N-vinyl-2-oxazolidinones: Efficient chiral dienophiles for the [4 + 2]-based de novo synthesis of new N-2-deoxyglycosides

Article abstract of DOI:10.1021/jo040102y

Under smooth Eu(fod)₃-catalyzed conditions, the inverse-electron demand hetero-Diels-Alder reactions between enantiopure N-vinyl-2-oxazolidinones 1a-f and representative β,γ-unsaturated α-ketoesters proceed with a high degree of endo and facial

Full text of DOI:10.1021/jo040102y

N-Vin yl-2-oxa zolid in on es: Efficien t Ch ir a l Dien op h iles for th e
[4 + 2]-Ba sed d e Novo Syn th esis of New N-2-Deoxyglycosid es
Catherine Gaulon,† Robert Dhal,† Teddy Chapin,† Vincent Maisonneuve,‡ and
Gilles Dujardin*,†
Unite´ de Chimie Organique Mole´culaire et Macromole´culaire (UMR CNRS 6011) et Laboratoire des
Oxydes et Fluorures (UMR CNRS 6010), Universite´ du Maine F-72085 Le Mans Cedex 9, France
dujardin@univ-lemans.fr
Received J anuary 5, 2004
Under smooth Eu(fod)3-catalyzed conditions, the inverse-electron demand hetero-Diels-Alder
reactions between enantiopure N-vinyl-2-oxazolidinones 1a -f and representative â,γ-unsaturated
R-ketoesters proceed with a high degree of endo and facial diastereoselectivity. The elucidation of
the stereostructure of these adducts, performed by X-ray analysis or chemical correlation, shows
that the endo-selective cycloaddition process is facially controlled in favor of the (2S,4S)-adduct
when starting from a (4S)-dienophile or vice versa. The specific interest of the adducts 10a -e,
derived from (E)-4-tert-butoxymethylene pyruvic acid methyl ester 9, has been exemplified by the
two-step and highly stereoselective transformation of these adducts into the new and valuable N-2-
deoxyglycosyl-oxazolidinones 12a -e, isolated in a pure diastereo- and enantiomeric form.
In tr od u ction
thermal inverse-electron demand [4 + 2] heterocycload-
dition of allenamides derived from lactams, oxazolidino-
nes, and imidazolidinones was described by Hsung’s
group in 1999.6 Good levels of stereoselectivity were
obtained with the chiral allenamide derived from Close’s
imidazolidinone toward a range of 1-oxabutadienes.
More recently, we have described the first examples
of an inverse-electron demand heterocycloaddition using
N-vinyl-2-oxazolidinone as the dienophile toward acti-
vated heterodienes under appropriate Lewis acid condi-
tions.7 Therefore, we oriented our work in evaluating the
stereochemical potential of 4-substituted and 4,5-disub-
stituted N-vinyl-2-oxazolidinones as new chiral dieno-
philes in a comparative or complementary way regarding
the chiral dienophiles (chiral vinyl ethers),8 chiral het-
erodienes,9 or chiral catalysts10 previously used for such
asymmetric [4 + 2] heterocycloadditions. Having gener-
alized a new mercury-free preparation method of such
N-vinylamides,11 we report herewith that these N-vinyl-
2-oxazolidinones are chiral dienophiles of choice toward
The discovery of new cycloreactants is a continuous
task in the field of pericyclic reactions. The use of
heterosubstituted dienes and dienophiles has provided
numerous and powerful asymmetric extensions1 and is
of specific interest for the application of [4 + 2] homo-
and hetero-Diels-Alder reactions2 to the synthesis of
natural and biologically active products. Regarding in-
verse-electron demand [4 + 2] heterocycloaddition meth-
ods, aza-substituted dienophiles have been used more
rarely than their oxygenated counterparts so far. Con-
tributions in this field have mainly concerned the use of
electron-rich enamines.3-4 Interestingly, the first orga-
nocatalytic asymmetric version of an inverse-electron
demand hetero-Diels-Alder reaction was recently de-
scribed, based on the dienophilicity of a transient chiral
enamine, generated in situ, toward an activated hetero-
diene.5 In contrast, the use of weaker dienophiles such
as enamides or enecarbamates was seldom reported. The
† Unite´ de Chimie Organique Mole´culaire et Macromole´culaire
(UMR CNRS 6011).
(6) (a) Wei, L.-L.; Xiong, H.; Douglas, C. J .; Hsung, R. P. Tetrahedron
Lett. 1999, 40, 6903. (b) Wei, L.-L.; Hsung, R. P.; Xiong, H.; Mulder, J .
A.; Nkansah, N. T. Org. Lett. 1999, 1, 2145. (c) Rameshkumar, C.;
Hsung, R. P. Synlett 2003, 1241.
‡ Laboratoire des Oxydes et Fluorures (UMR CNRS 6010).
(1) Chiral Auxiliaries in Cycloadditions; Ru¨ck-Braun, H. K., Ed.;
Wiley: Berlin; 1999.
(2) (a) Boger, D. L.; Weinreb, S. N. Hetero Diels-Alder Methodology
in Organic Synthesis; Academic Press: San Diego, 1987. (b) Tietze, L.
F.; Kettschau, G. Top. Curr. Chem. 1997, 189, 1-120.
(7) Gaulon, C.; Gizecki, P.; Dhal, R.; Dujardin, G. Synlett 2002, 952.
(8) (a) Dujardin, G.; Molato, S.; Brown, E. Tetrahedron: Asymmetry
1993, 4, 193. (b) Dujardin, G.; Rossignol, M.; Molato, S.; Brown, E.
Tetrahedron 1994, 50, 9037. (c) Dujardin, G.; Rossignol, M.; Brown,
E. Tetrahedron Lett. 1996, 37, 4007. (d) Dujardin, G.; Rossignol, M.;
Brown, E. Synthesis 1998, 763. (e) Gizecki, P.; Dhal, R.; Toupet, L.;
Dujardin, G. Org. Lett. 2000, 2, 585. (f) Gizecki, P.; Dhal, R.; Poulard,
C.; Gosselin, P.; Dujardin, G. J . Org. Chem. 2003, 68, 4338.
(9) (a) Tietze, L. F.; Schneider, C.; Montenbruck, A. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 980. (b) Tietze, L. F.; Montenbruck, A.;
Schneider, C. Synlett 1994, 509. (c) Tietze, L. F.; Schneider, C.; Grote,
A. Chem. Eur. J . 1996, 2, 139. (d) Hayes, P.; Dujardin, G.; Maignan,
M. Tetrahedron Lett. 1996, 37, 3687. (e) Dujardin, G.; Maudet, M.;
Brown, E. Tetrahedron Lett. 1997, 38, 1555. (f) Dujardin, G.; Maudet,
M.; Brown, E. Tetrahedron 1997, 53, 9679.
(3) Reviews: (a) Lenz, G. R. Synthesis 1978, 489. (b) Hickmott, P.
W. Tetrahedron 1982, 38, 1975. (c) Hickmott, P. W. Tetrahedron 1982,
38, 3363. (d) Whitesell, J . K.; Whitesell, M. A. Synthesis 1983, 517. (e)
Rappoport, Z. The Chemistry of Enamines in The Chemistry of
Functional Groups; J ohn Wiley and Sons: New York, 1994.
(4) (a) Fleming, I.; Karger, M. H. J . Chem. Soc. C 1967, 235. (b)
Chan, Y.; Epstein, W. W. Org. Synth. 1973, 53, 48. (c) Eiden, F.;
Winkler, W.; Wanner, K. T.; Markhauser, A. Arch. Pharm. 1985, 648.
(d) Eiden, F.; Winkler, W. Arch. Pharm. 1986, 704. (e) Eiden, F.;
Wu¨nsch, B.; Schu¨nemann, J . Arch. Pharm. 1990, 481. (f) Heathcock,
C. H.; Norman, M. H.; Dickman, D. A. J . Org. Chem. 1990, 55, 800.
(5) J uhl, K.; J ørgensen, K. A. Angew. Chem., Int. Ed. 2003, 32, 1498.
10.1021/jo040102y CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/20/2004
4192
J . Org. Chem. 2004, 69, 4192-4202

N-Vinyl-2-oxazolidinones
SCHEME 1
TABLE 1. Eu (fod )3-Ca ta lyzed Heter ocycloa d d ition of
â,γ-unsaturated R-ketoesters, leading to heterocycload-
ducts with high endo and facial selectivities under Eu-
(fod)3-catalyzed conditions. In addition, we considered in
this approach that, if efficient, the oxazolidinyl moiety
would act not only as a chiral inducing agent but also as
a valuable building block, providing new ways for the
stereocontrolled de novo synthesis of N-2-deoxyglycosides
or even sugar-R-amino acid hybrid12 derivatives. There-
fore, we describe hereby the efficient asymmetric syn-
theses of common potential precursors of such targets,
namely, the new N-2-deoxyglycosyl-oxazolidinones 12.
1a -f w ith 2
endo R/endo âf
(%)b endo/exof crude purified
yield
1
R1 R2 R3 timea
3
1
2
3
4
5
6
1a Et
1b
1c Ph
1d Bn
H
i-Bu
H
H
H
H
H
15 h
3a 77c
98/2
98/2
98/2
>98/2
>98/2
>98/2
96/4
3/97
96/4
>98/2 >98/2
<2/98 <2/98
<2/98 <2/98
>98/2
<2/98
96/4
H
6 days 3b 92d
9 days 3c 90e
38 h
H
3d 93
3e 80
1e
1f
H
H
Me Ph 38 h
Ph
Ph 4 days 3f
80
a
Reactions run on a 0.5 mmol scale; 1.0 equiv of each cyclore-
actant was used in all cases with 5 mol % Eu(fod)3 in refluxing
b
cyclohexane. Isolated yields after chromatography. c Isolated
yield of 75% was obtained on a 7 mmol scale, after 48 h of reaction.
Resu lts a n d Discu ssion
d
Isolated yield of 60% was obtained on a 9 mmol scale, after 7
days of reaction. e Isolated yield of 75% was obtained on a 2 mmol
scale, after 10 days of reaction. f Determined by 1H NMR (400
MHz).
As in the achiral series, we first investigated the
cycloaddition of a representative 2-activated heterodiene,
the (E)-benzylidene pyruvic acid methyl ester 2 (Scheme
1). Our previous study with achiral vinyloxazolidinone
showed that the best yields and endo selectivities were
obtained with the catalytic use of trivalent lanthanide
chelates (Eu-or Yb(fod)3, 5 mol %) in refluxing cyclohex-
ane.13 Under the same Lewis-acid catalyzed and mild
thermal conditions, the chiral N-vinyloxazolidinones 1a -
f11 displayed a fluctuating reactivity, depending on the
nature of the C-4 substituent. For less bulky dienophiles
1a , 1d , and 1e (R1 or R2 ) Et, Bn, and Me, respectively),
the completion of the cycloaddition occurred in less than
40 h. In contrast, for more bulky dienophiles 1b, 1c, and
1f (R1 or R2 ) i-Bu, Ph), a complete conversion required
an extended time period (entries 2, 3, 6, Table 1).
Interestingly, apart from the high endo selectivity ob-
served in each case, the level of facial selectivity was
noteworthy, being homogeneous and high, ranging from
96/4 to 98/2 or more for the six adducts 3a -f produced.
In addition, all heteroadducts except 3c were obtained
as a single endo diastereomer after chromatography and
in 77-93% isolated yields.
described in our laboratory for chiral vinyl ether-derived
heteroadducts. This method is based on the ozonolytic
cleavage of the dihydropyrane ring and subsequent
oxidation, thus leading after esterification to known
phenyl succinic acid methyl ester 8 (Scheme 2, Table 2).8b
Ozonolysis of adducts 3a -c at -78 °C in a methanolic
medium, followed by a treatment with acetic anhydride
and triethylamine, actually led to different results,
depending on the conditions. The use of a large excess of
acetic anhydride and triethylamine gave a minor amount
of the expected aldehyde-ester 4 (12-15%) as well as a
significant amount of N,O-acylal 5. With only 1.25 equiv
of NEt3 and 2.5 equiv of Ac2O, we obtained a 1:1 mixture
of the expected aldehyde-ester 4 and of the corresponding
N,O-hemiaminal 6. In this latter case, a further acidic
treatment (4 N H2SO4 in acetone) converted the N,O-
hemiaminal 6 into 4 efficiently. Thereby, J ones oxidation
of the aldehyde-ester 4 and a final esterification provided
the diester 8 in good overall yield (51% from 3b, entry
2). In the three cases studied, the specific rotation of the
latter compound 8 established the absolute configuration
at the C-4 center of the corresponding adduct unambigu-
ously. In the case of the adduct 3a , this attribution was
confirmed by X-ray analysis (see Supporting Information)
of the corresponding crystalline amido-ester 7a produced
by J ones oxidation of the N,O-acylal 5a . Finally, the
enantiopurity of 8, determined in every case by chiral
GC, was found to agree with the facial selectivity
established by 1H NMR for the corresponding adduct.
