A common approach to the total synthesis of l-arabino-, l-ribo-C 18-phytosphingosines, ent-2-epi-jaspine B and 3-epi-jaspine B from d-mannose

Article abstract of DOI:10.1016/j.tet.2013.07.028

A common strategy for the total syntheses of the protected l-arabino- and l-ribo-C₁₈-phytosphingosine (8 and 9, respectively), HCl salts of ent-2-epi-jaspine B (ent-6) and 3-epi-jaspine B (7) with efficient use of both flexible building blocks 26 and 27 was achieved. The key step of this approach was [3,3]-sigmatropic rearrangement of allylic trichloroacetimidate 21 and thiocyanate 22, which were derived from the known 2,3:5,6-di-O-isopropylidene-d- mannofuranose 18 as the source of chirality. The side chain functionality was installed utilizing a Wittig reaction.

Full text of DOI:10.1016/j.tet.2013.07.028

Tetrahedron 69 (2013) 8228e8244
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A common approach to the total synthesis of
phytosphingosines, ent-2-epi-jaspine B and 3-epi-jaspine B from
-mannose
L
-arabino-, -ribo-C18-
L
D
*
ꢀ
ꢀ
ꢀ
ꢀ
Miroslava Martinkova , Kvetoslava Pomikalova, Jozef Gonda, Maria Vilkova
ꢁ
ꢀ
ꢁ
Institute of Chemical Sciences, Department of Organic Chemistry, P. J. Safarik University, Moyzesova 11, Sk-040 01 Kosice, Slovak Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 April 2013
Received in revised form 21 June 2013
Accepted 9 July 2013
Available online 23 July 2013
A common strategy for the total syntheses of the protected L-arabino- and L-ribo-C18-phytosphingosine (8
and 9, respectively), HCl salts of ent-2-epi-jaspine B (ent-6) and 3-epi-jaspine B (7) with efficient use of
both flexible building blocks 26 and 27 was achieved. The key step of this approach was [3,3]-sigmatropic
rearrangement of allylic trichloroacetimidate 21 and thiocyanate 22, which were derived from the
known 2,3:5,6-di-O-isopropylidene-
D-mannofuranose 18 as the source of chirality. The side chain
functionality was installed utilizing a Wittig reaction.
Keywords:
Ó 2013 Elsevier Ltd. All rights reserved.
Sphingolipids
Phytosphingosine
Jaspine B
Rearrangements
Trichloroacetamides
Isothiocyanates
1. Introduction
anhydrophytosphingosine molecule is jaspine B (also known as
pachastrissamine, 5) that has been isolated independently from two
natural sources.4 This marine sponge product has been reported to
have a significant cytotoxicity against several cancer cell lines with
IC50 values in the submicromolar range.4,5a Moreover, Fujii and co-
workers revealed that 5 and its diastereoisomers inhibit sphingo-
sine kinases (SphKs) and atypical protein kinase C.5b Because of
these interesting functions as well as the rich structural features
(three contiguous stereogenic centres) of 1 and 5, there has been an
enormous interest in the preparation of both above-mentioned
structures and their diastereoisomers (Fig. 1).3b,d,5e8 One of the
best starting points for such endeavours are carbohydrates, as they
are inexpensive, readily available and afford at least two of three
desired stereogenic centres. Recently we developed a strategy for
Sphingolipids, a conspicuous class of natural products including
sphingomyelins, cerebrosides, more complex glycosphingolipids
and phytoceramides are essential building blocks of eukaryotic cell
membranes, which largely reside at the cell surface. Their biological
roles are complex and very often closely linked to each other.1 Their
ability to regulate many biological processes1 has led to a desire to
develop effective synthetic methods for the construction of novel
sphingolipid derivatives as promising therapeutic agents.2 Gener-
ally, one of the crucial factors for the successful synthesis of both
natural sphingolipids and their related unnatural analogues, is
primarily the construction of the convenient sphingoid bases3
representing the principal structural backbone of the aforemen-
tioned molecules. Among the sphingoid bases with long aliphatic
chains containing 2-amino-1,3-diol or a 2-amino-1,3,4-triol func-
tionality, phytosphingosines3b,d (Fig. 1) occupy a conspicuous posi-
the synthesis of -ribo-C18-phytosphingosine (1), its C20-analogue
D
together with their C-2 epimers, in which an amino function was
introduced by a [3,3]-sigmatropic rearrangement on the carbon that
tion due to the biological importance of
D
-ribo-phytosphingosine
originally comes from the anomeric position of D
-ribose.6f,r In the
(1), the most abundant member of phytosphingosine family.3b,c
Apart from the open chain forms, phytosphingosines also pos-
sesses cyclic anhydro structures. One such naturally occurring
present work, we demonstrate that our described method of the
phytosphingosine construction6f,r has a more general utility and can
also be useful for the stereoselective synthesis of the other amino-
polyol species commencing from the appropriate monosaccharide
templates. Based on this concept, we herein report the total syn-
thesis of 8, 9, ent-6$HCl and 7$HCl from
nient -lyxose is too expensive).
D-mannose (more conve-
* Corresponding author. Tel.: þ421 55 2342329; fax: þ421 55 6222124; e-mail
ꢀ
D
addresses: miroslava.martinkova@upjs.sk, mmartin@upjs.sk (M. Martinkova).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.028

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8229
OH
C14H29
NH2 OH
OH
H2N
HO
HO
O
5
jaspine B ( )
D-ribo-(2S,3S,4R)-phytosphingosine (1)
OH
C14H29
2-epi-jaspine B (6)
H2N
NH2 OH
O
OH
L-arabino-(2S,3R,4S)-phytosphingosine (2)
OH
C14H29
H2N
NH2 OH
HO
HO
O
OH
D-xylo-(2S,3R,4R)-phytosphingosine (3)
7
3-epi-jaspine B ( )
NH2 OH
OH
L-lyxo-(2S,3S,4S)-phytosphingosine (4)
Fig. 1. D-ribo-Phytosphingosine (1), jaspine B (5) and their diastereoisomers.
2. Results and discussion
hand, a two-step sequence, involving mesylation of 17 followed by
nucleophilic substitution with KSCN, afforded the desired thiocy-
anate 22 (90%).
The retrosynthetic analysis of 8, 9, ent-6$HCl, 7$HCl is illustrated
0
0
in Scheme 1. For our final molecules, disconnection of C3 eC4 bond
(Wittig reaction) led to the highly functionalized oxazolidinones
(10 and 11, respectively) with all requisite stereogenic centres and
the known phosphonium salt 12.6per,9 Compound 10 could be
produced from isothiocyanate 13 and/or carbamate 15. Further, we
planned to generate the second polar ‘head’ 11 from 16 as a major
diastereoisomer. Derivatives 13, 15 and 16 would be derived from
[3,3]-sigmatropic rearrangements of the chiral allylic substrates,
which were envisioned as arising from the common alcohol 17. For
With both trichloroacetimidate 21 and thiocyanate 22 in hand,
we were now in a position to explore the key rearrangement re-
actions. The thermal Overman rearrangement12 of 21, which was
carried out in o-xylene in the presence of K2CO313 in a sealed tube,
afforded the rearranged products 23a and 23b as a barely separable
mixture of diastereoisomers (23a/23bz1:2) in a maximum yield of
about 30% (Table 1, entries 2 and 4). The low yield was most likely
due to decomposition of 21 at high temperatures and longer reaction
times. On the other hand, the use of microwave heating6f,r,14 led to
significant shortening of the reaction times (4 or 10 times, see Table 1,
entries 1 and 3) and very good isolated yields of the rearranged
products compared to the thermally driven reaction. Further, it has
been reported that the Overman rearrangement proceeds effectively
in the presence of Hg(II), Pd(II), Pt(II), Pt(IV), Au(I) and Au(III) cata-
lysts and allows the reaction to be carried out at room temperature or
lower.15 However, the attempted PdCl2(CH3CN)2 catalyzed rear-
rangement of 21 resulted in failure; the successive consumption of
the starting trichloroacetimidate 21 was judged by TLC, but un-
identified by-products were generated in the reaction mixture. We
reason that this failure might be due to the sensitivity of the terminal
isopropylidene and trichloroacetiminoyl moieties to the Lewis
acidity of Pd(II).
the preparation of 17,
As shown in Scheme 2, our synthesis commenced with the
gram-scale preparation of 2,3:5,6-di-O-isopropylidene- -man-
nofuranose 1810 from the commercially available
-mannose. Its
D-mannose served as the starting material.
D
D
subsequent Wittig olefination (Ph3P]CHCO2Et, CH2Cl2, benzoic
acid, reflux) followed by chromatographic separation of the prod-
ucts, provided a mixture of a,b
-unsaturated esters (E)-1911 and (Z)-
19 (E/Z¼10.5:1, as determined by 1H NMR spectroscopy) in 90% and
8% isolated yields, respectively (Scheme 2). 1H NMR coupling con-
stant analysis of the vinylic protons for the major geometric isomer
19 assigned the (E)-configuration of the double bond (J3,2¼15.7 Hz),
while analysis of the minor derivative confirmed a (Z)-relationship
between olefinic protons (J3,2¼11.6 Hz).
To continue the synthesis, the secondary hydroxy group in
(E)-19 was protected as a tert-butyldimethylsilyl ether (TBDMSCl,
imidazole, DMF) to give 20 in 98% yield. The ester functionality in
20 was reduced using diisobutylaluminum hydride in CH2Cl2 to
furnish the corresponding allylic alcohol 17 (97%, Scheme 2), which
was then converted into the required aza-Claisen substrates
(compounds 21 and 22) for the key rearrangement processes. Thus,
its treatment with trichloroacetonitrile and DBU provided imidate
21 in excellent 98% yield after flash chromatography. On the other
In order to rationalize the observed stereoselectivity in the
Overman rearrangement of imidate 21, high-level density functional
theory (DFT) calculations, including electron correlation effects,
were carried out. A thorough conformational search was performed
on all transition states, whereas only the lowest energy conformers
are discussed here. The potential energy surface scans were used to
explore the conformational space of transition states TS1eTS4 with
the constrained transition bond lengths CeN and CeO. The sys-
tematic conformational search with rotationaround the single bonds

ꢀ
8230
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
O
R2
OH
R1
OH
HN
4
2
3
4`
4
5
3
2
1O
H
2`
1`
5
2`
1
10
3`
O
10
1`
OH
R1 = H, R2 = NH2.HCl: ent-6
R1 = NH2.HCl, R2 = H: 7
(4S)-8
(4R)-9
Wittig
O
O
O
OH PMBN
OH PMBN
or
HO
P+Ph3Br-
O
+
11
HO
6p-r,9
12
O
O
O
O
OH
OH
10
11
NHBoc
OR
O
OR
NCS
O
O
O
O
O
O
O
O
16
13
[3,3]-sigmatropic
rearrangements
and/or
NHBoc
OR
OR
D-mannose
OH
O
O
O
O
O
O
O
15
17
R = TBDMS
Scheme 1. Retrosynthetic analysis.
C5eC6, C6eC7 and C6eOSi was performed using semiempirical PM3
methodology. The conformers within a 4 kcal/mol energy range
were then optimized using B3LYP/6-31G(d)16 for a more accurate
description of the conformer distribution. The low energy con-
formers of the transition states were later fully optimized using the
same level of theory. It is worth noting that the bulky 4,5-O- and 7,8-
O-isopropylidene moieties and tert-butyldimethylsilyloxy group at
the carbon C6 cause low conformational flexibility of the backbone
of the transition states. Dihedral angles C4eC5eC6eC7 of the min-
imized structures are very similar (4TS1¼76.2, 4TS2¼76.3,
4TS3¼81.1, 4TS4¼81.2) and side chains are structurally conformed.
Coordinates of the stationary points, TS1.mol, TS2.mol, TS3.mol,
TS4.mol are attached as supplementary data. The potential energy
surface scans were used to explore the conformational space of the
reactant and products (imidate and amides) with the later full op-
timization using the same level of theory, but we focused only on the
energy differences between TSs as crucial for explanation of the
observed diastereoselectivity. Geometries of the transition states
were optimized using B3LYP/6-31G(d) with the Gaussian 03 pro-
gramme.16 The nature of the vacuum B3LYP transition states was
verified with frequency calculations, yielding only one large imagi-
the B3LYP density functional method and the cc-pvTZ basis set. The
solvent effect was taken into account via a single-point calculation in
a dielectric continuum representing o-xylene as the solvent. A
standard PCM solvation model was applied as implemented in
Gaussian 03.16 The Overman rearrangement of 21 occurs via transi-
tion states TS1, TS2, TS3 and TS4, with relative free energies 2.35, 0,
2.93 and 1.90 kcal/mol (Figs. 2 and 3). The process is concerted but
asynchronous, and the calculated geometries are in good agreement
with the results of Houk and co-workers.17 From the calculations, for
the pathway 21/TS2/23b, the activation energy was found to be
1.90 kcal/mol lower than for the pathway 21/TS4/23a. Thus, the
predicted diastereomeric ratio of 23a/23b at 170 ꢁC was 11:89. These
results are in relatively good agreement with the experimental data
(23a/23bz33:67) with the correct prediction of amide 23b as the
predominant diastereoisomer. These results provide an initial step in
understanding the rearrangement and the observed diaster-
eoselectivity seems to depend on many factors that are still to be
explored.
The allylic thiocyanate 22 was rearranged in n-heptane using
both the conventional thermal conditions and microwave heating
providing the corresponding isothiocyanates 13 and 14 as a sepa-
rable mixture of diastereoisomers in modest yields (Table 2). It
should be noted that during these experiments we recovered the
starting thiocyanate 22 in approximately 39e47% yields after
chromatographic separation, which could be reused to provide
additional amounts of 13 and 14. The prolonged heating turned out
nary frequency (TS1¼ꢀ391.45 cmꢀ1
,
TS2¼ꢀ411.33 cmꢀ1
,
TS3¼ꢀ403.34 cmꢀ1, TS4¼ꢀ436.32 cmꢀ1). Harmonic zero-point en-
ergy corrections at B3LYP/6-31G(d) obtained from the frequency
calculations of the vacuum transition states were applied to the
transition-state energies. Single-point energies were computed by

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8231
O
OH
OR
O
OH
CO2Et
CO2Et
c
O
H
O
O
a
b
O
O
O
O
O
O
O
O
,
11 90%
20
19
(E)-
10
18
(Z)-19, 8%
OR
O
NH
OR
R = TBDMS
d
OH
O
CCl3
O
O
O
O
O
O
O
17
21
f
e
OR
O
NHCOCCl3
OR
O
OR
NHCOCCl3
8`
7`
5` 4`
1`
3`
6`
SCN
2`
O
O
O
+
O
O
O
O
O
O
O
22
23b
23a
g
OR
NCS
NCS
OR
O
1
2
5
4
8
3
6
7
O
O
+
O
O
O
O
O
14
13
Scheme 2. Reagents and conditions: (a) Ph3P]CHCO2Et, CH2Cl2, benzoic acid, reflux, 98%; (b) TBDMSCl, imidazole, DMF, rt, 98%; (c) DIBAL-H, CH2Cl2, ꢀ15 ꢁC, 97%; (d) CCl3CN, DBU,
CH2Cl2, 0 ꢁC/rt, 98%; (e) (i) MsCl, Et3N, CH2Cl2, 0 ꢁC/rt; (ii) KSCN, CH3CN, rt, 90% over two-steps; (f) Table 1; (g) Table 2.
Table 1
Overman rearrangement of imidate 21
oxazolidinones 26 and 27 in 86% and 97% yields, respectively, by
NaH mediated intramolecular cyclization (Scheme 3). Compound
26 afforded single crystals suitable for X-ray measurements. As
seen in Fig. 4, the crystallographic analysis clearly showed that the
newly installed stereocentre in 26 bearing the amino functionality
is (S)-configured. Consequently, the minor diastereoisomer of the
Overman rearrangement 23a must possess the same stereochem-
istry at the requisite asymmetric centre. To establish the configu-
ration at C-6 (see numbering in Scheme 2) in both isomers 13 and
14, the chemical correlation of the major isothiocyanate 13 to
common oxazolidinone derivative 26 was executed (Scheme 3).
For this purpose, isothiocyanate 13 was treated with sodium
methoxide in CH3OH to generate the corresponding thiocarbamate
(52%), which was immediately reacted with mesitylnitrile oxide18
to provide the desired product 28 in 75% yield (Scheme 3). The
lower yield of the aforementioned thiourethane was due to the use
of harsh basic reaction conditions, which presumably resulted in
the formation of unidentified by-products. Subsequent ozonolysis
of the terminal double bond in 28 (O3, ꢀ78 ꢁC), followed by treat-
ment with NaBH4, afforded the primary alcohol 29 (80%). Base-
induced (NaH) ring-closure of 29 furnished oxazolidinone 26 in
92% yield (Scheme 3). The spectroscopic data (1H and 13C NMR)
Entry
Imidate
Conditionsa
MW, 150 ꢁC
Time (h)
Ratiob 23a/23b
Yieldc (%)
1
2
3
4
21
21
21
21
5
20
1
35:65
35:65
33:67
38:62
77
25
81
30
D
, 150 ꢁC
MW, 170 ꢁC
, 170 ꢁC
D
10
a
In o-xylene, in the presence of K2CO3.
b
c
Ratio in the crude reaction mixtures determined by 1H NMR.
Isolated combined yields.
to be ineffective; it had practically no influence on the overall yield
of the desired isothiocyanates 13 and 14. In addition, our initial
attempts to realize the rearrangement of 22 in o-xylene proved
problematic: the reaction rate was very slow and the equilibrium
was considerably shifted to the starting material 22. However, the
aza-Claisen rearrangement of 22 was found to show stereo-
selectivities better to those observed for the Overman rearrange-
ment of 21 (Table 1).
The stereochemistry of the newly constructed stereogenic cen-
tre in all rearranged products was confirmed by the following se-
quences. As shown in Scheme 3, deprotection of the trichloroacetyl
moiety in a mixture of trichloroacetamides 23a and 23b (23a/
23bz1:2, prepared from 21) under basic conditions (NaOH/H2O/
EtOH)15b and immediate Boc2O treatment of the liberated amines
afforded, after chromatographic separation, the corresponding N-
Boc derivatives 15 and 16 in 32% and 60% isolated yields, re-
spectively; their structures were assigned by NMR spectroscopic
analysis including 2D experiments. Ozonolysis of both compounds,
followed by NaBH4 reduction, successfully furnished alcohols 24
(84%) and 25 (75%), which were further converted into
together with [a] value for the obtained cyclic carbamate were
D
identical with those for compound 26 previously prepared from
23a. These findings revealed that major diastereoisomer of the aza-
Claisen rearrangement, product 13, has (6S)-configuration.
Having established the synthetic route to the polar fragments 26
and 27 possessing the requisite functionalities and the correct
stereochemistries, our next efforts led to the completion of the total
synthesis of 8, 9, ent-6$HCl and 7$HCl as shown in Scheme 4. After

