Di- and tetrahydropyrans with orthogonally protected hydroxymethyl side chains: A synthetic route and the structure elucidation of an unexpected acetal cleavage product

Article abstract of DOI:10.1016/S0040-4020(02)00913-4

A synthesis of dihydropyrans with orthogonally protected hydroxymethyl side chains is presented in this contribution. Key steps of the synthesis are the regioselective epoxide opening using vinyl cuprate reagents, selective protection of primary alcohols

Full text of DOI:10.1016/S0040-4020(02)00913-4

Tetrahedron 58 (2002) 7951–7958
Di- and tetrahydropyrans with orthogonally protected
hydroxymethyl side chains: a synthetic route and the structure
elucidation of an unexpected acetal cleavage product
a,*
a
Bernd Schmidt, Michael Pohler and Burkhard Costisella
b
a
Fachbereich Chemie der Universit a¨ t Dortmund, Organische Chemie, Fachbereich Chemie der Universit a¨ t Dortmund, Organische Chemie,
Otto-Hahn-Straße 6, D-44227 Dortmund, Germany
Gemeinsame Einrichtungen—NMR-Spektroskopie, Otto-Hahn-Straße 6, D-44227 Dortmund, Germany
b
Received 23 April 2002; revised 28 June 2002; accepted 22 July 2002
Abstract—A synthesis of dihydropyrans with orthogonally protected hydroxymethyl side chains is presented in this contribution. Key steps
of the synthesis are the regioselective epoxide opening using vinyl cuprate reagents, selective protection of primary alcohols and ring closing
metathesis. A strategy based on the intermediate formation of a rigid bicyclic acetal turned out to be unsuccessful due to the unexpected
formation of an annellated furanopyran rearrangement product 6. Elucidation of the structure was achieved using one- and two-dimensional
NMR-methods. q 2002 Elsevier Science Ltd. All rights reserved.
1
. Introduction
In this contribution we describe approaches to dihydro-
pyrans with differentiated hydroxymethyl side chains.
These are based on concepts for the synthesis of densely
functionalized di- and tetrahydropyrans developed over the
The synthesis of di- and tetrahydropyrans with two adjacent
hydroxymethyl side chains has attracted some interest in
natural products chemistry and especially in carbohydrate
chemistry. For example, pyranoses containing a substituent
at the C4 position have been used as building blocks
1
5
past few years in our laboratory.
1
–4
5,6
for bridged disaccharides,
1-methyl-carbapenems and
7
nucleoside analogues. Fried et al. investigated the use
of glycosides containing an alkoxymethyl side chain in the
C4-position for the synthesis of analogues of throm-
2. Results and discussion
2.1. Investigation of the rigid bicyclic acetal pathway
8
,9
10
boxanes.
Apart from the thromboxanes, there is a
variety of other interesting target molecules containing a
tetrahydropyran core with two different adjacent func-
We have previously described the acetal protected cyclic
enol ether 4, which is available from epoxide 3 in five
steps. Following the concept outlined above, we planned
to use 4 as a precursor for 2. For this purpose, the hydroxy
functionality in 4 was protected as an allyl ether 5a, which
was then treated with methanol and p-TSA to deprotect the
1
1
15
tionalized side chains, e.g. phospholine, the leustro-
1
2
13
ducsins and pironetin. The structural pattern in
question and its synthetic challenge is outlined in Scheme
1
for thromboxane A : a cyclic enol ether such as 1 would be
2
ideally suited as a starting material for thromboxanes and
structurally related compounds. If the three protecting
1
–3
1
groups PG
2
are orthogonal, subsequent removal of PG
and PG , followed by elaboration of the side chain, should
1
2
be possible. If PG and PG are non-orthogonal protecting
groups, a differentiation of the hydroxymethyl side chains
might be achieved by deprotection of both primary alcohols
and conversion of the deprotected intermediate to the rigid
bicyclic acetal 2. Related approaches start from levogluco-
sane which is converted to intermediates with C4 side
1
0,14
chains.
Keywords: tetrahydropyrans; dihydropyrans; furanopyran.
*
Corresponding author. Fax: þ49-231-755-5363;
e-mail: bschmidt@chemie.uni-dortmund.de
Scheme 1.
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00913-4

7952
B. Schmidt et al. / Tetrahedron 58 (2002) 7951–7958
Scheme 3. Mechanistic proposal for the formation of 6.
0
H6 , to H4 and to the CHOH signal. This is indicative for the
assigned relative configuration, where H4, H5 and CHOH
are on the same face of the molecule. A weak interaction
between H2 and H6 suggests the relative configuration at
C2. Important NOE interactions are summarized in Fig. 1,
where the numbering scheme used here is illustrated.
Scheme 2. (i) NaH, allyl bromide, THF, 658C (71%); (ii) Ac
DMAP, DCM, 08C (57%); (iii) MeOH, p-TSA, DCM (61%).
2 3
O, NEt ,
primary alcohols. Under the same conditions, we hoped to
achieve an intramolecular acetalization giving the desired
bicyclic acetal 2 (Scheme 2).
Obviously, the allyloxy group serves as a leaving group in
this case, thus, a similar outcome should be observed if the
allyl moiety in 5a is substituted by an acetyl group as in 5b.
Indeed, the same rearrangement product 6 results from 5b
upon treatment with methanol and p-TSA. In this experi-
ment, a very small amount of a methyl acetal 7 was isolated,
From the reaction mixture a single product was isolated in
fair yield, which, however, obviously was not the bicyclic
acetal 2. All signals for the allyloxy moiety are missing in
the NMR-spectra, instead 1 equiv. of methanol was
incorporated into the molecule. Additionally, for a bicyclic
acetal such as 2 a dH value for the acetal proton of
1
7,18
resulting from a Ferrier rearrangement.
It is not clear whether 7 is an intermediate in the formation
of 6 or a byproduct, however, based on this observation one
possible mechanistic scenario could be the following
(Scheme 3): in the first step, a Ferrier rearrangement and
cleavage of the acetal occur (1), followed by cleavage of the
methyl acetal ((2), attack of an additional equivalent of
methanol at C6). Finally, an unsaturated oxocarbenium ion
is formed by acid catalyzed abstraction of 1 equiv. of
methanol, followed by formation of the C4–O bond and the
C6–O bond (3).
1
6
approximately 5.5 ppm has to be expected. We observed a
d value of 4.63 ppm, which, together with a d value of
H
C
9
8.3 ppm is indicative for the presence of a methyl acetal
moiety. The combined use of H,H-correlation spectroscopy,
H,C-correlation spectroscopy and H,C-long range corre-
lation spectroscopy unrevealed the presence of a secondary
2
alcohol and two –CH O– moieties ( J values of 12.2 and
2
9
.5 Hz). The value of 12.2 Hz is indicative for a tetra-
hydropyran system, while a value of 9.5 Hz suggests the
presence of a tetrahydrofuran ring. From the spectroscopical
information and the HRMS data, we conclude that the
product has a furanopyran structure 6.
