. time yield of 3
R1 R2 R3 R4 (°C) (h)
(%)a
entry initiators
4b
yield, as white crystals); mp 115.4-116.2 °C (lit. 117-
1
1
2
3
4
5
6
7
8
9
V-70
2a Ph
H
H
H
H
H
H
H
H
H
25
25
10
25
25
10
25
25
10
24 3a 94
117.5 °C); H NMR (CDCl ) δ 1.46 (s, 6 H), 1.95 (s, 6 H),
3
2
5
92
49
4.45 (s, 1 H).
2
-(2-Bromo-10-iododecyl)malononitrile (3e): (78% yield,
V-70L 2a Ph
V-70H 2a Ph
24 3a 92
1
as white crystals); mp 43.5-45.5 °C; H NMR (CDCl
.33 (m, 12 H), 1.90 (m, 4 H), 2.49 (m, 2 H), 4.10 (m, 1 H),
3
) δ
2
5
93
62
1
4
-
1
.25 (dd, 1 H, J ) 4, 11 Hz); IR (KBr) cm 2245. Anal.
: C, 37.98; H, 4.90; N, 6.81. Found:
24 3a 85
Calcd for C13H20BrIN
2
2
5
80
38
C, 38.25; H, 4.84; N, 6.82.
Acetic acid, 1-bromomethyl-2,2-dicyanoethyl ester (3f):
1
1
0
1
V-70L 2d Me Me Me Me 25
V-70H 2d Me Me Me Me 25
1
1
3d 95
1
(
76% yield, as a pale yellow oil); H NMR (CDCl
3
) δ 2.17
3d
7
79b
(s, 3 H), 2.86 (dd, 2 H, J ) 5, 7 Hz), 4.15 (t, 1 H, J ) 7
1
1
2
3
V-70L 2i
V-70H 2i
cyclohexene
cyclohexene
25
25
4
4
3i
-
1
b
Hz), 6.77 (t, 1 H, J ) 5 Hz); IR (KBr) cm 2250, 1770.
-(2-Bromo-1-ethoxyethyl)malononitrile (3g): (72% yield,
3i 49
2
c
c
1
1
4
5
V-70L 2j
V-70H 2j
norbornene
norbornene
25
25
4
4
3j 81
3j 41
1
as a pale yellow oil); H NMR (CDCl ) δ 1.24 (t, 3 H, J )
3
7
Hz), 2.30 (dd, 2 H, J ) 4, 7 Hz), 3.56 (t, 1 H, J ) 7 Hz),
a
Isolation yield by column chromatography. The molar ratios of trans- to
3.99 (q, 2 H, J ) 7 Hz), 4.70 (t, 1 H, J ) 4 Hz); IR (KBr)
b
c
cis-isomer were 1.17 and 0.18 .
-1
cm 2257.
2
-(2-Bromocyclopentyl)malononitrile (3h): (88% yield, as
1
a pale yellow oil); H NMR (CDCl
.95 (m, 74/100 H), 4.15 (d, J ) 4 Hz) 4.62 (m, 26/100 H).
Anal. Calcd for C H BrN : C, 45.10; H, 4.26; N, 13.15.
3
) δ 1.69-2.68 (m, 7 H),
Experimental Section
3
Melting points are uncorrected. 1H NMR spectra were
8
9
2
measured in CDCl
with SiMe as the internal standard. E. Merck silica gel 60
70-230 mesh ASTM) for column chromatography and E.
3
on 200, 250, and 500 MHz spectrometers
Found: C, 45.33; H, 4.14; N, 13.43.
2-(2-Bromocyclohexyl)malononitrile (3i): (90% yield, as
4
1
a pale yellow oil); H NMR (CDCl
3
3
) δ 1.34-2.52 (m, 9 H),
(
.80 (m, 50/100 H), 3.94 (m, 50/100 H), 4.62 (d, 50/100 H,
Merck precoated TLC plates with silica gel F254 for
preparative TLC (PLC) were used. Azobis compounds
containing V-70 are commercially available from Wako Pure
Chemical Ind. Ltd., Japan. Alkenes 2a-j are commercially
available from Aldrich Chemical Company. The known
compounds 1 and 5 were prepared by the reported meth-
ods.2
+
J ) 3 Hz), 4.74 (m, 50/100 H); MS m/z (%) 228 (M + 2,
+
79
3
2
4
4
), 226 (M , 3), 147 (100); HRMS calcd for C
9
H
11 BrN
2
26.0105, found 226.0109. Anal. Calcd for C
7.60; H, 4.88; N, 12.34; Br, 35.18. Found: C, 47.61; H,
.86; N, 12.27; Br, 35.08.
9
H
11BrN : C,
2
2
-(3-Bromobicyclo[2.2.1]hept-2-yl)malononitrile (3j): (89%
,12
1
yield, as a pale yellow oil); H NMR (CDCl
3
) δ 1.23-2.69
Radical Adducts 3a-j, 6, and 7. Typical Procedure.
