Synthesis of 5-(hydroxymethyl)pyrrolidin-2-ones by cyclization of amide dianions with epibromohydrin

Article abstract of DOI:10.1055/s-2006-942354

The reaction of amide and thioamide dianions with epibromohydrin resulted in regioselective formation of 5-(hydroxymethyl)pyrrolidin-2-ones (pyroglutaminols) and -thiones. The cyclization of the dianion of N-(2-tert-butylphenyl)acetamide with epibromohydr

Full text of DOI:10.1055/s-2006-942354

PAPER
1807
Synthesis of 5-(Hydroxymethyl)pyrrolidin-2-ones by Cyclization of Amide
Dianions with Epibromohydrin
S
ynthesi
l
s
of 5-(
i
H
ydrox
a
ymethyl)pyrrolid
F
in-2-ones reifeld,a Holger Armbrust,b Peter Langer*c,d
a
b
c
Institut für Biochemie, Universität Greifswald, Soldmannstr. 16, 17487 Greifswald, Germany
Institut für Organische Chemie der Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany
Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Fax +381 4986412; E-mail: peter.langer@uni-rostock.de
Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
d
Received 16 November 2005; revised 27 January 2006
of the yield. The use of epichlorohydrin resulted in the
formation of a complex mixture. The formation of 3a can
be explained by nucleophilic attack of the carbon atom of
the dianion onto the CBr group and subsequent attack of
Abstract: The reaction of amide and thioamide dianions with epi-
bromohydrin resulted in regioselective formation of 5-(hydroxy-
methyl)pyrrolidin-2-ones (pyroglutaminols) and -thiones. The
cyclization of the dianion of N-(2-tert-butylphenyl)acetamide with
epibromohydrin afforded racemic axially chiral 1-(2-tert-butyl- the nitrogen atom onto the epoxide. Alternatively, the re-
phenyl)-5-(hydroxymethyl)pyrrolidin-2-one with high diastereo-
selectivity.
action may proceed by attack of the dianion onto the ter-
minal carbon atom of the epoxide and subsequent Payne
Key words: cyclizations, dianions, epoxides, heterocycles, regio-
selectivity
rearrangement. The regioselectivity is a result of the high-
er nucleophilicity of the nitrogen compared to the oxygen
atom. The formation of other regioisomers was not ob-
served.
Pyrrolidin-2-ones occur in several biologically relevant
natural products.1 In addition, they represent versatile
synthetic building blocks.1–3 1-Arylpyrrolidin-2-ones re-
present an important subclass of pyrrolidin-2-ones which
occurs in a number of natural products.4 They have been
used as synthetic building blocks5 and represent potent in-
fluenza A sialidase inhibitors.6 Axially chiral 1-(2-tert-
butylphenyl)pyrrolidin-2-ones represent important build-
ing blocks for stereoselective syntheses.7 For example,
diastereoselective alkylations of axially chiral pyrrolidin-
2-ones and diastereoselective reactions of pyrrolidin-2-
one derived iminium salts have been reported. In recent
years we developed a number of cyclization reactions8 of
ambident dianions with epibromohydrin.9 Herein, we re-
port what are, to the best of our knowledge, the first cy-
clizations of amide dianions10,11 with epibromohydrin.
These reactions allow an efficient and regioselective ap-
proach to 1-aryl-5-(hydroxymethyl)pyrrolidin-2-ones12
(N-arylpyroglutaminols).
1) 2.3 equiv n-BuLi
O
2)
O
O
Br
(2)
Ph
3) H+, H2O
N
Ph
Me
N
H
–78 °C
THF
20 °C
OH
1a
3a
H+, H2O
2 n-BuLi
O
O
–
Ph
–
Ph
N
H2C
2 Li+
N
–
O
B
2
O
Ph
O
_
–
LiBr
N
Li+
The reaction of epibromohydrin (2) with the dianion of
N-phenylacetamide (1a), generated by treatment of a THF
solution of 1a with n-BuLi (2.3 equiv), afforded 1-phenyl-
5-(hydroxymethyl)pyrrolidin-2-one (3a)12b (Scheme 1).
