Preparation of (2-methyl-propane-2-sulfonylimino) acetic acid ethyl ester

Article abstract of DOI:10.1055/s-2004-815925

Synthesis of (2-methyl-propane-2-sulfonylimino) acetic acid ethyl ester from tert-butylsulfonamide, thionyl chloride and ethyl glyoxylate is described. The N-tert-butylsulfonyl imino ester has served as a substitute of the corresponding N-toluenesulfonyl imino ester in allylation reactions.

Full text of DOI:10.1055/s-2004-815925

PRACTICAL SYNTHETIC PROCEDURES
967
Preparation of (2-Methyl-propane-2-sulfonylimino) Acetic Acid Ethyl Ester
Preparation of
(
2-Meth
a
yl-propane
r
-2-sulfon
c
ylimino)
A
e
cetic
A
cid
l
Ethyl Este
r
Schleusner, Stefan Koep, Markus Günter, Shashi K. Tiwari, Hans-Joachim Gais*
Institut für Organische Chemie der Rheinisch-Westfälischen Technischen Hochschule (RWTH) Aachen,
Prof.-Pirlet-Str. 1, 52056 Aachen, Germany
E-mail: Gais@RWTH-Aachen.de
PSP
Received 26 November 2003
No19
Abstract: Synthesis of (2-methyl-propane-2-sulfonylimino) acetic acid ethyl ester from tert-butylsulfonamide, thionyl chloride and ethyl
glyoxylate is described. The N-tert-butylsulfonyl imino ester has served as a substitute of the corresponding N-toluenesulfonyl imino ester
in allylation reactions.
Key words: imino ester, allylation, amino acids
NMe
Ph
O
RO2S
H
R
NMe
Ph
NH2
O
NMe
Ph
N
O
S
R
CF3SO3H
CH2Cl2
S
2
2
+
+
S
EtO2C
2
EtO2C
Ti(OiPr)2
R
NMe
O
S
CF3SO3H
CH2Cl2
N
SO2CMe3
Ph
N
H
2
Ti(OiPr)2
CO2Et
CO2Et
NMe
Ph
O
Me3CO2S
EtO2C
H
S
N
N
R
2
+
O
CF3SO3H
CH2Cl2
O
2
EtO2C
Ti(OiPr)2
H
H
R
R
Scheme 1 Asymmetric synthesis of a-amino acid derivatives from N-tert-butylsulfonyl imino ester and titanated allylic sulfoximines.
The N-toluenesulfonyl a-imino ester 1,1,2 (Figure 1) has
found numerous applications in asymmetric synthesis
through, for example ene,3 Diels–Alder,4 alkylation,5
Mannich,6 arylation,7 aziridination,8 and [2+2]-
cycloaddition9 reactions. However, a major drawback as-
sociated frequently with the utilization of the imino ester
1 has been that the N-tosyl group of the amine derivatives
formed thereof is difficult to remove.10–12 Recently we
have described the utilization of the N-tert-butylsulfonyl
a-imino ester 2 in the asymmetric synthesis of mono- and
bicyclic a-amino acid derivatives, the key step of which is
a highly diastereoselective allylation of 2 with titanated
allylic sulfoximines (Scheme 1).13–15 Aminoalkylations of
titanated allylic sulfoximines with 1 and 2 revealed no dif-
ferences in the reactivity of the two N-sulfonyl imino es-
ters. A ready deprotection of the N-tert-butylsulfonyl
protected amino acid derivatives was achieved according
to the method described by Weinreb et al.16 through treat-
ment with CF3SO3H in anhydrous CH2Cl2. Here the use of
anisole as cation scavenger was not required.16
SO2CH2CH2SiMe3
SO2CMe3
SO2C6H4Me
N
N
N
EtO2C
EtO2C
EtO2C
1
2
3
Figure 1 N-Sulfonyl imino esters.
