A new and efficient access to oxazoline-5-carboxylates and amino acid derivatives with cyclopropyl groups

Full text of DOI:10.1021/jo990170y

3850
J . Org. Chem. 2000, 65, 3850-3852
would be the first case in which an oxazoline would be
A New a n d Efficien t Access to
formed in a domino process consisting of a Michael
addition and immediately ensuing ring closure by in-
tramolecular nucleophilic substitution. The resulting
spirocyclopropanated oxazolinecarboxylates 5 would be
protected 2-hydroxy-2-(1'-aminocyclopropyl)acetic acid
derivatives with an interesting combination of function-
alities for further elaboration.
When methyl 2-chloro-2-cyclopropylideneacetate (1a )
in acetonitrile solution was treated with benzamide (2a )
in the presence of sodium hydride at 0 °C and the mixture
was allowed to warm to room temperature overnight, the
methyl 2-phenylspirocyclopropane-1',4-oxazoline-5-car-
boxylate (5a ) was isolated in 60% yield (Scheme 1). The
structure could be assigned on the basis of its 1H and
13C NMR and MS data, and it was rigorously proved by
X-ray crystallography.12
Oxa zolin e-5-ca r boxyla tes a n d Am in o Acid
Der iva tives w ith Cyclop r op yl Gr ou p s1
Marcus W. No¨tzel,† Markus Tamm,† Thomas Labahn,‡
Mathias Noltemeyer,‡ Mazen Es-Sayed,§ and
Armin de Meijere*,†
Institute fu¨r Organische und Anorganische Chemie der
Georg-August-Universita¨t Go¨ttingen, Tammannstrasse 2-4,
D-37077 Go¨ttingen, Germany and Bayer AG,
Landwirtschaftszentrum, Alfred-Nobel-Strasse 50,
Geb. 6510, D-40789 Monheim, Germany
Received J anuary 29, 1999
Cyclopropyl groups containing homologues of natural
amino acids are gaining an ever increasing interest as
potential enzyme inhibitors2 and conformationally re-
stricted building blocks for peptidomimetics.3 A wide
range of biological activities has been uncovered for such
unnatural amino acid analogues and small peptides
containing them.4 Quite a variety of such cyclopropane
amino acids and their derivatives have been prepared via
sequences of Michael addition, nucleophilic substitution,
and possible further transformations5-8 from the highly
reactive acrylate analogues methyl 2-chloro-2-cyclopro-
pylideneacetates 1.9 In view of the fact that even weakly
nucleophilic deprotonated oxazolidinones add to 1 under
appropriate conditions,7 it was of interest to study the
addition of primary carboxamides to 1, as the adducts
would have the potential to undergo ring closure to
oxazolines 5 by intramolecular substitution of the R-chlo-
rine.10 Such ring closures are well documented,11 but this
Nicotinamide (2b), furan-2-carboxamide (2c), and sub-
stituted benzamides 2d -o under the same conditions
gave the corresponding oxazolines 5b-o in yields ranging
from 38% to 77% (Table 1).
It is remarkable that of four possible diastereomers
only two are formed in the Michael additions of the
deprotonated amide 2 to the 2'-substituted 2-cyclopropy-
lideneacetates 1b,c, and of these two one is highly
favored in the cases of 5p -r ,t [diastereomeric ratio (dr)
up to 17:1]. This means one chiral center was formed
diastereoselectively during the addition of 2 to the two
prochiral centers of 1b,c. The relative configuration of
the major diastereomer of the 4-nitrophenyl-substituted
oxazolinecarboxylate 5s was proved by an X-ray crystal
structure analysis12 to be 4S*,5R*,2'R*.
The new oxazolinecarboxylates 5 are suitable precur-
sors to 2-(1'-aminocyclopropyl)-2-hydroxyacetic acid (7).
While hydrolysis of 5a under basic conditions (NaOH in
THF) led only to the oxazolinecarboxylic acid 6, the free
amino acid 7 could be obtained under acidic conditions.
However, 7 was not isolated but immediately benzoy-
lated to the more easily purified N-benzoyl derivative 8
(Scheme 2).
† Institut fu¨r Organische Chemie.
‡ Institut fu¨r Anorganische Chemie.
§ Bayer AG.
