Synthesis of non-natural cyclic amino acids from available unsaturated tertiary amines

Article abstract of DOI:10.1134/S1070428010090022

New approach is developed to the synthesis of cyclic amino acids derivatives. Unsaturated tertiary amines react with ethyl diazoacetate under the catalysis by copper catalyst Cu(F₃acac)₂ leading to the formation of products of [2,3]-sigmatropic rearrangement which via the metathesis of double bonds undergo a ring closure. The subsequent hydrogenation of compounds obtained furnished esters of 6- and 7-membered cyclic α-amino acids. Besides the racemic also optically active compounds were obtained, in particular, esters of (R)- and (S)-pipecolic acid.

Full text of DOI:10.1134/S1070428010090022

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 9, pp. 1277−1281. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © I.D. Titanyuk, I.P. Beletskaya, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 9, pp. 1281−1285.
Synthesis of Non-Natural Cyclic Amino Acids from Available
Unsaturated Tertiary Amines
I. D. Titanyuk and I. P. Beletskaya
Lomonosov Moscow State University, Moscow, 119992 Russia
e-mail: i-titan@yandex.ru
Received January 28, I 2010
Abstract—New approach is developed to the synthesis of cyclic amino acids derivatives. Unsaturated tertiary
amines react with ethyl diazoacetate under the catalysis by copper catalyst Cu(F3acac)2 leading to the formation
of products of [2,3]-sigmatropic rearrangement which via the metathesis of double bonds undergo a ring closure.
The subsequent hydrogenation of compounds obtained furnished esters of 6- and 7-membered cyclic α-amino
acids. Besides the racemic also optically active compounds were obtained, in particular, esters of (R)- and (S)-
pipecolic acid.
DOI: 10.1134/S1070428010090022
Amino acids are widely employed in all fields of
chemistry and biochemistry. However the use of cyclic
amino acid comes mainly to the naturally existing L-
proline whereas the other chiral homologs appear to
be too expensive for wide application for they require
complicated, frequently nontrivial, procedures of organic
synthesis. The ring closing metathesis (RCM) developed
by Grabbs [1] made it possible to prepare cyclic com-
pounds from acyclic dienes. This method provides a
possibility to carry out a synthesis of complex molecules
containing a large number of various functional groups
[2]. In certain cases cyclic amino acids were obtained
by olefins metathesis in sufficiently large yields [3–5].
However in these procedures a serious problem consisted
in the synthesis of compounds that were the precursors
of the metathesis reaction. These precursors are acyclic
α-amino acids containing two multiple bonds. One among
the known simple methodsof introduction of a double
bond into amino acids is a spontaneous [2,3]-sigmatropic
rearrangement of nitrogen ylides. Several examples were
described of nitrogen ylides generation from ethyl dia-
zoacetate and tertiary N-allylamines in the presence of
rhodium catalysts Rh6(CO)16 or Rh2(OAc)4 [6]. These
intermediates underwent the [2,3]-sigmatropic rear-
rangement forming derivatives of 2-amino-4-pentenic
acid. Proceeding from these facts we suggested that the
presence in the tertiary amine of the second unsaturated
alkyl group would make it possible to obtain in one stage
the derivatives of 2-amino-4-pentenic acid which would
be suitable for further metathesis. Inasmuch as further the
unsaturated cyclic amino acids should be converted into
saturated, it was important to have in the initial tertiary
amine a substituent readily eliminated by hydrogena-
tion (e.g., a benzyl group). In this report we for the first
time describe a method providing a possibility to obtain
non-natural cyclic amino acids by the following reaction
sequence: [2,3]-sigmatropic rearrangement–metathesis–
hydrogenation. As a result the target 6- and 7-membered
cyclic amino acids were prepared, both racemic and
optically pure.
We started the research from the investigation of the
reaction between ethyl diazoacetate and N,N-diallylben-
zylamine (Ia) (Scheme 1). Rh2(OAc)4 is the most com-
mon catalyst used in transformations of diazo compounds,
it has been frequently used for obtaining nitrogen ylides
and performing their [2,3]-sigmatropic rearrangement
[7, 8]. However the reaction of 5 equiv of amine Ia and
5 mol% of Rh2(OAc)4 with ethyl diazoacetate in toluene
resulted in ethyl 2-(N-allyl-N-benzylamino)pent-4-enoate
(IIa) in 15–19% yield (see the table, runs nos. 1, 2).
