Highly stereoselective De-Novo synthesis of protected 2-amino-3-C-methyl-2, 3-dideoxy-d-altrose

Article abstract of DOI:10.1016/j.tet.2010.05.101

A new strategy for the stereoselective synthesis of 2-amino-2-deoxy-aldoses is described. Therefore epoxy carbamates are reacted with isocyanates to furnish urethanes, which will form the title compounds with high diastereoselectivities under basic conditions and O,O-migration of the carbamoyl group.

Full text of DOI:10.1016/j.tet.2010.05.101

Tetrahedron 66 (2010) 6162e6166
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journal homepage: www.elsevier.com/locate/tet
Highly stereoselective De-Novo synthesis of protected
2-amino-3-C-methyl-2,3-dideoxy-
D-altrose
y
*
Sabine Kollmann, Elisa Nauha , Dieter Hoppe
€
€
Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat Münster, Corrensstraße 40, 48149 Münster, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A new strategy for the stereoselective synthesis of 2-amino-2-deoxy-aldoses is described. Therefore
epoxy carbamates are reacted with isocyanates to furnish urethanes, which will form the title com-
pounds with high diastereoselectivities under basic conditions and O,O-migration of the carbamoyl
group.
Received 5 May 2010
Accepted 27 May 2010
Available online 1 June 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Urethanes
Isocyanates
Branched carbohydrates
O,O-Migration
1. Introduction
OH
Ti(Oi-Pr)3
NiPr2
O
a)
R* CH O
R*
Modified carbohydrates play an important role in the synthesis of
antibodies,1 enzymes,2 and biologically active compounds.3 Recently
we published the highly stereoselective synthesis of methyl-
branched 2-amino-2-deoxy-aldoses from protected sugar aldehydes
1 (Scheme 1).4 Aldehydes 1 are elongated via introduction of the C-
1eC-3 unit by homoaldol reaction of enantioenriched homoenolate
reagent 2 to deliver enol carbamates 3.5 Diastereoselective epoxida-
tion6 provided epoxides 4 followed by aminolysis with sodium azide,
reduction, and protection furnish target furanosides 7.4
The synthesis of the framework turned out very straightforward
but for the introduction of the amino group some improvement
seemed to be possible since oxiranes are powerful alkylation
moieties. Intramolecular delivery of the amino group might en-
hance the rate of its attack.
O
OC b
1
2
3
(50-72%)
OH
b) t-BuOOH,
VO(acac)2
c) MeSO3H,
MeOH
OH
O
H
R*
R*
OMe
O
5
OCb
4
(69-85%)
(70-90%)
N3
e) Pd/C, H2,
Boc2O
d) Tf2O,
NaN3
NHBoc
OMe
H
H
R*
OMe
R*
O
6
O
7
(61-80%)
(62-70%)
O
2. Results and discussion
O
O
O
R* =
O
Consequently, oxirane 4a was refluxed with 4-bromophenyl
isocyanate (8a) in dioxane.7 The choice of the N-group was directed
not by its protecting group-properties but by the expectation
forming a crystalline product for facile structure elucidation
(Scheme 2). In a couple of examples, N-bromophenyl groups led to
crystallization of homoaldol products and their derivatives.8
O
O
b
O
O
O
O
a
c
O
O
MeO
d
O
O
* Corresponding author. Tel.: þ49 251 83 33275; fax: þ49 251 83 36531; e-mail
Scheme 1. Synthesis of furanosides 7. Reagents and conditions: (a) n-pentane/cyclo-
hexane (6.7:1), ꢀ78 ꢁC, 4 h; (b) t-BuOOH, VO(acac)2, CH2Cl2, rt, 15 h; (c) MeSO3H,
MeOH, CH2Cl2, ꢀ78 ꢁC, 15 h; (d) (i) (CF3SO2)2O, pyridine, ꢀ15 ꢁC/ꢀ5 ꢁC, 3 h; (ii) NaN3,
DMSO, 50 ꢁC, 5e15 h; (e) Boc2O, Pd/C, H2, THF, rt, 9 h.
address: dhoppe@uni-muenster.de (D. Hoppe).
y
X-ray crystal structural analysis. Permanent address: Nanoscience Center, P.O.
€
€
Box 35, FI-40014 University of Jyvaskyla, Finland.