Optimal yields (up to 81%) were obtained when the reac-
tion was carried out at –78 °C → 20 °C (warming the mix-
ture during 12 h and stirring at 20 °C for 5 h) and when 1.5
equivalents of the dianion (rather than only one) were
used. Further variation of the temperature and the addition
of a Lewis acid (LiCl, LiClO4) did not result in an increase
A
Scheme 1 Cyclization of dilithiated N-phenylacetamide with epi-
bromohydrin
The cyclization of epibromohydrin (2) with N-arylacet-
amides 1a–e afforded the 1-aryl-5-(hydroxymethyl)pyrro-
lidin-2-ones 3a–e12b,c in good yields (Scheme 2, Table 1).
The cyclization of 2 with the dianion of N-(trimethylsi-
lyl)acetamide13 afforded the labile TMS-substituted pyr-
rolidin-2-one 3f. The chromatographic purification (silica
gel) of crude 3f afforded parent pyroglutaminol (3g). The
pyrrolidine-2-thione 3h was prepared from dilithiated
N-phenylthioacetamide in good yield and, despite the nu-
SYNTHESIS 2006, No. 11, pp 1807–1810
x
x.
x
x
.
2
0
0
6
Advanced online publication: 05.05.2006
DOI: 10.1055/s-2006-942354; Art ID: T15705SS
© Georg Thieme Verlag Stuttgart · New York

1808
I. Freifeld et al.
PAPER
All solvents were dried by standard methods and all reactions were
carried out under an inert atmosphere using oven-dried (150 °C)
1) 2.3 equiv n-BuLi
X
X
2) 2
3) H+, H2O
R2
R1
R2
R1
1
glassware. THF was freshly distilled from Na. For the H and 13C
N
N
H
NMR spectra (1H NMR: 250 MHz, 13C NMR: 62.9 MHz), the deu-
terated solvents indicated were used. The multiplicities of the 13C
NMR signals were determined with the DEPT 135 technique. Mass
spectral data were obtained using the electron ionization (70 eV) or
the chemical ionization technique (CI, H2O). For preparative scale
chromatography, silica gel (Merck, 60–200 mesh) was used.
–78 °C
THF
20 °C
OH
1a–h
3a–i
Scheme 2 Synthesis of 5-(hydroxymethyl)pyrrolidin-2-ones 3a–i
5-(Hydroxymethyl)-1-phenylpyrrolidin-2-one (3a); Typical
Procedure 1
Table 1 Products and Yields Compounds 3
To a THF solution (20 mL) of 1a (0.67 g, 5.00 mmol) was added
n-BuLi (0.01 mol, 4.23 mL, 15% solution in n-hexane) at 0 °C and the
solution was stirred for 45 min. The solution was cooled to –78 °C
and a THF solution (20 mL) of LiClO4 (0.34 g) and, subsequently,
epibromhydrin (0.33 g, 2.40 mmol) were added. The mixture was
stirred for 5–8 h at –40 °C and for 10–12 h at 20 °C. A sat. aq solu-
tion of NH4Cl was added to the mixture. The organic and the aque-
ous layers were separated and the latter was extracted with Et2O
(2 × 50 mL) and CH2Cl2 (2 × 50 mL). The combined organic layers
were washed with brine, dried (Na2SO4) and filtered. The filtrate
was concentrated in vacuo. The residue was purified by chromato-
graphy (silica gel, Et2O) to give 3a (0.37 g, 81%) as a colorless sol-
id.
