Novel isomerization reaction of N,N-dimethyl-α-(methoxycarbonyl)-4- substituted-benzylammonium N-methylides

Article abstract of DOI:10.1021/jo981729h

Fluoride ion-induced desilylation of N,N-dimethyl-N- [(trimethylsilyl)methyl]-α-(methoxycarbonyl)4-substituted benzylammonium salts (7) gave two Stevens rearrangement products: methyl 3-(dimethylamino)- 2-(4-substituted phenyl)propionates (13) from N-methylides 8, and methyl 3- (dimethylamino)-3-(4-substituted phenyl)propionates (15) from N-benzylides 10. Additional Stevens rearrangement products, methyl 2-(dimethylamino)-3- (4-substituted phenyl)propionates (16), were competitively formed from ylides 12 when the cesium fluoride used was not predried. The mechanism of the isomerization from methylides 8, which was initially generated, to 10 and 12 is discussed.

Full text of DOI:10.1021/jo981729h

J . Org. Chem. 1999, 64, 581-586
581
Novel Isom er iza tion Rea ction of
N,N-Dim eth yl-r-(m eth oxyca r bon yl)-4-su bstitu ted -
ben zyla m m on iu m N-Meth ylid es
Chen Zhang, Hiroto Ito, Yasuhiro Maeda, Naohiro Shirai, Shin-ichi Ikeda, and Yoshiro Sato*
Faculty of Pharmaceutical Sciences, Nagoya City University,
Tanabe-dori, Mizuho-ku, Nagoya 467-8603, J apan
Received August 24, 1998
Fluoride ion-induced desilylation of N,N-dimethyl-N-[(trimethylsilyl)methyl]-R-(methoxycarbonyl)-
4-substituted benzylammonium salts (7) gave two Stevens rearrangement products: methyl
3-(dimethylamino)-2-(4-substituted phenyl)propionates (13) from N-methylides 8, and methyl
3-(dimethylamino)-3-(4-substituted phenyl)propionates (15) from N-benzylides 10. Additional
Stevens rearrangement products, methyl 2-(dimethylamino)-3-(4-substituted phenyl)propionates
(16), were competitively formed from ylides 12 when the cesium fluoride used was not predried.
The mechanism of the isomerization from methylides 8, which was initially generated, to 10 and
12 is discussed.
Sch em e 1
In tr od u ction
Fluoride ion-induced desilylation of R-(trimethylsilyl)-
alkylammonium salts provides a useful method for the
selective formation of N-alkylides.1 Since this reaction
proceeds quantitatively in nonbasic media, we previously
examined the possibility of N-methylide formation in
molecules with acidic hydrogen(s) which can be depro-
tonated under basic conditions.2,3 On the basis of the
results of the reaction of N-[(trimethylsilyl)methyl]ben-
zylammonium salts (1, R ) CO2Me or CN) with cesium
fluoride (Scheme 1), we presumed that N-methylides 2
are initially formed. However, two isomerization routes
subsequently occur to give ylides 3 by intramolecular [1,3]
proton transfer (path a) and ylides 4 by intermolecular
proton transfer with 1 (path c).2 Later, we noticed that
the direct deprotonation of 1 with cesium fluoride (path
b) is more important for the formation of 4 than path c.3
Thus, N-methylide formation by desilylation is not simple
in molecules with electron-withdrawing groups. In this
paper, we report the reaction of N,N-dimethyl-N-[(tri-
methylsilyl)methyl]-R-(methoxycarbonyl)-4-substituted
benzylammonium salts (7) with cesium fluoride.
with cesium fluoride in DMF at room temperature gave
a mixture of compounds 13a and 15a , and a third
compound 16a was also obtained when the cesium
fluoride used was not predried over phosphorus pentoxide
at 180 °C under reduced pressure (Table 1, entries 1, 2).
All of these products are constructed of methoxycarbonyl,
dimethylamino, and phenyl groups. Compound 16a was
easily separated by column chromatography and deter-
mined to be methyl 2-(dimethylamino)-3-phenylpropi-
onate. However, separation of 13a and 15a was difficult,
and some of 13a was deaminated to methyl 2-phenyl-
propenoate (14a ) during handling. When the methoxy-
carbonyl groups of 13a and 15a (7:3 mixture) were
reduced with lithium aluminum hydride to the corre-
sponding alcohols 17 and 18, the alcohols could be
separated by column chromatography (Scheme 3). The
structure of alcohol 17 was determined to be 3-(dimethy-
lamino)-2-phenylpropanol while 18 was 3-(dimethylamino)-
3-phenylpropanol. Thus, the original products 13a and
15a were assigned to be methyl 3-(dimethylamino)-2-
phenylpropionate and methyl 3-(dimethylamino)-3-
phenylpropionate, respectively.
Resu lts a n d Discu ssion
N,N-Dimethyl-N-[(trimethylsilyl)methyl]-R-(methoxy-
carbonyl)-4-substituted benzylammonium salts (7a -e)
were prepared by reacting R-(4-substituted phenyl)-
glycine methyl esters (6) with (chloromethyl)trimethyl-
silane followed by quaternization with iodomethane
(Scheme 2, Table 1).
The reaction of N,N-dimethyl-N-[(trimethylsilyl)-
methyl]-R-(methoxycarbonyl)benzylammonium iodide (7a)
Three isomers 13a , 15a , and 16a are the Stevens
rearrangement products formed from N-ylides 8a , 10a ,
and 12a , respectively. Ylide 8a should be initially formed
by the desilylation of 7a , and ylide 10a may be formed
from 8a via an azetidinium ring intermediate 9 which is
formed by nucleophilic attack of the carbonyl carbon by
the ylide-anion of 8a (Scheme 2).
* Corresponding author. Phone: 81-52-836-3459. Fax: 81-52-836-
3459. E-mail: ysato@phar.nagoya-cu.ac.jp.
(1) (a) Vedejs, E.; West, F. G. Chem. Rev. 1986, 86, 941. (b) Sato, Y.
J . Synth. Org. Chem. J pn. 1992, 50, 977. (c) Sato, Y.; Shirai, N.
Yakugaku Zasshi 1994, 114, 880.
(2) Zhang, C.; Maeda, Y.; Shirai, N.; Sato, Y. J . Chem. Soc. Perkin
Trans. 1 1997, 25.
(3) Zhang, C.; Maeda, Y.; Sato, Y. Chem. Pharm. Bull. 1998, 46,
572.
10.1021/jo981729h CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/29/1998

582 J . Org. Chem., Vol. 64, No. 2, 1999
Zhang et al.
