2-Silyloxy-1,2-oxazines, a New Type of Acetals of Conjugated Nitroso Alkenes

Article abstract of DOI:10.1021/jo034669a

3-Alkyl-substituted 1,2-oxazine N-oxides 2 can be selectively transformed into 2-silyloxy-1,2-oxazines 1 upon treatment with silylating reagents. In the solid state derivatives 1 adopt a chair conformation with the pyramidal nitrogen atom, whereas in solu

Full text of DOI:10.1021/jo034669a

CHART 1
2-Silyloxy-1,2-oxa zin es, a New Typ e of
Aceta ls of Con ju ga ted Nitr oso Alk en es
Alexander A. Tishkov,† Alexey V. Lesiv,†
Yulya A. Khomutova,† Yury A. Strelenko,†
Ivan D. Nesterov,‡ Michael Yu. Antipin,‡
Sema L. Ioffe,*,† and Scott E. Denmark§
SCHEME 1
N. D. Zelinsky Institute of Organic Chemistry,
Russian Academy of Sciences, 119991 Leninsky Prosp. 47,
Moscow, Russian Federation, A. N. Nesmeyanov Institute of
Organoelement Compounds, Russian Academy of Sciences,
119991 Vavilova str. 28, Moscow, Russian Federation, and
Department of Chemistry, University of Illinois at
Urbana-Champaign, 245 Roger Adams Laboratory,
Box 18-5, 600 S. Mathews Avenue, Urbana, Illinois 61801
iof@ioc.ac.ru
Received May 19, 2003
Abstr a ct: 3-Alkyl-substituted 1,2-oxazine N-oxides 2 can
be selectively transformed into 2-silyloxy-1,2-oxazines 1 upon
treatment with silylating reagents. In the solid state deriva-
tives 1 adopt a chair conformation with the pyramidal
nitrogen atom, whereas in solution they exist as an equili-
brating mixture of two conformers (∆Gq 55-60 kJ /mol). A
preliminary study of the reactivity of nitrosals 1 has shown
that they react with O- and N-stabilized carbocations to yield
1,2-oxazine N-oxides with a functionalized alkyl substituent
at the 3-position. Moreover, compounds 1 can rearrange into
silyloxy-1,2-oxazines 5 and react with morpholine to produce
3-morpholinoalkyl-1,2-oxazines 7 existing in a tautameric
equilibrium with open-chain oximes 6.
synthesis of enamines A seems more attractive. Because
many acyclic alkyl nitronates are relatively unstable,4 we
have chosen much more stable cyclic nitronates as objects
for the silylation.
In this connection, we have synthesized hitherto
unknown 2-silyloxy-1,2-oxazines 1a -j with good yields
by silylation of 1,2-oxazine N-oxides 2a -j (Scheme 1),
which are easily prepared employing the hetero Diels-
Alder reaction between nitroalkenes and olefins.5
In principle, the silylation of 1,2-oxazine N-oxides 2 can
lead to the formation of either endo or exo CdC isomers
(Scheme 1). The control of regioselectivity is achieved by
varying the bases of the silylating mixture. The condi-
tions of silylation and results obtained are summarized
in Table 1.
The mixture of Et3N and various silylating agents (Me3-
SiBr, t-BuMe2SiOTf, and EtMe2SiCl) leads to the forma-
tion of the target nitroso acetals 1. It is worthy of note
that even 1,2-oxazine N-oxide 2j, which possesses an
electron-withdrawing 4-NO2C6H4 substituent in the 4-po-
sition, can be selectively transformed into nitrosal 1j′′.
The use of pyridine in combination with Me3SiBr
dramatically changes the direction of the silylation. The
immediate products of this reaction, 1,2-oxazines B,
undergo [4 + 2] cycloreversion leading to R,â-unsaturated
oximes 3 and carbonyl fragments.6 The influence of the
base on the regioselectivity of this reaction is likely
connected with steric factors; however, this question
requires more detailed study.