2.2. The OBn/OTBS-protecting group combination
Starting from Z-butene-diol (8), the monoprotected alcohol
1
9
9
was obtained following a procedure described in the
0
2
The relative configuration of 6 was elucidated by selective
1D NOE-experiments using shaped pulses and pulsed field
gradients. H5 shows NOE effects to both protons H6 and
literature for the corresponding p-bromobenzyl ether.
was epoxidized with MCPBA to give the epoxide 10,
9
2
1
which was converted to the homoallylic alcohol 11 in high
regio- and diastereoselectivity by reaction with a cuprate
reagent derived from vinyl magnesium chloride and copper
iodide. If catalytic amounts of CuI are employed in the
reaction, a complex mixture of products results, with the
corresponding chlorohydrin being a major component. This
finding is in contrast to observations recently reported by
2
0
Jung et al. for a closely related reaction, where a vinyl
cuprate reagent derived from vinyl magnesium bromide and
catalytic amounts of copper iodide was successfully used to
prepare a homoallylic alcohol from the corresponding
epoxide. In the next step, the primary alcohol in 11 had to
be protected selectively with a protecting group orthogonal
Figure 1. Selected NOE-interactions in 6.

B. Schmidt et al. / Tetrahedron 58 (2002) 7951–7958
7953
Figure 2. First (A) and second (B) generation Grubbs’ catalyst.
to the benzyl group. Using the TBS group allows selective
protection of the primary alcohol and selective deprotection.
In the next step, allylation of the diprotected homoallylic
alcohol 12 had to be achieved. It is known that TBS groups
are often unstable at ambient temperature in the presence of
2
2
strongly basic reagents such as NaH. We were able to
avoid any scrambling of protecting groups by conducting
the allylation at 08C using NaH and allyl bromide. Ring
closing metathesis of the allylation product 13, catalyzed by
the ruthenium complex A (Fig. 2), is a facile process,
leading to the dihydropyran 14. At this step, we wanted to
confirm the assumed location of the protecting groups in 14
(
and hence the regioselectivity of the epoxide cleavage) by
NMR-methods. Unfortunately, the NMR-spectra of 14 were
not suited for this purpose due to overlapping signals in the
ether region. To avoid this difficulty, the TBS group was
cleaved off to leave the monoprotected dihydropyran 15
behind, which showed sufficiently separated signals in the
ether region of the H NMR-spectrum to allow a complete
signal assignment. NOE interactions between H4 and the
CH OH moiety and a coupling between H3 and the CH OH
Scheme 5. (i) TBSCl, NEt
t-BuOOH in decane, DCM, 408C (87%); (iii) CuI, H
68%); (iv) t-BuCOCl, NEt , DMAP, DCM (97%); (v) NaH, allyl bromide,
THF, 08C; (vi) H CvCHCOCl, NEt , DMAP, 08C (80%); (vii) B
(5 mol%), toluene, 1108C (84%).
3
, DCM (71%); (ii) VO(acac)
2
(5 mol%),
2
CvCHMgCl, 2408C
(
3
2
3
2.3. The OTBS/OPiv protecting group combination
2
2
substituent (observed in the H,H-COSY) are indicative for
the location of the protecting groups. As an example for
selective functionalization of the double bond in 14, we
investigated the osmium catalyzed dihydroxylation. Diol 16
is formed with a diastereomeric ratio of 7:1, the major
diastereomer results from attack trans to the substituent at
C3 (Scheme 4).
2
3
Monoprotected silyl ether 17 was prepared from diol 8.
Epoxidation of 17 was achieved using catalytic amounts of
VO(acac)2 and t-butyl hydroperoxide to give 18. This
method appeared to be superior to the use of MCPBA in our
hands. Epoxide opening with vinyl cuprate reagent gives the
diol 19 in good yield and selectivity. The primary alcohol in
19 was selectively protected as a pivaloate. Unfortunately,
attempted allylation under the conditions described above
for the preparation of 13 did not give 21. Instead, a complex
mixture of products is formed, with two major products
probably being the desired 21 and a regioisomer. Further-
more, products containing no pivaloate group appear to be
present in the mixture. This observation is in accord with
2
4
reports in the literature that pivaloates might be cleaved in
the presence of sodium alkoxides. Formation of the
corresponding acrylate 22 from 20 proceeded smoothly in
good yield. Ring closing metathesis of acrylates to
2
5–27
unsaturated lactones has been investigated recently.
This process is not straightforward compared to the
cyclization of simple allyl ethers, because inhibition of the
catalyst by coordination will occur if the first generation
2
8
Grubbs’ catalyst is used. This problem can be circum-
2
9
vented either by addition of a Lewis acid or by using the
3
0,31
second generation ruthenium catalyst B (Fig. 2).
Thus,
in the presence of 5 mol% B the acrylate 22 was smoothly
converted to the lactone 23 at elevated temperatures
(Scheme 5). The location of the protecting groups in 23
was also checked using two-dimensional NMR-methods.
Scheme 4. (i) NaH, THF, benzyl bromide, 08C (88%); (ii) MCPBA, DCM
(
(
88%); (iii) CuI, H
76% of 12); (v) NaH, allyl bromide, THF, 08C (89%); (vi) A (3 mol%),
Os(OH) (4.6 mol%), NMO
2 3
CvCHMgCl, 2408C (66%); (iv) TBSCl, NEt , DMAP
In conclusion, we have developed synthetic approaches to
dihydropyrans with orthogonally protected hydroxymethyl
side chains that are promising intermediates in the synthesis
DCM (97%); (vii) TBAF, THF (51%); (viii) K
65%).
2
6
(

7954
B. Schmidt et al. / Tetrahedron 58 (2002) 7951–7958
p
p
p
of interesting target molecules containing the bishydroxy-
methyl di- or tetrahydropyran core. In the course of this
project we discovered an interesting and unexpected
rearrangement reaction and achieved the structural eluci-
dation of the reaction product using modern one- and
two-dimensional NMR-methods.
3.1.2. (4S ,4aS ,9aS )-4-Acetoxy-7,7-dimethyl-4a,5,9,
9a-tetrahydro-4H-1,6,8-trioxabenzocycloheptene (5b).
To a solution of the alcohol 4 (200 mg, 1.0 mmol) and
acetic anhydride (0.15 mL, 1.5 mmol) in dry DCM (10 mL)
was added at 08C triethyl amine (0.50 mL, 2.5 mmol) and
DMAP (12 mg, 0.1 mmol). The mixture was stirred at
ambient temperature for 6 h, after which time the starting
material was fully consumed as indicated by TLC. After
aqueous workup the residue was purified by column
3. Experimental
1
chromatography to give the ester 5b (138 mg, 57%). H
3
.1. General
NMR (400 MHz, CDCl
.05 (dd, 1H, J¼5.8, 5.5 Hz, H5), 3.85–3.55 (6H, OCHH,
H2, H4), 2.01 (s, 3H, OvCCH
), 1.87 (dddd, 1H, J¼10.5,
10.5, 3.8, 3.8 Hz, H3), 1.34 (s, 3H, Me), 1.33 (s, 3H, Me).
3
): d 6.50 (d, 1H, J¼5.6 Hz, H6),
5
All experiments were conducted in dry reaction vessels in
an atmosphere of dry argon. Solvents were purified by
3
1
13
standard procedures. H NMR spectra were recorded at 200,
4
C NMR (100 MHz, CDCl ): d 170.5 (0), 148.0 (1), 101.3
3
00, 500, or 600 MHz in CDCl3 or C D with CHCl
3
(0), 101.1 (1), 72.6 (1), 65.4 (1), 62.8 (2), 59.4 (2), 43.7 (1),
24.8 (3), 24.7 (3), 21.1 (3). IR (NaCl, neat): 2962 (s), 1741
6
6
(
d¼7.24) or C D H (d¼7.18) as internal standard. Coupling
6
5
1
3
21
þ
constants are given in Hz. C NMR spectra were recorded
at 50, 100, 125 or 150 MHz in CDCl or C D with CDCl
3
(s), 1640 (s), 1081 (s) cm . MS (EI): m/z 242 (M , 5%),
169 (25), 153 (25), 94 (100), 66 (40).