Sch em e 2
Sch em e 3
Sch em e 4
products 13b,d ,e and 15b,d ,e were formed from 7b,d ,e
using predried cesium fluoride (entries 3, 5, and 7).
Contamination by a third Stevens product 16d was
observed when 7d was treated with cesium fluoride
which was not predried (entry 6). However, a 4-meth-
oxybenzyl analogue 7c gave only a normal rearrangement
product 13c (entry 4). The strong electron-releasing
ability of the methoxy group may inhibit the conversion
of 9c to 10c.
The formation of 16 in the presence of a trace amount
of water may result from the isomerization of 10 to 12
via ammonium hydroxides 11. Recently, J on’czyk and
Zdrojewski4 reported that equilibration of ylides PhCH--
N+CH2CN and PhCH2N+-CH-CN is facilitated in the
presence of water. We tried to generate 10a by reacting
N,N-dimethyl-N-(methoxycarbonyl)methyl-R-(trimethyl-
silyl)benzylammonium hexafluorophosphate (19) with
cesium fluoride (Scheme 4). When 3 mol equiv of cesium
fluoride were used, the main product was not 15a (20%)
but rather 16a (53%), despite the absence of water. The
use of an equimolar amount of cesium fluoride gave 16a
(30%) and methyl 2-(dimethylamino)-3-phenyl-3-(tri-
methylsilyl)propionate (21, 8%), which is a Stevens
rearrangement product of ylide 20. When isolated 21 was
stirred in a suspension of cesium fluoride in DMF at room
temperature, it was desilylated to 16a in 85% yield.5
These results suggest that fluoride ion acts on 19 as an
R-deprotonation reagent rather than a desilylation re-
agent, and the isomerization of ylide 10a to 12a does not
occur in the absence of water.
Ta ble 1. Rea ction of
N,N-Dim eth yl-N-[(tr im eth ylsilyl)m eth yl]-
r-(m eth oxyca r bon yl)-4-su bstitu ted -ben zyla m m on iu m
Sa lts (7) w ith CsF in DMF a t Room Tem p er a tu r e
product proportionsa
entry salt
R
X
total yield (%)
13
70
65
80
100
80
69
15
16
1
2
3
4
5
6
7
7a
7a
7b
7c
7d
7d
7e
H
H
I
I
81
30
16
20
0
20
19
23
0
19
0
0
0
27b
89
Me
OMe
F
ClO4
I
50
ClO4
ClO4
ClO4
86
F
33b
95c
12
0
Cl
77
a
Proportions of the products were determined by integration
of the 1H signals in 400- or 500-MHz NMR. b CsF was not predried.
c Includes methyl 2-(4-chlorophenyl)propenoate (14e, 9%).
The novel isomerization of ylides 8 to ylides 10 resulted
from the intramolecular nucleophilic attack of the car-
To examine the generality of this novel chemical
behavior of ylide 8a , 4-methylbenzylammonium (7b),
4-methoxybenzylammonium (7c), 4-fluorobenzylammo-
nium (7d ), and 4-chlorobenzylammonium salts (7e) were
similarly treated with cesium fluoride. The results are
listed in Table 1. Two types of Stevens rearrangement
(4) Zdrojewski, T.; J on’czyk, A. J . Org. Chem. 1998, 63, 452.
(5) Fluoride ion-induced desilylation of benzyltrimethylsilane has
been reported previously: Ricci, A.; Fioreza, M.; Grifagni, M. A.;
Batolini, G. Tetrahedron Lett. 1982, 48, 5079.

Novel Isomerization Reaction
Sch em e 5
J . Org. Chem., Vol. 64, No. 2, 1999 583
of 27 may occur by the fluoride ion-induced R-deproto-
nation of 27 to ylide 28 and vice versa.
Exp er im en ta l Section
DMF was dried by distillation from BaO under reduced
pressure. CsF was dried over P2O5 at 180 °C under reduced
pressure. Aluminum oxide (Merck Aluminum oxide 90, 70-
230 mesh) or silica gel (BW-200, Fuji-Silysia) was used for
column chromatography. Distillation was performed on a
Bu¨chi Kugelrohr distillation apparatus. All melting points and
boiling points are uncorrected.
N,N-Dim eth yl-N-[(tr im eth ylsilyl)m eth yl]-R-(m eth oxy-
ca r bon yl)-4-su bstitu ted -ben zyla m m on iu m Sa lts (7a -e).
Gen er a l P r oced u r e. A suspension of dl-R-phenylglycine
methyl ester hydrochloride (6a ) or an analogue; 4-methylphe-
nyl- (6b), 4-methoxyphenyl- (6c), 4-fluorophenyl- (6d ), or
4-chlorophenyl- (6e) (50 mmol), (chloromethyl)trimethylsilane
(9.2 g, 75 mmol), KI (12.5 g, 75 mmol), and K2CO3 (10.4 g, 75
mmol) in DMF (200 mL) was stirred at 100 °C for 1 h. The
mixture was poured into water (500 mL) and extracted with
EtOAc (4 × 100 mL). The extract was washed with water (3
× 100 mL) and saturated aqueous NaCl (2 × 50 mL), dried
(MgSO4), and concentrated under reduced pressure. The
residue was chromatographed on a silica gel column (EtOAc/
hexane, 1:10) and distilled to give the following esters.
Sch em e 6
Met h yl 2-[(t r im et h ylsilyl)m et h yl]a m in o-2-p h en yla c-
eta te: yield 6.82 g (54%); bp 100 °C (4 mmHg); IR (film) 1740,
1
1251, 854 cm-1; H NMR (270 ΜΗz, CDCl3) δ 0.05 (s, 9 H),
1.74 (s, 1 H), 1.92 and 1.98 (AB-q, J ) 13.4 Hz, 2 H), 3.67 (s,
3 H), 4.29 (s, 1 H), 7.27-7.38 (m, 5 H). Anal. Calcd for C13H21
-
NO2Si: C, 62.11; H, 8.42; N, 5.57. Found: C, 61.98; H, 8.53;
N, 5.55.
Met h yl 2-[(t r im et h ylsilyl)m et h yl]a m in o-2-(4-m et h yl-
p h en yl)a ceta te: yield 6.60 g (50%); bp 90 °C (0.5 mmHg);
1
IR (film) 1730, 1240, 850 cm-1; H NMR (400 MHz, CDCl3) δ
0.05 (s, 9 H), 1.72 (br s, 1 H), 1.92 and 1.97 (AB-q, J ) 13.1
Hz, 2 H), 2.34 (s, 3 H), 3.68 (s, 3 H), 4.26 (s, 1 H), 7.15 (d, J )
7.9 Hz, 2 H), 7.25 (d, J ) 7.9 Hz, 2 H). Anal. Calcd for C14H23
-
NO2Si: C, 63.35; H, 8.73; N, 5.28. Found: C, 63.34; H, 8.69;
N, 5.28.
