Ring opening reactions of 1,2-didehydroprolines. Part II. Synthesis of 5-amino-2,4-dihydroxypentanoic acids, their 2-piperidones and pentanolides [1]

Article abstract of DOI:10.1007/s00706-004-0246-y

NMR spectroscopic investigations on 1,2-didehydroproline in alkaline deuterium oxide revealed incorporation of deuterium at position C-3, presumably due to the presence of acyclic 5-amino-2-oxopentanoate in solution. Reduction of this equilibrium mixture

Full text of DOI:10.1007/s00706-004-0246-y

Monatshefte f€ur Chemie 136, 719–726 (2005)
DOI 10.1007/s00706-004-0246-y
Ring Opening Reactions of
1,2-Didehydroprolines. Part II. Synthesis
of 5-Amino-2,4-dihydroxypentanoic Acids,
their 2-Piperidones and Pentanolides [1]
ꢀ
¨ ¨
Johannes Hausler and Hanspeter Kahlig
Institute for Organic Chemistry of the University Vienna, A-1090 Vienna, Austria
Received June 17, 2004; accepted July 23, 2004
Published online April 8, 2005 # Springer-Verlag 2005
Summary. NMR spectroscopic investigations on 1,2-didehydroproline in alkaline deuterium oxide
revealed incorporation of deuterium at position C-3, presumably due to the presence of acyclic 5-
amino-2-oxopentanoate in solution. Reduction of this equilibrium mixture with hydride reagents
generally yields prolines together with the 2-hydroxy acids. It could be shown that the ratio of the
two products depends strongly on the pH. This allowed the optimization of reaction conditions for the
preparation of the target compounds (2R,4R)- and (2S,4R)-5-amino-2,4-dihydroxypentanoic acid. In
order to separate these isomers and unambiguously assign their respective structures, the (3R,5R)- and
(3S,5R)-3,5-dibenzoyloxy-2-piperidones were synthesized as the key intermediates by lactamization
and benzoylation. Lactames were also directly transformed to the corresponding lactones.
Keywords. 1,2-Didehydroprolines; Deuteroprolines; Carbonyl reduction; 2-Piperidones; Amino
acids.
Introduction
In aqueous solution 1,2-didehydroproline (2a) is in a structural equilibrium with
the acyclic 5-amino-2-oxopentanoic acid (4a). Fairly stable, 4a can be obtained on
a preparative scale [2]. The hydroxy derivative 2b, however, undergoes rapid elim-
ination of water, leading to pyrrole-2-carboxylic acid. As salts 1a, 1b, both 3a, and
3b show diminished tendency to decompose [2, 3].
NMR spectroscopic investigation of 1a in alkaline solution in deuterium oxide
(pH ꢁ 13) revealed incorporation of deuterium into position C-3, presumably due
ꢀ
to the presence of minor amounts of the 2-oxocarboxylate 3a or of its enolate.
These small amounts could not be detected by NMR, but the explanation is
ꢀ
Corresponding author. E-mail: johannes.haeusler@univie.ac.at

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J. Hausler and H. Kahlig
720
Scheme 1
Scheme 2
supported by the result that reduction of 2a and 2b generally yields the 2-hydro-
xyacids 5, 6a, and 6b apart from the expected prolines 7, 8a, and 8b.
Results and Discussion
We became interested in the reduction processes when it turned out that the ratio of
the products could be controlled by fixing the pH of the reaction medium. When
the reductions were carried out with sodium tetrahydroborate or with NH3 ꢂ BH3 at
pH ꢁ13, the acylic 2-hydroxy acids 5, 6a, and 6b formed in amounts up to 65%. At
pH values resulting from the hydrolysis of the tetrahydroborate or stabilized at ꢁ 8
by addition of ammonium chloride, formation of prolines 7, 8a, and 8b took place
exclusively, with only ꢁ 5% of 5, 6a, and 6b.
As an explanation for this dichotomy we would like to suggest that the primary
amino group in 3a or 3b (with strongly alkaline medium, in contrast to the proton-
ated species 4a and 4b at lower pH) attaches as a nucleophile to the reducing
agent, which then by intramolecular hydrogen transfer reduces the 2-oxo moiety.
