Synthesis of perhydroxazin-4-ones. Competitive Mukaiyama versus hetero Diels-Alder reaction in the cycloaddition of 2-aza-3-trimethylsilyloxy-1,3-butadiene and aldehydes

Article abstract of DOI:10.1016/S0957-4166(01)00051-9

The reactions of 2-aza-3-trimethylsilyloxy-1,3-butadiene with carbonyl dienophiles are described. 2-Aza-1,3-butadienes participate as dienes in the [4+2] cycloaddition with aldehydes to afford perhydroxazin-4-ones in good yields. Experimental results, however, show that a Mukaiyama type two-step reaction must be taken into account. The cycloadducts obtained have proved to be useful intermediates in the synthesis of α-amino-β-hydroxy acids.

Full text of DOI:10.1016/S0957-4166(01)00051-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 439–454
Synthesis of perhydroxazin-4-ones. Competitive Mukaiyama
versus hetero Diels–Alder reaction in the cycloaddition of
2-aza-3-trimethylsilyloxy-1,3-butadiene and aldehydes
Alessandro Bongini,a,* Mauro Panunzio,a,* Elisa Bandini,b Eileen Campana,b Giorgio Martellib and
Giuseppe Spuntab
aCSFM-CNR and University of Bologna, Dipartimento di Chimica ‘G. Ciamician’, Via Selmi 2, 40126 Bologna, Italy
bICoCEA-CNR, Via Gobetti 101, 40129 Bologna, Italy
Received 22 December 2000; accepted 1 February 2001
Abstract—The reactions of 2-aza-3-trimethylsilyloxy-1,3-butadiene with carbonyl dienophiles are described. 2-Aza-1,3-butadienes
participate as dienes in the [4+2] cycloaddition with aldehydes to afford perhydroxazin-4-ones in good yields. Experimental results,
however, show that a Mukaiyama type two-step reaction must be taken into account. The cycloadducts obtained have proved to
be useful intermediates in the synthesis of a-amino-b-hydroxy acids. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
aromatic and heteroaromatic aldehydes, with particular
emphasis on the diastereoselectivity of the reaction.
The hetero Diels–Alder (HDA) reaction using hetero-
dienes and/or dienophiles is a very useful method for
constructing heterocyclic rings and is widely used as a
key step in the synthesis of natural products.1–9 The use
of activated dienes containing strongly electron-donat-
ing groups, such as 1-methoxy-3-trimethylsilyloxybuta-
diene, has added versatility to this synthetic method,
opening the reaction to many useful applications since
its introduction.10 Ghosez reported on the synthesis and
use of 2-aza-3-trialkylsilyloxy-1,3-dienes as useful inter-
mediates in the HDA reaction for the preparation of
heterocyclic compounds,11–16 whilst Barluenga reported
the use of azadienes, obtained from N-trimethylsi-
lylimines, in the synthesis of nitrogen containing
heterocycles.17
2. Results
2.1. Synthesis of perhydroxazinones
2.1.1. Achiral azadiene. The first azadiene used was
obtained from reaction between phthaloyl chloride 1
and N-trimethylsilyl benzaldimine34 2. Scheme 1 illus-
trates the reported protocol for its synthesis.23
The (E,Z)-configuration and s-cis-conformation of 3
was determined by nOe experiments (see Section 5).
Treatment of 3 with benzaldehyde 4 in the presence of
a stoichiometric amount of boron trifluoride etherate
(CH2Cl2, −78 to 20°C for 8 h) gave rise to cycloadducts
5–7 (Scheme 2). Adducts 5 and 6 had a C-(5)H/C-(6)H
cis-configuration, as established by the relative coupling
constant (J=5.15 and 4.67 Hz, respectively), whereas 7,
with a C-(5)H/C-(6)H coupling constant of 10.46 Hz,
was assigned a trans-configuration (Table 1).
In conjunction with our current studies on N-
trimethylsilylimines as useful tools for the preparation
of biologically active compounds,18 we have reported
on the use of 2-aza-1,3-butadienes14,16,19–22 for the syn-
thesis of b-lactams,23–28 tetramic,29 and polyoxamic
acids,30 and for the generation of perhydroxazinones,
useful precursors of b-hydroxy-a-amino acids as well as
2,2-disubstituted b-hydroxyacids.29–33 Herein, we report
the extension of our protocol to a range of aliphatic,
* Corresponding authors. Tel.: +39 051 209 9508; fax: +39 051 209
9456 (M.P.); e-mail: panunzio@ciam.unibo.it
Scheme 1.
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00051-9

440
A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
Scheme 2. Reagents and conditions: (i) BF3·Et2O, −78°C, CH2Cl2.
Table 1. Coupling constants (J in Hz) and nOe for com-
pounds 5–7
tions, three cycloadducts 10–12 were obtained (Scheme
4).
Products
J5–6 (Hz)
nOe
Yield % (ratio %)
The cycloadducts 10 and 11 were assigned the C-(5)H/
C-(6)H cis-configuration on the basis of their coupling
constants of 5.64 and 4.64 Hz. Moreover, for com-
pounds 10 and 11, nOe experiments showed again the
characteristic basket conformation of C-(2)H, C-(5)H
and C-(6)H. The absolute configurations of C-(5) and
C-(6) were attributed taking into account the absolute
configuration of the C-(2) stereocentre. This configura-
tion was established from the C-(2)H and C-(1%)H
coupling constant and assumes that no epimerisation
occurs at the C-(1%) stereocentre during the reaction.
5
6
7
5.1 (cis)
4.7 (cis)
10.4 (trans)
2“6; 5“6 30 (50)
5“6
–
22 (36)
8 (14)
It is important to underline that in Scheme 2, for the
sake of simplicity, only one enantiomer for each couple
is shown. For compound 5 nOe effects between C-(2)H/
C-(6)H and C-(5)H/C-(6)H, respectively, are clear evi-
dence that these protons lie on the same face of the
diastereotopic plane. On this basis, for 5 the relative
configuration depicted in Scheme 2 was assigned. Con-
sequentially, the C-(5)H/C-(6)H cis-diastereomer 6 was
attributed the relative configuration shown in Scheme
2. Finally, the lack of any nOe effect, coupled with the
structural assignations of 5 and 6, allowed the configu-
ration of 7 to be established.
A full AM1 conformational analysis35 of the model
diastereoisomers (R,S) and (S,S) shows that in both
isomers the system is best described by the two confor-
mations (R,S)3 and (S,S)1 in which a bonding interac-
tion between the silyloxy oxygen and the amino group
is operating (see Fig. 1). The coupling constant of the
conformer (S,S)1, with the two hydrogens anti to each
other, was expected to be greater than that of the
(R,S)3-conformer, in which the two hydrogens have a
gauche-relationship. The experimentally observed cou-
pling constants of about 7 and 4 Hz, respectively (Table
2), allow the absolute configuration of the C-(2) stereo-
centres to be established. Since 10 presents a C-(2)H/C-
(1%)H coupling constant of 7.76 Hz, the stereocentres
must be (2S,1%S)-configured. From analysis of nOe
effects (see Table 2) of the stereocentres of 10, a
(2S,5S,6R)-configuration was assigned. Compound 11
with a J2–1% coupling constant of 3.62 Hz was assigned
the (2R,5R,6R)-configuration, and C-(5)H/C-(6)H
trans-stereoisomer 12, with a J2–1% of 4.10 Hz, must
have a (2R,5R,6R)-absolute configuration.
2.1.2. Single facial stereoinduction by a stereocentre
present in the imine moiety. The next step of our study
was to introduce a stereogenic centre in the azadiene
starting from the chiral N-trimethylsilylimine 8. The
imine 8 was first obtained from reaction between the
parent (S)-lactic aldehyde, protected on the hydroxy
functionality as a triisopropylsilyl (TIPS) ether, and
phthaloyl chloride 1, as shown in Scheme 3.
The preparation of azadienes 9 has already been
reported.23 Upon reaction with benzaldehyde 4 and
boron trifluoride etherate under the reported condi-
2.1.3. Single facial stereoinduction by a stereocentre
present in the acyl chloride moiety (Evans’ chiral auxil-
iary). In order to explore all possible combinations
between the two reactants in the preparation of azadi-
ene (chiral/achiral acyl chloride and chiral/achiral
imine, respectively), a new 3-silyloxy-2-aza-1,3-butadi-
Scheme 3.
Scheme 4. Reagents and conditions: (i) BF3·Et2O, −78°C, CH2Cl2.

A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
441
Figure 1. AM1 calculated percentage population of the (R,S)- and (S,S)-conformers.
Table 2. Coupling constants (J in Hz) for C-(2)H, C-(5)H
Full AM1 analysis35 showed a preferential conforma-
tion in which the carbonyl group of Evans’ oxazolidi-
none and the O-trimethylsilyl group are in an
anti-position with a torsional angle of −150° (see Fig.
2). The dienophile is forced to attack from the opposite
side of the diastereotopic plane in which the phenyl
group of the oxazolidine–Evans’ chiral auxiliary lies,
thus inducing complete (R)-configuration on the C-
(5)H (perhydroxazinone numbering) stereogenic centre.
The absolute configuration of the C-(6)H and C-(2)H
stereogenic centres was established by the C-(5)H/C-
(6)H coupling constant of 4.00 Hz for 16, and an nOe
effect between C-(2)H and C-(6)H, which, correlated
with the lack of any nOe effect between C-(2)H and the
methyl protons on C-(6), allowed the assignment of the
(2R,5R,6S)-configuration for 16.
and C-(6)H for 10–12
Products
J2–1% (Hz)
J5–6 (Hz)
nOe
Yield %
(ratio %)
10
11
12
7.7 (anti )
3.6 (syn)
4.3 (syn)
4.6 (cis)
5.6 (cis)
9.8 (trans)
2“6; 5“6 8.5 (17)
6“2; 6“5 30 (60)
–
11.5 (23)
ene 14 was synthesised in a one-pot two-step procedure
starting from benzaldehyde via the corresponding N-
trialkylsilylbenzaldimine 2 and acyl chloride 13.36,37
Scheme 5 illustrates the protocol.
The azadiene 14 was then reacted with acetaldehyde 15
under the above conditions (Scheme 6).
Consequently, since the epimeric cis-isomer shows an
nOe effect between C-(2)H and the methyl group on
C-(6), the configuration of epi-16 can be established.
Analogously, the presence or absence of nOe effects
between C-(2)H and the methyl group on C-(6) in the
trans-diastereoisomers allowed the stereochemistry of
17 and epi-17 to be established. To fully confirm the
configuration, acid hydrolysis of both 16 and epi-16
with methanolic HCl afforded the same acid, 18, with
the same specific rotation (Scheme 7).
Four stereoisomers were obtained: 16 and epi-16 with a
C-(5)H/C-(6)H cis-configuration (J=5.88 and 4.00 Hz,
respectively), and 17 and epi-17 presenting a C-(5)H/C-
(6)H trans-configuration (J=10.02 and 9.90 Hz, respec-
tively). From the results obtained in a previous paper,33
we have demonstrated, via chemical correlation with
the natural amino acid threonine, that Evans’ chiral
auxiliary induced (R)-configuration on the C-(5) stereo-
centre of the perhydroxazinone ring. A reasonable
explanation for the observed induction may be given by
analysing the preferential conformers arising from rota-
tion along the oxazolidinone NꢀC-(2) bond of azadiene
14.
At this point, a systematic study using aldehydes 19 was
performed (Scheme 8). Table 3 shows the results
obtained.
Since 3-formyl-indole 19h proved to be unreactive, the
corresponding N-Boc-3-formyl-indole 19i was prepared
according to a literature procedure.38 Reaction of 19i
with azadiene 14 gave rise to the trans-perhydroxazi-
nones 21h and epi-21h (Scheme 9).
The relative and absolute configurations of the stereo-
genic centres of the perhydroxazinones thus obtained
were determined on the basis of the C-(5)H/C-(6)H
coupling constants and nOe effects, if any, in analogy
Scheme 5.

442
A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
Scheme 6. Reagents and conditions: (i) BF3·Et2O, −78°C, CH2Cl2.
Figure 2. AM1 calculated preferential conformation of 16.
to that previously discussed. In the aromatic series,
fundamentally, the presence or absence of an nOe effect
between C-(2)H and C-(6)H allowed the direct identifi-
cation of 21 and epi-21. The coupling constants and the
nOe effects for the diagnostic protons are shown in
Table 4.
Table 3, entry 3). No cycloadducts were obtained with
the hindered tert-butyl group (use of pivaldehyde as
dienophile). It must be stressed that the two trans-
diastereomers are different only in the absolute configu-
ration of the C-(2) stereocentre.
2.1.4. Double stereoinduction by two stereocentres
present in the acyl chloride and imine moieties. The last
set of experiments concerned the use of homochiral
imines and homochiral acyl chlorides in the formation
of the azadiene. In order to achieve better control in the
formation of the C-(2), C-(5) and C-(6) stereogenic
centres, and using the positive results from the double
stereoinduction in the synthesis of b-lactams from aza-
dienes,24 two chiral centres were introduced into the
azadiene moiety by means of the N-trimethylsilylimine
of 2-(triisopropylsilyloxy)lactaldehyde 8 and Evans’ chi-
ral auxiliary. The corresponding azadiene 22 was pre-
pared according to the usual protocol (Scheme 10).24
As the data show, the C-(5) stereogenic centre forma-
tion is under stereochemical control, whereas the stereo-
chemical control in the formation of the C-(2) and
C-(6) stereogenic centres depends on the very nature of
the aldehyde dienophiles. Generally speaking with alde-
hydes bearing alkyl substituents, C-(5)H/C-(6)H cis-
diastereoselectivity
predominates,
whereas
with
aromatic and heteroaromatic substituents, C-(5)H/C-
(6)H trans-diastereoselection is preferred. Among the
alkyl groups, the straight chain groups provided the
greatest degree of cis-diastereoselection (Table 3,
entries 2 and 4) and the increase in steric requirements
from methyl to propyl and heptyl groups had no dra-
matic effect on the diastereoselectivity of the reaction.
The presence of branched side chains was found to be
more important: an isopropyl group gave rise to an
inversion of diastereoselectivity (cis/trans ratio of 3/7;
Reaction of azadiene 22 with a range of aliphatic,
aromatic and heteroaromatic aldehydes 19 using boron
trifluoride etherate in dichloromethane at −78 to 20°C
over
8 h (Scheme 11) gave rise to cis-/trans-
diastereoisomers in the yields and diastereomeric ratios
reported in Table 5.
In contrast to the results obtained using azadiene 13,
both aliphatic and aromatic aldehydes gave rise to two
diastereoisomers presenting either a cis- or trans-
configuration on the C-(5)/C-(6) stereogenic centres. No
other isomers were detected in the crude reaction mix-
tures. Table 6 reports the coupling constants between
Scheme 7. Reagents and conditions: (i) MeOH/HCl.