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8232
ꢂ
Fig. 2. Transition structures for the rearrangement 21/[TS1]/[TS2]/23b. Relative energies of transition states (in kcal/mol) and bond distances (in A) are shown.
ꢂ
Fig. 3. Transition structures for the rearrangement 21/[TS3]/[TS4]/23a. Relative energies of transition states (in kcal/mol) and bond distances (in A) are shown.
19
p-methoxybenzyl protection (PMBCl, NaH, TBAI) of the oxazolidi-
none ring in 26 and 27, the tert-butyldimethylsilyl group of the
resulting products 30 (88%) and 31 (88%) was removed under
standard conditions (TBAF, THF) to afford derivatives 32 and 33 in
93% and 98% isolated yields, respectively. The terminal iso-
propylidene ring in 32 and 33 was selectively cleaved by acid hy-
drolysis (AcOH/H2O) to produce the requisite triol intermediates 10
(90%) and 11 (60%). The lower yield for 11 was due to partial for-
mation of the pentol derivative 34 (19%). Applying other acids, such
as p-toulenesulfonic acid, pyridinium p-toluenesulfonate, CeCl3/
(COOH)2 either generated greater amounts of the undesirable
polyol product, or the starting material was recovered unchanged.
Oxidative fragmentation of 10 and 11 with NaIO4 furnished the
corresponding aldehydes, which were used immediately in the
Wittig olefination with triphenyl(tridecyl)phosphonium bromide
12,6per,9 employing freshly prepared LHMDS20 as a base. This pro-
cess resulted in the formation of barely separable mixtures of ole-
fins 35 (Z/E¼9:1) and 36 (Z/E¼12:1 ratio, as determined by 1H NMR
spectroscopy) in 74% and 71% isolated yields (over two-steps), re-
spectively (Scheme 4). Small amounts of the mixtures of 35 and 36

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8233
Table 2
were separated by column chromatography to give both geo-
metrical isomers 35a and 35b in pure form. In the case of a mixture
of 36 only (Z)-36a was obtained as an analytical sample. Their
structures including geometries of the double bonds were assigned
by NMR spectroscopic analysis. For example, the (E)-configuration
of the minor 35b and (Z)-configuration of the major 36a were
confirmed by the coupling constants of the vinylic protons
(Jtrans¼15.2 Hz and Jcis¼10.9 Hz, respectively). The subsequent
catalytic hydrogenation (H2, 10% Pd/C, EtOH) of 35 and 36 resulted
in formation of the saturated derivatives 37 (94%) and 38 (89%).
Next, the p-methoxybenzyl and isopropylidene protecting groups
of 37 and 38 were simultaneously removed by treatment with CAN
[3,3]-Sigmatropic rearrangement of thiocyanate 22
Entry
Thiocyanate
Conditionsa
Time (h)
Ratiob 13/14
Yieldc (%)
1
2
3
4
5
6
7
8
9
22
22
22
22
22
22
22
22
22
22
D
D
, 90 ꢁC
, 90 ꢁC
15
25
5
10
5
10
2
4
80:20
82:18
81:19
77:23
77:23
77:23
75:25
78:22
75:25
78:22
53
53
49
56
51
50
47
51
51
51
MW, 90 ꢁC
MW, 90 ꢁC
MW, 120 ꢁC
MW, 120 ꢁC
MW, 150 ꢁC
MW, 150 ꢁC
MW, 170 ꢁC
MW, 170 ꢁC
2
4
10
a
In n-heptane.
in CH3CN/H2O to give protected
L-arabino- and L-ribo-phytos-
b
c
Ratio in the crude reaction mixtures determined by 1H NMR.
Isolated combined yields.
NHBoc
OR
O
NHBoc
OR
O
NHCOCCl3
a
OR
O
+
O
O
O
O
O
O
O
O
O
16
, 60%
b
23a,b
15
, 32%
b
O
NHBoc
OR
O
NHBoc
OH
OR
O
HN
OR
O
c
O
OH
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
25
, 75%
26
24
, 84%
O
c
c
HN
OR
O
OR
NHCOOCH3
OH
OR
O
NHCOOCH3
O
b
O
O
O
27
, 97%
28
29
, 80%
d
R = TBDMS
13
Scheme 3. Reagents and conditions: (a) (i) NaOH, EtOH/H2O, rt; (ii) Boc2O, Et3N, CH2Cl2, rt; (b) (i) O3, CH3OH/CH2Cl2, ꢀ78 ꢁC; (ii) NaBH4, ꢀ78 ꢁC/rt; (c) NaH, THF, 0 ꢁC/rt, 86%
from 24, 92% from 29; (d) (i) CH3ONa, CH3OH, 0 ꢁC/rt, 52%; (ii) mesitylnitrile oxide, CH3CN, rt, 75%.
phingosine 8 and 9 in 72% and 60%, respectively. Their exposure to
6 M HCl unexpectedly afforded ent-2-epi-jaspine B (6) (78%) and 3-
epi-jaspine B (7) (79%) as their corresponding HCl salts (Scheme 4).
As additional confirmation of the anhydro structure, we con-
verted these aforementioned HCl salts of 7 and ent-6 to the cor-
responding N-Boc derivatives 395a,8e (90%) and 405b (83%) by
treatment with Boc2O and Et3N in dry THF. The spectroscopic data
and optical rotation of 39 and 40 were in good agreement with
those reported previously. Moreover, the NMR spectra of 40
matched the known values of ent-40.5a,21 Finally, exposure of 7$HCl
and ent-6$HCl to acetic anhydride in pyridine and in the presence of
DMAP resulted in the formation of acetyl derivatives 418e and 42 in
92% and 94% yields, respectively (Scheme 4). The 1H NMR spectrum
of 41 showed the small differences from Rao’s product.8e Its 13C
NMR spectroscopic data were in excellent agreement with those
reported,8e but the optical rotation {[
a]
26 ꢀ11.9 (c 0.21, CHCl3)} was
D
25
opposite in sign to that quoted in lit.8e {[
a
]
þ11.2 (c 1.1, CHCl3)}.
D
The spectroscopic properties and magnitude of [a]D for compound
42 were in good concordance with those reported for ent-42.21 As
seen in Fig. 5, NOE experiments of 7$HCl and 41 showed trans-re-
lationship between protons H-2 and H-3 and also between H-3 and
H-4 protons on the tetrahydrofuran core. On the other hand,
Fig. 4. ORTEP structure of 26 showing the crystallographic numbering.

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8234
27
26
a
a
O
O
O
O
R = TBDMS
PMBN
OR
O
PMBN
OR
O
O
O
O
O
O
O
30
, 88%
31
, 88%
b
b
O
O
O
O
O
O
PMB
PMBN
O
OH
PMBN
O
OH
OH OH
N
+
HO
HO
O
OH
O
OH
OH OH OH
34
, 19%
10
11
, 90%
c
, 60%
c
O
O
O
PMBN
O
PMBN
O
10
10
O
O
O
35
, 74%
d
36
, 71%
d
O
O
O
PMBN
PMBN
O
10
10
O
O
O
O
37
38
, 94%
e
, 89%
e
O
O
O
O
HN
HN
10
10
HO
OH
HO
OH
9
, 60%
8
, 72%
f
f
OH
OH
C14H29
OH
C14H29
OH
BocHN
ClH.H2N
ClH.H2N
BocHN
g
g
C14H29
, 90%
C14H29
, 83%
O
O
O
O
39
40
7
.HCl, 79%
h
6
ent- .HCl, 78%
h
OAc
AcHN
OAc
AcHN
C14H29
, 94%
C14H29
O
42
O
41
92%
Scheme 4. Reagents and conditions: (a) PMBCl, NaH, DMF, TBAI, 0 ꢁC/rt; (b) (i) TBAF, THF, 0 ꢁC/rt, 32, 93%, 33, 98%; (ii) AcOH/H2O, rt; (c) (i) NaIO4, CH3OH/H2O, rt; (ii) 12,6per,9
LHMDS, THF, rt; (d) 10% Pd/C, EtOH, rt; (e) CAN, CH3CN/H2O, rt; (f) 6 M HCl, reflux; (g) Boc2O, Et3N, THF, rt; (h) Ac2O, pyridine, DMAP, rt.
enhancements between H-3 and H-4 protons in the case of de-
rivative 42 proved their cis orientation on the aforementioned ring.
Because of the overlap of the proton signals (H-2, H-4, H-5, see
Experimental section) in ent-6$HCl in CD3OD solution, it was not
possible to determine their corresponding enhancements. Results
of these NOE analyses would serve as additional confirmation of
the stereochemistry of the newly incorporated stereocentre.
3. Conclusions
We have accomplished the total synthesis of the protected
L
-arabino- and
the HCl salts of ent-2-epi-jaspine B (6) and 3-epi-jaspine B (7)
starting from -mannose. The key transformation of our strategy
was the implementation of an amino-bearing asymmetric centre
L
-ribo-phytosphingosine (8 and 9, respectively) and
D

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8235
Fig. 5. Some selected NOE enhancements for 7$HCl, 41 and 42.
using [3,3]-heterosigmatropic rearrangements. In order to ratio-
nalize the stereochemical outcome of these aforementioned pro-
cesses, DFT calculations were carried out. Importantly, our
approach involving the aza-Claisen rearrangements on carbohy-
drate scaffolds, which established the required stereogenic centre
with nitrogen, followed by further functional group manipulations,
has the potential to be useful for the production of various phy-
tosphingosines in enantiomerically pure forms.
and the stabilized ylide, Ph3P]CHCO2Et (28.9 g, 83.0 mmol), and
the resulting mixture was stirred and heated at 46 ꢁC for 26 h. After
the starting material was completely consumed (judged by TLC),
the reaction was stopped and allowed to cool to room temperature.
The solvent was evaporated, the obtained residue was diluted with
hexane (50 mL), and the insoluble materials were removed by fil-
tration. After evaporation of the solvent under reduced pressure,
the chromatography of the residue on silica gel (hexane/ethyl ac-
etate, 5:1) gave 13.7 g (90%) of (E)-1911 and 1.22 g (8%) of (Z)-19.
Compound (E)-19: colourless oil; [
a
]
25 þ12.6 (c 0.66, CHCl3); IR
4. Experimental
D
(neat) nmax 3497, 2985, 2936, 1717, 1659, 1370, 1253, 1212, 1159,
1033 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d
1.30 (t, 3H, J¼7.1 Hz, CH3),
4.1. General methods
1.35 (s, 3H, CH3), 1.41 (s, 3H, CH3), 1.42 (s, 3H, CH3), 1.55 (s, 3H, CH3),
2.17 (d,1H, J6,OH¼7.7 Hz, OH), 3.42e3.47 (m,1H, H-6), 3.96e4.03 (m,
2H, H-7, H-8), 4.08e4.13 (m, 1H, H-8), 4.21 (q, 2H, J¼7.1 Hz, CH2),
4.46 (dd,1H, J5,4¼7.4 Hz, J6,5¼2.2 Hz, H-5), 4.83 (ddd,1H, J5,4¼7.4 Hz,
J4,3¼6.2 Hz, J4,2¼1.5 Hz, H-4), 6.10 (dd, 1H, J3,2¼15.7 Hz, J4,2¼1.5 Hz,
H-2), 7.07 (dd, 1H, J3,2¼15.7 Hz, J4,3¼6.2 Hz, H-3); 13C NMR
All commercial reagents wereused in the highest available purity
from Aldrich, Fluka, Merck or Acros Organics without further puri-
fication. Solvents were dried and purified before use according to
standard procedures. For flash column chromatography on silica gel,
Kieselgel 60 (0.040e0.063 mm, 230e400 mesh, Merck) was used.
Solvents for flash chromatography (hexane, ethyl acetate, methanol,
dichloromethane) were distilled before use. Thin layer chromatog-
raphy was run on Merck silica gel 60 F254 analytical plates; detection
was carried out with either ultraviolet light (254 nm), or spraying
with a solution of phosphomolybdic acid, a basic potassium per-
manganate solution, or a solution of concentrated H2SO4, with
subsequent heating. 1H NMR and 13C NMR spectra were recorded in
CDCl3, CD3OD and C6D6 on a Varian Mercury Plus 400 FT NMR
(400.13 MHz for 1H and 100.6 MHz for 13C) or on a Varian Premium
COMPACT 600 (599.87 MHz for 1H and 150.84 MHz for 13C) spec-
(100 MHz, CDCl3):
d
14.2 (CH3), 24.7 (CH3), 25.2 (CH3), 26.7 (2ꢂ
CH3), 60.6 (CH2), 67.2 (C-8), 70.5 (C-6), 76.1 (C-7), 76.6 (C-4), 77.3 (C-
5), 109.3 (Cq), 109.5 (Cq), 123.6 (C-2), 143.2 (C-3), 165.7 (C]O). Anal.
Calcd for C16H26O7: C, 58.17; H, 7.93. Found: C, 58.10; H, 7.98.
Compound (Z)-19: mp 88e89 ꢁC (recrystallized from n-hexane);
25
[a
]
ꢀ125.3 (c 0.32, CHCl3); IR (neat) nmax 3524, 2984, 2937, 1712,
D
1644, 1371, 1190 cmꢀ1 1H NMR (400 MHz, CDCl3):
; d 1.29 (t, 3H,
J¼7.1 Hz, CH3), 1.34 (s, 3H, CH3), 1.38 (s, 3H, CH3), 1.41 (s, 3H, CH3),
1.53 (s, 3H, CH3), 2.04 (d, 1H, J6,OH¼9.9 Hz, OH), 3.30e3.34 (m, 1H,
H-6), 3.97e4.07 (m, 3H, H-7, 2ꢂ H-8), 4.16 (q, 2H, J¼7.1 Hz, CH2),
4.79e4.81 (m, 1H, H-5), 5.64 (ddd, 1H, J5,4¼8.1 Hz, J4,3¼6.4 Hz,
J4,2¼1.8 Hz, H-4), 5.93 (dd, 1H, J3,2¼11.6 Hz, J4,2¼1.8 Hz, H-2), 6.52
(dd, 1H, J3,2¼11.6 Hz, J4,3¼6.4 Hz, H-3); 13C NMR (100 MHz, CDCl3):
trometer using TMS as internal reference. For 1H,
d
are given in parts
¼4.84) and C6D6
per million (ppm) relative toTMS (
d
¼0.0), CD3OD (
d
(d
¼7.15) and for 13C relative to CDCl3 (
d
¼77.0), CD3OD ( ¼49.05) and
d
C6D6 (
d
¼128.02). The multiplicity of the 13C NMR signals concerning
d
14.2 (CH3), 23.9 (CH3), 25.3 (CH3), 26.5 (CH3), 26.8 (CH3), 60.5
the 13Ce1H coupling was determined by the DEPT method. Chemical
shifts(inppm) andcouplingconstants (inHz) wereobtainedbyfirst-
order analysis; assignments were derived from COSY and H/C cor-
relation spectra. Infrared (IR) spectra were measured with a Nicolet
6700 FT-IR spectrometer and expressed in v values (cmꢀ1). Optical
rotations were measured on a P-2000 Jasco polarimeter and re-
(CH2), 66.6 (C-8), 69.8 (C-6), 75.3 (C-4), 76.3 (C-7), 77.3 (C-5), 108.7
(Cq), 109.3 (Cq), 120.3 (C-2), 148.2 (C-3), 165.8 (C]O). Anal. Calcd for
C16H26O7: C, 58.17; H, 7.93. Found: C, 58.22; H, 7.89.
4.3. Ethyl (4R,5R,6R,7R,2E)-6-[(tert-butyldimethylsilyl)oxy]-
4,5:7,8-bis(isopropylidenedioxy)oct-2-enoate (20)
ported as follows: [a] (c in grams per 100 mL, solvent). Melting
D
points were recorded on a Kofler hot block, and are uncorrected.
Microwave reactions were carried out on the focused microwave
system (CEM Discover). The temperature content of the vessel was
monitored using a calibrated infrared sensor mounted under the
vessel. At the end of all reactions the contents of vessel were cooled
rapidly using a stream of compressed air. Small quantities of re-
agents (mL) were measured with appropriate syringes (Hamilton).
All reactions were performed under an atmosphere of nitrogen,
unless otherwise noted.
To a solution of (E)-19 (13.7 g, 41.5 mmol) in dry DMF (27.5 mL)
was added imidazole (5.65 g, 83.0 mmol) followed by tert-butyl-
dimethylsilyl chloride (15.6 g, 103.5 mmol) and the resulting mix-
ture was stirred at room temperature for 72 h. After this period, the
mixture was partitioned between ice-water (275 mL) and Et2O
(275 mL), and the aqueous phase was extracted with another
portion of Et2O (275 mL). The combined organic layers were dried
over Na2SO4, stripped of solvent, and the residue was subjected to
flash chromatography on silica gel (hexane/ethyl acetate, 20:1) to
afford 18.1 g (98%) of compound 20 as a colourless oil; [
a]
25 þ61.5 (c
D
4.2. Ethyl (4R,5S,6R,7R,2E)-6-hydroxy-4,5:7,8-bis(isopropyli
denedioxy)oct-2-enoate [(E)-19] and ethyl (4R,5S,6R,7R,2Z)-6-
hydroxy-4,5:7,8-bis(isopropylidenedioxy)oct-2-enoate [(Z)-19]
0.46, CHCl3); IR (neat) nmax 2930, 1722, 1656, 1381, 1250, 1152,
834 cmꢀ1 1H NMR (400 MHz, CDCl3):
; d 0.07 (s, 3H, CH3), 0.09 (s,
3H, CH3), 0.87 (s, 9H, 3ꢂ CH3), 1.29 (t, 3H, J¼7.1 Hz, CH3), 1.34 (s, 3H,
CH3), 1.37 (s, 3H, CH3), 1.42 (s, 3H, CH3), 1.53 (s, 3H, CH3), 3.72e3.83
(m, 2H, H-6, H-8), 3.94e3.99 (m,1H, H-7), 4.09e4.13 (m, 2H, H-5, H-
8), 4.20 (q, 2H, J¼7.1 Hz, CH2), 4.69e4.72 (m, 1H, H-4), 6.05 (dd, 1H,
To a solution of the known 1810 (12.0 g, 46.1 mmol) in dry CH2Cl2
(310 mL) were successively added benzoic acid (0.57 g, 4.66 mmol)