N,N-Bis(silyloxy)enamines (BENA), readily available
acetals of conjugated nitroso alkenes,1 exhibit ambident
reactivity as moderate â-C-nucleophiles2 and formal â-C-
electrophiles.3 This versatility of the reactivity of BENA
allows one to consider them as promising reagents for
organic synthesis. However, the instability of BENA, due
to the presence of two SiO groups complicates their
practical use, which prompted us to look for more stable
analogues of these interesting compounds. Higher stabil-
ity could be expected for the unknown enamines A, which
contain one silyloxy and one alkyloxy group at the
nitrogen atom (Chart 1).
These compounds could be synthesized by either si-
lylation of alkyl nitronates or alkylation of silyl nitro-
nates. Whereas the double alkylation of aliphatic nitro
compounds is unknown, their double silylation is a well-
developed protocol.1 Therefore, the first approach to the
† N. D. Zelinsky Institute of Organic Chemistry.
‡ A. N. Nesmeyanov Institute of Organoelement Compounds.
§ University of Illinois at Urbana-Champaign.
The silylation of 3-ethyl-1,2-oxazine N-oxide 2h is
stereoselective and produces only the E-isomer of 3-eth-
ylidene-1,2-oxazine 1h (by NOE measurements). Nitroso
acetals 1 obtained as solids were purified by recrystal-
(1) For the discovery of BENA, see: (a) Feger, H.; Simchen, G.
Liebigs Ann. Chem. 1986, 1456. For the improved procedure for
preparation of BENA, see: (b) Dilman, A. D.; Tishkov, A. A.; Lyapkalo,
I. M.; Ioffe, S. L.; Strelenko, Yu. A.; Tartakovsky, V. A. Synthesis 1998,
181. (c) Dilman, A. D.; Tishkov, A. A.; Lyapkalo, I. M.; Ioffe, S. L.;
Kachala, V. V.; Strelenko, Yu. A.; Tartakovsky, V. A. J . Chem. Soc.,
Perkin Trans. 1 2000, 2926.
(2) (a) Dilman, A. D.; Lyapkalo, I. M.; Ioffe, S. L.; Strelenko, Yu. A.;
Tartakovsky, V. A. J . Org. Chem. 2000, 65, 8826. (b) Dilman, A. D.;
Ioffe, S. L.; Mayr, H. J . Org. Chem. 2001, 66, 3196.
(4) Torssell, K. B. G. Nitrile Oxides, Nitrones and Nitronates in
Organic Synthesis; VCH Publishers Inc.: New York, 1988; p 106.
(5) Denmark, S. E.; Thorarensen, A. Chem. Rev. 1996, 96, 137.
(6) This reaction, occurring upon silylation of C(3) unsubstituted 1,2-
oxazine N-oxides, was discussed in a previous publication: Tishkov,
A. A.; Lyapkalo, I. M.; Kozincev, A. V.; Ioffe, S. L.; Strelenko, Yu. A.;
Tartakovsky, V. A. Eur. J . Org. Chem. 2000, 3229.
(3) (a) Dilman, A. D.; Lyapkalo, I. M.; Ioffe, S. L.; Strelenko, Yu. A.;
Tartakovsky, V. A. Synthesis 1999, 1767. (b) Lesiv, A. V.; Ioffe, S. L.;
Strelenko, Yu. A.; Tartakovsky, V. A. Helv. Chim. Acta 2002, 85, 3489.
