Hetero Diels-Alder reactions of nitroso alkenes with alkoxyallene derivatives bearing carbohydrate auxiliaries: Asymmetric synthesis of 6H-1,2-oxazines and subsequent reductive transformations

Article abstract of DOI:10.1055/s-2002-33328

Alkoxyallene derivatives 1a-f bearing carbohydrate auxiliaries at the oxygen were examined in asymmetric hetero Diels-Alder reactions with nitroso alkenes. Diacetoneglucose derived compound aa turned out to be the best precursor furnishing the primary cyc

Full text of DOI:10.1055/s-2002-33328

PAPER
1553
Hetero Diels–Alder Reactions of Nitroso Alkenes with Alkoxyallene
Derivatives Bearing Carbohydrate Auxiliaries: Asymmetric Synthesis
of 6H-1,2-Oxazines and Subsequent Reductive Transformations
Asymmetric Syn
e
6
H
i
-1,2-O
n
xazines hold Zimmer,a Beate Orschel,b Stefan Scherer,b Hans-Ulrich Reissig*a
a
Institut für Chemie - Organische Chemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany
Fax +49(30)83855376; E-mail: Hans.Reissig@chemie.fu-berlin.de
b
Institut für Organische Chemie, Technische Universität Darmstadt, Petersenstrasse 22, 64287 Darmstadt, Germany
Received 10 April 2002; revised 16 May 2002
mediates for stereoselective preparation of various
interestingly functionalized compounds, for instance pyr-
rolidines C6 (Scheme 1). So far these reactions have only
been described with racemic 6H-1,2-oxazines as precur-
Abstract: Alkoxyallene derivatives 1a–f bearing carbohydrate
auxiliaries at the oxygen were examined in asymmetric hetero
Diels–Alder reactions with nitroso alkenes. Diacetoneglucose de-
rived compound 1a turned out to be the best precursor furnishing
the primary cycloadducts 3a–c with a diastereomeric ratio of ap- sor compounds. However, we had reported preliminary
examples on asymmetric hetero Diels–Alder reactions7
proximately 90:10. Isomerization provided the thermodynamically
more stable 6H-1,2-oxazines 4a–c. Similarly, diacetonefructose de-
demonstrating that enantiomerically highly enriched 6H-
rived allene 1f gave compounds 4h–j with good efficiency. Gratify-
1,2-oxazines can be obtained when an alkoxyallene with
ingly, it turned out that 1a and 1f were complementary with respect
a diacetoneglucose auxiliary was employed.8 These prom-
ising results encouraged us to study the [4+2] cycloaddi-
tion in more detail using different carbohydrate based
chiral auxiliaries.
to the preferential absolute configuration at C-6 of 6H-1,2-oxazines
4a–c and 4h–j, respectively. Cycloadducts derived from 1a have 6S
configuration in excess whereas those derived from 1f are predom-
inantly 6R configured. Exhaustive hydrogenolysis of 6H-1,2-ox-
azines 4a and 4h in the presence of palladium on charcoal furnished
the expected primary amine 5 in an enantioenriched form. If this re-
duction was performed under addition of hydrochloric acid, pyrrol-
idine derivative 6 together with secondary amine 7 as side product
were isolated.
Asymmetric Cycloadditions
The synthesis of the required enantiopure alkoxyallene
derivatives 1 with the auxiliary group R1 was published
earlier.9 Their reaction with in situ generated nitroso
alkenes10 is illustrated in Schemes 2– 4 and summarized
in Table 1. Treatment of the corresponding -halogen
oxime 2 with freshly ground sodium carbonate delivers a
low stationary concentration of the highly reactive nitroso
alkenes which were trapped by the alkoxyallene 1 present
(1–1.25 equiv). Thus, on trapping with the above-men-
tioned diacetoneglucose derived allene 1a, these three ni-
troso alkenes gave excellent yields of the primary hetero
Diels–Alder adducts 3a–c with an exocyclic 5-methylene
group (Scheme 2). The ratio of diastereomers (dr) was de-
termined by NMR spectroscopy and is in the range of
90:10 for these three examples (Table 1, entries 1–3).
Thus, the diacetoneglucose moiety has a surprisingly high
inducing quality.
Key words: allenes, carbohydrates, asymmetric synthesis, hetero
Diels–Alder reaction, 6H-1,2-oxazines, reduction, pyrrolidines
Introduction
6H-1,2-Oxazines A are heterocycles with promising po-
tential for stereoselective synthesis of polyfunctionalized
compounds. We already described their reductive conver-
sions into -amino alcohols, pyrrolidine derivatives, ami-
no acids and -lactams.1,2 Even more important are the
addition reactions to the 4,5-C,C double bond of 6H-1,2-
oxazines. Additions of nucleophilic and electrophilic re-
agents,3 cycloadditions4 and dihydroxylations5 furnish a
great variety of highly substituted 5,6-dihydro-4H-1,2-ox-
azines B. These heterocycles serve subsequently as inter-
Scheme 1
Synthesis 2002, No. 11, Print: 22 08 2002.
Art Id.1437-210X,E;2002,0,11,1553,1563,ftx,en;T04002SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1554
R. Zimmer et al.
PAPER
Scheme 2
The relatively labile primary adducts 3a–c were converted units in 1a with cyclohexyl moieties in 1b (dicyclohex-
into the thermodynamically more stable 5-methyl-6H- anoneglucose as auxiliary) had no dramatic effect on the
1,2-oxazines 4a–c with a catalytic amount of 1,8-diazabi- stereoselectivity of the cycloaddition. After base-cata-
cyclo[5.4.0]undec-7-ene (DBU).11 For 4a and 4c only one lyzed isomerization to 6H-1,2-oxazine 4d an even slightly
diastereomer could be detected by NMR whereas the dr reduced dr of 90:10 was determined (entry 4). The config-
for 4b decreased slightly during isomerization (Table 1, uration of the allenyloxy bearing carbon of the auxiliary
entries 1–3). It is not clear whether differences at the stage was then inverted which led to diacetoneallose derivative
of 3 and 4 are due to the inaccuracy of the NMR analysis 1c. Rather surprisingly, its cycloaddition with -nitroso-
or to enrichment of one diastereomer during the purifica- styrene was completely unselective furnishing a 50:50
tion of 4. It should also be mentioned that 1,2-oxazine-3- mixture of the two possible diastereomers of 4e (entry 5).
carboxylate 4b (and also 4i) is rather unstable and cannot The diastereoselectivity was again high when mannose
be purified completely. The yields for the syntheses of 4a derivative 1d was used as dienophile which furnished 6H-
and 4c over the two steps are good. From 4a suitable crys- 1,2-oxazine 4f as a 87:13 mixture (entry 6). We also stud-
tals could be obtained and an X-ray analysis showed that ied fenchol derivative 1e which provided the expected
C-6 of the 1,2-oxazine ring has an S configuration.12
heterocycle 4g in low yield and moderate diastereomeric
ratio (entry 7).