Met h yl 2-[(t r im et h ylsilyl)m et h yl]a m in o-2-(4-m et h -
oxyp h en yl)a ceta te: yield 6.11 g (45%); bp 90 °C (0.5 mmHg);
1
IR (film) 1740, 1251, 855 cm-1; H NMR (500 MHz, CDCl3) δ
bonyl-carbons by the ylide-anions. When N,N-dimethyl-
N-[(trimethylsilyl)methyl]-R-cyanobenzylammonium per-
chlorate (22) was prepared as an R-cyano-analogue of 7a
from N,N-dimethyl-R-cyanobenzylamine and treated with
cesium fluoride, a mixture of 2-phenylacrylonitrile (25,
25%) and N,N-dimethyl-2,4-dicyano-2,4-diphenylbutyl-
amine (26, 30%) was formed (Scheme 5). The former may
be produced from Stevens rearrangement product 24 of
ylide 23 by deamination, while the latter is a Michael-
type condensation product of 24 with 25. Isomerization
of 23 to other ylides did not occur in this reaction.
(S)-(+)-N,N-Dimethyl-N-[(trimethylsilyl)methyl]-1-
(methoxycarbonyl)-2-phenylethylammonium iodide (27),
which is a homologue of 7a , was prepared from l-
phenylalanine methyl ester and treated with cesium
fluoride (Scheme 6). dl-Methyl 2-benzyl-3-(dimethylami-
no)propionate (30, 61%, Stevens rearrangement product
of ylide 29) and methyl cinnamate (31, 13%, Hofmann
elimination product of 29) were obtained; however,
isomeric products of 30, which should be formed via
isomerization of ylide 29, were not obtained. It is well-
known that the configuration of the migrating group is
retained in a Stevens rearrangement.6 However, the
chirality of 27 was not retained in 30. Quick racemization
0.04 (s, 9 H), 1.73 (br s, 1 H), 1.92 and 1.96 (AB-q, J ) 13.1
Hz, 2 H), 3.68 (s, 3 H), 3.79 (s, 3 H), 4.24 (s, 1 H), 6.87 (d, J )
8.5 Hz, 2 H), 7.28 (d, J ) 8.5 Hz, 2 H). Anal. Calcd for C14H23
-
NO3Si: C, 59.75; H, 8.24; N, 4.98. Found: C, 59.59; H, 8.12;
N, 4.68.
Met h yl 2-[(t r im et h ylsilyl)m et h yl]a m in o-2-(4-flu or o-
p h en yl)a ceta te: yield 6.86 g (51%); bp 100-110 °C (1
mmHg); IR (film) 1746, 1248, 844 cm-1; H NMR (400 MHz,
1
CDCl3) δ 0.05 (s, 9 H), 1.67 (br s, 1 H), 1.89 and 1.98 (AB-q, J
) 13.2 Hz, 2 H), 3.69 (s, 3 H), 4.26 (s, 1 H), 7.03 (t, J F-H ) 8.8,
J ) 8.8 Hz, 2 H), 7.34 (dd, J F-H ) 5.4, J ) 8.8 Hz, 2 H); 13C
NMR (100 MHz, CDCl3) δ 2.7 (3 C), 37.8, 52.1, 68.4, 115.4 (d,
J F-C ) 21.7 Hz, 2 C), 129.2 (d, J F-C ) 8.3 Hz, 2 C), 134.1 (d,
J F-C ) 3.2 Hz), 162.0 (d, J F-C ) 246.2 Hz), 173.5. Anal. Calcd
for C13H20FNO2Si: C, 57.96; H, 7.48; N, 5.20. Found: C, 57.96;
H, 7.45; N, 5.21.
Met h yl 2-[(t r im et h ylsilyl)m et h yl]a m in o-2-(4-ch lor o-
p h en yl)a ceta te: yield 7.28 g (51%); bp 100-110 °C (1
mmHg); IR (film) 1745, 1250, 855 cm-1; H NMR (270 MHz,
1
CDCl3) δ 0.00 (s, 9 H), 1.64 (s, 1 H), 1.90 and 1.84 (AB-q, J )
13.4 Hz, 2 H), 3.63 (s, 3 H), 4.20 (s, 1 H), 7.26 (s, 4 H). Anal.
Calcd for C13H20ClNO2Si: C, 54.62; H, 7.05; N, 4.90. Found:
C, 54.43; H, 7.15; N, 4.86.
A mixture of methyl 2-[(trimethylsilyl)methyl]amino-2-(4-
substituted phenyl)acetate (20 mmol) described above, io-
domethane (28.4 g, 100 mmol), and K2CO3 (2.8 g, 20 mmol) in
MeCN (100 mL) was stirred for 12 h and filtered. The filtrate
was concentrated under reduced pressure to give the following
ammonium salts.
(6) Marko´, I. E. Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 3, p 913.

584 J . Org. Chem., Vol. 64, No. 2, 1999
Zhang et al.
N,N-Dim eth yl-N-[(tr im eth ylsilyl)m eth yl]-r-(m eth oxy-
ca r bon yl)ben zyla m m on iu m iod id e (7a ): yield 4.90 g (60%);
mp 165-167 °C (recrystallized from acetone-Et2O); IR (Nujol)
1750, 1210, 860 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.32 (s, 9
H), 3.36 and 3.82 (AB-q, J ) 13.4 Hz, 2 H), 3.40 (s, 3 H), 3.47
(s, 3 H), 3.75 (s, 3 H), 6.84 (s, 1 H), 7.47-7.59 (m, 3 H), 7.77-
7.79 (m, 2 H). Anal. Calcd for C15H26INO2Si: C, 44.23; H, 6.43;
N, 3.44. Found: C, 44.12; H, 6.29; N, 3.39.
J ) 10.1, 5.1 Hz, 1 H), 7.18-7.34 (m, 5 H); 15a : δ 2.17 (s, 6
H), 2.70 (dd, J ) 15.0, 7.6 Hz, 1 H), 2.97 (dd, J ) 15.0, 7.3 Hz,
1 H), 3.58 (s, 3 H), 3.88 (dd, J ) 7.6, 7.3 Hz, 1 H), 7.18-7.34
(m, 5 H); 13C NMR (100 MHz, CDCl3) 13a : δ 45.8 (2 C), 51.1,
52.6, 63.8; 15a : δ 39.0, 42.6, 52.1 (2 C), 67.8; others: 128.7,
128.9, 129.0 (2 C), 129.2 (2 C), 129.5 (2 C), 129.9 (2 C), 138.7,
139.2, 173.6, 175.1. Anal. Calcd for C12H17NO2: C, 69.54; H,
8.27; N, 6.76. Found: C, 69.46; H, 8.44; N, 6.51.