A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
443
Scheme 8. Reagents and conditions: (i) BF3·Et2O, −78°C, CH2Cl2. 19a, 20a, 21a: R=C3H7; 19b, 20b, 21b: R=i-Pr; 19c, 20c, 21c:
R=heptyl; 19d, 20d, 21d: R=phenyl; 19e, 20e, 21e: R=p-MeO-Ph; 19f, 20f, 21f: R=p-NO2-Ph; 19g, 20g, 21g: R=2-naphthyl;
19i, 20h, 21h: R=3-(N-Boc)-indolenyl.
Table 3. Perhydroxazinone from azadiene 14 and aldehydes 15 and 19
Entry
Aldehyde
R
Products
Total yield % (ratio %)
1
2
3
4
5
6
7
8
9
15
Methyl
n-Propyl
i-Propyl
Heptyl
16/epi-16; 17/epi-17
38 (36/20/18/26)
65 (78/0/3/19)
54 (0/30/16/54)
59 (75/0/4/21)
52 (0/0/43/57)
30 (0/0/83/17)
45 (0/0/87/13)
57 (0/0/84/16)
62 (0/0/82/18)
19a
19b
19c
19d
19e
19f
19g
19i
20a/epi-20a; 21a/epi-21a
20b/epi-20b; 21b/epi-21b
20c/epi-20c; 21c/epi-21c
20d/epi-20d; 21d/epi-21d
20e/epi-20e; 21e/epi-21e
20f/epi-20f; 21f/epi-21f
20g/epi-20g; 21g/epi-21g
20h/epi-20h; 21h/epi-21h
Phenyl
p-MeO-Phenyl
p-NO2-Phenyl
Naphthyl
3-(N-Boc)-Indolenyl
Scheme 9. Reagents and conditions: (i) Di-t-butyl-pyrocarbonate, TEA, DMAPcat.; (ii) BF3·Et2O, −78°C, CH2Cl2.
diagnostic protons and nOe, if any. It is noteworthy
that for the trans-isomers an nOe between C-(2)H and
C-(5)H is observed, in accord with the configuration
assigned to the perhydroxazin-2-one 24.
hyde oxygen syn to the hydrogen and force the R1
group into an endo-position in the transition state (TS),
leading to the cis-(2R,5R,6S)-products (Scheme 12,
pathway (a)). Aldehydes having R1 groups larger than
the coordinating LA can react via a pericyclic exo-
mode affording trans-(2R,5R,6R)-products (Scheme 12,
pathway (b)).
The nOe effect between C-(2)H and C-(5)H may result
from a boat conformation of the six-membered ring in
which all three bulky substituents are oriented equatori-
ally. Fig. 3 shows the proximity of the C-(2) and C-(5)
protons.
The HDA reaction was expected to produce endo- or
exo-products in which a cis-relationship is established
between C-(2)H and C-(5)H. However, analysis of the
reaction mixture shows the presence of diastereoisomers
with a trans-relationship between C-(2)H and C-(5)H.
There are two possible explanations for the formation
of C-(2)/C-(5) trans-products: the first involves epimer-
isation of the C-(2) and/or C-(5) stereogenic centres
3. Discussion
Diastereoselection in pericyclic reactions has been
explained in terms of exo-/endo-transition states
depending on the Lewis acid (LA) and the steric
demands of the substituents on the dienophile. A peri-
cyclic pathway (a) predominates with LAs such as
ZnCl2, Eu(fod)3 and MgBr2. These coordinate the alde-
during the reaction; alternatively,
a
stepwise
Mukaiyama mechanism may be occurring. The first
hypothesis is unlikely, in our opinion, since in a previ-
ous case24 quenching the reaction mixture at −78°C

444
A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
Table 4. Coupling constants (J in Hz) for C-(5)H and
The experimental evidence suggests that Mukaiyama-
like processes, responsible for the formation of CꢀC
and CꢀO bonds, are discrete, which gives rise to the
possibility of isolating and identifying the intermedi-
ates. Studies directed towards the isolation and identifi-
cation of an open chain product are currently
underway. In the light of our above reported experi-
mental results, it is reasonable that both mechanisms,
concerted HDA reaction and step-by-step Mukaiyama
reaction, may be operating in determining the
diastereomeric ratio of the products.
C-(6)H and nOe
Entry
R
Products J5–6 (Hz)
nOe
1
2
Methyl
Methyl
16
epi-16
4.0 (cis)
5.9 (cis)
2“6; 5“6
CH3“2;
5“6
3
Methyl
17
9.9 (trans)
–
4
5
Methyl
Propyl
epi-17
20a
10.0 (trans) 2“6
3.9 (cis)
2“6; 5“6
6
7
8
Propyl
i-Propyl
i-Propyl
epi-21a
epi-20b
21b
10.1 (trans) 2“6
2.8 (cis)
5“6
10.3 (trans)
–
9
i-Propyl
Hepthyl
Hepthyl
Phenyl
epi-21b
20c
epi-21c
21d
epi-21d
21e
epi-21e
21f
10.5 (trans) 2“6
4. Conclusions
10
11
12
13
14
15
16
17
18
19
20
21
4.0 (cis)
2“6; 5“6
10.0 (trans) 2“6
Boron trifluoride-mediated cycloaddition of aldehydes
10.2 (trans)
9.6 (trans) 2“6
10.0 (trans)
10.0 (trans) 2“6
10.0 (trans)
10.4 (trans) 2“6
10.0 (trans)
10.2 (trans) 2“6
10.0 (trans)
10.2 (trans) 2“6
–
and
2-aza-3-trimethylsilyloxy-1,3-diene
produces
Phenyl
adducts that may arise from a classical HDA reaction
or from a Mukaiyama aldol type reaction. The compet-
itive existence of both reaction pathways has been
demonstrated by the stereochemical analysis of the
products. The degree of diastereoselection in both
mechanisms appears to be dependent upon the steric
and electronic nature of the dienophile and the diene
used.
p-MeO-Phenyl
p-MeO-Phenyl
p-NO2-Phenyl
p-NO2-Phenyl
2-Naphthyl
2-Naphthyl
–
–
epi-21f
21g
epi-21g
–
N-Boc-3-Indolenyl 21h
N-Boc-3-Indolenyl epi-21h
–
The optimal conditions for the reaction were found to
be with the diene carrying two chiral auxiliaries, and,
under these conditions, the reactions take place with
high control of the diastereoselectivity. Studies on the
use of different Lewis acids under catalytic conditions
are currently under examination and will be reported in
due course. Finally, it has been demonstrated by us33
and other research groups11,12 that the resulting perhy-
droxazinones provide a scaffold for other synthetic
transformations and can be used to prepare proteino-
genic and non-proteinogenic amino acids in enan-
tiomerically pure forms.
Scheme 10.
after 3 h led to a decrease in yield but did not affect the
diastereomeric ratio of the perhydroxazin-2-ones. The
second hypothesis of a stepwise mechanism, competi-
tive with the classical HDA mechanism, is more likely.
In fact, formulation in terms of the Mukaiyama silyl
enol–ether aldol process leads to intermediates I-2 and
I-3 (Scheme 12, pathways (c) and (d)), which, upon ring
closure, give rise to cis-(2R,5R,6S)- and/or cis-
(2S,5R,6S)- and trans-(2S,5R,6R)- and/or trans-
(2R,5R,6R)-products.
5. Experimental
5.1. General
Melting points were taken on a Mel-Temp apparatus
1
and are uncorrected. H and 13C NMR spectra were
recorded in CDCl3 on a Varian Gemini 200 spectro-
meter. Chemical shifts are reported in the l scale and
coupling constants (J) are reported in hertz. The values
of diagnostic protons and carbons are reported in
Scheme 11. Reagents and conditions: (i) BF3·Et2O, −78°C, CH2Cl2. 19a, 23a, 24a: R=n-propyl; 19b, 23b, 24b: R=i-Pr; 19c, 23c,
24c: R=heptyl; 19d, 23d, 24d: R=phenyl; 19e, 23e, 24e: R=p-MeO-Ph; 19i, 23f, 24f: R=3-(N-Boc)-indolenyl; 19j, 23g, 24g:
R=cyclohexyl; 19k, 23h, 24h: R=C2H5; 19l, 23i, 24i: R=3-pyridyl; 19m, 23j, 24j: R=2-thienyl; 19n, 23k, 24k: R=2-furyl.

A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
Table 5. Perhydroxazinone from azadiene 22 and aldehydes 19
445
Entry
Aldehyde
R
Products
Ratio cis/trans
Yield (%)
1
2
3
4
5
6
7
8
19a
19b
19c
19d
19e
19i
19j
19k
19l
n-Propyl
i-Propyl
23a/24a
23b/24b
23c/24c
23d/24d
23e/24e
23f/24f
23g/24g
23h/24h
23i/24i
85/15
35/65
86/14
26/74
27/73
2/98
31/69
86/14
28/72
50/50
58/42
50
27
55
54
50
50
42
51
42
59
68
n-Hepthyl
Phenyl
p-MeO-Phenyl
3-(N-Boc)-Indolenyl
Cyclohexyl
Ethyl
3-Pyridyl
2-Thienyl
2-Furyl
9
10
11
19m
19n
23j/24j
23k/24k
Table 6. Coupling constants (J in Hz) for C-(2)H/C-(1%)H and C-(5)H/C-(6)H for 23 and 24 and nOe
Entry
R
Product
J2–2%
J5–6
nOe
1
2
3
4
5
6
7
8
n-Propyl
n-Propyl
i-Propyl
23a
24a
23b
24b
23c
24c
23d
24d
23e
24e
24f
23g
24g
23h
24h
23i
3.6 (syn)
4.0 (syn)
3.8 (syn)
3.8 (syn)
3.7 (syn)
4.0 (syn)
3.7 (syn)
4.5 (syn)
3.6 (syn)
4.3 (syn)
4.5 (syn)
3.8 (syn)
4.0 (syn)
3.7 (syn)
4.0 (syn)
3.2 (syn)
4.7 (syn)
3.8 (syn)
4.4 (syn)
3.6 (syn)
4.4 (syn)
4.8 (cis)
8.5 (trans)
3.8 (cis)
8.9 (trans)
4.4 (cis)
8.4 (trans)
5.3 (cis)
9.6 (trans)
5.1 (cis)
9.6 (trans)
9.3 (trans)
3.7 (cis)
9.1 (trans)
4.4 (cis)
8.5 (trans)
4.2 (cis)
2“6; 5“6
2“5
2“6; 5“6
2“5
2“6; 5“6
2“5
2“6; 5“6
2“5
2“6; 5“6
2“5
2“5
2“6; 5“6
2“5
2“6; 5“6
2“5
i-Propyl
n-Hepthyl
n-Hepthyl
Phenyl
Phenyl
9
p-MeO-Phenyl
p-MeO-Phenyl
3-(N-Boc)-Indolenyl
Cyclohexyl
Cyclohexyl
Ethyl
10
11
12
13
14
15
16
17
18
19
20
21
Ethyl
3-Pyridyl
3-Pyridyl
2-Thienyl
2-Thienyl
2-Furyl
5“6
2“5
2“6; 5“6
2“5
2“6; 5“6
2“5
24i
23j
24j
23k
24k
9.8 (trans)
5.2 (cis)
9.2 (trans)
4.4 (cis)
2-Furyl
9.2 (trans)
brackets. Infrared spectra were recorded as Nujol mulls
on a Nicolet 205 FT-IR spectrophotometer. Specific
rotation measurements were carried out on a Perkin–
Elmer 343 polarimeter and specific rotation [h]2D0 is
reported in deg per dm3 at the specified temperature
and with the concentration [c] given in g per 100 mL in
CHCl3. THF, toluene, and heptane were distilled from
benzophenone ketyl. Lithium bis(trimethylsilyl)amide
(LiHMSDA) (1 M solution in hexane) was purchased
from Lancaster Synthesis.
5.2. Materials
N-Trialkylsilylimines were prepared according to
reported procedures18 starting from the parent alde-
hydes. Triethylamine was dried over KOH. Other sol-
vents and reagents were obtained commercially and
were used as received. All reactions were performed
under nitrogen, on a 1.0 mmol scale, and the yields
reported refer to the whole process (starting from the
aldehyde used in the preparation of the imine).
5.3. Preparation of 1-phthalimido-2(trimethylsilyl)oxy-
3-aza-4-phenyl-1,3-butadiene 3
A solution of benzaldehyde (0.1 mL, 1 mmol) in hep-
tane (2 mL) was added to a solution of LiHMDSA (1
M in hexane, 1 mL) in heptane (5 mL) previously
Figure 3. Boat conformation of the model 2,5,6-equatorial
substituted perhydroxazin-2-one.