With -nitrosostyrene as the standard heterodiene we in-
vestigated the influence of other carbohydrate auxiliaries With respect to carbohydrate auxiliaries we finally em-
in 1 on the diastereoselectivity of the Diels–Alder reaction ployed diacetonefructose modified allene 1f (Table 1, en-
(Scheme 3, Table 1). Exchange of the (dimethyl)methyl tries 8–10, Scheme 4). Although the diastereoselectivities
Table 1 Synthesis of 3 and Isomerization to 4
Entry
1
R1O
R2
X
3
dra
4
(6S):(6R)
Total
Yield (%)
1
2
1a
1a
1a
1b
1c
1d
1e
1f
DAG
DAG
DAG
DCG
DAA
DAM
FEN
Ph
Cl
Br
Br
Cl
Cl
Cl
Cl
Cl
Br
Br
3a
3b
3c
3d
3e
3f
90:10
86:14
92:8
nd
4a
4b
4c
4d
4e
4f
>95:5
79:21
>95:5
90:10
50:50
87:13
68:32
22:78
19:81
15:85
51
82b
69
59
83
56
29
56
60b
63
CO2Et
CF3
Ph
3
4
5
Ph
nd
6
Ph
nd
7
Ph
3g
3h
3i
64:36
23:77
nd
4g
4h
4i
8
DAF
DAF
DAF
Ph
9
1f
CO2Et
CF3
10
1f
3j
18:82
4j
a nd = not determined.
b Crude product; purification by chromatography and distillation, respectively, was not possible.
Synthesis 2002, No. 11, 1553–1563 ISSN 0039-7881 © Thieme Stuttgart · New York

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Asymmetric Synthesis of 6H-1,2-Oxazines and Subsequent Reductive Transformations
1555
Scheme 3
Scheme 4
in its hetero Diels–Alder reactions with the three -nitroso has been studied in many examples.1,6b Reduction of 6H-
alkenes were in the range of 20:80 and not as high as those 1,2-oxazines with hydrogen first saturates the 4,5-C,C
with diacetoneglucose, the results are particularly intrigu- double bond and therefore leads to identical product
ing since with this auxiliary an inversion of the sense of types. In this paper, we describe singular examples which
diastereoselectivity could be observed. As shown by the allowed us to determine the predominating absolute con-
subsequent reactions described below 1,2-oxazines 4h–j figuration at C-6 of several 6H-1,2-oxazines 4 by compar-
have predominatly R configuration at C-6.
ison of the products with known compounds.
As depicted in Scheme 5, diacetoneglucose substituted
6H-1,2-oxazine 4a (dr >95:5) was hydrogenated under
standard conditions and furnished the expected 2-methyl-
4-phenyl-1-butylamine (5) in 68% yield. This sample dis-
played a specific optical rotation of +12.4 (CHCl3) and
therefore it could be assigned to be a compound with R
configuration (2R:2S, ca. 90:10).13 This newly generated
stereocentre is formed during the addition of hydrogen to
4a under the influence of the rather bulky 6-alkoxy group.
In many addition reactions we could observe very high or
Reductions of 6H-1,2-oxazines
Catalytic reduction of 5,6-dihydro-4H-1,2-oxazines with
hydrogen provides either pyrrolidine derivatives or – if
the substituent at C-3 is an aryl group – it may also furnish
acyclic amines which arise from reductive cleavage of the
benzylic C–N bond of the intermediate pyrrolidines.6 The
mechanism of this multi-step reactions has been described
and the behaviour of differently substituted 1,2-oxazines
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1556
R. Zimmer et al.
PAPER
exclusive trans-selectivity with respect to this substitu-
ent.3–5 Since the configuration at C-6 of 6H-1,2-oxazine
Discussion
4a was unambiguously determined to be S the highly se- The diastereotopic faces of the allenyloxy moieties of
lective formation of R-5 confirms this anticipated mecha- compounds 1 presented in this report are apparently
nistic scenario. Similar hydrogenation experiments shielded in different manner. Whereas the differentiation
performed with cycloadducts 4d, 4e and 4f also gave R-5 is already satisfying for mannose derivative 1d, which
in excess; thus, all these precursor 1,2-oxazines should bears the allenyloxy substitutent at the anomeric centre, it
have predominantly S configuration at C-6.14 Reduction is clearly surpassed by the diacetoneglucose unit of 1a. A
of diacetonefructose substituted 6H-1,2-oxazine 4h also sound interpretation of these results is complicated by the
provided primary amine 5 albeit in only 27% yield. Most conformational flexibility of these carbohydrate allene
interestingly, this sample has now a specific optical rota- derivatives, however, we assume that an approach of the
tion of –8.9 (CHCl3), thus the S-configured enantiomer is nitroso compounds to the Si face of the allene double bond
formed in excess (2S:2R, ca. 80:20). As mentioned above of 1a occurs as illustrated in Scheme 7. It is also the Si
we can now conclude that the starting 6H-1,2-oxazine 4h face which is attacked when simple enol ethers with the
has predominantly R-configuration at C-6.
diacetoneglucose auxiliary react with nitroso alk-
enes.7,16,17 In contrast, the Re face of diacetonefructose de-
rivative 1f is preferentially approached by the nitroso
compounds giving cycloadducts with 6R configuration
mainly.
Scheme 5
Finally, diacetoneglucose substituted 6H-1,2-oxazine 4a
was hydrogenated in the presence of 2 N HCl (Scheme 6).
Here the multi-step reduction process stops at the stage of
disubstituted pyrrolidine derivative 6, which is formed as
a 63:37 mixture of cis-trans isomers. In addition, the
product mixture contains the unexpected compound 7.
This amine is probably formed by isomerization of the
primary reduction product 8 to 5,6-dihydro-2H-1,2-ox-
azine 9 which undergoes a retro Diels–Alder reaction to
, -unsaturated imine 10 and a formyl ester. Imine 10 is
then rapidly reduced to furnish the isolated amine 7. Al-
though speculative this mechanism for formation of 7
seems rather plausible. Similar cleavage products, which
have lost C-6 of the precursor 1,2-oxazine were occasion-
ally observed in low yields when acid was present during
hydrogenolysis. Protons may catalyze the isomerization at
the 1,2-oxazine stage (e.g. 8 to 9) and particularly the retro
Diels–Alder reaction. 6c,15
Scheme 7
Scheme 6
Synthesis 2002, No. 11, 1553–1563 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Asymmetric Synthesis of 6H-1,2-Oxazines and Subsequent Reductive Transformations
1557
values are given in 10–1 deg cm2 g–1 and the concentrations are given
in g/100 cm3.
Conclusion
We could establish that two easily available carbohydrate Starting materials 1a–f,9 2a,20 2b,21 and 2c22 were prepared by liter-
auxiliaries18,19 are well suited for syntheses of 6H-1,2-ox-
azines with differing absolute configuration at C-6.
ature procedure. All other chemicals are commercially available
and were used as received.
Whereas diacetoneglucose derived alkoxyallene 1a pro-
vided heterocycles 4a–c with excellent diastereo-
To a solution of the corresponding -halogen oxime 2 in anhyd tert-
5-Methylene-4H-1,2-oxazines 3; General Procedure 1
selectivity and predominant 6S configuration, the
diacetonefructose compound 1f afforded the correspond-
ing 6H-1,2-oxazines 4h–j with slightly decreased stereo-
selection, but the major diastereomer has 6R
configuration. Other auxiliaries studied resulted in lower
asymmetric induction. The complementary 6H-1,2-ox-
azines 4a and 4h were transformed by catalytic hydroge-
nation into enantiomerically enriched primary amines 5.