This chemical correlation established a univocal relation-
ship between the inducing stereogenic center at C-4′ of
the oxazolidinyl ring and the two stereogenic centers
created on the dihydropyranic ring: the endo-selective
cycloaddition process proved to be facially controlled in
favor of the (2R,4R)-adduct 3 when starting from a (4R)-
dienophile and in favor of the (2S,4S)-adduct 3 when
starting from a (4S)-dienophile. Considering the strong
To determine the absolute configurations of the ad-
ducts 3a -f, we used a correlation method previously
(10) (a) Wada, E.; Yasuoka, H.; Kanemasa, S. Chem. Lett. 1994,
1637. (b) Wada, E.; Pei, W.; Yasuoka, H.; Kanemasa, S. Tetrahedron
1996, 52, 1205. (c) Evans, D. A.; J ohnson, J . S. J . Am. Chem. Soc. 1998,
120, 4895. (d) Thorhauge, J .; J ohannsen, M.; J ørgensen, K. A. Angew.
Chem., Int. Ed. 1998, 37, 2404. (e) Evans, D. A.; Olhava, E. J .; J ohnson,
J . S.; J aney, J . M. Angew. Chem., Int. Ed. 1998, 37, 3372. (f) Evans,
D. A.; J ohnson, J . S.; Olhava, E. J . J . Am. Chem. Soc. 2000, 122, 1635.
(g) Zhuang, W.; Thorhauge, J .; J ørgensen, K. A. Chem. Commun. 2000,
459-460. (h) Audrain, H.; Thorhauge, J .; Hazell, R. G.; J ørgensen, K.
A. J . Org. Chem. 2000, 65, 4487. (i) Gademann, K.; Chavez, D. E.;
J acobsen, E. N. Angew. Chem., Int. Ed. 2002, 31, 3059.
(11) Gaulon, C.; Dhal, R.; Dujardin, G. Synthesis 2003, 2269. The
N-vinyl-2-oxazolidinone 1f17a was prepared according this procedure
in 85% overall yield.
(12) Schweizer, F. Angew. Chem., Int. Ed. 2002, 41, 230. See also:
Taylor, C. M. Tetrahedron 1998, 54, 11317.
(13) Further experiments using SnCl4 as an alternative Lewis acid
confirmed our previous observations in achiral series: reaction pro-
ceeded at low temperature with low or without diastereoselectivities.
J . Org. Chem, Vol. 69, No. 12, 2004 4193

Gaulon et al.
SCHEME 2a
a
Reagents and conditions: (i) O3, CH2Cl2, MeOH, -78 °C. (ii) Ac2O (20 equiv), NEt3 (15 equiv). (iii) Ac2O (2.5 equiv), NEt3 (1.5 equiv).
(iv) CrO3-H2SO4/acetone. (v) CH2N2 or HCl/MeOH. (vi) H2SO4/acetone.
TABLE 2. Ster eoch em ica l Cor r ela tion of Ad d u cts 2a -c w ith P h en yl Su ccin ic Acid Ester 8
final products
yieldb (%)
starting adduct
R1
R2
R3
methoda
amide 7
diester 8
configurationc
eed
1
2
3
3a
3b
3c
Et
H
Ph
H
i-Bu
H
H
H
H
A
B
A
42
15
51
12
(S)-(+)
(R)-(-)
(S)-(+)
>98
96
92
56
a
Method A: steps i and ii, NEt3 (15 equiv), Ac2O (20 equiv), step iv on the mixture, and then step v (see Scheme 2). Method B: steps
i and iii, NEt3 (1.25 equiv), Ac2O (2.5 equiv), and then steps vi, iv, and v (see Scheme 2). Isolated yields. c Established by specific rotation.
Determined by chiral GC.
b
d
1
analogies that prevail between the H NMR data of all
adducts 3a -f (see Supporting Information), the configu-
rations of the (major) endo adducts 3d -f were assigned
on the assumption of the same relationship (Table 1).
modified conditions: reaction time extended to 4-5 days,
2-fold addition of the catalyst, and use of an excess of 9
(Table 3). Under these optimized conditions, adducts
10a -e were obtained in 40-66% isolated yields with a
nearly total endo selectivity and a high facial selectivity
(from 95/5 to 98/2 or more).
On the basis of these results, the study on heterocy-
cloaddition of chiral N-vinyloxazolidinones 1a -f was
extended to “prosugar” heterodienes (e.g., 4-alkoxy-
substituted). Our previous study with the unsubstituted
N-vinyloxazolidinone had shown that under the same
catalytic conditions, the best results and endo selectivities
in this series were obtained with the 4-tert-butoxymeth-
ylene pyruvic acid ester 9.7 Although notably less reactive
than its phenylated counterpart 2, the heterodiene 9 gave
rise to the expected cycloadducts with the N-vinyloxazo-
lidinones 1a -e (Scheme 3) when using the following
The moderate yields were possibly a consequence of
the lack of homogeneity of the reaction medium that
prevailed specifically when heterodiene 9 was employed
in refluxing cyclohexane. All our attempts to increase the
conversion rate by using another solvent (chloroform,
dichloromethane, toluene, perfluorocyclohexane) were
unsuccessful. Adducts 10a and 10d were obtained after
chromatography in a pure single diastereomeric form as
crystallized compounds, and X-ray analysis allowed the
4194 J . Org. Chem., Vol. 69, No. 12, 2004

N-Vinyl-2-oxazolidinones
F IGURE 1. Common strategy for the transformation of [4 + 2] heteroadducts into X-glycosides.
SCHEME 3
TABLE 3. Eu (fod )3-Ca ta lyzed Heter ocycloa d d ition of
particular case. In contrast, the application of the reac-
tion conditions described by Gonda and co-workers14
proved to be convenient: the low-temperature treatment
of adducts 10 with an excess of DIBAH in the presence
of a stoichiometric amount of BF3‚Et2O led to the desired
crude allylic alcohols 11 in high to quantitative yields
and with fair purities (Scheme 4, Table 4). It should be
noticed that a significant loss of material and purity was
observed in the crude product when the reduction was
conducted without the use of a Lewis acid. Attempts to
isolate these sensitive allylic alcohols 11 gave tedious
results (40-60% yield after chromatography on silicagel),
so we employed the crude allylic alcohols 11 in the
subsequent steps.
1a -f w ith 9
yield
entry
1
R1 R2 R3 timea 10b (%)c endo/exo endo R/endo â
1
2
3
4
5
6
1a Et
1b
1c Ph
1d
1e Me
1f Ph
H
i-Bu
H
Bn
H
H
H
H
H
H
5 days 10a
4 days 10b
4 days 10c
4 days 10d
52
40
54
42
66
97/3
98/2
>98/2
>98/2
>98/2
>98/2
5/95
>96/4
<2/98
97/3
H
H
Ph 4 days 10e
Ph 5 days 10f <20
a
b
Reactions run on 0.5 mmol scale. Reaction conditions: 9/1
ratio ) 1.0 for 10a and 1.5 for 10b-f; catalyst ) Eu(fod)3, 2 × 5
mol %; refluxing cyclohexane. c Isolated yields after chromatog-
raphy.
determination of their configuration (see Supporting
Information). Not surprisingly, the same relationship
between the inducing stereogenic center at C-4′ of the
oxazolidinyl ring and the two stereogenic centers created
on the dihydropyranic ring was found for adducts 10
when compared to adducts 3: the endo-selective cycload-
dition process proved to be facially biased in favor of the
configuration (2S,4S,4′S)- for 10d and of the configura-
tion (2R,4R,4′R)- for 10a . Considering the significant
The following hydroboration step was conducted with
excess BH3‚Me2S. Regarding the oxidation of the inter-
mediate organoborane, and given the predictable sensi-
tivity of the carbamate functionality under the harsh
basic conditions classically used (6 M NaOH, H2O2,
refluxing THF), Kabalka’s procedure using trimethyl-
amine N-oxide dihydrate in refluxing THF15 was selected.
In the relevant literature, de novo access to O-glycosides
via a classical hydroboration-oxidation sequence is not
commonly carried out on the allylic alcohol B, but more
frequently starting from the corresponding allylic acetate
C (Figure 1, P′ ) Ac). Previous results in our laboratory8c,16
pointed out that hydroboration-oxidation of the double
bond can be performed on unprotected substrates B in
acceptable yields and without a negative effect on the
selectivities. In the present case, due to the modification
introduced at the oxidation step by using Kabalka’s
procedure, the hydroboration-oxidation sequence was
then comparatively tested on both the unprotected di-
hydropyran 11a (R1 ) Et) and the corresponding allylic
acetate 13a (Scheme 5).
1
analogies that prevail again between the H NMR data
of all adducts 10a -e (See Supporting Information), the
configurations of whole adducts 10 were assigned on the
assumption of the same relationship.
In a final part of this work, de novo access to N-2-
deoxyglycosyl-oxazolidinones 12 was investigated start-
ing from adducts 10. For this purpose, we envisioned the
use of the strategy commonly employed to transform
heteroadducts (A) derived from other types of heterosub-
stituted dienophiles (such as vinyl ethers) into X-glyco-
sides (D) (O-alkyl-2-deoxyglucosides for instance): re-
duction of the ester function at C-6 (giving B), followed
by protection of the allylic hydroxyl function (giving C)
and then regio- and stereoselective hydroboration-oxida-
tion of C (or even of B in some cases) (Figure 1).
Application of this sequence to the acetate 13a led to
a mixture of 12a along with the corresponding monoac-
etate 14a (Scheme 5). Reacetylation of the mixture under
Nevertheless, given the presence of the oxazolidinyl
functionality, some modifications were introduced. In-
deed, the reduction of the ester function in the first step
had to be achieved with convenient chemoselectivity. Our
first assays had shown that LiAlH4 (classically used for
reduction of type-A adducts) was ineffective in this
(14) (a) Moriwake, T.; Hamano, S.; Miki, D.; Saito, S.; Torii, S. Chem.
Lett. 1986, 815. (b) Gonda, J .; Helland, A.-C.; Ernst, B.; Bell, D.
Synthesis 1993, 7, 729.
(15) Kabalka, G. W.; Hedgecock, H. C. J . Org. Chem. 1975, 40, 1776.
(16) Michelet, V.; Adieh, K.; Bulic, B.; Genet, J . P.; Dujardin, G.;
Rossignol, S.; Brown, E.; Toupet, L. Eur. J . Org. Chem. 1999, 2885.
J . Org. Chem, Vol. 69, No. 12, 2004 4195

Gaulon et al.
SCHEME 4a
a
Reagents and conditions: (i) DIBAH, BF3‚Et2O, CH2Cl2, -78 °C. (ii) BH3‚Me2S, THF, rt. (iii) Me3NO, diglyme, 110 °C.
SCHEME 5 a
a
Reagents and conditions: (i) Ac2O, DMAP, NEt3, rt. (ii) NaH, BnBr, DMF, rt. (iii) BH3‚Me2S, THF, rt. (iv) Me3NO, THF, reflux. (v)
Me3NO, diglyme, 110 °C.
TABLE 4. Syn th esis of N-Glycosyl-oxa zolid in on es
12a -e
state of overall diastereomeric purity (>98% in all cases).
Assignment of the common relative configuration for
1
N-glycosyl-oxazolidinones 12a -e was established by H
crude yield
of 11 (%)
isolated yield
10
10a Et
10b
10c Ph
10d
10e Me
R1
R2
R3 11
12
of 12a (%)
NMR NOE measurements for 12a and 12d and by
correlation between 1H NMR data for the other com-
pounds (see Supporting Information).
1
2
3
4
5
H
i-Bu
H
Bn
H
H
H
H
H
11a
11b
11c
11d
>95
95
71
90
>95
12a
12b
12c
12d
12e
46
61
44
52
48
H
Considering the limited yields observed in the latter
step starting from allylic alcohols 11a -e, other protected
analogues of 11a were finally tested: the allylic O-benzyl
ether 16a quantitatively obtained from 11a proved to be
a convenient substrate for this purpose, leading to the
orthogonally 4,6-diprotected N-glycoside 17a in a 61%
yield in a pure diastereomeric form (Scheme 5).