3
6
6
(
d¼77.0 ppm) or C D (d¼128.0 ppm) as internal standard.
6
6
p
p
p
p
The number of coupled protons was analyzed by DEPT or
APT experiments and is denoted by a number in parentheses
following the dC value. Signal assignment for cyclic
products follows a numbering scheme where the oxygen
atom is numbered 1 and the a-carbon atom bearing a
substituent C2 (see Scheme 1). Selective 1D NOE
experiments were conducted using shaped pulses and
pulsed field gradients at 600 MHz with a mixing time of
3.1.3. (3S ,3aR ,6R ,7aR )-6-Methoxy-hexahydro-furo-
[3,2]pyran-3-ol (6). To a solution of 5a (110 mg,
0.46 mmol) and methanol (0.20 mL, 5.0 mmol) in DCM
(5 mL) was added at ambient temperature p-toluene sulfonic
acid (p-TSA) (10 mg, 0.05 mmol). The mixture was stirred
for 15 h and then washed with aqueous NaHCO solution.
3
The aqueous layer was thoroughly extracted with ethyl
acetate and the combined organic extracts were dried with
8
00 ms. 2D NOESY-spectra were obtained at 500 MHz
MgSO . After column chromatography on silica using
4
with a mixing time of 1.5 s. IR spectra were recorded as
films on NaCl or KBr plates. The peak intensities are
defined as strong (s), medium (m) and weak (w). Mass
spectra were obtained at 70 eV. References for known
compounds are given with the experimental procedures.
cyclohexane/ethyl acetate mixtures as eluent, 6 (50 mg,
61%) was isolated. Analogously, 5b (130 mg, 0.54 mmol)
can be converted to 6 (38 mg, 41%). Varying amounts of 7
(approximately 10%) can be isolated in these experiments.
1
H NMR (600 MHz, C
D
): d 4.63 (dd, 1H, J¼6.6, 4.8 Hz,
6
6
3
2
The ruthenium catalyst Cl (Cy P) RuvCHPh (A) was
2
H2), 4.04 (m, 1H, CHOH), 3.84 (dd, 1H, J¼9.5, 2.2 Hz,
OCHH), 3.83 (ddd, 1H, J¼7.7, 4.4, 4.4 Hz, H4), 3.78 (dd,
1H, J¼12.1, 3.3 Hz, H6), 3.71 (dd, 1H, J¼12.1, 4.4 Hz,
H6), 3.44 (dd, 1H, J¼9.5, 5.1 Hz, OCHH), 3.17 (s, 3H,
OMe), 2.77 (d, 1H, J¼7.7 Hz, H4), 2.19 (ddd, 1H, J¼14.7,
4.8, 4.8 Hz, H3), 1.72 (ddd, 1H, J¼14.7, 6.6, 4.4 Hz, H3),
3
2
purchased from Fluka, the second generation catalyst B was
3
prepared following a literature procedure.
1
p
p
p
3
9
.1.1. (4S ,4aS ,9aS )-4-Allyloxy-7,7-dimethyl-4a,5,9,
a-tetrahydro-4H-1,6,8-trioxabenzocycloheptene (5a).
1
5
13
To a solution of the alcohol 4 (340 mg, 1.7 mmol) and
allyl bromide (0.19 mL, 2.2 mmol) in dry THF (10 mL) was
added NaH (60% dispersion in mineral oil, 102 mg,
1.62 (dddd, 1H, J¼7.7, 7.7, 4.4, 3.7 Hz, H5). C NMR
(100 MHz, C D ): d 98.3 (1, C2), 75.3 (2, OCH ), 74.3 (1,
6 6 2
C-OH), 73.6 (1, C4), 58.0 (2, C6), 54.9 (1, C2), 40.8 (1, C5),
2
1
2
.5 mmol). The mixture was stirred at ambient temperature
32.3 (C3). IR (film): 3444 (s, br.), 2929 (s), 1044 (s) cm .
MS (EI): m/z 173 (M 21, 100%), 143 (25), 113 (25), 96
þ
(20), 83 (65), 81 (45), 69 (100), 57 (45), 55 (80), 53 (40).
for 24 h. After this time the starting material was fully
consumed as indicated by TLC. After aqueous workup the
residue was purified by column chromatography to give the
þ
173.081, found 173.081. Spectroscopic data for 7 (1:1
HRMS (EI, 70 eV): calcd for C
H
13
O
(M 2H): m/z
8
4
1
ether 5a (290 mg, 71%). H NMR (400 MHz, CDCl ): d
3
1
6
5
.47 (d, 1H, J¼6.3 Hz, H6), 5.86 (dddd, 1H, J¼17.0, 10.6,
mixture of diastereomers): H NMR (500 MHz, CDCl ):
3
.0, 4.8 Hz, CHvCH ), 5.23 (ddm, 1H, J¼17.0, 1.5 Hz,
d 6.08–6.00 (1H, H4/H5), 5.84–5.76 (1H, H4/H5), 4.80
(s, br., 1/2H, H6), 4.76 (d, 1/2H, J¼2.5 Hz, H6), 4.18
(‘q’, 1/2H, J¼7.0 Hz, H2), 4.01–3.89 (2H, –CHHO–), 3.80
(dd, 1/2H, J¼8.0, 7.0 Hz, H2), 3.79–3.59 (2H, –CHHO–),
3.40 (s, 3/2H, OMe), 3.39 (s, 3/2H, OMe), 2.55 (m,
2
CHHvCH), 5.13 (ddm, 1H, J¼10.6, 1.5 Hz, CHHvCH),
5
5
3
.02 (dd, 1H, J¼6.3, 5.0 Hz, H5), 4.07 (ddm, 1H, J¼12.8,
.0 Hz, OCHHCHv), 3.91–3.72 (6H, OCHH, H2, H4),
.62 (dd, 1H, J¼12.6, 3.5 Hz, OCHH), 1.73 (dddd, 1H,
J¼10.8, 10.8, 3.4, 3.4 Hz, H3), 1.32 (s, 3H, CH ), 1.32 (s,
1/2H, H3), 2.12 (m, 1/2H, H3), 1.42 (s, 3/2H, Me), 1.39
3
1
3
13
3
H, CH ). C NMR (100 MHz, CDCl ): d 146.7 (1), 135.2
3
(s, 3/2H, Me), 1.33 (s, 3/2H, Me), 1.31 (s, 3/2H, Me).