This accelerating entropic effect recompenses the kinetic disadvantage due to the

Ring Opening Reactions of 1,2-Didehydroprolines
721
unfavorable equilibrium of 3a, 3b versus 1a, 1b. Whereas the assistance of
hydroxy and oxo groups in directing the hydride transfer towards certain function-
alities is well established [4], there are no references yet on the supporting role of
amines for reduction processes carried out in protic polar solvents.
Controlling the ratio of products by adjusting the pH allows the synthesis of
5-amino-2-hydroxycarboxylates and of prolines in moderate and good yields. A
result of our deuteration experiments is the synthesis of the deuterated 2-
hydroxyamino acid [3,3-2H2]-5 and of 3,3-dideuteroproline ([3,3-2H2]-7). The
latter compound is produced in 84% yield, thereby extending the list of published
deuterated prolines [5].
The main intention of the investigation was the synthesis and characterization
of yet unreported isomeric amino acids (2R,4R)- and (2S,4R)-5-amino-2,4-
dihydroxypentanoic acid (6a, 6b) and their lactames 9a, 9b. Traube and Fischer
have described [6] the synthesis of an ꢀ-amino-ꢁ,ꢂ-dioxyvaleric acid and the con-
version to the lactame and lactone but neglected to comment on the stereochem-
istry of their products. Six-membered nitrogen containing heterocycles with
hydroxyl groups frequently occur in natural products and are part of several bio-
logically active compounds [7].
Starting material for the sodium salt 1b was the readily available methyl (R)-
4-hydroxy-1-pyrroline-2-carboxylate [8], which was saponified and brought to
pH ꢁ 13 with aqueous sodium hydroxide. Reduction with NH3 ꢂ BH3 gave a mix-
ture of 56–60% 6a:6b (1:1) and 40–44% of the isomeric 4-hydroxyprolines
(8a, 8b), which were removed by ion exchange chromatography. The mixture of
6a and 6b obtained in about 50% yield could not be resolved and was therefore
converted to the dihydroxylactames 9a, 9b by the hexamethyldisilazan method
described by Pellegata et al. [9] in 40% yield. The mixture 9a, 9b also resisted
separation, but the corresponding dibenzoates 10a, 10b could be separated quanti-
tatively resulting in pure 10a and 10b. Diols 9a and 9b were recovered by tran-
sesterification according to Zemplen [10]. Since the free amino acids 6a and 6b are
known [6] to rapidly lactonize in the presence of excessive mineral acid, ring
opening of 9a and 9b was carried out with aqueous barium hydroxide followed
by the addition of sulfuric acid, avoiding any ion exchange procedure.
Scheme 3

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J. Hausler and H. Kahlig
722
Fig. 1. NOEs of 9a, 9b, 10a, and 10b
Using the aforementioned high lactonization tendency to advantage we
finally could show that the diastereomeric lactones 11a and 11b are readily
obtained as nicely crystallizing 4-methylbenzenesulfonates in a single step
hydrolyzing-recyclizing procedure starting with the dihydroxylactames 9a
and 9b.
The configurations of 6a (2R,4R) and 6b (2S,4R) were established by NMR
1
spectroscopy interpreting the vicinal H,1H-coupling constants of the dibenzoates
10a and 10b as well as by interpreting their 2D-NOESY spectra. The experimental
data indicate an unequivocal chair conformation for 10a and agree with the pre-
dicted NOEs and the expected long range W-couplings between H4 and H6 and H5
and NH, which were found to be 2.0 and 0.8 Hz. The unprotected 9a shows essen-
tially the same conformation. In the case of the cis-configured compounds 9b
differs significantly from 10b. The NMR data of 9b indicate a chair geometry with
both hydroxy groups in equatorial position. Reduced diaxial couplings (between
H4 and H5, and H5 and H6) point to a slightly distorted chair conformation in the
dibenzoyl lactame 10b. This is also borne out by small long range W-couplings (of
0.5 and 0.9 Hz) as well as by weak NOEs between the two proton pairs H4 and H6
and H4 and H6.
