Formal synthesis of (+)-varitriol. Application of Pd(II)/Cu(II)-catalysed bicyclisation of unsaturated polyols

Article abstract of DOI:10.1016/j.tet.2010.04.074

A formal and improved synthesis of natural (+)-varitriol from D-glucose and dimethyl L-tartrate, respectively, are reported. The key steps are the Pd(II)Cu(II)-catalysed bicyclisation of O-benzyl protected triols L-xylo-15 and L-xylo-15/L-lyxo-15, respect

Full text of DOI:10.1016/j.tet.2010.04.074

Tetrahedron 66 (2010) 5244e5249
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Formal synthesis of (þ)-varitriol. Application of Pd(II)/Cu(II)-catalysed
bicyclisation of unsaturated polyols
ꢀ
*
ꢀ
Miroslav Palík, Olga Karlubíková, Daniela Lackovicová, Angelika Lásiková, Tibor Gracza
Department of Organic Chemistry, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovakia
a r t i c l e i n f o
a b s t r a c t
Article history:
A formal and improved synthesis of natural (þ)-varitriol from
D-glucose and dimethyl L-tartrate, re-
spectively, are reported. The key steps are the Pd(II)/Cu(II)-catalysed bicyclisation of O-benzyl protected
Received 27 January 2010
Received in revised form 31 March 2010
Accepted 19 April 2010
triols
L-xylo-15 and L-xylo-15/L-lyxo-15, respectively, followed by ring opening of intermediate dianhydro-
L-gulitol 16. The syntheses of key intermediate of the furanoside portion 17 proceed in 13 steps with 5%
Available online 24 April 2010
(from bisacetone-D-glucose), and in 12 steps with 7.6% over-all yield from dimethyl L-tartrate,
respectively.
Keywords:
Ó 2010 Elsevier Ltd. All rights reserved.
Palladium(II)-catalysis
Bicyclisation
Diastereoselectivity
Natural products
Varitriol
1. Introduction
The tandem of diastereoselective bicyclisation reaction followed
by a regioselective ring opening of the bicyclic skeleton represents
a new synthetic access to heterocyclic compounds with defined
stereochemistry. In our previous paper,7 we described application
of this method for the construction of 2,3-trans-tetrahydrofuran
derivative en route to natural varitriol (þ)-1 (Fig. 1).
The direct oxidative bisfunctionalisation of alkenes represents
a powerful transformation in the field of chemical synthesis.
Considering the accessibility of alkenes and their robust nature,
there is clearly an increased interest to develop new catalytic
difunctionalisation reactions that add two functional groups
across alkenes in a regio- and stereocontrolled manner.1 Over the
past few decades, several protocols for transition metal mediated
direct diamination,2 amino-acetoxylation,3 diacetoxylation4 and
dioxygenation,4 have been developed. In the course of our pro-
gram directed towards the application of palladium(II)-catalysed
bicyclisation of unsaturated polyols5 in natural product synthesis,
we have developed a novel type of PdCl2/CuCl2-catalysed dia-
lkoxylation/aminoalkoxylation reaction of alkenes.6 The terminal
carbonecarbon double bond is bis-O/N,O-functionalised with two
hydroxyl/amino-hydroxyl groups by sequential intramolecular/
intramolecular process, which allows selective formation of two
distinct carboneheteroatom bonds by employing substrates
containing nucleophiles tethered to the alkene (Scheme 1).
Figure 1. (þ)-Varitriol.
Varitriol was isolated from a marine-derived strain of fungus
Emericella variecolor and shown to exhibit considerable cytotoxic
activity against several human tumour cell lines.8 Strikingly, (þ)-1
demonstrated increased potency towards selected renal, CNS and
breast cancer cell lines.8,9 The structure and relative stereochem-
istry of 1 was assigned on the basis of NMR spectroscopy and the
absolute configuration was determined in the course of the syn-
thesis of its unnatural enantiomer (ꢀ)-1.10
Meanwhile, growing attention is given to this cytotoxic com-
pound, as demonstrated by development of total synthesis of var-
itriol (þ)-1,11 its unnatural enantiomer (ꢀ)-110,12 and structural
analogues.13,14 Jennings10 and Taylor12 reported the total syntheses
Scheme 1. PdCl2/CuCl2-catalysed bicyclisation of unsaturated polyols and amino
polyols.
of (ꢀ)-1 from
D
-ribose utilising the alkene metathesis and the HWE/
€
conjugate addition/RambergeBacklund rearrangement sequence,
respectively. The synthesis of natural (þ)-1 is based on a cross
* Corresponding author. Tel.: þ421 2 593 25 160; fax: þ421 2 529 68 560;
e-mail address: tibor.gracza@stuba.sk (T. Gracza).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.04.074

M. Palík et al. / Tetrahedron 66 (2010) 5244e5249
5245
metathesis of the corresponding styrene and tetrahydrofuran
subunit, the latter obtained from methyl
-mannopyranoside.11
Recently, we described the synthesis of (þ)-1 starting with
a-D
dimethyl
L-tartrate using intramolecular Pd(II)/Cu(II)-catalysed
bisalkoxylation of corresponding alkene triol as the key step.7 We
report herein details of the optimised synthesis of the key tetra-
hydrofuran intermediate 17 from dimethyl
L-tartrate and a new
synthesis starting from -glucose, respectively (Scheme 2).
D
Scheme 2. Retrosynthetic analysis of (þ)-1.
2. Results and discussion
Scheme 3. Synthesis of L-xylo-15.
Our synthetic approach to (þ)-1 was based on the coupling of
furanoside subunit 2 with 2-acetoxymethyl-3-benzaldehyde 3 via
KocienskieJulia olefination.15 The key reactions: (i) olefination, (ii)
Pd(II)-catalysed bicyclisation and (iii) regioselective ring opening
worked well, as expected.7 The approach took advantage of our
preliminary work, showing that unsaturated polyols undergo
palladium(II)-catalysed bicyclisation with high xylo-substrate pref-
erence and excellent threo-selectivity.6a Thus, the mixture of
hydroxymethyl to methyl group. Selective tosylation of primary
hydroxyl group in pyridine, followed by hydride displacement
afforded -xylo-15 in 64% yield over two steps. The protected hex-
enitols 10, 12 and 12a, respectively, have, to the best of our knowl-
edge not been reported in the literature yet and we expect these to
be highly interesting, versatile building blocks in other areas as well.
