Domino reaction: Pd(II)-catalyzed cyclization of unsaturated polyols and cross-coupling

Article abstract of DOI:10.1016/j.tetasy.2012.05.020

The Pd-catalyzed cyclization and cross-coupling of hydroxylated alkenes in domino reactions are described. The alkenols undergo Pd-catalyzed cyclization and subsequent cross-coupling reactions with aryl bromides to afford (poly)hydroxylated tetrahydrofura

Full text of DOI:10.1016/j.tetasy.2012.05.020

Tetrahedron: Asymmetry 23 (2012) 818–827
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Domino reaction: Pd(II)-catalyzed cyclization of unsaturated polyols
and cross-coupling
Angelika Lásiková a, , Jana Dohánošová a,b, Lucia Hlavínová a, Martial Toffano b, Giang Vo-Thanh b,
⇑
⇑
,
ˇ
c
a,
⇑
ˇ
Jozef Kozíšek , Tibor Gracza
a Department of Organic Chemistry, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovakia
b Laboratoire de Catalyse Moléculaire, Institut de Chimie Moléculaire et des Matériaux d’Orsay, CNRS-UMR 8182, Université Paris-Sud 11, 91405 Orsay Cedex, France
c Department of Physical 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:
Received 21 March 2012
Accepted 25 May 2012
The Pd-catalyzed cyclization and cross-coupling of hydroxylated alkenes in domino reactions are
described. The alkenols undergo Pd-catalyzed cyclization and subsequent cross-coupling reactions with
aryl bromides to afford (poly)hydroxylated tetrahydrofuran derivatives. The relationship between the
stereoselectivity of the transformation and the steric and/or electronic effects of the substrates has also
been studied. The diastereoselectivity of the cyclization of c-hydroxyalkenes 1, 4–6 is influenced by the
allylic hydroxyl functionality in favor of 2,3-cis stereoselectivity. Substitution at the C-1 carbon in alken-
itols 7 and 8 ensured the formation of products with 2,5-trans diastereoselectivity (up to >19:1), indepen-
dent of additional substituents.
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
reaction between aryl or alkenyl bromides and c-hydroxy or c-ami-
noalkenes under strongly basic conditions in the presence of a
phosphine ligand. In contrast to the related Pd(II)-catalyzed
alkoxy-carbonylations, these reactions do not proceed through a
Wacker-type mechanism,7a but likely involve a rare syn-insertion
of an alkene into the Pd-O/N bond of a palladium(aryl)(alkoxide)/
(amide) intermediate followed by C–C bond-forming reductive
elimination and thus, have no previously mentioned limitations
on substrates.
The palladium(II)-catalyzed reactions of unsaturated polyols
such as oxycarbonylations1 or bicyclizations2 are powerful stereo-
selective methods for the preparation of heterocyclic structures
that are present in many natural or biologically attractive com-
pounds.3 The key intermediate of these transformations is an al-
kyl-r-Pd(II) complex A, which is trapped by carbon monoxide
and/or by cyclization with the help of a second hydroxyl function
specifically placed in the substrate to give bicyclic products B
and C (Scheme 1). As a logical consequence of that, the idea of trap-
ping intermediate A with other nucleophilic species to obtain
oxa/azaheterocyclic compounds D linked with various substituents
was raised.
Herein, we report a study of domino Wacker-cross coupling
reactions of hydroxylated alkenes and their applicability in the
stereoselective synthesis of (poly)hydroxylated tetrahydrofurans.
2. Results and discussion
In 1993, Semmelhack4 reported the trapping of an organo-Pd(II)
intermediate by alkenes in a chain extension by vinylation and
found out a suitable and efficient system for the reoxidation of
the excluded Pd(0). However, this process was limited to substrates
which could not undergo b-hydride elimination from an organo-
Pd(II) intermediate after cyclization. Later Tietze et al.5 described
the enantioselective domino Wacker–Heck reaction, which was
employed as the key step in the enantioselective total synthesis
of vitamin E5a,b and 4-dehydroxydiversonol.5c Wolfe6 et al. devel-
oped a stereoselective method for the synthesis of saturated hetero-
cycles via a Pd-catalyzed carboetherification7 and carboamination8
Our initial idea was to integrate an intramolecular Wacker-type
cyclization of unsaturated polyols into the cascade with a cross-
coupling reaction. This transformation would present a method
for the stereoselective installation of an aromatic moiety into sat-
urated heterocyclic skeletons, having a number of potential appli-
cations toward the synthesis of many natural products with an
incorporated (poly)hydroxylated tetrahydrofuran ring.
The trapping of the cyclic
r-alkylpalladium intermediate A by
organometallics or alkenes could allow the introduction of an addi-
tional C-group onto the Pd(II)-complex. We started our investiga-
tion with the premise that the coordination of Pd(II) with the
allylic hydroxyl group of the substrate (Scheme 2) might ensure
the trans-arrangement of the b-hydrogen E and thus prevent a
⇑
Corresponding authors.
E-mail address: angelika.lasikova@stuba.sk (A. Lásiková).
0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2012.05.020

A. Lásiková et al. / Tetrahedron: Asymmetry 23 (2012) 818–827
819
O
O
R
Y
CO
B
PdX2
Pdll
OH
OH
OH
O
Cu(ll)
Nu
PdX2
R
R
R
R
Y
Y
C
YH
Y = O, NP
YH
A
OH
alkyl σ-Pd(II) complex
Nu
R
Y
D
Scheme 1.
competitive b-hydride elimination F. The hydroxyl group can also
serve as a directing group and due to the potential chelation with
palladium could affect the diastereoselectivity as was observed in
similar alkoxycarbonylation reactions where the diastereoselectiv-
ity was dependent on the participation of allylic hydroxyl group in
the process.9
the transformation of model substrates 1–8 with aryl bromides
(Table 1 and Fig. 3).
We were especially interested in the compatibility of the hydro-
xyl function with the basic reaction conditions. The first experi-
ments were carried out with substrates 1–3 to examine the
effect of the possible complexation of an allylic alkoxide and palla-
dium. The desired product 12 was obtained only in the case of sub-
strate 1, but in low yield (15%) and very poor diastereoselectivity
with a slight preference for the cis-stereoisomer (1.2:1, entry 1).
Substrates 2 and 3 underwent oxidation and did not afford the tet-
rahydrofuran products (entries 2 and 3). For the successful realiza-
In order to study the domino reactions, the alkenediols 1–5 and
alkenetriols 6–8 were prepared10 (Fig. 1). The potential complexa-
tion of the
a-hydroxyl group with palladium and its influence on
the course of the reaction and diastereoselectivity were of particu-
lar interest. Therefore, the first experiments were carried out with
substrates 1–3, which contained a free
a
-hydroxyl group as a
tion of the desired transformation, the protection of the a-hydroxy
directing neighboring group under the standard reaction conditions
for a Wacker-type cyclization.11 The reactions were accomplished
with a Pd(II) salt as a catalyst in AcOH with AcONa and CuCl2 in
the presence of organometallic compounds or alkenes with electron
withdrawing substituents as coupling partners. Next, we explored
the transformation in a Pd(0)–Pd(II) redox system generating a
PdArX catalyst from Pd(0)-complexes and aryl halides in situ. How-
ever, all of these reaction conditions and modifications of redox sys-
tem (benzoquinone, O2), solvents (THF, CH3CN, CH2Cl2, ionic
liquids) and temperature did not provide the required tetra-
hydrofurans and instead gave complex mixtures of b-H elimination
and consequential products.