Experimental
Melting points (uncorrected) were determined on a Kofler heating table. Optical rotations were
measured on a Polarimeter 241 (Perkin-Elmer). NMR spectra were recorded on a Bruker Avance
DRX 400 WB NMR spectrometer in D2O solutions at a temperature of 298 K (if not otherwise
1
indicated). For H NMR spectra (resonance frequency 400.13 MHz) the HOD signal was used as
internal reference (ꢀ ¼ 4.90). 13C NMR spectra were recorded at a frequency of 100.62 MHz with
sodium 3-trimethylsilyl-1-propansulfonate as external reference (if not otherwise indicated).
Coupling constants for strongly coupled spin systems were derived from simulations with the
Xsim=NUMRIT software package (version 971120) [10] on a Silicon Graphics O2 workstation.
ꢀ
Acidities in D2O solutions are reported as pH – values. They are the result of measurements
with test paper and are not to be confused with pDs. Column dimensions used for ion exchange
and column chromatography were 20ꢃ1.4 cm (A), 35ꢃ3.5 cm (B), and 27ꢃ2 cm (C). The separa-
tion of benzoates 10a and 10b was performed by cyclic chromatography on a Chromatotron,
model 8924 (Co. Harrison Research, Palo Alto, USA); thickness of the silica layer 4 mm.
Elemental analyses of 6a, 6b, 9a, 9b, 10a, 10b, 11a, and 11b agreed favourably with the
calculated values.

Ring Opening Reactions of 1,2-Didehydroprolines
723
Incorporation of Deuterium into 2a and its Reduction Products
ꢀ
Solutions (ꢁ 0.2 M) of sodium 1-pyrroline-2-carboxylate (Na-1a) [3] in D2O adjusted to pH ꢁ 13
with aqueous NaOD (40%) were investigated by 1H and 13C NMR spectroscopy after equilibrating for
12d. Integration of the residual hydrogen at C-3 showed about 10 atomic %, practically exclusively
due to the monodeutero compound. The 13C NMR data of the C-3 dideuterated products are followed
by the data of the monodeuterated materials in brackets.
Sodium 3,3-Dideutero-1-pyrroline-2-carboxylate (Na-3,3-2H2-1a)
2
13C NMR (dioxane¼ 67.19 ppm): ꢀ ¼ 22.22 [22.32] (C-4), 35.73 (quint, J(13C, H)¼ 20Hz) [36.02,
t, J ¼ 20 Hz] (C-3), 60.81 (C-5), 142.47 (C¼N), 176.23 (CO) ppm.
ꢀ
Reduction at pH ꢁ 13
5-Amino-3,3-dideutero-2-hydroxypentanoic acid (3,3-2H2-5)
An equilibrated solution of Na-1a in D2O=NaOD was reduced (ice bath) with the sixfold molar amount
of NaBH4. After 12h the reaction mixture was adjusted to pH 2 with 6 M HCl and desalted as usual
(Dowex 50W, eluent 1 M NH3). After evaporation of the eluates in vacuo, the oily residue formed
crystals upon addition of hot methanol yielding 50–65% product. Minor amounts of by-product 3,3-
2H2-7 were obtained upon concentrating the mother liquors of the crystallization in vacuo to dryness
and passing the residue through a column of Dowex 50W (dimension A=4 mmol scale) with 5 dm3 of
H2O. 3,3-2H2-7 contained 13% D at C-2; 13C NMR (dioxane¼ 67.19 ppm): ꢀ ¼ 22.93 [23.02] (C-4),
2
30.48 (quint, J(13C, H)¼ 19.8Hz) [30.89, t, J ¼ 19Hz] (C-3), 39.68 (C-5), 71.73 [71.78] (C-2),
182.98 (CO) ppm; 13C NMR spectrum of the undeuterated material: Ref. [12].
