Highly diastereoselective synthesis of 1,2-amino alcohols via nucleophilic addition of organocerium reagents to 4- and 5- oxazolidinonecarbaldehydes

Article abstract of DOI:10.1139/v98-112

The reaction of chiral, non-racemic 4- and 5- oxazolidinonecarbaldehydes, 6 and 13, with organocerium reagents proceeds efficiently with good to excellent diastereoselectivity to give syn and anti alcohols, respectively. A model to explain the observed diastereoselectivity of the reaction of 6 and 13 is provided. The utility of this method for the synthesis of amino alcohols is exemplified by the synthesis of C-18-D-ribo- phytosphingosine from the anti alcohol 14f.

Full text of DOI:10.1139/v98-112

1070
Highly diastereoselective synthesis of 1,2-amino
alcohols via nucleophilic addition of
organocerium reagents to 4- and
5-oxazolidinonecarbaldehydes
Andrew G.H. Wee and Fuxing Tang
Abstract: The reaction of chiral, non-racemic 4- and 5-oxazolidinonecarbaldehydes, 6 and 13, with organocerium
reagents proceeds efficiently with good to excellent diastereoselectivity to give syn and anti alcohols, respectively. A
model to explain the observed diastereoselectivity of the reaction of 6 and 13 is provided. The utility of this method
for the synthesis of amino alcohols is exemplified by the synthesis of C-18-D-ribo-phytosphingosine from the anti
alcohol 14f.
Key words: oxazolidinonecarbaldehydes, organocerium, diastereoselective, amino alcohols, C-18-ribo-phytospingosine.
Résumé : La réaction de réactifs organiques du cérium avec les 4- et 5-oxazolidinonecarbaldéhydes chiraux et non
racémiques, 6 et 13, s’effectuent d’une façon efficace, avec des diastéréosélectivités allant de bonnes à excellentes, et
elles conduisent aux alcools syn et anti respectivement. On propose un modèle pour expliquer la diastéréosélectivité de
la réaction des produits 6 et 13. Comme exemple pour démontrer l’utilité de cette méthode pour la synthèse
d’aminoalcools, on propose la synthèse de la C-18-D-ribo-phytosphingosine à partir de l’alcool anti, 14f.
Mots clés : oxazolidinonecarbaldéhydes, organocérium, diastéréosélectif, aminoalcools, C-18-ribo-phytosphingosine.
[Traduit par la Rédaction] Wee and Tang 1081
gated (5). Two aspects that make them attractive synthetic
intermediates are (a) the 2-oxazolidinone moiety can be con-
The 1,2-amino alcohol moiety is a common subunit that is
found in many naturally occurring and medicinally impor-
tant compounds such as sphingolipids (1a), hydroxylated al-
kaloids (1b, 1c), amino acids (1d, 1e), HIV-enzyme
inhibitors (1f, 1g), and amino sugars (1h). As well, chiral
auxiliaries (2a) and ligands (2b) that are widely employed in
asymmetric synthesis possess the 1,2-amino alcohol unit as a
key structural feature. Much effort has, therefore, been de-
voted towards developing new strategies (for reviews, see
ref. 3) for the synthesis of 1,2-amino alcohols. The most
widely used method involves the nucleophilic addition of
C-centred nucleophiles to α-amino aldehydes (3a, 3c) How-
ever, some limitations of the method have been noted; for
example, the α-amino aldehyde is prone to racemization un-
der the reaction conditions (3a, 4). As well, the
diastereoselectivity of the nucleophilic addition reaction is
usually not as high as expected although, recently, methods
(3c) have been devised to overcome this problem.
sidered as a protected amino alcohol synthon, which can be
subsequently unmasked to reveal the 1,2-amino alcohol unit,
and (b) the reactions carried out on oxazolidinone deriva-
tives are usually highly stereoselective (5).
Herein, we report our studies on the nucleophilic addition
of organocerium reagents to chiral, non-racemic 4- and 5-
oxazolidinonecarbaldehydes (6 and 13, respectively) (for a
preliminary communication, see ref. 6). The addition was
found to proceed with good to excellent diastereoselectivity
to give syn or anti alcohol products in moderate to good
chemical yields. We also developed a procedure for the gen-
eration and in situ reaction of 4-oxazolidinonecarbaldehyde
6 with organocerium reagents.
Preparation of iodophenylsulfone (5) and benzylether
(8)
In comparison, the use of 2-oxazolidinones for the synthe-
sis of 1,2-amino alcohols has not been extensively investi-
The iodo phenylsulfone 5 serves as a convenient and
shelf-stable precursor of the aldehyde 6. The preparation of
5 is summarized in Scheme 1 and began with the oxidation
of the known phenylsulfide 1 (7a) (α:β ratio 8.5:1.5 based
on integration of H-1) with mCPBA to give a separable mix-
ture of α,β-anomers (8:2)2,3 of 2. The slightly light-sensitive
2 were then treated with n-butyllithium in the presence of
HMPA as a cosolvent to effect 1,2-elimination of a molecule
of acetone to give the ene alcohol 3 (for the use of
Received February 4, 1998.
A.G.H. Wee1 and F. Tang. Department of Chemistry,
University of Regina, Regina, SK S4S 0A2, Canada.
1
Author to whom correspondence may be addressed.
Telephone: (306) 585-4767. Fax: (306) 585-4894. E-mail:
andreghw@meena.cc.uregina.ca
Can. J. Chem. 76: 1070–1081 (1998)
© 1998 NRC Canada

Wee and Tang
1071
Scheme 1.
intermediate is prone to undergo a retro-Michael reaction.
This pathway is absent in the tert-butoxide-catalyzed reac-
tion because the phenylsulfone-stabilized carbanion is
protonated by the tert-butyl alcohol that is present.
OSiMe2Bu-t
O
OSiMe2Bu-t
O
SPh
SO2Ph
mCPBA
Desilylation of 4a to the primary alcohol 4b was accom-
plished using Me3SiCl in MeOH and was followed by reac-
tion of 4b with Ph3P–I2 (9) to give the iodo phenylsulfone 5.
O
O
O
O
1
2
1
BuLi, THF
HMPA
We were not able to ascertain from the H NMR spectra
of 4a,b whether the stereochemistry of the 1-phenylsulfonyl
group is α or β because of the overlap of the H-1, H-2, and
1
OR
PhCHN resonances. However, the H NMR of 5 was better
5
OSiMe2Bu-t
O
O
SO2Ph
resolved and showed H-1 as a doublet centred at δ 4.82 with
a vicinal coupling constant, J1,2, of 1.8 Hz. This small J
value3 suggests that the 1-phenylsulfonyl group has the
β-configuration. This outcome is unexpected when the con-
version of 3 to 4a is considered and it suggests that the
phenylsulfone-stabilized carbanion intermediate that is gen-
erated during the intramolecular carbamation reaction is
protonated from the more hindered, concave side of the bi-
cycle to give 4a. It should be noted that protonation from the
less hindered, convex side of the bicycle should, in princi-
ple, be more favoured; however, this would lead to a
sterically congested product wherein the α-phenylsulfonyl
moiety is engaged in severe nonbonded interactions with the
syn oxazolidinone moiety.
1
SO2Ph
3
PhCH2N=C=O
KOBu-t, THF
O
NBn
HO
O
4
3
2 equiv.
Me3SiCl,
MeOH
a; R = SiMe2Bu-t
b; R = H
Ph3P, I 2
PhMe, DCM
I
O
SO2Ph
O
Zn/Ag
O
NBn
The next step was the Zn–Ag4 (10) mediated reductive
elimination of 5 in dry THF at 60°C to afford the olefinic al-
dehyde 6. Subsequent reduction of 6 with NaBH4 proceeded
O
NBn
o
THF, 60
C
O
O
5
6
23
uneventfully to give crystalline primary alcohol 7 ([α]D
NaBH4
THF-EtOH
−15.2 (c 0.98, CHCl3))5 in high yield. Alcohol 7 was then
benzylated to give 8, which served as the precursor for the
5-oxazolidinonecarbaldehyde 13.
OBn
NBn
OH
5
4
1
The formation of 6 deserves some comments. The H and
PhCH2Br
O1 3 NBn
13C NMR spectra of the primary alcohol 7 that is derived
from 6 are in accord with the assigned structure. The salient
O
Bu4N I, NaH, THF
O
O
1
feature in the H NMR spectrum is the pseudo triplet due to
7
8
H-5 that was centred at δ 4.92. It has a J4,5 of 7.4 Hz6 that is
characteristic of a cis stereochemistry (11). This indicates
that no epimerization of the aldehyde to the trans
diastereomer had occurred under the reaction conditions
used in the reductive elimination step.
organosulfones in synthesis, see ref. 8). We found it unnec-
essary to treat α-2 and β-2 separately in this elimination re-
action since both anomers lead to the same ene alcohol with
no loss in yield. Compound 3 was found to be unstable dur-
ing storage (~ 3 d) and was utilized immediately in the
Formation and reaction of 4-oxazolidinonecarbaldehyde
(6) with RCeCl2
carbamation step. Base-catalyzed reaction of
benzylisocyanate afforded cis-bicycle 4a as
diastereomer in good yield.
It was found that the use of KOBu-t is essential for effi-
cient carbamation. With NaH as the base only a low yield of
the 4a was obtained; the uncyclized urethane, which had re-
sulted from the nucleophilic addition of only the alcohol unit
to the benzylisocyanate, was the major product. A likely ex-
planation for the lack of intramolecular Michael addition is
that, with NaH, the phenylsulfonyl-stabilized carbanion (8b)
3
with
single
a
It is well documented (3a, 4) that amino aldehydes (ex-
cept for a serine-derived aldehyde (12)) are, in general, un-
stable and are not amenable to isolation. To avoid potential
difficulties associated with the isolation of 6, we decided to
investigate its generation and in situ reaction with the pre-
formed organocerium reagent (13a, 13b) (hereafter referred
to as RCeCl 2; the exact speciation of the organocerium re-
agent is not known. See ref. 13c) as depicted in eq. [1]. The
2 Ratio is based on isolated yields. Decoupling of the H-3 multiplet (δ 4.72–4.81) in α-2 simplified the H-1,H-2 multiplet at δ 5.02–5.10; H-2
collapsed to a singlet at δ 5.9. H-1 was observed as a doublet centred at δ 5.7 and has a J1,2 of 3.8 Hz.
3 Typically, H-1 in the α-anomer shows a J1,2 in the range 3.8–4.4 Hz, and in the β-anomer J1,2 is in the range of 1.8–2.0 Hz (7).
4 We have also examined other Zn-based methods such as Zn dust, EtOH; Zn/Cu, THF; and ZnCl2–C8K, THF. These methods either gave
low yields of 6 and a substantial amount of the reduced product 2o3r decomposition products.
5
We have prepared ent-7 from D-mannose and it has [α]D = +14.8 (c 1.01, CHCl3).
6 Decoupling of the alkene methine multiplet at δ 5.99–6.19 collapsed the H-5 “triplet” to a broad doublet centred at δ 4.92. Typically, Jtrans
=
3.3–4.5 Hz and Jcis = 6.2–7.5 Hz (11).
© 1998 NRC Canada