H
Ph 11e
a
Isolated yield of pure diastereomer after chromatography.
classical conditions failed to provide a single final prod-
uct: after chromatography, the unprotected N-glycoside
12a , the monoacetate 14a , and the corresponding diac-
etate 15a were isolated in 23, 14, and 30% yields,
respectively. In contrast, applying the same hydrobora-
tion-oxidation conditions to the free allylic alcohol 11a
led to the desired N-glycoside 12a in a highly stereose-
lective manner and 40% yield. As a consequence, the
hydroboration-oxidation sequence was thus further in-
vestigated with unprotected subtrates. According to
previous observations,15 replacing THF with a solvent
with a higher boiling point such as diglyme proved to
enhance the oxidation rate significantly (Scheme 4, Table
4, entry 1). These conditions were successfully applied
to allylic alcohols 11a -e: the expected N-glycosyl-
oxazolidinones 12a -e were isolated in 32-58% overall
yields from the corresponding adducts 10 and in a high
Con clu sion
This study has demonstrated the usefulness and the
high potential of N-vinyloxazolidinones as new chiral
dienophiles in inverse-electron demand [4 + 2] hetero-
Diels-Alder reactions.17 Such heterocycloaddition meth-
ods involving â,γ-unsaturated R-ketoesters as the het-
erodienes were achieved with high, homogeneous di-
astereoselectivities, weakly dependent on the substitution
pattern of the chiral oxazolidinyl moiety. A univocal
relationship between the inducing stereogenic center at
C-4′ of the oxazolidinyl ring and the two stereogenic
centers created on the dihydropyranic ring was estab-
lished: the endo-selective Eu(fod)3-catalyzed cycloaddi-
tion process proved to be facially controlled in favor of
4196 J . Org. Chem., Vol. 69, No. 12, 2004

N-Vinyl-2-oxazolidinones
SCHEME 6
O), 1737 (CdO), 1643 (CdC), 1282, 1249, 1130 (C-O) cm-1
;
the (2S,4S)-adduct when starting from a (4S)-dienophile
and in favor of the (2R,4R)-adduct when starting from a
(4R)-dienophile (Scheme 6). We have shown not only that
these new cycloreactants can act as superior chiral
dienophiles but also that they have potential in chiron
approaches toward new and valuable targets. A first
validation of this strategy was exemplified by the asym-
metric synthesis of a series of new N-2-deoxyglycosyl-
oxazolidinones. Access to other 2-deoxyglucose-R-amino
acid hybrid derivatives by this approach is in progress
in our laboratory, together with the evaluation of the
potential of the title N-vinylic compounds in other
asymmetric pericyclic reactions.
1H NMR (400 MHz, CDCl3) δ 0.90 (3H, d, J ) 6.6 Hz), 0.97
(3H, d, J ) 6.6 Hz), 1.56 (1H, m), 1.67 (1H, ddd, J ) 14.0,
10.1 and 4.2 Hz), 1.80 (1H, ddd, J ) 14.0, 9.8 and 3.0 Hz),
2.15 (1H, dt, J ) 13.0 and 11.1 Hz), 2.26 (1H, ddt, J ) 13.0,
6.5 and 2 Hz), 3.81 (3H, s), 3.86 (1H, ddd, J ) 11.1, 6.5 and
2.4 Hz), 3.99 (1H, m), 4.04 (1H, dd, J ) 8.0 and 6.1 Hz), 4.40
(1H, t, J ) 8.0 Hz), 5.70 (1H, dd, J ) 11.1 and 2 Hz), 6.15
(1H, t, J ) 2 Hz), 7.22 (2H, d, J ) 6.9 Hz), 7.29 (1H, t, J ) 7.5
Hz), 7.36 (2H, dd, J ) 7.5 and 6.9 Hz); 13C NMR + DEPT 135
(100 MHz, CDCl3) δ 21.4 (CH3), 23.5 (CH3), 24.6 (CH), 33.9
(CH2), 39.1 (CH), 42.5 (CH2), 52.0 (CH), 52.2 (CH3), 68.0 (CH2),
81.5 (CH), 113.9 (CH), 126.9 (CH), 127.1 (CH), 128.6 (CH),
141.9 (C), 143.6 (C), 156.8 (C), 162.4 (C); HRMS (EI) calcd for
C
20H23NO4 [M - H2O]+ 341.16271, found 341.1608. [R]20
D
+1.45 (c 1.1, CH2Cl2).
Exp er im en ta l Section
(2R,4R)-2-[(4R)-4-P h en yl-2-oxo-1,3-oxa zolid in -3-yl]-4-
p h en yl-3,4-d ih yd r o-2H-p yr a n -6-ca r boxylic Acid Meth yl
Ester 3c. From 1c (94.5 mg, 0.5 mmol), 3c (endo/exo 98/2,
endo-R/â 96/4) was obtained after chromatography as a white
foam (170 mg, 90%). Major isomer 3c-endo-R: IR (neat) 1761
Gen er a l P r ep a r a tion of Heter o-a d d u cts 3a -f w ith Eu -
(fod )3. A solution of heterodiene 218 (1 equiv, 95 mg, 0.5 mmol),
N-vinyl-2-oxazolidinone 1a -f11,17 (1 equiv, 0.5 mmol), and Eu-
(fod)3 (0.05 equiv, 26 mg, 0.025 mmol) in cyclohexane (5 mL)
was refluxed under nitrogen for the time period indicated in
Table 1. After removal of solvent, the crude product was
chromatographed (silica gel 40/1; cyclohexane/AcOEt 80/20 to
50/50).
(2R,4R)-2-[(4R)-4-E t h yl-2-oxo-1,3-oxa zolid in -3-yl]-4-
p h en yl-3,4-d ih yd r o-2H-p yr a n -6-ca r boxylic Acid Meth yl
Ester 3a . From 1a (70.5 mg, 0.5 mmol), 3a (endo/exo 98/2,
endo-R/â 99/1) was obtained after chromatography as a yellow
oil (165 mg, 77%). Major isomer 3a -endo-R: IR (neat) 1757
(CdO), 1645 (CdC), 1423, 1367, 1284, 1216, 1132, 1091, 1032,
762, 731, 702 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.95 (3H, t,
J ) 7.4 Hz), 1.80 (2H, m), 2.12 (1H, dt, J ) 13.0 and 11.4 Hz),
2.25 (1H, ddt, J ) 13.0, 6.4 and 1.7 Hz), 3.80 (3H, s), 3.88 (1H,
ddd, J ) 11.4, 6.4 and 2.2 Hz), 3.90 (1H, m), 4.07 (1H, dd, J )
8.6 and 5.4 Hz), 4.37 (1H, t, J ) 8.6 Hz), 5.75 (1H, dd, J )
11.2 and 2 Hz), 6.15 (1H, t, J ) 2 Hz), 7.23 (2H, d, J ) 6.9
Hz), 7.29 (1H, t, J ) 7.4 Hz), 7.35 (2H, dd, J ) 7.4 and 6.9
Hz); 13C NMR + DEPT 135 (100 MHz, CDCl3) δ 7.8 (CH3),
26.4 (CH2), 34.1 (CH2), 39.0 (CH), 52.0 (CH3), 54.2 (CH), 67.0
(CH2), 81.3 (CH), 113.6 (CH), 126.9 (CH), 127.1 (CH), 128.7
(CdO), 1740 (CdO), 1646 (CdC), 1287, 1256, 1130 (C-O) cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.27 (1H, ddt, J ) 13.3, 6.1 and
1.7 Hz), 2.56 (1H, dt, J ) 13.3 and 11.3 Hz), 3.66 (1H, ddd, J
) 11.3, 6.1 and 2.2 Hz), 3.75 (3H, s), 4.16 (1H, dd, J ) 8.8 and
8.0 Hz), 4.66 (1H, t, J ) 8.8 Hz), 5.10 (1H, dd, J ) 8.8 and 8.0
Hz), 5.23 (1H, dd, J ) 11.3 and 1.7 Hz), 5.99 (1H, t, J ) 2 Hz),
7.10-7.50 (10H, m); 13C NMR + DEPT 135 (100 MHz, CDCl3)
δ 33.3 (CH2), 39.2 (CH), 51.9 (CH3), 59.2 (CH), 65.7 (CH2), 82.0
(CH), 113.9 (CH), 127.0-129.0 (CH), 137.4 (C), 141.9 (C), 143.3
(C), 156.7 (C), 162.3 (C); HRMS (EI) calcd for C22H21NO5 [M]+
379.14197, found 379.1448. [R]20 -67.9 (c 0.96, CH2Cl2).
D
(2R,4R)-2-[(4R)-4-Ben zyl-2-oxo-1,3-oxa zolid in -3-yl]-4-
p h en yl-3,4-d ih yd r o-2H-p yr a n -6-ca r boxylic Acid Meth yl
Ester 3d . From (4R)-1d (102 mg, 0.5 mmol), 3d (endo/exo >
98/2, endo-R/â > 98/2) was obtained after chromatography as
a white foam (183 mg, 93%). Major isomer 3d -endo-R: IR
(neat) 1760 (CdO), 1734 (CdO), 1641 (CdC), 1424, 1289, 1133,
1093, 1031, 764, 715 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.13
(1H, dt, J ) 11.6 and 13.0 Hz), 2.30 (1H, ddt, J ) 2.0, 6.4 and
13.0 Hz), 2.94 (1H, dd, J ) 8.6 and 14.0 Hz), 3.30 (1H, dd, J
) 3.9 and 14.0 Hz), 3.81 (3H, s), 3.87 (1H, ddd, J ) 2.5, 6.4
and 11.6 Hz), 4.10 (1H, dd, J ) 4.0 and 8.0 Hz), 4.17 (1H, t, J
) 8.0 Hz), 4.19 (1H, m), 5.78 (1H, dd, J ) 2.0 and 11.6 Hz),
6.16 (1H, t, J ) 2.0 Hz), 7.19-7.40 (10H, m); 13C NMR + DEPT
135 (100 MHz, CDCl3) δ 34.5 (CH2), 39.3 (CH), 40.0 (CH2), 52.3
(CH3), 54.5 (CH), 67.0 (CH2), 81.7 (CH), 114.0 (CH), 127.2-
129.5 (6xCH), 135.7 (C), 142.1 (C), 143.8 (C), 156.9 (C), 162.6
(C); HRMS (EI) calcd for C21H20NO3 [M - CO2CH3]+ 334.1443,
(CH), 142.0 (C), 143.7 (C), 156.9 (C), 162.4 (C). [R]20 +11.3 (c
0.92, CH2Cl2).
(2S,4S)-2-[(4S)-4-Isobu tyl-2-oxo-1,3-oxa zolid in -3-yl]-4-
p h en yl-3,4-d ih yd r o-2H-p yr a n -6-ca r boxylic Acid Meth yl
Ester 3b. From 1b (84.5 mg, 0.5 mmol), 3b (endo/exo 98/2,
endo-â/R 99/1) was obtained after chromatography as a yellow
oil (165 mg, 92%). Major isomer 3b-endo-â: IR (neat) 1759 (Cd
D
found 334.1421. [R]25 -28 (c 1.1, CH2Cl2).
D
(17) For efficient uses of chiral N-vinyloxazolidinones (i) in asym-
metric Pd-promoted carboacylations and alkylations, see: (a) Mont-
gomery, J .; Wieber, G. M.; Hegedus, L. S. J . Am. Chem. Soc. 1990,
112, 6255. (b) Masters, J . J . M.; Hegedus, L. S.; Tamariz, J . J . Org.
Chem. 1991, 56, 5666. (c) Laidig, G. J .; Hegedus, L. S. Synlett 1995,
527. (ii) In [2 + 2] photocycloadditions, see: (d) Miller, M.; Hegedus,
L. S. J . Org. Chem. 1993, 58, 6779. (e) Bach, T.; Schro¨der, J .; Brandl,
T.; Hecht, J .; Harms, K. Tetrahedron 1998, 54, 4507. (iii) In asymmetric
cyclopropanations, see: (f) Tamura, O.; Hashimoto, M.; Kobayashi, Y.;
Katoh, T.; Nakatani, K.; Kamada, M.; Hayakawa, I.; Akiba, T.;
Terashima, S. Tetrahedron Lett. 1992, 33, 3487. (g) Akiba, T.; Hash-
imoto, M.; Kobayashi, Y.; Katoh, T.; Nakatani, K.; Kamada, M.;
Hayakawa, I.; Terashima, S. Tetrahedron 1994, 50, 3905.
(18) Dujardin, G.; Leconte, S.; Be´nard, A.; Brown, E. Synlett 2001,
147.
