Stereoselective preparation of 4,5-dihydroxy-5,6-dihydro-4H-1,2-oxazines and their derivatives

Article abstract of DOI:10.1055/s-1999-3524

cis-Dihydroxylation of 6H-1,2-oxazines 1 proceeds efficiently either by potassium permanganate at low temperature (Method A) or by ruthenium trichloride/sodium periodate at 0-5°C (Method B). The resulting 4,5- dihydroxylated 1,2-oxazines 2 were usually ob

Full text of DOI:10.1055/s-1999-3524

PAPER
1223
Stereoselective Preparation of 4,5-Dihydroxy-5,6-dihydro-4H-1,2-oxazines
and Their Derivatives
Reinhold Zimmer, Kai Homann,1 Jörg Angermann,2 Hans-Ulrich Reissig*
Institut für Organische Chemie der Technischen Universität Dresden, D-01062 Dresden, Germany
Fax +49(351)4637030; E-mail: hans.reissig@chemie.tu-dresden.de
Received 22 December 1998; revised 18 February 1999
are introduced trans with respect to the 6-ethoxy substitu-
ent. All NMR data are in accordance with this assignment.
Abstract: cis-Dihydroxylation of 6H-1,2-oxazines 1 proceeds effi-
ciently either by potassium permanganate at low temperature
(Method A) or by ruthenium trichloride/sodium periodate at 0-5°C
(Method B). The resulting 4,5-dihydroxylated 1,2-oxazines 2 were
usually obtained as diastereomerically pure compounds with the
two newly introduced hydroxy groups positioned trans to the 6-
alkoxy group. These products can be protected by standard methods
either as acetals 4 or as diacetoxy compounds 5. In addition, the bi-
cyclic orthoesters 7 and 8, dimesylates 15, and cyclic sulfates 19
have been prepared. First experiments dealing with transformations
of the oxygen functionalities are described.
Method A: KMnO4, MgSO4, EtOH/H2O; –45°C, 50 min
Method B: RuCl3∑3 H2O, NaIO4, EtOAc/MeCN; 0–5°C, 5–6 min
Key words: 1,2-oxazine, cis-dihydroxylation, acetylation, mesyla-
tion, cyclic sulfate, elimination, 1,3,5-trioxa-6-azaindene
Com- R1
pound
R2
R3
Meth- Prod- Yielda
od
A
B
uct
2a
2a
2b
1a
1a
1b
Ph
Ph
H
H
H
OEt
OEt
OEt
78%
93%
73%
Polyhydroxylated heterocycles have been the subject of
intensive studies during the last decade mainly due to their
potential as biologically active compounds. Of particular
interest are polyhydroxylated pyrrolidine or piperidine
derivatives which may specifically inhibit glycosidases,
and therefore provide novel pharmaceutical lead com-
pounds for new drugs.3 In this report we describe synthe-
ses of a variety of 4,5-dihydroxylated 1,2-oxazines which
may function by themselves as biologically active com-
pounds but in addition they may be converted by several
methods either into other functionalized 1,2-oxazines or
by ring contraction into cis-dihydroxylated pyrrolidine
derivatives or by ring cleavage into acyclic amino alco-
hols.
A
1b
1c
1d
H
H
H
OEt
OEt
OEt
B
B
B
2b
2c
2d
95%
89%b
99%
1e
1e
1f
CO2Et
CO2Et
CF3
H
OEt
OEt
OEt
OEt
OMe
H
A
B
A
B
B
A
2e
2e
2f
88%
Our approach to 4,5-dihydroxylated 1,2-oxazines 2 is
based on the good availability of 6H-1,2-oxazines 1 by
hetero Diels–Alder reactions of a-nitroso alkenes with
suitable electron-rich olefins.4,5 Initial cis-dihydroxyla-
tion experiments were performed with osmium tetroxide
and different reoxidizing components. Heterocycle 1a
was treated according to standard protocols but led only to
rather low conversions into 2a even after very long reac-
H
99%
H
70%
1f
CF3
H
2f
79%
1g
1h
Ph
Me
H
2g
2h
98%c
quant.d
CO2Et
tion times. Dihydroxylated 1,2-oxazine 2a could be isolat- a Crude product.
b Two diastereomers (93:7).
ed in roughly 25% yield together with unconsumed
starting material 1a. Thus, we were very pleased that the
use of potassium permanganate in the presence of magne-
sium sulfate produced 4,5-dihydroxylated 1,2-oxazines
2a–h in good yields and high purities (Method A, Scheme
1).6 However, strict control of temperature and reaction
time is crucial for the successful performance of the reac-
tion. In all cases performed with Method A only one dias-
tereomer was isolated. It is very likely for mechanistic
reasons that the two new cis-positioned hydroxy groups
c Product contains 22% of compound 3.
d Product contains impurities.
Scheme 1
Synthesis 1999, No. 7, 1223–1235 ISSN 0039-7881 © Thieme Stuttgart · New York

1224
R. Zimmer et al.
PAPER
Although Method A allowed the preparation of 2 in good minor compound has all-cis-configuration; however, no
yields the experimental handling was relatively circum- plausible explanation can be offered for the lower stereo-
stantial. Shing’s method7 offered an extremely useful al- selectivity of this singular reaction. Dihydroxylation of 5-
ternative using catalytical amounts of ruthenium methyl substituted 6H-1,2-oxazine 1g with Method B fur-
trichloride and sodium periodate which perfectly worked nished the expected diol 2g together with its oxidation
for our purpose (Method B). As depicted in Scheme 1 this product 38 as minor component. This was the only case
procedure involving ruthenium tetroxide as dihydroxylat- where subsequent oxidation to a defined compound was
ing agent requires 0–5°C and it is complete after a few observed. Compounds 2a, 2b and 2d–h were routinely
minutes ("minute dihydroxylation") affording the desired protected at the hydroxy groups (Scheme 2), either as ac-
products 2 in excellent yields. When Methods A and B etals 4 with 2,2-dimethoxypropane (2,2-DMP), or by acy-
have been performed the latter generally provided consid- lation with acetic anhydride to give diacetoxy compounds
erably higher yields and it is experimentally more easier 5 (and the monoacetoxy product 6).
to execute. In the case of 1,2-oxazine 2c we obtained a
93:7 mixture of two diastereomers. We assume that the
In addition, singular 1,2-oxazines 2 were converted into
bicyclic orthoesters by acid catalyzed treatment with tri-
methyl orthoformiate or with trimethyl orthoacetate
(Scheme 3).9 As expected, compounds 7 and 8 were ob-
tained as a mixture of isomers with respect to substituent
R2. For orthoester 7a higher reaction temperature leads to
a shift of the ratio of isomers. We assume thermodynamic
control under these conditions.
Com- R1
pound
R2
R3
Prod- Yield
uct
R1
R2
Product Yield Ratio of
isomers
2a
2b
Ph
H
H
OEt
OEt
4a
4b
88%
66%
Ph
Ph
Ph
H
7a
7a
8a
56% 92:8a
82% 34:66
92% 57:43
H
Me
2d
H
OEt
4d
70%
Me
Me
8c
8e
85% 50:50b
78% 50:50
2e
2f
CO2Et
CF3
H
OEt
OEt
4e
4f
84%
95%
41%
28%
77%
79%
53%a
CO2Et
H
a Reaction at 102°C.
2g
2h
2a
2e
2g
Ph
Me
H
OMe 4g
b Product 8c contains 10% of the all-cis-isomer (50:50).
CO2Et
Ph
H
4h
5a
5e
Scheme 3
H
OEt
OEt
CO2Et
H
Ph
Me
OMe 5g
With compounds 8c and 8e we examined whether a regio-
selective dioxolane ring cleavage9 is feasible. However,
these orthoesters afforded both possible monoacetoxy
products 9 and 10 in ratios close to 1:1 (Scheme 4); during
purification of 9c/10c the minor components arising from
the all-cis-substituted starting material 8c disappeared.
a Additional 11% of compound 6.
Scheme 2
Synthesis 1999, No. 7, 1223–1235 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Preparation of 4,5-Dihydroxy-5,6-dihydro-4H-1,2-oxazines and Their Derivatives
1225
Scheme 4
An alternative way to regioselective orthoester cleavage
was tested on 1,2-oxazine 8a (Scheme 5).9 Unfortunately,
by treatment with acetyl bromide a mixture of 11, 12, 13,
and 14 (≈ 40:25:25:10) was obtained. It was hoped that
both bromo acetoxy compounds 11 and 12 could be trans-
formed into the epoxide 14 by base, however, stirring with
sodium hydroxide promoted further elimination to even-
tually produce the known 4-bromo-6H-1,2-oxazine 1310
as the only isolable product in low overall yield. Alterna-
tive routes to epoxide 14 have to be developed.11
Scheme 6
It turned out that dimesylates 15 are rather prone to elim-
ination already during purification attempts (Scheme 7).
