Efficient enantioselective synthesis of C(α)-methyl aspartic acid and 3-amino-3-methylpyrrolidin-2-one

Article abstract of DOI:10.1055/s-2000-6240

The asymmetric dipolar cycloaddition reaction of Me₃SiCHN₂ and auxiliary-bound methacrylate affords ready entry into optically active substituted pyrazolines. Herein we disclose an unusual alkaline fragmentation reaction of optically

Full text of DOI:10.1055/s-2000-6240

PAPER
135
Efficient Enantioselective Synthesis of Ca-Methyl Aspartic Acid and 3-Amino-
3-methylpyrrolidin-2-one
Hiroshi Sasaki, Erick M. Carreira*
Eidgenössische Technische Hochschule, Laboratorium für Organische Chemie, Universitätstrasse 16, CH-8092 Zürich, Switzerland
Fax +41(1)6321328; E-mail: carreira@org.chem.ethz.ch
Received 8 September 1999
we document an unusual ring-cleavage reaction of pyra-
Abstract: The asymmetric dipolar cycloaddition reaction of
zoline 1 which readily affords Ca-methyl aspartic acid 2 in
Me3SiCHN2 and auxiliary-bound methacrylate affords ready entry
68% yield. The process thus permits access to this unusual
amino acid through a short sequence of reactions (3 steps)
into optically active substituted pyrazolines. Herein we disclose an
unusual alkaline fragmentation reaction of optically active pyrazo-
line 1 that affords an efficient synthesis of the pharmacologically utilizing inexpensive, commercially available starting
important 2-methylaspartic acid in good yields. Additionally, in an
alternative transformation of the pyrazoline (1), reductive cleavage
provides the corresponding 3-amino-3-methylpyrrolidin-2-one.
materials. Fragmentation of the pyrazoline under reduc-
tive conditions affords 3-amino-3-methylpyrrolidin-2-one
3, an anhydrobisnorlysine derivative.6
Key words: amino acids, pyrazolines, asymmetric synthesis
H
N
Me
O
Me
O
OH–
68%
Me
[H]
HO
O
The Ca-methylated a-amino acids constitute an important
class of amino acids whose biophysical properties have
been extensively studied.1 The sterics associated with a
quaternary Ca-stereogenic center engenders unusual con-
formational constraints on the resulting derived peptides
which are of interest in the de novo design of protein
and enzyme mimetics. Some of these, a-aminoisobutyric
acid (Aib) and isovaline (Iva), have been identified in a
naturally occurring antiobics, such as the peptaibols
which form channels and alter the ion permeability of bi-
ological membranes.2 In addition to the interesting bio-
chemical characteristics, the synthesis of Ca-methylated
amino acids represent a synthetic challenge. Many excel-
lent synthetic methods for the asymmetric synthesis of op-
tically active Ca-amino acids have been developed;
however, only a subset of these may be utilized in the syn-
thesis of necessary chiral Ca-quaternary stereocenters.3
We have been interested in the study and development of
methodology for the preparation of optically active alka-
loids.4,5 In this regard, we have recently disclosed a dia-
stereoselective dipolar cycloaddition reaction between
Me3SiCHN2 and optically active enoates to give D2-pyra-
zolines 1 in good yields and diastereoselectivity (Equation
1). In order to demonstrate the versatility of such chiral
heterocycles as building blocks for asymmetric synthesis
we have initiated a study aimed at fragmentation reactions
that give useful optically active derivatives. In this report
OH
N
O2S
61%
Me NH2
O
NH
N
Me NH2•HOTs
2
1
3
Equation 1
Two general approaches have been devised for the prepa-
ration of 2. These include preparation of the racemate with
resolution and asymmetric syntheses.1c,7 The latter pro-
cesses have generally involved diastereoselective, auxil-
iary-controlled enolate alkylations as exemplified by the
synthetic routes of Schöllkopf,7f Seebach,7g Berkowitz,7m
and, more recently, Cativiela.7o In addition to 2, the asym-
metric synthesis of pyrrolidinone 3 is of some interest as
it constitutes an anhydro derivative of an unnatural amino
acid, namely, bisnorlysine and, moreover, may have use
as a novel chiral auxiliary. We reasoned retrosynthetically
that the disposition of functionality in 2 and 3 suggested