1072
Can. J. Chem. Vol. 76, 1998
Table 1. Reaction of 6 with RCeCl2 according to method A.
b
Entry
RCeCl2
T,°C/h
syn-9:anti-10
Yield (%)
1
2
3
4
5
6
7
8
9
a; MeLi
–78/5
–78/5
–78/5
–78/5
–78/5
–78/5
–78/5
–78/5; 0/1
–78/5
95:5
85
35
85
40
92
94
85
52
29
MeLia
89:11
>99:1
83:17
86:14c
>99:1
>99:1
88:12
88:12
b; CH2ϭCHMgBr
CH2ϭCHMgBra
c; CH2ϭC(OBu-t)O– Li+
d; PhCϵCLi
e; 2-Furanyl Li
f; PhMgBr
PhMgBr
aReaction was performed without CeCl3.
1
bAlcohols were inseparable. Ratio was based on the integration of Me resonance in the H NMR of acetate derivatives.
cRatio was based on the integration of the t-Bu singlet.
use of dry THF for the reductive elimination step was essen-
tial for the success of this procedure.
simplified the H-4 triplet (δ 3.11) to a doublet, J4,5 = 4.4 Hz.
Based on this small vicinal coupling constant (11) the rela-
tive stereochemistry of the methyl and dioxalanyl groups
was, therefore, assigned as trans. This result was confirmed
by the observation of a strong NOE enhancement (6.7%) for
the H-4 proton upon irradiation of the C-5 methyl doublet.
I
O
O
SO2Ph
Zn/Ag
THF
60 C
RCeCl2
[1]
O
NBn
(6 equiv.)
O
NBn
HO
o
o
C
THF, -78
OH
O
Me
Me
O
5
1) ) KOH, aq. EtOH
6
[2]
O
NBn
) 2) Boc2O, Et2O
HO
NBn
Boc
OH
OH
O
R
R
11
9a,10a
+
O
NBn
O
NBn
o
1
)
O3, MeOH, -78 C;
NaBH4
)
O
O
syn-9
anti-10
) 2) CH2=CH(OMe)Me
PPTS, DCM
3) ) NaH, THF, reflux
Me
As shown in Table 1, Grignard-derived and
organolithium-derived organocerium reagents reacted well
with 6. The nucleophilic addition reaction produced a crys-
talline, diastereomeric mixture of alcohols syn-9 and anti-10
in which the former was present as the predominant or ex-
clusive product. For reactions in which Grignard-derived
H
H
O
2
O
5
1
4
'
'
4 H
O
O
N
Bn
12
RCeCl reagents were used, it was advantageous to warm
2
Formation and reaction of 5-oxazolidinonecarbaldehyde
(13) with RCeCl2
Aldehyde 13 was prepared by ozonolysis of the benzyl
ether 8 in DCM followed by replacement of the DCM with
dry THF. The THF solution of crude 13 was then added to
RCeCl2 (4 equiv.) at –78°C (eq. [3]). Again, we found that it
the reaction mixture to 0°C and to maintain the reaction at
0°C for at least 1 h. Thus, quenching the PhCeCl2 reaction
after 5 h at –78°C yielded 29% of a mixture of 9f and 10f
(entry 9). However, a 52% yield of 9f, 10f was obtained
when the mixture was warmed to and maintained at 0°C for
1 h (entry 8). For the CH2ϭCHCeCl2 reaction, the reaction
mixture must be conducted at –78°C because the
organocerium reagent is unstable at 0°C (13b, 14). The use
of Grignard and organolithium reagents alone resulted in
lower diastereoselectivity and poorer chemical yields of
products (compare entries 1, 2 and 3, 4).
OBn
O
OBn
NBn
o
O3, DCM, -78 C;
O
NBn
O
[3]
Ph3P
O
O
The relative stereochemistry of the hydroxyl group and
the benzylamino moiety of the oxazolidinone unit in 9 was
assigned as syn on the basis of the data obtained from proton
decoupling and NOE experiments performed on 12. Com-
pound 12 was synthesized from 9a,10a using standard func-
tional group manipulations as summarized in eq. [2].
Decoupling of the C-5 methyl doublet (δ 1.25) in 12 col-
lapsed the H-5 quintet (br, δ 4.42) to a doublet, J5,4 = 4.4 Hz.
Similarly, irradiation of the H-4′ multiplet (δ 4.00–4.18)
8
13
OH
R
OBn
NBn
RCeCl2
(4 equiv.)
O
o
C
THF, T
O
anti-14
© 1998 NRC Canada

Wee and Tang
1073
Table 2. Reaction of 13 with RCeCl2 according to method B.
Entry
RCeCl2
T,°C/h
anti-14
Yield (%)b
1
2
3
4
5
6
7
8
9
a; MeLi
–78/5
–78/5
–78/5
–78/5
–78/5
–78/5
–78/5
–78/5; 0/1
–78/5
>99:1
Dec.
62
0
MeLia
b; CH2ϭCHMgBr
CH2ϭCHMgBra
c; PhCϵCLi
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
59
21
85
84
64
69
40
d; CH2ϭC(OBu-t)O– Li+
e; 2-Furanyl Li
f; C14H29MgBr
C14H29MgBr
aReaction was performed in the absence of CeCl3.
bIsolated yields.
was advantageous to warm the reactions involving Grig-
nard-derived RCeCl2 to 0°C before being quenched (Table
2, entries 8 and 9). In all cases, the alcohol product 14 was
obtained as an oil, and in moderate to good overall yields.
Chart 1.
O
H1'
O
H
CH2
O
O
1
H1'
NBn
Only one diastereomer was produced as evidenced by H
H5
and 13C NMR analysis of the crude product: the other
epimer was not detected.
H
O
-
BnN
R
H2C
H5
-
R
H H
O
The use of CeCl3 is essential for the success of the reac-
tion. For example, the use of MeLi only resulted in the com-
plete decomposition of 13 (Table 2, compare entries 1 and 2)
and the use of only CH2ϭCHMgBr gave a lower yield of 14
(compare entries 3 and 4). The relative stereochemistry be-
tween the hydroxyl and the oxygen atom of the
oxazolidinone unit was assigned as anti on the basis of the
conversion of compound 14f to C-18-D-ribo-phyto-
sphingosine 18 (see later).
B
A
Aldehyde 6
anti - 10
(minor)
syn - 9
(major)
O
H1'
O
H
Bn
H2C
It was also of interest to examine the diastereoselectivity
of nucleophilic addition reaction of 6 and 13 with
MeTi(OPr-i)3. It is well documented (15) that this
nucleophilic reagent reacts with α-alkoxy aldehydes in a
non-chelation controlled pathway because of the reduced
Lewis acidity of the titanium centre. Unfortunately, the reac-
tion of MeTi(OPr-i) 3 with 6 (using the same procedure de-
veloped for the conversion of 5 → 9, 10) resulted only in
decomposition products. On the other hand, the reaction of
MeTi(OPr-i)3 with 13 (eq. [4]) gave a good yield (72%) of
O
O
N
H5
H5
H
N
Bn
CH2
O
O
H
H
H1'
D
C
Bn
Bn
O
N
Cl
Cl
O
1
the addition product 15. The H NMR spectrum of 15 was
Ce
O
anti - 14
very similar to that of anti-14a. We therefore prepared the
H
O
RCeCl2
R
OH
O
OBn
NBn
(i-PrO)3TiMe
(1:1)
H H
Me
OBn
NBn
E
DCM - Et2O
O
Aldehyde
[4]
O
o
-40 to 0 C
13
O
O
O
then dil. HCl
O
13
15
MeTi(OPr-i)3
NBn
O
)
syn-15
1) KOH, EtOH
)
)
3) CH2=CH(OMe)Me,
PPTS
4) 10% Pd/C, H2
2) Boc2O
CH2OBn
H
H
-
Me
)
Me
'
2
)
F
H
5) NaH, THF, reflux
O
5
Me
O
'
4' O
H
Me
oxazolidinone derivative 16 (eq. [4]), which was subjected
to NOE analysis. In particular, irradiation of the C-5′ methyl
doublet centred at δ 1.05 resulted in a 3% enhancement of
the H-4′ double doublet centred at δ 4.44. On the basis of
this result, the configuration of the newly created carbinol
H
5
4
2
BnN
O
16
© 1998 NRC Canada