Deliberate conversion of 15a into monomesylate 16 suc-
ceeded by treatment with 1,8-diazabicyclo[5.4.0]undec-7-
ene (DBU) at room temperature. As alternative may be
used neutral aluminium oxide since during an attempt to
purify dimesylate 15e we obtained a 1:1 mixture of mo-
nomesylate 17 (29% yield) and starting material 15e. Fur-
ther experiments aiming at the substitution of one or two
mesyl groups by other functional groups were frustated by
the dominating elimination process.2
Scheme 5
Further experiments were carried out to transform the two
hydroxy substituents of 2 into better leaving groups which
would allow nucleophilic substitutions at C-4 and C-5 of
the 1,2-oxazine system. Thus, 2a, 2e and 2f were convert-
ed into the corresponding dimesylates 15a, 15e and 15f in
good yields by a standard protocol (Scheme 6). Surpris-
ingly, compound 15f was obtained as a 55:45 mixture of
two diastereomers. A mechanism involving base induced
elimination and readdition of methane sulfonic acid may
account for this fact,12 possibly, these steps are accelerat-
ed by the strongly electron-withdrawing 3-CF3 group.13
Scheme 7
An additional possibility to activate vicinally located hy-
droxy groups employs reaction with thionyl chloride, fol-
lowed by subsequent oxidation of the resulting cyclic
sulfites.14 Following these lines we could prepare sulfate
Synthesis 1999, No. 7, 1223–1235 ISSN 0039-7881 © Thieme Stuttgart · New York

1226
R. Zimmer et al.
PAPER
19 by ruthenium tetroxide promoted oxidation of interme- azines 2. Orientating experiments show that
diate 18 (Scheme 8). Treatment of 19 with sodium azide regioselective substitution of the 4/5-hydroxy functions is
in DMF at 70°C furnished a 60:40 mixture of azide 20 and difficult to achieve. However, reductive transformations
starting material 19. The regiochemistry of the ring open- of protected 4,5-dihydroxy-5,6-dihydro-4H-1,2-oxazines
ing of 19 to 20 is as tentative as the suggested trans,trans- are possible in several varations1 and will be reported in
configuration of the azide. More experiments are required due course.16
to substantiate the feasibility of this reaction which may
finally lead to 4-amino-5-hydroxy substituted 1,2-ox-
All reactions were performed under argon atmosphere in flame-
azines and derived products.
dried flasks, and the components were added by means of syringes.
All solvents were dried by standard methods. IR spectra were mea-
sured with a Perkin Elmer spectrometer IR-325 or Nicolet 205. 1H
and 13C NMR spectra were recorded on Bruker instruments (AC
200 or AC 300) in CDCl3 solution. The chemical shifts are given in
relative to the TMS or to the CDCl3 signal (dH = 7.27, dC = 77.0).
Missing signals of the minor isomer are hidden by signals of the ma-
jor isomer, or they could not be unambiguously identified due to
low intensity. Neutral alumina (activity III, Fa. Merck) was used for
column chromatography. Boiling points of compounds obtained in
small-scale experiments refer to the temperature in a Büchi Kugel-
rohroven. Melting points (uncorrected) were measured with an ap-
paratus from Büchi (SMP-20) and Gallenkamp (MPD 350). 2,2-
DMP, RuCl3 and DBU were commercially available and were used
as received.
Starting materials 6H-1,2-oxazines 1a–1f,4 1g,5 and 1h1 were pre-
pared by literature procedures.
cis-Dihydroxylation of 6H-1,2-Oxazines by KMnO4 ; General
Procedure 1
Method A: To a vigorously stirred solution of 1 (1 equiv) in EtOH
(10 mL/mmol of 1,2-oxazine) was added over a period of 20 min at
–45°C a solution of KMnO4 (0.975 equiv) and MgSO4 (0.875 equiv)
dissolved in H2O (6 mL/mmol of 1,2-oxazine). The resulting mix-
ture was stirred for further 30 min at this temperature. Then 40% aq
NaHSO3 solution (2 mL/mmol of 1,2-oxazine) was added, and the
mixture was allowed to warm up to r.t. After filtration of the suspen-
sion and evaporation of EtOH, the residue was saturated with NaCl.
The resulting mixture was extracted with EtOAc (3 × 10 mL/mmol
of 1,2-oxazine) and the combined organic phases were dried
(MgSO4). Evaporation of the solvent under reduced pressure gave
the corresponding 4,5-dihydroxylated compound 2 which was gen-
erally NMR spectroscopically pure (Tables 1, 3, 4).
Scheme 8
The protection of two 1,2-oxazines 2 into trimethylsiloxy
compounds 21 proceeded as expected without problems
(Scheme 9). Consecutive reactions of 21, e.g. fluoride in-
duced conversion into nonafluorobutanesulfonates,15
have been so far unsuccessful.2
cis-Dihydroxylation of 6H-1,2-Oxazines by RuCl3/NaIO4 ;
General Procedure 2
Method B: To a vigorously stirred solution of 1 (1 equivalent) in a
mixture of EtOAc/MeCN (18 mL each/mmol of 1,2-oxazine) was
added at 0–5°C a solution of RuCl3•3H2O (0.07 equiv) and NaIO4
(1.5 equiv) in H2O (5 mL/mmol of 1,2-oxazine). The mixture was
stirred vigorously for 5–6 min and then quenched with satd. aq
Na2S2O3 solution (10 mL/mmol of 1,2-oxazine). The aqueous phase
was separated, extracted with EtOAc (3 × 20 mL/mmol of 1,2-ox-
azine) and the combined organic extracts were dried (MgSO4).
Evaporation of the solvent under reduced pressure gave the corre-
sponding 4,5-dihydroxylated compound 2 which was generally
NMR spectroscopically pure (Tables 1, 3, 4).
Scheme 9
r-4,c-5-Dihydroxy-t-6-methoxy-t-5-methyl-3-phenyl-5,6-dihy-
dro-4H-1,2-oxazine (2g) and 5-Hydroxy-6-methoxy-5-methyl-3-
phenyl-5,6-dihydro-4H-1,2-oxazin-4-one (3)
According to the alternative dihydroxylation protocol as described
in Ref.7 (Method B) the reaction of 1,2-oxazine 1g (1.02 g, 5.00
mmol), RuCl3•3H2O (0.092 g, 0.352 mmol), NaIO4 (1.60 g, 7.52
mmol) in MeCN/H2O (60 mL/10 mL) (reaction time: 3 min at 0–
3°C) provided after purification by chromatography (EtOAc/hex-
In this paper we have demonstrated that 4,5-dihydroxy
substituted 1,2-oxazines 2 are easily available by cis-dihy-
droxylation of 6H-1,2-oxazines 1 either with potassium
permanganate or with (catalytic amounts of) ruthenium
tetroxide. Both methods proceed with high efficiency and
excellent diastereoselectivity. Further reactions were per-
formed to protect and to activate the resulting 1,2-ox-
Synthesis 1999, No. 7, 1223–1235 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Preparation of 4,5-Dihydroxy-5,6-dihydro-4H-1,2-oxazines and Their Derivatives
1227
Table 1 Synthesis of 4,5-Dihydroxy-4H-1,2-oxazines by Oxidation with KMnO4/MgSO4 (Method A) or RuCl3/NaIO4 (Method B)
1,2-Oxazine 1
g (mmol)
Reaction Conditions
g (mmol)
Prod- Yield
ucta
g (%)
mp (°C)
IR b
n [cm–1]
1a 3.25 (16.0)
1a 2.03 (10.0)
2.47 (15.6) KMnO4 / 1.69 (14.0) MgSO4 2a
0.183 (0.70) RuCl3 / 3.21 (15.0) NaIO4 2a
2.95 (78) 150–151 3490 (O–H), 3075–2760 (=CH, C–H),
2.20 (93) (dec)
1575 (C=N)
1b 0.350 (1.29)
1b 0.272 (1.00)
0.199 (1.26) KMnO4 / 0.136 (1.13) MgSO4 2b
0.018 (0.07) RuCl3 / 0.321 (1.50) NaIO4 2b
0.287 (73) oil
0.291 (95)
3440 (O–H), 3050–2920 (=CH, C–H),
1590 (C=N)
1c
0.440 (1.84)
0.034 (0.129) RuCl3 / 0.591 (2.76) NaIO4 2c
0.445 (89)c 126–129 3480 (O–H), 3080–2800 (=CH, C–H),
1580 (C=N), 1140, 1110 (C–F)
1d 0.15 (0.553) 0.010 (0.039) RuCl3 / 0.178 (0.83) NaIO4 2d
0.168 (99) oil
3460 (O–H), 3120–2860 (=CH, C–H),
1575 (C=N), 1145, 1120 (C–F)
1e
1e
5.31 (26.7)
0.996 (5.00)
4.11 (26.0) KMnO4 / 2.81 (23.4) MgSO4 2e
0.092 (0.35) RuCl3 / 1.61 (7.50) NaIO4 2e
5.48 (88)
1.16 (99)
91–92
3480 (O–H), 3100–2760 (=CH, C–H),
1715 (C=O), 1590 (C=N)
1f
1f
0.390 (2.00)
0.565 (2.90)
0.308 (1.95) KMnO4 / 0.211 (1.75) MgSO4 2f
0.053 (0.203) RuCl3 / 0.931 (4.35) NaIO4 2f
0.321 (70) oil
0.525 (79)
3370 (O–H), 2980–2900 (=CH, C–H),
1620 (C=N), 1150, 1130 (C–F)
1g 1.02 (5.00)
0.092 (0.352) RuCl3 / 1.60 (7.52) NaIO4
2g
1.17 (98)d oil
3470 (O–H), 3080–2780 (=CH, C–H),
1570 (C=N)
1h 0.310 (2.00)
0.308 (1.95) KMnO4 / 0.211 (1.75) MgSO4 2h
0.459e
oil
–
a Satisfactory microanalysis obtained: C ± 0.43, H ± 0.18, N ± 0.33; exceptions: 2f (N – 0.51); for 2d, 2g, 2h the elemental analyses were carried
out after the next reaction step.
b Oils as film or in CCl4, solids as KBr pellets.
c Mixture of diastereomers: 5,6-trans : 5,6-cis isomer = 93 : 7.
d Mixture of products: 2g and 3 = 78 : 22.
e Crude product with impurities.
ane, 3:1 → 1:0) 1.17 g (98%) of a mixture of 2g/3 (78:22). 1H and
Reaction of 4,5-Dihydroxy-4H-1,2-oxazines 2 with Orthoesters;
General Procedure 5
13C NMR data are identical with those reported earlier.8
To a solution of 1,2-oxazine 2 in the corresponding orthoester (5
mL/mmol of 1,2-oxazine) was added pTsOH (20 mg/mmol of 1,2-
oxazine). The mixture was stirred for 18–20 h at r.t., then solid
K2CO3 (100 mg/mmol of 1,2-oxazine) was added. After additional
2 h at r.t. the suspension was filtered and the solvent was removed
by distillation in vacuo. The residue was purified as indicated in the
individual experiments. The NMR data of 7 and 8 are given in Ta-
bles 3 and 4.