(1) Part 56 in the series “Cyclopropyl Building Blocks in Organic
Synthesis”. For Part 55 see: Winsel, H.; Gazizova, V.; Kulinkovich,
O.; Pavlov, V.; de Meijere, A. Synlett 1999, 1999-2003. For Part 54
see: de Meijere, A.; Nu¨ske, H.; Es-Sayed, M.; Schroen, M.; Labahn,
T.; Bra¨se, S. Angew. Chem. 1999, 111, 3881-3884; Angew. Chem., Int.
Ed. Engl. 1999, 38, 3669-3672.
(2) (a) Pirrung, M. C.; Cao, J .; Chen, J . J . Org. Chem. 1995, 60,
5790-5794. (b) Pirrung, M. C.; Han, H.; Chen, J . J . Org. Chem. 1996,
61, 4527-4531. (c) Pirrung, M. C.; Kaiser, L. M., Chen, J . Biochemistry
1993, 32, 7445-7450.
This benzoyl derivative 8 can be viewed as a cyclopro-
panated analogue of the side chain in Taxol (9). It
remains to be seen whether replacement of the natural
side chain in Taxol with the acyl residue of 8 would lead
to interesting properties of the pharmacophor.13
Simple alkanecarboxamides do not form the corre-
sponding oxazolinecarboxylates 5 in good yield, which is
probably a result of their C,H acidity R to the carbonyl
group. Acetamide (2p ) gave only 6% of 5w , whereas
propionamide (2q), butyramide (2r ), and pivalamide (2s)
(3) Burgess, K.; Ho, K.-K.; Moye-Sherman, D. Synlett 1994, 575-
583.
(4) (a) Salau¨n, J . Top. Curr. Chem. 1999, 207, 1-88. (b) Salau¨n, J .;
Baird, M. S. Curr. Med. Chem. 1995, 2, 511-542. (c) Huang, Z.; He,
Y.-B.; Raynor, K.; Tallent, M.; Reisine, T.; Goodman, M. J . Am. Chem.
Soc. 1992, 114, 9390-9401. (d) Zhu, Y.-F.; Yamazaki, T.; Tsang, J .
W.; Lok, S.; Goodman, M. J . Org. Chem. 1992, 57, 1074-1081.
(5) For reviews see: (a) de Meijere, A.; Wessjohann, L. Synlett 1990,
20-32. (b) de Meijere, A. In New Aspects of Organic Chemistry II,
Proceedings of the Fifth International Kyoto Conference on New
Aspects of Organic Chemistry-IKCOC 5, Kyoto, Nov 11-15 1991;
Oshiro, Y., Ed.; Kodansha: Tokyo, 1992; p 181. (c) de Meijere, A.;
Kozhushkov, S. I.; Hadjiarapoglou, L. Top. Curr. Chem. 1999, 207,
149-227.
(6) (a) Wessjohann, L.; Krass, N.; Yu, D.; de Meijere, A. Chem. Ber.
1992, 125, 867-882. (b) Tamm, M.; Thutewohl, M.; Ricker, C.; Bes,
M. T.; de Meijere, A. Eur. J . Org. Chem. 1999, 2017-2024.
(7) (a) Es-Sayed, M.; Gratkowski, C.; Krass, N.; de Meijere, A.
Synlett 1992, 962-964. (b) Es-Sayed, M.; Gratkowski, C.; Krass, N.;
Meyers, A. I.; de Meijere, A. Tetrahedron Lett. 1993, 34, 289-292.
(8) Wessjohann, L.; Giller, K.; Zuck, B.; Skattebøl, L.; de Meijere,
A. J . Org. Chem. 1993, 58, 6442-6450.
(11) For examples see: (a) Gabriel, S.; Elfeldt, P. Chem. Ber. 1891,
24, 3213-3228. (b) Cassebaum, H.; Uhlig, K. J . Prakt. Chem. 1973,
315, 1057-1066. (c) Flouzat, C.; Guillaumet, G. Synthesis 1990, 64-
66. (d) Nishiyama, H.; Yamaguchi, S.; Kondo, M.; Itoh, K. J . Org. Chem.
1992, 57, 4306-4309. (e) Perry, J . R.; Wilson, B. D. J . Org. Chem. 1992,
57, 6351-6354. (f) Minami, T.; Isonaka, T.; Okada, Y.; Ichikawa, J . J .
Org. Chem. 1993, 58, 7009-7015.
(12) Crystallographic data for the structures reported in this paper
have been deposited with the Cambridge Crystallographic Centre as
supplementary publication CCDC-113834 (5a ) and CCDC-135542 (5s).
Copies of the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge, CB2 1EZ, U.K. (a) Sheldrick, G.