1074
Can. J. Chem. Vol. 76, 1998
Scheme 2.
occur from the less hindered side of the carbonyl function,
leading to anti-14. This line of reasoning is further sup-
ported by the result from the reaction of 13 with
MeTi(OPr-i)3. In the absence of any chelation to the tita-
nium centre in the reagent, nucleophilic addition would pro-
ceed via F to give the syn diastereomer 15.
OH
O
HO
NHR
C
14H29
OBn
OR
KOH, EtOH
reflux
C
14H29
NBn
OH
17
O
anti-14f
a; R = Bn
b; R = H
Pd(OH)2, H2,
95% EtOH
Synthesis of C-18-D-ribo-phytosphingosine.
22
The oxazolidinone alcohol anti-14f ([α]D +35.0 (c 1.50,
CHCl3)) was hydrolyzed in alcoholic 2 M aqueous KOH to
provide 17a in 83% yield (Scheme 2). Hydrogenolysis of the
N,O-benzyl protecting groups in 17a using Pearlman’s cata-
lyst afforded phytosphingosine 17b as a powdery solid,
which was subsequently peracetylated to give the crystalline
tetraacetate derivative 18. The spectroscopic data and spe-
cific rotations of 17b and 18 are in excellent agreement with
those reported (19).
AcO
NHAc
Ac2O
OAc
(6 equiv.)
pyridine
C14H29
OAc
18
centre was assigned as S. That is, the addition reaction has
proceeded with syn diastereoselectivity.
Reaction pathway
The reactions of oxazolidinonecarbaldehydes 6 and 13
with organocerium reagents were found to proceed effi-
ciently and with good to excellent diastereoselectivity to af-
ford the corresponding secondary alcohol products.
Compounds 6 reacted to give syn alcohols 9 as the major or
exclusive products. With compounds 13, the anti alcohols 14
were formed as the exclusive products. The results suggest
that oxazolidinonecarbaldehyde 6 reacted with RCeCl 2 in a
non-chelation pathway but with 13 a cerium chelate is in-
volved. The method was applied to the synthesis of naturally
occurring amino alcohol C18-D-ribo-phytosphingosine. Fur-
ther application of this method and use of chiral,
non-racemic 2-oxazolidinonecarbaldehydes in synthesis are
in progress.
The diastereoselectivity observed in the reaction of alde-
hyde 6 can be understood if we consider the two reactive
conformers A and B (Chart 1). In each of the conformers,
the preferred orientation of the C-5-vinyl substituent with re-
spect to the rigid, planar oxazolidinone unit is the one in
which the vinyl H-1′ hydrogen is aligned antiperiplanar to
the oxazolidinone H-5 hydrogen. This arrangement is
adopted in order to relieve A1,3 strain (16). Conformer A
(17a) is more stable than B because in the latter a
destabilizing interaction is present. Preferential nucleophilic
attack via the sterically less hindered side in A leads to the
major syn diastereomer 9 whereas attack via the sterically
encumbered side in B results in the minor anti diastereomer
10. The conformers
C
and
D
correspond to the
Felkin–Anh-type model (17) but are considered less stable
than A and B because of the presence of destabilizing steric
interactions. C is destabilized by the steric interaction be-
tween the aldehydic hydrogen and the cis-vinyl group and
especially H-1′. Similarly, steric interaction between the
cis-vinyl group/H-1′ and the oxygen of the carbonyl function
in D results in its destabilization.
The involvement of a five-membered chelate intermediate
resulting from coordination of the carbonyl oxygen and the
nitrogen atom of the NBn moiety to Lewis acidic Ce(III)
(13a) is not likely because of the reduced basicity of the ni-
trogen atom resulting from conjugation of the nitrogen lone
pair of electrons with the π-bond of the carbonyl group of
the oxazolidinone unit.
In the case of 13, a possible explanation for the unexpect-
edly high diastereoselectivity is the involvement of a
seven-membered Ce(III) chelate E (Chart 1) (for the in-
volvement of 7-membered chelates, see ref. 18). Its forma-
tion is entropically favoured because of the cis relationship
of the aldehyde and BnOCH2 moieties. Also, it is well docu-
mented that the oxygen atom in benzyl ethers shows a pro-
pensity to coordinate to Lewis acids (15a). The chelate can
also accommodate a Felkin–Anh (17) arrangement. Thus,
both chelation control and stereoelectronic effects reinforce
one another in controlling the diastereoselectivity of the re-
action. Intramolecular or intermolecular delivery of R′ will
General
Melting points are uncorrected and were measured on a
Kofler hot-stage melting point apparatus. Infrared spectra
were recorded using
spectrophotometer: only diagnostic absorptions in the infra-
red spectrum are reported. 1H (200 MHz) and 13C
(50.3 MHz) NMR spectra were recorded in CDCl3 (unless
otherwise stated), using a Bruker 200QNP spectrometer.
Tetramethylsilane (δH = 0.00) and the CDCl3 resonance (δC
= 77.0) were used as references. Multiplicities “t”, “q”, and
“quintet” represent pseudo triplet, quartet, and quintet, re-
a
Perkin Elmer 1600FT
1
spectively, and are quoted as they appear in the H NMR
spectra. Where applicable, the signals of minor diastereomers
are given within square brackets. Proton assignments were
made using double irradiation experiments and, where nec-
essary, 2D-COSY-45 experiments. Numberings in com-
pounds 2–5 follow sugar numberings and, in compounds 6
onwards, numberings follow 2-oxazolidinone numberings.
Elemental analyses and high-resolution electron impact
(70 eV) and chemical ionization mass spectral analyses were
performed at the Chemistry Department, University of Sas-
katchewan. Optical rotations were measured using an Opti-
cal Activity AA-5 polarimeter.
© 1998 NRC Canada

Wee and Tang
1075
Reaction progress was monitored by thin-layer chroma-
tography on Merck silica gel 60F254 precoated (0.25 mm) on
aluminum backed sheets. Air- and moisture-sensitive reac-
tions were conducted under a static pressure of argon. All
organic extracts were dried over anhydrous Na2SO4. Flash
chromatography (20) was performed on Merck silica gel 60
(230–400 mesh). Unless stated otherwise, the eluent is a
mixture of petroleum ether:EtOAc in v/v ratio as follows:
solvent A, 1:1; solvent B, 2:1; solvent C, 3:1; solvent D, 4:1;
solvent E, 5:1. Abbreviations of solvents used: petroleum
ether (PE, bp 35–60°C), ethyl acetate (EtOAc), diethyl ether
(Et 2O), tetrahydrofuran (THF), and dichloromethane
(DCM). THF and Et2O were distilled from sodium-
benzophenone, and DCM was distilled from CaH2.
a mixture of dry THF (77 mL) containing dry HMPA
(3.2 mL) under Ar. The solution was cooled to –78°C and
n-BuLi (10.8 mL, 21.7 mmol, 2.1 M in hexanes) was added
dropwise via syringe to the mixture. A deep yellow-orange
solution resulted, which was stirred at –78°C for 1 h and
then the cooling bath was removed. The mixture was al-
lowed to warm slowly to rt, stirred at rt for 2 h, and then
recooled to 0°C. Saturated aqueous NH4Cl (15 mL) was
added, followed by EtOAc (50 mL). The organic layer was
removed and the aqueous phase was reextracted with EtOAc
(2 × 50 mL). The combined organic phases were washed
with saturated aqueous NaCl (70 mL), dried, filtered, and
evaporated. The residual yellow oil was chromatographed
(solvent C) to give 3 as a pale yellow oil (3.8 g, 71%) that
slowly crystallized on standing. The product was found to be
unstable and is best kept in the freezer for prolonged stor-
Organometallic reagents
1
age. IR, νmax: 3575–3275 cm–1. H NMR, δ: –0.02 (s, 3H,
Simple Grignard and organolithium reagents were pur-
chased from Aldrich. Tetradecylmagnesium bromide was
prepared from tetradecylbromide and magnesium metal as a
0.5 M solution in THF. Lithium phenylacetylide (21a),
2-lithiofuran (21b), and CH2 = C(OBu-t)O– Li+ (21c) were
prepared according to literature procedures. Organometallic
reagents were standardized before use by titration using ei-
ther 1,3-diphenylacetone p-tosylhydrazone (22a) (RLi) or
pyreneacetic acid (22b) (RMgBr) as indicators.
SiMe), –0.05 (s, 3H, SiMe), 0.78 (s, 9H, t-Bu), 2.08–2.20
(br hump, 1H, OH), 3.57 (dd, 1H, J = 11.5, 4.8 Hz, H-5),
3.69 (dd, 1H, J = 11.5, 4.8 Hz, H-5′), 4.50 (q, 1H, J =
4.9 Hz, H-4), 4.92–5.2 (m, 1H, H-3), 5.98 (d, 1H, J =
2.6 Hz, H-2), 7.46–7.71 (m, 3H, PhH), 7.92–8.01 (m, 2H,
PhH). 13C NMR, δ: –5.4, 18.2, 25.7, 62.5, 74.9, 92.7, 109.6,
128.7, 129.2, 134.3, 137.9, 157.9.
The above ene alcohol (3.8 g, 10.3 mmol) was dissolved
in dry THF (37 mL), under Ar. Benzyl isocyanate (1.4 mL,
11.4 mmol) was added and the reaction mixture was cooled
to 0°C. Potassium tert-butoxide (0.24 g, 2.2 mmol) was
added in one portion and the brown reaction mixture was
stirred at 0°C for 1 h and at rt for 20 h. Then saturated
NH4Cl (20 mL) and EtOAc (20 mL) were added. The or-
ganic phase was separated and the aqueous phase was
reextracted with EtOAc (3 × 30 mL). The combined organic
extracts were washed with brine (50 mL), dried, filtered, and
evaporated. The crude product was chromatographed (sol-
vent E) to give the bicyclic oxazolidinone 4a (4.6 g, 89%) as
Phenyl 5-O-(tert-butyldimethylsilyl)-2,3-O-isopropylidene-
α,β-D-ribofuranosyl sulfone (2)
The phenylthio furanoside (7 g, 18 mmol) was dissolved
in DCM (100 mL) and saturated aqueous NaHCO3 (200 mL)
was added. The biphasic mixture was cooled to 0°C in an
ice-bath and mCPBA (11 g, 39 mmol, 60% tech.) was added
portionwise. Then the mixture was stirred at room tempera-
ture (rt) for 20 h. The mixture was recooled to 0°C and 10%
aqueous NaHSO3 was added to destroy unreacted mCPBA.
The mixture was stirred at rt for 1 h, and the aqueous phase
was separated and back-extracted with DCM (50 mL). The
combined organic phases were washed with saturated
NaHCO3 (2 × 50 mL), dried, filtered, and evaporated. The
crude oil was chromatographed (solvent E) to give the de-
1
a pale yellow, viscous oil. IR, νmax: 1766, 1585 cm–1. H
NMR, δ: 0.30 (s, 6H, SiMe), 1.10 (s, 9H, t-Bu), 4.02 (dd,
1H, J = 10.9, 7.7 Hz, H-5), 4.08 (dd, 1H, J = 10.9, 6.0 Hz,
H-5′), 4.55–4.65 (m, 1H, H-4), 4.57 (d, 1H, J = 14.6 Hz,
PhCHN), 4.95 (d, 1H, J = 14.6 Hz, PhCHN), 4.98–5.05 (m,
2H, H-1, H-2), 5.09–5.18 (m, 1H, H-3), 7.50–8.10 (m, 10H,
PhH). 13C NMR, δ: –5.5, 18.1, 25.7, 47.2, 60.3, 62.0, 78.0,
89.1, 97.5, 128.3, 128.9, 129.2, 134.6, 135.0, 135.5, 156.6.
Anal. calcd. for C25H33NO6SSi: C 59.62, H 6.60, N 2.78;
found: C 59.71, H 6.77, N 2.81.
1
sired sulfone (6.2 g, 85%) as a thick, viscous oil. β-2: H
NMR, δ: 0.00 (s, 6H, SiMe2), 0.80 (s, 9H, t-Bu), 1.28 (s, 3H,
Me), 1.40 (s, 3H, Me), 3.66 (dd, 1H, J = 10.3, 7.6 Hz, H-5),
3.76 (dd, 1H, J = 10.3, 6.5 Hz, H-5′), 4.23 (dt, 1H, J = 6.5,
2.1 Hz, H-4), 4.65 (dd, 1H, J = 6.5, 2.1 Hz, H-3), 4.82 (d,
1H, J = 2.1 Hz, H-1), 5.24 (dd, 1H, J = 6.5, 2.1 Hz, H-2),
1
7.40–7.62 (m, 3H, PhH), 7.76–7.87 (m, 2H, PhH). α-2: H
NMR, δ: –0.06 (s, 3H, SiMe), –0.02 (s, 3H, SiMe), 0.70 (s,
9H, t-Bu), 1.15 (s, 3H, Me), 1.26 (s, 3H, Me), 3.63 (dd, 1H,
J = 11.4, 2.2 Hz, H-5), 3.75 (dd, 1H, J = 11.4, 2.2 H, H-5′),
4.27–4.32 (m, 1H, H-4), 4.72–4.81 (m, 1H, H-3), 5.02–5.13
(m, 2H, H-1, H-2), 7.42–7.62 (m, 3H, PhH), 7.94 (d, 2H, J =
7.5 Hz, PhH). 13C NMR, δ: –5.4, 17.9, 24.2, 25.1, 25.7,
65.0, 81.0, 82.1, 86.1, 96.3, 114.3, 128.5, 129.4, 133.4,
139.1. Anal. calcd. for C20H32O6SSi·¼H2O: C 55.46, H
7.57; found: C 55.41, H 7.52.
Phenyl 2-benzylamino-2N,3O-carbamoyl-2-deoxy-α-D-
ribofuranosyl sulfone (4b)
Compound 4a (6.7 g, 13.4 mmol) was dissolved in dry
MeOH (100 mL) under Ar, and the solution was cooled to
0°C. Freshly distilled Me3SiCl (3.4 mL, 27 mmol) was
added dropwise, via syringe, and the mixture was stirred at
0°C for 1 h. During this time, the white, fluffy, alcohol prod-
uct precipitated out of solution. The solid product was fil-
tered off and the filtrate was concentrated. The residue was
triturated with solvent D and the resulting white, fluffy,
product was filtered off. The filtrate was concentrated and
chromatographed (solvent A) to obtain more product. The
combined yield of 4b was 4.5 g (88%); mp 172–174°C. IR,
Phenyl 2-benzylamino-5-O-(tert-butyldimethylsilyl)-2-
deoxy-α-D-ribofuranosyl sulfone (4a)
The phenylsulfone 2 (6.2 g, 14.5 mmol) was dissolved in
© 1998 NRC Canada