In the presence of acid 4a provided pyrrolidine derivative
6 together with the fragmentation product 7.
butyl methyl ether (MtB; 20–25 mL/mmol of 2) was added the al-
lene derivative 1 (1–1.25 equiv). To this solution was added freshly
ground Na2CO3 (3.2–9.5 mmol/mmol of 2) and the suspension was
mechanically stirred at r.t. for the time indicated in Table 2. The
progress of the reaction was controlled by TLC. After consumption
of the oxime, the mixture was filtered through a sintered glass plug
which contained a pad of Celite. The filtrate was concentrated in
vacuo (30–35 °C/100 mbar); the crude 1,2-oxazine 3 was purified
by column chromatography on neutral alumina (activity III) or the
crude product was used as obtained in the next reaction. The
analytical and spectroscopic data of 3 are given in Tables 2 and
Tables 4–6.
All reactions were performed under argon in flame-dried flasks, and
the components were added by means of syringes. All solvents were
dried by standard methods. IR spectra were measured with Beck-
man IR Acculab 4, Beckman IR 5A, Perkin-Elmer IR 1420 or Per-
Isomerization to 6H-1,2-Oxazines 4; General Procedure 2
The primary cycloadduct 3 was dissolved in CH2Cl2 (approximately
10 mL/mmol) and stirred with the amount of DBU as indicated in
Table 3. The crude product 4 was purified by column chromatogra-
phy. For spectroscopic and analytical data see Tables 3, 4 and 7–8.
1
kin Elmer FT-IR spectrometer Nicolet 5 SXC. H and 13C NMR
spectra were recorded on Bruker instruments (AC 500, WM 300,
WH 270, AC 250) in CDCl3 solution. The chemical shifts are given
in relative to the TMS or to the CDCl3 signal ( H = 7.27, C = 77.0).
Higher order NMR spectra were approximately interpreted as first-
order spectra if possible. Missing signals of minor isomers are hid-
den by signals of major isomers, or they could not be unambiguous-
ly identified due to low intensity. Neutral alumina (activity III,
Merck) was used for column chromatography. Melting points (un-
corrected) were measured with an apparatus from Büchi (SMP-20).
Optical rotations were determined in a 1 mL cell with a pathlength
of 10 cm using a Perkin-Elmer 241 polarimeter (NaD line). The [ ]D
Catalytic Hydrogenation of 6H-1,2-Oxazines 4; General Proce-
dure 3
Anhyd MeOH (10–20 mL/mmol of 4) and 10% Pd/C (0.100 g/
mmol of 4) were saturated with H2 for 1 h at r.t. Then, the corre-
sponding 6H-1,2-oxazine 4 was added, and the mixture was stirred
under H2 atmosphere at normal pressure for 24–60 h at r.t. The sus-
pension was filtered through a sintered glass plug, which contained
a pad of Celite eluting with MeOH. The filtrate was concentrated in
vacuo and the crude product was purified by Kugelrohr distillation.
Table 2 Synthesis of 5-Methylen-4H-1,2-oxazines 3a–j (General Procedure 1)
1 [g (mmol)]
2 [g (mmol)]
Na2CO3 [g (mmol)]
0.636 (6.00)
2.00 (18.9)
Time (d)
Yield of 3 [g (%)]a
3a 0.442 (54)
drb
1a 0.715 (2.40)
1a 0.597 (2.00)
1a 0.597 (2.00)
1b 1.56 (4.12)
1c 0.197 (0.52)
1d 0.662 (2.22)
1e 1.00 (5.20)
1f 0.597 (2.00)
1f 0.655 (2.23)
1f 0.597 (2.00)
2a 0.322 (1.90)
2b 0.420 (2.00)
2c 0.412 (2.00)
2a 0.582 (3.43)
2a 0.074 (0.43)
2a 0.314 (1.85)
2a 0.882 (5.20)
2a 0.339 (2.00)
2b 0.468 (2.23)
2c 0.412 (2.00)
6
7
90:10
86:14
92:8
nd
3b 0.705 (82)
c
2.00 (18.9)
7
–
1.09 (10.3)
7
3d 1.60 (91)d
3e 0.183 (124)d
3f 0.50 (63)d
0.176 (1.66)
0.59 (5.57)
7
nd
7
nd
5.20 (49.1)
10
10
7
3g 0.658 (39)e
3h 0.925 (107)d
3i 0.929 (98)d
3j 0.874 (103)d,f
64:36
23:77
nd
0.636 (6.00)
1.91 (18.0)
1.91 (18.0)
7
18:82
a Yield of the crude product.
b Not determined.
c Chromatography (hexane–MtB, 3:2) of the crude product 3c yielded the isomerized compound 4c (0.586 g, 69%, dr >95:5).
d The crude product contains the corresponding allene 1.
e After purification by chromatography (hexane–MtB, 3:2).
f Chromatography (hexane–MtB, 3:2) of the crude product 3j yielded the isomerized compound 4j (0.531 g, 63%, dr 85:15).
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Table 3 Isomerization of 5-Methylen-4H-1,2-oxazines 3 to 6H-1,2-Oxazines 4 (General Procedure 2)
3a (g)
DBU
Time, Temp.
20 h, r.t.
2 d, r.t.
Yield of 4 [g (%)]b,c
4a 0.334 (91)
4b 0.241f
6S:6R
>95:5
79:21
90:10
50:50
87:13
68:32
22:78
19:81
3a 0.344d
3b 0.200e
3d 1.60
152 mg
200 mg
5 drops
1 d, r.t.
4d 1.04 (59)
4e 0.156 (83)
4f 0.448 (56)
4g 0.148 (74)
4h 0.484 (56)
4i 0.542 (57)f
3e 0.183
3f 0.500
3g 0.200g
3h 0.925
3i 0.929
5 drops
10 drops
200 mg
1 d, r.t.
1 d, r.t.
4 h, 40 °C
2 d, r.t.
10 drops
10 drops
3 d, r.t.
a Crude product, see Table 2.
b Satisfactory microanalysis obtained: C 0.33, H 0.27, N 0.36; exceptions: 4e (C +0.64), 4j (C –1.09).
c Total yield concerning the corresponding oxime 2.
d 0.797 mmol scale.
e 0.468 mmol scale.
f Purification of the crude product by chromatography was not possible.
g 0.615 mmol scale.
Table 4 Analytical Data for 5-Methylen-4H-1,2-oxazines 3 and 6H-1,2-Oxazines 4
Product
[ ]D
mp (°C)
IR (cm–1)b
(c, g/100 mL)a
3a
3g
4a
4c
4d
4e
4f
nd
oil
3140–2780 (C–H, =CH), 1670 (C=C), 1590 (C=N)
nd
134
–
+62 (c = 2)
+111 (c = 1.05)
+61 (c = 1.2)
+78 (c = 1.2)
+41 (c = 1.1)
nd
136
3150–2790 (C–H, =CH), 1670 (C=C), 1580 (C=N)
131
3000–2780 (C–H, =CH), 1670 (C=C), 1590 (C=N), 1205, 1185, 1145 (CF3)
3060–2860 (C–H, =CH), 1660 (C=C), 1540 (C=N)
73–75
112–114
132–134
132–135
51–53
oil
3100–2860 (C–H, =CH), 1660 (C=C), 1580 (C=N)
3060–2860 (C–H, =CH), 1660 (C=C), 1540 (C=N)
4g
4h
4j
3130–2820 (C–H, =CH), 1665 (C=C), 1585 (C=N)
nd
3100–2800 (C–H, =CH), 1660 (C=C), 1530 (C=N)
nd
3020–2820 (C–H, =CH), 1660 (C=C), 1570 (C=N), 1210, 1180, 1140 (CF3)
a Specific optical rotation determined in CHCl3; nd = not determined.
b Oils and resins as film or in CCl4, foams as KBr pellets.
