An acetone-derived chiral stabilised azomethine ylid: Synthesis of enantiomerically pure 5,5,-dimethylproline derivatives

Article abstract of DOI:10.1055/s-2001-18762

The chiral stabilised azomethine ylid 3 generated in situ via Lewis acid catalysed condensation of (5S)-5-phenylmorpholin-2-one with 2,2-dimethoxypropane call be trapped diastereoselectively with singly and doubly activated dipolarophiles. The cycloadducts may be dismantled in one pot to furnish enantiomerically pure 5,5-dimethylproline derivatives.

Full text of DOI:10.1055/s-2001-18762

1836
LETTER
An Acetone-derived Chiral Stabilised Azomethine Ylid: Synthesis of
Enantiomerically Pure 5,5,-Dimethylproline Derivatives
An
A
cetone-derive
a
d
C
hiral St
v
a
bilised
A
zo
i
methin
d
e
Y
lid J. Aldous,a,1 Michael G. B. Drew,b Estelle M.-N. Hamelin,b Laurence M. Harwood,*b Archie B. Jahans,b
Sukanthini Thurairatnama,1
a
Rhône Poulenc Rorer Limited, Rainham Road South, Dagenham, Essex RM10 7XS, UK
b
Department of Chemistry, University of Reading, Whiteknights, Reading, Berkshire RG6 6AD, UK
Fax +44(118)9316782; E-mail: l.m.harwood@reading.ac.uk
Received 22 August 2001
Dedicated to the memory of Professor J. K. (Hamish) Sutherland
R
X
H
Abstract: The chiral stabilised azomethine ylid 3 generated in situ
via Lewis acid catalysed condensation of (5S)-5-phenylmorpholin-
2-one with 2,2-dimethoxypropane can be trapped diastereoselec-
tively with singly and doubly activated dipolarophiles. The cycload-
ducts may be dismantled in one pot to furnish enantiomerically pure
5,5-dimethylproline derivatives.
X
R
Y
R
H
H
Y
R
Ph
N
N
CO2H
H
O
O
Key words: ketone-derived chiral stabilised azomethine ylid, 5,5-
dimethylprolines, Lewis acid
X
Y
5,5-Dimethylproline (dmP)2 has been shown to induce a
restrained cis-amide bond conformation when included in
peptidic systems. The racemic material has been incorpo-
rated into the dipeptide Boc-L-Phe-DL-dmP-OMe which
was shown to exist as 90% the cis-conformer.3 More re-
cently, enantiomerically pure L-dmP, obtained from the
racemate by resolution, has been incorporated into N-
acetylated tripeptides designed to mimic regions of RNase
A which possess cis-proline peptide linkages.4 In the case
of the tripeptide Ac-Tyr-L-dmP-Asn, 100% cis-confor-
mation could be achieved; whereas Ac-Asn-L-dmP-Tyr
gave an equilibrium mixture in which the cis-conformer
predominated. However, the lack of generality of the re-
ported synthetic approaches to the parent2,3 severely re-
stricts scope for investigation in this area using
functionalised analogues.
R
R
R
H
R
H
H
N
O
Ph
Ph
N
O
O
O
O
(1)
Scheme 1
conditions proved equally fruitless. Presumably the com-
bination of reduced electrophilicity of the ketone and the
increased steric hindrance associated with formation of
the ketone-derived azomethine ylid is responsible for this
lack of reactivity. We experienced no better fortune when
replacing acetone with 2-methoxypropene under a wide
variety of conditions, but when 1 was treated with 2,2-
dimethoxypropane in refluxing THF in the presence of
MgBr2 Et2O we observed disappearance of starting mate-
rial and the formation of a new product. This material was
very labile but could be sufficiently purified to identify it
as the adduct 2 (Scheme 2).6
With this in mind, we considered that our chiral azome-
thine ylid cycloaddition strategy for accessing enantio-
merically pure prolines5a–i could provide a convenient and
general approach to enantiomerically pure 5,5-disubstitut-
ed prolines if it were possible to generate an ylid by con-
densation of a ketone with (5S)-5-phenylmorpholinone 1
(Scheme 1). However, to the best of our knowledge, the
generation of ylids by condensing ketones with secondary
amines has not been reported, indicating potential pitfalls
to such a route.