M. Acta Crystallogr., Sect. A 1990, 46, 467. (b) Sheldrick, G. M.
SHELXL-93, program for crystal structure refinement: University of
Go¨ttingen: Go¨ttingen, 1993.
(9) Liese, T.; Seyed-Mahdavi, F.; de Meijere, A. Org. Synth. 1990,
69, 148-153.
(10) de Meijere, A.; Teichmann, S.; Yu, D.; Kopf, J .; Oly, M.; von
Thienen, N. Tetrahedron 1989, 45, 2957-2972.
10.1021/jo990170y CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/23/2000

Notes
J . Org. Chem., Vol. 65, No. 12, 2000 3851
Sch em e 1a
Sch em e 2
a
For details, see Table 1.
Ta ble 1. Syn th esis of Oxa zolin eca r boxyla tes 5 fr om Acid
Am id es 2 a n d Meth yl
2-Ch lor o-2-cyclop r op ylid en ea ceta tes 1
Michael
acceptor amide
yield
product (%) dr
R1
R2
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1c
1a
1a
1a
1a
2a
2b
2c
2d
2e
2f
2g
2h
2i
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
60
38
49
74
70
58
50
75
73
47
47
77
68
72
49
56
68
55
40
46
25
41
6
3-C5H4Na
2-C4H3Ob
p-CN-C6H4
o-Me-C6H4
m-Me-C6H4
p-Me-C6H4
m-F-C6H4
p-Br-C6H4
o-NO2-C6H4
p-NO2-C6H4
o-Cl-C6H4
p-Cl-C6H4
o-I-C6H4
Sch em e 3
2j
2k
2l
2m
2n
2o
2a
2e
2n
2k
2h
2b
2k
2p
2q
2r
m-I-C6H4
Ph
o-Me-C6H4
o-I-C6H4
p-NO2-C6H4
m-F-C6H4
3-C5H4Na
Et
Et
Et
Et
Et
Et
9:1
17:1
17:1
2:1
7:1
5:1
5s
5t
5u
5v
5w
5x
5y
5z
CH2CH2OBn p-NO2-C6H4
2:1
H
H
H
H
Me
Et
n-Pr
t-Bu
of 11 was used; with 2 equiv of 11 the bissulfonyl-
protected R,â-diamino acid 12 was obtained in 62% yield
(Scheme 3).
24
24
25
2s
a
b
In conclusion, methyl 2-chloro-2-cyclopropylideneace-
tates 1a -c upon treatment with carboxamides under
basic conditions undergo a domino transformation in-
volving a Michael addition followed by an intramolecular
nucleophilic substitution to afford 4-spirocyclopropane-
annelated oxazoline-5-carboxylates 5. The reactions of the
2'-substituted compounds 1b,c, with two prochiral cen-
ters, are remarkably diastereoselective in that only two
of four possible diastereomers are formed, and one of the
two in most cases is highly favored (dr up to 17:1). The
oxazoline-5-carboxylates 5 are protected R-hydroxy-â-
amino acids.
Nicotinic acid amide. Furan-2-carboxamide.
gave 5x-z in a moderate yield of 24% and 25%. Interest-
ingly, formamide in its reaction with methyl 2-chloro-2-
cyclopropylideneacetate (1a ) did not yield the 2-unsub-
stituted oxazolinecarboxylate of type 5 but the bis-
spirocyclopropanated pyrrolinedicarboxylate 13. The latter
apparently must have formed via the 1:2 Michael adduct
of formamide onto 1a . On the other hand, p-toluenesulfo-
nyl amide (11) reacted with 1a under the same conditions
to give the Michael addition-substitution product 12
rather than the N-p-toluenesulfonyl-substituted analogue
of 13. This product 12 dominated even when only 1 equiv
Exp er im en ta l Section
(13) (a) Holton, R. A.; Somoza, C.; Kim, H.-B.; Liang, F.; Biediger,
R. J .; Boatman, P. D.; Shindo, M.; Smith, C. C.; Kim, S.; Nadizadeh,
H.; Suzuki, Y.; Tao, C.; Vu, P.; Tang, S.; Zhang, P.; Murthi, K. K.;
Gentile, L. N.; Liu, J . H. J . Am. Chem. Soc. 1994, 116, 1597-1599. (b)
Holton, R. A.; Somoza, C.; Kim, H.-B.; Liang, F.; Biediger, R. J .;
Boatman, P. D.; Shindo, M.; Smith, C. C.; Kim, S.; Nadizadeh, H.;
Suzuki, Y.; Tao, C.; Vu, P.; Tang, S.; Zhang, P.; Murthi, K. K.; Gentile,
L. N.; Liu, J . H. J . Am. Chem. Soc. 1994, 116, 1599-1600. (c) Georg,
G. I.; Harriman, G. C. B.; Hepperle, M.; Himes, R. H. Bioorg. Med.
Chem. Lett. 1994, 4, 1381-1384. (d) Georg, G. I.; Harriman, G. C. B.;
Hepperle, M.; Clowers, J . S.; Vander Velde, D. G.; Himes, R. H. J . Org.