N,N-Dim eth yl-N-[(tr im eth ylsilyl)m eth yl]-r-(m eth oxy-
ca r bon yl)-4-m eth ylben zyla m m on iu m P er ch lor a te (7b).
The residue was not crystallized, and the counteranion was
changed to perchlorate as follows: a solution of the residue in
CHCl3 (20 mL) was stirred with a saturated aqueous solution
of NaClO4 (30 mL) for 3 h. The CHCl3 layer was separated,
and the aqueous layer was extracted with CHCl3 (4 × 50 mL).
The combined extracts were dried (MgSO4) and concentrated
under reduced pressure to give 7b (3.94 g, 50%); mp 124-126
°C (recrystallized from acetone-Et2O); IR (Nujol) 1740, 1260,
An aliquot of 13a was changed to methyl 2-phenylprope-
noate7 (14a ) during handling. Compound 14a was separated
on a silica gel column (EtOAc/hexane, 1:10): bp 72-75 °C (0.6
mmHg) [lit.7 73 °C (0.6 mmHg)].
B. The reaction described above was carried out with CsF
(Aldrich reagent was used without further drying) and worked
up to give a mixture of 13a , 15a , and methyl 2-(dimethyl-
amino)-3-phenylpropionate8 (16a ) (ratio 65:16:19, determined
from the proton ratios in 1H NMR), yield 112 mg (27%).
Compound 16a was separated from the mixture on an alumi-
num oxide column (EtOAc/hexane, 1:10): a colorless oil; bp
82-85 °C (0.7 mmHg) (lit.8 256-258 °C).
1
850 cm-1; H NMR (400 MHz, CDCl3) δ 0.31 (s, 9 H), 2.41 (s,
3 H), 3.32 and 3.50 (AB-q, J ) 14.6 Hz, 2 H), 3.27 (s, 3 H),
3.30 (s, 3 H), 3.77 (s, 3 H), 5.57 (s, 1 H), 7.31 (d, J ) 8.1 Hz, 2
H), 7.47 (d, J ) 8.1 Hz, 2 H). Anal. Calcd for C16H28ClNO6Si:
C, 48.78; H, 7.16; N, 3.56. Found: C, 48.59; H, 7.26; N, 3.59.
N,N-Dim eth yl-N-[(tr im eth ylsilyl)m eth yl]-r-(m eth oxy-
ca r bon yl)-4-m eth oxyben zyla m m on iu m iod id e (7c): yield
4.87 g (56%); a viscous oil. This salt was not crystallized and
was used for the next reaction without further purification.
LiAlH4 Red u ction of 13a a n d 15a . A mixture of 13a and
15a (238 mg, 1.15 mmol, ratio 7:3) was dissolved in Et2O (5
mL) and added dropwise to a suspension of LiAlH4 (46 mg,
1.2 mmol) in Et2O (5 mL). The mixture was stirred for 2 h at
room temperature, poured into saturated potassium sodium
tartrate, and extracted with Et2O (3 × 10 mL). The extract
was washed with water, dried (MgSO4), and concentrated
under reduced pressure. The residue was chromatographed
on an aluminum oxide column (EtOAc/hexane, 3:10) to give
3-(dimethylamino)-2-phenylpropanol (17) (140 mg, 68%) and
3-(dimethylamino)-3-phenylpropanol (18) (30 mg, 15%).
1
IR (Nujol) 1750, 1240, 840 cm-1; H NMR (270 MHz, CDCl3)
δ 0.29 (s, 9 H), 3.28 and 3.33 (AB-q, J ) 14.5 Hz, 2 H), 3.35 (s,
3 H), 3.39 (s, 3 H), 3.65 (s, 3 H), 3.81 (s, 3 H), 6.53 (s, 1 H),
6.95 (d, J ) 8.6 Hz, 2 H), 7.64 (d, J ) 8.6 Hz, 2 H); 13C NMR
(125 MHz, CDCl3) δ -0.19 (3 C), 51.0, 52.1 (2 C), 53.4, 55.5,
56.1, 76.5, 114.9 (2 C), 118.2 (2 C), 161.9, 167.6.
1
17: bp 100 °C (1.5 mmHg); IR (film) 3300 cm-1; H NMR
(400 MHz, CDCl3) δ 2.35 (s, 6 H), 2.55 (ddd, J ) 12.2, 3.1, 2.6
Hz, 1 H), 2.99 (t, J ) 12.2 Hz, 1 H), 3.15-3.22 (m, 1 H), 3.84
(ddd, J ) 10.5, 4.0, 2.6 Hz, 1 H), 3.96 (t, J ) 10.5 Hz, 1 H),
5.40-6.20 (br s, 1 H), 7.15-7.31 (m, 5 H); 13C NMR (100 MHz,
CDCl3) δ 43.4, 45.8 (2 C), 66.6, 70.5, 126.8, 127.4 (2 C), 128.5
(2 C), 140.4. Anal. Calcd for C11H17NO: C, 73.70; H, 9.56; N,
7.81. Found: C, 73.42; H, 9.83; N, 7.52.
N,N-Dim eth yl-N-[(tr im eth ylsilyl)m eth yl]-r-(m eth oxy-
ca r bon yl)-4-flu or oben zyla m m on iu m P er ch lor a te (7d ).
The iodide salt was not crystallized, and the counteranion was
changed to perchlorate in a manner similar to that described
for 7b: yield 7.55 g (95%); mp 168-170 °C (recrystallized from
water); IR (KBr) 1740, 1210, 849 cm-1 1H NMR (400 MHz,
;
18: bp 100 °C (1.5 mmHg) [lit.9 100 °C (1.5 mmHg)].
CD3OD) δ 0.32 (s, 9 H), 3.18 and 3.40 (AB-q, J ) 14.4 Hz, 2
H), 3.24 (s, 3 H), 3.29 (s, 3 H), 3.83 (s, 3 H), 5.52 (s, 1 H), 7.35
(t, J F-H ) 8.8, J ) 8.8 Hz, 2 H), 7.71 (dd, J F-H ) 5.1, J ) 8.8
Hz, 2 H); 13C NMR (100 MHz, CD3OD) δ -0.7 (3 C), 52.5, 53.3,
54.3, 58.4, 79.2, 117.9 (d, J F-H ) 21.7 Hz, 2 C), 124.3, 135.8
(d, J F-C ) 8.3 Hz, 2 C), 166.2, 168.2 (d, J F-C ) 252.4 Hz). Anal.