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.05.101

S. Kollmann et al. / Tetrahedron 66 (2010) 6162e6166
6163
O
R1
O
OH
O
NH
O
1
a)
b) K2CO3, MeOH
R
N
C
O
8
O
-OCb
O
O
OCb
O
OCb
4a
9
(87-96%)
O
O
O
R1
H
R1
O
N
N
MeOH
MeOH
O
OH
OMe
O
O
O
O
10
11
R1
O
O
HO
N
O
O
OMe
Figure 1. X-ray crystal structure of epoxy carbamate 9c.9,10
12
(54-72%)
Scheme 2. Synthesis of 2-amino-3-C-methyl-2,3-dideoxy-D-altroses 12. Reagents and
conditions: (a) ReN]C]O, dioxane, reflux, 24 h; (b) K2CO3, MeOH, reflux, 3 h.
from epoxide 9b turned out to be crystalline after O-benzoylation,
and we learned that oxazolidin-2-one 12 is the product (Fig. 2). We
assume that the hemiacetal anion formed from intermediate 11
undergoes an O-1eO-3 migration of the carbamoyl group under
the basic reaction conditions.
After heating for 24 h at 100 ꢁC, the carbamate ester 9a was
obtained with 87% yield. Similarly, the urethanes 9b and 9c, were
prepared from 4-tert-butylphenyl (8b) and 3-nitrophenyl (8c) iso-
cyanate (Table 1). Only the 3-nitrobenzoate 9c provided suitable
crystals for an X-ray analysis, which showed the epoxide group
being still present (Fig. 1).
By refluxing epoxy carbamates 9 with a suspension of solid
potassium carbonate in methanol, the intramolecular opening of
the epoxide moiety 9 took place at C-2 with inversion of the con-
figuration. We expected the formation of amino aldehydes 10 or the
corresponding hemiacetals 11. Fortunately, the product obtained
Table 1
Results of the reaction of 4a with various isocyanates
Isocyanate
Urethanea
(yield)
Oxazolidin-2-onea
(yield)
Br
Br
O
O
OH
N
O
NH
4-BreC6H4eN]C]O
(8a)
O
O
O
O
O
OMe
O
OCb
12a (54%)
9a (87%)
Figure 2. X-ray crystal structure of oxazolidin-2-one 13b.10,11
O
We have not yet explored the synthetic advantages of the
unique protecting group pattern of compounds 12, which bridges
N-2 and O-1 by a urethane moiety, combined with a free OH
group at C-4. Liberation of the aldehyde group appears possible
under acidic and under basic conditions via attack at the carbonyl
group.
O
O
NH
O
OH
N
4-t-BueC6H4eN]C]O
(8b)
O
O
O
O
OCb
O
OMe
9b(96%)
12b (72%)
3. Conclusion
O
O2N
O
A new and surprisingly simple method for the synthesis of
stereochemically pure 2-amino-2-deoxy-aldoses has been discov-
ered. Although demonstrated only for one type, a wide scope of
applicability is expected. By selection of the starting aldehyde and
the homoenolate reagent, a large variation in the structure seems to
be possible. In addition, the choice of the isocyanate should allow
for the introduction of optimal N-protecting groups.
O
NH
NO2
OH
N
3-NO2eC6H4eN]C]O
(8c)
O
O
O
O
O
OCb
O
OMe
9c (89%)
12c (65%)
For all compounds: dr>98:2, determined by 1H NMR analysis of the crude
a
product.

6164
S. Kollmann et al. / Tetrahedron 66 (2010) 6162e6166
4. Experimental
0.3 mmol) was reacted with 4-tert-butylphenyl isocyanate (72.9 mg,
0.45 mmol)in5 mLdioxanetoafford9b(150 mg,96%)asyellowsolid.
4.1. General
Rf 0.64 (EtOAc/c-hexane¼1:1); tR 9.37 min (HP 5); mp 113.6 ꢁC
20
(EtOAc); [
a
]
þ3.4 (c 0.90, CHCl3). 1H NMR (400 MHz, CDCl3):
d/
D
ppm¼1.11 (d, 3J3,3-CH3¼7.2 Hz, 3H, 3-CH3); 1.23 (d, 3J1 ,2 ¼6.8 Hz, 12H,
0
0
All moisture-sensitive reactions were carried out under an at-
mosphere of argon in flame-dried glassware sealed by rubber septa.
Unless otherwise specified, materials were obtained from com-
mercial sources and used without purification. All solvents were
dried according to standard procedures and purified by distillation
prior to use. Addition of chemicals was performed by using dis-
posable plastic syringes. Flash chromatography was performed
using Merck silica gel 60 (230e400 mesh) at a pressure of about
1.5 bar and monitored by TLC. Solvents for chromatography (cy-
clohexane, EtOAc) were distilled prior to use. For analytic thin layer
chromatography, Merck plastic sheets (60 F254 silica gel) were used.