Although isolation of 2 in satisfactory yields proved im-
possible, methoxymethylene analogues of 2 have been
used by Williams7 and ourselves8 as a means of generating
formaldehyde-derived azomethine ylids in situ. To our
satisfaction, repeating this reaction in the presence of N-
phenylmaleimide led to formation of two products with a
gross structure corresponding to isomeric cycloadducts,
indicating the intermediacy of the terminally disubstituted
azomethine ylid 3. The products were identified by spec-
troscopic analysis, particularly NOE difference experi-
ments,9 as the endo- and exo-cycloadducts 4a and 5a
isolated in 43% and 30% yield respectively and these as-
signments were subsequently confirmed by X-ray crystal-
lographic analysis.10
These fears were borne out by experience when attempts
at condensing acetone with 1 under conditions which had
previously been successful with aldehydes resulted in no
reaction. Surveying a range of Brønsted and Lewis acid
catalysts and a variety of increasingly forcing reaction
Synlett 2001, No. X, xx xx xx. Article Identifier:
1437-2096,E;2001,0,MM,1836,1840,ftx,en;G18301ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
An Acetone-derived Chiral Stabilised Azomethine Ylid
1837
Me
N
Me
H
Me
Me
H
OMe
O
H
H
N
Ph
Ph
N
Ph
(i)
O
O
O
O
O
(1)
(2)
(3)
X
Y
Z
4 (%)
43
5 (%)
30
Z
Y
a
b
c
–(CO)NPh(CO)–
–(CO)NMe(CO)–
CO2Me CO2Me
H
X
H
H
33
23
70
14
40
26
16
0
Z
Z
Me
Me
Me
Me
Y
Y
H
H
X
H
X
Ph
N
d
e
CO2Me
H
CO2Me
H
Ph
N
H
H
H
H
H
H
CO2Me
CN
H
H
0
O
O
O
O
(5)
(4)
f
0
exo–
endo–
g
CN
Cl
39a
Scheme 2 (i) 2,2-dimethoxypropane (2 equiv), MgBr2 Et2O, THF, . aIsolated as a circa 1:1 mixture of diastereoisomers.
Encouraged by this result, we surveyed several doubly ac- gio- and stereocontrol observed in MgBr2 Et2O-catalysed
tivated dipolarophiles and found that N-methylmaleimide aldehyde-derived ylid reactions (Figure).11 This is consis-
and dimethyl maleate furnished endo- (4b 33%; 4c 23%) tent with the inductively electron releasing methyl groups
and exo-cycloadducts (5b 26%; 5c 16%), dimethyl fuma- raising the ylid HOMO energy and increasing the reactiv-
rate furnished a single cycloadduct (4d 70%) but dimethyl ity of 3 with electron deficient alkene dipolarophiles. It
acetylenedicarboxylate did not react (Scheme 2). Spectro- also explains the unreactivity towards alkynes which react
scopic data for these adducts compared directly with those LUMOdipole–HOMOalkyne, under non-catalysed conditions
for 4a and 5a and X-ray crystallographic analyses were with these stabilised ylid systems.5c This implies that the
obtained for 5b, 4c–e.10
Lewis acid is playing a different role to that in the previ-
ously reported Lewis acid catalysed aldehyde-derived
azomethine ylid reactions. We therefore conclude that the
Lewis acid exerts its influence on azomethine ylid gener-
ation rather than complexing with the carbonyl of the
morpholinone as we have proposed to explain the regio-
and stereoselectivity reversal in the catalysed aldehyde
system.11
Monoactivated alkene dipolarophiles also reacted and, al-
though the yields were low to moderate, ylid 3 nonethe-
less exhibits a greater reactivity compared to the
corresponding aldehyde-derived ylids which react very
poorly, if at all, with monoactivated dipolarophiles.5a–i
Methyl acrylate and acrylonitrile afforded the correspond-
ing endo-adducts 4e and 4f in 14% and 40% yields respec-
tively as the sole cycloadducts and 1-chloroacrylonitrile This in turn provides a clue as to why the particular com-
afforded a roughly equal ratio of inseparable diastereo- bination of dimethoxypropane–MgBr2 Et2O succeeds in
meric addition products 4g and 5g in 39% combined yield generating 2 but 2-methoxypropene–Brønsted acid com-
(Table in Scheme 2). Spectroscopic data were consistent binations fail, as both would be expected to generate es-
with the regiochemistry and endo-stereochemistry for 4e– sentially the same oxonium species. Formation of the
g and an X-ray crystallographic analysis confirmed the oxonium species from 2-methoxypropene involves C-pro-
structure of 4e.9,10 However, the alkyne dipolarophile me- tonation; whereas 2,2-dimethoxypropane undergoes
thyl propynoate did not undergo cycloaddition.
