Total asymmetric synthesis of doubly branched carba-hexopyranoses and amino derivatives starting from the Diels-Alder adducts of maleic anhydride to furfuryl esters

Article abstract of DOI:10.1002/(SICI)1522-2675(19990609)82:6<821::AID-HLCA821>3.0.CO;2-K

The Diels-Alder adducts of maleic anhydride to furfuryl esters were reduced into 7-oxabicyclo[2.2.1]hept-5-ene-1,2-exo,3-exo-trimethanol (±)-15 and enantiomerically pure (-)-15 (Scheme 1). The tripivalate of (±)-15 was converted into (1RS,2RS,3RS,4RS,5SR,6SR)-1,5,6- tris(hydroxymethyl)cyclohexane-1,2,3,4-tetrol ((±)-23; Scheme2). Reaction of BBr₃ with the triacetate (±)-30 of (±)-15 gave (1RS,2RS,5R,6RS)-5-bromo- 6-hydroxycyclohex-3-ene-1,2,3-trimethyl triacetate ((±)-31) at -78°, and (1RS,2RS,5SR,8SR)-2-endo-hydroxy-6-oxabicylo[3.2.1]oct-3-ene-5,8-dimethyl diacetate ((±)-32) at 0°(Scheme 3). Single-crystal X-ray diffraction of (1RS,2RS,5SR,8SR)-2-acetoxy-6-oxabicyclo[3.2.1]oct-3-ene-5,8-dimethyl diacetate ((±)-33) was carried out. Displacement of bromide (+)-31 (derived from (-)-15) with azide anion gave (+)-38 which was transformed into (+)- (1R,2R,5S,6S)-5-amino-6-hydroxycyclohex-3-ene-1,2,3-trimethanol ((+)-40) (Scheme 4). Reaction of (±)-31 with BBr₃ at 0°, followed by azide disubstitution led to (1RS,2RS,5SR,6SR)-5-amino-3-(aminomethyl)-6- hydroxycyclohex-3-ene-1,2-dimethanol ((±)-45). Dihydroxylation of (±)-38 and further transformations gave (1RS,2RS,3SR,4RS,5SR,6RS)-5-amino-1,4,6- trihydroxycyclohexane-1,2,3-trimethanol ((±)-49) and (1RS,2RS,3SR,4RS,5SR,6RS)-2,3-dihydroxy-7-oxabicyclo[4.1.0]heptane-2,3,4- trimethanol ((±)-55) (Schemes 5 and 6). Expoxidation of the 4-nitrobenzoate (±)-61 of (±)-38 allowed the preparation of (1RS,2RS,3SR,4RS,5RS)-5-amino- 1,4-dihydroxycyclohexane-1,2,3-trimethanol ((±)-65) and of (1RS,2RS,3SR,4RS,5SR,6RS)-5-amino-4-hydroxy-7-oxabicyclo[4.1.0]heptane- 1,2,3-trimethanol ((±)-67) (Scheme 7). The new unprotected polyols and aminopolyols were tested for their inhibitory activity toward commercially available glycohydrolases. At 1 mM concentration, 34, 30, and 31% inhibition of β-galactosidase from bovine liver was observed for (+)-40, (±)-65, and (±)-67, respectively.

Full text of DOI:10.1002/(SICI)1522-2675(19990609)82:6<821::AID-HLCA821>3.0.CO;2-K

Helvetica Chimica Acta ± Vol. 82 (1999)
821
Total Asymmetric Synthesis of Doubly Branched Carba-hexopyranoses and
Amino Derivatives Starting from the Diels-Alder Adducts of Maleic
Anhydride to Furfuryl Esters
by Nathalie Jotterand and Pierre Vogel*
Â
Section de Chimie, BCH, Universite de Lausanne, CH-1015 Lausanne-Dorigny
and Kurt Schenk
Â
Institut de Cristallographie, BSP, Universite de Lausanne, CH-1015 Lausanne-Dorigny
The Diels-Alder adducts of maleic anhydride to furfuryl esters were reduced into 7-oxabicyclo[2.2.1]hept-5-
ene-1,2-exo,3-exo-trimethanol (Æ)-15 and enantiomerically pure ( )-15 (Scheme 1). The tripivalate of (Æ)-15
was converted into (1RS,2RS,3RS,4RS,5SR,6SR)-1,5,6-tris(hydroxymethyl)cyclohexane-1,2,3,4-tetrol ((Æ)-23;
Scheme 2). Reaction of BBr3 with the triacetate (Æ)-30 of (Æ)-15 gave (1RS,2RS,5RS,6RS)-5-bromo-6-
hydroxycyclohex-3-ene-1,2,3-trimethyl triacetate ((Æ)-31) at 788, and (1RS,2RS,5SR,8SR)-2-endo-hydroxy-6-
oxabicylo[3.2.1]oct-3-ene-5,8-dimethyl diacetate ((Æ)-32) at 08 (Scheme 3). Single-crystal X-ray diffraction of
(1RS,2RS,5SR,8SR)-2-acetoxy-6-oxabicyclo[3.2.1]oct-3-ene-5,8-dimethyl diacetate ((Æ)-33) was carried out.
Displacement of bromide (‡)-31 (derived from ( )-15) with azide anion gave (‡)-38 which was transformed
into (‡)-(1R,2R,5S,6S)-5-amino-6-hydroxycyclohex-3-ene-1,2,3-trimethanol ((‡)-40) (Scheme 4). Reaction of
(Æ)-31 with BBr3 at 08, followed by azide disubstitution led to (1RS,2RS,5SR,6SR)-5-amino-3-(aminomethyl)-6-
hydroxycyclohex-3-ene-1,2-dimethanol ((Æ)-45). Dihydroxylation of (Æ)-38 and further transformations gave
(1RS,2RS,3SR,4RS,5SR,6RS)-5-amino-1,4,6-trihydroxycyclohexane-1,2,3-trimethanol ((Æ)-49) and (1RS,2RS,
3SR,4RS,5SR,6RS)-2,3-dihydroxy-7-oxabicyclo[4.1.0]heptane-2,3,4-trimethanol ((Æ)-55) (Schemes 5 and 6).
Expoxidation of the 4-nitrobenzoate (Æ)-61 of (Æ)-38 allowed the preparation of (1RS,2RS,3SR,4RS,5RS)-5-
amino-1,4-dihydroxycyclohexane-1,2,3-trimethanol ((Æ)-65) and of (1RS,2RS,3SR,4RS,5SR,6RS)-5-amino-4-
hydroxy-7-oxabicyclo[4.1.0]heptane-1,2,3-trimethanol ((Æ)-67) (Scheme 7). The new unprotected polyols and
aminopolyols were tested for their inhibitory activity toward commercially available glycohydrolases. At 1 mm
concentration, 34, 30, and 31% inhibition of b-galactosidase from bovine liver was observed for (‡)-40, (Æ)-65,
and (Æ)-67, respectively.
Introduction. ± Inositol (cyclohexanehexol) derivatives [1] play a crucial role in
signal transduction in living organisms [2]. Their syntheses has stirred a lot of activity
recently [3]. Conduritols (cyclohexenetetrols) [4], conduramines (aminocyclohexene-
triols) [5], and their epoxides [6] have been of deep interest to the synthetic chemists due
to their potential as glycosidase inhibitors [7] or as antibiotics [8]. These systems can be
viewed as carba-pentopyranose derivatives [9]. Carba-hexopyranoses ((hydroxyme-
thyl)cyclohexanepolyols) have been synthesized first [10] and then found in Nature [11].
For instance, 5a-carba-a-d-galactopyranose (1) has been isolated as a weak antibiotic
from the fermentation broth of Streptomyces species [12]. Valienamine (2) is a
constituent of agricultural antibiotic validamycin [13], of the a-amylase inhibitor
acarbose [14], and of the trehalase inhibitors validoxylamine A [15] and salbostatin [16].
Gabosines (e.g., 3, gabosine A; 4, gabosine C) are carba-sugars isolated from
different Streptomyces [17]. Epoxides [18] such as pipoxide (5) [19] and crotepoxide
(6) [20] are natural products showing significant tumor-inhibitory activities; cyclo-

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Helvetica Chimica Acta ± Vol. 82 (1999)
phellitol (7) isolated from culture filtrates of Phellinus sp. [21] and its synthetic
stereoisomers [22] are glycosidase inhibitors [23]. Epoxy dione such as 8 is an antibiotic
isolated from Streptomyces species [24]. The ethanolic extract of the seeds of Uvaria
tonkinensis (Annonaceae) has delivered tonkinenin A (9) [25]. Herbicidal MK 7607
(10) is manufactured by cultivation of Curvularia species [26]. The glyoxalase-I
inhibitor 11 has been isolated from the culture broth of Streptomyces griseosporeus
[27], and its precursor 12 (( )-KD16-U1) from the culture broth of Streptomyces
filipinensis [28]. Synthetic carba-sugars are potential leads in all kinds of therapeutic
applications. For instance, the potent influenza neuraminidase inhibitor GS 4071 (13)
has been prepared [29] and shown to be promising for the prophylaxis and treatment of
influenza-virus infection [30].
Recently, we disclosed [31] a simple method for the preparation of enantiomerically
pure 7-oxabicyclo[2.2.1]hept-2-ene derivative (‡)-14, precursor in the synthesis of taxol
analogues [32]. We envisioned that (‡)-14 and its diastereoisomer, derived from (1R)-
camphanic acid, could be suitable starting materials to generate families of new types of
carba-sugars. We report here our exploratory studies on the conversion of (‡)-14 into
tri(hydroxymethyl)cyclohexanepolyols and amino derivatives; some of the reactions
presented here represent very short syntheses of these new doubly-branched
carbahexoses including conduritol-like systems and their epoxides.
Results and Discussion. ± Our exploratory studies were carried out starting from
racemic triol (Æ)-15 [33] (Scheme 1). In the case of the synthesis of (1R,2R,5S,6S)-5-
amino-6-hydroxycyclohex-3-ene-1,2,3-trimethanol ((Æ)-40), enantiomerically pure triol
( )-15 was used as starting material1).
1
)
For a partial preliminary report, see [35].

Helvetica Chimica Acta ± Vol. 82 (1999)
823
Scheme 1
1,5,6-Tris(hydroxymethyl)cyclohexane-1,2,3,4-tetrol(Æ)-23. Double exo-hydroxyla-
tion of the alkene moiety of (Æ)-15 (N-methylmorpholine N-oxide, OsO4 (cat.)) gave
(Æ)-16 which was esterified to pentaacetate (Æ)-17 (Ac2O, pyridine, 4-(dimethylami-
no)pyridine (DMAP) as catalyst; 91% yield) or to pentapivalate (Æ)-18 (PivCl,
pyridine; 80%) (Scheme 2). Pentaacetate (Æ)-17 did not react with BBr3 in CH2Cl2. On
heating, slow decomposition was observed. However, the pentapivalate (Æ)-18 reacted
smoothly with BBr3, already at 08, giving after aqueous workup (NaHCO3) diol (Æ)-19
in 88% yield (Scheme 2). The crude reaction mixture did not show any other product.
Diol (Æ)-19 was protected as bis(methoxymethyl) diether (Æ)-20 (97%) or as diacetate
(Æ)-21 (100%) under standard conditions. Oxidation of diol (Æ)-19 with H2CrO4
produced g-hydroxy ketone (Æ)-22 (100%). Saponification (MeONa, MeOH, 208) of
pentapivalate (Æ)-19 provided heptol (Æ)-23, which was fully characterized as its
hexaacetate (Æ)-24 (91%, 2 steps). The structures of 16 ± 24 were given by their
spectral data and their elemental analysis.
The exo-face selectivity of the dihydroxylation of 15 was confirmed by the 1H-NMR spectra of 16 ± 18
which did not show any coupling (< 0.5 Hz) between vicinal proton pairs H C(4) and H C(5) [34]. The
3
spectra exhibited coupling constants J(5,6) ˆ 6.0 ± 6.4 Hz for the endo vicinal proton pairs, confirming the cis
relationship between these protons [34]. The 1H-NMR spectra of 19 ± 21 and 24 showed coupling constants
between vicinal proton pairs of the six-membered ring (H C(2), H C(3), H C(4), H C(5), and H C(6)
that are all smaller than 5 Hz, in agreement with the proposed structures and conformations (no axial/axial
vicinal proton pairs). The 1H-NMR spectrum of ketone 22 showed coupling constants 3J(5,6) ˆ 4.5 Hz and
4J(3,5) ˆ 2 Hz, consistent with the proposed structure and conformation. Its 2D-NOESY data revealed NOEs
between one of the protons (d(H) 4.49, d, 2J ˆ 12 Hz) of CH2 C(1) with H C(2) (d(H): 1.67, m) and H C(3)
(d(H) 2.66, m). The other proton (d(H) 4.49, d, 2J ˆ 12 Hz) of CH2 C(1) showed NOEs with H C(6) (d(H)
5.78, d, 3J ˆ 4.5 Hz) and H C(5) (d(H) 5.66, dd, 3J ˆ 4.5, 4J ˆ 2.0 Hz). This established the trans relative
configuration of the 1-(pivaloyloxymethyl) substituent with respect to the 6-(pivaloyloxy) substituent. The 2D-
NOESY data of 24 confirmed the relative configuration and the conformation shown for this hexaacetate, with
NOEs between H C(6) (d(H) 2.24, 3J ˆ 7.6, 4.9, 5.0 Hz), H C(4) (d(H) 5.45, 3J ˆ 3.9, 2.8 Hz), and H C(2)
3
(d(H) 5.26, J ˆ 3.9 Hz).
The high yield and high stereoselectivity of the 7-oxa-ring-opening reaction/
quenching reaction 18 ! 19 is remarkable2). It can be interpreted in terms of the
formation of cationic intermediate 25A arising from the Lewis-acid-promoted
heterolysis of the C(1) O(7) bond in 18 with participation by the 1-(pivaloyloxy-
methyl) substituent. Because of the bulk of the pivaloyl group, BBr3 coordination of
2
)
For other examples of Lewis-acid-promoted oxa-ring openings of 7-oxabicyclo[2.2.1]heptane derivatives,
see [36].

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Helvetica Chimica Acta ± Vol. 82 (1999)
Scheme 2
the ester moieties is less important for the pentapivalate 18 than for the corresponding
pentaacetate 17, thus explaining the fast reaction observed with the former and the lack
of reactivity of the latter 7-oxabicyclo[2.2.1]heptane derivative. In the presence of H2O,
25A is expected to yield a hemiorthoester that rearranges to the 1-epimer of 19 that is
not detected by NMR of the crude reaction mixture. Opening of the dioxolanium
intermediate 25A with formation of isomeric tertiary carbenium ion intermediate 25B
is possible, but its reaction with H2O is expected to give a mixture of 19 and of its 1-
epimer, the latter product being preferred under conditions of kinetic control for steric
reasons. Although we cannot rule out a direct attack of H2O at the quaternary C(1)
center of 25A to generate 19, this intermolecular Sn2-type reaction looks unlikely.
We thus propose that 25A can equilibrate with intermediates 26 or/and 27 through
intramolecular displacements with complete inversion of configuration at C(1). The
cationic intermediates 26 and 27 might be more stable than 25A for reasons of steric
hindrance to solvatation, or may react faster than 25A (for steric reasons) with H2O

Helvetica Chimica Acta ± Vol. 82 (1999)
825
giving the corresponding hemiorthoesters that rearrange to form 19 exclusively.
Formation of isomeric tertiary pivalate is prevented for steric reasons (front strain). It
is interesting to mention that in the presence of a large excess of Bu4NBr or of KBr/
[18]crown-6 ether, the same product 19 was obtained on treating 18 with BBr3 first, and
then with H2O/NaHCO3. If 25A should react in a Sn2 fashion with H2O to produce 19,
the corresponding bromide should have been seen in the latter experiments, which was
not the case.
(1R,2R,5S,6S)-5-Amino-6-hydroxycyclohex-3-ene-1,2,3-trimethanol(Æ)-40 and Its
3-(Aminomethyl) Derivative 45. Esterification of triol (Æ)-15 with pivaloyl chloride in
pyridine provided (Æ)-28 (93%) (Scheme 1). Treatment of (Æ)-28 with BBr3 (CH2Cl2,
08, 5 min, aqueous workup) gave bromohydrine (Æ)-29 in 95% yield (Scheme 3).
Triacetate (Æ)-30 (Scheme 1) derived from (Æ)-15 (Ac2O, pyridine, CH2Cl2; 95%)
reacted with BBr3 already at 788 in CH2Cl2 to give the expected bromohydrine (Æ)-31
in 95% yield. When the reaction was carried out at 08 using a higher dilution, a second
product (Æ)-32 was formed and was isolated with a yield of up to 46%. The structures
and conformations of (Æ)-29 and (Æ)-31 were given by their spectral data, especially by
1
their H-NMR spectra that shared similarities for their coupling constants between
vicinal proton pairs.
3
Coupling constants J (4,5) < 1 Hz for (Æ)-29 and of 2.2 Hz for (Æ)-31 were observed that are typical for
the pseudoaxial proton at C(5). The H C(5) signal of (Æ)-29 (d(H) 4.93) is a broad s, therefore showing that
3J(5,6) is smaller than 1.5 Hz. In the case of (Æ)-31, 3J(5,6) ˆ 3.5 Hz, which cannot be associated with two axial
protons, therefore confirming the cis relationship between the 5-bromo and 6-hydroxy substituents. Protons
H
C(1) and H C(6) cannot both occupy axial positions as 3J(1,6) ˆ 3.9 Hz in (Æ)-29 and 2.0 Hz in (Æ)-31.
Again, this demonstrates the cis relationship between the substituents at C(1) and C(6), what is expected from
the mode of formation of (Æ)-29 and (Æ)-31 (heterolysis of the tertiary-allylic C O bond). The 13C-NMR
spectra of (Æ)-29 and (Æ)-31 established that the CˆC bond is between C(3) and C(4) (trisubstituted, not
disubstituted alkene). Coupling constant 3J(1,2) ˆ 1.5 Hz in (Æ)-29 and 5.5 Hz in (Æ)-31 suggested different
deformations of the pseudo-chair conformations between the tripivalate (Æ)-29 and the triacetate (Æ)-31 (in
cyclohexene, only 2 kcal/mol separate the pseudo-chair and boat conformations). But these coupling constants
are consistent with their cis relationship, as is expected since there is no reason for an epimerization at C(2) or/
and C(3) during the acid-induced oxa-ring openings. The cis relationship between H C(1) and H C(5) was
confirmed by the 2D-NOESY data of (Æ)-29 and (Æ)-31 that showed strong NOEs between these proton pairs.
The structures (Æ)-29 and (Æ)-31 were further confirmed by their derivatization as shown below (Scheme 6).
Acetylation of (Æ)-32 gave triacetate (Æ)-33 which was fully characterized by its
spectral data and elemental analysis. Its structure was established unambiguously by X-
ray diffraction of a monocrystal (see Exper. Part). Alcohol (Æ)-32 was oxidized to
enone (Æ)-34 (Jonesꢀ reagent, acetone) in 92% yield (Scheme 3). Bicyclic products
analogous to (Æ)-32 were not observed with the tripivalate (Æ)-28 treated under similar
conditions. Formation of (Æ)-29 and (Æ)-31 can be interpreted in terms of the
generation of allyl-cation intermediate 35A arising from the heterolysis of the allylic
C(6) O(7) bond of 7-oxabicyclo[2.2.1]hept-2-ene derivatives 28 and 30 under ether-
Lewis acid complex formation. Carbenium ion 35A can equilibrate with dialkoxycar-
benium ions 35B and 35C resulting from the intramolecular quenching of 35A by the
acetoxymethyl group at C(3) and C(2), respectively. If formed, the latter do not lead to
other products than (Æ)-29 (R ˆ Piv) or (Æ)-31 (R ˆ Ac). Intramolecular transfers of
bromide anion generate intermediates of type 36 which are then hydrolyzed to (Æ)-29
(R ˆ Piv) or (Æ)-31 (R ˆ Ac). The reaction 35 > 36 might be reversible at 08, not at

