Stereodivergent synthesis of 5a-carba-hexopyranoses from carbohydrates via 6-exo-dig radical cyclization: Preparation of 5a-carba-β-D-manno-, α-D-allo-, β-L-talo- and α-L-gulopyranose pentaacetates from D-mannose

Article abstract of DOI:10.1016/S0957-4166(03)00532-9

Four carbasugars, 5a-carba-β-D-manno-, α-D-allo-, β-L-talo- and α-L-gulopyranose pentaacetates, have been prepared in a stereodivergent manner from D-mannose. Alkynyl derivatives of 2,3:4,6-di-O-isopropylidene-D-mannopyranose, which are prepared by homolo

Full text of DOI:10.1016/S0957-4166(03)00532-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 2961–2974
Stereodivergent synthesis of 5a-carba-hexopyranoses from
carbohydrates via 6-exo-dig radical cyclization: preparation of
5a-carba-b-
D
-manno-, a-
D
-allo-, b-
L
-talo- and a-
L-gulopyranose
pentaacetates from
D
-mannose
Ana M. Go´mez,* Eduardo Moreno, Gerardo O. Danelo´n, Seraf´ın Valverde and J. Cristo´bal Lo´pez*
Instituto de Qu´ımica Orga´nica General, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
Received 28 April 2003; accepted 23 May 2003
Abstract—Four carbasugars, 5a-carba-b-
D
-manno-, a-
D
-allo-, b-
L
-talo- and a-
L
-gulopyranose pentaacetates, have been prepared
-mannopyranose, which are
in a stereodivergent manner from -mannose. Alkynyl derivatives of 2,3:4,6-di-O-isopropylidene-
D
D
prepared by homologation at C-1, by reaction with phenyl acetylide, undergo a 6-exo-dig radical cyclization, from a radical
located at C-5, to yield a mixture of highly functionalized cyclohexanes. Some of these compounds, after transformation of their
exocyclic double bond in a hydroxy function, were correlated with polyhydroxylated cyclohexanes, which were then selectively
deoxygenated either at position C-4 or C-5a (carbohydrate numbering) to afford carbasugars of the
© 2003 Elsevier Ltd. All rights reserved.
D- or L- series.
1. Introduction
As part of an ongoing program in our laboratory,
aimed at the preparation of carbocycles from carbohy-
drates,7–9 we have recently reported two synthetic
strategies based on radical cyclizations for the prepara-
tion of carbasugars.10,11 These methods, unlike others
based on radical cyclizations,12 were designed to corre-
late a given carbohydrate, 1, with its corresponding
carbasugar, 2 (Scheme 1).
The term ‘carbasugar’ is used to describe monosaccha-
ride analogues in which the ring oxygen has been
replaced by a methylene group.1 Carbasugars derived
from hexopyranoses, ‘carba-pyranoses’ e.g. 2 were first
prepared by McCasland et al.,2 prior to their isolation
from natural sources as components of biologically
important antibiotics.3 Many of these substances,
owing to their close resemblance to carbohydrates,2 are
endowed with an interesting array of biological
activities4 which has triggered the development of a
Our reported strategy for the preparation of 2a is
outlined in Scheme 2.11 The methylene group (C-5a) in
carba- -mannopyranose, 2a, was retrosynthetically cor-
D
plethora
of
synthetic
approaches
for
their
related, via polyoxygenated intermediate 3, with the
exocyclic double bond in alkenyl cyclohexane, 4. The
cyclohexane ring has been obtained by 6-exo-dig radi-
cal cyclization13 of secondary radical, I, readily pre-
pared from a carbohydrate-derived alkyne 5.
preparation.1,5–7
These methods, although well suited for the prepara-
tion of common carbasugars, would face the problem
of availability of the starting monosaccharides when the
preparation of
L-carbasugars or ‘rare’ D-carbasugars
would be required. Hence, we focused our interest in
the development of a stereodivergent approach to car-
basugars, which starting from readily available
monosaccharides, could allow access to a variety of
carbasugars. In this context, we have found that our
previous strategy11 (Scheme 2) could be extended to the
Scheme 1. Correlation of carbohydrates with carbasugars.
* Corresponding authors. Fax: +34 915644853; e-mail: anago@
iqog.csic.es; clopez@iqog.csic.es
0957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00532-9

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3. Study of the radical cyclization
3.1. Synthesis of the precursors for radical cyclization
The synthetic route started with 2,3:4,6-di-O-isopropy-
lidene-
step from
D
-mannopyranose, 1a, readily obtained in one
D
-mannose.15 Treatment of 1a with excess
phenylacetylide produced compounds, 9–12, consisting
of epimeric mixtures at C-1 of 2,3:4,6- 9 and 10 and
migrated 2,3:5,6-di-O-isopropylidene derivatives 11 and
12 from which, the faster running diol 9, could be easily
isolated in 57% yield on multigram runs (Scheme 4).
The stereochemistry at C-1 in alkynes 9 and 10 was
assigned at a later stage in the synthesis, and no
attempt was made to assign the stereochemistry at C-1
in compounds 11 and 12.
Scheme 2. Retrosynthesis of 5a-carba-D-mannopyranose
from
D-mannose.
preparation of different carbasugars. Herein, we dis-
close full details of this approach including the prepara-
tion of 5a-carba-b-
D
-manno-, 5a-carba-a-
D-allo-,
-gulopyranose pen-
5a-carba-b-
L
-talo- and 5a-carba-a-
L
taacetates 52, 63, 45 and 57, respectively, from
D
-
mannose.
Scheme 4. Retrosynthesis of 5a-carba-
from -mannose.
D-mannopyranose
D
2. Stereodivergent strategy
The next task to be undertaken was the selective protec-
tion of the 1-hydroxyl group (1-OH, carbohydrate
numbering) prior to activation of the 5-OH of diol 9.
Accordingly, treatment of diol 9 with ethyl chlorofor-
mate/pyridine in dichloromethane yielded monocarbon-
ate 13 as a very major isomer16 (60%) together with
mono- and dicarbonates 14 (10%) and 15 (23%), respec-
tively (Scheme 5). To activate the 5-OH group, and
allow generation of the requisite secondary radical (see
5 and I, Scheme 2), compound 13 was treated with an
excess of phenyl chlorothionoformate17,18 and pyridine
in acetonitrile and refluxed for 1h to provide the desired
thionocarbonate, 16, in 85% yield.
The stereodivergent approach to carbasugars from
D
-
mannose came from our observation that the key poly-
oxygenated intermediate 314 (e.g. 6, Scheme 3) could be
transformed into a 5a-carba-
D
-sugar 7 or a 5a-carba-L-
sugar derivative 8 by deoxygenation either at C-5a or at
C-4, respectively.
Similar chemoselectivity was observed in the silylation
of 9 (Scheme 6). Compound 17 (silylation at 1-OH) was
produced again as a very major isomer (65%), and
activation at 5-OH with phenyl chlorothionoformate
paved the way to 20. Deprotection of the silyl group at
C-1 then produced 21.
Cyclization precursors 23, 27, and 28 were prepared
from diol 10 (Scheme 7). Initial attempts to prepare
carbonate 22 by chemoselective reaction of 10 with
ethyl chloroformate (as above) resulted only in complex
reaction mixtures in which migration of the acetonides
was detected. Conversely, silylation took place reason-
ably well and led to 23 (63% yield), along with disilyl
derivative 24 (23%) and small amounts of 25 (4%).
Activation of 23 with phenyl chlorothionoformate
yielded 26, from which alcohol 27, and carbonate 28
were uneventfully prepared.
Scheme 3. Stereodivergent synthesis of carbasugars from
polyoxygenated intermediates.
The approach also takes advantage of the fact that the
radical cyclization of compound 5 yields compound 4
together with its epimer at C-5, vide infra, 5-epi-4. Both
compounds have been used in the preparation of the
carbasugars described in this article.

A. M. Go´mez et al. / Tetrahedron: Asymmetry 14 (2003) 2961–2974
2963
Scheme 5. Synthesis of precursor 16 for radical cyclization.
Scheme 7. Synthesis of precursors 26, 27 and 28 for radical
cyclization.
Scheme 6. Synthesis of precursors 20 and 21 for radical
cyclization.
3.2. Stereochemical outcome of the 6-exo-dig radical
cyclization: 6,6-trans versus 6,6-cis ring fusion
Although the carbasugars described in this paper have
been prepared from the major isomer 9, obtained by
the addition of phenylacetylide to
D-mannose diace-
tonide 1a, similar chemistry could be carried out with
10, leading to stereoisomeric carbasugars. Therefore, a
study of the cyclization of the radical precursors pre-
pared from 9 and 10 was conducted.
Radical ring closure of cyclic radicals onto alkenes, to
afford fused systems, followed a very general pattern:
that the ring fusion obtained was predominately or
exclusively cis (1,2 cis, radical numbering) for ‘small
rings’ ((a), Scheme 8).19,20 Therefore, even in the case of
6,6-ring fusions, 1,2-cis selectivity leading to 6,6-cis ring
fused systems would be expected ((a), n=2, Scheme
Scheme 8. Stereochemistry of radical cyclization of cyclic
radicals onto alkenes and alkynes to afford bicyclic systems.