Lewis acid O-complexation followed by anchimerically
assisted loss of a methoxy-group. As this latter step is rate
determining,12 formation of the oxonium species in this
instance is entropically favoured, presumably resulting in
a sufficiently enhanced equilibrium concentration of the
electrophile to overcome the deactivating stereoelectronic
bias.
The reactivity, regioselectivity and stereoselectivity of
this system are worthy of comment. The endo-selectivity
observed in all cases and the regioselection found with the
monoactivated dipolarophiles leads us to conclude that
these cycloadditions are proceeding via the HOMOdipole
LUMOdipolarophile pathway in keeping with the control pre-
–
viously observed in uncatalysed cycloadditions of these The final stage of the study was to remove the template to
ylids with alkene dipolarophiles5a–i but different to the re- obtain the free proline derivatives. The adducts 4a–e and
Synlett 2001, No. X, 1836–1840 ISSN 0936-5214 © Thieme Stuttgart · New York

1838
D. J. Aldous et al.
LETTER
R
H
R
H
H
R
H
H
R
Ph
N
O
Ph
N
O
Ph
N
O
O
O
L
O
aldehyde derived ylid
(thermal conditions)
aldehyde derived ylid
(Lewis acid complex)
ketone derived ylid
alkyne
alkene
alkene
alkyne
•
•
•
HOMOalkene–LUMOdipole
LUMOalkene–HOMOdipole
no reaction
HOMOalkene–LUMOdipole
Figure Schematic illustrating proposed HOMO–LUMO interactions of catalysed and uncatalysed reactions of aldehyde and uncatalysed
reactions of ketone-derived azomethine ylids with alkene and alkyne dipolarophiles.
5a–c were subjected to the hydrogenolysis in aqueous
Z
Z
Me
Me
Me
Me
Y
Y
methanol using Pearlman’s catalyst (Pd(OH)2/C) and
TFA under 5 atmospheres of hydrogen for 48 hours5b and
afforded the corresponding prolines 6a–e and 7a–c in
good yields (Scheme 3). Samples of the pure amino acids
were isolated by trituration with diethyl ether or by using
reverse-phase dry flash chromatography13 eluting with 1:1
methanol–water.14
H
H
X
X
Ph
N
H
Ph
N
H
H
H
H
O
O
O
O
(5)
(4)
(i)
In summary, we have developed a system which permits
us to generate and trap for the first time, stabilised azome-
thine ylid 3 formally derived by condensing the secondary
amine 1 with acetone. The reactivity of this system has
given us insights into the reaction mechanism operating.
The adducts 4 and 5 permit access to a novel range of
enantiomerically pure 5,5-dimethylprolines, constituting
the first such general synthesis and opening up prospects
for the synthesis of a wide range of 5,5-disubstituted pro-
lines.
Y
X
X
Y
Z
H
Z
H
Me
Me
H
Me
Me
H
N
H
N
H
CO2H
CO2H
(6)
(7)
7 (%)
81
X
Y
Z
6 (%)
72
a
b
c
d
e
–(CO)NPh(CO)–
H
Acknowledgement
E. M.-N. H. thanks Rhône Poulenc Rorer Limited for financial sup-
port.
–(CO)NMe(CO)–
CO2Me CO2Me
H
H
71
65
72
60
References
CO2Me
H
H
CO2Me quant.
78
(1) Current address: Aventis Pharmaceuticals Inc., Mail Code:
N2334, Route 202-206, P.O. Box 6800, Bridgewater, NJ,
08807-0800, USA.
CO2Me
H
(2) Bonnett, R.; Clark, V. M.; Giddey, A.; Todd, S. A. J. Chem.
Soc. 1959, 2087.
Scheme 3 (i) Pd(OH)2, aq MeOH, TFA, H2 (5 atm).
(3) Magaard, V. W.; Sanchez, R. M.; Bean, J. W.; Moore, M. L.
Tetrahedron Lett. 1993, 34, 381.