ꢀ
Reduction at pH ꢁ 8
3,3-Dideuteroproline (3,3-2H2-7)
The strongly basic solution of Na-3,3-2H2-1a was brought to pHꢁ 7–8 with 6 M HCl and buffered by
addition of NH4Cl (2.4 molar amount) before the reducing agent was added. Reduction and isolation of
ꢀ
the product by washing the Dowex 50 W with H2O were carried out as described for pH ꢁ 13 (see
above). Yield of 3,3-2H2-7 84%; D content at C-2 7%; 13C NMR (dioxane ¼ 67.19ppm): ꢀ ¼ 23.95
2
[24.05] (C-4), 28.77 (quint, J(13C, H)¼ 20.9Hz) [29.08, t, J ¼ 20.6 Hz] (C-3), 46.47 (C-5), 61.49
[61.55] (C-2), 175.02 (CO) ppm.
(3R,5R)- and (3S,5R)-3,5-Dibenzoyloxy-2-piperidone 10a and 10b
Crude methyl (R)-4-hydroxy-1-pyrroline-2-carboxylate (prepared on a 40 mmol scale according to
Ref. [8]) was dissolved under Ar in 70cm3 of 1 M NaOH in an ice bath. NH3 ꢂ BH3 (1.0g, 32mmol)
was added to the stirred solution, and stirring was continued for 72 h at room temperature. The reaction
mixture was adjusted to pH 2 by addition of 6 M HCl and was desalted as usual (Dowex 50 W, column
B). Evaporation of the eluates in vacuo afforded about 6 g of an oil that partly crystallized. NMR
analysis indicated that the mixture consisted of 6aþ 6b (56–60%, 1:1) and of the hydroxyprolines
8aþ 8b (40–44%, 1:4). To remove 8a, 8b the oil was passed through a Dowex 50W column
(dimension C) by rinsing with 15 dm3 of H2O. Elution with 1 M NH3 and evaporation of the fractions
left behind the crude 6a, 6b (3.2g, 54%) as a foam. Cyclization to the lactames 9a and 9b was
achieved by the hexamethyldisilazane method described in Ref. [9]. Yield 1.12 g (40%); colourless
needles.

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J. Hausler and H. Kahlig
724
The benzoylation of 9a, 9b was carried out in 30cm3 of ice cold CHCl3 with the four times molar
amount of benzoyl chloride and pyridine, and catalysis with 4-(dimethylamino)pyridine (5mol%).
After 10h at room temp. the solvent was removed in vacuo. The residue was taken up in 80cm3 of
ethyl acetate, and the solution was extracted subsequently with H2O, 1 M HCl, and finally with satd.
aqueous NaHCO3. The organic layer was dried (Na2SO4) and the solvent evaporated in vacuo. Thin
layer analysis (silica, CHCl3:MeOH¼ 95:5) of the crude oil (3.8g) indicated 10a (Rf ¼ 0.46), 10b
(Rf ¼ 0.30), and components at the start and the front. Chromatography of the oil on a Chromatotron
(CHCl3:MeOH ¼ 99:1) afforded 10a and 10b (1.3 g each, 90%).
(3R,5R)-3,5-Dibenzoyloxy-2-piperidone (10a, C19H17NO5)
20
Colourless needles, mp 147–149ꢄC (CHCl3:ether¼ 1:9); ½ꢁꢅD ¼ 172.5ꢄ cm2 gꢆ1 (c ¼ 1.53, CHCl3);
1H NMR (CDCl3): ꢀ ¼ 2.44 (ddd, J ¼ 2.9, 11.4, 13.7 Hz, C–CHH–C), 2.70 (dddd, J ¼ 2.0, 4.5, 6.4,
13.7Hz, C–CHH–C), 3.62 (dddd, J ¼ 2.0, 2.9, 2.9, 13.6Hz, N–CHH), 3.80 (ddd, J ¼ 1.4, 3.8, 13.6Hz,
N–CHH), 5.60 (ddddd, J ¼ 0.8, 2.9, 2.9, 3.8, 4.5 Hz, O–CH), 5.79 (dd, J ¼ 6.4, 11.4Hz, O–CH), 6.15
(bs, NH), 7.35–7.48 (m, 4HAr), 7.51–7.63 (m, 2HAr), 7.99–8.11 (m, 4HAr) ppm; 13C NMR (CDCl3):
ꢀ ¼ 31.58 (CH2), 46.20 (N–CH2), 66.34 (O–CH), 66.39 (O–CH), 128.38, 128.58, 129.77, 129.97,
133.34, 133.60 (Ar), 129.30, 129.49 (Arqu), 165.62, 165.70, 168.40 (CO) ppm.