446
A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
cooled to 0°C. The reaction mixture was stirred at 0°C
for 1 h. Imine formation was confirmed by IR analysis
(wCN=1655 cm−1). Trimethylsilyl chloride (0.13 mL, 1
mmol) was added in one portion. After stirring for 10
min at 0°C, the mixture was allowed to stir for 1 h at rt
wherein a white precipitate formed. The mixture was
cooled to 0°C and triethylamine (0.3 mL, 2 mmol) was
added in one portion and the mixture stirred for 5 min.
Phthalimidoyl chloride (0.22 g, 1 mmol) dissolved in
toluene (5 mL) was added dropwise and the resultant
mixture stirred for 1 h wherein a thick precipitate
formed. The mixture was filtered through Celite under
argon and the solvent was removed from the filtrate in
vacuo to afford an oil, which was analysed by 1H NMR
spectroscopy. Structure 3 shows the nOe between the
C-(1)H and C-(4)H diagnostic protons. IR (CHCl3):
5.4. General procedure for the preparation of perhydro-
xazin-4-ones 5–7
Azadiene 3, prepared as reported above, was dissolved
in dichloromethane (5 mL). The solution was cooled to
−78°C and benzaldehyde (0.11 mL, 1 mmol) in
dichloromethane (2 mL) was added, followed by the
very slow addition of boron trifluoride diethyl etherate
(0.13 mL, 1 mmol) dissolved in dichloromethane (10
mL). The reaction was stirred at −78°C for 3 h and
allowed to warm to rt overnight. The crude reaction
mixture was diluted with dichloromethane (10 mL),
poured into saturated aqueous NaHCO3 solution, and
extracted further with dichloromethane. The organic
layers were washed with brine, and then dried over
MgSO4. After filtration, the solvent was removed under
reduced pressure and the crude reaction mixture was
purified by flash chromatography on silica gel, eluting
with dichloromethane/acetone 9/1. Compounds 5–7
were obtained in 63% overall yield in a 50/36/14
diastereomeric ratio as oils. Spectral data for each
compound are as follows.
1
1721, 1687; H NMR: 8.57 (s, 1H, C-(4)H), 7.88 (m,
4H), 7.75 (m, 2H), 7.47 (m, 3H), 5.92 (s, 1H, C-(1)H),
0.16 (s, 9H); 13C NMR: 166.76 (C1), 158.38, 154.62,
134.09 (C2), 132.20, 131.80, 130.078, 129.17, 128.77,
123.39, 95.08 (C4), 0.283.
5.4.1. (2R*,5R*,6S*)-2-Phenyl-5-phthalimido-6-phenyl-
1,3-oxazinan-4-one 5. IR (CHCl3): 1721, 1687; 1H
NMR: 7.90–7.10 (m, 14H), 6.68 (s, 1H, NH), 6.00 (s,
1H, C-(2)H), 5.42 (d, 1H, J=5.1, C-(5)H), 5.14 (d, 1H,
J=5.1, C-(6)H); 13C NMR: 166.81 (C4), 164.57, 137.52,
135.39, 133.93, 130.27, 129.03, 128.17, 127.67, 125.79,
123.26, 86.82 (C2), 80.23 (C6), 52.06 (C5); MS m/z: 398
Scheme 12.

A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
447
(M+), 292, 249, 187, 145. Anal. calcd for C24H18N2O4:
C, 72.35; H, 4.55; N, 7.03. Found: C, 72.51; H, 4.51; N,
6.9%.
21H), 0.08 (s, 9H); 13C NMR: 167.44, 166.68 (C4),
153.62 (C2), 134.11, 132.14, 123.39, 95.71 (C1), 70.50
(C5), 21.98, 17.93, 17.66, 12.23, 0.16.
5.4.2. (2S*,5R*,6S*)-2-Phenyl-5-phthalimido-6-phenyl-
1,3-oxazinan-4-one 6. IR (CHCl3): 1721, 1687; 1H
NMR: 7.70–7.10 (m, 15H), 6.52 (d, 1H, J=3.1, C-
(2)H), 5.21 (d, 1H, J=4.7, C-(5)H), 5.02 (d, 1H, J=4.7,
C-(6)H); 13C NMR: 167.09 (C4), 165.70, 137.69, 135.40,
133.98, 131.38, 129.44, 128.94, 128.10, 126.92, 125.97,
125.29, 83.12 (C2), 72.76 (C6), 52.84 (C5); MS m/z: 398
(M+), 292, 249, 187, 145. Anal. calcd for C24H18N2O4:
C, 72.35; H, 4.55; N, 7.03. Found: C, 72.23; H, 4.58; N,
7.18%.
5.6. Preparation of perhydroxazin-4-ones 10–12
A solution of azadiene 9 in dichloromethane (5 mL),
cooled at −78°C, and benzaldehyde (0.11 mL, 1 mmol)
in methylene chloride (2 mL) was added followed by
very slow addition of boron trifluoride diethyl etherate
(0.13 mL, 1 mmol) dissolved in methylene chloride (10
mL). The reaction was stirred at −78°C for 3 h and
then allowed to warm to rt overnight. The crude reac-
tion mixture was diluted with dichloromethane (10
mL), poured into a saturated aqueous NaHCO3 solu-
tion, and extracted with dichloromethane. The organic
extracts were combined, washed with brine and dried
over MgSO4. After filtration, the solvent was removed
under reduced pressure and the crude reaction mixture
purified by flash chromatography on silica gel, eluting
with dichloromethane/acetone 9/1. Compounds 10–12
were obtained in 50% overall yield and a 60/17/23
diastereomeric ratio. Spectral data are as follows.
5.4.3. (2R*,5R*,6R*)-2-Phenyl-5-phthalimido-6-phenyl-
1,3-oxazinan-4-one 7. IR (CHCl3): 1721, 1692; 1H
NMR: 7.80–7.20 (m, 14H), 7.12 (s, 1H), 6.28 (d, 1H,
J=2.0, C-(2)H), 5.34 (d, 1H, J=10.5, C-(5)H), 5.08 (d,
1H, J=10.5, C-(6)H); 13C NMR: 166.42 (C4), 137.72,
136.37, 134.15, 131.52, 129.55, 129.03, 128.80, 128.67,
127.45, 127.02, 123.62, 83.68 (C2), 69.95 (C6), 53.51
(C5); MS m/z: 398 (M+), 292, 249, 187, 145. Anal. calcd
for C24H18N2O4: C, 72.35; H, 4.55; N, 7.03. Found: C,
72.57; H, 4.53; N, 6.87%.
5.6.1. (2S,5S,6R)-6-Phenyl-5-phthalimido-2-[1(S)-triiso-
propylsilanyloxyethyl]-1,3-oxazinan-4-one 10. [h]2D01=
−104.7 (c 0.64, CHCl3); IR (CHCl3): 1722, 1686; H
NMR: 7.70 (m, 4H), 7.25 (m, 5H), 6.98 (s, 1H, NH),
5.22 (d, 1H, J=4.6, C-(5)H), 5.03 (d, 1H, J=4.6,
C-(6)H), 4.74 (d, 1H, J=7.8, C-(2)H), 4.35 (m, 1H,
C-(1%)H), 1.38 (d, 3H, J=6.1), 1.18 (s, 21H); 13C NMR:
164.04 (C4), 135.53, 133.81, 128.16, 125.71, 123.21,
87.83 (C3), 79.37 (C6), 71.06 (C1%), 52.73 (C5), 19.85,
18.20, 18.12, 12.75; MS m/z: 523 (M++1), 479 (M+−43),
373, 321, 276, 250, 187. Anal. calcd for C29H38N2O5Si:
C, 66.64; H, 7.33; N, 5.36. Found: C, 66.74; H, 7.30; N,
5.53%.
5.5. Preparation of (5S)-1-phthalimido-2(trimethylsilyl)-
oxy-3-aza-5-triisopropylsilyloxyhexa-1,3-diene 9
A solution of (S)-lactimine 8 was prepared by the
dropwise addition of a heptane solution (5 mL) of
(S)-1-triisopropylsiloxylactaldehyde (0.23 g, 1 mmol) to
a cooled (0°C) hexane solution of lithium bis(trimethyl-
disilyl)amide (LiHMDSA) (1 mL of 1 M soln in hep-
tane). After addition of the aldehyde, the reaction
mixture was stirred at 0°C for 1 h. Imine formation was
confirmed by IR analysis of the reaction mixture (wCN
=
1685 cm−1). To the imine solution, trimethylsilyl chlo-
ride (0.13 mL, 1 mmol) was added in one portion, and
the mixture allowed to stir at 0°C for 15 min and for a
further 1 h at rt. The mixture was cooled to 0°C and
triethylamine (0.3 mL, 2.0 mmol) was added in one
portion, and the mixture stirred for 5 min at 0°C. A
solution of phthaloyl chloride (0.22 g, 1 mmol) in
toluene was added very slowly (over 5 min). Stirring
was maintained for 30 min at 0°C and a further 1 h at
rt. The yellow–orange mixture was filtered through
Celite and the solvent was removed in vacuo. A sample
was removed from the reaction mixture, concentrated
5.6.2. (2R,5R,6S)-6-Phenyl-5-phthalimido-2-[1(S)-triiso-
propylsilanyloxyethyl]-1,3-oxazinan-4-one 11. [h]2D0=
+93.7 (c 0.44, CHCl3); IR (CHCl3): 1722, 1684; 1H
NMR: 7.65 (m, 4H), 7.20 (m, 5H), 6.85 (s, 1H), 5.30 (d,
1H, J=5.6, C-(5)H), 5.16 (d, 1H, J=3.6, C-(2)H), 5.12
(d, 1H, J=5.6, C-(6)H), 4.32 (dq, 1H, J=3.6, 6.2,
C-(1%)H), 1.54 (d, 3H, J=6.2), 1.08 (s, 21H); 13C NMR:
164.88 (C4), 135.40, 133.87, 128.19, 125.70, 123.17,
85.54 (C3), 80.15 (C6), 68.88 (C1%), 52.33 (C5), 18.04,
18.00, 16.37, 12.20; MS m/z: 523 (M++1), 479 (M+−43),
373, 321, 276, 250, 187. Anal. calcd for C29H38N2O5Si:
C, 66.64; H, 7.33; N, 5.36. Found: C, 66.40; H, 7.36; N,
5.53%.
1
to an oil, and analysed by H NMR to check for the
presence of the azadiene species 9. IR (CHCl3): 1721,
1
1687; H NMR: 7.92 (d, 1H, J=4.8, C-(4)H), 7.86 (m,
2H), 7.72 (m, 2H), 5.74 (s, 1H, C-(1)H), 4.52 (dq, 1H,
J=4.8, 6.8, C-(5)H), 1.35 (d, 3H, J=6.8), 1.04 (m,
5.6.3. (2R,5R,6R)-6-Phenyl-5-phthalimido-2-[1(S)-triiso-
1
propylsilanyloxyethyl]-1,3-oxazinan-4-one 12. H NMR:
7.65 (m, 4H), 7.20 (m, 5H), 6.60 (s, 1H, NH), 5.66 (d,
1H, J=9.8, C-(5)H), 5.28 (d, 1H, J=4.3, C-(2)H),
5.02 (d, 1H, J=9.8, C6H), 4.22 (m, 1H, C-(1%)H),
1.38 (d, 3H, J=6.1), 1.05 (s, 21H); 13C NMR: 154.81
(C4), 139.38, 134.10, 128.71, 126.96, 123.56, 83.70 (C3),
73.07 (C6), 69.51 (C1%), 53.95 (C5), 18.02, 17.98, 17.50,
12.18.