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8236
J3,2¼15.6 Hz, J4,2¼1.5 Hz, H-2), 7.08 (dd, 1H, J3,2¼15.6 Hz, J4,3¼5.7 Hz,
H-3); 13C NMR (100 MHz, CDCl3):
(CH3), 18.4 (Cq), 25.4 (2ꢂ CH3), 25.9 (3ꢂ CH3), 26.2 (CH3), 27.8 (CH3),
60.4 (CH2), 68.1 (C-8), 72.5 (C-6), 76.5 (C-4), 77.2 (C-7), 81.0 (C-5),
108.4 (Cq), 109.8 (Cq), 123.3 (C-2), 144.9 (C-3), 166.1 (C]O). Anal.
Calcd for C22H40O7Si: C, 59.43; H, 9.07. Found: C, 59.38; H, 9.13.
and then for 25 min at room temperature. After evaporating of the
solvent, the residue was diluted with Et2O (20 mL), the salts were
filtered off and washed with Et2O. The solvent was removed under
reduced pressure to afford a crude mesylate that was used in the
subsequent reaction directly without purification.
d
ꢀ4.7 (CH3), ꢀ3.9 (CH3), 14.2
To a solution of the crude mesylate (2.86 g, 5.96 mmol) in dry
CH3CN (52 mL) that had been pre-cooled to 5 ꢁC was added KSCN
(0.87 g, 8.95 mmol). After stirring at room temperature for 21 h,
the solvent was evaporated in vacuo, the obtained residue was
diluted with Et2O (20 mL), and the insoluble materials were re-
moved by filtration. Evaporating of the solvent and chromatogra-
phy of the residue on silica gel (hexane/ethyl acetate, 9:1) provided
4.4. (4R,5R,6R,7R,2E)-6-[(tert-Butyldimethylsilyl)oxy]-4,5:7,8-
bis(isopropylidenedioxy)oct-2-en-1-ol (17)
Diisobutylaluminum hydride (91.6 mL, 109.91 mmol, 1.2 M tolu-
ene solution) was added dropwise to a solution of 20 (18.1 g,
40.7 mmol) in dry CH2Cl2 (185 mL) that had been pre-cooled to
ꢀ15 ꢁC for 1 h. The resulting mixture was stirred at the same tem-
perature for another 15 min, then quenched with CH3OH (28 mL),
and poured into a 30% solution of K/Na tartrate (610 mL). After stir-
ring for 1 h at room temperature, the aqueous phase was extracted
with CH2Cl2 (4ꢂ250 mL). The combined organic layers were dried
over Na2SO4, the solvent was evaporated, and the residue was pu-
2.38 g (90%) of compound 22 as white crystals; mp 63e64 ꢁC
25
(recrystallized from n-hexane); [
a
]
þ45.6 (c 0.27, CHCl3); IR
1H
0.25 (s, 3H, CH3), 0.31 (s, 3H, CH3), 1.01 (s,
D
(neat) nmax 2928, 2146, 1471, 1381, 1216, 1145, 1056, 875 cmꢀ1
NMR (400 MHz, C6D6):
;
d
9H, 3ꢂ CH3), 1.26 (s, 3H, CH3), 1.29 (s, 3H, CH3), 1.41 (s, 3H, CH3),
1.49 (s, 3H, CH3), 2.41‒2.52 (m, 2H, 2ꢂ H-8), 3.89 (dt, 1H,
J2,1¼7.6 Hz, J2,1¼6.4 Hz, J3,2¼6.4 Hz, H-2), 3.95 (dd, 1H, J4,3¼9.4 Hz,
J5,4¼5.6 Hz, H-4), 4.02‒4.08 (m, 2H, 2ꢂ H-1), 4.15 (dd, 1H,
J4,3¼9.4 Hz, J3,2¼6.4 Hz, H-3), 4.46‒4.49 (m, 1H, H-5), 5.41‒5.49 (m,
1H, H-7), 5.81 (ddt, 1H, J7,6¼15.2 Hz, J6,5¼6.4 Hz, J8,6¼1.0 Hz,
rified by flash chromatography on silica gel (hexane/ethyl acetate,
25
2:1) to furnish 15.9 g (97%) of compound 17 as a colourless oil; [a]
D
þ54.4 (c 0.18, CHCl3); IR (neat) nmax 2930, 2856, 1461, 1379, 1216,
1149, 1052, 834 cmꢀ1; 1H NMR (400 MHz, C6D6):
0.19 (s, 3H, CH3),
d
J8,6¼1.0 Hz, H-6); 13C NMR (100 MHz, C6D6):
d
ꢀ4.2 (CH3), ꢀ3.6
0.26 (s, 3H, CH3),1.02 (s, 9H, 3ꢂ CH3),1.27 (s, 6H, 2ꢂ CH3),1.41 (s, 3H,
CH3),1.48 (s, 3H, CH3),1.82 (br s,1H, OH), 3.83‒3.95 (m, 5H, H-8, H-6,
H-5, 2ꢂ H-1), 3.98‒4.01 (m, 1H, H-8), 4.06‒4.09 (m, 1H, H-7), 4.39‒
4.42 (m, 1H, H-4), 5.69 (dtd, 1H, J3,2¼15.3 Hz, J2,1¼4.9 Hz, J2,1¼4.9 Hz,
J4,2¼0.6 Hz, H-2), 5.88 (ddt, 1H, J3,2¼15.3 Hz, J4,3¼7.9 Hz, J3,1¼1.6 Hz,
(CH3), 18.7 (Cq), 25.8 (2ꢂ CH3), 26.3 (3ꢂ CH3), 26.7 (CH3), 28.2
(CH3), 35.4 (C-8), 68.0 (C-1), 72.2 (C-3), 77.5 (C-5), 77.8 (C-2), 80.9
(C-4), 108.1 (Cq), 109.5 (Cq), 111.6 (SCN), 125.8 (C-7), 134.8 (C-6).
Anal. Calcd for C21H37NO5SSi: C, 56.85; H, 8.41; N, 3.16. Found: C,
56.91; H, 8.36; N, 3.12.
J3,1¼1.6 Hz, H-3); 13C NMR (100 MHz, C6D6):
ꢀ4.2 (CH3), e3.7 (CH3),
d
18.8 (Cq), 25.5 (CH3), 25.8 (CH3), 26.3 (3ꢂ CH3), 26.6 (CH3), 28.4 (CH3),
62.5 (C-1), 66.1 (C-8), 71.9 (C-7), 76.8 (C-6), 78.5 (C-4), 80.4 (C-5),
108.1 (Cq), 109.1 (Cq), 127.4 (C-3), 134.4 (C-2). Anal. Calcd for
4.7. N-{(30S,40R,50R,60R,70R)-60-[(tert-Butyldimethylsilyl)oxy]-
40,50:70,80-bis(isopropylidenedioxy)oct-10-en-30-yl}-2,2,2-trich
loroacetamide (23a) and N-{(30R,40R,50R,60R,70R)-60-[(tert-bu-
tyldimethylsilyl)oxy]-40,50:70,80-bis(isopropylidenedioxy)oct-
10-en-30-yl}-2,2,2-trichloroacetamide (23b)
C20H38O6Si: C, 59.67; H, 9.51. Found: C, 59.72; H, 9.47.
4.5. (40R,50R,60R,70R,20E)-60-[(tert-Butyldimethylsilyl)oxy]-
40,50:70,80-bis(isopropylidenedioxy)oct-20-en-10-yl 2,2,2-trichlo
roacetimidate (21)
4.7.1. Conventional method. To a solution of imidate 21 (0.20 g,
0.365 mmol) in o-xylene (4.9 mL) was added anhydrous K2CO3
(57.61 mg, 0.417 mmol), and the resulting mixture was heated in
a sealed tube (for the temperatures and reaction times, see Table 1).
After cooling to room temperature, the solvent was evaporated in
vacuo, and the residue was chromatographed on silica gel (hexane/
ethyl acetate, 15:1) to furnish trichloroacetamides 23a and 23b as
a barely separable mixture of diastereoisomers (for the combined
yields, see Table 1).
To a solution of 17 (13.5 g, 33.53 mmol) in dry CH2Cl2 (178 mL)
that had been pre-cooled to 0 ꢁC were successively added DBU
(0.50 mL, 3.35 mmol) and trichloroacetonitrile (6.72 mL, 67.0 mmol).
The resulting mixture was stirred for further 30 min at 0 ꢁC and then
for 20 min at room temperature. Afterevaporating of the solvent, the
residue was flash-chromatographed through a short silica gel col-
umn (hexane/ethyl acetate, 3:1) to give 18 g (98%) of imidate 21 as
a colourless oil; [
a
]
D
25 þ40.0 (c 0.32, CHCl3); IR (neat) nmax 2930, 2856,
4.7.2. Microwave-assisted synthesis. Imidate 21 (0.20 g, 0.365
mmol) was weighed into a 10-mL glass pressure microwave tube
equipped with a magnetic stirbar. o-Xylene (4.9 mL) and anhydrous
K2CO3 (57.6 mg, 0.417 mmol) were added, the tube was closed with
a silicone septum, and the reaction mixture was subjected to mi-
crowave irradiation (for the temperatures and reaction times, see
Table 1). Removal of the solvent and chromatography on silica gel
(hexane/ethyl acetate, 15:1) afforded a mixture of the rearranged
products 23a,b (for the combined yields, see Table 1). A small
amount of this mixture was repeatedly chromatographed on silica
gel (hexane/ethyl acetate, 15:1) to afford each diastereoisomer in
pure form as an analytical sample.
1663,1461,1380,1216,1150,1076, 833, 795 cmꢀ1; 1H NMR (400 MHz,
C6D6):
d
0.16 (s, 3H, CH3), 0.23 (s, 3H, CH3),1.00 (s, 9H, 3ꢂ CH3),1.25 (s,
6H, 3ꢂ CH3), 1.37 (s, 3H, CH3), 1.45 (s, 3H, CH3), 3.85‒3.93 (m, 4H, H-
50, H-60, 2ꢂ H-80), 3.97‒4.01 (m, 1H, H-70), 4.41‒4.44 (m, 1H, H-40),
4.59‒4.61 (m, 2H, 2ꢂ H-10), 5.73 (dtd, 1H, J3 ,2 ¼15.5 Hz,0J2 ,1 ¼5.4 Hz,
0
0
0
0
0
0
0
0
0
J2 ,1 ¼5.3 Hz, J4 ,2 ¼0.8 Hz, H-2 ), 5.98‒6.04 (m, 1H, H-3 ), 8.31 (br s,
1H, NH). 13C NMR (100 MHz, C6D6):
d
ꢀ4.2 (CH3), ꢀ3.6 (CH3), 18.7
(Cq), 25.6 (CH3), 25.8 (CH3), 26.3 (3ꢂ CH3), 26.6 (CH3), 28.3 (CH3),
0
0
0
0
0
0
0
66.9 (C8 ), 68.6 (C1 ), 72.0 (C7 ), 77.1 (C5 or C6 ), 77.8 (C4 ), 80.7 (C5
0
0
0
or C6 ), 91.9 (CCl3), 108.2 (Cq), 109.3 (Cq), 127.1 (C2 ), 131.8 (C3 ), 162.2
(C]NH). Anal. Calcd for C22H38Cl3NO6Si: C, 48.31; H, 7.00; N, 2.56.
Found: C, 48.36; H, 7.05; N, 2.50.
Requiring a greater amount of the mixture of 23a and 23b,
aforementioned procedure was repeated several times at 170 ꢁC
using the same amount of the starting imidate 21.
4.6. tert-Butyldimethyl{[(2R,3R,4R,5R,6E)-1,2:4,5-bis(isopro
pylidenedioxy)-8-thiocyanatooct-6-en-3-yl]oxy}silane (22)
Diastereoisomer 23a: colourless oil; [
a
]
25 þ30.2 (c 0.44, CHCl3);
D
1H NMR (400 MHz, CDCl3):
d
0.04 (s, 3H, CH3), 0.07 (s, 3H, CH3), 0.84
Et3N (1.68 mL, 11.95 mmol) was added to a solution of 17 (2.40 g,
5.96 mmol) in dry CH2Cl2 (52 mL) and after cooling to 0 ꢁC,
methanesulfonyl chloride (0.93 mL, 12.0 mmol) was added drop-
wise. The resulting mixture was stirred for a further 15 min at 0 ꢁC
(s, 9H, 3ꢂ CH3), 1.36 (s, 3H, CH3), 1.39 (s, 3H, CH3), 1.49 (s, 3H, CH3),
1.58 (s, 3H, CH3), 3.79‒3.86 (m, 2H, H-60, H-80), 3.90‒3.96 (m, 1H,
H-70), 4.20‒4.25 (m, 2H, H-50, H-80), 4.34‒4.36 (m, 1H, H-40), 5.10‒
5.14 (m, 1H, H-30), 5.21‒5.27 (m, 2H, 2ꢂ H-10), 5.81 (ddd, 1H,

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8237
0
0
0
0
0
0
0
J2 ,1 trans¼17.2 Hz, J2 ,1 cis¼10.4 Hz, J3 ,2 ¼5.2 Hz, H-2 ), 7.09 (br d, 1H,
H-8cis), 5.41‒5.46 (m, 1H, H-8trans), 5.98 (ddd, 1H, J8trans,7¼17.0 Hz,
J3 ,NH¼9.0 Hz, NH); 13C NMR (100 MHz, CDCl3):
d
ꢀ4.5 (CH3), ꢀ3.5
J8cis,7¼10.3 Hz, J7,6¼5.6 Hz, H-7); 13C NMR (100 MHz, CDCl3):
ꢀ4.1
d
0
(CH3), 18.3 (Cq), 24.0 (CH3), 25.8 (3ꢂ CH3), 25.9 (CH3), 26.3 (CH3),
26.6 (CH3), 53.0 (C-30), 69.5 (C-80), 71.8 (C-60), 78.0 (C-40), 78.5 (C-
70), 80.1 (C-50), 92.7 (CCl3), 107.8 (Cq), 110.3 (Cq), 116.0 (C-10), 135.7
(C-20), 160.8 (C]O). Anal. Calcd for C22H38Cl3NO6Si: C, 48.31; H,
7.00; N, 2.56. Found: C, 48.26; H, 6.95; N, 2.60.
(CH3), ꢀ3.8 (CH3), 18.5 (Cq), 25.0 (CH3), 25.1 (CH3), 26.0 (3ꢂ CH3),
26.3 (CH3), 26.5 (CH3), 60.2 (C-6), 67.4 (C-1), 71.2 (C-3), 77.4 (C-2),
78.9 (C-5), 79.6 (C-4), 108.7 (Cq), 109.6 (Cq), 118.5 (C-8), 125.5 (NCS),
132.9 (C-7). Anal. Calcd for C21H37NO5SSi: C, 56.85; H, 8.41; N, 3.16.
Found: C, 56.90; H, 8.37; N, 3.12.
Diastereoisomer 23b: colourless crystals; mp 72e73 ꢁC
(recrystallized from n-hexane); [
a
]
25 þ86.9 (c 0.32, CHCl3); IR (neat)
4.9. tert-Butyl [(3S,4R,5R,6R,7R)-6-[(tert-butyldimethylsilyl)
oxy]-4,5:7,8-bis(isopropylidenedioxy)oct-1-en-3-yl]carbamate
(15) and tert-butyl [(3R,4R,5R,6R,7R)-6-[(tert-butyldimethyl
silyl)oxy]-4,5:7,8-bis(isopropylidenedioxy)oct-1-en-3-yl]car-
bamate (16)
D
nmax 3417, 2934, 2893, 1716, 1495, 1382, 1210, 1075, 835 cmꢀ1
;
1H
NMR (400 MHz, CDCl3): d 0.08 (s, 3H, CH3), 0.10 (s, 3H, CH3), 0.87 (s,
9H, 3ꢂ CH3), 1.36 (s, 3H, CH3), 1.37 (s, 3H, CH3), 1.50 (s, 3H, CH3), 1.52
(s, 3H, CH3), 3.79‒3.83 (m, 1H, H-80), 3.94‒3.99 (m, 1H, H-70), 4.08‒
4.19 (m, 3H, H-50, H-60, H-80), 4.28 (dd,1H, J5 ,4 ¼5.8 Hz, J4 ,3 ¼2.3 Hz,
H-40), 4.99‒5.03 (m, 1H, H-30), 5.31‒5.37 (m, 2H, 2ꢂ H-10), 5.98‒
0
0
0
0
A 6 M aq solution of NaOH (125.5 mL) was added dropwise to
a solution of 23a,b (12.88 g, 23.5 mmol) in EtOH (125.5 mL) at room
temperature. After stirring for 5 h at the same temperature, the
mixture was diluted with Et2O (150 mL), and aqueous phase was
then extracted with further portions of Et2O (2ꢂ200 mL). The
combined organic layers were dried over Na2SO4, stripped of sol-
vent, and the residue was used immediately in the next reaction
without purification. To a solution of crude amines in CH2Cl2
(29 mL) were successively added Et3N (3.3 mL, 23.5 mmol) and
Boc2O (12.82 g, 58.74 mmol). The resulting mixture was stirred for
16 h at room temperature, then was diluted with CH2Cl2 (70 mL)
and washed with a 1 M KHSO4 solution (100 mL) and a 1 M NaHCO3
solution (100 mL). The organic layer was dried over Na2SO4, the
solvent was evaporated in vacuo, and the residue was chromato-
graphed on silica gel (hexane/ethyl acetate, 11:1) to give 3.78 g
(32%) of 15 and 7.08 g (60%) of 16.
6.07 (m, 1H, H-20), 7.01 (br d, 1H, J3 ,NH¼8.8 Hz, NH); 13C NMR
0
(100 MHz, CDCl3):
d
ꢀ4.4 (CH3), ꢀ3.6 (CH3), 18.4 (Cq), 24.9 (CH3),
25.4 (CH3), 25.9 (3ꢂ CH3), 26.2 (2ꢂ CH3), 54.6 (C-30), 68.6 (C-80),
71.4 (C-50 or C-60), 77.6 (C-70), 78.3 (C-40), 80.3 (C-50 or C-60), 92.8
(CCl3), 108.1 (Cq), 110.4 (Cq), 118.8 (C-10), 134.0 (C-20), 160.6 (C]O).
Anal. Calcd for C22H38Cl3NO6Si: C, 48.31; H, 7.00; N, 2.56. Found: C,
48.36; H, 6.96; N, 2.51.
4.8. tert-Butyldimethyl{[(2R,3R,4R,5R,6S)-1,2:4,5-bis(isopropy
lidenedioxy)-6-isothiocyanatooct-7-en-3-yl]oxy}silane (13)
and tert-butyldimethyl{[(2R,3R,4R,5R,6R)-1,2:4,5-bis(isopropy
lidenedioxy)-6-isothiocyanatooct-7-en-3-yl]oxy}silane (14)
4.8.1. Conventional method. Thiocyanate 22 (0.10 g, 0.225 mmol)
was dissolved in n-heptane (3 mL) and the resulting solution was
stirred and heated under a nitrogen atmosphere (for the temper-
atures and reaction times, see Table 2). After cooling to room
temperature, the solvent was taken down, and the residue was
chromatographed on silica gel (hexane/ethyl acetate, 25:1) to give
the corresponding isothiocyanates 13 and 14 as colourless oils (for
the combined yields, see Table 2).
Diastereoisomer 15: colourless oil; [
a
]
24 þ55.4 (c 0.28, CHCl3); 1H
D
NMR (400 MHz, CDCl3):
d
0.08 (s, 3H, CH3), 0.11 (s, 3H, CH3), 0.86 (s,
9H, 3ꢂ CH3), 1.35 (s, 6H, 2ꢂ CH3), 1.45 (s, 12H, 4ꢂ CH3), 1.53 (s, 3H,
CH3), 3.78‒3.82 (m, 1H, H-8), 3.92‒3.95 (m, 1H, H-7), 4.02‒4.06 (m,
1H, H-6), 4.15‒4.22 (m, 3H, H-4, H-5, H-8), 4.61 (m,1H, H-3), 4.86 (br
d, 1H, J3,NH¼8.0 Hz, NH), 5.14‒5.19 (m, 2H, 2ꢂ H-1), 5.81 (ddd, 1H,
J2,1trans¼17.0 Hz, J2,1cis¼10.4 Hz, J3,2¼4.9 Hz, H-2); 13C NMR (100 MHz,
Requiring a greater amount of the pure rearranged products 13
and 14, they were obtained on a multigram scale by the conven-
tional method in n-heptane at 90 ꢁC.
CDCl3):
d
ꢀ4.6 (CH3), ꢀ3.7 (CH3),18.3 (Cq), 24.3 (CH3), 25.9 (4ꢂ CH3),
26.3 (CH3), 26.4 (CH3), 28.4 (3ꢂ CH3), 52.4(C-3), 69.2 (C-8), 71.5(C-6),
78.5 (C-4 or C-5,C-7), 79.1(Cq), 79.8 (C-4orC-5),107.4(Cq),109.9 (Cq),
114.6 (C-1), 137.9 (C-2), 154.8 (C]O). Anal. Calcd for C25H47NO7Si: C,
59.85; H, 9.44; N, 2.79. Found: C, 59.89; H, 9.39; N, 2.83.
4.8.2. Microwave-assisted synthesis. Thiocyanate 22 (0.10 g,
0.225 mmol) was weighed in a 10-mL glass pressure microwave
tube equipped with a magnetic stirbar. n-Heptane (3 mL) was
added, the tube was closed with a silicon septum, and the resulting
mixture was subjected to microwave irradiation (for the tempera-
tures and reaction times, see Table 2). Evaporating of the solvent
and chromatography on silica gel (hexane/ethyl acetate, 25:1) gave
Diastereoisomer 16: white crystals; mp 84e86 ꢁC (recrystallized
24
from n-hexane); [
a
]
þ78.1 (c 0.26, CHCl3); IR (neat) nmax 3332,
D
2930, 1714, 1519, 1369, 1246, 1150, 836 cmꢀ1
CDCl3):
;
1H NMR (400 MHz,
d
0.09 (s, 3H, CH3), 0.11 (s, 3H, CH3), 0.87 (s, 9H, 3ꢂ CH3),
1.33 (s, 3H, CH3), 1.36 (s, 3H, CH3), 1.44 (s, 9H, 3ꢂ CH3), 1.47 (s, 3H,
CH3), 1.51 (s, 3H, CH3), 3.77‒3.81 (m, 1H, H-8), 3.98‒4.07 (m, 3H, H-
4, H-5, H-7), 4.11‒4.18 (m, 2H, H-6, H-8), 4.42 (m, 1H, H-3), 5.13 (br
d, 1H, J3,NH¼7.3 Hz, NH), 5.21‒5.28 (m, 2H, 2ꢂ H-1), 5.94‒6.02 (m,
isothiocyanates 13 and 14 (for the combined yields, see Table 2).
23
Diastereoisomer 13: [
a]
þ27.9 (c 0.80, CHCl3); IR (neat) nmax
D
2930, 2102, 1461, 1381, 1213, 1057, 832 cmꢀ1
CDCl3):
;
1H NMR (400 MHz,
d
0.17 (s, 6H, 2ꢂ CH3), 0.87 (s, 9H, 3ꢂ CH3), 1.32 (s, 3H, CH3),
1H, H-2); 13C NMR (100 MHz, CDCl3):
d
ꢀ4.5 (CH3), ꢀ3.8 (CH3), 18.4
1.35 (s, 3H, CH3), 1.40 (s, 3H, CH3), 1.60 (s, 3H, CH3), 3.80‒3.84 (m,
1H, H-1), 3.93‒3.98 (m, 1H, H-2), 4.04‒4.08 (m, 2H, H-3, H-5), 4.14‒
4.17 (m, 1H, H-4), 4.20 (dd, 1H, J1,1¼8.2 Hz, J2,1¼6.2 Hz, H-1), 4.68‒
4.70 (m, 1H, H-6), 5.29‒5.36 (m, 2H, 2ꢂ H-8), 5.91 (ddd, 1H,
J8trans,7¼16.9 Hz, J8cis,7¼10.2 Hz, J7,6¼6.0 Hz, H-7); 13C NMR
(Cq), 25.4 (2ꢂ CH3), 25.9 (3ꢂ CH3), 26.2 (CH3), 26.9 (CH3), 28.4 (3ꢂ
CH3), 52.9 (C-3), 68.1 (C-8), 70.4 (C-6), 77.8 (C-7), 78.9 (C-4 or C-5),
79.2 (Cq), 80.2 (C-4 or C-5), 107.7 (Cq), 109.8 (Cq), 116.4 (C-1), 136.4
(C-2), 154.7 (C]O). Anal. Calcd for C25H47NO7Si: C, 59.85; H, 9.44;
N, 2.79. Found: C, 59.89; H, 9.47; N, 2.82.
(100 MHz, CDCl3):
d
ꢀ4.6 (CH3), ꢀ3.6 (CH3), 18.4 (Cq), 24.9 (2ꢂ CH3),
25.9 (3ꢂ CH3), 26.3 (CH3), 26.6 (CH3), 59.9 (C-6), 69.2 (C-1), 72.2 (C-
3), 77.9 (C-2), 78.0 (C-5), 80.1 (C-4),108.8 (Cq),109.9 (Cq),117.3 (C-8),
133.2 (NCS), 134.0 (C-7). Anal. Calcd for C21H37NO5SSi: C, 56.85; H,
4.10. tert-Butyl [(2S,3R,4R,5R,6R)-5-[(tert-butyldimethylsilyl)
oxy]-1-hydroxy-3,4:6,7-bis(isopropylidenedioxy)heptan-2-yl]
carbamate (24)
8.41; N, 3.16. Found: C, 56.79; H, 8.46; N, 3.11.
24
Diastereoisomer 14: [
(400 MHz, CDCl3):
a]
ꢀ137.8 (c 0.32, CHCl3); 1H NMR
Ozone was introduced to a solution of 15 (3.78 g, 7.53 mmol) in
CH3OH/CH2Cl2 (282.5 mL, 5:1) at ꢀ78 ꢁC for 15 min. After the
complete consumption of the starting material (judged by TLC),
nitrogen was passed through the cold solution in order to remove
excess ozone. Then, NaBH4 (1.28 g, 33.8 mmol) was added
D
d
0.10 (s, 3H, CH3), 0.11 (s, 3H, CH3), 0.88 (s, 9H,
3ꢂ CH3), 1.34 (s, 3H, CH3), 1.36 (s, 3H, CH3), 1.45 (s, 3H, CH3), 1.48 (s,
3H, CH3), 3.84‒3.87 (m,1H, H-1), 4.01‒4.14 (m, 4H, H-1, H-2, H-3, H-
4), 4.24‒4.27 (m,1H, H-5), 4.63‒4.66 (m,1H, H-6), 5.37‒5.39 (m,1H,