Herein we describe a practical procedure for the synthesis
of 2, which may find widespread application as a substi-
tute for 1 in organic synthesis. The N-tert-butylsulfonyl
imino ester 2 was prepared from amide 4 according to the
method of Kresze (Scheme 2).2 Thus amide 417 was treat-
ed with SOCl2 at reflux temperature in toluene to afford
the tert-butylsulfonyl isothiocyanate (5), which was not
isolated18 but treated with freshly distilled ethyl glyoxy-
late at reflux temperature to give the imino ester 2 as a yel-
low oil in 63% yield, based on amide 4. The overall yield
of the a-imino ester 2 compares favorably with the one re-
ported for the synthesis of 1.1,2 Similarly the (trimethyl-
silylethyl)sulfonyl imino ester 3 can be prepared from the
corresponding sulfonyl amide according to the procedure
used for the synthesis of 2.13
SYNTHESIS 2004, No. 6, pp 0967–0969
x
x
.
x
x
.2
0
0
4
Advanced online publication: 26.01.2004
DOI: 10.1055/s-2004-815925; Art ID: E10103SS
© Georg Thieme Verlag Stuttgart · New York

968
M. Schleusner et al.
PRACTICAL SYNTHETIC PROCEDURES
O
SO2CMe3
N
, ∆
EtO2C
SOCl2, ∆
− HCl
H2N SO2CMe3
O
S
N
SO2CMe3
EtO2C
− SO2
5
4
2
O
O
SO2Cl2
H2O2
NaN3,
Me3CSSCMe3
Me3C S SCMe3
4
Me3C S Cl
AcOH
MeCN, H20, ∆
− N2
6
7
8
Scheme 2 Synthesis of N-tert-butylsulfonyl imino ester.
13C NMR (CDCl3, 100 MHz): d = 13.93 (d, CH3CH2), 23.63 [d,
C(CH3)3], 58.98 [u, C(CH3)3], 63.00 (u, CH3CH2), 160.88 (u, C=O),
163.40 (d, CH).
The amide 4 was prepared from the disulfide 6 on a 1 mol
scale in 82% overall yield as outlined in Scheme 2 follow-
ing known procedures. Thus oxidation of 6 with H2O2
gave the sulfinate 719 which was not isolated but treated
with SOCl217 to afford the sulfinyl chloride 817,19 in 92%
yield. Treatment of 8 with NaN3 in MeCN in the presence
of a small amount of H2O at elevated temperatures by the
slow addition of the sulfinyl chloride to a suspension of
the azide gave the amide 417 in 89% yield.
Acknowledgement
Financial support of this work by the Deutsche Forschungsgemein-
schft (SFB 380, ‘Asymmetric Synthesis by Chemical and Biologi-
cal Methods’) is gratefully acknowledged.
References
(1) Tschaen, D. M.; Turos, E.; Weinreb, S. M. J. Org. Chem.
1984, 49, 5058.
2-Methylpropane-2-sulfinyl Chloride (8); Typical Procedure
The sulfinyl chloride 8 was prepared from the disulfide 6 on a 1 mol
scale in 93% yield in two steps by the procedures described previ-
ously.17,19 For the first step, the oxidation of the disulfide 6, the pro-
cedure reported by Prinzbach et al.19 was followed while for the
second step, the chlorination of the sulfinate 7, the procedure of
Sharpless et al.17 by using SOCl2 was used.
(2) Albrecht, R.; Kresze, G. Chem. Ber. 1965, 98, 1431.
(3) (a) Mikami, K.; Yajima, T.; Kaneko, M. Amino Acids 1998,
14, 311. (b) Yao, S.; Fang, X.; Jørgensen, K. A. Chem.
Commun. 1998, 2547. (c) Drury, W. J. III; Ferraris, D.; Cox,
C.; Young, B.; Lectka, T. J. Am. Chem. Soc. 1998, 120,
11006.
(4) (a) Yao, S.; Johannsen, M.; Hazell, R. G.; Jorgensen, K. A.
Angew. Chem. Int. Ed. 1998, 37, 3121; Angew. Chem. 1998,
110, 3318. (b) Jørgensen, K. A. Angew. Chem., Int. Ed.
2000, 39, 3558; Angew. Chem. 2000, 112, 3702. (c) Yao,
S.; Saaby, S.; Hazell, R. G.; Jørgensen, K. A. Chem.–Eur. J.