(4) An, S. S. A.; Lester, C. C.; Peng, J.-I.; Li, Y.-J.; Rothwarf,
D. M.; Welker, E.; Thannhauser, T. W.; Zhang, L. S.; Tam,
J. T.; Scheraga, H. A. J. Am. Chem. Soc. 1999, 121, 11558.
Synlett 2001, No. X, 1836–1840 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
An Acetone-derived Chiral Stabilised Azomethine Ylid
requires 391.1657, 391(55), 104(100).
1839
(5) (a) Anslow, A. S.; Harwood, L. M.; Phillips, H.; Watkin, D.
Tetrahedron: Asymmetry 1991, 2, 169. (b) Anslow, A. S.;
Harwood, L. M.; Phillips, H.; Watkin, D. Tetrahedron:
Asymmetry 1991, 2, 997. (c) Anslow, A. S.; Harwood, L.
M.; Phillips, H.; Watkin, D. J.; Wong, L. F. Tetrahedron:
Asymmetry 1991, 2, 1343. (d) Harwood, L. M.; Lilley, I. A.
Tetrahedron Lett. 1993, 537. (e) Harwood, L. M.; Kitchen,
L. C. Tetrahedron Lett. 1993, 6603. (f) Anslow, A. S.; Cox,
G. G.; Harwood, L. M. Chemistry of Heterocyclic
N-Phenyl (2S,6S,7S,8R)-9,9-dimethyl-2-phenyl-1-aza-4-
oxa[4.3.01,6]bicyclononan-5-one-7,8-dicarboximide (5a):
Colourless crystals (30%), mp 188–189 °C, [ ]D25 –50.5 (c
0.45, CHCl3); (Found C, 70.68; H, 5.65; N, 7.08.
C23H22N2O4 requires C, 70.75; H, 5.68; N, 7.17%.);
max
(KBr disc): 1754, 1712 cm–1; 1H NMR (250 MHz, CDCl3)
= 7.57–7.30 (10 H, m), 4.53 (1 H, s), 4.47 (1 H, m), 4.30 (1
H, m), 4.24 (1 H, d, J’= 8.4 Hz), 4.06 (1 H, t, J = 11.5 Hz),
3.23 (1 H, d, J = 8.4 Hz), 1.24 (3 H, s), 1.01 (3 H, s); NOE
Compounds 1995, 10, 1393. (g) Harwood, L. M.; Lilley, I.
A. Tetrahedron: Asymmetry 1995, 6, 1557. (h) Anslow, A.
S.; Harwood, L. M.; Lilley, I. A. Tetrahedron: Asymmetry
1995, 6, 2465. (i) Harwood, L. M.; Lilley, I. A. Synlett 1996,
1010.
H6
H3 10.0%; 13C NMR (62.5 MHz, CDCl3):
=
176.4, 174.3, 171.8, 139.0, 131.4, 129.4, 128.9, 128.2,
126.4, 70.9, 66.2, 60.9, 54.6, 54.2, 44.1, 26.7, 23.6; MS
(C.I.): m/z 391.1643 [MH+] C23H22N2O4 requires 391.1657,
391 (56), 104 (100).
(6) Preparation of (5S)-N-(methoxy-1-methylethyl)-5-
phenylmorpholin-2-one (2):
Methyl (2S,6S,8S)-9,9-dimethyl-2-phenyl-1-aza-4-
oxa[4.3,01,6]bicyclononan-5-one-8-carboxylate (4e):
Colourless crystals (14%), mp 100–106 °C, [ ]D25 +6.3 (c
0.20, CHCl3); max (KBr disc): 1750, 1741 cm–1; 1H NMR
(250 MHz, CDCl3): = 7.47–7.29 (5 H, m), 4.28–4.10 (4 H,
m), 3.70 (3 H, s), 2.99–2.80 (2 H, m), 2.43–2.34 (1 H, m),
0.90 (6 H, s); 13C NMR (63 MHz, CDCl3): = 175.0, 172.3,
142.0, 129.0, 128.4, 127.5, 71.2, 64.2, 56.6, 56.2, 54.2 52.2,
28.3, 26.4, 16.3; MS (C.I.): m/z 304.1554 [MH+] C17H22N4
requires 304.1548.