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Helvetica Chimica Acta ± Vol. 82 (1999)
Scheme 3
788. If 35A ± C survive long enough, the acetoxymethyl group at C(1) can react with
the cationic moiety and generate oxonium ion 37A, which loses MeCOBr to generate,
after aqueous workup, the bicyclic product 32. Rearrangement 35 ! 37 is probably too
slow with the tripivalate for steric reasons, thus explaining why the dipivalate analogue
of 32 was not observed. The acetoxymethyl groups at C(2) and C(3) of 35 do not
participate in the intramolecular quenching of the allyl cationic intermediate, probably
because it would lead to more strained bicyclic systems than with the 6-oxabicy-
clo[3.2.1]oct-3-ene derivative 32.
The intermediacy of 37A may appear unlikely since cationic intermediates 35A ± C
are expected to be more stable. Since reaction 30 ! 32 does not occur below 08, it
implies a free enthalpy of activation of ca. 20 kcal/mol. This leaves a significant
enthalpy difference between intermediates 37A and 35A ± C which could be larger than
the difference in stability between oxonium ions of type 37A and the isomeric
dialkoxycarbenium ions 35B,C. Proton affinities (PAs) of ethers and carboxylic esters
(PA(Et2O) ˆ 198.1 kcal/mol, PA(Me2O) ˆ 189.6 kcal/mol, PA(AcOEt) ˆ 195.0 kcal/
mol, PA(AcOMe) ˆ 198.1 kcal/mol, PA(HCOOMe) ˆ 188.0 kcal/mol [37]) show that
dialkyloxonium ions and alkoxy(hydroxy)carbenium ions of similar size have similar
stabilities. High-level quantum calculations [38] reproduce the experimental gas-phase
proton affinities with good accuracy. They predict that the difference in enthalpy

Helvetica Chimica Acta ± Vol. 82 (1999)
827
between the alkoxy-protonated form (acyl-oxonium ion) and the isomeric carbonyl-
protonated form (alkoxy(hydroxy)carbenium ion) of an ester or a lactone [39] is only
15 kcal/mol in favor of the carbonyl-protonated form. This enthalpy difference could be
even smaller for alkoxy-alkylated vs. carbonyl-alkylated esters in solution. The
calculations suggest also for g-butyrolactone that its alkoxy-protonated form undergoes
a facile C O cleavage with formation of the corresponding g-hydroxyacyl cation [39a]
[40]. This leaves open the hypothesis that 35A ± C could undergo a two-step (via 37A)
‡
or a concerted fragmentation to 37B ‡ CH3CO (Scheme 3). Alternatively, intermedi-
ates 35A ± C could undergo intramolecular bromide-anion transfer from the tribro-
moborate moiety to the vicinal acetoxymethyl group at C(1) with formation of
zwitterion 37C. For steric reasons, this reaction is too slow in the case of the tripivalate
28. Then 37C undergoes direct cyclization to generate 32 and MeCOBr, or equilibrates
with the dibromoborate 37D with elimination of MeCOBr. Intermediate 37D could
then cyclize into the dibromoborate of 32 with liberates 32 under aqueous workup.
Displacement of allylic bromide (Æ)-31 with tetramethylguanidinium azide [41]
occurred in MeCN without allylic rearrangement and with complete inversion of
configuration (Sn2 rather than Sn1 or Sn2') giving azide (Æ)-38 in 93% yield
(Scheme 4). Ammonolysis provided tetrol (Æ)-39 (85%), the azido moiety of which
could be reduced with Na2S ´ H2O/Et3N in MeOH [42]. The crude conduramine (Æ)-40
‡
was purified by column chromatography (Dowex 50WX8 H ; 80 ± 95% yield). Alter-
natively, catalytic (10% Pd/C) hydrogenation of (Æ)-39 led to pure (Æ)-40 (97%) fully
characterized as its benzyl carbamate (Æ)-41. Starting with enantiomerically pure
triacetate (‡)-31, enantiomerically pure (‡)-38, (‡)-39, and (‡)-40 were obtained with
similar ease. The trans relationship between the 5-azido and 6-hydroxy substituents in
(Æ)-38 was established by analysis of the product of double-bond cis-hydroxylation
(Æ)-49 (see below, Scheme 5). The 1H-NMR spectra of 38 ± 41 showed coupling
3
3
constants J(4,5) and J(5,6) that vary as a function of the nature of the substituents,
suggesting various conformer equilibria for these compounds (H-bridging effect?;
presence of boat conformations?).
Scheme 4
The treatment of (Æ)-31 with BBr3 in CH2Cl2 led to the selective substitution of the
allylic acetate to give dibromide (Æ)-42 in 98% yield (Scheme 4). Double displacement
of dibromide (Æ)-42 with tetramethylguanidinium azide produced (Æ)-43 (80%), the
methanolysis of which provided triol (Æ)-44 (96%). Catalytic (Pd/C) hydrogenation of
(Æ)-44 generated the diaminotriol (Æ)-45 (85%), characterized as its double benzyl
carbamate (Æ)-46 (83%).

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Helvetica Chimica Acta ± Vol. 82 (1999)
5-Amino-1,4,6-trihydroxycyclohexane-1,2,3-trimethanol (Amino[tris(hydroxyme-
thyl)]cyclitol) 49. Double hydroxylation of the alkene moiety of (Æ)-38 with RuCl3 ´
H2O/NaIO4 in H2O was face-selective and led to a 6.3 : 1 mixture of two isomeric triols
from which the major product (Æ)-47 could be isolated (37%) (Scheme 5). Its 1H-NMR
spectrum and 2D-NOESY established the structure and the conformation shown
(3J(5,6) ˆ 9.0, 3J(5,4) ˆ 10.5 Hz, typical for axial/axial vicinal protons; 3J(2,3) ˆ 5.0 Hz,
3J(3,4) ˆ 4.9 Hz typical for axial/equatorial vicinal proton pairs; NOE: d(H) 4.27 (Ha
of CH2 C(1))/3.31 (H C(6)); 3.59 H C(4)/2.04 (H C(2)) and 2.04 (H C(2))/3.90
(Hb of CH2 C(1))). The structure of (Æ)-47 established the cis relationship between
the 1-(acetoxymethyl), 6-hydroxy, and 5-bromo substituents of (Æ)-31 (Scheme 3).
Deacetylation of (Æ)-47 (NH3/MeOH) provided hexol (Æ)-48, the hydrogenation (H2,
Pd/C) of which furnished the expected aminohexol (Æ)-49 (90%; Scheme 5). This
aminocyclitol derivative was fully characterized as its N-acetyl-polyacetate (Æ)-50.
Scheme 5
1
3
3
The H-NMR spectrum of (Æ)-50 showed coupling constants J(2,3) ˆ 6.0 Hz and J(3,4) ˆ 5.5 Hz typical
for equatorial/axial vicinal proton pairs on one hand, and 3J(4,5) ˆ 11.0 Hz and 3J(5,6) ˆ 10.6 Hz typical for
axial/axial vicinal proton pairs on the other hand. The relative configuration of the quaternary center C(1) was
given by the mode of formation of (Æ)-50 and confirmed by its 2D-NOESY data, which showed strong NOEs
between CH2 C(1) (d(H) 3.97, 3.93) and H C(2) (d(H) 2.27 and H C(6) (d(H) 4.88 ppm).
Epoxides 55 and 67 of Tris(hydroxymethyl)conduritol and -conduramine, Respec-
tively. Dess-Martin periodinane oxidation of alcohol (Æ)-31 gave enone (Æ)-51 (96%)
(Scheme 6). Elimination of HBr from (Æ)-31 on treatment with DBU provided
epoxide (Æ)-52 in low yield. However, treatment of (Æ)-31 with 1.5 equiv. of LiBr in
DMF (208, 2 h) generated the epimeric bromide (Æ)-31' (95%) which eliminated HBr
on treatment with DBU, giving (Æ)-52 quantitatively. Reaction of (Æ)-31' with NaN3
provided azide (Æ)-38', the 5-epimer of azide (Æ)-38, which constitutes another
confirmation of the structure proposed above for the latter.
The 2D-NOESY data of enone (Æ)-51 showed a NOE between H C(5) (d(H) 5.18) and H C(1) (d(H)
3.25), thus establishing that the 5-bromo-6-oxocyclohex-3-ene moiety has not been epimerized under the
oxidation conditions. The structure of (Æ)-52 was confirmed by its 1H-NMR spectrum which showed 3J(5,6) ˆ
3
4.2 Hz (bond angle expected to be ca. 208), 4J(3,5) ˆ 1.4 Hz, J(2,3) ˆ 7.0 Hz (quasi-eclipsed cis C H bonds),
3J(1,2) ˆ 2.0 Hz (bond angle of ca. 708), and 3J(1,6) ˆ 4.2 Hz. Furthermore, a NOE was detected between
H
C(6) (d(H) 3.39) and H C(3) (d(H) 2.62) on one hand, and between H C(6) (d(H) 3.39) and H C(2)
(d(H) 2.27) on the other hand. The structure of (Æ)-38' was given by its 1H-NMR spectrum and its 2D-NOESY
data that showed an NOE between H C(5) (d(H) 4.00) and H C(1) (d(H) 2.21).

Helvetica Chimica Acta ± Vol. 82 (1999)
829
Scheme 6
Double hydroxylation of allyl bromide (Æ)-31 (RuCl3/NaIO4) was highly face
selective, the sterically less-hindered face of the alkene reacting to give triol (Æ)-53 in
1
90% yield. The structure and conformation of (Æ)-53 was given by its H-NMR
spectrum and confirmed that of (Æ)-31 (cis relationship between 5-bromo and 6-
hydroxy substituent, see Scheme 3).
The 1H-NMR spectrum of (Æ)-53 showed typical coupling constants between vicinal pairs: 3J(2eq, 3ax)
4.5 Hz, 3J(3ax,4eq) < 2 Hz, 3J(4eq,5ax) ˆ 2.9 Hz, and 3J(5ax,6ax) ˆ 10.2 Hz. Coupling constants 3J(4,OH) ˆ
3J(6,OH) ˆ 4.5Hz were also observed; they vanished on adding D2O. The relative configuration of the
quaternary center C(1) was given by the 2D-NOESY data that showed NOE between H C(6) (d(H) 4.02) and
one of the protons of the CH2 C(1) group (d(H) 4.47) on one hand, and between OH C(1) (d(H) 2.89, s) and
H
C(5) (d(H) 4.39, dd) on the other hand.
Treatment of (Æ)-53 with BEMP on resin (2-[(tert-butyl)imino]-2-(diethylamino)-
1,3-dimethylperhydro-1,3,2-diazaphosphorine) at 408 for 2 days generated a major
epoxide (Æ)-54 isolated in low yield (44%) due to its instability. As expected,
elimination of HBr from the trans-bromohydrine moiety at C(5), C(6) was favored
over that from the cis-bromohydrine moiety at C(5), C(4). Methanolysis of (Æ)-54
gave the unprotected epoxy pentol (Æ)-55, an unstable compound that underwent

830
Helvetica Chimica Acta ± Vol. 82 (1999)
polymerization in the condensed state. Dess-Martin periodinane oxidation [43] of
epoxy diol (Æ)-54 produced g-hydroxy ketone (Æ)-56. The structure of (Æ)-56
confirmed those proposed for (Æ)-54 and (Æ)-55.
The 1H-NMR spectra of (Æ)-54 and (Æ)-55 were consistent with the conformation shown in Scheme 6 for
3
these compounds as J(5,6) ˆ 1.5 Hz for (Æ)-54 and 1.7 Hz for (Æ)-55. The epoxide moiety resides on centers
C(1) and C(6) because H C(1) (d(H) 3.23 for (Æ)-54, 3.09 for (Æ)-55) couples with H C(6) (d(H) 3.49 for
(Æ)-54, 3.22 ppm for (Æ)-55). If the epoxide ring resided on centers C(1) and C(2), only one 1H signal would be
seen for the epoxide. If it were residing between C(5) and C(6) (atom numbering shown in 54, Scheme 6), both
signals attributed to the epoxide protons would be dd, which is not the case; H C(1) shows a d (3J ˆ 3.4 Hz for
(Æ)-54, 3.6 Hz for (Æ)-55) and H C(6) a dd. The chemical shifts observed for H C(1) and H C(6) in the
1H-NMR spectra of (Æ)-54 and (Æ)-55 are consistent only with an epoxide, not with an oxetane or
tetrahydrofuran ring. The 2D-NOESY data of (Æ)-56 showed NOEs between OH C(2) (d(H) 3.21) and
H
C(3) (d(H) 2.53) and H C(4) (d(H) 3.47) on one hand, and between H C(1) (d(H) 3.56) and CH2 C(2)
(d(H) 4.28 and 4.38) on the other hand. The coupling constants 4J(1,3) ˆ 1.3 Hz and 3J(3,4) ˆ 5.0 Hz are
consistent with the near-sofa conformation shown (Scheme 6).
Selective acetylation of triol (Æ)-53 (Ac2O, pyridine) gave successively tetraacetate
(Æ)-57 (100%) and pentaacetate (Æ)-58 (100%). Methanolysis (MeOH, NH3) of
(Æ)-53 provided bromo hexol (Æ)-59 (86%). Dess-Martin periodinane oxidation [43] of
(Æ)-57 gave (Æ)-60, confirming the structure of 57 (tertiary alcohol, secondary
acetate).
The 1H-NMR spectrum of (Æ)-59 was similar to that of (Æ)-53, in agreement with the structure and
conformation proposed (Scheme 6). Typical 1H-NMR data of (Æ)-60 were: 3J(4ax,5ax) ˆ 10.3 Hz,
3J(1ax,2eq) ˆ 6.5Hz; NOE between OH (d(H) 3.19, s) and H C(2) (d(H) 4.08) and between H C(4)
(d(H) 5.63) one H of CH2 C(3) (d(H) 4.33, d, 2J ˆ 12.5 Hz).
Esterification of (Æ)-38 with 4-nitrobenzoyl chloride (CH2Cl2, pyridine) afforded
(Æ)-61 (100%) which was epoxidized with 3-chloroperbenzoic acid (mCPBA; 408,
CH2Cl2) leading to a 3.6 : 1 mixture of two epoxides. Low-temperature column
chromatography (108, silica gel) permitted isolation of the major isomer (Æ)-62 in 46%
yield, together with the minor isomer (Æ)-63 (2%) and a mixture (Æ)-62/(Æ)-63 (26%).
Ammonolysis of (Æ)-62 (Scheme 7) furnished tetrol (Æ)-64 (84%), and hydrogenation
(H2, 20% Pd(OH)2 on charcoal, 12 h) provided the amino pentol (Æ)-65 (90%), which
was fully characterized as its N-acetyl-peracetate (Æ)-66.
The structure of (Æ)-65 was given by its 1H-NMR spectrum (in D2O) that showed typical coupling constants
3J(2ax,3eq) ˆ 5.4 Hz, 3J(3eq,4ax) ˆ 5.4 Hz, 3J(4ax,5ax) ˆ 10.4 Hz, 3J(5ax,6ax) ˆ 13.0 Hz, and 3J(5ax,6eq) ˆ
3.7 Hz. The relative configuration of the quaternary center C(1) was established by the NOEs between one
H of CH2 C(1) (d(H) 3.44, d, 2J ˆ 11.6 Hz) and H C(2) (d(H) 1.95), on one hand, and between the other H of
CH2 C(1) (d(H) 3.37, d, 2J ˆ 11.6 Hz) and Heq C(6) and (d(H) 1.84, dd, 2J ˆ 13.0 Hz, 3J ˆ 3.7 Hz), on the
other hand. Similar data were collected for (Æ)-66, its 2D-NOESY data (CDCl3) showing a NOE between
OH C(1) (d(H) 3.50, s) and H C(5) (d(H) 4.40, dddd). The relative configuration of epoxides (Æ)-62 and
(Æ)-63 was confirmed by the observation of coupling constants 3J(1,2) < 1 Hz (see sofa conformation of 67) for
3
(Æ)-62 (ꢀantiꢁ relationship between the epoxide and azido moieties) and J(1,2) ˆ 3.1 Hz for (Æ)-63.
When the hydrogenation catalyst was 10% Pd on charcoal (15 min) instead of
Pd(OH)2 on charcoal, the epoxide moiety of (Æ)-64 was not reduced, and the amino-
epoxide (Æ)-67 was obtained in 98% yield. The structure of (Æ)-67 was deduced from
its mode of formation and from its spectral data.

Helvetica Chimica Acta ± Vol. 82 (1999)
831
Scheme 7
An NOE was observed between H C(6) (d(H) 2.98) and H C(2) (d(H) 2.52) in the 2D-NOESY of (Æ)-
67. The coupling constants 3J(2,3) ˆ 6.0 Hz, 3J(3,4) ˆ 3.6 Hz, 3J(4pseudoax, 5pseudoax) ˆ 7.1 Hz, and 3J(5,6) <
1 Hz measured for (Æ)-67 are consistent with the average conformation shown in Scheme 7 for this compound.
1
Similar coupling constants were measured in the H-NMR spectra of (Æ)-62 and (Æ)-64.
Enzymatic Assays. ± Compounds (Æ)-23, (Æ)-40, (‡)-40, (Æ)-45, (Æ)-49, (Æ)-59,
(Æ)-65, and (Æ)-67 were tested for their inhibitory activity toward a a-l-fucosidase
(from bovine placenta), toward three a-d-galactosidases (from coffee bean, Aspergil-
lus niger, Escherichia coli), five b-d-galactosidases (from E. coli, bovine liver,
Aspergillus niger, Aspergillus orizae, jack bean), two maltases (a-glucosidases from
yeast, rice), one isomaltase (a-glucosidase from bakerꢁs yeast), two amyloglucosidases
(from Aspergillus niger, Rhizopus mold), two b-glucosidases (from almond, Caldo-
cellum saccharolyticum, two a-mannosidases (from jack bean, almond), one b-
mannosidase (from Helix pomatia), one b-xylosidase (from Aspergillus niger), one a-
N-acetylgalactosaminidase (from chicken liver), and three b-N-acetylglucosaminidases
(from jack bean, bovine epididymis A and B). At 1 mm concentration of the potential
inhibitor, 29, 30, and 31% inhibition of b-galactosidase from bovine liver was evaluated
for (Æ)-40, (Æ)-65, and (Æ)-67, respectively. No inhibitory activity was found for the
other enzymes with the other polyols (Æ)-23, (Æ)-45, (Æ)-49, and (Æ)-59. At 1 mm,
enantiomerically pure conduramine analogue (‡)-40 showed 34% inhibition of b-
galactosidase from bovine liver, suggesting that (‡)-40 is more active than enantiomer
( )-40.