the use of the same optically active pyrazoline 1 as precur-
sor (Scheme 1). The implementation of such a strategy
would require the development and study of two different
fragmentation protocols. The reductive cleavage of 1 to
give 4 would require the identification of appropriate tran-
sition-metal catalysts for concomitant C=N and N-N
bond reduction, a process possessing considerable prece-
dent.8 The fragmentation of pyrazoline 1 to the corre-
CO2H
N
O
Me
NH2
H
N
O
Me
Me
CO2H
CO2H
Me
5
HO2C
H
Xc
O
OR
NH2
NH
NH2 NH2
N
CO2H
Me
NH2
Me NH2•HOTs
2
1
4
3
NH2
6
Scheme 1
Synthesis 2000, No. 1, 135–138 ISSN 0039-7881 © Thieme Stuttgart · New York

136
H. Sasaki, E. M. Carreira
PAPER
sponding acid is unusual, requiring a fragmentation of the
pyrazoline to the corresponding amino nitrile 5 or amino
amide 6 followed by hydrolysis.9
H
2 (1 atm)
Me
H
N
cat. PtO2
p-TsOH, MeOH
23°C, 22h
Me
O
Me
O
N
O2S
NH
N
The asymmetric synthesis of the requisite chiral pyrazo-
line commences with the dipolar cycloaddition reaction of
Me3SiCHN2 and N-methacrylate derivative of Oppolzer’s
chiral sultam auxiliary (Equation 2). Importantly, each of
these starting materials is readily available from commer-
cial sources at affordable costs. As we have previously re-
ported, the dipolar cycloaddition reaction affords adduct
in 65% yield as a 94:6 mixture of diastereomers which are
easily separated by chromatography on silica gel. The re-
action can be conducted on multigram scale to afford pre-
paratively useful quantities of optically active pyrazoline.
61%
Me NH2•HOTs
3
1
H
N
O
(Boc)2O, Et3N
THF, 23 °C, 14h
69%
Me NHBoc
8
Scheme 3
preparation is effected from a readily available optically
active pyrazoline which can be accessed from the diaste-
reoselective dipolar cycloaddition reaction of
Me3SiCHN2 and methacrylate/camphorsultam derivative.
The synthesis of Ca-methyl aspartic acid involves an un-
usual fragmentation reaction of the substituted pyrazoline
under alkaline conditions. Alternatively, C=N and N-N
reduction of the pyrazoline affords 3-amino-3-methylpyr-
rolidin-2-one. Further exploration of pyrazoline ring-frag-
mentations and functionalization reactions are currently
under investigation and will be reported in due time.
Me
Me
Me
Me
O
O
Me
Me3SiCHN2
N
O2S
N
O2S
then
acidic workup
NH
N
Me
94:6 diastereoselectivity
65%
Equation 2
A number of reaction conditions were examined to effect
the desired fragmentation reaction. We found that simply
heating a 5M aqueous NaOH solution of 2 in an autoclave
at 150 °C for 5h affords 2-methylaspartic acid in 68%
yield after chromatographic purification of the hydrochlo-
ride salt on cellulose DS-0 (Scheme 2). This amino diacid
could be easily converted to the corresponding bisbenzyl
ester N-acetamide derivative through a two-step se-
Where appropriate, reagents were purified prior to use by standard
procedures. Raney nickel of ready-to-use grade was purchased from
Fluka. Platinum(IV) oxide was purchased from Aldrich Chemical
Company.
(R)-(+)-a-Methoxy-a-(trifluoromethyl)phenylacetic
acid was also purchased from Aldrich Chemical Company. Tolu-
ene, CH2Cl2 and THF were purified through alumina column prior
to use. Et3N was distilled from calcium hydride prior to use. Air-
quence of reactions (BnOH/p-TsOH and Ac2O/Et3N) to and moisture-sensitive liquids were transferred via syringe. Organic
solutions were concentrated by rotary evaporation below 35 °C us-
afford 7 in 63% (two steps).
ing a rotary evaporator. Aqueous solutions were concentrated simi-
larly at 50 °C. Chromatographic purification of products was
carried out using forced-flow chromatography on Fluka silica gel 60
Me
O
Me
O
(230-400 mesh) as a normal phase and on Fluka cellulose powder
DS-0 as a reversed phase. Thin-layer chromatography was per-
formed on Merck 0.25 mm silica gel 60F plates (230-400 mesh) as
a normal phase and Analtech RPSF as a reversed phase. Visualiza-
tion of the developed chromatogram was performed by staining ei-
ther with 5% phosphomolybdic acid ethanol solution or 5%
ninhydrin acetone solution.