448
A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
5.7. 1-[(4S)-2-Oxo-4-phenyloxazolidin-3-yl]-2-trimethyl-
silyloxy-3-aza-4-phenylbuta-1,3-diene 14
68.17; H, 7.95; N, 5.72. Found: C, 68.10; H, 7.93; N,
5.53%.
To a solution of imine 2, prepared as above, cooled at
0°C, triethylamine (0.3 mL, 2 mmol) was added in one
portion. After stirring for 5 min, a solution of the acid
chloride 13 (prepared from the corresponding acid (0.26
g, 1.2 mmol) and oxalyl chloride (0.16 mL, 1.8 mmol)
according to the literature procedure36,37) in dry toluene
(5 mL) was added dropwise. Stirring was maintained
for 1 h wherein a thick precipitate formed. The precipi-
tate was filtered through Celite under argon and the
solvent was removed in vacuo. The oil obtained was
5.8.3. (2R,5R,6R)-6-Methyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one 17. [h]2D0=
+57.9 (c 0.38, CHCl3); IR (CHCl3): 1757, 1683; 1H
NMR: 7.45 (m, 10H), 6.30 (s, 1H, NH), 5.94 (d, 1H,
J=1.9, C-(2)H), 5.24 (dd, 1H, J=8.7, 10.0), 4.72 (t,
1H, J=8.7), 4.58 (dq, 1H, J=6.2, 9.9, C-(6)H), 4.25
(dd, 1H, J=8.7, 10.0), 3.18 (d, 1H, J=9.9, C-(5)H),
0.90 (d, 3H, J=6.2); 13C NMR: 168.39 (C4), 158.84,
137.82, 136.02, 129.68, 129.43, 129.20, 128.71, 128.67,
127.41, 83.11 (C2), 70.50, 64.39 (C6), 64.23 (C5), 58.80,
18.60; MS m/z: 352 (M+), 308, 202, 191, 176, 130, 104.
Anal. calcd for C20H20N2O4: C, 68.17; H, 7.95; N, 5.72.
Found: C, 68.22; H, 7.91; N, 5.89%.
1
analysed by NMR spectroscopy. H NMR: 8.20 (s, 1H,
C-(4)H), 7.68 (m, 2H), 7.40–7.10 (m, 8H), 6.02 (s, 1H,
C-(1)H), 5.46 (dd, 1H, J=3.4, 8.0), 4.66 (t, 1H, J=8.5),
4.24 (dd, 1H, J=3.4, 8.5), 0.25 (s, 9H); 13C NMR:
156.66 (C4), 154.78, 139.36 (C2), 135.53, 131.22, 130.09,
128.98, 128.68, 128.61, 126.21, 100.09 (C1), 70.24, 59.48,
0.62.
5.8.4. (2S,5R,6R)-6-Methyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one epi-17. [h]2D01=
+153.4 (c 1.76, CHCl3); IR (CHCl3): 1755, 1684; H
NMR: 7.45 (s, 5H), 7.40 (s, 5H), 6.24 (s, 1H, NH), 5.92
(s, 1H, C-(2)H), 5.28 (dd, 1H, J=8.8, 10.0), 4.74 (m,
2H, C-(6)H), 4.30 (dd, 1H, J=8.8, 10.0), 3.20 (d, 1H,
J=10.0, C-(5)H), 1.05 (d, 3H, J=6.2); 13C NMR:
168.66 (C4), 158.91, 137.42, 135.94, 130.00, 129.74,
129.22, 128.89, 128.70, 126.78, 85.48 (C2), 72.39 (C5),
70.47, 64.42 (C6), 58.36, 18.89; MS m/z: 352 (M+), 308,
202, 191, 176, 130, 104. Anal. calcd for C20H20N2O4: C,
68.17; H, 7.95; N, 5.72. Found: C, 67.94; H, 7.94; N,
5.60%.
5.8. Preparation of perhydroxazin-4-ones 16, epi-16, 17
and epi-17
5.9. Hydrolysis of perhydroxazin-4-ones 16 and epi-16:
synthesis of (2R,3R)-2-[(4S)-2-oxo-4-phenyloxazolidin-3-
yl]-3-hydroxybutanoic acid 18
Following the procedure reported for compounds 10–
12, perhydroxazin-4-ones 16, epi-16, 17, and epi-17
were obtained starting from azadiene 14 and acetalde-
hyde in 38% yield and a 36/20/18/26 diastereomeric
ratio. Spectral data for these compounds are as follows.
From 16: A solution of perhydroxazinone 16 (0.030 g,
0.085 mmol) in MeOH was cooled to 0°C and a previ-
ously prepared saturated solution of HCl in MeOH (3
mL) was added. The reaction was stirred overnight at
0°C. The solvent was removed in vacuo, a saturated
solution of NaHCO3 was added and the mixture was
extracted with ethyl acetate. Column chromatography
on silica gel (CH2Cl2/acetone 80/20) afforded the target
compound in almost quantitative yield. [h]2D0=+57.9 (c
0.21, CHCl3).
5.8.1. (2R,5R,6S)-6-Methyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one 16. [h]2D01=
+132.89 (c 0.90, CHCl3); IR (CHCl3): 1754, 1686; H
NMR: 7.30 (m, 10H), 5.98 (s, 1H, NH), 5.68 (s, 1H,
C-(2)H), 5.20 (dd, 1H, J=6.8, 8.8), 4.64 (t, 1H, J=8.8),
4.32 (d, 1H, J=4.0, C-(5)H), 4.16 (m, 2H, C-(6)H), 1.38
(d, 3H, J=6.5); 13C NMR: 165.85 (C4), 159.12, 137.27,
136.76, 129.95, 129.11, 128.78, 127.87, 126.81, 86.09
(C2), 75.32 (C6), 70.73, 61.32 (C5), 55.53, 16.50; MS
m/z: 352 (M+), 308, 203, 191, 176, 145, 104. Anal. calcd
for C20H20N2O4: C, 68.17; H, 7.95; N, 5.72. Found: C,
67.88; H, 7.98; N, 5.90%.
From epi-16: A solution of perhydroxazinone (0.020 g,
0.057 mmol) in dry MeOH was cooled at 0°C and a
previously prepared saturated solution of HCl in
MeOH (3 mL) was added. The reaction was stirred
overnight at 0°C. The solvent was removed in vacuo, a
saturated solution of NaHCO3 was added and the
mixture was extracted with ethyl acetate. Column chro-
matography on silica gel (CH2Cl2/acetone 80/20)
afforded the target compound in almost quantitative
5.8.2. (2S,5R,6S)-6-Methyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one epi-16. [h]2D01=
+112.4 (c 0.76, CHCl3); IR (CHCl3): 1756, 1685; H
NMR: 7.40 (m, 10H), 6.10 (s, 1H, NH), 5.72 (s, 1H,
C-(2)H), 5.16 (dd, 1H, J=8.4, 8.8), 4.67 (t, 1H, J=8.8),
4.20 (dd, 1H, J=8.4, 8.8), 4.10 (d, 1H, J=5.9, C-(5)H),
4.00 (m, 1H), 1.40 (d, 3H, J=6.6); 13C NMR: 165.52
(C4), 158.62, 137.66, 136.90, 129.60, 129.48, 128.95,
128.84, 128.12, 126.60, 81.23 (C2), 70.41, 69.59 (C6),
62.89 (C5), 55.64, 15.48; MS m/z: 352 (M+), 308, 203,
191, 176, 145, 104. Anal. calcd for C20H20N2O4: C,
1
yield. [h]2D0=+54.4 (c 0.11, CHCl3); H NMR: 7.39 (s,
5H), 6.55 (bs, 1H), 5.24 (dq, 1H, J=7.4, 8.8), 4.76 (t,
1H, J=8.8), 4.71 (d, 1H, J=8.4, C-(2)H), 4.37 (dq, 1H,
J=7.4, 8.8), 4.24 (m, 1H, C-(3)H), 3.63 (d, 1H, J=4.0,
OH), 1.19 (d, 3H, J=6.8); MS m/z: 265, 247, 229, 220,
203, 188, 176, 130, 104. Anal. calcd for C24H18N2O4: C,
72.35; H, 4.55; N, 7.03. Found: C, 72.23; H, 4.58; N,
7.18%.

A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
449
5.10. General procedure for the synthesis of
perhydroxazin-4-ones
146. Anal. calcd for C22H24N2O4: C, 69.46; H, 6.36; N,
7.36. Found: C, 69.18; H, 6.32; N, 7.4%.
Following the above procedure for the synthesis of
perhydroxazin-4-ones, compounds 5–7 were prepared
from the corresponding azadiene and aldehydes. The
yields and diastereomeric ratios are reported in Table 3.
5.10.5. (2S,5R,6R)-6-i-Propyl-5-[(4S)-2-oxo-4-phenylox-
azolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one
epi-21b.
[h]2D0=+121.6 (c 1.01, CHCl3); IR (CHCl3): 1753, 1697;
1H NMR: 7.40 (m, 10H), 6.58 (s, 1H, NH), 5.85 (s, 1H,
C-(2)H), 5.25 (dd, 1H, J=8.7, 10.1), 4.69 (t, 1H, J=
8.7), 4.48 (dd, 1H, J=1.6, 10.5, C-(6)H), 4.32 (dd, 1H,
J=8.7, 10.1), 3.40 (d, 1H, J=10.5, C-(5)H), 1.72
(dquint., 1H, J=1.6, 6.9), 0.93 (d, 3H, J=7.0), 0.15 (d,
3H, J=6.8); 13C NMR: 169.36 (C4), 158.70, 137.87,
135.98, 129.69, 129.55, 129.19, 128.81, 128.63, 126.52,
85.15 (C2), 78.99 (C6), 70.12, 64.39 (C5), 53.86, 27.74,
19.88, 12.86; MS m/z: 380 (M+), 337, 309, 265, 176,
146. Anal. calcd for C22H24N2O4: C, 69.46; H, 6.36; N,
7.36. Found: C, 69.70; H, 6.39; N, 7.21%.
5.10.1. (2R,5R,6S)-6-Propyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one 20a. [h]2D01=
+149.0 (c 0.31, CHCl3); IR (CHCl3): 1752, 1684; H
NMR: 7.40–7.08 (m, 10H), 6.70 (s, 1H, NH), 5.63 (s,
1H, C-(2)H), 5.12 (dd, 1H, J=5.6, 8.7), 4.58 (t, 1H,
J=8.7), 4.43 (d, 1H, J=3.9, C-(5)H), 4.06 (dd, 1H,
J=5.6, 8.7), 3.96 (m, 1H, C-(6)H), 1.55 (m, 4H), 0.95 (t,
3H, J=6.8); 13C NMR: 165.93 (C4), 159.09, 137.45,
136.71, 129.69, 128.84, 128.59, 128.55, 127.60, 126.58,
86.04 (C2), 79.37 (C6), 70.76, 60.55 (C5), 55.00, 32.43,
18.97, 13.84; MS m/z: 380 (M+), 308, 265, 176, 145.
Anal. calcd for C22H24N2O4: C, 69.46; H, 6.36; N, 7.36.
Found: C, 69.72; H, 6.39; N, 7.43%.
5.10.6. (2R,5R,6S)-6-(Hept-1-yl)-5-[(4S)-2-oxo-4-phenyl-
oxazolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one 20c. [h]2D01=
+133.8 (c 0.27, CHCl3); IR (CHCl3): 1752, 1682; H
NMR: 7.38–7.20 (m, 10H), 6.43 (s, 1H, NH), 5.64 (s,
1H, C-(2)H), 5.13 (dd, 1H, J=8.8, 5.6), 4.59 (t, 1H,
J=8.8), 4.45 (d, 1H, J=4.0, C-(5)H), 4.09 (dd, 1H,
J=8.8, 5.6), 3.95 (m, 1H, C-(6)H), 1.70–1.00 (m, 12H),
0.86 (t, 3H, J=7.3); 13C NMR: 165.92 (C4), 159.06,
137.41, 135.60, 129.74, 128.88, 128.61, 128.57, 127.60,
126.60, 86.07 (C2), 79.66 (C6), 70.75, 60.57 (C5), 54.95,
31.71, 30.44, 29.32, 29.07, 25.70, 22.58, 14.16; MS m/z:
436 (M+), 308, 286, 242, 176, 145, 106, 91. Anal. calcd
for C26H32N2O4: C, 71.53; H, 7.39; N, 6.42. Found: C,
71.44; H, 7.42; N, 6.28%.
5.10.2. (2R,5R,6R)-6-Propyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one epi-21a. [h]2D01=
+148.4 (c 0.36, CHCl3); IR (CHCl3): 1755, 1683; H
NMR: 7.46 (s, 5H), 7.40 (s, 5H), 6.38 (s, 1H, NH), 5.87
(s, 1H, C-(2)H), 5.26 (dd, 1H, J=8.8, 10.0), 4.71 (t, 1H,
J=8.8), 4.58 (m, 1H, C-(6)H), 4.30 (dd, 1H, J=8.8,
10.0), 3.28 (d, 1H, J=10.1, C-(5)H), 1.55 (m, 1H), 1.12
(m, 3H), 0.75 (t, 3H, J=6.8); 13C NMR: 168.96 (C4),
158.88, 137.63, 136.02, 129.81, 129.70, 129.17, 128.80,
128.73, 126.64, 85.40 (C2), 75.54 (C6), 70.35, 64.38 (C5),
56.48, 34.14, 17.48, 13.74; MS m/z: 380 (M+), 309, 265,
176, 145. Anal. calcd for C22H24N2O4: C, 69.46; H,
6.36; N, 7.36. Found: C, 69.18; H, 6.33; N, 7.21%.
5.10.7. (2S,5R,6R)-6-(Hept-1-yl)-5-[(4S)-2-oxo-4-phenyl-
oxazolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one
epi-21c.
5.10.3. (2S,5R,6S)-6-i-Propyl-5-[(4S)-2-oxo-4-phenylox-
azolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one epi-20b. Mp
240–242°C; [h]2D0=+118.0 (c 0.79, CHCl3); IR (CHCl3):
[h]2D0=+126.5 (c 0.34, CHCl3); IR (CHCl3): 1754, 1682;
1H NMR: 7.43 (s, 5H), 7.38 (s, 5H), 6.31 (s, 1H, NH),
5.88 (s, 1H, C-(2)H), 5.26 (dd, 1H, J=9.0, 10.0), 4.72
(t, 1H, J=9.0), 4.56 (m, 1H, C-(6)H), 4.31 (dd, 1H,
J=9.0, 10.0), 3.28 (d, 1H, J=10.0, C-(5)H), 1.50–1.00
(m, 12H), 0.86 (t, 3H, J=7.3); 13C NMR: 168.94 (C4),
158.88, 137.54, 135.94, 129.81, 129.69, 129.14, 128.79,
128.72, 126.64, 85.37 (C2), 75.72 (C6), 70.34, 64.38 (C5),
56.41, 32.09, 31.76, 29.34, 29.03, 24.20, 22.59, 14.06;
MS m/z: 436 (M+), 308, 286, 242, 176, 145, 106, 91.
Anal. calcd for C26H32N2O4: C, 71.53; H, 7.39; N, 6.42.
Found: C, 71.44, H, 7.42; N, 6.28%.
1
1751, 1685; H NMR: 7.35 (m, 10H), 5.65 (s, 1H, NH),
5.48 (d, 1H, J=1.7, C-(2)H), 5.18 (dd, 1H, J=5.4, 9.0),
4.66 (t, 1H, J=8.8), 4.60 (d, 1H, J=2.8, C-(5)H), 4.23
(dd, 1H, J=5.4, 8.8), 3.24 (dd, 1H, J=2.8, 10.1, C-
(6)H), 1.82 (m, 1H), 0.80 (t, 6H, J=6.4); 13C NMR:
165.76 (C4), 158.35, 138.03, 137.38, 137.38, 129.27,
129.08, 128.60, 128.47, 128.12, 126.76, 82.63 (C2), 76.55
(C6), 70.61, 60.30 (C5), 53.45, 28.58, 19.37, 18.19; MS
m/z: 380 (M+), 337, 309, 265, 176, 146. Anal. calcd for
C22H24N2O4: C, 69.46; H, 6.36; N, 7.36. Found: C,
69.70; H, 6.38; N, 7.52%.
5.10.8. (2R,5R,6R)-6-Phenyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one 21d. [h]2D0=
+63.4 (c 0.76, CHCl3); IR (CHCl3): 1755, 1683; 1H
NMR: 7.60–7.00 (m, 13H), 6.74 (s, 1H, NH), 6.55 (d,
2H, J=7.2), 6.10 (d, 1H, J=1.6, C-(2)H), 5.56 (d, 1H,
J=10.2, C-(6)H), 5.18 (dd, 1H, J=8.4, 10.8), 4.55 (t,
1H, J=8.4), 3.87 (dd, 1H, J=8.4, 10.8), 3.48 (d, 1H,
J=10.2, C5H); 13C NMR: 168.97 (C4), 159.43, 137.80,
137.78, 135.21, 129.74, 129.11, 129.00, 128.89, 128.74,
128.72, 127.87, 127.71, 127.37, 83.80 (C2), 71.07, 69.81
(C6), 64.73 (C5), 59.10; MS m/z: 414 (M+), 308, 264,
220, 146, 104. Anal. calcd for C25H22N2O4: C, 72.45; H,
5.35; N, 6.76. Found: C, 72.51; H, 5.38; N, 6.88%.
5.10.4. (2R,5R,6R)-6-i-Propyl-5-[(4S)-2-oxo-4-phenylox-
azolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one 21b. [h]2D0=
+47.3 (c 1.88, CHCl3); IR (CHCl3): 1755, 1679; 1H
NMR: 7.40 (m, 10H), 6.50 (s, 1H, NH), 5.95 (d, 1H,
J=1.9, C-(2)H), 5.20 (dd, 1H, J=8.8, 10.1), 4.70 (t,
1H, J=8.8), 4.26 (m, 2H, C-(6)H), 3.42 (d, 1H, J=
10.3, C-(5)H), 1.62 (m, 1H), 0.62 (d, 3H, J=7.0), 0.10
(d, J=6.8); 13C NMR: 169.74 (C4), 158.85, 137.79,
136.15, 129.66, 129.22, 129.14, 128.78; 128.45, 127.35,
82.90 (C2), 70.78 (C6), 70.20, 64.31 (C5), 54.57, 27.11,
19.61, 13.00; MS m/z: 380 (M+), 337, 309, 265, 176,