Visualization was accomplished with permanganate solution and
vanilline solution. 1H and 13C NMR spectra were recorded on
a Bruker ARX 400 or a Varian Inova 500 spectrometer. Chemical
20-CH3); 1.30 (s, 9H, C(CH3)3); 1.33,1.38 (each s, 6H, C(CH3)2); 2.14 (m,
3
3
1H, 3-H1); 3.01 (dd, J1,2¼2.8 Hz, J2,3¼9.3 Hz, 1H, 2-H1); 3.73, 4.09
(eachbrs, 2H,10-H1);3.95(dd,3J5,6A¼5.7 Hz, 3J6A,6B¼8.5 Hz,1H, 6-HA);
3
4.10 (m, 1H, 6-HB); 4.39 (m, 1H, 5-H1); 5.13 (dd, J3,4¼3.6 Hz,
3J4,5¼6.1 Hz, 1H, 4-H1); 5.63 (d, 1H, 1-H1); 6.74 (s, 1H, NH); 7.24e7.35
(m, 4H, AreH);13CNMR(100 MHz,CDCl3):
d
/ppm¼13.5 (3-CH3);20.3,
21.4 (C-20); 25.2, 26.6 (C(CH3)2); 31.3 (C(CH3)3); 34.3 (C(CH3)3); 34.5
(C-3); 45.3, 45.8 (C-10); 56.2 (C-2); 66.1 (C-6); 74.8 (C-4); 75.8 (C-1);
77.2 (C-5); 109.3 (C(CH3)2); 120.9, 125.7, 126.0 (CH, CAr); 135.5, 147.0
ꢀ1
~
n
(Cq, CAr); 153.6 (OC]O); 154.1 (NC]O). IR (ATR):
/cm ¼3307, 3055,
2965, 2904, 2873,1705, 1598,1529,1434,1296,1214,1050, 834, 1135.
Anal. Calcd for C28H44N2O7: C, 64.59; H, 8.52; N, 5.38. Found: C, 64.77;
H, 8.53; N, 5.12.
shifts are given in parts per million (
d
), with tetramethylsilane (1H)
and CDCl3
(
13C) as internal standard. The multiplicities are in-
4.2.3. [1S,2R,3R,4S,5R]-1,2-Epoxy-4,5,6-trihydroxy-5,6-O-iso-
propylidene-3-methyl-4-O-(3-nitrophenylcarbamoyl)-hexyl N,N-dii-
sopropylcarbamate (9c). According to GPA, carbamate 4a (158 mg,
0.30 mmol) was reacted with 3-nitrophenyl isocyanate (0.35 g,
1.0 mmol) in 15 mL dioxane to afford 9c (450 mg, 89%) as yellow
dicated by s (singlet), br s (broad singlet), d (doublet), t (triplet), and
m (multiplet). The numbering of the compounds may differ from
the IUPAC nomenclature. Optical rotations were measured at 20 ꢁC
with a Perkin-Elmer 341 at the sodium D line, the IR spectra were
recorded using a Varian 3100 Excalibur series spectrometer. Ele-
mental analysis was performed at the Chemistry Department of the
University of Münster. ESI (Exact Mass Determination) was carried
out with a Quattro LCZ (Waters-Micromass, Manchester, UK) with
nanospray inlet.
crystals. Rf 0.55 (EtOAc/c-hexane¼1:1); tR 11.73 min (HP 5); mp
20
130.8 ꢁC (EtOAc); [
a
]
þ6.4 (c 0.61, CHCl3). 1H NMR (400 MHz,
D
3
CDCl3):
d
/ppm¼1.14 (d, J3,3-CH3¼7.2 Hz, 3H, 3-CH3); 1.23 (d,
0
3
0
0
J1 ,2 ¼6.8 Hz, 12H, 2 -CH3); 1.34, 1.39 (each s, 6H, C(CH3)2); 2.13 (m,
3
3
1H, 3-H1); 3.01 (dd, J1,2¼2.9 Hz, J2,3¼9.4 Hz, 1H, 2-H1); 3.73, 4.11
(each br s, 2H, 10-H1); 3.96 (dd, 3J5,6A¼5.7 Hz, 3J6A,6B¼8.6 Hz, 1H, 6-
HA); 4.08e4.14 (m, 1H, 6-HB); 4.41 (m, 1H, 5-H1); 5.18 (dd,
4.2. General procedure for the synthesis of compounds 9
(GPA)
3J3,4¼4.4 Hz, J4,5¼5.7 Hz, 1H, 4-H1); 5.62 (d, 1H, 1-H1); 7.18 (s, 1H,
3
NH); 7.38e8.40 (m, 4H, AreH). 13C NMR (100 MHz, CDCl3):
1,2-Epoxy-4-hydroxyalkylcarbamate 4a (1.0 equiv) and 1.5 equiv
isocyanate8a, 8b or 8cweredissolved in dioxane(10 mL/mmol), and
the solution was stirred for 24 h under reflux. The reaction was
stopped by addition of water (10 mL/mmol) and the aqueous layer
was separated and extracted with Et2O (3ꢂ10 mL/mmol). The
combined organic phases were dried over MgSO4, the solvent was
evaporated, and the residue was purified by column chromatogra-
phy (EtOAc/c-hexane¼1:2/1:1).