Acetalization of 4,5-Dihydroxy-4H-1,2-oxazines 2 with 2,2-
DMP; General Procedure 3
To a solution of the well dried 1,2-oxazine 2 in acetone (4–20 mL/
mmol of 1,2-oxazine) were added 2,2-DMP (1–10 mL/mmol of 1,2-
oxazine) and pTsOH (20 mg/mmol of 1,2-oxazine). The mixture
was stirred for 4 h at r.t., then an excess of solid NaHCO3 was add-
ed. The mixture was filtered, the solvent removed in vacuo, and the
resulting crude product 4 was purified by column chromatography
(hexane/EtOAc, 4:1 or 8:1). The IR and NMR data of 4 are given in
Tables 2–4.
r-4-Acetoxy-3-(2’,4’-difluorophenyl)-t-6-ethoxy-c-5-hydroxy-
5,6-dihydro-4H-1,2-oxazine (9c) and c-5-Acetoxy-3-(2’,4’-diflu-
orophenyl)-t-6-ethoxy-r-4-hydroxy-5,6-dihydro-4H-1,2-ox-
azine (10c)
A solution of 1,2-oxazine 8c (0.100 g, 0.304 mmol) in CH2Cl2 (3
mL) was treated with pTsOH (1.5 mg) and H2O (10 mL). After 5 h
at r.t. the volatile components were removed in vacuo and the resi-
due was purified by chromatography (silica gel, hexane/EtOAc,
2:1). Yield: 0.031 g (32%) of a mixture of 9c/10c (53:47). The NMR
data are given in Tables 3 and 4.
Acetylation of 4,5-Dihydroxy-4H-1,2-oxazines 2 with Ac2O;
General Procedure 4
To a solution of 1,2-oxazine 2 (1 equiv) in anhyd. pyridine (20 mL/
mmol of 1,2-oxazine) was added Ac2O (50 equiv), and the solution
was stirred at r.t. After 4 h MeOH (5 mL/mmol of 1,2-oxazine), and
after further 2 h H2O (15 mL/mmol of 1,2-oxazine) were added and
the mixture was stirred for additional 17 h at r.t. The solution was
concentrated in vacuo, and the residue was dissolved in Et2O (50
mL/mmol of 1,2-oxazine). The solution was washed successively
with 2 N HCl solution (2 × 45 mL/mmol of 1,2-oxazine), aq satd.
NaHCO3 solution (2 × 45 mL/mmol of 1,2-oxazine), and H2O (2 ×
45 mL/mmol of 1,2-oxazine), and dried (MgSO4). The evaporation
of the solvent gave the crude product 5 which was purified by
Kugelrohr distillation (105°C/0.02 mbar) or by column chromatog-
raphy (hexane/EtOAc, 6:1 → 1:1). The NMR data are given in Ta-
bles 3 and 4.
IR (neat): n = 3450 (O–H), 3080–2870 (=C–H, C–H), 1750 (C=O),
1610 (C=N), 1140, 1120 cm–1 (C–F).
Anal. calcd. for C14H15F2NO5 (315.3): C, 53.33; H, 4.81; N, 4.44.
Found: C, 53.10; H, 5.27; N, 4.14.
Ethyl r-4-Acetoxy-t-6-ethoxy-c-5-hydroxy-5,6-dihydro-4H-1,2-
oxazine-3-carboxylate (9e) and Ethyl c-5-Acetoxy-t-6-ethoxy-r-
4-hydroxy-5,6-dihydro-4H-1,2-oxazine-3-carboxylate (10e)
A solution of 1,2-oxazine 8e (0.356 g, 1.23 mmol) in CH2Cl2 (12.5
mL) was treated with pTsOH (6 mg) and H2O (30 mL). After 5 h at
r.t. the volatile components were removed in vacuo and the residue
was purified by chromatography (hexane/EtOAc, 2:1). Yield: 0.180
Synthesis 1999, No. 7, 1223–1235 ISSN 0039-7881 © Thieme Stuttgart · New York

1228
R. Zimmer et al.
PAPER
Table 2 Preparation of Derivatives 4, 5, 7, 8, 15 and 21 According to General Procedures 3–7
1,2-Oxazine
g (mmol)
Producta Yield
g (%)
mp
(°C)
General
Proced.
IRb
ν (cm–1)
2a
2b
2d
1.86 (7.76)
0.29 (0.945)
0.168 (0.55)
4a
4b
4d
1.90 (88)
98–103.5
oil
3
3
3
3100–2700 (=C–H, C–H), 1575 (C=N)
3070–2880 (=C–H, C–H), 1570 (C=N)
0.216 (66)
0.133 (70)
oil
3070–2930 (=C–H, C–H), 1630 (C=N),
1170, 1130 (C–F)
2e
2f
5.48 (23.5)
0.321 (1.4)
4e
4f
5.38 (84)
0.359 (95)
81.5–83
38–41
3
3
3100–2640 (=C–H, C–H), 1725 (C=O),
1590 (C=N)
3050–2930 (=C–H, C–H), 1625 (C=N),
1170, 1135 (C–F)
2g
2h
0.455 (2.0)
0.459 (2.0)
4g
4h
0.214 (41)
0.129 (28)
oil
oil
3
3
3170–2780 (=C–H, C–H), 1757 (C=N)
3120–2700 (=C–H, C–H), 1725 (C=O),
1580 (C=N)
2a
2e
2g
0.42 (1.77)
1.12 (4.8)
1.17c
5a
5e
5g
0.496 (77)
1.52 (79)
0.829 (53)d
95–96.5
69.5–73.5
oil
4
4
4
3100–2740 (=C–H, C–H), 1740 (C=O),
1570 (C=N)
2990, 2950, 2890 (=C–H, C–H), 1760,
1730 (C=O), 1605 (C=N)
3040–2880 (=C–H, C–H), 1745 (C=O),
1590 (C=N)
2a
2a
2a
0.238 (1.0)
0.105 (0.44)
0.238 (1.0)
7a
7a
8a
0.228 (82)e
0.069 (56)f
0.271 (92)h
75–76
5
3070–2940 (=C–H, C–H), 1500 (C=N)
5g
5
79–81
3100–2640 (=C–H, C–H), 1725 (C=O),
1590 (C=N)
j
2c
2e
0.413 (1.5)
2.0 (8,5)
8c
8e
0.421 (85)i
1.92 (78)k
resin
oil
5
5
–
2980–2940 (C–H), 1730 (C=O), 1610
(C=N)
2a
2e
2f
0.10 (0.421)
0.226 (0.97)
0.458 (2.0)
15a
15e
15f
0.138 (83)
0.375 (99)
0.547 (71)l
oil
oil
oil
6
6
6
3070–2950 (=C–H, C–H, 1630 (C=N),
1370, 1180 (SO2)
2990–2940 (C–H), 1730 (C=O), 1620
(C=N), 1370, 1180 (SO2)
2970–2950 (C–H), 1625 (C=N), 1370,
1180 (SO2), 1150 (C–F)
2a
2e
0.237 (1.0)
0.933 (4.0)
21a
21e
0.347 (91)
1.23 (84)
oilm
oil
7
7
3080–2900 (=C–H, C–H), 1600 (C=N)
2980–2900 (C–H), 1720 (C=O), 1600
(C=N)
a Satisfactory microanalyses obtained: C ± 0.46, H ± 0.27, N ± 0.18; exceptions: 4b (C + 0.67) 4d (H + 0.60), 4f (C – 0.88), 5g (H–0.57).
b Oils as film or in CCl4, solids as KBr pellets.
c Mixture of 2g/3 (79:22).
d Additional 0.224 g (11 %) of compound 6.
e Mixture of two diastereomers (a:b = 66:34).
f Mixture of two diastereomers (a:b = 8:92).
g Reaction was performed at 102°C.
h Mixture of two diastereomers (57:43).
i Mixture of four diastereomers (45:45:5:5).
j Compound 8c was not sufficiently stable for full characterization, which was carried out on the next step (see 9c/10c).
k Mixture of two diastereomers (50:50).
l Mixture of two diastereomers (55:45).
m Compound 21a contains ca. 4 % of hexamethyldisilazane.
