Stereoselective synthesis of 8-oxabicyclo[3.2.1]octane-2,3,4,6,7-pentols and total asymmetric synthesis of 2,6-anhydrohepturonic acid derivatives and of β-C-manno-pyranosides suitable for the construction of (1 → 3)-C,C-linked trisaccharides

Helvetica Chimica Acta ± Vol. 84 (2001)

1363

Stereoselective Synthesis of 8-Oxabicyclo[3.2.1]octane-2,3,4,6,7-pentols

and Total Asymmetric Synthesis of 2,6-Anhydrohepturonic Acid

Derivatives and of b-C-manno-Pyranosides Suitable for the Construction

of (1 ! 3)-C,C-Linked Trisaccharides

by Patrick Gerber¹) and Pierre Vogel*

Â

Section de Chimie, Universite de Lausanne, BCH, CH-1015 Lausanne-Dorigny

Dedicated to Prof. Edgar Heilbronner on the occasion of his 80th birthday

Enantiomerically pure ()-(1S,4S,5S,6S)-6-endo-(benzyloxy)-5-exo-{[(tert-butyl)dimethylsilyl]oxy}-7-oxa-

bicyclo[2.2.1]heptan-2-one (()-5) and its enantiomer ( )-5, obtained readily from the Diels-Alder addition of

furan to 1-cyanovinyl acetate, can be converted with high stereoselectivity into 8-oxabicyclo[3.2.1]octane-2,3,4,6,7-

pentol derivatives (see 23 ± 28 in Scheme 2). A precursor of them, (1R,2S,4R,5S,6S,7R,8R)-7-endo-(benzyloxy)-

8-exo-hydroxy-3,9-dioxatricyclo[4.2.1.0^2,4]non-5-endo-yl benzoate (( )-19), is transformed into (1R,2R,5S,

6S,7R,8S)-6-exo,8-endo-bis(acetyloxy)-2-endo-(benzyloxy)-4-oxo-3,9-dioxabicyclo[3.3.1]non-7-endo-yl benzoate

(( )-43) (see Scheme 5). The latter is the precursor of several protected 2,6-anhydrohepturonic acid derivatives

such as the diethyl dithioacetal ( )-57 of methyl 3,5-di-O-acetyl-2,6-anhydro-4-O-benzoyl-d-glycero-d-galacto-

hepturonate (see Schemes 7 and 8). Hydrolysis of ( )-57 provides methyl 3,5-di-O-acetyl-2,6-anhydro-4-O-

benzoyl-d-glycero-d-galacto-hepturonate 48 that undergoes highly diastereoselective Nozaki-Oshima conden-

sation with the aluminium enolate resulting from the conjugate addition of Me₂AlSPh to (1S,5S,6S,7S)-7-endo-

(benzyloxy)-6-exo-{[(tert-butyl)dimethylsilyl]oxy}-8-oxabicyclo[3.2.1]oct-3-en-2-one (( )-13) derived from

()-5 (Scheme 12). This generates a b-C-mannopyranoside, i.e., methyl (7S)-3,5-di-O-acetyl-2,6-anhydro-4-O-

benzoyl-7-C-[(1R,2S,3R,4S,5R,6S,7R)-6-endo-(benzyloxy)-7-exo-{[(tert-butyl)dimethylsilyl]oxy}-4-endo-hydroxy-2-

exo-(phenylthio)-8-oxabicyclo[3.2.1]oct-3-endo-yl]-l-glycero-d-manno-heptonate (( )-70; see Scheme 12),

that is converted into the diethyl dithioacetal ( )-75 of methyl 3-O-acetyl-2,6-anhydro-4,5-dideoxy-4-C-

{[methyl (7S)-3,5,7-tri-O-acetyl-2,6-anhydro-4-O-benzoyl-l-glycero-d-manno-heptonate]-7-C-yl}-5-C-(phenyl-

sulfonyl)-l-glycero-d-galacto-hepturonate (76; see Scheme 13). Repeating the Nozaki-Oshima condensation to

enone ( )-13 and the aldehyde resulting from hydrolysis of ( )-75, a (1 ! 3)-C,C-linked trisaccharide precursor

(

)-77 is obtained.

Introduction. ± Carbohydrate mimics are potentially useful molecular tools for

biology [2] and may become leads for drug discovery [3]. In particular, C-linked

disaccharides and oligosaccharides offer the advantage of being resistant to acidic and

enzymatic hydrolysis [4]. They are potential inhibitors of glycosidases and glycosyl-

transferases [5][6]. They represent non-hydrolyzable epitopes [7]. Since the first

È

synthesis of b-d-Glcp-CH₂(1 ! 6)-d-Glcp by Rouzaud and Sinay [8], several ap-

proaches to C-disaccharides and C-linked oligosaccharides have been reported

[4][9][10]. Although several proposals have appeared for the preparation of b-C-

manno-hexopyranosides [11], only three examples of C-disaccharides involving b-C-

1

)

Taken from the Ph.D. Thesis of Patrick Gerber [1]. Current address: Serono Pharmaceutical Research

Institute, Plan-les-Ouates, Geneva, Switzerland.

1364

Helvetica Chimica Acta ± Vol. 84 (2001)

mannosides are known (b-d-Manp-CH₂(1 ! 1)-b-d-Glc [11], b-d-Manp-CH₂(1 ! 4)-d-

Glc-OMe [12], and b-d-Manp-CH₂(1 ! 6)-d-Glc [9a]).

In 1993, we demonstrated [13] that enantiomerically pure 2-cyano-7-oxabicy-

clo[2.2.1]hept-5-en-2-yl acetate, a ꢀnaked sugar of the first generationꢁ [14], can be

converted into enantiomerically pure 8-oxabicyclo[3.2.1]oct-6-en-2-one (both enantio-

meric forms) and that the latter can be converted with high stereoselectivity into b-C-

pyranosides either of gulo-hexuronic acid or of altro-hexodialdose. In a preliminary

communication [1], we have announced that ( )-7-oxabicyclo[2.2.1]hept-5-en-2-one

(( )-1), another ꢀnaked sugar of the first generationꢁ [14]) can be converted into ( )-6-

exo-{[(tert-butyl)dimethylsilyl]oxy}-7-endo-(benzyloxy)-8-oxabicyclo[3.2.1]oct-3-en-2-

one (( )-13) and methyl 3,5-di-O-acetyl-2,6-anhydro-4-O-benzoyl-d-glycero-d-galac-

to-hepturonate, two new compounds that were condensed under Oshima-Nozaki

conditions [15] to give a single aldol. This aldol could be transformed into a b-d-

ManAp-CH(OAc)(1 ! 3)-a-l-GulAp-CH(SEt)₂derivative. We describe here the

details of this chemistry that realizes a new approach to the total synthesis of b-C-

manno-pyranosides. We show also how these C-disaccharides can be used in the

construction of (1 ! 3)-C,C-trisaccharides.

Stereoselective Synthesis of 8-Oxabicyclo[3.2.1]octane-2,3,4,6,7-pentol Deriva-

tives. ± We had shown earlier that 7-oxabicyclo[2.2.1]hept-5-en-2-one (()- or ( )-1)

can be converted in 3 steps into the 5-exo,6-endo-dihydroxy-7-oxabicyclo[2.2.1]heptan-

2-one derivative 4 in 65% overall yield [16]. A procedure has now been developed to

obtain (Æ)-4 from (Æ)-1 without isolation and purification of intermediates 2 and 3.

Silylation of (Æ)-4 with (t-Bu)Me₂SiCl and 1H-imidazole in DMF provided (Æ)-5 in

96% yield. Although both enantiomeric forms of 5 are available with the same ease

starting from the ꢀnaked sugars of the first generationꢁ ()- and ( )-1 [14][17], we

applied the resolution method of Johnson and Zeller [18] to ketone (Æ)-5. Thus, after

treatment with the reagent ()-6, the diastereoisomeric sulfoximides ()-7 and ( )-8

were separated in 42 and 44% yield, respectively, with diastereoisomer excesses better

than 99% (¹H-NMR, ¹³C-satellites). Their thermolysis (2208) delivered enantiomeri-

cally pure ketones ()- and ( )-5, respectively, both in 88% yield (Scheme 1).

Ring enlargement of (Æ)-5 was accomplished applying the method of Saegusa and

coworkers [19]. Enol ethers (Æ)-9 and (Æ)-10 were prepared (Scheme 2) and submitted

to the Simmons-Smith [20] cyclopropanation under the conditions recommended by

Denmark and coworkers [21]. This led to the unstable products (Æ)-11 and (Æ)-12,

respectively. Oxidation of (Æ)-11 with FeCl₃gave enone (Æ)-13 in 15 ± 40% yield

(based on ketone (Æ)-5). Better reproductibility was observed with the oxidation of

(Æ)-12 that furnished (Æ)-13 in 57% yield. Similarly, ( )-13 was obtained from ()-5

(see Exper. Part).

Reduction of enone (Æ)-13 under Lucheꢁs conditions [22] gave endo-alcohol (Æ)-14

that was esterified into (Æ)-15 with benzoyl chloride in pyridine (Scheme 2).

Epoxidation of (Æ)-15 with 3-chloroperbenzoic acid (mCPBA) was a slow reaction

(11 days at 258), affording epoxy derivative (Æ)-16 in mediocre yield (50%). An

alternative route to (Æ)-16 from (Æ)-13 (66% overall yield) was opened by epoxidizing

enone (Æ)-13 with tert-butyl hydroperoxide in the presence of DBU (1,8-diazabicy-

clo[5.4.0]undec-7-ene) [23]. This provided epoxy ketone (Æ)-17 in 99% yield that was

Helvetica Chimica Acta ± Vol. 84 (2001)

1365

Scheme 1²)

O

RO

O

BnOTMs

TMSOTf

mCPBA

HSO₃F

BnOH

OBn

CHCl₃

CH₂Cl₂

O

OBn

3

2

(+)-4 R = H

(+)-5 R = TBS

(-)-1

O

TBSO

Ph

BuLi, THF

-25^o

(±)-5

MeN

S

Me

+

S

TBSO

Ph

NMe

S

Ph

OH

O

NMe

OBn

OH

O

OBn

(+)-6

(+)-7

(-)-8

220^o0.2 Torr

(+)-5

(-)-5

reduced with NaBH₄stereoselectively into endo-alcohol (Æ)-18 in 91% yield.

Benzoylation of (Æ)-18 furnished (Æ)-16. Selective deprotection of the silyl ether

moiety of the latter with tetrabutylammonium fluoride provided alcohol (Æ)-19.

Analogously, ( )-19 was prepared²f)rom ( )-13 via ()-17, ( )-18, and ( )-16).

The structure of compounds 9 ± 19 were given by their ¹H- and ¹³C-NMR spectra and confirmed by

their 2D-NOESY ¹H-NMR data. In particular for 19, a vicinal coupling constant ³J(5,6) 5.1 Hz confirmed the

endo relative configuration of the benzoate. The smaller vicinal coupling constants ³J(1,2) 1.3 Hz and

³J(4,5) < 0.5 Hz demonstrated the exo relative configuration of the epoxide moiety. This was confirmed by the

observation of an NOE between signals at d(H) 4.42 (br. d, ³J 8.5 Hz; coupling disappeared on addition of

D₂O to the CDCl₃solution) and 3.18 (br. d, ³J 3.9 Hz) assigned to H C(8) and H C(2) of 19.

With the hope that benzyl enol ethers of type 29 ± 31 would be intermediates for the

preparation of 2,6-anhydrohepturonic acid derivatives 32 (Scheme 2) via oxidative

cleavage of their alkene moieties, we converted alcohol 19 into the corresponding

mesylate 20, tosylate 21, and nosylate 22 applying standard procedures. Attempts to

induce a syn elimination from these sulfonates under basic conditions (DBN (1,5-

diazabicyclo[4.3.0]non-5-ene), THF; DBN, MeCN, 708, 10 days; CsF, DMF, 1408, 3

days; Al₂O₃, CH₂Cl₂, 208; NaI, HMPA (hexamethylphosphoric triamide), 1008, 15 h)

led only to decomposition products; no trace of enol ether 29 could be seen by

¹H-NMR of the crude reaction mixtures. Since the epoxide moiety of 20 ± 22

contributes probably to the instability of these sulfonates and of 29, we converted

20 ± 22 into the corresponding diols 23 ± 25 by dissolution in CF₃COOH/CH₂Cl₂at

room temperature. This acidic treatment induced smooth heterolysis of the epoxide

2

)

The following abbreviations are used: BnPhCH₂, BzPhCO, TMS Me₃Si, TBS t-BuMe₂Si, TfO

CF₃SO₃, mCPBA 3-ClC₆H₄CO₃H, LDA Li(i-Pr)₂N, DMAP N,N-dimethylpyridin-4-amine, and

pyr pyridine. In the case of racemates, only one enantiomer is shown; enantiomers are characterized

by the sign of optical rotation preceding their key numbers.

1366

Helvetica Chimica Acta ± Vol. 84 (2001)

Scheme 2²)

O

TBSO

FeCl₃, pyr.

DMF, 60^o

1) LDA, THF

-78^o

ICH₂Cl, Et₂Zn

(+)-5

CH₂Cl₂

-20 to 20^o

2) RCl

-78 to 20^o

OR

O

OR

OBn

9 R = Me₃Si

10 R = Et₃Si

11 R = Me₃Si

12 R = Et₃Si

(-)-13

t-BuO₂H DBU

O

H

O

TBSO

NaBH₄

MeOH

0^o

NaBH₄

mCPBA

CH₂Cl₂

20^o

13

CeCl₃6 H₂O

MeOH, 0^o

H

O

OR

OBn

14 R = H

15 R = Bz

(-)-16 R = Bz

(-)-18 R = H

(+)-17

BzCl, pyr.

O ³

O

OH

OAc

Ac₂O

pyr.

2

1

'RO

2

3

Bu₄NF

CF₃COOH

CH₂Cl₂, 20^o

8

4

7

H

(-)-16

4

7

DMAP

20^o

H

5

6

5

OBz

AcO

OR

OH

OBn

23 R' = MeSO₂(80%)

24 R' = Ts (78%)

25 R' = p-NO₂C₆H₄SO₂(72%) 28 R' = p-NO₂C₆H₄SO₂(95%)

26 R' = MeSO₂(87%)

27 R' = Ts (85%)

(-)-19 R = Bz, H, R' = H

R'Cl, Et₃N

CH₂Cl₂

20^oC

20 R = Bz, R' = MeSO₂(79%)

21 R = Bz, R' = Ts (89%)

22 R = Bz, R' = p-NO₂C₆H₄SO₂(77%)

base

O

OH

OAc

H

OBz

AcO

BnO

OR

BnO

OH

30

31

29

O

H

?