10.1021/jo034669a CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/06/2003
J . Org. Chem. 2003, 68, 9477-9480
9477

TABLE 1. Silyla tion of 1,2-oxa zin e N-oxid es 2
1,2-Oxazine N-oxide 2
reagent
conditions
T, °C/t, h
product
(yield, %)
entry
R1
R2
R3
R4
R5
Me
Me
Me
H
OEt
Me
Me
H
OBu-n
Me
Me
H
R6Me2SiX/Et3N
1
2
3
4
5
6
7
8
2a
2a
2a
2b
2c
2d
2d
2e
2f
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
Me
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
C6H5
C6H5
C6H5
C6H5
C6H5
H
H
H
H
H
H
H
H
H
H
H
OMe
OMe
OMe
OEt
Me3SiBr/Et3N
-78/24
20/72
-78/1
-78/24
-78/24
-78/24
-78/1
-78/1
-78/1
-78/24
-78/24
-78/24
-78/1
-30/24
-30/24
-30/24
1a (67)
1a ′ (62)
1a ′′ (71)
1b (98)
1c (98)
1d (97)
1d ′′ (94)
1e′′ (95)
1f′′ (93)
1g (95)
1h (95)
1i (95)
EtMe2SiCl/Et3N
t-BuMe2SiOTf/Et3N
Me3SiBr/Et3N
Me3SiBr/Et3N
Me3SiBr/Et3N
t-BuMe2SiOTf/Et3N
t-BuMe2SiOTf/Et3N
t-BuMe2SiOTf/Et3N
Me3SiBr/Et3N
Me3SiBr/Et3N
Me3SiBr/Et3N
H
OMe
OMe
OBu-n
H
9
10
11
12
13
14
15
16
2g
2h
2i
Me
C6H5
OMe
(CH2)4
(CH2)4
OMe
OMe
OMe
4-MeOC6H4
4-NO2C6H4
4-MeOC6H4
C6H5
(CH2)4
(CH2)4
H
H
H
2j
H
t-BuMe2SiOTf/Et3N
Me3SiBr/C5H5N
Me3SiBr/C5H5N
Me3SiBr/C5H5N
1j′′ (98)
4a (89)
4d (81)
4h (64)
2a
2d
2h
Me
Me
Me
C6H5
F IGURE 1. The structure of 3-methylene-1,2-oxazine 1a .
lization, while oily products were either thoroughly
evaporated in high vacuum or distilled in a short-path
apparatus. The purity of all nitrosals 1 was proved by
elemental analysis.
Compound 1a was studied by means of X-ray analysis
(Figure 1),7 which revealed that in the solid state 2-si-
lyloxy-1,2-oxazines 1 adopt a chair conformation with the
pyramidal nitrogen atom (the sum of the valence angles
at N is 317.3 grad) and an equatorial arrangement of the
SiO group. The lengths of CdC and CsN bonds in
nitrosal 1a are similar with these parameters in BENA.8
According to the NMR analysis, nitroso acetals 1 exist
in solution as equilibrium mixtures of two conformers,
which quickly interconvert at room temperature (Table
2). A typical example of NMR spectra of nitrosals 1 at
variable temperatures is presented in Figure 2.
The activation parameters of this dynamic process
coincide with the ∆Gq for nitrogen inversion measured
for BENA (50-60 kJ /mol).8 However, in contrast to
BENA, one can observe the second, faster dynamic
process in DNMR spectra of nitrosals 1. Unfortunately,
the quantitative analysis of this dynamic process is
complicated by the restriction of the rotation motion of
the substituents in the ring of the 1,2-oxazine; the nature
F IGURE 2. 1H NMR spectra of nitrosal 1g at variable
temperatures. a, b, and c: signals of major conformer of 1g.
a′, b′, and c′: signals of minor conformer of 1g. a,a′ and b,b′:
signals of CH2dC protons. c,c′: signals of HC(4) protons of 1g.
of stereodynamics peculiar to nitroso acetals 1 is not
completely clear now.
The thermal stability of nitroso acetals 1 depends
strongly on the substitution at the CdC bond (R1):
3-methylene-1,2-oxazine 1e′′ can be distilled at 120-125
°C (5 × 10-5 mmHg), whereas 3-ethylidene-1,2-oxazine
1h rearranges chemo- and stereoselectively into silyloxy-
1,2-oxazine 5 in 1 day at room temperature (Scheme 2).9
Preliminary studies of the reactivity of nitroso acetals 1
revealed that these compounds as BENA can react with
both electrophiles and nucleophiles.
Usual alkylating agents, such as MeOCH2Cl, do not
react with 2-silyloxy 1,2-oxazines 1. However, the nu-
cleophilicity of the CdC bond of nitroso acetals 1 is
sufficient to participate in reactions with more electro-
(7) The structure of 1,2-oxazine N-oxide 2a was also studied by X-ray
analysis (see Supporting Information). The configuration of the ste-
reocenters in positions 4 and 6 of 1,2-oxazine’s ring remains intact in
the course of the silylation of N-oxides 2.