450
A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
5.10.9. (2S,5R,6R)-6-Phenyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one epi-21d. [h]2D01=
+168.2 (c 0.82, CHCl3); IR (CHCl3): 1754, 1685; H
NMR: 7.50–7.15 (m, 11H), 7.00 (t, 2H, J=8.00), 6.58
(d, 2H, J=6.8), 6.40 (s, 1H, NH), 6.10 (s, 1H, C-(2)H),
5.75 (d, 1H, J=9.6, C-(5)H), 5.25 (dd, 1H, J=8.5,
10.6), 4.57 (t, 1H, J=8.5), 3.92 (dd, 1H, J=8.5, 10.6),
3.53 (d, 1H, J=9.6, C-(6)H); 13C NMR: 168.72 (C4),
159.30, 137.48, 137.24, 134.78, 129.98, 128.82, 128.79,
128.68, 128.64, 128.56, 127.58, 127.08, 126.84, 85.87
(C2), 77.72 (C6), 70.89, 64.57 (C5), 58.53; MS m/z: 414
(M+), 308, 264, 220, 146, 104. Anal. calcd for
C25H22N2O4: C, 72.45; H, 5.35; N, 6.76. Found: C,
72.18; H, 5.37; N, 6.67%.
8H), 6.97 (t, 2H, J=8.0), 6.67 (d, 2H, J=8.0), 6.34 (s,
1H, NH), 6.10 (s, 1H, C-(2)H), 5.82 (d, 1H, J=10.4,
C-(6)H), 5.16 (dd, 1H, J=8.8, 10.4), 4.65 (t, 1H, J=
8.8), 4.06 (dd, 1H, J=8.8, 10.4), 3.48 (d, 1H, J=10.4,
C-(5)H); 13C NMR: 167.80 (C4), 159.20, 148.10, 144.28,
136.64, 134.77, 130.38, 129.16, 129.00, 128.79, 127.99,
127.67, 126.83, 123.62, 86.12 (C2), 76.81 (C6), 70.67,
64.16 (C5), 58.45; MS m/z: 460 (M++1), 298, 265. Anal.
calcd for C25H21N3O6: C, 65.35; H, 4.61; N, 9.15.
Found: C, 65.63; H, 4.57; N, 9.36%.
5.10.14.
(2R,5R,6R)-6-(2-Naphthyl)-5-[(4S)-2-oxo-4-
phenyloxazolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one 21g.
[h]2D0=−36.6 (c 1.65, CHCl3); IR (CHCl3): 1754, 1683;
1H NMR: 7.85 (m, 1H), 7.75–7.40 (m, 10H), 7.15 (m,
2H), 6.95 (m, 1H), 6.52 (m, 2H), 6.38 (m, 2H), 6.20 (s,
1H, C-(2)H), 5.70 (d, 1H, J=10.0, C-(6)H), 5.13 (dd,
1H, J=8.6, 10.1), 4.51 (t, 1H, J=8.6), 3.82 (dd, 1H,
J=8.6, 10.1), 3.60 (d, 1H, J=10.0, C-(5)H); 13C NMR:
168.77 (C4), 159.20, 139.50, 137.69, 134.89, 133.51,
133.07, 129.44, 128.77, 128.51, 128.41, 128.24, 127.52,
127.48, 126.61, 126.33, 126.17, 124.42, 83.63 (C2), 70.68,
69.89 (C6), 64.35 (C5), 58.96; MS m/z: 464 (M+), 446,
402, 301, 196, 155, 104. Anal. calcd for C29H24N2O4: C,
74.98; H, 5.21; N, 6.03. Found: C, 75.25; H, 5.22; N,
5.85%.
5.10.10. (2R,5R,6R)-6-(4-Methoxyphenyl)-5-[(4S)-2-oxo-
4-phenyloxazolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one
21e. [h]2D0=−1.4 (c 1.61, CHCl3); IR (CHCl3): 1755,
1
1683; H NMR: 7.60–6.60 (m, 15H), 6.20 (s, 1H, C-
(2)H), 5.45 (d, 1H, J=10.0, C-(6)H), 5.14 (dd, 1H,
J=8.6, 10.2), 4.52 (t, 1H, J=8.6), 3.85 (m, 4H), 3.47 (d,
1H, J=10.0, C-(5)H); 13C NMR: 168.97 (C4), 159.81,
159.00, 137.79, 135.26, 129.72, 129.25, 128.74, 128.65,
128.60, 128.31, 127.73, 127.37, 113.81, 83.37 (C2), 70.70,
69.31 (C6), 64.27 (C5), 58.81, 55.29; MS m/z: 444 (M+),
426, 382, 309, 281, 177, 146, 135, 104. Anal. calcd for
C26H24N2O5: C, 70.26; H, 5.44; N, 6.30. Found: C,
70.18; H, 5.40; N, 6.19%.
5.10.15.
(2S,5R,6R)-6-(2-Naphthyl)-5-[(4S)-2-oxo-4-
phenyloxazolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one epi-
5.10.11.
(2S,5R,6R)-6-(4-Methoxyphenyl)-5-(2-oxo-4-
21g. [h]2D0=+81.3 (c 1.07, CHCl3); IR (CHCl3): 1753,
1
phenyloxazolidin-3-yl)-2-phenyl-1,3-oxazinan-4-one epi-
1686; H NMR: 7.85–7.25 (m, 13H), 6.90 (m, 1H), 6.45
21e. [h]2D0=+166.2 (c 0.74, CHCl3); IR (CHCl3): 1753,
(m, 4H), 6.16 (s, 1H, C-(2)H), 5.88 (d, 1H, J=10.2,
C-(6)H), 5.17 (dd, 1H, J=8.6, 10.4), 4.54 (t, 1H, J=
8.6), 3.88 (dd, 1H, J=8.6, 10.4), 3.60 (d, 1H, J=10.2,
C-(5)H); 13C NMR: 168.67 (C4), 159.29, 137.35, 134.84,
134.73, 133.63, 133.12, 130.01, 128.84, 128.54, 128.39,
128.24, 127.60, 127.52, 126.90, 126.19, 126.42, 126.26,
85.97 (C2), 78.01 (C6), 70.79, 64.45 (C5), 58.69; MS m/z:
464 (M+), 446, 402, 301, 196, 155, 104. Anal. calcd for
C29H24N2O4: C, 74.98; H, 5.21; N, 6.03. Found: C,
74.62; H, 5.18; N, 6.17%.
1
1685; H NMR: 7.50–6.40 (m, 14H), 6.28 (s, 1H, NH),
6.08 (s, 1H, C-(2)H), 5.66 (d, 1H, J=10.0, C-(6)H),
5.22 (dd, 1H, J=8.5, 9.8), 4.59 (t, 1H, J=8.5), 3.95 (dd,
1H, J=8.5, 9.8), 3.84 (s, 3H), 3.52 (d, 1H, J=10.0,
C-(5)H); 13C NMR: 168.83 (C4), 160.04, 159.28, 137.39,
135.12, 129.98, 129.78, 128.69, 128.37, 127.76, 126.85,
119.97, 85.86 (C2), 77.53 (C6), 70.88, 64.53 (C5), 58.70,
55.39; MS m/z: 444 (M+), 426, 382, 309, 281, 177, 146,
135, 104. Anal. calcd for C26H24N2O5: C, 70.26; H,
5.44; N, 6.30. Found: C, 70.53; H, 5.46; N, 6.45%.
5.10.16. (2R,5R,6R)-6-(1-t-Butoxycarbonylindol-3-yl)-5-
[(4S)-2-oxo-4-phenyloxazolidin-3-yl]-2-phenyl-1,3-ox-
azinan-4-one 21h. [h]2D0=+20.9 (c 2.49, CHCl3); IR
5.10.12. (2R,5R,6R)-6-(4-Nitrophenyl)-5-[(4S)-2-oxo-4-
phenyloxazolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one 21f.
[h]2D0=−33.9 (c 0.81, CHCl3); IR (CHCl3): 1756, 1687;
1H NMR: 8.05 (d, 2H, J=8.80), 7.58 (m, 2H), 7.43 (m,
3H), 7.23 (m, 3H), 7.03 (s, 1H, NH), 6.96 (t, 2H,
J=8.0), 6.20 (d, 2H, J=6.8), 6.15 (d, 1H, J=1.2,
C-(2)H), 5.60 (d, 1H, J=10.0, C-(6)H), 5.10 (dd, 1H,
J=8.8, 9.6), 4.60 (t, 1H, J=8.8), 4.00 (dd, 1H, J=8.8,
9.6), 3.42 (d, 1H, J=10.0, C-(5)H); 13C NMR: 167.95
(C4), 159.03, 147.94, 144.43, 137.04, 134.87, 129.74,
129.08, 128.89, 128.76, 127.98, 127.61, 127.34, 123.45,
83.69 (C2), 70.54, 68.73 (C6), 64.10 (C5), 58.74; MS m/z:
460 (M++1), 298, 265. Anal. calcd for C25H21N3O6: C,
65.35; H, 4.61; N, 9.15. Found: C, 65.19; H, 4.63; N,
9.01%.
1
(CHCl3): 1752, 1682; H NMR: 8.12 (d, 1H, J=8.30),
7.62 (m, 2H), 7.42 (m, 3H), 7.28 (m, 3H), 7.15 (m, 3H),
6.80 (m, 2H), 6.54 (m, 2H), 6.15 (d, 1H, J=1.6, C-
(2)H), 5.70 (d, 1H, J=10.0, C-(6)H), 5.05 (dd, 1H,
J=8.7, 9.8), 4.54 (t, 1H, J=8.7), 3.90 (dd, 1H, J=8.7,
9.8), 3.74 (d, 1H, J=10.0, C-(5)H), 1.65 (s, 9H); 13C
NMR: 168.52 (C4), 158.97, 149.28, 137.43, 135.30,
135.07, 129.48, 128.80, 128.74, 128.16, 127.62, 127.57,
124.60, 124.02, 122.86, 119.30, 117.66, 115.23, 83.83,
83.59 (C2), 70.47, 64.15 (C6), 63.95 (C5), 58.40, 28.19;
MS m/z: 553 (M+), 479, 435, 390, 334, 309, 185, 146.
Anal. calcd for C32H30N3O6: C, 69.55; H, 5.47; N, 7.60.
Found: C, 69.81; H, 5.50; N, 7.76%.
5.10.13. (2S,5R,6R)-(6-(4-Nitrophenyl)-5-[(4S)-2-oxo-4-
phenyloxazolidin-3-yl]-2-phenyl-1,3-oxazinan-4-one epi-
21f. [h]2D0=+92.0 (c 0.50, CHCl3); IR (CHCl3): 1756,
1686; 1H NMR: 8.08 (d, 2H, J=8.0), 7.50–7.15 (m,
5.10.17. (2S,5R,6R)-6-(1-t-Butoxycarbonylindol-3-yl)-5-
[(4S)-2-oxo-4-phenyloxazolidin-3-yl]-2-phenyl-1,3-oxa-
zinan-4-one epi-21h. [h]2D0=+111.0 (c 1.36, CHCl3); IR
1
(CHCl3): 1749, 1684; H NMR: 8.12 (d, 1H, J=8.20),