O

OBz

O

OR

OBn

32

moiety with participation of the 5-endo-(benzoyloxy) group. Intermediate cations of

type 33 are expected to be formed in these reactions (Scheme 3). They react with the

nucleophile (CF₃COOH) giving the corresponding trifluoroacetates 34 that are rapidly

hydrolyzed on aqueous workup giving orthoester intermediates 35. The latter are

transformed preferentially into 23 ± 25 rather than into the isomeric products of type 36,

for thermodynamic reasons. Indeed, a 2-endo-benzoate moiety in 36 would suffer from

gauche interactions with the 7-endo-(benzyloxy) group, a repulsive steric interaction

that is more severe than that of the 4-endo-hydroxy group of 23 ± 25. Products 23 ± 28

are the first representatives of 8-oxabicyclo[3.2.1]octane-2,3,4,6,7-pentol derivatives

ever reported.

Helvetica Chimica Acta ± Vol. 84 (2001)

1367

Scheme 3

O

OH

'RO

H

CF₃COO^-

H

O

H

O

H

CF₃COOH

OH

OBz

O

OBn

X

Ph

33

34 X = CF₃COO

35 X = OH

36

23 - 25

All our attempts to induce elimination of sulfonic acids from 23 ± 25 to generate the

desired benzyl enol ether derivative 30 failed. We thus protected diols 23 ± 25 as

diacetates applying standard conditions. This provided products 26 ± 28 in good yield.

None of them furnished the corresponding enol ether derivative 31 upon heating with

various bases (see above, and t-BuOK/THF). We were thus forced to explore another

route to convert 19 into the desired ꢀb-C-mannopyranosylformaldehydeꢁ derivatives of

type 32.

Synthesis of 2,6-Anhydro-d-glycero-d-galacto-hepturonic Acid Derivatives. ± For

3-substituted 7-oxabicyclo[2.2.1]heptan-2-ones 37, we had shown [24] that their Baeyer-

Villiger oxidation gives the corresponding urono-6,1-lactones 38 due to preferred C(1)

migration. This was not the case anymore for derivatives with 3-X substituents being a

better releasing group than the ethereal 7-oxa bridge. Indeed when X MeO or (t-

Bu)Me₂SiO, the Bayer-Villiger oxidation led to the corresponding 3,8-dioxabicy-

clo[3.2.1]octan-2-ones 39 due to preferred C(3) migration (Scheme 4). Ogawa and

coworkers have reported that cyclohexanones a-substituted with an acyloxy group and

a'-substituted with a benzyloxy group undergo the Baeyer-Villiger oxidation with

preferred migration of the (benzyloxy)alkyl group [25].

Scheme 4

O

A

mCPBA

NaHCO₃

CH₂Cl₂

mCPBA

NaHCO₃

CH₂Cl₂

O

X

O

X

B

O

38 X = H, alkyl, RCOO, R'SO₃

37

39 X = MeO, R₃SiO

We thus oxidized alcohol (Æ)-19 into ketone (Æ)-40 (90%) with the Dess-Martin

periodinane [26] (Scheme 5). Oxidation of (Æ)-19 with pyridinium chlorochromate

proceeded with lower yield (27%). Treatment of (Æ)-40 with CF₃COOH in CH₂Cl₂at

208 led to diol (Æ)-41 in 98% yield. Esterification of (Æ)-41 with Ac₂O/pyridine and

DMAP (N,N-dimethylpyridin-4-amine) provided (Æ)-42 (95%). Conversion of alcohol

(Æ)-19 into (Æ)-42 could be done without isolation and purification of (Æ)-40 and (Æ)-

41 in 79% overall yield (Scheme 5). Subsequent Baeyer-Villiger oxidation of ketone

(Æ)-42 with mCPBA (CH₂Cl₂, NaHCO₃, 208) then afforded a single lactone (Æ)-43

1368

Helvetica Chimica Acta ± Vol. 84 (2001)

Scheme 5²)

O

OAc

O

OR

O³

5

mCPBA

NaHCO₃

CH₂Cl₂

20^o

2

1

O

4

6

8

3

CF₃COOH

CH₂Cl₂

20^o

H

Dess-Martin

periodinane

7

³O

O

OBz

(-)-19

4

H

7

6

5

H

OBz

7

6

5

4

H

2

8

1

OBz

OR

OBn

OAc

BnO

H

(83%)

(-)-40

(-)-41 R = H

(-)-43

Ac₂O, pyr.

DMAP

(+)-42 R = Ac (72% from (-)-19)

OAc

2

1

O

8

mCPBA

3

O

OBz

42

7

H

4

5

6

OAc

BnO

H

44

arising from the favored (benzyloxy)alkyl-group migration. The regioisomeric lactone

(Æ)-44 that arises from the migration of the s(C(1) C(8)) bond of (Æ)-40 was not

observed. Similarly, the enantiomer ( )-19 afforded ( )-43 via ( )-40, ( )-41, and ()-42.

The ¹H-NMR spectrum of (Æ)-43 displayed a d at d(H) 4.63 (³J(1,2) 4.8 Hz) assigned to the acetal proton

H

C(2). This assignment was confirmed by the 2D CH-COR NMR spectrum that correlated the signal at d(C)

100.7, typical of the acetal center C(2), with the signal at d(H) 4.63 (H C(2)). A larger chemical shift (d(H)

5.3 ± 5.7) would have been expected for the bridgehead proton H C(1) of uronolactone 44 [24]. Moreover, the

¹H-NMR spectrum of (Æ)-43 showed ³J(1,8) 5.9, ³J(8,7) 3.7, ³J(7,6) 3.3, and ³J(6,5) 1.8 Hz that are

consistent with pairs of vicinal protons occupying axial/equatorial or equatorial/equatorial positions of an

averaged chair conformation for the tetrahydro-2H-pyran ring O(9) C(1) C(8) C(7) C(6) C(5)).

Acetals have been used as precursors for oxyalkyl-cation intermediates that can

react with enoxysilanes [27][28]. The treatment of (Æ)-43 with 1-phenyl-1-[(trime-

thylsilyl)oxy]ethene (trimethylsilyl enol ether of acetophenone) in the presence of

trimethylsilyl triflate (MeNO₂, 208, 17 h), followed by reaction with MeOH (208, 17 h)

led to a 1:1 mixture of diastereoisomeric b-(benzyloxy) ketones (Æ)-45a and (Æ)-45b

(45a,b) that could not be separated by column chromatography (Scheme 6). The

reaction of (Æ)-43 with Me₃SiOTf and allyltrimethylsilane (MeCN, 08, 1 h) followed by

quenching with MeOH gave a 1:4.3 mixture of (Æ)-46a and (Æ)-46b (46a,b) that

could be separated by column chromatography (overall yield 76%). The reaction of

(Æ)-43 with Me₃SiOTf and trimethylsilyl cyanide, followed by quenching with MeOH

gave a mixture 17a,b from which (Æ)-47a and (Æ)-47b could be isolated in 20 and 40%

yield, respectively. The relative configuration of the newly created stereogenic centers

of 45a,b ± 47a,b was not established.

Since the C C forming reactions from acetal (Æ)-43 were little diastereoselective

(Scheme 6), we decided to transform (Æ)-43 into the corresponding 2,6-anhydrohep-

turonic acid esters such as (Æ)-48. Attempts to generate mixtures of cyanohydrins by

hydrogenolysis of 47a,b, cyanohydrines that should eliminate HCN to give (Æ)-48 by

treatment with formaline, were not met with success. We thus chose to transform (Æ)-43

into the corresponding uronic acid esters with the aldehyde protected as an acetal or a

Helvetica Chimica Acta ± Vol. 84 (2001)

Scheme 6²)

1369

⁷COOMe

¹COOMe

OBn

H

1

2

6

CHO

O

7

1) Me₃SiOTf

O

R

(±)-43

OBz OAc

2

5

3

6

Me₃SiR, solvent

2) MeOH, 20^o

O

AcO

3

4

5

4

45a,b R = Ph

CH₂(63%)^a)

46a,b R = CH₂=CH⁸-CH₂(76%)^a)

47a,b R = CN (60%)

(60%)^a)

(±)-48

10

9

^a) The numbering in the formula refers to 46a,b and 47a,b.

thioacetal. Good results were obtained with the following experiments. Treatment of

(Æ)-43 with BnOSiMe₃and Me₃SiOTf in CHCl₃at 108 for 30 min, followed by

quenching with MeOH ( 10 to 208, 24 h) furnished the racemic methyl uronate

dibenzyl acetal 51 in 82% yield (Scheme 7). The process implies probably the cationic

intermediate 49 resulting from the Lewis acid-promoted acetal heterolysis, followed by

reaction with Me₃SiOBn that gives a second intermediate 50, which is expected to react

with MeOH giving 51. With PhSSiMe₃as nucleophile instead of BnOSiMe₃, a 1.7:1

mixture of two monothioacetals 52 and 53 was obtained in 66% yield from (Æ)-43. In

this case, the hypothetical intermediate 49 reacts with PhSSiMe₃giving an other

intermediate 54, the reaction of which with MeOH gives rise to 52/53 (Scheme 7).

Attempts to liberate the carbaldehyde group from dibenzyl acetal 51 (hydrogenolysis,

acidic hydrolysis) or from the O-benzyl S-phenyl monothioacetals 52/53 (hydro-

genolysis, treatment with Hg(OAc)₂/MeCN, acidic hydrolysis) gave the desired product

(Æ)-48 in low yield as decomposition could not be aboided.

We thus decided to prepare the corresponding racemic dithioacetals 55 ± 57

(Scheme 8). Treatment of (Æ)-43 with an excess of thiophenol in the presence of triflic

acid in anh. CH₂Cl₂(208, 1 h), followed by quenching with benzyl alcohol (208, 18 h)

provided the racemic benzyl uronate diphenyldithioacetal 55 in 60% yield. Using EtSH

instead of PhSH led to 56 in 46% yield. The same procedure using EtSH/CF₃SO₃H/

CH₂Cl₂followed by quenching with MeOH provided (Æ)-57 in 74% yield. The

structures of 55 ± 57 were deduced from their spectral data (see Exper. Part). For

3

instance, in the case of 55, J(2,3) 1.1, J(3,4) 3.4, J(4,5) 10.2, J(5,6) 10.1 Hz

were measured in its ¹H-NMR spectrum, establishing the b-C-mannopyranosyl

structure [29]. Treatment of dithioacetal (Æ)-57 with Hg(ClO₄)2 ´ x H₂O (2.2 equiv.,

x 3.4) and then with Ag₂CO₃in MeCN gave rise to the desired aldehyde (Æ)-48 in

96% yield. Similarly, ( )-43 yielded optically active 48 via ( )-57. The benzyl uronate

analog 58 was obtained by treatment of racemic 56 with CdCO₃and HgCl₂in acetone

(Scheme 7). Aldehydes 48 and 58 were decomposed during our attempts to purify

them, and were thus used as crude products in the condensations described below. They

represent the first examples of 2,6-anhydrohepturonic acid derivatives, and they can be

obtained in both enantiomerically pure forms starting from ()-5 and ( )-5 (see

above).

Nozaki-Oshima Condensations with 8-Oxabicyclo[3.2.1]oct-3-en-2-ones. ± The

addition of Me₂AlSPh to enone (Æ)-13 (Scheme 2) (anh. THF, 788) generated the

1370

Helvetica Chimica Acta ± Vol. 84 (2001)

Scheme 7²)

Scheme 8

7

COOR'

1

1) RSH, CF₃SO₃H

CH₂Cl₂, 20^o

2) R'OH, 20^o

6

CH(SR)

O

55 R = Ph, R' = Bn (60%)

56 R = Et, R' = Bn (46%)

(±)-57 R = Et, R' = Me (68%)

(±)-43

OBz OAc

2

5

AcO

4

3

Scheme 5

Scheme 2

(+)-5

(-)-19

(-)-43

(-)-57

opt.active 48 (not isolated)

enolate 59 that was trapped with propanal ( 788, 12 h) giving a single racemic b-

hydroxy ketone 60 (Scheme 9). The latter was not isolated but reduced directly under

Lucheꢁs conditions (NaBH₄, CeCl₃´ 6 H₂O, MeOH) [22] giving rise to a single racemic

diol 61 isolated in 63% yield based on (Æ)-13. Out of sixteen possible diastereoisomers

that can be formed by this reaction cascade starting from (Æ)-13, only 61 was formed.

This result can be interpreted in terms of steric factors. The exo face of the bicyclic

enone (Æ)-13 is more readily available for the conjugate addition than its endo face.

With the phenylthio substituent of enolate 59 occupying the exo face, the endo face

becomes preferred for the crossaldol reaction with propanal giving rise to b-hydroxy

ketone 60. The relative (1RS,1'RS)-configuration of the reduced b-hydroxy ketone, i.e.,

Helvetica Chimica Acta ± Vol. 84 (2001)

1371

of 61, arises from a closed transition structure [31] shown with 59' (Scheme 9). Finally,

the diastereoselective reduction of the b-hydroxy ketone 60 is exo-face selective

because of the 3-endo-alkyl substituent. The structure of 61 was established by its NMR

data and by those of its acetonide 62, obtained from 61 in 95% yield on treatment with

Me₂C(OMe)₂/acetone and a catalytic amount of TsOH.