L
With diastereomerically pure triol -xylo-15 in our hands the
L
diastereomeric triols
standard bicyclisation reaction conditions, provided the bicyclic
dianhydro-alditol 16 solely from -xylo-diastereomer of the starting
alkenol. Unfortunately, at the same time its major -lyxo counterpart
was transformed to a set of undesired products, complicating the
purification of 16. Undesirable ratio of triols -xylo-15/ -lyxo-15 (3:7)
L-xylo-15/L-lyxo-15 in a ratio 3/7, subjected to
synthesis was set up for the first key reaction of the sequenced
intramolecular Pd(II)/Cu(II)-catalysed bisalkoxylation (Scheme 4).
The reaction, performed under standard reaction conditions6a,7
with PdCl2 as catalyst (0.1 equiv), CuCl2 (3 equiv), NaOAc (3 equiv)
in AcOH as buffer at room temperature, proceeded very cleanly,
providing bicyclic dianhydro-alditol 16 in good yield (83%) and
with excellent threo-diastereoselectivity. The second crucial step of
the synthesis is the opening of less substituted ring of bicyclic
skeleton 16. This was accomplished by treatment of dianhydro-
alditol 16 with TBAI/TMSCl/HCl in dichloromethane at room tem-
perature for 3 days. The required furan derivative 17 was formed
with high exo-regioselectivity and in good yield (76%).
L
L
L
L
and impossibility to isolate the bicycle 16 in pure form decreased the
total yield of target (þ)-1. In connection with the above-mentioned,
we were interested in obtaining a reliable access to pure -xylo-15.
L
Optically pure triol
commercially available bisacetone-
a standard carbohydrate chemistry (Scheme 3). Silylation of bisa-
cetone- -glucose 4 followed by selective hydrolysis of the terminal
L-xylo-15 was finally synthesised from
D-glucose in 11 steps, adopting
D
acetonide, O-mesylation of both unprotected hydroxyl groups,
reductive elimination with sodium iodide16 and subsequent
hydrolysis of the second acetonide with 50% aq acetic acid fur-
nished
borohydride reduction to provide alkene 10.
Introduction of an
-O-benzyl protecting group,6a required for
D-xylo-5-hexenose 9 that subsequently underwent sodium
a
Pd/Cu-bicyclisation was accomplished in two steps; acetalisation of
10 with benzaldehyde dimetyl acetal in the presence of p-toluene-
sulfonic acid followed by reduction of benzylidene ring with
Scheme 4. Pd/Cu-catalysed bicyclisation of L-xylo-15 and ring-opening of bicyclic di-
anhydro-alditol 16.
NaBH3CN/TiCl4 system, furnishing the
(45%) along with its regioisomer 12a (38%). The synthesis continued
with desilylation of 12 using TBAF in THF affording triol 13 in good
a
-OBn-protected tetraol 12
Next, we decided to improve the efficiency of our previous
varitriol synthesis7 from dimethyl
L-tartrate. The weak spot of this
approach is the unfavourable stereochemical outcome of vinyl-
yield (85%). The first key intermediate, 1-deoxy-L-xylo-5-hexenitol
magnesium bromide addition to aldose 18, providing the required
L-xylo-15, was obtained in two-steps sequence to convert
diastereomer
L
-xylo-19 only as a minor product along with -lyxo-19
L

5246
M. Palík et al. / Tetrahedron 66 (2010) 5244e5249
in the ratio of 3:7 and in 63% yield (Scheme 5). In order to reverse
the diastereomeric triols distribution a stereoselective reduction of
ketone 20 was examined. Thus, DesseMartin oxidation of the
4. Experimental section
4.1. General methods
mixture of alcohols
L
-xylo-19/ -lyxo-19 afforded ketone 20, which
L
was subjected without purification to the reduction under various
reaction conditions.
Commercial reagents were used without further purification. All
solvents were distilled before use. Hexanes refer to the fraction
boiling at 60e65 ꢁC. Flash column liquid chromatography (FLC) was
performed on silica gel Kieselgel 60 (40e63 mm, 230e400 mesh)
and analytical thin-layer chromatography (TLC) was performed on
aluminium plates pre-coated with either 0.2 mm (DC-Alufolien,
Merck) or 0.25 mm silica gel 60 F254 (ALUGRAMÒ SIL G/UV254
,
Macherey/Nagel). The compounds were visualised by UV fluores-
cence and by dipping the plates in an aqueous H2SO4 solution of
cerium sulfate/ammonium molybdate followed by charring with
a heat-gun. Optical rotations were measured with a POLAR L-
polarimeter (IBZ Messtechnik) with a water-jacketed 10,000 cm
cell at the wavelength of sodium line D (
mP
l¼589 nm). Specific rota-
tions are given in units of 10ꢀ1 deg cm2 gꢀ1 and concentrations are
given in g/100 mL. Elemental analyses were run on FISONS EA1108
instrument. FTIR spectra were obtained on a Nicolet 5700 spec-
trometer (Thermo Electron) equipped with a Smart Orbit (diamond
crystal ATR) accessory, using the reflectance technique
(4000e400 cmꢀ1). 1H and 13C NMR spectra were recorded on either
300 (75) MHz MercuryPlus or 600 (150) MHz Unity Inova spec-
Scheme 5. Synthesis of L-xylo-19/L-lyxo-19.
Table 1 summarises results of a series of micro scale experi-
ments with several metal hydrides in the presence of different
Lewis acids. General syn-diastereoselectivity, observed in this set
of reactions is in agreement with literature references describing
additions of C-nucleophiles to analogous isopropylidene-threose
derivatives.5j,17 The best result was noted with NaBH4 (1 equiv) in
the presence of CeCl3$7H2O (1.1 equiv) in methanol at ꢀ78 ꢁC
trometers from Varian. Chemical shifts (d) are quoted in parts per
million and are referenced to the tetramethylsilane (TMS) as in-
ternal standard. Compounds are numbered according to carbohy-
drate naming scheme.
4.1.1. 3-O-[(tert-Butyl)-diphenylsilyl]-1,2:5,6-di-O-isopropylidene-
a-
D
-glucofuranose (5). To the solution of bisacetone- -glucose 4 (20 g,
D
(entry 4), affording the requisite
74% yield.
L-xylo-diastereomer in dr 4:1 and
76.8 mmol) and imidazole (23 g, 307.2 mmol, 4.4 equiv) in dry
dimethylformamide (200 mL) a solution of (tert-butyl)-diphenyl-
silylchloride (46.46 g, 169 mmol, 2.2 equiv) in dry dimethyl-
formamide (100 mL) was added dropwise at room temperature
over 30 min. After 80 h stirring at 50 ꢁC the mixture was concen-
trated in vacuo (rotary evaporator, 50 ꢁC, 5 mbar). The residue was
dissolved in ethyl acetate (200 mL) and washed with water (50 mL)
and brine (50 mL). The solution was dried over Na2SO4 and con-
centrated under reduced pressure. The crude product (38.76 g,
colourless oil, Rf 0.2, 5% AcOEt/hexanes) was used without further
purification in the next step.