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A. M. Go´mez et al. / Tetrahedron: Asymmetry 14 (2003) 2961–2974
8).19 Along these lines, radical ring closure of cyclic
radicals onto alkynes, takes place with 1,2-cis selectivity
to generate 6,6-cis ring fusion exclusively ((b), Scheme
8).21
tion of the hydroxyl group at C-1 in the stereochemistry
of the radical cyclization.
The results obtained for the radical cyclizations are
outlined in Table 1. In accordance with literature prece-
dents, adducts with 6,6-cis ring fusion prevailed in all
cases. However, synthetically useful amounts of 6,6-
trans isomers could be obtained by appropriate changes
in the protecting group at 1-OH (entries 1 and 6).
Accordingly, in precursors arising from 9 (1S isomers,
entries 1–3), the use of a TBS protecting group (entry
1), resulted in a ratio in favor of the trans isomer (1.5:1
cis:trans), while cyclization of unprotected 21 favored
formation of the cis isomer (entry 3, 4.2:1 cis:trans). An
opposite tendency was found, however, in precursors
arising from epimeric 10 [(1R) isomers, entries 4–6)].
The use of a silyl protecting group at 1-OH (as in 26)
favored formation of the cis isomer 35 (entry 4, 3.5:1
cis:trans), while the presence of a free hydroxyl group
resulted in a higher proportion of trans isomer 40 (entry
6, 1.7:1 cis:trans). Derivatives with ethylcarbonyl sub-
stituents (entries 2 and 5) displayed an intermediate
behavior in either series.
The synthesis of 5a-carba-D-mannopyranose, in our
initial work,11 required the formation of an intermedi-
ate with 6,6-trans ring fusion ((c), Scheme 8) rather
than the favored (and expected) 6,6-cis ring fusion. We
have already disclosed some preliminary results, which
indicated that changes in the protecting group on the
hydroxy function a- to the radical acceptor could exert
some stereocontrol in favor of the trans 6,6-ring
fusion.11 In this work, we have completed this study by
investigating the effect of the change in the configura-
Table 1. Influence of the substituent and the stereochem-
istry at C-1 in the stereochemical outcome of the radical
cyclization
Radical ring closure in 2-but-3-enylcyclohexyl radicals
(Scheme 8a) has been extensively studied by Rajan-
Babu,22 who has shown that transition states having an
equatorial and an axial butenyl side chain may com-
pete. In our case, radical cyclization of 2-pent-4-ynylcy-
clohexyl radicals could analogously take place with
either axial or equatorial disposition of the side chain
(Scheme 9). Axial orientation of the chain in the transi-
tion state, because of geometrical restrictions, would
lead to cis-decalin type systems (6,6-cis ring fusion). On
the other hand, an equatorial disposition of the side
chain give rise to either cis- or trans-dioxadecalins
depending on the substituent at C-1 (see Scheme 9).
Scheme 9. Possible dispositions on the radical cyclizations of
2-pent-4-ynyl cyclohexyl radicals.
Accordingly, in compounds arising from 9 [(1S) isomer,
Scheme 10)] transition state B, leading to 6,6-cis iso-
mers, would be more sensitive to steric interactions
than transition state A (Scheme 10). Therefore, the use
of a (bulky) silyl-protecting group resulted in a higher
proportion of the 6,6-trans isomer when compared with

A. M. Go´mez et al. / Tetrahedron: Asymmetry 14 (2003) 2961–2974
2965
Scheme 11. Synthesis of 5a-carba-b-
etate 45.
L
-talopyranose pentaac-
Scheme 10. Illustration of potential steric interaction that
may destabilize the transition states with equatorial disposi-
tion of the side chain leading to product with 6,6-ring fusion.
the cyclization of the corresponding free hydroxyl com-
pound (compare entry 1 versus entry 3, Table 1).
Conversely, the use of the more sterically demanding
silyl substituent at 1-OH in compounds derived from 10
[(1R) isomer)] might result in a relatively high-energy
transition state C leading to 6,6-trans isomers. By corol-
lary, release of steric demands at C-1 in compounds
arising from 10 [(1R) isomer)] would lead to higher
amounts of bicycles with 6,6-trans ring junction (com-
pare entry 4 versus entry 6, Table 1).
4. Synthesis of carbasugars
4.1. Syntheses of 5a-carba-b-
L-talo- and 5a-carba-b-D-
mannopyranose pentaacetates from compound 30
Scheme 12. Synthesis of 5a-carba-b-
D-mannopyranose pen-
Compound 30 [two isomers at C-7, 1:1 ratio: l 2.89
(ddt, J4,5=J5,6ax=10.8, J5,6eq=4.5 Hz, J5,Holef=2.8 Hz,
H-5 one isomer), 2.48 (ddt, J4,5=J5,6ax=11.1 Hz,
taacetate 52.
J
5,6eq=5.1 Hz, J5,Holef=2.3 Hz, H-5 other isomer)] was
transformed into carbasugars of the -talo- and D-
L
to afford thiocarbonate 43 (70%), in which an unex-
pected rearrangement of the 4,6-O-isopropylidene
group to a 5a,6-O-isopropylidene ring had taken place
prior to the activation step at 4-OH. Compound 44,
which was smoothly obtained by treatment of 43 with
tri-n-butyltin hydride (TBTH) in toluene, was then
manno- series by deoxygenation at C-4 and C-5a,
respectively, following the transformations outlined in
Schemes 11 and 12.
Ozonolysis of 30 (Scheme 11) yielded ketone 41, which
upon reduction (NaBH4·CeCl3) gave, in a stereoselec-
tive manner, the highly functionalized cyclohexane, 42,
(50%, two steps). The latter was then treated with
phenyl chlorothionoformate in the presence of pyridine
uneventfully transformed in 5a-carba-b-L-talopyranose
pentaacetate 4523 {[h]D21=+5.2 (c 0.4, CHCl3), mp=
135–138°C}.

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A. M. Go´mez et al. / Tetrahedron: Asymmetry 14 (2003) 2961–2974
In order to carry out the deoxygenation at C-5a
efficiently, the above-mentioned isopropylidene ring
rearrangement had to be avoided. Therefore, a benzyl
group, stable towards the reaction conditions for the
installation of the xanthate, was placed at 1-OH
(Scheme 12). Accordingly, after a change in the protect-
ing group at 1-OH in 30 to afford 46 (OTBS“OBn),
ozonolysis was carried out to yield ketone 47, which
upon stereoselective reduction (BH3·SMe2 or
NaBH4·CeCl3) gave the cyclohexane 48 (J5a,1=3.8 Hz)
(55%, two steps). The hydroxy function at C-5a was
deoxygenated under radical conditions, via its xanthate,
49, to afford 5a-carba- -mannopyranose derivative 50
D
(63%, two steps). Hydrolysis of the acetals followed by
acetylation yielded benzyl derivative 51 (85%, two
steps), which upon hydrogenation and acetylation gave
5a-carba-b-
D
-mannopyranose
pentaacetate
5224–26
(75%, two steps) ([h]D21=+2.0 (c 0.6, CHCl3), mp=116–
118°C. Lit. ([h]2D1=+2.9 (c 1.1, CHCl3), mp=117–
118°C);24 ([h]D21=+2.53 (c 1.67, CHCl3), mp=119°C);25
([h]2D1=+2.9 (c 1.28, CHCl3), mp=119°C).26
4.2. Synthesis of 5a-carba-a-
D-allo- and 5a-carba-a-L-
Scheme 14. Synthesis of 5a-carba-a-
etate 63.
D-allopyranose pentaac-
gulopyranose pentaacetates from compound 33
Compound 33 was transformed into carbasugars of the
-gulo- and -allo- series by deoxygenation at C-5a and
C-4, respectively, following the transformations out-
lined in Schemes 13 and 14.
diacetonide 59. Deprotection of the acid labile iso-
propylidene groups in 59 resulted in the formation of
tetraol 60. Transformation of 60 into compound 61, in
which the 4-OH group had been differentiated, was
carried out through a sequence of reactions, which
involved regioselective silylation of the primary
hydroxyl group followed by selective protection of the
cis diol moiety as an O-isopropylidene acetal. Deoxy-
genation at C-4, in compound 61 via the corresponding
phenyl thiocarbonate paved the way to allo-derivative
62, which upon conventional deprotection steps and
L
D
acetylation led to 5a-carba-a-
-allopyranose 63.27,29,30
D
([h]2D1=+36.0 (c 1.0, CHCl3, mp=95–98°C), Lit.
([h]2D1=+78.7 (c 1.5, CHCl3, mp=96–97°C).13
5. Summary
We have reported a stereodivergent strategy for the
preparation of carbasugars from enantiomerically pure
polyhydroxy methylenecyclohexanes, which are readily
available by 6-exo-dig radical cyclization of monosac-
charide-derived alkynes. In this approach, three (C-2,
C-3 and C-4) out of the four stereogenic centers present
Scheme 13. Synthesis of 5a-carba-b-
etate 57.
L-gulopyranose pentaac-
Protection of the 1-OH group in 33 as a benzyl ether
led to 53 (Scheme 13), which upon ozonolysis and
reduction afforded compound 54, as a 1:1 epimeric
mixture at C-5a. Deoxygenation at C-5a in 54, via the
in
D-mannose are preserved in the polyoxygenated key
methyl cyclohexane intermediates. The stereochemistry
of the remaining stereogenic centers (C-1, C-5, C-5a) in
the final carbasugars emanates from the synthetic steps
in the sequence: (a) the stereochemistry at C-5 is related
to the facial selectivity in the radical addition to the
triple bond; (b) the configuration at C-1 arises from the
nucleophilic addition of the acetylide to C-1; and (c) the
stereocenter at C-5a is generated upon reduction of a
keto group. During the course of this work, we have
prepared carbasugars 45, 52, 57 and 63 from synthetic
intermediates 4 and C-5-epi-4, which only differed in
the stereochemistry at C-5. By corollary, the scope of
corresponding xanthates, 55, furnished
L-gulo deriva-
tive 56. Routine transformations in 56, then led to
5a-carba-a-
-gulopyranose pentaacetate 57.27,28 ([h]D21=
L
−34.0 (c 0.32, CHCl3), Lit. ([h]2D1=−29.5 (c 1.5,
CHCl3).12
The synthetic process for the deoxygenation at C-4 in
compound 33 (Scheme 14) involved ozonolysis of the
latter followed by reduction of the resulting carbonyl
group to yield diol 58, which was benzylated to afford