(8) Tishkov, A. A.; Dilman, A. D.; Faustov, V. I.; Birukov, A. A.;
Lysenko, K. S.; Belyakov, P. A.; Ioffe,S. L.; Strelenko, Yu. A.; Antipin,
M. Yu. J . Am. Chem. Soc. 2002, 124, 11358-11367.
(9) The configuration of a new stereocenter was not established.
9478 J . Org. Chem., Vol. 68, No. 24, 2003

TABLE 2. Ster eod yn a m ics of Nitr osa ls 1
SCHEME 4
SCHEME 5
a
b
An ) 4-MeOC6H4. For a conversion of major conformer into
minor. c The ratio of conformers varies only slightly within the
studied temperature range.
SCHEME 2
TABLE 3. In ter a ction of Nitr osa ls 1 w ith Electr op h iles
conditions
product
entry
R
X
n
Y
T, °C (t, h) (yield, %)
1
2
3
4
1e′′ Ph
1f′′ Ph
O
O
O
N
1
1
1
2
OTf -78 (6)
OTf -78 (6)
OTf -78 (1.5)
2k (45)
2l (55)
2m (55)
2n (89)
In conclusion, we have developed a method for the
transformation of 3-alkyl-1,2-oxazine N-oxides 2 into
previously unknown 2-silyloxy-1,2-oxazines 1, a new type
of acetals of conjugated nitroso alkenes. This preliminary
study of their reactivity demonstrated the promising
synthetic potential of these new derivatives.
1e′′ 4-MeOC6H4
1e′′
H
Cl
0 (1)
SCHEME 3
Moreover, our results have expanded the traditional
palette of reactions of cyclic alkyl nitronates 2, readily
available substrates, which are easily built from simple
molecules (Scheme 5). Previously the application of 1,2-
oxazine N-oxides 2 was mainly limited by their involve-
ment in the inter- and intramolecular dipolar cycloaddi-
tions [reaction 1].4,5 At the same time, now we can
functionalize the position 3 of nitronates 2 [reactions 3
and 4], synthesize the Si-derivatives of conjugated
enoximes 3 [reaction 2] and various types of 1,2-oxazines
5 and 7 [reactions 5 and 6]. According to our preliminary
results, reactions 3, 5, and 6 can be expected to be highly
diastereoselective. Our following publications will contain
the convenient protocols as well as scopes and limitations
for the transformations of cyclic alkyl nitronates 2,
presented in Scheme 5.
philic O- and N-stabilized carbocations (Scheme 3, Table
3). These processes afford 1,2-oxazine N-oxides 2k -n
with a functionalized substituent at C(3) position.
The action of nucleophiles on nitrosals 1 brings about
the formation of different products. For example, interac-
tion of compounds 1a or 1d with morpholine produces
in solution a tautomeric mixture of compounds 6 and 7
(Scheme 4). By analogy with BENA,10 one can propose
that the mechanism of this reaction includes the genera-
tion of strongly electrophilic nitroso alkenes C, which
react with the nucleophilic amine.
Exp er im en ta l Section
Typ ica l P r oced u r es for P r ep a r a tion of Nitr oso Aceta ls
1. (a ) r el-(4R,6R)-6-Meth oxy-6-m eth yl-2-tr im eth ylsilyloxy-
3-m et h ylen e-4-(4-m et h oxyp h en yl)-2,3,5,6-t et r a h yd r o-1,2-
oxa zin e (1a ). To a stirred solution of nitronate 2a (0.27 g,
(10) Makarenkova, L. M.; Bliznets, I. V.; Ioffe, S. L.; Strelenko, Yu.
A.; Tartakovsky, V. A. Russ. Chem. Bull. 2000, 49, 1261 (English ed.);
2000, 49, 1265 (Russian ed.).