1076
Can. J. Chem. Vol. 76, 1998
νmax: 3565–3307, 1754 cm–1. 1H NMR, δ: 3.30–3.40 (m, 1H,
OH), 3.66–3.84 (m, 1H, H-5′), 3.86–3.99 (m, 1H, H-5), 4.36
(d, 1H, J = 14.4 Hz, PhCHN), 4.57–4.63 (m, 1H, H-4), 4.73
(d, 1H, J = 14.4 Hz, PhCHN), 4.77–4.87 (m, 2H, H-1, H-2),
5.03–5.12 (m, 1H, H-3), 7.30–7.85 (m, 10H, PhH). 13C
NMR, δ: 47.1, 61.2, 62.8, 78.6, 89.9, 98.5, 128.3, 128.7,
128.9, 128.9, 129.4, 134.8, 135.2, 135.5, 156.2. Anal. calcd.
for C19H19NO6S: C 58.60, H 4.92, N 3.60; found: C 58.53,
H 5.13. N 3.67.
was stirred at 0°C for 2 h and then at rt overnight. The reac-
tion mixture was recooled to 0°C and glacial AcOH
(0.5 mL) was carefully added to destroy excess NaBH 4. Af-
ter effervescence had subsided, the reaction mixture was
evaporated and the residual oil was taken into EtOAc
(15 mL). The organic phase was washed with water
(10 mL), saturated aqueous NaHCO 3 (3 × 10 mL), and brine
and then dried. The filtered solution was evaporated to give
the crude crystalline primary alcohol. Chromatographic puri-
fication of the alcohol 7 (40:1 DCM:acetone) yielded white,
fine needles (106 mg, 90%); mp 138–140°C. IR νmax
:
Phenyl 2-benzylamino-2N,3O-carbamoyl-
2,5-dideoxy-5-iodo-α-D-ribofuranosyl sulfone (5)
3518–3330, 1724, 1713 cm–1. H NMR, δ (CDCl3-CD3CN):
2.87 (t, 1H, J = 5.1 Hz, OH), 3.50–3.76 (m, 3H, H-4,
CH2O), 4.20 (d, 1H, J = 14.4 Hz, PhCH), 4.80 (d, 1H, J =
14.4 Hz, PhCH), 4.95 (“t”, 1H, J = 8.2 Hz, H-5), 5.32–5.51
(m, 2H, CH2ϭ), 5.99–6.19 (m, 1H, ϭCH). 13C NMR, δ
(CDCl3-CD3CN): 45.7, 57.8, 58.1, 77.1, 116.5, 119.8, 127.1,
127.3, 128.1, 131.1, 135.9, 157.9. Anal. calcd. for
C13H15NO3: C 66.94, H 6.48, N 6.00; found: C 66.70, H
6.68, N 5.89.
1
The alcohol 4b (2.9 g, 7.5 mmol) was dissolved in a mix-
ture of dry toluene (60 mL), dry DCM (28 mL), and dry
pyridine (1.8 mL, 26 mmol), under Ar. In a separate flask,
Ph 3P (2.5 g, 9.4 mmol) was dissolved in dry toluene
(30 mL) and iodine (2 g, 7.9 mmol) was added. The mixture
was heated at 60°C for 30 min and then the temperature was
raised to 80°C. The solution of the alcohol was added
dropwise, via cannula, to the Ph P–I2 mixture. After addi-
3
tion was complete, the mixture was heated at 80°C (oil bath)
for 4 h, during which time the reddish brown precipitate was
consumed and a white precipitate was formed. The reaction
mixture was cooled to rt, filtered through a Florisil pad, and
the solid residue was washed with EtOAc (2 × 30 mL). The
combined filtrates were evaporated to leave a thick oil.
Chromatographic purification (30:1 DCM:acetone) gave the
desired iodide 5 (3.6 g, 95%) as a white solid; mp
(4S,5R,)-3-Benzyl-4-(benzyloxymethyl)-5-vinyl-2-
oxazolidinone (8)
The primary alcohol 7 (106 mg, 0.455 mmol) was dis-
solved in dry THF (5 mL), under Ar. The solution was
added to a suspension of NaH (66 mg, 50% dispersion in
mineral oil) in dry THF (10 mL) containing benzyl bromide
(70 µL, 0.59 mmol) at 0°C. The mixture was stirred at 0°C
to rt overnight (20 h). Then saturated NH4Cl (5 mL), fol-
lowed by saturated NaCl (5 mL) and EtOAc (10 mL), was
added. The aqueous phase was separated and reextracted
with EtOAc (5 mL). The combined organic phases were
washed with water (10 mL), saturated NaCl (10 mL), dried,
filtered, and evaporated. The crude oil was chromatographed
(solvent C) to give the benzyl ether 8 as a pale yellow oil
1
188–190°C. IR, νmax: 1747, 1584 cm–1. H NMR, δ : 3.43
(dd, 1H, J = 10.1, 6.3 Hz, H-5), 3.52 (dd, 1H, J = 10.1,
8.2 Hz, H-5′), 4.37 (d, 1H, J = 14.6 Hz, PhCH), 4.64 (dq,
1H, J = 8.5, 6.1, 2.2 Hz, H-4), 4.71 (d, 1H, J = 14.6 Hz,
PhCH), 4.82 (d, 1H, J = 1.8 Hz, H-1), 4.89 (dd, 1H, J = 8.4,
1.8 Hz, H-2), 4.96 (dd, 1H, J = 8.4, 2.2 Hz, H-3), 7.30–7.40
(m, 5H, PhH), 7.50–7.80 (m, 3H, PhH), 7.80–7.90 (m, 2H,
PhH). 13C NMR, δ: 2.9, 47.5, 60.9, 79.9, 89.4, 97.8, 128.5,
128.9, 129.0, 129.4, 134.7 134.8, 135.1, 155.9. Anal. calcd.
for C19H18INO5S: C 45.70, H 3.63, N 2.81; found: C 45.70,
H 3.59, N 2.82.
21
(127 mg, 86%). [α]D –8.8 (c 1.70, CHCl3). IR, νmax: 3086,
1
3063, 3031, 1760 cm–1. H NMR, δ: 3.43 (dd, 1H, J = 14.7,
5.3 Hz, CHOBn), 3.51 (dd, 1H, J = 14.7, 3.5 Hz, CHOBn),
3.75 (“quintet”, 1H, J = 4.4 Hz, H-4), 4.12 (d, 1H, J =
14.3 Hz, PhCHN), 4.39 (d, 1H, J = 14.1 Hz, PhCHO), 4.47
(d, 1H, J = 14.1 Hz, PhCHO), 4.81 (d, 1H, J = 14.3 Hz,
PhCHN), 4.93 (“t”, 1H, J = 8.5 Hz, H-5), 5.30–5.53 (m, 2H,
ϭCH2), 5.87–6.06 (m, 1H, ϭCH), 7.15–7.45 (m, 10H,
PhH). 13C NMR, δ: 46.6, 57.1, 66.6, 73.2, 77.1, 120.3,
127.7, 127.8, 128.0, 126.4, 128.6, 131.1, 136.2, 137.2,
157.9. HRMS, calcd. for C20H21NO3(M+): 323.1521; found:
323.1525. Anal. calcd. for C20H21NO3: C 74.28, H 6.55 N
4.33; found: C 73.99, H 6.43, N 4.35.
(4S,5R)-3-Benzyl-4-(hydroxymethyl)-5-vinyl-2-
oxazolidinone (7)
Activated Zn dust (0.73g, 0.011 g atoms) was added to a
solution of AgOAc (0.29 g, 1.77 mmol) in glacial AcOH
(87 mL) at 110°C (oil bath). The mixture was stirred at
110°C for
35–40 s and then was allowed to cool slightly. Glacial
AcOH was decanted off and the Zn/Ag couple was washed
thoroughly with dry THF (4 × 10 mL) and then was covered
with dry THF (10 mL). The slurry of the Zn/Ag couple in
dry THF was heated to 60°C and a solution of the
iodosulfone 5 (0.250 g, 0.50 mmol) was added dropwise via
cannula to the Zn/Ag couple. The reaction mixture was
heated at 60°C for 1 h, allowed to cool to rt, and the THF
supernatant containing the aldehyde 6 was filtered through
glass wool plug into a clean flask. The reaction flask was
rinsed with THF (2 × 5 mL) and the washings filtered into
the flask. The THF filtrate was cooled to 0°C and 95% etha-
nol (10 mL) was added, at which time the reaction mixture
turned cloudy. Sodium borohydride (0.19 g, 5 mmol) was
added, portionwise, to the mixture and the reaction mixture
General procedure for the preparation of RCeCl2 and
reaction with oxazolidinonecarbaldehydes (6) and (13)
Anhydrous CeCl3 (see also ref. 23)
Powdered CeCl3·7H2O (3 g) was placed in a 100 mL
round-bottom flask containing a stir bar. The flask was fitted
with an outlet tap and then connected to a high-vacuum
pump (0.01–0.015 Torr; 1 Torr = 133.3 Pa). The flask was
carefully evacuated, during which time a small amount of
water was removed, and the salt had a whitish appearance.
The flask was immersed in an oil bath that was heated at be-
tween 60 and 70°C and the salt was vigorously stirred. The
© 1998 NRC Canada