832
Helvetica Chimica Acta ± Vol. 82 (1999)
Conclusion. ± Simple and stereoselective methods were found to convert the Diels-
Alder adducts of maleic anhydride to furfuryl camphanates into a variety of
polyfunctional tris(hydroxymethyl)cyclohexane derivatives including conduritol, con-
duramine analogues, and their epoxides. All the new polyols and amino polyols
presented in this report can be prepared enantiomerically pure in both their
enantiomeric forms. They constitute new classes of cyclitol and aminocyclitol
derivatives. For the moment, their inhibitory activities toward commercially available
glycohydrolases are either nonexistent or weak toward b-galactosidase from bovine
liver (only in the case of (‡)-40, (Æ)-65, and (Æ)-67).
We are grateful to the Swiss National Science Foundation, the Fonds Herbette, Lausanne, and the
Stipendienfonds der Basler Chemischen Industrie for financial support. We thank Mr. Raynald Demange for
measuring the inhibitory activities reported in this work.
Experimental Part
General. See [44]. Abbreviations: DBU, 1,8-diazabicyclo[5.4.0]undec-7-ene; DMAP, 4-(dimethylamino)-
pyridine; NMO, N-methylmorpholine N-oxide; PET, light petroleum ether; FC, flash chromatography; CC,
3
column chromatography; Piv, pivaloyl (ˆ 2,2-dimethylpropanoyl) ). TLC: Merck silica gel 60F254 plates. All the
1H-NMR signal assignments were confirmed by 2D-1H-NMR spectroscopy (COSY, NOESY).
Enzymatic Assays. Appropriate 4-nitrophenyl glycosides buffered to optimum pH of the enzymes were
used; for details, see [45].
5-exo,6-exo-Dihydroxy-7-oxabicyclo[2.2.1]heptane-1,2-exo,3-exo-trimethanol ((Æ)-16). To a soln. of (Æ)-15
(1 g, 5.35 mmol) [33] in MeOH (20 ml) and H2O (2 ml). NMO (1 g, 8.03 mmol), 750 ml of OsO4 (0.07m in CCl4)
were added. The soln. was stirred at 408 under Ar for two days and then evaporated. The residue was dried under
high vacuum. An anal. sample was obtained by FC (silica gel; AcOEt/MeOH 8 : 1) 943 mg (80%) of (Æ)-16.
White solid, very hygroscopic. M.p. >2558. Rf (AcOEt/MeOH 8 : 1) 0.05. IR (KBr): 3280, 2995, 2955, 2925,
2885, 1720, 1485, 1375, 1345, 1255, 1130, 1050, 1035, 975, 945, 865, 835, 735, 700, 635, 585. 1H-NMR (250 MHz,
CD3OD): 4.07 (s, H C(4)); 3.99, 3.76 (2d, 2Jˆ11.0, CH2 C(1)); 3.88, 3.83 (2d, 3Jˆ6.2, H C(5), H C(6));
3.68, 3.38 (2dd, 2Jˆ10.5, 3Jˆ4.0, 8.5, CH2); 3.64, 3.58 (2dd, 2Jˆ11.0, 3Jˆ6.0, CH2); 2.08 ± 1.97 (m, H C(2),
H
C(3)). 13C-NMR (100.6 MHz, CD3OD): 89.6 (m, C(1)); 84.6 (d, Jˆ158, C(4)); 74.8, 74.3 (2d, Jˆ153,
C(5), C(6)); 60.3, 58.9, 58.2 (3t, Jˆ140, CH2); 45.3, 44.9 (2d, Jˆ132, C(2), C(3)). CI-MS (NH3): 81(83),
95(61), 111(100), 125(47), 153(29), 167(36), 185(25), 203(6), 221(33).
5-exo,6-exo-Diacetoxy-7-oxabicyclo[2.2.1]heptane-1,2-exo-3-exo-trimethyl Triacetate ((Æ)-17). A mixture
of (Æ)-16 (0.5 g, 2.3 mmol), Ac2O (2 ml), pyridine (2 ml), and DMAP (10 mg) was stirred at 208 for 1 d.
Toluene (10 ml) was added, and the solvents were evaporated. This was repeated twice. The residue was purified
by FC (silica gel; AcOEt/PET 2.1): 790 mg (80%) of (Æ)-17. White solid. M.p. 116 ± 1178. Rf (AcOEt/PET 2 : 1)
0.44. IR (CH2Cl2): 3625, 3635, 3100, 3080, 3000, 2950, 2670, 1740, 1730, 1360, 1200, 1110, 1060, 1030, 975, 925,
880. 1H-NMR (250 MHz, CDCl3): 5.14, 4.97 (2d, 3Jˆ6.0, H C(5), H C(6)); 4.40 (s, H C(4)); 4.61, 4.19
(2d, 2Jˆ12.0, CH2 C(1)); 4.30 (dd, 2Jˆ11.5, 3Jˆ2.5, 1 H); 4.26 (dd, 2Jˆ11.0, 3Jˆ6.0, 1 H, CH2); 4.03
(dd, 2Jˆ11.5, 3Jˆ7.0, 1 H); 3.95 (dd, 2Jˆ11.0, 3Jˆ10.0, 1 H, CH2); 2.35 ± 2.39 (m, H C(2), H C(3)); 2.02,
2.03, 2.04, 2.06, 2.07 (5s, 5 Me). 13C-NMR (100.6 MHz, CDCl3): 170.6, 170.4, 170.0, 169.9, 169.3 (5m, CˆO);
86.0 (s, C(1)); 81.8 (d, Jˆ163, C(4)); 75.1, 74.7 (2d, Jˆ158, C(5), C(6)); 61.6, 60.5, 58.8 (3t, Jˆ150, 3 CH2);
41.7, 41.1 (2d, Jˆ136, C(2), C(3)); 20.9, 20.6, 20.6, 20.5, 20.2, (5q, Jˆ130, 5 Me). CI-MS (NH3); 107(3),
148(5), 208(7), 250(4), 310(1), 371(6), 390(1), 448(100). Anal. calc. for C19H26O11 (430.41): C 53.02, H 6.09;
found: C 53.05, H 6.04.
5-exo-6-exo-Bis(pivaloyloxy)-7-oxabicyclo[2.2.1]heptane-1,2-exo,3-exo-trimethyl Tripivalate ((Æ)-18). A
3
mixture of (Æ)-16 (68 mg, 0.312 mmol), dry pyridine (1 ml), and pivaloyl chloride ) (PivCl; 0.5 ml) was stirred
at 208 for 15 h. The excess of PivCl was hydrolyzed by addition of ice, and the solvents were evaporated with
toluene (6 ml, 3 times). The residue was taken in CH2Cl2 (150 ml), washed with aq. sat. NaHCO3 soln. (50 ml)
3
)
For convenience, pivaloyl (ˆ 2,2-dimethylpropanoyl) and pivalate (ˆ 2,2-dimethylpropanoate) were also
used in systematic names.

Helvetica Chimica Acta ± Vol. 82 (1999)
833
and H2O (30 ml), dried (MgSO4), and evaporated. Crystallization (Et2O/PET) gave 150 mg (80%) of (Æ)-18.
White solid. M.p. 157.5 ± 1598. Rf (Et2O/PET 1 : 2) 0.28. IR (CH2Cl2): 3680, 2925, 2885, 1710, 1690, 1670, 1600,
1120, 1065, 1030, 920, 980. 1H-NMR (250 MHz, CDCl3): 5.06, 4.92 (2d, 3Jˆ6.4, H C(5), H C(6)); 4.56, 4.29
(2d, 2Jˆ12.0, CH2 C(1)); 4.33 (s, H C(4)); 4.42 (dd, 2Jˆ11.3, 3Jˆ4.1, 1 H); 4.38 (dd, 2Jˆ11.3, 3Jˆ4.5, 1 H);
4.02, 3.94 (2d, 2Jˆ10.1, CH2); 3.34, 2.45 (2dd, 3Jˆ8.0, 4.1, 8.0, 4.5, H C(2), H C(3)); 1.23, 1.21, 1.20, 1.18 (4s,
45 H, 5 t-Bu). 13C-NMR (100.6 MHz, CDCl3): 177 ± 178 (5s, CˆO); 86.1 (s, C(1)); 83.0 (d, Jˆ164, C(4)); 75.6,
75.4 (2d, Jˆ157, 159, C(5), C(6)); 61.9, 60.9, 59.1 (3t, Jˆ150, 3 CH2); 42.0, 41.5 (2d, Jˆ132, 136, C(2), C(3));
38.8 (s); 27.1 ± 27.3 (5q, Jˆ128, 5 t-Bu). CI-MS (NH3): 85(93), 148(38), 250(37), 334(100), 539(43), 423(42),
597(1), 641(51). Anal. calc. for C34H56O11 (640.82): C 63.73, H 8.81; found: C 63.55, H 8.77.
(1RS,2RS,3SR,4RS,5RS,6RS)-1,4-Dihydroxy-5,6-bis(pivaloyloxy)cyclohexane-1,2,3-trimethyl Tripivalate
((Æ)-19). BBr3 (80 ml, 0.82 mmol) was added slowly to a stirred soln. of (Æ)-18 (350 mg, 0.548 mmol) in anh.
CH2Cl2 (5 ml) under Ar and cooled to 08. After 10 min at 08, aq. sat. NaHCO3 soln. (20 ml) was added and the
soln. extracted with CH2Cl2 (150 ml). The org. phase was washed with H2O (50 ml), dried (MgSO4), and
evaporated. FC (silica gel; PET/Et2O 2 : 1) gave 308 mg (88%) of (Æ)-19. White solid (PET/Et2O). M.p. 161 ±
1628. Rf (Et2O/PET 1 : 2) 0.14. UV (MeCN): 205(3360), 200(3729). IR (KBr): 2960, 2900, 2890, 1725, 1710,
1480, 1390, 1365, 1280, 1150, 1060, 1030, 980, 945, 890, 770. 1H-NMR (250 MHz, CDCl3): 5.40 (d, 3Jˆ4, H C(6));
5.29 (t, 3Jˆ4, H C(5)); 4.62 (dd, 2Jˆ12.0, 3Jˆ8.0, 1 H); 4.44 ± 4.52 (m, 2 H); 4.41, 3.95 (2d, 2Jˆ12.0,
CH2 C(1)); 4.27 (dd, 2Jˆ10.0, 3Jˆ7.0, 1 H, CH2 (3)); 4.00 (br. d, 3Jˆ4.0, H C(4)); 2.79 (s, OH C(1));
2.74, 2.21 (2m, H C(2), H C(3)); 1.97 (br. s, OH C(4)); 1.22, 1.21, 1.20, 11.9 (5s, 45 H, 5 t-Bu). 13C-NMR
(100.6 MHz, CDCl3): 178.4, 178.3, 178.1, 176.2 (4s, CˆO); 74.7 (s, C(1)); 70.1, 67.6 (2d, Jˆ145, 146, C(5),
C(6)); 69.1 (d, Jˆ154, C(4)); 67.0 (t, Jˆ150); 61.9, 62.7 (2td, Jˆ150, 5, 2 CH2); 38.6 ± 38.9 (5s); 41.7, 37.0
(2d, Jˆ134, 126, C(2), C(3)); 26.9 ± 27.2 (5q, Jˆ128, 5 Piv). CI-MS (NH3): 85(45), 120(59), 148(14),
232(36), 250(63), 284(13), 334(100), 335(92), 352(13), 455(13), 539(16), 557(17). Electrospray-MS: 99(3),
149(5), 256(6). Anal. calc. for C34H58O12 (658.79): C 62.00, H 8.87; found: C 62.12, H 8.80.
(1RS,2RS,3SR,4RS,5RS,6RS)-1,4-Bis(methoxymethoxy)-5,6-bis(pivaloyloxy)cyclohexane-1,2,3-trimethyl
Tripivalate ((Æ)-20). An excess of P2O5 was added in one portion to a stirred mixture of (Æ)-19 (90 mg,
0.137 mmol), CH2Cl2 (1.5 ml), and (MeO)2CH2 (1.5 ml). The suspension was vigorously stirred for 5 min. It
was then filtered and washed with CH2Cl2. The filtrate was diluted with CH2Cl2 (150 ml), washed with aq. sat.
NaHCO3 soln. (40 ml), dried (MgSO4), and evaporated. Crystallization (Et2O/PET) gave 100 mg (97%) of
(Æ)-20. White solid. M.p. 94.5 ± 968. Rf (Et2O/PET 1 : 2) 0.35. IR (KBr): 2975, 2365, 1735, 1480, 1400, 1370, 1285,
1150, 1035, 925, 880, 825, 770, 655, 590, 435. 1H-NMR (250 MHz, CDCl3): 5.52 (d, 3Jˆ3.6, H C(6)); 5.27
(t, 3Jˆ3.6,
H
C(5)); 4.90, 4.73 (2d, 2Jˆ7, 6, OCH2O); 4.68, 4.58 (2d, 2Jˆ6.5, OCH2O); 4.54 ± 4.49
(m, CH2 C(3)); 4.39 ± 4.20 (m, CH2 (2), CH2 C(1)); 4.04 (br. d, 3Jˆ3.6, H C(4)); 3.42, 3.36 (2s, MeO);
2.72, 2.42 (2m, H C(2), H C(3)); 1.24, 1.22, 1.20, 1.19, 1.18 (5s, 5 Piv). 13C-NMR (100.6 MHz, CDCl3): 182
(m, CˆO); 98.3, 91.7 (2t, Jˆ147, OCH2O); 80.1 (br. s, C(1)); 73.9, 71.2 (2d, Jˆ145, C(5), C(6)); 68.5
(d, Jˆ154, C(4)); 63.3, 62.8, 62.1 (3t, Jˆ156, 3 CH2); 56.7, 56.4 (q, Jˆ128, 2 MeO); 39.6, 36.9 (2d, Jˆ134, 124,
C(2), C(3)); 38.9 (br. s); 27.1 ± 27.4 (5q, Jˆ127, 5 t-Bu). CI-MS (NH3): 85(7), 148(1), 249(2), 383(3),
467(7), 539(9), 569(26), 641(25), 658(35), 686(8). Anal. calc. for C38H66O14 (746.94): C 61.11, H 8.91; found:
C 61.21, H 8.93.
(1RS,2RS,3SR,4RS,5RS,6RS)-1,4-Diacetoxy-5,6-bis(pivaloyloxy)cyclohexane-1,2,3-trimethyl Tripivalate
((Æ)-21). A mixture of (Æ)-19 (9 mg, 0.014 mmol), CH2Cl2 (0.5 ml), pyridine (0.5 ml), Ac2O (0.5 ml), and
DMAP (1 mg) was stirred at 208 for 15 h. The solvents were evaporated with toluene (5 ml, 3 times), and the
residue was purified by FC (silica gel; PET/Et2O 3 : 1): 10 mg (100%) of (Æ)-21. White solid. M.p. 177 ± 1788. Rf
(Et2O/PET 1 : 2) 0.40. IR (CH2Cl2): 2975, 2935, 2910, 2875, 1740, 1480, 1460, 1400, 1365, 1280, 1225, 1185, 1150,
1055. 1H-NMR (250 MHz, CDCl3): 5.55 (d, 3Jˆ4.1, H C(6)); 5.50 (br. d, 3Jˆ4.1, H C(4)); 5.30 (t, 3Jˆ4.1,
H
C(5)); 4.90, 4.40 (2d, 2Jˆ12.6, CH2 C(1)); 4.61 (dd, 2Jˆ12.3, 3Jˆ8.8, 1 H), 4.44 (dd, 2Jˆ12.3, 3Jˆ3.9, 1 H,
CH2 C(2)); 4.25 (dd, 2Jˆ11.2, 3Jˆ8.4, 1 H), 3.98 (dd, 2Jˆ11.2, 3Jˆ7.7, 1 H, CH2 C(3)); 3.33 (br. m, 3Jˆ8.4,
7.7, H C(3)); 2.63 (br. m, 3Jˆ8.8, 3.9, H C(2)); 2.12, 2.09 (2s, 2 Ac); 1.25, 1.23, 1.20, 1.19, 1.12 (5s, 5 Piv).
13C-NMR (100.6 MHz, CDCl3): 175.9 ± 179.0 (5s, CˆO (Piv)); 169.5, 168.8 (2s, CˆO (Ac)); 84.1 (s, C(1)); 67.6
(dt, Jˆ142, 4, C(5)); 66.8 (dd, Jˆ156, 6, C(4)); 66.5 (d, Jˆ147, C(6)); 61.5 (t, Jˆ158, CH2 C(1)); 60.9, 60.8
(2t, Jˆ148, 2 CH2); 38.8 (s); 38.7, 35.6 (2d, Jˆ132, 127, C(2), C(3)); 27.3 ± 27.0 (5q, Jˆ122, 5 t-Bu); 22.0, 20.9
(2q, Jˆ130, 2 Me). CI-MS (NH3): 85 (100), 148(13), 232(37), 292(6), 334(21), 376(17), 497(3), 641(4),
761(4). Anal. calc. for C38H61O14 (741.90): C 61.52, H 8.29; found: C 61.50, H 8.35.
(1RS,2RS,3SR,5SR,6RS)-1-Hydroxy-4-oxo-5,6-bis(pivaloyloxy)cyclohexane-1,2,3-trimethyl Tripivalate
((Æ)-22). At 08 and under stirring, aq. 4n Jonesꢀ reagent (CrO3, H2SO4, 0.15 ml) was added to a soln. of (Æ)-
19 (194 mg, 0.296 mmol) in acetone (5 ml). After 10 min, the suspension was stirred at 208, and more reagent