NMR (125 MHz, CDCl ): d 129.9, 129.3, 127.0, 126.6
3
C
3
(
(
1), 116.4 (2), 101.1 (1), 100.6 (0), 72.5 (1), 68.7 (2), 67.7
1), 63.0 (2), 60.3 (2), 45.1 (1), 24.7 (3), 24.6 (3). IR (NaCl,
(1), 97.2, 97.2 (0), 95.1, 94.6 (1), 75.7, 75.7 (1), 67.5,
66.8, 58.8, 58.0 (2), 55.3, 55.3 (3), 38.0, 37.0 (1), 26.7, 26.5,
25.4, 25.2 (3). GC–MS (EI): first diastereomer m/z 213
neat): 2990 (m), 2942 (m), 2821 (m), 1637 (s), 1381 (m),
2
1
1
2
372 (m), 1220 (s), 1081 (s), 839 (m) cm . MS (EI): m/z
þ
þ þ
39 (M 21, 20%), 183 (50), 125 (85), 99 (100). Anal. calcd
(M 2H, 5%), 183 (65, M 2OMe), 101 (100); second
þ
þ
for C H O : C, 65.0%; H, 8.4%; found: C, 64.9%; H,
1
diastereomer m/z 213 (M 2H, 7%), 183 (100, M 2OMe),
101 (65).
3 20 4
8
.3%.

B. Schmidt et al. / Tetrahedron 58 (2002) 7951–7958
7955
1
3
3
pound
.1.4. (Z)-4-Benzyloxy-but-2-en-1-ol (9). The title com-
9
2.35 (dddd, 1H, J¼9.0, 7.5, 6.0, 4.2 Hz, CH–Vn). C NMR
1
was prepared following a slightly modified
procedure published for the corresponding p-bromo benzyl
(100 MHz, CDCl ): d 137.7 (0), 134.6 (1), 128.4 (1), 127.7
3
(1), 127.7 (1), 118.7 (2), 73.3 (2), 72.7 (2), 70.8 (1), 64.0 (2),
48.7 (1).
2
0
ether. To a suspension of NaH (60% dispersion in mineral
oil, 4.80 g, 120 mmol) in THF (400 mL) was added
Z-butene-1,4-diol (49.4 mL, 600 mmol) at 08C. The mixture
was warmed to ambient temperature, and stirring was
continued for 30 min. After this time, benzyl bromide
p
p
3.1.7. (2S ,3R )-1-Benzyloxy-3-(t-butyldimethyl-silanyl-
oxymethyl)-pent-4-en-2-ol (12). To a solution of 11
(2.60 g, 11.7 mmol) and TBSCl (1.96 g, 13.0 mmol) in
DCM (120 mL) was added triethyl amine (1.80 mL,
13.0 mmol), followed by DMAP (150 mg, 1.2 mmol). The
mixture was stirred at ambient temperature for 24 h, washed
with water, dried with MgSO , filtered and the solvent was
4
evaporated. The residue was purified by flash chroma-
tography on silica using cyclohexane/MTBE mixtures as
(
11.9 mL, 100 mmol) was added. The reaction mixture was
stirred for 20 h at ambient temperature. After evaporation of
the THF the residue was taken up in ether (250 mL) and
washed with water (4£100 mL). The organic layer was
dried with MgSO , filtered and the solvent evaporated. The
4
crude product was distilled (bp 978C, 0.25 mbar) to yield 9
1
1
(
15.6 g, 88%). H NMR (400 MHz, CDCl ): d 7.29–7.24
3
eluent, to give 12 (3.00 g, 76%). H NMR (400 MHz,
CDCl ): d 7.34–7.30 (5H, Ph), 5.89 (ddd, 1H, J¼17.3, 10.3,
(
1
5H, Ph), 5.71 (dt, 1H, J¼11.2, 6.0 Hz, HCvCH), 5.64 (dt,
3
H, J¼11.2, 6.0 Hz, HCvCH), 4.44 (s, 2H, OCH Ph), 4.05
9.0 Hz, CHvCH ), 5.14 (dd, 1H, J¼10.3, 2.0 Hz,
2
2
(d, 2H, J¼6.0 Hz, OCH HCv), 4.00 (d, 2H, J¼6.0 Hz,
OCH CHv), 2.83 (s, br., 1H, OH). C NMR (100 MHz,
CHHvCH), 5.09 (dd, 1H, J¼17.3, 2.0 Hz, CHHvCH),
4.55 (d, 1H, J¼11.8 Hz, CHH–Ph), 4.50 (d, 1H, J¼11.8 Hz,
CHH–Ph), 4.09 (m, 1H, CHOH), 3.76 (dd, 1H, J¼9.8,
6.0 Hz, OCHH), 3.72 (dd, 1H, J¼9.8, 4.5 Hz, OCHH),
2
1
3
2
CDCl ): d 137.6 (0), 132.3 (1), 128.3 (1), 127.6 (1), 127.6
3
(
1), 72.2 (2), 63.4 (2), 58.1 (2).
3
.48–3.44 (dd, 2H, OCHH), 2.93 (s, br., 1H, OH), 2.33 (m,
p
.1.5. ((2S ,3R )-3-Benzyloxymethyl-oxiranyl)-metha-
p
13
3
1H, CH–Vn), 0.87 (s, 9H, t-Bu), 0.03 (s, 6H, SiMe2).
NMR (100 MHz, CDCl ): d 138.1 (0), 135.0 (1), 128.4 (1),
C
2
1
nol (10). To a solution of 9 (3.56 g, 20 mmol) in DCM
50 mL) was added MCPBA (70% dispersion in water,
.40 g, 30 mmol). After 1 h the starting material was
3
(
7
127.7 (1), 127.6 (1), 118.0 (2), 73.3 (2), 72.8 (2), 71.0 (1),
65.5 (2), 48.0 (1), 25.8 (3), 18.2 (0), 25.6 (3), 25.6 (3). IR
(film): 3481 (br w), 2961 (s), 2921 (s), 2865 (s), 1653 (w),
1472 (m), 1256 (s), 1097 (s), 1005 (m), 837 (s), 777
completely converted and the reaction was quenched by
addition of saturated Na SO solution (30 mL). The mixture
was diluted with ether, the organic layer was separated,
2
3
(s) cm2 . MS (EI): m/z 337 (M , 5%), 91 (100), 75 (25).
1
þ
dried with MgSO , filtered and the solvent was evaporated
4
Anal. calcd for C H O Si: C, 67.8%; H, 9.6%; found: C,
19 32 3
67.7%; H, 9.6%.
to give the epoxide 10 (3.41 g, 88%), which was sufficiently
1
pure for preparative purposes. H NMR (400 MHz, CDCl ):
3
p
p
d 7.37–7.25 (5H, Ph), 4.59 (d, 1H, J¼11.8 Hz, CHH–Ph),
3.1.8. [(R )-2-((S )-1-Allyloxy-2-benzyloxyethyl)but-3-
enyloxy]-t-butyldimethylsilane (13). To a solution of 12
(1.37 g, 4.1 mmol) in THF (25 mL) was added NaH (60%
dispersion in mineral oil, 250 mg, 6.4 mmol) and NaI
(100 mg). The mixture was cooled to 08C, and allyl bromide
(0.55 mL, 6.2 mmol) was added. The mixture was allowed
to warm to ambient temperature, and stirring was continued
for 24 h. The reaction mixture was diluted with MTBE
(100 mL) and washed with water. The organic layer was
separated, the aqueous layer was extracted with MTBE, and
the combined organic extracts were dried with MgSO4.