A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
451
7.52–7.22 (m, 8H), 7.12 (m, 1H), 6.95 (m, 1H), 6.80 (m,
2H), 6.56 (m, 2H), 6.35 (s, 1H, NH), 6.12 (s, 1H,
C-(2)H), 5.90 (d, 1H, J=10.2, C-(6)H), 5.10 (dd, 1H,
J=8.7, 10.1), 4.58 (t, 1H, J=8.7), 4.00 (dd, 1H, J=8.7,
10.1), 3.78 (d, 1H, J=10.2, C-(5)H), 1.65 (s, 9H); 13C
NMR: 168.50 (C4), 160.00, 149.30, 137.17, 135.41,
134.87, 130.03, 128.90, 128.85, 128.10, 127.60, 126.82,
124.23, 122.96, 119.24, 117.56, 115.33, 86.10 (C2), 83.97,
72.10 (C6), 70.55, 64.28 (C5), 57.89, 28.22; MS m/z: 553
(M+), 479, 435, 390, 334, 309, 185, 146. Anal. calcd for
C32H30N3O6: C, 69.55; H, 5.47; N, 7.60. Found: C,
69.38; H, 5.44; N, 7.45%.
compounds were prepared. The yields and
diastereomeric ratio are reported in Table 5.
5.12.1. (2R,5R,6S)-6-Propyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin - 3 - yl] - 2 - [1(S) - triisopropylsilanyloxyethyl] - 1,3-
oxazinan-4-one 23a. [h]2D0=+102.0 (c 1.72, CHCl3); IR
1
(CHCl3): 1755, 1683; H NMR: 7.35 (s, 5H), 6.16 (s,
1H, NH), 5.10 (dd, 1H, J=5.4, 8.8), 4.71 (d, 1H,
J=3.6, C-(2)H), 4.64 (t, 1H, J=8.8), 4.30 (d, 1H,
J=4.8, C-(5)H), 4.12 (dd, 1H, J=5.4, 8.8), 4.03 (dq,
1H, J=3.6, 6.4, C-(1%)H), 3.78 (m, 1H, C-(6)H), 1.72–
1.30 (m, 4H), 1.00 (m, 27H); 13C NMR: 165.57 (C4),
158.72, 137.38, 128.86, 128.45, 127.15, 86.50 (C2), 79.33
(C6), 70.90, 68.51 (C1%), 60.87 (C5), 55.51, 32.51, 19.10,
18.10, 18.06, 16.51, 14.00, 12.27; MS m/z: 504 (M+),
461 (M+−43), 389, 303, 230. Anal. calcd for
C27H44N2O5Si: C, 64.25; H, 8.79; N, 5.55. Found: C,
64.42; H, 8.76; N, 5.41%.
5.11. Preparation of (5S)-1-[(4S)-2-oxo-4-phenyloxazol-
idin-3-yl]-2-trimethylsilyloxy-3-aza-5-triisopropylsilyl-
oxyhexa-1,3-diene 22
A
solution
trimethylsilylimine 8 was prepared by dropwise addi-
tion of solution of (S)-1-triisopropylsiloxyethyl
of
(S)-1-triisopropylsiloxyethyl-N-
5.12.2. (2R,5R,6R)-6-Propyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin - 3 - yl] - 2 - [1(S) - triisopropylsilanyloxyethyl] - 1,3-
oxazinan-4-one 24a. [h]2D0=+75.4 (c 1.26, CHCl3); IR
a
aldehyde (0.23 g, 1.00 mmol) in heptane (5 mL) to a
cooled (−10°C) THF solution of lithium bis(trimethylsi-
lyl)amide (LiHMDSA) (1.10 mL, 1.10 mmol). The reac-
tion mixture was stirred for 1 h at 0°C. Imine formation
was confirmed by IR analysis of the reaction mixture
(wCN=1685 cm−1). To the imine solution was added
trimethylsilyl chloride (0.13 mL, 1.00 mmol) in one
portion, and the mixture was allowed to stir for 1.5 h.
The mixture was stirred for 15 min at 0°C and 1 h at rt.
Triethylamine (0.30 mL, 2.00 mmol) was added in one
portion and the mixture stirred for 5 min at 0°C. A
solution of oxazolidinone-acetyl chloride 13 (1.2 equiv.)
in toluene (prepared according Boger’s method) was
added very slowly (over 5 min) by syringe. Stirring was
maintained for 30 min at 0°C and 1 h at rt. This
yellow–orange mixture was then filtered through Celite.
An aliquot of this mixture was evaporated and analysed
1
(CHCl3): 1755, 1683; H NMR: 7.43 (s, 5H), 6.24 (bs,
1H, NH), 5.15 (dd, 1H, J=8.8, 9.6), 4.88 (dd, 1H,
J=1.2, 4.0, C-(2)H), 4.72 (t, 1H, J=8.8), 4.65 (m, 1H,
C-(6)H), 4.23 (dd, 1H, J=8.8, 9.6), 4.03 (dq, 1H,
J=4.0, 6.8, C-(1%)H), 3.18 (d, 1H, J=8.5, C-(5)H), 1.22
(d, 3H, J=6.8), 1.04 (m, 4H), 0.84 (t, 3H, J=6.3); 13C
NMR: 167.80 (C4), 158.37, 136.23, 129.38, 129.01,
128.20, 81.97 (C2), 71.31 (C6), 70.44, 69.59 (C1%), 63.80
(C5), 56.99, 34.33, 18.12, 18.09, 17.93, 16.97, 14.02,
12.35; MS m/z: 504 (M+), 461 (M+−43), 443, 389, 303,
230, 186. Anal. calcd for C27H44N2O5Si: C, 64.25; H,
8.79; N, 5.55. Found: C, 64.03; H, 8.82; N, 5.66%.
5.12.3. (2R,5R,6S)-6-(2-Methyl)-ethyl-5-[(4S)-2-oxo-4-
phenyloxazolidin - 3 - yl] - 2 - [1(S) - triisopropylsilanyloxy-
ethyl]-1,3-oxazinan-4-one 23b. [h]2D0=+92.4 (c 0.92,
1
by H and 13C NMR spectroscopy, showing that it was
1
CHCl3); IR (CHCl3): 1754, 1684; H NMR: 7.30 (m,
essentially pure 22. [h]2D0=+72.2 (c 1.6, CHCl3); IR
5H), 6.00 (s, 1H, NH), 5.05 (dd, 1H, J=2.6, 8.3), 4.70
(d, 1H, J=3.8, C-(5)H), 4.64 (d, 1H, J=3.8, C-(2)H),
4.57 (t, 1H, J=8.3), 4.04 (dd, 1H, J=2.6, 8.3), 3.94 (dq,
1H, J=3.8, 6.2, C-(1%)H), 3.34 (dd, 1H, J=3.8, 10.0,
C-(6)H), 1.85 (m, 1H), 1.00 (m, 27H), 0.75 (d, 1H,
J=6.2); 13C NMR: 165.86 (C4), 158.91, 138.02, 128.74,
128.55, 126.76, 87.25 (C2), 85.64 (C6), 71.28, 68.55 (C1%),
59.87 (C5), 54.11, 28.90, 19.30, 18.65, 17.98, 17.94,
16.42, 12.51; MS m/z: 504 (M+), 461 (M+−43), 389, 303,
230. Anal. calcd for C27H44N2O5Si: C, 64.25; H, 8.79;
N, 5.55. Found: C, 64.41; H, 8.82; N, 5.47%.
1
(CHCl3): 1748; H NMR (200 MHz, CDCl3): 7.52 (d,
1H, J=4.6, C-(4)H), 7.35 (m, 5H), 5.80 (s, 1H, C-(1)H),
5.32 (dd, 1H, J=3.7, 8.6), 4.65 (t, 1H, J=8.6), 4.30 (m,
2H, C5H), 1.25 (d, 3H, J=6.4), 1.02 (m, 3H), 0.95 (s,
18H); 13C NMR (50 MHz, CDCl3): 163.4 (C4), 156.5,
146.7, 139.1 (C2), 128.9, 128.6, 126.3, 102.0 (C1), 70.3,
70.1 (C5), 59.4, 21.7, 17.8, 17.0, 12.1, 0.4.
5.12.4. (2R,5R,6R)-6-(2-Methyl)-ethyl-5-[(4S)-2-oxo-4-
phenyloxazolidin - 3 - yl] - 2 - [1(S) - triisopropylsilanyloxy-
ethyl]-1,3-oxazinan-4-one 24b. [h]2D0=+63.7 (c 1.82,
CHCl3); IR (CHCl3): 1758, 1680; 1H NMR: 7.40 (s,
5H), 6.28 (s, 1H, NH), 5.12 (dd, 1H, J=8.8, 9.6), 4.87
(d, 1H, J=3.8, C-(2)H), 4.70 (t, 1H, J=8.8), 4.54 (dd,
1H, J=2.7, 8.9, C-(6)H), 4.26 (dd, 1H, J=8.8, 9.6),
4.00 (dq, 1H, J=3.8, 6.3, C-(1%)H), 3.30 (d, 1H, J=8.9,
C-(5)H), 1.80 (m, 1H), 1.18 (d, 3H, J=6.3), 1.02 (s,
21H), 0.90 (d, 3H, J=6.8), 0.28 (d, 3H, J=6.7); 13C
NMR: 168.43 (C4), 158.66, 136.48, 129.53, 129.15,
128.57, 82.35 (C2), 74.90 (C6), 70.17, 69.79 (C1%), 63.70
5.12. General procedure for the synthesis of
perhydroxazin-4-ones
Following the procedure reported above for the synthe-
sis of perhydroxazin-4-ones 5–7, starting from the cor-
responding azadiene and aldehydes, the following