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Helvetica Chimica Acta ± Vol. 82 (1999)
(0.05 ml) was added. After 50 min i-PrOH was added slowly until the orange color disappeared. The suspension
was filtered over a Celite pad. The filtrate was diluted with CH2Cl2 (200 ml), washed with aq. sat. NaHCO3 soln.
(50 ml), dried (MgSO4), and evaporated. Recrystallization (PET/Et2O) gave 192 mg (100%) of (Æ)-22. White
solid. M.p. 78 ± 79.58. Rf (Et2O/PET 1 : 2) 0.35. UV (MeCN): 191 (4900). 1H-NMR (250 MHz, CDCl3): 5.78
(d, 3Jˆ4.5, H C(6)); 5.66 (dd, 3Jˆ4.5, 4J(5,3)ˆ2.0, H C(5)); 4.61 (dd, 2Jˆ11.5, 3Jˆ8.0, 1 H); 4.49, 4.08
3
3
(2d, 2Jˆ12.0, CH2 C(1)); 4.24 (dd, 2Jˆ12.0, Jˆ4.5, 1 H); 4.10 (dd, 2Jˆ11.5, Jˆ5.0, 1 H, CH2 C(3)); 3.94
(dd, 2Jˆ12.0, 3Jˆ8.0, 1 H, CH2 C(2)); 3.64 (s, OH C(1)); 2.66, 1.67 (2m, H C(2), H C(3)); 1.25 ± 1.18
(5s, 5 Piv). 13C-NMR (100.6 MHz, CDCl3): 200.2 (s, C(4)); 176.1 ± 179.1 (5 br. s, CˆO); 74.4 (d, Jˆ154, C(5));
73.7 (dd, Jˆ148, 5, C(6)); 74.1 (br. s, C(1)); 66.3, 61.5, 60.3 (3t, Jˆ149, 3 CH2); 47.1, 45.8 (2d, Jˆ135, 129,
C(2), C(3)); 38.6 ± 39.1 (5 br. s); 26.8 ± 27.3 (5q, Jˆ129, 5 t-Bu). CI-MS (NH3): 85(97), 151(100), 235(66),
248(25), 337(22), 350(22), 350(17), 501(8), 539(3), 674(3), 435(15), 452(21). Anal. calc. for C34H56O12
(656.82): C 62.17, H 8.59; found: C 62.21, H 8.64.
(1RS,2RS,3RS,4RS,5SR,6RS)-1,5,6-Tris(hydroxymethyl)cyclohexane-1,2,3,4-tetrol ((Æ)-23). A mixture of
(Æ)-19 (280 mg, 0.425 mmol), anh. MeOH (2 ml), and 5.4m NaOMe in MeOH (0.5 ml) was stirred at 208 for
24 h. The soln. was neutralized with 1n HCl, evaporated, and dried under high vacuum. An anal. sample was
obtained by CC (silica gel; AcOEt/MeOH 3 : 2): 62.8 mg (62%) of (Æ)-23. Very hygroscopic white solid. Rf
(AcOEt/MeOH 3 : 2) 0.16. 1H-NMR (250 MHz, CD3OD): 4.02 (dd, 3Jˆ3.2, 2.4, H C(4)); 3.93, 3.77
(2d, 2Jˆ11.6, CH2 C(1)); 3.87 (dd, 2Jˆ11.2, 7.9, 1 H); 3.85 (dd, 3Jˆ3.9, 3.2, H C(3)); 3.82 (dd, 2Jˆ12.0,
3Jˆ5.0, 1 H); 3.77 (dd, 2Jˆ11.2, 3Jˆ7.0, 1 H, CH2 C(5)); 3.72 (dd, 2Jˆ12.0, 3.1, 1 H, CH2 C(6)); 3.70
(d, 3Jˆ3.9, H C(2)); 2.42 (dtd, 3Jˆ7.9, 7.0, 2.4, H C(5)); 2.08 (ddd, 3Jˆ7.0, 5.0, 3.1, H C(6)). 13C-NMR
(400 MHz, D2O): 78.9 (s, C(1)); 74.6, 71.7, 70.5 (3d, Jˆ147, 148, 142, C(2), C(3), C(4)); 67.3 (t, Jˆ143, CH2);
63.1 (td, Jˆ142, 7, CH2); 59.7 (tt, Jˆ144, 5, CH2); 45.2, 42.2 (2d, Jˆ125, 124, C(5), C(6)). CI-MS (NH3):
79(85), 95(100), 110(68), 124(83), 154(61), 167(11), 203(4), 221(9), 239(3).
(1RS,2RS,3SR,4RS,5RS,6RS)-1-Hydroxy-4,5,6-triacetoxycyclohexane-1,2,3-trimethyl Triacetate ((Æ)-24).
The crude reaction residue from the methanolysis of (Æ)-19 was acetylated with dry pyridine/Ac2O 1 : 1
(2 ml) and DMAP (5 mg) for 24 h at 208. The solvents were evaporated with toluene (5 ml, 3 times), and the
residue was purified by FC (silica gel; AcOEt/PET 1 : 2, then 2 : 1): 158 mg (76%) of (Æ)-24. Colorless oil. Rf
(AcOEt/PET 2 : 1) 0.48. IR (film): 3470, 2970, 1745, 1730, 1650, 1435, 1370, 1230, 1100, 1045, 970, 735. 1H-NMR
(400 MHz, CDCl3): 5.45 (dd, 3Jˆ3.9, 2.8, H C(4)); 5.35 (t, 3Jˆ3.9, H C(3)); 5.26 (d, 3Jˆ3.9, H C(2)); 4.54
3
3
(dd, 2Jˆ12.4, Jˆ7.6, 1 H); 4.48, 3.98 (2d, 2Jˆ11.9, CH2 C(1)); 4.38 (dd, 2Jˆ12.4, Jˆ4.9, 1 H, CH2 C(6));
4.17 (dd, 2Jˆ11.1, 3Jˆ9.3, 1 H); 4.11 (dd, 2Jˆ11.1, 3Jˆ5.4, 1 H, CH2 C(5)); 3.12 (s, OH C(1)); 2.86
(dddd, 3Jˆ9.3, 5.4, 5.0, 2.8, H C(5)); 2.24 (ddd, 3Jˆ7.6, 4.9, 5.0, H C(6)); 2.10, 2.09, 2.08, 2.05, 2.04, 1.94 (6s,
6 Ac). 13C-NMR (100.6 MHz, CDCl3): 170.8, 169.2 (6s, CˆO); 73.9 (s, C(1)); 69.2, 67.9, 67.4 (3d, Jˆ152, 145,
154, C(2), C(3), C(4)); 66.2 (t, Jˆ150, CH2 C(1)); 62.0, 60.9 (2t, Jˆ148, 150, 2 CH2); 41.9, 35.4 (2d, Jˆ132,
129, C(6), C(5)); 21.0 ± 20.5 (6q, 6 Me). Anal. calc. for C21H30O13 (490.46): C 51.43, H 6.17; found: C 51.50,
H 6.27.
7-Oxabicyclo[2.2.1]hept-5-ene-1,2-exo,3-exo-trimethyl Tripivalate ((Æ)-28). To a soln. of (Æ)-15 (200 mg,
1.074 mmol) [33] in dry pyridine (1 ml) and dry CH2Cl2 (0.5 ml), PivCl (0.529 ml, 4.296 mmol) was added, and
the soln. was stirred at 208 for 15 h. The excess of PivCl was hydrolyzed by addition of ice, and the residue was
taken in CH2Cl2 (150 ml), washed with aq. NaHCO3 soln. (50 ml) and H2O (30 ml), dried (MgSO4), and
evaporated. The excess of pyridine was evaporated with toluene (10 ml). Crystallization (CH2Cl2/PET) gave
438 mg (93%) of (Æ)-28. White solid. M.p. 63.0 ± 64.58. Rf (AcOEt/PET 1 : 2) 0.67. UV (MeCN): 192 (7600). IR
(KBr): 2970, 2875, 1730, 1480, 1460, 1400, 1365, 1285, 1165, 1120, 1035, 995, 940, 895, 815, 770, 700, 635, 525.
1H-NMR (250 MHz, CDCl3): 6.39 (dd, 3Jˆ5.7, 1.4, H C(5)); 6.25 (d, 3Jˆ5.7, H C(6)); 4.82 (d, 3Jˆ1.4,
H
C(4)); 4.75, 4.35 (2d, 2Jˆ12.4, CH2 C(1)); 4.35 (dd, 2Jˆ11.5, 3Jˆ5.1, 1 H); 4.30 (dd, 2Jˆ11.5, 3Jˆ4.8, 1 H,
CH2); 4.09 (dd, 2Jˆ12.4, Jˆ7.9, 1 H); 4.01 (dd, 2Jˆ12.4, Jˆ10.4, 1 H, CH2); 2.17 ± 2.11 (br. m, 3Jˆ10.4, 7.9,
5.1, 4.8, H C(2), H C(3)); 1.23, 1.21, 1.20 (3s, 3 Me). 13C-NMR (100.6 MHz, CDCl3): 177.8 (m, CˆO); 136.4,
135.9 (2d, Jˆ178, C(5), C(6)); 89.2 (s, C(1)); 80.2 (d, Jˆ161, C(4)); 63.4, 61.9, 61.8 (3t, Jˆ150, 3 CH2); 41.4,
40.9 (2d, Jˆ137, 139, C(2), C(3)); 38.8 (s); 27.1 ± 27.0 (3q, 3 t-Bu). CI-MS (NH3): 81(34), 98(5), 182(5),
235(13), 274(1), 319(11), 439(7), 456(100). Anal. calc. for C24H38O7 (438.60): C 65.75, H 8.76; found: C 65.84,
H 8.60.
3
3
(1RS,2RS,5RS,6SR)-5-Bromo-6-hydroxycyclohex-3-ene-1,2,3-trimethyl Tripivalate ((Æ)-29). BBr3
(0.018 ml, 0.20 mmol) was added to a stirred soln. of (Æ)-28 (100 mg, 0.228 mmol) in CH2Cl2 (1 ml) cooled
to 08 under Ar. The soln. was stirred at 08 for 5 min. It was then diluted with CH2Cl2 (100 ml), washed twice with
H2O (20 ml), dried (MgSO4), and evaporated. FC (silica gel; AcOEt/PET 1 : 2) gave 112 mg (95%) of (Æ)-29.
M.p. 118±1198. Rf (AcOEt/PET 1 : 2) 0.52. IR (film): 3490, 2970, 1730, 1480, 1400, 1365, 1285, 1230, 1155, 1035, 980,

Helvetica Chimica Acta ± Vol. 82 (1999)
835
865. 1H-NMR (400 MHz, CDCl3): 5.81 (br. d, 4Jˆ4.0, H C(4)); 4.72, 4.66, 4.63 (3 br. s); 4.93 (br. s, H C(5));
4.55 (dd, 2Jˆ12.0, 3Jˆ4.1, 1 H); 4.42 (dd, 2Jˆ11.2, 3Jˆ8.4, 1 H); 4.34 (dd, 2Jˆ11.2, 3Jˆ6.9, 1 H, CH2 C(1));
4.18 (dd, 2Jˆ12.0, 3Jˆ6.6, 1 H, CH2 C(2)); 4.04 (br. d, 3Jˆ3.9, H C(6)); 2.57 (m, 3Jˆ6.6, 4.1, 1.5, H C(2));
2.36 (dddd, 3Jˆ8.4, 6.9, 3.9, 1.5, H C(1)); 1.22, 1.21, 1.20 (3s, 3 t-Bu). 13C-NMR (100.6 MHz, CDCl3): 177.8
(m, CˆO); 138.0 (s, C(3)); 124.1 (d, Jˆ166, C(4)); 66.4 (d, Jˆ153, C(6)); 65.6, 64.6, 63.4 (3t, Jˆ152, 3 CH2);
55.1 (d, Jˆ154, C(5)); 40.9 (d, Jˆ127, C(2)); 35.5 (d, Jˆ127, C(1)); 38.8 (s); 27.0 ± 27.2 (q, Jˆ129, 3 t-Bu). CI-
MS (NH3): 79(11), 81(5), 85(100), 104(36), 105(32), 120(42), 121(23), 133(94), 205(19), 235(15), 319(5),
439(4). Anal. calc. for C24H39BrO7 (519.48): C 55.49, H 7.51, Br 15.40; found: C 55.50, H 7.52, Br 15.33.
7-Oxabicyclo[2.2.1]hept-5-ene-1,2-exo,3-exo-trimethyl Triacetate (( )-30).
A soln. of ( )-15 (1 g,
5.37 mmol) [31] in dry CH2Cl2 (2 ml), dry pyridine (2 ml), and Ac2O (2 ml) was stirred at 208 until complete
protection. Toluene (10 ml) was added, and the solvents were evaporated under reduced pressure at 308. This
was repeated twice. The residue was purified by FC (silica gel; AcOEt/PET 1:1): 1.424 g (95%) of ( )-30. White
25
25
25
25
solid. M.p. 81 ± 828. Rf (AcOEt/PET 2 :1) 0.50. [a]
ˆ
7, [a]
ˆ
2, [a]
ˆ
4, [a]
ˆ
6 (cˆ0.3,
589
577
546
405
CHCl3). UV (MeCN): 192 (5850). IR (KBr): 2965, 1740, 1370, 1280, 1245, 1120, 1040, 995, 945, 900, 865, 845,
805, 705, 635, 605, 440. 1H-NMR (250 MHz, CDCl3): 6.42 (dd, 3Jˆ5.8, 1.6, H C(5)); 6.27 (d, 3Jˆ5.8, H C(6));
4.82 (d, 3Jˆ1.6, H C(4)); 4.74, 4.33 (2d, 2Jˆ12.6, CH2 C(1)); 4.32 (dd, 2Jˆ12.0, 3Jˆ3.0, 1 H); 4.25
(dd, 2Jˆ12.0, 3Jˆ5.0, 1 H); 4.08 (dd, 2Jˆ11.5, 3Jˆ8.5, 1 H), 3.99 (dd, 2Jˆ11.5, 3Jˆ9.0, CH2); 2.17 ± 2.12 (br. m,
3Jˆ9.0, 8.5, 5.0, 3.0, H C(2), H C(3)); 2.09, 2.08, 2.07 (3s, 3 Me). 13C-NMR (100.6 MHz, CDCl3): 170.4,
170.3, 170.0 (3s, CˆO); 135.8, 135.7 (2d, Jˆ176, C(5), C(6)); 88.5 (s, C(1)); 80.0 (d, Jˆ161, C(4)); 63.1, 61.8,
61.5 (3t, Jˆ163, CH2); 41.0, 40.4 (2d, Jˆ137, 140, C(2), C(3)); 20.8, 20.5, 20.4 (3q, Jˆ130, 3 Me). CI-MS
(NH3): 81(12), 98(57), 133(29), 175(6), 193(45), 211(10), 235(13), 313(12), 330(100). Anal. calc. for
C15H7O20 (312.32): C 57.69, H 6.41, O 35.90; found: C 57.63, H 6.32, O 35.95.
(1R,2R,5R,6S)-5-Bromo-6-hydroxycyclohex-3-ene-1,2,3-trimethyl Triacetate ((Æ)-31). BBr3 (0.23 ml,
3.2 mmol) was added dropwise to a stirred soln. of ( )-30 [31] (0.5 g, 1.603 mmol) in anh. CH2Cl2 (5 ml)
cooled to 788 under Ar. After complete dissolution of BBr3, the soln. was stirred for 15 min. It was then diluted
with CH2Cl2 (500 ml), washed twice with H2O (100 ml), dried (MgSO4), and evaporated. FC (silica gel;
AcOEt/PET 2 : 1) gave 598 mg (95%) of (‡)-31. Beige, unstable solid (storage in the freezer). M.p. 79 ± 818. Rf
25
25
25
25
(AcOET/PET 2 : 1) 0.35. [a] ˆ ‡15, [a] ˆ ‡12, [a] ˆ ‡13, [a] ˆ ‡12 (cˆ0.37, CHCl3). IR (KBr):
589
577
546
405
3440, 2900, 1745, 1720, 1485, 1470, 1365, 1345, 1275, 1240, 1180, 1155, 1100, 1035, 960, 915, 865, 755, 715, 655, 605,
525. 1H-NMR (250 MHz, CDCl3): 5.83 (dq, 3Jˆ2.2, 4Jˆ1.2, H C(4)); 4.91 (br. m, 3Jˆ3.5, 2.2, H C(5)); 4.73,
4.57 (2 br. d, 2Jˆ13.5, CH2 C(3)); 4.50 (dd, 2Jˆ11.7, 3Jˆ4.7, 1 H); 4.38 (d, 3Jˆ7.4, CH2 C(1)); 4.21
(dd, 2Jˆ11.7, 3Jˆ6.8, 1 H, CH2 C(2)); 4.07 (br. ddd, 3Jˆ4.2, 3.5, 2.0, H C(6)); 2.61 (br. ddd, 3Jˆ6.8, 5.5, 4.7,
H
C(2)); 2.33 (tdd, 3Jˆ7.4, 5.5, 2.0, H C(1)); 2.48 (d, 3Jˆ4.2, OH); 2.10, 2.08, 2.05 (3s, 3 Me). 13C-NMR
(100.6 MHz, CDCl3): 171.1, 170.8, 170.7 (3s, CˆO); 137.7 (s, C(3)); 125.4 (dq, Jˆ166, 5, C(4)); 66.6 (d, Jˆ147,
C(6)); 66.0 (t, Jˆ149, CH2 C(3)); 63.7, 63.1 (2t, Jˆ149, 2 CH2); 55.0 (d, Jˆ152, C(5)); 41.0 (d, Jˆ128, C(2));
35.8 (d, Jˆ130, C(1)); 21.3, 21.2, 21.2 (3q, Jˆ130, 3 Me). CI-MS (NH3): 79(10), 81(5), 91(34), 104(25),
105(26), 107(159, 120(34), 121(27), 132(20), 133(100), 134(27), 151(16), 163(31), 193(38), 211(12),
275(12), 273(9), 313(6).
(1RS,2RS,5SR,8SR)-2-endo-Hydroxy-6-oxabicyclo[3.2.1]oct-3-ene-5,8-dimethyl Diacetate ((Æ)-32). BBr3
(46 ml, 0.48 mmol) was added to a stirred soln. of (Æ)-30 (50 mg, 0.16 mmol) in anh. CH2Cl2 (4 ml) cooled to
788 under Ar. After stirring at 08 for 20 min, the soln. was diluted with CH2Cl2 (100 ml), washed with H2O
(20 ml), dried (MgSO4), and evaporated. FC (silica gel; AcOEt/PET 2 : 1) gave 20.1 mg (46%) of (Æ)-32 and
29.3mg (47%) of (Æ)-31. Data of (Æ)-32: colorless oil. Rf (AcOEt/PET 2 : 1) 0.20. IR (film): 3450, 3040, 2955,
2895, 1745, 1430, 1370, 1235, 1115, 1080, 1040, 995, 910, 735. 1H-NMR (250 MHz, CDCl3): 5.92 (dd, 3Jˆ9.6,
4Jˆ2.0,
H
C(4)); 5.76 (dt, 3Jˆ9.6, 2.0, 4Jˆ2.0,
H
C(3)); 4.67 (br. t, 3Jˆ2.0,
H C(2)); 4.29, 4.23
(2d, 2Jˆ11.5, CH2 C(5)); 4.15 (dd, 2Jˆ11.2, 3Jˆ6.5, 1 H); 4.11 (dd, 2Jˆ9.0, Jˆ4.0, 1 H); 4.03 (dd, 2Jˆ11.2,
3Jˆ7.0, 1 H, CH2 C(8)); 3.95 (dd, 2Jˆ9.0, 3Jˆ6.0, 1 H, CH2 C(1)); 2.59 (br. dd, 3Jˆ6.0, 4.0, H C(1)); 2.32
(dd, 3Jˆ7.0, 6.5, H C(8)); 2.11, 2.07 (2s, 2 Me). 13C-NMR (100.6 MHz, CDCl3): 170.9, 170.7 (2m, CˆO);
131.2, 131.4 (2 br. d, Jˆ165, C(3), C(4)); 78.7 (s, C(5)); 72.0 (d, Jˆ144, C(2)); 64.8, 64.6, 62.6 (3t, Jˆ147,
3 CH2); 47.3, 45.1 (2d, Jˆ140, C(8), C(1)); 20.8, 20.9 (2q, Jˆ130, 2 Me). CI-MS (NH3): 79(13), 81(22),
80(3), 91(25), 104(100), 107(35), 121(39), 121(33), 133(18), 150(55), 211(17), 253(6), 271(10). Anal. calc.
for C13H18O6 (270.28): C 57.77, H 6.71; found: C 57.85, H 6.61.
3
(1RS,2RS,5SR,8SR)-2-Acetoxy-6-oxabicyclo[3.2.1]oct-3-ene-5,8-dimethyl Diacetate ((Æ)-33). A mixture of
(Æ)-32 (20 mg, 0.074 mmol), pyridine (0.5 ml), Ac2O (0.5 ml), and DMAP (2 mg) was stirred at 208 for 24 h.
The solvents were evaporated with toluene (5 ml, 3 times), and the residue was purified by FC (silica gel;
AcOEt/PET 1 : 2). Crystallization (CH2Cl2/Et2O) gave 23 mg (96%) of (Æ)-33. Colorless crystals. M.p. 89 ± 908.