J . Org. Chem, Vol. 68, No. 24, 2003 9479

1 mmol) in CH2Cl2 (2 mL) were added at -78 °C NEt3 (0.17 mL,
1.2 mmol) and Me3SiBr (0.15 mL, 1.1 mmol). The reaction
mixture was stirred for 24 h at -78 °C, diluted with hexane
(5 mL), and poured in a mixture of hexane (15 mL) and H2O
(5 mL). The organic layer was washed with a solution of
NaHSO4‚H2O (0.12 g, 0.87 mmol) in H2O (6 mL), H2O (6 mL),
and brine (5 mL), treated with activated charcoal, and dried over
Na2SO4. Solvents were evaporated in a vacuum, and the residue
was recrystallized from hexane to give title compound 1a as
colorless prisms (0.23 g, 67%). Mp: 68-70 °C.
(b) r el-(4R,6R)-6-Meth oxy-6-m eth yl-2-(ter t-bu tyld im eth -
ylsilyloxy)-3-m et h ylen e-4-(4-m et h oxyp h en yl)-2,3,5,6-t et -
r a h yd r o-1,2-oxa zin e (1a ′′). To a stirred solution of nitronate
2a (0.27 g, 1 mmol) in CH2Cl2 (2 mL) were added at -78 °C
NEt3 (0.21 mL, 1.5 mmol) and t-BuMe2SiOTf (0.28 mL, 1.2
mmol). The reaction mixture was stirred for 1 h at -78 °C,
diluted with hexane (5 mL), and poured in a mixture of hexane
(15 mL) and H2O (5 mL). The organic layer was washed with
H2O (2 × 6 mL) and brine (5 mL), treated with an activated
charcoal, and dried over Na2SO4. Solvents were evaporated in
a vacuum, and the residue was recrystallized from hexane to
give title compound 1a ′′ as colorless prisms (0.27 g, 71%). Mp:
62-65 °C. Analytical data for 1a and 1a ′′ are presented in
Supporting Information.
The solvents were evaporated in a vacuum, and the yellow
residue was separated on preparative MPLC (Rexchrom 5/100
silica, 25 cm × 21.1 mm, flow rate 15 mL/min, eluent hexane/
i-PrOH 1:30). The upper product was distilled and recrystallized
to give the major isomer of the title compound 2k (0.08 g, 30%),
and the lower product was recrystallized (Et2O/hexane) to give
the minor isomer of the title compound 2k (0.03 g, 15%) of white
crystals. Analytical data for both isomers are in Supporting
Information.
r el-(4R,6R)-6-Bu toxy-3-(2-(dim eth ylam in o)-eth yl)-4-ph en -
yl-5,6-d ih yd r o-4H-1,2-oxa zin e N-Oxid e (2n ). To a cold (0 °C)
solution of nitrosal 1e′′ (0.38 g, 1.01 mmol) in CH2Cl2 (2 mL)
was added solid methylenedimethylammonium chloride (0.19 g,
2.03 mmol). The mixture was allowed to warm to 20 °C in 1 h
with stirring and poured into a mixture of Et2O (20 mL) and
H2O (10 mL). The organic layer was separated, and the water
phase was back-extracted with Et2O (3 × 15 mL). The combined
organic layers were washed with H2O (15 mL), saturated
aqueous solution of NaHCO3 (10 mL), H2O (15 mL), and brine
(10 mL), dried over Na2SO4, and evaporated in a vacuum. The
residue was recrystallized from hexane to give title compound
1
2n as white crystals (0.29 g, 89%). Mp: 40-42 °C (hexane). H
NMR (500 MHz, 300 K, CDCl3): δ 7.34 (tt, J ) 1.3, 6.9, 2 H),
7.28 (tt, J ) 1.3, 6.0, 1 H), 7.21 (dt, J ) 2.1, 7.1, 2 H), 5.33 (t,
J ) 2.6, 1 H), 4.00 (dt, J ) 6.6, 9.4, 1 H), 3.96 (dd, J ) 7.7, 11.2,
1 H), 3.64 (dt, J ) 6.4, 9.4, 1 H), 2.62-2.53 (m, 2 H), 2.29-2.21
(m, 2 H), 2.16-2.06 (m, 8 H), 1.65-1.58 (m, 2 H), 1.43-1.38 (m,
2 H), 0.94 (t, J ) 7.5, 3 H). 13C NMR (126 MHz, 300 K, CDCl3):
δ 140.5, 129.5, 128.5, 128.0, 125.8, 101.5, 69.3, 53.9, 45.4, 40.4,
34.8, 31.7, 29.1, 19.5, 14.1. Rf 0.28 [silica gel, Et2O/i-PrOH, 2/1,
anisaldehyde].