Chem. 1996, 61, 2664-2676. (e) Li, L.; Thomas, S. A.; Klein, C. M.;
Yeung, C. M.; Maring C. J .; Grampovnik, D. J .; Lartey, A.; Plattner,
J . J . J . Med. Chem. 1994, 37, 2655-2663.
Gen er a l. All chemicals used are commercially available
except for methyl 2-chloro-2-cyclopropylideneacetates 1a -c,14
which were prepared by the literature method,8 and some of the
benzamides, which were prepared according to a general pro-
cedure.15 All reactions were performed in anhydrous solvents
under an atmosphere of N2. Solvents were distilled under N2
(14) The immediate precursor to 1a , 1-chloro-1-(trichloroethenyl)-
cyclopropane, is commercially available from Merck-Schuchardt.
(15) Autorenkollektiv Organikum, 15. Aufl., VEB Dt.; Verlag der
Wissenschaften: Berlin 1984.

3852 J . Org. Chem., Vol. 65, No. 12, 2000
Notes
from sodium benzophenone (THF), 3 Å molecular sieve (aceto-
nitrile), or CaH2 (DMF). All other reagents and solvents such
as light petroleum and diethyl ether were purified by standard
procedures. Reactions were monitored by thin-layer chromatog-
raphy. Eluents for column chromatography were distilled before
use. NMR spectra were run at 250 MHz (1H) and 62.9 MHz (13C)
in CDCl3; for the oxazolinecarboxylic acid 6, DMSO-d6 was used
as solvent. Melting points are uncorrected.
Met h yl p -Tolu en esu lfon a m id o(1-p -t olu en esu lfon a m i-
d ocyclop r op yl)a ceta te (12). To a solution of p-toluenesulfona-
mide (11) (1.20 g, 7.01 mmol) in a mixture of 15 mL of THF and
5 mL of DMF was added NaH (280 mg, 7.00 mmol, 60%
dispersion in mineral oil) at
0 °C, and the mixture was
subsequently stirred for 2 h and then cooled to -78 °C. A
precooled solution of methyl 2-chloro-2-cyclopropylideneacetate
1a (500 mg, 3.41 mmol) in 5 mL of THF was added dropwise.
The mixture was stirred for 24 h and allowed to warm to room
temperature. Then 150 mL of saturated NaHCO3 (aqueous) was
added, and the mixture was extracted with CHCl3 (3 × 100 mL).
The combined organic phases were dried over Na2SO4 and the
solvents were evaporated in vacuo. Column chromatography
(column 1.5 × 30 cm; 30 g of silica gel; Et2O) yielded 950 mg
(62%) of 12 as a colorless solid, mp 160 °C, Rf 0.34 (Et2O): IR
(KBr) 3283 (NH), 2962 (C-H), 1732 (CdO), 1352 (SO2), 1157
cm-1 (SO2); 1H NMR δ 0.60-0.89 (m, 4 H), 2.41 (s, 3 H), 2.42 (s,
3 H), 3.51 (s, 1 H), 3.56 (s, 3 H), 5.65 (s, 1 H), 6.11 (s, 1 H),
7.26-7.30 (m, 4 H), 7.67-7.73 (m, 4 H); 13C NMR (DEPT) δ 12.6
(-), 13.5 (-), 21.5 (+), 21.5 (+), 37.7 (Cquat), 52.8 (+), 61.5 (+),
127.1 (+), 127.2 (+), 129.6 (+), 129.7 (+), 136.9 (Cquat), 138.4
(Cquat), 143.6 (Cquat), 143.8 (Cquat), 169.5 (Cquat); MS m/z (%) 393
(4) [M+ - CO2Me], 297 (65) [M+ - MePhSO2], 155 (58) [Me-
Gen er a l P r oced u r e. Meth yl 2-P h en ylsp ir o(cyclop r o-
p a n e-1',4-oxa zolin e)-5-ca r boxyla te (5a ). A solution of methyl
2-chloro-2-cyclopropylideneacetate (1a ) (510 mg, 3.48 mmol) and
benzamide (421 mg, 3.48 mmol) in 15 mL of anhydrous aceto-
nitrile was treated with NaH (160 mg, 4.00 mmol, 60% disper-