Synthesis 1999, No. 7, 1223–1235 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Preparation of 4,5-Dihydroxy-5,6-dihydro-4H-1,2-oxazines and Their Derivatives
1229
Table 3 1H NMR Data of Compounds 2, 4 – 12 and 14 – 21
Compound
1H NMR (300 MHz, CDCl3 / TMS); d, J (Hz)
2aa
7.76–7.70, 7.39–7.35 (2 m, 2 H, 3 H, C6H5), 5.10 (d, J = 4, 1 H, 6-H), 4.74 (d, J = 5, 1 H, 4-H), 4.63, 4.26 (2 br s, 1 H each,
2 OH), 3.98 (mc, 1 H, 5-H), AB part of ABX3 system (dA = 3.87, dB = 3.67, JAX = JBX = 7, JAB = 10, 2 H, OCH2), 1.18 (t, J
= 7, 3 H, CH3)
2b
7.45–7.44, 7.35–7.28 (2 m, 1 H, 2 H, C6H3Cl2), 5.18 (d, J = 3.2, 1 H, 6-H), 4.80 (d, J = 4.7, 1 H, 4-H), 4.09 (dd, J = 3.2,
4.7, 1 H, 5-H), 4.02–3.92, 3.76–3.63 (2 m, 2 H, OCH2), 2.52, 1.67 (2 br s, 1 H each, 2 OH) 1.26 (t, J = 7, 3 H, CH3)
2c
7.48–7.34, 7.10–6.85 (2 m, 1 H, 2 H, C6H3F2), 5.01 (d, J = 3, 1 H, 6-H), 4.61–3.83 (m, 4 H, 4-H, 5-H, 2 OH), 3.79–3.67,
3.65–3.47 (2 m, 1 H each, OCH2), 1.06 (t, J = 7, 3 H, CH3)
(trans) a,b
2c (cis) a,b,e
5.42 (d, J = 6, 1 H, 6-H)
2da,b
8.03 (s, 1 H, 2'-H), 7.92, 7.66 (2 d, J = 7.7 each, 2 H, 4'-H, 6'-H), 7.52 (t, J = 7.7, 1 H, 5'-H), 5.16 (d, J = 3.8, 1 H, 6-H),
4.75 (d, J = 4.9, 1 H, 4-H), 4.13–4.01 (m, 2 H, 5-H, OH), 3.98–3.86, 3.76–3.61 (2 m, 1 H each, OCH2), 2.80 (br s, 1 H,
OH), 1.23 (t, J = 7, 3 H, CH3)
2eb
5.11 (d, J = 3.5, 1 H, 6-H), 4.64, 4.52 (2 mc, 1 H each, 4-H, 5-H), 4.27 (q, J = 7, 2 H, OCH2 [ester]), AB part of ABX3 system
(dA = 3.86, dB = 3.69, JAX = JBX = 7, JAB = 9.5, 2 H, OCH2), 3.94, 3.09 (2 mc, 1 H each, 2 OH), 1.30, 1.18 (2 t, J = 7 each,
3 H each, CH3)
2fa,b
5.06 (d, J = 3.3, 1 H, 6-H), 4.54 (br s, 1 H, OH), 4.33 (d, J = 4.6, 1 H, 4-H), 3.90–3.86 (m, 1 H, 5-H), 3.81–3.39 (m, 3 H,
OCH2, OH), 1.05 (t, J = 7, 3 H, CH3)
2hb
4a
4.53 (mc, 1 H, 4-H), 4.37 (q, J = 7, 2 H, OCH2 [ester]), 4.32–3.93 (m, 5 H, 5-H, 6-H, 2 OH), 1.38 (t, J = 7, 3 H, CH3)
7.88–7.81, 7.44–7.36 (2 m, 2 H, 3 H, C6H5), 4.97 (d, J = 3.5, 1 H, 6-H), 4.96 (d, J = 7, 1 H, 4-H), 4.39 (dd, J = 3.5, 7, 1 H,
5-H), AB part of ABX3 system (dA = 3.95, dB = 3.68, JAX = JBX = 7, JAB = 10, 2 H, OCH2), 1.44, 1.41 (2 s, 3 H each, 2 CH3),
1.18 (t, J = 7, 3 H, CH3)
4ba
4da
7.46–7.45, 7.32–7.31 (2 m, 1 H, 2 H, C6H3Cl2), 5.11 (d, J = 2.9, 1 H, 6-H), 4.95 (d, J = 6.9, 1 H, 4-H), 4.44 (dd, J = 2.9,
6.9, 1 H, 5-H), 3.99–3.87, 3.76–3.64 (2 m, 2 H, OCH2), 1.49, 1.37 (2 s, 3 H each, 2 CH3), 1.24 (t, J = 7, 3 H, CH3)
8.14 (s, 1 H, 2'-H), 8.03, 7.68 (2 d, J = 7.8 each, 1 H each, 4'-H, 6'-H), 7.54 (t, J = 7.8, 1 H, 5'-H), 5.04 (d, J = 3.4, 1 H,
6-H), 4.94 (d, J = 6.7, 1 H, 4-H), 4.42 (dd, J = 3.4, 6.7, 1 H, 5-H), 4.03–3.88, 3.78–3.62 (2 m, 1 H each, OCH2), 1.46, 1.41
(2 s, 3 H each, 2 CH3), 1.23 (t, J = 7, 3 H, CH3)
4e
5.12 (d, J = 3, 1 H, 6-H), 4.88 (d, J = 6.5, 1 H, 4-H), 4.38 (q, J = 7, 2 H, OCH2 [ester]), 4.36 (dd, J = 3, 6.5, 1 H, 5-H),
AB part of ABX3 system (dA = 3.89, dB = 3.66, JAX = JBX = 7, JAB = 10, 2 H, OCH2), 1.41 (s, 6 H, 2 CH3), 1.39, 1.21 (2 t,
J = 7 each, 3 H each, CH3)
4f
5.18 (d, J = 2.5, 1 H, 6-H), 4.65 (d, J = 6.5, 1 H, 4-H), 4.38 (dd, J = 2.5, 6.5, 1 H, 5-H), AB part of ABX3 system (dA = 3.89,
dB = 3.68, JAX = JBX = 7, JAB = 10, 2 H, OCH2), 1.44, 1.42 (2 s, 3 H each, 2 CH3), 1.21 (t, J = 7, 3 H, CH3)
4g
4h
5a
7.87–7.84, 7.44–7.39 (2 m, 2 H, 3 H, C6H5), 4.64, 4.62 (2 s, 1 H each, 4-H, 6-H), 3.61 (s, 3 H, OCH3), 1.51 (s, 3 H, CH3),
1.42 (s, 6 H, 2 CH3)
4.82 (d, J = 6.5, 1 H, 4-H), 4.49–4.34 (m, 3 H, 5-H, OCH2 [ester]), AB part of ABX system (dA = 4.13, dB = 3.92, JAX
JBX = 6, JAB = 12, 2 H, 6-H), 1.44 (s, 6 H, 2 CH3), 1.38 (t, J = 7, 3 H, CH3)
=
7.51–7.46, 7.42–7.29 (2 m, 2 H, 3 H, C6H5), 6.19 (d, J = 5, 1 H, 6-H), 5.39 (dd, J = 3.5, 5, 1 H, 5-H), 5.17 (d, J = 3.5, 1 H,
4-H), AB part of ABX3 system (dA = 3.95, dB = 3.70, JAX = JBX = 7, JAB = 9.5, 2 H, OCH2), 2.12, 1.93 (2 s, 3 H each,
2 COCH3), 1.24 (t, J = 7, 3 H, CH3)
5e
5.96 (d, J = 5, 1 H, 6-H), 5.29 (dd, J = 3.5, 5, 1 H, 5-H), 5.18 (d, J = 3.5, 1 H, 4-H), 4.34 (mc, 2 H, OCH2 [ester]), AB part
of ABX3 system (dA = 3.92, dB = 3.69, JAX = JBX = 7, JAB = 9.5, 2 H, OCH2), 2.12, 2.07 (2 s, 3 H each, 2 COCH3), 1.36,
1.23 (2 t, J = 7 each, 3 H each, CH3)
5g
6
7.44–7.34 (m, 5 H, C6H5), 6.16 (s, 1 H, 6-H), 5.73 (s, 1 H, 4-H), 3.55 (s, 3 H, OCH3), 2.07, 1.95 (2 s, 3 H each, 2 COCH3),
1.61 (s, 3 H, 5-CH3)
7.45–7.36 (m, 5 H, C6H5), 5.55 (s, 1 H, 6-H), 3.64 (s, 3 H, OCH3), 2.14 (s, 3 H, COCH3), 1.56 (s, 3 H, 5-CH3)
7aa
(isomer a)
7.87–7.83, 7.45–7.37 (2 m, 2 H, 3 H, C6H5), 5.84 (s, 1 H, CH), 5.13 (d, J = 7, 1 H, 4-H), 4.96 (d, J = 4, 1 H, 6-H), 4.55
(dd, J = 4, 7, 1 H, 5-H), 4.03–3.88, 3.77–3.16 (2 m, 1 H each, OCH2), 3.40 (s, 3 H, OCH3), 1.24 (t, J = 8, 3 H, CH3)
7aa
(isomer b)
7.86–7.82, 7.45–7.41 (2 m, 2 H, 3 H, C6H5), 5.93 (s, 1 H, CH), 5.13 (d, J = 3.5, 1 H, 6-H), 5.01 (d, J = 7.5, 1 H, 4-H), 4.46
(dd, J = 3.5, 7.5, 1 H, 5-H), 4.04–3.92, 3.78–3.66 (2 m, 1 H each, OCH2), 3.17 (s, 3 H, OCH3), 1.23 (t, J = 7, 3 H, CH3)
Synthesis 1999, No. 7, 1223–1235 ISSN 0039-7881 © Thieme Stuttgart · New York