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Helvetica Chimica Acta ± Vol. 82 (1999)
Rf (AcOEt/PET 1 : 2) 0.11. IR (CH2Cl2): 3045, 2950, 2910, 1745, 1650, 1480, 1470, 1390, 1365, 1260, 1185, 1085,
1040, 1025, 985, 895. 1H-NMR (250 MHz, CDCl3): 6.01 (dd, 3Jˆ9.6, 4Jˆ1.6, H C(4)); 5.73 (ddd, 3Jˆ9.6, 2.0,
4Jˆ2.0, H C(3)); 5.65 (ddd, 3Jˆ4.0, 2.0, 4Jˆ1.6, H C(2)); 4.28, 4.24 (2d, 2Jˆ11.3, CH2 C(5)); 4.13
3
3
(dd, 2Jˆ11.3, Jˆ7.7, 1 H); 4.09 (dd, 2Jˆ9.4, Jˆ1.1, Ha C(7)); 3.99 (dd, 2Jˆ11.3, 3Jˆ6.9, 1 H, CH2 C(8));
3.94 (dd, 2Jˆ9.4, 3Jˆ1.6, Hb C(7)); 2.73 (br. ddd, 3Jˆ4.0, 1.6, 1.1, H C(1)); 2.41 (dd, 3Jˆ7.7, 6.9, H C(8));
2.11, 2.08, 2.07 (3s, 3 Me). 13C-NMR (100.6 MHz, CDCl3): 170.7, 170.5, 170.3 (3m, CˆO); 133.4 (dd, Jˆ164.0,
4.6, C(4)); 127.7 (dd, Jˆ165.0, 6.0, C(3)); 78.7 (s, C(5)); 74.6 (d, Jˆ155, C(2)); 65.4, 64.4, 62.2 (3t, Jˆ159, 149,
147, 3 CH2); 47.4 (d, Jˆ137, C(1)); 42.3 (d, Jˆ141, C(8)); 21.1, 20.8, 20.7 (3q, Jˆ130, 3 Me). CI-MS (NH3):
91(28), 104(100), 120(37), 150(16), 192(4), 253(9). Anal. calc. for C25H20O7 (312.32): C 57.69, H 6.45; found:
C 57.42, H 6.64.
For the single-crystal X-ray diffraction of (Æ)-33, see below.
(1RS,5SR,8SR)-2-Oxo-6-oxabicyclo[3.2.1]oct-3-ene-5,8-dimethyl Diacetate ((Æ)-34). Aq. 4n Jonesꢁ reagent
(CrO3, H2SO4, 60 ml) was added to a stirred soln. of (Æ)-32 (12 mg, 0.044 mmol) in acetone cooled to 08. After
stirring at 208 for 10 min TLC control (silica gel, AcOEt/PET 2 : 1)), i-PrOH was added dropwise till a green
color persisted. The suspension was diluted with CH2Cl2 (50 ml), filtered, washed with sat. aq. NaHCO3 soln.
(10 ml) and H2O (10 ml), dried (MgSO4), and evaporated to afford 11.9 mg (100%) of (Æ)-34. If necessary,
further purification by FC (silica gel; AcOEt/PET 1 : 1) afforded pure (Æ)-34 (11 mg, 92%). Colorless oil. Rf
(AcOEt/PET 2 : 1) 0.40. IR (CH2Cl2): 3035, 2955, 2895, 2360, 1740, 1650, 1430, 1370, 1235, 1180, 1115, 1080,
1040, 995, 930, 910, 850, 735, 680. 1H-NMR (250 MHz, CDCl3): 7.14 (d, 3Jˆ9.5, H C(4)); 6.16 (dd, 3Jˆ9.5,
4Jˆ1.5, H C(3)); 4.42, 4.32 (2d, 2Jˆ11.0, CH2 C(5)); 4.29 (dd, 2Jˆ10.0, 3Jˆ6.0, Ha C(7)); 4.13, 3.95
(2dd, 2Jˆ11.0, 3Jˆ7.0, CH2 C(8)); 3.67 (d, 2Jˆ10.0, Hb C(7)); 3.16 (dd, 3Jˆ6.0, 4Jˆ1.5, H C(1)); 2.69
(t, 3Jˆ7.0, H C(8)); 2.14, 2.08 (2s, 2 Me). 13C-NMR (100.6 MHz, CDCl3): 200.0 (s, C(2)); 174.0 (m, CˆO);
151.0 (d, Jˆ165, C(4)); 129.9 (d, Jˆ168, C(3)); 77.6 (s, C(5)); 65.6 (t, Jˆ150); 63.8, 63.2 (2t, Jˆ146, 2 CH2);
53.3 (d, Jˆ145, C(1)); 49.6 (d, Jˆ140, C(8)); 20.7 (q, Jˆ133, 2 Me). CI-MS (NH3): 107(2), 120(8), 149(7),
179(8), 209(5), 269(5), 269(100), 286(49). Anal. calc. for C13H16O6 (268.27): C 58.20, H 6.01; found: C 58.06,
H 6.03.
(1R,2R,5S,6S)-5-Azido-6-hydroxycyclohex-3-ene-1,2,3-trimethyl Triacetate ((Æ)-38). A mixture of (‡)-31
(4 g, 10.18 mmol), anh. MeCN (9 ml), and tetramethylguanidinium azide (1.77 g, 11.19 mmol) was prepared at
08. After stirring at 08 for 5 min, the soln. was poured into CH2Cl2 (1 l). The org. phase was washed rapidly with
cooled 1n aq. HCl (100 ml, ice), dried (MgSO4), and evaporated to give 3.7 g of an oil which was purified by FC
(silica gel; AcOEt/PET 1 : 1): 3.37 g (93%) of (‡)-38 (storage at 228). Slightly orange oil. Rf (AcOEt/PET
25
25
25
25
25
2 : 1) 0.35. [a] ˆ ‡192, [a] ˆ ‡210, [a] ˆ ‡231, [a] ˆ ‡417, [a] ˆ ‡516 (cˆ0.25, CHCl3). UV
589
577
546
435
405
(MeCN): 199 (9400). IR (film): 3475, 2910, 2100, 1740, 1435, 1370, 1235, 1035, 905, 665. 1H-NMR (400 MHz,
CDCl3): 5.86 (br. d, 3Jˆ3.8, H C(4)); 4.69, 4.62 (2d, 2Jˆ13.7, CH2 C(3)); 4.46 (dd, 2J ˆ11.6, Jˆ7.4, 1 H);
3
4.41 (dd, 2Jˆ11.5, Jˆ5.8, 1 H); 4.15 (dd, 2Jˆ11.6, 3Jˆ5.4, 1 H, CH2 C(1)); 4.23 (dd, 2Jˆ11.5, 3Jˆ6.9, 1 H,
3
CH2 C(2)); 3.94 (br. dd, 3Jˆ3.8, 3.5, H C(5)); 3.90 (br. dd, 3Jˆ3.5, 2.6, H C(6)); 2.75 (br. ddd, 3Jˆ6.9, 6.0,
5.8, H C(2)); 2.33 (dddd, 3Jˆ7.4, 6.0, 5.4, 2.6, H C(1)); 2.10, 2.09 (2s, 3 Me). 13C-NMR (100.6 MHz, CDCl3):
171.2, 170.4, 170.3 (3m, CˆO); 138.5 (s, C(3)); 121.8 (d, Jˆ161, C(4)); 69.0 (d, Jˆ148, C(6)); 65.5 (td, Jˆ148,
6.4, CH2 C(3)); 63.5, 62.3 (2t, Jˆ150, 141, 2 CH2); 60.3 (d, Jˆ147, C(5)); 37.8 (d, Jˆ130, C(2)); 36.4
(d, Jˆ139, C(1)); 20.9, 20.83, 20.81 (3q, Jˆ130, 3 Me). CI-MS (NH3): 91(98), 120(100), 147(36), 163(17),
‡
178(12), 193(17), 253(8), 313(3), 356 (0.2 M ). Anal. calc. for C15H23N3O7 (355.35): C 50.70, H 5.96; found:
C 50.47, H 5.75.
(1RS,2RS,5SR,6SR)-5-Azido-6-hydroxycyclohex-3-ene-1,2,3-trimethyl Triacetate ((Æ)-38). As described
for (‡)-38, from (Æ)-31.
(1R,2R,5S,6S)-5-Azido-6-hydroxycyclohex-3-ene-1,2,3-trimethanol ((‡)-39). Gaseous NH3 was bubbled
carefully through a soln. of (‡)-38 (100 mg, 0.283 mmol) in anh. MeOH (2 ml) for 15 min (pH control). After
stirring at 208 for 14 h, the solvent was evaporated and the residue purified by FC (silica gel; AcOEt/PET 8 :1):
25
25
25
55 mg (85%) of (‡)-39. Colorless oil. Rf (AcOEt/MeOH 8 :1) 0.38. [a] ˆ ‡263, [a] ˆ ‡284, [a] ˆ ‡339,
589
577
546
25
25
[a] ˆ ‡613, [a] ˆ ‡754 (cˆ0.1, CHCl3). UV (MeCN): 209.6 (7500). IR (film): 3340, 2895, 2110, 1665,
435
405
1615, 1455, 1300, 1165, 1025, 900, 665. 1H-NMR (400 MHz, CDCl3): 5.87 (br. s, H C(4)); 4.20, 4.15
(2 br. dm, 2Jˆ14.0, Jˆ1.6, CH2 C(3)); 3.84 ± 3.82 (br. m, CH2); 3.78 (dd, 2Jˆ11.7, Jˆ7.4, 1 H, CH2 C(1));
5
3
3.77 (dd, 2Jˆ11.9, 3Jˆ4, 1 H); 3.64 (dd, 3Jˆ2.2, 1.6,
H
C(6)); 3.31 (dq, 3Jˆ5Jˆ1.6,
H C(5)); 2.72
(br. m, 3Jˆ7.2,
H
C(2)); 2.20 (dtd, 3Jˆ7.4, 7.2, 2.2,
H
C(1)). 13C-NMR (100.6 MHz, CD3OD): 145.6
(s, C(3)); 119.0 (d, Jˆ160, C(4)); 68.9 (d, Jˆ150, C(6)); 64.6 (t, Jˆ141, CH2 C(3)); 62.0 (d, Jˆ148, C(5));
61.6, 58.3 (2t, Jˆ141, 142, 2 CH2); 41.8 (d, Jˆ128, C(2)); 38.9 (d, Jˆ124, C(1)). CI-MS (NH3): 80(74), 91(100),

Helvetica Chimica Acta ± Vol. 82 (1999)
837
108(80), 122(37), 151(17), 169(5), 208(2), 230(8). Anal. calc. for C9H15N3O4 (229.24): C 47.16, H 6.60; found:
C 47.05, H 6.58.
(1RS,2RS,5SR,6SR)-5-Azido-6-hydroxycyclohex-3-ene-1,2,3-trimethanol ((Æ)-39). As described for (‡)-
39, from (Æ)-38.
(1R,2R,5S,6S)-5-Amino-6-hydroxycyclohex-3-ene-1,2,3-trimethanol ((‡)-40). Method A: A mixture of (‡)-
39 (16 mg, 0.07 mmol), anh. MeOH (0.5 ml), Na2S (36 mg, 0.147 mmol), and Et3N (1 ml) was stirred at 408 in the
dark for 12 h (TLC control (silica gel; AcOEt/MeOH 8 :1)). The suspension was then acidified with conc. HCl
‡
soln. and deposited on Dowex-50WX8 (H form). The resin was first washed with H2O (15 ml) and then with
MeOH (15 ml). Elution with 5% aq. NH3 soln. and evaporation of the basic fractions afforded 13.5 mg (95%) of
(‡)-40.
Method B: MeOH (5 ml) and 10% Pd/C (40 mg) were degassed and purged with H2. The catalyst was
activated for 30 min by shaking, then (‡)-39 (50 mg, 0.218 mmol) was added. After shaking for 15 min, the
suspension was filtered through a Celite pad, and the catalyst was washed with MeOH (5 ml). Evaporation
afforded 44 mg (97%) of (‡)-40. Further purification by Dowex resin can be done as above. Slightly yellow oil.
25
25
25
25
25
[a] ˆ ‡77, [a] ˆ ‡535, [a] ˆ ‡124, [a] ˆ ‡210, [a] ˆ ‡243 (cˆ0.08, CHCl3). IR (film): 3320, 3280,
589
577
546
435
405
2890, 1660, 1585, 1460, 1360, 1260, 1220, 1160, 1100, 1025, 985, 875, 665. 1H-NMR (400 MHz, CD3OD): 5.81
(s, H C(4)); 4.19, 4.09 (2d, 2Jˆ13.1, CH2 C(3)); 3.85 (d, 3Jˆ7.3, CH2 C(1)); 3.80 (dd, 2Jˆ11.8, 3Jˆ4.5, 1 H);
3.74 (br. t, 3Jˆ2.5, H C(6)); 3.70 (dd, 2Jˆ11.8, 3Jˆ2.7, 1 H, CH2 C(2)); 3.27 (br. d, 3Jˆ2.5, H C(5)); 2.73
(br. ddd, 3Jˆ7.0, 4.5, 2.7, H C(2)); 2.31 (br. tdd, 3Jˆ7.3, 7.0, 2.5, H C(1)). 13C-NMR (100.6 MHz, D2O): 139.9
(s, C(3)); 125.0 (d, Jˆ162, C(4)); 70.2 (d, Jˆ145, C(6)); 63.8 (t, Jˆ143, CH2 C(3)); 60.7, 58.0 (2t, Jˆ148, 145,
2 CH2); 51.8 (d, Jˆ141, C(5)); 39.7 (d, Jˆ126, C(2)); 37.8 (d, Jˆ126, C(1)). CI-MS (NH3): 91(100), 108(84),
121(28), 129(24), 172(10), 204(51).
(1RS,4SR,5SR,6RS)-Benzyl (6-Hydroxy-3,4,5-tris(hydroxymethyl)cyclohex-2-enyl)carbamate ((Æ)-41). A
mixture of (Æ)-40 (10 mg, 0.049 mmol), 50% aq. EtOH (1 ml), NaHCO3 (7.4 mg, 0.088 mmol), and
benzylcarbonyl chloride (8 ml, 0.058 mmol) was stirred at 208 for 15 h. Evaporation and FC (silica gel;
AcOEt/MeOH 8 : 1) gave 15 mg (90%) of (Æ)-41. Colorless oil. Rf (AcOEt/MeOH 8 : 1) 0.20. UV (MeCN):
200.5 (11900). IR (film): 3320, 2895, 1695, 1540, 1505, 1455, 1305, 1250, 1130, 1030, 750, 665. 1H-NMR
(400 MHz, CD3OD): 7.31 ± 7.25 (m, arom. H); 5.66 (d, 3Jˆ4.7, H C(2)); 5.06, 5.02 (2d, 2Jˆ12.3, PhCH2);
4.06, 4.03 (2d, 2Jˆ13.5, CH2 C(3)); 4.01 (br. s, H C(6)); 3.78 ± 3.72 (m, CH2, H C(1)); 3.70 (dd, 2Jˆ11.7,
3Jˆ4.3, 1 H); 3.57 (dd, 2Jˆ12.1, 3Jˆ1.9, 1 H, CH2); 2.62 (br. m, H C(4)); 2.15 (br. m, H C(5)). 13C-NMR
(100.6 MHz, CD3OD): 158.1 (s, CˆO); 142.6 (s); 138.3 (s, C(3)); 129.5 (dd, Jˆ160, 5.5); 129.0, 128.9
(2d, Jˆ157, arom. C ar); 122.9 (d, Jˆ159, C(2)); 69.3 (d, Jˆ147, C(6)); 67.5, 64.9, 62.0, 58.3 (4t, Jˆ141, 141,
140, 145, 4 CH2); 53.4 (d, Jˆ141, C(1)); 41.1 (d, Jˆ126, C(4)); 38.5 (d, Jˆ125, C(5)). CI-MS (NH3): 91(100),
108(55), 152(2), 241(1), 301(0.5), 320(0.5), 338(0.3). Anal. calc. for C17H23NO6 (337.37): C 60.52, H 6.87;
found: C 60.15, H 6.88.
(1RS,2RS,5RS,6SR)-5-Bromo-3-(bromomethyl)-6-hydroxycyclohex-3-ene-1,2-dimethyl Diacetate ((Æ)-42).
BBr3 (37 ml, 0.38 mmol) was added to a stirred soln. of (Æ)-31 (0.1 g, 0.254 mmol) in anh. CH2Cl2 (1 ml) cooled
to 08. After 5 min at 08, the soln. was stirred at 208 for 25 min. It was then diluted with CH2Cl2 (200 ml), washed
with H2O (50 ml), dried (MgSO4), and evaporated to afford 103 mg (98%) of (Æ)-42. An anal. sample was
obtained by FC (silica gel; AcOEt/PET 1 : 1). Colorless, unstable oil that crystallized (storage in the freezer). Rf
(AcOEt/PET 2 : 1) 0.50. IR (film): 3470, 2960, 2925, 2905, 1735, 1655, 1485, 1465, 1400, 1360, 1340, 1265, 1230,
1180, 1155, 1100, 1040, 955, 945, 920, 880, 870, 850, 815, 755, 710, 650, 620, 605, 565, 520, 480. 1H-NMR
(250 MHz, CDCl3): 5.95 (br. s, H C(4)); 4.86 (dd, 3Jˆ4.5, 1.6, H C(5)); 4.60 (dd, 2Jˆ11.8, 3Jˆ4.4, 1 H); 4.45
3
3
(dd, 2Jˆ11.5, Jˆ6.5, 1 H); 4.38 (dd, 2Jˆ11.5, Jˆ7.0, 1 H, CH2 C(1)); 4.31, 3.98 (2d, 2Jˆ10.4, CH2 C(3));
4.13 (dd, 2Jˆ11.8, 3Jˆ6.8, 1 H, CH2 C(2)); 4.06 (br. d, 3Jˆ4.5, H C(6)); 2.92 (br. ddd, 3Jˆ6.8, 6.0, 4.4,
5Jˆ1.6, H C(2)); 2.45 (br. s, OH); 2.33 (br. ddd,3Jˆ7.0, 6.5, 6.0, H C(1)); 2.10, 2.09 (2s, 2 Me). 13C-NMR
(100.6 MHz, CDCl3): 183.0 (m, CˆO); 139.4 (s, C(3)); 127.3 (d, Jˆ159, C(4)); 66.2 (d, Jˆ151, C(6)); 64.5, 63.4
(2t, Jˆ150, 153, CH2); 54.6 (d, Jˆ153, C(5)); 40.9 (d, Jˆ124, C(2)); 35.7 (t, Jˆ148, CH2 C(3)); 35.0
(d, Jˆ125, C(1)); 21.09, 20.9 (2q, Jˆ129, 2 Me). CI-MS (NH3): 91(11), 105(13), 117(33), 121(15), 134(22),
177(92), 237(100), 253(18), 255(20), 272(33), 353(27), 355(53), 357(27), 430(41), 432(81), 434(38).
(1RS,2RS,5SR,6SR)-5-Azido-3-(azidomethyl)-6-hydroxycyclohex-3-ene-1,2-dimethyl Diacetate ((Æ)-43).
Tetramethylguanidinium azide (80.3 mg, 0.507 mmol) was added in one portion to a soln. of (Æ)-42 (100 mg,
0.242 mmol) in dry MeCN/DMF 4 : 1 (1.5 ml) at 08 under Ar. The soln. was stirred at 08 for 10 min and at 208 for
10 min. It was diluted with AcOEt (100 ml), washed with aq. 1n HCl (30 ml) and aq. sat. NaCl soln. (10 ml),
dried (MgSO4), and evaporated. If necessary, the crude residue could be purified by FC (silica gel; AcOEt/PET
1 : 1): 57 mg (80%) of (Æ)-43 (storage at 228). Colorless oil. Rf (AcOEt/PET 2 : 1) 0.40. IR (film): 3475, 2965,