After filtration, the solvent was evaporated, and the residue
was purified by flash chromatography on silica, using
4
5
3
1
5
2
.51 (d, 1H, J¼11.8 Hz, CHH–Ph), 3.71 (dd, 1H, J¼12.8,
.5 Hz, OCHH), 3.68 (dd, 1H, J¼12.8, 5.8 Hz, OCHH),
.67 (dd, 1H, J¼11.3, 5.0 Hz, OCHH), 3.63 (dd, 1H, J¼
1.3, 5.0 Hz, CHH–OBn), 3.27 (ddd, 1H, J¼6.0, 5.0,
.0 Hz, CHO), 3.19 (ddd, 1H, J¼6.0, 5.5, 5.5 Hz, CHO),
1
3
.60 (s, br., 1H, OH). C NMR (100 MHz, CDCl ): d 137.3
3
(
(
0), 128.5 (1), 127.9 (1), 127.8 (1), 73.4 (2), 67.9 (2), 60.6
2), 55.7 (1), 54.7 (1).
p
.1.6. (2R ,3S )-4-Benzyloxy-2-vinyl-butane-1,3-diol
11). To a suspension of CuI (3.60 g, 18.9 mmol) in
p
3
(
3
3
ether (70 mL) was added vinyl magnesium chloride (1.7 M
solution in THF, 31.8 mL, 54.0 mmol) at 2788C. A solution
of 10 (3.50 g, 18.0 mmol) in ether (20 mL) was added and
the mixture was stirred at 2408C for 24 h. The reaction
cyclohexane/MTBE mixtures as eluent, to give 13 (1.37 g,
1
89%). H NMR (400 MHz, CDCl ): d 7.36–7.28 (5H, Ph),
3
5.93 (dddd, 1H, J¼17.0, 9.8, 5.5, 5.0 Hz, CH –CHvCH ),
2
2
mixture was poured onto saturated NH Cl solution
4
5.76 (ddd, 1H, J¼16.8, 10.3, 9.0 Hz, CH–CHvCH ), 5.26
2
(
100 mL) and all precipitates were filtered off. The organic
(ddm, 1H, J¼17.0, 1.8 Hz, CHHvCH–CH ), 5.16–5.05
2
layer was separated, and the aqueous layer was extracted
twice with ethyl acetate. The combined organic layers were
dried with MgSO , filtered, and the solvent was evaporated.
(3H, CHHvCH–CH ), 4.55 (d, 1H, J¼12.0 Hz, CHH–Ph),
2
4.50 (d, 1H, J¼12.0 Hz, CHH–Ph), 4.25 (dd, 1H, J¼12.8,
5.5 Hz, CHH–CHvCH ), 4.08 (dd, 1H, J¼12.8, 5.0 Hz,
4
2
The residue was purified by flash chromatography on silica
1
CHH–CHvCH ), 3.86 (m, 1H, CH–OAll), 3.73 (dd, 1H,
2
to give 11 (2.64 g, 66%). H NMR (400 MHz, CDCl ): d
3
J¼9.5, 5.9 Hz, OCHH), 3.60–3.53 (2H, OCHH), 3.57 (dd,
1H, J¼9.8, 6.5 Hz, OCHH), 3.50 (dd, 1H, J¼9.8, 5.1 Hz,
OCHH), 2.45 (dddd, 1H, J¼9.0, 9.0, 5.9, 3.2 Hz, CH–Vn),
7
.36–7.26 (5H, Ph), 5.84 (ddd, 1H, J¼17.3, 10.3, 9.0 Hz,
CHvCH ), 5.18 (dd, 1H, J¼10.3, 1.8 Hz, CHHvCH), 5.13
2
1
3
(
1
dd, 1H, J¼17.3, 1.8 Hz, CHHvCH), 4.54 (d, 1H, J¼
0.90 (s, 9H, t-Bu), 0.05 (s, 6H, SiMe ). C NMR (100 MHz,
2
1.8 Hz, CHH–Ph), 4.50 (d, 1H, J¼11.8 Hz, CHH–Ph),
.02 (ddd, 1H, J¼7.2, 4.2, 4.2 Hz, CHOH), 3.71 (dd, 1H,
CDCl ): d 138.5 (0), 135.6 (1), 135.3 (1), 128.3 (1), 127.5
3
4
(1), 127.5 (1), 117.9 (2), 116.0 (2), 76.5 (1), 73.2 (2), 72.3
(2), 72.2 (2), 63.1 (2), 49.1 (1), 25.9 (3), 18.2 (0), 25.4 (3),
25.4 (3). IR (film): 2955 (s), 2928 (s), 2857 (s), 1471 (m),
J¼10.8, 7.5 Hz, CHH–OH), 3.68 (dd, 1H, J¼10.8, 6.0 Hz,
CHH–OH), 3.46 (dd, 1H, J¼9.6, 4.2 Hz, CHH–OBn), 3.44
1256 (m), 1097 (s), 837 (s) cm2 . MS (EI): m/z 377 (M ,
þ
1
(
dd, 1H, J¼9.6, 7.2 Hz, CHH–OBn), 3.15 (s, br., 2H, OH),

7956
B. Schmidt et al. / Tetrahedron 58 (2002) 7951–7958
5%), 197 (10), 171 (10), 131 (15), 91 (100), 75 (25). Anal.
calcd for C H O Si: C, 70.2%; H, 9.6%; found: C, 70.0%;
H, 9.5%.
J¼12.0 Hz, CHHPh), 4.50 (d, 1H, J¼12.0 Hz, CHHPh),
4.06 (d, 1H, J¼12.5 Hz, H6), 3.89 (dd, 1H, J¼10.4, 3.2 Hz,
CHH–OTBS), 3.75 (s, br., 1H, H5), 3.72 (dd, 1H, J¼
2
2 36 3
1
0.4 Hz, H4), 3.62 (dd, 1H, J¼10.6, 2.5 Hz, CHH–OBn),
p
p
3
.1.9. ((2S ,3R )-2-Benzyloxymethyl-3,6-dihydro-2H-
3.56–3.51 (2H, CHHOBn, CHHOTBS), 3.49 (d, 1H, J¼
pyran-3-ylmethoxy)t-butyl-dimethyl-silane (14). To a
solution of 13 (780 mg, 2.1 mmol) in DCM (20 mL) was
added complex A (52 mg, 3.0 mol%). The mixture was
stirred until the starting material was fully consumed as
indicated by TLC (cyclohexane/MTBE 10:1). The solvent
was evaporated, and the residue purified by flash chroma-
tography on silica to give 14 (710 mg, 97%). Analytically
12.5 Hz, H6), 3.35 (m, 1H, H2), 1.94 (m, 1H, H3), 0.84 (s,
9H, t-Bu), 0.01 (s, 3H, SiMe ), 20.02 (s, 3H, SiMe ). C
NMR (150 MHz, CDCl ): d 137.9 (0, ipso-C, Ph), 128.4 (1,
1
3
2
2
3
Ph), 127.9 (1, Ph), 127.9 (1, Ph), 76.7 (1, C2), 73.5 (2,
OCHHPh), 70.8 (1, C4), 70.5 (2, CHHOBn), 70.0 (2, C6),
67.9 (1, C5), 61.4 (2, CHHOTBS), 41.4 (1, C3), 25.8 (3,
t-Bu), 18.1 (0, t-Bu), 25.7 (3, SiMe ), 25.8 (3, SiMe ). MS
2
2
þ
pure 14 was obtained by additional Kugelrohr distillation
1
(EI, 70 eV): m/z 383 (M , 5%), 185 (15), 91 (100), 75 (15).