Calcd for C15H25ClFNO6Si: C, 45.28; H, 6.33; N, 3.52. Found:
C, 45.19; H, 6.09; N, 3.55.
Rea ction of 7b w ith CsF . In a manner similar to that
described for 7a (A), salt 7b (0.76 g, 2 mmol) was allowed to
react with CsF (0.96 g, 6 mmol) in DMF (10 mL) and worked
up to give a mixture of methyl 3-(dimethylamino)-2-(4-meth-
ylphenyl)propionate (13b) and methyl 3-(dimethylamino)-3-
(4-methylphenyl)propionate (15b), yield 394 mg (89%), ratio
80:20 (determined by the integrated values in 1H NMR of the
mixture); bp 85-90 °C (0.5 mmHg); 1H NMR (500 MHz, CDCl3)
13b: δ 2.26 (s, 6 H), 2.31 (s, 3 H), 2.42 (dd, J ) 12.2, 5.2 Hz,
1 H), 3.12 (dd, J ) 12.2, 10.1 Hz, 1 H), 3.66 (s, 3 H), 3.77 (dd,
J ) 10.1, 5.2 Hz, 1 H), 7.11 (d, J ) 7.2 Hz, 2 H), 7.20 (d, J )
7.2 Hz, 2 H); 15b: δ 2.16 (s, 6 H), 2.32 (s, 3 H), 2.67 (dd, J )
15.0, 7.9 Hz, 1 H), 2.95 (dd, J ) 15.0, 7.3 Hz, 1 H), 3.57 (s, 3
H), 3.87 (dd, J ) 7.9, 7.3 Hz, 1 H), 7.11 (d, J ) 7.4 Hz, 2 H),
7.40 (d, J ) 7.4 Hz, 2 H); 13C NMR (125 MHz, CDCl3) 13b: δ
20.9, 45.6 (2 C), 49.8, 51.9, 62.9; 15b: δ 21.0, 38.2 (2 C), 42.0,
51.4, 65.7; the others: 127.7 (2 C), 128.1 (2 C), 128.7 (2 C),
129.3 (2 C), 134.4, 135.3, 136.9, 137.0, 172.2, 173.7. Anal. Calcd
for C13H19NO2: C, 70.56; H, 8.65; N, 6.33. Found: C, 70.34;
H, 8.67; N, 6.09.
Rea ction of 7c w ith CsF . A solution of 7c (0.88 g, 2 mmol)
in DMF (30 mL) was placed in a 50-mL three-neck flask, and
an aliquot of DMF was distilled off at 80 °C (25 mmHg) to
remove any remaining water. To the remaining solution (ca.
15 mL) was added CsF (0.96 g, 6 mmol), and the mixture was
stirred for 12 h, poured into water (100 mL), and extracted
with EtOAc (4 × 50 mL). The extract was washed with water,
dried (MgSO4), concentrated under reduced pressure, and
distilled to give methyl 3-(dimethylamino)-2-(4-methoxy-
phenyl)propionate (13c), yield 118 mg (50%); bp 120-130 °C
N,N-Dim eth yl-N-[(tr im eth ylsilyl)m eth yl]-r-(m eth oxy-
ca r bon yl)-4-ch lor oben zyla m m on iu m P er ch lor a te (7e). In
the same way, the counteranion was changed to perchlorate:
yield 4.22 g (51%); mp 159-163 °C (recrystallized from EtOH-
1
Et2O); IR (Nujol) 1750, 1240, 1210, 850 cm-1; H NMR (270
MHz, CDCl3) δ 0.27 (s, 9 H), 3.35 and 3.60 (AB-q, J ) 14.3
Hz, 2 H), 3.35 (s, 3 H), 3.38 (s, 3 H), 3.69 (s, 3 H), 6.65 (s, 1 H),
7.50 (d, J ) 8.8 Hz, 2 H), 7.60 (d, J ) 8.8 Hz, 2 H). Anal. Calcd
for C15H25Cl2NO6Si: C, 43.48; H, 6.08; N, 3.38. Found: C,
43.19; H, 5.96; N, 3.54.
Rea ction of 7a w ith CsF . A. Salt 7a (0.81 g, 2 mmol) was
placed in a 20-mL flask equipped with a magnetic stirrer, a
septum, and a test tube which was connected to the flask with
a short bent glass tubing. CsF (0.96 g, 6 mmol) was placed in
the test tube. The apparatus was dried under reduced pressure
and flushed with N2. DMF (10 mL) was added to the flask with
a syringe, and CsF was added from the test tube. The mixture
was stirred for 12 h at room temperature, poured into water
(100 mL), and extracted with Et2O (4 × 50 mL). The extract
was washed with water (3 × 100 mL) and saturated aqueous
NaCl (50 mL), dried (MgSO4), and concentrated under reduced
pressure to give a mixture of methyl 3-(dimethylamino)-2-
phenylpropionate (13a ) and methyl 3-(dimethylamino)-3-
phenylpropionate (15a ), yield 335 mg (81%); ratio 70:30
(determined by the integrated values of 1H NMR of the
(7) Heck, R., F.; Winstein, S. J . Org. Chem. 1972, 37, 820.
(8) Corey, E. J .; McCaully, R. J .; Sachdev, H. S. J . Am. Chem. Soc.
1970, 92, 2476.
1
mixture); a colorless oil; bp 100 °C (1 mmHg); H NMR (500
MHz, CDCl3) 13a : δ 2.27 (s, 6 H), 2.44 (dd, J ) 12.4, 5.1 Hz,
1 H), 3.15 (dd, J ) 12.4, 10.1 Hz, 1 H), 3.68 (s, 3 H), 3.81 (dd,
(9) Stelmeah, H.; Connors, K. A. J . Am. Chem. Soc. 1970, 92, 863.

Novel Isomerization Reaction
J . Org. Chem., Vol. 64, No. 2, 1999 585
1
(0.75 mmHg); IR (film) 1740, 1040 cm-1; H NMR (500 MHz,
CDCl3) δ 2.27 (s, 6 H), 2.43 (dd, J ) 12.3, 5.3 Hz, 1 H), 3.11
(dd, J ) 12.3, 10.0 Hz, 1 H), 3.67 (s, 3 H), 3.77 (dd, J ) 10.0,
5.3 Hz, 1 H), 3.78 (s, 3 H), 6.85 (d, J ) 6.6 Hz, 2 H), 7.24 (d,
J ) 6.6 Hz, 2 H); 13C NMR (125 MHz, CDCl3) δ 45.7 (2 C),
49.4, 52.0, 55.2, 62.9, 114.1 (2 C), 128.9 (2 C), 129.5, 159.0,
173.9. Anal. Calcd for C13H19NO3: C, 65.80; H, 8.07; N, 5.90.
Found: C, 65.96; H, 8.29; N, 5.64.