The desired products were only observed in the case of sub-
strate 3 by adoption of Semmelhack’s conditions4 (Scheme 3).
Product 9 was obtained as a mixture of stereoisomers and product
10 was obtained as a single diastereomer. The structure of bicycle
10 was proven by X-ray analysis12 (Fig. 2).
group appeared to be crucial. We chose tert-butyldimethylsilyl as
the protecting group because of its stability under basic conditions.
The reactions of partially silyl-protected diols 4 and 5 proceeded in
moderate yields (31–52%) and diastereoselectivity (2.3–2.6:1)
favoring the cis-diastereomer (entries 5, 6, 8 and 9). The relative
configuration of cis-15 was confirmed by X-ray analysis14 after
TBS-deprotection (Fig. 4). It is noteworthy that in the presence of
the dppb ligand the diastereoselectivity was worse (1:1.2) and
opposite to the reactions where dpe-phos and xant-phos ligands
were used (entries 4 and 7).
In continuation of our efforts to apply this reaction in the syn-
thesis of target (poly)hydroxylated tetrahydrofurans, we explored
the transformation with enantiomerically pure substrates. The
transformations of the known triol10d 6 with different aryl bro-
mides (entries 10–12) proceeded in a similar manner with good
yields (66–72%) albeit with moderate diastereoselectivity (2.3–
3:1) in favor of the 2,3-cis-stereoisomers. While the reactions of
6 with the electron-neutral and electron-rich aryl bromides (en-
tries 10 and 11) gave Heck products 23 and 24 (Fig. 5) as by-prod-
ucts (<15%), the reaction with an electron-deficient aryl bromide
(entry 12) was slower providing 19 as the sole product with
slightly higher diastereoselectivity (3:1).
A stereoselective synthesis of saturated heterocycles via Pd-cat-
alyzed carboetherification6,7 was recently published. The scope,
limitations, and stereoselectivity of this transformation were
tested on a wide range of alkyl and aryl substituted
c-hydroxy al-
kenes. We decided to adopt the described conditions and examine
OH
OH
HO
HO
PdII
R
R
R
R
R
PdII
O
O
O
O
H
H
H
cross-coupling
β-H elimination
E
F
Scheme 2.

820
A. Lásiková et al. / Tetrahedron: Asymmetry 23 (2012) 818–827
OH
OTBS
OH
OH
OH
OH
OH
OH
1
2
3
4
O
O
O
O
O
O
OH
OTBS
HO
HO
HO
Ph
Me
5
6
7
8
Figure 1. Substrates 1–8.
O
OH
OH
OH
O
O
i
O
O
+
+
O
O
O
O
3
9 (24%)
rac-10 (12%)
Scheme 3. Reagents and conditions: (i) methyl acrylate (5 equiv), Pd(OAc)2 (0.1 equiv), CuCl (1 equiv), O2, DMF (4 mL/mmol 3), rt, 56 h.
In order to enhance the diastereoselectivity of the cyclization,
the effect of the substitution at C-1 of alkenol 6 was examined. Tri-
ols 711e and 811f were synthesized by Swern oxidation of 6 followed
by the addition of Grignard reagents to pentenal 2611e,f (Scheme 7).
The inseparable mixture of alcohols syn-7/anti-7 in a ratio of 5:2.
and anti-8/syn-8 in a ratio of 2:3 were obtained, respectively.
The diastereomeric mixtures 7 and 8 were then subjected to a
domino process with 2-naphthyl bromide (Scheme 8) providing
the desired tetrahydrofurans in moderate to good yields with
excellent diastereocontrol (>19:1).
Only the 2,5-trans diastereomers (2,3-trans, 2,5-trans 20a, 21a,
and 2,3-cis, 2,5-trans 20b, 21b), were identified in the reaction mix-
tures. The formation of the 2,5-cis diastereomers was not observed.
The abundance of stereomers 20a, 20b and 21a, 21b depended on
the composition of the starting diastereomeric mixtures of 7 and 8.
The relative configuration of the tetrahydrofuran derivatives 20
Figure 2. An ORTEP12 view of the crystal and molecular structure of compound 10.
and 21 was determined by 1H NMR and NOE experiments. The
structure of diastereomer 21b was confirmed by X-ray analysis14
(Fig. 6).
The stereoselectivity observed is in contrast to the study pub-
lished in the literature,8 where the transformations of pent-4-en-
1-ol derivatives bearing an alkyl or aryl substituent at the C3-posi-
tion afforded the 2,3-trans-isomers with fair to excellent diastere-
oselectivity (1.3–20:1). The yield and the stereoselectivity were
dependent on the size of the alkyl or aryl substituent (Scheme 4).7
A possible explanation for the opposite stereochemical outcome
and lower diastereoselectivity of these transformations of model
substrates 1, 4–6 (Scheme 5) could be due to the duality of the
reaction pathway as shown in Scheme 6. The cis-preference in 5-
exo-trig cyclizations initiated by an electrophile is directed by an
allylic O-function usually with excellent diastereoselectivity
(>20:1).15 The electrophilic attack is preferred on the OH-in-plane
Apparently, a substituent at C-1 ensured high 2,5-trans- diatere-
oselectivity for the cyclization (>19:1). Additional ether substitu-
ents at C-2 and C-3 in
7 and 8 did not influence the
stereochemical course of the transformation. It seems that the ster-
eoselective formation of 2,3,4,5-tetrasubstituted tetrahydrofurans
is not effected by the allylic OR group and thus is governed by sub-
stitution at the C-1 carbon. The origin of the high diastereoselectiv-
ity is rationalized by the energy difference between the transition
states of the insertion of an alkene into Pd-O bond (Scheme 9).
3. Conclusion
conformer G (Chamberlein’s model of TS) from the face of the
p
In conclusion, we have investigated the possibility to utilize the
bond syn to the allylic hydrogen providing the cis-diastereo-
mer.15c,d On the other hand, the simultaneous insertion of the al-
kene into the Pd-O bond on conformer H (Wolfe’s model of TS)
as the trans-diastereomer formation determining step is consid-
ered to diminish the expected high cis-stereoselectivity in our
experiments.