(2S,4S)-2-[(4S,5R)-4-Meth yl-2-oxo-5-p h en yl-1,3-oxa zo-
lid in -3-yl]-4-p h en yl-3,4-d ih yd r o-2H -p yr a n -6-ca r b oxylic
Acid Meth yl Ester 3e. From (4S,5R)-1e (102 mg, 0.5 mmol),
3e (endo/exo > 98/2, endo-â/R > 98/2) was obtained after
chromatography as white crystals (157 mg, 80%). Major isomer
3e-endo-â: mp 206-207.5 °C (ether); IR (KBr) 1764 (CdO),
1735 (CdO), 1639 (CdC), 1455, 1419, 1380, 1289, 1239, 1216,
1144, 1088, 1037, 971, 871, 764, 711 cm-1; 1H NMR (400 MHz,
CDCl3) δ 0.92 (3H, d, J ) 6.6 Hz), 2.12 (1H, dt, J ) 11.3 and
13.0 Hz), 2.35 (1H, ddt, J ) 2.0, 6.4 and 13.0 Hz), 3.78 (3H, s),
3.89 (1H, ddd, J ) 2.0, 6.4 and 11.3 Hz), 4.24 (1H, qt, J ) 6.6
Hz), 5.62 (1H, d, J ) 7.6 Hz), 5.78 (1H, dd, J ) 2.0 and 11.3
J . Org. Chem, Vol. 69, No. 12, 2004 4197

Gaulon et al.
Hz), 6.15 (1H, t, J ) 2.0 Hz), 7.21-7.43 (10H, m); 13C NMR +
DEPT 135 (100 MHz, CDCl3) δ 16.6 (CH3), 34.8 (CH2), 39.2
(CH), 52.2 (CH3), 53.7 (CH), 79.4 (CH), 81.3 (CH), 113.7 (CH),
126.1-128.9 (6 x CH), 134.3 (C), 142.2 (C), 143.9 (C), 156.2
(C), 162.6 (C). Anal. Calcd for C23H23NO5: C, 70.21; H, 5.89;
dure A. After chromatography, the succinate (S)-8 was ob-
tained as a colorless oil (35 mg, 15% from 3a ) along with 7a
as colorless crystals (130 mg, 42% from 3a ).
1
(S)-(+)-Dim eth yl P h en ylsu ccin a te (S)-8: H NMR (400
MHz, CDCl3) δ 2.67 (1H, dd, J ) 5.1 and 16.7 Hz), 3.21 (1H,
dd, J ) 10.3 and 16.7 Hz), 3.68 (3H, s), 4.09 (1H, dd, J ) 5.1
N, 3.56. Found: C, 69.98; H, 5.81; N, 3.31. [R]25 -9 (c 1.03,
D
and 10.3 Hz), 7.25-7.40 (5H, m); [R]20 +78 (c 1.26, MeOH)
CH2Cl2).
D
{lit.19 [R]20D +124 (c 0.5, MeOH)}; ee > 98%; tR (S)-8 141.3 min
(2S,4S)-2-[(4S,5R)-4,5-Dip h en yl-2-oxo-1,3-oxa zolid in -3-
yl]-4-ph en yl-3,4-dih ydr o-2H-pyr an -6-car boxylic Acid Meth -
yl Ester 3f. From (4S,5R)-1f (80 mg, 0.3 mmol), 3f (endo/exo
> 98/2, endo-â/R > 98/2) was obtained after chromatography
as white crystals (109 mg, 80%). Major isomer 3f-endo-â: mp
190-191 °C; IR (KBr) 1766 (CdO), 1737 (CdO), 1651 (CdC),
(>99%), tR (R)-8 143.7 min (<1%) (105 °C).
(2S)-4-[(4R)-4-Eth yl-2-oxo-1,3-oxa zolid in -3-yl]-4-oxo-2-
p h en yl-bu tyr ic Acid Meth yl Ester 7a : mp 93.5-95 °C; IR
(KBr) 1783 (CdO), 1733 (CdO), 1699 (CdO), 1496, 1453, 1387,
1337, 1270, 1233, 1164, 1124, 1060, 1009, 964, 844, 773 cm-1
;
1H NMR (400 MHz, CDCl3) δ 0.89 (3H, t, J ) 7.4 Hz), 1.70
(1H, m), 1.82 (1H, m), 3.24 (1H, dd, J ) 3.6 and 18.5 Hz), 3.68
(3H, s), 3.81 (1H, dd, J ) 11.3 and 18.5 Hz), 4.12 (1H, m),
4.15 (1H, dd, J ) 3.6 and 11.3 Hz), 4.41 (2H, m), 7.25-7.35
(5H, m); 13C NMR + DEPT 135 (100 MHz, CDCl3) δ 7.9 (CH3),
24.8 (CH2), 39.4 (CH2), 46.3 (CH), 52.1 (CH3), 54.9 (CH), 66.8
(CH2), 127.5-128.7 (5xCH), 137.2 (C), 153.5 (C), 171.0 (C),
173.5 (C). Anal. Calcd for C16H19NO5: C, 62.94; H, 6.27; N,
4.59. Found: C, 62.93; H, 6.38; N, 4.61. [R]20D +26 (c 1.13, CH2-
Cl2).
1
1282, 1253, 1142 (C-O) cm-1; H NMR (400 MHz, CDCl3) δ
2.42 (1H, ddt, J ) 1.5, 6.4 and 13.3 Hz), 2.56 (1H, dt, J ) 11.3
and 13.3 Hz), 3.69 (1H, ddd, J ) 2.0, 6.4 and 11.3 Hz), 3.74
(3H, s), 5.37 (2H, m), 5.87 (1H, d, J ) 8.4 Hz), 6.02 (1H, d, J
) 1.5 Hz), 6.93-7.33 (15H, m); 13C NMR + DEPT 135 (100
MHz, CDCl3) δ 33.9 (CH2), 39.2 (CH), 52.0 (CH3), 63.8 (CH),
79.9 (CH), 82.3 (CH), 113.9 (CH), 126.0-128.7 (15 x CH), 134.1
(2 x C), 142.0 (C), 143.4 (C), 156.8 (C), 162.4 (C). Anal. Calcd
for C28H25NO5: C, 73.83; H, 5.53; N, 3.08. Found: C, 73.02;
H, 5.74; N, 2.76. [R]25 +51 (c 0.87, CH2Cl2).
D
Sequ en tia l Tr a n sfor m a tion of Heter o-a d d u ct 3c. (a )
After ozonolysis with Procedure A from 3c (103 mg, 0.27
mmol), a crude mixture (1/4) of aldehyde 4 and diastereoiso-
meric N,O-acylals 5c was obtained.
Gen er a l P r oced u r e for Sequ en tia l Tr a n sfor m a tion of
Heter o-a d d u cts 3a -c in to Dim eth yl P h en ylsu ccin a te 8.
(a ) Ozon olysis: P r oced u r e A. A cooled mixture at -78 °C
under nitrogen of the hetero-adduct 3 (1 equiv, on a 0.3-2.4
mmol scale), with MeOH (2.5 equiv) and NaHCO3 (0.1 equiv)
in dichloromethane (20 mL), was treated by ozone (15-20 min)
until the persistence of a blue color. After nitrogen stripping
of the excess of ozone at -78 °C, triethylamine (2 mL/mmol)
and acetic anhydride (2 mL/mmol) were added and the reaction
mixture was stirred under nitrogen at room temperature for
16 h. The organic layer was washed with water (3 × 15 mL),
dried (MgSO4), and concentrated in vacuo after negative
peroxide test. P r oced u r e B. The same conditions were applied
using triethylamine (1.25 equiv) and acetic anhydride (2.5
equiv). (b) Oxid a tion . To a cooled solution at -10 °C of the
crude product of ozonolysis in acetone (20 mL/mmol) was added
dropwise J ones reagent (1.3 equiv), and the reaction mixture
was stirred at room temperature for 16 h. After elimination
of the chromium salts by filtration on Celite, the solvent was
removed by concentration. (c) Ester ifica tion : P r oced u r e A.
A solution of the crude product of oxidation in methanol (10
mL/mmol) was treated with diazomethane until the persis-
tence of a yellow color. The excess of diazomethane was
canceled by glacial acetic acid, and the reaction mixture was
stirred at room temperature for 3 h. After removal of solvent,
the crude product was chromatographed (silica gel 30/1;
cyclohexane/ether 90/10). P r oced u r e B. A solution of the
crude product of oxidation in methanol (10 mL/mmol), treated
with an anhydrous HCl-methanol solution (0.5 g/10 mL, 10
equiv), was refluxed for 5-10 min. After removal of solvent,
the crude product was chromatographed.
(2S)-4-Acetoxy-4-[(4R)-2-oxo-4-p h en yl-1,3-oxa zolid in -3-
yl]-2-p h en yl-bu tyr ic Acid Meth yl Ester 5c: 1H NMR (400
MHz, CDCl3) δ diastereomer 1, 1.86 (3H, s), 2.37 (1H, ddd, J
) 6.1, 8.6 and 14.5 Hz), 2.95 (1H, ddd, J ) 6.4, 8.0 and 14.5
Hz), 3.55 (4H, m), 4.12 (1H, dd, J ) 6.9 and 8.9 Hz), 4.36 (1H,
t, J ) 8.9 Hz), 4.79 (1H, dd, J ) 6.9 and 8.9 Hz), 5.50 (1H, dd,
J ) 6.1 and 8.0 Hz), 7.10-7.40 (10H, m); diastereomer 2, 2.08
(3H, s), 2.50 (1H, ddd, J ) 6.1, 8.6 and 14.5 Hz), 3.04 (1H,
ddd, J ) 6.4, 8.0 and 14.5 Hz), 3.56 (4H, m), 4.16 (1H, dd, J )
6.9 and 8.9 Hz), 4.42 (1H, t, J ) 8.9 Hz), 4.81 (1H, dd, J ) 6.9
and 8.9 Hz), 5.60 (1H, dd, J ) 6.1 and 8.0 Hz), 7.10-7.40 (10H,
m).
(b) After oxidation of the mixture of 4 and 5c, the crude
mixture (18/82) of (S)-phenyl succinic acid 1-methyl ester and
N-acyl oxazolidinone 7c obtained was treated with methanol.
N-Acyl oxazolidinone 7c was thus isolated as white crystals
(53 mg, 56% from 3c).
(2S)-4-Oxo-4-[(4R)-2-oxo-4-p h en yl-1,3-oxa zolid in -3-yl]-
2-p h en yl-bu tyr ic Acid Meth yl Ester 7c: mp 179.5-180.5
°C (ether); IR (KBr) 1779 (CdO), 1733 (CdO), 1701 (CdO),
1495, 1454, 1377, 1234, 1167 cm-1; 1H NMR (400 MHz, CDCl3)
δ 3.18 (1H, dd, J ) 2.6 and 17.7 Hz), 3.65 (3H, s), 3.91 (1H,
dd, J ) 11.6 and 17.7 Hz), 4.07 (1H, dd, J ) 2.6 and 11.6 Hz),
4.29 (1H, dd, J ) 3.3 and 8.8 Hz), 4.72 (1H, t, J ) 8.8 Hz),
5.42 (1H, dd, J ) 3.3 and 8.8 Hz), 7.20-7.40 (10H, m); 13C
NMR + DEPT 135 (100 MHz, CDCl3) δ 39.4 (CH2), 46.1 (CH),
52.1 (CH3), 57.3 (CH), 70.0 (CH2), 125.7-130 (10 x CH), 137.2
(C), 137.8 (C), 153.5 (C), 170.6 (C), 173.5 (C). Anal. Calcd for
Sequ en tia l Tr a n sfor m a tion of Heter o-a d d u ct 3a . (a )
After ozonolysis with Procedure A from 3a (338 mg, 1.02
mmol), a crude mixture (1/9) of aldehyde 4 and diastereoiso-
meric N,O-acylals 5a was obtained.
C
20H19NO5: C, 67.98; H, 5.42; N, 3.96. Found: C, 67.98; H,
5.52; N, 3.94. [R]20 +39.7 (c 0.35, CH2Cl2).
D
(c) After esterification of the residual (S)-phenyl succinic
acid 1-methyl ester with Procedure A, the (S)-(+)-dimethyl
phenylsuccinate (S)-8 was isolated by chromatography (7 mg,
12% from 3c): [R]20D +80 (c 0.12, MeOH); ee ) 92.3%; tR (S)-8
141.3 min (96.2%), tR (R)-8 143.7 min (3.9%) (105 °C).
