Hydrazidohydroxylation of styrenes with N-acetylaminophthalimide using phenyliodine(III) bis(trifluoroacetate) (PIFA)

Article abstract of DOI:10.1055/s-2007-1000819

Regioselective hydrazidohydroxylation of styrenes with N- acetylaminophthalimide using phenyliodine(III) bis(trifluoroacetate) was carried out to afford 1-aryl-2-(N-acetyl-N-phthalimido)aminoethyl trifluoroacetates in high yields. The procedure is operationally simple and removal of trifluoroacetyl and phthalimido groups was performed by treatment of the trifluoroacetate with hydrazine hydrate in good yield. A synthetic study and a mechanistic proposal for the hydrazidohydroxylation are presented. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-1000819

32
PAPER
Hydrazidohydroxylation of Styrenes with N-Acetylaminophthalimide Using
Phenyliodine(III) Bis(trifluoroacetate) (PIFA)
H
ydrazidohydroxy
o
lation of Sty
u
renes suke Murata, Masato Tsukamoto, Takeshi Sakamoto, Setsuo Saito,* Yasuo Kikugawa*
Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan
Fax +81(49)2717984; E-mail: saitoset@josai.ac.jp
Received 4 September 2007; revised 4 October 2007
generated from the corresponding N-acylaminophthalim-
Abstract: Regioselective hydrazidohydroxylation of styrenes with
N-acetylaminophthalimide using phenyliodine(III) bis(trifluoroace-
tate) was carried out to afford 1-aryl-2-(N-acetyl-N-phthalimi-
do)aminoethyl trifluoroacetates in high yields. The procedure is
operationally simple and removal of trifluoroacetyl and phthalimi-
do groups was performed by treatment of the trifluoroacetate with
hydrazine hydrate in good yield. A synthetic study and a mechanis-
tic proposal for the hydrazidohydroxylation are presented.
ides using PIFA.7 In an extension of this work, we have
investigated the reaction of olefins 1 with N-acetylami-
R1
R2
R
Ph
1i: R1 = Me, R2 = H
1j: R1 = H, R2 = Me
1a: R = H
1e: R = 2-Me
1f: R = 3-Me
1g: R = 4-Me
1h: R = 4-COOMe
1b: R = 2-Cl
1c: R = 3-Cl
1d: R = 4-Cl
Key words: hydrazidohydroxylation, styrene, N-acetylamino-
phthalimide, nitrenium ion, phenyliodine(III) bis(trifluoroacetate)
CF3COO
Ac
N
O
NPhth
NPhth
Me
N
H
R
Divalent positively charged nitrogen species (nitrenium
ions) which are stabilized by the neighboring groups have
been widely applied in the field of synthetic organic
chemistry.1
2
3e: R = 2-Me
3f: R = 3-Me
3g: R = 4-Me
3h: R = 4-COOMe
3a: R = H
3b: R = 2-Cl
3c: R = 3-Cl
3d: R = 4-Cl
Previously, we have reported that nitrenium ions I
(Figure 1) can be generated from the corresponding N-
methoxy- or N-allyloxy-N-chloroamides by the action of
silver2 or zinc3 ions or triethylamine4 or by direct oxida-
tion of the corresponding amides with phenyliodine(III)
bis(trifluoroacetate) (PIFA).5
Ac
CF3COO
Ph
Ac
N
N
Ph
NPhth
NPhth
Me
3i
3j
Ac
NPhth
N
O
O
HO
Ac
N
OR2
NPhth
OCOCF3
R1
R1
N
N
+
R
NH2
+
R
I
II
3a': R = R1 = H
a: R2 = Me
b: R2 = allyl
a: R = Me
6
3d': R = 4-Cl, R1 = H
3g': R = 4-Me, R1 = H
3j': R = H, R1 = Me
O
N
-NPhth =
O
HO
Ac
NPhth
N
O
Me
N
NPhth
Figure 1 Nitrenium ions I and II
R
5a: R = H
5d: R = Cl
5g: R = Me
More recently, hypervalent iodine compounds such as
PIFA have been often utilized because these reagents have
low toxicity, are readily available, are easy to handle, and
are environmentally friendly.6 We recently reported a fun-
damentally new protocol for the construction of nitrogen
heterocycles by the intramolecular electrophilic aromatic
substitution with N-acyl-N-phthalimidonitrenium ions II
I
5h: R = COOMe
4
Ac
NPhth
OH
N
R
5a': R = H
5d': R = Cl
5g': R = Me
SYNTHESIS 2008, No. 1, pp 0032–0038
Advanced online publication: 07.12.2007
x
x
.
x
x
.2
0
0
7
DOI: 10.1055/s-2007-1000819; Art ID: F15507SS
© Georg Thieme Verlag Stuttgart · New York
Figure 2 Compounds 1–6

PAPER
Hydrazidohydroxylation of Styrenes
33
nophthalimide (2) using PIFA anticipating that hydrazide
derivatives having a trifluoroacetoxy group on the adja-
cent carbon might be formed (Figure 2).
Table 1 Hydrazidohydroxylation of Styrenes with N-Acetylami-
nophthalimide Using PIFAa
CF3COO
R
Ac
N
Ac
NPhth
PIFA
R
N
H
Initially, we examined the reaction of 4-chlorostyrene
(1d) with 2 using PIFA in various solvents such as chlo-
roform, acetonitrile, tetrahydrofuran, and 2,2,2-trifluoro-
ethanol. Treatment of 1d and 2 (1.1 molar equiv) with
PIFA (1.2 molar equiv) in chloroform at reflux for 30
minutes gave 2-(N-acetyl-N-phthalimido)-1-(4-chlo-
rophenyl)aminoethyl trifluoroacetate (3d) in 85% yield.
The structural determination of 3d was performed by the
comparison of the chemical shifts of the benzylic proton
of 3d and of the corresponding proton of the hydrolyzed
3d (5d). The signal of the benzylic proton of 5d appeared
at considerably higher field (1 ppm) compared with the
benzylic proton of 3d, which indicates that the oxygen
function attached to the benzylic position. In acetonitrile
or tetrahydrofuran the reaction mixture contained several
unidentifiable products (TLC) and 3d was obtained in
poor yield. In 2,2,2-trifluoroethanol PIFA reacted with 2
for one hour in the presence of 1a at room temperature to
form the adduct, the iodophenyl group of which rear-
ranged to the amide nitrogen to give N-acetyl-N-(4-io-
dophenyl)aminophthalimide (4) in 80% yield. A similar
N-iodophenylation reaction of acetanilides using PIFA
was reported previously.8 Accordingly, several styrenes
reacted in chloroform, and the results are presented in
Table 1.