3
a
b
c
d
e
f
R1
R2
H
X
O
O
O
O
O
O
O
S
Yield (%)a
Ph
81
4-MeC6H4
3-MeC6H4
4-MeOC6H4
4-EtOC6H4
SiMe3
H
H
72
H
76
H
78
H
67
H
62b
98c
73
1H NMR (CDCl3, 250 MHz): d = 2.17 (m, 2 H, 4-H), 2.54 (m, 2 H,
3-H), 3.58 (m, 2 H, CH2OH), 4.26 (m, 1 H, 5-H), 7.17–7.38 (m, 5
g
h
i
H
Ph
H
Harom).
Ph
Me
O
64d
13C NMR (CDCl3, 75 MHz): d = 21.0, 31.4 (CH2), 61.2 (CH), 62.1
(CH2OH), 124.2, 126.1, 129.1 (CHarom), 137.3 (Carom), 175.3 (C=O).
MS (EI, 70 eV): m/z (%) = 191 (M+, 22), 160 (100), 132 (10), 117
(6), 104 (9), 83 (9), 77 (12), 51 (3), 41 (4).
a Yield of isolated product.
b Crude product.
c By chromatography (silica gel) of 3f.
d A 2:1 mixture of diastereomers (assignment arbitrary).
Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85. Found: C, 69.11; H,
6.83.
cleophilicity of the sulfur atom, with very good C/N-re-
gioselectivity. The cyclization of 2 with the dianion of
N-phenylpropionamide afforded 3i as a 2:1 mixture of
diastereomers.
5-(Hydroxymethyl-1-(4-methylphenyl)pyrrolidin-2-one (3b);
Typical Procedure 2
To a THF solution (50 mL) of N-(4-methylphenyl)acetamide (1b;
746 mg, 5.00 mmol) was added n-BuLi (10.67 mmol, 4.51 mL, 3.2
M solution in hexane) under argon at 0 °C. After stirring for 60 min
at 0 °C, the solution was cooled to –78 °C and epibromohydrin
(0.29 mL, 3.33 mmol) was added. The solution was warmed to
20 °C during 12 h and was subsequently stirred for 6 h. A sat. aq
NH4Cl solution (40 mL) was added. The aqueous layer was extract-
ed with Et2O (2 ×) and with CH2Cl2 (2 ×) and the combined organic
layers were dried (MgSO4), filtered and the solvent was removed in
vacuo. The residue was purified by column chromatography (silica
gel, Et2O) to give 3b (492 mg, 72%) as a colorless solid.
1H NMR (CDCl3, 250 MHz): d = 1.97–2.09 (m, 2 H, 4-H), 2.26 (s,
3 H, CH3), 2.33–2.39 (m, 1 H, 3-H), 2.47–2.61 (m, 1 H, 3-H), 3.30–
3.42 (m, 2 H, CH2OH), 3.92 (br, 1 H, OH), 4.02–4.10 (m, 1 H, 5-H),
7.06 (d, J = 7.8 Hz, 2 Harom), 7.16 (d, J = 7.8 Hz, 2 Harom).
13C NMR (CDCl3, 62.9 MHz): d = 21.90 (CH3), 21.0 (C-4), 31.4 (C-
3), 61.7 (C-5), 61.7 (CH2OH), 124.4 (2 CHarom), 129.6 (2 CHarom),
135.9 (Carom), 135.9 (Carom), 175.5 (C=O).
The cyclization of the dianion of N-(2-tert-butylphen-
yl)acetamide (1j) with epibromohydrin afforded the
axially chiral, configurationally stable pyrrolidin-2-one
3j with very good diastereoselectivity (dr > 98:2)
(Scheme 3). The other diastereomer could not be detected.
t-Bu
O
1) 2.3 equiv n-BuLi
2) 2
3) H+, H2O
O
N
Me
N
H
–78 °C
THF
20 °C
OH
3j (rac)
t-Bu
1j
Scheme 3 Synthesis of racemic axially chiral pyrrolidin-2-one 3j
MS (EI, 70 eV): m/z (%) = 205 (23, M+), 174 (100), 132 (5), 118 (6),
91 (7).