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8238
portionwise, and the resulting mixture was stirred for 30 min at
ꢀ78 ꢁC. After warming to room temperature (approximately
30 min), the solvents were evaporated in vacuo, and the residue
was partitioned between EtOAc (190 mL) and a saturated NH4Cl
solution (114 mL). The aqueous phase was washed with further
portions of EtOAc (2ꢂ150 mL), the organic layers were dried over
Na2SO4, the solvent was taken down, and the residue was subjected
to flash chromatography on silica gel (hexane/ethyl acetate, 2:1) to
4.30 (dd, 1H, J5,5¼8.3 Hz, J5,4¼5.9 Hz, H-5), 4.36‒4.40 (m, 1H, H-5),
4.80 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3):
d
ꢀ4.3 (CH3), ꢀ3.6
(CH3), 18.4 (Cq), 24.9 (CH3), 25.3 (CH3), 25.8 (3ꢂ CH3), 26.2 (CH3),
26.4 (CH3), 52.3 (C-4), 67.6 (C-5), 68.6 (C-50), 72.6 (C-30), 76.9 (C-10),
77.5 (C-40), 79.8 (C-20), 108.6 (Cq), 109.9 (Cq), 159.3 (C]O). Anal.
Calcd for C20H37NO7Si: C, 55.66; H, 8.64; N, 3.25. Found: C, 55.69; H,
8.69; N, 3.22.
furnish 3.2 g (84%) of compound 24 as a colourless oil; [
a]
24 þ46.0
D
4.13. (4R)-4-[(10R,20R,30R,40R)-30-[(tert-Butyldimethylsilyl)
oxy]-10,20:40,50-bis(isopropylidenedioxy)pentyl]oxazolidin-2-
one (27)
(c 0.30, CHCl3); IR (neat) nmax 3316, 2984, 2931, 1704, 1506, 1368,
1159, 1076, 838 cmꢀ1 1H NMR (400 MHz, CD3OD):
; d 0.09 (s, 3H,
CH3), 0.12 (s, 3H, CH3), 0.88 (s, 9H, 3ꢂ CH3), 1.32 (s, 3H, CH3), 1.33 (s,
3H, CH3), 1.45 (s, 12H, 3ꢂ CH3, CH3), 1.49 (s, 3H, CH3), 3.45‒3.47 (m,
2H, 2ꢂ H-1), 3.84‒3.88 (m, 1H, H-7), 3.94‒4.04 (m, 2H, H-2, H-6),
4.07‒4.17 (m, 3H, H-4, H-5, H-7), 4.31‒4.32 (m, 1H, H-3), 5.30 (br d,
According to the same procedure described for the preparation
of 26, compound 25 (5.35 g, 10.58 mmol) and NaH (0.85 g,
35.42 mmol, 60% dispersion in mineral oil) afforded after stirring
(21 h) at room temperature and flash chromatography on silica gel
1H, J2,NH¼9.4 Hz, NH); 13C NMR (100 MHz, CD3OD):
d
ꢀ3.8 (CH3),
ꢀ3.2 (CH3), 19.2 (Cq), 24.8 (CH3), 25.8 (CH3), 26.5 (3ꢂ CH3), 26.7
(CH3), 26.8 (CH3), 28.9 (3ꢂ CH3), 52.6 (C-2), 64.1 (C-1), 68.6 (C-7),
72.4 (C-4 or C-5), 76.3 (C-3), 79.2 (C-6), 80.5 (Cq), 80.7 (C-4 or C-5),
108.9 (Cq), 110.9 (Cq), 157.1 (C]O). Anal. Calcd for C24H47NO8Si: C,
57.00; H, 9.37; N, 2.77. Found: C, 57.09; H, 9.32; N, 2.81.
(hexane/ethyl acetate, 2:1) 4.43 g (97%) of crystalline oxazolidinone
22
27; mp 121e122 ꢁC (recrystallized from n-hexane); [
a
]
D
ꢀ55.6 (c
0.34, CHCl3); IR (neat) nmax 3386, 2928, 2887, 2856, 1766, 1471, 1381,
1240, 1211, 1117, 1039, 838 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d
0.11
(s, 6H, 2ꢂ CH3), 0.87 (s, 9H, 3ꢂ CH3), 1.34 (s, 3H, CH3), 1.36 (s, 3H,
CH3), 1.40 (s, 3H, CH3), 1.52 (s, 3H, CH3), 3.71‒3.75 (m, 1H, H-20),
3.79‒3.83 (m,1H, H-50), 3.94‒4.12 (m, 4H, H-4, H-10, H-30, H-40), 4.16
4.11. tert-Butyl [(2R,3R,4R,5R,6R)-5-[(tert-butyldimethylsilyl)
oxy]-1-hydroxy-3,4:6,7-bis(isopropylidenedioxy)heptan-2-yl]
carbamate (25)
0
0
0
0
0
(dd, 1H, J5 ,5 ¼8.1 Hz, J5 ,4 ¼6.0 Hz, H-5 ), 4.37‒4.44 (m, 2H, 2ꢂ H-5),
6.09 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3):
d
ꢀ4.5 (CH3), ꢀ3.8
(CH3), 18.4 (Cq), 25.1 (CH3), 25.2 (CH3), 25.9 (3ꢂ CH3), 26.3 (CH3),
27.7 (CH3), 51.2 (C-4), 67.3 (C-5), 68.5 (C-50), 71.6 (C-20), 77.4 (C-40),
78.5 (C-10), 80.2 (C-30), 107.8 (Cq), 110.6 (Cq), 159.2 (C]O). Anal.
Calcd for C20H37NO7Si: C, 55.66; H, 8.64; N, 3.25. Found: C, 55.69; H,
8.67; N, 3.29.
Using the same procedure as described for the preparation of 24,
ozonolysis of compound 16 (7.08 g, 14.11 mmol) followed by NaBH4
(2.40 g, 63.5 mmol) treatment afforded after flash chromatography
on silica gel (hexane/ethyl acetate, 2:1) 5.35 g (75%) of derivative 25
24
as white crystals; mp 38e39 ꢁC (recrystallized from n-hexane); [
a]
D
þ74.0 (c 0.30, CHCl3); IR (neat) nmax 3360, 2982, 2931, 1713, 1510,
1367,1160, 1053, 835 cmꢀ1; 1H NMR (400 MHz, CDCl3):
0.10 (s, 3H,
d
4.14. Methyl [(3S,4R,5R,6R,7R)-6-[(tert-butyldimethylsilyl)
oxy]-4,5:7,8-bis(isopropylidenedioxy)oct-1-en-3-yl]carbamate
(28)
CH3), 0.12 (s, 3H, CH3), 0.87 (s, 9H, 3ꢂ CH3), 1.35 (s, 6H, 2ꢂ CH3), 1.45
(s, 9H, 3ꢂ CH3), 1.48 (s, 3H, CH3), 1.51 (s, 3H, CH3), 2.36 (m, 1H, OH),
3.75‒3.84 (m, 4H, 2ꢂ H-1, H-2, H-7), 4.02‒4.13 (m, 5H, H-3, H-4, H-5,
H-6, H-7), 5.41‒5.42 (1H, m, NH); 13C NMR (100 MHz, CDCl3):
d
ꢀ4.6
Sodium methoxide (0.35 g, 6.48 mmol) was added to a solution
of 13 (1.9 g, 4.28 mmol) in dry CH3OH (42.5 mL) that had been pre-
cooled to 0 ꢁC. After stirring for 30 min at 0 ꢁC and then at room
temperature for 46 h, the solvent was evaporated, and the mixture
was partitioned between CH2Cl2 (57 mL) and water (14 mL). The
aqueous phase was washed with further portions of CH2Cl2
(2ꢂ57 mL). The combined organic layers were dried over Na2SO4,
the solvent was evaporated in vacuo, and the residue was flash-
chromatographed through a short silica gel column (hexane/ethyl
acetate, 11:1). This procedure yielded 1.06 g (52%) of thiocarbamate
as a colourless oil, which was immediately used in the subsequent
reaction. To a solution of the aforementioned compound (1.06 g,
2.23 mmol) in dry CH3CN (21.5 mL) was added MNO (0.54 g,
3.35 mmol). After stirring at room temperature for 24 h, the solvent
was removed under reduced pressure, and the residue was sub-
(CH3), ꢀ3.9 (CH3), 18.4 (Cq), 25.3 (CH3), 25.5 (CH3), 25.9 (3ꢂ CH3),
26.2 (CH3), 27.5 (CH3), 28.3 (3ꢂ CH3), 51.6 (C-2), 64.0 (C-1), 68.0 (C-
7), 70.0 (C-3 or C-4 or C-5 or C-6), 76.1 (C-3 or C-4 or C-5 or C-6), 78.0
(C-3 or C-4 or C-5 or C-6), 79.9 (Cq), 80.0 (C-3 or C-4 or C-5 or C-6),
107.8 (Cq), 109.6 (Cq), 155.7 (C]O). Anal. Calcd for C24H47NO8Si: C,
57.00; H, 9.37; N, 2.77. Found: C, 57.09; H, 9.33; N, 2.74.
4.12. (4S)-4-[(10R,20R,30R,40R)-30-[(tert-Butyldimethylsilyl)
oxy]-10,20:40,50-bis(isopropylidenedioxy)pentyl]oxazolidin-2-
one (26)
To a solution of 24 (3.20 g, 6.33 mmol) in dry THF (7.3 mL) that
was pre-cooled to 0 ꢁC was added NaH (0.51 g, 21.25 mmol, 60%
dispersion in mineral oil). After stirring at 0 ꢁC for 10 min and then
at room temperature for 28 h, another portion of NaH (0.23 g,
9.58 mmol) was added at 0 ꢁC, and stirring was continued for fur-
ther 20 h at room temperature. After cautious addition of CH3OH
(0.5 mL), the reaction mixture was concentrated and partitioned
between CH2Cl2 (82 mL) and water (55 mL). The organic layer was
dried over Na2SO4, the solvent was evaporated in vacuo, and the
residue was chromatographed on silica gel (hexane/ethyl acetate,
jected to flash chromatography on silica gel (hexane/ethyl acetate,
15:1) to give 0.77 g (75%) of compound 28 as a colourless oil; [a]
25
D
þ42.3 (c 0.44, CHCl3); IR (neat) nmax 3453, 2986, 2931, 2857, 1726,
1504, 1371, 1211, 1075, 835 cmꢀ1; 1H NMR (400 MHz, C6D6):
0.12
d
(s, 3H, CH3), 0.22 (s, 3H, CH3), 0.96 (s, 9H, 3ꢂ CH3), 1.13 (s, 3H, CH3),
1.28 (s, 3H, CH3), 1.34 (s, 3H, CH3), 1.53 (s, 3H, CH3), 3.49 (s, 3H, CH3),
3.90‒3.95 (m, 1H, H-7), 4.02‒4.06 (m, 1H, H-8), 4.13 (dd, 1H,
J6,5¼9.2 Hz, J5,4¼6.7 Hz, H-5), 4.21 (m, 1H, H-4), 4.25‒4.30 (m, 2H,
H-6, H-8), 5.03‒5.05 (m, 3H, H-1cis, H-3, NH), 5.26 (d, 1H,
J2,1trans¼17.1 Hz, H-1trans), 5.81‒5.89 (m, 1H, H-2); 13C NMR
2:1). This procedure yielded 2.34 g (86%) of crystalline compound
22
26; mp 149e151 ꢁC (recrystallized from n-hexane); [
a
]
þ67.1 (c
D
0.28, CHCl3); 1H NMR (400 MHz, CDCl3):
3H, CH3), 0.87 (s, 9H, 3ꢂ CH3), 1.32 (s, 3H, CH3), 1.38 (s, 3H, CH3),
d 0.12 (s, 3H, CH3), 0.13 (s,
(100 MHz, C6D6):
d
ꢀ4.8 (CH3), ꢀ3.6 (CH3),18.6 (Cq), 24.4 (CH3), 26.2
0
0
1.40 (s, 3H, CH3), 1.53 (s, 3H, CH3), 3.66 (dd, 1H, J3 ,2 ¼9.2 Hz,
(4ꢂ CH3), 26.4 (CH3), 26.5 (CH3), 51.8 (CH3), 52.9 (C-3), 69.9 (C-8),
72.1 (C-6), 79.2 (C-7), 79.3 (C-4), 80.4 (C-5), 107.5 (Cq), 110.3 (Cq),
114.7 (C-1), 138.8 (C-2), 155.9 (C]O). Anal. Calcd for C22H41NO7Si:
C, 57.49; H, 8.99; N, 3.05. Found: C, 57.53; H, 9.06; N, 3.10.
0
0
0
0
0
0
0
0
J4 ,3 ¼7.6 Hz, H-3 ), 3.81 (dd,1H, J5 ,5 ¼8.1 Hz, J5 ,4 ¼7.4 Hz, H-5 ), 3.97
0
0
0
0
0
0
0
(dt, 1H, J5 ,4 ¼7.4 Hz, J4 ,3 ¼7.40 Hz, J5 ,4 ¼6.4 Hz, H-4 ), 4.05 (dd, 1H,
0
0
0
0
0
J2 ,1 ¼5.6 Hz, J4,1 ¼2.5 Hz, H-1 ), 4.13‒4.24 (m, 3H, H-4, H-2 , H-5 ),