(R)-(+)-2-Methyl-4-phenyl-1-butylamine [(R)-(+)-5]
Hydrogenation of 4a to Pyrrolidine 6 and Amine 7
According to the general procedure 3, a mixture of 4a (0.820 g, 1.90
mmol, dr 95:5) and 10% Pd/C (0.250 g) in MeOH (20 mL) was
stirred for 24 h at r.t. The resulting residue was purified by Kugel-
rohr distillation (100 °C/0.08 mbar) to give the amine 5 (0.162 g,
68%) as a colourless oil; [ ]D20 +12.4 (c = 2.0, CHCl3); ee ca 80%.13
According to the general procedure 3, a mixture of 4a (0.431 g, 1.00
mmol, dr 95:5) and 10% Pd/C (0.100 g) in MeOH (10 mL) and 2
N HCl solution (1 mL) was stirred for 24 h at r.t. The resulting res-
idue was purified by Kugelrohr distillation (50 °C/0.09 mbar) to
give an oily 66:34-mixture of pyrrolidine 6 and amine 7 (0.068 g,
44%; 6 as a mixture of 2 diastereomers, 63:37). Pyrrolidine 6 slowly
crystallized out from this mixture and a few pure crystals could be
isolated; mp 80–82 °C.
(S)-(–)-2-Methyl-4-phenyl-1-butylamine [(S)-(–)-5]
According to the general procedure 3, a mixture of 4h (0.393 g, 0.91
mmol, dr 78:22) and 10% Pd/C (0.100 g) in MeOH (10 mL) was
stirred for 24 h at r.t. The resulting residue was purified by Kugel-
rohr distillation (100 °C/0.09 mbar) to give the amine 5 (0.040 g,
27%) as a colourless oil; [ ]D20 –8.9 (c = 1.4, CHCl3); ee ca 60%.13
1H and 13C NMR data of pyrrolidine 6 are identical with those re-
ported earlier.1
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Asymmetric Synthesis of 6H-1,2-Oxazines and Subsequent Reductive Transformations
1559
Table 5 1H NMR Data for 5-Methylen-4H-1,2-oxazines 3 (300 MHz, CDCl3/TMS); , J (Hz)
Product
Oxazine Part
Auxiliary Part
3a (major)
7.74–7.69, 7.43–7.38 (2 m, 2 H and 3 H, C6H5), 5.56 (s, 1 5.76 (d, J = 3.5, 1 H, 1-H), 4.64–3.96 (m, 6 H, 2-H, 3-H,
H, 6-H), 5.24, 5.14 (2 d, J = 2.5, 2 H, =CH2), 3.49, 3.20
(dt, d, J = 2.5, JAB = 18, 2 H, 4-H)
4-H, 5-H, 6-H), 1.49, 1.44, 1.36, 1.27 (4 s, 3 H each, 4
CH3)
3a (minor)a
3b (major)
5.55 (s, 1 H, 6-H), 5.24, 5.16 (2 d, J = 2.5, 2 H, =CH2),
3.45, 3.25 (dt, d, J = 2.5, JAB = 20, 2 H, 4-H)
–
5.60 (s, 1 H, 6-H), 5.24, 5.14 (2 d, J = 2.5, 2 H, =CH2),
3.22 (mc, 2 H, 4-H), 1.40 (t, J = 7, 3 H, OCH2CH3)b
5.81 (d, J = 3.5, 1 H, 1-H), 4.60–3.90 (m, 8 H, 2-H, 3-H,
4-H, 5-H, 6-H), 1.48, 1.42, 1.34, 1.27 (4 s, 3 H each, 4
CH3)
3b (minor)a
3c (major)
5.58 (s, 1 H, 6-H), 5.27, 5.17 (2 d, J = 2.5, 2 H, =CH2),
3.22 (mc, 2 H, 4-H)
5.74 (d, J = 3.5, 1 H, 1-H)
5.60 (s, 1 H, 6-H), 5.31, 5.21 (2 d, J = 2.5, 2 H, =CH2),
3.24, 2.98 (dt, d, J = 2.5, JAB = 18, 2 H, 4-H)
5.82 (d, J = 3.6, 1 H, 1-H), 4.60–3.94 (m, 6 H, 2-H, 3-H,
4-H, 5-H, 6-H), 1.49, 1.44, 1.36, 1.27 (4 s, 3 H each, 4
CH3)
3c (minor)a
3g (major)
5.51 (s, 1 H, 6-H), 5.34, 5.24 (2 d, J = 2.5, 2 H, =CH2)
–
7.71–7.41 (m, 5 H, C6H5), 5.18, 5.05 (2 d, J = 2.5, 2
H, = CH2), 5.17 (s, 1 H, 6-H), 3.48, 3.28 (dt, d, J = 2.5,
JAB = 19, 2 H, 4-H)
3.32 (mc, 1 H, 2-H), 1.30–0.81 (m, 7 H, 4-H, 5-H, 6-H, 7-
H), 1.07, 1.04, 0.88 (3 s, 3 H each, 3 CH3)
3g (minor)a
3h (major)
5.26 (s, 1 H, 6-H), 3.49, 3.21 (dt, d, J = 2.5, JAB = 19, 2 H, 3.34 (mc, 1 H, 2-H), 1.63–0.81 (m, 7 H, 4-H, 5-H, 6-H, 7-
4-H) H), 1.09, 1.02, 0.81 (3 s, 3 H each, 3 CH3)
7.69–7.65, 7.41–7.34 (2 m, 2 H and 3 H, C6H5), 5.91 (s, 1 4.42–3.84 (m, 7 H, 1-H, 3-H, 4-H, 5-H, 6-H), 1.65, 1.41,
H, 6-H), 5.31, 5.14 (2 d, J = 2.5, 2 H, =CH2), 3.48, 3.23
(dt, d, J = 2.5, JAB = 19.6, 2 H, 4-H)
1.39, 1.22 (4 s, 3 H each, 4 CH3)
3h (minor)a
3i (major)
5.63 (s, 1 H, 6-H), 5.24 (d, J = 2.5, 1 H, =CH2), 3.24 (d,
JAB = 19.6, 1 H, 4-H)
–
5.93 (s, 1 H, 6-H), 5.32, 5.16 (2 d, J = 2.5, 2 H, =CH2),
4.35 (t, J = 7, 2 H, OCH2CH3), 3.24, 3.18 (dt, d, J = 2.5,
JAB = 18.5, 2 H, 4-H), 1.36 (t, J = 7, 3 H, OCH2CH3)
4.25–3.84 (m, 7 H, 1-H, 3-H, 4-H, 5-H, 6-H), 1.62, 1.44,
1.38, 1.30 (4 s, 3 H each, 4 CH3)
3j (major)
3j (minor)a
5.93 (s, 1 H, 6-H), 5.39, 5.21 (2 d, J = 2.5, 2 H, =CH2),
3.25, 2.98 (dt, d, J = 2.5, JAB = 20.5, 2 H, 4-H)
4.39–3.85 (m, 7 H, 1-H, 3-H, 4-H, 5-H, 6-H), 1.62, 1.46,
1.39, 1.32 (4 s, 3 H each, 4 CH3)
5.63 (s, 1 H, 6-H), 5.30, 5.19 (2 d, J = 2.5, 2 H, =CH2)
–
a Missing signals are hidden by signals of the major isomer.
b For OCH2 signal see column ‘auxiliary part’ (multiplet at 4.60–3.90).