A. M. Go´mez et al. / Tetrahedron: Asymmetry 14 (2003) 2961–2974
2967
this methodology could still be enhanced by finding
6.4. General procedure for ozonolysis
stereoselective transformations leading to polyoxy-
genated cyclohexanes epimeric at C-1 and C-5a. In this
context, the use of the above strategy for the prepara-
tion of additional carbasugars and derivatives is under-
way in our laboratory and will be described in due
course.
Ozone was bubbled through a solution of the corre-
sponding olefin in MeOH:CH2Cl2 (1:1 mixture, 20 mL/
mmol) at −78°C until TLC showed complete
consumption of the starting compound, oxygen was
then bubbled through the solution for 5 min. Next, the
mixture was treated with dimethyl sulfide (1 mL/mmol)
and the solution was allowed to warm to room temper-
ature over 2 h. After stirring for an additional 1 h, the
solvent was removed and the residue purified by flash
chromatography.
6. Experimental
6.1. General methods
6.5. General procedure for reduction with
NaBH4·CeCl3
All reactions were performed in dry flasks fitted with a
glass stopper or rubber septa under a positive pressure
of argon, unless otherwise noted. Air- and moisture-
sensitive liquids and solutions were transferred via
syringe or stainless steel cannula. Flash column chro-
matography was performed employing 230–400 mesh
silica gel. Thin-layer chromatography was conducted in
Kieselgel 60 F254 (Merck). Detection was first by UV
(254 nm) then charring with a solution of 20% aqueous
sulfuric acid (200 mL) in acetic acid (800 mL). Anhy-
drous MgSO4 or NaSO4 was used to dry the organic
solutions during work-ups, and the removal of the
solvents was done under vacuum with a rotoevapora-
tor. Solvents were dried and purified using standard
To a solution of the corresponding ketone in MeOH
(20 mL/mmol) CeCl3·H2O (2 equiv.) was added under a
stream of argon. The mixture was cooled to 0°C,
treated with NaBH4 (4 equiv.) and then allowed to
warm to room temperature and stirred overnight. The
reaction mixture was then diluted with EtOAc and
washed with water and brine. The organic layer was
dried and concentrated to give a residue, which was
purified by flash chromatography.
6.6. General procedure for radical deoxygenation of
thionoformates or xanthates
1
methods. H and 13C NMR spectra were recorded in
A thoroughly degassed (argon) solution of the substrate
in toluene (0.02 M) was heated to 85°C. A solution of
HSnBu3 (1.6 equiv.) and AIBN (0.1 equiv.) in toluene
(5 mL/mmol) was then added and the reaction mixture
was kept at that temperature for 30 min. After cooling,
the organic solvent was evaporated and the residue
purified by flash chromatography.
CDCl3 at 300, 400 or 500 and 75 or 50 MHz, respec-
tively. Chemical shifts are expressed in parts per million
(l scale) downfield from tetramethylsilane and are ref-
erenced to residual protium in the NMR solvent
(CHCl3: l 7.25). The structural assignment for C-7 was
carried out by diagnostic nuclear Overhauser effect
(NOE) between the vinylic hydrogen (H-7) and either
H-1 or H-5 in at least one of the isomeric E:Z pairs.
6.7. General method for sequential isopropylidene group
hydrolysis–peracetylation
6.2. General procedure for the preparation of phenyl
thiocarbonates
The compound containing the isopropylidene group
was dissolved in a previously prepared mixture of
AcOH/THF/H2O 4:2:1 (10 mL/mmol). The resulting
solution was warmed to 85°C, and stirred at that
temperature until consumption of the starting material
was observed (TLC, usually between 40 and 60 min).
The reaction mixture was then evaporated. The crude
polyols were subjected to standard acetylation condi-
tions by treatment with pyridine and excess of acetic
anhydride. After stirring overnight, the mixture was
concentrated to yield a crude material, which was
purified by flash chromatography.
A solution of the corresponding alcohol in acetonitrile
(20 mL/mmol) was treated with pyridine (3 equiv.) and
phenyl chlorothionoformate (3 equiv.). The reaction
mixture was heated at 85°C for 1 h after which it was
cooled to room temperature and then quenched with
water. The solution was diluted with CH2Cl2 and
washed successively with HCl (10%), saturated
NaHCO3, and brine. The organic phase was dried,
filtered and concentrated under vacuum.
6.8. 1-Phenyl-1,2-dideoxy-4,5:6,8-di-O-isopropyliden-
D-
6.3. General procedure for radical cyclization
talo- -glycero-oct-1-yne 9
D
A thoroughly degassed (argon) solution of thiocarbon-
ate in toluene (0.02 M) was heated to 85°C under
argon. A solution of HBu3Sn (1.6 equiv.) and AIBN
(0.1 equiv.) in toluene (5 mL/mmol) was then added
and the reaction mixture was kept at that temperature
over 12 h. After cooling, the organic solvent was evap-
orated and the residue purified.
To a solution of phenylacetylene (12.6 mL, 115.3
mmol) in dry THF (100 mL) under argon at −78°C was
added BuLi (86.4 mmol, 54 mL solution 1.6 M in
n-hexane). A solution of 1a (7.5 g, 28.8 mmol) in dry
THF (80 mL) was added dropwise and the reaction
mixture was allowed to reach room temperature after
which time, stirring was continued for 10 h. The reac-