Further search for the optimum catalyst for this reaction
showed that inexpensive copper catalysts were more ef-
ficient than the rhodium catalysts, although they required
a higher heating temperature to start the reaction (com-
1277

TITANYUK, BELETSKAYA
1278
Scheme 1.
over 3 h, therefore it was dissolved in a large volume of
CH2Cl2 and was gradually added to amine Ia–Ic heated
at high temperature. Therewith the dichloromethane was
distilled off from the reaction mixture.
N2CHCO2Et,
catalyst
The same protocol was used with N-allyl-N-ben-
zylalkenamines Ib, Ic. The reaction products IIb and IIc
were obtained in 61 and 57% yield respectively.
toluene, Δ
N
N
CO2Et
Ph
Ph
Ia
IIa
The olefin metathesis is known to be very sensitive to
the presence in the molecule of nucleophilic centers, in
particular, like amino group. The attempt to carry out the
metathesis of compound IIa in the presence of Grabbs
catalysts I and II gave only trace amounts of cyclic amine
IIIa. However the addition into the reaction mixture of
titanium ethylate Ti(OEt)4 that was a strong Lewis acid
and suppressed the nucleophilicity of the nitrogen atom
[8] allowed us the isolation of compound IIIa in 34%
yield with Grabbs catalyst I and in 80% yield with Grabbs
catalyst II. Under similar conditions with the help of
Grabbs catalyst II we obtained from ester IIb the ester of
cyclic amino acid IIIb containing a seven-membered ring
in 78% yield. Regretfully, we failed to obtain in plausible
yield the eight-membered cycle IIIc. Its signals in the
mixture with other compounds of acyclic structure were
observed in the NMR spectra.
monly 80–100°C). In the presence of copper powder,
CuI, or copper acetylacetonate compound IIa formed in
moderate yields (see the table, runs nos. 3–9). However
the use as a catalyst of the copper trifluoroacetylacetonate
Cu(F3acac)2 allowed obtaining ester IIa in ~70% yield.
Further we used this catalyst in all reactions. Some special
features of performing this reaction are worth mention-
ing. To obtain the best yield a large concentration of
amine and its excess with respect to ethyl diazoacetate
is required. We usually used 5-fold excess of amine Ia
without solvent, and 4 equiv of the initial compound we
succeeded to recover. It was also important to introduce
the ethyl diazoacetate to the reaction mixture very slowly,
Yield of ethyl 2-(N-allyl-N-benzylamino)pent-4-enoate (IIa)
in reaction of N,N-diallylbenzylamine (Ia) with ethyl diazo-
acetatea
Scheme 2.
Run
no.
1
Yield,
%
15
Catalyst
Rh2(OAc)4
Rh2(OAc)4
mol% T, oC
b
N2CHCO2Et
nN
nN
CO2Et
IIa_IIc
5
5
50
Cu(F3acac)2, Δ
2
3
100
19
Ph
Ia_Ic
Ph
nN
c
–
Cu(acac)2
Cu(acac)2
10
10
10
10
10
10
10
10
10
50
80
c
–
4
Grabbs catalyst II
Ti(OEt)4, CH2Cl2
5
Cu(acac)2
100
80
34
CO2Et
c
–
6
Cu powder
Cu powder
CuI
Ph
7
100
80
39
IIIa_IIIc
n = 1 (a), 2 (b), 3 (c).
c
–
8
9
CuI
100
100
100
30
50
69
10
Cu[MeC(O)CHC(O)CF3]2
The hydrogenation of esters of unsaturated cyclic
amino acids IIIa and IIIb was performed with molecular
hydrogen in the presence of catalyst Pd/C (5 mol%) in
methanol. Simultaneously with the hydrogenation of the
double bond the benzyl group was removed (Scheme 3).
The hydrogenation products IVa and IVb were isolated
in nearly quantitative yield.
11d Cu[MeC(O)CHC(O)CF3]2
a
Reaction conditions: 5 equiv of Ia, 1 equiv of N2CHCO2Et, catalyst,
toluene.
b Yield of the isolated reaction product.
c
Reaction does not occur.
d Without solvent.