51.1, 69.4, 128.5 (2 C), 130.5 (2 C), 132.3, 136.7, 171.7. Anal.
Calcd for C12H16ClNO2: C, 59.63; H, 6.67; N, 5.79. Found: C,
59.55; H, 6.90; N, 5.66.
N,N-Dim et h yl-N-[(m et h oxyca r b on yl)m et h yl]-r-(t r i-
m eth ylsilyl)ben zylam m on iu m Hexaflu or oph osph ate (19).
Methyl bromoacetate (3.20 g, 20.8 mmol) was added dropwise
to a solution of N,N-dimethyl-R-(trimethylsilyl)benzylamine11
(2.85 g, 13.8 mmol) in MeCN (30 mL) at room temperature,
and the mixture was stirred for 24 h. The solvent was
evaporated under reduced pressure. The residue was dissolved
in CHCl3 (30 mL) and stirred with saturated aqueous NH4-
PF6 (10 mL) for 30 min. The CHCl3 layer was separated, and
the aqueous layer was extracted with CHCl3 (3 × 20 mL). The
combined extracts were dried (MgSO4) and concentrated under
reduced pressure to give 19 (1.94 g, 33%): mp 121 °C
(recrystallized from EtOH-Et2O); IR (Nujol) 1759, 1462, 833
cm-1; 1H NMR (500 MHz, CDCl3) δ 0.26 (s, 9 H), 3.31 (s, 3 H),
3.51 (s, 3 H), 3.79 (s, 3 H), 3.93 and 4.07 (AB-q, J ) 17.1 Hz,
2 H), 4.75 (s, 1 H), 7.21-7.54 (m, 5 H). Anal. Calcd for C15H26F6-
NO2PSi: C, 42.35; H, 6.16; N, 3.29. Found: C, 42.17; H, 6.21;
N, 3.34.
Rea ction of 7d w ith CsF . A. In a manner similar to that
described for 7a (A), salt 7d (0.89 g, 2 mmol) was allowed to
react with CsF (0.96 g, 6 mmol) in DMF (10 mL) and worked
up to give a mixture of methyl 3-(dimethylamino)-2-(4-fluo-
rophenyl)propionate (13d ) and methyl 2-(dimethylamino)-3-
(4-fluorophenyl)propionate (15d ), yield 386 mg (86%), bp 85-
90 °C (0.6 mmHg), ratio 80:20 (determined by the integrated
values in H NMR of the mixture); 1H NMR (500 MHz, CDCl3)
1
13d : δ 2.26 (s, 6 H), 2.44 (dd, J ) 12.5, 5.5 Hz, 1 H), 3.08 (dd,
J ) 12.5, 10.0 Hz, 1 H), 3.68 (s, 3 H), 3.79 (dd, J ) 10.0, 5.5
Hz, 1 H), 7.01 (dd, J F-H ) 11.9, J ) 5.5 Hz, 2 H), 7.30 (dd,
J F-H ) 8.9, J ) 5.5 Hz, 2 H); 15d : δ 2.16 (s, 6 H), 2.66 (dd, J
) 14.9, 8.2 Hz, 1 H), 2.95 (dd, J ) 14.9, 6.7 Hz, 1 H), 3.57 (s,
3 H), 3.85 (dd, J ) 8.2, 6.7 Hz, 1 H), 6.99-7.03 (m, 2 H), 7.22
(dd, J F-H ) 8.8, 5.5 Hz, 2 H); 13C NMR (125 MHz, CDCl3)
13d : δ 45.7 (2 C), 49.5, 52.1, 62.9; 15d : δ 38.4, 42.2 (2 C),
51.6, 65.6; the others: 115.0 (d, J F-C ) 20.7 Hz, 2 C), 115.6
(d, J F-C ) 21.7 Hz, 2 C), 129.5 (d, J F-C ) 7.2 Hz, 2 C), 129.8
(d, J F-C ) 8.3 Hz, 2 C), 133.2 (d, J F-C ) 3.1 Hz), 134.6, 162.1
(d, J F-C ) 245.2 Hz), 162.2 (d, J F-C ) 246.2 Hz), 172.1, 173.6.
Anal. Calcd for C12H16FNO2: C, 63.98; H, 7.16; N, 6.22.
Found: C, 63.87; H, 7.21; N, 6.05.
B. In a manner similar to that described for 7a (B), salt 7d
(0.80 g, 2 mmol) was allowed to react with CsF (0.96 g, 6 mmol,
not predried) in DMF and worked up to give a mixture of 13d ,
15d , and methyl 2-(dimethylamino)-3-(4-fluorophenyl)propi-
onate (16d ), yield 140 mg (33%), ratio 69:19:12. Compound 16d
was separated on an aluminum oxide column (EtOAc/hexane,
Rea ction of 19 w ith CsF . A. In a manner similar to that
described for 7a (A), 19 (0.46 g, 1 mmol) was allowed to react
with 3 mol equiv of CsF (0.46 g, 3 mmol) in DMF (10 mL) and
worked up to give a mixture of 15a and 16a (151 mg, 73%,
ratio 28:72). The product ratio was determined by the inte-
grated values in 1H NMR of the mixture.
B. In the same way, 19 (0.34 g, 0.8 mmol) was treated with
an equimolar amount of CsF (0.13 g, 0.8 mmol) in DMF (10
mL) and worked up. The residue from the ethereal extract was
chromatographed on an aluminum oxide column (Et2O/hexane,
1:3) to give 16a (57 mg, 30%) and methyl 2-(dimethylamino)-
3-phenyl-3-(trimethylsilyl)propionate 21 (18 mg, 8%), a color-
1
less oil; IR (film) 1749, 849 cm-1; H NMR (270 MHz, CDCl3)
δ -0.06 (s, 9 H), 2.33 (s, 6 H), 2.72 (d, J ) 13.2 Hz, 1 H), 3.43
(s, 3 H), 3.71 (d, J ) 13.2 Hz, 1 H), 7.01-7.09 (m, 3 H), 7.16-
7.22 (m, 2 H); 13C NMR (125 MHz, CDCl3) δ -1.6 (3 C), 37.1,
42.1 (2 C), 50.4, 69.8, 125.0 (2 C), 128.1, 128.2 (2 C), 141.2,
170.1. Anal. Calcd for C15H25NO2Si: C, 64.47; H, 9.02; N, 5.01.
Found: C, 64.23; H, 9.03; N, 4.99.