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8239
4.15. Methyl [(2S,3R,4R,5R,6R)-5-[(tert-butyldimethylsilyl)
oxy]-1-hydroxy-3,4:6,7-bis(isopropylidenedioxy)heptan-2-yl]
carbamate (29)
mp 145e147 ꢁC (recrystallized from n-hexane); [
a
]
22 þ38.7 (c 0.54,
D
CHCl3); IR (neat) nmax 2931, 2895, 1746, 1614, 1516, 1370, 1238, 1033,
833 cmꢀ1 1H NMR (400 MHz, CDCl3):
; d 0.06 (s, 3H, CH3), 0.09 (s,
3H, CH3), 0.85 (s, 12H, 3ꢂ CH3, CH3), 1.09 (s, 3H, CH3), 1.38 (s, 3H,
0
0
0
0
0
Using the same procedure as described for the preparation of
24, ozonolysis of compound 28 (0.77 g, 1.68 mmol) followed by
NaBH4 (0.286 g, 7.56 mmol) treatment provided after flash chro-
matography on silica gel (hexane/ethyl acetate, 2:1) 0.62 g (80%) of
derivative 29, which after NMR spectroscopic analysis was im-
mediately converted into the common oxazolidinone 26.
CH3), 1.52 (s, 3H, CH3), 3.37 (dd, 1H, J3 ,2 ¼9.8 Hz, J4 ,3 ¼6.9 Hz, H-3 ),
3.65‒3.73 (m, 2H, H-40, H-50), 3.78 (s, 3H, OCH3), 3.98 (d, 1H,
JH,H¼15.4 Hz, NCH2), 4.00‒4.05 (m, 2H, H-4, H-50), 4.13‒4.22 (m, 2H,
0
H-5, H-20), 4.35 (dd, 1H, J2 ,1 ¼6.6 Hz, J4,1 ¼1.7 Hz, H-1 ), 4.56 (dd, 1H,
J5,5¼8.5 Hz, J5,4¼4.0 Hz, H-5), 4.93 (d,1H, JH,H¼15.4 Hz, NCH2), 6.85‒
6.87 (m, 2H, Ph), 7.20‒7.22 (m, 2H, Ph); 13C NMR (100 MHz, CDCl3):
0
0
0
Modification of 29 into 26: Using the same procedure as de-
scribed for the transformation of 24 to 26, compound 29 (0.62 g,
1.34 mmol) and NaH (0.108 g, 4.50 mmol, 60% dispersion in mineral
oil) afforded after stirring (1 h) at room temperature and flash
chromatography on silica gel (hexane/ethyl acetate, 2:1) 0.53 g
d
ꢀ4.5 (CH3), ꢀ3.7 (CH3), 18.3 (Cq), 24.7 (CH3), 25.0 (CH3), 25.4
(CH3), 25.8 (3ꢂ CH3), 26.1 (CH3), 44.8 (NCH2), 54.4 (C-4), 55.3
(OCH3), 62.8 (C-50), 68.2 (C-5), 72.0 (C-30), 72.5 (C-10), 77.4 (C-40),
79.6 (C-20), 108.3 (Cq), 109.9 (Cq), 114.2 (2ꢂ CHPh), 128.2 (Ci), 129.0
(2ꢂ CHPh), 158.6 (C]O), 159.3 (Ci). Anal. Calcd for C28H45NO8Si: C,
60.95; H, 8.22; N, 2.54. Found: C, 60.92; H, 8.25; N, 2.57.
(92%) of derivative 26.
24
Alcohol 29: colourless oil; [
(400 MHz, CDCl3):
a
]
þ51.0 (c 0.60, CHCl3); 1H NMR
D
d
0.03 (s, 3H, CH3), 0.06 (s, 3H, CH3), 0.85 (s, 9H,
3ꢂ CH3), 1.34 (s, 3H, CH3), 1.36 (s, 3H, CH3), 1.47 (s, 3H, CH3), 1.53 (s,
3H, CH3), 2.28 (br s, 1H, OH), 3.63‒3.68 (m, 5H, OCH3, 2ꢂ H-1),
3.81‒3.85 (m, 1H, H-7), 3.88‒3.93 (m, 1H, H-5), 3.97‒4.01 (m, 1H, H-
6), 4.15‒4.32 (m, 4H, H-2, H-3, H-4, H-7), 5.13 (br d,1H, J2,NH¼9.2 Hz,
4.18. (4S)-4-[(10R,20S,30R,40R)-30-Hydroxy-10,20:40,50-bis(isopro-
pylidenedioxy) pentyl]-3-(p-methoxybenzyl)oxazolidin-2-one
(32)
NH); 13C NMR (100 MHz, CDCl3):
24.5 (CH3), 25.8 (CH3), 25.9 (3ꢂ CH3), 26.1 (CH3), 26.4 (CH3), 51.5 (C-
2), 52.1 (CH3), 65.7 (C-1), 69.2 (C-7), 71.5 (C-6), 77.0 (C-3), 78.4 (C-
5), 80.0 (C-4), 107.7 (Cq), 110.0 (Cq), 156.7 (C]O). Anal. Calcd for
d
ꢀ5.1 (CH3), ꢀ4.0 (CH3), 18.3 (Cq),
A 1 M solution of TBAF (4.7 mL, 4.71 mmol) was added to a so-
lution of 30 (2.60 g, 4.71 mmol) in dry THF (47 mL) that was pre-
cooled to 0 ꢁC. The resulting mixture was stirred at 0 ꢁC for
10 min and then for further 30 min at room temperature. Evapo-
rating of the solvent and chromatography of the residue on silica
C
21H41NO8Si: C, 54.40; H, 8.91; N, 3.02. Found: C, 54.44; H, 8.99;
N, 3.09.
gel (hexane/ethyl acetate, 2:1) afforded 1.92 g (93%) of compound
22
32 as a colourless viscous oil; [
a
]
ꢀ2.7 (c 0.22, CHCl3); 1H NMR
D
4.16. (4S)-4-[(10R,20R,30R,40R)-30-[(tert-Butyldimethylsilyl)
oxy]-10,20:40,50-bis(isopropylidenedioxy)pentyl]-3-(p-methox-
ybenzyl)oxazolidin-2-one (30)
(400 MHz, CDCl3): d 1.32 (s, 3H, CH3), 1.36 (s, 3H, CH3), 1.38 (s, 3H,
CH3), 1.56 (s, 3H, CH3), 2.03‒2.08 (m, 1H, OH), 3.04‒3.08 (m, 1H, H-
30), 3.79 (s, 3H, OCH3), 3.87 (dd, 1H, J5,5¼8.7 Hz, J5,4¼4.8 Hz, H-5),
3.92‒4.00 (m, 2H, H-40, H-50), 4.01‒4.06 (m, 1H, H-50), 4.15‒4.20 (m,
1H, H-4), 4.30‒4.34 (m, 1H, H-5), 4.37‒4.44 (m, 3H, H-10, H-20,
NCH2), 4.80 (d,1H, JH,H¼14.6 Hz, NCH2), 6.83‒6.85 (m, 2H, Ph), 7.24‒
7.27 (m, 2H, Ph); 13C NMR (100 MHz, CDCl3): 24.2 (CH3), 25.0 (CH3),
26.6 (CH3), 26.9 (CH3), 47.0 (NCH2), 53.4 (C-4), 55.2 (OCH3), 63.8 (C-
5), 66.6 (C-50), 70.7 (C-30), 75.0 (C-10), 75.9 (C-40), 80.7 (C-20), 109.3
(Cq), 109.6 (Cq), 113.9 (2ꢂ CHPh), 128.5 (Ci), 130.0 (2ꢂ CHPh), 158.1
(C]O), 159.2 (Ci). Anal. Calcd for C22H31NO8: C, 60.40; H, 7.14; N,
3.20. Found: C, 60.45; H, 7.18; N, 3.23.
To a solution of 26 (2.34 g, 5.42 mmol) in dry DMF (13.7 mL) that
was pre-cooled to 0 ꢁC were successively added NaH (0.335 g,
13.96 mmol, 60% dispersion in mineral oil), p-methoxybenzyl
chloride (1.11 mL, 8.19 mmol) and TBAI (0.40 g, 1.08 mmol). After
stirring at 0 ꢁC for 10 min and then for further 30 min at room
temperature, the mixture was poured into ice water (137 mL) and
extracted with Et2O (2ꢂ137 mL). The combined organic layers were
dried over Na2SO4, the solvent was evaporated in vacuo, and the
residue was subjected to flash chromatography on silica gel (hex-
ane/ethyl acetate, 3:1). This procedure yielded 2.63 g (88%) of
22
compound 30 as a colourless oil; [
a
]
þ28.2 (c 0.44, CHCl3); IR
4.19. (4R)-4-[(10R,20S,30R,40R)-30-Hydroxy-10,20:40,50-bis(isopro-
pylidenedioxy) pentyl]-3-(p-methoxybenzyl)oxazolidin-2-one
(33)
D
(neat) nmax 2930, 1751, 1612, 1513, 1245, 1212, 1068, 1034, 835 cmꢀ1
;
1H NMR (400 MHz, CDCl3):
d
0.07 (s, 3H, CH3), 0.08 (s, 3H, CH3), 0.84
(s, 9H, 3ꢂ CH3), 1.25 (s, 3H, CH3), 1.27 (s, 3H, CH3), 1.35 (s, 3H, CH3),
1.54 (s, 3H, CH3),03.59‒3.63 (m, 1H, H-50), 3.67 (dd, 1H, J5 ,5 ¼8.1 Hz,
Using the same procedure as described for the preparation of
32, compound 31 (4.98 g, 9.03 mmol) and TBAF (9.0 mL,
9.03 mmol) yielded after flash chromatography on silica gel
0
0
0
0
0
J5 ,4 ¼6.5 Hz, H-5 ), 3.77‒3.81 (m, 4H, H-3 , OCH3), 3.88‒3.93 (m, 1H,
H-4), 4.00‒4.07 (m, 2H, H-5, H-40), 4.17‒4.19 (m, 1H, H-20), 4.25‒
4.30 (m, 2H, H-5, H-10), 4.37 (d, 1H, JH,H¼15.2 Hz, NCH2), 4.90 (d, 1H,
JH,H¼15.2 Hz, NCH2), 6.86‒6.88 (m, 2H, Ph), 7.19‒7.21 (m, 2H, Ph);
(hexane/ethyl acetate, 1:1) 3.87 g (98%) of compound 33 as
22
a colourless viscous oil; [
a
]
þ21.2 (c 0.42, CHCl3); 1H NMR
D
13C NMR (100 MHz, CDCl3):
d
ꢀ3.8 (CH3), ꢀ3.6 (CH3), 18.5 (Cq), 24.9
(400 MHz, CDCl3): d 1.27 (s, 3H, CH3) 1.29 (s, 3H, CH3), 1.36 (s, 3H,
(2ꢂ CH3), 26.0 (3ꢂ CH3), 26.2 (2ꢂ CH3), 46.7 (NCH2), 53.2 (C-4), 55.3
(OCH3), 65.5 (C-5), 66.7 (C-50), 73.4 (C-30), 76.3 (C-40), 78.6 (C-20),
80.4 (C-10), 109.2 (2ꢂ Cq), 114.2 (2ꢂ CHPh), 128.5 (Ci), 129.1 (2ꢂ
CHPh), 158.7 (C]O), 159.2 (Ci). Anal. Calcd for C28H45NO8Si: C,
60.95; H, 8.22; N, 2.54. Found: C, 60.99; H, 8.18; N, 2.57.
CH3), 1.52 (s, 3H, CH3), 2.16‒2.20 (m, 1H, OH), 3.25‒3.30 (m, 1H,
H-30), 3.79‒3.82 (m, 4H, H-4, OCH3), 3.89‒3.96 (m, 2H, H-40, H-50),
4.01‒4.07 (m, 1H, H-5), 4.11 (d, 1H, JH,H¼15.4 Hz, NCH2), 4.23‒4.27
0
0
0
0
0
(m, 1H, H-5), 4.31 (dd, 1H, J2 ,1 ¼7.8 Hz, J3 ,2 ¼2.2 Hz, H-2 ), 4.40
0
0
0
0
(dd, 1H, J2 ,1 ¼7.8 Hz, J4,1 ¼1.4 Hz, H-1 ), 4.45 (dd, 1H, J5,5¼9.2 Hz,
J5,4¼4.8 Hz, H-5), 4.83 (d, 1H, JH,H¼15.4 Hz, NCH2), 6.85‒6.89 (m,
4.17. (4R)-4-[(10R,20R,30R,40R)-30-[(tert-Butyldimethylsilyl)
oxy]-10,20:40,50-bis(isopropylidenedioxy)pentyl]-3-(p-methox-
ybenzyl)oxazolidin-2-one (31)
2H, Ph), 7.19‒7.21 (m, 2H, Ph); 13C NMR (100 MHz, CDCl3):
d 24.3
(CH3), 25.0 (CH3), 25.9 (CH3), 26.5 (CH3), 45.2 (NCH2), 54.9 (C-4),
55.3 (OCH3), 63.6 (C-5), 66.8 (C-50), 69.3 (C-30), 72.9 (C-10), 75.3
(C-20), 76.5 (C-40), 108.9 (Cq), 109.5 (Cq), 114.2 (2ꢂ CHPh), 127.8 (Ci),
129.1 (2ꢂ CHPh), 158.5 (C]O), 159.3 (Ci). Anal. Calcd
for C22H31NO8: C, 60.40; H, 7.14; N, 3.20. Found: C, 60.44; H, 7.19;
N, 3.24.
According to the same procedure described for the preparation
of 30, compound 27 (4.43 g, 10.26 mmol) was transformed to de-
rivative 31 (4.98 g, 88%, hexane/ethyl acetate, 3:1, white crystals);