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SYNTHESIS OF NON-NATURAL CYCLIC AMINO ACIDS
1279
Scheme 3.
Scheme 5.
(1) H2, Pd/C, MeOH
(2) HCl
VIIa
VIIa
VIIb
VIIb
n
N
OEt
nN
OEt
N
CO2Et
N
CO2Et
.
.
H HCl
H HCl
H
O
.
O
VIIIa
VIIIa
HCl
IVa, IVb
Ph
IIIa, IIIb
from compound VIIb, (+)-(R)-pipecolicaя qandCлOta,
[α]D22 +26.0° (c 0.2, H2O) {[α]D25 +26.3° (c 1, H2O) [10]}.
n = 1 (a), 2 (b)
Hence by the use of the three-stage sequence [2,3]-sig-
matropic rearrangement–metathesis–hydrogenation we
obtained esters of 6- and 7-membered cyclic non-natural
amino acids, both racemic and optically pure.
In order to obtain enantiomerically pure derivatives of
cyclic amino acids we applied the known (S)-N,N-diallyl-
1-phenylethylamine (V) [9]. The sterical hindrances at the
nitrogen atom from the methyl group strongly affected the
yield in the reaction with ethyl diazoacetate. Compound
VI was isolated only in 19% yield as an inseparable mix-
ture of diastereomers. In the presence of Ti(OEt)4 using
Grabbs catalyst I we converted compound VI into the
cyclic unsaturated amino acid as a mixture of diastereo-
mers VII and VIIb in the ratio 1:1 and an overall yield
82% (Scheme 4). The isomers were easily separated by
column chromatography.
EXPERIMENTAL
NMR spectra were registered on spectrometers
Bruker AV-300 and AV-400, operating frequencies 300
and 400 MHz (1H), 75 and 100 MHz (13C). All solvents
used in the reactions were dried with appropriate drying
agents. The reaction progress was monitored by TLC on
plates with silica gel Merck 60 F254 (development by UV
irradiation or by treating with cerium molibdate solution
in 5% solution of H2SO4). In the column chromatography
silica gel Merck 60 (230–400 mesh ASTM) was used.
Scheme 4.
N2CHCO2Et,
Cu(F3acac)2, 100oC
Reaction of ethyl diazoacetate with tertiary N-allyl-
amines. General procedure. Into a flask equipped with
a magnetic stirrer, a dropping funnel, and a distillation
head with a Liebig condenser was charged 10 mmol of
tertiary amine Ia–Ic. Into the flask was charged 36.9 mg
(0.1 mmol) of copper(II) trifluoroacetylacetonate, and
the mixture was heated to 90°C at stirring. From the
dropping funnel was added during 3 h 228 mg (2 mmol)
of ethyl diazoacetate in 50 ml of anhydrous CH2Cl2,
therewith the most of dichloromethane was distilled off
from the reactor flask through the Liebig condenser into
a receiver. On completing the addition the mixture was
cooled, and the reaction product IIa–IIc was isolated by
column chromatography (eluent ethyl acetate–petroleum
ether, 1:20 v/v).
N
N
CO2Et
Ph
Ph
V
VI
Grabbs catalyst I,
Ti(OEt)4, CH2Cl2,
20oC, 16 h
+
CO2Et
N
N
CO2Et
Ph
Ph
VIIa
VIIb
Each of diastereomers VIIa and VIIb was subjected
to hydrogenation, and as a result optically active ethyl
esters of (R)- and (S)-pipecolic acid were isolated in the
form of hydrochlorides (Scheme 5).
Ethyl 2-[allyl(benzyl)amino]pent-4-enoate (IIa).
Colorless oily substance. Yield 69%. 1H NMR spectrum
(CDCl3), δ, ppm: 1.29 t (3H, J 7.1 Hz), 2.52 m (2H),
3.25 m (1H), 3.45 m (1H), 3.65 m (2H), 4.11 d (1H,
J 10.1 Hz), 4.25 m (2H), 5.20 m (4H), 5.80 m (2H),
7.41 m (5H). 13C NMR spectrum (CDCl3), δ, ppm: 14.5,
34.2, 53.6, 54.2, 60.1, 61.5, 116.8, 117.3, 126.9, 128.2,
128.7, 135.1, 136.5, 139.9, 172.5. Found, %: C 74.82;
The absolute configuration of ethers obtained was esti-
mated after hydrolysis with 6 N HCl by comparison of the
optical properties of obtained enantiomers of free amino
acid with the published data. The comparison showed that
from compound VIIa formed (–)-(S)-pipecolic acid, [α]D22
–25.8° (c 0.2, H2O) {[α]D25 –26.3° (c 1, H2O) [10]}, and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 9 2010

TITANYUK, BELETSKAYA
1280
1
H 8.40; N 5.20. C17H23NO2. Calculated, %: C 74.69; H
8.48; N 5.12.