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A. M. Go´mez et al. / Tetrahedron: Asymmetry 14 (2003) 2961–2974
tion mixture was then diluted with Et2O (250 mL) and
washed with water. The organic layer was dried and
concentrated and the residue was purified by flash
chromatography (hexane–EtOAc 8:2) to give diols 9
(5.9 g, 57%), 10 (1.4 g, 13%), 11 (1.6 g, 15%) and 12 (1.5
g, 14%). For 9: mp=52–55°C, [h]2D1 −43.4 (c 0.4,
CHCl3), 1H NMR (200 MHz, CDCl3) l (ppm): 7.45–
7.39 (m, 2H); 7.33–7.29 (m, 3H); 4.89 (dd, J=4.8, 8.8
Hz, 1H); 4.67 (dd, J=1.5, J=6.9 Hz, 1H); 4.43 (dd,
J=4.8, J=6.9 Hz, 1H); 4.30 (dd, J=1.5, 8.4 Hz, 1H);
4.26 (d, J=8.8 Hz, 1H); 4.02 (m, 1H); 3.91 (dd, J=5.4,
10.9 Hz, 1H); 3.67 (dd J=9.3, 10.9 Hz, 1H); 2.16 (d,
J=5.6 Hz, 1H); 1.57 (s, 3H); 1.55 (s, 3H); 1.46 (s, 3H);
1.40 (s, 3H). 13C NMR (75 MHz, CDCl3) l (ppm):
131.6, 128.6, 128.3, 122.3, 108.9, 99.5, 87.7, 85.6, 78.8,
74.7, 71.9, 64.5, 63.0, 62.1, 28.4, 26.4, 25.4, 19.2. MS
m/e=347.1 (M+−15). Anal. calcd for C20H26O6: C,
66.28; H, 7.23. Found: C, 65.98; H, 6.94.
(×2), 128.5, 128.2 (×2), 126.5, 122.7, 121.9 (×2), 110.2,
100, 88.8, 86.6, 79.5, 75.5, 75.8, 68.7, 62.7, 61.5, 26.3,
26.1, 25.8 (×3), 22.6, 22.2, 18.1, −3.0, −4.1.). Anal. calcd
for C33H44O7SSi: C, 64.67; H, 7.24. Found: C, 65.49; H,
7.56.
6.11. 1-Phenyl-1,2-dideoxy-7-O-(phenoxythiocarbonyl)-
4,5:6,8-di-O-isopropyliden-D-talo-D-glycero-oct-1-yne 21
To a cooled (0°C) solution of 20 (700 mg, 1.14 mmol)
in dry THF (25 mL) was added a solution prepared
with hydrogen fluoride–pyridine complex (7.5 mL), pyr-
idine (15 mL) and dry THF (30 mL). The solution was
warmed to room temperature and stirred for 36 h. The
mixture was again cooled to 0°C, and the reaction was
quenched by slow addition of saturated NaHCO3 solu-
tion and extracted with Et2O (3×50 mL). The combined
organic extracts were washed with saturated NaHCO3
and water and dried. Evaporation of the solvents gave
a residue that was purified by chromatography (hex-
ane–EtOAc 9:1) to yield 21 (470 mg, 82%): [h]2D1 −20.6
6.9. 1-Phenyl-1,2-dideoxy-4,5:6,8-di-O-isopropyliden-3-
O-(tert-butyldimethylsilyl)-D-talo-D-glycero-oct-1-yne 17
1
(c 0.6, CDCl3). H NMR (200 MHz, CDCl3) l (ppm):
To a solution of diol 9 (5 g, 13.8 mmol) in dry CH2Cl2
(110 mL) containing Et3N (2.9 mL, 20.7 mmol) was
added tert-butyldimethylchlorosilane (TBSCl) (2.7 g,
17.94 mmol) and 4-dimethylaminopyridine (100 mg).
The solution was stirred at room temperature for 48 h.
The mixture was then diluted with CH2Cl2 and washed
with water. The organic layer was dried (Na2SO4) and
concentrated, giving a residue which was purified by
flash chromatography (hexane–EtOAc 9:1) to give
silylethers 17 (4.3 g, 65%), 18 (1.02 g, 15%) and 19 (1.36
g, 17%). For 17: mp=49–51°C; [h]2D1 −32.25 (c 0.67,
7.46–7.02 (m, 10H), 5.59 (ddd, J=5.1, 6.4, 8.7 Hz, 1H),
4.96 (dd, J=4.9, 8.2 Hz, 1H), 4.65 (d, J=8.7 Hz, 1H),
4.49–4.44 (m, 2H), 4.27 (dd, J=5.1, 12.1 Hz, 1H), 3.93
(dd, J=6.4, 12.1 Hz, 1H), 3.67 (d, J=8.2 Hz, 1H), 1.58
(s, 6H), 1.47 (s, 3H), 1.41 (s, 3H). 13C NMR (50 MHz,
CDCl3) l (ppm): 193.9, 153.5, 131.8 (×2), 129.5 (×2),
128.6, 128.3 (×2), 126.7, 122.3, 121.7 (×2), 109.4, 100.4,
87.8, 85.5, 78.8, 75.9, 75.3, 68.6, 62.0, 60.9, 26.8, 26.3,
25.5, 21.1. MS m/e 483.1 (M+−15). Anal. calcd for
C27H30O7S: C, 65.04; H, 6.06. Found: C, 65.38; H, 6.25.
1
CHCl3). H NMR (300 MHz, CDCl3) l (ppm): 7.48–
7.45 (m, 2H), 7.32–7.30 (m, 3H), 4.95 (d, J=9.0 Hz,
1H), 4.46 (dd, J=1.2, 6.3 Hz, 1H), 4.35 (dd, J=6.3, 9.0
Hz, 1H), 3.99–3.87 (m, 3H), 3.63 (dd, J=10.2, 12.7 Hz,
1H); 1.55 (s, 3H), 1.51 (s, 3H), 1.43 (s, 3H), 1.41 (s,
3H), 0.92 (s, 9H), 0.26 (s, 3H), 0.23 (s, 3H). 13C NMR
(75 MHz, CDCl3) l (ppm): 131.7 (×2), 128.4, 128.2
(×2), 122.7, 109.8, 98.6, 89.0, 86.5, 79.6, 75.0, 72.5, 64.9,
63.2, 62.8, 28.5, 26.4, 26.1, 25.8 (×3), 19.8, 18.1, −3.1,
−4.2. MS m/e=476.3 (M+), 461.3 (M+−15). Anal. calcd
for C26H40O6Si: C, 65.51; H, 8.46. Found: C, 65.55; H,
8.70.
6.12. (3aS,4S,5aR,9aR,9bS)-5-Benzylidene-2,2,8,8-tetra-
methylhexahydro-3aH-[1,3]dioxolo[4,5-h][1,3]benzodi-
oxin-4-yl tert-butyl(dimethyl)silyl ether 30
Radical cyclization of thiocarbonate 20 (2.5 g, 4.1
mmol) afforded after (hexane–EtOAc 95:5) compound
29 (only the Z isomer was detected) (1.09 g, 58%)
followed by 30 as a 1:1 mixture of Z/E isomers (721
mg, 38%). For 30: 1H NMR (for two isomers, 300
MHz, CDCl3) l (ppm): 7.35–7.30 (m, 8H), 7.28 (m,
2H), 6.55 (d, J=2 Hz, 1H), 6.50 (d J=2.7 Hz, 1H),
5.05 (s, 1H), 4.85 (m, 2H), 4.37 (s, 1H), 4.23–4.18 (m,
4H), 4.15 (dd, J=5.0, 10.9 Hz, 1H), 3.96 (t, J=10.9
Hz, 1H), 3.82 (dd J=4.5, 11.0 Hz, 1H), 3.57 (t, J=11
Hz, 1H), 2.89 (ddt, J=2.8, 4.5, 10.8 Hz, 1H); 2.48 (ddt,
J=2.3, 5.1, 11.1 Hz, 1H); 1.56 (s, 3H), 1.55 (s, 6H),
1.54 (s, 3H), 1.49 (s, 3H), 1.48 (s, 3H), 1.44 (s, 3H), 1.37
(s, 3H), 0.95 (s, 9H); 0.81 (s, 9H), 0.16 (s, 3H), 0.14 (s,
3H), −0.23 (s, 3H), −0.41 (s, 3H). 13C NMR (for two
isomers, 50 MHz, CDCl3) l (ppm): 136.1, 135.8, 135.7,
134.6, 131.6, 129.3, 128.6 (×2), 128.5 (×2), 128.0 (×2),
127.7 (×2), 127.3, 127.1, 109.3 (×2), 99.0, 98.9, 76.5,
76.2, 75.8, 75.5, 75.4, 71.8, 71.3, 65.5, 65.3, 62.5, 38.3,
36.9, 29.5, 29.4, 26.0, 25.8, 25.6 (×3), 25.5 (×3), 24.0,
23.7, 19.4, 19.3, 17.7, 17.6, −4.9, −4.6, −5.1, −5.4.).
Anal. calcd for C26H40O5Si: C, 67.79; H, 8.75. Found:
C, 67.97; H, 8.83.
6.10. 1-Phenyl-1,2-dideoxy-7-O-(phenoxythiocarbonyl)-
4,5:6,8-di-O-isopropyliden-3-O-(tert-butyldimethylsilyl)-
D
-talo-D-glycero-oct-1-yne 20
Prepared from alcohol 17 following the general proce-
dure for the preparation of phenyl thionoformates,
(85% yield). White solid: mp=53–57°C, [h]2D1 −61.5 (c
1
0.6, CHCl3), IR (thin film): 1200 cm−1. H NMR (300
MHz, CDCl3) l (ppm): 7.51–7.09 (m, 10H), 5.55 (dt,
J=4.3, 8.2 Hz, 1H), 4.96 (d, J=9.0 Hz, 1H), 4.35 (m,
3H), 4.20 (dd, J=4.5, 12.7 Hz, 1H), 3.95 (dd, J=4.3,
12.7 Hz, 1H), 1.56 (s, 6H), 1.44 (s, 3H), 1.43 (s, 3H),
0.94 (s, 9H), 0.28 (s, 3H), 0.26 (s, 3H). 13C NMR (75
MHz, CDCl3) l (ppm): 194.3, 153.5, 131.8 (×2), 129.5