(3S,5R)-3,5-Dibenzoyloxy-2-piperidone (10b, C19H17NO5)
20
Colourless fluffy needles, mp 114–116ꢄC (CHCl3:ether¼ 1:9); ½ꢁꢅD ¼ 59.2ꢄ cm2 gꢆ1 (c ¼ 1.03, CHCl3);
1H NMR (CDCl3): ꢀ ¼ 2.46 (dddd, J ¼ 0.9, 6.7, 8.0, 14.2Hz, C–CHH–C), 2.74 (dddd, J ¼ 0.5, 4.9, 7.1,
14.2Hz, C–CHH–C), 3.63 (dddd, J ¼ 0.9, 3.8, 4.9, 13.1Hz, N–CHH), 3.71 (dddd, J ¼ 0.5, 2.4, 4.0,
13.1Hz, N–CHH), 5.46 (ddddd, J ¼ 0.5, 4.0, 4.9, 4,9, 6.7 Hz, O–CH), 5.62 (dd, J ¼ 7.1, 8.0 Hz, O–CH),
6.21 (bs, NH), 7.30–7.44 (m, 4HAr), 7.47–7.59 (m, 2HAr), 7.97–8.04 (m, 4HAr) ppm; 13C NMR
(CDCl3): ꢀ ¼ 32.59 (CH2), 45.49 (N–CH2), 65.48 (O–CH), 66.29 (O–CH), 128.27, 128.45, 129.77,
129.94, 133.24, 133.43 (Ar), 129.34, 129.41 (Arqu), 165.54, 165.61, 168.40 (CO) ppm.
(3R,5R)- and (3S,5R)-3,5-Dihydroxy-2-piperidones 9a and 9b
Under Ar three small drops of a 1 M solution of NaOCH3 in CH3OH were added to solutions of
1.5 mmol of 10a or 10b in 50cm3 of dry CH3OH. After 48–60h the starting materials and the
intermediate mono benzoates could not longer be detected by thin layer chromatography (silica 60,
CHCl3:MeOH ¼ 9:1). Acetic acid (1 drop) was added, the solvent was evaporated in vacuo, and the
residue was filtered through a short column of silica (eluent: CHCl3:MeOH ¼ 7:3) and crystallized
from CH3OH–ether.
(3R,5R)-3,5-Dihydroxy-2-piperidone (9a, C5H9NO3)
20
1
Yield 83%; colourless needles, mp 131–133ꢄC; ½ꢁꢅD ¼ 61.8ꢄ cm2 gꢆ1 (c ¼ 1.2, MeOH); H NMR:
ꢀ ¼ 2.13 (ddd, J ¼ 2.9, 10.8, 13.6Hz, C–CHH–C), 2.49 (dddd, J ¼ 1.8, 5.1, 6.3, 13.6Hz, C–CHH–C),
3.41 (ddd, J ¼ 1.8, 3.4, 13.5Hz, N–CHH), 3.70 (dd, J ¼ 3.8, 13.5Hz, N–CHH), 4.48 (dddd, J ¼ 2.9,
3.4, 3.8, 5.1 Hz, O–CH), 4.53 (dd, J ¼ 6.3, 10.8Hz, O–CH) ppm; 13C NMR: ꢀ ¼ 35.91 (CH2), 48.39
(N–CH2), 63.63 (O–CH), 64.69 (O–CH), 175.18 (CO) ppm.