(
0.5 mbar, 1808C). H NMR (400 MHz, CDCl ): d 7.36–
3
7
5
.27 (5H, Ph), 5.79 (dddd, 1H, J¼10.3, 3.0, 2.0, 2.0 Hz, H5),
3.1.12. (Z)-4-t-Butyl-dimethylsilanyloxy)-but-2-ene-1-ol
2
3
.70 (dddd, 1H, J¼10.3, 2.3, 2.3, 2.0 Hz, H4), 4.58 (s, 2H,
(17). To a solution of 8 (19.2 mL, 233.0 mmol) in DCM
(200 mL) was added triethyl amine (83.6 mL, 60.8 mmol),
followed by t-butyl dimethyl silyl chloride (7.05 g,
46.8 mmol) and DMAP (570 mg, 4.6 mmol). The mixture
was stirred at ambient temperature for 3 h and then washed
with water. The organic layer was dried with MgSO4,
filtered and evaporated. The residue was purified by flash
chromatography on silica using cyclohexane/MTBE
CH Ph), 4.16 (dddd, 1H, J¼16.6, 3.0, 3.0, 2.0 Hz, H6), 4.10
2
(
dddd, 1H, J¼16.6, 3.3, 2.3, 2.3 Hz, H6), 3.73–3.52 (4H,
OCHH, H2), 3.48 (dd, 1H, J¼10.0, 5.5 Hz, OCHH), 2.32
1
3
(
NMR (100 MHz, CDCl ): d 138.3 (0), 128.3 (1), 127.7 (1),
m, 1H, H3), 0.86 (s, 9H, t-Bu), 0.03 (s, 6H, SiMe ).
C
2
3
1
6
27.5 (1), 127.1 (1), 125.9 (1), 74.9 (1), 73.4 (2), 71.3 (2),
4.5 (2), 64.3 (2), 38.8 (1), 25.8 (3), 18.2 (0), 25.5 (3), 25.5
1
(
3). IR (film): 2954 (m), 2929 (m), 2857 (m), 1472 (w), 1255
2
mixtures as eluent to give 17 (6.69 g, 71%). H NMR
(400 MHz, CDCl ): d 5.67 (dt, 1H, J¼11.3, 5.8 Hz,
1
(
m), 1098 (m), 837 (s), 777 (m) cm . MS (EI): m/z 349
3
þ
C, 68.9%; H, 9.3%; found: C, 68.7%; H, 9.1%.
(
M , 25%), 91 (100), 73 (20). Anal. calcd for C H O Si:
20 32 3
HCvCH), 5.62 (dt, 1H, J¼11.3, 5.5 Hz, HCvCH), 4.22
(d, 2H, J¼5.5 Hz, CH O), 4.15 (d, 2H, J¼11.3, 5.8 Hz,
2
CH O), 2.39 (s, br., 1H, OH), 0.87 (s, 9H, t-Bu), 0.05 (s, 6H,
2
p
.1.10. ((2S ,3R )-2-Benzyloxymethyl-3,6-dihydro-2H-
p
13
3
pyran-3-yl)-methanol (15). To a solution of 14 (1.22 g,
SiMe2). C NMR (100 MHz, CDCl ): d 131.2 (1), 130.0
3
(1), 59.5 (2), 58.7 (2), 25.8 (3), 18.4 (0), 25.3 (3).
3
7
.5 mmol) in THF (50 mL) was added TBAF (1.90 g,
.3 mmol). After 4 h the starting material was completely
p
p
3.1.13. [(2S ,3R )-3-(t-Butyl-dimethyl-silanyloxymethyl)-
2
3
consumed as indicated by TLC. The reaction mixture was
diluted with MTBE and washed with water. After usual
workup, the residue was purified by flash chromatography
oxiranyl]methanol (18). To a solution of 17 (6.65 g,
32.9 mmol) in DCM (150 mL) was added t-butyl hydro-
peroxide (5.5 M solution in decane, 43.0 mmol, 7.80 mL),
1
on silica to give alcohol 15 (414 mg, 51%). H NMR
(
followed by VO(acac) (436 mg, 5 mol%). The mixture was
2
400 MHz, CDCl ): d 7.35–7.24 (5H, Ph), 5.84 (dddd, 1H,
3
heated to reflux for 3 h, cooled to ambient temperature, and
excess peroxide was destroyed by addition of aqueous
solution of Na SO . After aqueous workup and evaporation
of all volatiles, the residue was purified by flash chroma-
tography on silica (cyclohexane/MTBE 2:1) to give 18
J¼10.3, 3.0, 2.3, 2.3 Hz, H5), 5.65 (dddd, 1H, J¼10.3, 2.3,
2
1
.3, 2.3 Hz, H4), 4.60 (d, 1H, J¼12.1 Hz, CHHPh), 4.55 (d,
H, J¼12.1 Hz, CHHPh), 4.16–4.12 (2H, H6), 3.68–3.61
2
3
(3H, H2, CH –OBn), 3.57–3.51 (2H, CH –OH), 2.47 (s,
br., 1H, OH), 2.40 (m, 1H, H3). C NMR (100 MHz,
2
2
1
3
1
(6.24 g, 87%). H NMR (400 MHz, CDCl ): d 3.89 (dd, 1H,
3
CDCl ): d 137.6 (0), 128.4 (1), 127.9 (1), 127.9 (1), 127.8
3
J¼11.8, 5.5 Hz, CHHOTBS), 3.76–3.72 (2H, CHHOH),
3.70 (dd, 1H, J¼11.8, 5.2 Hz, CHHOTBS), 3.20–3.13 (2H,
CHO), 2.47 (s, br., 1H, OH), 0.87 (s, 9H, t-Bu), 0.06 (s, 3H,
(
4
1), 125.3 (1), 75.1 (1), 73.5 (2), 71.5 (2), 64.7 (2), 64.1 (2),
0.0 (1). IR (film): 3435 (w, br.), 2929 (m), 2867 (m), 1454
2
1
þ
13
(
w), 1096 (m), 699 (m) cm . MS (EI): m/z 234 (M , 4),
SiMe ), 0.05 (s, 3H, SiMe ). C NMR (100 MHz, CDCl3):
2
2
1
73 (100).
.1.11. (3R ,4S ,5S ,6S )-6-Benzyloxymethyl-5-(t-
d 61.6 (2), 60.8 (2), 56.3 (1), 56.0 (1), 25.8 (3), 18.2 (0),
5.3 (3), 25.5 (3).