In summary, we have reported the synthesis of 5-
(hydroxymethyl)pyrrolidin-2-ones (glutaminols) and
-thiones by regioselective cyclization of amide and thio-
amide dianions with epibromohydrin. The cyclization of
the dianion of N-(2-tert-butylphenyl)acetamide with epi-
bromohydrin afforded axially chiral 1-(2-tert-butylphe-
HRMS (EI, 70 eV): m/z calcd for C12H15NO2 [M+]: 205.1103;
found: 205.1103 2.
Anal. Calcd for C12H15NO2: C, 70.22; H, 7.37. Found: C, 69.95; H,
7.04.
5-(Hydroxymethyl)-1-(3-methylphenyl)pyrrolidin-2-one (3c)
The reaction was carried out according to the typical procedure 2.
Starting with 1c (0.741 g, 5.00 mmol) and n-BuLi (4.51 mL, 10.67
nyl)-5-(hydroxymethyl)pyrrolidin-2-one
diastereoselectivity.
with
high
Synthesis 2006, No. 11, 1807–1810 © Thieme Stuttgart · New York

PAPER
Synthesis of 5-(Hydroxymethyl)pyrrolidin-2-ones
3g
1809
mmol, 3.2 M in hexane), 3c was isolated as a pink solid; yield: 0.520
g (76%).
Chromatographic purification (silica gel, Et2O) of crude 3f afforded
the known desilylated product 3g (98%). The spectroscopic data
were identical with those of an authentic sample.
1H NMR (CDCl3, 250 MHz): d = 1.99–2.20 (m, 2 H, 4-H), 2.25 (s,
3 H, CH3), 2.29–2.48 (m, 1 H, 3-H), 2.48–2.59 (m, 1 H, 3-H), 3.40–
3.51 (m, 2 H, CH2OH), 3.82 (br, 1 H, OH), 4.05–4.10 (m, 1 H, 5-H),
6.90–6.96 (m, 1 Harom), 7.04–7.18 (m, 3 Harom).
13C NMR (CDCl3, 62.9 MHz): d = 21.0 (C-4), 21.4 (CH3), 31.4 (C-
3), 61.6 (C-5), 61.8 (CH2OH), 121.5, 125.2, 127.1, 128.8, 137.2,
138.9 (Ar), 175.5 (C=O).
5-(Hydroxymethyl)-1-phenylpyrrolidin-2-thione (3h)
The reaction was carried out according to the procedure 2. Starting
with 1h (0.756 g, 5.00 mmol), n-BuLi (4.51 mL, 10.67 mmol, 3.2
M solution in hexane) and 2 (0.29 mL, 3.33 mmol), 3h was isolated
as a yellowish solid; yield: 0.511 g (73%).
1H NMR (CDCl3, 250 MHz): d = 1.41–1.60 (m, 2 H, 4-H), 1.89–
2.27 (m, 1 H, 3-H), 2.48–2.59 (m, 1 H, 3-H), 2.75–2.99 (m, 2 H,
CH2OH), 3.60–3.81 (m, 1 H, 5-H), 6.93–7.11 (m, 1 Harom), 7.29–
7.49 (m, 4 Harom).
MS (EI, 70 eV): m/z (%) = 205 (21), 174 (100), 91 (9), 65 (3), 41
(3).
HRMS (EI, 70 eV): m/z calcd for C12H17NO2 [M+]: 205.1203;
found: 205.1203 2.
13C NMR (CDCl3, 62.9 MHz): d = 26.1 (C-4), 29.6 (C-3), 53.1 (C-
5), 65.0 (CH2OH), 120.2, 124.4, 128.9 (CHarom), 137.9 (Carom),
170.8 (C=S).
5-(Hydroxymethyl)-1-(4-methoxyphenyl)pyrrolidin-2-one (3d)
The reaction was carried out according to the typical procedure 2.