(3S,5R)-3,5-Dihydroxy-2-piperidone (9b, C5H9NO3)
20
Yield 79%; colourless crystals, mp 138ꢄC; ½ꢁꢅD ¼ 17.3ꢄ cm2 gꢆ1 (c ¼ 1.1, MeOH); 1H NMR: ꢀ ¼ 1.94
(ddd, J ¼ 8.8, 10.5, 12.7Hz, C–CHH–C), 2.68 (dddd, J ¼ 1.3, 4.8, 6.8, 12.7Hz, C–CHH–C), 3.34

Ring Opening Reactions of 1,2-Didehydroprolines
725
(dd, J ¼ 7.0, 12.6Hz, N–CHH), 3.59 (ddd, J ¼ 1.3, 4.7, 12.6Hz, N–CHH), 4.369 (dddd, J ¼ 4.7, 4.8,
7.0, 8.8 Hz, O–CH), 4.372 (dd, J ¼ 6.8, 10.5Hz, O–CH) ppm; 13C NMR: ꢀ ¼ 37.72 (CH2), 47.64
(N–CH2), 63.31 (O–CH), 65.75 (O–CH), 175.53 (CO) ppm.
(2R,4R)- and (2S,4R)-5-Amino-2,4-dihydroxypentanoic Acids 6a and 6b
Under Ar a solution of 1 mmol of 9a or 9b in 5 cm3 of half saturated aqueous Ba(OH)2 was heated to
100ꢄC (1.5h). The mixture was brought to room temperature and was carefully adjusted to pH 6 with
1 M H2SO4. Then BaSO4 was removed by filtration. The filtrate and washings were concentrated
in vacuo and the viscous residue was covered with little CH3OH. On chilling in the refrigerator crys-
tallization initiated.
(2R,4R)-5-Amino-2,4-dihydroxypentanoic acid (6a, C5H11NO4)
20
1
Yield 76%; colourless crystals, mp>185ꢄC (dec); ½ꢁꢅD ¼ 19.0ꢄ cm2 gꢆ1 (c ¼ 1.03, H2O); H NMR:
ꢀ ¼ 1.67, 1.86 (AB-part of an ABMX-spin system, J ¼ 2.0, 3.1, 9.4, 9.6, 14.1Hz, m, CH2), 2.90, 3.10
(AB-part of an ABM-spin system, J ¼ 3.0, 9.5, 13.2Hz, CH2–N), 4.00 (M-part, J ¼ 3.0, 3.1, 9.4,
9.5 Hz, CH–O), 4.12 (X-part, J ¼ 2.0, 9.6 Hz, CH–CO) ppm; 13C NMR: ꢀ ¼ 39.20 (CH2), 45.1
(CH2–N), 65.30 (CH–O), 69.20 (CH–CO), 181.54 (CO) ppm.
(2S,4R)-5-Amino-2,4-dihydroxypentanoic acid (6b, C5H11NO4)
20
1
Yield 69%; colourless leaflets, mp>175ꢄC (dec); ½ꢁꢅD ¼ ꢆ28.6ꢄ cm2 gꢆ1 (c ¼ 1.02, H2O); H NMR:
ꢀ ¼ 1.85, 1.90 (AB-part of an ABMX-spin system, J ¼ 5.0, 6.1, 6.9, 7.3, 14.5 Hz, CH2), 2.93, 3.17
(AB-part of an ABM-spin system, J ¼ 3.3, 9.2, 13.1Hz, CH2–N), 4.00 (M-part, J ¼ 3.3, 6.1, 6.9,
9.2 Hz, CH–O), 4.07 (X-part, J ¼ 5.0, 7.3 Hz, CH–CO) ppm; 13C NMR: ꢀ ¼ 39.12 (CH2), 44.63
(CH2–N), 65.81 (CH–O), 69.82 (CH–CO), 180.97 (CO) ppm.
(2R,4R)- and (2S,4R)-5-Amino-2-hydroxy-4-pentanolide,
4-Methylbenzenesulfonates 11a and 11b
A solution of 79mg (0.6mmol) of 9a or 9b, resp., and 130mg (0.68 mmol) of 4-methylbenzenesul-
fonic acid hydrate in 0.2 cm3 of H2O was heated to 100ꢄC (3h). The water was evaporated in vacuo.