sion in mineral oil) at 0 °C. The suspension was subsequently
stirred for 24 h and allowed to warm to room temperature. After
filtration (200 mL Et2O, column 1.5 cm × 3 cm; 5 g of silica gel)
the solvent was evaporated in vacuo. The dark yellow residue
was purified by chromatography (light petroleum/Et2O ) 3:1,
300 mL; 1:1, 500 mL; column 1.5 cm × 30 cm; 30 g of silica gel)
to yield 486 mg (60%) of 5a as a colorless solid, mp 47 °C, Rf
0.34 (light petroleum/Et2O 1:1): IR (KBr) 3073 (C-H), 3004 (C-
H), 2949 (C-H), 1726 (CdO), 1652 (CdN) cm-1; 1H NMR δ 0.87-
1.03 (m, 2 H), 1.16-1.25 (m, 1 H), 1.30-1.38 (m, 1 H), 3.77 (s,
3 H), 4.91 (s, 1 H), 7.37-7.51 (m, 3 H), 7.92-7.97 (m, 2 H); 13C
NMR (DEPT) δ 10.4 (-), 14.7 (-), 52.2 (+), 53.2 (Cquat), 79.6 (+),
126.9 (Cquat), 127.9 (+), 128.3 (+), 131.4 (+), 163.4 (Cquat), 169.4
(Cquat); MS m/z (%) 231 (47) [M+], 172 (100) [M+ - CO2Me], 144
(49) [M+ - CO2Me - C2H4]. Anal. Calcd for C13H13NO3: C, 67.52;
H, 5.67; N, 6.05. Found: C, 67.46; H, 5.55; N, 6.00.
PhSO2+], 142 (46) [M+
C20H24N2O6S2: C, 53.08; H, 5.35; N, 6.19; S, 14.17. Found: C,
53.16; H, 5.31; N, 6.21; S, 14.15.
- 2MePhSO2]. Anal. Calcd for
Dim eth yl 4-F or m yl-4-a za d isp ir o[2.1.2.2]n on -8-en e-8,9-
d ica r boxyla te (13). To a solution of formamide (310 mg, 6.89
mmol) and methyl 2-chloro-2-cyclopropylideneacetate (1a ) (500
mg, 3.41 mmol) in 20 mL of DMF was added NaH (180 mg, 4.50
mmol, 60% dispersion in mineral oil) at -10 °C. The light grey
suspension was subsequently stirred for 15 h and allowed to
warm to room temperature. Then 20 mL of H2O was added, and
the mixture was extracted with Et2O (3 × 30 mL). The combined
organic phases were dried over Na2SO4, and the solvents were
evaporated in vacuo. Column chromatography (light petroleum/
Et2O 10:1, 500 mL; 1:1, 500 mL; column 30 cm × 1.5 cm; 30 g of
silica gel) yielded as a first fraction 80 mg of 1a (16% recovered)
and, as a second fraction, 227 mg (50%) of 13, which could be
crystallized from Et2O at -20 °C as colorless sharp needles, mp
75 °C, Rf 0.22 (light petroleum/Et2O 1:1): IR (KBr) 3015 (C-
H), 2958 (C-H), 1722 (CdO), 1673 (CdO), 1635 (CdC), 1261
2-P h en ylsp ir o(cyclop r op a n e-1',4-oxa zolin e)-5-ca r boxy-
lic Acid (6). To a solution of oxazoline 5a (250 mg, 1.08 mmol)
in 20 mL of THF was added at room temperature 3 mL of 5 N
NaOH. The solution was subsequently stirred for 24 h, then 5
mL of 100% acetic acid was added, and the solvent was
evaporated in vacuo. The residue was dissolved in dichlo-
romethane and filtered over 10 g of silica gel. Crystallization
from Et2O gave 239 mg (quantitative) of the carboxylic acid 6,
mp 171 °C (dec): IR (KBr) 3305 (O-H), 3030 (C-H), 2924 (C-
1
H), 1652 (CdN) cm-1; H NMR δ 0.93-1.19 (m, 4 H), 4.99 (s, 1
H), 7.45-7.59 (m, 3 H), 7.82-7.86 (m, 2 H); 13C NMR (DEPT) δ
9.7 (-), 14.1 (-), 53.0 (Cquat), 78.7 (+), 126.7 (Cquat), 127.4 (+),
128.7 (+), 131.6 (+), 162.4 (Cquat), 170.2 (Cquat); MS m/z (%) 217
(52) [M+], 172 (100) [M+ - COOH], 144 (63) [M+ - COOH -
C2H4]. Anal. Calcd for C12H11NO3: C, 66.36; H, 5.10; N, 6.44.