Dimethoxypropane (0.16 mL, 1.36 mmol, 2 equiv) was
added via syringe to a suspension of (5S)-5-phenyl-
morpholin-2-one (120 mg, 0.68 mmol, 1 equiv) and
magnesium bromide etherate (174 mg, 0.68 mmol, 1 equiv)
in 10 mL THF. The reaction mixture was heated to reflux
under nitrogen for 2.5 h. The solution was then allowed to
cool down to r.t. and was filtered through a short pad of
silica, washing with ethyl acetate. The solvent was removed
in vacuo and flash chromatography on silica using petroleum
ether–ethyl acetate 1:1 furnished the title compound as a
yellow oil (yields variable). max(film): 1741 cm–1; 1H NMR
(400 MHz, CDCl3): = 7.43–7.26 (5 H, m), 4.30 (1 H, t, J =
7.9 Hz), 4.17 (1 H, t, J = 7.9 Hz), 3.67 (1 H, t, J = 7.9 Hz),
3.51 (3 H, s), 3.37 (1 H, d, J = 16.5 Hz), 3.28 (1 H, d, J = 16.5
Hz), 1.46 (3 H, s), 1.30 (3 H, s); 13C NMR (100 MHz,
CDCl3): = 172.4, 128.9, 128.7, 128.2, 128.1, 128.0, 127.6,
95.5, 72.2, 65.7, 51.7, 48.4, 27.9, 22.4; MS (C.I.): m/z
250.1441 [MH+] C14H20NO3 requires 250.1443.
(10) Crystallographic data for the structures reported in this paper
have been deposited with the Cambridge Crystallographic
Data Centre; reference numbers CCDC 169323 (4a), 169324
(4c), 169325 (4d), 169326 (4e), 169327 (5a), 169328 (5b).
Copies of the data can be obtained on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK (fax:
+44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk).
(11) Harwood, L. M.; Manage, A. C.; Robin, S.; Hopes, S. F. G.;
Watkin, D. J.; Williams, C. E. Synlett 1993, 777.
(7) (a) Williams, R. M.; Zhai, W.; Aldous, D. J.; Aldous, S. C.
J. Org. Chem. 1992, 57, 6527. (b) Sebaha, R.; Williams, R.
M. J. Am. Chem. Soc. 2000, 122, 5666.
(8) Alker, D.; Harwood, L. M.; Williams, C. E. Tetrahedron
1997, 53, 12671.
(12) Cordes, E. H. Prog. Phys. Org. Chem. 1967, 4, 1.
(13) O' Neil, I. Synlett 1991, 661.
(14) General Method for the Preparation of Prolines 6a–e,
7a–c: The cycloadduct (1 equiv) was dissolved in aq
methanol (20:1 MeOH:H2O, 20 mL mmol–1) in a Fisher
Porter bottle. TFA (9 L, 0.12 mmol, 1 equiv) and
Pearlman’s Catalyst (palladium hydroxide, 1 equiv by mass)
were added to the stirred suspension, which was then
degassed and subjected to hydrogen at 5 atm for two days.
The solution was then passed through a pad of Celite® to
remove the catalyst and the solvent removed in vacuo.
Trituration of the crude mixture with diethyl ether allowed in
some cases the precipitation of the amino acid as a colourless
powder, which was then filtered and dried in vacuo. If the
amino acid could not be obtained by trituration, it was
purified by reverse phase dry flash column chromato-
graphy,13 eluting with methanol–water 1:1.
(9) General Method for Preparation of Cycloadducts 4a–e
and 5a–c: Dimethoxypropane (2 equiv) was added via
syringe to a suspension of (5S)-5-phenylmorpholin-2-one
(1 equiv), dipolarophile (2 equiv) and magnesium bromide
etherate (1 equiv) in THF (15 mL mmol–1 of morpholinone).
The reaction mixture was heated to reflux under nitrogen for
2.5 h. The solution was then allowed to cool down to r.t. and
was filtered through a short pad of silica, washing with ethyl
acetate. Removal of the solvent in vacuo yielded the crude
mixture along with excess dipolarophile. Flash chromato-
graphy using gradient elution, typically petroleum ether–
ethyl acetate 3:1 to petroleum ether–ethyl acetate 1:1,
furnished the pure compounds.