Sequ en tia l Tr a n sfor m a tion of Heter o-a d d u ct 3b. (a )
After ozonolysis (20 min) with Procedure B, from 3b (885 mg,
2.46 mmol), a crude mixture (1/1) of aldehyde 4 and N,O-
hemiaminal 6b was obtained.
(2S)-4-Acet oxy-4-[(4R)-4-et h yl-2-oxo-1,3-oxa zolid in -3-
yl]-2-p h en yl-bu tyr ic Acid Meth yl Ester 5a : 1H NMR (400
MHz, CDCl3) δ diastereomer 1, 0.83 (3H, t, J ) 7.4 Hz), 1.99
(3H, s), 1.40-1.80 (2H, m), 2.45 (1H, dt, J ) 7.4 and 14.8 Hz),
2.85 (1H, m), 3.64 (2H, m), 3.66 (3H, s), 3.85 (1H, dd, J ) 6.1
and 8.4 Hz), 4.04 (1H, t, J ) 8.4 Hz), 5.93 (1H, t, J ) 7.4 Hz),
7.24-7.40 (5H, m); diastereomer 2, 0.87 (3H, t, J ) 7.4 Hz),
2.07 (3H, s), 1.40-1.80 (2H, m), 2.59 (1H, dt, J ) 7.4 and 14.8
Hz), 2.85 (1H, m), 3.64 (2H, m), 3.67 (3H, s), 3.99 (1H, dd, J )
6.1 and 8.4 Hz), 4.32 (1H, t, J ) 8.4 Hz), 5.99 (1H, t, J ) 7.4
Hz), 7.24 a` 7.40 (5H, m).
(2R)-4-Hyd r oxy-4-[(4S)-4-isobu tyl-2-oxo-1,3-oxa zolid in -
3-yl)-2-p h en yl-bu tyr ic Acid Meth yl Ester 6b: 1H NMR
(400 MHz, CDCl3) δ 0.90 (3H, d, J ) 6.4 Hz), 0.92 (3H, d, J )
(b) After oxidation of the mixture of 4 and 5a , the crude
mixture (18/82) of (S)-phenyl succinic acid 1-methyl ester and
N-acyl oxazolidinone 7a obtained was esterified using Proce-
(19) Bettoni, G.; Cellucci, C.; Tortorella, V. J . Heterocycl. Chem.
1976, 1053.
4198 J . Org. Chem., Vol. 69, No. 12, 2004

N-Vinyl-2-oxazolidinones
6.4 Hz), 1.35-1.75 (3H, m), 2.20 (1H, ddd, J ) 8.9, 4.9 and
13.8 Hz), 2.67 (1H, ddd, J ) 6.4, 8.9 and 13.8 Hz), 3.66 (3H,
s), 3.78 (1H, dd, J ) 6.4 and 8.9 Hz), 3.95 (1H, m), 4.22 (1H,
t, J ) 8.4 Hz), 4.50 (1H, t, J ) 8.4 Hz), 4.93 (1H, dt, J ) 4.9
and 8.9 Hz), 5.28 (1H, m), 7.25-7.40 (5H, m).
4.2 and 10.1 Hz), 5.91 (1H, m); 13C NMR + DEPT 135 (100
MHz, CDCl3) δ 7.7 (CH3), 26.3 (CH2), 27.8 (CH3), 32.7 (CH2),
51.9 (CH3), 54.0 (CH), 63.0 (CH), 66.9 (CH2), 74.6 (C), 80.3
(CH), 113.9 (CH), 142.9 (C), 156.8 (C), 162.1 (C); HRMS (EI)
calcd for C12H17NO6 [M - C4H8]+• 271.10559, found 271.1060.
Anal. Calcd for C16H25NO6: C, 58.70; H, 7.70; N, 4.28. Found:
(b) After oxidation of the mixture of 4 and 6b, the crude
mixture of (S)-phenyl succinic acid 1-methyl ester and N-acyl
oxazolidinone 7b obtained was esterified with Procedure B.
After chromatography, succinate (R)-8 was obtained as a
colorless oil (82 mg, 30% from 3b) along with 7b as white
crystals (157 mg, 38% from 3b).
C, 58.98; H, 7.81; N, 4.01. [R]20 -6 (c 0.9, CH2Cl2).
D
(2S,4S)-4-(ter t-Bu toxy)-2-[(4S)-4-isobu tyl-2-oxo-1,3-ox-
a zolid in -3-yl]-3,4-d ih yd r o-2H -p yr a n -6-ca r b oxylic Acid
Meth yl Ester 10b. From 1b (583 mg, 3.45 mmol), 9 (1.06 g,
5.17 mmol), and Eu(fod)3 (2 × 311 mg, 0.6 mmol), after
chromatography (15/1, cyclohexane/AcOEt 8/2), the hetero-
adduct 10b (endo/exo 98/2, endo-â/R 95/5) was obtained as
colorless crystals (473 mg, 39%). Major isomer 10b-endo-â: mp
144-147 °C (ether); IR (KBr) 1765 (CdO), 1748 (CdO), 1644
(R)-(-)-Dim eth yl P h en ylsu ccin a te (R)-8: [R]20 -102.5
D
(c 1.19, MeOH); ee ) 93%; tR (S)-8 141.3 min (3.5%), tR (R)-8
143.7 min (96.5%) (105 °C).
(2R)-4-[(4S)-4-Isobu tyl-2-oxo-1,3-oxa zolid in -3-yl)-4-oxo-
2-p h en yl-bu tyr ic Acid Meth yl Ester 7b: mp 118-119.5 °C;
IR (KBr) 1774 (CdO), 1735 (CdO), 1698 (CdO), 1497, 1438,
1399, 1339, 1288, 1231, 1170, 1137, 1084, 1029, 953, 850, 767
(CdC), 1428, 1393, 1368, 1286, 1262, 1150, 863, 767, 703 cm-1
;
1H NMR (400 MHz, CDCl3) δ 0.92 (3H, d, J ) 6.6 Hz), 0.94
(3H, d, J ) 6.6 Hz), 1.25 (9H, s), 1.62 (2H, m), 1.83 (1H, ddd,
J ) 3.0, 10.0 and 13.4 Hz), 2.07 (2H, m), 3.78 (3H, s), 4.00
(1H, m), 4.05 (1H, dd, J ) 6.1 and 8.0 Hz), 4.40 (1H, t, J ) 8.0
Hz), 4.56 (1H, ddd, J 2.3, 8.6 and 10.4 Hz), 5.71 (1H, dd, J )
4.9 and 9.3 Hz), 5.92 (1H, d, J 4-3 ) 2.3 Hz); 13C NMR + DEPT
135 (100 MHz, CDCl3) δ 21.4 (CH3), 23.6 (CH3), 24.7 (CH), 27.9
(CH3), 32.9 (CH2), 42.4 (CH2), 52.1 and 52.2 (CH3 + CH), 63.2
(CH), 67.9 (CH2), 74.8 (C), 80.8 (CH), 114.2 (CH), 143.1 (C),
156.8 (C), 162.2 (C). Anal. Calcd for C18H29NO6: C, 60.83; H,
1
cm-1; H NMR (400 MHz, CDCl3) δ 0.94 (3H, d, J ) 6.4 Hz),
0.95 (3H, d, J ) 6.4 Hz), 1.46 (1H, m), 1.60 (1H, m), 1.74 (1H,
ddd, J ) 3.4, 9.0 and 12.3 Hz), 3.18 (1H, dd, J ) 3.4 and 18.7
Hz), 3.68 (3H, s), 3.83 (1H, dd, J ) 11.3 and 18.7 Hz), 4.12
(1H, dd, J ) 2.5 and 8.8 Hz), 4.15 (1H, dd, J ) 3.4 and 11.3
Hz), 4.40 (1H, t, J ) 8.8 Hz), 4.49 (1H, m), 7.25-7.35 (5H, m);
13C NMR + DEPT 135 (100 MHz, CDCl3) δ 21.5 (CH3), 23.3
(CH3), 24.7 (CH), 39.5 (CH2), 41.2 (CH2), 46.4 (CH), 52.2 (CH3),
53.0 (CH), 67.7 (CH2), 127.5-128.8 (5 x CH), 137.4 (C), 153.5
(C), 170.9 (C), 173.6 (C). Anal. Calcd for C18H23NO5: C, 64.85;
H, 6.95; N, 4.20. Found: C, 64.64; H, 6.86; N, 4.14. [R]20D -33.3
(c 1.52, CH2Cl2).
8.22; N, 3.94. Found: C, 60.59; H, 8.19; N, 3.65. [R]25 +25.1
D
(c 1.1, CH2Cl2).
(2R,4R)-4-(ter t-Bu t oxy)-2-[(4R)-2-oxo-4-p h en yl-1,3-ox-
a zolid in -3-yl]-3,4-d ih yd r o-2H -p yr a n -6-ca r b oxylic Acid
Meth yl Ester 10c. From 1c (182.5 mg, 0.96 mmol), 9 (295
mg, 1.44 mmol), and Eu(fod)3 (2 × 87 mg, 0.168 mmol), after
chromatography (15/1, cyclohexane/AcOEt 85/15 to 70/30), the
hetero-adduct 10c (endo/exo > 98/2, endo-R/â > 96/4) was
obtained as a yellow oil (194 mg, 54%). Major isomer 10c-endo-
R: IR (neat) 1762 (CdO), 1743 (CdO), 1648 (CdC), 1436, 1393,
1366, 1281, 1253, 1174, 860, 766, 707 cm-1; 1H NMR (400 MHz,
CDCl3) δ 1.20 (9H, s), 2.11 (1H, ddt, J ) 2.0, 6.6 and 12.8 Hz),
2.25 (1H, ddd, J ) 9.3, 11.5 and 12.8 Hz), 3.68 (3H, s), 4.14
(1H, dd, J ) 7.1 and 8.8 Hz), 4.40 (1H, ddd, J ) 2.3, 6.6 and
9.3 Hz), 4.64 (1H, t, J ) 8.8 Hz), 5.06 (1H, dd, J ) 7.1 and 8.8
Hz), 5.48 (1H, dd, J ) 2.0 and 11.5 Hz), 5.76 (1H, t, J ) 2.0
Hz), 7.31-7.43 (5H, m); 13C NMR + DEPT 135 (100 MHz,
CDCl3) δ 27.7 (CH3), 32.5 (CH2), 51.8 (CH3), 58.3 (CH), 62.8
(CH), 70.3 (CH2), 74.5 (C), 80.9 (CH), 113.8 (CH), 127.1 (CH),
128.7 (2xCH), 137.6 (C), 142.7 (C), 156.8 (C), 161.9 (C). Anal.
Calcd for C20H25NO6: C, 63.99; H, 6.71; N, 3.73. Found: C,
(d ) Va r ia tion . After ozonolysis (20 min) with Procedure B,
from 3b (68 mg, 0.19 mmol), the crude mixture (1/1) of
aldehyde 4 and N,O-hemiaminal 6b obtained was hydrolyzed
with 4 M H2SO4 (30 µL, 0.12 mmol, 1.3 equiv). After chroma-
tography (cyclohexane/ether 90/10 to 1/1), (4S)-4-isobutyl-1,3-
oxazolidinone was recovered (28 mg) and the purified aldehyde
(R)-4 thus obtained (22 mg, 61%) was oxidized. After esteri-
fication of the crude (R)-phenyl succinic acid 1-methyl ester
with Procedure B and chromatography, the succinate (R)-8
was obtained as a colorless oil (21 mg, 83% from 4).
(2R)-2-(F or m ylm eth yl)p h en yla cetic Acid Meth yl Ester
(R)-4: 1H NMR (200 MHz, CDCl3) δ 2.81 (1H, dd, J ) 3.9 and
18.7 Hz), 3.41 (1H, dd, J ) 9.5 and 18.7 Hz), 3.68 (3H, s), 4.29
(1H, dd, J ) 3.9 and 9.5 Hz), 7.20-7.35 (5H, m), 9.80 (1H, s).
(R)-P h en yl Su ccin ic Acid 1-Meth yl Ester : 1H NMR (400
MHz, CDCl3) δ 2.72 (1H, dd, J ) 5.1 and 17.3 Hz), 3.26 (1H,
dd, J ) 10.3 and 17.3 Hz), 3.70 (3H, s), 4.09 (1H, dd, J ) 5.1
and 10.3 Hz), 7.20-7.35 (5H, m).
63.72; H, 6.77; N, 3.54. [R]25 -82.4 (c 1.0, CH2Cl2).