alkyl-r-Pd(II) intermediate in domino Wacker-type cyclization
and cross-coupling reactions of hydroxylated alkenes with partici-
pation of a neighboring group. Chelation of the palladium with hy-
droxyl group at the allylic position under the reaction conditions
examined appeared to be insufficient to avoid competing b-H-
elimination. The transformation proceeds toward the desired prod-

A. Lásiková et al. / Tetrahedron: Asymmetry 23 (2012) 818–827
821
Table 1
Domino Pd(II)-catalyzed cyclization/cross-coupling reactions
R5
R4
R1
R2
R3
Time
O
OH
Ar
i
Ar-Br
R1
R2
+
R4
R3
R5
Entry
Substrate
Ar-Br
Ligand13
Product (yielda%)
dr (cis/trans)
1.2:1
1
2
3
4
5
6
7
8
1
2
3
4
4
4
5
5
5
6
6
6
2-BrNaph
2-BrNaph
2-BrNaph
2-BrNaph
2-BrNaph
2-BrNaph
2-BrNaph
2-BrNaph
2-BrNaph
2-BrNaph
dpe-phos
dpe-phos
dpe-phos
dppb
xant-phos
dpe-phos
dppb
xant-phos
dpe-phos
dpe-phos
dpe-phos
dpe-phos
dpe-phos
dpe-phos
8 h
1 d
30 h
1 d
2 h
4 h
1 d
3 h
8 h
2 h
2 h
8 h
3 h
3 h
12 (15)
13 (0)
14 (0)
15 (32)
15 (31)
15 (52)
16 (36)
—
—
1:1.2g
2.3:1g
2.6:1g
1:1.2g
1.2:1g
2:1g
16 (39b,c
16 (48d)
17 (72e)
18 (66e)
19 (72)
20 (70)
21 (46)e
)
9
10
11
12
13
14
2.5:1f
2.3:1f
3:1f
4-BrC6H4OMe
4-BrC6H4CN
2-BrNaph
syn-7/anti-7
syn-8/anti-8
>1:19f
>1:19f
2-BrNaph
Reaction conditions: (i) Ar-Br (1.5–2 equiv), tBuONa (1.5–2 equiv), Pd(dba)2 (10 mol %), ligand (12 mol %), THF (2 mL/mmol Ar-Br), 65 °C. Conversions were complete, except
in the entries marked.
a
Yield of isolated product after column chromatography on SiO2.
Heck product was isolated (<10%).
82% conversion.
95% conversion.
b
c
d
e
Heck product was isolated (<15%).
f
Dr was determined by 1H NMR of crude product.
g
Dr and conversions were determined by GC of crude product.
O
O
O
O
Naph
Naph
Naph
Naph
Naph
OTBS
OH
OH
OH
12
13
14
15
O
O
O
O
Naph
OTBS
O
O
O
O
O
O
O
CN
16
17
18
19
O
O
O
O
Ph
Ph
Naph
Naph
Naph
Naph
O
O
O
O
O
O
O
O
20a
20b
21a
21b
Figure 3. Products of the domino Pd-cyclization/cross-coupling 12–21.
ucts only on substrates with terminal unsymmetrically disubsti-
tuted alkenes.
We also explored the synthesis of (poly)hydroxylated tetra-
hydrofurans by the palladium-catalyzed reaction of aryl bromides
the tetrahydrofuran products in satisfactory yields. Substitution at
the C-1 carbon had a significant impact on the stereocontrol of
the reaction and ensured the formation of products with 2,5-trans
diastereoselectivity, independent of additional substitutions. This
suggests that the domino transformation of corresponding alkene
triols could be used in the synthesis of natural compounds such
as goniothalesdiol, varitriol, etc. and/or their analogues. The
with substituted
presence of phosphine ligands. The protection of the hydroxyl
groups, except for the -hydroxyl, is a prerequisite for obtaining
c-hydroxyalkenes under basic conditions in the
c

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A. Lásiková et al. / Tetrahedron: Asymmetry 23 (2012) 818–827
4. Experimental
All syntheses were performed using standard Schlenk tech-
niques under an argon atmosphere. Solvents were commercially
obtained at the highest commercial quality and were used without
further purification. Column chromatography was performed on
silica gel grade 60 (230–400 mesh). Analytical TLC was performed
using Silica Gel 60, F254 plates from Merck, which were visualized
by UV and phosphomolybdic acid staining. Optical rotations were
measured with a POLAR L-lP polarimeter (IBZ Messtechnik) with
Figure 4. An ORTEP14 view of the crystal and molecular structure of the
deprotected compound cis-15.
a water-jacketed 10.000 cm cell at the wavelength of sodium line
D (k = 589 nm) and 25 °C. Specific rotations are given in units of
10ꢀ1 deg cm2 gꢀ1 and concentrations are given in g/100 mL. Melt-
ing points were determined using a Büchi Melting Point B-540
instrument and are uncorrected. Fourier transform infra red spec-
tra were recorded on a Philips Analytical PU9800 FTIR spectrome-
ter or a Perkin Elmer Spectrum One FT-IR spectrometer. HRMS
were recorded on a micrOTOF-Q II (Bruker) spectrometer by elec-
trospray ionization (ESI) using tandem quadrupole coupled with
a time-of-flight mass analyzer. The 1H and 13C NMR spectra were
recorded on a Varian VXR-300 or Varian Inova 600 spectrometer;
chemical shifts (d) are given in ppm and are referenced to residual
solvent peaks. Compounds 1–6 were prepared by previously de-
scribed methods.11a–d
OH
R4
R1
R2
Ar
R3
R1, R2= Me; R3= H; R4= OTBS; Ar = 2-Naph
23 R1, R2= H; R3, R4= O-isopropylidene; Ar = 2-Naph
22
R1, R2= H; R3, R4= O-isopropylidene; Ar = 4-C6H4OMe
24
25 R1= H or Me; R2= H or Me; R3, R4= O-isopropylidene;
Ar = 2-Naph
4.1. General procedure for the addition of MeMgI to esters
Figure 5. Heck products 22–25.
An oven or flame-dried flask was purged with argon and
charged with MeMgI (23 mL, 69 mmol, 3.0 M in diethyl ether).
Additional ether was then added to provide a 1.0 M solution of
MeMgI, which was then cooled to 0 °C. The appropriate ester
(17.3 mmol) was added dropwise via syringe, and the resulting
mixture was warmed to rt and stirred for 4–5 h until the starting
cyclization of c-hydroxyalkenes without a substituent at the C-1
carbon is influenced by allylic hydroxyl functionality in favor of
2,3-cis diastereoselectivity.
O
OH
R
2
1:3 - 20:1 dr (ref.7)
78 - 55%
i
3
Ar - Br
Ar - Br
Ar
+
5
1
3
2
4
R
OH
O
i
2
+
Ar
1.5 - 2:1 dr (ref.7)
70-88%
4
R
R
R = Me, Et, Ph, t-Bu
Scheme 4. Reagents and conditions: (i) Ar-Br (2 equiv), tBuONa (2 equiv), Pd2(dba)3 (0.01 equiv), dpe-phos (0.02 equiv), THF, 65 °C.
R1
O
OH
OR2
OR3
R1
Ar
Ar
i
1.2-2.6:1 dr
R1
Ar - Br
Ar - Br
+
+
15 - 52%
R1
1, 4-5
OR2
12, 15-16
OH
O
i
2.5 - 3:1 dr
66 - 72%
OR3
R3O
17-19
OR3
6
R1 = H, CH3; R2 = H, TBS; R3 = isopropylidene
Scheme 5. Reagents and conditions: (i) Ar-Br (2 equiv), tBuONa (2 equiv), Pd(dba)2 (0.01 equiv), dpe-phos (0.02 equiv), THF, 65 °C.

A. Lásiková et al. / Tetrahedron: Asymmetry 23 (2012) 818–827
823
PdLn(Ar)(Br)
H
HO
O
H
H
LnPd(0)
ArBr
+
Ar
base
RO
-O
H
OR
RO
1, 4-6
RO
OR
OR
12
15
19
cis- , cis- - cis-
G
R = H, TBS, acetonide
Ar
O
L
L
H
H
Pd
H
H
O
HO
LnPd(0)
base
Ar
ArBr
RO
RO
H
H
OR
OR
RO
1, 4-6
OR
H
trans-12, trans-15 - trans-19
Scheme 6. Reaction pathways considered.