838
Helvetica Chimica Acta ± Vol. 82 (1999)
2910, 2105, 1740, 1435, 1370, 1245, 1155, 1105, 1040, 980, 920, 850. 1H-NMR (400 MHz, CDCl3): 5.84 (br. s,
H
C(4)); 4.48 (dd, 2Jˆ11.4, 3Jˆ7.4, 1 H); 4.45 (dd, 2Jˆ11.9, 3Jˆ5.4, 1 H); 4.23 (dd, 2Jˆ11.4, 3Jˆ7.0, 1 H,
CH2 C(1)); 4.14 (dd, 2Jˆ11.9, 3Jˆ5.1, 1 H, CH2 C(2)); 3.95 (s, CH2 N3, H C(6)); 3.90 (br. s, H C(5));
2.74 (br. ddd, 3Jˆ5.4, 5.1, 5.8, H C(2)); 2.33 (dddd, 3Jˆ7.4, 7.0, 5.8, 2.6, H C(1)); 2.10, 2.08 (2s, 2 Me).
13C-NMR (100.6 MHz, CDCl3): 171.3, 170.3 (2s, CˆO); 138.2 (s, C(3)); 122.3 (d, Jˆ161, C(4)); 68.9 (d, Jˆ149,
C(6)); 63.4, 62.3 (2t, Jˆ151, 148, 2 CH2); 60.4 (d, Jˆ146, C(5)); 54.9 (dt, Jˆ6.4, 145, CH2 N3); 37.8 (d, Jˆ125,
C(2)); 36.5 (d, Jˆ125, C(1)); 20.9, 20.8 (2q, Jˆ134, 2 Me). CI-MS (NH3): 80(75), 91(100), 106(95), 148(26),
189(13), 236(4), 296(11), 315(7), 356(5). Anal. calc. for C13H18N6O5 (338.32): C 46.15, H 5.36; found: C 45.75,
H 5.29.
(1RS,2RS,5SR,6SR)-5-Azido-3-(azidomethyl)-6-hydroxycyclohex-3-ene-1,2-dimethanol ((Æ)-44). Gaseous
NH3 was bubbled carefully through a soln. of (Æ)-43 (83 mg, 0.28 mmol) in anh. MeOH (2 ml) for ca. 10 s (pH
control). After stirring at 208 for 12 h (TLC control (silica gel; AcOEt/MeOH 8 : 1)), the solvent was
evaporated and the crude product purified by FC (silica gel; AcOEt/MeOH 8 : 1): 61 mg (96%) of (Æ)-44.
Colorless oil. Rf (AcOEt) 0.32. UV (MeCN): 192.3 (1000). IR (film): 3290, 2920, 2895, 2105, 1735, 1600, 1450,
1245, 1165, 1075, 1030, 915. 1H-NMR (400 MHz, CDCl3): 5.91 (br. d, 3Jˆ3.0, H C(4)); 4.00 ± 3.95 (m, 1 H of
CH2 C(1), H C(5), H C(6)); 4.00 (dd, 2Jˆ11.0, 3Jˆ6.0, 1 H of CH2 C(1)); 3.91 (dd, 2Jˆ11.9, 3Jˆ4.4,
3
1 H); 3.86 (dd, 2Jˆ11.9, Jˆ2.2, 1 H, CH2 C(2)); 2.68 (br. ddd, 3Jˆ6.4, 4.4, 2.2, H C(2)); 2.41 (br. s, OH);
2.27 (dddd, 3Jˆ6.4, 6.0, 6.0, 2.5, H C(1)). 13C-NMR (100.6 MHz, CDCl3): 138.1 (s, C(3)); 123.7 (d, Jˆ160,
C(4)); 68.5 (d, Jˆ151, C(6)); 61.9, 58.2 (2t, Jˆ143, 144, 2 CH2); 60.4 (d, Jˆ150, C(5)); 54.9 (dt, Jˆ6.4, 144,
CH2 C(3)); 39.9 (d, Jˆ125, C(2)); 39.0 (d, Jˆ122, C(1)). CI-MS (NH3): 80(77), 91(100), 94(83), 106(93),
122(39), 154(5). Anal. calc. for C9H14N6O3 (254.25): C 45.52, H 5.55; found: C 45.47, H 5.61.
(1RS,2RS,5SR,6SR)-5-Amino-3-(aminomethyl)-6-hydroxycyclohex-3-ene-1,2-dimethanol ((Æ)-45). For
30 min, 10% Pd/C (10 mg) in MeOH (4 ml) was activated by shaking under H2. Then (Æ)-44 (38 mg,
0.15 mmol) was added. The suspension was shaken until no starting material remained (TLC control (silica gel;
AcOEt/MeOH 8 : 1)), then it was filtered through a Celite pad and evaporated. The crude product was dissolved
‡
in 1n HCl in H2O/MeOH 1 : 1 (200 ml) and loaded onto Dowex 50WX-8 resin (H form). The resin was washed
with H2O (20 ml) and then with MeOH (20 ml). Elution with 5% NH3 soln. and evaporation of the alkaline
fractions afforded 25.7 mg (85%) of (Æ)-45. Colorless oil. Rf (MeOH/NH3 5% 10 : 1) 0.067. IR (film): 3345,
2890, 1645, 1560, 1570, 1470, 1455, 1410, 1095, 1025. 1H-NMR (400 MHz, CD3OD): 5.66 (br. d, 3Jˆ3.0,
3
H
C(4)); 3.77 (d, 3Jˆ7.3, CH2 C(1)); 3.71 (dd, 2Jˆ12.0, Jˆ4.0, 1 H); 3.65 (br. dd, 3Jˆ3.0, 2.5, H C(6));
3.61 (dd, 2Jˆ12.0, 3Jˆ2.9, 1 H, CH2 C(2)); 3.28, 3.24 (2d, 2Jˆ16.0, CH2 C(3)); 3.19 (br. t, 3Jˆ3.0, H C(5));
2.55 (br. ddd, 3Jˆ4.0, 2.9, 2.5, H C(2)); 2.22 (tdd, 3Jˆ7.3, 7.0, 2.5, H C(1)). 13C-NMR (100.6 MHz, CD3OD):
141.0 (s, C(3)); 126.3 (d, Jˆ156, C(4)); 72.6 (d, Jˆ147, C(6)); 61.7, 59.1 (2t, Jˆ139, 143, 2 CH2); 53.6
(d, Jˆ137, C(5)); 46.0 (t, Jˆ129, CH2 C(3)); 41.7 (d, Jˆ125, C(5)); 40.7 (d, Jˆ122, C(6)). CI-MS (NH3):
81(62), 91(71), 106(100), 149(9), 168(11), 186(11), 203(5).
(1RS,4SR,5SR,6RS)-Benzyl (6-Hydroxy-4,5-bis(hydroxymethyl)-3-{{[(phenylmethoxy)carbonyl]amino}-
methyl}cyclohex-2-enyl)carbamate ((Æ)-46). To a soln. of (Æ)-45 (8 mg, 0.040 mmol) in 50% aq. EtOH soln.
(0.5 ml), NaHCO3 (10 mg, 0.119 mmol) and benzyl carbonochloridate (CbzCl; 13.5 ml, 0.095 mmol) were
added. The mixture was stirred at 208 for 1 h. After evaporation, the residue was purified by FC (silica gel;
AcOEt/MeOH 8 : 1): 15.5 mg (83%) of (Æ)-46. White solid (needles, MeOH/CH2Cl2/PET). M.p. 61 ± 628. Rf
(AcOEt/MeOH 8 : 1) 0.50. UV (MeCN): 205.4 (20100). IR (KBr): 3340, 3035, 2895, 1700, 1675, 1525, 1455,
1435, 1295, 1255, 1165, 1020, 910, 750, 730, 695. 1H-NMR (400 MHz, CD3OD): 7.37 ± 7.24 (m, 10 arom. H); 5.59
(d, 3Jˆ4.3, H C(2)); 5.09, 5.04 (2d, 2Jˆ12.4, 2 Bn); 4.01 (br. s, H C(6)); 3.86, 3.69 (2d, 2Jˆ16.2, CH2 C(3));
3.78 ± 3.65 (m, 2 CH2, H C(1)); 2.49 (br. m, H C(4)); 2.17 (br. t, 3Jˆ7.0, H C(5)). 13C-NMR (100.6 MHz,
CD3OD): 159.1, 157.9 (2s, CˆO); 140.3, 138.3 (2s, arom. C); 129.5, 129.0, 128.9 (3d, Jˆ160, 3 arom. C); 128.7
(s, C(3)); 123.0 (d, Jˆ153, C(2)); 68.9 (d, Jˆ149, C(6)); 67.6, 67.5 (2t, Jˆ145, 2 PhCH2); 62.1, 57.9 (2t, Jˆ142,
144, 2 CH2); 53.4 (d, Jˆ141, C(1)); 45.4 (t, Jˆ137, CH2 C(3)); 40.8 (d, Jˆ127, C(4)); 39.0 (d, Jˆ126, C(5)).
CI-MS (NH3): 79(79), 91(60), 108(100), 242(0.4), 301(0.1), 471(0.1). Anal. calc. for C25H30N2O7 (470.52):
C 63.82, H 6.43; found: C 63.72, H 6.34.
(1RS,2RS,3SR,4RS,5SR,6RS)-5-Azido-1,4,6-trihydroxycyclohexane-1,2,3-trimethyl Triacetate ((Æ)-47). To
a vigorously stirred soln. of (Æ)-38 (100 mg, 0.283 mmol) in AcOEt/MeCN 1 : 1 (5 ml) at 0 ± 58 (ice-water bath),
a soln. of RuCl3 hydrate (41% Ru, 0.012 mmol) and NaIO4 (90.8 mg, 0.425 mmol) in distilled H2O (700 ml) was
added dropwise. The two-phase mixture was stirred vigorously for 1 min and quenched with a cooled sat.
aq. Na2S2O3 soln. (10 ml). The aq. phase was immediately extracted with AcOEt (50 ml, 3 times). The
combined org. phases were dried (MgSO4) and evaporated and the dark residue containing two isomers (6.3 : 1)
submitted to FC (silica gel; 108, AcOEt/PET 2 : 1): 41 mg (47%) of pure major isomer (Æ)-47 and 49 mg (44%)

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of a mixture. Colorless oil. Data of (Æ)-47: Rf (AcOEt/PET) 0.15. IR (film) 3440, 2970, 2920, 2110, 1730, 1470,
1435, 1370, 1250, 1130, 1040, 665. 1H-NMR (400 MHz, CDCl3): 4.50 (dd, 2Jˆ12.2, 3Jˆ5.7, 1 H); 4.45
(dd, 2Jˆ12.2, 3Jˆ4.8, 1 H, CH2 C(3)); 4.37 (d, 3Jˆ6.8, CH2); 4.27, 3.90 (2d, 2Jˆ11.5, CH2 C(1)); 3.64
(dd, 3Jˆ10.5, 9.0, H C(5)); 3.59 (dd, 3Jˆ10.5, 4.9, H C(4)); 3.50 (br. s, OH); 3.31 (d, 3Jˆ9.0, H C(6)); 3.00
(br. s, OH); 2.58 (dddd, 3Jˆ5.7, 5.0, 4.9, 4.8, H C(3)); 2.09, 2.06, 2.04 (3s, Me); 2.09 ± 2.00 (m, 3Jˆ5.0,
H
C(2)). 13C-NMR (100.6 MHz, CDCl3): 171.3, 171.2, 170.9 (3s, CˆO); 73.9 (s, C(1)); 72.4, 72.2 (2d, Jˆ141,
146, C(6), C(4)); 65.4 (d, Jˆ140, C(5)); 62.8 (dd, Jˆ149, 152, CH2 C(1)); 61.7, 61.5 (2t, Jˆ149, 2 CH2); 40.7,
37.9 (2d, Jˆ132, 129, C(2), C(3)); 21.1, 20.8 (2q, Jˆ130, 2 Me). CI-MS (NH3): 70(100), 108(52), 136(60),
183(24), 209(12), 256(13), 312(37), 330(44), 37(8), 372(36), 390(13), 407(22). Anal. calc. for C15H23N3O9
(389.40): C 6.27, H 5.95, N 10.79; found: C 46.19, H 5.99, N 10.67.
(1RS,2RS,3SR,4RS,5SR,6RS)-5-Azido-1,4,6-trihydroxycyclohexane-1,2,3-trimethanol ((Æ)-48). Gaseous
NH3 was bubbled through a soln. of (Æ)-47 (50 mg, 0.128 mmol) in anh. MeOH (2 ml) and the soln. stirred
at 208 for 16 h. MeOH was then evaporated to afford a mixture of (Æ)-48 (100%) and acetamide. FC (silica gel;
AcOEt/MeOH 8 : 1) gave 30.6 mg (91%) of pure (Æ)-48. Slightly yellow oil that partially crystallized in the
1
freezer. Rf (AcOEt/MeOH 8 : 1) 0.30. IR (film): 3550, 2900, 2110, 1700, 1665, 1375, 1255, 1040, 885. H-NMR
(400 MHz, D2O): 3.85 (dd, 2Jˆ11.5, 3Jˆ5.3, 1 H); 3.84 (dd, 2Jˆ11.5, 3Jˆ3.4, 1 H); 3.70 (dd, 2Jˆ11.5, 3Jˆ3.8,
1 H, CH2 C(3)); 3.72 (dd, 3Jˆ10.5, 10.0, H C(5)); 3.66 (dd, 2Jˆ11.5, 3Jˆ8.5, 1 H, CH2 C(2)); 3.56
(dd, 3Jˆ10.5, 6.0,
H
C(4)); 3.34 (d, 3Jˆ10.0,
H
C(6)); 3.58, 3.36 (2d, 2Jˆ11.5, CH2 C(1)); 2.30
(br. dddd, 3Jˆ6.0, 5.3, 3.8, 3.4, H C(3)); 1.96 (ddd, 3Jˆ8.5, 5.3, 5.3, H C(2)). 13C-NMR (100.6 MHz,
CD3OD): 75.5 (s, C(1)); 74.0, 73.9 (2d, Jˆ143, C(4), C(6)); 69.1 (d, Jˆ144, C(5)); 62.6 (t, Jˆ143, CH2 C(1));
60.1, 58.2 (2t, Jˆ134, 141, 2 CH2); 43.7, 41.6 (2d, Jˆ127, 122, C(2), C(3)). Anal. calc. for C9H17N3O6 (263.30)
containing 2% of H2O (as titrated by the Karl Fischer technique): C 41.06, H 6.51; found: C 39.99, H 6.46.
(1RS,2RS,3SR,4RS,5SR,6RS)-5-Amino-1,4,6-trihydroxycyclohexane-1,2,3-trimethanol ((Æ)-49). A mixture
of (Æ)-48 (11.7 mg, 0.044 mmol), MeOH (0.5 ml), and 20% Pd/C (4 mg) was degassed and shaken under H2 at
208 for 15 h. The soln. was filtered through a Celite pad and evaporated. The residue was dissolved in 1n HCl in
‡
H2O/MeOH 1 : 1 (100 ml) and deposited on Dowex 50 WX-8 (H form). The resin was washed with H2O
(10 ml) and then with MeOH (10 ml). Elution with 5% aq. NH3 soln. and evaporation of the alkaline fraction
gave 0.5 mg (90%) of pure (Æ)-49. Colorless oil. IR (film): 3350, 2900, 1650, 1585, 1465, 1415, 1235, 1085, 1045,
882. 1H-NMR (400 MHz, D2O): 4.01 (dd, 2Jˆ11.5, 3Jˆ5.6, 1 H); 3.98 (dd, 2Jˆ12.2, 3Jˆ3.0, 1 H); 3.87
(dd, 2Jˆ12.2, 3Jˆ5.0, 1 H, CH2 C(3)); 3.82 (dd, 2Jˆ11.5, 3Jˆ8.5, 1 H, CH2 C(2)); 3.71, 3.51 (2d, 2Jˆ11.4,
CH2 C(1)); 3.62 (dd, 3Jˆ10.5, 5.9, H C(4)); 3.34 (d, 3Jˆ10.5, H C(6)); 3.19 (t, 3Jˆ10.5, H C(5)); 2.41
(dddd, 3Jˆ5.9, 5.6, 5.0, 3.0, H C(3)); 2.11 (ddd, 3Jˆ8.5, 5.6, 5.6, H C(2)). 13C-NMR (100.6 MHz, D2O): 76.5
(s, C(1)); 74.1, 74.0 (2d, Jˆ141, C(4), C(6)); 63.0 (t, Jˆ145, CH2 C(1)); 60.8, 59.1 (2t, Jˆ143, 145, 2 CH2);
56.4 (d, Jˆ148, C(5)); 43.9, 42.3 (2d, Jˆ131, 125, C(2), C(3)). CI-MS (NH3): 81(40), 91(56), 108(38),
122(34), 136(15), 170(12), 188(93), 202(16), 220(33), 238(100).
(1RS,2RS,3SR,4RS,5SR,6RS)-5-Acetamido-4,6-diacetoxy-1-hydroxycyclohexane-1,2,3-trimethyl Triacetate
((Æ)-50. A mixture of (Æ)-49 (10 mg, 0.042 mmol) in dry pyridine/Ac2O 1 : 1 (0.1 ml) was stirred at 208 for 24 h.
The solvents were evaporated with toluene (2 ml, 3 times). The residue was purified by FC (silica gel; AcOEt):
16 mg (77%) of (Æ)-52. Colorless oil. IR (film): 3355, 2925, 1740, 1665, 1550, 1435, 1370, 1240, 1195, 1095, 1035,
980, 730. 1H-NMR (400 MHz, CDCl3): 5.41 (d, 3Jˆ9.8, NH); 4.89 (dd, 3Jˆ11.0, 5.5, H C(4)); 4.88 (d, 3Jˆ10.6,
H
C(6)); 4.63 (ddd, 3Jˆ11.0, 10.6, 9.8, H C(5)); 4.54 (dd, 2Jˆ12.3, 3Jˆ4.2, 1 H); 4.41 (dd, 2Jˆ12.3, 3Jˆ6.1,
1 H, CH2 C(3)); 4.39 (d, 3Jˆ6.7, CH2 C(2)); 3.97, 3.93 (2d, 2Jˆ11.6, CH2 C(1)); 2.79 (s, OH); 2.68
(dddd, 3Jˆ6.1, 6.0, 5.5, 4.2, H C(3)); 2.27 (td, 3Jˆ6.7, 6.0, H C(2)); 2.09 ± 2.02 (5s, 6 Me). 13C-NMR
(100.6 MHz, CDCl3): 171.0, 170.6, 170.4, 170.0 (5s, CˆO); 73.7 (s, C(1)); 72.9, 72.0 (2d, Jˆ154, 145, C(2),
C(4)); 62.3, 61.4, 61.2 (3t, Jˆ148, 146, 145, CH2); 48.8 (d, Jˆ137, C(3)); 38.9, 38.5 (2d, Jˆ129, 127, C(5),
C(6)); 23.2 (q, Jˆ129, 6 Me). CI-MS (NH3): 72(47), 135(28), 236(9), 296(25), 356(309, 430(30), 490(100).
Anal. calc. for C21H31NO12 (489.48): C 51.53, H 6.38; found: C 51.75, H 6.21.
(1RS,2RS,5RS)-5-Bromo-6-oxocyclohex-3-ene-1,2,3-trimethyl Triacetate ((Æ)-51). A mixture of (Æ)-31
(21 mg, 0.053 mmol), CH2Cl2 (2 ml), and 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (45 mg,
0.107 mmol) was stirred overnight at 208, diluted with CH2Cl2 (100 ml), washed successively with 5% aq.
Na2S2O3 soln. (20 ml), sat. aq. NaHCO3 soln. (20 ml), and H2O (20 ml). Drying (MgSO4) and evaporation gave
20 mg (96%) of (Æ)-51. Colorless, unstable oil (storage at 288). IR (film): 2920, 1740, 1435, 1370, 1230, 1040,
1
975, 870, 725. H-NMR (250 MHz, CDCl3): 6.16 (br. d, 3Jˆ3.9, H C(4)); 5.18 (br. d, 3Jˆ3.9, H C(5)); 4.74
(d, 2Jˆ13.8, 1 H); 4.64 (br. d, 2Jˆ13.8, CH2 C(3)); 4.64 (dd, 2Jˆ11.5, 3Jˆ5.8, 1 H); 4.19 (dd, 2Jˆ11.0, 3Jˆ3.0,
1 H); 4.18 (dd, 2Jˆ11.0, 3Jˆ3.1, 1 H, CH2 C(2)); 4.17 (dd, 2Jˆ11.5, 3Jˆ8.2, 1 H, CH2 C(1)); 3.25
(ddd, 3Jˆ8.2, 6.0, 5.8, H C(1)); 3.00 (ddd, 3Jˆ6.0, 3.1, 3.0, H C(2)); 2.13, 2.07, 2.04 (3s, 3 Me). 13C-NMR