Scheme 9²)

The coupling constants measured in the ¹H-NMR spectrum of 61 are consistent with an averaged boat

3

conformation for the six-membered ring C(1) C(2) C(3) C(4) C(5) O(8); typical J(1,2) 7.6, J(2,3)

4.5, ³J(3ax,4ax) 9.9, and ³J(4,5) < 0.5 Hz were found. For acetonide 62, ³J(1,2) 6.7,³J(2,7) 8.2, ³J(7,8) 3.3,

3

and J(8,9) < 0.5 Hz suggested a deformed boat conformation for its tetrahydro-2H-pyrane ring (flattening of

the boat of 61 toward a sofa). The relatively large ³J(6,7) of 10.0 Hz demonstrated the trans-relationship

between these two protons. The ¹³C-NMR spectrum of 62 showed two similar chemical shifts (d(C) 25.4 and

27.7) for the two Me groups of the acetonide, thus suggesting a boat or near-boat conformation of the 1,3-

dioxane moiety C(2) C(7) C(6) O(6) C(4) O(3) [32]. These assignments were confirmed by the 2D ¹H-

NOESY data of 62 that showed NOEs between the proton signals indicated in Scheme 9. Most significant was

the large NOE cross-peak between d(H) 4.01 and 4.18 assigned to H C(10) and H C(6), respectively. The

signal at d(H) 3.19 assigned to H C(8) also witnessed strong NOEs with d(H) 4.01 and 4.18.

The addition of Me₂AlSeMe to enone (Æ)-13 (THF, 788) followed by the addition

of propanal (THF, 788) gave a single b-hydroxy ketone 63 (Scheme 10) that was

oxidized in situ with 3-chloroperbenzoic acid ( 78 to 208). This provided the stable

enone 64 isolated in 79% yield (from (Æ)-13). The relative configuration at the

exocyclic OH-substituted C(1') of 64 was not established unambiguously but is

suggested to be (1RS,1'RS) in analogy to 61 and 62.

1372

Helvetica Chimica Acta ± Vol. 84 (2001)

Scheme 10²)

O

SeMe

H

1) Me₂AlSeMe

THF, -78^o, 30 min

2) Propanal

TBSO

mCPBA

-78^oto -20^o

(79% based

on 13)

(±)-13

-78^o, 12 h

H

O

OH

O

OH

OBn

63

64

Enantioselective Nozaki-Oshima Condensation. ± The successive addition of

Me₂AlSPh to racemic (Æ)-13 (THF, 788, 1 h), then of enantiomerically pure aldehyde

( )-65 derived readily from d-galactose [33] (THF, 788, 16 h) led to a mixture from

which unreacted enone 13 was recovered and product ()-66 isolated in 17% yield

(Scheme 11). No other diastereoisomeric condensation product could be isolated by

column chromatography. An analogous experiment using Me₂AlSeMe instead of

Me₂AlSPh, followed by oxidative elimination (mCPBA), led to ()-66 isolated in 27%

as single product. The unreacted enone 13 was optically enriched and corresponded to

( )-13 with ca. 30% ee for the latter experiment (comparison of [a]²_D⁵). These

observations suggest a high enantioselectivity for the cross-aldol reaction of aldehyde

( )-65 with the bicyclic enolates 59 and 69 derived from (Æ)-13 (Scheme 11). Our

results can be interpreted in terms of the formation of enolates (1R)-59 (or (1R)-69)

and (1S)-59 (or (1S)-69) with selective addition of (1R)-59 (or (1R)-69) that leads to

enone ()-66. The unreacted (1S)-59 is converted probably into ketone 67 that

Scheme 11²)

O

X

OAlMe₂

TBSO

Me₂AlX

THF

TBSO

(±)-13

+

X

OAlMe₂

OBn

O

OBn

(1R)-59 X = PhS

(1R)-69 X = MeSe

(1S)-59 X = PhS

(1S)-69 X = MeSe

67 X = PhS

68 X = MeSe

CHO

O

1) (-)-65, THF, -78^o

2) silica gel ((1R)-59)

silica gel (67)

mCPBA (68)

O

or mCPBA ((1R)-69)

O

TBSO

(-)-65

5S

4

5'

6'

3'

6S

7S

TBSO

3

(+)-5

H

1'

1S

2

^7'OBn

2'

_6ROH

O

OBn

5

O

1

(-)-13

4

O

2

3

O

(+)-66

Helvetica Chimica Acta ± Vol. 84 (2001)

1373

undergoes b-elimination during the chromatographic (silica gel) purification giving

( )-13. The unreacted (1S)-69 is converted into ketone 68 that undergoes oxidative

elimination (mCPBA) also giving the enantiomerically enriched enone ( )-13. The

(1S,5S,6S,7S) configuration of the latter was established by its independent synthesis

starting from ketone ()-5 (Scheme 1). The (6R)-configuration at the newly created

exocyclic OH-substituted stereogenic center of ()-66 was not established, but is

proposed to result from an aldol reaction implying a closed transition structure

(Zimmerman-Traxler model [31]), by analogy with all other related condensations

involving bicyclic aluminium enolates [34].

Experiments outlined in Scheme 11 were not optimized. They suggested, however,

the possibility to prepare C-disaccharides applying the Nozaki-Oshima condensation to

aldehydes 48 (and 58) and bicyclic enone 13.

Synthesis of b-C(1 ! 3)-Linked Disaccharides. ± When racemic aluminium enolate

59, resulting from the addition of Me₂AlSPh to (Æ)-13 (see above, Scheme 9), was

trapped with racemic aldehyde (Æ)-48, a single b-hydroxy ketone was formed that was

not isolated but directly reduced under Lucheꢁs conditions [22] to afford a single diol

(Æ)-70 isolated in 56% (Scheme 12; yield based on dithioacetal (Æ)-57, see above

Scheme 7). This result demonstrates the existence of chiral matching for the Nozaki-

Oshima condensation of (Æ)-13 and (Æ)-48. The same reaction cascade applied to

enantiomerically pure enone ( )-13 and optically active aldehyde 48 derived from

thioacetal ( )-57 afforded enantiomerically pure ( )-70. The 400-MHz ¹H-NMR

spectra of (Æ)-70 and ( )-70 were identical. Both ( )-13 and ( )-57 were derived from

7-oxanorbornanone ()-5 (Schemes 1, 2, 5, and 8).

Scheme 12²)

1

H

COOMe

RO

O

O^8'

TBSO

3'

2

O

7

1) Me₂AlSPh

2) COOMe

3) NaBH₄

CeCl₃6H₂O

MeOH

2'

1'

3

OBz

OAc

₆PhS

7'

^4'RO^5'

OTBS

AcO

O

4

5

6'

O

OBn

OBz OAc

OBn

(-)-13

AcO

(-)-70 R = H^a)

(-)-72 R = Ac^a)

Ac₂O/pyr., DMAP

48

Scheme 2

(+)-5

Schemes 7 and 8

Scheme 2

(-)-19

(-)-43

1

Scheme 5

H

O

COOMe

O^8'

RO

3'

4'

2

1) Me₂AlSeMe, THF, -78^o

2) (±)−48, -78^o

3) mCPBA, -78 to -20^o

O

7

5'

(±)-13

3

OBz

OAc

6'

6

OTBS

2'

1'

AcO

7'

4

5

OBn

(±)-71

^a) The numbering in the formula refers to ( )-72.

1374

Helvetica Chimica Acta ± Vol. 84 (2001)

The addition of Me₂AlSeMe to enone (Æ)-13, followed by trapping of the resulting

aluminium enolate with (Æ)-48 gave also a single b-hydroxy ketone that was not

isolated but directly oxidized with mCPBA affording enone (Æ)-71 in 49% yield (from

dithioacetal (Æ)-57; Scheme 12). The relative configuration of the hydroxymethano

linker C(7) of (Æ)-70 and (Æ)-71 was not established unambiguously. The configuration

proposed corresponds to that expected for a cross aldol reaction following the

Zimmerman-Traxler model [31], as demonstrated with 62 and several other related

Nozaki-Oshima condensations involving bicyclic enones and sugar-derived carbox-

aldehydes [34].

Synthesis of a Precursor of a C,C-Trisaccharide with C(1 ! 3)-Linkages. ±

Desilylation of the acetate derivative ( )-72 of ( )-70 with 40% aqueous HF solution

in MeCN (0 ± 208, 2 h) followed by Dess-Martin oxidation of the resulting alcohol

provided ketone ( )-73 quantitatively (Scheme 13). Baeyer-Villiger oxidation of ( )-

73 with 90% mCPBA and NaHCO₃in CHCl₃(208, 16 h) led to ( )-74 in quantitative

yield. Concomittent oxidation of the phenylthio group to the phenylsulfonyl group

could not be avoided. Importantly, the Baeyer-Villiger oxidation was highly regiose-

lective, as in the case of ()-42 ! ( )-43 (Scheme 5). Treatment of the uronolactone

( )-74 with EtSH under acidic conditions (CH₂Cl₂, CF₃SO₂H), followed by

esterification of the resulting uronic acid with diazomethane gave the C-disaccharide

C-glycoside derivative ( )-75 in 61% yield (from diol ( )-70). Hydrolysis of the

dithioacetal moiety of ( )-75 promoted by mercuric and silver salts provided the

unstable aldehyde 76 that was used without purification in the subsequent Nozaki-

Oshima condensation implying ( )-13 and Me₂AlSeMe. After an oxidative workup

with mCPBA, the C,C-trisaccharide precursor ( )-77 was isolated in 40% yield based

on dithioacetal derivative ( )-75. The spectral data and elemental analyses (Exper.

Part) of ( )-73, ( )-74, and ( )-77 were in agreement with the proposed structures that

were deduced from their mode of formation (see above).

Conclusion. ± Starting from the Diels-Alder adduct of furan to 1-cyanovinyl acetate,

enantiomerically pure 6,7-dihydroxy-8-oxabicyclo[3.2.1]oct-3-en-2-one and 8-oxabicy-

clo[3.2.1]octane-2,3,4,6,7-pentol derivatives were prepared for the first time. Highly

stereoselective Nozaki-Oshima condensation and reduction cascades were found to

occur with 8-oxabicyclo[3.2.1]oct-3-en-2-one and various carboxaldehyde derivatives.

With enantiomerically pure aldehydes derived from sugars, highly enantioselective

Nozaki-Oshima condensations were observed. This allows us to present a new

approach to the total asymmetric synthesis of C-linked disaccharides and of C,C-linked

trisaccharide precursors, thus demonstrating the possibility of iterative synthesis of

oligosaccharide mimetics with C(1 ! 3) linkages. Benzyl 3,5-di-O-acetyl-2,6-an-

hydro-4-O-benzoyl-d-glycero-d-galacto-hepturonate (76) was derived from

()-(1S,4S,5S,6S)-6-endo-(benzyloxy)-5-exo-{[(tert-butyl)dimethylsilyl]oxy}-7-oxabicyclo-

[2.2.1]heptan-2-one (()-5). It allows one to construct b-C-mannopyranosides includ-

ing a disaccharide analog with a b-C(1 ! 3) linkage. All the products described in this

work can be obtained in both their enantiomeric forms as bicyclic ketones ()- and ( )-5

are available with the same ease [14][17]. A number of our synthetic intermediates do

not have to be isolated and purified for successful further transformations.

Helvetica Chimica Acta ± Vol. 84 (2001)

Scheme 13²)

1375

H

MeOOC

AcO

3'

1) 40% HF, MeCN

0-20^o

2) Dess-Martin

periodinane

O

2

O

7

2'

1'

90% mCPBA

3

OBz

OAc

(-)-72

₆PhS

H

7'

NaHCO₃, CHCl₃

4'

AcO^5'

AcO

4

5

^6'OBn

O

(-)-73

1

H

AcO

MeOOC

H

AcO

6

7'

2'

O

2

7'

R

O

OAc

O

7

6'

5'

H

1) EtSH, CF₃SO₃H

CH₂Cl₂

4'

6

5

3

2

3'

OBz

OBz OAc

AcO

6'

PhO₂S

O ^3'

OBn

8'

AcO

AcO^1'

2) CH₂N₂/Et₂O

4'

4

5'

3

4

5

PhSO₂

2'

COOMe

O

(-)-74

(-)-75 R = CH(SEt)₂

76 R = CHO

1) Hg(ClO₄)₂xH₂O, MeCN

2) Ag₂CO₃

AcO

HO

H

MeOOC

O

4''

H

O^8''

2

2'

1) Me₂AlSeMe, THF, -78^o

2) 76, -78^o, 2 h

3) mCPBA, -78 to -20^o

O

7'

O

7

3''

5''

3

6

OAc

3'

OBz

AcO

6'

(-)-13

^6''OTBS

2''

1''

AcO

4'

4

5'

5

PhSO₂

7''

OBn

COOMe

(-)-77 (46% based on (-)-75)

Experimental Part

General. See [35]. The procedures described for racemic products were applied to the preparation of

enantiomerically pure products. Apart from the [a] values and m.p., all other data were identical for

enantiomerically pure products and the corresponding racemates. ¹H-NMR Signal assignments were confirmed

by 2D COSY and NOESY ¹H-NMR data. Flash chromatography (FC): silica gel (Merck No. 9385, 240 ±

400 mesh). Electron-spray mass spectromer: Perkin Elmer AP1 150 EX.

(1S,2S,4S,5S,6S)- and (1R,2R,4R,5R,6R)-6-endo-(Benzyloxy)-5-exo-{[(tert-butyl)dimethylsilyl]oxy}-2-

exo-{[S(S)]-N-methyl-S-phenylsulfonimidoyl}methyl}-7-oxabicyclo[2.2.1]heptan-2-endo-ol (()-7 and ( )-8,

resp.). BuLi (1.6m in hexane; 26.9 ml, 43 mmol) was added dropwise to a stirred soln. of ()-(S)-N,S-dimethyl-

S-phenylsulfoximide (6.32 g, 37.3 mmol) in anh. THF (150 ml) cooled to 258 under Ar. After stirring at 258

for 30 min, the deep yellow soln. was cooled to 608 to which a cooled ( 608) soln. of (Æ)-5 [16][36] (10.0 g,

28.7 mmol) in anh. THF (50 ml) was canulated under stirring. The mixture was stirred and allowed to warm to

208 within ca. 3 h. Sat. aq. NH₄Cl soln. (400 ml) was added and the mixture extracted with Et₂O (400 ml, 5 Â ).

The combined org. extract was dried (MgSO₄) and evaporated and the yellowish oil (18.0 g) purified by FC

(10 Â 31 cm, light petroleum ether/AcOEt 1:1): 6.25 g (42%) of ()-7 and 6.59 g (44%) of ( )-8, both as

colorless oils.