Wee and Tang
1077
salt was heated at 60–70°C for 6 h and then the temperature
of the bath was raised to 80–90° C and heating was contin-
ued for 2 h. After this period, the temperature was raised
slowly, over a period of 1 h, to 140°C and the salt was
stirred at this temperature for 18 h. The salt was cooled
slowly to rt and then stored under Ar. The salt has an
off-white appearance.
(4S,5R)-3-Benzyl-4-[(1R)-1-(hydroxy-2-propenyl)]-5-
vinyl-2-oxazolidinone (9b)
Method A: Solvent B: Yield, 85%; mp 157–159°C. IR, νmax
:
1
3471–3213, 1715, 1704 cm–1. H NMR, δ: 2.08 (d, 1H, J =
7.7 Hz, OH), 3.70 (dd, 1H, J = 8.5, 2.5 Hz, H-4), 4.25 (d,
1H, J = 15.4 Hz, PhCHN), 4.27–4.35 (m, 1H, CHOH), 4.90
(“t”, 1H, J = 8.5 Hz, H-5), 4.95 (d, 1H, J = 15.4 Hz,
PhCHN), 5.24–5.58 (m, 4H, 2× ϭCH2), 5.81–6.00 (m, 1H,
ϭCH), 6.08–6.23 (m, 1H, ϭCH), 7.16–7.40 (m, 5H, PhH).
13C NMR, δ: 47.2, 60.7, 70.5, 78.3, 116.6, 121.1, 127.9,
128.0, 128.8, 131.6, 136.2, 137.9, 158.7. LRMS-CI, NH3
(m/z, rel. intensity): 277 (M + 18, 8.4), 260 (M + 1, 100),
Method A: Dry THF (5 mL, at rt) was added to anhydrous
CeCl3 (1.2 mmol) under Ar and the mixture was stirred
briefly. Then the suspension was sonicated for 1 h and al-
lowed to stir at rt for 18 h. The white suspension was cooled
to –78°C and RLi or RMgBr reagent (1.2 mmol) was added
slowly. After addition was complete, the mixture assumed a
light yellow or yellow-orange colour. The organometallic re-
agent was allowed to stir at –78°C for 1.5 h before use. The
aldehyde 6 was generated from iodosulfone 5 (0.2 mmol)
using a Zn/Ag couple (prepared using 292 mg Zn dust and
119 mg AgOAc) in dry THF (5 mL) according to the proce-
dure used in the preparation of 7. The THF supernatant was
filtered (5 mL THF rinse) under Ar into a clean flask. This
solution of 6 was transferred via cannula to the RCeCl2 and
the mixture was stirred at –78°C for the specified time (see
Table 1). Then the mixture was quenched by addition of sat-
urated NH4Cl (5 mL) and stirred at rt for 20 min. The mix-
ture was filtered through Florisil, and the residue washed
with THF (2 × 10 mL). The combined filtrates were concen-
trated and the aqueous mixture was extracted with EtOAc (3
× 10 mL). The combined organic extracts were washed with
brine, dried, filtered, and evaporated. The residual product
was purified by chromatography.
+
202 (M – CH2ϭCHCHOH, 45), 91 (PhCH2 , 70). HRMS,
calcd. for C15H18NO3 (M + 1): 260.1286; found: 260.1275.
(4S,5R)-3-Benzyl-4-[(1R,S)-2-(tert-butyloxycarbonyl)-1-
(hydroxyethyl)]-5-vinyl-2-oxazolidinone (9c,10c)
Method A: Solvent C: Yield, 92%; mp: 97–99°C. IR, νmax
:
3618–3131, 1726 cm–1. 1H NMR, δ: 1.40 (s, t-Bu) and
[1.43, s, t-Bu](9H), 2.31 (dd, J = 15.4, 3.8 Hz) and
2.40–2.58 (m)(2H, CH2CO), 3.14 (d, J = 5.1 Hz, OH) and
[3.49, d, J = 5.1 Hz, OH](1H), 3.60 (dd, J = 7.7, 5.1 Hz,
H-4) and [3.76, dd, J = 7.7, 2.3 Hz, H-4], 4.08–4.21 (m, 1H,
CHOH), 4.31 (d, J = 14.9 Hz, PhCHN) and [4.33, d, J =
14.9 Hz, PhCHN](1H), 4.85 (“t”, 1H, J = 7.7 Hz, H-5), 4.91
(d, 1H, J = 14.9 Hz, PhCHN), 5.34–5.55 (m, 2H, ϭCH2),
[5.80–5.97, m, ϭCH] and 5.98–6.17 (m, ϭCH)(1H),
7.20–7.35 (m, 5H, PhH). 13C NMR, δ: 28.0, [30.0], [37.0],
39.1, [47.3], 48.0, 60.0, [60.6], 67.0, [68.1], 77.9, [81.2],
82.2, [85.2], [120.6], 120.8, 127.8, 128.0, [128.4], 128.7,
128.8, [128.9], [129.3], [130.6], 131.6, [134.6], 136.2,
[157.5], 158.8, 171.5, [172.0]. Anal. calcd. for C19H25NO5:
C 65.69, H 7.25, N 4.03; found: C 65.59, H 7.38, N 3.95.
Method B: The organocerium reagent was prepared as de-
scribed in Method A except that 4 mol- equiv. of RCeCl2
(0.62 mmol dry CeCl3 and 0.62 mmol RLi or RMgBr) was
used. The aldehyde 13 was generated by ozonolysis of olefin
8 (0.16 mmol) in dry DCM (5 mL) at –78°C. Ph3P
(0.19 mmol) was added and the mixture was slowly warmed
to rt, under Ar, and stirred at rt for 18 h. The DCM was re-
moved at rt under high vacuum and dry THF (5 mL) was
added under Ar. The THF solution of 13 was added to the
organocerium reagent and the mixture was stirred at –78°C
for the specified time (see Table 2). The reaction mixture
was processed as described in Method A.
(4S,5R)-3-Benzyl-4-[(1R)-1-hydroxy-(3-phenyl-2-
propynyl)]-5-vinyl-2-oxazolidinone (9d)
Method A: Solvent C: Yield, 94%; mp 119–121°C. IR, νmax
:
1
3550–3125, 2212, 1743, 1725, 1595, 1500 cm–1. H NMR,
δ: 2.90–3.20 (br hump, 1H, OH), 3.90 (dd, 1H, J = 8.2,
3.3 Hz, H-4), 4.60 (d, 1H, J = 15.2 Hz, PhCHN), 4.75 (d,
1H, J = 3.1 Hz, CHOH), 4.94 (“t”, 1H, J = 8 Hz, H-5), 5.02
(d, 1H, J = 15.2 Hz, PhCHN), 5.38–5.56 (m, 2H, ϭCH2),
6.10–6.33 (m, 1H, ϭCH), 7.23–7.44 (m, 10H, PhH). 13C
NMR, δ: 47.4, 61.0, 61.2, 78.2, 87.3, 121.8, 128.0, 128.2,
128.5, 128.8, 129.0, 131.2, 131.6, 136.4, 158.4. LRMS-CI,
NH3 (m/z, rel. intensity): 351 (M + 18, 12), 334 (M + 1,
(4S,5R)-3-Benzyl-4-[(1RS)-1-(hydroxyethyl)]-5-vinyl-2-
oxazolidinone (9a,10a)
+
Method A: Solvent B: Yield, 85%; mp 95–97°C. IR, νmax
:
100), 202 (M – PhCCHOH, 52), 91 (PhCH2 , 66). HRMS,
3600–3250, 1731 cm–1. H NMR, δ: 1.22 (d, J = 6.6 Hz,
Me) and [1.48, d, J = 6.6 Hz, Me](3H), 2.46 (d, 1H, J =
5.6 Hz, OH), 3.52 (dd, J = 8, 4.8 Hz, H-4) and [3.71, dd, J =
8, 2.1 Hz, H-4](1H), 3.85–4.05 (m, 1H, CHOH), 4.41 (d,
1H, J = 15.2 Hz, PhCH), 4.85 (“t”, 1H, J = 7.5 Hz, H-5),
4.93 (d, 1H, J = 15.2 Hz, PhCH), 5.36–5.54 (m, 2H, ϭCH2),
5.90–6.12 (m, 1H, ϭCH), 7.24–7.42 (m, 5H, PhH). 13C
NMR, δ: 21.1, 48.4, 62.3, 66.6, 78.4, 121.0, 127.8, 128.0,
128.9, 131.4, 136.6, 159.3. LRMS-CI, NH3 (m/z, rel. inten-
sity): 265 (M + 18, 7.4), 248 (M + 1, 100), 202 (M –
1
calcd. for C21H20NO3(M + 1): 334.1443; found: 334.1426.
(4S,5R)-3-Benzyl-4-[(1S)-1-(2-furanyl)-1-(hydroxymethyl)]-
5-vinyl-2-oxazolidinone (9e)
Method A: Solvent C: Yield, 85%; mp 137–139°C. IR νmax
:
3500–3150, 1715, 1703 cm–1. 1H NMR, δ (CD3CN): 3.75 (d,
1H, J = 15 Hz, PhCHN), 3.93 (d, 1H, J = 6 Hz, OH), 4.08
(dd, 1H, J = 7.2, 3.6 Hz, H-4), 4.73 (d, 1H, J = 15 Hz,
PhCHN), 4.75–4.85 (m, 1H, CHOH), 4.95 (“t”, 1H, J =
7.2 Hz, H-5), 5.30–5.46 (m, 2H, ϭCH2), 5.95–6.18 (m, 1H,
ϭCH), 6.28–6.45 (m, 2H, furan-H), 7.05 (dd, 1H, J = 6.6,
+
MeCHOH, 32), 91 (PhCH2 , 57). HRMS, calcd. for
C14H17NO3 (M+): 247.1208; found: 247.1207.
© 1998 NRC Canada