+
Phth
1
2
3
Entry
Starting material
Product (yield, %)b
3a (90)
1
2
1a
1b
1c
1d
1e
1f
3b (92)
3
3c (74)
4
3d (85)
5
3e (82)
6
3f (74)
7
1g
1h
1i
3g (80)
8
3h (68), 5h (10)c
3i (90)
9
10
1j
3j (32), 3j¢ (44)
a Reaction conditions: 1a–j (1 mmol), 2 (1.1 mmol), and PIFA (1.2
mmol) in CHCl3 (10 mL); stirred for 0.5–1 h at reflux.
b Isolated yields of the pure products.
c A hydrolyzed product of 3h was detected in this case.
Table 2 Hydrolysis of the Trifluoroacetates of 3 in Acidic Condi-
tionsa
Normally, the nitrenium ion IIa could attack both a- and
b-carbons of styrenes to afford two regioisomers. In prac-
tice, however, HPLC analysis of the reaction mixture re-
vealed that the reaction is extremely regioselective and
one regioisomer alone is obtained in the case of unsubsti-
tuted and a-methyl substituted styrenes in high yield
(Table 1, entries 1–9).9 For b-methyl-substituted styrenes,
two regioisomers were obtained (entry 10).
Ac
R
NPhth
OH
CF3COO
R
Ac
N
AcOH–H2O
NPhth
HO
Ac
N
N
R
NPhth
3
5
5'
Entry
Starting material
Product (yield, %)b
5a (68), 5a¢ (22)
5d (63), 5d¢ (11)
5g (61), 5g¢ (29)
1
2
3
3a
3d
3g
Next, we tried the hydrolysis of 3. Initially the hydrolysis
was performed in 10% aqueous sodium bicarbonate solu-
tion at room temperature. However, no products were ex-
tracted from the aqueous solution, probably because the
phthalimido ring opened in addition to the hydrolysis of
trifluoroacetate. Next, a weakly acidic solvent (AcOH–
H2O = 2:1) was used for hydrolysis. To our surprise, the
two corresponding regioisomeric alcohols were obtained
from pure 3a, 3d and 3g. The results are presented in
Table 2.
a Reaction conditions: A mixture of 3 (0.1 mmol) in AcOH–H2O (2:1,
9 mL) was heated at 70 °C for 0.5 h.
b Isolated yields of the pure deprotected products.
nitrogen to form the aziridinium ion. The solvent water at-
tacks both the a and b positions of this new intermediate
to give the two regioisomers 5a and 5a¢, respectively.
The described transformation can be rationalized as de-
picted in Scheme 1. Thus the trifluoroacetyl group of 3a
is eliminated by the assistance of the adjacent acetamido
These regioisomers thus obtained were trifluoroacetylated
with trifluoroacetic anhydride to give 3a¢, 3d¢, and 3g¢ and
NPhth
Ac
Ac
Ph
NPhth
OH
HO
Ac
N
N
CF3COO
Ph
Ac
N
N
Ph
NPhth
NPhth
Ph
3a
5a
5a'
H2O and H2O
aziridinum ion intermediate
Scheme 1 Probable reaction mechanism for the hydrolysis of 3a
Synthesis 2008, No. 1, 32–38 © Thieme Stuttgart · New York

34
K. Murata et al.
PAPER
CF3COO–
Ph
CF3COO
Ph
Ac
N
Ac
N
NPhth
NPhth
3a
PIFA
1a
2
NPhth
Ac
N
Ph
–OCOCF3
Scheme 2 Proposed reaction mechanism for hydrazidohydroxylation
r.t. The mixture was stirred for 0.5 h at reflux. The solvent was
evaporated and the residue was purified by column chromatography
on silica gel using EtOAc–hexane (20–50%) to give the product 3a
(520 mg, 90%). Crystallization from Et2O–hexane afforded white
crystals; mp 115–119 °C (Table 1). HPLC (Shimpak C18 reverse-
phase column, MeCN–H2O (75:25), 0.3 mL/min, l = 254 nm),
tR = 18.18.
were used as authentic samples in the HPLC analysis. The
phthaloyl and trifluoroacetyl groups of 3a were deprotec-
ted by the action of hydrazine hydrate as usual to give
N-(2-hydroxy-2-phenylethyl)acetohydrazide (6) in 75%
yield. Synthesis of hydrazinoethanols is rarely reported10
and this method will offer an alternative for their synthe-
sis.
IR (KBr): 1790, 1750, 1700, 1690, 1220, 1180 cm–1.
1H NMR (270 MHz, CDCl3, rotamers): d = 1.98 (s, 2.4 H), 2.38 (s,
0.6 H), 3.90 (dd, J = 15.4, 9.7 Hz, 1 H), 4.43 (dd, J = 15.4, 2.4 Hz,
1 H), 5.98 (dd, J = 11.3, 3.5 Hz, 0.2 H), 6.14 (dd, J = 9.7, 2.4 Hz,
0.8 H), 7.31–7.49 (m, 5 H), 7.78–7.81 (m, 4 H).
13C NMR (125.7 MHz, DMSO-d6, rotamers): d = 19.6, 20.2, 50.0,
53.9, 77.3, 77.5, 114.2 (q, J = 286.1 Hz), 123.7, 123.90, 123.91,
124.1, 126.6, 126.9, 128.76, 128.79, 129.2, 129.3, 129.5, 129.60,
129.64, 129.7, 134.9, 135.2, 135.3, 155.52 (q, J = 41.7 Hz), 155.54
(q, J = 41.7 Hz), 164.7, 165.0, 165.1, 165.4, 168.5, 171.6.
Taking the above-mentioned mechanism of hydrolysis
into consideration, a plausible pathway for the original
hydrazidohydroxylation reaction is shown in Scheme 2.
The hydrazidohydroxylation reaction proceeds in an elec-
trophilic attack of IIa to the double bond, and subsequent-
ly without formation of aziridinium ions,11the created
carbocationic species can be captured by a free trifluoro-
acetate anion or quenched by the elimination of an adja-
cent hydrogen (entry 9) to afford the products.
FABMS (3-nitrobenzyl alcohol + NaI): m/z (%) = 443 (M+ + Na,
28.7).
In conclusion, we have achieved highly regioselective
vicinal difunctionalization in a simple single-step reac-
tion. Thus, the reaction of the nitrenium ion IIa with sty-
Anal. Calcd for C20H15F3N2O5: C, 57.15; H, 3.60; N, 6.66. Found:
C, 57.33; H, 3.48; N, 6.49.
renes gave hydrazide derivatives
having
a
1-(2-Chlorophenyl)-2-[N-(1,3-dioxoisoindolin-2-yl)acet-
amido]ethyl 2,2,2-Trifluoroacetate (3b)
White crystals; mp 127–130 °C (Et2O–hexane).
IR (KBr): 1800, 1740, 1700, 1220, 1150 cm–1.