1-Phenyl-1-butylamine (7)23
(2) Zimmer, R.; Homann, K.; Reissig, H.-U. Liebigs Ann.
Chem. 1993, 1145.
(3) (a) Zimmer, R.; Hiller, F.; Reissig, H.-U. Heterocycles 1999,
50, 393. (b) Buchholz, M.; Reissig, H.-U. Synthesis 2002,
1412. (c) Buchholz, M.; Hiller, F.; Reissig, H.-U. Eur. J.
Org. Chem. 2002, in press.
1H NMR (CDCl3, 300 MHz): = 7.25–7.16 (m, 5 H, C6H5), 3.87 (t,
J = 6.9 Hz, 1 H, 1-H), 2.10 (s, 2 H, NH2), 1.67–1.57 (m, 2 H, 2-H),
1.40–1.20 (m, 2 H, 3-H), 0.90 (t, J = 7.3 Hz, 3 H, 4-H).
13C NMR (CDCl3, 75.5 MHz): = 146.7, 126.7, 126.4, 126.2 (s, 3
d, Ph), 55.9 (d, C-1), 41.7 (t, C-2), 19.6 (t, C-3), 13.9 (q, C-4).
(4) Schmidt, E. Ph.D. Thesis; Technische Universität Dresden:
Germany, 2001.
(5) (a) Angermann, J.; Homann, K.; Reissig, H.-U.; Zimmer, R.
Synlett 1995, 1014. (b) Zimmer, R.; Homann, K.;
Angermann, J.; Reissig, H.-U. Synthesis 1999, 1223.
(6) (a) Hippeli, C.; Reissig, H.-U. Liebigs Ann. Chem. 1990,
475. (b) Buchholz, M. Ph.D. Thesis; Freie Universität
Berlin: Germany, 2002. (c) Tishkov, A. A.; Reissig, H.-U.;
Ioffe, S. L. Synlett 2002, 863.
Acknowledgements
We are most grateful for the generous support of this work by the
Fonds der Chemischen Industrie and the Deutsche Forschungsge-
meinschaft. We thank Dr. Ulrich Koop (TU Darmstadt) for experi-
mental assistance.
(7) Arnold, T.; Orschel, B.; Reissig, H.-U. Angew. Chem., Int.
Ed. Engl. 1992, 31, 1033; Angew. Chem. 1992, 104, 1084.
References
(1) Zimmer, R.; Hoffmann, M.; Reissig, H.-U. Chem. Ber. 1992,
125, 2243.
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Table 6 13C NMR Data for 5-Methylen-4H-1,2-oxazines 3 (75.5 MHz, CDCl3); , J (Hz)
Product
Oxazine Part
Auxiliary Part
3a (major)
156.7 (s, C-3), 137.1, 133.7, 129.6, 128.4, 125.9 (2 s, 3 d, 111.9, 109.1 [2 s, 2 C(CH3)2], 105.4 (d, C-1), 83.5, 80.1,
C6H5, C-5), 112.7 (t, =CH2), 98.7 (d, C-6), 26.2 (t, C-4)
134.4, 129.1, 127.9 (s, 2 d, C6H5, C-5), 112.5 (t, =CH2)
162.3, 62.1, 13.9 (s, t, q, CO2CH2CH3), 150.5 (s, C-3),
80.0 (3 d, C-2, C-3, C-4), 72.6 (d, C-5), 67.9 (t, C-6), 26.6,
26.5, 26.0, 25.9 (4 q, 4 CH3)
3a (minor)
3b (major)
105.0 (d, C-1), 80.0, 79.5 (2 d, C-2, C-3, C-4), 65.5 (t, C-
6), 27.1, 24.1 (2 q, 2 CH3)
109.1, 108.9 [2 s, 2 C(CH3)2], 105.4 (d, C-1), 83.5, 80.1,
132.1 (s, C-5), 113.7 (t, =CH2), 99.1 (d, C-6), 25.4 (t, C-4) 80.0 (3 d, C-2, C-3, C-4), 72.6 (d, C-5), 67.9 (t, C-6), 26.6,
26.5, 26.0, 25.9 (4 q, 4 CH3)
3b (minor)
3c (major)
162.4, 61.6 (s, t, CO2CH2CH3), 150.2 (s, C-3), 117.0
(t, =CH2), 96.1 (d, C-6), 25.7 (t, C-4)
109.2, 108.7 [2 s, 2 C(CH3)2], 83.0, 79.8 (2 d, 2 CH), 72.8
(d, C-5), 67.3 (t, C-6)
148.7 (q, 2JCF = 34, C-3), 130.4 (s, C-5), 120.1 (q,
1JCF = 275, CF3), 114.7 (t, =CH2), 99.1 (d, C-6), 23.4 (t,
C-4)
112.1, 109.3 [2 s, 2 C(CH3)2], 105.1 (d, C-1), 83.3, 81.2,
81.0 (3 d, C-2, C-3, C-4), 72.3 (d, C-5), 67.9 (t, C-6), 26.7,
26.6, 26.0, 25.1 (4 q, 4 CH3)
3c (minor)
3g (major)
117.0 (t, =CH2), 97.5 (d, C-6)
83.1, 81.8, 81.2 (3 d, C-2, C-3, C-4), 67.3 (t, C-6)
155.7 (s, C-3), 135.6, 135.3, 129.7, 128.5, 125.6 (2 s, 3 d, 91.1 (d, C-2), 49.4, 39.6 (2 s, C-1, C-3), 48.6 (d, C-4), 41.4,
C6H5, C-5), 111.1 (t, =CH2), 100.2 (d, C-6), 26.1 (t, C-4) 27.6, 26.2 (3 t, C-5, C-6, C-7), 30.0, 21.2, 19.9 (3 q, 3 CH3)
3g (minor)
3h (major)
155.4 (s, C-3), 135.2, 129.6 (s, d, C6H5), 110.9 (t, =CH2), 88.2 (d, C-2), 41.1, 27.4, 25.9 (3 t, C-5, C-6, C-7), 31.8,
98.3 (d, C-6) 20.6, 19.4 (3 q, 3 CH3)
156.8 (s, C-3), 134.6, 134.4, 129.9, 128.5, 125.5 (2 s, 3 d, 111.8, 109.3 [2 s, 2 C(CH3)2], 104.1 (s, C-2), 77.8 (d, C-4),