HO
HO
O
R
OH
R
ii or iii
i
O
O
O
O
O
O
O
O
+
26
6
R = Ph
R = Me syn-8
syn-7
(5 : 2)
(2 : 3)
anti-7
anti-8
Scheme 7. Reagents and conditions: (i) (COCl)2, DMSO, Et3N, DCM, ꢀ78 °C; (ii) (1) PhMgBr, Et2O, rt; (2) NH4Cl, H2O, 48% over two steps from 6, dr 5:2; (iii) (1) MeMgI, Et2O, rt;
(2) NH4Cl, H2O, 31% over two steps from 6, dr 2:3.
HO
O
O
R
R
R
i
Naph
+
Naph
O
O
O
O
O
O
syn-7 / anti-7 (5 : 2)
syn-8 / anti-8 (2 : 3)
20a
21a
20b
21b
(2:1)
(1:2)
Scheme 8. Reagents and conditions: (i) 2-BrNaph (2 equiv), tBuONa (2 equiv), Pd(dba)2 (10 mol %), dpe-phos (12 mol %), THF (2 mL/mmol Ar-Br), 65 °C, combined yield 70%
for 20, 46% for 21 (drs of isolated products).
(2 ꢁ 20 mL). The combined organic layers were dried over anhy-
drous Na2SO4, filtered, and concentrated in vacuo. The crude ter-
tiary alcohol product was then purified by flash chromatography
on silica gel.
4.1.1. 2-Methylhex-5-ene-2,4-diol 2
Yellowish liquid (72%); 1H NMR (300 MHz, CDCl3): d 1.26 (s,
3H), 1.34 (s, 3H), 1.55 (dd, 1H, J = 2.5, 14.6 Hz), 1.73 (dd, 1H,
J = 14.6, 10.8 Hz), 3.76 (br s, 1H), 3.96 (br s, 1H), 4.47–4.52 (m,
1H), 5.08 (d, 1H, J = 10.4 Hz), 5.24 (d, 1H, J = 17.2 Hz), 5.86 (ddd,
1H, J = 17.2, 10.4, 5.8 Hz) ppm. 13C NMR (75 MHz, CDCl3): d 27.6,
31.6, 47.5, 70.7, 71.4, 114.1, 140.9 ppm. IR (KBr):
m 3320, 2971,
Figure 6. An ORTEP14 view of crystal and molecular structure of diastereomer 21b.
1381, 1366, 1150, 989, 910, 850 cmꢀ1
.
4.1.2. 2-Methyl-4-tertbutyldimethylsilyloxy-hex-5-en-2-ol 5
Colorless liquid (74%); 1H NMR (300 MHz, CDCl3): d 0.06 (s, 3H),
0.12 (s, 3H), 0.89 (s, 9H), 1.19 (s, 3H), 1.28 (s, 3H), 1.49 (dd, 1H,
J = 14.5, 3.2 Hz), 1.81 (dd, 1H, J = 14.5, 10.4 Hz), 4.12 (br s, 1H),
4.50 (ddd, 1H, J = 10.5, 7.7, 3.2 Hz), 5.04 (d, 1H, J = 10.2 Hz), 5.12
material was found to be completely consumed as judged by TLC
analysis. A saturated solution of aqueous NH4Cl (1:1 by volume
with the reaction mixture) was added dropwise and the resulting
mixture was then diluted with ethyl acetate (70 mL). The layers
were separated, and the aqueous layer extracted with ethyl acetate

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A. Lásiková et al. / Tetrahedron: Asymmetry 23 (2012) 818–827
H
R
R
H
H
L
L
O
O
O
O
Pd
Ar
H
H
HO
Ar
O
O
R
i
favoured
L
20b, 21b
R
Ar
O
O
O
H
O
R
Pd
L
H
H
Ar
H
anti-7
anti-8
O
H
O
O
H
O
disfavoured
H
H
H
H
H
O
L
L
O
O
O
Ar
Pd
R
H
R
O
HO
Ar
O
R
i
disfavoured
H
O
O
Ar
L
H
O
Pd
H
R
L
O
Ar
R
O
syn-7
syn-8
H
O
O
H
O
20a, 21a
favoured
Scheme 9. Reagents and conditions: (i) Ar-Br (2 equiv), tBuONa (2 equiv), Pd(dba)2 (0.01 equiv), dpe-phos (0.02 equiv), THF, 65 °C.
(d, 1H, J = 17.2 Hz), 5.80 (ddd, 1H, J = 17.2, 10.2, 7.7 Hz) ppm. 13C
NMR (75 MHz, CDCl3): d ꢀ4.8, ꢀ3.3, 17.9, 25.8, 28.0, 31.1, 48.6,
the activation, bromobenzene or iodomethane (1.8 mmol) in
diethyl ether (3.5 mL) was added. The discoloration of the reaction
mixture indicated the start of reaction. The mixture was stirred at
rt until complete consumption of magnesium. To a solution of
Grignard reagent the crude aldehyde 26 (168 mg, 1.1 mmol) was
added at 0 °C. The reaction mixture was stirred for 2 h and
quenched with satd NH4Cl (10 mL). The water phase was extracted
with diethyl ether. The combined organic layers were dried over
MgSO4 and concentrated in vacuo. The crude alcohol was purified
by flash chromatography on silica gel (ethyl acetate/hexanes 1:5).
70.4, 74.1, 114.8, 141.7 ppm. IR (KBr):
m 2930, 1252, 1073, 921,
835, 776 cmꢀ1
;
HRMS (ESI): calcd for C13H28O2Si [M+Na]+
267.1756; found [M+Na]+ 267.1747.
4.2. (4R,5R)-2,2-Dimethyl-5-vinyl-1,3-dioxolane-4-carbal
dehyde 2610g–i
To a ꢀ78 °C solution of oxalyl chloride (0.55 mL, 6.4 mmol) in
dichloromethane (13 mL) was added DMSO (0.6 mL, 8.0 mmol) in
dichloromethane (1.6 mL). The reaction was stirred at ꢀ78 °C for
15 min, then alcohol 611d (500 mg, 3.2 mmol) in dichloromethane
(1.6 mL) was added. The reaction was stirred for 20 min at ꢀ78 °C
followed by the addition of triethylamine (2.7 mL, 19.2 mmol).
The mixture was stirred at ꢀ78 °C for 10 min and then allowed to
warm to 0 °C. After 30 min of stirring, the reaction was diluted with
diethyl ether (50 mL) upon which a white precipitate of triethyl-
amine hydrochloride was formed. The slurry was filtered through
a pad of celite and concentrated to afford the crude aldehyde 26
which was immediately used in the next reaction without purifica-
tion. Crude yield: 485 mg (contaminated with DMSO), volatile li-
quid. 1H NMR (300 MHz, CDCl3): d 1.45 (s, 1H); 1.63 (s, 1H); 4.42
(dd, 1H, J = 7.5, 3.1 Hz); 4.87 (t, 1H, J = 7.2 Hz); 5.33 (dt, 1H,
J = 10.4, 1.1 Hz); 5.47 (dt, 1H, J = 17.2, 1.2 Hz); 5.76 (ddd, 1H,
J = 17.2, 10.4, 7.2 Hz); 9.56 (d, 1H, J = 3.1 Hz) ppm; 13C NMR
(75 MHz, CDCl3): d 25.3, 27.3, 79.0, 82.2, 111.2, 119.7, 131.2,
4.3.1. (2S,3R)-2,3-O-Isopropylidene-1-phenyl-pent-4-en-1,2,3-
triol 710e
Colorless oil (48% over two steps from 6); dr syn-7/anti-7, 5:2.