452
A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
(C5), 54.66, 28.15, 19.73, 17.96, 17.66, 16.74, 14.04,
12.23; MS m/z: 461 (M+−43), 389, 303, 230. Anal. calcd
for C27H44N2O5Si: C, 64.25; H, 8.79; N, 5.55. Found:
C, 64.05; H, 8.76; N, 5.64%.
84.25 (C2), 72.15 (C6), 70.71, 69.42 (C1%), 64.08 (C5),
58.74, 17.92, 17.60, 12.25; MS m/z: 538 (M+), 495, 337,
292, 266, 188. Anal. calcd for C30H42N2O5Si: C, 66.88;
H, 7.86; N, 5.20. Found: C, 67.17; H, 7.83; N, 5.29%.
5.12.5. (2R,5R,6S)-6-(Hept-1-yl)-5-[(4S)-2-oxo-4-phenyl-
oxazolidin-3-yl]-2-[1(S)-triisopropylsilanyloxyethyl]-1,3-
oxazinan-4-one 23c. [h]2D0=+94.3 (c 0.81, CHCl3); IR
5.12.9. (2R,5R,6R)-6-(4-Methoxyphenyl)-5-[(4S)-2-oxo-
4-phenyloxazolidin-3-yl]-2-[1(S)-triisopropylsilanyloxy-
ethyl]-1,3-oxazinan-4-one 23e. [h]2D0=+143.2 (c 1.48,
1
1
(CHCl3): 1755, 1682; H NMR: 7.35 (s, 5H), 6.15 (s,
CHCl3); IR (CHCl3): 1754, 1684; H NMR: 7.22 (m,
1H, NH), 5.08 (dd, 1H, J=5.1, 8.5), 4.66 (d, 1H,
J=3.7, C-(2)H), 4.60 (t, 1H, J=8.5), 4.25 (d, 1H,
J=4.4, C-(5)H), 4.08 (dd, 1H, J=5.1, 8.5), 3.98 (dq,
1H, J=3.7, 6.3, C-(1%)H), 3.73 (m, 1H, C-(6)H), 1.65–
1.20 (m, 12H), 1.00 (s, 24H), 0.88 (t, 3H, J=7.3); 13C
NMR: 165.94 (C4), 158.74, 137.33, 128.74, 128.36,
127.13, 86.59 (C2), 79.23 (C6), 70.66, 68.45 (C1%), 60.66
(C5), 55.19, 31.52, 30.14, 29.09, 28.84, 25.40, 22.37,
17.53, 16.33, 13.84, 11.95; MS m/z: 561 (M++1), 517
(M+−43), 389, 359, 286. Anal. calcd for C31H52N2O5Si:
C, 66.39; H, 9.35; N, 4.99. Found: C, 66.12; H, 9.30; N,
5.15%.
6H), 6.90 (m, 4H), 6.35 (s, 1H, NH), 5.03 (d, 1H,
J=5.1, C-(6)H), 4.92 (d, 1H, J=3.6, C-(2)H), 4.78 (dd,
1H, J=5.9, 8.3), 4.55 (m, 1H), 4.14 (dq, 1H, J=3.6,
6.3, C-(1%)H), 3.85 (m, 4H C-(5)H), 3.75 (dd, 1H,
J=5.9, 8.3), 1.00 (s, 24H); 13C NMR: 166.40 (C4),
159.58, 159.10, 137.15, 128.73, 128.05, 127.51, 127.29,
126.93, 113.96, 86.13 (C2), 80.06 (C6), 70.86, 68.51 (C1%),
60.84 (C5), 55.34, 17.98, 17.93, 16.11, 12.18; MS m/z:
525 (M+−43), 432, 389, 322, 296, 204, 187. Anal. calcd
for C31H44N2O6Si: C, 65.46; H, 7.80; N, 4.93. Found:
C, 65.63; H, 7.83; N, 4.90%.
5.12.10. (2R,5R,6R)-6-(4-Methoxyphenyl)-5-[(4S)-2-oxo-
4-phenyloxazolidin-3-yl]-2-[1(S)-triisopropylsilanyloxy-
ethyl]-1,3-oxazinan-4-one 24e. [h]2D0=+55.8 (c 2.24,
5.12.6. (2R,5R,6R)-6-(Hept-1-yl)-5-[(4S)-2-oxo-4-phenyl-
oxazolidin-3-yl]-2-[1(S)-triisopropylsilanyloxyethyl]-1,3-
oxazinan-4-one 24c. [h]2D0=+84.2 (c 0.43, CHCl3); IR
1
CHCl3); IR (CHCl3): 1757, 1684; H NMR: 7.32–6.98
1
(CHCl3): 1755, 1682; H NMR: 7.40 (s, 5H), 6.31 (s,
(m, 5H), 6.80 (d, 2H, J=8.7), 6.58 (m, 3H), 5.75 (d, 1H,
J=9.6, C-(6)H), 5.08 (dd, 1H, J=8.6, 10.2), 5.00 (d,
1H, J=4.3, C-(2)H), 4.56 (t, 1H, J=8.6), 4.14 (m, 1H,
C-(1%)H), 3.83 (m, 4H), 3.30 (d, 1H, J=9.6, C5H), 1.28
(d, 3H, J=6.2), 0.96 (s, 21H); 13C NMR: 168.18 (C4),
159.93, 158.87, 135.54, 130.05, 128.76, 128.33, 127.62,
113.79, 84.15 (C2), 71.90 (C6), 70.66, 69.48 (C1%), 63.99
(C5), 55.32, 17.91, 17.56, 12.25; MS m/z: 525 (M+−43),
432, 389, 322, 296, 204, 187. Anal. calcd for
C31H44N2O6Si: C, 65.46; H, 7.80; N, 4.93. Found: C,
65.28; H, 7.76; N, 4.84%.
1H, NH), 5.11 (dd, 1H, J=8.9, 9.6), 4.83 (d, 1H,
J=4.0, C2H), 4.69 (t, 1H, J=8.8), 4.60 (m, 1H, C-
(6)H), 4.20 (dd, 1H, J=8.8, 9.6), 4.02 (dq, 1H, J=4.01,
6.4, C-(1%)H), 3.13 (d, 1H, J=8.4, C-(5)H), 1.75–1.15
(m, 12H), 0.95 (s, 24H), 0.88 (t, 3H, J=7.3); 13C NMR:
168.10 (C4), 160.44, 136.32, 128.80, 128.15, 127.63,
82.19 (C2), 77.90 (C6), 70.86, 68.05 (C1%), 63.76 (C5),
56.29, 31.82, 30.22, 29.19, 28.51, 24.11, 22.40, 16.83,
16.44, 12.34, 11.82; MS m/z: 561 (M++1), 517 (M+−43),
389, 359, 286.
5.12.7. (2R,5R,6S)-6-Phenyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin-3-yl]-2-[1(S)-triisopropylsilanyloxyethyl]-1,3-oxa-
zinan-4-one 23d. [h]2D0=+183.2 (c 1.19, CHCl3); IR
(CHCl3): 1756, 1685; 1H NMR: 7.48–6.95 (m, 10H),
6.35 (s, 1H, NH), 5.10 (d, 1H, J=5.3, C-(5)H), 4.92 (d,
1H, J=3.7, C-(2)H), 4.77 (dd, 1H, J=5.87, 8.37), 4.64
(bs, 1H), 4.15 (dq, 1H, J=3.7, 6.28, C-(1%)H), 3.85 (t,
1H, J=8.3), 3.72 (m, 1H, C-(6)H), 1.02 (s, 24H); 13C
NMR: 165.81 (C4), 158.87, 137.13, 135.53, 128.65,
128.58, 128.50, 128.28, 127.25, 125.64, 86.02 (C2), 80.34
(C6), 70.71, 68.50 (C1%), 60.75 (C5), 55.80, 17.94, 17.90,
16.06, 12.14; MS m/z: 538 (M+), 495, 432, 390, 338,
293, 267, 187. Anal. calcd for C30H42N2O5Si: C, 66.88;
H, 7.86; N, 5.20. Found: C, 66.65; H, 7.88; N, 5.11%.
5.12.11. (2R,5R,6R)-6-(1-t-Butoxycarbonylindol-3-yl)-5-
[(4S)-2-oxo-4-phenyloxazolidin-3-yl]-2-[1(S)-triisopropyl-
silanyloxyethyl]-1,3-oxazinan-4-one 24f. [h]2D0=+84.3 (c
1
1.48, CHCl3); IR (CHCl3): 1753, 1733, 1684; H NMR:
8.18 (d, 1H, J=8.2), 7.44 (d, 1H, J=8.0), 7.35–7.00 (m,
4H), 6.85 (m, 2H), 6.53 (m, 3H), 6.03 (d, 1H, J=9.3,
C-(6)H), 5.02 (m, 2H, C-(2)H), 4.57 (t, 1H, J=8.8),
4.15 (dq, 1H, J=4.5, 6.2, C-(1%)H), 3.89 (dd, 1H, J=
8.8, 10.0), 3.62 (d, 1H, J=9.3, C5H), 1.65 (s, 9H), 1.32
(d, 3H, J=6.2), 0.97 (s, 21H); 13C NMR: 167.77 (C4),
158.87, 149.31, 135.42, 135.27, 128.84, 128.30, 127.56,
124.70, 124.25, 122.97, 119.49, 117.90, 115.22, 83.89,
83.77 (C2), 70.51, 69.45 (C6), 67.01 (C1%), 63.88 (C5),
58.10, 28.18, 17.94, 17.45, 12.22; MS m/z: 677 (M+),
634, 591, 534, 471, 432, 389, 305, 187. Anal. calcd for
C37H51N3O7Si: C, 64.93; H, 7.72; N, 6.31. Found: C,
65.15; H, 7.70; N, 6.43%.
5.12.8. (2R,5R,6R)-6-Phenyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin-3-yl]-2-[1(S)-triisopropylsilanyloxyethyl]-1,3-oxa-
zinan-4-one 24d. Mp 69°C; [h]2D0=+82.3 (c 3.02,
1
CHCl3); IR (CHCl3): 1757, 1687; H NMR: 7.25 (m,
5.12.12.
(2R,5R,6S)-6-Cyclohexyl-5-[(4S)-2-oxo-4-
6H), 7.00 (m, 2H), 6.75 (s, 1H, NH), 6.50 (d, 2H,
J=8.3), 5.82 (d, 1H, J=9.6, C6H), 5.10 (dd, 1H, J=
8.5, 10.2), 5.03 (d, 1H, J=4.5, C-(2)H), 4.55 (t, 1H,
J=8.5), 4.18 (m, 1H, C-(1%)H), 3.8 (dd, 1H, J=8.6,
10.2), 3.32 (d, 1H, J=9.6, C5H), 1.30 (d, 3H, J=6.3),
0.98 (s, 21H); 13C NMR: 168.14 (C4), 158.97, 137.90,
135.30, 128.84, 128.64, 128.47, 128.37, 127.52, 127.14,
phenyloxazolidin - 3 - yl] - 2 - [1(S) - triisopropylsilanyloxy-
ethyl]-1,3-oxazinan-4-one 23g. [h]2D0=+116.2 (c 1.67,
CHCl3); IR (CHCl3): 1754, 1684; 1H NMR: 7.25 (s,
5H), 6.00 (s, 1H, NH), 5.08 (dd, 1H, J=2.6, 8.3), 4.58
(m, 3H, C-(2)H, C-(5)H), 4.06 (dd, 1H, J=2.6, 8.3),
3.94 (dq, 1H, J=3.8, 6.2, C-(1%)H), 3.45 (dd, 1H, J=
3.7, 9.8, C-(6)H), 2.15–1.10 (m, 11H), 0.95 (s, 21H),

A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
453
0.72 (d, 3H, J=6.2); 13C NMR: 165.97 (C4), 158.89,
137.88, 128.71, 128.52, 126.68, 86.99 (C2), 84.01 (C6),
71.36, 68.37 (C1%), 59.81 (C5), 53.78, 38.17, 29.14, 28.49,
26.24, 25.63, 25.49, 17.95, 17.91, 16.29, 12.12; MS m/z:
342 (M+−202), 326, 292, 233. Anal. calcd for
C30H48N2O5Si: C, 66.14; H, 8.88; N, 5.14. Found: C,
65.95; H, 8.92; N, 5.05%.
J=6.2), 1.05 (s, 21H); 13C NMR: 168.84 (C4), 160.64,
135.73, 133.61, 129.49, 127.69, 77.42 (C2), 71.42 (C6),
70.86, 69.81 (C1%), 62.25 (C5), 61.51, 18.55, 18.07, 18.01,
12.43; MS m/z: 496 (M+−43), 389, 267, 187. Anal. calcd
for C29H41N3O5Si: C, 64.53; H, 7.66; N, 7.79. Found:
C, 64.70; H, 7.70; N, 7.76%.
5.12.17. (2R,5R,6R)-6-(3-Pyridyl)-5-[(4S)-2-oxo-4-phen-
yloxazolidin-3-yl]-2-[1(S)-triisopropylsilanyloxyethyl]-
1,3-oxazinan-4-one 24i. [h]2D0=+77.0 (c 0.80, CHCl3); IR
5.12.13. (2R,5R,6R)-6-Cyclohexyl-5-[(4S)-2-oxo-4-phen-
yloxazolidin-3-yl]-2-[1(S)-triisopropylsilanyloxyethyl]-
1,3-oxazinan-4-one 24g. [h]2D0=+66.5 (c 1.08, CHCl3);
1
(CHCl3): 1758, 1689; H NMR: 8.60 (bs, 1H), 8.48 (bs,
1
IR (CHCl3): 1759, 1681; H NMR: 7.40 (s, 5H), 6.28 (s,
1H), 7.45 (m, 1H), 7.20 (m, 2H), 7.05 (m, 2H), 6.58 (d,
2H, J=7.0), 6.43 (s, 1H, NH), 5.87 (d, 1H, J=9.8,
C-(6)H), 5.05 (m, 2H, C-(2)H), 4.60 (t, 1H, J=8.7),
4.16 (dq, 1H, J=4.7, 6.2, C-(1%)H), 3.95 (dd, 1H, J=
8.7, 10.3), 3.28 (d, 1H, J=9.8, C5H), 1.30 d, 3H,
J=6.2), 1.00 (s, 21H); 13C NMR: 167.60 (C4), 158.99,
134.95, 134.86, 129.05, 128.95, 127.55, 84.47 (C2), 70.65
(C6), 70.21, 69.24 (C1%), 63.97 (C5), 58.53, 17.92, 17.73,
12.22; MS m/z: 496 (M+−43), 389, 267, 187. Anal. calcd
for C29H41N3O5Si: C, 64.53; H, 7.66; N, 7.79. Found:
C, 64.31; H, 7.63; N, 7.92%.
1H, NH), 5.12 (dd, 1H, J=8.7, 9.6), 4.85 (d, 1H,
J=4.0, C-(2)H), 4.70 (t, 1H, J=8.7), 4.54 (dd, 1H,
J=1.9, 9.1, C-(6)H), 4.26 (dd, 1H, J=8.7, 9.6), 3.98
(dq, 1H, J=4.0, 3.3, C-(1%)H), 3.35 (d, 1H, J=9.1,
C-(5)H), 1.70–1.10 (m, 12H), 1.00 (s, 21H), 0.85 (m,
2H); 13C NMR: 168.65 (C4), 158.80, 136.50, 129.49,
129.12, 128.51, 82.26 (C2), 74.57 (C6), 70.25, 69.75 (C1%),
63.78 (C5), 53.91, 37.80, 30.13, 26.45, 26.16, 25.99,
24.43, 17.95, 16.73, 12.17; MS m/z: 501 (M+−43), 342,
325, 292, 233. Anal. calcd for C30H48N2O5Si: C, 66.14;
H, 8.88; N, 5.14. Found: C, 66.40; H, 8.85; N, 5.03%.
5.12.18. (2R,5R,6S)-6-(2-Thienyl)-5-[(4S)-2-oxo-4-phen-
yloxazolidin - 3 - yl] - 2 - [1(S) - triisopropylsilanyloxyeth-
yl]-1,3-oxazinan-4-one 23j. [h]2D0=+124.4 (c 1.16,
5.12.14. (2R,5R,6S)-6-Ethyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin-3-yl]-2-[1(S)-triisopropylsilanyloxyethyl]-1,3-oxa-
zinan-4-one 23h. [h]2D01=+100.0 (c 1.04, CHCl3); IR
(CHCl3): 1756, 1684; H NMR: 7.32 (s, 5H), 6.10 (s,
1H, NH), 5.10 (dd, 1H, J=5.2, 8.5), 4.70 (d, 1H,
J=3.7, C-(2)H), 4.61 (t, 1H, J=8.5), 4.30 (d, 1H,
J=4.4, C-(5)H), 4.08 (dd, 1H, J=5.2, 8.5), 4.02 (dq,
1H, J=3.7, 6.3, C-(1%)H), 3.67 (m, 1H, C-(6)H), 1.60
(m, 2H), 1.00 (m, 27H); 13C NMR: 165.89 (C4), 158.89,
137.66, 129.01, 128.67, 128.38, 86.69 (C2), 81.22 (C6),
70.86, 68.66 (C1%), 61.10 (C5), 55.38, 23.76, 17.99, 16.42,
12.24, 10.26; MS m/z: 447 (M+−43), 389, 289, 216.
Anal. calcd for C26H42N2O5Si: C, 63.64; H, 8.63; N,
5.71. Found: C, 63.80; H, 8.67; N, 5.60%.
1
CHCl3); IR (CHCl3): 1754, 1686; H NMR: 7.40 (d,
1H, J=4.80), 7.29 (m, 3H), 7.10 (m, 3H), 7.00 (m, 1H),
6.32 (s, 1H, NH), 5.33 (d, 1H, J=5.2, C-(6)H), 4.95 (d,
1H, J=3.8, C-(2)H), 4.89 (dd, 1H, J=5.6, 8.4), 4.71 (d,
1H, J=5.2, C-(5)H), 4.14 (dq, 1H, J=3.8, 6.4, C-
(1%)H), 4.08 (t, 1H, J=8.4), 3.86 (dd, 1H, J=5.6, 8.4),
1.04 (s, 21H), 0.98 (d, 3H, J=6.4); 13C NMR: 165.04
(C4), 158.89, 137.37, 137.17, 128.59, 128.48, 127.18,
126.98, 125.38, 124.89, 86.20 (C2), 78.05 (C6), 71.09,
68.30 (C1%), 60.54 (C5), 55.91, 18.12, 18.07, 16.16, 12.27;
MS m/z: 544 (M+), 501 (M+−43), 432, 389, 298, 272,
187. Anal. calcd for C28H40N2O5SSi: C, 61.73; H, 7.40;
N, 5.14. Found: C, 61.94; H, 7.36; N, 5.03%.
5.12.15. (2R,5R,6R)-6-Ethyl-5-[(4S)-2-oxo-4-phenyloxa-
zolidin-3-yl]-2-[1(S)-triisopropylsilanyloxyethyl]-1,3-oxa-
zinan-4-one 24h. [h]2D0=+80.5 (c 0.88, CHCl3); IR
5.12.19. (2R,5R,6R)-6-(2-Thienyl)-5-[(4S)-2-oxo-4-phen-
yloxazolidin - 3 - yl] - 2 - [1(S) - triisopropylsilanyloxyeth-
yl]-1,3-oxazinan-4-one 24j. [h]2D0=+103.7 (c 0.98,
1
(CHCl3): 1759, 1684; H NMR: 7.40 (s, 5H), 6.25 (s,
1
1H, NH), 5.15 (dd, 1H, J=8.7, 9.8), 4.86 (dd, 1H,
J=1.2, 4.0, C-(2)H), 4.70 (t, 1H, J=8.7), 4.60 (dt, 1H,
J=3.3, 8.5, C-(6)H), 4.20 (dd, 1H, J=8.7, 9.8), 4.02
(dq, 1H, J=4.0, 6.2, C-(1%)H), 3.15 (d, 1H, J=8.5,
C-(5)H), 1.60 (m, 2H), 1.20 (d, 3H, J=6.2), 1.00 (s,
21H), 0.76 (t, 3H, J=7.3); 13C NMR: 168.09 (C4),
158.61, 136.55, 129.54, 129.22, 128.36, 82.19 (C2), 72.57
(C6), 70.43, 69.73 (C1%), 63.84 (C5), 56.79, 25.13, 17.99,
16.93, 12.33, 8.91; MS m/z: 447 (M+−43), 389, 289, 216.
Anal. calcd for C26H42N2O5Si: C, 63.64; H, 8.63; N,
5.71. Found: C, 63.43; H, 8.60; N, 5.83%.
CHCl3); IR (CHCl3): 1758, 1688; H NMR: 7.28 (m,
2H), 7.17 (m, 2H), 7.02 (m, 2H), 6.77 (m, 2H), 6.42 (s,
1H, NH), 6.14 (d, 1H, J=9.2, C-(6)H), 5.13 (dd, 1H,
J=8.6, 10.0), 5.07 (dd, 1H, J=1.6, 4.40 C-(2)H), 4.65
(t, 1H, J=8.6), 4.15 (dq, 1H, J=4.4, 6.4, C-(1%)H), 3.98
(dd, 1H, J=8.6, 10.0), 3.46 (d, 1H, J=9.2, C-(5)H),
1.30 (d, 3H, J=6.4), 1.04 (s, 21H); 13C NMR: 167.06
(C4), 158.68, 140.98, 135.45, 128.83, 128.74, 127.43,
126.50, 126.36, 125.78, 82.90 (C2), 70.83, 69.78 (C6),
69.24 (C1%), 63.91 (C5), 59.43, 18.12, 18.09, 17.14, 12.36;
MS m/z: 501 (M+−43), 432, 389, 298, 272, 187. Anal.
calcd for C28H40N2O5SSi: C, 61.73; H, 7.40; N, 5.14.
Found: C, 61.50; H, 7.37; N, 5.27%.
5.12.16. (2R,5R,6S)-6-(3-Pyridyl)-5-[(4S)-2-oxo-4-phen-
yloxazolidin-3-yl]-2-[1(S)-triisopropylsilanyloxyethyl]-
1,3-oxazinan-4-one 23i. [h]2D0=+63.9 (c 1.38, CHCl3); IR
5.12.20. (2R,5R,6S)-6-(2-Furyl)-5-[(4S)-2-oxo-4-phenyl-
oxazolidin-3-yl]-2-[1(S)-triisopropylsilanyloxyethyl]-1,3-
oxazinan-4-one 23k. [h]2D0=+94.8 (c 0.48, CHCl3); IR
1
(CHCl3): 1730, 1683; H NMR: 8.55 (bs, 1H), 8.35 (bs,
1H), 7.58 (d, 1H, J=7.5), 7.35–7.15 (m, 4H), 6.85 (d,
2H, J=6.8), 6.00 (bs, 1H, NH), 5.26 (m, 1H, C-(6)H),
5.10 (m, 2H, C-(2)H), 4.55 (t, 1H, J=8.9), 4.08 (m, 2H,
C-(1%)H), 3.92 (d, 1H, J=4.2, C-(5)H), 1.25 (d, 3H,
1
(CHCl3): 1757, 1688; H NMR: 7.51 (m, 1H), 7.32 (m,
3H), 7.16 (m, 2H), 6.50 (m, 2H), 6.28 (s, 1H, NH), 5.10
(m, 2H, C-(6)H), 4.90 (d, 1H, J=3.6, C-(2)H), 4.65 (d,