Table 1
Diastereoselective reduction of ketone 20
Entry
Reagent (equiv)
Lewis
acid
Solvent/
Temp ꢁC
L
-xylo-19/
L-
Yieldb
%
lyxo-19a
1
2
3
4
5
6
7
8
9
LAH (0.5)
d
Et2O/ꢀ78
Et2O/ꢀ78
MeOH/0
MeOH/ꢀ78
CH2Cl2/ꢀ40
THF/ꢀ78
THF/ꢀ50
THF/ꢀ78
THF/ꢀ78
75:25
76:24
75:25
80:20
74:26
55:45
60:40
64:26
70:30
16
32
43
74
13
60
35
70
33
LAH (1)
MgBr2
CeCl3
CeCl3
d
c
NaBH4 (1)
NaBH4 (1)
DIBAL (1)
c
DIBAL (2)
MgBr2
d
L-Selectride (3)
L-Selectride (3)
Red-Al (4)
4.1.2. 3-O-[(tert-Butyl)-diphenylsilyl]-1,2-O-isopropylidene-a-D-glu-
MgBr2
MgBr2
cofuranose (6). Crude bisacetonide 5 (38.76 g), dissolved in aq
acetic acid (75%, 30 mL), was stirred at 40 ꢁC for 50 h (TLC-moni-
toring). Removal of solvents in vacuo (20 mbar) furnished a yellow
oil, which was purified by flash chromatography (silica gel, 30%
AcOEt/hexanes). The furanose monoacetonide 6 was obtained as
a colourless oil; yield 32.76 g (93% after two steps); [found: C,
Relative ratios were determined from crude reaction mixture by 1H and 13C
a
NMR spectroscopy.
b
Total isolated yield of both diastereomers.
CeCl3$7H2O was used.
c
65.72; H, 7.51. C25H34O6Si requires C, 65.47; H, 7.47%]; Rf (30%
25
3. Conclusions
AcOEt/hexanes) 0.2; [
a
]
ꢀ7.4 (c 0.325, MeOH); nmax (ATR) 3514,
D
3396 (br), 2939, 2856, 1429, 1375, 1100, 1075, 1014, 969, 823, 739,
In summary, a new formal and improved synthesis of natural
701 cmꢀ1
;
dH (300 MHz CDCl3) 1.09 (s, 9H, C(CH3)3), 1.12, 1.38 (2ꢂs,
(þ)-varitriol has been developed from bisacetone-
D-glucose and
6H, C(CH3)2), 1.98, 2.16 (2ꢂbr s, 2H, OH), 3.70e3.83 (m, 2H, H-6),
3.99, 4.46 (2ꢂbr s, 3H, H-3, H-4, H-5), 4.26 (d, 1H, J1,2 3.6 Hz, H-2)
5.82 (d, 1H, J1,2 3.6 Hz, H-1), 7.37e7.49, 7.65e7.70 (2ꢂm, 10H, Ph); dC
(75 MHz CDCl3) 19.4 (s, C(CH3)3), 26.0, 26.7 (all q, C(CH3)2), 26.9 (q,
C(CH3)3), 64.6 (t, C-6), 68.5, 76.6, 81.2, 84.4 (all d, C-2, C-3, C-4, C-5),
104.8 (d, C-1), 111.6 (s, C(CH3)2), 127.9, 128.0, 130.1, 130.2 (all d, Ph),
132.3, 133.6 (all s, i-Ph), 135.6, 135.7 (all d, Ph).
dimethyl -tartrate, respectively. The key intermediate of the
L
furanoside part of varitrioldiodide 17 was constructed using two
key reactions, namely threo-diastereoselective Pd(II)/Cu(II)-cata-
lysed intramolecular bisalkoxylation of -xylo-15 unsaturated triol
followed by exo-regioselective ring opening of bicyclic dianhydro-
alditol 16. Facility and effects of the two-reaction sequence
L
performed with pure -xylo-15 demonstrates the applicability of
L
the bicyclisation strategy in the synthesis of 2,3-trans-substituted
4.1.3. 3-O-[(tert-Butyl)-diphenylsilyl]-1,2-O-isopropylidene-5,6-di-
tetrahydrofurans, the latter being hardly accessible by other means.
O-mesyl-a-D
-glucofuranose (7). To the cooled (0 ꢁC) solution of diol
The total yield of 17 from dimethyl
L
-tartrate was doubled7
6 (12 g, 26.1 mmol) in pyridine (150 mL) a solution of methane-
utilising stereoselective reduction of the ketone 20.
sulfonyl chloride (6.58 g, 57.5 mmol, 2.2 equiv) in pyridine (50 mL)

M. Palík et al. / Tetrahedron 66 (2010) 5244e5249
5247
was added dropwise under vigorous stirring, keeping the reaction
temperature below 10 ꢁC. After 10 h stirring at rt the mixture was
concentrated under reduced pressure and the remainder distrib-
uted between AcOEt (200 mL) and water (150 mL). Organic layer
was dried over Na2SO4 and concentrated in vacuo to provide
130.0, 130.2, 130.3, 131.8, 132.8, 132.9, 133.6, 135.8, 135.8, 135.9,
136.0 (all d, Ph), 134.0, 134.3 (d, C-5).
4.1.6. 3-O-[(tert-Butyl)-diphenylsilyl]- -xylo-5-hexenitol (10). To the
L
solution of aldofuranose 9 (5.5 g, 14.30 mmol) in a mixture of
MeOH/H2O (3:1, 700 mL) solid NaBH4 (3.727 g, 100 mmol, 7 equiv)
was portionwise added. After 5 days stirring at rt the solution was
concentrated to a third of original volume (rotary evaporator,
30 mbar) and acidified by addition of concd H2SO4 (several drops)
to attain pH 5e6. The residue was distributed between AcOEt
(200 mL) and water (50 mL) and separated water layer was
extracted with AcOEt (6ꢂ50 mL). Combined organic extracts were
dried over Na2SO4 and after solvent removal separated by flash
column chromatography on silica (20% AcOEt/hexanes). Yield of 10
as a colourless oil: 4.147 g (75%); [found: C, 68.72; H, 7.51.