Typ ica l P r oced u r e for P r ep a r a t ion of Con ju ga t ed
En oxim es 4. 2-P h en yl-bu t-1-en -3-on e Oxim e (4d ). To a
stirred solution of nitronate 2d (0.24 g, 1 mmol) in CH2Cl2 (2
mL) were added at - 30 °C pyridine (0.12 mL, 1.5 mmol) and
Me3SiBr (0.16 mL, 1.2 mmol). The reaction mixture was stirred
for 24 h at -30 °C, diluted with hexane (5 mL), and poured in
a mixture of hexane (15 mL) and H2O (5 mL). The organic layer
was washed with a solution of NaHSO4‚H2O (0.35 g, 2.54 mmol)
in H2O (15 mL), H2O (10 mL), and brine (5 mL), treated with
activated charcoal, and dried over Na2SO4. Solvents were
evaporated in a vacuum, the residue was dissolved in MeOH (5
mL), and NH4F (5 mg, 0.14 mmol) was added. After being stirred
for 3 h, the mixture was filtered though a pad of Celite and
evaporated. The residue was recrystallized from EtOAc/hexane
mixture to give title compound 4d as a white crystals (0.12 g,
6-Meth yl-3-m or p h olin -4-ylm eth yl-4-p h en yl-5,6-d ih yd r o-
4H-1,2-oxa zin -6-ol (6a ) a n d 1-Mor p h olin -4-yl-3-p h en yl-h ex-
a n e-2,5-d ion e 2-Oxim e (7a ). To a solution of nitrosal 1d (0.31
g, 1 mmol) in CH2Cl2 (1 mL) was added simultaneously at
ambient temperature morpholine (0.13 mL, 1.5 mmol). The
reaction mixture was stirred for 5 min, and CH2Cl2 was carefully
evaporated at 300 mmHg. The resulting solution was maintained
at ambient temperature for 24 h, diluted with MeOH (3 mL),
and after 3 h of stirring evaporated in a vacuum. The residue
was recrystallized from a mixture of EtOAc and hexane 1:10 to
give a mixture of title compounds 6a and 7a (0.18 g, 60%) as
white powder. The ratio of tautomers 6a and 7a in DMSO is
1:1 at 20 °C and 1:3 at 70 °C. Mp: 99-103 °C (hexane/EtOAc,
10:1). 6a : 1H NMR (300.13 MHz, 300 K, DMSO-d6): δ 7.4-7.2
(m, 5 H), 6.44 (s, 1 H), 3.79 (dd, J ) 5.2, 12.5, 1 H), 3.56 (m, 4
H), 2.80 (d, J ) 12.3, 1 H), 2.56 (d, J ) 12.3, 1 H), 2.4-2.0 (m,
5 H), 1.89 (dd, J ) 12.4, 12.5, 1 H), 1.49 (s, 3 H). 13C NMR (75.47
MHz, 300 K, DMSO-d6): δ 156.6, 140.6, 128.5, 128.1, 126.6, 94.6,
66.2, 59.7, 52.6, 37.9, 37.0, 26.8. 7a : 1H NMR (300.13 MHz, 300
K, DMSO-d6): δ 10.81 (s, 1 H), 7.4-7.2 (m, 5 H), 4.79 (dd, J )
7.8, 7.3, 1 H), 3.51 (m, 4 H), 3.28 (dd, J ) 7.8, 17.1, 1 H), 3.05
(dd, J ) 7.3, 17.1, 1 H), 2.93 (d, J ) 12.5, 1 H), 2.69 (d, J ) 12.5,
1 H), 2.4-2.0 (m, 4 H), 2.12 (s, 3 H). 13C NMR (75.47 MHz, 300
K, DMSO-d6): δ 205.8, 154.7, 140.7, 128.4, 127.9, 126.1, 66.0,
59.7, 53.0, 44.6, 37.6, 29.8. For both: Rf 0.11 (silica gel, EtOAc,
UV).