2
p
p
p
p
3
p
p
butyl-dimethylsilanyloxymethyl)-tetra-hydro-pyran-
,4-diol (16). To a solution of 13 (590 mg, 1.7 mmol) in
3.1.14. (2R ,3S )-4-(t-Butyl-dimethyl-silanyloxy)-2-
vinyl-butane-1,3-diol (19). Following the procedure given
above for the preparation of 11, 18 (6.24 g, 28.6 mmol) was
3
acetone (24 mL) and water (6 mL) was added N-methyl
morpholine N-oxide (820 mg, 5.6 mmol), followed by
K Os(OH) (50 mg, 4.6 mol%). After stirring at ambient
reacted with the vinyl cuprate reagent to give homoallylic
1
alcohol 19 (4.76 g, 68%). H NMR (200 MHz, CDCl ): d
3
2
6
temperature for 4 h, the reaction was quenched by addition
of aqueous Na SO solution. Stirring was continued for 1 h,
and the mixture was extracted with ethyl acetate. The
5.85 (ddd, 1H, J¼17.1, 10.5, 8.8 Hz, CHvCH ), 5.20 (dd,
2
1H, J¼10.5, 2.0 Hz, CHHvCH), 5.14 (ddd, 1H, J¼17.1,
2.0, 0.7 Hz, CHHvCH), 3.87–3.50 (5H, CHHO, CHOH),
2.48 (s, br., 1H, OH), 2.36 (dddd, 1H, J¼9.7, 8.8, 6.0,
2
3
combined organic layers were dried with MgSO , filtered
4
and the solvent was evaporated. Upon flash chromatography
on silica (cyclohexane/MTBE 1:1) 16 (417 mg, 65%) was
obtained as a 7:1 mixture of diastereoisomers. NMR-data
3.4 Hz, CHCHv), 0.87 (s, 9H, t-Bu), 0.03 (s, 3H, SiMe ),
2
1
3
0.03 (s, 3H, SiMe2). C NMR (100 MHz, CDCl ): d 134.9
3
(1), 118.6 (2), 72.6 (1), 65.3 (2), 64.3 (2), 48.5 (1), 25.8 (3),
18.2 (0), 25.4 (3), 25.4 (3). IR (film) 3386 (br, s), 2930 (s),
1
are given for the major diastereoisomer: H NMR
(
2858 (s), 1472 (m), 1255 (s), 1093 (s), 838 (s), 777 (s) cm2
1
.
600 MHz, CDCl ): d 7.34–7.24 (5H, Ph), 4.59 (d, 1H,
3

B. Schmidt et al. / Tetrahedron 58 (2002) 7951–7958
7957
þ
for C H O Si: C, 58.5%; H, 10.6%; found: C, 58.6%; H,
p
p
MS (EI) m/z 246 (M , 5%), 117 (10), 75 (100). Anal. calcd
3.1.17. 2,2-Dimethylpropionic acid (2S ,3R )-2-(t-butyl-
dimethyl-silanyloxymethyl)-6-oxo-3,6-dihydro-2-pyran-
3-ylmethyl ester (23). To a solution of the acrylate 22
12 26 3
1
0.2%.
(
384 mg, 1.0 mmol) in toluene (50 mL) was added the
p
p
3
.1.15. 2,2-Dimethylpropionic acid (R )-2-[(S )-2-(t-
butyl-dimethyl-silanyloxy)-1-hydroxy-ethyl]-but-3-enyl
ruthenium complex B (42 mg, 5 mol%). The mixture was
heated to reflux for 5 h. After this time the starting material
was completely converted. The solvent was evaporated, and
ester (20). To a solution of 19 (3.25 g, 13.2 mmol) in DCM
(50 mL) pivaloyl chloride (1.85 mL, 15.0 mmol) followed
by triethyl amine (7.4 mL, 53 mmol) and DMAP (180 mg,
the residue purified by flash chromatography on silica to
1
give 23 (300 mg, 84%). H NMR (500 MHz, CDCl ): d 6.72
3
1
1
.5 mmol) was added. The reaction mixture was stirred for
8 h at ambient temperature and then quenched by addition
(dd, 1H, J¼10.0, 3.7 Hz, H4), 6.03 (dd, 1H, J¼10.0, 2.0 Hz,
H5), 4.41 (ddd, 1H, J¼6.7, 4.5, 4.5 Hz, H2), 4.22 (dd, 1H,
J¼11.5, 5.5 Hz, CHHOPiv), 4.18 (dd, 1H, J¼11.5, 4.7 Hz,
CHHOPiv), 3.82 (d, 2H, J¼4.5 Hz, CHHOTBS), 3.02 (m,
1H, H3), 1.16 (s, 9H, OPiv), 0.85 (s, 9H, OTBS), 0.05 (s,
of aqueous Na CO3 solution. The organic layer was
2
separated, and the aqueous layer was extracted with ether.
The combined organic extracts were washed with aqueous
NH Cl solution, dried with MgSO , filtered and evaporated.
The residue was purified by flash chromatography on silica
using cyclohexane/MTBE (3:1) as eluent, giving 20 (4.23 g,
1
3
3H, SiMe ), 0.04 (s, 3H, SiMe ). C NMR (125 MHz,
2
4
4
2
t
CDCl ): d 178.1 (0, COBu ), 162.6 (0, C6), 145.1 (1, C4),
3
121.9 (1, C5), 79.0 (1, C2), 62.7 (2, CHHO), 62.7 (2,
CHHO), 38.9 (0, OPiv), 34.6 (1, C3), 27.1 (3, OPiv), 25.7
(3, OTBS), 18.2 (0, OTBS), 25.4 (3, SiMe ), 25.5 (3, 3,
1
9
7%). H NMR (400 MHz, CDCl ): d 5.78 (ddd, 1H,
3
J¼17.3, 10.3, 9.5 Hz, CHvCH ), 5.16 (dd, 1H, J¼10.3,
2
2
1
4
.5 Hz, CHHvCH), 5.10 (dm, 1H, J¼17.3 Hz, CHHvCH),
.19 (dd, 1H, J¼10.8, 7.0 Hz, CHH–OPiv), 4.09 (dd, 1H,
SiMe ). IR (film): 2957 (s), 2930 (s), 1733 (s), 1481 (s),
2
1282 (s), 1146 (s), 835 (s). FAB-HRMS: calcd for
þ
J¼10.8, 6.5 Hz, CHH–OPiv), 3.72 (ddd, 1H, J¼7.8, 4.0,
C H O NaSi (M þNa) 379.1917, found 379.1949.
1
8 32 5
4
.0 Hz, CH–OH), 3.55 (dd, 1H, J¼10.0, 4.0 Hz, CHH–
OTBS), 3.50 (dd, 1H, J¼10.0, 7.8 Hz, CHH–OTBS), 2.51
(
1
3
dddd, 1H, J¼9.5, 7.0, 6.5, 4.0 Hz, CH–Vn), 2.40 (s, br.,
Acknowledgements
H, OH), 1.16 (s, 9H, t-Bu–CO), 0.85 (s, 9H, t-Bu), 0.03 (s,
H, SiMe ), 0.03 (s, 3H, SiMe ). C NMR (100 MHz,
1
3
2
2
This work was generously supported by the Deutsche
Forschungsgemeinschaft and the Fonds der Chemischen
Industrie.
CDCl ): d 178.5 (0), 134.1 (1), 118.7 (2), 70.8 (1), 65.2 (2),
3
6
(
4.3 (2), 45.7 (1), 38.8 (0), 27.2 (3), 25.8 (3), 18.2 (0), 25.4
3), 25.4 (3). IR (film): 3512 (br w), 2958 (s), 2859 (m),
732 (s), 1473 (m), 1285 (m), 1160 (s), 838 (s), 777
1
(
m) cm2 . MS (EI): m/z 331 (M , 5%), 313 (25), 229 (30),
þ
1
7
5 (30), 57 (100). Anal. calcd for C H O Si: C, 61.8%; H,
1
References
7 34 4
1
0.4%; found: C, 62.2%; H, 10.0%.
1
. Preuss, R.; Jung, K.-H.; Schmidt, R. R. Liebigs Ann. Chem.