25

Data of ()-7: R_f0.60; d.e. >99%. [a] 51, [a] 53, [a] 60, [a] 107, [a] 130

589

577

546

435

405

(c 1.2, CHCl₃). UV (MeCN): 272 (1900), 265 (2300), 209 (1400), 197 (15000). IR (film): 3450, 3225, 3065,

1

2955, 2930, 2885, 2860, 2245, 1445, 1355, 1240, 1150, 1120, 1085, 1005, 875, 840, 775, 740. H-NMR (400 MHz,

3

CDCl₃): 7.90, 7.64 ± 7.55, 7.40 ± 7.30 (3m, 2 H, 3 H, 5 H, arom. H); 6.16 (s, OH C(2)); 4.83 (br. d, J(1,6) 4.8,

H

C(1)); 4.76, 4.62 (2d, ²J 11.4, PhCH₂O); 4.16 (br. d, ³J(4,3exo) 6.5, H C(4)); 4.06 (m, ³J(6,1) 4.8,

³J(6,5) 2.4, H C(6)); 4.01 (d, ³J(5,6) 2.4, H C(5)); 3.51, 3.46 (2d, ²J 14.0, CH₂C(2)); 2.70 (s, SNMe);

2.07 (dd, ³J(3exo,3endo) 13.4, ³J(3exo,4) 6.5, H_exoC(3)); 1.71 (d, ³J(3endo,3exo) 13.4, H_endoC(3)); 0.89

(s, t-BuSi); 0.09, 0.08 (2s, Me₂Si). ¹³C-NMR (100.6 MHz, CDCl₃): 139.1, 137.1 (2s, arom. C); 132.9, 129.3, 129.0,

128.4, 128.2, 127.9 (6d, ¹J(C,H) 160, arom. C); 91.1 (d, ¹J(C,H) 150, C(6)); 84.8 (d, ¹J(C,H) 160, C(4)); 80.0

(s, C(2)); 79.9 (d, ¹J(C,H) 144, C(5)); 76.8 (d, ¹J(C,H) 160, C(1)); 72.9 (t, ¹J(C,H) 141, PhCH₂O); 64.3

(t, ¹J(C,H) 139, CH₂C(2)); 43.4 (t, ¹J(C,H) 134, C(3)); 29.1 (q, ¹J(C,H) 138, SNMe); 25.7

1376

Helvetica Chimica Acta ± Vol. 84 (2001)

(q, ¹J(C,H) 125, Me₃CSi); 17.9 (s, Me₃CSi); 4.7, 4.8 (2q, ¹J(C,H) 118, Me₂Si). CI-MS (NH₃): 518 (27,

[M 1] ), 366 (11), 170 (26, [PhS(O)(NHMe)Me] ), 156 (53, [PhS(O)(NHMe)H] ), 154 (11,

[PhS(O)(NMe)] ), 125 (27), 108 (17, BnOH ), 107 (36, BnO ), 91 (100, C₇H₇), 77 (12, C₆H₅). Anal. calc.

for C₂₇H₃₉NO₅SSi (517.83): C 62.62, H 7.61, N 2.71, S 6.19, Si 5.42; found: C 62.68, H 7.67, N 2.68, S 6.01, Si 5.42.

Data for ()-8: R_f0.42; d.e. >99%. [a]_D²⁵

17, [a]

18, [a]

20, [a]

27, [a]

30 (c

25

577

546

435

405

1.0, CH₂Cl₂). UV (MeCN): 271 (1800), 264 (2200), 208 (14500), 200 (14000). IR (film): 3440, 3230, 3065, 2955,

2930, 2885, 2860, 2245, 1445, 1410, 1390, 1350, 1240, 1150, 1125, 1085, 1010, 870, 840, 780, 745. ¹H-NMR

(400 MHz, CDCl₃): 7.86, 7.60 ± 7.50, 7.38 ± 7.29 (3m, 2 H, 3 H, 5 H, arom. H); 5.85 (s, OH C(2)); 4.78, 4.62

(2d, ²J 11.4, PhCH₂O); 4.65 (br. d, ³J(1,6) 4.9, H C(1)); 4.19 (br. d, ³J(4,3exo) 6.5, H C(4)); 4.07

(m, ³J(6,1) 4.9, J(6,5) 2.3, H C(6)); 3.99 (d, ³J(5,6) 2.3, H C(5)); 3.57, 3.47 (2d, ²J 14.3, CH₂C(2));

3

2.64 (s, SNMe); 2.37 (dd, ³J(3exo,3endo) 13.4, ³J(3exo,4) 6.5, H_exoC(3)); 1.68 (d, ³J(3exo,3endo) 13.4,

H_endoC(3)); 0.88 (s, t-BuSi); 0.07 (s, Me₂Si). ¹³C-NMR (100.6 MHz, CDCl₃): 139.2, 136.8 (2s, arom. C); 132.6,

129.1, 129.0, 128.4, 128.1, 128.0 (6d, ¹J(C,H) 160, arom. C); 91.3 (d, ¹J(C,H) 151, C(6)); 84.9 (d, ¹J(C,H)

161, C(4)); 80.3 (s, C(2)); 79.8 (d, ¹J(C,H) 145, C(5)); 76.3 (d, ¹J(C,H) 166, C(1)); 73.1 (t, ¹J(C,H) 143,

PhCH₂O); 63.8 (t, ¹J(C,H) 138, CH₂C(2)); 42.6 (t, ¹J(C,H) 135, C(3)); 29.1 (q, ¹J(C,H) 137,

SNMeCH₃); 25.7 (q, ¹J(C,H) 125, Me₃CSi); 17.9 (s, Me₃CSi)); 4.7, 4.8 (2q, ¹J(C,H) 118, Me₂Si). CI-

MS (NH₃): 518 (44, [M 1] ), 366 (23), 170 (51, [PhS(O)(NHMe)Me] ), 156 (47,

[PhS(O)(NHMe)H] ), 154 (18, [PhS(O)(NMe)] ), 125 (27), 108 (24, BnOH ), 107 (28, BnO ), 91

(100, C₇H₇), 77 (14, C₆H₅). Anal. calc. for C₂₇H₃₉NO₅SSi (517.83): C 62.62, H 7.61, N 2.71, S 6.19, Si 5.42;

found: C 62.59, H 7.54, N 2.60, S 6.00, Si 5.45.

()-(1S,4S,5S,6S)-6-endo-(Benzyloxy)-5-exo-{[(tert-butyl)dimethylsilyl]oxy}-7-oxabicyclo[2.2.1]heptan-2-

one (()-5). In a Büchi ꢀKugelrohrꢁ oven, ()-7 (7.63 g, 14.7 mmol) was heated to 2208/0.2 mm Torr. The same

operation was repeated twice. The combined products of distillation were dissolved in heptane (20 ml). After

staying at 48 overnight, 5.87 g of pure ()-5 was collected as colorless crystals. The mother liquor was evaporated

and the residue purified by FC (7 Â 25 cm, light petroleum ether/Et₂O 4 :1 ! 3 :2, then CH₂Cl₂/MeOH 9 :1):

8.24 g (92%) of ()-5 (global yield) as white crystals and 7.42 g (99%) of ()-(S)-N,S-dimethyl-S-phenyl-

25

sulfoximide as yellowish oil. ()-5: [a]_D²⁵ 53, [a] 56, [a] 63, [a] 102, [a] 119 (c 1.3, CH₂Cl₂).

577

546

435

405

(

)-(1R,4R,5R,6R)-6-endo-(Benzyloxy)-5-exo-{[(tert-butyl)dimethylsilyl]oxy}-7-oxabicyclo[2.2.1]hep-

tan-2-one (( )-5). As described for ()-5, with ( )-8 (1.37 g, 2.65 mmol): 0.80 g (87%) of ( )-5 as colorless solid

25

and 0.45 g (99%) of chiral sulfonimide as yellowish oil. ( )-5: [a]_D²⁵

51, [a]

55, [a]

62, [a]

577

546

435

25

101, [a]

119 (c 0.7, CH₂Cl₂).

405

(1RS,4RS,5RS,6RS)-6-endo-(Benzyloxy)-5-exo-{[(tert-butyl)dimethylsilyl]oxy}-2-[(trimethylsilyl)oxy]-7-

oxabicyclo[2.2.1]hept-2-ene ((Æ)-9). BuLi (1.6m in hexane; 2.6 ml, 4.16 mmol) was added dropwise under

stirring to a soln. of (i-Pr)₂NH (0.64 ml, 457 mg, 4.52 mmol) in anh. THF (10 ml) cooled to 158 in a Schlenk

tube. After stirring at 158 for 15 min, the soln. was cooled to 788. A soln. of (Æ)-5 (1.14 g, 3.27 mmol) in anh.

THF (10 ml) cooled to 788 was canulated into the Li(i-Pr)₂N soln. under stirring. After stirring at 788 for

90 min, Me₃SiCl (0.8 ml, 687 mg, 6.33 mmol) was added dropwise and the mixture stirred at 788 for 2 h, then

allowed to warm to 208, and stirred for additional 2 h. Then the mixture was concentrated to ca. 5 ml. Pentane

(12 ml) was added, the precipitate filtered off (Celite), and the solvent evaporated: 1.33 g (96%) of (Æ)-9.

Yellowish solid used as such in the next step. M.p. 45 ± 468. IR (KBr): 2955, 2855, 1625, 1470, 1350, 1320, 1255,

1225, 1105, 1030, 950, 865, 775, 700, 665. ¹H-NMR (400 MHz, C₆D₆): 7.32,7.19, 7.12 (3m, 2 H, 2 H, 1 H, arom. H);

4.76 (d, ³J(3,4) 2.2, H C(3)); 4.68 (m, ³J(4,3) 2.2, ⁴J(4,1) 0.7, H C(4)); 4.57 (dd, ³J(1,6) 4.0, ⁴J(1,4)

0.7, H C(1)); 4.44, 4.33 (2d, ²J 11.4, PhCH₂O); 4.05 (d, ³J(5,6) 0.9, H C(5)); 4.01 (br. dd, ³J(6,1) 4.0,

³J(6,5) 0.9, H C(6)); 1.04 (s, t-BuSi); 0.16, 0.14 (2s, Me₂Si); 0.12 (s, Me₃Si). ¹H-NMR (400 MHz, CDCl₃):

7.34 ± 7.28 (m, 5 arom. H); 4.95 (d, ³J(3,4) 2.2, H C(3)); 4.58, 4.53 (2d, ²J 11.3, PhCH₂O); 4.51 (m, ³J(4,3)

2.2, H C(4)); 4.50 (br. d, ³J(1,6) 4.0, H C(1)); 3.89 (br. dd, ³J(6,1) 4.0, ³J(6,5) 0.7, H C(6)); 3.87

(d, ³J(5,6) 0.7, H C(5)); 0.92 (s, t-BuSi); 0.20 (s, Me₃Si); 0.11, 0.10 (2s, Me₂Si). ¹³C-NMR (100.6 MHz,

CDCl₃): 162.0 (s, C(3)); 137.9 (s, arom. C); 128.2, 127.9, 127.7 (3d, ¹J(C,H) 160, arom. C); 100.1 (d, ¹J(C,H)

173, C(3)); 86.5 (d, ¹J(C,H) 164, C(4)); 84.7 (d, ¹J(C,H) 152, C(6)); 79.5 (d, ¹J(C,H) 152, C(5)); 78.8

(d, ¹J(C,H) 163, C(1)); 72.3 (t, ¹J(C,H) 141, PhCH₂O); 25.9 (q, ¹J(C,H) 125, Me₃CSi); 18.2 (s, Me₃CSi);

0.4 (q, ¹J(C,H) 120, Me₃Si); 4.6, 4.7 (2q, ¹J(C,H) 118, Me₂Si). Anal. calc. for C₂₂H₃₆O₄Si₂(420.76):

C 62.80, H 8.64, Si 13.35; found: C 62.85, H 8.70, Si 13.43.

(1RS,4RS,5RS,6RS)-6-endo-(Benzyloxy)-5-exo-{[(tert-butyl)dimethylsilyl]oxy}-2-[(triethylsilyl)oxy]-7-

oxabicyclo[2.2.1]hept-2-ene ((Æ)-10). As described for (Æ)-9, with Et₃SiCl instead of Me₃SiCl: 100% of (Æ)-10.

1

The crude product was used directly in the next step. H-NMR (400 MHz, CDCl₃): 7.35 ± 7.27 (m, 5 arom. H);

4.95 (d, ³J(3,4) 2.2, H C(3)); 4.61, 4.53 (2d, ²J 11.5, PhCH₂O); 4.50 (br. d, ³J(4,3) 2.2, H C(4)); 4.49

Helvetica Chimica Acta ± Vol. 84 (2001)

1377

(br. d, ³J(1,6) 3.6, H C(1)); 3.88 (br. d, ³J(6,1) 3.6, H C(6)); 3.87 (br. s, H C(5)); 0.95 (m, (MeCH₂)₃Si);

0.91 (s, t-BuSi); 0.73 ± 0.66 (m, (MeCH₂)₃Si); 0.11, 0.10 (2s, Me₂Si). ¹³C-NMR (100.6 MHz, CDCl₃): 162.4

(s, C(3)); 137.9 (s, arom. C); 128.2, 127.8, 127.6 (3d, ¹J(C,H) 160, arom. C); 100.2 (d, ¹J(C,H) 170, C(3)); 86.5

(d, ¹J(C,H) 166, C(4)); 84.6 (d, ¹J(C,H) 152, C(6)); 79.5 (d, ¹J(C,H) 151, C(5)); 78.9 (d, ¹J(C,H) 163,

C(1)); 72.3 (t, ¹J(C,H) 141, PhCH₂O); 25.9 (q, ¹J(C,H) 125, Me₃CSi); 18.2 (s, Me₃CSi); 6.5 (q, ¹J(C,H) 126,

(MeCH₂)₃Si); 4.4 (t, ¹J(C,H) 117, (MeCH₂)₃Si); 4.6, 4.7 (2q, ¹J(C,H) 118, Me₂Si).

(1RS,2RS,4SR,5RS,6RS,7RS)-7-endo-(Benzyloxy)-6-exo-{[(tert-butyl)dimethylsilyl]oxy}-2-endo-[(trimeth-

ylsilyl)oxy]-8-oxatricyclo[3.2.1.0^2,4]octane ((Æ)-11). Et₂Zn (1m in hexane; 6.3 ml, 6.3 mmol) was added dropwise

to a stirred soln. of ICH₂Cl (0.92 ml, 2.22 g, 12.6 mmol) in anh. ClCH₂CH₂Cl (20 ml) cooled to 108 under N₂.