Starting with 1d (0.830 g, 5.00 mmol), n-BuLi (4.51 mL, 10.67
mmol, 3.2 M solution in hexane) and 2 (0.29 mL, 3.33 mmol), 3d
was isolated as a yellowish solid; yield: 0.611 g (78%).
1H NMR (CDCl3, 250 MHz): d = 2.03–2.30 (m, 2 H, 4-H), 2.38–
2.51 (m, 1 H, 3-H), 2.57–2.67 (m, 1 H, 3-H), 3.47–3.66 (m, 2 H,
CH2OH), 3.76 (s, 3 H, OCH3), 4.06–4.13 (m, 1 H, 5-H), 6.86 (d, 2
MS (EI, 70 eV): m/z (%) = 207 (46), 174 (48), 115 (10), 106 (16),
93 (100).
HRMS (EI, 70 eV): m/z calcd for C11H13NOS [M+]: 207.0718;
found: 207.0718 2.
Anal. Calcd for C11H13NSO: C, 63.74; H, 6.32. Found: C, 63.52; H,
6.58.
Harom, J = 8.9 Hz), 7.22 (d, 2 Harom, J = 8.9 Hz).
13C NMR (CDCl3, 62.9 MHz): d = 21.01 (C-4), 31.26 (C-3), 55.43
(OCH3), 61.87 (C-5), 62.15 (CH2OH), 114.42 (CHarom), 126.33
(CHarom), 129.98 (Carom), 157.89 (Carom), 175.53 (C=O).
5-(Hydroxymethyl)-3-methyl-1-phenylpyrrolidin-2-one (3i)
The reaction was carried out according to the procedure 2. Starting
with 1i (0.250 g, 1.68 mmol), n-BuLi (1.53 mL, 5.38 mmol, 3.2 M
solution in hexane) and 2 (0.096 mL, 1.12 mmol), 3i was isolated as
a colorless solid; yield: 0.220 g 64%, dr = 2:1).
1H NMR (CDCl3, 250 MHz): d = 1.23–1.35 (m, 1 H, 4-H), 1.22 (d,
3 H, J = 6.9 Hz, CH3), 1.76–1.95 (m, 1 H, 4-H), 2.81–2.90 (m, 1 H,
3-H), 3.54–3.66 (m, 2 H, CH2OH), 4.18 (m, 1 H, 5-H), 6.93–7.11
(m, 1 Harom), 7.29–7.49 (m, 4 Harom).
MS (EI, 70 eV): m/z (%) = 221 (39), 190 (100), 148 (4), 134 (7) 122
(6).
HRMS (EI, 70 eV): m/z calcd for C12H15NO3 [M+]: 221.1642;
found: 221.1642 2.
Anal. Calcd for C12H15NO3: C, 65.14; H, 6.83. Found: C, 64.86; H,
6.64.
13C NMR (CDCl3, 62.9 MHz): d (major diastereomer) = 16.6
(CH3), 30.4 (C-4), 36.8 (C-3), 59.2 (C-5), 62.3 (CH2OH), 123.5,
125.8, 129.1 (CHarom), 137.7 (Carom), 177.7 (C=S).
1-(4-Ethoxyphenyl)-5-(hydroxymethyl)pyrrolidin-2-one (3e)
The reaction was carried out according to the typical procedure 2.
Starting with 1e (0.896 g, 5.00 mmol), n-BuLi (4.51 mL, 10.67
mmol, 3.2 M solution in hexane) and 2 (0.29 mL, 3.33 mmol), 3e
was isolated as a brownish solid; yield: 0.556 g (67%).