1H NMR (270 MHz, CDCl3, rotamers): d = 1.98 (s, 2.1 H), 2.37 (s,
0.9 H), 3.92–4.32 (m, 2 H), 6.37–6.55 (m, 1 H), 7.26–7.43 (m, 5 H),
7.8–8.01 (m, 4 H).
13C NMR (125.7 MHz, DMSO-d6, rotamers): d = 19.6, 20.1, 50.0,
52.6, 74.8, 75.6, 115.0, (q, J = 286.2 Hz), 123.9, 124.0, 124.10,
124.13, 127.8, 128.0, 128.2, 128.7, 129.2, 129.26, 129.31, 129.8,
130.0, 131.0, 131.2, 131.5, 131.75, 131.82, 132.5, 135.4, 135.5,
135.6, 155.5 (q, J = 41.5 Hz), 155.7 (q, J = 41.5 Hz), 164.0, 164.7,
165.1, 165.4, 168.5, 171.9.
trifluoroacetoxy group on the adjacent carbon in good
yields. Further application of this methodology for the
synthesis of lactams having a trifluoroacetoxy group in a
molecule is underway.
All required fine chemicals were used directly without purification.
CHCl3 and THF used for the reactions were of commercial anhy-
drous grade. Silica gel (230–400 mesh) was used for column chro-
matography, while 250 mm silica gel plates were used for TLC
analysis. The purities of several compounds were analyzed by high-
performance liquid chromatography using Shimpack C18 reverse
phase column (4.6 mm × 150 mm), with flow rate 0.3 mL/min and
a tunable UV detector set at 254 nm. A mixture of MeCN–H2O
(75:25) was used as mobile phase. 1H NMR spectra were recorded
at 270 or 500 MHz using TMS as reference. 13C NMR spectra were
recorded at 67.8 or 125.7 MHz. Mass spectra were measured with a
direct inlet system at 70 eV. Elemental analyses were performed in
the Microanalytical Laboratory of Josai University.
FABMS (3-nitrobenzyl alcohol): m/z (%) = 431 (M+ + H, 0.9), 154
(100), 137 (72.5), 136 (84.6).
Anal. Calcd for C20H14ClF3N2O5: C, 52.82; H, 3.10; N, 6.16. Found:
C, 52.65; H, 2.99; N, 6.02.
N-Acetylaminophthalimide (2) was prepared according to the pre-
viously reported method;1 colorless crystals; mp 237–240 °C (Lit.12
mp 226–228 °C).
1-(3-Chlorophenyl)-2-[N-(1,3-dioxoisoindolin-2-yl)acet-
amido]ethyl 2,2,2-Trifluoroacetate (3c)
White crystals; mp 125–127 °C (Et2O–hexane).
IR (KBr): 1850, 1800, 1765 cm–1.
2-[N-(1,3-Dioxoisoindolin-2-yl)acetamido]-1-phenylethyl 2,2,2-
Trifluoroacetate (3a); Typical Procedure
To a mixture of styrene (1a; 100 mg, 0.960 mmol) and N-acetylami-
nophthalimide (2; 216 mg, 1.056 mmol) in CHCl3 (5 mL) was add-
ed phenyliodine(III) bis(trifluoroacetate) (496 mg, 1.152 mmol) at
1H NMR (500 MHz, DMSO-d6, rotamers): d = 1.91 (s, 1.8 H), 2.34
(s, 1.2 H), 3.71 (dd, J = 14.8, 3.1 Hz, 0.6 H), 3.82 (dd, J = 15.9, 2.9
Hz, 0.4 H), 4.60–4.69 (m, 1 H), 6.09 (m, 1 H), 7.42–7.56 (m, 4 H),
7.97–8.09 (m, 4 H).
Synthesis 2008, No. 1, 32–38 © Thieme Stuttgart · New York

PAPER
Hydrazidohydroxylation of Styrenes
35
13C NMR (125.7 MHz, DMSO-d6, rotamers): d = 19.6, 20.2, 49.7,
53.7, 76.4, 114.18 (q, J = 285.7 Hz), 114.20 (q, J = 285.7 Hz),
123.7, 123.9, 124.0, 124.1, 124.8, 125.1, 125.5, 126.8, 127.1, 128.8,
129.1, 129.3, 129.5, 129.6, 129.7, 130.7, 130.8, 133.3, 133.4, 135.3,
136.2, 137.2, 137.5, 155.6 (q, J = 42.0 Hz), 155.8 (q, J = 42.0 Hz),
164.7, 165.1, 165.4, 168.5, 171.6.
138.1, 155.5 (q, J = 40.7 Hz), 155.8 (q, J = 41.7 Hz), 164.6, 165.0,
165.1, 165.3, 168.5, 171.5.
FABMS (3-nitrobenzyl alcohol + NaI): m/z (%) = 457 (M+ + Na,
26.7).
Anal. Calcd for C21H17F3O5N2: C, 58.07; H, 3.94; N, 6.45. Found:
C, 58.15; H, 4.04; N, 6.39.
FABMS (3-nitrobenzyl alcohol + NaI): m/z (%) = 477 (M+ + Na,
50.0).
2-[N-(1,3-Dioxoisoindolin-2-yl)acetamido]-1-p-tolylethyl 2,2,2-
Trifluoroacetate (3g)
White crystals; mp 95–97 °C (Et2O–hexane).
Anal. Calcd for C20H14ClF3N2O5: C, 52.82; H, 3.10; N, 6.16. Found:
C, 52.89; H, 3.26; N, 6.16.
IR (KBr): 1790, 1750, 1700, 1230, 1150 cm–1.
1-(4-Chlorophenyl)-2-[N-(1,3-dioxoisoindolin-2-yl)acet-
amido]ethyl 2,2,2-Trifluoroacetate (3d)
White crystals; mp 122–123 °C (Et2O–hexane).
IR (KBr): 1860, 1800, 1700, 1260, 1175 cm–1.
1H NMR (270 MHz, CDCl3, rotamers): d = 1.98 (s, 2.7 H), 2.30 (s,
0.3 H), 3.87 (dd, J = 15.4, 9.5 Hz, 1 H), 4.40 (dd, J = 15.4, 2.7 Hz,
1 H), 5.95 (dd, J = 9.5, 3.5 Hz, 0.1 H), 6.11 (dd, J = 9.5, 2.7 Hz, 0.9
H), 7.26–7.44 (m, 4 H), 7.81–8.01 (m, 4 H).
13C NMR (125.7 MHz, DMSO-d6, rotamers): d = 19.6, 20.2, 49.7,
53.7, 76.5, 76.8, 114.2 (q, J = 285.34 Hz), 114.3 (q, J = 287.90 Hz),
123.7, 123.9, 123.9, 124.1, 127.8, 128.1, 128.7, 128.8, 129.0, 129.5,
129.6, 129.6, 129.7, 133.8, 133.9, 134.0, 134.1, 135.3, 155.5 (q,
J = 42.0 Hz), 155.8 (q, J = 41.7 Hz), 164.7, 165.1, 165.1, 165.4,
168.5, 171.6.