D
(2S,4S)-2-[(4S)-4-Ben zyl-2-oxo-1,3-oxa zolid in -3-yl]-4-
(ter t-Bu t oxy)-3,4-d ih yd r o-2H -p yr a n -6-ca r b oxylic Acid
Meth yl Ester 10d . From (4S)-1d (650 mg, 3.2 mmol), 9 (982
mg, 4.8 mmol), and Eu(fod)3 (579 mg, 0.56 mmol), after
chromatography (15/1, cyclohexane/AcOEt 90/10 to 70/30 with
1% of Et3N), the hetero-adduct 10d (endo/exo > 98/2, endo-
â/R > 98/2) was obtained as colorless crystals (522 mg, 42%).
Major isomer 10d -endo-â: mp 153.5-155 °C (ether); IR (KBr)
1767 (CdO), 1747 (CdO), 1650 (CdC), 1438, 1396, 1365, 1288,
(R)-(-)-Dim eth yl P h en ylsu ccin a te (R)-8: ee ) 95.5%; tR
(S)-8 141.3 min (2.25%), tR (R)-8 143.7 min (97.75%) (105 °C).
Gen er a l P r ep a r a t ion of H et er o-a d d u ct s 10a -f w it h
Eu (fod )3. A solution of N-vinyl-2-oxazolidinone 1 (1 equiv),
heterodiene 98d (1-1.5 equiv, slightly polluted with 8-13 mol
% dimethyl oxalate), and Eu(fod)3 (0.05 equiv) in cyclohexane
(10 mL per mmol of 1) was refluxed under nitrogen for 2-3
days. After introduction of additional Eu(fod)3 (0.05 equiv), the
mixture was refluxed for the total time indicated in Table 3.
After removal of solvent the crude product was chromato-
graphed on silica gel.
(2R,4R)-4-(ter t-Bu toxy)-2-[(4R)-4-eth yl-2-oxo-1,3-oxa zo-
lid in -3-yl]-3,4-d ih yd r o-2H-p yr a n -6-ca r boxylic Acid Meth -
yl Ester 10a . From 1a (900 mg, 6.38 mmol), 9 (1.23 g, 6.38
mmol), and Eu(fod)3 (2 × 165 mg, 0.32 mmol), after chroma-
tography (25/1, cyclohexane/AcOEt 90/10 to 60/40), the hetero-
adduct 10a (endo/exo 97/3, endo-R/â > 98/2) was obtained as
colorless crystals (887 mg, 52%). Major isomer 10a -endo-R: mp
133-134 °C (ether); IR (KBr) 1756 (CdO), 1746 (CdO), 1645
(CdC), 1426, 1392, 1367, 1287, 1264, 1146, 768 cm-1; 1H NMR
(400 MHz, CDCl3) δ 0.93 (3H, t, J ) 7.4 Hz), 1.25 (9H, s), 1.66-
1.95 (2H, m), 2.04-2.15 (2H, m), 3.77 (3H, s), 3.94 (1H, m),
4.07 (1H, dd, J ) 5.2 and 8.6 Hz), 4.40 (1H, t, J ) 8.6 Hz),
4.56 (1H, ddd, J ) 2.2, 7.4 and 9.5 Hz, H-3), 5.72 (1H, dd, J )
1265, 1189, 867, 767, 749, 707 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 1.27 (9H, s), 2.16 (1H, ddt, J ) 2.1, 6.9 and 12.0 Hz),
2.24 (1H, dt, J ) 9.6 and 12.0 Hz), 2.88 (1H, dd, J ) 9.8 and
14.0 Hz), 3.33 (1H, dd, J ) 3.8 and 14.0 Hz), 3.78 (3H, s), 4.12
(2H, m), 4.20 (1H, m), 4.60 (1H, ddd, J ) 2.1, 7.0 and 9.6 Hz),
5.78 (1H, dd, J ) 2.1 and 12.0 Hz), 5.96 (1H, t, J ) 2.1 Hz),
7.20-7.38 (5H, m); 13C NMR + DEPT 135 (100 MHz, CDCl3)
δ 27.8 (CH3), 33.2 (CH2), 39.4 (CH2), 52.0 (CH3), 53.9 (CH),
63.1 (CH), 66.5 (CH2), 74.7 (C), 80.6 (CH), 114.2 (CH), 126.9
(CH), 128.6 (CH), 129.1 (CH), 135.3 (C), 143.0 (C), 156.6 (C),
162.1 (C). Anal. Calcd for C21H27NO6: C, 64.77; H, 6.99; N,
3.60. Found: C, 65.06; H, 7.03; N, 3.69. [R]25 +78.4 (c 0.74,
D
CH2Cl2).
(2R,4R)-4-(ter t-Bu t oxy)-2-[(4R,5S)-4-m et h yl-2-oxo-5-
p h en yl-1,3-oxa zolid in -3-yl]-3,4-d ih yd r o-2H-p yr a n -6-ca r -
J . Org. Chem, Vol. 69, No. 12, 2004 4199

Gaulon et al.
boxylic Acid Meth yl Ester 10e. From (4R,5S)-1e (1 g, 4.9
mmol), 9 (1.5 g, 7.35 mmol), and Eu(fod)3 (2 × 439 mg, 0.82
mmol), after chromatography (15/1, CH2Cl2/AcOEt 100/0 to 98/
2), the hetero-adduct 10e (endo/exo > 98/2, endo-R/â ) 97/3)
was obtained as colorless crystals (1.17 g, 61%). Major isomer
10c-endo-R: mp 179-180.5 °C (ether); IR (KBr) 1754 (CdO),
1744 (CdO), 1640 (CdC), 1430, 1391, 1366, 1261, 1226, 1156,
861, 767, 700 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.90 (3H, d,
J ) 6.6 Hz), 1.25 (9H, s), 2.11 (1H, dt, J ) 9.5 and 11.5 Hz),
2.17 (1H, m), 3.74 (3H, s), 4.26 (1H, qt, J ) 6.6 Hz), 4.57 (1H,
ddd, J ) 2.2, 7.0 and 9.5 Hz), 5.62 (1H, d, J ) 7.8 Hz), 5.76
(1H, dd, J ) 2.4 and 11.5 Hz), 5.91 (1H, t, J ) 2.2 Hz), 7.29-
7.44 (5H, m); 13C NMR + DEPT 135 (100 MHz, CDCl3) δ 16.4
(CH3), 27.9 (CH3), 33.4 (CH2), 52.1 (CH3), 53.5 (CH), 63.1 (CH),
74.7 (C), 79.3 (CH), 80.3 (CH), 113.9 (CH), 125.9 (CH), 128.5
(2 x CH), 134.0 (C), 143.1 (C), 156.3 (C), 162.3 (C). Anal. Calcd
for C21H27NO6: C, 64.77; H, 6.99; N, 3.60. Found: C, 64.89;
33.6 (CH2), 57.7 (CH), 61.8 (CH2), 63.0 (CH), 70.5 (CH2), 74.1
(C), 80.3 (CH), 101.4 (CH), 127.0 (CH), 128.7 (4 x CH), 138.7
(C), 152.3 (C), 157,1 (C).
(4S)-4-Be n zyl-3-[(2S,4S)-4-(ter t-b u t oxy)-6-(h yd r oxy-
m e t h yl)-3,4-d ih yd r o-2H -p yr a n -2-yl]-1,3-oxa zolid in -2-
on e 11d . From 10d (637 mg, 1.64 mmol) and DIBAH (9 mL,
9 mmol) at -78 °C, with a slow increase in temperature to
-20 °C over 4 h, allyl alcohol 11d was obtained as a crude
yellow oil (532 mg, 90%): 1H NMR (400 MHz, CDCl3) δ 1.25
(9H, s), 2.18 (2H, m), 2.76 (1H, dd, J ) 10.5 and 14.0 Hz),
3.35 (1H, dd, J ) 3.7 and 14.0 Hz), 4.00 (2H, m), 4.10 (2H, m),
4.17 (1H, m), 4.53 (1H, t, J ) 8.0 Hz), 4.85 (1H, broad s), 5.74
(1H, dd, J ) 2.4 and 11.8 Hz), 7.10-7.40 (5H, m); 13C NMR +
DEPT 135 (100 MHz, CDCl3) δ 28.0 (CH3), 34.2 (CH2), 39.7
(CH2), 54.1 (CH), 62.0 (CH2), 63.3 (CH), 66.5 (CH2), 74.3 (C),
80.1 (CH), 102.1 (CH), 126.9 (CH), 128.8 and 129 (4 x CH),
135.5 (C), 153.0 (C), 157.0 (C).
H, 7.11; N, 3.55. [R]25 +6.5 (c 0.76, CH2Cl2).
D
(4R,5S)-3-[(2R,4R)-4-(ter t-Bu toxy)-6-(h yd r oxym eth yl)-
3,4-d ih yd r o-2H-p yr a n -2-yl]-4-m eth yl-5-p h en yl-1,3-oxa zo-
lid in -2-on e 11e. From 10e (1.02 g, 2.63 mmol) and DIBAH
Gen er a l P r oced u r e for Red u ction of Heter o-a d d u cts
10a -e. To a cooled solution of hetero-adduct 10 (1 equiv) in
dry dichloromethane (5 mL/mmol) at -78 °C under nitrogen
was successively added dropwise BF3‚Et2O (1.2 equiv) and
DIBAH (1 M solution in toluene, 3.5-6.5 equiv). The reaction
mixture was stirred at -78 °C (with fresh DIBAH) or slowly
warmed at -20 °C (with old DIBAH) until complete disap-
pearance of 10 (monitoring by TLC). The excess DIBAH was
canceled by slow addition of MeOH (0.2-0.3 mL/mmol of
DIBAH), and the reaction mixture was warmed at room
temperature. After treatment of aluminum salts with an
aqueous solution of potassium sodium tartrate (30 wt %, 1.5-
2.5 mL/mmol of DIBAH), the organic layer was separated and
the aqueous layer was extracted with dichloromethane or ethyl
acetate. The combined organic layers were dried with MgSO4.
After removal of solvent, the crude product 11 was used
without further purification.
(17 mL, 17 mmol) at -78 °C, with
a slow increase in
temperature to -20 °C over 4.5 h, allyl alcohol 11e was
obtained as a crude yellow oil (953 mg, 100%): IR (neat) 3450
(OH), 1752 (CdO), 1676 (CdC), 1417, 1388, 1365, 1228, 1193,
1174, 1069, 1047, 1018, 701 cm-1; 1H NMR (400 MHz, CDCl3)
δ 0.87 (3H, d, J ) 6.4 Hz), 1.23 (9H, s), 2.05 (1H, td, J ) 9.8
and 12.3 Hz), 2.14 (1H, ddt, J ) 2.0, 7.0 and 12.3 Hz), 3.91
and 3.98 (2H, 2d, J ) 13.7 Hz), 4.25 (1H, dq, J ) 6.4 and 7.9
Hz), 4.50 (1H, t, J ) 7.9 Hz), 4.80 (1H, broad s), 5.61 (1H, d,
J ) 7.9 Hz), 5.71 (1H, dd, J ) 2.0 and 12.3 Hz), 7.28-7.44
(5H, m); 13C NMR + DEPT 135 (100 MHz, CDCl3) δ 16.3 (CH3),
28.0 (CH3), 34.2 (CH2), 53.5 (CH), 62.1 (CH2), 63.2 (CH), 74.2
(C), 79.2 (CH), 79.7 (CH), 101.8 (CH), 125.7 (CH), 128.4 (4 x
CH), 133.9 (C), 152.9 (C), 156.7 (C).
(4R)-3-[(2R,4R)-6-(Acetoxym eth yl)-4-(ter t-bu toxy)-3,4-
d ih yd r o-2H-p yr a n -2-yl]-4-eth yl-1,3-oxa zolid in -2-on e 13a .
To a cooled solution at 0 °C under nitrogen of crude allyl
alcohol 11a (75 mg, 0.25 mmol) and DMAP (3 mg, 0.025 mmol)
in anhydrous dichloromethane (3 mL) were successively added
triethylamine (35 µL, 0.25 mmol) and acetic anhydride drop-
wise (47 µL, 0.5 mmol), and the reaction mixture was stirred
for 1 h at room temperature. The organic layer was succes-
sively washed with water and then brine and dried with
MgSO4. After removal of solvent, the crude product obtained
(84 mg, 99%) was used without further purification: 1H NMR
(400 MHz, CDCl3) δ 0.90 (3H, t, J ) 7.4 Hz), 1.22 (9H, s), 1.68
(1H, m), 1.84 (1H, m), 2.06 (2H, m), 2.23 (3H, s), 3.94 (1H, m),
4.06 (1H, dd, J ) 4.9 and 8.6 Hz), 4.36 (1H, t, J ) 8.6 Hz),
4.41 (2H, 2s), 4.48 (1H, t, J ) 8.0 Hz), 4.83 (1H, broad s), 5.70
(1H, dd, J ) 5.6 and 8.6 Hz).