1
81%). Mp: 100-101 °C (hexane/EtOAc, 10/1). H NMR (300.13
MHz, 300 K, CDCl3): δ 9.30 (br, 1 H), 7.32 (m, 5 H), 5.61 (s, 1
H), 5.43 (s, 1 H), 2.06 (s, 3 H). 13C NMR (75.47 MHz, 300 K,
CDCl3): δ 156.8, 146.7, 139.1, 128.3, 128.2, 127.7, 117.8, 12.0.
Rf 0.68 (silica gel, hexane/EtOAc, 1/1, UV).
6-Meth oxy-6-m eth yl-4-p h en yl-3-(1-tr im eth ylsilyloxyeth -
yl)-5,6-d ih yd r o-4H-1,2-oxa zin e (5). 1,2-Oxazine 1h (0.32 g, 1
mmol) was maintained for 24 h at room temperature. The
resulting title compound 5 was purified by column chromatog-
raphy on silica gel in hexane/EtOAc 3:1 to give title compound
1
5 (0.30 g, 92%) as an oil. H NMR (300.13 MHz, 300 K, CDCl3):
δ 7.35-7.15 (m, 5 H), 4.29 (q, J ) 5.8,1 H), 3.84 (dd, J ) 8.1,
12.5, 1 H), 3.31 (s, 3 H), 2.29 (dd, J ) 13.1, 8.1, 1 H), 1.88 (dd,
J ) 13.1, 12.5, 1 H), 1.44 (s, 3 H), 1.33 (d, J ) 5.8, 3 H), 0.12 (s,
9 H). 13C NMR (75.47 MHz, 300 K, CDCl3): δ 162.5, 141.3, 128.9,
128.8, 126.9, 96.4, 68.6, 49.6, 40.6, 36.6, 21.7, 20.7, 0.3. 29Si NMR
(59.63 MHz, 300 K, CDCl3): δ 17.09. Rf 0.71 [hexane/EtOAc 3:1].
Typ ica l P r oced u r e for Rea ction s of Com p ou n d s 1 w ith
Acetals. r el-(4R,6R)-6-Bu toxy-3-(2-m eth oxy-2-ph en yl-eth yl)-
4-p h en yl-5,6-d ih yd r o-4H-1,2-oxa zin e N-Oxid e (2k ). To a cold
(-78 °C) solution of pyridine (3 µL, 0.037 mmol) in CH2Cl2 (0.7
mL) were added successively Me3SiOTf (0.15 mL, 0.799 mmol)
and a solution of benzaldehyde dimethyl acetal (0.122 g, 0.803
mmol) in CH2Cl2 (0.7 mL). Then a solution of nitrosal 1e′′ (0.25
g, 0.66 mmol) in CH2Cl2 (1.3 mL) was added dropwise. The
resultant mixture was stirred at -78 °C for 6 h, and a solution
of BnEt3NCl (0.27 g, 1.187 mmol) in CH2Cl2 (2 mL) followed by
Et3N (0.26 mL, 1.871 mmol) were added successively. After 5
min of stirring the mixture was poured into a mixture of H2O
(20 mL) and ether, the organic layer was separated, and the
aqueous phase was diluted with brine (5 mL) and back-extracted
with ether (2 × 10 mL). The combined organic layers were
washed with H2O (15 mL), saturated aqueous NH4Cl solution
(10 mL), H2O (15 mL), saturated aqueous NaHCO3 solution (10
mL), H2O (15 mL), and brine (10 mL) and dried over Na2SO4.
Ack n ow led gm en t. This work was performed with
the financial support of Russian Basic Research Foun-
dation (grant 02-03-33350) and Federal Program Inte-
gration (project B0062). A.A.T. is grateful to UNESCO
for a fellowship.
Su p p or tin g In for m a tion Ava ila ble: Full experimental
procedures, analytical data for all compounds, CIF files and
complete crystal structure data for 1a and 2a ; general proce-
dure for measurement of ∆∆Gq by dynamic NMR; rate
constants and activation parameters of dynamic process 1a -
d . This material is available free of charge via the Internet at
http://pubs.acs.org.
J O034669A
9480 J . Org. Chem., Vol. 68, No. 24, 2003