A. M. Go´mez et al. / Tetrahedron: Asymmetry 14 (2003) 2961–2974
2969
6.13. (3aR,4S,5E,5aS,9aR,9bS)-5-Benzylidene-2,2,8,8-
tetramethyl hexahydro-3aH-[1,3]dioxolo[4,5-h][1,3]-
benzodioxil-4-ol (Z)-33 and (3aR,4S,5Z,5aS,9aR,9bS)-
5-benzylidene-2,2,8,8-tetramethyl hexahydro-3aH-
[1,3]dioxolo[4,5-h][1,3]benzodioxil-4-ol (E)-33
(s, 9H), 0.12 (s, 3H), 0.11 (s, 3H). 13C NMR (50 MHz,
CDCl3) l (ppm): 195.0, 155.6, 129.6 (×2), 126.4 (×2),
120.6, 110.0, 99.9, 82.1, 77.2, 74.7, 69.8, 67.3, 60.0, 39.3,
27.3, 26.4, 25.9 (×3), 24.4, 23.1, 18.2, −4.2, −4.5.
6.16. 1,2:4,6-Di-O-Isopropilidene-3-O-tertbutyldimethyl-
silyl-5a-carba-b-L-talopyranose 44
Radical cyclization of 21 (400 mg, 0.8 mmol) afforded
after flash chromatography (hexane–EtOAc 9:1) (Z)-33
(68 mg, 24%) followed by (E)-33 (45 mg, 16%) and
(E)-34 (28 mg, 10%). For (Z)-33: mp=142–144°C, [h]D21
Colorless oil, (114 mg, 90%): [h]2D1 −10.2 (c 0.5, CHCl3).
1H NMR (300 MHz, CDCl3) l (ppm): 4.08 (dt, J=6.2,
10.6 Hz, 1H), 3.97 (dd, J=3.8, 6.2 Hz, 1H), 3.89 (t,
J=3.8 Hz, 1H), 3.84 (t, J=3.8 Hz, 1H), 3.78 (dd,
J=4.0, 11.0 Hz, 1H), 3.55 (dd, J=6.1, 11.0 Hz, 1H),
2.17 (q, J=12.0 Hz, 1H), 1.60–1.48 (m, 2H, H5), 1.56
(s, 3H), 1.41 (s, 3H), 1.40 (s, 3H), 1.34 (s, 3H), 0.93 (s,
9H), 0.11 (s, 6H). 13C NMR (75 MHz, CDCl3) l (ppm):
108.9, 99.4, 75.3, 74.1, 70.9, 68.2, 63.7, 33.5, 28.7, 27.6,
26.5, 26.1 (×3), 26.0, 25.1, 18.2, −4.3, −4.5.
1
+58.5 (c 0.6, CHCl3). H NMR (300 MHz, CDCl3) l
(ppm): 7.38–7.19 (m, 5H), 6.94 (s, 1H), 4.84 (t, J=3.7
Hz, 1H), 4.54 (dd, J=1.8, 3.8 Hz, 1H), 4.28–4.17 (m,
4H), 2.89 (m, 1H), 2.40 (s, 1H), 1.56 (s, 3H), 1.51 (s,
3H), 1.40 (s, 6H). 13C NMR (75 MHz, CDCl3) l (ppm):
137.2, 135.9, 130.4, 128.6 (×2), 128.1 (×2), 126.8, 108.7,
99.2, 76.4, 75.2, 69.2, 66.2, 61.7, 33.1, 29.1, 26.1, 24.6,
19.4. MS m/e: 346.2 (M+), 331.1 (M+−15). Anal. calcd
for C20H26O5: C, 69.34; H, 7.56. Found: C, 69.60; H,
1
7.80. For (E)-33: [h]2D1 +22.7 (c 0.4, CHCl3). H NMR
6.17. 1,2,3,4,6-Penta-O-Acetyl-5a-carba-™-L-talopyran-
ose 45
(300 MHz, CDCl3) l (ppm): 7.37–7.20 (m, 5H), 6.70 (s,
1H), 4.87 (m, 1H), 4.58 (dd, J=4.2, 7.2 Hz, 1H), 4.48
(dd, J=3.8, 7.2 Hz, 1H), 4.32 (t, J=3.8 Hz, 1H), 3.85
(dd, J=5.6, 11.7 Hz, 1H), 3.60 (dd, J=4.3, 11.7 Hz,
1H), 3.31 (m, 1H), 2.28 (d, J=10.9 Hz, 1H), 1.43 (s,
3H), 1.38 (s, 3H), 1.37 (s, 3H), 1.35 (s, 3H). 13C NMR
(50 MHz, CDCl3) l (ppm): 138.8, 136.1, 128.5 (×2),
128.1 (×2), 126.5, 124.5, 109.9, 98.0, 76.7, 74.9, 68.9,
65.8, 62.5, 33.4, 28.4, 26.1, 24.6, 20.3. Anal. calcd for
C20H26O5: C, 69.34; H, 7.56. Found: C, 69.66; H, 7.78.
To a solution of 44 (100 mg, 0.27 mmol) in THF (10
mL) was added Bu4NF (208 mg, 0.81 mmol, 3 equiv.)
and the reaction mixture was stirred overnight. Then
the reaction was diluted with CH2Cl2 and washed with
water and brine. The organic layer was dried, filtered
and concentrated to give a residue, which was purified
by flash chromatography (hexane–EtOAc 1:1) to yield
1,2:4,6-di-O-isopropylidene-5a-carba-b-L-talopyranose
([h]2D1 −12.9 (c 0.4, CHCl3). 1H NMR (300 MHz,
CDCl3) l (ppm): 4.30 (t, J=4.6 Hz, 1H), 4.18 (m, 2H),
4.09 (dd, J=3.0, 11.6 Hz, 1H), 3.76 (dt, J=4.6, 10.4
Hz, 1H), 3.60 (dd, J=2.2, 11.6 Hz, 1H), 2.86 (d,
J=10.4 Hz, 1H), 2.26 (dt, J=10.6, 13.3 Hz, 1H),
1.62–1.49 (m, 1H), 1.57 (s, 3H), 1.46–1.30 (m, 1H); 1.45
(s, 3H); 1.43 (s, 3H); 1.37 (s, 3H). 13C NMR (75 MHz,
CDCl3) l (ppm): 109.1, 99.4, 74.8, 74.3, 69.2, 67.9, 64.1,
31.1, 29.5, 28.4, 26.2, 26.1, 18.9. This compound was
then submitted to the standard procedure for cleavage
of the isopropylidene group and peracetyation to fur-
nish pentaacetate 45 (84 mg, 80%): mp=135–138°C,
6.14. (3aS,4S,5R,5aS,9aR,9bS)-4-{[Tertbutyl(dimethyl)-
silyl]oxy}-2,2,8,8-tetramethylhexahydro-3aH-[1,3]-diox-
olo[4,5-h][1,3]benzodioxin-5-ol 42
Ozonolysis of olefin 30 (500 mg, 1.33 mmol) afforded
ketone 41, which without further purification was
reduced (NaBH4 and CeCl3, general method). Flash
chromatography (hexane–EtOAc 8:2) yielded alcohol
42 (210 mg, 50%) as a white solid: mp=86–88°C, [h]D21
1
−29.9 (c 0.6, CDCl3). H NMR (200 MHz, CDCl3) l
(ppm): 4.31 (t, J=4.7 Hz, 1H), 4.28 (dd, J=7.8, 11.6
Hz, 1H), 4.17 (t, J=11.3 Hz, 1H), 3.96 (dd, J=4.7, 7.8
Hz, 1H), 3.84 (t, J=4.7 Hz, 1H), 3.76 (dd, J=4.9, 11.3
Hz, 1H), 3.72 (m, 1H), 2.73 (s, 1H), 1.55 (s, 3H),
1.50–1.40 (m, 1H), 1.51 (s, 3H), 1.41 (s, 3H), 1.33 (s,
3H), 0.91 (s, 9H), 0.13 (s, 3H), 0.12 (s, 3H). 13C NMR
(75 MHz, CDCl3) l (ppm): 109.5, 99.0, 78.4, 77.4, 70.4,
70.3, 68.8, 61.1, 37.7, 29.6, 28.7, 25.8, 25.7 (×3), 19.1,
18.2, −4.6, −4.7. Anal. calcd for C20H26O5: C, 58.73; H,
9.34. Found: C, 59.02; H, 9.56.
1
[h]2D1 +5.2 (c 0.4, CHCl3). H NMR (500 MHz, CDCl3)
l (ppm): 5.49 (t, J=3.1 Hz, 1H), 5.38 (t, J=2.9 Hz,
1H), 4.93 (m, 2H), 4.05 (dd, J=8.8, 11.1 Hz, 1H), 3.91
(dd, J=6.3, 11.1 Hz, 1H), 2.20–2.10 (m, 1H), 2.11 (s,
3H), 2.07 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H), 1.96 (s,
3H), 1.88 (q, J=12.5 Hz, 1H), 1.69 (dt, J=4.0, 12.5
Hz, 1H). 13C NMR (75 MHz, CDCl3) l (ppm): 170.8,
170.1, 170.0, 169.8, 169.6, 69.0, 68.9, 68.7, 66.1, 63.0,
29.7, 23.5, 26.8 (×2), 20.7, 20.6, 20.5. Anal. calcd for
C17H24O10: C, 52.57; H, 6.23. Found: C, 52.71; H, 6.43.
6.15. O-(3aS,4S,4aR,8aS,9R,9aS)-4-{[Tertbutyl(dime-
thyl)silyl]oxy}-2,2,6,6-tetramethylhexahydro-3aH-[1,3]-
dioxolo[4,5-h][1,3]benzodioxin-9-yl-O-phenyl thiocarbon-
ate 43
6.18. (3aR,4R,5aR,9aS,9bS)-5-Benzylidene-4-(benzyl-
oxy)-2,2,8,8-tetramethylhexahydro-3aH-[1,3]-dioxolo-
[4,5-h][1,3]benzodioxine 46
Colorless oil, (189 mg, 70%): [h]2D1 −28.3 (c 0.6, CHCl3).
1H NMR (200 MHz, CDCl3) l (ppm): 7.43–7.10 (m,
5H), 6.38 (dd, J=8.2 Hz, 11.2 Hz, 1H), 4.32 (t, J=8.2
Hz, 1H), 4.18 (m, 2H), 4.00 (dd, J=2.6, 7.8 Hz, 1H),
3.91 (dd, J=9.1, 11.1 Hz, 1H), 3.78 (dd J=5.1, 11.1
Hz, 1H), 2.05 (m, 1H), 1.40 (s, 9H), 1.37 (s, 3H), 0.96
To a solution of 30 (700 mg, 1.52 mmol) in THF (52
mL) was added Bu4NF (2.4 g, 9.12 mmol) and the
reaction mixture was stirred overnight. The reaction
was then diluted with CH2Cl2 and washed with water
and brine. The organic layer was dried, filtered and
concentrated to give a residue which was purified by