1230
R. Zimmer et al.
PAPER
Table 3 (continued)
Compound
1H NMR (300 MHz, CDCl3 / TMS); d, J (Hz)
7.86–7.77, 7.45–7.32 (2 m, 2 H, 3 H, C6H5), 5.14 (d, J = 2.9, 1 H, 6-H), 4.98 (d, J = 7.5, 1 H, 4-H), 4.46 (dd, J = 2.9, 7.5,
8aa
(major)
1 H, 5-H), 4.00–3.84, 3.75–3.59 (2 m, 1 H each, OCH2), 3.12 (s, 3 H, OCH3), 1.60 (s, 3 H, CH3), 1.20 (t, J = 7, 3 H, CH3)
8aa,e
(minor)
5.11 (d, J = 7.3, 1 H, 4-H), 4.96 (d, J = 3.5, 1 H, 6-H), 4.54 (dd, J = 3.5, 7.3, 1 H, 5-H), 3.36 (s, 3 H, OCH3), 1.55
(s, 3 H, CH3), 1.22 (t, J = 7, 3 H, CH3)
8ca,c
(major)
7.70–7.56, 6.99–6.83 (2 m, 1 H, 2 H, C6H3F2), 5.16 (dd, JHF = 1, JHH = 7, 0.5 H, 4-H), 5.09 (d, J = 3.5, 0.5 H, 6-H), 5.07
(dd, JHF = 1.5, JHH = 7.5, 0.5 H, 4-H), 4.99 (d, J = 3.5, 0.5 H, 6-H), 4.55 (dd, J = 3.5, 7, 0.5 H, 5-H), 4.47 (dd, J = 3.5, 7.5,
0.5 H, 5-H), 4.05–3.88, 3.78–3.62 (2 m, 1 H each, OCH2), 3.31, 3.13 (2 s, 1.5 H each, OCH3), 1.56, 1.53 (2 s, 1.5 H each,
CH3), 1.25 (t, J = 7, 3 H, CH3)
8ca,c,d,e
4.96–4.93 (m, 1 H, 4-H), 4.83, 4.79 (2 d, J = 5 each, 0.5 H each, 6-H), 4.41–4.36 (m, 1 H, 5-H), 3.40, 3.29 (2 s, 1.5 H each,
(minor)
OCH3), 1.68, 1.59 (2 s, 1.5 H, CH3)
8ea,d
5.15 (d, J = 2.2, 0.5 H, 6-H), 5.04 (d, J = 2.6, 0.5 H, 6-H), 4.98 (d, J = 7.2, 0.5 H, 4-H), 4.84 (d, J = 7.4, 0.5 H, 4-H), 4.46
(dd, J = 2.6, 7.2, 0.5 H, 5-H), 4.39–4.24 [m, 2.5 H, OCH2 (ester), 5-H], 3.87–3.72, 3.67–3.49 (2 m, 1 H each, OCH2), 3.25,
3.11 (2 s, 1.5 H each, OCH3), 1.50, 1.46 (2 s, 3 H each, 2 CH3), 1.31 (t, J = 7, 1.5 H, CH3), 1.28 (t, J = 7, 1.5 H, CH3), 1.13
(t, J = 7, 3 H, CH3)
9c
9e
7.65–7.56, 6.97–6.83 (2 m, 1 H, 2 H, C6H3F2), 5.24 (d, J = 2.8, 1 H, 6-H), 5.19 (dd, J = 2.8, 5, 1 H, 5-H), 4.94 (br d, J ª 5,
1 H, 4-H), 4.02–3.89, 3.77–3.63 (2 m, 1 H each, OCH2), 2.24 (br s, 1 H, OH), 2.15 (s, 3 H, COCH3), 1.26 (t, J = 7, 3 H, CH3)
5.86 (d, J = 4.8, 1 H, 6-H), 5.12 (d, J = 4.1, 1 H, 4-H), 4.37 (q, J = 7, 2 H, OCH2 [ester]), 4.11 (br t, J ª 4.5, 1 H, 5-H),
4.00–3.84, 3.73–3.62 (2 m, 1 H each, OCH2), 3.76 (br s, 1 H, OH), 2.15 (s, 3 H, COCH3), 1.35 (t, J = 7, 3 H, CH3),
1.24 (t, J = 7, 3 H, CH3)
10c
10e
7.65–7.56, 6.97–6.83 (2 m, 1 H, 2 H, C6H3F2), 5.89 (dd, J = 2, 4.6, 1 H, 5-H), 5.16 (d, J = 2, 1 H, 6 H), 4.27 (br d, J ª 5, 1
H, 4-H), 4.02–3.89, 3.77–3.63 (2 m, 1 H each, OCH2), 2.27 (br s, 1 H, OH), 2.00 (s, 3 H, COCH3), 1.24 (t, J = 7, 3 H, CH3)
5.25 (dd, J = 3, 4.9, 1 H, 5-H), 5.21 (d, J = 3, 1 H, 6-H), 4.77 (d, J = 4.9, 1 H, 4-H), 4.38 (q, J = 7, 2 H, OCH2 [ester]),
4.00–3.84, 3.73–3.62 (2 m, 1 H each, OCH2), 2.76 (br s, 1 H, OH), 2.14 (s, 3 H, COCH3), 1.41 (t, J = 7, 3 H, CH3), 1.21
(t, J = 7, 3 H, CH3)
11a
7.77–7.54, 7.44–7.39 (2 m, 2 H, 3 H, C6H5), 5.31, 5.26 (2 d, J = 5 each, 1 H each, 4-H, 6-H), 5.12 (t, J = 5, 1 H, 5-H),
4.08–3.90, 3.80–3.59 (2 m, 1 H each, OCH2), 2.20 (s, 3 H, COCH3), 1.26 (t, J = 7, 3 H, CH3)
12a,e
14
5.51 (dd, J = 1.5, 2.5, 1 H, 5-H), 5.17 (dd, J = 0.5, 2.5, 1 H, 6-H), 4.62 (dd, J = 0.5, 1.5, 1 H, 4-H), 2.12 (s, 3 H, COCH3),
1.26 (t, J = 7, 3 H, CH3)
7.83–7.73, 7.49–7.38 (2 m, 2 H, 3 H, C6H5), 5.42 (s, 1 H, 6-H), 3.83 (s, 2 H, 4-H, 5-H), AB part of ABX3 system (dA = 3.96,
dB = 3.69, JAX = JBX = 7, JAB = 9.5, 2 H, OCH2), 1.24 (t, J = 7, 3 H, CH3)
15aa
15ea,b
7.67–7.62, 7.49–7.46 (2 m, 2 H, 3 H, C6H5), 6.03 (d, J = 4.5, 1 H, 6-H), 5.46 (d, J = 4.1, 1 H, 4-H), 5.24 (dd, J = 4.1, 4.5,
1 H, 5-H), 4.04–3.78 (m, 2 H, OCH2), 3.31, 3.14 (2 s, 3 H each, 2 SO2CH3), 1.24 (t, J = 7, 3 H, CH3)
5.71 (d, J = 4.5, 1 H, 6-H), 5.48 (d, J = 4.5, 1 H, 4-H), 5.16 (t, J = 4.5, 1 H, 5-H), 4.44–4.23, 3.98–3.83 (2 m, 2 H each,
2 OCH2), 3.35, 3.30 (2 s, 3 H each, 2 SO2CH3), 1.35, 1.25 (2 t, J = 7 each, 3 H each, 2 CH3)
15fa,b
(major)
5.79 (d, J = 4.4, 1 H, 6-H), 5.31 (t, J ª 4.3, 1 H, 5-H), 4.90–4.80 (m, 1 H, 4-H), 3.98–3.72 (m, 2 H, OCH2), 3.31, 3.27
(2 s, 3 H each, 2 SO2CH3), 1.24 (t, J = 7, 3 H, CH3)
15fa,b,e
(minor)
5.63 (d, J = 3.6, 1 H, 6-H), 5.45 (t, J ª 3.4, 1 H, 5-H), 4.42–4.38 (m, 1 H, 4-H), 3.41, 3.35 (2 s, 3 H each, 2 SO2CH3),
1.22 (t, J = 7, 3 H, CH3)
16a
17a
7.63–7.57, 7.47–7.40 (2 m, 2 H, 3 H, C6H5), 6.31, 5.85 (2 d, J = 5 each, 1 H each, 5-H, 6-H), 4.13–3.94, 3.90–3.63
(2 m, 1 H each, OCH2), 2.71 (s, 3 H, SO2CH3), 1.22 (t, J = 7, 3 H, CH3)
6.22, 5.86 (2 d, J = 5 each, 1 H each, 5-H, 6-H), 4.42–4.28, 4.00–3.88, 3.85–3.62 (3 m, 1 H, 2 H, 1 H, 2 OCH2), 3.25
(s, 3 H, SO2CH3), 1.42, 1.21 (2 t, J = 7 each, 3 H each, 2 CH3)
18a
(major)
7.84–7.76, 7.50–7.39 (2 m, 2 H, 3 H, C6H5), 5.74 (d, J = 7, 1 H, 4-H), 5.18 (dd, J = 4, 7, 1 H, 5-H), 5.08 (d, J = 4, 1 H,
6-H), 4.10–3.95, 3.90–3.71 (2 m, 1 H each, OCH2), 1.26 (t, J = 7, 3 H, CH3)
18a,e
5.52 (d, J = 7.5, 1 H, 4-H), 5.29 (d, J = 4.5, 1 H, 6-H), 4.83 (dd, J = 4.5, 7.5, 1 H, 5-H), 1.27 (t, J = 7, 3 H, CH3)
(minor)
19a
7.77–7.72, 7.51–7.42 (2 m, 2 H, 3 H, C6H5), 5.70 (d, J = 7, 1 H, 4-H), 5.29 (d, J = 3.5, 1 H, 6-H), 5.17 (dd, J = 3.5, 7, 1 H,
5-H), 3.97–3.75 (m, 2 H, OCH2), 1.25 (t, J = 7, 3 H, CH3)
Synthesis 1999, No. 7, 1223–1235 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Preparation of 4,5-Dihydroxy-5,6-dihydro-4H-1,2-oxazines and Their Derivatives
1231
Table 3 (continued)
Compound
1H NMR (300 MHz, CDCl3 / TMS); d, J (Hz)
20a
7.72–7.65, 7.43–7.34 (2 m, 2 H, 3 H, C6H5), 5.04 (d, J = 3, 1 H, 6-H), 4.13 (dd, J = 2.5, 3, 1 H, 5-H), 3.96–3.81, 3.74–3.55
(2 m, 2 H, 1 H, 4-H, OCH2), 2.55 (br s, 1 H, OH), 1.19 (t, J = 7, 3 H, CH3)
21a
21e
7.58–7.49, 7.38–7.34 (2 m, 2 H, 3 H, C6H5), 5.02 (d, J = 6.3, 1 H, 4-H), 4.62 (d, J = 3.8, 1 H, 6-H), 4.09–3.99, 3.75–3.64
(2 m, 1 H each, OCH2), 3.85 (dd, J = 3.8, 6.3, 1 H, 5-H), 1.28 (t, J = 7, 3 H, CH3), 0.19, 0.03 [2 s, 9 H each, 2 Si(CH3)3]
4.82 (d, J = 7.4, 1 H, 4-H), 4.42 (d, J = 3.9, 1 H, 6-H), 4.24–4.07 (m, 2 H, OCH2 [ester]), 3.90–3.79, 3.59–3.45 (2 m, 1 H
each, OCH2), 3.53 (dd, J = 3.9, 7.4, 1 H, 5-H), 1.19, 1.11 (2 t, J = 7 each, 3 H each, 2 CH3), 0.00, –0.04 [2 s, 9 H each,
2 Si(CH3)3]
a Recorded on a 200 MHz spectrometer.