C6H5, C-5), 112.6 (t, =CH2), 97.2 (d, C-6), 27.0 (t, C-4)
73.8, 72.4 (2 d, C-3, C-5), 71.6 (t, C-1), 59.9 (t, C-6), 27.3,
26.3, 26.1, 25.1 (4 q, 4 CH3)
3h (minor)
3i (major)
155.9 (s, C-3), 134.7, 134.5 (2 s, C6H5, C-5), 112.4
(t, =CH2), 98.4 (d, C-6)
–
162.3, 62.1, 13.9 (s, t, q, CO2CH2CH3), 151.0 (s, C-3),
111.9, 109.3 [2 s, 2 C(CH3)2], 103.8 (s, C-2), 77.5 (d, C-4),
132.4 (s, C-5), 113.6 (t, =CH2), 97.6 (d, C-6), 25.8 (t, C-4) 73.7, 72.9 (2 d, C-3, C-5), 71.7 (t, C-1), 59.9 (t, C-6), 28.0,
26.3, 26.2, 26.0 (4 q, 4 CH3)
3j (major)
3j (minor)
148.7 (q, 2JCF = 35, C-3), 130.4 (s, C-5), 119.9 (q,
1JCF = 276, CF3), 114.5 (t, =CH2), 97.7 (d, C-6), 23.4 (t,
C-4)
111.8, 109.3 [2 s, 2 C(CH3)2], 103.5 (s, C-2), 77.3 (d, C-4),
73.6, 73.2 (2 d, C-3, C-5), 71.4 (t, C-1), 59.8 (t, C-6), 27.8,
26.6, 26.0, 25.6 (4 q, 4 CH3)
130.6 (s, C-5), 114.1 (t, =CH2), 98.5 (d, C-6), 23.3 (t, C-4) 111.4, 108.9 [2 s, 2 C(CH3)2], 103.3 (s, C-2), 75.6 (d, C-4),
74.9, 72.9 (2 d, C-3, C-5), 72.6 (t, C-1), 61.0 (t, C-6)
(8) Reviews on alkoxyallenes: (a) Zimmer, R. Synthesis 1993,
165. (b) Zimmer, R.; Khan, F. A. J. Prakt. Chem. 1996, 338,
92.
(9) Hausherr, A.; Orschel, B.; Scherer, S.; Reissig, H.-U.
Synthesis 2001, 1377.
(10) Review: Gilchrist, T. L. Chem. Soc. Rev. 1983, 12, 53.
(11) Zimmer, R.; Reissig, H.-U. Liebigs Ann. Chem. 1991, 553.
(12) (a) Scherer, S. Diploma Thesis; Technische Hochschule
Darmstadt: Germany, 1992. (b) Lindner, H. J.; Richter, J.,
unpublished results.
(13) (a) The value of the specific optical rotation of 5 is rather
sensitive to the circumstances of its determination
(impurities); the highest [ ]D20 values for optically pure
samples were +16 or –16 (b) Arnold, T. Ph.D. Thesis;
Technische Hochschule: Darmstadt, Germany, 1992. (c) A
value of +12.4 would thus reflect a ratio of enantiomers in
the range of 89:11; actually, this ratio might even be higher
(14) Scherer, S.; Reissig, H.-U., unpublished results.
(15) (a) Shatzmiller, S.; Shalom, E. Liebigs Ann. Chem. 1983,
897. (b) Faragher, R.; Gilchrist, T. L. J. Chem. Soc., Perkin
Trans. 1 1979, 258.
(16) (a) For calculations dealing with the cycloadditions of
nitrosoethylene and enol ethers, see: Liu, J.; Niwayama, S.;
You, Y.; Houk, K. N. J. Org. Chem. 1998, 63, 1064.
(b) Although the ground states of enol ethers involve an S-
cis conformation the corresponding S-trans conformation is
involved in the transition state of nitrosoethylene
cycloadditions; we expect similar effects for alkoxyallenes
such as 1a and 1f
(17) For a study of the conformational behaviour of
alkoxyallenes bearing furanose auxiliaries, see: Lysek, R.;
Krajewski, P.; Urbanczyk-Lipkowska, Z.; Furman, B.;
Kaluza, Z.; Kozerski, L.; Chmielewski, M. J. Chem. Soc.,
Perkin Trans. 2 2000, 61.
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Asymmetric Synthesis of 6H-1,2-Oxazines and Subsequent Reductive Transformations
1561
Table 7 1H NMR Data for 6H-1,2-Oxazines 4 (300 MHz, CDCl3/TMS); , J (Hz)
Product
Oxazine Part
Auxiliary Part
4a (major)
7.72–7.65, 7.42–7.34 (2 m, 2 H, 3 H, C6H5), 6.34 (q, J = 1, 5.75 (d, J = 3.5, 1 H, 1-H), 4.63 (d, J = 3.5, 1 H, 2-H),
1 H, 4-H), 5.61 (s, 1 H, 6-H), 2.09 (d, J = 1, 3 H, 5-CH3)
2.13 (d, J = 1.5, 3 H, 5-CH3)
4.44–3.96 (m, 5 H, 3-H, 4-H, 5-H, 6-H), 1.49, 1.44, 1.36,
1.27 (4 s, 3 H each, 4 CH3)
4a (minor)a
4b (major)
–
6.29 (q, J = 2, 1 H, 4-H), 5.68 (s, 1 H, 6-H), 4.61–3.94 (m, 5.94 (d, J = 3.5, 1 H, 1-H), 4.61–3.96 (m, 8 H, 2-H, 3-H, 4-