1H NMR (500 MHz, DMSO-d6 rotamers): d = 1.92 (s, 1.7 H), 2.30,
2.31, 2.34 (s each, 4.3 H), 3.72 (dd, J = 14.8, 2.9 Hz, 0.5 H), 3.83
(dd, J = 15.9, 3.1 Hz, 0.5 H), 4.56–4.65 (m, 1 H), 6.06–6.11 (m, 1
H), 7.22 (d, J = 10.0 Hz, 1 H), 7.25 (d, J = 10.0 Hz, 1 H), 7.34 (d,
J = 10.0 Hz, 1 H), 7.45 (d, J = 10.0 Hz, 1 H) 7.95–8.08 (m, 4 H).
13C NMR (125.7 Hz, DMSO-d6 rotamers): d = 19.6, 20.2, 20.69,
20.71, 49.9, 53.9, 64.7, 77.3, 77.5, 114.2 (q, J = 285.7 Hz), 123.7,
123.89, 123.90, 124.1, 126.7, 127.0, 129.28, 129.32, 129.5, 129.61,
129.64, 129.7, 131.9, 132.2, 135.3, 138.7, 138.9, 155.5 (q, J = 40.0
Hz), 155.8 (q, J = 41.4 Hz), 164.7, 165.0, 165.1, 165.3, 168.5,
171.6.
FABMS (3-nitrobenzyl alcohol + NaI): m/z (%) = 457 (M+ + Na,
19.8).
Anal. Calcd for C21H17F3N2O5: C, 58.07; H, 3.94; N, 6.45. Found:
C, 58.28; H, 4.04; N, 6.56.
FABMS (3-nitrobenzyl alcohol + NaI): m/z (%) = 477 (M+ + Na,
27.9).
Anal. Calcd for C20H14ClF3N2O5: C, 52.82; H, 3.10; N, 6.16. Found:
C, 53.18; H, 3.25; N, 6.12.
Methyl 4-{2-[N-(1,3-Dioxoisoindolin-2-yl)acetamido]-1-(2,2,2-
trifluoroacetoxy)ethyl}benzoate (3h)
White crystals; mp 155–156 °C (Et2O–hexane).
2-[N-(1,3-Dioxoisoindolin-2-yl)acetamido]-1-o-tolylethyl 2,2,2-
Trifluoroacetate (3e)
White crystals; mp 125–126.5 °C (Et2O–hexane).
IR (KBr): 1800, 1755, 1700 cm–1.
IR (KBr): 1790, 1740, 1710, 1210, 1230, 1150 cm–1.
1H NMR (270 MHz, CDCl3, rotamers): d = 1.98 (s, 2.7 H), 2.29 (s,
0.3 H), 3.81–3.86 (m, 1 H), 3.91 (s, 3 H), 4.48 (dd, J = 15.4, 2.2 Hz,
1 H), 6.02 (d, J = 6.9 Hz, 0.1 H), 6.19 (d, J = 6.9 Hz, 0.9 H), 7.5 (d,
J = 8.4 Hz, 2 H), 7.9 (d, J = 8.4 Hz, 2 H), 7.91–8.11 (m, 4 H).
13C NMR (67.8 MHz, DMSO-d6, rotamers): d = 19.5, 20.2, 49.6,
52.18, 52.22, 53.6, 76.6, 76.9, 114.1 (q, J = 285.7 Hz), 123.7, 123.9,
124.1, 126.9, 127.1, 129.46, 129.50, 129.55, 129.59, 129.64, 130.2,
130.3, 135.3, 139.8, 140.1, 155.5 (q, J = 42.1 Hz), 155.8 (q, J = 41.7
Hz), 164.6, 165.0, 165.1, 165.4, 165.7, 168.5, 171.5.
1H NMR (500 MHz, DMSO-d6, rotamers): d = 1.94 (s, 2 H), 2.34 (s,
1 H), 2.41, 2.44 (s each, 3 H), 3.93–4.01 (m, 1 H), 4.30 (dd, J = 15.2,
9.9 Hz, 0.7 H), 4.62 (dd, J = 16.1, 10.3 Hz, 0.3 H), 6.17 (dd,
J = 10.2, 2.8 Hz, 0.3 H), 6.33 (dd, J = 9.9, 2.2 Hz, 0.7 H), 7.22–7.37
(m, 4 H), 7.96–8.06 (m, 4 H).
13C NMR (125.7 MHz, DMSO-d6, rotamers): d = 18.5, 18.7, 19.6,
20.2, 51.0, 53.2, 75.6, 75.8, 114.3 (q, J = 285.7 Hz), 123.8, 124.0,
124.1, 126.0, 126.5, 126.6, 126.7, 129.1, 129.3, 129.4, 129.6, 130.7,
130.8, 132.9, 133.5, 135.4, 135.4, 135.5, 135.9, 155.6 (q, J = 42.0
Hz), 156.0 (q, J = 41.3 Hz), 164.6, 164.8, 165.2, 165.6, 168.6,
172.0.
FABMS (3-nitrobenzyl alcohol): m/z (%) = 479 (M+ + H, 4.2), 365
(100).
Anal. Calcd for C22H17F3N2O7: C, 55.24; H, 3.58; N, 5.86. Found:
C, 54.94; H, 3.68; N, 5.81.
FABMS (3-nitrobenzyl alcohol + KI): m/z (%) = 473 (M+ + K,
42.9).
Methyl 4-{2-[N-(1,3-Dioxoisoindolin-2-yl)acetamido]-1-hy-
droxyethyl}benzoate (5h)
Anal. Calcd for C21H17F3N2O5: C, 58.07; H, 3.94; N, 6.45. Found:
C, 58.28; H, 4.05; N, 6.47.
White crystals; mp 136–138 °C (Et2O–hexane).
IR (KBr): 3500, 1800, 1740, 1620, 1380, 1280 cm–1.
1H NMR (500 MHz, DMSO-d6 + D2O, rotamers): d = 1.91 (s, 1.6
H), 2.15 (s, 1.4 H), 3.58–3.61 (m, 0.7 H), 3.72 (dd, J = 15.3, 5.0 Hz,
0.8 H), 3.84 (s, 3 H), 3.97 (dd, J = 15.3, 5.0 Hz, 0.5 H), 4.07 (dd,
J = 14.4, 5.0 Hz, 0.5 H), 4.80 (dd, J = 8.0, 5.0 Hz, 0.5 H), 4.92 (dd,
J = 8.0, 5.0 Hz, 0.5 H), 7.50 (d, J = 8.2 Hz, 1 H), 7.65 (d, J = 8.2 Hz,
1 H), 7.89 (d, J = 8.2 Hz, 1 H), 7.94 (d, J = 8.2 Hz, 1 H), 7.95–8.01
(m, 4 H).