b In acetone-d6.
c Two isomers (50:50).
d Minor compounds refer to the all-cis-isomer of 7c.
e Missing signals are hidden by the signals of the major isomer.
g (53%) of a mixture of 9e/10e (40:60). The NMR data are given in
Tables 3 and 4.
IR (neat): n = 2980–2750 (C–H), 1655 (C=C), 1625 (C=N), 1375,
1180 cm–1 (SO2).
IR (neat): n = 3470 (O–H), 2980–2910 (C–H), 1730 (C=O), 1600
cm–1 (C=N).
Anal. calcd. for C13H15NO5S (297.3): C, 52.52; H, 5.09; N, 4.71; S,
10.76. Found: C, 52.00; H, 5.13; N, 4.66; S, 10.69.
Anal. calcd. for C11H17NO7 (275.3): C, 47.99; H, 6.24; N, 5.08.
Found: C, 47.54; H, 6.30; N, 5.12.
Ethyl 6-Ethoxy-4-(methylsulfonyloxy)-6H-1,2-oxazine-3-car-
boxylate (17)
Dimesylate 15e (0.190 g, 0.488 mmol) was dissolved in EtOAc (5
mL). The solution was filtered through an Al2O3 column (neutral,
activity III; elution with hexane/EtOAc, 1:1). The filtrate was con-
centrated, and the residue was dried in vacuo (30°C/2 mbar). Yield:
0.095 g of a 1:1 mixture of 17 and 15e (calcd. yield for 17: 29%).
The NMR data are given in Tables 3 and 4.
4-Bromo-6-ethoxy-3-phenyl-6H-1,2-oxazine (13)
1,2-Oxazine 8a (0.440 g, 1.50 mmol) was dissolved in CH2Cl2 (8
mL) and the solution was treated with freshly distilled acetyl bro-
mide (135 mL, 1.80 mmol). After 24 h the volatile components were
removed in vacuo to yield 0.497 g of a mixture of 11, 12, 13, and 14
(40:25:25:10). The resulting crude product mixture was used for the
subsequent step without further purification. The NMR data are giv-
en in Tables 3 and 4.
7-Ethoxy-3a,5,6a,7-tetrahydro-5-oxo-3-phenyl-dioxathio-
lan[4,5-d]-1,2-oxazine (18)
A solution of the mixture of 11, 12, 13, and 14 (0.171 g), as isolated
above, in MeOH/THF (3 mL/1 mL) was treated with finely divided
NaOH (0.040 g, 1.00 mmol) and the resulting mixture was stirred
for 1 h at 0°C. The solution was allowed to warm up to r.t., and was
left at r.t. for further 2 h. The mixture was then diluted with Et2O (15
mL), washed successively with H2O and brine (15 mL each), dried
(Na2SO4) and the solvent was concentrated in vacuo. The purifica-
tion by kugelrohr distillation (bp 120°C/0.01 mbar) gave 0.046 g
(31%) of 13 as a yellow oil. 1H and 13C NMR data are identical with
those reported earlier.10
Diol 2a (0.356 g, 1.50 mmol) and pyridine (0.356 g, 4.50 mmol)
were dissolved in anhyd. THF (5 mL) and the solution was cooled
to –20°C. To the stirred solution SOCl2 (0.286 g, 2.25 mmol) was
slowly added. Stirring was continued for 2 h at –10°C. Then the
mixture was quenched with H2O (5 mL) and the aqueous layer was
extracted with Et2O (5 × 10 mL). The combined organic extracts
were dried (Na2SO4), and the solvent was removed under reduced
pressure. Yield: 0.314 g (74%) of 18 (2 diastereomers = 70:30) as a
yellow solid (mp 179–183°C). The NMR data are given in Tables 3
and 4.
MS (EI, 70 eV): m/z (%) = 283 (M+, 12), 181 (14), 180 (69), 159
(16), 158 (100), 152 (12), 151 (25), 146 (17), 145 (74), 144 (84),
135 (15), 132 (17), 130 (38), 117 (22), 116 (12), 115 (20), 107 (25),
106 (27), 105 (14), 104 (55), 103 (Ph – C≡N+, 68), 102 (16), 91 (14),
Mesylation of 4,5-Dihydroxy-4H-1,2-oxazines 2 with Methane-
sulfonyl Chloride; General Procedure 6
The solution of 4H-1,2-oxazines 2 (1 equiv) in anhyd. THF (10 mL/
mmol of 1,2-oxazine) was cooled to –20°C. Then freshly distilled
NEt3 (3.5 equiv) and MeSO2Cl (3 equiv) were added slowly. The
mixture was allowed to warm up successively to –10°C (2 h) and
then to r.t. After 1 h at r.t. the mixture was quenched with H2O (10
mL/mmol of 1,2-oxazine), the aqueous layer was extracted with
Et2O (5 × 10 mL/mmol of 1,2-oxazine) and the combined organic
extracts were dried (Na2SO4). Evaporation of the solvent furnished
the dimesylate 15 which was used without further purification in the
subsequent step. The NMR data of 15 are given in Tables 3 and 4.
+
90 (18), 89 (19), 87 (30), 79 (16), 77 (C6H5 , 83), 76 (23), 71 (12),
+
64 (SO2 , 10), 63 (14), 61 (14), 59 (32), 51 (27), 50 (19), 43 (16).
No correct elemental analysis could be obtained for the crude prod-
uct.
7-Ethoxy-3a,5,6a,7-tetrahydro-5,5-dioxo-3-phenyl-dioxathio-
lan[4,5-d]-1,2-oxazine (19)
To a vigorously stirred solution of 1,2-oxazine 18 (0.295 g, 1.04
mmol) in MeCN (5 mL) was added at 0 °C a solution of RuCl3 tri-
hydrate (5 mg) and NaIO4 (0.334 g, 1.56 mmol) in H2O (2 mL). The
reaction mixture was stirred for 1 h at r.t. and then diluted with Et2O
(10 mL). The organic phase was separated and washed successively
with H2O, aq satd NaHCO3 solution, and brine (10 mL each), and
dried (Na2SO4). Evaporation of the solvent under reduced pressure
led to 19 (0.224 g, 72%) as a pale yellow solid (mp 112–114°C).
The NMR data are given in Tables 3 and 4.
6-Ethoxy-4-(methylsulfonyloxy)-3-phenyl-6H-1,2-oxazine (16)
A solution of dimesylate 15a (0.072 g, 0.183 mmol) and DBU
(0.042 g, 0.275 mmol) in CH2Cl2 (1 mL) was stirred for 2 h at r.t.
Then the solvent was removed and the residue was filtered through
a pad of Al2O3 (hexane/EtOAc, 3:1). Yield: 0.039 g (72%) of 16 as
a yellow oil. The NMR data are given in Tables 3 and 4.