1078
Can. J. Chem. Vol. 76, 1998
2.4 Hz, furan-H), 7.20–7.45 (m, 5H, PhH). 13C NMR, δ
(CD3CN): 48.2, 60.7, 67.0, 78.9, 107.9, 112.1, 121.9, 128.2,
128.9, 129.5, 133.0, 143.2, 157.0, 160.6. LRMS-CI, NH3
(m/z, rel. intensity): 300 (M + 1, 100), 202 (M –
7.1 Hz, Me), 1.25 and [1.32] (s, 3H, Me), 1.35 and [1.42] (s,
3H, Me), 1.49 (s, 9H, t-Bu), 3.42–3.95 (m, 3H), 4.05–5.85
(m, 5H), 7.18–7.40 (m, 5H, PhH).
The ketal (26 mg, 0.071 mmol) was dissolved in dry THF
(2 mL) and was transferred, via cannula, to a suspension of
NaH (2.5 mg, 0.11 mmol, 50% dispersion in mineral oil) in
dry THF (2 mL). The mixture was refluxed under Ar for 2 h
and then cooled to rt. Saturated NH 4Cl (4 drops) was added
and the mixture was concentrated in vacuo. EtOAc (5 mL)
and saturated NaCl (4 mL) were added and the organic layer
was separated. The aqueous layer was reextracted with
EtOAc (3 mL) and the combined organic extracts were
dried, filtered, and evaporated to crude ketal oxazolidinone.
Chromatographic purification (solvent C) furnished crystal-
line 2-oxazolidinone 12 (16 mg, 77%); mp 88–90°C. IR,
+
furan-CHOH, 22), 91 (PhCH2 , 56). HRMS, calcd. for
C17H17NO4 (M+): 299.1157; found: 299.1152.
(4S,5R)-3-Benzyl-4-[(1R,S)-1-hydroxy-1-phenylmethyl]-
5-vinyl-2-oxazolidinone (9f,10f)
Method A: Solvent B: Yield, 52%; mp 142–144°C. IR νmax
:
3600–3283, 3075, 3025, 1751 cm–1. H NMR, δ: [2.28, d, J
= 4.4 Hz, OH] and 2.47 (d, J = 4.4 Hz, OH)(1H), 3.56 (d,
1H, J = 15.4 Hz, PhCHN), 3.90 (dd, 1H, J = 8, 2.2 Hz, H-4),
4.80 (d, 1H, J = 15.2 Hz, PhCHN), 4.85–5.00 (m, 2H,
CHOH, H-5), 5.30–5.70 (m, 2H, ϭCH2), 6.00–6.27 (m, 1H,
ϭCH), 7.12–7.50 (m, 10H, PhH). 13C NMR, δ: 47.7, [48.1],
60.7, 62.6, 71.3, 78.1, 118.7, 121.3, 125.7, [126.9], 127.8,
128.1, 128.5, 128.6, [128.7], 131.2, 136.2, 140.7, 158.2.
LRMS-CI, NH3 (m/z, rel. intensity): 310 (M + 1, 100), 232
1
1
νmax: 1745 cm–1. H NMR, δ: 1.25 (s, 3H, Me), 1.27 (d, 3H,
J = 7.0 Hz, Me), 1.35 (s, 3H, Me), 3.11 (t, 1H, J = 4.2 Hz,
H-4), 3.51 (dd, 1H, J = 7.9, 5.5 Hz, H-4′), 3.90 (br “t”, 1H, J
= 7.9 Hz, H-5′), 4.07 (d, 1H, J = 14.3 Hz, PhCHN),
4.06–4.16 (m, 1H, H-5′), 4.42 (br “quintet”, 1H, J = 4.2 Hz,
H-5), 4.82 (d, 1H, J = 14.3 Hz, PhCHN), 7.10–7.40 (m, 5H,
PhH). Anal. calcd. for C16H21NO4: C 65.96, H 7.27, N 4.81;
found: C 66.14, H 7.46, N 4.62.
+
(M – Ph, 10), 202 (M – PhCHOH, 30), 91 (PhCH2 , 90).
HRMS, calcd. for C19H20NO3 (M + 1): 310.1443; found:
310.1453.
(4S,5S)-3-Benzyl-4-benzyloxymethyl-5-[(1R)-1-
(hydroxyethyl)]-2-oxazolidinone (14a)
(4R,5R)-3-Benzyl-5-methyl-4-[(4S)-4-(2,2-dimethyl-1,3-
dioxolanyl)]-2-oxazolidinone (12)
Compound 9a,10a (111 mg. 0.45 mmol) was hydrolyzed
using 2 M aqueous KOH (2.6 mL) in 95% EtOH (6.4 mL) at
reflux for 20 h. The cooled reaction mixture was evaporated
to dryness and distilled water (1 mL) was added followed by
DCM (2 mL). The mixture was cooled to 0°C and Boc2O
(108 mg, 0.49 mmol) was added and the mixture was stirred
under Ar for 20 h. The DCM layer was separated and satu-
rated aqueous NaCl and solid NaCl were added to the aque-
ous layer. The mixture was stirred for 1 h and extracted with
DCM (2 × 5 mL). The combined organic phases were dried,
filtered, and evaporated to give the crude diol as a thick oil.
Chromatographic separation (solvent B) gave 81 mg (59%)
Method B: Solvent A: Yield, 62%. IR, νmax: 3450–3000,
1735 cm–1. 1H NMR, δ: 1.32 (d, 3H, J = 5.7 Hz, Me),
3.23–3.32 (br hump, 1H, OH), 3.53 (dd, 1H, J = 8.9, 4.3 Hz,
CHOBn), 3.62 (t, 1H, J = 8.9 Hz, CHOBn), 3.78 (td, 1H, J =
8.9, 8.9, 4.3 Hz, H-4), 3.70–4.70 (m, 1H, CHOH), 4.00 (d,
1H, J = 15.2 Hz, PhCHN), 4.14 (dd, 1H, J = 8.9, 6.6 Hz,
H-5), 4.51 (s, 2H, OCH2Ph), 4.76 (d, 1H, J = 15.2 Hz,
PhCHN), 7.14–7.45 (m, 10H, PhH). 13C NMR, δ: 20.1, 45.5,
55.9, 64.5, 64.6, 73.8, 80.5, 127.9, 128.0, 128.1, 128.4,
128.7, 128.8, 135.4, 136.1, 157.1. Anal. calcd. for
C20H23NO4·¼H2O: C 69.43, H 6.85, N 4.05; found: C 69.46,
H 6.90, N 4.02.
1
of diol 11. IR νmax: 3680–3113, 1690, 1660 cm–1. H NMR,
δ: 0.80 (d, 3H, J = 7 Hz, Me), 1.50 (s, 9H, t-Bu), 2.90–3.10
(m, 1H), 3.25–3.42 (m, 1H), 3.95–4.25 (m, 1H), 4.65 (d, 1H,
J = 12.6 Hz, PhCHN), 4.65–4.78 (m, 1H), 4.95–5.30 (m,
3H), 5.67–5.90 (m, 1H, ϭCH), 7.15–7.35 (m, 5H, PhH).
The diol 11 (40 mg) was dissolved in dry MeOH (3 mL)
and was ozonized at –78°C until the blue color of ozone is
visible. Argon was bubbled into the cold mixture and then
NaBH 4 (25 mg, 0.65 mmol) was added. The mixture was al-
lowed to stir at –78°C for 15 min and then warmed slowly to
rt and stirred at rt for 20 h. Glacial AcOH (4 drops) was
added to destroy unreacted NaBH4. The mixture was con-
(4S,5S)-3-Benzyl-4-(benzyloxymethyl)-5-[(1R)-(1-
hydroxy-2-propenyl)]-2-oxazolidinone (14b)
Method B: Solvent B: Yield, 59%. IR, νmax: 3550–3000,
1
1727, 1644 cm–1. H NMR, δ: 3.24 (d, 1H, J = 4.1 Hz, OH),
3.55–3.66 (m, 2H, CH2OBn), 3.68–3.82 (m, 1H, H-4), 3.99
(d, 1H, J = 14.8 Hz, PhCHN), 4.24 (dd, 1H, J = 9.1, 6.8 Hz,
H-5), 4.33–4.43 (m, 1H, CHOH), 4.45 (d, 1H, J = 12.5 Hz,
PhCHO), 4.55 (d, 1H, J = 12.5 Hz, PhCHO), 4.77 (d, 1H, J
= 14.8 Hz, PhCHN), 5.22–5.46 (m, 2H, ϭCH2), 5.87–6.07
(m, 1H, ϭCH), 7.12–7.45 (m, 10H, PhH). 13C NMR, δ:
45.5, 56.1, 64.8, 69.3, 73.8, 78.6, 117.2, 127.9, 128.1, 128.4,
128.7, 128.9, 136.1, 136.4, 157.5. Anal. calcd. for
C21H23NO4: C 71.37, H 6.56, N 3.96; found: C 71.40, H
6.77, N 3.90.
centrated and saturated aqueous NaHCO
(5 mL) was
3
added. The mixture was thoroughly extracted with DCM (2
× 10 mL), the combined organic phases were dried, filtered,
and evaporated to furnish crude triol (40 mg). Without fur-
ther
purification,
the
triol
was
treated
with
2,2-dimethoxypropane (20 µL, 0.16 mmol) in dry DCM
(2 mL) in the presence of p-TSO3H·H2O (1 crystal). After
reaction was complete, dry Et N was added, the mixture
was evaporated, and the residue3was chromatographed (sol-
(4S,5S)-3-Benzyl-4-(benzyloxymethyl)-5-[(1R)-1-
hydroxy-(3-phenyl-2-propynyl)]-2-oxazolidinone (14c)
Method B: Solvent B: Yield, 85%. IR, νmax: 3575–3175,
1
vent C) to give the ketal (26 mg, 55%) as an oil. IR, νmax
:
3060, 3025, 2212, 1743, 1738, 1581, 1500 cm–1. H NMR,
1
3577–3224, 1691, 1675 cm–1. H NMR, δ: 1.08 (d, 3H, J =
δ: 3.69–4.00 (m, 4H, CH2OBn, OH, H-4), 4.05 (d, 1H, J =
© 1998 NRC Canada