2970
A. M. Go´mez et al. / Tetrahedron: Asymmetry 14 (2003) 2961–2974
flash chromatography (hexane–EtOAc 8:2). The pure-
material (380 mg, 1.10 mmol) was then dissolved in dry
THF (45 mL) and treated with NaH (79 mg 60%, 1.97
mmol) at 0°C for 30 min. Then the mixture was treated
with benzyl bromide (170 mL, 1.43 mmol) and Bu4NI
(405 mg, 1.1 mmol). After 3 h the reaction was diluted
with Et2O and washed with water. The organic phase
was dried, concentrated and the residue purified by
flash chromatography (hexane–EtOAc 9:1) to yield 46
as an inseparable 4:1 mixture of isomers (308 mg, 66%).
1H NMR (200 MHz, CDCl3, only signals for the main
isomer are shown) l (ppm): 7.40–7.20 (m, 10H), 6.52
(d, J=2.7 Hz, 1H), 4.79 (dd, J=7.4, 11.0 Hz, 1H), 4.68
(d, J=12.4 Hz, 1H), 4.59 (d, J=12.4 Hz, 1H), 4.36–
4.22 (m, 2H), 4.12 (m, 1H), 3.79 (dd, J=4.5, 11.1 Hz,
1H), 3.42 (t, J=11.1 Hz, 1H), 2.86 (ddt, J=2.7, 4.5,
11.1 Hz, 1H), 1.56 (s, 3H), 1.55 (s, 3H), 1.39 (s, 3H),
1.38 (s, 3H). 13C NMR (75 MHz, CDCl3) l (ppm):
138.6, 136.2, 134.1, 131.9, 131.6, 128.7 (×2), 128.3 (×2),
128.1 (×2), 127.7, 127.3, 127.1 (×2), 126.9, 110.2, 110.1,
99.2, 99.1, 82.1, 76.7 (×2), 76.1, 75.9, 72.7, 72.6, 71.9,
70.9, 70.4, 64.8, 62.4, 37.4, 36.8, 29.6 (×2), 26.3, 26.1,
24.9, 24.6, 19.4 (×2). Anal. calcd for C27H32O5: C,
74.29; H, 7.39. Found: C, 74.51; H, 7.27.
J=12.6 Hz, 1H), 4.57 (d, J=12.6 Hz, 1H), 4.33 (t,
J=4.3 Hz, 1H), 3.84 (dd, J=4.9, 7.8 Hz, 1H), 3.69–
3.53 (m, 4H), 1.50 (m, 1H), 1.51 (s, 3H), 1.40 (s, 3H),
1.35 (s, 3H), 1.34 (s, 3H), 1.35–1.19 (m, 2H). 13C NMR
(75 MHz, CDCl3) l (ppm): 138.2, 128.4 (×2), 127.8
(×3), 110.3, 99.8, 78.6, 75.2, 74.8, 74.0, 70.9, 64.1, 33.1,
29.7, 28.4, 26.2, 26.0, 18.0.
6.21. 2,3:4,6-Tetra-O-Acetyl-1-O-benzyl-5a-carba-b-D-
mannopyranose 51
Compound 50 (270 mg, 0.61 mmol) was submitted to
the procedure for cleavage of the isopropylidene group
followed by acetylation. The residue was purified by
flash chromatography (hexane–EtOAc 6:4) to yield 51
as white solid (53 mg, 85%): mp=113–115°C, [h]D21
1
+9.96 (c 0.78, CHCl3). H NMR (300 MHz, CDCl3): l
7.33–7.26 (m, 5H), 5.77 (s, 1H), 5.23 (t, J=10 Hz, 1H),
4.88 (dd, J=2.9, 10.0 Hz, 1H), 4.63 (d, J=11.6 Hz,
1H), 4.42 (d, J=11.6 Hz, 1H), 4.02 (m, 2H), 3.59 (m,
1H), 2.18 (s, 3H), 2.06 (s, 3H), 2.03 (s, 3H), 2.00 (s,
3H), 2.00–1.90 (m, 3H). 13C NMR (75 MHz, CDCl3) l
(ppm): 170.8, 170.4, 170.2, 170.1, 137.4, 128.5 (×2),
127.9, 127.7 (×2), 73.6, 72.2, 70.8, 69.5, 68.2, 63.9, 35.9,
28.6, 21.0, 20.8 (×2), 20.7. Anal. calcd for C20H28O5: C,
68.94; H, 8.10. Found: C, 69.12; H, 8.25.
6.19. (3aR,4R,5R,5aS,9aS,9bS)-4-(Benzyloxy)-2,2,8,8-
tetramethylhexahydro-3aH-[1,3]-dioxolo[4,5-h][1,3]-
benzodioxin-5-ol 48
6.22. 1,2,3,4,6-Penta-O-Acetyl-5a-carba-b-D-mannopy-
ranose 52
Ozonolysis of olefin 46 (270 mg, 0.61 mmol) afforded
ketone 47 which, without further purification was
reduced (NaBH4 and CeCl3, general method). Purifica-
tion was carried out by flash chromatography (hexane–
EtOAc 8:2) to yield alcohol 48 (122 mg, 55% overall):
[h]2D1 −42.2 (c 0.62, CHCl3). 1H NMR (300 MHz,
CDCl3) l (ppm): 7.40–7.24 (m, 5H), 4.79 (d, J=12.4
Hz, 1H), 4.67 (d, J=12.4 Hz, 1H), 4.42 (t, J=4.5 Hz,
1H), 4.26 (dd, J=7.8, 11.6 Hz, 1H), 4.15 (t, J=11.3
Hz, 1H), 3.94 (m, 2H), 3.73 (dd, J=4.9, 11.3 Hz, 1H),
3.51 (t, J=3.6 Hz, 1H), 2.72 (s, 1H), 1.56 (s, 3H), 1.49
(s, 3H), 1.42 (m, 1H), 1.38 (s, 3H), 1.36 (s, 3H). 13C
NMR (75 MHz, CDCl3) l (ppm): 137.1, 128.6 (×2),
128.2, 127.9 (×2), 110.0, 99.1, 78.5, 75.7, 74.4, 70.6,
69.0, 66.9, 61.1, 37.7, 29.6, 28.6, 26.1, 19.1.
A solution of benzyl ether 51 (50 mg, 0.12 mmol) in
MeOH (32 mL) was hydrogenolyzed in the presence of
10% Pd/C (10 mg) at 35 psi at room temperature for 60
min. The reaction mixture was filtered, through a short
pad of Celite, and concentrated to give a residue, which
was acetylated. The reaction mixture was concentrated
and the crude material purified by flash chromatogra-
phy (hexane–EtOAc 7:3) to yield carba-b-D-mannopy-
ranose pentaacetate 52 (33 mg, 75% overall):
1
mp=116–118°C, [h]2D1 +2.0 (c 0.6, CHCl3). H NMR
(300 MHz, CDCl3) l (ppm): 5.49 (t, J=2.7 Hz, 1H),
5.15 (t, J=10.1 Hz, 1H), 4.89 (dd, J=2.7, 10.1 Hz,
1H), 4.88 (m, 1H), 3.99 (dd, J=5.6, 11.3 Hz, 1H), 3.93
(dd, J=3.5, 11.3 Hz, 1H), 2.11 (s, 3H), 2.00 (s, 3H),
2.00–1.89 (m, 2H), 1.97 (s, 3H), 1.94 (s, 3H), 1.91 (s,
1
6.20. 2,3:4,6-Di-O-isopropylidene-1-O-benzyl-5a-carba-
3H), 1.79 (q, J=12.5 Hz, 1H): H NMR (400 MHz,
b-D
-mannopyranose 50
C6D6) l (ppm): 5.86 (t, J=2.6 Hz, 1H), 5.46 (t, J=0.3
Hz, 1H), 5.01 (dd, J=2.6, 10.3 Hz, 1H), 4.72 (ddd,
J=2.6, 4.7 Hz, J=12.4 Hz, 1H), 4.06 (dd, J=5.3, 11.3
Hz, 1H), 3.74 (dd, J=3.5, 11.3 Hz, 1H), 1.86 (q,
J=12.4 Hz, 1H), 1.72–1.68 (m, 1H), 1.69 (s, 3H), 1.67
(s, 6H), 1.65 (s, 3H), 1.61 (s, 3H), 1.44–1.34 (m, 1H).
13C NMR (75 MHz, CDCl3) l (ppm): 171.0 (×2), 170.8
(×3), 72.7, 70.8, 70.2, 69.4, 64.7, 37.9, 28.3, 21.7 (×3),
21.5 (×2). Anal. calcd for C17H24O10: C, 52.57; H, 6.23.
Found: C, 52.71; H, 6.43.
Alcohol 48 (112 mg, 0.31 mmol) was dissolved in dry
THF (15 mL) and treated with NaH (25 mg 60%, 0.62
mmol) at 0°C for 30 min. Then, the mixture was treated
with CS2 (37.4 mL, 0.62 mmol) at room temperature for
60 min after which time MeI was added (130 mL, 2.1
mmol). Stirring was maintained for additional 30 min
and then the reaction was diluted with CH2Cl2, washed
with water, dried and concentrated to give a residue
which was chromatographed (hexane–EtOAc 8:2) to
give xanthate 49 (98 mg, 70%). This material was
dissolved in toluene and the general procedure for
radical deoxygenation was carried out to afford a
residue which was purified by flash chromatography
(hexane–EtOAc 7:3) to yield 50 (67 mg, 90%). 1H NMR
(300 MHz, CDCl3) l (ppm): 7.26–7.22 (m, 5H), 4.65 (d,
6.23. (3aR,4R,5Z,5aS,9bS)-5-Benzylidene-4-(benzyl-
oxy)-2,2,8,8-tetramethylhexahydro-3aH-[1,3]-diox-
olo[4,5-h][1,3]benzodioxine 53
A solution of (Z)-33 (290 mg, 0.84 mmol) in dry DMF
at 0°C (15 mL) was treated with NaH (67.2 mg 60%,