Synthesis 1999, No. 7, 1223–1235 ISSN 0039-7881 © Thieme Stuttgart · New York

1232
R. Zimmer et al.
PAPER
Table 4 13C NMR Dataa of 1,2-Oxazines 2, 4 – 12 and 14 – 21; d, J (Hz)
Compound
C-3 (s)
158.6
C-4 (d)
61.0
C-5 (d)
65.6
C-6 (d)
101.1
Other Signals
2a
135.6, 129.8, 128.8, 128.2 (s, 3 d, C6H5), 65.0 (t, OCH2), 15.4
(q, CH3)
2b
159.3
61.5
64.0
64.5
99.7
136.0, 133.7, 131.5, 131.9, 129.6, 127.3 (3 s, 3 d, C6H3Cl2),
64.8 (t, OCH2), 15.0 (q, CH3)
2cb,c
(trans)
157.0 (d
61.7 (dd
101.2
164.2 (dd, 1,3JCF = 253, 12, =CF), 161.9 (dd, 1,3JCF = 253, 12,
=CF), 132.6 (ddd, 3,3JCF = 6, 10, =CH), 120.4 (dd, 2,4JCF = 12,
4, i-C), 111.9 (ddd, 2,4JCF = 4, 22, =CH), 104.4 (td, 2,2JCF = 27,
=CH), 64.8 (t, OCH2), 15.3 (q, CH3)
3JCF = 2)
4JCF = 4)
2cb,c
(cis)
–
63.3 (dd
–
106.5
99.8
64.7 (t, OCH2), 14.6 (q, CH3)
4JCF = 4)
2db
157.6
60.2
64.8
134.1 (s, C-1'), 130.9 (q, 2JCF = 26, C-3'), 130.7 (dq, 4JCF = 1,
C-5'), 128.8 (d, C-6'), 126.4, 124.3 (2 dq, 3JCF = 4 each, C-2',
C-4'), 123.9 (q, 1JCF = 275, CF3), 65.2 (t, OCH2), 15.0 (q, CH3)
2eb,c
2fb,c
153.8
60.1
58.8
64.6
63.0
101.5
100.5
163.6 (s, CO2Et), 65.5, 62.1 (2 t, OCH2), 15.3, 14.4 (2 q,
2CH3)
149.5 (q
120.0 (q, 1JCF = 277, CF3), 65.4 (t, OCH2), 14.6 (q, CH3)
2JCF = 32)
2hc
4a
149.6
157.4
58.9
72.3
62.3
65.5
67.9 (t)
97.8
163.2 (s, CO2Et), 62.1 (t, OCH2), 14.0 (q, CH3)
133.5, 130.2, 128.6, 126.8 (s, 3 d, C6H5), 111.1 (s, CMe2),
65.0 (t, OCH2), 27.1, 26.0 [2 q, C(CH3)2], 15.0 (q, CH3)
4bb
4db
158.6
156.3
71.9
72.1
65.8
64.0
96.2
97.5
136.0, 133.6, 131.6, 132.1, 129.8, 127.3 (3 s, 3 d, C6H3Cl2),
111.5 (s, CMe2), 64.5 (t, OCH2), 27.0, 25.7 [2 q, C(CH3)2],
14.8 (q, CH3)
134.4 (s, C-1'), 131.5 (q, 2JCF = 30, C-3'), 130.0 (dq, 4JCF = 1,
C-5'), 129.0 (d, C-6'), 126.5, 123.5 (2 dq, 3JCF = 4 each, C-2',
C-4'), 124.2 (q, 1JCF = 268, CF3), 111.2 (s, CMe2), 65.0
(t, OCH2), 27.0, 25.9 [2 q, C(CH3)2], 14.8 (q, CH3)
4e
4f
4g
4h
5a
5e
5g
6
151.4
70.7
62.9
97.6
97.2
161.8 (s, CO2Et), 111.1 (s, CMe2), 64.9, 61.9 (2 t, OCH2),
26.7, 25.6 [2 q, C(CH3)2], 14.4, 13.8 (2 q, 2CH3)
149.6 (q
70.4
62.1
120.1 (q, 1JCF = 277, CF3), 112.2 (s, CMe2), 65.2 (t, OCH2),
26.7, 25.8 [2 q, C(CH3)2], 14.5 (q, CH3)
2JCF = 33)
156.5
150.4
154.9
148.8
154.6
154.2
156.7
157.4
72.7
77.4 (s)
62.7
102.6
67.2(t)
97.2
133.1, 129.9, 128.3, 126.3 (s, 3 d, C6H5), 110.6 (s, CMe2),
57.3 (q, OCH3), 27.4d [q, C(CH3)2], 19.1 (q, CH3)
68.7
162.2 (s, CO2Et), 111.0 (s, CMe2), 62.1 (t, OCH2), 27.2, 25.7
[2 q, C(CH3)2], 13.9 (q, CH3)
59.3
62.9
169.9, 169.5 (2 s, COMe), 132.5, 129.6, 128.9, 126.5 (s, 3 d,
C6H5), 64.7 (t, OCH2), 20.5, 20.2 (2 q, COCH3), 14.7 (q, CH3)
58.6
62.5
98.1
169.9, 169.0 (2 s, COMe), 160.8 (s, CO2Et), 65.6, 62.3 (2 t,
OCH2), 20.7, 20.4 (2 q, COCH3), 14.8, 14.0 (2 q, CH3)
65.6
77.2 (s)
73.5 (s)
64.7
99.8
169.9, 169.4 (2 s, COMe), 132.3, 129.6, 128.4, 126.8 (s, 3 d,
C6H5), 56.8 (q, OCH3), 21.8, 20.6 (2 q, COCH3), 17.6 (q, CH3)
188.0 (s)
71.7
106.8
67.2(t)
97.13
169.5 (s, COMe), 133.0, 129.8, 128.4, 128.0 (s, 3 d, C6H5),
57.8 (q, OCH3), 21.5 (q, OCH3), 16.9 (q, CH3)
7ab
(isomer a)
132.9, 130.4, 128.6, 126.6 (s, 3 d, C6H5), 115.9 (d, C-2), 65.0
(t, OCH2), 52.2 (q, OCH3), 14.8 (q, CH3)
7ab
(isomer b)
72.9
64.5
133.2, 130.2, 128.5, 126.7 (s, 3 d, C6H5), 116.6 (d, C-2), 64.9
(t, OCH2), 51.0 (q, OCH3), 14.9 (q, CH3)
Synthesis 1999, No. 7, 1223–1235 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereoselective Preparation of 4,5-Dihydroxy-5,6-dihydro-4H-1,2-oxazines and Their Derivatives
1233
Table 4 (continued)
Compound
C-3 (s)
157.2
C-4 (d)
72.3
C-5 (d)
64.0
C-6 (d)
96.5
Other Signals
8ab
133.3, 130.2, 128.5, 126.6 (s, 3 d, C6H5), 123.5 (s, COMe),
(major)
64.6 (t, OCH2), 49.3 (q, OCH3), 23.0 (q, CH3), 14.8 (q, CH3)
8ab
157.2
73.1
65.3
97.0
133.1, 130.3, 128.5, 126.6 (s, 3 d, C6H5), 122.9 (s, COMe),
(minor)
64.8 (t, OCH2), 50.1 (q, OCH3), 21.9 (q, CH3), 14.8 (q, CH3)
8cb,e
(major)
157.2 (d
66.6, 66.0
(2 dd
72.6, 74.5
97.5, 97.2
164.2 (dd, 1,3JCF = 253, 12, =CF), 161.0 (dd, 1,3JCF = 254, 12,
=CF), 131.4 (ddd, 3,3JCF = 4, 10, =CH), 126.6, 122.9 (2 s,
3JCF = 2)
4JCF = 6)
2 COMe), 120.0 (dd, 2,4JCF = 11, 3, i-C), 111.9 (ddd, 2,4JCF
=
3, 21, =CH), 104.7 (td, 2JCF = 26, =CH), 65.0 (t, OCH2), 49.9,
49.8 (2 q, 2 OCH3), 22.3, 22.1 (2 q, 2 CH3), 14.9, 14.8 (2 q,
2CH3)
8eb,e
9c
151.5,
151.4
71.7, 70.9
61.8, 63.1
65.2
96.6, 96.5
100.0
161.8, 161.6 (2 s, 2 CO2Et), 123.5, 123.1 (2 s, 2 COMe), 65.1,
64.9, 62.3, 62.2 (4 t, 4 OCH2), 49.8, 49.2 (2 q, 2 OCH3), 22.7,
22.3 (2 q, 2 CH3), 14.6, 14.5, 14.0, 13.9 (4 q, 4 CH3)
155.7
59.7 (dd
169.5 (s, COMe), 163.9 (dd, 1,3JCF = 251, 12, =CF), 159.3
(dd, 1,3JCF = 251, 12, =CF), 131.3 (ddd, 3,3JCF = 6.5, 10, =CH),
117.6 (dd, 2,4JCF = 17, 4, i-C), 111.8 (ddd, 2,4JCF = 3, 22, =CH),
104.2 (td, 2JCF = 26, =CH), 64.9 (t, OCH2), 20.9 (q, COCH3),
14.9 (q, CH3)
4JCF = 5)
9e
148.9
152.8
61.2f
62.7f
62.0
100.4
97.4
169.4 (s, COMe), 161.1 (s, CO2Et), 65.6, 62.1 (2 t, 2 OCH2),
20.6 (q, COCH3), 14.8, 13.9 (2 q, 2 CH3)
10c
64.3 (dd
170.6 (s, COMe), 111.9 (ddd, 2,4JCF = 3, 21, =CH), 104.0
(td, 2JCF = 26, =CH), 65.0 (t, OCH2), 20.5 (q, COCH3), 14.9
(q, CH3)
4JCF = 4)
10e
11b
150.6
155.2
153.7
158.3
154.0
147.4
64.1
66.5
58.2
36.7
69.1
55.6
71.1
70.5
71.8
69.3
114.5
113.2
68.3
70.2
67.7
98.2
94.7
97.2
93.8
98.4
99.2
100.0
99.9
95.7
96.4
95.9
97.4
94.4
170.3 (s, COMe), 163.1 (s, CO2Et), 65.4, 62.5 (2 t, 2 OCH2),
20.7 (q, COCH3), 14.7, 13.9 (2 q, 2 CH3)
169.9 (s, COMe), 133.1, 129.7, 128.8, 128.0 (s, 3 d, C6H5),
64.3 (t, OCH2), 20.7 (q, COCH3), 14.8 (q, CH3)
12
28.3
169.4 (s, COMe), 133.0, 130.1, 128.4, 126.6 (s, 3 d, C6H5),
65.3 (t, OCH2), 20.6 (q, COCH3), 14.9 (q, CH3)
14
41.3
133.7, 130.4, 128.8, 126.3 (s, 3 d, C6H5), 64.9 (t, OCH2), 14.9
(q, CH3)
15ab
15eb,c
66.7
133.3, 130.8, 129.3, 128.4 (s, 3 d, C6H5), 39.1, 38.8 (2 q,
SO2CH3), 15.2 (q, CH3)
66.0
161.5 (s, CO2Et), 66.9, 63.2 (2 t, 2 OCH2), 39.0, 38.8 (2 q,
2 SO2CH3), 15.1, 14.1 (2 q, 2 CH3)
15fb,c
(major)
144.3(q)
67.9
121.1 (q, 1JCF = 275, CF3), 66.4 (t, OCH2), 39.1, 39.0 (2 q,
2 SO2CH3), 15.1 (q, CH3)
2JCF = 34)
15fb,c
(minor)
–
64.6
120.5 (q, 1JCF = 275, CF3), 67.0 (t, OCH2), 38.8, 38.4 (2 q,
2 SO2CH3), 15.0 (q, CH3)
16b
17b
152.9
145.9
154.3
156.1
153.0
137.2 (s)
135.7 (s)
74.3
131.7, 130.2, 128.6, 127.4 (s, 3 d, C6H5), 64.6 (t, OCH2), 38.3
(q, SO2CH3), 14.9 (q, CH3)
159.9 (s, CO2Et), 66.3, 62.6 (2 t, 2 OCH2), 38.2 (q, SO2CH3),
14.8, 14.0 (2 q, 2 CH3)
18b
(major)
130.9, 131.8, 128.8, 126.5 (s, 3 d, C6H5), 65.6 (t, OCH2), 14.7
(q, CH3)
18b
(minor)
78.0
130.7, 132.1, 128.7, 126.8 (s, 3 d, C6H5), 65.8 (t, OCH2), 14.8
(q, CH3)
19b
74.7
131.0, 131.2, 129.0, 126.5 (s, 3 d, C6H5), 65.7 (t, OCH2), 14.7
(q, CH3)
Synthesis 1999, No. 7, 1223–1235 ISSN 0039-7881 © Thieme Stuttgart · New York