(4R)-3-[(2R,4R)-6-(Ben zyloxym et h yl)-4-(ter t-b u t oxy)-
3,4-d ih yd r o-2H-p yr a n -2-yl]-4-eth yl-1,3-oxa zolid in -2-on e
16a . To a cooled solution of crude allyl alcohol 11a (555 mg,
1.85 mmol) in anhydrous dimethylformamide (15 mL) at 0 °C
under nitrogen was added NaH (40 wt % dispersion in oil, 167
mg, 2.77 mmol), and the reaction mixture was stirred for 20
min at 0 °C. Benzyl bromide (288 µL, 2.40 mmol) was added
dropwise and the reaction mixture was stirred for 3 h at room
temperature. After slow addition of methanol (5 mL) at 0 °C,
the reaction mixture was stirred for 1 h at room temperature
and concentrated under reduced pressure. The residue was
recovered with dichloromethane, and the organic layer was
successively washed with water and then brine and dried with
MgSO4. After removal of solvent, the crude product obtained
(720 mg, 100%) was used without further purification: 1H
NMR (400 MHz, CDCl3) δ 0.88 (3H, t, J ) 7.6 Hz), 1.22 (9H,
s), 1.65 (1H, m), 1.85 (1H, m), 2.05 (2H, m), 3.87 (2H, s), 3.92
(1H, m), 4.05 (1H, dd, J ) 4.9 and 8.4 Hz), 4.35 (1H, t, J ) 8.4
Hz), 4.48 (1H, t, J ) 8.0 Hz), 4.83 (1H, broad s), 5.69 (1H, dd,
J ) 3.0 and 11.0 Hz), 7.20-7.40 (5H, m).
(4R)-3-[(2R,4R)-4-(ter t-Bu toxy)-6-(h yd r oxym eth yl)-3,4-
d ih yd r o-2H-p yr a n -2-yl]-4-eth yl-1,3-oxa zolid in -2-on e 11a .
From 10a (160 mg, 0.49 mmol) and DIBAH (2.45 mL, 2.45
mmol) at -78 °C for 1.5 h, allyl alcohol 11a was obtained as
a crude yellow oil (146.5 mg, 100%): 1H NMR (400 MHz,
CDCl3) δ 0.91 (3H, t, J ) 7.5 Hz), 1.23 (9H, s), 1.67 (1H, m),
1.84 (1H, m), 2.05 (2H, m), 3.95 (3H, m), 4.07 (1H, dd, J ) 4.6
and 8.6 Hz), 4.37 (1H, t, J ) 8.6 Hz), 4.49 (1H, t, J ) 8.0 Hz),
4.80 (1H, m), 5.68 (1H, t, J ) 7.0 Hz); 13C NMR + DEPT 135
(100 MHz, CDCl3) δ 7.9 (CH3), 26.5 (CH2), 28.0 (CH3), 33.8
(CH2), 54.1 (CH), 62.1 (CH2), 63.2 (CH), 67.0 (CH2), 74.2 (C),
79.9 (CH), 101.8 (CH), 152.9 (C), 157.1 (C).
(4S)-3-[(2S,4S)-4-(ter t-Bu toxy)-6-(h yd r oxym eth yl)-3,4-
d ih yd r o-2H -p yr a n -2-yl]-4-isob u t yl-1,3-oxa zolid in -2-on e
11b. From 10b (449 mg, 1.26 mmol) and DIBAH (6.3 mL, 6.3
mmol) at -78 °C for 1 h, allyl alcohol 11b was obtained as a
crude yellow oil (389 mg, 95%): 1H NMR (400 MHz, CDCl3) δ
0.92 (3H, d, J ) 6.4 Hz), 0.94 (3H, d, J ) 6.4 Hz), 1.23 (9H, s),
1.56 (2H, m), 1.82 (1H, ddd, J ) 3.0, 10.8 and 14.3 Hz), 2.04
(2H, m), 3.91-4.04 (3H, m), 4.05 (1H, dd, J ) 5.4 and 8.4 Hz),
4.38 (1H, t, J ) 8.4 Hz), 4.49 (1H, t, J ) 7.9 Hz), 4.81 (1H, m),
5.66 (1H, dd, J ) 4.9 and 9.4 Hz); 13C NMR + DEPT 135 (100
MHz, CDCl3) δ 21.3 (CH3), 23.6 (CH3), 24.6 (CH), 28.0 (CH3),
33.8 (CH2), 42.5 (CH2), 52.1 (CH), 62.1 (CH2), 63.4 (CH), 67.8
(CH2), 74.3 (C), 80.2 (CH), 102.0 (CH), 153.0 (C), 157.1 (C).
(4R)-3-[(2R,4R)-4-(ter t-Bu toxy)-6-(h yd r oxym eth yl)-3,4-
dih ydr o-2H-pyr an -2-yl]-4-ph en yl-1,3-oxazolidin -2-on e 11c.
From 10c (194 mg, 0.52 mmol) and DIBAH (2.6 mL, 2.6 mmol)
at -78 °C, with a slow increase in temperature to -20 °C over
2.5 h, allyl alcohol 11c was obtained as a crude yellow oil (128
mg, 71%): IR (neat) 3453 (OH), 1755 (CdO), 1679 (CdC), 1391,
1367, 1228, 1191, 1056, 1019 cm-1; 1H NMR (400 MHz, CDCl3)
δ 1.19 (9H, s), 2.11 (2H, m), 3.62 (2H, broad s), 4.19 (1H, dd,
J ) 6.0 and 8.8 Hz), 4.37 (1H, ddd, J ) 1.5, 7.9 and 9.6 Hz),
4.60 (1H, m), 4.65 (1H, t, J ) 8.8 Hz), 4.98 (1H, dd, J ) 6.0
and 8.8 Hz), 5.63 (1H, dd, J ) 5.4 and 8.8 Hz), 7.12-7.42 (5H,
m); 13C NMR + DEPT 135 (100 MHz, CDCl3) δ 27.9 (CH3),
Gen er a l P r oced u r e for P r ep a r a tion of N-2-Deoxygly-
cosyl-oxa zolid in on es 12. (a ) Hyd r obor a tion . To a cooled
4200 J . Org. Chem., Vol. 69, No. 12, 2004

N-Vinyl-2-oxazolidinones
solution of crude allyl alcohol 11 (1 equiv) in THF (6.7 mL/
mmol) at 0 °C under nitrogen was added BH3‚Me2S (2 M
solution in THF, 3.5 equiv), and the reaction mixture was
stirred for 1.5 h at 0 °C and then 15 h at room temperature.
(b) Oxid a tion . P r oced u r e A. After dilution with THF (6.7
mL/mmol), trimethylamine N-oxide dihydrate (3 equiv) was
added and the reaction mixture was refluxed for 1 h. After
the mixture was cooled, brine (8 mL) was added and the
reaction mixture was stirred for 5 min. After removal of THF,
the aqueous layer was extracted with ethyl acetate (3 × 8 mL)
and the combined organic layers were dried with MgSO4. After
removal of solvent, the crude product was chromatographed
on silica gel. P r oced u r e B. After replacement of THF by
diglyme (10 mL/mmol), trimethylamine N-oxide dihydrate (3.5
equiv) was added and the reaction mixture was warmed at
110 °C for 4.5-6 h. After the mixture was cooled and diluted
with ether, the organic layer was washed with brine (3 × 5
mL); the resulting aqueous layer was extracted with ethyl
acetate, and the combined organic layers were dried with
MgSO4. After removal of solvent, the crude product was
chromatographed.
3.21 (1H, dt, J ) 3.1 and 9.1 Hz), 3.44-3.58 (3H, m), 4.23 (1H,
dd, J ) 5.9 and 8.9 Hz), 4.65 (1H, t, J ) 8.9 Hz), 4.91 (1H, dd,
J ) 5.9 and 8.9 Hz), 5.16 (1H, d, J ) 11.3 Hz), 7.38 (5H, m);
13C NMR + DEPT 135 (100 MHz, CDCl3) δ 28.9 (CH3), 36.5
(CH2), 58.1 (CH), 61.8 (CH2), 69.3 (CH2), 70.5 (CH), 72.4 (CH),
74.9 (C), 77.5 (CH), 80.4 (CH), 127.5 (CH), 128.9 and 129.1 (4
x CH), 139.6 (C), 157.2 (C); HRMS (FAB) calcd for C19H27NO6-
Na [M + Na]+ 388.17361, found 388.1731. [R]20 -98 (c 0.91,
D
CH2Cl2).
(4S)-4-Be n zyl-3-[(2S,4R,5R,6R)-4-(ter t-b u t oxy)-5-h y-
d r oxy-6-(h yd r oxym eth yl)-tetr a h yd r o-2H-p yr a n -2-yl]-1,3-
oxa zolid in -2-on e 12d . From 11d (150 mg, 0.41 mmol), after
hydroboration-oxidation (Procedure B, 4.5 h), 12d was ob-
tained after chromatography (silica gel 40 /1, cyclohexane/
AcOEt 50/50 to 40/60) as white crystals (81 mg, 52%): mp
141-144 °C; IR (KBr) 3505 (OH), 1749 (CdO), 1427, 1400,
1362, 1287, 1267, 1234, 1189, 1127, 1088, 1023, 976, 878, 750
cm-1; 1H NMR (400 MHz, CDCl3) δ 1.28 (9H, s), 2.00 (1H, m),
2.10 (1H, ddd, J ) 2.2, 4.3 and 12.3 Hz), 2.52 (1H, broad s),
2.75 (1H, dd, J ) 9.8 and 13.7 Hz), 3.31 (1H, dd, J ) 3.7 and
13.7 Hz), 3.38 (1H, t, J ) 9.0 Hz), 3.50 (1H, ddd, J ) 3.7, 4.7
and 9.0 Hz), 3.65 (1H, ddd, J ) 4.3, 9.0 and 10.8 Hz), 3.78
(1H, dd, J ) 4.7 and 11.8 Hz), 3.91 (1H, dd, J ) 3.7 and 11.8
Hz), 4.04-4.20 (3H, m), 5.25 (1H, dd, J ) 2.2 and 11.3 Hz),
7.15-7.36 (5H, m); 13C NMR + DEPT 135 (100 MHz, CDCl3)
δ 28.8 (CH3), 36.8 (CH2), 40.2 (CH2), 54.3 (CH), 62.9 (CH2),
66.6 (CH2), 70.9 (CH), 72.4 (CH), 74.9 (C), 77.5 (CH), 80.1 (CH),
127.1 (CH), 128.8 and 129.1 (4 x CH), 135.6 (C), 157.0 (C).
HRMS (FAB) calcd for C20H29NO6Na [M + Na]+ 402.18926,
found 402.1896; calcd for C20H29NO6K [M + K]+ 418.16320,
(4R)-3-[(2R,4S,5S,6S)-4-(ter t-Bu toxy)-5-h yd r oxy-6-(h y-
d r oxym eth yl)-tetr a h yd r o-2H-p yr a n -2-yl]-4-eth yl-1,3-ox-
a zolid in -2-on e 12a . From 11a (89 mg, 0.3 mmol), after
hydroboration-oxidation (Procedure A), 12a was obtained
after chromatography (silica gel 40 /1, cyclohexane/AcOEt 20/
80) as a colorless oil (39 mg, 41%): 1H NMR (400 MHz, CDCl3)
δ 0.91 (3H, t, J ) 7.4 Hz), 1.26 (9H, s), 1.63 (1H, m), 1.85 (2H,
m), 2.00 (1H, ddd, J ) 2.5, 4.5 and 12.3 Hz), 2.44 (1H, d, J )
2.0 Hz), 3.34 (1H, td, J ) 2.0 and 9.0 Hz), 3.46 (1H, ddd, J )
3.4, 4.5 and 9.0 Hz), 3.63 (1H, ddd, J ) 4.5, 9.0 and 10.8 Hz),
3.76 (1H, dd, J ) 4.5 and 11.8 Hz), 3.88 (1H, m) and (1H, dd,
J ) 3.4 and 11.8 Hz), 4.04 (1H, dd, J ) 4.9 and 8.9 Hz), 4.35
(1H, t, J ) 8.9 Hz), 5.22 (1H, dd, J ) 2.5 and 11.1 Hz); 13C
NMR + DEPT 135 (100 MHz, CDCl3) δ 7.9 (CH3), 26.8 (CH2),
28.5 (CH3), 36.3 (CH2), 54.2 (CH), 62.8 (CH2), 66.8 (CH2), 70.7
(CH), 72.3 (CH), 74.7 (C), 77.1 (CH), 79.7 (CH), 157.1 (C).