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8240
4.20. (4S)-4-[(10R,20S,30R,40R)-30,40,50-Trihydroxy-10,20-(iso-
propylidenedioxy)pentyl]-3-(p-methoxybenzyl)oxazolidin-2-
one (10)
room temperature for 1 h, the mixture was diluted with CH2Cl2
(10 mL), the solid parts were filtered off, the solvent was evaporated
in vacuo, and the obtained crude aldehyde was immediately used in
the next reaction without further purification.
A solution of 32 (1.92 g, 4.38 mmol) in a mixture of 1:1 AcOH/
H2O (15.4 mL) was stirred at room temperature for 15 h before
evaporating of the solvent. The obtained residue was subjected to
To a solution of 1,1,1,3,3,3-hexamethyldisilazane (2.35 mL,
11.06 mmol) in dry THF (11.7 mL) was added n-BuLi (6.91 mL,
11.06 mmol, a 1.6 M solution in n-hexane) at room temperature.
The solution of hexamethyldisilazide (LHMDS) thus generated was
treated with the known salt 126per,9 (4.36 g, 8.30 mmol), and the
resulting dark mixture was stirred for 5 min at the same temper-
ature. Then, a solution of the obtained aldehyde (1.32 g, 3.94 mmol)
in dry THF (11.7 mL) was added. After stirring for 1 h, the mixture
was poured into a saturated NH4Cl solution (70 mL), and the
aqueous phase was washed with EtOAc (2ꢂ100 mL). The combined
organic layers were dried over Na2SO4, stripped solvent, and the
residue was purified by flash chromatography on silica gel (hexane/
ethyl acetate, 5:1) to afford 1.47 g (74%) of a mixture of geometrical
isomers 35. Repeated chromatography (hexane/ethyl acetate, 5:1)
of a small amount of such mixture furnished each diastereoisomer
in pure form as colourless oils.
flash chromatography on silica gel (ethyl acetate) to afford 1.57 g
21
(90%) of compound 10 as a colourless foam; [
a]
ꢀ2.2 (c 0.18,
D
CH3OH); 1H NMR (400 MHz, CD3OD):
d
1.35 (s, 3H, CH3), 1.53 (s, 3H,
CH3), 3.22‒3.24 (m, 1H, H-40), 3.54‒3.61 (m, 2H, H-30, H-50), 3.69‒
3.72 (m, 1H, H-50), 3.77 (s, 3H, OCH3), 4.09 (dd, 1H, J5,5¼8.2 Hz,
J5,4¼4.9 Hz, H-5), 4.32‒4.35 (m, 1H, H-4), 4.37‒4.45 (m, 2H, H-5, H-
10), 4.50 (d, 1H, JH,H¼14.8 Hz, NCH2), 4.54‒4.55 (m, 1H, H-20), 4.69
(d, 1H, JH,H¼14.8 Hz, NCH2) 6.86‒6.88 (m, 2H, Ph), 7.24‒7.26 (m, 2H,
Ph); 13C NMR (100 MHz, CD3OD):
d 24.9 (CH3), 27.0 (CH3), 48.0
(NCH2), 55.7 (C-4, OCH3), 64.6 (C-50), 65.8 (C-5), 70.7 (C-40), 73.1 (C-
30), 76.6 (C-20), 82.3 (C-10), 110.4 (Cq), 115.0 (2ꢂ CHPh), 130.1 (Ci),
130.8 (2ꢂ CHPh), 160.8 (Ci or C]O), 161.0 (Ci or C]O). Anal.
Calcd for C19H27NO8: C, 57.42; H, 6.85; N, 3.52. Found: C, 57.46; H,
6.89; N, 3.50.
Alkene (Z)-35a: [
CDCl3):
a
]
22 þ43.6 (c 0.22, CHCl3); 1H NMR (400 MHz,
D
d
0.88 (t, 3H, J¼6.8 Hz, CH3), 1.26‒1.36 (m, 20H, 10ꢂ CH2),
4.21. (4R)-4-[(10R,20S,30R,40R)-30,40,50-Trihydroxy-10,20-(iso-
propylidenedioxy)pentyl]-3-(p-methoxybenzyl)oxazolidin-2-
one (11) and (4R)-3-(p-methoxybenzyl)-4-[(10R,20R,30R,40R)-
10,20,30,40,50-pentahydroxypentyl]oxazolidin-2-one (34)
1.37 (s, 3H, CH3), 1.53 (s, 3H, CH3), 1.93‒2.02 (m, 1H, H-50), 2.09‒2.18
(m, 1H, H-50), 3.65‒3.75 (m, 2H, H-4, H-5), 3.80 (s, 3H, OCH3), 4.09‒
0
0
0
0
4.14 (m, 1H, H-5), 4.29 (dd, 1H, J4,1 ¼9.0 Hz, J2 ,1 ¼6.6 Hz, H-1 ), 4.38
(d, 1H, JH,H¼14.7 Hz, NCH2), 4.79 (d, 1H, JH,H¼14.7 Hz, NCH2), 4.92‒
4.96 (m, 1H, H-20), 5.23‒5.28 (m, 1H, H-30), 5.57‒5.63 (m, 1H, H-40),
6.84‒6.87 (m, 2H, Ph), 7.27‒7.29 (m, 2H, Ph); 13C NMR (100 MHz,
According to the same procedure described for the preparation
of 10, acid hydrolysis of compound 33 (3.87 g, 8.85 mmol) fur-
nished after stirring (8 h) and chromatography on silica gel (ethyl
acetate) 2.11 g (60%) of 11 and 0.67 g (19%) of derivative 34 as white
crystals.
CDCl3):
d
14.1 (CH3), 22.6 (CH2), 25.1 (CH3), 27.5 (C-50), 27.9 (CH3),
29.3 (2ꢂ CH2), 29.4 (CH2), 29.5 (CH2), 29.6 (4ꢂ CH2), 31.9 (CH2), 46.7
(NCH2), 54.0 (C-4), 55.2 (OCH3), 63.6 (C-5), 72.2 (C-20), 81.7 (C-10),
109.8 (Cq), 113.9 (2ꢂ CHPh), 124.3 (C-30), 128.6 (Ci), 130.0 (2ꢂ CHPh),
136.2 (C-40), 158.3 (C]O), 159.2 (Ci). Anal. Calcd for C30H47NO5: C,
71.82; H, 9.44; N, 2.79. Found: C, 71.86; H, 9.48; N, 2.83.
Compound 11: mp 153e154 ꢁC (recrystallized from ethyl ace-
22
tate); [
d
a
]
þ48.6 (c 0.22, CH3OH); 1H NMR (400 MHz, CD3OD):
D
1.39 (s, 3H, CH3), 1.54 (s, 3H, CH3), 3.40 (d0d, 1H, J3 ,2 ¼8.6 Hz,
Alkene (E)-35b: [
CDCl3):
a]
24 þ38.3 (c 0.06, CHCl3); 1H NMR (400 MHz,
0
0
D
0
0
0
0
J4 ,3 ¼2.6 Hz, H-3 ), 3.56‒3.63 (m, 2H, H-4 , H-5 ), 3.71‒3.76 (m, 1H,
H-50), 3.80 (s, 3H, OCH3), 3.94 (dd, 1H, J5,4¼8.7 Hz, J5,4¼3.8 Hz, H-4),
4.22‒4.28 (m, 2H, H-5, NCH2), 4.48‒4.50 (m, 1H, H-10), 4.56‒4.60
(m, 2H, H-5, H-20), 4.69 (d, 1H, JH,H¼15.4 Hz, 1H, NCH2), 6.91‒6.94
(m, 2H, Ph), 7.26‒7.28 (m, 2H, Ph); 13C NMR (100 MHz, CD3OD):
d
0.88 (t, 3H, J¼6.9 Hz, CH3),1.23‒1.30 (m, 20H,10ꢂ CH2),1.35
(s, 3H, CH3),1.53 (s, 3H, CH3),1.94‒2.05 (m, 2H, 2ꢂ H-50), 3.69 (dt,1H,
0
J4,1 ¼9.2 Hz, J5,4¼9.2 Hz, J5,4¼6.2 Hz, H-4), 3.81‒3.85 (m, 4H, H-5,
0
0
0
OCH3), 4.08‒4.13 (m,1H, H-5), 4.28 (dd,1H, J4,1 ¼9.2 Hz, J2 ,1 ¼6.6 Hz,
H-10), 4.39 (d, 1H, JH,H¼14.7 Hz, NCH2), 4.53 (dd, 1H, J3 ,2 ¼9.2 Hz,
0
0
0
0
0
d
24.7 (CH3), 26.3 (CH3), 45.8 (NCH2), 55.8 (OCH3), 57.7 (C-4), 64.6
J2 ,1 ¼6.6 Hz, H-2 ), 4.78 (d, 1H, JH,H¼14.7 Hz, NCH2), 5.206 (ddt, 1H,
(C-50), 66.0 (C-5), 69.2 (C-30), 73.7 (C-40), 74.5 (C-10), 76.9 (C-20),
109.5 (Cq), 115.3 (2ꢂ CHPh), 129.5 (Ci), 130.3 (2ꢂ CHPh), 160.9 (Ci or
C]O), 161.2 (Ci or C]O). Anal. Calcd for C19H27NO8: C, 57.42; H,
6.85; N, 3.52. Found: C, 57.46; H, 6.88; N, 3.48.
J4 ,3 ¼15.2 Hz, J3 ,2 ¼9.2 Hz, J5 ,3 ¼1.2 Hz, J5 ,3 ¼1.2 Hz, H-3 ), 5.72 (dt,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1H, J4 ,3 ¼15.2 Hz, J5 ,4 ¼6.8 Hz, J5 ,4 ¼6.8 Hz, H-4 ), 6.85‒6.89 (m, 2H,
Ph), 7.28‒7.31 (m, 2H, Ph); 13C NMR (100 MHz, CDCl3):
d
14.1 (CH3),
22.7 (CH2), 25.1 (CH3), 27.8 (CH3), 28.9 (CH2), 29.3 (2ꢂ CH2), 29.4
(CH2), 29.6 (4ꢂ CH2), 31.9 (CH2), 32.3 (C-50), 46.6 (NCH2), 54.2 (C-4),
55.3 (OCH3), 63.5 (C-5), 78.6 (C-20), 81.5 (C-10), 109.7 (Cq), 113.9 (2ꢂ
CHPh), 124.8 (C-30), 128.6 (Ci), 130.1 (2ꢂ CHPh), 138.1 (C-40), 158.4 (Ci
or C]O), 159.2 (Ci or C]O). Anal. Calcd for C30H47NO5: C, 71.82; H,
9.44; N, 2.79. Found: C, 71.86; H, 9.40; N, 2.81.
Compound 34: mp 187e189 ꢁC (recrystallized from ethyl ace-
24
tate); [
a
]
þ6.0 (c 0.20, CH3OH); IR (neat) nmax 3378, 2934, 1714,
D
1614, 1515, 1444, 1245, 1078, 1017 cmꢀ1
;
1H NMR (400 MHz,
3.62‒3.69 (m, 3H, H-30 or H-40, H-20, H-50), 3.73‒3.74 (m,
CD3OD):
d
1H, H-30 or H-40), 3.79‒3.83 (m, 4H, H-50, OCH3), 4.06‒4.11 (m, 3H,
H-4, H-10, NCH2), 4.25‒4.30 (m, 1H, H-5), 4.46 (dd, 1H, J5,5¼8.5 Hz,
J5,4¼6.0 Hz, H-5), 4.77 (d,1H, JH,H¼15.4 Hz, NCH2), 6.90‒6.92 (m, 2H,
4.23. (4R)-4-[(10R,20S,30Z)-10,20-(Isopropylidenedioxy)hexadec-
30-en-10-yl]-3-(p-methoxybenzyl)oxazolidin-2-one (36a) and
(4R)-4-[(10R,20S,30E)-10,20-(isopropylidenedioxy)hexadec-30-en-
10-yl]-3-(p-methoxybenzyl)oxazolidin-2-one (36b)
Ph), 7.25‒7.27 (m, 2H, Ph); 13C NMR (100 MHz, CD3OD):
d 45.7
(NCH2), 55.8 (OCH3), 57.2 (C-4), 63.9 (C-5), 65.1 (C-50), 67.1 (C-10),
70.8 (C-20 or C-30 or C-40), 71.4 (C-20 or C-30 or C-40), 72.9 (C-20 or C-
30 or C-40), 115.3 (2ꢂ CHPh), 129.3 (Ci), 130.5 (2ꢂ CHPh), 160.9 (Ci),
161.5 (C]O). Anal. Calcd for C16H23NO8: C, 53.78; H, 6.49; N, 3.92.
Found: C, 53.81; H, 6.53; N, 3.88.
According to the same procedure described for the preparation
of 35, compound 11 (2.0 g, 5.03 mmol) was converted into a mix-
ture of olefins 36 (1.79 g, 71%, hexane/ethyl acetate, 5:1). Repeated
chromatography on silica gel (hexane/ethyl acetate, 5:1) afforded
only (Z)-36a in pure form as white crystals.
4.22. (4S)-4-[(10R,20S,30Z)-10,20-(Isopropylidenedioxy)hexadec-
30-en-10-yl]-3-(p-methoxybenzyl)oxazolidin-2-one (35a) and
(4S)-4-[(10R,20S,30E)-10,20-(isopropylidenedioxy)hexadec-30-en-
10-yl]-3-(p-methoxybenzyl)oxazolidin-2-one (35b)
Alkene (Z)-36a: mp 45e46 ꢁC (recrystallized from n-hexane);
[
a
]
24 þ50.8 (c 0.40, CHCl3); 1H NMR (400 MHz, CDCl3):
d 0.88 (t, 3H,
D
J¼6.8 Hz, CH3), 1.20‒1.31 (m, 20H, 10ꢂ CH2), 1.38 (s, 3H, CH3), 1.52
To a solution of 10 (1.57 g, 3.95 mmol) in CH3OH (9 mL) was
(s, 3H, CH3), 1.62‒1.69 (m, 1H, H-50), 1.84‒1.91 (m, 1H, H-50), 3.46
0
added NaIO4 (2.12 g, 9.91 mmol) in water (9 mL). After stirring at
(ddd, 1H, J5,4¼8.9 Hz, J5,4¼5.2 Hz, J4,1 ¼1.6 Hz, H-4), 3.79 (s, 3H,

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8241
OCH3), 4.04 (d, 1H, JH,H¼15.2 Hz, 1H, NCH2), 4.10‒4.15 (m, 1H, H-5),
the aqueous phase was then washed with EtOAc (2ꢂ20 mL). The
combine organic layers were dried over Na2SO4, the solvent was
taken down, and the residue was subjected to flash chromatogra-
phy through a short silica gel column (hexane/ethyl acetate, 1:2) to
afford 0.68 g (72%) of compound 8 as white crystals; mp 110e112 ꢁC
0
0
4.29 (dd, 1H, J5,5¼8.6 Hz, J5,4¼5.2 Hz, H-5), 4.40 (dd, 1H, J2 ,1 ¼7.7 Hz,
0
0
J4,1 ¼1.6 Hz, H-1 ), 4.86 (d, 1H, JH,H¼15.2 Hz, 1H, NCH2), 4.98‒5.02
(m, 1H, H-20), 5.11‒5.16 (m, 1H, H-30), 5.53 0(dddd, 1H, J4 ,3 ¼10.9 Hz,
0
0
0
0
0
0
0
0
J5 ,4 ¼8.2 Hz, J5 ,4 ¼6.7 Hz, J4 ,2 ¼1.5 Hz, H-4 ), 6.84‒6.87 (m, 2H, Ph),
7.18‒7.21 (m, 2H, Ph); 13C NMR (100 MHz, CDCl3):
d
14.1 (CH3), 22.7
(recrystallized from n-hexane and ethyl acetate); [
a
]
D
25 þ17.3 (c 0.30,
(CH2), 24.3 (CH3), 26.3 (CH3), 28.4 (C-50), 29.1 (CH2), 29.2 (CH2), 29.3
(CH2), 29.4 (CH2), 29.6 (3ꢂ CH2), 29.7 (CH2), 31.9 (CH2), 45.2 (NCH2),
54.7 (C-4), 55.2 (OCH3), 62.9 (C-5), 72.8 (C-20), 73.6 (C-10), 109.0
(Cq), 114.2 (2ꢂ CHPh), 124.6 (C-30), 127.6 (Ci), 129.4 (2ꢂ CHPh), 135.6
(C-40), 158.4 (C]O), 159.3 (Ci). Anal. Calcd for C30H47NO5: C, 71.82;
H, 9.44; N, 2.79. Found: C, 71.85; H, 9.41; N, 2.82.
CH3OH); IR (neat) nmax 3334, 2916, 2849, 1774, 1471, 1417, 1056,
1035 cmꢀ1
;
1H NMR (400 MHz, CD3OD):
d
0.89 (t, 3H, J¼6.9 Hz,
CH3), 1.28 (m, 24H, 11ꢂ CH2, HeCH, H-30), 1.52‒1.56 (m, 1H, HeCH),
1.73‒1.78 (m, 1H, H-30), 3.18 (dd, 1H, J4,1 ¼8.1 Hz, J2 ,1 ¼4.1 Hz, H-1 ),
3.39‒3.43 (m, 1H, H-20), 4.10‒4.15 (m, 1H, H-4), 4.28 (dd, 1H,
J5,5¼8.7 Hz, J5,4¼6.3 Hz, H-5), 4.45‒4.49 (m, 1H, H-5); 13C NMR
0
0
0
0
(100 MHz, CD3OD):
d 14.5 (CH3), 23.8 (CH2), 26.6 (CH2), 30.5 (CH2),
4.24. (4S)-4-[(10R,20S)-10,20-(Isopropylidenedioxy)hexadecyl]-
3-(p-methoxybenzyl)oxazolidin-2-one (37)
30.8 (7ꢂ CH2), 30.9 (CH2), 33.1 (CH2), 35.2 (C-30), 55.9 (C-4), 69.2 (C-
5), 73.7 (C-20), 76.4 (C-10), 162.8 (C]O). Anal. Calcd for C19H37NO4:
C, 66.43; H, 10.86; N, 4.08. Found: C, 66.46; H, 10.90; N, 4.12.
To a solution of the mixture of olefins 35 (1.47 g, 2.93 mmol) in
EtOH (23 mL) was added 10% Pd/C (0.207 g). The resulting mixture
was stirred for 30 min at room temperature under an atmosphere
of hydrogen and then filtered through a pad of Celite. Evaporating
of the solvent and chromatography on silica gel (hexane/ethyl ac-
4.27. (4R)-4-[(10R,20S)-10,20-Dihydroxyhexadecyl]oxazolidin-2-
one (9)
Using the same procedure as described for the preparation of 8,
compound 38 (1.60 g, 3.18 mmol) and CAN (6.10 g, 11.13 mmol)
afforded after stirring (3 h) and flash chromatography on silica gel
(hexane/ethyl acetate, 1:3) 0.65 g (60%) of derivative 9 as white
etate, 5:1) gave 1.39 g (94%) of compound 37 as a colourless oil;
26
[
a]
ꢀ23.2 (c 0.22, CHCl3); IR (neat) nmax 2922, 2852, 1752, 1612,
D
1513, 1242, 1174, 1069 cmꢀ1 1H NMR (400 MHz, CDCl3):
; d 0.88 (t,
3H, J¼6.8 Hz, CH3), 1.24‒1.30 (m, 26H, 13ꢂ CH2), 1.34 (s, 3H, CH3),
crystals; mp 118e120 ꢁC (recrystallized from n-hexane and ethyl
0
1.49 (s, 3H, CH3), 3.72 (dt, 1H, J4,1 ¼9.0 Hz, J5,4¼9.0 Hz, J5,4¼5.8 Hz,
25
acetate); [
a
]
ꢀ5.0 (c 0.22, CH3OH); IR (neat) nmax 3293, 2915,
D
H-4), 3.80 (s, 3H, OCH3), 3.89 (dd, 1H, J5,5¼8.9 Hz, J5,4¼5.8 Hz, H-5),
4.07‒4.12 (m, 1H, H-20), 4.20‒4.27 (m, 2H, H-5, H-10), 4.40 (d, 1H,
JH,H¼14.7 Hz, NCH2), 4.80 (d, 1H, JH,H¼14.7 Hz, NCH2), 6.85‒6.88 (m,
2849, 1736, 1470, 1418, 1076, 1014 cmꢀ1
CD3OD):
;
1H NMR (400 MHz,
d
0.89 (t, 3H, J¼6.8 Hz, CH3), 1.28 (m, 24H, 11ꢂ CH2, HeCH,
H-30), 1.51‒1.55 (m, 1H, HeCH), 1.62‒1.70 (m, 1H, H-30), 3.40 (m, 2H,
H-10, H-20), 4.08‒4.12 (m, 1H, H-4), 4.36‒4.40 (m, 1H, H-5), 4.45 (dd,
1H, J5,5¼8.7 Hz, J5,4¼6.0 Hz, H-5); 13C NMR (100 MHz, CD3OD):
2H, Ph), 7.27‒7.29 (m, 2H, Ph); 13C NMR (100 MHz, CDCl3):
d 14.1
(CH3), 22.7 (CH2), 25.7 (CH3), 25.9 (CH2), 28.2 (CH3), 29.3 (CH2), 29.4
(CH2), 29.5 (2ꢂ CH2), 29.6 (6ꢂ CH2), 31.9 (CH2), 46.8 (NCH2), 53.7
(C-4), 55.2 (OCH3), 63.7 (C-5), 76.7 (C-20), 81.0 (C-10), 109.2 (Cq),
113.9 (2ꢂ CHPh), 128.6 (Ci), 130.0 (2ꢂ CHPh), 158.2 (C]O), 159.2 (Ci).
Anal. Calcd for C30H49NO5: C, 71.53; H, 9.80; N, 2.78. Found: C,
71.56; H, 9.84; N, 2.81.
d
14.5 (CH3), 23.8 (CH2), 26.7 (CH2), 30.5 (CH2), 30.8 (7ꢂ CH2), 30.9
(CH2), 33.1 (CH2), 34.8 (C-30), 55.5 (C-4), 67.3 (C-5), 73.7 (C-10), 75.7
(C-20), 162.8 (C]O). Anal. Calcd for C19H37NO4: C, 66.43; H, 10.86; N,
4.08. Found: C, 66.47; H, 10.82; N, 4.11.
4.25. (4R)-4-[(10R,20S)-10,20-(Isopropylidenedioxy)hexadecyl]-
3-(p-methoxybenzyl)oxazolidin-2-one (38)
4.28. (2S,3R,4S)-4-Amino-2-tetradecyltetrahydrofuran-3-ol
hydrochloride (7$HCl)
Using the same procedure as described for the preparation of 37,
a mixture of alkenes 36 (1.79 g, 3.57 mmol) was hydrogenated (10%
Pd/C) and furnished after flash chromatography on silica gel (hex-
Compound 8 (0.68 g,1.98 mmol) was treated with a 6 M aqueous
HCl solution (90 mL), and the resulting mixture was stirred and
heated at 120 ꢁC for 2 h. After cooling to room temperature, the
solvent was evaporated in vacuo, and the residue was diluted with
Et2O. The solid part was filtered off and dried on a pump for 10 h at
ane/ethyl acetate, 5:1) 1.60 g (89%) of derivative 38 as white crys-
22
tals; mp 33e34 ꢁC (recrystallized from Et2O); [
a]
þ29.3 (c 0.42,
D
CHCl3); IR (neat) nmax 2919, 2850,1725,1612,1513,1240,1030 cmꢀ1
;
room temperature. This procedure yielded 0.525 g (79%) of com-
1H NMR (400 MHz, CDCl3):
d
0.88 (t, 3H, J¼6.9 Hz, CH3), 1.14‒1.32
pound 7$HCl as a white amorphous solid; [
a
]
þ9.0 (c 0.21,
24
D
(m, 26H, 13ꢂ CH2), 1.35 (s, 3H, CH3), 1.49 (s, 3H, CH3), 3.50‒3.54 (m,
1H, H-4), 3.80 (s, 3H, OCH3), 4.04 (d, 1H, JH,H¼15.3 Hz, NCH2), 4.14‒
CH3OH); IR (neat) nmax 3464, 2914, 2849, 1471, 1061, 1007,
718 cmꢀ1; 1H NMR (400 MHz, CD3OD):
d
0.87 (t, 3H, J¼6.8 Hz, CH3),
4.22 (m, 2H, H-5, H-20), 4.27 (dd, 1H, J2 ,1 ¼7.1 Hz, J4,1 ¼1.7 Hz, H-1 ),
4.41 (dd, 1H, J5,5¼8.6 Hz, J5,4¼4.9 Hz, H-5), 4.88 (d, 1H, JH,H¼15.3 Hz,
1H, NCH2), 6.86‒6.90 (m, 2H, Ph), 7.19‒7.22 (m, 2H, Ph); 13C NMR
1.26‒1.52 (m, 24H, 12ꢂ CH2), 1.56‒1.74 (m, 2H, 2ꢂ H-10), 3.48‒3.52
(m, 1H, H-2), 3.54‒3.57 (m, 1H, H-4), 3.78 (dd, 1H, J3,2¼6.4 Hz,
J4,3¼3.4 Hz, H-3), 3.83 (dd, 1H, J1,1¼10.7 Hz, J2,1¼2.9 Hz, H-5), 3.99
(dd, 1H, J1,1¼10.7 Hz, J2,1¼6.0 Hz, H-5); 13C NMR (100 MHz, CD3OD):
0
0
0
0
(100 MHz, CDCl3):
d 14.1 (CH3), 22.7 (CH2), 24.6 (CH3), 26.4 (CH3),
26.9 (CH2), 29.3 (CH2), 29.4 (CH2), 29.5 (2ꢂ CH2), 29.6 (5ꢂ CH2),
29.9 (CH2), 31.9 (CH2), 45.1 (NCH2), 54.5 (C-4), 55.3 (OCH3), 63.0 (C-
5), 73.1 (C-10), 76.2 (C-20), 108.4 (Cq), 114.2 (2ꢂ CHPh), 127.7 (Ci),
129.2 (2ꢂ CHPh), 158.4 (C]O), 159.3 (Ci). Anal. Calcd for C30H49NO5:
C, 71.53; H, 9.80; N, 2.78. Found: C, 71.56; H, 9.77; N, 2.82.
d
14.5 (CH3), 23.8 (CH2), 27.2 (CH2), 30.5 (CH2), 30.7 (CH2), 30.8 (6ꢂ
CH2), 33.1 (CH2), 33.9 (C-10), 60.2 (C-4), 69.7 (C-5), 80.5 (C-3), 86.7
(C-2); 1H NMR (600 MHz, CD3OD):
d
0.89 (t, 3H, J¼7.0 Hz, CH3),
1.28‒1.43 (m, 23H, 11ꢂ CH2, HeCH), 1.46‒1.53 (m, 1H, HeCH), 1.58‒
1.64 (m,1H, H-10),1.68‒1.74 (m,1H, H-10), 3.51 (ddd,1H, J2,1 ¼8.3 Hz,
0
0
J3,2¼6.4 Hz, J2,1 ¼4.7 Hz, H-2), 3.56 (td, 1H, J5,4¼6.3 Hz, J5,4¼3.2 Hz,
4.26. (4S)-4-[(10R,20S)-10,20-Dihydroxyhexadecyl]oxazolidin-2-
one (8)
J4,3¼3.2 Hz, H-4), 3.76 (dd, 1H, J3,2¼6.4 Hz, J4,3¼3.5 Hz, H-3), 3.82
(dd, 1H, J5,5¼10.7 Hz, J5,4¼3.0 Hz, H-5), 4.00 (dd, 1H, J5,5¼10.7 Hz,
J5,4¼6.1 Hz, H-5); 13C NMR (150 MHz, CD3OD):
d 14.5 (CH3), 23.8
CAN (5.30 g, 9.67 mmol) was added to a solution of 37 (1.39 g,
2.76 mmol) in CH3CN (9.6 mL) and water (2.4 mL). After stirring for
20 min at room temperature, the mixture was diluted with a small
volume of EtOAc, poured into a saturated NaCl solution (12 mL), and
(CH2), 27.2 (CH2), 30.5 (CH2), 30.7 (2ꢂ CH2), 30.8 (6ꢂ CH2), 33.1
(CH2), 33.9 (C-10), 60.2 (C-4), 69.7 (C-5), 80.6 (C-3), 86.8 (C-2). Anal.
Calcd for C18H38ClNO2: C, 64.35; H,11.40; N, 4.17. Found: C, 64.40; H,
11.44; N, 4.11.