1234
R. Zimmer et al.
PAPER
Table 4 (continued)
Compound
C-3 (s)
154.1
C-4 (d)
53.1
C-5 (d)
67.7
C-6 (d)
97.0
Other Signals
20b
132.8, 130.6, 128.6, 126.4 (s, 3 d, C6H5), 65.5 (t, OCH2), 14.5
(q, CH3)
21a
21e
157.9
150.8
65.5
63.4
69.0
67.8
100.7
101.4
134.1, 129.2, 128.1, 127.4 (s, 3 d, C6H5), 65.5 (t, OCH2), 15.2
(q, CH3), 0.6, 0.3 [2 q, 2 Si(CH3)3]
162.5 (s, CO2Et), 66.2, 61.9 (2 t, 2 OCH2), 15.1, 14.1 (2 q,
2 CH3), 0.43, 0.22 [2 q, 2 Si(CH3)3]
a 75.5 MHz, CDCl3.
b Recorded on 50.3 MHz spectrometer.
c In acetone-d6.
d Signal has double intensity.
e Two diastereomers (50:50).
f Assignment ambiguous; signals are exchangeable within the line.
References
MS (EI, 70 eV): m/z (%) = 299 (M+, 11), 253 (23), 237 (27), 203
(10), 202 (74), 174 (23), 173 (50), 159 (11), 158 (57), 146 (36), 145
(91), 144 (57), 133 (14), 131 (11), 130 (23), 122 (33), 117 (24), 116
(13), 115 (44), 105 (23), 104 (69), 103 (Ph – C≡N+, 100), 102 (18),
(1) Homann, K. Dissertation, Technische Hochschule Darmstadt,
1994.
(2) Angermann, J. Dissertation, Technische Universität
Dresden,1997.
(3) For excellent up-to-date reviews, see: Iminosugars as
Glycosidase Inhibitors – Nojirimycin and Beyond; Stütz, A.
E.; Ed., Wiley-VCH: Weinheim, 1999.
+
91 (17), 90 (10), 89 (18), 78 (10), 77 (C6H5 , 94), 76 (25), 65 (19),
+
64 (SO2 , 9), 63 (14), 59 (24), 58 (17), 55 (14), 51 (33), 50 (13).
IR (neat): n = 2990–2790 (C–H), 1650 (C=C), 1620 (C=N), 1080
cm–1 (SO2).
Bols, M. Acc. Chem. Res. 1998, 31, 1.
Anal. calcd. for C12H13NO6S (299.3): C, 48.16; H, 4.37; N, 4.68; S,
10.71. Found: C, 48.37; H, 4.50; N, 4.73; S, 9.73.
For recent synthetic work, see: Defoin, A.; Sarazin, H.;
Sifferlen, T.; Strehler, C.; Streith, J. Helv. Chim. Acta 1998,
81, 1417.
Kieß, F.-M.; Poggendorf, P.; Picasso, S.; Jäger, V. Chem.
Commun. 1998, 19.
r-4-Azido-c-6-ethoxy-t-5-hydroxy-3-phenyl-5,6-dihydro-4H-
1,2-oxazine (20)
1,2-Oxazine 19 (0.024 g, 0.085 mmol) and NaN3 (0.011 g, 0.169
mmol) were dissolved in anhyd. DMF (3 mL) and the solution was
heated at 70°C for 23 h. After cooling to r.t. 25% aq H2SO4 solution
(2.5 mL) was added and the mixture was extracted with EtOAc (2 ×
10 mL). The combined organic phases was washed successively
with 2N H2SO4 solution, H2O, satd NaHCO3 solution and brine (5
mL each), and dried (Na2SO4). After removal of the solvent under
reduced pressure 0.017 g of a mixture of 20/19 (60:40) was isolated.
The NMR data of 20 are given in Tables 3 and 4.
Hümmer, W.; Dubois, E.; Gracza, T.; Jäger, V. Synthesis
1997, 634.
Defoin, A.; Sarazin, H.; Streith, J. Tetrahedron 1997, 53,
13769.
Defoin, A.; Sifferlen, T.; Streith, J.; Dosbaâ, I.; Foglietti, M.-
J. Tetrahedron: Asymmetry 1997, 8, 363.
Streith, J.; Defoin, A. Synlett 1996, 189.
(4) Homann, K.; Angermann, J.; Collas, M.; Zimmer, R.; Reissig,
H.-U. J. Prakt. Chem. 1998, 340, 649.
(5) Zimmer, R.; Reissig, H.-U. Angew. Chem. 1988, 100, 1576;
Angew. Chem. Int. Ed. Engl. 1988, 27, 1518.
Zimmer, R.; Reissig, H.-U. Liebigs Ann. Chem. 1991, 553.
(6) Preliminary communication: Angermann, J.; Homann, K.;
Reissig, H.-U.; Zimmer, R. Synlett 1995, 1014.
(7) Shing, T. K. M.; Tai, V. W.-F.; Tam, E. K. W. Angew. Chem.
1994, 106, 2408; Angew. Chem. Int. Ed. Engl. 1994, 33, 2312.
Shing, T. K. M.; Tam, E. K. W.; Tai, V. W.-F.; Chung, I. H.
F.; Jiang, Q. Chem. Eur. J. 1996, 2, 50.
(8) Zimmer, R.; Angermann, J.; Hain, U.; Hiller, F.; Reissig, H.-
U. Synthesis 1997, 1467.
(9) Kolb, H. C.; Sharpless, K. B. Tetrahedron 1992, 48, 10515.
Wang, Z.-M.; Kolb, H. C.; Sharpless, K. B. J. Org. Chem.
1994, 59, 5104.
IR (KBr): n = 3440 (br, O–H), 3000–2840 (=C–H, C–H), 2110 (N3),
1610 cm–1 (C=N).
Silylation of 4,5-Dihydroxy-4H-1,2-oxazines; General Proce-
dure 7
To a mixture of 1,2-oxazine 2 and hexamethyldisilazane (2.5–5 mL/
mmol of 1,2-oxazine) was added TMSCl (0.25–0.5 mL/mmol of
1,2-oxazine). After heating at 100°C for 5–7 h the suspension was
cooled to r.t., the volatile components were removed in vacuo
(40°C/50–0.01 mbar) and the residue was purified by filtration
(neutral alumina, activity III; tBuOMe) to give the silylated product
21. The NMR data of 21 are given in Tables 3 and 4.
Oikawa, M.; Wada, A.; Okazaki, F.; Kusumoto, S. J.
Org. Chem. 1996, 61, 4469.
(10) Paulini, K.; Gerold, A.; Reissig, H.-U. Liebigs Ann. 1995, 667.
(11) Angermann, J.; Collas, M.; Homann, K.; Reissig, H.-U.
unpublished results.
(12) The NMR data do not exclude the possibility of anomerization
at C-6, however, we can not see a reason why this should
occur with 15f and not with the related compounds 15a and
15e.
Acknowledgement
We are most grateful for generous support of this work by the Deut-
sche Forschungsgemeinschaft (Graduiertenkolleg: "Struktur-Ei-
genschafts-Beziehungen bei Heterocyclen") and the Fonds der
Chemischen Industrie. We thank Robert Pulz, Ute Hain, and the late
Elke Marks for experimental help.
(13) Zimmer, R.; Reissig, H.-U. J. Org. Chem. 1992, 57, 339.
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Article Identifier:
1437-210X,E;1999,0,07,1223,1235,ftx,en;H11298SS.pdf
Synthesis 1999, No. 7, 1223–1235 ISSN 0039-7881 © Thieme Stuttgart · New York