2 H, OCH2CH3), 2.06 (d, J = 2, 3 H, 5-CH3), 1.40 (t, J = 7, H, 5-H, 6-H), 1.50, 1.39, 1.35, 1.32 (4 s, 3 H each, 4 CH3)
3 H, OCH2CH3)b
4b (minor)a
4c (major)
4d (major)
6.49 (q, J = 2, 1 H, 4-H), 5.61 (s, 1 H, 6-H), 2.03 (d, J = 2, 5.78 (d, J = 3.5, 1 H, 1-H)
3 H, 5-CH3)
6.10 (q, J = 2, 1 H, 4-H), 5.69 (s, 1 H, 6-H), 2.10 (d, J = 2, 5.79 (d, J = 3.5, 1 H, 1-H), 4.53–3.96 (m, 6 H, 2-H, 3-H, 4-
3 H, 5-CH3)
H, 5-H, 6-H), 1.50, 1.44, 1.35, 1.31 (4 s, 3 H each, 4 CH3)
7.66–7.61, 7.38–7.31 (2 m, 2 H, 3 H, C6H5), 6.27 (q,
5.68 (d, J = 3.5, 1 H, 1-H), 4.52 (d, J = 3.5, 1 H, 2-H), 4.39
J = 1.5, 1 H, 4-H), 5.58 (s, 1 H, 6-H), 2.03 (d, J = 1.5, 3 H, (d, J = 3, 1 H, 3-H), 4.17–3.99, 3.90 (m, dd, J = 4.9, 8.5, 3
5-CH3)
H, 1 H, 4-H, 5-H, 6-H), 1.60–1.10 (m, 20 H, 10 CH2)
4d (minor)a
5.55 (s, 1 H, 6-H)
5.78 (d, J = 3.5, 1 H, 1-H), 4.54 (d, J = 3, 1 H, 2-H)
4e
7.72–7.66, 7.41–7.36 (2 m, 2 H, 3 H, C6H5), 6.38–6.36 (m, 5.89 (d, J = 4, 0.5 H, 1-H), 5.71 (d, J = 4, 0.5 H, 1-H),
1 H, 4-H), 5.70, 5.61 (2 s, 0.5 H each, 6-H), 2.10, 2.09 (2
d, J = 1.5 each, 1.5 H each, 5-CH3)
4.86–4.81 (m, 1 H, 2-H), 4.47, 4.35–4.28, 4.20–3.92, 3.88,
3.74 (d, J = 8.6, 2 m, dd, J = 6.4, 8.2, t, J = 8.2, 0.5 H, 1.5
H, 2 H, 0.5 H, 0.5 H, 3-H, 4-H, 5-H, 6-H), 1.62–1.21 (m,
12 H, 4 CH3)
4f (major)
7.74–7.68, 7.44–7.39 (2 m, 2 H, 3 H, C6H5), 6.37 (q,
5.58 (s, 1 H, 1-H), 4.74 (dd, J = 3.7, 5.9, 1 H, 3-H), 4.56
J = 1.5, 1 H, 4-H), 5.71 (s, 1 H, 6-H), 2.05 (d, J = 1.5, 3 H, (d, J = 5.9, 1 H, 2-H), X part of ABX-system ( X = 4.43,
5-CH3)
J = 7.1, 1 H, 5-H), AB part of ABX-system ( A = 4.14,
B = 4.06, JAB = 8.7, JAX = 6.3, JBX = 4.6, 1 H, 6-H), 3.97
(dd, J = 3.6, 7.3, 1 H, 4-H), 1.46, 1.39, 1.28 (3 s, 6 H, 3 H,
3 H, 4 CH3)
4f (minor)a
4g (major)
4g (minor)a
4h (major)
5.30 (s, 1 H, 6-H), 2.07 (d, J = 1.5, 3 H, 5-CH3)
5.65 (s, 1 H, 1-H), 4.58 (d, J = 5.8, 1 H, 2-H), 4.40–4.36
(m, 1 H, 5-H), 1.37, 1.31, 1.26 (3 s, 6 H, 3 H, 3 H, 4 CH3)
7.71–7.41 (m, 5 H, C6H5), 6.29 (d, J = 1.5, 1 H, 4-H), 5.32 3.32 (mc, 1 H, 2-H), 1.60–0.84 (m, 7 H, 4-H, 5-H, 6-H, 7-
(s, 1 H, 6-H), 2.07 (d, J = 1.5, 3 H, 5-CH-3)
H), 1.07, 1.04, 0.88 (3 s, 3 H each, 3 CH3)
5.37 (s, 1 H, 6-H)
3.40 (mc, 1 H, 2-H), 1.40–0.89 (m, 7 H, 4-H, 5-H, 6-H, 7-
H), 1.11, 1.01, 0.95 (3 s, 3 H each, 3 CH3)
7.67–7.64, 7.44–7.38 (2 m, 2 H, 3 H, C6H5), 6.32 (q,
4.29 (dd, J = 5.4, 7.5, 1 H, 4-H), 4.21–4.00 (m, 5 H, 1-H,
J = 1.5, 1 H, 4-H), 5.90 (s, 1 H, 6-H), 2.13 (d, J = 1.5, 3 H, 5-H, 6-H), 3.94 (d, J = 8.9, 1 H, 3-H), 1.64, 1.43, 1.39,
5-CH3) 1.12 (4 s, 3 H each, 4 CH3)
4h (minor)a
4i (major)
7.73–7.70 (m, 2 H, C6H5), 6.33 (q, J = 1.5, 1 H, 4-H), 5.73 4.44 (dd, J = 4.8, 6.8, 1 H, 4-H), 3.76 (d, J = 12.5, 1 H, 6-
(s, 1 H, 6-H), 2.12 (d, J = 1.5, 3 H, 5-CH3) H), 1.50, 1.42, 1.32 (3 s, 6 H, 3 H, 3 H, 4 CH3)
6.44 (q, J = 1.7, 1 H, 4-H), 5.99 (s, 1 H, 6-H), 4.37 (t, J = 7, 4.33–3.90 (m, 7 H, 1-H, 3-H, 4-H, 5-H, 6-H), 1.61, 1.44,
2 H, OCH2CH3), 2.08 (d, J = 1.7, 3 H, 5-CH3), 1.37 (t,
J = 7, 3 H, OCH2CH3)
1.38, 1.36 (4 s, 3 H each, 4 CH3)
4i (minor)a
4j (major)
5.80 (s, 1 H, 6-H)
–
6.07 (q, J = 1.5, 1 H, 4-H), 5.96 (s, 1 H, 6-H), 2.12 (d,
J = 1.5, 3 H, 5-CH3)
4.26 (dd, J = 5.4, 7.7, 1 H, 4-H), 4.20–4.07 (m, 5 H, 1-H,
5-H, 6-H), 4.02 (d, J = 7.7, 1 H, 3-H), 1.62, 1.45, 1.38,
1.20 (4 s, 3 H each, 4 CH3)
4j (minor)a
5.79 (s, 1 H, 6-H), 2.11 (d, J = 1.5, 3 H, 5-CH3)
1.51, 1.49, 1.40, 1.35 (4 s, 3 H each, 4 CH3)
a Missing signals are hidden by signals of the major isomer.
b For OCH2 signal see column ‘auxiliary part’ (multiplet at 4.61–3.96).