After stirring at 108 for 30 min, the mixture was cooled to 308. A soln. of (Æ)-9 (1.33 g, 3.15 mmol) in anh.

ClCH₂CH₂Cl (10 ml) was added dropwise under stirring, the rate of the addition being adapted to maintain the

temp. at 308. After 1 h at 308, the mixture was stirred at 208 for 2 h. H₂O (20 ml) and sat. aq. NH₄Cl soln.

(20 ml) were added under stirring. The aq. layer was extracted with CH₂Cl₂(4 Â 35 ml) and the combined org.

extract dried (MgSO₄) and evaporated: 1.33 g (97%) of crude (Æ)-11. Yellowish viscous oil, which was used

directly in the next step.

(1RS,2SR,4RS,5RS,6RS,7RS)-7-endo-(Benzyloxy)-6-exo-{[(tert-butyl)dimethylsilyl]oxy}-2-endo-[(tri-

ethylsilyl)oxy]-8-oxatricyclo[3.2.1.0^2,4]octane ((Æ)-12). As described for (Æ)-11, with (Æ)-10 instead of (Æ)-9:

100% of (Æ)-12. Yellowish oil which was used directly in the next step.

(1RS,5RS,6RS,7RS)-7-endo-(Benzyloxy)-6-exo-{[(tert-butyl)dimethylsilyl]oxy}-8-oxabicyclo[3.2.1]oct-3-

en-2-one ((Æ)-13). Anh. pyridine (14 ml, 13.8 g, 174 mmol), then (Æ)-12 (14.9 g, 32.9 mmol) in anh. DMF

(100 ml) were added to an anh. FeCl₃(8.5 g, 52 mmol) soln. in DMF (200 ml) stirred at 08. After stirring at 08 for

15 min, the mixture was heated to 708 for 2 h. Then AcOEt (1 l) was added and the soln. washed with 1n HCl

(2 Â 400 ml), sat. aq. NaHCO₃soln. (300 ml), and brine (300 ml). The aq. phases were extracted with AcOEt

(2 Â 400 ml) and the combined org. extracts dried (MgSO₄) and evaporated at 10 ²Torr. The dark residue was

purified by FC (7.5 Â 23 cm, light petroleum ether/Et₂O 3 :1): 5.79 g (57% based on (Æ)-5) of (Æ)-13 as yellowish

oil. An anal. sample was obtained by a second FC (light petroleum ether/CH₂Cl₂/Et₂O 14 :19 :1): 4.61 g (45%

based on (Æ)-5) of (Æ)-13. Colorless solid. M.p. 468. UV (MeCN): 207 (11700), 196 (11600). IR (KBr): 2935,

1

2920, 2860, 1700, 1260, 1095, 1050, 830, 785, 750, 700. H-NMR (400 MHz, CDCl₃): 7.36 ± 7.26 (m, 5 arom. H);

7.19 (dd, ³J(4,3) 9.9, ³J(4,5) 4.8,

H

C(4)); 6.12 (dd, ³J(3,4) 9.9, ⁴J(3,1) 1.1,

H C(3)); 4.83

(br. dd, ³J(1,7) 7.0, ⁴J(1,3) 1.1, H C(1)); 4.58, 4.40 (2d, ²J 11.2, PhCH₂O); 4.45 (br. d, ³J(5,4) 4.8,

H

C(5)); 4.30 (m, ³J(7,1) 7.0, H C(7)); 4.27 (br. s, H C(6)); 0.90 (s, t-BuSi); 0.11, 0.10 (2s, Me₂Si).

¹³C-NMR (100.6 MHz, CDCl₃): 194.1 (s, C(2)); 147.9 (d, ¹J(C,H) 163, C(4)); 136.8 (s, arom. C); 128.5, 128.4,

128.2, 128.1 (4d, ¹J(C,H) 160, arom. C, C(3)); 86.3 (d, ¹J(C,H) 153, C(7)); 83.6 (d, ¹J(C,H) 157, C(1)); 81.3

(d, ¹J(C,H) 158, C(5)); 79.6 (d, ¹J(C,H) 155, C(6)); 73.7 (t, ¹J(C,H) 144, PhCH₂O); 25.7 (q, ¹J(C,H) 125,

Me₃CSi); 18.0 (s, Me₃C); 4.9 (q, ¹J(C,H) 119, Me₂Si). CI-MS (NH₃): 360 (1, M ), 211 (10), 187 (7), 97 (12),

91 (100, C₇H₇), 75 (8), 74 (6), 73 (18). Anal. calc. for C₂₀H₂₈O₄Si (360.57): C 66.62, H 7.84, Si 7.79; found:

C 66.71, H 7.78, Si 7.69.

(1S,5S,6S,7S)-7-endo-(Benzyloxy)-6-exo-{[(tert-butyl)dimethylsilyl]oxy}-8-oxabicyclo[3.2.1]oct-3-en-2-

one (( )-13). As described for (Æ)-13, from ()-5, without purification of the intermediates 10 and 11: 58%

25

(based on ()-5) of ( )-13. Colorless oil. [a]_D²⁵

915 (c 0.9, CHCl₃).

124, [a]

131, [a]

161, [a]

461, [a]

577

546

435

405

(1RS,2SR,5SR,6SR,7SR)-7-endo-(Benzyloxy)-6-exo-{[(tert-butyl)dimethylsilyl]oxy}-8-oxabicyclo[3.2.1]-

oct-3-en-2-endo-ol ((Æ)-14). CeCl₃´ 6H₂O (443 mg, 1.25 mmol) was added portionwise to a stirred soln. of (Æ)-

13 (0.3 g, 0.83 mmol) in MeOH (6 ml) cooled to 08. NaBH₄(35 mg, 0.93 mmol) was then added portionwise, and

the mixture was stirred at 08 for 30 min. AcOH (0.1 ml), then sat. aq. NaHCO₃soln. were added. The mixture

was extracted with AcOEt (50 ml, then 3 Â 25 ml). The combined org. extract was dried (MgSO₄) and

evaporated and the residue purified by FC (3 Â 13 cm, light petroleum ether/Et₂O 3 :1): 280 mg of (Æ)-14.

Colorless solid. M.p. 558. UV (MeCN): 212 (7900). IR (film): 3515, 3035, 2955, 2930, 2895, 2855, 1470, 1415,

1255, 1095, 1055, 840. ¹H-NMR (400 MHz, CDCl₃): 7.40 ± 7.30 (m, 5 arom. H); 5.91 (ddd, ³J(3,4) 9.9, ³J(3,2)

1.5, ⁴J(3,1) 1.4, H C(3)); 5.86 (ddd, ³J(4,3) 9.9, ³J(4,5) 3.8, ⁴J(4,2) 1.3, H C(4)); 4.76, 4.57 (2d, ²J

11.5, PhCH₂O); 4.62 (m, ³J(1,7) 6.9,⁴J(1,3) 1.4, ³J(2,OH) 11.6, ³J(2,3) 1.5, ⁴J(2,4) 1.3, H C(1),

H

C(2)); 4.44 (br. d, ³J(7,1) 6.9, H C(7)); 4.27 (br. s, H C(6)); 4.10 (br. d, ³J(5,4) 3.8, H C(5)); 3.65

(d, 3J(OH,2) 11.6, OH C(2)); 0.93 (s, t-BuSi); 0.14, 0.12 (2s, Me₂Si). ¹³C-NMR (100.6 MHz, CDCl₃): 136.6

(s, arom. C); 132.6 (d, ¹J(C,H) 164, C(3)); 128.7, 128.2, 127.6 (3d, ¹J(C,H) 160, arom. C); 127.1 (d, ¹J(C,H)

163, C(4)); 93.0 (d, ¹J(C,H) 151, C(7)); 81.4 (d, ¹J(C,H) 149, C(6)); 80.3 (d, ¹J(C,H) 162, C(5)); 75.5

(d, ¹J(C,H) 150, C(1)); 73.6 (t, ¹J(C,H) 146, PhCH₂O); 68.8 (d, ¹J(C,H) 147, C(2)); 25.7 (q, ¹J(C,H) 125,

1378

Helvetica Chimica Acta ± Vol. 84 (2001)

Me₃CSi); 17.9 (s, Me₃CSi); 4.5, 4.8 (2q, ¹J(C,H) 118, Me₂Si). CI-MS (NH₃): 380 (100, [M NH₄] ), 363

(15, [M H] ). Anal. calc. for C₂₀H₃₀O₄Si (362.59): 66.25, H 8.36, Si 7.75; found: 66.19, H 8.47, Si 7.87.

(1RS,2SR,5SR,6SR,7SR)-7-endo-(Benzyloxy)-6-exo-{[(tert-butyl)dimethylsilyl]oxy}-8-oxabicyclo[3.2.1]-

oct-3-en-2-endo-yl Benzoate ((Æ)-15). A mixture of (Æ)-14 (100 mg, 0.28 mmol), anh. pyridine (3 ml), and

benzoyl chloride (0.1 ml, 121 mg, 0.86 mmol) was stirred at 208 for 3 h. H₂O (3 ml) was added and stirring

continued for 2 h. After the addition of AcOEt (30 ml), the soln. was washed successively with 1n HCl (3 Â

15 ml), sat. aq. NaHCO₃soln. (3 Â 15 ml), sat. aq. NaHCO₃soln. (3 Â 15 ml), and brine (15 ml). The aq. phases

were extracted with AcOEt (2 Â 30 ml) and the combined org. extracts dried (MgSO₄) and evaporated. The

residue was purified by FC (2 Â 20 cm, light petroleum ether/AcOEt 10 :1): 117 mg (89%) of (Æ)-15. Colorless

solid. M.p. 718. UV (MeCN): 228 (9600). IR (film): 2955, 2925, 2855, 1705, 1260, 1105, 1095, 980, 835, 775, 695.

¹H-NMR (400 MHz, C₆D₆): 8.09, 7.22, 7.12, 6.97 (4m, 2 H, 2 H, 4 H, 2 H, arom. H); 6.29 (m, ³J(2,1) 4.7,

³J(2,3) 1.7, ⁴J(2,4) 2.1, H C(2)); 5.81 (ddd, ³J(3,4) 10.0, ³J(3,2) 1.7, ⁴J(3,1) 1.6, H C(3)); 5.66

(ddd, ³J(4,3) 10.00, ³J(4,5) 4.1, ⁴J(4,2) 2.1, H C(4)); 5.01 (ddd, ³J(1,7) 6.4, ³J(1,2) 4.7, ⁴J(1,3) 1.6,

H

C(1)); 4.42 (s, PhCH₂O); 4.38 (br. d, ³J(7,1) 6.4, H C(7)); 4.37 (br. s, H C(6)); 4.18 (br. d, ³J(5,4) 4.1,

C(5)); 0.96 (s, t-BuSi); 0.05, 0.03 (2s, Me₂Si). ¹³C-NMR (100.6 MHz, CDCl₃): 166.4 (s, CO); 137.7, 129.9

(2s, arom. C); 132.9, 129.8 (2d, ¹J(C,H) 160, arom. C); 129.3 (d, ¹J(C,H) 154, C(4)); 128.2, 127.6, 127.5, 127.4

(4d, ¹J(C,H) 160, arom. C, C(3)); 91.8 (d, ¹J(C,H) 148, C(7)); 82.3 (d, ¹J(C,H) 150, C(6)); 80.4

(d, ¹J(C,H) 160, C(5)); 75.3 (d, ¹J(C,H) 152, C(1)); 73.5 (t, ¹J(C,H) 142, PhCH₂O); 70.3 (d, ¹J(C,H)

158, C(2)); 25.7 (q, ¹J(C,H) 125, Me₃CSi); 18.0 (s, Me₃CSi); 4.7, 4.8 (2q, ¹J(C,H) 118, Me₂Si). ES-MS

(pos. mode): 489 (100, [M Na] ), 484 (50, [M NH₄] ), 467 (15, [M H] ). Anal. calc. for C₂₇H₃₄O₅Si

(466.70): C 69.48, H 7.36, Si 6.02; found: C 69.64, H 7.37, Si 5.98.

(1RS,2RS,4SR,5SR,6RS,7RS,8SR)-7-endo-(Benzyloxy)-8-exo-{[(tert-butyl)dimethylsilyl]oxy}-3,9-dioxa-

tricyclo[4.2.1.0^2,4]non-5-endo-yl Benzoate ((Æ)-16). As described for (Æ)-15, with crude (Æ)-18 (3.83 g,

10.1 mmol), pyridine (60 ml), and benzoyl chloride (4 ml, 4.84 g, 34.4 mmol). Purification by solvent

evaporation gave 4.89 g (100%) of (Æ)-16, pure enough for the next step. An anal. sample was prepared by

FC (1 Â 14 cm, light petroleum ether/AcOEt 9 :1 ! 4 :1): white solid. M.p. 99 ± 1008. UV (MeCN): 272 (2000),

228 (14000), 200 (18500). IR (KBr): 3060, 3035, 2960, 2935, 2900, 2860, 1720, 1605, 1450, 1280, 1255, 1115, 840,

700. ¹H-NMR (400 MHz, CDCl₃): 7.90, 7.52, 7.31 ± 7.21 (3m, 2 H, 1 H, 7 H, arom. H); 5.32 (dd, ³J(5,6) 5.2,

⁴J(5,2) 0.7, H C(5)); 4.78 (ddd, ³J(6,7) 6.7, ³J(6,5) 5.2, ⁴J(6,4) 1.6, H C(6)); 4.57, 4.53 (2d, ²J 11.8,

PhCH₂O); 4.42 (m, ³J(8,7) 1.0, H C(8)); 4.27 (m, ³J(1,2) 1.2, ⁴J(1,7) 1.7, ⁴J(1,4) 0.6, H C(1)); 4.20

(ddd, ³J(7,6) 6.7, ³J(7,8) 1.0, ⁴J(7,1) 1.7, H C(7)); 3.42 (ddd, ³J(4,2) 3.9, ⁴J(4,6) 1.6, ⁴J(4,1) 0.6,

3

4

H

C(4)); 3.14 (ddd, ³J(2,4) 3.9, J(2,1) 1.2, J(2,5) 0.7, H C(2)); 0.91 (s, t-BuSi); 0.13, 0.12 (2s, Me₂Si).