1
1:10): a colorless oil; H NMR (500 MHz, CDCl3) δ 2.38 (s, 6
H), 2.89 (dd, J ) 13.4, 5.8 Hz, 1 H), 3.02 (dd, J ) 13.4, 9.4 Hz,
1 H), 3.37 (dd, J ) 9.4, 5.8 Hz, 1 H), 3.61 (s, 3 H), 6.96 (dd,
J F-H ) 8.8, J ) 8.5 Hz, 2 H), 7.15 (dd, J F-H ) 5.5, J ) 8.5 Hz,
2 H); 13C NMR (125 MHz, CDCl3) δ 35.0, 41.9 (2 C), 51.1, 69.6,
115.1 (d, J F-C ) 21.7 Hz, 2 C), 130.5 (d, J F-C ) 8.3 Hz, 2 C),
Rea ction of 21 w ith CsF . A mixture of 21 (13 mg, 0.05
mmol) and CsF (23 mg, 0.15 mmol) in DMF (2 mL) was stirred
at room temperature for 24 h and worked up in a manner
similar to that described above to give 16a (9 mg, 85%).
N,N-Dim eth yl-N-[(tr im eth ylsilyl)m eth yl]-r-cyan oben z-
yla m m on iu m P er ch lor a te (22). (Trimethylsilyl)methyl tri-
flate (4.72 g, 20 mmol) was added to a solution of N,N-
dimethyl-R-cyanobenzylamine12 (3.2 g, 20 mmol) in CH2Cl2
(100 mL), and the mixture was stirred at room temperature
for 24 h. The mixture was concentrated under reduced pres-
sure. The residue was dissolved in CHCl3 (20 mL) and stirred
with saturated aqueous NaClO4 (30 mL) for 3 h. The CHCl3
layer was separated, and the aqueous layer was extracted with
CHCl3 (3 × 20 mL). The combined extracts were dried (MgSO4)
and concentrated under reduced pressure to give 22 (2.42 g,
35%): mp 152-153 °C (recrystallized from MeOH-Et2O); IR
(KBr) 2250, 1470, 850 cm-1; 1H NMR (270 MHz, CDCl3) δ 0.35
(s, 9 H), 3.23 (s, 2 H), 3.27 (s, 3 H), 3.35 (s, 3 H), 6.23 (s, 1 H),
7.58-7.80 (m, 5 H); 13C NMR (67.8 MHz, CDCl3) δ -0.6 (3 C),
51.4, 52.1, 56.9, 71.6, 113.2, 124.1, 130.2 (2 C), 132.3 (2 C),
133.2. Anal. Calcd for C14H23ClN2O4Si: C, 48.48; H, 6.68; N,
8.06. Found: C, 48.17; H, 6.86; N, 8.03.
133.8, 161.6 (d, J F-C ) 234.1 Hz), 171.7. Anal. Calcd for C12H16
FNO2: C, 63.98; H, 7.16; N, 6.22. Found: C, 63.90; H, 7.25;
N, 6.11.
-
Rea ction of 7e w ith CsF . In a manner similar to that
described for 7a (A), salt 7e (0.89 g, 2 mmol) was allowed to
react with CsF (0.96 g, 6 mmol) in DMF (10 mL) and worked
up. The ethereal extract was concentrated, and the residue
was chromatographed on an aluminum oxide column (EtOAc/
hexane, 1:10) to give methyl 3-(dimethylamino)-2-(4-chloro-
phenyl)propionate (13e) (311 mg, 66%), methyl 2-(4-chloro-
phenyl)propenoate10 (14e) (44 mg, 9%), and methyl 2-(di-
methylamino)-3-(4-chlorophenyl)propionate (15e) (93 mg, 20%).
13e: a colorless oil; IR (film) 1740, 1490, 1200 cm-1; 1H NMR
(500 MHz, CDCl3) δ 2.27 (s, 6 H), 2.46 (dd, J ) 12.3, 5.5 Hz,
1 H), 3.08 (dd, J ) 12.3, 9.5 Hz, 1 H), 3.68 (s, 3 H), 3.78 (dd,
J ) 9.5, 5.5 Hz, 1 H), 7.26 (d, J ) 8.8 Hz, 2 H), 7.28 (d, J ) 8.8
Hz, 2 H); 13C NMR (125 MHz, CDCl3) δ 45.6 (2 C), 49.6, 52.1,
62.7, 128.8 (2 C), 129.3 (2 C), 133.3, 135.9, 173.2. Anal. Calcd
for C12H16ClNO2: C, 59.63; H, 6.67; N, 5.79. Found: C, 59.51;
H, 6.82; N, 5.59.
Rea ction of 22 w ith CsF . In a manner similar to that
described for 7a , 22 (0.56 g, 1.6 mmol) was allowed to react
with CsF (0.96 g, 6 mmol) and worked up. The residue of the
ethereal extract was chromatographed on a silica gel column
(EtOAc/hexane, 1:10) to give 2-phenylacrylonitrile13 (25) (52
mg, 25%) and N,N-dimethyl-2,4-dicyano-2,4-diphenylbutyl-
amine (26) (80 mg, 30%, a 1:1 mixture of diastereoisomers), a
colorless oil; bp 170 °C (0.55 mmHg); IR (film) 2250, 1450,
14e: a colorless oil (lit.10); IR (film) 1720, 1500, 1200, 1095
cm-1; 1H NMR (400 MHz, CDCl3) δ 3.82 (s, 3 H), 5.89 (s, 1 H),
6.38 (s, 1 H), 7.31-7.54 (m, 4 H); 13C NMR (67.8 MHz, CDCl3)
δ 55.3, 130.3, 131.3 (2 C), 132.7 (2 C), 137.2, 138.1, 143.2, 169.8.
15e: a colorless oil; IR (film) 1740, 1470, 1180 cm-1; 1H NMR
(500 MHz, CDCl3) δ 2.37 (s, 6 H), 2.89 (dd, J ) 13.6, 6.2 Hz,
1 H), 3.01 (dd, J ) 13.6, 9.2 Hz, 1 H), 3.38 (dd, J ) 9.2, 6.2
Hz, 1 H), 3.61 (s, 3 H), 7.12 (d, J ) 8.2 Hz, 2 H), 7.23 (d, J )
8.2 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ 35.1, 41.8 (2 C),
(11) Maeda, Y.; Sato, Y. J . Chem. Soc. Perkin Trans. 1 1997, 1491.