C22H30O4Si requires C, 68.36; H, 7.82]; Rf (20% AcOEt/CH2Cl2) 0.21;
product 7 as a yellow oil [15.23 g, 95%, Rf 0.2, 20%AcOEt in hexanes,
25
[
a]
þ6.1 (c 0.314, MeOH)], which was used without further pu-
D
rification in the next reaction; nmax (ATR) 2947, 2851, 1428, 1356,
1174, 1075, 916, 821, 740, 701 cmꢀ1
;
dH (600 MHz CDCl3) 1.06 (s, 3H,
CH3), 1.10 (s, 9H, C(CH3)3), 1.37 (s, 3H, CH3), 2.97, 3.04 (2ꢂs, 6H,
SO2CH3), 4.22 (d, 1H, J1,2 3.5 Hz, H-2), 4.36 (dd, 1H, J3,4 2.6, J4,5
4.6 Hz, H-4), 4.53e4.58 (m, 2H, J3,4 2.6, J5,6A 6.8 Hz, H-3, H-6A), 4.69
(dd, 1H, J5,6B 2.0, J6A,6B 11.8 Hz, H-6B) 5.11e5.16 (m, 1H, J5,6B 2.0, J5,6A
6.8 Hz, H-5), 5.68 (d, 1H, J1,2 3.5 Hz, H-1), 7.42e7.47, 7.65e7.72
(2ꢂm, 10H, Ph); dC (150 MHz CDCl3) 19.4 (s, C(CH3)3), 25.9, 26.6 (all
q, C(CH3)2), 26.9 (q, C(CH3)3), 37.4, 39.0 (all q, SO2CH3), 68.7 (t, C-6),
75.9, 76.8, 80.3, 83.7 (all d, C-2, C-3, C-4, C-5), 104.4 (d, C-1), 112.1 (s,
C(CH3)2), 128.0, 128.2, 130.3, 130.4 (all d, Ph),131.9,133.3 (all s, i-Ph),
135.6, 135.7 (all d, Ph).
[a
]
25.þ15.7 (c 0.28, MeOH); nmax (ATR) 3384 (br), 2930, 2856, 1471,
D
1427, 1110, 997, 823, 700 cmꢀ1
;
dH (300 MHz CDCl3) 1.09 (s, 9H, C
(CH3)3), 2.83, 2.90 (2ꢂbr s, 3H, 3ꢂOH), 3.56, 3.76e3.81 (2ꢂm, 4H,
H-1, H-2, H-3), 4.22e4.25 (m,1H, H-4), 5.25 (ddd,1H, J4,6E¼J6Z,6E 1.2,
J5,6E 10.5 Hz, H-6E), 5.38 (ddd, 1H, J4,6Z 1.2, J6Z,6E 1.3, J5,6Z 17.2 Hz, H-
6Z), 5.87 (ddd, 1H, J4,5 6.2, J5,6E 10.5, J5,6Z 17.1 Hz, H-5), 7.36e7.47,
7.63e7.68 (2ꢂm, 10H, Ph); dC (75 MHz CDCl3) 19.2, (s, C(CH3)3),
26.8, (q, C(CH3)2), 65.6 (t, C-1), 71.7, 73.1, 74.2 (all d, C-2, C-3, C-4),
117.6 (t, C-6), 127.8, 127.8, 129.9, 129.9 (all d, Ph),132.6, 132.7 (all s, i-
Ph), 135.4, 135.5 (all d, Ph), 136.8 (d, C-5).
4.1.4. 3-O-[(tert-Butyl)-diphenylsilyl]-1,2-O-isopropylidene-a-D-
xylo-5-hexenofuranose (8). Varying the procedure given by Bladon
and Owen,16 a solution of crude dimesylate 7 (15.23 g) and NaI
(31.24 g, 209 mmol, 8 equiv) in DMF (150 mL) was heated at 120 ꢁC
for 3 h. The solvent was removed on a rotavapor (45 ꢁC, 5 mbar), the
residue was distributed between Na2S2O3 solution (10% in H2O,
100 mL) and AcOEt (100 mL). Inorganic phase was extracted with
AcOEt (3ꢂ50 mL) and combined organic phases were dried over
Na2SO4. Concentrated crude mixture was purified by chromatog-
raphy (silica gel, 2.5% AcOEt in hexanes). Yield of 8 as a colourless
oil: 9.1 g (82% calculated from 6); [found: C, 70.56; H, 7.71.
4.1.7. 2,4-O-Benzylidene-3-O-[(tert-butyl)-diphenylsilyl]-L-xylo-5-
hexenitol (11). To a solution of hexenitol 10 (4 g, 10.34 mmol) in
toluene (150 mL) was added benzaldehyde dimethyl acetal (3.1 g,
20.68 mmol, 2 equiv) and PTSA (98 mg, 0.517 mmol, 0.05 equiv).
The resulting solution was stirred at room temperature for 18 h
(TLC-monitoring). After concentration (rotavapor) the residue was
purified by flash column chromatography (silica gel, 5% AcOEt/
hexanes) to provide 3.3 g (68%) of benzylidene acetal 11 as a col-
ourless oil; [found: C, 73.12; H, 7.31. C29H34O4Si requires C, 73.38; H,
C25H32O4Si requires C, 70.72; H, 7.60]; Rf (2.5% AcOEt/hexanes) 0.1;
26
[
a]
ꢀ14.7 (c 0.375, MeOH); nmax (ATR) 2931, 2858, 1427, 1373,
D
1164,1112,1075, 1018, 990, 823, 730, 701 cmꢀ1
; dH (600 MHz CDCl3)
1.07 (s, 9H, C(CH3)3), 1.16, 1.42 (2ꢂs, 6H, C(CH3)2), 4.24e4.26 (m, 2H,
H-2, H-3), 4.52 (dd, 1H, J3,4 2.6, J4,5 7.4 Hz, H-4), 5.24 (d, 1H, ddd, J4,6E
0.8, J6E,6Z 1.7, J5,6E 10.4 Hz, H-6E) 5.33 (ddd, 1H, J4,6Z 1.0, J6E,6Z 1.7, J5,6Z
17.4 Hz, H-6Z), 5.91 (d, 1H, J1,2 3.5 Hz, H-1), 5.96 (ddd, 1H, J4,5 7.4,
J5,6E 10.4, J5,6Z 17.5 Hz, H-5), 7.34e7.47, 7.62e7.67 (2ꢂm, 10H, Ph); dC
(150 MHz CDCl3) 19.4 (s, C(CH3)3), 26.1, 26.7 (all q, C(CH3)2), 26.9 (q,
C(CH3)3), 78.4, 82.6, 85.1 (all d, C-2, C-3, C-4), 104.6 (d, C-1), 111.4 (s,
C(CH3)2), 119.3 (t, C-6),127.6,127.7,129.9,130.0 (all d, Ph),132.7 (s, i-
Ph), 132.8 (d, C-5), 133.6 (s, i-Ph), 135.8, 135.9 (all d, Ph).