d
/ppm¼13.4 (3-CH3); 20.3, 21.5 (C-20); 25.1, 26.6 (C(CH3)2); 34.6 (C-
3); 45.8, 47.0 (C-10); 56.3 (C-2); 65.8 (C-6); 74.8 (C-4); 75.7 (C-1);
77.2 (C-5); 109.4 (C(CH3)2); 118.2, 129.9 (CH, CAr); 139.0, 148.8 (Cq,
ꢀ1
~
CAr); 152.7 (OC]O); 154.1 (NC]O). IR (ATR):
n
/cm ¼3291, 3096,
2975, 2938, 2880, 1686, 1600, 1530, 1350, 1296, 1214, 1051, 753,
1135; ESI-MS (m/z): 532.23 [(MþNa)þ].
4.3. General procedure for the synthesis of compounds 12
(GPB)
4.2.1. [1S,2R,3R,4S,5R]-4-O-(4-Bromophenylcarbamoyl)-1,2-epoxy-
4,5,6-trihydroxy-5,6-O-isopropylidene-3-methyl-hexyl N,N-diisopro-
pylcarbamate (9a). According to GPA, carbamate 4a (69 mg,
0.2 mmol) was reacted with 4-bromophenyl isocyanate (57.9 mg,
0.3 mmol) in 4 mL dioxane to afford 9a (94.3 mg, 87%) as yellow
Urethane 9 (1.0 equiv) was dissolved in MeOH (5 mL/mmol) and
the solution was treated with 1.0 equiv finely grind K2CO3, and
stirred for 3e6 h under reflux. The reaction was stopped by addi-
tion of satd NH4Cl (10 mL/mmol), the aqueous layer was separated
and extracted with Et2O (3ꢂ10 mL/mmol). The combined organic
phases were dried over MgSO4, the solvent was evaporated, and the
residue was purified by column chromatography (EtOAc/c-hexane
1:2/1:1).
solid. Rf 0.59 (EtOAc/c-hexane¼1:1); tR 8.46 min (HP 5); mp
20
135.5 ꢁC (EtOAc); [
a
]
þ7.1 (c 0.59, CHCl3). 1H NMR (500 MHz,
D
3
CDCl3):
d
/ppm¼1.11 (d, J3,3-CH3¼7.3 Hz, 3H, 3-CH3); 1.22 (d,
0
3
0
0
J1 ,2 ¼6.8 Hz, 12H, 2 -CH3); 1.32, 1.37 (each s, 6H, C(CH3)2); 2.12 (m,
1H, 3-H1); 2.99 (dd, 3J1,2¼2.8 Hz, 3J2,3¼9.2 Hz, 1H, 2-H1); 3.72, 4.09
(each br s, 2H, 10-H1); 3.94 (dd, 3J5,6A¼8.7 Hz, 3J6A,6B¼5.7 Hz, 1H, 6-
HA); 4.07e4.11 (m, 1H, 6-HB); 4.38 (m, 1H, 5-H1); 5.13 (dd,
4.3.1. [4S,5S,5(1R,2S,2(4R))]-3-(4-Bromophenyl)-4-[2-hydroxy-1-
methyl-2-(2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl]-5-methoxy-ox-
azolidin-2-one (12a). According to GPB urethane 9a (0.11 g,
0.20 mmol) was dissolved in 7.0 mL of dry MeOH and treated with
K2CO3 (28 mg, 0.2 mmol). Work-up and purification of the crude
product by flash chromatography (EtOAc/c-hexane¼1:1) yielded
3J3,4¼4.2 Hz, J4,5¼6.0 Hz, 1H, 4-H1); 5.61 (d, 1H, 1-H1); 6.96 (s, 1H,
3
NH); 7.31e7.41 (m, 4H, AreH). 13C NMR (100 MHz, CDCl3):
d/
ppm¼13.4 (3-CH3); 20.3, 21.4 (C-20); 25.1, 26.5 (C(CH3)2); 34.5 (C-
3); 45.7, 47.0 (C-10); 56.3 (C-2); 65.9 (C-6); 74.8 (C-1); 75.8 (C-5);
77.2 (C-4); 109.3 (C(CH3)2); 120.2 (CH, CAr); 132.0, 136.9 (Cq, CAr);
47 mg (54%) oxazolidin-2-one 12a as yellow crystals. Rf 0.21 (EtOAc/
ꢀ1
20
152.8 (OC]O); 154.1 (NC]O). IR (ATR):
n
/cm ¼3306, 3061, 2975,
c-hexane¼1:1); tR 23.62 min (HP 5); mp 98.7 ꢁC (EtOAc); [
a]
D
~
2935, 2878, 1687, 1595, 1531, 1371, 1305, 1211, 1046, 825, 1135. ESI-
þ47.6 (c 0.54, CHCl3). 1H NMR (400 MHz, CDCl3):
/ppm¼0.86 (d,
d
MS (m/z): 565.15 [(MþNa)þ].