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Table 8 13C NMR Data for 6H-1,2-Oxazines 4 (75.5 MHz, CDCl3); , J (Hz)
Product
Oxazine Part
Auxiliary Part
4a (major)
154.1 (s, C-3), 137.1, 133.7, 129.6, 128.4, 125.9 (2 s, 3 d, 112.0, 109.4 [2 s, 2 C(CH3)2], 105.2 (d, C-1), 83.2, 81.1,
C6H5, C-5), 112.5 (d, C-4), 96.7 (d, C-6), 18.7 (q, 5-CH3) 80.5 (3 d, C-2, C-3, C-4), 72.6 (d, C-5), 67.7 (t, C-6), 26.6,
26.5, 26.0, 25.9 (4 q, 4 CH3)
4b (major)
162.1, 62.2, 14.0 (s, t, q, CO2CH2CH3), 148.2 (s, C-3),
139.8 (s, C-5), 110.8 (d, C-4), 97.6 (d, C-6), 18.6 (q,
5-CH3)
112.0, 109.1 [2 s, 2 C(CH3)2], 105.4 (d, C-1), 83.5, 80.1,
80.0 (3 d, C-2, C-3, C-4), 72.6 (d, C-5), 67.9 (t, C-6), 26.6,
26.5, 26.0, 25.9 (4 q, 4 CH3)
4b (minor)
4c (major)
134.0 (s, C-5), 111.0 (d, C-4), 94.6 (d, C-6), 18.5 (q,
5-CH3)
–
147.8 (q, 2JCF = 34, C-3), 138.8 (s, C-5), 120.3 (q,
1JCF = 275, CF3), 108.1 (d, C-4), 97.5 (d, C-6), 18.9 (q,
5-CH3)
112.0, 109.4 [2 s, 2 C(CH3)2], 105.5 (d, C-1), 83.4, 81.5,
81.3 (3 d, C-2, C-3, C-4), 72.5 (d, C-5), 68.1 (t, C-6), 26.9,
26.7, 26.3, 25.3 (4 q, 4 CH3)
4d (major)
154.4 (s, C-3), 134.4, 133.9, 130.0, 128.6, 126.2 (2 s, 3 d, 112.6, 109.7 [2 s, 2 C(CH2)5], 105.2 (d, C-1), 83.0, 81.4,
C6H5, C-5), 112.4 (d, C-4), 96.9 (d, C-6), 19.1 (q, 5-CH3) 80.9, 72.2 (4 d, C-2, C-3, C-4, C-5), 67.6 (t, C-6), 36.5,
36.4, 35.6, 35.0, 26.9, 25.1, 24.8, 24.1, 23.9, 23.5 (10 t, 10
CH2)
4d (minor)
154.0 (s, C-3), 134.0, 133.7, 125.9 (2 s, d, C6H5, C-5),
112.3 (d, C-4), 19.0 (q, 5-CH3)
68.2 (t, C-6)
4e
154.3 (s, C-3), 137.6, 137.0, 134.1, 133.9, 129.8, 129.7,
128.7, 128.5, 126.3, 126.1 (4 s, 6 d, C6H5, C-5), 112.8,
111.8 (2 d, C-4), 96.1, 93.6 (2 d, C-6), 19.1, 19.0 (2 q, 5-
CH3)
113.0, 112.9, 109.9, 109.7 [4 s, 2 C(CH3)2], 104.7, 103.2
(2 d, C-1), 79.8, 77.9, 77.8, 77.0, 76.7, 75.3, 74.7, 72.8 (8
d, C-2, C-3, C-4, C-5), 66.2, 64.6 (2 t, C-6), 27.1, 27.0,
26.7, 26.5, 26.4, 26.1, 25.9, 24.8 (8 q, 4 CH3)
4f (major)
154.0 (s, C-3), 137.0, 133.9, 129.8, 128.6, 126.1 (2 s, 3 d, 112.8, 109.2 [2 s, 2 C(CH3)2], 102.7 (d, C-1), 84.8, 81.0,
C6H5, C-5), 112.2 (d, C-4), 91.5 (d, C-6), 19.0 (q, 5-CH3) 79.3, 73.0 (4 d, C-2, C-3, C-4, C-5), 66.8 (t, C-6), 26.9,
25.8, 25.2, 24.5 (4 q, 4 CH3)
4f (minor)
4g (major)
136.9, 129.9 (s, d, C6H5, C-5), 112.0 (d, C-4), 95.1 (d, C-
6), 18.8 (q, 5-CH3)
106.2 (d, C-1), 85.5, 81.3, 79.6, 72.8 (4 d, C-2, C-3, C-4,
C-5), 67.3 (t, C-6), 26.7, 26.0, 25.5, 24.8 (4 q, 4 CH3)
153.5 (s, C-3), 137.3, 134.5, 129.4, 128.6, 126.1 (2 s, 3 d, 92.0 (d, C-2), 50.0, 39.9 (2 s, C-1, C-3), 48.9 (d, C-4), 41.0,
C6H5, C-5), 111.7 (d, C-4), 98.0 (d, C-6), 19.5 (q, 5-CH3) 26.0, 25.9 (3 t, C-5, C-6, C-7), 30.1, 20.2, 19.8 (3 q, 3 CH3)
4g (minor)
4h (major)
154.0 (s, C-3), 137.7 (s, C-5), 111.6 (d, C-4), 95.9 (d, C-6) 87.9 (d, C-2), 49.2 (d, C-4), 41.4 (t, CH2), 21.5 (q, CH3)
159.9 (s, C-3), 138.1, 134.0, 129.7, 128.7, 126.1 (2 s, 3 d, 112.0, 109.4 [2 s, 2 C(CH3)2], 104.3 (s, C-2), 77.8 (d, C-4),
C6H5, C-5), 111.6 (d, C-4), 95.5 (d, C-6), 19.0 (q, 5-CH3) 73.9, 72.8 (2 d, C-3, C-5), 71.2 (t, C-1), 59.7 (t, C-6), 28.3,
27.1, 26.5, 25.3 (4 q, 4 CH3)
4h (minor)
4i (major)
154.0 (s, C-3), 137.6 (s, C-5), 111.9 (d, C-4), 96.6 (d, C-6), 110.4, 109.5 [2 s, 2 C(CH3)2], 103.6 (s, C-2), 74.4 (d, C-4),
19.1 (q, 5-CH3)
73.6, 72.4 (2 d, C-3, C-5), 74.3 (t, C-1), 62.8 (t, C-6), 26.9,
26.6, 25.9, 25.2 (4 q, 4 CH3)
163.1, 61.9, 13.8 (s, t, q, CO2CH2CH3), 148.3 (s, C-3),
137.0 (s, C-5), 109.9 (d, C-4), 95.4 (d, C-6), 18.4 (q,
5-CH3)
111.8, 109.1 [2 s, 2 C(CH3)2], 103.8 (s, C-2), 77.3 (d, C-4),
73.4, 73.0 (2 d, C-3, C-5), 71.0 (t, C-1), 59.6 (t, C-6), 28.0,
26.7, 26.1, 25.2 (4 q, 4 CH3)
4i (minor)
4j (major)
147.7 (s, C-3), 109.1 (d, C-4), 96.7 (d, C-6)
–
148.5 (q, 2JCF = 34, C-3), 139.6 (s, C-5), 120.4 (q,
1JCF = 275, CF3), 107.3 (d, C-4), 96.0 (d, C-6), 18.9 (q,
5-CH3)
112.3, 109.5 [2 s, 2 C(CH3)2], 103.5 (s, C-2), 75.5 (d, C-4),
73.9, 73.7 (2 d, C-3, C-5), 71.1 (t, C-1), 59.8 (t, C-6), 28.3,
27.0, 26.4, 25.2 (4 q, 4 CH3)
4j (minor)
147.3 (q, 2JCF = 34, C-3), 138.7 (s, C-5), 107.6 (d, C-4),
96.9 (d, C-6), 19.0 (q, 5-CH3)
110.9, 109.7 [2 s, C(CH3)2], 75.4 (d, C-4), 73.8, 72.5 (2 d,
C-3, C-5), 73.9 (t, C-1), 62.4 (t, C-6), 26.9, 26.4, 25.9, 25.3
(4 q, 4 CH3)
Synthesis 2002, No. 11, 1553–1563 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Asymmetric Synthesis of 6H-1,2-Oxazines and Subsequent Reductive Transformations
1563
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and references cited therein. (b) Yu, H.; Ballard, E. E.;
Wang, B. Tetrahedron Lett. 2001, 42, 1835; and references
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(20) Korten, H.; Scholl, R. Ber. Dtsch. Chem. Ges. 1901, 34,
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(23) Landor, S. R.; Sonola, O. O.; Taxchell, A. R. J. Chem. Soc.,
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Synthesis 2002, No. 11, 1553–1563 ISSN 0039-7881 © Thieme Stuttgart · New York