1H NMR (600 MHz, CDCl3): d (syn-7) 1.42 (s, 3H); 1.60 (s, 3H);
2.75 (d, 1H, J = 4.6 Hz); 4.41 (dd, 1H, J = 6.5, 5.7 Hz); 4.55 (dd, 1H,
J = 7.2, 6.6 Hz); 4.64 (t, 1H, J = 4.8 Hz); 5.25 (dt, 1H, J = 10.2,
1.0 Hz); 5.29 (dt, 1H, J = 17.4, 1.1 Hz); 5.96 (ddd, 1H, J = 17.4,
10.2, 7.5 Hz); 7.32–7.40 (m, 5H) ppm; d (anti-7) 1.31 (s, 3H); 1.47
(s, 3H); 2.05 (d, 1H, J = 3.4 Hz); 4.31 (dd, 1H, J = 8.7, 6.2 Hz); 4.68
(dd, 1H, J = 8.7, 3.2 Hz); 4.75 (dd, 1H, J = 7.2, 6.2 Hz); 5.35 (dt, 1H,
J = 10.4, 1.0 Hz); 5.49 (dt, 1H, J = 17.2, 1.4 Hz); 6.16 (ddd, 1H,
J = 17.4, 10.4, 7.2 Hz); 7.32–7.40 (m, 5H) ppm; 13C NMR
(150 MHz, CDCl3): d (syn-7) 25.1, 27.5, 72.2, 78.8, 81.4, 108.9,
119.2, 127.3, 128.0, 128.3, 133.7, 140.4; d (anti-7) 25.2, 27.8,
72.4, 78.9, 80.8, 108.9, 118.3, 127.0, 128.0, 128.3, 134.1,
141.2 ppm. IR (KBr):
m .
3369, 1452, 1214, 1025, 992, 699 cmꢀ1
200.6 ppm; IR (KBr):
m .
3307, 1715, 1405, 1005, 949 cmꢀ1
4.3.2. (3S,4R)-3,4-O-Isopropylidene-hex-5-ene-2,3,4-triol 810f
Yellowish oil (31% over two steps from 6); dr anti-8/syn-8, 3:2.
1H NMR (600 MHz, CDCl3): d (anti-8) 1.28 (d, 3H, J = 6.6 Hz); 1.38
(s, 3H); 1.48 (s, 3H); 3.82–3.87 (m, 1H); 3.93 (dd, 1H, J = 9.6,
6.5 Hz); 4.66 (dd, 1H, J = 7.4, 6.5 Hz); 5.32 (ddd, 1H, J = 10.8, 1.3,
1.0 Hz); 5.44 (dt, 1H, J = 17.4, 1.3 Hz); 6.04 (ddd, 1H, J = 17.4,
4.3. General procedure for the addition of Grignard reagents to
carbaldehyde 26
A three-necked flask equipped with a condenser was filled with
magnesium chips (45 mg, 1.8 mmol) and a small iodine grain. After

A. Lásiková et al. / Tetrahedron: Asymmetry 23 (2012) 818–827
825
10.2, 7.8 Hz). d (syn-8) 1.16 (d, 3H, J = 6.6 Hz); 1.40 (s, 3H); 1.52 (s,
3H); 3.74–3.79 (m, 1H); 3.95 (dd, 1H, J = 8.2, 6.5 Hz); 4.56 (t, 1H,
J = 6.5 Hz); 5.29 (ddd, 1H, J = 10.2, 1.3, 1.0 Hz); 5.34 (dt, 1H,
J = 17.3, 1.3 Hz); 5.93 (ddd, 1H, J = 17.3, 10.2, 8.1 Hz) ppm; IR
127.5, 127.6, 127.8, 127.9, 132.2, 133.6, 136.1 ppm. HRMS (ESI):
calcd for C21H30O2Si [M+Na]+ 365.1913; found [M+Na]+ 365.1891.
4.4.5. ( )-cis/trans-3-(tert-Butyldimethylsilyloxy)-5,5-dimethyl-
2-(naphthalen-2ylmethyl)-tetrahydrofuran 16
(KBr):
m .
3367, 2960, 2924, 1259, 1016, 797 cmꢀ1
Non-separable mixture of diastereomers; 1H NMR (300 MHz,
CDCl3): d (major isomer cis-16) 0.04 (s, 3H), 0.09 (s, 3H), 0.99 (s,
9H), 1.26 (s, 3H), 1.45 (s, 3H), 1.89 (dd, 1H, J = 13.2, 2.3 Hz), 1.98
(dd, 1H, J = 13.2, 5.1 Hz), 3.10 (dd, 1H, J = 14.2, 6.7 Hz), 3.16 (dd,
1H, J = 14.2, 6.1 Hz), 4.22 (dd, 1H, J = 10.2, 6.5 Hz), 4.29 (m, 1H),
7.41–7.45 (m, 3H), 7.71–7.82 (m, 4H) ppm; 1H NMR (300 MHz,
CDCl3): d (minor isomer trans-16) ꢀ0.13 (s, 3H), ꢀ0.04 (s, 3H),
0.84 (s, 9H), 1.26 (s, 3H), 1.37 (s, 3H), 1.71 (dd, 1H, J = 12.7,
4.3 Hz), 1.87 (dd, 1H, J = 12.7, 7.0 Hz), 3.02 (d, 2H, J = 6.0 Hz, 4.08
(ddd, 1H, J = 6.8, 4.5, 4.5 Hz), 4.16–4.24 (m, 1H), 7.39–7.48 (m,
3H), 7.69–7.83 (m, 4H) ppm; 13C NMR (75 MHz, CDCl3): d (major
isomer cis-16) ꢀ5.1, ꢀ4.2, 18.2, 25.9, 29.3, 30.1, 36.3, 48.2, 74.2,
79.6, 82.9, 125.0, 125.7, 127.3, 127.4, 127.5, 127.6, 128.0, 132.0,
133.6, 137.2 ppm; 13C NMR (75 MHz, CDCl3): d (minor isomer
trans-16) ꢀ5.1, ꢀ4.7, 17.8, 25.6, 28.5, 30.1, 40.3, 47.4, 76.2, 80.4,
85.8, 125.1, 125.7, 127.5, 127.6, 127.6, 127.8, 128.3, 132.2, 133.5,
136.0 ppm. HRMS (ESI): calcd for C23H34O2Si [M+Na]+ 393.2220;
found [M+Na]+ 393.2208.
4.4. General procedure for the Pd(II) catalyzed cyclization and
cross-coupling
A flame-dried Schlenk tube was cooled under a stream of argon
and charged with Pd(dba)2 (0.1 equiv), dpe-phos (0.12 equiv),
tBuONa (2.0 equiv), and the aryl bromide (2.0 equiv) The tube
was purged with argon, and the unsaturated alcohol substrate
(1.0 equiv), and THF (4 mL/mmol aryl bromide) were added. The
reaction mixture was heated to 65 °C until the alcohol substrate
was consumed as judged by TLC. The reaction mixture was cooled
to rt and filtered through a pad of Celite. After the addition of silica
gel (1 g/mmol of alcohol substrate), the solvent was evaporated
and the crude product purified by flash column chromatography.