2000, 2435.
2-Methyl-propane-2-sulfonic Acid Amide (4); Typical Proce-
dure
The amide 4 was prepared from the sulfinyl chloride 8 on a 1 mol
scale in 89% yield by the procedure described by Sharpless et al.17
except that the purification was done by washing of the crude mater-
ial with Et2O instead of recrystallization.
(5) (a) Yamamoto, Y.; Nishii, S.; Maruyama, K.; Komatsu, T.;
Ito, W. J. Am. Chem. Soc. 1986, 108, 7778. (b) Fang, X.;
Johannson, M.; Yao, S.; Gathergood, N.; Hazell, R.;
Jørgensen, K. A. J. Org. Chem. 1999, 64, 4844.
(2-Methyl-propane-2-sulfonylimino) Acetic Acid Ethyl Ester
(2); Typical Procedure
A dry, argon flushed 500 mL four necked round bottomed flask,
equipped with an efficient reflux condenser, a magnetic stirring bar,
a thermometer and an argon inlet on top of the condenser, was filled
with the amide 4 (12.20 g, 89.00 mmol) and anhyd toluene (200
mL). Freshly distilled SOCl2 (9.0 mL, 123.36 mmol) was added and
the slightly yellow turbid mixture was heated first for 2 h at 80 °C
and then at reflux temperature for 8 h. Then, the mixture was al-
lowed to cool to approximately 80 °C and freshly distilled (vide in-
fra) ethyl glyoxylate20 (7.80 g, 89.00 mmol) was added. The
reaction mixture was heated at reflux for 3 d. Then the reflux con-
denser was replaced by a downward distillation condenser and tol-
uene was removed under atmospheric pressure. A brown and highly
viscous oil remained, which was dissolved in absolute THF (50
mL). The solution was transferred to a distillation flask, THF was
evaporated under reduced pressure and the flask was connected to a
vacuum distillation apparatus. High vacuum distillation gave 13.2 g
(63%) of the pure imino ester 2 as a pale yellow oil; bp 95–105 °C/
0.2 mbar. Occasionally small amounts of amide 4 were isolated,
which crystallized in the condenser.
(c) Ferraris, D.; Young, B.; Cox, C.; Drury, W. J. III;
Dudding, T.; Lectka, T. J. Org. Chem. 1998, 63, 6090.
(d) Ferraris, D.; Young, B.; Dudding, T.; Lectka, T. J. Am.
Chem. Soc. 1998, 120, 4548. (e) Halland, N.; Jorgensen, K.
A. J. Chem. Soc., Perkin Trans. 1 2001, 11, 1290.
(f) Knudsen, K. R.; Risgaard, T.; Nishiwaki, N.; Gothelf, K.
V.; Jørgensen, K. A. J. Am. Chem. Soc. 2001, 123, 5843.
(g) Kagoshima, H.; Uzawa, T.; Akiymama, T. Chem. Lett.
2002, 3, 298. (h) Ferraris, D.; Young, B.; Cox, C.; Dudding,
T.; Drury, W. J. III; Lev, R.; Taggi, A. E.; Lectka, T. J. Am.
Chem. Soc. 2002, 124, 67.
(6) (a) Juhl, K.; Gathergood, N.; Jørgensen, K. A. Angew.
Chem., Int. Ed. 2001, 40, 2995; Angew. Chem. 2001, 113,
3083. (b) Marigo, M.; Kjaersgaard, A.; Juhl, K.;
Gathergood, N.; Jorgensen, K. A. Chem.–Eur. J. 2003, 9,
2359. (c) Bernardi, L.; Gothelf, A. S.; Hazell, R. G.;
Jorgensen, K. A. J. Org. Chem. 2003, 68, 2583.
(d) Kobayashi, S.; Matsubara, R.; Nakamura, Y.; Kitagawa,
H.; Sugiura, M. J. Am. Chem. Soc. 2003, 125, 2507.
(7) (a) Saaby, S.; Fang, X.; Gathergood, N.; Jørgensen, K. A.