The residual oil crystallized on covering with acetonitrile. Crystals were obtained in nearly quantitative
yields after washing with acetonitril.
(2R,4R)-5-Amino-2-hydroxy-4-pentanolide, 4-Methylbenzenesulfonates
(11a, C12H17NO6S)
20
Colourless needles, mp>160ꢄC (dec); ½ꢁꢅD ¼ ꢆ34.6ꢄ cm2 gꢆ1 (c ¼ 1.2, H2O); 1H NMR (310K):
ꢀ ¼ 2.23 (ddd, J ¼ 10.4, 10.8, 12.7Hz, CH–CHH–CH), 2.62 (s, CH3), 3.09 (ddd, J ¼ 5.6, 8.6,
12.7Hz, CH–CHH–CH), 3.52 (dd, J ¼ 9.0, 14.1Hz, CHH–N), 3.70 (dd, J ¼ 2.6, 14.1 Hz, CHH–N),
5.03 (dd, J ¼ 8.6, 10.8 Hz, CO–CH), 5.06 (dddd, J ¼ 2.6, 5.6, 9.0, 10.4Hz, CH–O), 7.57–7.99 (m,
4HAr) ppm; 13C NMR: ꢀ ¼ 21.22 (Me), 34.33 (CH2), 43.39 (CH2–N), 68.24 (CH–CO), 74.41 (CH–O),
126.11, 130.20 (Ar), 140.17, 143.25 (Arqu) ppm.
(2S,4R)-5-Amino-2-hydroxy-4-pentanolide, 4-Methylbenzenesulfonates
(11b, C12H17NO6S)
20
1
Colourless leaflets, mp>175ꢄC (dec); ½ꢁꢅD ¼ ꢆ46.5ꢄ cm2 gꢆ1 (c ¼ 1, H2O); H-NMR: ꢀ ¼ 2.52 (s,
CH3), 2.56, 2.59 (AB-part of an ABMX-spin system, J ¼ 3.8, 7.6, 8.6, 8.6, 13.6Hz, CH–CH2–CH),

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J. Hausler and H. Kahlig: Ring Opening Reactions of 1,2-Didehydroprolines
726
3.36. 3.50 (AB-part of an ABX-spin system, J ¼ 2.9, 10.8, 14.0Hz, CH2–N), 4.82 (M-part, J ¼ 7.6,
8.6, CH–CO), 5.12 (X-part, J ¼ 2.9, 3.8, 8.6, 10.8Hz, CH–O), 7.47–7.85 (m, 4HAr) ppm; 13C NMR:
ꢀ ¼ 21.21 (Me), 33.28 (CH2), 43.55 (CH2–N), 67.06 (CH–CO), 75.81 (CH–O), 126.09, 129.62 (Ar),
140.15, 143.24 (Arqu) ppm.
References
€
[1] Part I: Hausler J (1992) Liebigs Ann Chem 1231
[2] Macholan L, Vencalkova J (1963) Chem Ber 96: 237
€
[3] Hausler J, Schmidt U (1979) Liebigs Ann Chem 1881
[4] Dalla V, Catteau JP, Pale P (1999) Tetrahedron Lett 5193 and refs. cited therein
[5] Kelly NM, Sutherland A, Willis C (1997) Natural Product Reports 14: 205
[6] Traube W, Fischer W (1924) Liebigs Ann Chem 167
[7] Reviews: Pinder AR (1992) Natural Product Reports 491; Plankett AO (1994) ibid 581;
O’Hagan D (1997) ibid 637; O’Hagan D (2000) ibid 435
€
[8] Hausler J (1987) Monatsh Chem 118: 865
[9] Pellegata R, Pinza M, Pifferi G (1978) Synthesis 614 (method A)
[10] Provided from Kirk Marat, Department of Chemistry, University of Manitoba, Winnipeg,
Manitoba, Canada
[11] Zemplen G, Pacsu E (1929) Chem Ber 62: 1613
[12] Sefler AM, Kozlowski M, Guo T, Bartlett PA (1997) J Org Chem 62: 93