4.4.1. ( )-cis-2-(Naphthalen-2-ylmethyl)tetrahydrofuran-3-ol
cis-12
Recrystallization from hexane provided a white solid, mp 75–
79 °C; 1H NMR (600 MHz, CDCl3): d 1.89 (br s, 1H), 1.94 (m, 1H),
2.16 (m, 1H), 3.15 (d, 1H, J = 6.6 Hz), 3.79 (ddd, 1H, J = 9.6, 8.4,
4.8 Hz), 3.91 (ddd, 1H, J = 7.2, 7.2, 3.0 Hz), 4.10 (ddd, 1H, J = 8.4,
7.8, 7.8 Hz), 4.17 (m, 1H), 7.40–7.45 (m, 3H), 7.73 (s, 1H); 7.77–
7.80 (m, 3H) ppm. 13C NMR (150 MHz, CDCl3): d 35.3, 35.6, 65.8,
72.1, 83.8, 125.3, 125.9, 127.4, 127.5, 127.6, 127.6, 128.0, 132.2,
4.4.6. (E)-4-tert-Butyldimethylsilyloxy-2-methyl-6-(naphtha
len-3-yl)hex-5-ene-2-ol 22
Yellow oil; 1H NMR (300 MHz, CDCl3): d 0.09 (s, 3H), 0.18 (s,
3H), 0.93 (s, 9H), 1.25 (s, 3H), 1.37 (s, 3H), 1.63 (dd, 1H, J = 14.3,
3.1 Hz), 1.98 (dd, 1H, J = 14.3, 10.6 Hz), 4.27 (br s, 1H), 4.76 (ddd,
1H, J = 10.6, 8.0, 2.9 Hz), 6.27 (dd, 1H, J = 15.9, 8.0 Hz), 6.64 (d,
1H, J = 15.9 Hz), 7.44–7.48 (m, 2H), 7.58 (dd, 1H, J = 8.6, 1.7 Hz),
133.6, 136.2 ppm. HRMS (ESI): calcd for
C
15H16O2 [M+Na]+
251.1048; found [M+Na]+ 251.1038.
4.4.2. ( )-trans-(2-Naphthalen-2-ylmethyl)tetrahydrofuran-3-ol
trans-12
7.71–7.73 (m, 1H), 7.79–7.83 (m, 3H) ppm; IR (film on NaCl):
m
3516, 2959, 2930, 2857, 1471, 1257, 1150, 965, 837, 666 cmꢀ1
.
Yellowish oil; 1H NMR (600 MHz, CDCl3): d 1.78 (m, 1H), 1.96
(br s, 1H), 2.01 (m, 1H), 2.88 (dd, 1H, J = 13.8, 6.6 Hz), 2.97 (dd,
1H, J = 13.8, 7.2 Hz), 3.89 (ddd, 1H, J = 9.0, 9.0, 6.6 Hz), 3.93 (ddd,
1H, J = 8.4, 8.4, 3.6 Hz), 4.01 (ddd, 1H, J = 6.6, 6.6, 3.0 Hz), 4.11
(m, 1H), 7.35 (dd, 1H, J = 8.4, 1.8 Hz), 7.43 (m, 2H), 7.65 (s, 1H),
7.77 (m, 3H) ppm; 13C NMR (75 150 MHz, CDCl3): d 34.6, 39.9,
66.4, 75.3, 86.6, 125.4, 126.0, 127.5, 127.5, 127.6, 127.6, 128.0,
132.2, 133.5, 135.5 ppm. HRMS (ESI): calcd for C15H16O2 [M+Na]+
251.1048; found [M+Na]+ 251.1041.
4.4.7. (3R,4S)-3,4-O-Isopropylidene-2-((naphtalene-2-yl)methyl)
tetrahydrofuran-3,4-diol 17
Non-separable mixture of diastereomers; 1H NMR (300 MHz,
CDCl3): d (major isomer cis-17) 1.36 (s, 3H), 1.59 (s, 3H), 3.17
(dd, 1H, J = 13.8, 7.2 Hz), 3.25 (dd, 1H, J = 13.8, 6.5 Hz), 3.45 (dd,
1H, J = 10.8, 3.9 Hz), 3.70 (ddd, 1H, J = 6.8, 6.8, 3.5 Hz), 4.04 (d,
1H, J = 10.8 Hz), 4.57 (dd, 1H, J = 6.1, 3.6 Hz), 4.76 (dd, 1H, J = 6.1,
3.7 Hz), 7.41–7.49 (m, 3H), 7.77–7.80 (m, 4H) ppm; 1H NMR
(300 MHz, CDCl3): d (minor isomer trans-17) 1.30 (s, 3H), 1.50 (s,
3H), 2.87 (dd, 1H, J = 14.1, 6.9 Hz), 2.96 (dd, 1H, J = 14.1, 7.8 Hz),
3.96 (dd, 1H, J = 10.6, 3.6 Hz), 4.00 (dd, 1H, J = 10.6, 2.0 Hz), 4.42
(ddd, 1H, J = 7.4, 7.4, 1.6 Hz), 4.54–4.58 (m, 1H), 4.82 (ddd, 1H,
J = 6.0, 3.7, 2.2 Hz), 7.35–7.49 (m, 3H), 7.77–7.80 (m, 4H) ppm;
13C NMR (75 MHz, CDCl3): d (major isomer cis-17) 25.0, 26.2,
35.0, 72.8, 80.8, 81.0, 83.6, 112.0, 125.3, 125.8, 127.5, 127.6,
127.6, 127.8, 127.9, 132.2, 133.5, 136.0 ppm; 13C NMR (75 MHz,
CDCl3): d (minor isomer trans-17) 25.1, 26.6, 37.2, 72.0, 81.0,
84.1, 85.1, 112.8, 125.5, 126.0, 127.4, 127.5, 127.6, 127.9, 128.2,
132.2, 133.5, 135.0 ppm. HRMS (ESI): calcd for C18H20O3 [M+Na]+
307.1305; found [M+Na]+ 307.1301.
4.4.3. ( )-cis-3-(tertButyldimethylsilyloxy)-2-(naphthalen-2-
ylmethyl)tetrahydrofuran cis-15
Yellowish oil; 1H NMR (600 MHz, CDCl3): d 0.08 (s, 3H), 0.10 (s,
3H), 0.96 (s, 9H), 1.89–1.93 (m, 1H), 2.07–2.13 (m, 1H), 3.03 (dd,
1H, J = 14.3, 4.9 Hz), 3.09 (dd, 1H, J = 14.3, 8.2 Hz), 3.78 (ddd, 1H,
J = 12.8, 8.5, 4.4 Hz), 4.01 (ddd, 1H, J = 8.4, 4.9, 3.7 Hz), 4.07 (dd,
1H, J = 15.6, 8.0 Hz), 4.31–4.33 (m, 1H), 7.38–7.44 (m, 3H), 7.71–
7.79 (m, 4H) ppm; 13C NMR (150 MHz, CDCl3): d ꢀ4.9, ꢀ4.4, 18.2,
25.9, 36.0, 36.1, 66.0, 73.0, 83.8, 125.1, 125.7, 127.3, 127.5, 127.5,
127.8, 127.8, 132.1, 133.6, 137.2 ppm. HRMS (ESI): calcd for
C
21H30O2Si [M+Na]+ 365.1913; found [M+Na]+ 365.1890.