HRMS (FAB) calcd for C15H27NO6Na [M + Na]+ 340.1736,
found 340.1736; calcd for C15H27NO6K [M + K]+ 356.1476,
found 418.1635. [R]20 +55.6 (c 1.34, CH2Cl2).
D
(4R,5S)-3-[(2R,4S,5S,6S)-4-(ter t-Bu t oxy)-5-h yd r oxy-6-
(h yd r oxym eth yl)-tetr a h yd r o-2H-p yr a n -2-yl]-4-m eth yl-5-
p h en yl-1,3-oxa zolid in -2-on e 12e. From 11e (72 mg, 0.2
mmol), after hydroboration-oxidation (Procedure B, 6 h), 12e
was obtained after chromatography (silica gel 40/1, cyclohex-
ane/AcOEt 40/60 to 30/70) as white crystals (36 mg, 48%): mp
137-138 °C; IR (KBr) 3473 (OH), 1755 (CdO), 1459, 1429,
1384, 1355, 1290, 1228, 1190, 1143, 1086, 1058, 978, 880, 765
found 356.1454. [R]20 -38 (c 0.79, CH2Cl2).
D
1
cm-1; H NMR (400 MHz, CDCl3) δ 0.84 (3H, d, J ) 6.4 Hz),
(4S)-3-[(2S,4R,5R,6R)-4-(ter t-Bu toxy)-5-h yd r oxy-6-(h y-
d r oxym eth yl)-tetr a h yd r o-2H-p yr a n -2-yl]-4-isobu tyl-1,3-
oxa zolid in -2-on e 12b. From 11b (214 mg, 0.65 mmol), after
hydroboration-oxidation (Procedure B, 6 h), 12b was obtained
after chromatography (silica gel 40/1, cyclohexane/AcOEt 50/
50 to 30/70) as a colorless oil (138 mg, 61%): IR (neat) 3454
(OH), 1747 (CdO), 1470, 1427, 1394, 1366, 1282, 1256, 1227,
1193, 1127, 1073, 1013, 959, 877, 768 cm-1; 1H NMR (400 MHz,
CDCl3) δ 0.93 (3H, d, J ) 6.4 Hz), 0.95 (3H, d, J ) 6.4 Hz),
1.26 (9H, s), 1.55 (2H, m), 1.75-1.90 (2H, m), 2.00 (1H, ddd,
J ) 2.0, 4.4 and 12.3 Hz), 2.49 (1H, broad s), 3.33 (1H, td, J )
2.0 and 9.0 Hz), 3.46 (1H, dt, J ) 4.4 and 9.0 Hz), 3.62 (1H,
ddd, J ) 4.4, 9.0 and 10.8 Hz), 3.76 (1H, m), 3.91 (2H, m),
4.02 (1H, dd, J ) 5.4 and 8.4 Hz), 4.36 (1H, t, J ) 8.4 Hz),
5.19 (1H, d, J ) 10.8 Hz); 13C NMR + DEPT 135 (100 MHz,
CDCl3) δ 21.4 (CH3), 23.6 (CH3), 24.6 (CH), 28.6 (CH3), 36.3
(CH2), 42.9 (CH2), 52.2 (CH), 62.8 (CH2), 67.8 (CH2), 70.7 (CH),
72.2 (CH), 74.7 (C), 77.5 (CH), 80.0 (CH), 157.1 (C). HRMS
(FAB) calcd for C17H31NO6Na [M + Na]+ 368.20491, found
368.2048; calcd for C17H31NO6K [M + K]+ 384.17885, found
1.27 (9H, s), 1.85 (1H, td, J ) 11.3 and 12.3 Hz), 2.11 (1H,
ddd, J ) 2.0, 4.5 Hz and 12.3 Hz), 2,50 (1H, d, J ) 2.0 Hz),
3.32 (1H, td, J ) 2.0 and 9.0 Hz), 3.47 (1H, ddd, J ) 3.4, 4.7
and 9.0 Hz), 3.65 (1H, ddd, J ) 4.5, 9.0 and 10.8 Hz), 3.74
(1H, m), 3.87 (1H, m), 4.19 (1H, m), 5.25 (1H, dd, J ) 2.0 and
11.3 Hz), 5.59 (1H, d, J ) 7.9 Hz), 7.25-7.45 (5H, m); 13C NMR
+ DEPT 135 (100 MHz, CDCl3) δ 16.7 (CH2), 28.8 (CH3), 36.9
(CH2), 53.7 (CH), 62.8 (C-6), 70.9 (CH), 72.5 (CH), 74.7 (C),
77.4 (CH), 79.1 (CH), 79.9 (CH), 125.9 (CH), 128.4 (4 x CH),
134.3 (C), 156.6 (C). Anal. Calcd for C20H29NO6: C, 63.31; H,
7.70; N, 3.69. Found: C, 63.04; H, 7.75; N, 3.58. [R]20 +13.9
D
(c 0.36, CH2Cl2).
(4R)-3-[(2R,4S,5S,6S)-6-(b en zyloxym et h yl)-4-(ter t-b u -
t oxy)-5-h yd r oxy-t et r a h yd r o-2H -p yr a n -2-yl]-4-et h yl-1,3-
oxa zolid in -2-on e 17a . From 16a (97 mg, 0.25 mmol), after
hydroboration-oxidation (Procedure B, 7 h), 17a was obtained
after chromatography (silica gel 30/1, cyclohexane/AcOEt 70/
30 to 10/10) as a colorless oil (62 mg, 61%): IR (neat) 3456
(OH), 1746 (CdO), 1424, 1393, 1365, 1272, 1225, 1193, 1077,
384.1792. [R]20 +50.9 (c 1.46, CH2Cl2).
D
1
1026, 910, 875, 768, 701 cm-1; H NMR (400 MHz, CDCl3) δ
(4R)-3-[(2R,4S,5S,6S)-4-(ter t-Bu toxy)-5-h yd r oxy-6-(h y-
d r oxym et h yl)-t et r a h yd r o-2H -p yr a n -2-yl]-4-p h en yl-1,3-
oxa zolid in -2-on e 12c. From 11c (101 mg, 0.29 mmol), after
hydroboration-oxidation (Procedure B, 4.5 h), 12c was ob-
tained after chromatography (silica gel 40 /1, cyclohexane/
AcOEt 50/50 to 20/80) as white crystals (47 mg, 44%): mp
141.5-142 °C; IR (KBr) 3548, 3432 (OH), 1749 (CdO), 1481,
1460, 1417, 1392, 1361, 1284, 1228, 1192, 1132, 1086, 1032,
972, 870, 768 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.23 (9H, s),
1.90 (1H, dt, J ) 11.3 and 12.3 Hz), 2.04 (1H, ddd, J ) 2.2,
4.4 and 12.3 Hz), 2.27 (1H, broad s), 3.06 (1H, t, J ) 9.1 Hz),
0.88 (3H, t, J ) 7.4 Hz), 1.25 (9H, s), 1.65 (1H, m), 1.87 (2H,
m), 1.98 (1H, ddd, J ) 2.3, 4.5 and 12.3 Hz), 2.68 (1H, broad
s), 3.43 (1H, t, J ) 9.3 Hz), 3.52 (1H, dt, J ) 3.9 and 9.3 Hz),
3.62 (1H, m), 3.70 (1H, dd, J ) 3.9 and 10.8 Hz), 3.79 (1H, dd,
J ) 4.2 and 10.8 Hz), 3.87 (1H, m), 4.02 (1H, dd, J ) 4.9 and
8.6 Hz), 4.33 (1H, t, J ) 8.6 Hz), 4.57 (1H, d, J ) 4.4 Hz), 5.18
(1H, dd, J ) 2.3 and 11.5 Hz); 13C NMR + DEPT 135 (100
MHz, CDCl3) δ 8.0 (CH3), 26.8 (CH2), 28.8 (CH3), 36.4 (CH2),
54.3 (CH), 66.9 (CH2), 70.2 (C-6), 71.0 (CH), 72.4 (CH), 73.4
(CH2), 74.7 (C), 76.5 (CH), 79.8 (CH), 127.4 (2 x CH), 128.2 (2
J . Org. Chem, Vol. 69, No. 12, 2004 4201

Gaulon et al.
x CH), 138.1 (C), 157.1 (C); HRMS (FAB) calcd for C22H33NO6-
Na [M + Na]+ 430.2206, found 430.2202. [R]20D -27.4 (c 1.015,
CH2Cl2).
(1H, m), 4.03 (1H, dd, J ) 4.9 and 8.6 Hz), 4.33 (1H, t, J ) 8.6
Hz), 4.34 (2H, m), 5.20 (1H, dd, J ) 2.3 and 11.5 Hz).
(4R)-3-[(2R,4S,5S,6S)-5-Acet oxy-6-(a cet oxym et h yl)-4-
(ter t-b u t oxy)-t et r a h yd r o-2H -p yr a n -2-yl]-4-et h yl-1,3-ox-
a zolid in -2-on e 15a : 1H NMR (400 MHz, CDCl3) δ 0.90 (3H,
t, J ) 7.6 Hz), 1.18 (9H, s), 1.67 (1H, qt, J ) 7.6 Hz), 1.86 (1H,
m), 1.93-2.05 (2H, m), 2.04 (3H, s), 2.08 (3H, s), 3.61 (1H, ddd,
J ) 2.4, 4.4 and 9.3 Hz), 3.75 (1H, ddd, J ) 5.4, 9.3 and 10.3
Hz), 3.89 (1H, m), 4.04 (1H, dd, J ) 4.6 and 8.6 Hz), 4.08 (1H,
dd, J ) 2.4 and 12.3 Hz), 4.17 (1H, dd, J ) 4.4 and 12.3 Hz),
4.34 (1H, t, J ) 8.6 Hz), 4.82 (1H, t, J ) 9.3 Hz), 5.22 (1H, dd,
J ) 2.5 and 11.3 Hz).
Hyd r obor a tion -Oxid a tion of Allylic Alcoh ol Aceta te
13a . From 13a (84 mg, 0.24 mmol), after hydroboration-
oxidation (Procedure A), partial desacetylation of the crude
product was observed (1H NMR). To a cooled solution of the
residue and DMAP (3 mg, 0.025 mmol) in anhydrous dichlo-
romethane (3 mL) at 0 °C under nitrogen were successively
added triethylamine (70 µL, 0.5 mmol) and acetic anhydride
dropwise (94 µL, 1 mmol), and the reaction mixture was stirred
for 2 h at room temperature and refluxed for 1 h. The organic
layer was successively washed with water and then brine, and
the aqueous layer was extracted with AcOEt. After drying
(MgSO4) of the combined organic layers, removal of solvent,
and chromatography (silica gel 40 /1, cyclohexane/AcOEt 70/
30 to 0/100) of the crude product, alcohol 12a (18 mg, 23%),
monoacetate 14a (13 mg, 14%), and diacetate 15a (30 mg, 30%)
were obtained as colorless oils.
Ack n ow led gm en t. C. Gaulon is grateful to the
Ministe`re Franc¸ais de la Recherche et de la Technologie
for her Ph.D. grant (2000-2003).
Su p p or tin g In for m a tion Ava ila ble: Crystal structure
(4R)-3-[(2R,4S,5S,6S)-6-(Acetoxym eth yl)-4-(ter t-bu toxy)-
5-h yd r oxy-tetr a h yd r o-2H-p yr a n -2-yl]-4-eth yl-1,3-oxa zo-
1
data of amidoester 7a and adducts 10a ,d ; copies of H NMR
spectra of all new compounds lacking elemental analysis; and
tables of 1H NMR correlations between adducts 3a -f, adducts
10a -e, and N-glycosides 12a -e. This material is available free
of charge via the Internet at http://pubs.acs.org.
1
lid in -2-on e 14a : H NMR (400 MHz, CDCl3) δ 0.89 (3H, t, J
) 7.4 Hz), 1.26 (9H, s), 1.63 (1H, m), 1.83 (2H, m), 2.00 (1H,
ddd, J ) 2.5, 4.5 and 12.3 Hz), 2.06 (3H, s), 2.49 (1H, d, J )
2.5 Hz), 3.27 (1H, td, J ) 2.5 and 9.5 Hz), 3.54 (1H, dt, J )
3.4 and 9.5 Hz), 3.62 (1H, ddd, J ) 4.9, 9.5 and 11.0 Hz), 3.88
J O040102Y
4202 J . Org. Chem., Vol. 69, No. 12, 2004