3J3,3-CH3¼7.3 Hz, 3H, 3-CH3); 1.38, 1.41 (each s, 6H, C(CH3)2);
1.99e2.08 (m, 1H, 3-H1); 2.42 (br s, 1H, 4-OH); 3.56 (s, 3H, OCH3);
3.71e3.79 (m, 1H, 4-H1); 3.85 (dd, 3J5,6A¼6.4 Hz, 3J6A,6B¼8.3 Hz, 1H,
4.2.2. [1S,2R,3R,4S,5R]-4-O-4-tert-(Butylphenylcarbamoyl)-1,2-ep-
oxy-4,5,6-trihydroxy-5,6-O-isopropylidene-3-methylhexyl N,N-diiso-
propylcarbamate (9b). According to the GPA, carbamate 4a (0.10 mg,
3
6-HA); 3.99 (dd, J5,6B¼6.5 Hz, 1H, 6-HB); 4.19 (m, 1H, 5-H1); 4.68
3
3
(dd, J1,2¼1.8 Hz, J2,3¼2.9 Hz, 1H, 2-H1); 5.38 (d, 1H, 1-H1);

S. Kollmann et al. / Tetrahedron 66 (2010) 6162e6166
6165
7.40e7.50 (m, 4H, AreH); 13C NMR (100 MHz, CDCl3):
d
/ppm¼9.65
1H, 3-H1); 3.53 (s, 3H, OCH3); 3.86 (dd, 3J5,6A¼5.9 Hz, 3J6A,6B¼8.5 Hz,
1H, 6-HA); 4.08 (dd, 3J5,6B¼6.2 Hz,1H, 6-HB); 4.38 (ddd, 3J4,5¼7.5 Hz,
(3-CH3); 25.1, 26.5 (C(CH3)2); 33.3 (C-3); 56.4 (OeCH3); 62.2 (C-2);
64.9 (C-6); 72.1 (C-4); 76.3 (C-5); 98.9 (C-1); 109.3 (C(CH3)2); 122.3,
132.1 (CH, CAr); 135.2 (Cq, CAr); 153.9 (OC]O). IR (ATR):
3
3
1H, 5-H1); 4.62 (dd, J1,2¼1.7 Hz, J2,3¼2.8 Hz, 1H, 2-H1); 5.34 (dd,
1H, 4-H1); 5.40 (d, 1H, 1-H1); 7.37e7.67, 8.02e8.06 (m, 9H, PheH).
ꢀ1
n
/cm ¼3483, 3075, 2985, 2936, 2885, 2360,1726,1494,1425,1382,
13C NMR (100 MHz, CDCl3):
(CH3)2); 31.3 (C(CH3)3); 32.9 (C(CH3)3); 34.4 (C-3); 56.1 (OeCH3);
62.5 (C-2); 67.2 (C-6); 74.9 (C-5); 75.4 (C-4); 98.9 (C-1); 109.9 (C
(CH3)2); 121.2, 126.0, 128.7, 129.6 (CH, CAr); 133.0, 133.7, 148.2 (Cq,
d
/ppm¼10.3 (3-CH3); 25.4, 26.5 (C
~
1208, 1070, 993, 827, 1109, 753. ESI-MS (m/z): 452.07 [(MþNa)þ];
883.14 [(2MþNa)þ].
ꢀ1
~
n
4.3.2. [4S,5S,5(1R,2S,2(4R))]-3-(4-tert-Butylphenyl)-4-[2-hydroxy-1-
methyl-2-(2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl]-5-methoxy-ox-
azolidin-2-one (12b). According to GPB urethane 9b (0.47 g,
0.90 mmol) was dissolved in 20.0 mL of dry MeOH and treated with
K2CO3 (0.13 g, 0.90 mmol). Work-up and purification of the crude
product by flash chromatography (EtOAc/c-hexane¼1:2/1:1)
yielded 26 mg (72%) oxazolidin-2-one 12b as colorless solid. Rf 0.48
(EtOAc/c-hexane¼1:1); tR 23.63 min (HP 5); mp 79.5 ꢁC (EtOAc);
CAr); 154.1 (O(C]O)N); 165.5 (OC]O). IR (ATR):
/cm ¼3036,
2963, 2876, 2360, 1761, 1724, 1520, 1388, 1347, 1213, 1070, 992, 837,
1099, 711. Anal. Calcd for C29H37NO7: C, 68.08; H, 7.29; N, 2.74.