454
A. Bongini et al. / Tetrahedron: Asymmetry 12 (2001) 439–454
1H, J=4.4, C-(5)H), 4.35 (t, 1H, J=8.8), 4.13 (dq, 1H,
J=3.6, 6.4 C-(1%)H), 3.93 (dd, 1H, J=5.2, 8.4), 1.04 (m,
24H); 13C NMR: 164.84 (C4), 158.70, 148.30, 142.76,
137.52, 128.66, 128.45, 126.96, 110.68, 108.92, 86.35
(C2), 75.81 (C6), 71.18, 68.38 (C1%), 60.53 (C5), 55.20,
18.12, 18.07, 16.28, 12.30; MS m/z: 485 (M+−43), 389,
256, 187. Anal. calcd for C28H40N2O6Si: C, 63.61; H,
7.63; N, 5.30. Found: C, 63.49; H, 7.67; N, 5.45%.
10. Danishefsky, S. J.; De Ninno, M. P. Angew. Chem., Int.
Ed. Engl. 1987, 26, 15.
11. Ntirampebura, D.; Ghosez, L. Tetrahedron Lett. 1999,
40, 7079.
12. Jnoff, E.; Ghosez, L. J. Am. Chem. Soc. 1999, 121, 2617.
13. Ghosez, L.; Jnoff, E.; Bayard, P.; Sainte, F.; Beaudeg-
nies, R. Tetrahedron 1999, 55, 3387.
14. Ghosez, L.; Bayard, P.; Nshimyumukiza, P.; Gouverneur,
V.; Sainte, F.; Beaudegnies, R.; Rivera, M.; Frisque-Hes-
bain, A. M.; Wynants, C. Tetrahedron 1995, 51, 11021.
15. Ghosez, L. Pure Appl. Chem. 1996, 68, 15.
16. Gouverneur, V.; Ghosez, L. Tetrahedron 1996, 52, 7585.
17. Barluenga, J.; Suarez-Sobrino, A.; Lopez, L. A.
Aldrichim. Acta 1999, 32, 4.
5.12.21. (2R,5R,6R)-6-(2-Furyl)-5-[(4S)-2-oxo-4-phenyl-
oxazolidin-3-yl]-2-[1(S)-triisopropylsilanyloxyethyl]-1,3-
oxazinan-4-one 24k. [h]2D0=+151.3 (c 0.96, CHCl3); IR
1
(CHCl3): 1760, 1692; H NMR: 7.30 (m, 4H), 6.94 (m,
2H), 6.48 (bs, 1H, NH), 6.37 (m, 2H), 5.85 (d, 1H,
J=9.2, C-(6)H), 5.14 (dd, 1H, J=8.6, 10.2), 5.07 (dd,
1H, J=2.0, 4.4, C-(2)H), 4.65 (t, 1H, J=8.6), 4.10 (dq,
1H, J=4.4, 6.4, C-(1%)H), 3.98 (dd, 1H, J=8.6, 10.2),
3.88 (d, 1H, J=9.2, C-(5)H), 1.25 (d, 3H, J=6.4), 1.02
(s, 21H); 13C NMR: 167.03 (C4), 158.62, 150.03, 142.91,
135.69, 128.94, 128.80, 127.39, 110.57, 82.06 (C2), 70.72,
68.61 (C6), 67.44 (C1%), 63.79 (C5), 55.27, 18.08, 18.04,
16.80, 12.35; MS m/z: 485 (M+−43), 389, 256, 187.
Anal. calcd for C28H40N2O6Si: C, 63.61; H, 7.63; N,
5.30. Found: C, 63.82; H, 7.60; N, 5.22%.
18. Panunzio, M.; Zarantonello, P. Org. Process Res. Dev.
1998, 2, 49.
19. Gandon, V.; Bertua, P.; Szymoniak, J. Tetrahedron 2000,
56, 4467.
20. Gandon, V.; Bertus, P.; Szymoniak, J. Tetrahedron Lett.
2000, 41, 3053.
21. Trost, B. M.; Fleming, I. Comprehensive Organic Synthe-
sis; Pergamon: Oxford, 1991; Vol. 5, p. 451.
22. Barluenga, J.; Joglar, J.; Gonzales, F. J.; Fustero, S.
Synlett 1990, 129.
23. Bandini, E.; Martelli, G.; Spunta, G.; Bongini, A.;
Panunzio, M. Tetrahedron Lett. 1996, 37, 4409.
24. Bongini, A.; Panunzio, M.; Piersanti, G.; Bandini, E.;
Martelli, G.; Spunta, G.; Venturini, A. Eur. J. Org.
Chem. 2000, 2379.
Acknowledgements
25. Martelli, G.; Spunta, G.; Panunzio, M. Tetrahedron Lett.
This work was partially supported by ‘Progetto Strate-
gico sulle applicazioni delle Micronde, CNR, Rome’.
Thanks are due to MURST, Cofin’98 (Rome) for finan-
cial support and to Dr. Giovanni Piersanti for helpful
discussions. E.C. thanks Farchemia s.r.l. Treviglio
(BG), Italy, for financial support.
1998, 39, 6257.
26. Panunzio, M.; Bacchi, S.; Campana, E.; Fiume, L.;
Vicennati, P. Tetrahedron Lett. 1999, 40, 8495.
27. Bacchi, S.; Bongini, A.; Panunzio, M.; Villa, M. Synlett
1998, 843.
28. Bandini, E.; Favi, G.; Martelli, G.; Panunzio, M.; Pier-
santi, G. Org. Lett. 2000, 1077.
29. Bandini, E.; Bongini, A.; Martelli, G.; Panunzio, M.;
Piersanti, G.; Spunta, G. Tetrahedron: Asymmetry 1999,
10, 1445.
References
1. Tietze, L. F.; Ketteschan, G. Stereoselective Heterocyclic
Synthesis 1; Springer: Berlin, 1997; Vol. 189, pp. 1–120.
2. Kagan, H. B.; Riant, O. Chem. Rev. 1992, 92, 1007.
3. Boger, D. L.; Weinreb, S. M. Hetero Diels–Alder
Methodology in Organic Synthesis; Academic Press: New
York, 1987; Vol. 47.
4. Jørgensen, K. A.; Johannsen, M.; Yao, S.; Audrian, H.;
Thorhauge, J. Acc. Chem. Res. 1999, 32, 605.
5. Jørgensen, K. A. Angew. Chem., Int. Ed. 2000, 39, 3558.
6. Cozzi, F.; Molteni, V. Stereoselective Synthesis of Dihy-
dropyrans by Hetero Diels–Alder Reactions; Societa`
Chimica Italiana: Rome, 1997; Vol. XXII.
30. Bandini, E.; Martelli, G.; Spunta, G.; Bongini, A.;
Panunzio, M.; Piersanti, G. Tetrahedron: Asymmetry
1997, 8, 3717.
31. Panunzio, M.; Villa, M.; Missio, A.; Rossi, T.; Seneci, P.
Tetrahedron Lett. 1998, 39, 6585.
32. Bandini, E.; Martelli, G.; Spunta, G.; Bongini, A.;
Panunzio, M. Synlett 1999, 1735.
33. Bongini, A.; Panunzio, M.; Bandini, E.; Martelli, G.;
Spunta, G. J. Org. Chem. 1997, 62, 8911.
34. Hart, D. J.; Kanai, K.; Thomas, D. G.; Yang, T.-K. J.
Org. Chem. 1983, 48, 289.
35. Hypercube, Inc. HyperChem; Rel. 5.11 ed.: Waterloo,
7. Carruthers, W. Cycloaddition Reactions in Organic Syn-
thesis; Pergamon: Oxford, 1990.
8. Waldmann, H. Synthesis 1994, 585.
9. Jurczak, J.; Bauer, T.; Chapuis, C. Hetero 4+2 Cycload-
dition. In Houben-Weyl Methods of Organic Chemistry;
Hoffmann, R. W.; Mulzer, J.; Schaumann, E., Eds.;
Thieme Verlag: Stuttgart, 1995; Vol. E21c, p. 2905.
Ontario, Canada.
36. Gage, J. R.; Evans, D. A. Organic Synthesis; John Wiley
& Sons, New York, 1990; Vol. 68; p. 77.
37. Boger, D. L.; Meyers, Jr., J. B. J. Org. Chem. 1991, 56,
5385.
38. Kutschy, P.; Dzurilla, M.; Takasugi, M.; Toeroek, M.;
Achbergerova, I. Tetrahedron 1998, 54, 3549.
.