80%. H NMR spectrum (CDCl3), δ, ppm: 1.30 t (3H,
J 7.1 Hz), 2.50 m (2H), 3.17 m (1H), 3.46 m (1H), 3.58 m
(1H), 3.82AB system (1H, J 9 Hz), 3.92AB system (1H,
J 9 Hz), 4.25 q (2H, J 7.0 Hz), 5.71 br.s (2H), 7.31 m (5H).
13C NMR spectrum (CDCl3), δ, ppm: 14.5, 28.6, 48.8,
58.1, 59.4, 67.6, 122.4, 125.7, 127.1, 128.3, 128.9, 138.7,
172.6. Found, %: C 73.32; H 7.84, N 5.59. C15H19NO2.
Calculated, %: C 73.44; H 7.81; N 5.71.
Ethyl 2-[benzyl(but-3-enyl)amino]pent-4-enoate
(IIb). Colorless oily substance. Yield 61%. H NMR
1
spectrum (CDCl3), δ, ppm: 1.29 t (3H, J 7.1 Hz), 2.25 m
(2H), 2.45 m (1H), 2.50 m (2H), 2.58 m (1H), 3.45 t
(1H, J 8.3 Hz), 3.62 AB system (1H, J 12.0 Hz), 3.98
AB system (1H, J 12.0 Hz), 4.23 m (2H), 5.10 m (4H),
5.60 m (2H), 7.31 m (5H). 13C NMR spectrum (CDCl3), δ,
ppm: 14.5, 33.1, 34.4, 50.3, 55.1, 60.1, 62.3, 115.5, 116.7,
126.9, 128.2, 128.7, 135.2, 136.8, 140.1, 172.5. Found,
%: C 75.43; H 8.68; N 4.67. C18H25NO2. Calculated, %:
C 75.22; H 8.77; N 4.87.
Ethyl 1-benzyl-2,3,6,7-tetrahydro-1H-azepine-2-
carboxylate (IIIb). Colorless oily substance. Yield 78%.
1H NMR spectrum (CDCl3), δ, ppm: 1.30 t (3H, J 7.1 Hz),
2.20 m (1H), 2.40 m (1H), 2.55 m (1H), 2.75 m (2H),
3.20 m (1H), 3.65 d (1H, J 8.1 Hz), 3.85 s (2H), 4.19 m
(2H), 5.75 m (1H), 5.81 m (1H), 7.26 m (1H), 7.33 t (2H,
J 8.5 Hz), 7.43 d (2H, J 8.5 Hz). 13C NMR spectrum
(CDCl3), δ, ppm: 14.3, 27.7, 30.0, 48.5, 58.7, 60.3, 64.8,
127.0, 127.8, 128.2, 128.8, 132.2, 139.4, 173.4. Found,
%: C 74.18; H 8.20; N 5.35. C16H21NO2. Calculated, %:
C 74.10; H 8.16; N 5.40.
Ethyl 2-[benzyl(pent-4-enyl)amino]pent-4-enoate
1
(IIc). Colorless oily substance. Yield 57%. H NMR
spectrum (CDCl3), δ, ppm: 1.30 t (3H, J 7.1 Hz), 1.66 m
(2H), 1.98 m (1H), 2.07 m (1H), 2.45 m (1H), 2.52 m
(2H), 2.62 m (1H), 3.45 t (1H, J 8.3 Hz), 3.60AB system
(1H, J 12.0 Hz), 3.95AB system (1H, J 12.0 Hz), 4.23 m
(2H), 5.0 m (4H), 5.60 m (2H), 7.33 m (5H). 13C NMR
spectrum (CDCl3), δ, ppm: 14.5, 27.6, 33.3, 34.3, 50.2,
55.1, 60.0, 62.3, 114.4, 116.7, 126.8, 128.1, 128.7, 135.2,
138.7, 140.2, 172.5. Found, %: C 75.53; H 9.25; N 4.84.