1992, 377–382.
p
p
.1.16. Acrylic acid (1S ,2R )-1-(t-butyldimethylsilanyl-
3
oxymethyl)-2-(2,2-dimethyl-propanoyloxymethyl)-but-
-enyl ester (22). To a solution of 20 (1.40 g, 4.2 mmol) in
DCM (50 mL) was added at 08C triethyl amine (2.8 mL,
0.0 mmol) and acryloyl chloride (0.8 mL, 10.0 mmol),
2. Eisele, T.; Ishida, H.; Hummel, G.; Schmidt, R. R. Liebigs
Ann. 1995, 2113–2121.
3
3. Daly, S. M.; Armstrong, R. W. Tetrahedron Lett. 1989, 30,
5713–5716.
2
followed by DMAP (50 mg, 0.4 mmol). The mixture was
stirred until the starting material was completely as
indicated by TLC. The organic layer was washed with
4. Armstrong, R. W.; Teegarden, B. R. J. Org. Chem. 1992, 57,
915–922.
5. Udodong, U. E.; Fraser-Reid, B. J. Org. Chem. 1988, 53,
2131–2132.
water, dried with MgSO , filtered and evaporated. The
4
residue was purified by flash chromatography on silica using
1
6. Udodong, U. E.; Fraser-Reid, B. J. Org. Chem. 1989, 54,
2103–2112.
cyclohexane/MTBE mixtures, to give 22 (1.29 g, 80%). H
NMR (400 MHz, CDCl ): d 6.36 (d, 1H, J¼17.2 Hz,
3
7. Bj o¨ rsne, M.; Classon, B.; Kvarnstrom, I.; Samuelsson, B.
Tetrahedron 1993, 49, 8637–8644.
COCHvCH ), 6.08 (dd, 1H, J¼17.2, 10.4 Hz,
2
COCHvCH ), 5.80 (d, 1H, J¼10.4 Hz, COCHvCH ),
8. Witkowski, S.; Rao, Y. K.; Premchandran, R. H.; Halushka,
P. V.; Fried, J. J. Am. Chem. Soc. 1992, 114, 8464–8472.
9. Premchandran, R. H.; Ogletree, M. L.; Fried, J. J. Org. Chem.
1993, 58, 5724–5731.
10. Pelyv a´ s, I. F.; Thiem, J.; T o´ th, Z. G. J. Carbohydr. Chem.
1998, 17, 1–26.
2
2
5
.71 (ddd, 1H, J¼17.3, 10.3, 9.3 Hz, CHCHvCH ), 5.18
2
(
d, 1H, J¼10.3 Hz, CHCHvCH ), 5.16 (d, 1H, J¼17.3 Hz,
2
CHCHvCH ), 4.07 (dd, 1H, J¼11.1, 6.8 Hz, CHHOPiv),
2
4
.02 (dd, 1H, J¼11.1, 7.0 Hz, CHHOPiv), 3.67 (dd, 1H,
J¼10.5, 5.8 Hz, CHHOTBS), 3.61 (dd, 1H, J¼110.5,
5
9
3
1
6
.8 Hz, CHHOTBS), 2.83 (m, 1H, CHCHvCH ), 1.16 (s,
2
11. Ozasa, T.; Suzuki, K.; Sasamata, M.; Tanaka, K.; Kobori, M.;
Kadota, S.; Nagai, K.; Saito, T.; Watanabe, S.; Iwanami, M.
J. Antibiot. 1989, 42, 1331–1338.
H, OPiv), 0.84 (s, 9H, OTBS), 0.00 (s, 3H, SiMe ), 0.00 (s,
2
1
3
H, SiMe2). C NMR (100 MHz, CDCl ): d 178.2 (0),
3
65.3 (0), 133.4 (1), 130.9 (2), 128.3 (1), 119.4 (2), 72.7 (1),
3.6 (2), 62.0 (2), 42.8 (1), 38.7 (0), 27.1 (3), 25.7 (3), 18.1
12. Shibata, T.; Kurihara, S.; Yoda, K.; Haruyama, H. Tetrahedron
1995, 51, 11999–12012.
(
(
0), 25.5 (3), 25.5 (3). IR (film): 2958 (s), 2931 (s), 1732
s), 1638 (s), 1623 (m), 1406 (s), 1189 (s). FAB-HRMS:
13. Gurjar, M. K.; Chakrabarti, A.; Rao, A. V. R. Heterocycles
1997, 45, 7–10.
14. K a´ l e´ , V. N.; Clive, D. L. J. J. Org. Chem. 1984, 49,
1554–1563.
þ
calcd for C H O NaSi(M þNa) 407.2230, found
2
0 36 5
4
07.2249.

7958
B. Schmidt et al. / Tetrahedron 58 (2002) 7951–7958
1
5. Schmidt, B.; Wildemann, H. Eur. J. Org. Chem. 2000,
145–3163.
25. Ram Reddy, M. V.; Yucel, A. J.; Ramachandran, P. V. J. Org.
Chem. 2001, 66, 2512–2514.
3
1
6. White, J. D.; Bolton, G. L.; Dantanarayana, A. P.; Fox, C. M.
J.; Hiner, R. N.; Jackson, R. W.; Sakuma, K.; Warrier, U. S.
J. Am. Chem. Soc. 1995, 117, 1908–1939.
26. Cossy, J.; Pradaux, F.; BouzBouz, S. Org. Lett. 2001, 3,
2233–2235.
27. Held, C.; Fr o¨ hlich, R.; Metz, P. Angew. Chem. 2001, 113,
1091–1093, Angew. Chem., Int. Ed. Engl. 2001, 40, 1058–
1060.
17. Ferrier, R. J.; Prasad, N. J. Chem. Soc. (C) 1969, 570–574.
8. Wieczorek, E.; Thiem, J. J. Carbohydr. Chem. 1998, 17,
1
7
85–809.
28. F u¨ rstner, A.; Thiel, O. R.; Lehmann, C. W. Organometallics
2002, 21, 331–335.
1
9. Yokokawa, F.; Sugiyama, H.; Shioiri, T.; Katagiri, N.; Oda,
O.; Ogawa, H. Tetrahedron 2001, 57, 4759–4766.
29. F u¨ rstner, A.; Langemann, K. Synthesis 1997, 792–803.
30. F u¨ rstner, A.; Thiel, O. R.; Ackermann, L.; Schanz, H.-J.;
Nolan, S. P. J. Org. Chem. 2000, 65, 2204–2207.
31. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett.
1999, 1, 953–956.
2
2
2
0. Jung, M. E.; Nichols, C. E. J. Org. Chem. 1998, 63, 347–355.
1. Tius, M. A.; Fauq, A. H. J. Org. Chem. 1983, 48, 4131–4132.
2. Kocienski, P. J. Protecting Groups. Georg Thieme: Stuttgart,
1
994; p 33.
3. Souli e´ , J.; Ta, C.; Lallemand, J.-Y. Tetrahedron 1992, 48,
43–452.
4. Redlich, H.; Schneider, B. Liebigs Ann. Chem. 1983,
12–424.
2
2
32. Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc.
1996, 118, 100–110.
4
33. Nagai, M.; Kato, K.; Takita, T.; Nishiyama, S.; Yamamura, S.
Tetrahedron 1990, 46, 7703–7710.
4