7.22]; Rf (5% AcOEt/hexanes) 0.3; [
a
]
27 þ17.4 (c 0.219, MeOH); nmax
D
(ATR) 3469 (br), 2929, 2856, 1471, 1427, 1105, 1025, 823, 688 cmꢀ1
;
dH (600 MHz CDCl3) 1.06 (s, 9H, C(CH3)3), 3.75 (br s, 1H, H-3), 3.85
(A of ABX, dd, 1H, J1A,2 5.4, J1A,1B 10 Hz, H-1A), 3.98 (B of ABX, ddd,
1H, J1B,2 6.6, J1A,1B 10 Hz, H-1B), 4.05 (X of ABX, ddd, 1H, J2,3 1.2, J1A,2
5.4, J1B,2 6.6 Hz, H-2), 4.44 (dddd, 1H, J3,4 1.4, J4,6E¼J4,6E 1.5, J4,5
5.2 Hz, H-4), 5.34 (ddd, 1H, J4,6E¼J6Z,6E 1.5, J5,6E 10.7 Hz, H-6E), 5.47
(ddd, 1H, J4,6Z¼J6Z,6E 1.5, J5,6Z 17.4 Hz, H-6Z), 5.66 (s, 1H, CHPh), 6.03
(ddd, 1H, J4,5 5.2, J5,6E 10.7, J5,6Z 17.4 Hz, H-5), 7.34e7.42 (m, 9H, Ph),
7.49e7.50 (m, 2H, Ph), 7.68e7.72 (m, 4H, Ph); dC (150 MHz CDCl3)
19.2, (s, C(CH3)3), 26.8, (q, C(CH3)2), 63.0 (t, C-1), 65.9 (d, C-3), 80.3,
80.9 (all d, C-2, C-4), 100.9 (s, CHPh), 117.6 (t, C-6), 126.1, 127.7, 127.9,
128.2, 128.9 (all d, Ph), 133.1, 133.3 (all s, i-Ph), 134.4 (d, C-5), 135.6,
135.5 (all d, Ph), 137.7 (s, i-Ph).
4.1.5. 3-O-[(tert-Butyl)-diphenylsilyl]-a/b-D-xylo-5-hexenofuranose
(9). The silyl-furanose 8 (8 g, 18.75 mmol) was dissolved in 50%
aqueous AcOH (100 mL) and heated to 90 ꢁC for 3 days (TLC con-
trol). Removal of solvents in vacuo (20 mbar) left a yellow oil, which
was purified by chromatography on silica gel (eluent 5% AcOEt/
CH2Cl2). The furanose 9 was obtained as a yellow, but analytically
pure oil; yield 6.34 g (88%); [found: C, 68.56; H, 7.30. C22H28O4Si
25
requires C, 68.71; H, 7.34]; [
a
]
þ22.7 (c 0.22, MeOH); nmax (ATR)
4.1.8. 4-O-Benzyl-3-O-[(tert-butyl)-diphenylsilyl]-L-xylo-5-hexenitol
D
3384 (br), 2929, 2856, 1471, 1427, 1104, 1021, 989, 820, 699 cmꢀ1
(600 MHz CDCl3) mixture of -anomers (2:1); -anomer: 1.08 (s,
;
dH
(12). To a solution of acetal 11 (1780 mg, 3.75 mmol) and NaBH3CN
(307 mg, 4.875 mmol, 1.3 equiv) in dry MeCN (80 mL) TiCl4
(925 mg, 0.536 mL, 4.875 mmol, 1.3 equiv) was added dropwise
through septum at ꢀ35 ꢁC over 5 min under Ar. The reaction mix-
ture was stirred for 2 h, while the temperature reached rt. After
hydrolysis with satd aq K2CO3 soln (20 mL), the mixture was
evaporated in vacuo. The residue was extracted with AcOEt
(3ꢂ20 mL), combined organic extracts were dried (Na2SO4) and
evaporated in vacuo. Separation of the crude reaction mixture by
FLC (silica gel, 20% AcOEt/hexanes) provided fraction one contain-
ing 4-O-benzylated hexenitol 12, 804 mg (45%), colourless oil;
[found: C, 73.22; H, 7.56. C29H36O4Si requires C, 73.07; H, 7.61]; Rf
a
/b
a
9H, C(CH3)3), 2.30 (d, 1H, J 4.6 Hz, OH), 3.68 (m, 1H, H-2), 3.87 (m,
1H, OH), 4.23e4.26 (m, 1H, H-3), 4.52e4.58 (m, 1H, H-4), 5.22e5.32
(m, 2H, H-6), 5.51 (dd, 1H, J1,OH 4.5, J1,2 5.4 Hz, H-1), 5.98 (ddd, 1H,
J4,5 7.5, J5,6E 10.3, J5,6Z 17.7 Hz, H-5), 7.34e7.47, 7.61e7.69 (2ꢂm, 10H,
Ph); b-anomer: 1.09 (s, 9H, C(CH3)3), 1.71 (d, 1H, J 4.3 Hz OH), 3.58
(d, 1H, J1,2 11.3 Hz H-2), 3.91e3.94 (m, 1H, OH), 4.19e4.23 (m, 1H, H-
3), 4.52e4.58 (m, 1H, H-4), 5.06 (d, 1H, J1,2 11.2 Hz, H-1), 5.26e5.41
(m, 2H, H-6) 6.04 (ddd, 1H, J4,5 7.3, J5,6E 10.2, J5,6Z 17.6 Hz, H-5),
7.34e7.47, 7.61e7.69 (2ꢂm,10H, Ph); dC (150 MHz CDCl3) mixture of
anomers (a/b, 2:1): 19.2, 19.3 (s, C(CH3)3), 26.9, 27.0 (q, C(CH3)2),
76.9, 77.2, 78.6, 79.6, 80.3, 81.4, 83.8, 83.9 (all d, C-2, C-3, C-4), 96.2,
103.6 (d, C-1), 118.7, 118.9 (t, C-6), 127.7, 127.8, 127.8, 127.9, 129.9,
(25% AcOEt/hexanes) 0.25; [
after evaporation and drying (P2O5, 0.1 mbar) gave analytically pure
a
]
25 ꢀ7.2 (c 0.415, MeOH); fraction two
D

5248
M. Palík et al. / Tetrahedron 66 (2010) 5244e5249
regioisomer 2-O-benzyl-3-O-[(tert-butyl)-diphenylsilyl]-
L
-xylo-5-
requires C, 70.24; H, 8.16]; Rf (10% AcOEt/CH2Cl2) 0.15; [
a
]
25 ꢀ26.8 (c
D
hexenitol 12a, 679 mg, (38%), colourless oil; [found: C, 72.89; H,
7.73. C29H36O4Si requires C, 73.07; H, 7.61]; Rf (25% AcOEt/hexanes)
0.190, MeOH); nmax (ATR) 3417 (br), 2927, 2871, 1496, 1454, 1047,
1027, 991, 735, 697 cmꢀ1
; dH (300 MHz CDCl3) 1.19 (d, 3H, H-1), 2.57
0.15; [
a
]
25þ19.6 (c 0.458, MeOH).