A mixture of 1 (1.45 g, 10 mmol), 2a (2.08 g, 20 mmol),
(
m, 9 H), 3.67 (d, 17/100 H, J ) 8 Hz), 3.90 (d, 83/100 H,
+
J ) 8 Hz), 3.95 (m, 17/100 H); MS m/z (%) 240 (M + 2,
+
79
and V-70 (308 mg, 5.0 mol %) in CH
Cl
2 2
(10 mL) was stirred
1), 238 (M , 1); HRMS calcd for C10
found 238.0103. Anal. Calcd for C10
H, 4.64; N, 11.72; Br, 33.42. Found: C, 50.05; H, 4.55; N,
1.77; Br, 33.00.
-(4-(Dicyanomethyl)-5,5-dimethoxypentyl)benzoic acid
H
11
N
2
Br 238.0105,
H11BrN : C, 50.23;
at room temperature in the dark. After 12 h, the mixture
was concentrated in vacuo. The residue was recrystallized
from 2-propanol (10 mL) to give 3a in 79% yield. Com-
pounds 3b-j, 6, and 7 were purified by flash column
chromatography on silica gel [3b (hexane/AcOEt, 5:1), 3c
2
1
4
1
methyl ester (6): (a pale yellow oil); H NMR (CDCl ) δ
3
1
3
4
7
.65-1.84 (m, 4 H), 2.26 (m, 1 H), 2.72-2.75 (m, 2 H),
(
hexane/AcOEt, 5:1), 3d (hexane/AcOEt, 3:1), 3e (hexane/
AcOEt, 5:1), 3f (hexane/AcOEt, 4:1), 3g (hexane/AcOEt,
:1), 3h (hexane/AcOEt, 5:1), 3i (hexane/AcOEt, 6:1), 3j
hexane/AcOEt, 8:1)]. The physical data for 3a-j, 6, and
are summarized below.
-(2-Bromo-2-phenylethyl)malononitrile (3a): (79% yield,
.39 (s, 3 H), 3.44 (s, 3 H), 3.90 (s, 3 H), 4.12 (d, 1 H, J )
Hz), 4.31 (d, 1 H, J ) 5 Hz), 7.26 (d, 2 H, J ) 8 Hz),
8
(
7
-1
.97 (d, 2 H, J ) 8 Hz); IR (KBr) cm 2255, 1720; MS
+
m/z (%) 330 (M , 1), 266 (100); HRMS calcd for C18
H
22
N
2
O
4
3
30.1579, found 330.1582. Anal. Calcd for C18
H
22
N
2
O
4
:
2
C, 65.44; H, 6.71; N, 8.45. Found: C, 65.08; H, 6.61; N,
8.40.
4b
as white crystals) mp 60.2-61.8 °C (lit. 60.5-61.0 °C);
1
H NMR (CDCl
3
) δ 2.82 (m, 2 H), 4.01 (dd, 1 H, J ) 6, 10
4-(5,5-Dimethoxypentyl)benzoic acid methyl ester (7): (a
1
Hz), 5.08 (dd, 1 H, J ) 6, 10 Hz), 7.41 (bs, 5 H); MS m/z
colorless oil); H NMR (CDCl
3
) δ 1.32-1.48 (m, 2 H),
+
+
(
%) 250 (M + 2, 2), 248 (M , 2), 104 (100); HRMS calcd
1.57-1.72 (m, 4 H), 2.67 (t, 2 H, J ) 8 Hz), 3.30 (s, 6 H),
3.89 (s, 3 H), 4.34 (t, 1 H, J ) 5 Hz), 7.23 (d, 2 H, J ) 9
79
9 2
for C11H BrN 247.9949, found 247.9948.
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253

Hz), 7.95 (d, 2 H, J ) 9 Hz); IR (KBr) cm-1 1721; HRMS
calcd for C15 266.1518, found 266.1517.
Separation of the Diastereomers of V-70. Typical
Procedure. V-70 (5.00 g) in Et O (25 mL) was stirred at
0 °C for 30 min to precipitate only V-70H (2.46 g; content
dry nitrogen. After a small amount of galvinoxyl was added,
the mixture was concentrated in vacuo below room temper-
ature. The purification by column chromatography on silica
gel (eluent, AcOEt/hexane ) 1/5) gave 3a in 93% yield.
22 4
H O
2
1
1
Supporting Information Available
of 100% from H NMR). On the other hand, the filtrate,
Ortep representations and X-ray crystallographic details
(5 pages). See any current masthead page for ordering
information and Web access instructions.
upon cooling to -10 °C for 2 days, gave crystallized V-70L
1
(
1.05 g; content of 100% from H NMR).
Comparison of the Activity between the Diastereomers
of V-70. Typical Procedure. A mixture of 1 (1 mmol), 2a
1 mmol) and V-70L (5 mol %) in CDCl (1 mL) was stirred
at 25 °C for 2 h in the dark under a positive atmosphere of
Received for review November 28, 1997.
OP970059Z
(
3
254
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