Wee and Tang
1079
15.4 Hz, PhCHN), 4.39 (d, 1H, J = 12 Hz, PhCHO), 4.55 (d,
1H, J = 12 Hz, PhCHO), 4.62 (dd, 1H, J = 7.7, 5.1 Hz, H-5),
4.75 (d, 1H, J = 15.4 Hz, PhCHN), 4.92 (dd, 1H, J = 7.7,
5.1 Hz, CHO), 7.05–7.45 (m, 15H, PhH). 13C NMR, δ: 46.5,
56.1, 61.7, 65.0, 73.7, 77.4, 86.0, 86.8, 122.0, 127.9, 128.0,
128.1, 128.3, 128.4, 128.7, 128.8, 128.9, 131.7, 131.8,
135.9, 136.4, 157.8. Anal. calcd. for C27H25NO4: C 75.86, H
5.89, N 3.28; found: C 75.78, H 5.95, N 3.20.
(4S,5S)-3-Benzyl-4-(benzyloxymethyl)-5-[(1S)-1-
(hydroxyethyl)]-2-oxazolidinone (15)
The MeTi(OPr-i)3 reagent was prepared by treatment of
ClTi(OPr-i)3 (0.22 mL, 0.90 mmol) with MeLi (0.90 mL,
0.90 mmol) in dry ether (5 mL) at –40°C. Then the mixture
was warmed slowly to rt and stirred at rt for 1.5 h. The mix-
ture turned cloudy and a yellow precipitate was formed. In a
separate flask the olefin 8 was dissolved in dry DCM (5 mL)
and then oxidized (O3; Pah3) as described in Method B to
provide 13. The solution of 13 was added to the ethereal so-
lution of MeTi(OPr-i)3 at –40°C and the mixture was stirred
at –40°C for 1 h. After this time, the reaction mixture was
warmed slowly to rt and stirred at rt for 1.5 h. The reaction
mixture was quenched by addition of aqueous 1 M HCl
(10 mL) followed by DCM (10 mL). The aqueous phase was
separated and reextracted with DCM (10 mL). The com-
bined organic extracts were washed with brine, dried, fil-
tered, and evaporated. Chromatographic purification (solvent
(4S,5S)-3-Benzyl-4-(benzyloxymethyl)-5-[(1R)-2-(tert-
butyloxycarbonyl)-1-(hydroxyethyl)]-2-oxazolidinone
(14d)
Method B: Solvent B: Yield, 84%. IR, νmax: 3575–3275,
1
3075, 3030, 1748, 1731, 1625, 1587, 1520. 1500 cm–1. H
NMR, δ: 1.50 (s, 9H, t-Bu), 2.43 (dd, 1H, J = 16.7, 7.5 Hz,
CHCO2), 2.79 (dd, 1H, J = 16.7, 2 Hz, CHCO2), 3.57–3.84
(m, 4H, H-4, CH2OBn, OH), 3.95 (d, 1H, J = 14.9 Hz,
PhCHN), 4.20–4.39 (m, 2H, H-5, CHO), 4.45 (d, 1H, J =
11.5 Hz, PhCHO), 4.54 (d, 1H, J = 11.5 Hz, PhCHO), 4.78
B) of the residual oil gave 15 (57 mg, 74%). IR, νmax
:
3450–3050, 1735 cm–1. 1H NMR, δ: 1.29 (d, 3H, J = 5.7 Hz,
Me), 3.34 (d, 1H, J = 8.5, 3.6 Hz, CHOBn), 3.62 (t, 1H, J =
8.5 Hz, CHOBn), 3.78 (td, J = 8.5, 8.5, 3.6 Hz, H-4),
3.92–4.06 (m, 1H, CHOH), 3.99 (d, 1H, J = 15.4 Hz,
PhCHN), 4.14 (dd, 1H, J = 8.5, 6.8 Hz, H-5), 4.50 (s, 2H,
OCH2Ph), 4.76 (d, 1H, J = 15.4 Hz, PhCHN), 7.10–7.48 (m,
10H, PhH). 13C NMR, δ: 20.1, 46.4, 55.9, 64.5, 64.6, 73.8,
80.5, 127.9, 127.9, 128.0, 128.4, 128.7, 128.8, 135.8, 136.1,
157.4. Anal. calcd. for C20H23NO4: C 70.36, H 6.79, N 4.10;
found: C 70.17, H 7.00, N 3.90.
(d, 1H, J = 14.7 Hz, PhCHN), 7.10–7.45 (m, 10H, PhH). 13
C
NMR, δ: 28.0, 38.8, 46.3, 56.1, 64.8, 65.8, 73.4, 76.9, 81.6,
127.8, 127.9, 127.9, 128.0, 128.5, 128.7, 135.9, 136.9,
157.3, 171.8. Anal. calcd. for C25H31NO6: C 67.99, H 7.08,
N 3.17; found: C 67.68, H 7.32, N 3.48.
(4S,5S)-3-Benzyl-4-(benzyloxymethyl)-5-[(1S)-1-(2-
furanyl)-1-(hydroxymethyl)]-2-oxazolidinone (14e)
Method B: Solvent B: Yield, 64%. IR, νmax: 3637–3125,
(4R)-3-Benzyl-4-[(4S,5R)-4-(2,2,5-trimethyl-1,3-
dioxolanyl)]-2-oxazolidinone (16)
1
3100, 3050, 1731, 1606, 1581, 1500 cm–1. H NMR, δ: 3.43
(d, 1H, J = 5.6 Hz, OH), 3.64 (“d” 2H, J = 4.3 Hz,
CH2OBn), 3.82 (dt, 1H, J = 7.5, 4.1 Hz, H-4), 3.96 (d, 1H, J
= 15 Hz, PhCHN), 4.45 (d, 1H, J = 11.6 Hz, PhCHO), 4.55
(d, 1H, J = 11.6 Hz, PhCHO), 4.78 (“t”, 1H, J = 7.5 Hz,
H-5), 4.78 (d, 1H, J = 15 Hz, PhCHN), 4.98 (dd, 1H, J =
8.5, 5.6 Hz, CHO), 6.31–6.39 (m, 2H, furan-H), 7.12–7.45
(m, 11H, PhH, furan-H). 13C NMR, δ: 45.3, 56.0, 64.6, 65.2,
73.6, 76.5, 108.5, 110.4, 127.9, 128.1, 128.3, 128.7, 128.8,
135.9, 136.1, 142.6, 152.2, 157.4. Anal. calcd. for
C23H23NO5: C 70.21, H 5.89, N 3.56; found: C 69.97, H
6.02, N 3.51.
2-Oxazolidinone 15 (33 mg, 0.097 mmol) was dissolved
in a mixture of 95% EtOH (5 mL) and 2 M aqueous KOH
(2 mL). The mixture was refluxed under Ar for 20 h. The
cooled reaction mixture was evaporated to dryness and dis-
tilled water (2 mL) was added. Then Et O (4 mL) and
2
Boc2O (25 mg, 0.12 mmol) were added and the mixture
stirred at rt, under Ar, for 4 h. The aqueous phase was re-
moved and solid NaCl (1 g) was added. The mixture was
stirred for 1 h; the aqueous phase was removed and then
back-extracted with Et2O (3 × 5 mL). The combined ether
extracts were dried, filtered, and evaporated to leave crude
diol as an oil (34 mg). Without further purification, the diol
(34 mg) was dissolved in dry DCM (3 mL), and PPTS
(11 mg) and 2-methoxypropene (0.2 mL) were added. The
mixture was stirred under Ar for 3 h and then dry Et3N
(0.5 mL) was added. The mixture was evaporated to dryness
and the crude residue was chromatographed (PE:EtOAc,
10:1) to give the ketal (30 mg).
The ketal (30 mg) was dissolved in dry MeOH (2 mL)
and was hydrogenated (H 2, 1 atm (101.3 kPa), balloon) over
10% Pd/C (15 mg) for 4 h. The mixture was filtered through
a Celite pad, the residue washed with dry MeOH (4 mL),
and the combined filtrate was evaporated to leave an oil.
The crude oil was dried under high vacuum for 2 h and then
dissolved in dry THF (2 mL). The solution was added to a
suspension of hexane-washed NaH (7 mg, 50% dispersion in
mineral oil) in dry THF (2 mL). The mixture was refluxed
for 45 min, cooled, and saturated NH4Cl (4 drops) was
added. The mixture was evaporated, and EtOAc (5 mL) and
(4S,5S)-3-Benzyl-4-(benzyloxymethyl)-5-[(1R)-1-
(hydroxytetradecyl)]-2-oxazolidinone (14f)
Method B: Solvent D: Yield, 69%. IR, νmax: 3600–3150,
1
1737, 1500 cm–1. H NMR, δ: 0.90 (t, 3H, J = 6.5 Hz, Me),
1.12–1.55 (m, 25H, CH2), 1.65–1.85 (m, 1H, CH), 3.23 (d,
1H, J = 3.6 Hz, OH), 3.52 (dd, 1H, J = 9.7, 3.4 Hz,
CHOBn), 3.60 (“t”, 1H, J = 9.7 Hz, CHOBn), 3.70–3.85 (m,
2H, H-4, CHO), 3.99 (d, 1H, J = 15.4 Hz, PhCHN), 4.17
(dd, 1H, J = 9.5, 6.8 Hz, H-5), 4.46 (d, 1H, J = 12 Hz,
PhCHO), 4.55 (d, 1H, J = 12 Hz, PhCHO), 4.75 (d, 1H, J =
15.4 Hz, PhCHN), 7.15–7.40 (m, 10H, PhH). 13C NMR, δ:
14.1, 22.6, 24.8, 29.3, 29.6, 29.6, 31.9, 33.5, 46.4, 56.0,
64.5, 68.1, 73.8, 79.1, 127.6, 127.9, 128.0, 128.1, 128.4,
128.7, 128.8, 135.9, 136.1, 157.4. Anal. calcd. for
C33H49NO4: C 75.60, H 9.44, N 2.68; found: C 75.68, H
9.59, N 2.94.
© 1998 NRC Canada