(12) Taylor, H. M.; Hauser, C. R. Organic Syntheses; Wiley: New
York, 1973; Coll. Vol. 5, p 437.
(10) Takaoka, T.; Tanaka, K.; Kato, K. J pn. Kokai Tokkyo Koho. J P-
05125115, 1993. (Chem. Abstr. 1993, 119, 272538s).
(13) Steward, J . M.; Chang, C. H. J . Org. Chem. 1956, 21, 635.

586 J . Org. Chem., Vol. 64, No. 2, 1999
Zhang et al.
1040, 700 cm-1. The diastereomers were separated by prepara-
tive TLC (Al2O3, EtOAc-hexane, 1:4).
3 H), 7.24-7.37 (m, 5 H). Anal. Calcd for C14H23NO2Si: C,
63.35; H, 8.73; N, 5.28. Found: C, 63.12; H, 8.68; N, 5.22.
26 (isomer-1): 1H NMR (500 MHz, CDCl3) δ 2.28 (s, 6 H),
2.64 (dd, J ) 14.0, 8.6 Hz, 1 H), 2.65 (dd, J ) 14.0, 5.5 Hz, 1
H), 2.79 and 2.82 (AB-q, J ) 14.0 Hz, 2 H), 3.82 (dd, J ) 8.6,
5.5 Hz, 1 H), 7.23-7.54 (m, 10 H); 13C NMR (125 MHz, CDCl3)
δ 34.0, 42.9, 47.6, 48.9, 69.3, 119.5, 121.0, 126.3, 126.7, 127.4,
127.6, 128.7, 129.0 (2 C), 129.1, 129.2, 129.3, 129.3, 134.9,
135.3. Anal. Calcd for C20H21N3: C, 79.17; H, 6.98; N, 13.85.
Found: C, 79.25; H, 7.04; N, 13.70.
Iodomethane (7.1 g, 50 mmol) was added to a mixture of
(S)-(+)-methyl 2-[(trimethylsilyl)methyl]amino-3-phenylpro-
pionate (1.3 g, 5 mmol) and K2CO3 (0.7 g, 5 mmol) in MeCN
(15 mL). The mixture was stirred for 12 h and filtered, and
the filtrate was concentrated to give 27 (1.1 g, 40%): mp 132-
133.5 °C (recrystallized from acetone-Et2O); [R]22 +2.7° (c
D
1
0.1, MeOH); H NMR (500 MHz, CDCl3) δ 0.38 (s, 9 H), 3.17
(t, J ) 12.2 Hz, 1 H), 3.50 (s, 3 H), 3.51 and 3.71 (AB-q, J )
14.6 Hz, 2 H), 3.58 (s, 3 H), 3.62 (s, 3 H), 3.70 (dd, J ) 12.2,
4.6 Hz, 1 H), 5.0 (dd, J ) 12.2, 4.6 Hz, 1 H), 7.30-7.36 (m, 5
H). Anal. Calcd for C16H28INO2Si: C, 45.60; H, 6.70; N, 3.32.
Found: C, 45.34; H, 6.66; N, 3.23.
26 (isomer-2): 1H NMR (500 MHz, CDCl3) δ 2.29 (s, 6 H),
2.35 (dd, J ) 14.7, 4.9 Hz, 1 H), 2.87 (dd, J ) 14.7, 14.0 Hz, 2
H), 2.94 (dd, J ) 14.0, 8.5 Hz, 1 H), 3.77 (dd, J ) 8.5, 4.9 Hz,
1 H), 7.13-7.39 (m, 10 H); 13C NMR (125 MHz, CDCl3) δ 34.0,
42.6, 47.5, 48.6, 69.1, 120.0, 120.9, 126.3, 127.4 (2 C), 127.6,
128.3, 128.4 (2 C), 129.1, 129.2 (2 C), 129.3, 135.5, 135.8. Anal.
Calcd for C20H21N3: C, 79.17; H, 6.98; N, 13.85. Found: C,
79.25; H, 7.04; N, 13.70.
(S )-(+)-N ,N -Dim e t h yl-N -[(t r im e t h ylsilyl)m e t h yl]-1-
(m eth oxycar bon yl)-2-ph en yleth ylam m on iu m Iodide (27).
In a manner similar to that described for 7, a mixture of
l-phenylalanine methyl ester hydrochloride (2.0 g, 9.6 mmol),
(chloromethyl)trimethylsilane (2.5 g, 20 mmol), KI (3.4 g, 20
mmol), and K2CO3 (2.1 g, 15 mmol) in DMF (30 mL) was
stirred for 1 h and worked up to give (S)-(+)-methyl 2-[(tri-
methylsilyl)methyl]amino-3-phenylpropionate (2.0 g, 37%): bp
100 °C (2 mmHg); [R]22D +33.1° (c 0.22, MeOH); 1H NMR (270
MHz, CDCl3) δ 0.08 (s, 9 H), 1.41 (br s, 1 H), 1.98 and 2.11
(AB-q, J ) 13.2 Hz, 2 H), 2.99 (dd, J ) 13.2, 7.1 Hz, 1 H), 3.02
(dd, J ) 13.2, 7.1 Hz, 1 H), 3.50 (t, J ) 7.1 Hz, 1 H), 3.70 (s,
Rea ction of 27 w ith CsF . In a manner similar to that
described for 7a , 27 (0.42 g, 1 mmol) was allowed to react with
CsF (0.46 g, 3 mmol) in DMF (5 mL) and worked up. The
residue was chromatographed on a silica gel column (Et2O/
hexane, 1:10) to give methyl 2-[(dimethylamino)methyl]-3-
phenylpropionate (30) (142 mg, 64%) and methyl cinnamate
(31) (16 mg, 10%).
30: bp 120-130 °C (0.75 mmHg); [R]22D 0.00° (c 0.1, MeOH);
1
IR (film) 1750, 1150 cm-1; H NMR (270 MHz, CDCl3) δ 2.22
(s, 6 H), 2.28 (dd, J ) 12.2, 4.4 Hz, 1 H), 2.68 (dd, J ) 12.2,
7.8 Hz, 1 H), 2.80-2.89 (m, 3 H), 3.59 (s, 3 H), 7.15-7.21 (m,
3 H), 7.25-7.29 (m, 2 H). Anal. Calcd for C13H19NO2: C, 70.56;
H, 8.65; N, 6.33. Found: C, 70.62; H, 8.66; N, 6.23.
J O981729H