(d, 1H, J2,OH 5.5 Hz, OH-2), 2.80 (d, 1H, J3,OH 5.1 Hz, OH-3), 3.31e3.35
(m, 1H, J2,3 2.8, J3,OH 5.1 Hz, H-3), 3.81e3.86 (m, 1H, H-2), 3.91 (dd,
1H, J3,4 5.6, J4,5 8.0 Hz, H-4), 4.34 (d, 1H, J 11.6 Hz, CH2Ph), 4.65 (d,
1H, J 11.6 Hz, CH2Ph), 5.36e5.43 (m, 2H, J4,6E¼J4,6Z 0.8, J6Z,6E 1.6, J5,6E
10.6, J5,6Z 17.0 Hz, H-6), 5.86 (ddd, 1H, J4,5 8.0, J5,6E 10.6, J5,6Z 17.0 Hz,
H-5), 7.30e7.36 (m, 5H, Ph); dC (75 MHz CDCl3) 20.0 (q, C-1), 70.3 (t,
CH2Ph), 67.5, 76.6, 81.9 (all d, C-2, C-3, C-4), 120.4 (t, C-6), 127.9 (d,
p-Ph), 128.0 (d, o-Ph), 128.5 (d, m-Ph), 134.9 (d, C-5), 137.6 (s, i-Ph).
D
Compound 12: nmax (ATR) 3469 (br), 2929, 2856, 1722, 1471, 1427,
1110, 1051, 823, 700 cmꢀ1
; dH (300 MHz CDCl3) 1.04 (s, 9H, C(CH3)3),
2.68, 2.89 (2ꢂbr s, 2H, 2ꢂOH), 3.69e3.72 (m, 4H, H-1, H-2, H-3), 3.96
(dd, 1H, J3,4¼J4,5 7.4 Hz, H-4), 4.35 (d, 1H, J 11.4 Hz, CH2Ph), 4.65 (d,
1H, J 11.4 Hz, CH2Ph), 5.37e5.43 (m, 2H, H-6), 5.77 (m, 1H, J5,6E 10.7,
J5,6Z 17.1 Hz, H-5), 7.30e7.39 (m, 11H, Ph), 7.64e7.65 (m, 4H, Ph); dC
(75 MHz CDCl3) 19.2, (s, C(CH3)3), 26.8, (q, C(CH3)2), 65.0 (t, C-1), 70.5
(t, CH2Ph), 70.8, 72.3 (all d, C-2, C-3), 81.9, (d, C-4), 120.7 (t, C-6),
127.6,127.7,127.8,127.9,128.5,129.7,129.8 (all d, Ph),133.1,133.2 (all
s, i-Ph), 134.7 (d, C-5), 135.6, 135.5 (all d, Ph), 137.7 (s, i-Ph).
4.1.11. 6-Deoxy-1,4:2,5-di-anhydro-3-O-benzyl-
L
-gulitol
(16). The
mixture of alkenitol 15 (87 mg, 0.391 mmol), PdCl2 (7 mg,
0.039 mmol, 0.1 equiv), anhydrous CuCl2 (159 mg, 1.174 mmol,
3 equiv) and anhydrous AcONa (96 mg, 1.174 mmol, 3 equiv) in
glacial AcOH (10 mL) was stirred at room temperature for 12 h.
Solvent was evaporated in vacuo and the residue distributed be-
tween an aq soln of ammonia (10%, 25 mL) and AcOEt (20 mL).
Water phase was extracted with AcOEt (5ꢂ20 mL). The combined
organic extracts were dried over Na2SO4, filtered and concentrated
under reduced pressure. Purification of the resultant residue by FLC
(30 g of silica gel, 15% AcOEt in hexanes) yielded 71 mg (83%) of
bicycle 16 as a colourless oil; [found: C, 70.07; H, 7.43. C13H16O3
Compound 12a: nmax (ATR) 3400 (br), 2929, 2856, 1724, 1471,
1427, 1110, 1070, 823, 700 cmꢀ1
; dH (300 MHz CDCl3) 1.06 (s, 9H, C
(CH3)3), 2.69, 2.96 (2ꢂbr s, 2H, 2ꢂOH), 3.55 (ddd, 1H, J2,3 3.2, J1A,2
4.9, J1B,2 5.6 Hz, H-2), 3.63e3.69 (m, 1H, H-3), 3.84 (dd, 1H, J1A,2 4.8,
J1A,1B 10.9 Hz, H-1A), 3.91 (dd, 1H, J1B,2 5.6, J1A,1B 10.9 Hz, H-1B), 4.16
(dd, 1H, J3,4 5.9, J4,5 6.1 Hz, H-4), 4.39 (d, 1H, J 11.5 Hz, CH2Ph), 4.63
(d, 1H, J 11.5 Hz, CH2Ph), 5.20 (ddd, 1H, J4,6Z 1.2, J6E,6Z 1.6, J5,6E
10.4 Hz, H-6E), 5.22 (ddd, 1H, J4,6E 1.4, J6E,6Z 1.6, J5,6Z 17.3 Hz, H-6E),
5.79 (ddd, 1H, J4,5 6.3, J5,6E 10.5, J5,6Z 17.2 Hz, H-5), 7.22e7.45 (m,
11H, Ph), 7.66e7.70 (m, 4H, Ph); dC (75 MHz CDCl3) 19.1, (s, C(CH3)3),
26.8, (q, C(CH3)2), 62.8 (t, C-1), 72.5 (t, CH2Ph), 73.3, 73.4 (all d, C-2,
C-3), 78.4, (d, C-4), 117.4 (t, C-6), 127.7, 127.8, 127.9, 128.0, 128.5,
129.8, 129.9 (all d, Ph), 132.8, 133.0 (all s, i-Ph), 135.5, 135.6 (all d,
Ph), 137.1 (d, C-5), 137.6 (s, i-Ph).