13C NMR (125.7 Hz, DMSO-d6, rotamers): d = 19.9, 20.6, 52.0,
52.1, 52.2, 57.8, 70.5, 70.8, 123.67, 123.71, 123.9, 124.0, 126.4,
126.6, 128.5, 128.6, 129.00, 129.04, 129.52, 129.56, 129.64,
135.20, 135.21, 135.3, 148.29, 148.31, 164.5, 164.9, 165.1, 165.2,
166.07, 166.11, 169.1, 171.7.
2-[N-(1,3-Dioxoisoindolin-2-yl)acetamido]-1-m-tolylethyl 2,2,2-
Trifluoroacetate (3f)
White crystals; mp 127–128 °C (Et2O–hexane).
IR (KBr): 1790, 1740, 1700, 1420, 1370, 1210 cm–1.
1H NMR (500 MHz, DMSO-d6, rotamers): d = 1.92 (s, 1.8 H), 2.30,
2.32, 2.34 (s each, 4.2 H), 3.70 (dd, J = 15.0, 3.0 Hz, 0.5 H), 3.82
(dd, J = 15.0, 3.0 Hz, 0.5 H), 4.6 (dd, J = 15.0, 10.0 Hz, 1 H), 6.07
(dd, J = 10.0, 3.0 Hz, 1 H) 7.11–7.38 (m, 4 H), 7.96–8.08 (m, 4 H).
13C NMR (125.7 MHz, DMSO-d6, rotamers): d = 19.6, 20.2, 20.8,
20.9, 50.0, 53.9, 77.3, 77.5, 114.2 (q, J = 286.6 Hz), 123.56, 123.64,
123.8, 123.85, 123.88, 124.07, 127.09, 127.4, 128.66, 128.70, 129.5
129.58, 129.61, 129.7, 129.78, 129.84, 134.8, 135.1, 135.2, 138.0,
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K. Murata et al.
PAPER
FABMS (3-nitrobenzyl alcohol + NaI): m/z (%) = 405 (M+ + Na,
100).
135.6, 135.8, 135.9, 136.0, 138.1, 156.6 (q, J = 36.2 Hz), 164.10,
164.13, 164.6, 165.0, 165.8, 166.0, 166.2, 166.7, 166.8, 167.9,
168.6, 168.7, 168.9, 169.0, 170.0, 170.5, 171.0.
FABMS (3-nitrobenzyl alcohol + NaI): m/z (%) = 457 (M+ + Na,
Anal. Calcd for C20H18N2O6: C, 62.82; H, 4.74; N, 7.33. Found: C,
62.77; H, 4.78; N, 7.36.
52.0).
N-(1,3-Dioxoisoindolin-2-yl)-N-(2-phenylallyl)acetamide (3i)
White crystals: mp 112–115 °C (Et2O–hexane).
IR (KBr): 1800, 1740, 1690 cm–1.
Anal. Calcd for C21H17F3N2O5: C, 58.07; H, 3.94; N, 6.45. Found:
C, 57.99; H, 3.94; N, 6.35.
N-(1,3-Dioxoisoindolin-2-yl)-N-(2-hydroxy-2-phenylethyl)acet-
amide (5a) and N-(1,3-Dioxoisoindolin-2-yl)-N-(2-hydroxy-1-
phenylethyl)acetamide (5a¢)
A mixture of 3a (71 mg, 0.169 mmol) in AcOH–H2O (2:1, 9 mL)
was heated at 70 °C for 0.5 h. After the reaction was complete, the
mixture was diluted with EtOAc (50 mL). The organic layer was
washed with brine (2 × 30 mL) and dried (Na2SO4). After removal
of the solvent in vacuo, the residue was purified by column chroma-
tography on silica gel using 50% EtOAc–hexanes to give the prod-
ucts 5a (37 mg, 68%) and 5a¢ (12 mg, 22%) (Table 2).
1H NMR (500 MHz, DMSO-d6, rotamers): d = 1.91 (s, 2.1 H), 2.24
(s, 0.9 H), 4.73 (s, 1.4 H), 4.87 (s, 0.6 H), 5.28 (s, 0.7 H), 5.48 (s,
0.7 H), 5.53 (s, 0.3 H), 5.69 (s, 0.3 H), 7.23–7.57 (m, 5 H), 7.93–
8.04 (m, 4 H).
13C NMR (125.7 MHz, DMSO-d6, rotamers): d = 15.4, 15.8, 20.1,
20.2, 20.3, 20.7, 49.6, 54.3, 115.7, 117.5, 122.5, 123.7, 123.8,
123.9, 124.0, 124.1, 125.86, 125.91, 126.21, 126.23, 127.77,
127.84, 128.0, 128.2, 128.3, 128.4, 128.4, 128.5, 129.0, 129.2,
129.3, 129.4, 134.6, 135.3, 135.38, 135.42, 135.5, 138.0, 138.5,
138.9, 139.4, 141.4, 142.1, 164.3, 164.4, 164.5, 164.7, 169.0, 169.1,
170.2, 171.4.
5a
FABMS (3-nitrobenzyl alcohol): m/z (%) = 321 (M+ + H, 100).
White crystals; mp 122–123 °C (EtOAc–hexane).
IR (KBr): 3420, 1800, 1740, 1660 cm–1.
Anal. Calcd for C19H16N2O3: C, 71.24; H, 5.03; N, 8.74. Found: C,
71.17; H, 5.05; N, 8.70.
1H NMR (270 MHz, CDCl3 + D2O, rotamers): d = 2.02 (s, 1.8 H),
2.38 (s, 1.2 H), 3.59–3.79 (m, 1 H), 3.95 (dd, J = 14.8, 9.7 Hz, 0.4
H), 4.13 (dd, J = 14.8, 2.1 Hz, 0.6 H), 4.84 (dd, J = 14.8, 2.7 Hz, 0.4
H), 5.02 (d, J = 9.4 Hz, 0.6 H) 7.19–7.42 (m, 5 H), 7.82–8.02 (m, 4
H).
13C NMR (125.7 MHz, DMSO-d6, rotamers): d = 19.9, 20.5, 52.3,
58.2, 70.7, 71.3, 123.66, 123.70, 123.9, 124.0, 125.9, 126.3, 127.27,
127.32, 128.07, 128.11, 129.5, 129.58, 129.61, 135.21, 135.23,
135.3, 142.8, 143.0, 164.5, 165.0, 165.06, 165.14, 169.0, 171.7.