Found: C, 66.33; H, 5.16; N, 6.33.
1
(C-O) cm-1; H NMR δ 0.97-1.23 (br s, 4 H), 1.37-1.63 (br s,
2 H), 2.12-2.40 (br s, 2 H), 3.72 (s, 6 H), 7.63 (s, 1 H); 13C NMR
(DEPT) δ 9.6 (-), 14.0 (-), 48.1 (Cquat), 50.8 (Cquat), 52.4 (+),
130.9 (Cquat), 140.5 (Cquat), 155.3 (+), 161.4 (Cquat), 162.8 (Cquat);
MS m/z (%) 265 (12) [M+], 147 (23) [M+ - 2CO2Me], 119 (43)
[M+ - 2CO2Me - C2H4], 91 (36) [M+ - 2CO2Me - 2C2H4]. Anal.
Calcd for C13H15NO5: C, 58.86; H, 5.70; N, 5.28. Found: C, 58.89;
H, 5.68; N, 5.26.
2-H yd r oxy-2-(1'-b en zoyla m in ocyclop r op yl)a cet ic Acid
(8). A solution of oxazoline 5a (1.00 g, 4.32 mmol) in 10 mL of
1 N HCl was heated to 100 °C for 30 min. Subsequently 15 mL
of 5 N NaOH was added to the hot solution, which was then
cooled to 0 °C, and 1.00 g (7.11 mmol) of benzoyl chloride was
added dropwise. The mixture was then stirred for 2 h and
allowed to warm to room temperature. Next, 3 N HCl was added
until a pH of under 2 was reached, and the water phase was
extracted with 3 × 50 mL of Et2O. After drying of the organic
phases over Na2SO4, the solvents were evaporated in vacuo, and
the residue was chromatographed on silica gel (column 1.5 cm
× 20 cm; 20 g of silica gel; light petroleum/Et2O 1:1, 200 mL;
Et2O, 200 mL; CHCl3, 200 mL; to each eluent 0.1% of acetic acid
was added). After crystallization from CHCl3/light petroleum 3:1
at -20 °C, 710 mg (70%) of 8 was obtained as a colorless solid,
mp 140 °C, Rf 0.24 (Et2O): IR (KBr) 3435 (OH), 3318 (NH), 3080
(CH), 2880-2530 (br. COOH assoc.), 1713 (COOH), 1625 (CONH),
Ack n ow led gm en t. This work was supported finan-
cially by the Deutsche Forschungsgemeinschaft (SFB
416, Project A3), the Fonds der Chemischen Industrie,
and the Bayer AG, as well as through generous gifts of
chemicals by the BASF AG. M.N. is particularly grateful
to the Bayer AG for a two months stay in their
Agriculture Research Station. The authors are indebted
to Dr. Burkhard Knieriem, Go¨ttingen, for his careful
reading of the final manuscript.
1
1536 (CONH), 1314 (OH) cm-1; H NMR δ 0.73-1.09 (m, 4 H),
3.37 (br s, 1 H), 4.03 (s, 1 H), 7.39-7.54 (m, 3 H), 7.80-7.83 (m,
2 H), 8.78 (s, 1 H), 12.30 (br s, 1 H); 13C NMR (DEPT) δ 10.6
(-), 11.6 (-), 35.7 (Cquat), 72.4 (+), 127.5 (+), 128.2 (+), 131.4
(Cquat), 134.1 (+), 168.4 (Cquat), 173.9 (Cquat); MS m/z (%) 235 (1)
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterizations for compounds 5b-z, ORTEP
drawings for 5a and (4S*,5R*,2'R*)-5s and details of the data
acquisition. This material is available free of charge via the
Internet at http://pubs.acs.org.
[M+], 218 (8) [M+ - OH], 190 (63) [M+ - COOH], 172 (7) [M+
-
H2O - COOH], 105 (100) [PhCO+]. Anal. Calcd for C12H13NO4:
C, 61.27; H, 5.57. Found: C, 61.20; H, 5.54.
J O990170Y