1H NMR (CDCl3, 250 MHz): d = 1.31 (t, 3 H, J = 7.0 Hz, CH3),
1.95–2.18 (m, 2 H, 4-H), 2.24–2.38 (m, 1 H, 3-H), 2.48–2.60 (m, 1
H, 3-H), 3.36–3.46 (m, 2 H, CH2OH), 3.85–3.97 (m, 4 H, 5-H,
MS (EI, 70 eV): m/z (%) = 205 (18), 171 (100), 141 (5), 121 (10),
107 (16).
HRMS (EI, 70 eV): m/z calcd for C12H17NO2 [M+]: 205.1203;
found: 205.1203 2.
Anal. Calcd for C12H15NO2: C, 70.22; H, 7.37. Found: C, 69.88; H,
7.08.
OCH2CH3, OH), 6.86 (d, 2 Harom, J = 8.8 Hz), 7.12 (d, 2 Harom
J = 8.8 Hz).
,
trans-1-[2-(tert-Butylphenyl)]-5-(hydroxymethyl)pyrrolidin-2-
one (3j)
The reaction was carried out according to the procedure 1. Starting
with 1j (0.20 g, 1.00 mmol), 3j was isolated as a colorless solid;
yield: 0.13 g (77%, cis/trans < 2:98). The configuration was estab-
lished by NOESY experiments.
13C NMR (CDCl3, 62.9 MHz): d = 14.8 (CH3), 21.0 (C-4), 31.2 (C-
3), 61.7 (OCH2CH3), 62.0 (C-5), 62.5 (CH2OH), 114.8 (CHarom),
126.3 (CHarom), 129.8 (Carom), 157.2 (Carom), 175.6 (C=O).
MS (EI, 70 eV): m/z (%) = 235 (19), 204 (100), 148 (11), 134 (11),
108 (15).
HRMS (EI, 70 eV): m/z calcd for C13H17NO3 [M+]: 235.2355;
found: 235.2355 2.
IR (neat): 3347 (s), 2957 (s), 2929 (m), 2874 (w), 1665 (s), 1493
(m), 1462 (w), 1447 (s), 1414 (s), 1292 (w), 1114 (w), 1085 (w),
1050 (w), 782 (m) cm–1.
Anal. Calcd for C13H17NO3: C, 66.36; H, 7.28. Found: C, 66.64; H,
7.19.
1H NMR (CDCl3, 250 MHz): d = 1.37 [s, 9 H, (CH3)3], 2.06–2.77
2
3
(m, 4 H, 3-H, 4-H), 3.46 (dd, J = 16.0 Hz, J = 5.0 Hz, 1 H,
CH2OH), 3.60 (dd, 2J = 16.0 Hz, 3J = 7 Hz, 1 H, CH2OH), 3.81 (m,
1 H, 5-H), 7.07 (dd, J = 5.0 Hz, J = 1.0 Hz, 1 Harom), 7.20 (dt,
3J = 5.0 Hz, 4J = 1.0 Hz, 1 Harom), 7.28 (dt, 3J = 5.0 Hz, 4J = 1.0 Hz,
1 Harom), 7.49 (dd, 3J = 5.0 Hz, 4J = 1.0 Hz, 1 Harom).
5-(Hydroxymethyl)pyrrolidin-2-ones 3f and 3g
The reaction was carried out according to the typical procedure 1.
The reaction of 1f with 2 afforded 3f, which was isolated as a crude
product; yield: 62%.
3
4
13C NMR (CDCl3, 75 MHz): d = 22.0, 30.5 (CH2), 31.7 [C(CH3)3],
35.7 [C(CH3)3], 62.1 (CH2OH), 63.6 (CH), 126.9, 128.4, 128.6,
132.3 (CHarom), 134.8, 148.1 (Carom), 177.1 (C=O).
3f
1H NMR (CDCl3, 250 MHz): d = 0.10 [s, 9 H, Si(CH3)3], 1.20–1.35
(m, 1 H, 4-H), 1.60–1.80 (m, 1 H, 4-H), 2.10–2.40 (m, 2 H, 3-H),
3.35–3.60 (m, 2 H, CH2OH), 3.75 (m, 1 H, 5-H), 5.97 (br, 1 H, OH).