2-[N-(1,3-Dioxoisoindolin-2-yl)acetamido]-1-phenylpropyl
2,2,2-Trifluoroacetate (3j)
White crystals (mixture of two diastereomers); mp 176–178 °C
(Et2O–hexane).
IR (KBr): 1790, 1750, 1690, 1380, 1220 cm–1.
1H NMR (500 MHz, DMSO, rotamers): d = 0.77 (d, J = 6.7 Hz, 0.8
H), 0.86 (d, J = 6.7 Hz, 0.3 H), 1.08 (d, J = 6.9 Hz, 1.2 H), 1.26 (d,
J = 6.9 Hz, 0.7 H), 1.87 (s, 0.7 H), 1.92 (s, 1.2 H), 2.32 (s, 0.8 H),
2.41 (s, 0.3 H), 3.60–3.70 (m, 0.4 H), 4.56–4.73 (m, 0.2 H), 4.84–
5.01 (m, 0.4 H), 5.50 (d, J = 7.6 Hz, 0.4 H), 6.23 (d, J = 1.8 Hz, 0.4
H), 6.38 (d, J = 2.8 Hz, 0.2 H), 7.27–7.43 (m, 5 H), 8.00–8.05 (m, 4
H).
13C NMR (125.7 MHz, DMSO-d6, rotamers): d = 8.6, 10.8, 14.8,
20.1, 20.80, 20.83, 21.3, 56.4, 56.7, 58.8, 61.9, 78.7, 81.0, 82.2,
114.07 (q, J = 286.6 Hz), 114.14 (q, J = 285.3 Hz), 123.1, 123.8,
124.1, 124.2, 124.6, 125.0, 125.8, 127.1, 127.2, 127.8, 128.1, 128.2,
128.5, 128.7, 128.7, 128.8, 128.9, 129.0, 129.3, 129.8, 134.7, 135.6,
135.8, 135.9, 136.0, 138.1, 154.8 (q, J = 41.0 Hz), 155.2 (q, J = 41.0
Hz), 165.2, 165.99, 166.04, 167.1, 167.3, 168.0, 169.4, 171.5.
EIMS: m/z (%) = 324 (M+, 0.1), 175 (100), 148 (56), 130 (46).
Anal. Calcd for C18H16N2O4: C, 66.66; H, 4.97; N, 8.64. Found: C,
66.66; H, 5.00; N, 8.60.
5a¢
White crystals; mp 151–152 °C (EtOAc–hexane).
IR (KBr): 3340, 1790, 1750, 1720 cm–1.
1H NMR (270 MHz, CDCl3 + D2O): d = 2.12 (s, 3 H), 3.36 (dd,
J = 13.2, 4.1 Hz, 1 H), 3.51 (dd, J = 13.5, 9.1 Hz, 1 H), 5.9 (dd,
J = 8.9, 3.9 Hz, 1 H), 7.25–7.38 (m, 5 H), 7.71–7.86 (m, 4 H).
13C NMR (125.7 MHz, DMSO-d6): d = 20.7, 54.2, 74.5, 123.0,
126.3, 127.8, 128.3, 130.0, 134.5, 139.0, 166.7, 169.5.
FABMS (3-nitrobenzyl alcohol + NaI): m/z (%) = 457 (M+ + Na,
35.7).
FABMS (3-nitrobenzyl alcohol): m/z (%) = 325 (M+ + H, 26.1), 307
Anal. Calcd for C21H17F3N2O5: C, 58.07; H, 3.94; N, 6.45. Found:
C, 57.88; H, 3.96; N, 6.31.
(100), 265 (32.2), 154 (46.2), 136 (38.9).
Anal. Calcd for C18H16N2O4: C, 66.66; H, 4.97; N, 8.64. Found: C,
66.28; H, 5.01; H, 8.57.
1-[N-(1,3-Dioxoisoindolin-2-yl)acetamido]-1-phenylpropan-2-
yl 2,2,2-Trifluoroacetate (3j¢)
White crystals; mp 155–156 °C (Et2O–hexane).
IR (KBr): 1800, 1750, 1690 cm–1.
Deprotection of the Phthaloyl and Trifluoroacetyl Groups in
3a,d,d¢,g,g¢; N-(2-Hydroxy-2-phenylethyl)acetohydrazide (6);
Typical Procedure
A mixture of 3a (519 mg, 1.235 mmol) and 80% hydrazine mono-
hydrate (386 mg, 6.168 mmol) in EtOH (5 mL) was stirred for 0.5
h at reflux. After the reaction was complete, the mixture was evap-
orated and the residue was diluted with EtOAc (30 mL). The mix-
ture was filtered off and the filtrate was evaporated again. The
residue was purified by column chromatography on silica gel using
EtOAc to give the product 6 (176 mg, 74%); white crystals; mp
128–130 °C (EtOAc–hexane).
IR (KBr): 3230, 3200, 1655, 1620 cm–1.
1H NMR (500 MHz, DMSO-d6 + D2O, rotamers): d = 1.79 (s, 0.9
H), 2.04 (s, 2.1 H), 3.34 (dd, J = 14.5, 4.8 Hz, 0.3 H), 3.47 (dd,
1H NMR (500 MHz, DMSO-d6, rotamers): d = 0.88 (d, J = 6.7 Hz,
0.8 H), 0.99 (d, J = 6.7 Hz, 2.2 H), 1.84 (s, 0.8 H), 2.44 (s, 2.2 H),
4.93–4.99 (m, 0.7 H), 5.31–5.38 (m, 0.3 H), 5.73 (d, J = 5.4 Hz, 0.7
H), 5.79 (d, J = 5.4 Hz, 0.3 H), 7.37–7.47 (m, 3.7 H), 7.55–7.56 (m,
1.3 H), 7.96–8.15 (m, 4 H).
13C NMR (125.7 MHz, DMSO-d6, rotamers): d = 12.8, 13.7, 13.9,
13.9, 14.4, 20.35, 20.38, 20.5, 21.0, 56.4, 57.7, 59.4, 59.46, 59.51,
60.06, 60.09, 60.12, 60.2, 60.6, 62.7, 74.4, 75.0, 78.4, 79.8, 80.7,
114.6 (q, J = 286.5 Hz), 114.8 (q, J = 288.5 Hz), 122.7, 123.1,
123.8, 124.1 124.2, 124.6, 125.0, 125.8, 127.1, 127.2, 127.8, 128.1,
128.2, 128.5, 128.7, 128.7, 128.8, 128.9, 129.0, 129.3, 129.8, 134.7,
Synthesis 2008, No. 1, 32–38 © Thieme Stuttgart · New York

PAPER
Hydrazidohydroxylation of Styrenes
37
J = 13.5, 9.3 Hz, 0.7 H), 3.54–3.63 (m, 1 H), 4.85 (dd, J = 9.5, 3.8
Hz, 0.7 H), 4.89 (dd, J = 8.0, 4.5 Hz, 0.3 H), 7.22–7.34 (m, 5 H).