4.4.4. ( )-trans-3-(tert-Butyldimethylsilyloxy)-2-(naphthalen-2-
ylmethyl)tetrahydrofuran trans-15
4.4.8. (E)-(2S,3R)-2,3-O-Isopropylidene-5-(naphtalene-2-yl)pent
-4-ene-1,2,3-triol 23
Yellowish oil; 1H NMR (600 MHz, CDCl3): d ꢀ0.09 (s, 3H), ꢀ0.05
(s, 3H), 0.82 (s, 9H), 1.75–1.80 (m, 1H), 1.96–2.02 (m, 1H), 2.93 (dd,
1H, J = 14.0, 7.0 Hz), 2.96 (dd, 1H, J = 14.0, 6.0 Hz), 3.91 (ddd, 1H,
J = 15.2, 8.5, 7.0 Hz), 3.95 (ddd, 1H, J = 12.2, 8.2, 4.0 Hz), 4.00
(ddd, 1H, J = 6.8, 6.2, 3.7 Hz), 4.08–4.10 (m, 1H), 7.38–7.45 (m,
3H), 7.66–7.80 (m, 4H) ppm; 13C NMR (150 MHz, CDCl3): d ꢀ4.9,
ꢀ4.7, 17.9, 25.7, 35.2, 40.0, 66.8, 75.7, 86.7, 125.2, 125.8, 127.5,
1H NMR (300 MHz, CDCl3): d 1.46 (s, 3H), 1.58 (s, 3H), 3.68 (d,
2H, J = 5.5 Hz), 4.35 (dt, 1H, J = 6.6, 5.7 Hz), 4.88 (ddd, 1H, J = 7.8,
6.9, 0.8 Hz), 6.34 (dd, 1H, J = 15.9, 7.8 Hz), 6.85 (d, 1H,
J = 15.9 Hz), 7.43–7.47 (m, 2H), 7.76–7.81 (m, 4H) ppm; 13C NMR
(75 MHz, CDCl3): d 25.2, 27.8, 62.1, 78.2, 78.6, 108.9, 123.6,
124.2, 126.1, 126.4, 126.9, 127.7, 128.0, 132.1, 133.5, 134.2 ppm.

826
A. Lásiková et al. / Tetrahedron: Asymmetry 23 (2012) 818–827
4.4.9. (3R,4S)-3,4-O-Isopropylidene-2-(4-methoxybenzyl)tetra-
hydrofuran-3,4-diol 18
CDCl3): d 26.3, 26.5, 35.4, 81.7, 81.8, 84.6, 87.5, 112.6, 125.3,
125.5, 125.9, 127.3, 127.5, 127.6, 127.8, 127.9, 128.6, 132.2,
133.6, 136.1, 138.8 ppm. HRMS (ESI): calcd for C24H24O3 [M+Na]+
383.1618; found [M+Na]+ 383.1610.
Non-separable mixture of diastereomers; 1H NMR (300 MHz,
CDCl3): d (major isomer cis-18) 1.35 (s, 3H), 1.55 (s, 3H), 2.95
(dd, 1H, J = 13.8, 6.9 Hz), 3.04 (dd, 1H, J = 13.8, 6.9 Hz), 3.43 (dd,
1H, J = 10.8, 3.9 Hz), 3.55 (dt, 1H, J = 6.8, 3.6 Hz), 3.78 (s, 3H), 4.01
(d, 1H, J = 10.8 Hz), 4.53 (dd, 1H, J = 6.1, 3.5 Hz), 4.74 (dd, 1H,
J = 6.1, 3.7 Hz), 6.84 (d, 2H, J = 8.7 Hz), 7.23 (d, 2H, J = 8.7 Hz). 1H
NMR (300 MHz, CDCl3): d (minor isomer trans-18) 1.31 (s, 3H),
1.50 (s, 3H), 2.65 (dd, 1H, J = 14.1, 7.2 Hz), 2.73 (dd, 1H, J = 14.1,
7.5 Hz), 3.78 (s, 3H), 3.91 (d, 1H, J = 4.2 Hz), 3.89 (dd, 1H, J = 10.7,
4.1 Hz), 3.95 (dd, 1H, J = 10.7, 1.8 Hz), 4.25 (dt, 1H, J = 7.4, 1.6 Hz),
4.50 – 4.54 (m, 1H), 4.79 (ddd, 1H, J = 6.0, 4.1, 1.8 Hz), 6.84 (d,
2H, J = 8.7 Hz), 7.12 (d, 2H, J = 8.7 Hz); 13C NMR (75 MHz, CDCl3):
d (major isomer cis-18) 25.0, 26.1, 33.9, 55.2, 72.8, 80.7, 81.0,
83.9, 112.0, 113.8, 130.2, 130.5, 158.1; 13C NMR (75 MHz, CDCl3):
d (minor isomer trans-18) 25.1, 26.6, 36.2, 55.2, 72.0, 80.9, 84.0,
85.3, 112.8, 114.0, 130.0, 130.5, 158.2 ppm. HRMS (ESI): calcd for
4.4.14. (2R,3R,4S,5R)-3,4-O-Isopropylidene-5-methyl-2-
((naphtalene-2-yl)methyl)tetrahydrofuran-3,4-diol 21a
1H NMR (300 MHz, CDCl3): d 1.30 (s, 3H), 1.33 (d, 3H, J = 6.3 Hz),
1.48 (s, 3H), 2.84 (dd, 1H, J = 14.0, 7.8 Hz), 3.00 (dd, 1H, J = 14.0,
7.6 Hz), 4.10 (dd, 1H, J = 7.5, 3.8 Hz), 4.42 (t, 1H, J = 7.7 Hz), 4.62–
4.65 (m, 2H), 7.40–7.47 (m, 3H), 7.75–7.80 (m, 4H); 13C NMR
(75 MHz, CDCl3): d 14.0, 25.2, 26.3, 37.4, 75.8, 82.3, 84.4, 84.9,
119.8, 125.2, 125.8, 127.5, 127.6, 127.8, 127.9, 132.2, 134.5,
135.1 ppm; IR (film on NaCl):
m 3059, 2964, 1373, 1267, 1207,
1072, 749 cmꢀ1
.
HRMS (ESI): calcd for C19H22O3 [M+Na]+
321.1461; found [M+Na]+ 321.1456.
4.4.15. (2S,3R,4S,5S)-3,4-O-Isopropylidene-5-methyl-2-
((naphtalene-2-yl)methyl)tetrahydrofuran-3,4-diol 21b
Recrystallization from hexane provided a white solid mp 93–
C
15H20O4 [M+Na]+ 287.1254; found [M+Na]+ 287.1246.