A. M. Go´mez et al. / Tetrahedron: Asymmetry 14 (2003) 2961–2974
2971
1.68 mmol) and the reaction mixture was allowed to
warm to room temperature. Stirring was continued for
20 min and benzyl bromide (150 mL, 1.26 mmol) was
added. After 6 h the reaction was diluted with Et2O and
washed with water. The organic phase was dried, con-
centrated, and the residue purified by flash chromatog-
raphy (hexane–EtOAc 95:5) to yield (Z)-53 (292 mg,
80%): mp=75–78°C, [h]2D1 +68.2 (c 0.8, CHCl3). 1H
NMR (300 MHz, CDCl3) l (ppm): 7.28–7.10 (m, 10H),
6.97 (s, 1H), 4.62 (d, J=5.0 Hz, 1H), 4.58 (dd, J=1.2,
4.0 Hz, 1H), 4.37 (t, J=5.0 Hz, 1H), 4.29 (d, J=12.2
Hz, 1H), 4.20 (dd, J=4.0, 12.0 Hz, 1H), 4.18 (m, 1H),
4.12 (dd, J=2.4, 12.0 Hz, 1H), 4.10 (d, J=12.2 Hz,
1H), 2.86 (m, 1H), 1.53 (s, 3H), 1.49 (s, 3H), 1.38 (s,
3H), 1.30 (s, 3H). 13C NMR (75 MHz, CDCl3) l (ppm):
137.9, 136.7, 134.8, 130.6, 128.5 (×2), 128.0 (×2), 127.8
(×2), 127.7 (×2), 127.2, 126.6, 109.1, 99.1, 76.6, 75.6,
73.4, 70.2, 68.8, 61.4, 34.1, 28.7, 25.5, 25.4, 19.3. MS
m/e: 436.2 (M+).
Hz, 1H), 4.62 (d, J=12.4 Hz, 1H), 4.45 (dd, J=2.7, 7.3
Hz, 1H), 4.11 (dd, J=2.0, 7.3 Hz, 1H), 4.10 (m, 1H),
4.02 (dd, J=1.6, 11.5 Hz, 1H), 3.94 (t, J=2.0 Hz, 1H),
3.54 (d, J=11.5 Hz, 1H), 1.62–1.33 (m, 3H); 1.48 (s,
3H), 1.39 (s, 3H), 1.35 (s, 3H), 1.21 (s, 3H). 13C NMR
(75 MHz, CDCl3) l (ppm): 138.4, 128.3 (×2), 128.1
(×2), 127.6, 108.9, 98.4, 76.4, 73.4, 71.5, 70.7, 68.2, 65.4,
29.3, 27.0, 26.3, 24.2, 24.1, 18.8.
6.26. 1,2,3,4,6-Penta-O-Acetyl-5a-carba-a-L-gulopyran-
ose 57
A solution of benzyl ether 56 (50 mg, 0.15 mmol) in
MeOH (25 mL) was hydrogenolyzed in the presence of
10% Pd/C (10 mg) at 35 psi at room temperature for 60
min. The reaction mixture was filtered through a short
pad of Celite and concentrated to give a residue which
was subjected to the general procedure for the cleavage
of the isopropylidene moiety. After acetylation, the
reaction mixture was concentrated and the crude mate-
rial purified by flash chromatography (hexane–EtOAc
6.24. (3aR,4R,5aR,9aS,9bS)-4-(Benzyloxy)-2,2,8,8-tet-
ramethylhexahydro-3aH-[1,3]-dioxolo[4,5-h][1,3]benzo-
dioxin5-ol 54
6:4) to yield carba-a- -gulopyranose pentaacetate 57
L
1
(39 mg, 70% overall): [h]2D1 −34.1 (c 0.3, CHCl3). H
NMR (300 MHz, CDCl3) l (ppm): 5.28–5.20 (m, 4H),
4.11–3.98 (m, 2H), 2.60 (m, 1H), 2.07 (s, 3H), 2.06 (s,
3H), 2.05 (s, 3H), 2.05–2.02 (m, 2H), 2.04 (s, 3H), 2.03
Ozonolysis of olefin 53 (270 mg, 0.61 mmol) afforded
the corresponding ketone which was filtered through
silica gel and then immediately subjected to reduction
with NaBH4 and CeCl3. Flash chromatography of the
residue (hexane–EtOAc 8:2) yielded an inseparable, 1:1
mixture of isomeric alcohols 54 (142 mg, 64% overall).
1H NMR (for two isomers, 300 MHz, CDCl3) l (ppm):
7.31–7.20 (m, 10H), 4.87 (d, J=12.2 Hz, 1H), 4.81 (d,
J=12.2 Hz, 1H), 4.79 (d, J=12.2 Hz, 1H), 4.70 (d,
J=12.2 Hz, 1H,), 4.52 (m, 2H), 4.28–4.13 (m, 4H),
4.09–3.92 (m, 8H), 3.00 (d, J=7.2 Hz, 1H), 2.86 (d,
J=8.6 Hz, 1H), 2.23 (m, 1H), 1.90 (m, 1H), 1.50 (s,
3H), 1.44 (s, 3H), 1.43 (s, 3H), 1.39 (s, 3H), 1.34 (s,
3H), 1.33 (s, 3H), 1.27 (s, 3H), 1.16 (s, 3H). 13C NMR
(75 MHz, CDCl3) l (ppm): 137.8, 129.8, 128.5 (×2),
128.3 (×4), 128.1 (×2), 127.9, 127.6, 109.4, 109.0, 99.2,
98.7, 78.0, 76.3, 76.1, 75.7, 75.2, 74.8, 73.4, 72.6, 71.3,
68.7, 67.6, 66.9, 63.6, 60.7, 38.5, 32.6, 29.4, 29.1, 26.2
(×2), 23.9, 23.8, 18.9, 18.5. MS m/e: 364.2 (M+), 349.2
(M+−15). Anal. calcd for C20H28O6: C, 65.91; H, 7.74.
Found: C, 66.13; H, 7.89.
1
(s, 3H). H NMR (300 MHz, C6D6) l (ppm): 5.83 (dd,
J=3.2, 6.5 Hz, 1H), 5.72 (m, 2H), 5.61 (dt, J=3.0, 6.7
Hz, 1H), 4.24 (dd, J=7.0, 10.8 Hz, 1H), 4.02 (dd,
J=6.7, 10.8 Hz, 1H), 2.76 (m, 1H), 1.96 (m, 2H), 1.97
(s, 3H), 1.91 (s, 3H), 1.90 (s, 3H), 1.89 (s, 3H), 1.80 (s,
3H). 13C NMR (75 MHz, CDCl3) l (ppm): 169.8,
169.7, 169.5, 169.4, 169.3, 69.1, 68.3, 67.5, 62.9, 53.3,
30.2, 26.9, 20.5, 20.3, 20.2, 20.0, 18.5. MS m/e: 411.2
(M+Na+). Anal. calcd for C17H24O10: C, 52.57; H, 6.23.
Found: C, 52.81; H, 6.51.
6.27. (3aR,4R,5R,5aR,9aS,9bS)-4-(Benzyloxy)-2,2,8,8-
tetramethylhexahydro-3aH-[1,3]-dioxolo[4,5-h][1,3]-
benzodioxin-5-ol 58
Ozonolysis of olefin 33 (270 mg, 0.78 mmol) yielded the
corresponding ketone which was filtered through silica
gel (hexane–EtOAc 8:2) and then immediately reduced
with NaBH4 and CeCl3. Flash chromatography (hex-
ane–EtOAc 8:2) yielded alcohol 58 (133 mg, 62%):
mp=102–104°C. 1H NMR (200 MHz, CDCl3) l (ppm):
4.48 (dd, J=3.3, 6.8 Hz, 1H), 4.23–4.02 (m, 5H), 2.85
(d, J=6.7 Hz, 1H), 2.40 (d, J=10.9 Hz, 1H), 1.84 (m,
1H), 1.50 (s, 3H), 1.45 (s, 3H), 1.37 (s, 3H), 1.33 (s,
3H). 13C NMR (75 MHz, CDCl3) l (ppm): 109.9, 98.9,
76.0, 75.6, 68.7, 67.6, 67.2, 62.3, 36.9, 29.5, 26.3, 24.0,
18.5. Anal. calcd for C20H28O6: C, 65.91; H, 7.74.
Found: C, 66.23; H, 7.87.
6.25. 1-O-Benzyl-2,3:4,6-di-O-Isopropylidene-5a-carba-
a-L-gulopyranose 56
Alcohols 54 (110 mg, 0.30 mmol) were dissolved in dry
THF (15 mL) and treated with NaH (24 mg 60%, 0.60
mmol) at 0°C for 30 min. Then, the mixture was treated
with CS2 (36.2 mL, 0.60 mmol) at room temperature for
60 min after which MeI was added (124 mL, 2 mmol).
Stirring was maintained for additional 30 min and then
the reaction was diluted with CH2Cl2, washed with
water, dried and concentrated to give a residue which
was chromatographed (hexane–EtOAc 8:2) to give a 1:1
mixture of xanthates 55 (96 mg, 75%). This mixture was
deoxygenated and the residue purified by flash chro-
matography (Hexane–EtOAc 7:3) to yield carbagulose
derivative 56 (66 mg, 90%). 1H NMR (300 MHz,
CDCl3) l (ppm): 7.42–7.28 (m, 5H), 4.70 (d, J=12.4
6.28. (3aR,4R,5R,5aR,9aS,9bS)-4,5-Bis-(benzyloxy)-
2,2,8,8-tetramethylhexahydro-3aH-[1,3]-dioxolo[4,5-h]-
[1,3]benzodioxine 59
Diol 58 (290 mg, 0.84 mmol) was converted into the
dibenzylether following the conditions previously
described for 53. Flash chromatography (hexane–
EtOAc 95:5) gave 59 (267 mg, 70%) as a colorless oil.