¹³C-NMR (100.6 MHz, CDCl₃): 165.7 (s, CO); 137.5, 129.4 (2s, arom. C); 133.1, 129.8, 128.3, 128.2, 127.7,

127.4 (6d, ¹J(C,H) 160, arom. C); 88.3 (d, ¹J(C,H) 148, C(7)); 79.7 (d, ¹J(C,H) 141, C(8)); 78.8

(d, ¹J(C,H) 158, C(1)); 73.5 (t, ¹J(C,H) 140, PhCH₂O); 73.1 (d, ¹J(C,H) 157, C(6)); 67.5 (d, ¹J(C,H)

154, C(5)); 52.7 (d, ¹J(C,H) 183, C(4)); 49.0 (d, ¹J(C,H) 178, C(2)); 25.7 (q, ¹J(C,H) 125, Me₃CSi); 18.0

(s, Me₃CSi); 4.6, 4.7 (2q, ¹J(C,H) 118, Me₂Si). CI-MS (NH₃): 483 (0.5, [M 1] ), 425 (7, [M C₄H₉] ),

105 (37, Bz ), 91 (100, C₇H₇), 77 (12, C₆H₅). Anal. calc. for C₂₇H₃₄O₆Si (482.70): C 67.18, H 7.11, Si 5.82;

found: C 67.24, H 7.12, Si 5.82.

(1S,2S,4R,5R,6S,7S,8R)-7-endo-(Benzyloxy)-8-exo-{[(tert-butyl)dimethylsilyl]oxy}-3,9-dioxatricyclo[4.2.1.0^2,4]-

non-5-endo-yl Benzoate (( )-16). As described for (Æ)-16, from ( )-13 via ()-17 and ( )-18, without

purification of the intermediates. White solid. M.p. 90 ± 918. [a]_D²⁵

20, [a]

21, [a]

24, [a]

25

577

546

435

25

38, [a]

45 (c 0.8, CH₂Cl₂).

405

(1RS,2SR,4SR,6RS,7RS,8SR)-7-endo-(Benzyloxy)-8-exo-{[(tert-butyl)dimethylsilyl]oxy}-3,9-dioxatricy-

clo[4.2.1.0^2,4]nonan-5-one ((Æ)-17). A mixture of (Æ)-13 (4.0 g, 11.1 mmol), DBU (2.0 ml, 2.0 g, 13.4 mmol),

and t-BuOOH (3m in isooctane; 7.4 ml, 22.2 mmol) in anh. CH₂Cl₂(100 ml) was stirred at 208 for 3 h. After the

addition of CHCl₃(100 ml), the soln. was washed successively with 10% aq. NaHSO₃soln. (150 ml), 1n HCl

(150 ml), and sat. aq. NaHCO₃soln. (150 ml). The aq. phases were extracted with CHCl₃(3 Â 150 ml) and the

combined org. extracts dried (MgSO₄) and evaporated: 4.5 g (100%) of (Æ)-17. Yellowish solid pure enough for

the next step. An anal. sample was obtained by FC (0.5 Â 10 cm, light petroleum ether/AcOEt 9 :1): colorless

solid. M.p. 81 ± 828. UV (MeCN): 292 (850), 263 (950), 205 (8500), 195 (9800). IR (KBr): 2955, 2930, 2855, 1735,

1

1470, 1410, 1390, 1255, 1105, 1065, 1030, 880, 845, 790, 755, 705, 430. H-NMR (400 MHz, CDCl₃): 7.38 ± 7.26

(m, 5 arom. H); 4.67 (br. d, ³J(6,7) 7.2, H C(6)); 4.53, 4.38 (2d, ²J 11.1, PhCH₂O); 4.43 (m, ³J(1,2) 1.7,

⁴J(1,7) 1.2, H C(1)); 4.35 (br. d, ³J(8,7) 1.3, H C(8)); 4.21 (ddd, ³J(7,6) 7.2, ³J(7,8) 1.3, ⁴J(7,1) 1.2,

H

C(7)); 3.40 (dd, ³J(2,4) 3.7, ³J(2,1) 1.7, H C(2)); 3.30 (br. d, ³J(4,2) 3.7, H C(4)); 0.91 (s, t-BuSi);

0.13, 0.12 (2s, Me₂Si). ¹³C-NMR (100.6 MHz, CDCl₃): 197.9 (s, C(5)); 136.3 (s, arom. C); 128.5, 128.2

Helvetica Chimica Acta ± Vol. 84 (2001)

1379

(2d, ¹J(C,H) 160, arom. C); 88.6 (d, ¹J(C,H) 153, C(7)); 82.9 (d, ¹J(C,H) 161, C(6)); 79.0 (d, ¹J(C,H)

158, C(1)); 78.7 (d, ¹J(C,H) 146, C(8)); 73.3 (t, ¹J(C,H) 141, PhCH₂O); 52.0 (d, ¹J(C,H) 188, C(4)); 49.0

(d, ¹J(C,H) 183, C(2)); 25.6 (q, ¹J(C,H) 125, Me₃CSi); 18.0 (s, Me₃CSi); 4.8, 4.9 (2q, ¹J(C,H) 118,

Me₂Si). CI-MS (NH₃): 394 (31, [M 18] ), 319 (10, [M C₄H₉] ), 185 (11), 129 (11), 108 (25, BnOH ), 91

(100, C₇H₇). Anal. calc. for C₂₀H₂₈O₅Si (376.57): C 63.79, H 7.51, Si 7.46; found: C 63.84, H 7.46, Si 7.35.

(1S,2R,4R,6S,7S,8R)-7-endo-(Benzyloxy)-8-exo-{[(tert-butyl)dimethylsilyl]oxy}-3,9-dioxatricyclo[4.2.1.0^2,4]-

nonan-5-one (()-17). As described for (Æ)-17, with ( )-13. Colorless oil. [a]²_D⁵ 29, [a] 31, [a] 35,

25

577

546

25

[a] 67, [a] 87 (c 1.1, CH₂Cl₂).

435

405

(1RS,2RS,4RS,5SR,6SR,7RS,8SR)-7-endo-(Benzyloxy)-8-exo-{[(tert-butyl)dimethylsilyl]oxy}-3,9-dioxa-

tricyclo[4.2.1.0^2,4]nonan-5-endo-ol ((Æ)-18). A mixture of (Æ)-17 (4.5 g, 11.9 mmol), MeOH (200 ml), and

NaBH₄(0.48 g, 12.7 mmol) was stirred at 08 for 30 min. H₂O (180 ml) and brine (180 ml) were added, and the

mixture was extracted with Et₂O (500 ml, then 4 Â 250 ml). The combined org. extracts were dried (MgSO₄) and

evaporated: 3.83 g (85%) of (Æ)-18. Yellowish oil that can be used directly in the next step. An anal. sample was

obtained by FC (0.5 Â 10 cm, light petroleum ether/AcOEt 4 :1): colorless oil. UV (MeCN): 207 (8200), 196

(9000). IR (film): 3510, 2955, 2930, 2900, 2860, 1470, 1410, 1360, 1255, 1110, 1070, 860, 840, 780. ¹H-NMR

(400 MHz, CDCl₃): 7.38, 7.30 (2m, 3 H, 2 H, arom. H); 4.77, 4.55 (2d, ²J 11.4, PhCH₂O); 4.46 (ddd, ³J(6,7) 7.0,

³J(6,5) 2.5, ⁴J(6,4) 1.6, H C(6)); 4.39 (br. s, H C(8)); 4.32 (br. d, ³J(7,6) 7.0, H C(7)); 4.20 (m, ³J(1,2)

1.0, H C(1)); 4.02 (s, OH C(5)); 4.01 (d, ³J(5,6) 2.5, H C(5)); 3.23 (dd, ³J(4,2) 3.8, ⁴J(4,6) 1.6,

H

C(4)); 3.06 (dd, ³J(2,4) 3.8, ³J(2,1) 1.0, H C(2)); 0.93 (s, t-BuSi); 0.18, 0.15 (2s, Me₂Si). ¹³C-NMR

(100.6 MHz, CDCl₃): 136.1 (s, arom. C); 128.8, 128.5, 127.7 (3d, ¹J(C,H) 160, arom. C); 90.1 (d, ¹J(C,H) 152,

C(7)); 79.0 (d, ¹J(C,H) 156, C(1)); 78.8 (d, ¹J(C,H) 141, C(8)); 73.6 (t, ¹J(C,H) 148, PhCH₂O); 73.0

(d, ¹J(C,H) 156, C(6)); 66.4 (d, ¹J(C,H) 152, C(5)); 54.9 (d, ¹J(C,H) 181, C(4)); 49.1 (d, ¹J(C,H) 177,

C(2)); 25.6 (q, ¹J(C,H) 125, Me₃CSi); 17.9 (s, Me₃CSi); 4.4, 4.7 (2q, ¹J(C,H) 119, Me₂Si). CI-MS (NH₃):

396 (1, [M 18] ), 379 (3, [M 1] ), 321 (14, [M C₄H₉] ), 288 (2, [M Bn H] ), 108 (9, BnOH ), 91 (100,

C₇H₇). Anal. calc. for C₂₀H₃₀O₅Si (378.59): C 63.45, H 8.00, Si 7.42; found: C 63.31, H 7.93, Si 7.42.

(1S,2S,4S,5R,6R,7S,8R)-7-endo-(Benzyloxy)-8-exo-{[(tert-butyl)dimethylsilyl]oxy}-3,9-dioxatricyclo[4.2.1.0^2,4]-

nonan-5-endo-ol (( )-18). As described for (Æ)-18, with ()-17. Colorless oil. [a]_D²⁵

21, [a]

22,

25

577

25

[a]

25, [a]

40, [a]

47 (c 0.9, CH₂Cl₂).

546

435

405

(1RS,2SR,4RS,5SR,6SR,7RS,8RS)-7-endo-(Benzyloxy)-8-exo-hydroxy-3,9-dioxatricyclo[4.2.1.0^2,4]non-5-

endo-yl Benzoate ((Æ)-19). A mixture of (Æ)-16 (4.89 g, 10.1 mmol), anh. THF (170 ml), and Bu₄NF (1m in

THF; 12.6 ml, 12.6 mmol) was stirred at 08 for 3.5 h. After the addition of H₂O (600 ml), the mixture was

extracted with CH₂Cl₂(2 Â 500 ml, then 4 Â 250 ml). The combined org. extract was dried (MgSO₄) and

evaporated and the residue crystallized from Et₂O ( 208, 24 h): 1.90 g of white crystals. The mother liquor was

evaporated and the residue purified by FC (4.5 Â 18 cm, light petroleum ether/AcOEt 2 :3): 0.79 g of colorless

crystals. Global yield: 2.69 g (66% based on (Æ)-13) of (Æ)-16. M.p. 122 ± 1238. UV (MeCN): 280 (1050), 272

(1250), 268 (1200), 228 (9400). IR (KBr): 3315, 2965, 2390, 1720, 1715, 1450, 1280, 1270, 1120, 1035, 860, 710.

¹H-NMR (400 MHz, CDCl₃): 7.92, 7.54, 7.31 (3m, 2 H, 1 H, 7 H, arom. H); 5.31 (d, ³J(5,6) 5.1, H C(5)); 4.80

(ddd, ³J(6,7) 6.8, ³J(6,5) 5.1, ⁴J(6,4) 1.7,

H

C(6)); 4.70, 4.58 (2d, ²J 11.8, PhCH₂O); 4.42

(br. d, ³J(8,OH) 8.5, H C(8)); 4.39 (m, ⁴J(1,7) 1.7, H C(1)); 4.17 (br. dd, ³J(7,6) 6.8, ⁴J(7,1) 1.7,

H

C(7)); 3.45 (dd, ³J(4,2) 3.9, ⁴J(4,6) 1.7,

H

C(4)); 3.18 (br. d, ³J(2,4) 3.9,

H C(2)); 2.08

(d, ³J(OH,8) 8.5, OH C(8)). ¹³C-NMR (100.6 MHz, CDCl₃): 165.7 (s, CO); 137.4, 129.4 (2s, arom. C);

133.2, 129.8, 128.4, 128.3, 127.8, 127.4 (6d, ¹J(C,H) 160, arom. C); 87.4 (d, ¹J(C,H) 149, C(7)); 78.8

(d, ¹J(C,H) 164, C(1)); 78.4 (d, ¹J(C,H) 150, C(8)); 73.4 (d, ¹J(C,H) 159, C(6)); 73.4 (t, ¹J(C,H) 141,

PhCH₂O); 67.4 (d, ¹J(C,H) 152, C(5)); 53.0 (d, ¹J(C,H) 184, C(4)); 48.8 (d, ¹J(C,H) 179, C(2)). CI-MS

(NH₃): 369 (2, [M 1] ), 263 (7, [M Bz] ), 105 (100, Bz ), 91 (66, C₇H₇), 81 (11, C₅H₅O ), 77 (20, C₆H₅).

Anal. calc. for C₂₁H₂₀O₆(368.38): C 68.46, H 5.48; found: C 68.53, H 5.54.

(1R,2S,4R,5S,6S,7R,8R)-7-endo-(Benzyloxy)-8-exo-hydroxy-3,9-dioxatricyclo[4.2.1.0^2,4]non-5-endo-yl

Benzoate (( )-19). As described for (Æ)-19, with ( )-16. Yield 75% based on ( )-13. White solid. M.p. 95 ± 968.

[a]²_D⁵

46, [a]

48, [a]

55, [a]

91, [a]

109 (c 1.0, CH₂Cl₂).

25

577

546

435

405

(1RS,2RS,4SR,5RS,6RS,7RS,8SR)-7-endo-(Benzyloxy)-8-exo-[(methylsulfonyl)oxy]-3,9-dioxatricyclo-

[4.2.1.0^2,4]non-5-endo-yl Benzoate (20). A mixture of (Æ)-19 (150 mg, 0.41 mmol), anh. CH₂Cl₂(3 ml),

MeSO₂Cl (40 ml, 0.52 mmol), and Et₃N (85 ml, 0.61 mmol) was stirred at 208 for 30 min. After the addition of

CH₂Cl₂(30 ml), the soln. was washed successively with 1n HCl (25 ml) and sat. aq. NaHCO₃soln. (25 ml). The

aq. phases were extracted with CH₂Cl₂(2 Â 30 ml) and the combined org. extracts dried (MgSO₄) and

evaporated. The residue was purified by FC (1 Â 15 cm, light petroleum ether/AcOEt 1:1): 143 mg of 20 (79%).