C19H27NO2. Calculated, %: C 75.71; H 9.03; N 4.65.
Ethyl R- and S-piperidine-2-carboxylates. In 10 ml
of anhydrous CH2Cl2 was dissolved 250 mg oif compound
VI and 284 mg (1 mmol) of titanium(IV) ethylate, to the
solution was added 20 mg (0.05 mmol) of Grabbs catalyst
II, and the mixture was stirred in a closed flask under an
argon atmosphere at room temperature over 16 h. Then the
solution was evaporated in a vacuum on a rotary evapora-
tor, and the residue was subjected to chromatography on
silica gel (eluent ethyl acetate–petroleum ether, 1 : 10 v/v).
Ethyl 2-{allyl[(S)-1-phenylethyl]amino}pent-4-eno-
ate (VI). Colorless oily substance. Yield 19%, inseparable
mixture of diastereomers. 1H NMR spectrum (CDCl3), δ,
ppm: 1.24 + 1.25–1.33 (6H), 2.40–2.52 m (2H), 2.76 +
2.90 + 3.20 (2H), 3.30–3.65 m (3H), 3.80 + 4.0–4.35 (2H),
5.0–5.3 m (4H), 5.40 + 5.70 (2H), 7.15–7.41 m (5H).
13C NMR spectrum (CDCl3), δ, ppm: 14.2, 14.6, 19.1,
19.9, 35.2, 39.5, 50.0, 53.0, 53.3, 59.4, 60.0, 60.3, 61.3,
67.4, 68.0, 115.1, 116.3, 116.8, 117.1, 126.9, 127.7, 127.9,
128.2, 135.2, 135.5, 136.4, 138.1, 139.2, 172.1. Found,
%: C 75.33; H 8.78; N 4.64. C18H25NO2. Calculated, %:
C 75.22; H 8.77; N 4.87.
First compound VIIb was eluted, then compound
VIIa.
Ethyl (S)-1-[(S)-1-phenylethyl]-1,2,3,6-tetrahydro-
pyridine-2-carboxylate (VIIa). Yield 41%. Colorless
oily substance, Rf 0.2, [α] 22 –101.05° (c 0.5, CHCl3). 1H
NMR spectrum (CDCl3),Dδ, ppm: 1.30 t (3H, J 7.1 Hz),
1.42 d (3H, J 8.0 Hz), 2.30 m (1H), 2.44 m (1H), 3.38
AB system (1H, J 9 Hz), 3.60 s (2H), 4.21 m (2H + 1H),
5.45 m (1H), 5.55 m (1H), 7.21–7.40 m (5H). 13C NMR
spectrum (CDCl3), δ, ppm: 14.3, 22.1, 29.1, 45.7, 55.4,
59.8, 61.8, 122.4, 126.2, 127.1, 127.3, 128.5, 145.3,
173.1.
Esters of unsaturated cyclic racemic amino acids.
General procedure. In 10 ml of anhydrous CH2Cl2 was
dissolved 1 mmol of compound IIa–IIc and 284 mg
(1 mmol) of titanium(IV) ethylate, to the solution was
added 20 mg (0.05 mmol) of Grabbs catalyst II, and the
mixture was stirred in a closed flask under an argon atmo-
sphere at room temperature over 16 h. Then the solution
was evaporated in a vacuum on a rotary evaporator, and
the residue was subjected to chromatography on silica gel
(eluent ethyl acetate–petroleum ether, 1 : 10 v/v).