13C NMR (125.7 MHz, DMSO-d6, rotamers): d = 14.1, 20.5, 20.8,
21.2, 56.6, 58.6, 59.8, 69.6, 70.8, 125.8, 126.0, 127.1, 127.2, 128.1,
143.3, 143.5, 168.1, 172.1.
N-(1,3-Dioxoisoindolin-2-yl)-N-(2-hydroxy-1-p-tolylethyl)acet-
amide (5g¢)
White crystals; mp 126–127 °C (EtOAc–hexane).
IR (KBr): 3450, 1790, 1750, 1720, 1400 cm–1.
1H NMR (500 MHz, DMSO-d6 + D2O): d = 1.91 (s, 3 H), 2.24 (s, 3
H) 3.20 (dd, J = 10.0, 5.0 Hz, 1 H), 3.35 (dd, J = 15.0, 10.0 Hz, 1
H), 5.67 (dd, J = 10.0, 5.0 Hz, 1 H), 7.13 (d, J = 7.9 Hz, 2 H), 7.21
(d, J = 7.9 Hz, 2 H), 7.87 (s, 4 H).
13C NMR (125.7 MHz, DMSO-d6): d = 20.2, 20.4, 53.9, 74.0, 122.5,
126.0, 128.4, 129.7, 134.1, 135.6, 136.7, 166.1, 169.0.
EIMS: m/z (%) = 194 (M+, 10.6), 107 (52), 88 (100).
Anal. Calcd for C10H14N2O2: C, 61.84; H, 7.27; N, 14.42. Found: C,
61.72; H, 7.29; N, 14.28.
N-[2-(4-Chlorophenyl)-2-hydroxyethyl]-N-(1,3-dioxoisoindo-
lin-2-yl)acetamide (5d)
White crystals; mp 131–132 °C (EtOAc–hexane).
IR (KBr): 3525, 1800, 1740, 1700, 1220 cm–1.
1H NMR (270 MHz, CDCl3 + D2O, rotamers): d = 2.01 (s, 1.8 H),
2.38 (s, 1.2 H), 3.55–3.73 (m, 1 H), 3.90 (dd, J = 14.9, 10.4 Hz, 0.4
H), 4.07–4.16 (m, 0.6 H), 4.79 (d, J = 10.0 Hz, 0.4 H) 5.01 (d,
J = 10.0 Hz, 0.6 H), 7.26–7.33 (m, 5 H), 7.83–7.99 (m, 4 H).
EIMS: m/z (%) = 338 (M+, 0.8), 278 (86), 175 (100), 130 (31.2).
Anal. Calcd for C19H18N2O4: C, 67.45; H, 5.36; N, 8.28. Found: C,
67.54; H, 5.35; N, 8.36.
Trifluoroacetylation of 5a¢, 5d¢, 5g¢; 2-[N-(1,3-Dioxoisoindolin-
2-yl)acetamido]-2-phenylethyl 2,2,2-Trifluoroacetate (3a¢);
Typical Procedure
Trifluoroacetic anhydride (0.1 mL, 0.525 mmol) was added to a so-
lution of 5a¢ (34 mg, 0.105 mmol) in pyridine (0.1 mL, 0.525 mmol)
and THF (2.4 mL) at 0 °C. After stirring for 5 min, the reaction was
quenched with 1% HCl (4 mL) and the mixture was extracted with
Et2O (2 ´ 20 mL). The combined organic solvents were washed with
brine (15 mL), dried (Na2SO4), and concentrated. The residue was
purified by short column chromatography on silica gel using 60%
EtOAc–hexane to give the product 3a¢ (31 mg, 70%); colorless
crystals; mp 121–123 °C (Et2O–hexane); HPLC: tR = 21.08.
13C NMR (67.8 MHz, DMSO-d6): d = 19.9, 20.6, 52.2, 57.9, 70.0,
70.4, 123.5, 123.5, 123.75, 123.80, 127.75, 127.82, 128.0, 129.3,
129.7, 129.4, 131.6, 131.7, 135.0, 135.1, 141.6, 141.7, 164.3, 164.7,
164.8, 164.9, 168.7, 171.4.
FABMS (3-nitrobenzyl alcohol + NaI): m/z (%) = 381 (M+ + Na,
67.9).
Anal. Calcd for C18H15ClN2O4: C, 60.26; H, 4.21; N, 7.81. Found:
C, 60.13; H, 4.07; N, 7.81.
IR (KBr): 3420, 1810, 1750, 1720, 1240, 1200 cm–1.
N-[1-(4-Chlorophenyl)-2-hydroxyethyl]-N-(1,3-dioxoisoindo-
lin-2-yl)acetamide (5d¢)
White crystals; mp 141–143 °C (EtOAc–hexane).
IR (KBr): 3450, 1800, 1750, 1720, 1220, 890, 720 cm–1.
1H NMR (270 MHz, CDCl3, rotamers): d = 1.95 (s, 2.6 H), 2.06 (s,
0.4 H), 4.05 (dd, J = 14.9, 9.6 Hz, 1 H), 4.25 (dd, J = 14.9, 3.2 Hz,
1 H), 5.94 (dd, J = 9.6, 3.1 Hz, 1 H), 7.26–7.37 (m, 5 H), 7.84–8.01
(m, 4 H).
1H NMR (270 MHz, CDCl3 + D2O): d = 2.11 (s, 3 H), 3.33 (dd,
J = 13.2, 4.5 Hz, 1 H), 3.49 (dd, J = 13.2, 9.1 Hz, 1 H), 5.82 (dd,
J = 9.0, 4.2 Hz, 1 H), 7.31 (s, 4 H), 7.73–7.87 (m, 4 H).
13C NMR (67.8 MHz, DMSO-d6): d = 20.8, 53.9, 73.7, 122.8,
128.05, 128.14, 129.8, 132.2, 134.3, 137.8, 166.4, 169.3.
FABMS (3-nitrobenzyl alcohol + NaI): m/z (%) = 381 (M+ + Na,
88.2).
13C NMR (125.7 MHz, DMSO-d6, rotamers): d = 20.5, 20.7, 53.4,
54.8, 71.1, 71.8, 115.2 (q, J = 288.4 Hz), 116.3 (q, J = 288.1 Hz),
124.2, 124.4, 124.5, 126.16, 126.21, 126.4, 128.3, 128.5, 128.6,
129.0, 129.2, 129.4, 135.7, 135.8, 136.9, 137.3, 143.0, 157.4 (q,
J = 34.4 Hz), 158.7 (q, J = 34.4 Hz), 163.7, 163.9, 169.2, 169.4.