Me
HO
aq 5M NaOH
OH
N
O2S
Me NH2
150 °C, 5h
O
NH
N
1
2
68%
1. BnOH, p-TsOH
2. Ac2O, Et3N
O
BnO
OBn
63%
Me NHAc
NMR spectra were recorded on either a Varian Mercury 300 oper-
ating at 300 MHz for 1H, 75 MHz for 13C, and 282 MHz for 19F or
a Varian Gemini 300 operating at 300 MHz for 1H and 75 MHz for
13C. 1H NMR spectra were referenced internally to residual protio
solvent signals. Data for 1H are reported as follows: chemical shift
(d, ppm), integration, multiplicity, and coupling constant (J, Hz).
Data for 13C and 19F are reported in terms of chemical shift (d, ppm).
IR spectra were recorded on a Perkin-Elmer Spectrum RXI FT-IR
system spectrometer with samples prepared as either KBr pellets or
thin films on NaCl salt plates and are reported in terms of frequency
of absorption (n, cm-1). Mps were determined on a Büchi 510 melt-
ing point apparatus and are uncorrected. Combustion analysis was
performed by the analytical laboratory at ETH-Zentrum. Optical ro-
O
7
Scheme 2
Conversion of pyrazoline 1 to the corresponding pyrroli-
dinone was subsequently examined. Thus, the desired re-
duction/cyclization sequence was effected by treatment of
1 with PtO2 in MeOH under 1 atm of H2 (23 °C, 22h) in
the presence of acid, affording 3 in 61% yield. Pyrroli-
dinone 3 could be protected as the N-Boc carbamate upon
reaction with (Boc)2O, Et3N in THF (23 °C, 14h), yielding tations were measured on a JASCO DIP-1000 digital polarimeter
operating at 589 nm and are reported as follows: [a]Dtemp(°C), concen-
8 (69%) (Scheme 3).
tration (g/ 100 mL) and solvent. HPLC analysis were conducted
We have documented a novel synthesis of Ca-methyl as-
partic acid and 3-amino-3-methylpyrrolidin-2-one. Their
with a Hitachi/Merck LaChrom system.
Synthesis 2000, No. 1, 135–138 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Efficient Enantioselective Synthesis of Ca-Methyl Aspartic Acid and 3-Amino-3-methylpyrrolidin-2-one
137
(S)-(+)-2-Methylaspartic Acid (2)
mg, 0.506 mmol) and MeOH (1.5 mL) was stirred at 23 °C for 22 h
A mixture of (1R,3’S)-N-[3’-2D-(3’-methyl)pyrazoline]carbonyl-
2,10-camphorsultam4 (326 mg, 1.00 mmol), NaOH (215 mg, 5.38
mmol), and H2O (1.0 mL) was stirred at 150 °C for 5 h in a 2-mL
autoclave. After cooling to ambient temperature, the mixture was
diluted with H2O (10 mL) and washed with CH2Cl2 (3 x 5 mL).10
The aqueous solution was acidified with HCl (4 M, 2 mL) and con-
centrated by rotary evaporation. Purification of 2-methylaspartic
acid was performed in a modification of the method of Terashima
et al..7d The residue was extracted with EtOH (3 x 10 mL), and the
combined solution was concentrated by rotary evaporation to yield
a brown oil (262 mg). Purification by reversed phase column chro-
matography on cellulose DS-0 (EtOH/2M NH4OH = 85/15-65/35)
afforded 2-methylaspartic acid as an ammonium salt (105 mg). To
the salt was added aq NaOH (1 M, 3.2 ml), and the solution was
heated to 80 °C at atmospheric pressure and concentrated to ca. 1
mL. To the residue was added HCl (4 M, 2.4 mL), and H2O was re-
moved by rotary evaporation. The residue was extracted with EtOH
(10 mL), and concentration of the EtOH solution afforded 2-meth-
ylaspartic acid HCl salt (125 mg, 68%) as an ivory colored solid.