Found: C, 67.86; H, 7.26; N, 2.69.
Acknowledgements
This work was supported by the Deutsche For-
schungsgemeinschaft (SFB 424).
[
a
]
20 þ38.8 (c 0.64, CHCl3). 1H NMR (400 MHz, CDCl3):
d/ppm¼0.87
D
(d, 3J3,3-CH3¼7.0 Hz, 3H, 3-CH3); 1.31 (s, 9H, C(CH3)3); 1.38,1.42 (each
3
s, 6H, C(CH3)2); 2.00 (m, 1H, 3-H1); 2.32 (d, J4,4-OH¼2.8 Hz, 1H, 4-
Supplementary data
OH); 3.56 (s, 3H, OCH3); 3.75e3.80 (m, 1H, 4-H1); 3.87 (dd,
3J5,6A¼6.8 Hz, 3J6A,6B¼8.3 Hz, 1H, 6-HA); 3.96 (dd, 3J5,6B¼6.5 Hz, 1H,
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2010.05.101. These data in-
clude MOL files and InChIKeys of the most important compounds
described in this article.
3
3
6-HB); 4.20 (ddd, J4,5¼4.3 Hz, 1H, 5-H1); 4.70 (dd, J1,2¼1.9 Hz,
3J2,3¼2.8 Hz, 1H, 2-H1); 5.33 (d, 1H, 1-H1); 7.35e7.48 (m, 4H, PheH).
13C NMR (100 MHz, CDCl3):
d/ppm¼9.55 (3-CH3); 25.1, 26.5 (C
(CH3)2); 31.3 (C(CH3)3); 33.8 (C(CH3)3); 34.3 (C-3); 56.3 (OeCH3);
62.5 (C-2); 64.3 (C-6); 71.5 (C-4); 76.5 (C-5); 98.9 (C-1); 109.3 (C
(CH3)2); 120.9,ꢀ1126.1 (CH, CAr); 133.3, 148.0 (Cq, CAr); 154.3 (OC]O).
~
References and notes
1. Selected examples: (a) Zhang, C.; Fu, Q.; Albermann, C.; Li, L.; Thorson, J. S.
ChemBioChem 2007, 8, 385; (b) Sarabia, F.; Martin-Ortiz, L.; Lopez-Herrera, F. J.
Org. Lett. 2003, 5, 3927; (c) Hanessian, S.; Kloss, J. Tetrahedron Lett. 1985, 26,
1261.
IR (ATR):
n
/cm ¼3476, 3078, 2935, 2890, 2888, 2844, 1739, 1531,
1385, 1348, 1205, 1068, 751, 1094. ESI-MS (m/z): 430.22 [(MþNa)þ].
2. Selected examples: (a) Anizon, F.; Belin, L.; Moreau, P.; Sancelme, M.; Voldoire,
A.; Prudhomme, M.; Ollier, M.; Sevère, D.; Riou, J.-F.; Bailly, C.; Fabbro, D.;
Meyer, T. J. Med. Chem. 1997, 40, 3456; (b) El-Hamamsy, M. H. R. I.; Smith, A. W.;
Thompson, A. S.; Threadgil, M. D. Bioorg. Med. Chem. 2007, 15, 4552.
3. Selected examples: (a) Zhang, C.; Griffith, B. R.; Fu, Q.; Albermann, C.; Fu, X.;
Lee, I.-K.; Li, L.; Thorson, J. S. Science 2006, 313, 1291; (b) Ahmed, S. A.; Odde, S.;
Daga, P. R.; Bowling, J. J.; Mesbah, M. K.; Youssef, D. T.; Khalifa, S. I.; Doerksen,
R. J.; Hamann, M. Org. Lett. 2007, 9, 4773.
4.3.3. [4S,5S,5(1R,2S,2(4R))]-4-[2-Hydroxy-1-methyl-2-(2,2-di-
methyl-[1,3]dioxolan-4-yl)-ethyl]-5-methoxy-3-(3-nitrophenyl)-ox-
azolidin-2-one (12c). According to GPB urethane 9a (0.15 g,
0.30 mmol) was dissolved in 10.0 mL of dry MeOH and treated with
K2CO3 (42 mg, 0.30 mmol). Work-up and purification of the crude
product by flash chromatography (EtOAc/c-hexane¼1:2/1:1)
yielded 770 mg (65%) oxazolidin-2-one 12c as colorless solid. Rf
€
4. Kollmann, S.; Frohlich, R.; Hoppe, D. Synthesis 2010, 749.
0.44 (EtOAc/c-hexane¼1:1); tR 22.89 min (HP 5); mp 67.7 ꢁC
5. (a) Hoppe, D.; Zschage, O. Angew. Chem. 1989, 101, 67; Angew. Chem. Int. Ed. Engl.