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8242
4.29. (2S,3R,4R)-4-Amino-2-tetradecyltetrahydrofuran-3-ol
hydrochloride (ent-6$HCl)
4.32. (2S,3R,4S)-4-Acetamido-2-tetradecyltetrahydrofuran-3-
yl acetate (41)
According to the same procedure described for the preparation
of 7$HCl, compound 9 (0.65 g, 1.98 mmol) was converted into ent-
To a solution of 7$HCl (0.10 g, 0.298 mmol) in pyridine (9.5 mL)
were successively added Ac2O (0.56 mL, 5.96 mmol) and DMAP
(18.2 mg, 0.149 mmol). After stirring at room temperature for 15 h,
the reaction mixture was concentrated and co-evaporated three
times with toluene. The obtained residue was subjected to flash
chromatography on silica gel (hexane/ethyl acetate, 1:1) to give
22
6$HCl (0.495 g, 78%, white amorphous solid); [
a
]
D
ꢀ29.6 (c 0.48,
CH3OH); IR (neat) nmax 3298, 3056, 2915, 2849, 1510, 1469, 1052,
1021, 556 cmꢀ1; 1H NMR (400 MHz, CD3OD):
d
0.87 (t, 3H, J¼6.8 Hz,
CH3), 1.26‒1.52 (m, 25H, 12ꢂ CH2, H-10), 1.56‒1.63 (m, 1H, H-10),
3.65‒3.74 (m, 3H, H-5, H-4, H-2), 4.00‒4.03 (m, 1H, H-3), 4.11‒4.16
105 mg (92%) of crystalline compound 41; mp 70e71 ꢁC (recrys-
25
(m, 1H, H-5); 13C NMR (100 MHz, CD3OD):
d
14.5 (CH3), 23.8 (CH2),
tallized from n-hexane); [
a
]
ꢀ11.9 (c 0.21, CHCl3), [lit.8e thick
D
25
26.9 (CH2), 30.5 (CH2), 30.7 (CH2), 30.8 (7ꢂ CH2), 33.1 (CH2), 34.1 (C-
syrup, [
a
]
þ11.2 (c 1.1, CHCl3)]; IR (neat) nmax 3304, 2918, 2850,
D
10), 53.7 (C-4), 69.4 (C-5), 74.4 (C-3), 85.2 (C-2); 1H NMR (600 MHz,
1743, 1655, 1546 cmꢀ1 1H NMR (400 MHz, CDCl3):
; d 0.88 (t, 3H,
CD3OD):
d
0.89 (t, 3H, J¼6.9 Hz, CH3), 1.28‒1.39 (m, 23H, 11ꢂ CH2,
J¼6.8 Hz, CH3), 1.25‒1.48 (m, 24H, 12ꢂ CH2), 1.52‒1.61 (m, 1H, H-
10), 1.67‒1.75 (m, 1H, H-10), 1.99 (s, 3H, CH3), 2.09 (s, 3H, CH3),
3.69‒3.73 (m, 1H, H-2), 3.77 (dd, 1H, J5,5¼9.8 Hz, J5,4¼3.1 Hz, H-5),
4.07 (dd, 1H, J5,5¼9.8 Hz, J5,4¼5.6 Hz, H-5), 4.27‒4.32 (m, 1H, H-4),
4.72 (dd, 1H, J3,2¼4.9 Hz, J4,3¼2.6 Hz, 1H, H-3), 5.65 (br d, 1H,
HeCH), 1.43‒1.53 (m, 2H, H-10, HeCH), 1.58‒1.64 (m, 1H, H-10),
3.67‒3.74 (m, 3H, H-5, H-4, H-2), 4.01 (m, 1H, H-3), 4.13 (dd, 1H,
J5,5¼9.0 Hz, J5,4¼5.3 Hz, H-5). Anal. Calcd for C18H38ClNO2: C, 64.35;
H, 11.40; N, 4.17. Found: C, 64.31; H, 11.45; N, 4.21.
J4,NH¼4.9 Hz, NH); 13C NMR (100 MHz, CDCl3):
d 14.1 (CH3), 20.9
(CH3), 22.7 (CH2), 23.1 (CH3), 25.9 (CH2), 29.3 (CH2), 29.5 (2ꢂ CH2),
29.6 (4ꢂ CH2), 29.7 (2ꢂ CH2), 31.9 (CH2), 33.4 (C-10), 56.5 (C-4),
71.8 (C-5), 81.8 (C-3), 83.0 (C-2), 170.0 (C]O), 170.7 (C]O); 1H
4.30. tert-Butyl [(3S,4R,5S)-4-hydroxy-5-tetradecyltetrahydro
furan-3-yl]carbamate (39)
NMR (600 MHz, CD3OD):
d
0.89 (t, 3H, J¼7.1 Hz, CH3), 1.28‒1.37
Et3N (0.05 mL, 0.36 mmol) followed by di-tert-butyl dicarbonate
(68 mg, 0.31 mmol) was added to an emulsion of 7$HCl (0.10 g,
0.298 mmol) in THF (2.2 mL). After stirring at room temperature for
1 h, the solvent was evaporated in vacuo, and the residue was
chromatographed through a short silica gel column (hexane/ethyl
(m, 23H, 12ꢂ CH2, HeCH), 1.41‒1.47 (m, 1H, HeCH), 1.58‒1.71 (m,
2H, 2ꢂ H-10), 1.93 (s, 3H, CH3), 2.05 (s, 3H, CH3), 3.68‒3.71 (m, 1H,
H-2), 3.76 (dd, 1H, J5,5¼9.7 Hz, J5,4¼3.3 Hz, H-5), 3.96 (dd, 1H,
J5,5¼9.7 Hz, J5,4¼5.9 Hz, H-5), 4.22 (td, 1H, J5,4¼5.9 Hz, J5,4¼3.0 Hz,
J4,3¼3.0 Hz, H-4), 4.80 (dd, 1H, J3,2¼4.2 Hz, J4,3¼2.7 Hz, H-3); 13C
acetate, 5:1) to provide 107 mg (90%) of crystalline compound 39;
NMR (150 MHz, CD3OD): d 14.5 (CH3), 20.9 (CH3), 22.4 (CH3), 23.8
25
mp 94e95 ꢁC (recrystallized from n-hexane); [
a]
ꢀ28.1 (c 0.21,
(CH2), 27.0 (CH2), 30.5 (CH2), 30.6 (CH2), 30.7 (2ꢂ CH2), 30.8 (4ꢂ
CH2), 30.9 (CH2), 33.1 (CH2), 34.1 (C-10), 57.8 (C-4), 71.8 (C-5), 83.3
(C-3), 85.2 (C-2), 172.0 (C]O), 173.3 (C]O). Anal. Calcd for
D
25
CHCl3), [lit.5a mp 94e96 ꢁC, [
a]
ꢀ31.7 (c 1.09, CHCl3), lit.8e mp
D
25
94e96 ꢁC, [
a
]
ꢀ30.2 (c 1.3, CHCl3)]; IR (neat) nmax 3345, 2915,
D
2848, 1685, 1525, 1168 cmꢀ1
;
1H NMR (400 MHz, CDCl3):
d
0.88 (t,
C22H41NO4: C, 68.89; H, 10.77; N, 3.65. Found: C, 68.93; H, 10.81;
3H, J¼6.8 Hz, CH3), 1.25 (s, 24H, 12ꢂ CH2), 1.45 (s, 9H, 3ꢂ CH3), 1.53‒
1.68 (m, 2H, 2ꢂ H-10), 3.60‒3.67 (m, 3H, H-2, H-5, OH), 3.77‒3.78
(m, 1H, H-3), 3.92‒3.93 (m, 1H, H-4), 4.05 (dd, 1H, J5,5¼9.5 Hz,
J5,4¼6.6 Hz, H-5), 4.82 (d, 1H, J4,NH¼3.8 Hz, NH); 13C NMR (100 MHz,
N, 3.62.
4.33. (2S,3R,4R)-4-Acetamido-2-tetradecyltetrahydrofuran-3-
yl acetate (42)
CDCl3):
d
14.1 (CH3), 22.7 (CH2), 25.9 (CH2), 28.3 (3ꢂ CH3), 29.4
(CH2), 29.5 (CH2), 29.6 (4ꢂ CH2), 29.7 (3ꢂ CH2), 31.9 (CH2), 33.7
(C-10), 60.3 (C-4), 70.3 (C-5), 80.3 (Cq), 82.7 (C-3), 84.9 (C-2), 156.5
(C]O), for numbering of the protons and carbons in these NMR
spectra, see Scheme 1. Anal. Calcd for C23H45NO4: C, 69.13; H, 11.35;
N, 3.51. Found: C, 69.17; H, 11.38; N, 3.54.
According to the same procedure described for the prepara-
tion of 41, compound ent-6$HCl (0.10 g, 0.298 mmol), Ac2O
(0.56 mL, 5.96 mmol) and DMAP (18.2 mg, 0.149 mmol) in pyri-
dine (9.5 mL) gave after stirring (1 h) and flash chromatography
on silica gel (hexane/ethyl acetate, 1:2) 107 mg (94%) of derivative
42 as white crystals; mp 75e76 ꢁC (recrystallized from n-hexane);
24
22
[
a
]
þ17.7 (c 0.13, CHCl3), [for ent-42: lit.21 mp 72e73 ꢁC, [
a]
D
D
26
4.31. tert-Butyl [(3R,4R,5S)-4-hydroxy-5-tetradecyltetrahydro
furan-3-yl]carbamate (40)
ꢀ15.4 (c 1.0, CHCl3), lit.6g mp not reported, [
a
]
ꢀ15.1 (c 1.2,
D
CHCl3), lit.22 mp 65e67 ꢁC, [
a
]
ꢀ14.6 (c 0.5, CHCl3)]; IR (neat)
21
D
nmax 3290, 2915, 2847, 1733, 1650, 1561, 1375, 1232 cmꢀ1; 1H NMR
Using the same procedure as described for the preparation of 39,
compound ent-6$HCl (0.10 g, 0.298 mmol), Et3N (0.05 mL,
0.36 mmol) and Boc2O (68 mg, 0.31 mmol) afforded after stirring
(1 h) and flash chromatography on silica gel (hexane/ethyl acetate,
5:1) 99 mg (83%) of derivative 40 as white crystals; mp 87e89 ꢁC
(400 MHz, CDCl3):
d
0.88 (t, 3H, J¼6.8 Hz, CH3), 1.25‒1.45 (m, 24H,
12ꢂ CH2), 1.49‒1.72 (m, 2H, 2ꢂ H-10), 2.01 (s, 3H, CH3), 2.13 (s, 3H,
CH3), 3.50‒3.54 (m, 1H, H-5), 3.84‒3.88 (m, 1H, H-2), 4.18 (dd, 1H,
J5,5¼8.4 Hz, J5,4¼7.2 Hz, H-5), 4.62‒4.69 (m, 1H, H-4), 4.91 (dd, 1H,
J4,3¼5.9 Hz, J3,2¼2.6 Hz, H-3), 5.65 (br d, 1H, J4,NH¼7.9 Hz, NH); 13
C
(recrystallized from n-hexane); [
a
]
25 ꢀ10.0 (c 0.23, CHCl3), [lit.5b mp
NMR (100 MHz, CDCl3): d 14.1 (CH3), 21.0 (CH3), 22.7 (CH2), 23.3
D
25
80e81 ꢁC, [
a
]
D
ꢀ7.76 (c 0.29, CHCl3)]; IR (neat) nmax 3365, 2918,
(CH3), 25.5 (CH2), 29.3 (CH2), 29.4 (CH2), 29.5 (CH2), 29.6 (4ꢂ
CH2), 29.7 (2ꢂ CH2), 31.9 (CH2), 33.5 (C-10), 49.8 (C-4), 69.8 (C-5),
76.7 (C-3), 84.1 (C-2), 169.8 (C]O), 169.9 (C]O); 1H NMR
2848, 1691, 1526, 1467, 1169 cmꢀ1 1H NMR (400 MHz, CDCl3):
;
d
0.88 (t, 3H, J¼6.8 Hz, CH3),1.25‒1.32 (m, 24H,12ꢂ CH2),1.45 (s, 9H,
3ꢂ CH3), 1.51‒1.58 (m, 2H, 2ꢂ H-10), 2.33 (br s, 1H, OH), 3.48‒3.53
(m,1H, H-5), 3.69‒3.73 (m,1H, H-2), 3.93 (m,1H, H-3), 4.11‒4.15 (m,
2H, H-4, H-5), 5.01 (d, 1H, J4,NH¼6.6 Hz, NH); 13C NMR (100 MHz,
(600 MHz, CD3OD):
d
0.89 (t, 3H, J¼7.0 Hz, CH3), 1.28‒1.45 (m,
24H, 12ꢂ CH2), 1.51‒1.62 (m, 2H, 2ꢂ H-10), 1.94 (s, 3H, CH3), 2.08
(s, 3H, CH3), 3.57 (t, 1H, J5,5¼8.7 Hz, J5,4¼8.7 Hz, H-5), 3.85 (ddd,
0
0
CDCl3):
d
14.1 (CH3), 22.7 (CH2), 25.8 (CH2), 28.3 (3ꢂ CH3), 29.4
1H, J2,1 ¼8.0 Hz, J2,1 ¼5.6 Hz, J3,2¼3.5 Hz, H-2), 4.07 (m, 1H, H-5),
(CH2), 29.5 (CH2), 29.6 (2ꢂ CH2), 29.7 (3ꢂ CH2), 29.8 (2ꢂ CH2), 31.9
(CH2), 33.6 (C-10), 53.0 (C-4), 70.3 (C-5), 74.9 (C-3) 80.0 (Cq), 85.2 (C-
2), 156.0 (C]O), for numbering of the protons and carbons in these
NMR spectra, see Scheme 1. Anal. Calcd for C23H45NO4: C, 69.13; H,
11.35; N, 3.51. Found: C, 69.19; H, 11.38; N, 3.47.
4.53 (m, 1H, H-4), 4.94 (dd, 1H, J4,3¼6.0 Hz, J3,2¼3.4 Hz, H-3); 13C
NMR (150 MHz, CD3OD):
d 14.5 (CH3), 20.8 (CH3), 22.4 (CH3), 23.8
(CH2), 26.7 (CH2), 30.5 (CH2), 30.6 (CH2), 30.7 (2ꢂ CH2), 30.8 (4ꢂ
CH2), 30.9 (CH2), 33.1 (CH2), 34.7 (C-10), 51.6 (C-4), 70.1 (C-5), 77.2
(C-3), 84.8 (C-2), 171.8 (C]O), 173.5 (C]O). Anal. Calcd