Ethyl (R)-1-[(S)-1-phenylethyl]-1,2,3,6-tetrahy-
dropyridine-2-carboxylate (VIIb). Yield 41%. Color-
less oily substance, Rf 0.4, [α]D22 +19.0° (c 0.5, CHCl3)
1H NMR spectrum (CDCl3), δ, ppm: 1.30 t (3H, J 7.1 Hz),
1.37 d (3H, J 8.0 Hz), 2.50 m (1H), 2.65 m (1H), 3.00AB
system (1H, J 9 Hz), 3.26AB system (1H, J 9 Hz), 3.98 q
(1H, J 8.0 Hz), 4.08 d (1H, J 9.1 Hz), 4.22 m (2H), 5.62 m
(1H), 5.72 m (1H), 7.21 m (1H), 7.33 t (2H, J 8.5 Hz),
Ethyl 1-benzyl-1,2,3,6-tetrahydropyridine-2-
carboxylate (IIIa). Colorless oily substance. Yield
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SYNTHESIS OF NON-NATURAL CYCLIC AMINO ACIDS
1281
13
Hydrolysis of ethyl esters of (R)- and (S)-piperi-
dine-2-carboxylic acid. The hydrochloride of ethyl (R)-
or (S)-piperidine-2-carboxylate was dissolved in 6 N HCl
and was heated at 90°C for 6 h. The pH of the solution
was adjusted at 5.5 by gradual adding water solution of
NaHCO3, then the solution was evaporated to dryness on
a rotary evaporator.According to the 1H NMR spectra the
free acid in both cases formed in the quantitative yield.
7.39 d (2H, J 8.5 Hz). C NMR spectrum (CDCl3), δ,
ppm: 14.4, 21.1, 29.1, 47.3, 54.2, 59.9, 62.1, 121.8, 126.2,
126.8, 127.2, 128.3, 145.9, 173.5.
Esters of saturated cyclic amino acids. General
procedure. To a solution of compound IIIa, IIIb or VIIa,
VIIb in 10 ml of methanol was added 5 mol% of pal-
ladium on carbon (5% Pd), then a rubber ball filled with
hydrogen was connected to the flask, and the mixture
was stirred in the hydrogen atmosphere for 4 h at room
temperature. After the total disappearance of the initial
compound (TLC monitoring) the reaction mixture was
filtered, acidified to pH 2, and evaporated in a vacuum on
a rotary evaporator. The residue was washed with ethyl
acetate and dried in a vacuum for 30 min.
The study was carried out under a financial support
of the Russian Foundation for Basic Research (grant no.
07-03-00833).
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Ethyl 1-piperidine-2-carboxylate hydrochloride
(IVa). Colorless crystals. Yield 92%. 1H NMR spectrum
(D2O), δ, ppm: 1.30 t (3H, J 7.1 Hz), 1.50–1.70 m (3H),
1.8 m (2H), 2.50 m (1H), 3.08 t (1H, J 12 Hz), 3.45 d (1H,
J 12 Hz), 4.00 d (1H, J 12 Hz), 4.25 q (2H, J 7.0 Hz).
13C NMR spectrum (D2O), δ, ppm: 13.2, 21.2, 25.6, 44.1,
56.9, 63.5, 169.7. Found, %: C 49.70; H 8.40; N 7.14.
C8H16ClNO2. Calculated, %: C 49.61; H 8.33; N 7.23.
Ethyl 1-azacycloheptane-2-carboxylate hydro-
chloride (IVb). Colorless oily substance. Yield 90%.
1H NMR spectrum (D2O), δ, ppm: 1.15 t (3H, J 7.1 Hz),
1.30–1.80 m (7H), 2.20 m (1H), 3.12 m (1H), 3.25 m (1H),
13
4.00 d (1H, J 11 Hz), 4.15 q (2H, J 7.0 Hz). C NMR
spectrum (D2O), δ, ppm: 13.3, 21.2, 24.6, 25.1, 43.8,
56.8, 63.3, 169.3. Found, %: C 41.95; H 8.62, N 6.65.
C9H18ClNO2. Calculated, %: C 52.05; H 8.74; N 6.74.
Ethyl (S)-(–)-1-piperidine-2-carboxylate hydro-
chloride was obtained by hydrogenation of compound
22
1
VIIa. Yield 80%, [α]D –2.1° (c 0.15, H2O). H and
13C NMR spectra are identical to those of compound IVa.
Ethyl (R)-(+)-1-piperidine-2-carboxylate hydro-
chloride was obtained by hydrogenation of compound
10. Watanabe, L.A., Haranaka, S., Jose, B., Yoshida, M.,
Kato, T., Moriguchi, M., Sodaf, K., and Nishino, N., Tet-
rahedron Asymmetry, 2005, vol. 16, p. 903.
1
VIIb. Yield 80%, [α]D22 +1.82° (c 0.2, H2O). H and
13C NMR spectra are identical to those of compound IVb.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 9 2010