1989, 26, 69; (b) Paulsen, H.; Graeve, C.; Hoppe, D. Synthesis 1996, 141; (c)
20
(EtOAc); [
a
]
D
þ18.5 (c 1.07, CHCl3). 1H NMR (400 MHz, CDCl3):
d/
€
Kollmann, S.; Frohlich, R.; Hoppe, D. Synthesis 2007, 883 For reviews see: (d)
3
ppm¼0.92 (d, J3,3-CH3¼7.2 Hz, 3H, 3-CH3); 1.41, 1.43 (each s, 6H, C
Hoppe, D.; Hense, T. Angew. Chem. 1997, 109, 2376; Angew. Chem., Int. Ed. 1997,
36, 2282; (e) Hoppe, D.; Marr, F.; Brüggemann, M. Top. Organomet. Chem. 2003,
5, 61; (f) Christoph, G.; Hoppe, D. In The Chemistry of Organolithium Compounds;
Rappoport, Z., Marek, I., Eds.; Wiley: Chichester, UK, 2004; p 1055; (g) Hoppe,
D. Synthesis 2009, 43.
6. (a) Ohshima, T. Chem. Pharm. Bull. 2004, 52, 1031; (b) Torres, G.; Torres, W.;
Prieto, J. A. Tetrahedron 2004, 60, 10245; (c) Wang, Z.; Schreiber, S. L. Tetrahe-
dron Lett. 1990, 31, 31; (d) Sharpless, K. B.; Verhoeven, T. Aldrichim. Acta 1979,
12, 63; (e) Tarara, G.; Hoppe, D. Synthesis 1989, 89; (f) Hoppe, D.; Tarara, G.;
Wilckens, M. Synthesis 1989, 83; (g) Hoppe, D.; Lüßmann, J.; Jones, P. G.;
Schmidt, D.; Sheldrick, G. M. Tetrahedron Lett. 1986, 27, 3591 For reviews see:
(h) Marco-Contelles, I.; Molina, M. T.; Anjum, S. Chem. Rev. 2004, 104, 2857; (i)
Sharpless, K. B. Angew. Chem. 2002, 114, 2126; Angew. Chem. Int. Ed. 2002, 41,
2024; (j) Katsuki, T. Curr. Org. Chem. 2001, 5, 663; (k) Sharpless, K. B.; Johnson,
R. A. In Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH: New
York, NY, 2000; p 231.
(CH3)2); 2.18 (m, 1H, 3-H1); 3.58 (s, 3H, OCH3); 3.75 (t, 3J3,4¼6.5 Hz,
3
3
1H, 4-H1); 3.88 (dd, J5,6A¼5.7 Hz, J6A,6B¼8.4 Hz, 1H, 6-HA); 4.08
3
(dd, J5,6B¼6.2 Hz, 1H, 6-HB); 4.22 (m, 1H, 5-H1); 4.78 (dd,
3
3J1,2¼1.7 Hz, J2,3¼2.8 Hz, 1H, 2-H1); 5.53 (d, 1H, 1-H1); 7.56e8.42
(m, 4H, AreH). 13C NMR (100 MHz, CDCl3):
d/ppm¼9.8 (3-CH3);
25.0, 26.6 (C(CH3)2); 32.9 (C-3); 56.6 (OCH3); 62.1 (C-2); 65.9 (C-6);
73.2 (C-4); 76.1 (C-5); 99.3 (C-1); 109.8 (C(CH3)2); 114.7, 119.1, 125.9,
130.0 (CH, CAr); 137.6, 148.8 (Cq, CAr); 153.9 (OC]O). IR (ATR):
ꢀ1
~
n
/cm ¼3446, 3005, 2964, 2906, 2884, 2360,1734, 1520,1427, 1384,
1214, 1066, 992, 836, 1101. ESI-MS (m/z): 419.14 [(MþNa)þ]; 815.30
[(2MþNa)þ].
7. For intramolecular epoxy opening in diepoxyurethanes see: Kühlmeyer, R.;
Seitz, B.; Weller, T.; Fritz, H.; Schwesinger, R.; Prinzbach, H. Chem. Ber. 1989, 122,
1729.
4.4. Synthesis of benzoyl-substituted oxazolidin-2-one 13b
€
8. (a) Bou Chedid, R.; Brümmer, M.; Wibbeling, B.; Frohlich, R.; Hoppe, D. Angew.