FABMS (3-nitrobenzyl alcohol): m/z (%) = 421 (M+ + H, 3.3), 361
(100).
Anal. Calcd for C20H15F3N2O5: C, 57.15; H, 3.60; N, 6.66. Found:
C, 56.99; H, 3.45; N, 6.58.
Anal. Calcd for C18H15ClN2O4: C, 60.26; H, 4.21; N, 7.81. Found:
C, 60.06; H, 4.16; N, 7.77.
2-(4-Chlorophenyl)-2-[N-(1,3-dioxoisoindolin-2-yl)acetami-
do]ethyl 2,2,2-Trifluoroacetate (3d¢)
N-(1,3-Dioxoisoindolin-2-yl)-N-(2-hydroxy-2-p-tolylethyl)acet-
amide (5g)
White crystals; mp 124–125 °C (EtOAc–hexane).
IR (KBr): 3500, 1800, 1740, 1680, 1380, 1210 cm–1.
White crystals; mp 121–122 °C (EtOAc–hexane).
IR (KBr): 1800, 1750, 1720, 1220 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 1.91 (s, 3 H), 3.89 (dd,
J = 14.4, 3.7 Hz, 1 H), 4.41 (dd, J = 14.4, 10.1 Hz, 1 H), 5.87 (dd,
J = 9.9, 3.9 Hz, 1 H), 7.42–7.46 (m, 4 H), 8.02–8.12 (m, 4 H).
13C NMR (125.7 MHz, DMSO-d6): d = 20.6, 52.9, 71.1, 114.9 (q,
J = 288.8 Hz), 124.3, 124.4, 128.3, 128.4, 128.9, 129.0, 132.9,
135.8, 136.2, 157.2 (q, J = 36.5 Hz), 163.6, 163.8, 169.3.
1H NMR (500 MHz, DMSO-d6 + D2O, rotamers): d = 1.92 (s, 1.8
H), 2.11 (s, 1.2 H), 2.22 (s, 1.8 H), 2.30 (s, 1.2 H), 3.49 (dd, J = 10.0,
7.5 Hz, 0.4 H), 3.65 (dd, J = 15.0, 4.2 Hz, 0.4 H), 3.88 (dd, J = 15.0,
8.2 Hz, 0.6 H), 4.05 (dd, J = 14.0, 3.4 Hz, 0.6 H), 4.63 (dd, J = 8.2,
3.4 Hz, 0.6 H), 4.77 (dd, J = 8.2, 4.2 Hz), 7.07 (d, J = 7.9 Hz, 1 H),
7.14 (d, J = 7.9 Hz, 1 H), 7.17 (d, J = 7.9 Hz, 1 H), 7.35 (d, J = 7.9
Hz, 1 H), 7.84–8.00 (m, 4 H).
13C NMR (125.7 MHz, DMSO-d6, rotamers): d = 19.9, 20.55,
20.62, 20.7, 52.1, 58.2, 70.5, 71.1, 71.3, 123.6, 123.7, 123.89,
123.94, 125.8, 126.2, 126.5, 128.0, 128.59, 128.63, 129.56, 129.60,
129.6, 135.18, 135.20, 136.3, 136.4, 139.8, 139.9, 164.5, 164.9,
165.0, 165.1, 169.0, 171.6.
FABMS (3-nitrobenzyl alcohol): m/z (%) = 455 (M+ + H, 3.2), 395
(40.3).
Anal. Calcd for C18H15ClN2O4: C, 52.82; H, 3.10; N, 6.16. Found:
C, 52.94; H, 3.22; N, 6.31.
2-[N-(1,3-Dioxoindolin-2-yl)acetamido]-2-p-tolylethyl
2,2,2-Trifluoroacetate (3g¢)
White crystals; mp 94–95 °C (Et2O–hexane).
EIMS: m/z (%) = 338 (M+, 0.9), 176 (99), 148 (100), 130 (42.5), 121
(25.2).
IR (KBr): 1800, 1760, 1720, 1230, 1200 cm–1.
Anal. Calcd for C19H18N2O4: C, 67.45; H, 5.36; N, 8.28. Found: C,
67.28; H, 5.32; N, 8.39.
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38
K. Murata et al.
PAPER
1H NMR (500 MHz, DMSO-d6): d = 2.0 (s, 3 H), 2.27 (s, 3 H), 3.88
(dd, J = 3.5, 14.5 Hz, 1 H), 4.39 (dd, J = 10.4, 14.3 Hz, 1 H), 5.87
(dd, J = 3.6, 10.2 Hz, 1 H), 7.17 (d, J = 8.1 Hz, 2 H), 7.29 (d, J = 8.1
Hz, 2 H), 8.01–8.11 (m, 4 H).
13C NMR (125.7 Hz, DMSO-d6): d = 20.7, 53.3, 71.6, 115.2 (q,
J = 297.7 Hz), 124.4, 124.5, 126.4, 129.0, 129.1, 129.2, 134.3,
135.8, 137.7, 157.3 (q, J = 36.2 Hz), 163.7, 163.9, 169.4.
SanMartín, R. Tetrahedron Lett. 2002, 43, 8273.
(g) Wardrop, D. J.; Burge, M. S.; Zhang, W.; Ortíz, J. A.
Tetrahedron Lett. 2003, 44, 2587. (h) Correa, A.; Herrero,
M. T.; Tellitu, I.; Domínguez, E.; Moreno, I.; SanMartín, R.
Tetrahedron 2003, 59, 7103. (i) Chang, C.-Y.; Yang, T.-K.
Tetrahedron: Asymmetry 2003, 14, 2081. (j) Serena, S.;
Tellitu, I.; Domínguez, E.; Moreno, I.; SanMartín, R.
Tetrahedron Lett. 2003, 44, 3483. (k) Serena, S.; Tellitu, I.;
Domínguez, E.; Moreno, I.; SanMartín, R. Tetrahedron
2004, 60, 6533. (l) Sema, S.; Tellitu, I.; Domínguez, E.;
Moreno, I.; SanMartín, R. Org. Lett. 2005, 7, 3073.
(m) Correa, A.; Tellitu, I.; Domínguez, E.; Moreno, I.;
SanMartín, R. J. Org. Chem. 2006, 71, 8316. (n) Tellitu, I.;
Sema, S.; Herrero, T.; Moreno, I.; Domínguez, E.;
SanMartín, R. J. Org. Chem. 2007, 72, 1526.
FABMS (3-nitrobenzylalcohol + NaI): m/z (%) = 457 (M+ + Na,
100).
Anal. Calcd for C21H17F3N2O5: C, 58.07; H, 3.94; N, 6.45. Found:
C, 58.16; H, 4.09; N, 6.46.
References
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Synthesis 2008, No. 1, 32–38 © Thieme Stuttgart · New York