Colorless solid. M.p. 113 ± 1148. UV (MeCN): 272 (1500), 229 (12000), 200 (13500). IR (KBr): 3435, 3060, 3030,

1380

Helvetica Chimica Acta ± Vol. 84 (2001)

2935, 2865, 1715, 1455, 1370, 1280, 1180, 1120, 955, 710, 530, 510. ¹H-NMR (400 MHz, CDCl₃): 7.91, 7.55, 7.35 ±

7.23 (3m, 2 H, 1 H, 7 H, arom. H); 5.32 (d, ³J(5,6) 5.2, H C(5)); 5.27 (s, H C(8)); 4.82 (ddd, ³J(6,7) 6.8,

³J(6,5) 5.2, ⁴J(6,4) 1.6,

H

C(6)); 4.73, 4.59 (2d, ²J 11.8, PhCH₂O); 4.66 (br. s,

H C(1)); 4.48

(br. d, ³J(7,6) 6.8,

H

C(7)); 3.47 (dd, ³J(4,2) 3.8, ⁴J(4,6) 1.6,

H

C(4)); 3.26 (br. d, ³J(2,4) 3.8,

H

C(2)); 3.07 (s, MeSO₂). ¹³C-NMR (100.6 MHz, CDCl₃): 165.6 (s, CO), 136.8, 129.2, (2s, arom. C);

133.3, 129.8, 128.4, 128.0, 127.7 (5d, ¹J(C,H) 160, arom. C); 84.2 (d, ¹J(C,H) 151, C(7)); 83.2 (d, ¹J(C,H)

155, C(8)); 76.6 (d, ¹J(C,H) 164, C(1)); 73.6 (t, ¹J(C,H) 141, PhCH₂O); 73.0 (d, ¹J(C,H) 159, C(6)); 66.9

(d, ¹J(C,H) 154, C(5)); 52.6 (d, ¹J(C,H) 186, C(4)); 48.1 (d, ¹J(C,H) 181, C(2)); 38.7 (q, ¹J(C,H) 140,

MeSO₂). CI-MS (NH₃): 447 (13, [M H] ), 367 (1, [M Ms] ), 341 (32, [M Bz] ), 261 (6, [M Bn

OMs H] ), 235 (5, [M Bn OBz H] ), 122 (5, BzOH ), 105 (82, Bz ), 91 (100, C₇H₇), 77 (24, C₆H₅).

Anal. calc. for C₂₂H₂₂O₈S (446.51): C 59.13, H 4.98, S 7.18; found: C 59.31, H 4.99, S 7.12.

(1RS,2RS,4SR,5RS,6RS,7RS,8SR)-7-endo-(Benzyloxy)-8-exo-{[(4-methylphenyl)sulfonyl]oxy}-3,9-dioxa-

tricyclo[4.2.1.0^2,4]non-5-endo-yl Benzoate (21). As described for 20, with (Æ)-19 (150 mg, 0.41 mmol), TsCl

(170 mg, 0.89 mmol), and Et₃N (280 ml, 2.01 mmol). FC (2 Â 15 cm; light petroleum ether/AcOEt 3 :1): 189 mg

(89%) of 21. Colorless solid. M.p. 142 ± 1438. UV (MeCN): 272 (2600), 263 (2700), 227 (23000), 200 (22500). IR

(KBr): 3035, 2970, 2880, 1710, 1595, 1455, 1370, 1270, 1180, 1140, 1115, 985, 965, 790, 720. ¹H-NMR (400 MHz,

CDCl₃): 7.86, 7.52, 7.39, 7.31 ± 7.21, 7.12 (5m, 4 H, H, 2 H, 5 H, 2 H, arom. H); 5.27 (d, ³J(5,6) 5.3, H C(5));

5.07 (m, ³J(8,7) 1.2, H C(8)); 4.74 (ddd, ³J(6,7) 6.9, ³J(6,5) 5.3, ⁴J(6,4) 1.6, H C(6)); 4.47, 4.39 (2d, ²J

11.7, PhCH₂O); 4.43 (m, ⁴J(1,7) 1.5, H C(1)); 4.40 (ddd, ³J(7,6) 6.9, ³J(7,8) 1.2, ⁴J(7,1) 1.5, H C(7));

3.40 (dd, ³J(4,2) 3.7, ⁴J(4,6) 1.6, H C(4)); 3.13 (br. d, ³J(2,4) 3.7, H C(2)); 2.47 (s, MeC₆H₄). ¹³C-NMR

(100.6 MHz, CDCl₃): 165.6 (s, CO); 145.7, 136.7, 133.2, 129.2 (4s, arom. C); 133.2, 130.2, 129.8, 128.3, 127.9,

127.8, 127.4 (7d, ¹J(C,H) 160, arom. C); 84.8 (d, ¹J(C,H) 154, C(8)); 84.6 (d, ¹J(C,H) 149, C(7)); 76.3

(d, ¹J(C,H) 160, C(1)); 73.3 (t, ¹J(C,H) 143, PhCH₂O); 72.7 (d, ¹J(C,H) 159, C(6)); 66.9 (d, ¹J(C,H) 151,

C(5)); 52.4 (d, ¹J(C,H) 185, C(4)); 48.2 (d, ¹J(C,H) 180, C(2)); 21.7 (q, ¹J(C,H) 127, MeC₆H₄). CI-MS

(NH₃): 523 (1, [M H] ), 417 (7, [M Bz] ), 155 (5, Ts ), 122 (12, BzOH ), 105 (82, Bz ), 91 (100, C₇H₇), 77

(18, C₆H₅). Anal. calc. for C₂₈H₂₆O₈S (522.61): C 64.35, H 5.02, S 6.13; found: C 64.36, H 5.06, S 6.02.

(1RS,2RS,4SR,5RS,6RS,7RS,8SR)-7-endo-(Benzyloxy)-8-exo-{[(4-nitrophenyl)sulfonyl]oxy}-3,9-dioxatri-

cyclo[4.2.1.0^2,4]non-5-endo-yl Benzoate (22). As described for 20, with (Æ)-19 (150 mg, 0.41 mmol), 4-

nitrobenzenesulfonyl chloride (0.2 g, 0.90 mmol), and Et₃N (280 ml, 2.01 mmol). FC (2 Â 15 cm, light petroleum

ether/AcOEt 7 :3): 174 mg (77%) of 22. Yellowish solid. M.p. 162 ± 1638. UV (MeCN): 231 (20500), 200

(25500). IR (KBr): 3110, 3070, 2940, 2875, 1720, 1605, 1535, 1450, 1370, 1350, 1270, 1190, 1120, 1095, 960, 865,

840, 740, 715, 615. ¹H-NMR (400 MHz, CDCl₃): 8.41, 8.13, 7.89, 7.54, 7.33 ± 7.23, 7.15 (6m, 2 H, 2 H, 2 H, H, 5 H,

2 H, arom. H); 5.30 (d, ³J(5,6) 5.2, H C(5)); 5.23 (m, ³J(8,7) 1.2, H C(8)); 4.78 (ddd, ³J(6,7) 6.8,

³J(6,5) 5.2, ⁴J(6,4) 1.6, H C(1)); 4.57, 4.51 (2d, ²J 11.8, PhCH₂O); 4.54 (m, ⁴J(1,7) 1.3, H C(1)); 4.43

(ddd, ³J(7,6) 6.8, ³J(7,8) 1.2, ⁴J(7,1) 1.3, H C(7)); 3.45 (dd, ³J(4,2) 3.7, ⁴J(4,6) 1.6, H C(4)); 3.21

(br. d, ³J(2,4) 3.7, H C(2)). ¹³C-NMR (100.6 MHz, CDCl₃): 165.6 (s, CO); 151.0, 141.8, 136.5, 129.1 (4s,

arom. C); 133.4, 129.8, 128.5, 128.4, 128.1, 127.4 (6d, ¹J(C,H) 160, arom. C); 129.2, 124.7 (2d, ¹J(C,H) 170,

arom. C); 85.7 (d, ¹J(C,H) 155, C(8)); 84.3 (d, ¹J(C,H) 148, C(7)); 76.3 (d, ¹J(C,H) 163, C(1)); 73.6

(t, ¹J(C,H) 140, PhCH₂O); 72.9 (d, ¹J(C,H) 154, C(6)); 66.8 (d, ¹J(C,H) 152, C(5)); 52.4 (d, ¹J(C,H) 183,

C(4)); 48.0 (d, ¹J(C,H) 179, C(2)). CI-MS (NH₃): 571 (59, [M 18] ), 554 (100, [M 1] ), 481 (5, [M Bn

H 18] ), 465 (6, [M BzH 18] ), 448 (9, [M Bz] ), 351 (2, [M ONs] ), 122 (9, BzOH ), 108 (31,

BnOH ), 105 (91, Bz ), 91 (85, C₇H₇), 77 (13, C₆H₅). Anal. calc. for C₂₇H₂₃NO₁₀S (553.57): C 58.58, H 4.20,

N 2.53, S 5.79; found: C 58.41, H 4.31, N 2.48, S 5.73.

(1RS,2SR,3SR,4SR,5SR,6RS,7SR)-6-endo-(Benzyloxy)-2-exo,4-endo-dihydroxy-7-exo-[(methylsulfonyl)-

oxy]-8-oxabicyclo[3.2.1]oct-3-endo-yl Benzoate (23). To a soln. of 20 (122 mg, 0.27 mmol) in CH₂Cl₂(3 ml),

CF₃COOH (210 ml, 2.74 mmol) was added, and the mixture was stirred at r.t. for 20 min. After dilution with sat.

NaHSO₃soln. (20 ml), the mixture was extracted with CH₂Cl₂(6 Â 20 ml). The combined org. layers were dried

(MgSO₄) and evaporated. FC (light petroleum ether/AcOEt 1 :2) afforded 23 (102 mg, 80%). White solid. M.p.

99 ± 1008. UV (MeCN): 273 (2000), 229 (12500), 199 (19000). IR (KBr): 3421, 3014, 2856, 1700, 1352, 1276, 1174,

1

1127, 1115, 961, 710. H-NMR (400 MHz, CDCl₃): 8.05, 7.53, 7.35, 7.29 (4m, 2 H, 1 H, 5 H, 2 H, arom. H); 5.63

(d, ³J(7,6) 2.9, H C(7)); 5.51 (br. d, ³J(3,4) 5.6, H C(3)); 4.85, 4.79 (2d, ²J 11.2, PhOCH₂); 4.63

(br. dd, ³J(6,5) 6.7, ³J(6,7) 2.9,

H

C(7)); 4.55 (dd, ³J(5,6) 6.7, ³J(5,4) 5.0,

H C(5)); 4.38

(ddd, ³J(4,OH) 11.6, ³J(4,3) 5.6, ³J(4,5) 5.0, H C(4)); 4.32 (br. s, H C(1)); 4.10 (br. s, H C(2)); 3.19

(br. d, ³J(OH,4) 11.6, OH C(4)); 3.03 (s, MeSO₂); 2.85 (br. s, OH C(2)). ¹³C-NMR (100.6 MHz, CDCl₃):

165.5 (s, CO); 136.1, 128.9 (2s, arom. C); 133.6, 129.9, 128.8, 128.6, 128.5, 128.2 (6d, ¹J(C,H) 160, arom. C);

86.6 (d, ¹J(C,H) 150, C(6)); 82.8 (d, ¹J(C,H) 159, C(1)); 81.7 (d, ¹J(C,H) 154, C(7)); 74.7 (t, ¹J(C,H) 143,

Helvetica Chimica Acta ± Vol. 84 (2001)

1381

PhCH₂O); 74.0 (d, ¹J(C,H) 155, C(5)); 71.4 (d, ¹J(C,H) 156, C(3)); 68.9 (d, ¹J(C,H) 147, C(2)); 66.2

(d, ¹J(C,H) 147, C(4)); 38.4 (q, ¹J(C,H) 139, MeSO₂). CI-MS (NH₃): 482 (15, [M 18] ), 465 (10, [M

1] ), 447 (16, [M OH] ), 359 (16, [M Bz] ), 263 (16, [M Bz MsOH] ), 105 (100, Bz ), 91 (93, C₇H₇),

77 (26, C₆H₅). Anal. calc. for C₂₂H₂₄O₉S (464.53): C 56.88, H 5.21, S 6.90; found: C 56.76, H 5.32, S 6.85.

(1RS,2SR,3SR,4SR,5SR,6RS,7SR)-6-endo-(Benzyloxy)-2-exo,4-endo-dihydroxy-7-exo-{[(4-methylphen-

yl)sulfonyl]oxy}-8-oxabicyclo[3.2.1]oct-3-endo-yl Benzoate (24). As described for 23, starting from 21 (115 mg,

0.22 mmol). FC (1 Â 13 cm, light petroleum ether/AcOEt 1:1): 93 mg (78%) of 24. White solid. M.p. 143 ± 1458.

UV (MeCN): 273 (2800), 266 (2900), 226 (23500), 201 (24000). IR (KBr): 3455 (br.), 3065, 2915, 1725, 1600,

1450, 1365, 1265, 1180, 1115, 1095, 1075, 970, 840, 715. ¹H-NMR (400 MHz, CDCl₃): 7.90, 7.63, 7.55, 7.35, 7.19, 7.06

(6m, 2 H, 2 H, 1 H, 3 H, 4 H, 2 H, arom. H); 5.38 (br. d, ³J(3,4) 5.4, H C(3)); 5.21 (d, ³J(7,6) 3.2, H C(7));

4.58 (br. dd, ³J(6,5) 6.8, ³J(6,7) 3.2, H C(6)); 4.56, 4.46 (2d, ²J 11.0, PhCH₂O); 4.50 (dd, ³J(5,6) 6.8,

³J(5,4) 5.0, H C(5)); 4.33 (ddd, ³J(4,OH) 12.0, J(4,3) 5.4, J(4,5) 5.0, H C(4)); 4.23 (br. s, H C(1));

3

3.90 (br. d, ³J(2,OH) 8.4,

H

C(2)); 3.11 (d, ³J(OH,4) 12.0, OH C(4)); 2.69 (d, ³J(OH,2) 8.4,

OH C(2)); 2.36 (s, MeC₆H₄). ¹³C-NMR (100.6 MHz, CDCl₃): 165.3 (s, CO); 136.1, 133.3, 128.9 (3s, arom.