requires C, 70.89; H, 7.32]; Rf (20% AcOEt/hexanes) 0.2; [
a
]
25 þ33.3
D
(c 0.03, MeOH); nmax (ATR) 2924, 2852, 1724, 1452, 1270, 1091, 1028,
699 cmꢀ1
; dH (300 MHz CDCl3) 1.33 (d, 3H, J5,6 6.5 Hz, H-6), 3.87 (s,
2H, H-1), 3.94e3.95 (m, 1H, J4,5 0.8, J3,4 2.2 Hz, H-4), 4.21e4.22 (m,
2H, J3,4 2.2 Hz, H-2, H-3), 4.43 (dq, 1H, J4,5 0.8, J5,6 6.5 Hz, H-5), 4.43
(d, 1H, J 11.8 Hz, CH2Ph), 4.68 (d, 1H, J 11.8 Hz, CH2Ph), 7.36e7.38 (m,
5H, Ph); dC (75 MHz CDCl3) 15.3 (q, C-6), 72.3, 73.6 (2ꢂt, CH2Ph, C-
1), 76.6, 77.6, 77.8, 81.9 (all d, C-2, C-3, C-4, C-5), 127.9 (d, o-Ph),
128.0 (d, p-Ph), 128.5 (d, m-Ph), 137.5 (s, i-Ph).
4.1.9. 4-O-Benzyl- -xylo-5-hexenitol (13). A mixture of silylated
L
hexenitol 12 (461 mg, 0.967 mmol) and TBAFꢂ3H2O (671 mg,
2.127 mmol, 2.2 equiv) in THF (20 mL) was stirred at room tem-
perature for 18 h. Removal of solvents in vacuo (20 mbar) gave
a yellow oil, which was purified by flash chromatography (silica gel,
50% AcOEt/CH2Cl2). The benzyl-hexenitol 13 was obtained as
a colourless oil; yield 195 mg (85%); [found: C, 65.72; H, 7.34.
C13H18O4 requires C, 65.53; H, 7.61]; Rf (50% AcOEt/CH2Cl2) 0.15;
4.1.12. 3-O-Benzyl-1,6-dideoxy-1-iodo-2,5-anhydro- -gulitol (17). In
L
accord with the described procedure;7 dianhydro-gulitol 16
(45 mg, 0.204 mmol), trimethylsilyl chloride (33 mg, 0.306 mmol,
1.5 equiv), tetrabutylammonium iodide (150 mg, 0.449 mmol,
2.2 equiv) and concd HCl (0.08 mL) were stirred in CH2Cl2 (5 mL) at
room temperature for 3 days. The crude product, a yellowish oil,
was purified by flash chromatography (silica gel, 30% AcOEt in
toluene), and a colourless, analytically pure oil of 17 was obtained;
[
a]
26 ꢀ16.1 (c 0.223, MeOH); nmax (ATR) 3363 (br), 2927, 2871, 1720,
D
1496, 1454, 1421, 1392, 1054, 735, 698 cmꢀ1
;
dH (300 MHz CDCl3)
2.76e2.81 (m, 3H, 3ꢂOH), 3.59 (d, 1H, J 6.7 Hz, H-2), 3.64e3.72 (m,
3H, H-1, H-3), 3.98 (dd, 1H, J3,4¼J4,5 7.2 Hz, H-4), 4.35 (d, 1H, J
11.5 Hz, CH2Ph), 4.65 (d, 1H, J 11.5 Hz, CH2Ph), 5.42e5.44 (m, 2H, H-
6), 5.80 (ddd, 1H, J4,5 8.0, J5,6E 10.0, J5,6Z 17.8 Hz, H-5), 7.29e7.36 (m,
5H, Ph); dC (75 MHz CDCl3) 65.0 (t, C-1), 70.5 (t, CH2Ph), 70.5, 74.4,
81.7 (all d, C-2, C-3, C-4), 120.9 (t, C-6), 127.9 (d, p-Ph), 128.0 (d, o-
Ph), 128.6 (d, m-Ph), 134.4 (d, C-5), 137.6 (s, i-Ph).
yield 53 mg (76%); Rf (30% AcOEt/toluene) 0.4; [
a
]
25 þ12.5 (c 0.126,
D
20
MeOH){lit., [
a]
þ14.2 (c 0.6, CHCl3). The spectral data were in
D
good agreement with that reported.7
4.1.13. 4-O-Benzyl-1-deoxy-2,3-O-isopropylidene-
L
-xylo-5-hexenitol
-lyxo-5-
-lyxo-19). 4.1.13.1. Preparative procedure with NaBH4,
CeCl3$7H2O. DesseMartin periodinane (364 mg, 0.87 mmol,
1.5 equiv) was added to a solution of triols7
-lyxo-19/ -xylo-19
4.1.10. 4-O-Benzyl-1-deoxy-
L
-xylo-5-hexenitol (15). To the solution
(L
-xylo-19) and 4-O-benzyl-1-deoxy-2,3-O-isopropylidene-
L
of hexenitol 13 (176 mg, 0.738 mmol) in pyridine (15 mL) p-tolue-
nesulfonyl chloride (148 mg, 0,775 mmol, 1.05 equiv) was added at
room temperature. After 10 h stirring at rt the mixture was con-
centrated in vacuo (rotary evaporator, 50 ꢁC, 5 mbar). The residue
was dissolved in ethyl acetate (50 mL) and washed with water
(20 mL) and brine (20 mL). The solution was dried over Na2SO4
a concentrated under reduced pressure. The crude tosylated
product 14 (295 mg, yellow oil, Rf 0.7, 50% AcOEt/CH2Cl2) was dis-
solved in Et2O (5 mL) and added dropwise to a stirred suspension of
LAH (56 mg, 1.476 mmol, 2 equiv) in Et2O (10 mL) at 0 ꢁC. The re-
action mixture was then warmed to room temperature, and stirring
continued for another 10 h. Glauber salt (300 mg) was added until
the colour of the mixture changed from grey to white to quench the
excess reducing agent. The mixture was diluted with ether (50 mL)
and filtered through a Celite bed. The filtrate and washings were
combined and concentrated under reduced pressure. Purification of
the crude product by FLC (silica gel, 10% AcOEt in CH2Cl2) provided
15, 105 mg (64%), colourless oil; [found: C, 69.97; H, 8.22. C13H18O3
hexenitol (
L
L
L
(100 mg, 0.58 mmol, ratio 69:31 by GC) in dry CH2Cl2 (15 mL) at
0 ꢁC. After stirring for 2 h, saturated solution of NaHCO3 (15 mL)
and aqueous Na2S2O3 (20 mL) were added successively and stirring
was continued for another 1 h. The mixture was extracted with
CH2Cl2 (3ꢂ10 mL), washed with brine and dried (Na2SO4). The
combined organic layer was concentrated under reduced pressure
to give clear oil (98 mg). To the mixture of crude ketone 20 (98 mg)
and CeCl3$7H2O (216 mg, 0.58 mmol, 1 equiv) in MeOH (5 mL) at
ꢀ78 ꢁC was added NaBH4 (22 mg, 0.58 mmol, 1 equiv) and the re-
action mixture was stirred at the same temperature for 3 h. An
aqueous solution of NH4Cl (5 mL) was added and resulting mixture
was extracted with Et2O (3ꢂ10 mL). The combined organic phase
was dried over Na2SO4 and concentrated under reduced pressure,
to give 19 after column chromatography (silica gel, 50% AcOEt/
hexanes, 74 mg, 74% over two steps) as a mixture of diastereomers

M. Palík et al. / Tetrahedron 66 (2010) 5244e5249
5249
-lyxo-19/
-xylo-19 (25:75, 1H NMR). The spectral data were in good
L
3. (a) Alexanian, E. J.; Lee, C.; Sorensen, E. J. J. Am. Chem. Soc. 2005, 127,
7690e7691; (b) Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 7179e7181; (c)
Desai, L. V.; Sanford, M. S. Angew. Chem., Int. Ed. 2007, 46, 5737e5740; (d)
Michaelis, D. J.; Williamson, K. S.; Yoon, T. P. Tetrahedron 2009, 65, 5118e5124.