Synthesis 2006, No. 11, 1807–1810 © Thieme Stuttgart · New York

1810
I. Freifeld et al.
PAPER
MS (EI, 70 eV): m/z (%) = 247 (M+, 1), 216 (100), 190 (57), 160 (5),
144 (7), 130 (7), 118 (9), 91 (18), 77 (6), 57 (10), 41 (7).
HRMS (EI, 70 eV): m/z calcd for C15H21NO2 [M+]: 247.3328;
found: 247.3328 2.
(6) (a) Brouillette, W. J.; Atigadda, V. R.; Luo, M.; Air, G. M.;
Babu, Y. S.; Bantia, S. Bioorg. Med. Chem. Lett. 1999, 9,
1901. (b) Atigadda, V. R.; Brouillette, W. J.; Duarte, F.; Ali,
S. M.; Babu, Y. S. J. Med. Chem. 1999, 42, 2332.
(7) (a) Curran, D. P.; Qi, H.; Geib, S. J.; DeMello, N. C. J. Am.
Chem. Soc. 1994, 116, 3131. (b) Fujita, M.; Kitagawa, O.;
Izawa, H.; Dobashi, A.; Fukaya, H.; Taguchi, T.
Tetrahedron Lett. 1999, 40, 1941; and references cited
therein. (c) Kitagawa, O.; Fujita, M.; Kohriyama, M.;
Hasegawa, H.; Taguchi, T. Tetrahedron Lett. 2000, 41,
8539. (d) Godfrey, C. R. A.; Simpkins, N. S.; Walker, M. D.
Synlett 2000, 388. (e) Bach, T.; Schröder, J.; Harms, K.
Tetrahedron Lett. 1999, 40, 9003. (f) Fujita, M.; Kitagawa,
O.; Izawa, H.; Dobashi, A.; Fukaya, H.; Taguchi, T.
Tetrahedron Lett. 1999, 40, 1949. (g) Fujita, M.; Kitagawa,
O.; Yamada, Y.; Izawa, H.; Hasegawa, H.; Taguchi, T. J.
Org. Chem. 2000, 65, 1108.
Acknowledgment
Financial support from the Fonds der Chemischen Industrie and
from the Deutsche Forschungsgemeinschaft is gratefully acknow-
ledged.
References
(1) Römpp-Lexikon Naturstoffe; Steglich, W.; Fugmann, B.;
Lang-Fugmann, S., Eds.; Thieme: Stuttgart, 1997, 533 ff;
and references cited therein.
(8) For a review of cyclization reactions of dianions, see:
Langer, P.; Freiberg, W. Chem. Rev. 2004, 104, 4125.
(9) For cyclization reactions of epibromohydrin from our
laboratory, see: (a) Langer, P.; Freifeld, I. Chem. Eur. J.
2001, 7, 565. (b) Langer, P.; Freifeld, I. Org. Lett. 2001, 2,
3903. (c) Langer, P.; Armbrust, H.; Eckardt, T.; Magull, J.
Chem. Eur. J. 2002, 8, 1443. (d) Albrecht, U.; Langer, P.
Synlett 2004, 2200. (e) Albrecht, U.; Gerwien, K.; Langer,
P. Tetrahedron Lett. 2005, 46, 1017. (f) Dang, T. T.;
Albrecht, U.; Gerwien, K.; Siebert, M.; Langer, P. J. Org.
Chem. 2006, in press.
(10) (a) Barnish, I. T.; Hauser, C. R. J. Org. Chem. 1968, 33,
2116. (b) Tanaka, K.; Horiuchi, H.; Yoda, H. J. Org. Chem.
1989, 54, 63.