2972
A. M. Go´mez et al. / Tetrahedron: Asymmetry 14 (2003) 2961–2974
1H NMR (200 MHz, CDCl3) l (ppm): 7.40–7.35 (m,
4H), 7.33–7.20 (m, 6H), 4.78 (d, J=11.8 Hz, 1H); 4.68
(d, J=11.8 Hz, 1H), 4.54 (d, J=11.8 Hz, 1H), 4.44 (d,
J=11.8 Hz, 1H), 4.43 (m, 1H), 4.20 (dd, J=4.8, 6.2 Hz,
1H), 4.12 (dd, J=1.5, 11.9 Hz, 1H), 3.98–3.91 (m, 3H),
3.79 (dd, J=2.3, 10.4 Hz, 1H), 2.25 (ddd, J=2.6, 4.5,
10.4 Hz, 1H), 1.43 (s, 6H), 1.31 (s, 3H), 1.27 (s, 3H).
13C NMR (75 MHz, CDCl3) l (ppm): 138.8, 138.5,
128.2 (×2), 128.1 (×4), 127.7 (×2), 127.5, 127.2, 109.1,
98.8, 76.5, 74.5, 74.4, 74.3, 73.2, 72.1, 68.2, 59.8, 39.5,
29.6, 25.7, 25.5, 18.8.
(dd, J=4.7, 7.0 Hz, 1H), 4.27 (d, J=11.6 Hz, 1H); 4.15
(t, J=3.6 Hz, 1H), 3.99 (d, J=3.0 Hz, 1H), 3.98 (d,
J=3.0 Hz, 1H), 3.84 (dd, J=3.6, 8.3 Hz, 1H), 3.54 (d,
J=2.8 Hz, 1H), 2.38 (ddt, J=3.0, 4.7, 8.3 Hz, 1H), 1.50
(s, 3H), 1.37 (s, 3H), 1.05 (s, 9H). 13C NMR (75 MHz,
CDCl3) l (ppm): 138.8, 138.6, 135.7 (×2), 135.6 (×2),
132.5, 132.4, 130.0, 129.9, 128.2 (×4), 127.9 (×2), 127.8
(x2), 127.7 (×2), 127.4 (×2), 127.3, 127.2, 109.5, 77.9,
74.6, 74.4, 74.2, 73.6, 72.1, 71.2, 63.5, 41.2, 26.1 (×3),
26.4, 24.8, 19.1. MS m/e: 637.1 (M+−15). Anal. Calcd
for C40H48O6Si: C, 73.58; H, 7.41. Found: C, 73.78; H,
7.65.
6.29. Preparation of tetraol 60
6.31. 3,4-Di-O-benzyl-6-O-tertbutyldiphenylsilyl-1,2-O-
Prepared from diacetonide 59 (50 mg, 0.11 mmol)
according to the general procedure (hexane–EtOAc
isopropyliden-5a-carba-a-D-allopyranose 62
1
3:7). Colorless oil: [h]2D1 +69.5 (c 1.1, CHCl3). H NMR
Alcohol 61 (152 mg, 0.23 mmol) was converted in the
corresponding thiocarbonate according to conditions
described in the general procedure. After aqueous
work-up the crude material was dissolved in toluene
and the general procedure for the radical deoxygena-
tion was carried out to afford a residue which was
purified by flash chromatography (hexane–EtOAc 7:3)
to yield carba-allose derivative 62 (84 mg, 58%): [h]D21
(300 MHz, CDCl3) l (ppm): 7.36 (m, 5H), 7.33 (m,
5H), 4.94 (d, J=11.2 Hz, 1H), 4.72 (d, J=11.6 Hz,
1H), 4.65 (d, J=11.2 Hz, 1H), 4.55 (d, J=11.6 Hz,
1H), 4.21 (s, 2H), 4.11 (m, 1H), 3.08 (m, 3H), 3.74–3.60
(m, 3H), 3.08 (m, 1H), 2.39 (s, 1H), 2.25 (m, 1H). 13C
NMR (50 MHz, CDCl3) l (ppm): 137.7, 137.6, 128.4
(×2), 128.3 (×2), 127.8 (×3), 127.7, 127.6 (×2), 79.7,
75.7, 75.6, 74.5, 72.6, 71.9, 67.1, 61.9, 37.2.
1
+50.5 (c 0.6, CHCl3). H NMR (300 MHz, CDCl3) l
(ppm): 7.65–7.61 (m, 4H); 7.44–7.19 (m, 16H), 4.84 (d,
J=12.1 Hz, 1H), 4.72 (d, J=12.1 Hz, 1H), 4.54 (d,
J=11.7 Hz, 1H), 4.44 (dt, J=5.5, 6.5 Hz, 1H), 4.37 (d,
J=11.7 Hz, 1H), 4.18 (dd, J=4.3, 6.5 Hz, 1H), 3.96
(dd, J=2.4, 4.3 Hz, 1H), 3.89 (dd, J=3.9, 9.9 Hz, 1H),
3.62 (dd, J=2.8, 9.9 Hz, 1H), 3.47 (dd, J=2.4, 8.7 Hz,
1H), 2.38 (m, 1H), 2.17 (dt, J=5.5, 14.6 Hz, 1H), 1.94
(ddd, J=5.5, 8.7, 14.6 Hz, 1H), 1.51 (s, 3H), 1.37 (s,
3H), 1.05 (s, 9H). 13C NMR (100 MHz, CDCl3) l
(ppm): 138.9, 138.6, 135.6 (×4), 133.4, 129.6 (×2), 128.2
(×2), 128.1 (×2), 127.7 (×2), 127.6 (×4), 127.4 (×3),
127.3, 127.2, 108.0, 76.9, 75.6, 74.3, 73.7, 72.7, 71.5,
64.6, 35.6, 28.2, 26.9 (×3), 26.2, 25.1, 19.2. MS m/e: 636
(M+), 621 (M+−15).
6.30. (3aS,4R,5S,6R,7R,7aR)-6,7-Bis-(benzyloxy)-5-
({[tertbutyl(dimethyl)silyl]oxy}methyl)-2,2-dimethylhex-
ahydro-1,3-benzodioxyl-4-ol 61
To a solution of tetraol 60 (240 mg, 0.64 mmol) in
DMF was added imidazole (56 mg, 0.83 mmol) and
tert-butyldiphenylchlorosilane (TPSCl) (194 mg, 0.70
mmol) and the reaction mixture was stirred at room
temperature for 12 h. The crude was then diluted with
Et2O and washed with water. The organic layer was
dried and concentrated, giving a residue which was
purified by flash chromatography (hexane–EtOAc 1:1)
to yield an intermediate silyl ether: [h]2D1 +31.4 (c 1.1,
CHCl3). 1H NMR (300 MHz, C6D6) l (ppm): 7.66–7.62
(m, 5H), 7.42–7.36 (m, 5H), 7.25–7.19 (m, 10H), 4.87
(d, J=11.1 Hz, 1H), 4.71 (d, J=11.3 Hz, 1H), 4.59 (d,
J=11.1 Hz, 1H), 4.50 (d, J=11.3 Hz, 1H), 4.37–4.27
(m, 3H), 4.07–3.98 (m, 4H), 3.85 (m, 1H), 3.48 (m, 1H),
2.83 (m, 1H), 2.27 (m, 1H), 1.09 (s, 9H). 13C NMR (50
MHz, CDCl3) l (ppm): 137.7, 135.5, 135.4, 132.1,
131.8, 129.9, 128.4 (×2), 128.3 (×2), 127.8 (×4), 127.7
(×4), 127.5, 127.3, 80.0, 75.1, 74.9, 73.9 (×2), 71.8, 67.3,
63.7, 36.9, 26.7 (×3), 18.9. This material was then
dissolved in DMF (30 mL) and sikkon (200 mg), 2-
methoxypropene (114 mL, 1.2 mmol) and p-toluenesul-
fonic acid (15 mg) were added. After 2 h, CH2Cl2 was
added and the reaction mixture was filtered through a
small pad of Celite. The filtrate was washed with
NaHCO3 and water. The organic layer was dried and
concentrated to give a residue which was purified by
flash chromatography (hexane–EtOAc 9:1) affording
cyclohexane 61 (176 mg, 45% two steps): [h]2D1 +27.2 (c
0.6, CHCl3). 1H NMR (300 MHz, CDCl3) l (ppm):
7.80–7.60 (m, 6H), 7.48–7.34 (m, 6H), 7.33–7.22 (m,
6H), 7.18–7.13 (m, 2H), 4.83 (d, J=12.1 Hz, 1H), 4.68
(d, J=12.1 Hz, 1H), 4.58 (d, J=11.6 Hz, 1H), 4.45 (dt,
J=2.8, 4.7 Hz, 1H), 4.37 (dd, J=3.6, 7.0 Hz, 1H), 4.28
6.32. 1,2,3,4,6-Penta-O-acetyl-5a-carba-˜-D-allopyran-
ose 63
Desilylation of 62 (84 mg, 0.13 mmol) was carried out
as described for 30. Flash chromatography (hexane–
EtOAc 7:3) yielded 3,4-O-isopropylidene-1-O-benzyl-
5a-carba-a-
D
-allopyranose (mp=59–61°C), [h]2D1 +120.9
1
(c 0.8, CHCl3). H NMR (300 MHz, CDCl3) l (ppm):
7.45–7.40 (m, 3H), 7.33–7.25 (m, 7H), 4.88 (d, J=12.0
Hz, 2H), 4.72 (d, J=12.0 Hz, 2H), 4.54 (d, J=11.7 Hz,
2H), 4.29 (d, J=11.7 Hz, 2H), 4.27 (m, 1H), 4.09 (t,
J=5.1 Hz, 1H), 3.96 (dd, J=2.2, 5.1 Hz, 1H), 3.68 (dd,
J=3.4, 10.7 Hz, 1H), 3.54 (dd, J=6.2, 10.7 Hz, 1H),
3.23 (dd, J=2.2, 10.0 Hz, 1H), 2.53 (m, 1H), 2.11 (ddd,
J=3.0, 5.2, 15.0 Hz, 1H), 1.51 (ddd, J=5.2, 11.1, 15.0
Hz, 1H), 1.50 (s, 3H), 1.36 (s, 3H). 13C NMR (75 MHz,
CDCl3) l (ppm): 138.8, 138.7, 128.5 (×2), 128.1 (×2),
128.0 (×2), 127.9, 127.8 (×2), 127.3, 109.2, 80.2, 75.7,
74.3, 73.3, 72.2, 70.9, 65.6, 35.6, 27.6, 26.0, 25.5. MS
m/e: 398.2 (M+), 383.2 (M+−15). Anal. calcd for
C24H30O5: C, 72.32; H, 7.59. Found: C, 72.07; H, 7.82.
This compound was hydrogenolyzed under the same
conditions as for 56, to give a residue, which was

A. M. Go´mez et al. / Tetrahedron: Asymmetry 14 (2003) 2961–2974
2973
subjected to the general procedure for the cleavage of
the isopropylidene moiety. After acetylation, the reac-
tion mixture was concentrated and the crude material
purified by flash chromatography (hexane–EtOAc 6:4)
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to yield carba-a- -allopyranose pentaacetate 63 (43 mg,
D
86% overall): mp=95–98°C, [h]2D1 +36.0 (c 1.0, CHCl3).
1H NMR (300 MHz, CDCl3) l (ppm): 5.54 (t, J=3.1
Hz, 1H), 5.38 (m, 1H), 4.96 (t, J=3.1 Hz, 1H), 4.89
(dd, J=3.1, 11.3 Hz, 1H), 4.18 (dd, J=4.7, 11.3 Hz,
1H), 4.00 (dd, J=2.9, 11.3 Hz, 1H), 2.56 (m, 1H), 2.14
(s, 3H), 2.11 (s, 3H), 2.10 (s, 3H), 2.02 (s, 3H), 2.01 (m,
1H), 2.00 (s, 3H), 1.71 (dt, J=2.9, 14.0 Hz, 1H). 13C
NMR (75 MHz, CDCl3) l (ppm): 170.8, 170.1, 170.0,
169.7, 169.6, 69.3, 68.9, 68.5, 67.1, 63.0, 30.7, 29.3, 20.9,
20.8, 20.7, 20.6, 20.5. Anal. calcd for C17H24O10: C,
52.57; H, 6.23. Found: C, 52.76; H, 6.51.
Acknowledgements
This research was supported with funds from Janssen-
Cilag and from the Direccio´n General de Investigacio´n
Cient´ıfica y Te´cnica (grants: PB96-0822, PB97-1244,
PPQ2000-1330, and BQU2001-0582).
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D