Angew. Chem., Int. Ed. 2000, 39, 4114; Angew. Chem. 2000,
112, 4280. (b) Hao, J.; Taktak, S.; Aikawa, K.; Yusa, Y.;
Hatano, M.; Mikami, K. Synlett 2001, 9, 1443.
1H NMR (CDCl3, 400 MHz): d = 1.40 (t, J = 7.1 Hz, 3 H, CH3CH2),
1.49 [s, 9 H, C(CH3)3], 4.41 (q, J = 7.1 Hz, 2 H, CH3CH2), 8.38 (s,
1 H, CH).
Synthesis 2004, No. 6, 967–969 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES Synthesis of (2-Methyl-propane-2-sulfonylimino) Acetic Acid Ethyl Ester 969
(8) (a) Juhl, K.; Hazell, R.; Jørgensen, K. A. J. Chem. Soc.,
Perkin Trans. 1 1999, 2293. (b) Aggarwal, V. K.; Alonso,
E.; Ferrara, M.; Spey, S. E. J. Org. Chem. 2002, 67, 2335.
(c) Aggarwal, V. K.; Ferrara, M. Org. Lett. 2000, 2, 4107.
(9) (a) Wack, H.; Drury, W. J. III; Taggi, A. E.; Ferraris, D.;
Lectka, T. Org. Lett. 1999, 1, 1985. (b) Taggi, A. E.; Hafez,
A. M.; Wack, H.; Young, B.; Drury, W. J. III; Lectka, T. J.
Am. Chem. Soc. 2000, 122, 7831. (c) Hafez, A. M.; Taggi,
A. E.; Wack, H.; Drury, W. J. III; Lectka, T. Org. Lett. 2000,
2, 3963. (d) Hafez, A. M.; Taggi, A. E.; Dudding, T.; Lectka,
T. J. Am. Chem. Soc. 2001, 123, 10853. (e) Taggi, A. E.;
Wack, H.; Hafez, A. M.; France, S.; Lectka, T. Org. Lett.
2002, 4, 627. (f) France, S.; Wack, H.; Hafez, A. M.; Taggi,
A. E.; Witsil, D. R.; Lectka, T. Org. Lett. 2002, 4, 1603.
(g) Taggi, A. E.; Hafez, A. M.; Dudding, T.; Lectka, T.
Tetrahedron 2002, 58, 8351. (h) Akiyama, T.; Daidouji, K.;
Fubhibe, K. Org. Lett. 2003, 5, 3691.
(12) For a two-step conversion of N-tosyl amines to N-Boc
amines, see: Nyasse, B.; Grehn, L.; Ragnarsson, U. J. Chem.
Soc., Chem. Commun. 1997, 1017; and ref.7.
(13) Schleusner, M.; Gais, H.-J.; Koep, S.; Raabe, G. J. Am.
Chem. Soc. 2002, 124, 7789.
(14) Koep, S.; Gais, H.-J.; Raabe, G. J. Am. Chem. Soc. 2003,
125, 13243.
(15) Günther, M.; Gais, H.-J. J. Org. Chem. 2003, 68, 8037.
(16) Sun, P.; Weinreb, S. M.; Shang, M. J. Org. Chem. 1997, 62,
8604.
(17) Gontcharov, A. V.; Liu, H.; Sharpless, K. B. Org. Lett. 1999,
1, 783.
(18) If desired 5 can be isolated, see ref.13
(19) Netscher, T.; Prinzbach, H. Synthesis 1987, 683.
(20) A technical 50% solution of ethyl glyoxylate in toluene was
concentrated at atmospheric pressure and the residue was
distilled to give ethyl glyoxylate as a turbid yellow oil. A
second distillation of this material at atmospheric pressure
by using a 20 cm Vigreux column at a bath temperature of
160–180 °C furnished ethyl glyoxylate as a yellow fluid,
which was used immediately and transferred to the reaction
mixture by a syringe.
(10) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley: New York, 1999.
(11) Kocienski, P. J. Protecting Groups; Thieme: Stuttgart, 1994.
Synthesis 2004, No. 6, 967–969 © Thieme Stuttgart · New York