4. (a) Chevrin, C.; Le Bras, J.; Henin, F.; Muzart, J. Synthesis 2005, 2615e2618; (b)
Schultz, M. J.; Sigman, M. S. J. Am. Chem. Soc. 2006, 128, 1460e1461; (c) Thiery,
E.; Chevrin, C.; Le Bras, J.; Harakat, D.; Muzart, J. J. Org. Chem. 2007, 72,
1859e1862; (d) Zhang, Y.; Sigman, M. S. J. Am. Chem. Soc. 2007, 129, 3076e3077;
(e) Li, Y.; Song, D.; Dong, V. M. J. Am. Chem. Soc. 2008, 130, 2962e2964; Jensen,
K. H.; Pathak, T. P.; Zhang, Y.; Sigman, M. S. J. Am. Chem. Soc. 2009, 131,
17074e17075.
L
agreement with those reported.7
4.1.13.2. Typical procedure for reduction of ketone 20 (see Table 1).
Reducing agent (0.5e4 equiv) was added to the solution of crude
ketone 20 (50 mg, 0.29 mmol) in 10 mL of corresponding solvent at
chosen temperature and the mixture kept at initial temperature for
additional 3 h, then left to reach rt. Reaction was left until no 20 was
observed, but no longer than 24 h. Reactions were quenched with
satd NH4Cl (10 mL), extracted with Et2O and dried over Na2SO4.
Crude oils were analysed by 1H and 13C NMR spectroscopy.
€
5. (a) Gracza, T.; Hasenohrl, T.; Stahl, U.; Jager, V. Synthesis 1991, 1108e1118; (b)
€
Jager, V.; Gracza, T.; Dubois, E.; Hasenohrl, T.; Hümmer, W.; Kautz, U.; Kirsch-
baum, B.; Lieberknecht, A.; Remen, L.; Shaw, D.; Stahl, U.; Stephan, O. Pd(II)-
catalyzed carbonylation of unsaturated polyols and aminopolyols In Organic
Synthesis via Organometallics OSM 5; Helmchen, G., Dibo, J., Flubacher, D., Wi-
ese, B., Eds.; Vieweg: Braunschweig, 1997; pp 331e360; (c) Hümmer, W.; Du-
4.1.13.3. Typical procedure for reduction of ketone 20 in the
presence of Lewis acid. Lewis acid (1.1 mmol) was dissolved or
suspended in corresponding solvent (10 mL) and cooled to chosen
temperature. Freshly prepared ketone 20 (50 mg, 0.29 mmol) in
solvent (5 mL) was added and mixture was left to stir for 30 min.
Reducing agent (0.5e4 equiv) was added within 10 min, and the
mixture stirred at initial temperature for 3 h, then left to reach rt;
until no 20 was observed, but no longer than 24 h. Workup as de-
scribed above.
€
€
bois, E.; Gracza, T.; Jager, V. Synthesis 1997, 6, 634e642; (d) Gracza, T.; Jager, V.
€
Synlett 1992, 191e193; (e) Gracza, T.; Jager, V. Synthesis 1994, 1359e1368; (f)
Dixon, D. J.; Ley, S. V.; Gracza, T.; Szolcsányi, P. J. Chem. Soc., Perkin Trans. 1 1999,
839e841; (g) Szolcsányi, P.; Gracza, T.; Koman, M.; Pronayová, N.; Liptaj, T.
Chem. Commun. 2000, 471e472; (h) Szolcsányi, P.; Gracza, T.; Koman, M.;
Pronayová, N.; Liptaj, T. Tetrahedron: Asymmetry 2000, 11, 2579e2597; (i)
Babjak, M.; Kapitán, P.; Gracza, T. Tetrahedron Lett. 2002, 43, 6983e6985; (j)
Babjak, M.; Kapitán, P.; Gracza, T. Tetrahedron 2005, 61, 2471e2479.
6. (a) Babjak, M.; Remen, L.; Szolcsányi, P.; Zalupsky, P.; Miklos, D.; Gracza, T. J.
Organomet. Chem. 2006, 691, 928e940; (b) Babjak, M.; Remen, L.; Karlubíková,
O.; Gracza, T. Synlett 2005, 1609e1611; (c) Szolcsányi, P.; Gracza, T. Chem.
Commun. 2005, 3948e3950.
ꢀ ꢀ
7. Palík, M.; Karlubíková, O.; Lásiková, A.; Kozísek, J.; Gracza, T. Eur. J. Org. Chem.
Acknowledgements
2009, 709e715.
8. Malmstrøm, J.; Christophersen, C.; Barrero, A. F.; Oltra, J. E.; Justicia, J.; Rosales,
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9. Mayer, A. M. S.; Gustafson, K. R. Eur. J. Cancer 2004, 40, 2676e2704.
10. Clemens, R. T.; Jennings, M. P. Chem. Commun. 2006, 2720e2721.
11. Kumar, V.; Shaw, A. K. J. Org. Chem. 2008, 73, 7526e7531.
12. McAllister, G. D.; Robinson, J. E.; Taylor, R. J. K. Tetrahedron 2007, 63,
12123e12130.
This work was supported by Slovak Grant Agencies (VEGA,
Slovak Academy of Sciences and Ministry of Education, Bratislava,
projects No. 1/0115/10, No. 1/0236/09 and APVV, Bratislava, project
No. APVV-20-000305, project No. LPP-0071-09).
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