4.4.1. [1S,2R,2(4S,5S),1(4R)]-3-(4-tert-Butylphenyl)-4-[2-benzoy-
loxy-1-methyl-2-(2,2-dimethyl-[1,3]dioxolan-4-yl)-ethyl]-5-me-
thoxy-oxazolidin-2-one (13b). Oxazolidin-2-one 12b (79.7 mg,
0.18 mmol) and DMAP (16 mg, 0.009 mmol) were dissolved in
CH2Cl2 cooled to 0 ꢁC, and treated with benzoic anhydride (71 mg,
0.31 mmol). After 1 h stirring at room temperature, aqueous work-
up and purification by flash chromatography on silica gel (EtOAc/
c-hexane¼1:1) benzoyl-substituted oxazolidin-2-one 13b was iso-
Chem. 2007, 119, 3192; Angew. Chem. Int. Ed. 2007, 46, 3131; (b) Ünaldi, S.;
€
Özlügedik, M.; Frohlich, R.; Hoppe, D. Adv. Synth. Catal. 2005, 347, 1621; (c)
€
Özlügedik, M.; Kristensen, J.; Wibbeling, B.; Frohlich, R.; Hoppe, D. Eur. J. Org.
Chem. 2002, 414.
9. Crystal data for C24H35N3O9 (9c), M¼509.55, orthorhombic, space group
P212121 (No. 19), a¼7.1888(3), b¼9.1608(3), c¼40.0831(17) Ǻ, V¼2639.68(18) Ǻ3,
Dc¼1.282 g cmꢀ3
,
m
¼0.824 mmꢀ1, Z¼4,
¼1.54178 Ǻ, T¼223(2) K, 12,208 re-
l
flections collected (ꢃh, ꢃk, ꢃl), [(sin
q
)/
l
]¼0.60 Ǻꢀ1, 4015 independent (Rint¼0.
066), and 3147 observed reflections [Iꢄ2
s(I)], 335 refined parameters, R¼0.047,
wR2¼0.112, Flack ꢀ0.3(3).
10. Data sets were collected with a Nonius KappaCCD diffractometer. Programs
used: data collection COLLECT (Nonius B.V., 1998), data reduction Denzo-SMN
(Z. Otwinowski, W. Minor, Methods in Enzymology, 1997, 276, 307e326), ab-
sorption correction Denzo (Z. Otwinowski, D. Borek, W. Majewski, W. Minor,
Acta Cryst. 2003, A59, 228e234), structure solution SHELXS-97 (G.M.
lated as colorless solid (76.7 mg, 86%). Rf 0.29 (EtOAc/c-
20
hexane¼1:1); mp 66.6 ꢁC (EtOAc); [
a]
þ45.4 (c 1.12, CHCl3). 1H
D
3
NMR (400 MHz, CDCl3):
d
/ppm¼0.98 (d, J3,3-CH3¼7.1 Hz, 3H, 3-
CH3); 1.32 (s, 9H, C(CH3)3); 1.32, 1.40 (each s, 6H, C(CH3)2); 2.50 (m,

6166
S. Kollmann et al. / Tetrahedron 66 (2010) 6162e6166
Sheldrick, Acta Cryst. 1990, A46, 467e473), structure refinement SHELXL-97
12 Union Road, Cambridge CB2 1EZ, UK; fax: (internet.) þ44(1223)336 033, E-
mail: deposit@ccdc.cam.ac.uk].
(G.M. Sheldrick, Acta Cryst. 2008, A64, 112e122), graphics DIAMOND (G.
Bergerhoff, M. Berndt, K. Brandenburg, J. Res. Natl. Inst. Stand. Technol. 1996,
101, 221e225). R-Value is given for the observed, wR2-value for all reflections.
Linderman, R.J.; Siedlecki, J.M. J. Org. Chem. 1996, 61, 6492e6492. CCDC
773262 and 773263 contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge at <www.ccdc.cam.ac.uk/
conts/retrieving.html> [or from the Cambridge Crystallographic Data Centre,
11. Crystal data for C29H37NO7 (13b), M¼511.60, monoclinic, space group P21 (No.
4), a¼12.0080(2), b¼8.9588(1), c¼12.9416(2) Ǻ,
b
¼92.568(2)ꢁ, V¼1390.82(4)
Ǻ3, Dc¼1.222 g cmꢀ3
,
m
¼0.709 mmꢀ1, Z¼2,
¼1.54178 Ǻ, T¼223(2) K, 17,451 re-
l
flections collected (ꢃh, ꢃk, ꢃl), [(sin
q
)/
l
s
]¼0.60 Ǻꢀ1, 4773 independent (Rint¼0.
042), and 4550 observed reflections [Iꢄ2
(I)], 342 refined parameters, R¼0.040,
wR2¼0.103.