(11) For cyclization reactions of amide dianions from our
laboratory, see: (a) Langer, P.; Döring, M.; Görls, H.;
Beckert, R. Liebigs Ann. Chem. 1997, 2553. (b) Langer, P.;
Wuckelt, J.; Döring, M.; Beckert, R. Eur. J. Org. Chem.
1998, 1467. (c) Langer, P.; Döring, M.; Schreiner, P. R.;
Görls, H. Chem. Eur. J. 2001, 7, 2617.
(12) For N-aryl-5-(hydroxymethyl)pyroglutaminols, see:
(a) Arunachalam, T.; Fan, H.; Pillai, K. M. R.; Ranganathan,
R. S. J. Org. Chem. 1995, 60, 4428. For compounds 3a,b,
see: (b) Giang, L.-T.; Fetter, J.; Kajtar-Peredy, M.; Lempert,
K.; Bertha, F.; Keseru, G.; Czira, G. J. Chem. Res., Miniprint
2000, 0601. For 3d, see: (c) Giang, L.-T.; Fetter, J.;
Lempert, K.; Kajtar-Pereby, M.; Gomory, A. Tetrahedron
1996, 52, 10169.
(2) For the synthesis of amino alcohols, see: (a) Cossy, J.;
Tresnard, L.; Pardo, D. G. Synlett 2000, 409. For the use of
5-hydroxymethyl-g-lactams in the synthesis of peptide
mimetics, see: (b) Olson, G. L.; Cheung, H.-C.; Chiang, E.;
Madison, V. S.; Sepinwall, J.; Vincent, G. P.; Winokur, A.;
Gary, K. A. J. Med. Chem. 1995, 38, 2866; and references
cited therein. For the synthesis of (–)-stemoamide, see:
(c) Kinoshita, A.; Mori, M. J. Org. Chem. 1996, 61, 8356.
For other applications, see: (d) Keusenkothen, P. F.; Smith,
M. B. Tetrahedron 1992, 48, 2977.
(3) (a) Thottathil, J. K.; Moniot, J. L.; Müller, R. H.; Wong, M.
K. Y.; Kissick, T. P. J. Org. Chem. 1986, 51, 3140.
(b) Ohta, T.; Hosoi, A.; Nozoe, S. Tetrahedron Lett. 1988,
29, 329. (c) Baldwin, J. E.; Miranda, T.; Moloney, M. G.;
Hokelek, T. Tetrahedron 1989, 45, 7459. (d) Armstrong, R.
W.; DeMattei, J. A. Tetrahedron Lett. 1991, 32, 5749.
(4) (a) Takei, H.; Fukuda, Y.; Sugaya, K.; Taguchi, T.; Kawara,
T. Chem. Lett. 1980, 1307. (b) Nacci, V.; Campiani, G.;
Garofalo, A. J. Heterocycl. Chem. 1990, 27, 1329.
(c) Martin, P.; Steiner, E.; Streith, J.; Winkler, T.; Bellus, D.
Tetrahedron 1985, 41, 4057. (d) Casadei, M. A.; Gessner,
A.; Inesi, A.; Jugelt, W.; Liebezeit, H.; Micheletti-Moracci,
F. Bull. Soc. Chim. Fr. 1989, 650. (e) Kar, G. K.;
Chatterjee, B. G.; Ray, J. K. Synth. Commun. 1993, 23,
1953. (f) Mandal, S. B.; Achari, B.; Chattopadhyay, S.
Tetrahedron Lett. 1992, 33, 1647. (g) Takahata, H.; Wang,
E.-C.; Yamazaki, T. Synth. Commun. 1988, 18, 1159.
(5) Arpin, N.; Favre-Bonvin, J.; Thivend, S. Tetrahedron Lett.
1977, 819.
(13) Kuzma, P. C.; Brown, L. E.; Harris, T. M. J. Org. Chem.
1984, 49, 2015.
Synthesis 2006, No. 11, 1807–1810 © Thieme Stuttgart · New York