1080
Can. J. Chem. Vol. 76, 1998
saturated aqueous NaCl were added. The aqueous phase was
separated and reextracted with EtOAc (4 mL). The com-
bined organic phases were dried, filtered, and evaporated to
give crude 16. Chromatographic purification (solvent C)
in dry pyridine (2 mL) containing DMAP (30 mg), and
Ac2O (150 µL, 1.60 mmol) was added. The mixture was
kept at rt for 18 h and then diluted with EtOAc (15 mL).
The organic layer was washed twice with aqueous 1 N
H2SO4 (10 mL), water (10 mL), and saturated NaHCO3,
then dried, filtered, and evaporated. The crude product was
chromatographed (solvent B) to give 18 (126 mg, 98%); mp
gave crystalline 16 (17 mg, 89%); mp 134–135°C. IR, νmax
:
1748 cm–1. H NMR, δ: 1.05 (d, 3H, J = 6.3 Hz, Me), 1.34
(s, 3H, Me), 1.50 (s, 3H, Me), 3.57 (dq, 1H, J = 8.9, 5.6,
2.1 Hz, H-4), 4.13 (d, 1H, J = 15.9 Hz, PhCHN), 4.25 (“t”,
1H, J = 8.2 Hz, H-5), 4.27 (dd, 1H, J = 8.2, 2.1 Hz, H-5),
4.37 (“q”, 1H, J = 6.3 Hz, H-5′), 4.44 (dd, 1H, J = 8.9,
5.2 Hz, H-4′), 4.93 (d, 1H, J = 15.9 Hz, PhCHN), 7.25–7.50
(m, 5H, PhH). 13C NMR, δ: 15.2, 24.48, 26.4, 45.7, 54.8,
63.0, 71.6, 73.3, 108.4, 127.8, 127.9, 128.9, 135.7, 158.5.
Anal. calcd. for C16H21NO4: C 65.96, H 7.27, N 4.81; found:
C 65.97, H 7.40, N 4.60.
1
21
46–48°C (lit. (19c) mp 48°C; (19a) mp 34–37°C).[α]D
21
+28.9 (c 0.95, CHCl3), [α]D +4 (c 1.25, DMF) (lit. (19a) [
24
30
α]D +28 (c, 1.30, CHCl3); (19b) [α]D +4.4 (c 1.12,
DMF)). IR, νmax: 3236–3342, 1746, 1660 cm–1. H NMR, δ:
1
0.87 (t, 3H, J = 6.8 Hz, Me), 1.18–1.33 (m, 24H, CH2),
1.55–1.75 (m, 2H, CH2), 2.20 (s, 3H, OAc), 2.50 (s, 6H,
OAc), 2.80 (s, 3H, OAc), 4.00 (dd, 1H, J = 10.9, 2.8 Hz,
CHOAc), 4.29 (dd, 1H, J = 10.9, 4.2 Hz, CHOAc),
4.40–4.55 (m, 1H), 4.94 (dt, 1H, J = 8.3, 3.4 Hz), 5.11 (dd,
1H, J = 8.0, 3.1 Hz), 6.05 (d, 1H, J = 8.3 Hz). 13C NMR, δ:
14.1, 20.6, 20.7, 21.0, 22.6, 23.2, 25.5, 28.1, 29.2, 29.3,
29.4, 29.5, 29.6, 29.6, 31.9, 47.5, 62.8, 71.9, 72.9, 76.4,
76.9, 77.6, 169.7, 170.0, 170.8, 171.1. HRMS, calcd. for
C23H42NO5 (M – CH2OAc): 412.3063; found: 412.3056.
(2S,3S,4R)-2-Benzylamino-1,3,4-dihydroxyoctadecane
(17a)
The 2-oxazolidinone 14f (270 mg, 0.528 mmol) was dis-
solved in 95% EtOH (10 mL) and aqueous 2 M KOH
(4 mL) was added. The mixture was refluxed under Ar for
20 h, then cooled to rt, at which time a fluffy white precipi-
tate was formed. The reaction mixture was concentrated and
saturated NaCl (10 mL) was added. The mixture was thor-
oughly extracted with DCM (3 × 10 mL), the combined or-
ganic extracts were dried, filtered, and evaporated. The
crude solid was chromatographed (DCM:MeOH, 190:2) to
Financial support from the Natural Sciences and Engi-
neering Research Council of Canada and the University of
Regina is gratefully acknowledged. We thank Dr. R. Kirk
Marat of the Prairie Regional High-Field NMR Centre, Win-
nipeg, for the NOE experiments and Mr. K. Thoms for per-
forming high-resolution mass spectral and elemental
analyses.
23
give crystalline 17a (256 mg, 83%); mp 75–77°C. [α]D
+21.4 (c 1.75, CHCl3). IR, νmax: 3154–3448 cm–1. H NMR,
1
δ: 0.90 (t, 3H, J = 6.5 Hz, Me), 1.15–1.75 (m, 26H, CH2),
2.92 (dt, 1H, J = 6.8, 4 Hz), 3.10–3.30 (br hump, 3H), 3.47
(“t”, 1H, J = 6.8 Hz), 3.55–3.85 (m, 5H), 4.49 (d, 1H, J =
13 Hz, PhCHO), 4.56 (d, 1H, J = 13 Hz, PhCHO),
7.20–7.42 (m, 10H, PhH). 13C NMR, δ: 14.1, 22.7, 25.3,
29.3, 29.7, 29.8, 31.9, 33.9, 51.3, 60.3, 67.1, 72.1, 73.3,
74.4, 76.4, 77.0, 77.6, 127.3, 127.8, 127.9, 128.2, 128.5,
137.7, 139.1. HRMS, calcd. for C32H51NO3 (M+): 497.3869;
found: 497.3868.
1. Sphingolipids: (a) C.C. Sweeley. In Biochemistry of lipids and
membranes. Edited by D.E. Vance and J.E. Vance.
Benjamin/Cummings, Menlo Park, Calif. 1985. Chap. 12.
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of the amino acids. HIV protease inhibitors. Edited by G.C.
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Synthetic (2S,3S,4R)-2-Amino-1,2,3-trihydroxy-
octadecane (phytosphingosine) (17b)
The amino alcohol 17a (256 mg) was dissolved in 95%
EtOH (15 mL) and Pd(OH)2 (281 mg) was added. The mix-
ture was hydrogenated (H2 at 50 psi (1 psi = 6.9 kPa)) for
16 h using a Parr apparatus. The mixture was filtered
through Celite and the residue washed with 95% EtOH (3 ×
2 mL). The combined filtrate was concentrated to about
8 mL, distilled water was added until the mixture was
slightly turbid, and the mixture was placed in the freezer.
The white powdery solid was filtered off and dried. Yield of
17b was 130 mg (80%); mp 99–100°C (lit. (19b) mp
21
98–100°C; (19c) mp 103°C). [α]D +8.3 (c 1.2, pyridine)
(lit. (19a) [α]D24 +8.7 (c 0.80, pyridine); (19c) [α]D20 +7.9 (c
1
1.0, pyridine)). H NMR, δ (DMSO-d6): 0.85 (t, 3H, J =
6.5 Hz, Me), 1.15–1.35 (m, 24H, CH2), 1.40–1.65 (m, 2H,
CH2), 2.60–2.75 (m, 1H, CHO), 3.05 (t, 1H, J = 6.7 Hz,
CHO), 3.20–3.40 (m, 5H), 3.52 (dd, 1H, J = 9.6, 3.6 Hz),
4.40–4.60 (m, 1H).
Synthetic phytosphingosine tetraacetate (18)
Phytosphingosine 17b (84 mg, 0.27 mmol) was dissolved
© 1998 NRC Canada

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© 1998 NRC Canada