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Helvetica Chimica Acta ± Vol. 82 (1999)
(100.6 MHz, CDCl3): 198.5 (s, C(6)); 170.5 (m, CˆO); 136.6 (s, C(3)); 128.4 (dq, Jˆ167, 6.4, C(4)); 60.4, 60.3,
64.7 (3t, Jˆ153, 153, 148, 3 CH2); 48.8 (d, Jˆ126, C(5)); 47.8 (d, Jˆ148, C(1)); 39.5 (d, Jˆ134, C(2)); 20.82,
20.76 (2q, Jˆ139, 2 Me). CI-MS (NH3): 77(17), 91(39), 120(100), 149(32), 210(13), 273(4), 311(5).
(1RS,2SR,3SR,6SR)-7-Oxabicyclo[4.1.0]hept-4-ene-2,3,4-trimethyl Triacetate ((Æ)-52). A mixture of (Æ)-
31 (100 mg, 0.25 mmol), toluene (2.5 ml), and DBU (37 ml, 0.25 mmol) was stirred at 208 for 40 min, then the
resulting suspension was filtered. Evaporation under high vacuum gave 78 mg (100%) of (Æ)-52. Colorless oil.
Rf (AcOEt/PET 2 : 1) 0.30. IR (film): 2925, 2955, 1740, 1665, 1650, 1435, 1370, 1230, 1035, 870. 1H-NMR
(250 MHz, CDCl3): 6.10 (dt, 3Jˆ4.2, 4Jˆ1.4, H C(5)); 4.67, 4.60 (2dd, 2Jˆ12.4, 4Jˆ1.4, CH2 C(4)); 4.50
(dd, 2Jˆ11.2, 3Jˆ7.2, 1 H); 4.40 (dd, 2Jˆ11.2, 3Jˆ7.8, 1 H, CH2 C(2)); 4.27 (dd, 2Jˆ11.3, 3Jˆ6.6, 1 H); 4.09
(dd, 2Jˆ11.3, 3Jˆ5.6, 1 H, CH2 C(3)); 3.52 (dd, 3Jˆ4.2, 2.0, H C(1)); 3.39 (t, 3Jˆ4.2, H C(6)); 2.62
(dddd, 3Jˆ7.0, 6.6, 5.6, 2.0, H C(3)); 2.27 (ddd, 3Jˆ7.8, 7.2, 7.0, H C(2)); 2.12, 2.11, 2.05 (3s, 3 Me).
13C-NMR (100.6 MHz, CDCl3): 170.7, 170.4 (2s, CˆO); 140.5 (s, C(4)); 122.3 (d, Jˆ162, C(5)); 66.9, 65.8, 63.7
(3t, Jˆ151, 148, 148, 3 CH2): 55.9 (d, Jˆ175, C(6)); 47.0 (dd, Jˆ180, 7.6, C(1)); 37.2 (d, Jˆ134, C(3)); 35.9
(d, Jˆ125, C(2)); 20.9, 20.83, 20.8 (3q, Jˆ129, 3 Me). CI-MS (NH3): 91(44), 104(100), 120(79), 150(30),
163(12), 179(3), 193(8), 210(5), 235(1). Anal. calc. for C15H20O7 (312.32): C 57.69, H 6.45; found: C 57.50,
H 6.41.
(1RS,2SR,3RS,4SR,5SR,6SR)-5-Bromo-1,4,6-trihydroxycyclohexane-1,2,3-trimethyl Triacetate ((Æ)-53). A
soln. of RuCl3 ´ H2O (41% Ru, 0.0178 mmol) and NaIO4 (81 mg, 0.38 mmol) in H2O (0.7 ml) was added to a
vigorously stirred soln. of (Æ)-31 (100 mg, 0.254 mmol) in AcOEt/MeCN 1 : 1 (5 ml) at 0 ± 58 (ice-water bath).
The two-phase mixture was stirred vigorously for 1 min and quenched with a cooled sat. aq. Na2S2O3 soln.
(10 ml). The aq. phase was immediately extracted with AcOEt (50 ml, 3 times). The combined org. phases were
dried (MgSO4) and evaporated and the dark residue submitted to FC (silica gel; AcOEt/PET 2 : 1): 97.8 mg
(90%) of (Æ)-53. Colorless crystals. M.p. 127 ± 1288. Rf (AcOEt/PET 2 : 1) 0.15. UV (MeCN): 206 (3090),
201(3295), 199(3390). IR (KBr): 3510, 2975, 1740, 1370, 1370, 1230, 1125, 1080, 1040, 985, 955, 940, 855, 710,
650, 610, 465. 1H-NMR (250 MHz, CDCl3): 4.47, 4.14 (2d, 2Jˆ12.0, CH2 C(1)); 4.44 (dd, 2Jˆ11.3, 3Jˆ2.4,
1 H); 4.39 (dd, 3Jˆ10.2, 2.9, H C(5)); 4.30 (dd, 2Jˆ12.9, 3Jˆ3.3, 1 H); 4.24 (dd, 2Jˆ11.3, 3Jˆ5.5, 1 H,
CH2 C(3)); 4.13 (dd, 2Jˆ12.9, 3Jˆ8.0, 1 H, CH2 C(2)); 4.11 (br. dd, 3Jˆ4.5, 2.9,
H C(4)); 4.02
(dd, 3Jˆ10.2, 4.5, H C(6)); 2.75 (d, 3Jˆ4.5, OH C(4)); 2.89 (s, OH C(1)); 2.96 (d, 3Jˆ4.5, OH C(6));
2.67 (br. ddd, 3Jˆ5.5, 4.5, 2.4, H C(3)); 2.39 (ddd, 3Jˆ8.0, 4.5, 3.3, H C(2)); 2.10, 2.08, 2.01 (3s, 3 Me).
13C-NMR (100.6 MHz, CDCl3): 171.3, 171.0, 170.7 (3s, CˆO); 75.4 (s, C(1)); 70.5, 70.0 (2d, Jˆ149, 153, C(4),
C(6)); 67.1 (t, Jˆ148, CH2 C(1)); 63.3, 62.0 (2td, Jˆ151, 8, 2 CH2); 62.9 (d, Jˆ153, C(5)); 42.7, 38.0
(2d, Jˆ127, 133, C(2), C(3)); 20.9 (q, Jˆ130, 3 Me). CI-MS (NH3): 110(2), 167(4), 209(5), 289(11),
351(44), 369(96), 411(6), 427(6). Anal. calc. for C15H23BrO9 (427.20): C 42.17, H 5.43, Br 18.70; found:
C 42.03, H 5.40, Br 18.66.
(1RS,2RS,3SR,4RS,5SR,6RS)-2,5-Dihydroxy-7-oxabicyclo[4.1.0]heptane-2,3,4-trimethyl Triacetate ((Æ)-
54). A mixture of (Æ)-53 (214 mg, 0.5 mmol), MeCN (4 ml), BEMP (2-[(tert-butyl)imino]-2-(diethylamino)-
1,3-dimethylperhydro-1,3,2-diazaphosphorine) on resin (2.3 mmol/g) was stirred at 408 for 2 d. The suspension
was filtered, washed with MeCN (4 ml), and evaporated. The residue was purified by FC (Florisil; AcOEt/PET
2 : 1, 108): 75 mg (44%) of (Æ)-54. Colorless oil. Rf (AcOEt/PET 2 : 1) 0.10. IR (CH2Cl2): 3460, 2920, 2850, 2285,
1730, 1435, 1370, 1240, 1170, 1040, 940. 1H-NMR (250 MHz, CDCl3): 4.71 (dd, 2Jˆ11.3, 3Jˆ9.6, 1 H); 4.30
(dd, 2Jˆ12.0, 3Jˆ3.4, 1 H); 4.26 (d, 3Jˆ4.1, CH2 C(2)); 4.16 (br. ddd, 3Jˆ4.9, 2.8, 1.5, H C(5)); 3.99
(dd, 2Jˆ11.3, 3Jˆ5.4, CH2 C(4)); 3.94 (dd, 2Jˆ12.0, 3Jˆ8.5, CH2 C(3)); 3.49 (dd, 3Jˆ3.4, 1.5, H C(6));
3.33 (d, 3Jˆ4.9, OH C(5)); 3.23 (d, 3Jˆ3.4, H C(1)); 2.94 (s, OH C(2)); 2.14, 2.10, 2.00 (3s, 3 Me); 2.12
(dddd, 3Jˆ9.5, 5.4, 3.0, 2.8, H C(4)); 1.91 (ddd, 3Jˆ8.5, 3.4, 3.0, H C(3)). 13C-NMR (100.6 MHz, CDCl3):
172.3, 170.8 (2s, CˆO); 69.2 (s, C(2)); 63.6 (d, Jˆ144, C(5)); 63.2, 61.3 (2t, Jˆ150, CH2); 57.3, 54.1
(2d, Jˆ180, 170, C(1), C(6)); 42.0, 33.1 (2d, Jˆ133, 129, C(3), C(4)); 21.0, 20.9 (q, Jˆ129, 3 Me). CI-MS
(NH3): 148(1), 190(2), 227(2), 269(3), 304(2), 348(6), 364(100). Anal. calc. for C15H22O9 (346.34): C 52.02,
H 6.40; found: C 52.17, H 6.54.
(1RS,2RS,3SR,4RS,5SR,6RS)-2,5-Dihydroxy-7-oxabicyclo[4.1.0]heptane-2,3,4-trimethanol ((Æ)-55). NH3
was carefully bubbled through a soln. of (Æ)-54 (23.4 mg, 0.068 mmol) in dry MeOH (1.5 ml) at 08 for ca. 10 s.
The soln. was stirred at 208 for 20 h. The solvent was quickly evaporated (308) to afford (Æ)-55 contaminated
with acetamide. FC (Florisil; AcOEt/MeOH 8 : 1) gave 10 mg (70%) of (Æ)-55. Colorless, unstable oil. Rf
(AcOEt/MeOH 8 : 1) 0.18. IR (film): 3355, 2920, 1725, 1650, 1465, 1430, 1370, 1265, 1165, 1065, 1020, 920, 855,
665. 1H-NMR (400 MHz, CD3OD): 4.15 (dd, 3Jˆ3.6, 1.7, H C(5)); 3.81, 3.74 (2d, 2Jˆ11.4, CH2 C(2)); 3.80
(dd, 2Jˆ10.9, 3Jˆ6.6, 1 H); 3.69 (dd, 2Jˆ12.5, 3Jˆ3.4, 1 H); 3.62 (dd, 2Jˆ10.9, 3Jˆ7.5, CH2 C(4)); 3.54
(dd, 2Jˆ12.5, 3Jˆ3.7, 1 H, CH2 C(3)); 3.22 (dd, 3Jˆ3.6, 1.7, H C(6)); 3.09 (d, 3Jˆ3.6, H C(1)); 2.15

Helvetica Chimica Acta ± Vol. 82 (1999)
841
(dddd, 3Jˆ7.5, 6.6, 3.6, 3.6, H C(4)); 1.69 (ddd, 3Jˆ3.7, 3.6, 3.4, H C(3)). 13C-NMR (100.6 MHz, CD3OD):
71.8 (s, C(2)); 68.0 (t, Jˆ143, CH2 C(2)); 65.3 (d, Jˆ145, C(5)); 61.9, 58.1 (2t, Jˆ141, 137, 2 CH2); 57.9, 56.7
(2d, Jˆ177, 178, C(1), C(6)); 43.9, 36.7 (2d, Jˆ126, C(4), C(3)). CI-MS (NH3): 70(27), 81(38), 95(30),
111(28), 125(20), 153(25), 167(37), 185(48), 203(28), 221(100), 238(44).
(1RS,2RS,3SR,4RS,6SR)-2-Hydroxy-5-oxo-7-oxabicyclo[4.1.0]heptane-2,3,4-trimethyl Triacetate ((Æ)-56).
As described for (Æ)-51, from (Æ)-54 (22 mg, 0.064 mmol): 21 mg (99%) of (Æ)-56. Colorless, unstable oil. Rf
(AcOEt/PET 2 : 1) 0.20. IR (film): 2960, 1745, 1565, 1440, 1370, 1230, 1140, 1040, 980, 900, 740. 1H-NMR
(250 MHz, CDCl3): 4.50 (dd, 2Jˆ11.9, 3Jˆ5.8, 1 H); 4.38, 4.28 (2d, 2Jˆ11.8, CH2 C(2)); 4.27 (dd, 2Jˆ12.9,
3Jˆ3.9, 1 H); 4.14 (dd, 2Jˆ11.9, 3Jˆ7.7, 1 H, CH2 C(4)); 3.96 (dd, 2Jˆ12.9, 3Jˆ3.3, 1 H, CH2 C(3)); 3.56
(dd, 3Jˆ3.8, 4Jˆ1.3, H C(1)); 3.48 (d, 3Jˆ3.8, H C(6)); 3.47 (ddd, 3Jˆ7.7, 5.8, 5.0, H C(4)); 3.21 (s, OH);
2.53 (dddd, 3Jˆ5.0, 3.9, 3.3, 4Jˆ1.3, H C(3)); 2.17, 2.05, 1.98 (3s, 3 Me). 13C-NMR (100.6 MHz, CDCl3): 203.0
(s, C(5)); 170.6 (s, CˆO); 69.3 (s, C(2)); 66.9, 59.7, 59.6 (3t, Jˆ147, 148, 148, 3 CH2); 60.4 (d, Jˆ182, C(6));
56.5 (d, Jˆ187, C(1)); 47.7 (d, Jˆ131, C(4)); 40.2 (d, Jˆ129, C(3)); 20.8, 20.4 (2q, Jˆ130, 3 Me). CI-MS
(NH3): 81(42), 94(37), 107(52), 123(96), 164(100), 195(19), 211(27), 225(21), 248(4), 267(46), 285(11),
302(1), 327(13), 262(2).
(1RS,2SR,3RS,4SR,5SR,6SR)-6-Acetoxy-5-bromo-1,4-dihydroxycyclohexane-1,2,3-trimethyl Triacetate
((Æ)-57). A mixture of (Æ)-53 (21 mg, 0.049 mmol), pyridine (0.5 ml), and Ac2O (0.25 ml) was stirred at 208
for 30 min. Toluene (5 ml) was added, and the solvents were evaporated. The residue was purified by FC (silica
gel; AcOEt/PET 2 : 1): 21.5 mg (100%) of (Æ)-57. Beige solid. M.p. 129.5 ± 130.58. IR (CH2Cl2): 3505, 3480,
3470, 3450, 2970, 2910, 1740, 1735, 1370, 1235, 1090, 1045. 1H-NMR (250 MHz, CDCl3): 5.48 (d, 3Jˆ10.7,
H
C(6)); 4.50 (dd, 3Jˆ10.7, 2.7, H C(5)); 4.43 (dd, 2Jˆ11.1, 3Jˆ6.0, 1 H); 4.41 (dd, 2Jˆ12.5, 3Jˆ2.5, 1 H);
4.30 (dd, 2Jˆ11.1, 3Jˆ5.7, 1 H, CH2 C(3)); 4.17 (dd, 2Jˆ12.5, 3Jˆ8.5, 1 H, CH2 C(2)); 4.15 (dd, 3Jˆ2.7, 5.8,
H
C(4)); 4.14 (s, OH C(1)); 2.69 (dddd, 3Jˆ6.0, 5.7, 5.8, 4.0,
H C(3)); 2.62 (s, OH C(4)); 2.39
(ddd, 3Jˆ8.5, 4.0, 2.5, H C(2)); 2.17, 2.09, 2.08, 2.02 (4s, 4 Me). 13C-NMR (100.6 MHz, CDCl3): 170.9, 168.9
(2s, CˆO); 75.7 (s, C(1)); 71.3 (d, Jˆ149, C(6)); 70.4 (d, Jˆ149, C(4)); 66.5 (t, Jˆ148, CH2 C(1)); 63.1, 61.7
(2t, Jˆ140, CH2); 57.5 (d, Jˆ155, C(5)); 43.4, 37.7 (2d, Jˆ134, 136, C(2), C(3)); 20.9, 20.8 (2q, Jˆ129, 4 Me).
CI-MS (NH3): 91(56), 135(74), 209(100), 251(60), 277(9), 311(95), 335(16), 337(15), 393(23), 391(22).
Anal. calc. for C17H25BrO10 (469.29): C 43.51, H 5.37, Br 17.03; found: C 43.52, H 5.43, Br 17.08.
(1RS,2SR,3RS,4SR,5SR,6SR)-4,6-Diacetoxy-5-bromo-1-hydroxycyclohexane-1,2,3-trimethyl Triacetate
((Æ)-58). A mixture of (Æ)-53 (15 mg, 0.035 mmol), pyridine (0.25 ml), and Ac2O (0.25 ml) was stirred at
208 for 1 d. Toluene (5 ml) was added, and the solvents were evaporated. The residue was purified by FC (silica
gel; AcOEt/PET 1 : 1): 18 mg (100%) of (Æ)-57. Colorless oil. Rf (AcOEt/PET 2 : 1) 0.40. IR (CH2Cl2): 2970,
2925, 2850, 2790, 1750, 1745, 1735, 1720, 1710, 1560, 1460, 1370, 1225, 1045, 1385. 1H-NMR (250 MHz, CDCl3):
5.66 (br. dd, 3Jˆ3.4, 2.4, H C(4)); 5.40 (d, 3Jˆ10.9, H C(6)); 4.48 (dd, 3Jˆ10.9, 3.4, H C(5)); 4.34
3
3
(dd, 2Jˆ12.6, Jˆ4.3, 1 H); 4.20, 4.12 (2d, 2Jˆ12.1, CH2 C(1)); 4.15 (dd, 2Jˆ12.6, Jˆ7.9, 1 H, CH2 C(2));
4.19 ± 4.07 (d, 3Jˆ7.0, CH2 C(3)); 2.70 (s, OH C(1)); 2.87 (tdd, 3Jˆ7.0, 4.8, 2.4, H C(3)); 2.43 (ddd, 3Jˆ7.9,
4.8, 4.3, H C(2)); 2.18, 2.17, 2.11, 2.08, 2.04 (5s, 5 Me). 13C-NMR (100.6 MHz, CDCl3): 170.6 ± 169.4
(m, CˆO); 75.3 (m, C(1)); 71.7, 70.6 (2d, Jˆ153, 159, C(5), C(6)); 66.5 (t, Jˆ149, CH2 C(1)); 62.1, 61.1
(2t, Jˆ149, 147, 2 CH2); 51.0 (d, Jˆ153, C(5)); 43.1, 37.0 (2d, Jˆ137, 132, C(2), C(3)); 20.7 ± 20.8 (5q, Jˆ130,
5 Me). CI-MS (NH3): 91(2), 149(4), 209(8), 251(4), 311(6), 451(91), 391(22), 495(36), 530(100). Anal.
calc. for C19H27BrO11 (511.32): C 44.63, H 5.32; found: C 44.48, H 5.26.
(1RS,2SR,3RS,4SR,5SR,6SR)-5-Bromo-1,4,6-trihydroxycyclohexane-1,2,3-trimethanol ((Æ)-59). Gaseous
NH3 was bubbled through a soln. of (Æ)-53 in anh. MeOH (1.5 ml) and the soln. stirred at 208 for 18 h (TLC
control, AcOEt/MeOH 8 : 1). MeOH was evaporated giving (Æ)-59 (100%) contaminated with acetamide. FC
(silica gel; AcOEt/MeOH 4 : 1) gave 27.3 mg (86%) of pure (Æ)-59. White solid. M.p. 174 ± 1758. Rf (AcOEt/
MeOH 4 : 1) 0.19. IR (KBr): 3490, 3230, 2885, 1460, 1385, 1360, 1275, 1250, 1175, 1050, 1035, 995, 915, 720, 660,
535. 1H-NMR (400 MHz, CD3OD): 4.31 (br. d, 3Jˆ10.9, H C(6)); 4.02 (s, H C(4)); 3.87 (d, 3Jˆ10.9,
H
C(5)); 3.80, 3.69 (2d, 2Jˆ11.6, CH2 C(1)); 3.73 (d, 2Jˆ11.2, 1 H); 3.66 (d, 2Jˆ11.1, 1 H); 3.58
(dd, 2Jˆ11.2, 3Jˆ6.4, 1 H, CH2 C(3)); 3.52 (dd, 2Jˆ11.1, 3Jˆ5.6, 1 H, CH2 C(2)); 2.42 (br. m, 3Jˆ6.4,
H
C(3)); 2.11 (br. m, 3Jˆ5.6,
H
C(2)). 13C-NMR (100.6 MHz, CD3OD): 78.4 (s, C(1)); 72.5, 71.0
(2d, Jˆ147, 150, C(4), C(6)); 66.8 (t, Jˆ141, CH2 C(1)); 63.8 (d, Jˆ150, C(5)); 62.4, 59.6 (2t, Jˆ145, 149,
2 CH2); 45.6, 42.5 (2d, Jˆ127, 126, C(2), C(3)). CI-MS (NH3): 81(78), 91(100), 107(56), 123(43), 135(22),
149(17), 167(35), 185(13), 229(7), 285(3), 283(3). Anal. calc. for C9H17BrO6 (301.13): C 35.90, H 5.69;
found: C 35.96, H 5.73.
(1RS,2SR,3RS,4SR,5RS)-4-Acetoxy-5-bromo-3-hydroxy-6-oxocyclohexane-1,2,3-trimethyl Triacetate ((Æ)-
60). As described for (Æ)-51, from (Æ)-57 (25 mg, 0.053 mmol): 24 mg (99%) of (Æ)-60. Colorless oil. Rf