4.4.10. (E)-(2S,3R)-2,3-O-Isopropylidene-5-(4-methoxybenzyl)
pent-4-ene-1,2,3-triol 24
95 °C; ½a 2D6
ꢂ
¼ þ77:2 (c 0.246, CHCl3); 1H NMR (600 MHz, CDCl3):
d 1.11 (d, 3H, J = 7.2 Hz), 1.35 (s, 3H), 1.60 (s, 3H), 3.11 (dd, 1H,
J = 13.7, 6.3 Hz), 3.25 (dd, 1H, J = 13.7, 7.2 Hz), 4.10 (dt, 1H,
J = 6.6, 3.9 Hz), 4.29 (q, 1H, J = 6.9 Hz), 4.43 (d, 1H, J = 6.0 Hz),
4.58 (dd, 1H, J = 6.0, 3.6 Hz), 7.41–7.48 (m, 3H), 7.76–7.81 (m,
4H); 13C NMR (150 MHz, CDCl3): d 16.9, 25.1, 26.4, 35.3, 79.6,
80.3, 81.2, 86.4, 112.3, 125.3, 125.8, 127.5, 127.6, 127.8, 127.9,
1H NMR (300 MHz, CDCl3): d 1.43 (s, 3H), 1.56 (s, 3H), 1.86 (t,
1H, J = 6.1 Hz), 3.65 (dd, 2H J = 5.7, 5.4 Hz), 3.81 (s, 3H), 4.31 (dt,
1H, J = 6.9, 5.4 Hz), 4.82 (ddd, 1H, J = 7.2, 7.2, 0.5 Hz), 6.08 (dd,
1H, J = 15.9, 8.1 Hz), 6.64 (d, 1H, J = 15.9 Hz), 6.86 (d, 2H,
J = 8.7 Hz), 7.33 (d, 2H, J = 8.7 Hz) ppm.
132.2, 133.5, 136.2 ppm; IR (KBr):
m 3059, 2964, 1373, 1267,
4.4.11. (3R,4S)-3,4-O-Isopropylidene-2-(4-cyanobenzyl)tetra-
hydrofuran-3,4-diol 19
1207, 1072, 749 cmꢀ1. HRMS (ESI): calcd for C19H22O3 [M+Na]+
321.1461; found [M+Na]+ 321.1456.
Non-separable mixture of diastereomers; 1H NMR (300 MHz,
CDCl3): d (major isomer cis-19) 1.35 (s, 3H), 1.55 (s, 3H), 3.03–
3.15 (m, 2H), 3.45 (dd, 1H, J = 10.8, 3.6 Hz), 3.59 (dt, 1H, J = 6.6,
3.6 Hz), 4.03 (d, 1H, J = 10.8 Hz), 4.54 (dd, 1H, J = 6.0, 3.6 Hz), 4.77
(dd, 1H, J = 6.3, 3.9 Hz), 7.43 (d, 2H, J = 8.4 Hz), 7.59 (d, 2H,
J = 8.4 Hz); 1H NMR (300 MHz, CDCl3): d (minor isomer trans-19)
1.33 (s, 3H), 1.50 (s, 3H), 2.80–2.82 (m, 2H), 3.93 (dd, 1H, J = 10.7,
3.9 Hz), 3.97 (dd, 1H, J = 10.7, 2.3 Hz), 4.22–4.27 (m, 1H), 4.49
(dd, 1H, J = 6.3, 2.1 Hz), 4.83 (ddd, 1H, J = 6.2, 3.9, 2.2 Hz), 7.33 (d,
2H, J = 8.4 Hz), 7.60 (d, 2H, J = 8.4 Hz); 13C NMR (75 MHz, CDCl3):
d (major isomer cis-19) 24.9, 26.0, 35.1, 72.8, 80.7, 81.0, 82.7,
110.2, 112.2, 119.0, 130.1, 132.1, 144.3; 13C NMR (75 MHz, CDCl3):
d (minor isomer trans-19) 25.1, 26.6, 37.2, 71.9, 80.8, 84.3, 84.6,
110.4, 113.2, 118.9, 129.9, 132.2, 143.4 ppm. HRMS (ESI): calcd
for C15H17NO3 [M+Na]+ 282.1101; found [M+Na]+ 282.1089.
4.4.16. (E)-(3S,4R)-3,4-O-Isopropylidene-6-(naphthalene-2-
yl)hex-5-ene-2,3,4-triol 25
1H NMR (300 MHz, CDCl3): d (major isomer) 1.20 (d, 3H,
J = 6.3 Hz), 1.46 (s, 3H), 1.60 (s, 3H), 3.87 (qi, 1H, J = 6.2 Hz), 4.03
(dd, 1H, J = 6.3, 4.3 Hz), 4.81 (ddd, 1H, J = 8.4, 6.6, 0.5 Hz), 6.40
(dd, 1H, J = 15.8, 8.5 Hz), 6.81 (d, 1H, J = 15.8 Hz), 7.45–7.48 (m,
2H), 7.62–7.63 (m, 1H), 7.76–7.82 (m, 4H) ppm; 1H NMR
(300 MHz, CDCl3): d (major isomer) 1.31 (d, 3H, J = 6.1 Hz), 1.44
(s, 3H), 1.56 (s, 3H), 3.96 (q, 1H, J = 6.2 Hz), 4.22 (dd, 1H, J = 5.9,
3.7 Hz), 4.90 (ddd, 1H, J = 7.4, 6.3, 0.9 Hz), 6.49 (dd, 1H, J = 15.9,
7.8 Hz), 6.89 (d, 1H, J = 15.9 Hz), 7.45–7.48 (m, 2H); 7.59–7.60
(m, 1H); 7.76–7.82 (m, 4H) ppm.
Acknowledgments
4.4.12. (2R,3R,4S,5R)-3,4-O-Isopropylidene-5-phenyl-2-
((naphthalene-2-yl)methyl)tetrahydrofuran-3,4-diol 20a
This work was supported by Slovak Grant Agencies (VEGA, Slo-
vak Academy of Sciences and Ministry of Education, Bratislava,
project No. 1/0236/09, APVV-0203-10, 1/0679/11 and ASFU, Brati-
slava, ITMS project No. 26240120001). We would like to thank ‘le
conseil général de l’Essonne’ for funding for the acquisition of THAR
SFC analysis apparatus, the University Paris-Sud 11 and the French
½
a 2D5
ꢂ
¼ ꢀ19:5 (c 0.83, CHCl3); 1H NMR (600 MHz, CDCl3): d 1.22
(s, 3H), 1.42 (s, 3H), 2.96 (dd, 1H, J = 14.1, 8.1 Hz), 3.12 (dd, 1H,
J = 14.1, 7.2 Hz), 4.63 (t, 1H, J = 7.5 Hz), 4.75 (d, 1H, J = 5.9 Hz),
4.84 (dd, 1H, J = 5.9, 3.8 Hz), 5.05 (d, 1H, J = 3.8 Hz), 7.27–7.46 (m,
8H), 7.68–7.81 (m, 4H); 13C NMR (150 MHz, CDCl3): d 24.8, 26.1,
37.3, 82.0, 82.6, 84.6, 84.6, 112.6, 125.5, 126.0, 127.4, 127.5,
127.6, 127.7, 127.8, 127.9, 128.3, 132.3, 133.6, 134.9, 136.1 ppm.
ˇ
Embassy for financial support for J. Dohánošová stay in Orsay.
C
24H24O3 [M+Na]+ 383.1618; found
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[M+Na]+ 383.1604.
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13. Ligand
abbreviations:
dppb = 1,4-bis(diphenylphosphino)butane;
xanthphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxantene;
phos = bis(2-diphenylphosphinophenyl)ether.
dpe-
14. CCDC-88254 (for cis-15) and CCDC-882585 [for compound 21b] contain the
supplementary crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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