The salt was dissolved in a mixture of EtOH (1.5 mL), H2O (0.1
mL) and pyridine (68 mg, 0.86 mmol) to give pure (S)-2-methylas-
partic acid (72.8 mg, 0.494 mmol, 49%) as a colorless solid; mp
240-241 °C (dec.); [a]D25+49.2 (c = 0.505, H2O).
under H2 at atmospheric pressure. The resulting mixture was fil-
tered through a short plug of Celite (0.2 cm x 0.5 cm) followed by a
MeOH wash (3 mL). The combined MeOH filtrate was concentrat-
ed, and the resulting oily solid was washed with THF (1 mL)11 to
give (S)-3-amino-3-methylpyrrolidin-2-one p-toluenesulfonate
(87.4 mg, 0.305 mmol, 61%) as a colorless solid; mp 200-201 °C
(dec.); [a]D25 -17.6 (c = 0.560, MeOH).
IR (KBr): n = 3218, 2981, 1699, 1532, 1305, 1193, 1126, 1034,
1012, 817, 682, 572 cm−1.
1H NMR (DMSO-d6, 300 MHz): d = 8.36 (3H, br s), 8.26 (1H, br s),
7.50 (2H, d, J = 8.1 Hz), 7.13 (2H, d, J = 8.1 Hz), 3.3-3.2 (2H, m),
2.29 (3H, s), 2.3-2.0 (2H, m), 1.33 (3H, s).
13C NMR (DMSO-d6, 75 MHz): d = 173.7, 145.1, 137.9, 128.1,
125.4, 56.3, 37.4, 32.2, 20.7, 20.2.
Anal. Calcd. for C12H18N2O4S: C, 50.33; H, 6.34; N, 9.78%. Found:
C, 50.22; H, 6.24; N, 9.61%.
Reduction was performed also with another method as follows:
Raney nickel (0.33 g, wet) was washed with MeOH (3 × 3 mL) un-
der a stream of N2, and a solution of (1R,3’S)-N-[3’-2D-(3’-meth-
yl)pyrazoline]carbonyl-2,10-camphorsultam (325 mg, 1.00 mmol)
in MeOH (3 mL) was added. The mixture was stirred at 23 °C for
29 h under H2 at atmospheric pressure. The resulting mixture was
filtered through a short plug of Celite (0.5 cm x 0.5 cm) followed
washing with MeOH (4 mL). To the solution was added p-toluene-
sulfonic acid monohydrate (193 mg, 1.01 mmol), and the mixture
was concentrated in vacuo. The resulting oily solid was washed
with THF (1.5 mL) to give (S)-3-amino-3-methylpyrrolidin-2-one
p-toluenesulfonate (153 mg, 0.536 mmol, 54%) as a colorless solid.
IR (KBr) n = 3158, 3050, 2826, 1619, 1495, 1340, 1186, 880, 632,
554 cm−1.
1H NMR (D2O, 300 MHz): d = 3.07 (1H, d, J = 17.9 Hz), 2.82 (1H,
d, J = 17.9 Hz), 1.53 (3H, s).
13C NMR (D2O, 75 MHz): d = 178.7, 177.5, 61.3, 43.3, 25.2.
Anal. Calcd. for C5H9NO4: C, 40.82; H, 6.17; N, 9.52%. Found: C,
40.64; H, 6.28; N, 9.27%.
The stereosiomeric purity of the pyrrolidine adduct was assayed by
conversion to the corresponding Mosher amide.
(S)-(+)-N-Acetyl-2-methylaspartic Acid Dibenzyl Ester (7)
A mixture of (S)-2-methylaspartic acid (33.7 mg, 0.229 mmol), p-
toluenesulfonic acid monohydrate (49.7 mg, 0.261 mmol), benzyl
alcohol (0.30 ml, 2.9 mmol), and toluene (0.5 ml) was stirred at
130 °C for 3 h with removal of H2O. To the resulting solution was
added CH2Cl2 (2 mL), Et3N (1.3 mL, 9.3 mmol) and Ac2O (0.70 ml,
7.4 mmol). The mixture was stirred at 23 °C for 15 h, and the reac-
tion was quenched with sat. aq NaHCO3 (20 mL). The organic layer
was separated, and the aqueous layer was extracted with CH2Cl2 (20
mL). The combined organic solution was dried (Na2SO4). Removal
of solvent by rotary evaporation provided the unpurified reaction
product. Purification by column chromatography on silica gel (hex-
anes/EtOAc = 50/50) afforded (S)-(+)-N-acetyl-2-methylaspartic
acid dibenzyl ester (53.1 mg, 0.144 mmol, 63%) as a colorless oil;
[a]D25+4.6 (c = 0.505, CHCl3).