842
Helvetica Chimica Acta ± Vol. 82 (1999)
(AcOEt/PET 2 : 1) 0.35. IR (film): 2925, 1745, 1370, 1240, 1115, 1090, 1045, 910. 1H-NMR (250 MHz, CDCl3):
5.63 (d, 3Jˆ10.3, H C(4)); 4.90 (d, 3Jˆ10.3, H C(5)); 4.61 (dd, 2Jˆ11.8, 3Jˆ6.3, 1 H); 4.34 (dd, 2Jˆ11.8,
3Jˆ3.2, 1 H); 4.33, 4.15 (2d, 2Jˆ12.5, CH2 C(3)); 4.11 (dd, 2Jˆ11.8, 3Jˆ8.1, 1 H, CH2 C(1)); 4.08
3
(dd, 2Jˆ11.8, Jˆ1.3, 1 H, CH2 C(2)); 3.61 (ddd, 3Jˆ8.1, 6.5, 6.3, H C(1)); 3.19 (s, OH); 2.63 (ddd, 3Jˆ6.5,
3.2, 1.3, H C(2)); 2.21, 2.11, 2.06, 2.01 (4s, 4 Me). 13C-NMR (100.6 MHz, CDCl3): 195.7 (s, C(6)); 169.4, 169.7,
170.9, 170.7 (4s, CˆO); 75.2 (s, C(3)); 76.5 (d, Jˆ155, C(4)); 65.9, 60.2, 58.9 (3t, Jˆ149, 3 CH2); 57.0
(d, Jˆ148, C(5)); 43.9 (d, Jˆ129, C(1)); 42.7 (d, Jˆ133, C(2)); 20.8, 20.7, 20.5, 20.4 (4q, Jˆ130, 4 Me). CI-MS
(NH3): 84(100), 107(28), 135(33), 157(44), 215(46), 267(28), 311(14), 391(3). Anal. calc. for C17H23BrO10
(467.27): C 43.69, H 4.96; found: C 43.67, H 4.92.
(1RS,2RS,5SR,6SR)-4,5,6-Tris(acetoxymethyl)-2-azidocyclohex-3-en-1-yl 4-Nitrobenzoate ((Æ)-61). A
mixture of (Æ)-38 (262 mg, 0.741 mmol), anh. CH2Cl2 (0.7 ml), anh. pyridine (0.3 ml), and 4-nitrobenzoyl
chloride (206 mg, 1.11 mmol) was stirred under Ar at 208 for 12 h. It was then diluted with CH2Cl2 (500 ml) and
washed with H2O (100 ml). The org. phase was dried (MgSO4) and evaporated with toluene and the residue
purified by FC (silica gel; AcOEt/PET 1 : 2): 360 mg (100%) of (Æ)-61. Colorless, unstable oil that partially
crystallized in the freezer. Rf (AcOEt/PET 2 : 1) 0.54. IR (film): 3115, 2960, 2105, 1740, 1610, 1530, 1370, 1350,
1270, 1235, 1095, 1040, 875, 720, 665. 1H-NMR (400 MHz, CDCl3): 8.30, 8.17 (2d, 3Jˆ8.9, 4 arom. H); 5.84
(br. d, 3Jˆ4.0,
H
C(3)); 5.32 (dd, 3Jˆ4.0, 3.0,
H
C(1)); 4.70, 4.66 (2d, 2Jˆ13.9, CH2 C(4)); 4.36
(dd, 2Jˆ11.5, 3Jˆ6.5, 1 H); 4.33 (dd, 2Jˆ12.5, 3Jˆ6.4, 1 H); 4.30 (dd, 2Jˆ12.5, 3Jˆ6.5, 1 H, CH2 C(6));
4.24 (dd, 2Jˆ11.5, 3Jˆ6.6, 1 H, CH2 C(5)); 4.19 (br. t, 3Jˆ4.0, H C(2)); 2.93 (br. ddd, 3Jˆ6.6, 6.5, 6.0,
H
C(5)); 2.61 (dddd, 3Jˆ6.5, 6.4, 6.0, 3.0, H C(6)); 2.11, 2.06, 2.03 (3s, 3 Me). 13C-NMR (100.6 MHz,
CDCl3): 170.6, 170.5, 170.3 (3s, CˆO); 164.0 (s, CˆO); 150.8 (s); 138.7 (s); 134.5 (d, 3Jˆ7.8, C(4)); 130.8, 123.7
(2d, Jˆ169, 172, 2 arom. C); 121.5 (d, Jˆ157, C(3)); 73.0 (d, Jˆ155, C(1)); 65.1 (t, Jˆ146, CH2 C(4)); 64.0,
61.2 (2t, Jˆ148, 149, 2 CH2); 57.6 (d, Jˆ149, C(2)); 36.7 (d, Jˆ128, C(5)); 36.4 (d, Jˆ130, C(6)); 20.78, 20.75,
20.73 (3q, Jˆ130, 3 Me). CI-MS (NH3): 76(31), 104(57), 150(100), 189(9), 296(5), 342(1), 402(3), 462(4).
(1RS,2SR,3RS,4SR,5RS,6RS)- and (1RS,2RS,3SR,4RS,5SR,6RS)-4,5,6-Tris(acetoxymethyl)-2-azido-7-ox-
abicyclo[4.1.0]hept-3-yl 4-Nitrobenzoate ((Æ)-62 and (Æ)-63, resp.). A mixture of (Æ)-61 (112 mg, 0.228 mmol),
CH2Cl2 (1 ml), and mCPBA (95%, Fluka; 39.4 mg, 0.228 mmol) was stirred at 408 for 28 h. The soln. was then
diluted with CH2Cl2 (150 ml) and washed rapidly with a cooled aq. sat. Na2S2O3 soln. (30 ml) and with aq. sat.
NaHCO3 soln. (50 ml). The org. phase was dried (MgSO4) and evaporated. The residue containing two
epoxides (ꢀantiꢁ/ꢀsynꢁ/3.6 : 1) was purified by FC (Florisil; AcOEt/PET 1 : 2, 108): 52.4 mg (46%) of (Æ)-62,
23 mg (20%) of a mixture and 2 mg (2%) of minor isomer (Æ)-63.
Data of (Æ)-62: Colorless oil. Rf (AcOEt/PET 2 : 1) 0.54. UV (MeCN): 264 (9800), 257(10500),
202(8100). IR (film): 3115, 2965, 2110, 1740, 1610, 1530, 1435, 1370, 1350, 1320, 1270, 1240, 1100, 1040, 1015,
875, 720, 665. 1H-NMR (400 MHz, CDCl3): 8.34, 8.21 (2d, 2Jˆ9.0, 4 arom. H); 5.16 (dd, 3Jˆ4.9, 3.0, H C(3));
4.53 (dd, 2Jˆ11.3, 3Jˆ7.7, 1 H); 4.34 (dd, 2Jˆ11.3, 3Jˆ6.4, 1 H, CH2 C(4)); 4.35, 4.20 (2d, 2Jˆ12.0,
CH2 C(6)); 4.23 (dd, 2Jˆ11.5, 3Jˆ5.7, 1 H); 4.19 (dd, 2Jˆ11.5, 3Jˆ6.3, 1 H, CH2 C(5)); 4.20 (d, 3Jˆ4.9,
H
C(2)); 3.31 (s, H C(1)); 2.78 (ddd, 3Jˆ7.0, 6.3, 5.7, H C(5)); 2.52 (dddd, 3Jˆ7.7, 7.0, 6.4, 3.0, H C(4));
2.13, 2.11, 1.99 (3s, 3 Me). 13C-NMR (100.6 MHz, CDCl3): 170.5, 170.2, 164.0 (3s, CˆO); 150.9 (s, C NO2);
134.4 (s, arom. C); 130.9, 123.8 (2d, Jˆ169, 172, 2 arom. C); 72.5 (d, Jˆ151, C(3)); 64.7 (t, Jˆ150, CH2 C(6));
62.2, 60.9 (2t, Jˆ150, 152, 2 CH2); 59.4 (s, C(6)); 57.3 (d, Jˆ186, C(1)); 56.9 (d, Jˆ146, C(2)); 34.9, 34.6
(2d, Jˆ134, 132, C(4), C(5)); 20.9, 20.7, 20.6 (3q, Jˆ130, 3 Me). CI-MS (NH3): 76(40), 104(54), 150(100),
210(2), 299(2). Anal. calc. for C22H24N3O10 (506.44): C 50.77, H 4.65; found: C 50.62, H 4.54.
Data of (Æ)-63: White solid, Rf (AcOEt/PET 2 : 1) 0.50. 1H-NMR (400 MHz, CDCl3): 8.35, 8.22 (2d,
3Jˆ8.6, 4 arom. H); 5.23 (dd, 3Jˆ4.3, 3.6, H C(3)); 4.44, 4.16 (2d, 2Jˆ12.4, CH2 C(6)); 4.39 ± 4.37 (m, CH2);
4.28 (dd, 2Jˆ11.7, 3Jˆ6.8, 1 H); 4.22 (dd, 2Jˆ11.7, 3Jˆ5.6, 1 H, CH2); 3.97 (dd, 3Jˆ4.3, 3.1, H C(2)); 3.48
(d, 3Jˆ3.1, H C(1)); 2.84 (ddd, 3Jˆ6.8, 6.0, 5.6, H C(5)); 2.71 (m, 3Jˆ6.0, 3.6, H C(4)); 2.13, 2.09, 2.08
(3s, 3 Me). 13C-NMR (100.6 MHz, CDCl3): 170.5, 170.4, 170.1 (3s, CˆO); 163.8 (s, CˆO); 150.9 (s, C NO2);
134.1 (s, arom. C); 130.9, 123.9, 123.8 (3d, Jˆ169, 172, 172, 3 arom. C); 72.6 (d, Jˆ152, C(3)); 64.3 (t, Jˆ148,
CH2 C(6)); 62.3, 60.9 (2t, Jˆ143, 142, 2 CH2); 60.4 (s, C(6)); 58.9 (d, Jˆ142, C(2)); 56.7 (d, Jˆ181, C(1));
36.4, 35.4 (2d, Jˆ133, C(5), C(4)); 20.8, 20.7, 20.6 (3q, Jˆ130, 3 Me). CI-MS (NH3): 71(93), 104(82),
150(100), 220(6), 312(2). Anal. calc. for C22H24N3O11 (506.44): C 50.77, H 4.65; found: C 50.61, H 4.57.
(1RS,2RS,3SR,4RS,5SR,6RS)-5-Azido-4-hydroxy-7-oxabicyclo[4.1.0]heptane-1,2,3-trimethanol ((Æ)-64).
Gaseous NH3 was bubbled through a soln. of (Æ)-62 (88 mg, 0.179 mmol) in anh. MeOH (4 ml) cooled to 08.
The soln. was stirred at 208 for 20 h. MeOH was evaporated and the residue purified by FC (Florisil, CH2Cl2,
then AcOEt, then AcOEt/MeOH 8 : 1): 37.7 mg (84%) of (Æ)-64. Colorless oil. Rf (AcOEt/MeOH 8 : 1) 0.11.
IR (film): 3330, 2920, 2110, 1660, 1435, 1255, 1050, 665. 1H-NMR (400 MHz, CD3OD): 3.92 (dd, 2Jˆ11.2,

Helvetica Chimica Acta ± Vol. 82 (1999)
843
3Jˆ6.1, 1 H of CH2 C(2)); 3.86 ± 3.82 (4 H, 1 H of CH2 C(2), CH2 C(3), H C(5)); 3.73 (dd, 3Jˆ7.4, 3.6,
H
C(4)); 3.76, 3.53 (2d, 2Jˆ12.4, CH2 C(1)); 3.14 (s, H C(6)); 2.53 (td, 3Jˆ6.2, 6.1, H C(2)); 2.17
(dtd, 3Jˆ6.4, 6.2, 3.6, H C(3)). 13C-NMR (100.6 MHz, CD3OD): 72.8 (d, Jˆ145, C(4)); 64.2 (t, Jˆ143,
CH2 C(1)); 63.3 (s, C(1)); 61.8 (d, Jˆ145, C(6)); 60.8, 60.4 (2t, Jˆ143, 2 CH2); 58.7 (d, Jˆ179, C(5)); 42.1,
39.4 (2d, Jˆ128, 125, C(2), C(3)). CI-MS (NH3): 81(89), 95(100), 107(52), 122(68), 138(15), 167(3). Anal.
calc. for C9H15N3O5 (245.23): C 44.08, H 6.17, N 17.13; found: C 44.09, H 6.19, N 17.01.
(1RS,2RS,3SR,4RS,5RS)-5-Amino-1,4-dihydroxycyclohexane-1,2,3-trimethanol ((Æ)-65).
A mixture of
(Æ)-64 (9 mg, 0.036 mmol), MeOH (1 ml), and 20% Pd(OH)2 on charcoal (4 mg) was degassed and shaken
overnight under H2 at 208. The soln. was then filtered through a Celite pad and evaporated: 8 mg (98%) of (Æ)-
65. For further purification, the residue was dissolved in 1n HCl in MeOH/H2O 1 : 1 (0.1 ml) and loaded onto
‡
Dowex-50WX8 (H form). The resin was washed with H2O (10 ml) and MeOH (10 ml), then eluted with 5%
aq. NH3. Evaporation of the alkaline fractions: 7.3 mg (90%) of pure (Æ)-65. Colorless oil. IR (film): 3290,
2940, 2865, 1740, 1650, 1465, 1435, 1385, 1295, 1255, 1220, 1130, 1085, 1050, 1025, 835, 780, 675. 1H-NMR
(400 MHz, D2O): 3.83 (dd, 2Jˆ12.1, 3Jˆ3.5, 1 H); 3.79 (dd, 2Jˆ11.5, 3Jˆ5.4, 1 H); 3.78 (dd, 2Jˆ12.1, 3Jˆ6.0,
1 H, CH2 C(3)); 3.63 (dd, 2Jˆ11.5, 3Jˆ8.0, 1 H, CH2 C(2)); 3.57 (dd, 3Jˆ10.4, 5.4, H C(4)); 3.44, 3.37
(2d, 2Jˆ11.6, CH2 C(1)); 3.29 (ddd, 3Jˆ13.0, 10.4, 3.7, H C(5)); 2.34 (dtd, 3Jˆ6.0, 5.4, 3.5, H C(3)); 1.95
(dt, 3Jˆ8.0, 5.4, H C(2)); 1.84 (dd, 2Jˆ13.0, 3Jˆ3.7, Ha C(6)); 1.48 (t, 2Jˆ13.0, Hb C(6)). 13C-NMR
(100.6 MHz, D2O): 77.4 (s, C(1)); 75.4 (d, Jˆ147, C(4)); 69.2 (t, Jˆ142, CH2 C(1)); 61.4, 59.8 (2t, Jˆ142, 141,
2 CH2); 50.5 (d, Jˆ143, C(5)); 45.8, 44.9 (2d, Jˆ122, 131, C(2), C(3)); 41.8 (t, Jˆ128, C(6)). CI-MS (NH3):
83(24), 106(100), 120(36), 136(17), 154(50), 172(88), 186(3), 202(1), 222(5). Elemental analysis, see
(Æ)-66.
(1RS,2RS,3SR,4RS,5RS)-5-Acetamido-4-acetoxy-1-hydroxycyclohexane-1,2,3-trimethyl Triacetate ((Æ)-66).
A mixture of (Æ)-65 (11 mg, 0.05 mmol), anh. pyridine (50 ml) and Ac2O (50 ml) was stirred at 208 for 24 h.
Solvent evaporation and FC (silica gel; AcOEt): 17.4 mg (81%) of (Æ)-66. Colorless oil. Rf (AcOEt) 0.057. IR
(film): 3360, 2925, 1740, 1660, 1650, 1555, 1435, 1370, 1240, 1130, 1040, 905, 730. 1H-NMR (400 MHz, CDCl3):
3
3
5.69 (d, 3Jˆ8.1, NH); 4.83 (dd,3Jˆ11.4, 5.4, H C(4)); 4.53 (dd, 2Jˆ12.2, Jˆ4.4); 4.43 (dd, 2Jˆ12.2, Jˆ5.8,
CH2 C(3)); 4.40 (dddd, 3Jˆ11.7, 11.4, 8.1, 4.5, H C(5)); 4.36 (dd, 2Jˆ11.7, Jˆ6.7, 1 H); 4.29 (dd, 2Jˆ11.7,
3
3Jˆ6.4, 1 H, CH2 C(2)); 4.04, 3.97 (2d, 2Jˆ11.3, CH2 C(1)); 3.50 (s, OH C(1)); 2.64 (dddd, 3Jˆ5.8, 5.4, 5.0,
4.4, H C(3)); 2.23 (dd, 2Jˆ13.9, Jˆ4.5, Ha C(6)); 2.10, 2.09, 2.04, 2.02, 1.94 (5s, 16 H, Me, H C(2)); 1.43
3
(dd, 2Jˆ13.9, Jˆ11.7, Hb C(6)). 13C-NMR (100.6 MHz, CDCl3): 171.7, 170.6, 170.4, 170.1 (4s, CˆO); 74.5
3
(d, Jˆ154, C(4)); 71.9 (s, C(1)); 69.1 (t, Jˆ149, CH2 C(1)); 62.2, 61.6 (2t, Jˆ150, 149, 2 CH2); 45.4 (d, Jˆ148,
C(5)); 41.8, 39.6 (2d, Jˆ125, 132, C(2), C(3)); 40.9 (t, Jˆ127, C(6)); 23.4 (q, Jˆ128, 3 Me); 21.1, 21.0, 20.8
(3q, Jˆ130, 3 Me). CI-MS (NH3): 72(100), 191(41), 233(79), 298(45), 338(13), 372(18), 432(48). Anal.
calc. for C19H29NO10 (431.44): C 52.89, H 6.78; found: C 52.81, H 6.74.
(1RS,2RS,3SR,4RS,5SR,6RS)-5-Amino-4-hydroxy-7-oxabicyclo[4,1.0]heptane-1,2,3-trimethanol ((Æ)-67).
A suspension of 10% Pd/C (8 mg) in MeOH (1 ml) was shaken for 30 min under H2. After addition of (Æ)-
64 (8 mg, 0.033 mmol), the suspension was shaken for 5 min and then filtered over a Celite pad. The filtrate was
evaporated: 7 mg (98%) of (Æ)-67 (storage at 288). Colorless, instable oil. IR (film): 3345, 2895, 1730, 1645,
1460, 1570, 1415, 1245, 1035, 925. 1H-NMR (400 MHz, CD3OD): 3.91 (dd, 2Jˆ11.3, 3Jˆ6.0, 1 H); 3.82
(dd, 2Jˆ11.3, 3Jˆ6.7, CH2 C(2), 1 H); 3.81 (dd, 2Jˆ10.8, 3Jˆ7.0, 1 H); 3.77 (dd, 2Jˆ10.8, 3Jˆ6.0,
CH2 C(3)); 3.74, 3.47 (2d, 2Jˆ12.1, CH2 C(1)); 3.46 (dd, 3Jˆ7.1, 3.6, H C(4)); 3.09 (d, 3Jˆ7.1, H C(5));
2.98 (s, H C(6)); 2.52 (dt, 3Jˆ6.7, 6.0, H C(2)); 2.16 (dtd, 3Jˆ7.0, 6.0, 3.6, H C(3)). 13C-NMR (100.6 MHz,
CD3OD): 75.0 (d, Jˆ141, C(4)); 64.9 (t, Jˆ143, CH2 C(1)); 63.2 (s, C(1)); 61.4 (d, Jˆ176, C(6)); 61.0, 60.7
(2t, Jˆ143, 147, 2 CH2); 51.7 (d, Jˆ139, C(5)); 41.7, 39.7 (2d, Jˆ127, 126, C(2), C(3)). CI-MS (NH3): 70(24),
77(55), 91(100), 107(72), 121(45), 135(21), 147(10), 188(10), 201(3), 220(3).
X-Ray Crystal-Structure Determination of (1RS,2RS,5SR,8SR)-2-Acetoxy-6-oxabicyclo[3.2.1]oct-3-ene-
5,8-dimethyl Diacetate ((Æ)-33). Crystal data and measurement conditions are given in the Table. A colorless,
irregular, plate-shaped chip of a larger cystal was mounted. On a Stoe IPDS (oscillation 18, sample-IP distance
70 mm, graphite-monochromatized l(MoKa) 0.71073 Š), 200 images were recorded for 6 min each at
T 293(2)K. All crystals studied were pseudo-merohedric twins, and the interpretation of the images was carried
out with two orientation matrices. Neither decay nor absorption corrections were performed. Solution by direct
methods (SHELXTL [46]), refinement with the full matrix and weights [s2(F02 )] 1. H-Atoms were refined with
IDPs and coordinates, except methyl H-atoms which were made to ride on their C-atoms. Crystallographic data
for (Æ)-33 have been deposited at the Cambridge Crystallographic Data Centre as Supplementary Publication
No. CCDC-117983.

844
Helvetica Chimica Acta ± Vol. 82 (1999)
Table. Crystal Data and Structure Refinement of (Æ)-33
Empirical formula
Formula weight
Crystal system
Space group
C15H20O7 q Range [8]
2.53 to 24.99
312.31
Index ranges
9 ꢀ h ꢀ 9, 10 ꢀ k ꢀ 11, 14 ꢀ l ꢀ 14
triclinic
P1
Reflect. collected
Independent reflect.
5774
Å
2639 (R(int) ˆ 0.0234)
Unit cell dimensions a [Š] 8.427(2) Completeness to 2q ˆ 24.998 91.9%
b [Š] 9.256(2) Refinement method
c [Š] 11.726(2) Data/restraints/parameters
a [8] 68.21(3) Goodness-of-fit on F2
b [8] 81.98(3) Final R indices (I > 2s(I))
g [8] 73.10(3) R indices (all data)
Full-matrix least-squares on F2
2636/0/243
4.236
R1 ˆ 0.0539, wR2 ˆ 0.0848
R1 ˆ 0.0688, wR2 ˆ 0.0853
0.213 and 0.163
Volume [Š3]
812.1(3) Largest difference peak
3
and hole [e ´ A
]
Z
2
3
Density calc. [Mgm
Absorption coeff. [mm
F(000)
]
1.277
0.102
332
1
]
Crystal size [mm]
0.5 Â 0.2 Â 0.1
Fig. 1. ORTEP Representation of (Æ)-33 showing heavy atoms with 50% probability and atom numbering
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Received February 24, 1999