Selected Spectroscopic Data of (2S,3R,4S)-5,5-Dimethyl-
3,4-(N-phenyldicarboximido)pyrrolidine-2-carboxylic
Acid (6a): Colourless powder (72%), mp 220–228 °C, [ ]D
Selected Spectroscopic Data of N-Phenyl-(2S,6S,7R,8S)-
9,9-dimethyl-2-phenyl-1-aza-4-oxa[4.3.01,6]bicyclo-
nonan-5-one-7,8-dicarboximide (4a): Colourless crystals
(43%), mp 210–216 °C, [ ]D25 +16.2 (c 0.55, CHCl3);
(Found C, 70.40; H, 5.62; N, 7.00. C23H22N2O4 requires C,
70.75; H, 5.68; N, 7.17%.); max (KBr disc): 1751, 1712
cm–1; 1H NMR (250 MHz, CDCl3): = 7.53–7.29 (10 H, m),
4.59 (1 H, d, J = 8.4 Hz,), 4.51 (1 H, dd, J = 5.7, J’ = 11.3
Hz), 4.33 (1 H, dd, J = 5.7, J’= 10.1 Hz), 4.16 (1 H, dd, J =
10.1, J’= 11.5 Hz), 3.90 (1 H dd, J = 8.4, J’= 10.0 Hz), 3.34
(1 H, d, J = 10.0 Hz), 1.23 (3 H, s), 1.12 (3 H, s); NOE H6
25
44.4 (c 0.45, MeOH); max (KBr disc): 3400, 1716, 1710,
1704 cm–1; 1H NMR (250 MHz, CD3OD): = 7.50–7.29 (5
H, m), 4.80 (1 H, d, J = 8.6 Hz), 4.17 (1 H, t, J = 8.6 Hz),
3.50 (1 H, d, J = 8.6 Hz), 1.65 (3 H, s,), 1.59 (3 H, s); 13
C
NMR (62.5 MHz, MeOD): = 175.0, 134.1, 130.5, 130.3,
128.6, 66.5, 61.6, 54.3, 48.1, 28.1, 23.0; MS (C.I.): m/z
289.1184 [MH+] C15H16N2O4 requires 289.1188.
(2S,3S,4R)-5,5-Dimethyl-3,4-(N-phenyldicarbox-
imido)pyrrolidine-2-carboxylic acid (7a): Colourless
powder (81%), mp 168–170 °C, [ ]D25 +51.3 (c 0.30,
MeOH); max (KBr disc): 3400, 1721, 1716, 1711 cm–1; 1H
NMR (250 MHz, CD3OD): = 7.57–7.31 (5 H, m), 4.70
(1 H, d, J = 4.2 Hz), 4.31 (1 H, dd, J = 4.2, J’ = 9.3 Hz), 3.59
H3 8.5%, H7
H6 8.0%; 13C NMR (62.5 MHz,
CDCl3): = 175.0, 173.5, 170.3, 139.3, 131.8, 129.2, 129.0,
128.7, 128.3, 126.6, 71.8, 65.0, 58.6, 55.7, 54.8, 44.4, 30.4,
18.3 (CH3); MS (C.I.): m/z 391.1643 [MH+] C23H22N2O4
Synlett 2001, No. X, 1836–1840 ISSN 0936-5214 © Thieme Stuttgart · New York

1840
D. J. Aldous et al.
LETTER
(1 H, d, J = 9.3 Hz), 1.61 (6 H, s);13C NMR (62.5 MHz,
MeOD). = 176.8, 176.8, 174.8, 133.7, 130.5, 130.3, 128.3,
67.9, 62.5, 54.9, 49.0, 28.4, 22.8; MS (C.I.): m/z 289.1198
[MH+] C15H16N2O4 requires 289.1188.
(2S,4S)-4-(Carbomethoxy)-5,5-dimethylpyrrolidine-2-
carboxylic Acid (6e): Colourless powder (78%), [ ]D25 –3.3
(c 0.25, H2O); max (KBr disc): 3430, 1731, 1640 cm–1; 1H
NMR (250 MHz, CD3OD): = 4.36 (1 H, t, J = 9.25 Hz),
3.74 (3 H, s), 3.12 (1 H, dd, J = 7.7, J’ = 9.6 Hz), 2.71 (1 H,
m), 2.54 (1 H, m), 1.60 (3 H, s), 1.34 (3 H, s); 13C NMR (62.5
MHz, MeOD): = 173.3, 172.3, 67.8, 59.0, 53.9, 53.2, 31.6,
26.2, 22.0; MS (C.I.): m/z 202.2306 [MH+] C9H16NO4
requires 202.2303.
Synlett 2001, No. X, 1836–1840 ISSN 0936-5214 © Thieme Stuttgart · New York