(S)-3-[(R)-2-Methoxy-2-(trifluoromethyl)phenylacetyl]amino-
3-methylpyrrolidin-2-one
To (S)-3-amino-3-methylpyrrolidin-2-one p-toluenesulfonate (28.7
mg, 0.100 mmol) was added (R)-(+)-a-methoxy-a-(trifluorometh-
yl)phenylacetic acid (46.4 mg, 0.198 mmol), N,N’-dicyclohexylcar-
bodiimide (40.8 mg, 0.198 mmol), and 4-(dimethylamino)pyridine
(24.4 mg, 0.200 mmol) in CH2Cl2 (2 mL). The mixture was stirred
at 35 °C for 7 h, and the solids were removed by filtration. The fil-
trate was diluted with CH2Cl2 (5 mL), washed with H2O (1 mL) fol-
lowed by sat. aq NaHCO3 (1 mL), and dried (Na2SO4). Removal of
solvent and purification by column chromatography on silica gel
(EtOAc) afforded (S)-3-[(R)-2-methoxy-2-(trifluoromethyl)phe-
nylacetyl]amino-3-methylpyrrolidin-2-one (26.0 mg, 0.0787 mmol,
79%) as a colorless solid.
1H NMR (CDCl3, 300 MHz): d = 7.6-7.5 (2H, m), 7.5-7.3 (2H, m),
7.3-7.2 (1H, m), 6.58 (1H, br s), 3.5-3.2 (2H, m), 3.45 (3H, d,
J = 1.6 Hz), 2.6-2.4 (2H, m), 1.44 (3H, s).
13C NMR (CDCl3, 75 MHz): d = 177.5, 166.1, 132.7, 129.5, 128.6,
127.5, 123.7 (q, J = 290 Hz), 83.8 (q, J = 26 Hz), 57.2, 55.1, 39.1,
34.8, 21.2.
IR (thin film): n = 3302, 1738, 1732, 1661, 1652, 1455, 1216, 1120,
697 cm−1.
1H NMR (CDCl3, 300 MHz): d 7.4-7.2 (10H, m), 6.59 (1H, br s),
5.16 (1H, d, J = 12.1 Hz), 5.14 (1H, d, J = 12.1 Hz), 5.05 (1H, d,
J = 12.1 Hz), 5.03 (1H, d, J = 12.1 Hz), 3.58 (1H, d, J = 16.5 Hz),
3.00 (1H, d, J = 16.5 Hz), 1.89 (3H, s), 1.64 (3H, s).
19F NMR (CDCl3, 282 MHz): d = -68.8 ppm (only signal), whereas
a sample of Mosher amide from racemic pyrrolidinone gave two re-
solved peaks at d -68.8 and -69.0 ppm.
13C NMR (CDCl3, 75 MHz): d = 173.7, 170.8, 169.9, 135.9, 135.5,
128.9, 128.8, 128.7, 128.6, 128.5, 67.9, 66.5, 57.9, 40.0, 23.9, 23.3.
Anal. Calcd. for C21H23NO5: C, 68.28; H, 6.28; N, 3.79%. Found:
C, 67.98; H, 6.48; N, 3.94%. HPLC (Chiralpak AD column, 25
cm x 0.46 cm i.d., Hexanes/i-PrOH = 90/10, flow 1.0 ml/min): r.t.
28.6 min detected by examination of absorption at l = 254 nm.