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8243
for C22H41NO4: C, 68.89; H, 10.77; N, 3.65. Found: C, 68.92; H,
4.36. Supplementary data
10.81; N, 3.62.
Complete crystallographic data for the structural analysis have
been deposit with the Cambridge Crystallographic Data Centre,
CCDC No. 886350. These data can be obtained free of charge from
the Director, Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge, CB2 1EZ, UK (fax: þ44 1223 336033; e-mail:
deposit@ccdc.cam.ac.uk or via: www.ccdc.cam.ac.uk).
4.34. Triphenyl(tridecyl)phosphonium bromide (12)
To a solution of 1-bromotridecane (2.87 g, 10.9 mmol) in dry
toluene (9 mL) was added Ph3P (3.43 g, 13.08 mmol), and the
resulting mixture was stirred and heated at reflux for 26 h. After
cooling to room temperature, the solvent was evaporated in vacuo,
the solid material was washed repeatedly with Et2O to remove Ph3P
and then chromatographed on silica gel (CH2Cl2/MeOH, 20:1) to
afford 4.87 g (85%) of compound 12 as a white solid; mp 79e80 ꢁC
Acknowledgements
The present work was supported by the Grant Agency (No. 1/
0568/12 and No. 1/0433/11) of the Ministry of Education, Slovak
(recrystallized from n-hexane); 1H NMR (400 MHz, CDCl3):
d 0.83 (t,
ꢁ ꢁ
Republic. We thank to Professor Jozef Kozísek (Slovak University of
3H, J¼6.9 Hz, CH3), 1.19‒1.30 (m, 18H, 9ꢂ CH2), 1.62‒1.63 (m, 4H, 2ꢂ
ꢁ
ꢀ
ꢀ
Technology in Bratislava) and Dr. Juraj Kuchar (P. J. Safarik Univer-
CH2), 3.70‒3.77 (m, 2H, CH2), 7.70‒7.74 (m, 6H, Ph), 7.79‒7.87 (m,
9H, Ph); 13C NMR (100 MHz, CDCl3):
d 14.0 (CH3), 22.5 (CH2), 22.9
ꢁ
sity in Kosice) for X-ray measurements.
(CH2), 29.1 (2ꢂ CH2), 29.2 (CH2), 29.4 (2ꢂ CH2), 29.5 (2ꢂ CH2), 30.2
(CH2), 30.4 (CH2), 31.7 (CH2), 117.8 (2ꢂ Ci), 118.6 (Ci), 130.3 (3ꢂ
CHPh), 130.4 (3ꢂ CHPh), 133.5 (3ꢂ CHPh), 133.6 (3ꢂ CHPh), 134.9 (3ꢂ
CHPh). Anal. Calcd for C31H42BrP: C, 70.85; H, 8.06. Found: C, 70.89;
H, 8.00.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.07.028.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
4.35. X-ray techniques
Single crystals of 26 suitable for X-ray diffraction were obtained
from n-hexane by slow evaporation at room temperature. The in-
tensities were collected at 293 K on an Oxford Diffraction Gemini R
References and notes
1. For structure, biosynthesis, metabolic pathways and functions, see: (a) Kolter,
T.; Sandhoff, K. Angew. Chem., Int. Ed. 1999, 38, 1532e1568; (b) Vankar, Y. D.;
Schmidt, R. R. Chem. Soc. Rev. 2000, 29, 201e206; (c) Merrill, A. H., Jr.; Sandhoff,
K. In Biochemistry of Lipids, Lipoproteins, and Membranes, 4th ed.; Vance, D. E.,
Vance, J. E., Eds.; Elsevier Amsterdam: 2002; pp 373e407; (d) Liao, J.; Tao, J.;
Lin, G.; Liu, D. Tetrahedron 2005, 61, 4715e4733; (e) Wennekes, T.; van den Berg,
R. J. B. H. N.; Boot, R. G.; van der Marel, G. A.; Overkleeft, H. S.; Aerts, J. M. F. G.
Angew. Chem., Int. Ed. 2009, 48, 8848e8868.
ꢂ
CCD diffractometer using Mo K
a
radiation (
l
¼0.71073 A). Selected
crystallographic and other relevant data for the compound 26 are
listed in Table 3. The structure was solved by direct methods.23 All
non-hydrogen atoms were refined anisotropically by full-matrix
least squares calculations based on F2.23 All hydrogen atoms were
included in calculated positions as riding atoms, with SHELxL9723
ꢁ
2. For selected examples, see: (a) Enders, D.; Terteryan, V.; Palecek, J. Synthesis
24
2010, 2979e2984 and references cited therein; (b) Schombs, M.; Park, F. E.; Du,
W.; Kulkarni, S. S.; Gervay-Hague, J. J. Org. Chem. 2010, 75, 4891e4898; (c)
Khaja, S. D.; Kumar, V.; Ahmad, M.; Xue, J.; Matta, K. L. Tetrahedron Lett. 2010, 51,
4411e4414; (d) Liu, Z.; Byun, H.-S.; Bittman, R. Org. Lett. 2010, 12, 2974e2977;
(e) Roy, B.; Ferdjani, S.; Tellier, C.; Rabiller, C. Tetrahedron 2011, 67, 5176e5183;
(f) Jervis, P. J.; Cox, L. R.; Besra, G. S. J. Org. Chem. 2011, 76, 320e323; (g) Zhu, X.;
Dere, R. T.; Jiang, J. Tetrahedron Lett. 2011, 52, 4971e4974; (h) Veerapen, N.;
Reddington, F.; Salio, M.; Cerundolo, V.; Besra, G. S. Bioorg. Med. Chem. 2011, 19,
221e228; (i) Liu, Z.; Bittman, R. Org. Lett. 2012, 14, 620e623; (j) Tashiro, T.;
Shigeura, T.; Watarai, H.; Taniguchi, M.; Mori, K. Bioorg. Med. Chem. 2012, 20,
4540e4548; (k) Shiozaki, M.; Tashiro, T.; Koshino, H.; Shigeura, T.; Watarai, H.;
Taniguchi, M.; Mori, K. Carbohydr. Res. 2013, 370, 46e66.
defaults. The
programme was used for structure analysis
PLATON
and molecular and crystal structure drawings.
Table 3
Crystal data and structure refinement parameters for compound 26
26
Empirical formula
Formula weight
C20H37NO7Si
431.60
239(2)
0.71073
Monoclinic
P21
3. For reviews on the synthesis and biological functions of sphingoid bases, see: (a)
Koskinen, P. M.; Koskinen, A. M. P. Synthesis 1998, 1075e1091; (b) Howell, A. R.;
Ndakala, A. J. Curr. Org. Chem. 2002, 6, 365e391; (c) Howell, A. R.; So, R. C.; Ri-
chardson, S. K. Tetrahedron 2004, 60, 11327e11347; (d) Morales-Serna, J. A.; Lla-
Temperature, T (K)
ꢂ
Wavelength,
l
(A)
Crystal system
Space group
ꢀ
veria, J.; Díaz, Y.; Matheu, M. I.; Castillon, S. Curr. Org. Chem. 2010, 14, 2483e2521.
Unit cell dimensions
4. (a) Kuroda, I.; Musman, M.; Ohtani, I.; Ichiba, T.; Tanaka, J.; Garcia-Gravalos, D.;
Higa, T. J. Nat. Prod. 2002, 65, 1505e1506; (b) Ledroit, V.; Debitus, C.; Lavaud, C.;
Massoit, G. Tetrahedron Lett. 2003, 44, 225e228.
5. (a) Canals, D.; Mormeneo, D.; Fabrias, G.; Llebaria, A.; Casas, J.; Delgado, A.
Bioorg. Med. Chem. 2009, 17, 235e241; (b) Yoshimitsu, Y.; Oishi, S.; Miyagaki, J.;
Inuki, S.; Ohno, H.; Fujii, N. Bioorg. Med. Chem. 2011, 19, 5402e5408.
ꢂ
a (A)
15.7607(5)
9.5337(3) b
17.8434(6)
2598.57(15)
4
1.103
0.125
936
ꢂ
b (A)
¼104.254(3)ꢁ
ꢂ
c (A)
ꢃ
3
ꢂ
V (A )
Formula per unit cell, Z
Dcalcd (g/cm3)
6. For examples of syntheses of D-ribo-phytosphingosine, its stereoisomers and/or
(mmꢀ1
)
analogues, see: Refs. 3b,d and (a) Pandey, G.; Tiwari, D. K. Tetrahedron Lett.
2009, 50, 3296e3298; (b) Dubey, A.; Kumar, P. Tetrahedron Lett. 2009, 50,
3425e3427; (c) Kumar, P.; Dubey, A.; Puranik, V. G. Org. Biomol. Chem. 2010, 8,
5074e5086; (d) Liu, Z.; Byun, H.-S.; Bittman, R. J. Org. Chem. 2010, 75,
4356e4364; (e) Lee, Y. M.; Beak, D. J.; Lee, S.; Kim, D.; Kim, S. J. Org. Chem. 2011,
Absorption coefficient,
F(000)
m
Crystal size (mm)
0.7546ꢂ0.2925ꢂ0.1918
q
Range for data collection (o)
2.36e25.00
Index ranges
ꢀ18ꢃhꢃ18
ꢀ
ꢀ
ꢁ ꢁ
ꢀ
76, 408e416; (f) Martinkova, M.; Gonda, J.; Pomikalova, K.; Kozísek, J.; Kuchar, J.
Carbohydr. Res. 2011, 346, 1728e1738; (g) Rao, G. S.; Rao, B. V. Tetrahedron Lett.
2011, 52, 4861e4864; (h) Lee, Y. M.; Lee, S.; Jeon, H.; Beak, D. J.; Seo, J. H.; Kim,
D.; Kim, S. Synthesis 2011, 867e872; (i) Perali, R. S.; Mandava, S.; Chalapala, S.
Tetrahedron 2011, 67, 9283e9290; (j) Rao, G. S.; Rao, B. V. Tetrahedron Lett. 2011,
52, 6076e6079; (k) Mu, Y.; Jin, T.; Kim, G.-W.; Kim, J.-S.; Kim, S.-S.; Tian, Y.-S.;
Oh, C.-Y.; Ham, W.-H. Eur. J. Org. Chem. 2012, 2614e2620; (l) Rao, G. S.; Chan-
drasekhar, B.; Rao, B. V. Tetrahedron: Asymmetry 2012, 23, 564e569; (m) Mu, Y.;
Kim, J.-Y.; Jin, X.; Park, S.-H.; Joo, J.-E.; Ham, W.-H. Synthesis 2012, 44,
2340e2346; (n) Xarnod, C.; Huang, W.; Ren, R.-G.; Liu, R.-C.; Wei, B.-G. Tetra-
hedron 2012, 68, 6688e6695; (o) Cresswell, A. J.; Davies, S. G.; Lee, J. A.; Morris,
M. J.; Roberts, P. M.; Thomson, J. E. J. Org. Chem. 2012, 77, 7262e7281; (p) Mettu,
R.; Thatikonda, N. R.; Olusegun, O. S.; Vishvakarma, R.; Vaidya, J. R. ARKIVOC
ꢀ11ꢃkꢃ11
ꢀ21ꢃlꢃ21
Independent reflections (Rint)
Absorption correction
9158 (0.0331)
Analytical
Max. and min transmission
Refinement method
0.980 and 0.933
Full-matrix least-squares on F2
9158/17/551
1.026
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I>2
R indices (all data)
Largest diff. peak and hole (e/A
s
(I)]
R1¼0.0690, wR2¼0.1829
R1¼0.0997, wR2¼0.2053
0.335 and ꢀ0.321
0.0080(13)
ꢂꢀ3
)
Extinction coefficient
ꢀ
ꢀ
2012, 421e436; (q) Martinkova, M.; Pomikalova, K.; Gonda, J. Chem. Pap. 2013,

ꢀ
M. Martinkova et al. / Tetrahedron 69 (2013) 8228e8244
8244
ꢁ
ꢀ
ꢀ
ꢀ
ꢀ
67, 84e91; (r) Yen, Y.-F.; Sawant, R. C.; Luo, S.-Y. Synthesis 2013, 45, 511e517; (s)
2837e2847; (c) Martinkova, M.; Gonda, J.; Uhríkova, A.; Spakova Raschmanova,
ꢀ
Devi, T. J.; Saikia, B.; Barua, N. C. Tetrahedron 2013, 69, 3817e3822.
7. For a review on isolation, chemistry and syntheses of jaspine B and its 2-epi-
anolog, see: Abraham, E.; Davies, S. G.; Roberts, P. M.; Russell, A. J.; Thomson, J.
E. Tetrahedron: Asymmetry 2008, 19, 1027e1047.
J.; Kuchar, J. Carbohydr. Res. 2012, 352, 23e36.
15. For some examples of the catalysed Overman rearrangement, see: (a) Overman,
L. E. J. Am. Chem. Soc. 1974, 96, 597e599; (b) Overman, L. E. J. Am. Chem. Soc.
1976, 98, 2901e2910; (c) Gonda, J.; Helland, A.-C.; Ernst, B.; Bellus, D. Synthesis
ꢁ
8. Forrecent selectedexamples of syntheses of jaspine B andits isomers, see: Refs. 5,
7 and (a) Enders, D.; Terteryan, V.; Palecek, J. Synthesis 2008, 2278e2282; (b)
1993, 729e734; (d) Andersom, C. E.; Overman, L. E. J. Am. Chem. Soc. 2003, 125,
12412e12413; (e) Jaunzeme, I.; Jirgensons, A. Synlett 2005, 2984e2986; (f)
Jaunzeme, I.; Jirgensons, A. Tetrahedron 2008, 64, 5794e5799; (g) Sutherland,
A.; Swift, M. D. Tetrahedron 2008, 64, 9521e9527.
ꢁ
Ichikawa, Y.; Matsunaga, K.; Masuda, T.; Kotsuki, H.; Nakano, K. Tetrahedron 2008,
64,11313e11318; (c) Reddipalli, G.; Venkataiah, M.; Mishra, M. K.; Fadnavis, N. W.
Tetrahedron: Asymmetry 2009, 20, 1802e1805; (d) Yoshimitsu, Y.; Inuki, S.; Oishi,
S.; Fujii, N.; Ohno, H. J. Org. Chem. 2010, 75, 3843e3846; (e) Rao, G. S.; Sudhakar,
N.; Rao, B. V.; Basha, S. J. Tetrahedron: Asymmetry 2010, 21,1963e1970; (f) Vichare,
P.; Chattopadhyay, A. Tetrahedron: Asymmetry 2010, 21,1983e1987; (g) Jayachitra,
G.; Sudhakar, N.; Anchoori, R. K.; Rao, B. V.; Roy, S.; Banerjee, R. Synthesis 2010,
115e119; (h) Salma, Y.; Ballereau, S.; Maaliki, C.; Ladeira, S.; Andrie-Abadie, N.;
16. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman,
J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.;
Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega,
N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.;
Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.;
Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg,
J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick,
D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul,
A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.;
Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Na-
nayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M.
W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Revision C.02; Gaussian: Wallingford CT,
2004.
ꢀ
Genisson, Y. Org. Biomol. Chem. 2010, 8, 3227e3243; (i) Llaveria, J.; Díaz, Y.;
ꢀ
Matheu, M. I.; Castillon, S. Eur. J. Org. Chem. 2011, 1514e1519; (j) Prasad, K. R.;
Penchalaiah, K. Tetrahedron: Asymmetry 2011, 22, 1400e1403; (k) Cruz-Gregorio,
S.; Espinoza-Rojas, C.; Quinter, L.; Sartillo-Piscil, F. Tetrahedron Lett. 2011, 52,
ꢀ
6370e6371; (l) Sanchez-Eleuterio, A.; Quintero, L.; Sartillo-Piscil, F. J. Org. Chem.
2011, 76, 5466e5471; (m) Bae, H.; Jeon, H.; Beak, D. J.; Lee, D.; Kim, S. Synthesis
2012, 44, 3609e3612; (n) Lee, D. Synlett 2012, 2840e2844; (o) Zhao, M.-L.; Zhang,
E.; Gao, J.; Zhang, Z.; Zhao, Y.-T.; Qu, W.; Lui, H.-M. Carbohydr. Res. 2012, 351,
126e129; (p) Yoshimitsu, Y.; Miyagaki, J.; Oishi, S.; Fujii, N.; Ohno, H. Tetrahedron
2013, 69, 4211e4220.
€
€
17. Ҫelebi-Olҫum, N.; Aviyente, V.; Houk, K. N. J. Org. Chem. 2009, 74, 6944e6952.
ꢁ
ꢀ
ꢀ
9. Baskaran, S.; Baig, M. H. A.; Banerjee, S.; Baskaran, C.; Bhanu, K.; Deshpande, S.
P.; Trivedi, G. K. Tetrahedron 1996, 52, 6437e6452.
10. Singh, P. P.; Gharia, M. M.; Dasgupta, F.; Srivastava, H. C. Tetrahedron Lett. 1977,
5, 439e440.
11. Collins, P. M.; Overend, W. G.; Shing, T. J. Chem. Soc., Chem. Commun. 1981,
1139e1140.
18. Kniezo, L.; Bernat, J.; Martinkova, M. Chem. Pap. 1994, 48, 103e107.
19. Battistini, L.; Curti, C.; Zanardi, F.; Rassu, G.; Auzzas, L.; Casiraghi, G. J. Org. Chem.
2004, 69, 2611e2613.
20. Azuma, H.; Tamagaki, S.; Ogino, K. J. Org. Chem. 2000, 65, 3538e3541.
21. van den Berg, R. J. B. H. N.; Boltje, T. J.; Verhagen, C. P.; Litjens, R. E. J. N.; van der
Marel, G. A.; Overkleeft, H. S. J. Org. Chem. 2006, 71, 836e839.
22. Abraham, E.; Brock, E. A.; Candela-Lena, J. I.; Davies, S. G.; Georgiou, M.;
12. (a) Overman, L. E.; Carpenter, N. E. In Organic Reactions; Overman, L. E., Ed.;
Wiley: New York, NY, 2005; Vol. 66, pp 1e107; and references cited therein.
13. Nishikawa, T.; Asai, M.; Ohyabu, N.; Isobe, M. J. Org. Chem. 1998, 63, 188e192.
ꢀ
ꢀ
Nicholson, R. L.; Perkins, J. H.; Roberts, P. M.; Russell, A. J.; Sanchez-Fernandez,
E. M.; Scott, P. M.; Smith, A. D.; Thomson, J. E. Org. Biomol. Chem. 2008, 6,
1665e1673.
ꢁ
ꢀ
ꢁ
ꢀ
ꢀ
ꢀ
14. (a) Gonda, J.; Martinkova, M.; Zadrosova, A.; Sotekova, M.; Raschmanova, J.;
ꢁ
ꢁ
ꢀ
Conka, P.; Gajdosíkova, E.; Kappe, C. O. Tetrahedron Lett. 2007, 48, 6912e6915;
(b) Gajdosíkova, E.; Martinkova, M.; Gonda, J.; Conka, P. Molecules 2008, 13,
23. Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112e122.
24. Spek, A. L. J. Appl. Crystallogr. 2003, 36, 7e13.
ꢁ
ꢁ
ꢀ
ꢀ