(S)-3-tert-Butoxycarbonylamino-3-methylpyrrolidin-2-one (8)
To a solution of (S)-3-amino-3-methylpyrrolidin-2-one p-toluene-
sulfonate (68.2 mg, 0.238 mmol) in THF (2 mL) were added Et3N
(0.10 mL, 0.72 mmol) and di-tert-butyl dicarbonate (57 mg, 0.26
mmol). The mixture was stirred at 23 °C for 14 h and then concen-
trated in vacuo. The resulting residue was dissolved in sat. aq
NaHCO3 (2 mL) and extracted with Et2O (14 mL) followed by
CH2Cl2 (6 mL). The combined organic extracts were washed with
(S)-3-Amino-3-methylpyrrolidin-2-one p-Toluenesulfonate (3)
A mixture of (1R,3’S)-N-[3’-2D-(3’-methyl)pyrazoline]carbonyl-
2,10-camphorsultam (164 mg, 0.504 mmol), platinum(IV) oxide
(11.4 mg, 0.0502mmol), p-toluenesulfonic acid monohydrate (96.2
Synthesis 2000, No. 1, 135–138 ISSN 0039-7881 © Thieme Stuttgart · New York

138
H. Sasaki, E. M. Carreira
PAPER
brine (10 mL) and dried (Na2SO4). Removal of solvent provided the
unpurified product as an oily solid. The solid was washed with hex-
anes (5 mL) to give (S)-3-tert-butoxycarbonylamino-3-methylpyr-
rolidin-2-one (35.4 mg, 0.165 mmol, 69%) as a colorless solid; mp
133-134 °C; [a]D25+22.8 (c = 0.350, CHCl3).
(4) Mish, M. R.; Guerra, F. M.; Carreira, E. M. J. Am. Chem. Soc.
1997, 119, 8379.
(5) Whitlock, G. A.; Carreira, E. M. J. Org. Chem. 1997, 62,
7916.
(6) (a) Thorsett, E. D. (Merck and Co., Inc.). South African Patent
ZA 83 09532; Chem. Abstr. 1986, 105, 226395f.
(b) Parsons, W. H. (Merck and Co., Inc.). South African
Patent ZA 85 04765; Chem. Abstr. 1987, 106, 32870g.
(7) (a) Stosius, K.; Philippi, E. Monatsch. Chem. 1924, 45, 457.
(b) Cocker, W.; Lapworth, A. J. Chem. Soc. 1931, 1391.
(c) Pfeiffer, P.; Heinrich, E. J. Prakt. Chem. 1936, 146, 105.
(d) Terashima, S.; Achiwa, K.; Yamada, S. Chem. Pharm.
Bull. 1966, 14, 572.
1
IR (KBr):
n
= 3362, 1720, 1686, 1527, 1370, 1279, 1173, 1086 cm− .
1H NMR (CDCl3, 300 MHz): d = 5.67 (1H, br s), 5.08 (1H, br s),
3.48-3.37 (1H, m), 3.37-3.24 (1H, m) 2.66-2.52 (1H, m), 2.38-
2.24 (1H, m), 1.44 (9H, s), 1.39 (3H, s).
13C NMR (CDCl3, 75 MHz): d = 178.5, 155.0, 79.9, 56.6, 38.7, 34.8,
28.4, 22.3.
Anal. Calcd. for C10H18N2O3: C, 56.06; H, 8.47; N, 13.07%. Found:
C, 56.22; H, 8.36; N, 13.27%.
(e) Terashima, S.; Achiwa, K.; Yamada, S. Chem. Pharm.
Bull. 1966, 14, 1138.
(f) Schöllkopf, U. Tetrahedron 1983, 39, 2085.
(g) Aebi, J. D.; Seebach, D. Helv. Chim. Acta 1985, 68, 1507.
(h) Fadel, X. A.; Salaün, J. Tetrahedron Lett. 1987, 28, 2243.
(i) Georg. G. I.; Guan, X.; Kant, J. Tetrahedron Lett. 1988, 29,
403.
Acknowledgement
The generous support of ETH-Zentrum and F. Hoffmann-La Roche
AG is gratefully acknowledged. We thank UBE Industries Ltd., To-
kyo, Japan for sponsoring H. S.
(j) Altmann, E.; Nebel, K.; Mutter, M. Helv. Chim. Acta 1991,
74, 800.
(k) Chan, C.; Crich, D.; Natarajan, S. Tetrahedron Lett. 1992,
33, 3405.
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(10) The combined CH2Cl2 solution was concentrated and purified
by column chromatography on silica gel (hexanes/
EtOAc = 60/40) to afford (1R)-2,10-camphorsultam (90.4 mg,
0.420 mmol, 42%).
(11) The THF solution was concentrated and purified by column
chromatography on silica gel (hexanes/EtOAc = 60/40) to
afford (1R)-2,10-camphorsultam (69.2 mg, 0.321 mmol,
64%).
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Article Identifier:
1437-210X,E;2000,0,01,0135,0138,ftx,en;Z06699SS.pdf
Synthesis 2000, No. 1, 135–138 ISSN 0039-7881 © Thieme Stuttgart · New York