C); 133.4, 130.1, 129.9, 128.7, 128.5, 127.9, 127.8 (7d, ¹J(C,H) 160, arom. C); 86.5 (d, ¹J(C,H) 152, C(6)); 82.9

(d, ¹J(C,H) 153, C(7)); 82.7 (d, ¹J(C,H) 163, C(1)); 74.3 (t, ¹J(C,H) 144, PhCH₂O); 73.9 (d, ¹J(C,H) 157,

C(5)); 71.7 (d, ¹J(C,H) 158, C(3)); 68.8 (d, ¹J(C,H) 146, C(2)); 66.1 (d, ¹J(C,H) 143, C(4)); 21.7

(q, ¹J(C,H) 128, MeC₆H₄). CI-MS (NH₃): 540 (1, M ), 523 (2, [M OH] ), 435 (13, [M Bz] ), 236 (3,

M

TsOH Bz] ), 155 (3, Ts ), 122 (6, BzOH ), 105 (92, Bz ), 91 (100, C₇H₇), 77 (32, C₆H₅). Anal. calc. for

C₂₈H₂₈O₉S (540.63): C 62.20, H 5.23, S 5.93; C 62.10, H 5.08, S 5.93.

(1RS,2SR,3SR,4SR,5SR,6RS,7SR)-6-endo-(Benzyloxy)-2-exo,4-endo-dihydroxy-7-exo-{[(4-nitrophenyl)-

sulfonyl]oxy}-8-oxabicyclo[3.2.1]oct-3-endo-yl Benzoate (25). As described for 23, with 22 (127 mg,

0.23 mmol): 95 mg (72%) of 25. Colorless solid. M.p. 1478. UV (MeCN): 232 (17000), 200 (22500). IR

(KBr): 3520, 3420, 3105, 3065, 2950, 2915, 1715, 1535, 1375, 1350, 1275, 1255, 1190, 1115, 1100, 1075, 965, 850,

725, 610. ¹H-NMR (400 MHz, CDCl₃): 8.04, 7.91, 7.84, 7.53, 7.38, 7.21, 7.12 (7m, 2 H, 2 H, 2 H, 1 H, 3 H, 2 H, 2 H,

arom. H); 5.37 (dm, ³J(3,4) 5.5, H C(3)); 5.19 (d, ³J(7,6) 3.2, H C(7)); 4.67, 4.51 (2d, ²J 10.6, PhCH₂O);

4.61 (ddm, ³J(6,5) 6.6, ³J(6,7) 3.2,

H

C(6)); 4.57 (dd, ³J(5,6) 6.6, ³J(5,4) 4.8,

H C(5)); 4.36

(ddd, ³J(4,OH) 11.9, ³J(4,3) 5.5, ³J(4,5) 4.8, H C(4)); 4.33 (br. s, H C(1)); 4.02 (br. d, ³J(2,OH) 8.3,

H

C(2)); 2.96 (d, ³J(OH,4) 11.9, OH C(4)); 2.57 (br. d, ³J(OH,2) 8.3, OH C(2)). ¹³C-NMR (100.6 MHz,

CDCl₃): 165 (s, CO); 150.8, 140.8, 135.9, 128.6 (4s, arom. C); 133.8, 129.8, 128.9, 128.8, 128.5, 128.1

(6d, ¹J(C,H) 160, arom. C); 129.2, 124.4 (2d, ¹J(C,H) 173, arom. C); 86.4 (d, ¹J(C,H) 146, C(6)); 84.2

(d, ¹J(C,H) 155, C(7)); 82.2 (d, ¹J(C,H) 160, C(1)); 75.0 (t, ¹J(C,H) 143, PhCH₂O); 73.8 (d, ¹J(C,H) 157,

C(5)); 71.7 (d, ¹J(C,H) 158, C(3)); 68.6 (d, ¹J(C,H) 151, C(2)); 66.0 (d, ¹J(C,H) 145, C(4)). CI-MS (NH₃):

589 (19, [M 18] ), 572 (2, [M H] ), 554 (2, [M OH] ), 466 (6, [M Bz] ), 386 (15, [M Ns H] ), 369

(11, [M ONs] ), 311 (12, [M C₆H₄NO₂OBz OH] ), 296 (12, [M Bn Ns 2 H] ), 282 (19, [M

Bz Ns 2 H] ), 279 (14, [M Bn ONs H] ), 108 (17, BnOH ), 105 (100, Bz ), 91 (92, C₇H₇), 77 (15,

C₆H₅). Anal. calc. for C₂₇H₂₅NO₁₁S (571.60): C 56.73, H 4.42, N 2.45, S 5.61; found: C 56.81, H 4.51, N 2.39,

S 5.64.

(1RS,2SR,3SR,4SR,5RS,6RS,7SR)-2-exo,4-endo-Bis(acetyloxy)-6-endo-(benzyloxy)-7-exo-[(methylsulfo-

nyl)oxy]-8-oxabicyclo[3.2.1]oct-3-endo-yl Benzoate (26). DMAP (2 mg) was added to a stirred mixture of 23

(70 mg, 0.151 mmol), Ac₂O (0.8 ml), and pyridine (0.8 ml) cooled to 08. After stirring at 08 for 30 min, stirring

was continued at 208 for 4 h. The solvent was evaporated and the residue purified by FC (1 Â 15 cm, light

petroleum ether/AcOEt 3 :2): 72 mg (87%) of 26. White solid. M.p. 172 ± 1758. UV (MeCN): 274 (2600), 230

(15500), 199 (25000). IR (KBr): 3020, 2950, 1740, 1600, 1500, 1460, 1360, 1270, 1235, 1220, 1175, 1120, 1055, 965,

715. ¹H-NMR (400 MHz, CDCl₃): 8.10, 7.49, 7.26, 7.18 (4m, 2 H, 1 H, 2 H, 5 H, arom. H); 5.78 (d, ³J(7,6) 3.4,

H

C(7)); 5.61 (m, ³J(3,4) 5.1, ³J(3,2) 1.7, H C(3)); 5.53 (dd, ³J(4,3) 5.1, ³J(4,5) 4.8, H C(4)); 5.10

(dd, ³J(2,3) 1.7, ³J(2,1) 1.7, H C(2)); 4.65, 4.58 (2d, ²J 11.2, PhCH₂O); 4.60 (br. dd, ³J(5,6) 6.3, ³J(5,4)

4.8, H C(5)); 4.56 (br. dd, ³J(6,5) 6.3, ³J(6,7) 3.4, H C(6)); 4.46 (m, ³J(1,2) 1.7, H C(1)); 3.05

(s, MeSO₂); 2.18, 1.92 (2s, 2 Ac). ¹³C-NMR (100.6 MHz, CDCl₃): 169.6, 169.4, 165.3 (3s, CO); 136.8, 128.8

(2s, arom. C); 133.4, 130.1, 128.3, 128.2, 127.7, 127.3 (6d, ¹J(C,H) 160, arom. C); 85.9 (d, ¹J(C,H) 149, C(6));

82.8 (d, ¹J(C,H) 155, C(7)); 80.4 (d, ¹J(C,H) 161, C(1)); 73.7 (t, ¹J(C,H) 140, PhCH₂O); 73.5 (d, ¹J(C,H)

155, C(5)); 70.4 (d, ¹J(C,H) 153, C(2)); 67.0 (d, ¹J(C,H) 159, C(3)); 66.5 (d, ¹J(C,H) 148, C(4)); 38.3

(q, ¹J(C,H) 139, MeSO₂); 20.8, 20.5 (2q, ¹J(C,H) 130, 2 MeCO₃). CI-MS (NH₃): 548 (1, M ), 505 (1, [M

Ac] ), 443 (9, [M Bz] ), 122 (9, BzOH ), 105 (100, Bz ), 91 (99, C₇H₇), 77 (22, C₆H₅). Anal. calc. for

C₂₆H₂₈O₁₁S (548.61): C 56.62, H 5.15, S 5.85; found: C 56.91, H 5.10, S 5.71.

1382

Helvetica Chimica Acta ± Vol. 84 (2001)

(1RS,2SR,3SR,4SR,5RS,6RS,7SR)-2-exo,4-endo-Bis(acetyloxy)-6-endo-(benzyloxy)-7-exo-{[(4-methyl-

phenyl)sulfonyl]oxy}-8-oxabicyclo[3.2.1]oct-3-endo-yl Benzoate (27). As described for 26, with 24 (75 mg,

0.139 mmol): 74 mg (85%) of 27. Colorless solid. M.p. 156 ± 1588. UV (MeCN): 272 (2800), 265 (2900), 227

(18500), 198 (29500). IR (KBr): 3070, 2960, 1735, 1600, 1450, 1370, 1270, 1225, 1175, 1100, 1050, 995, 720, 555.

¹H-NMR (400 MHz, CDCl₃): 7.96, 7.75, 7.49, 7.23 ± 7.06 (4m, 2 H, 2 H, 1 H, 9 H, arom. H); 5.52 (m, ³J(3,4) 5.1,

³J(3,2) 1.8, H C(3)); 5.46 (dd, ³J(4,3) 5.1, ³J(4,5) 4.8, H C(4)); 5.41 (d, ³J(7,6) 3.5, H C(7)); 4.93

(dd, ³J(2,3) 1.8, ³J(2,1) 1.8, H C(2)); 4.54 (dd, ³J(5,6) 6.3, ³J(5,4) 4.8, H C(5)); 4.49, 4.31 (2d, ²J 11.2,

PhCH₂O); 4.47 (dd, ³J(6,5) 6.3, ³J(6,7) 3.5, H C(6)); 4.36 (m, ³J(1,2) 1.8, H C(1)); 2.37 (s, MeC₆H₄),

2.17, 1.90 (2s, 2 Ac). ¹³C-NMR (100.6 MHz, CDCl₃): 169.6, 139.1, 165.1 (3s, 3 CO); 145.3, 137.0, 132.5, 128.8

(4s, arom. C); 133.2, 130.1, 130.0, 128.2, 128.1, 128.0, 127.6, 127.1 (8d, ¹J(C,H) 160, arom. C); 85.7 (d, ¹J(C,H)

147, C(6)); 83.4 (d, ¹J(C,H) 155, C(7)); 80.4 (d, ¹J(C,H) 161, C(1)); 73.5 (t, ¹J(C,H) 142, PhCH₂O); 73.2

(d, ¹J(C,H) 158, C(5)); 70.0 (d, ¹J(C,H) 152, C(2)); 67.1 (d, ¹J(C,H) 158, C(3)); 66.6 (d, ¹J(C,H) 148,

C(4)); 21.7 (q, ¹J(C,H) 127, MeC₆H₄); 20.9, 20.6 (2q, ¹J(C,H) 130, 2 MeCO). CI-MS (NH₃): 642 (1, [M

18] ), 624 (1, M ), 519 (19, [M Bz] ), 155 (6, Ts ), 122 (13, BzOH ), 105 (86, Bz ), 91 (100, C₇H₇), 77 (19,

C₆H₅). Anal. calc. for C₃₂H₃₂O₁₁S (624.71): C 61.52, H 5.17, S 5.13; found: C 61.64, H 5.19, S 5.18.

(1RS,2SR,3SR,4SR,5RS,6RS,7SR)-2-exo,4-endo-Bis(acetyloxy)-6-endo-(benzyloxy)-7-exo-{[(4-nitrophen-

yl)sulfonyl]oxy}-8-oxabicyclo[3.2.1]oct-3-endo-yl Benzoate (28). As described for 26, with 25 (75 mg,

0.131 mmol): 82 mg (95%) of 28. White solid. M.p. 192 ± 1948. UV (MeCN): 232 (18000), 202 (19500). IR

(KBr): 3110, 3070, 3035, 3960, 1745, 1725, 1535, 1375, 1275, 1235, 1185, 1055, 715. ¹H-NMR (400 MHz, CDCl₃):

8.11, 7.99, 7.52, 7.26, 7.18, 7.07 (6m, 2 H, 4 H, 1 H, 1 H, 4 H, 2 H, arom. H); 5.54 (dddd, ³J(3,4) 5.2, ³J(3,2) 1.8,

⁴J(3,5) 1.5, ⁴J(3,1) 1.5, H C(3)); 5.49 (d, ³J(7,6) 3.8, H C(7)); 5.48 (dd, ³J(4,3) 5.2, ³J(4,5) 5.0,

H

C(4)); 4.96 (dd, ³J(2,1) 1.9, ³J(2,3) 1.8, H C(2)); 4.57 (m, ³J(5,6) 6.3, ³J(5,4) 5.0, ⁴J(5,3) 1.5,

3

C(5)); 4.56, 4.30 (2d, ²J 10.8, PhCH₂O); 4.48 (dd, ³J(6,5) 6.3, J(6,7) 3.8, H C(6)); 4.38 (m, ³J(1,2)

1.9, ⁴J(1,3) 1.5, H C(1)); 2.17, 1.92 (2s, 2 Ac). ¹³C-NMR (100.6 MHz, CDCl₃): 169.4, 169.2, 165.0 (3s, CO);

150.8, 141.2, 136.6, 128.7 (4s, arom. C); 133.6, 130.1, 128.3, 128.1, 127.3 (5d, ¹J(C,H) 160, arom. C); 129.3, 124.5

(2d, ¹J(C,H) 170, arom. C); 85.8 (d, ¹J(C,H) 147, C(6)); 84.7 (d, ¹J(C,H) 156, C(7)); 79.9 (d, ¹J(C,H) 161,

C(1)); 73.9 (t, ¹J(C,H) 140, PhCH₂); 73.3 (d, ¹J(C,H) 156, C(5)); 69.9 (d, ¹J(C,H) 152, C(2)); 67.2

(d, ¹J(C,H) 159, C(3)); 66.4 (d, ¹J(C,H) 147, C(4)); 20.8, 20.6 (2q, ¹J(C,H) 130, MeCO). CI-MS (NH₃): 655

(1, M ), 550 (5, [M Bz] ), 122 (5, BzOH ), 105 (95, Bz ), 91 (100, C₇H₇), 77 (22, C₆H₅). Anal. calc. for

C₃₁H₂₉NO₁₃S (655.68): C 56.78, H 4.47, N 2.14, S 4.89; found: C 56.89, H 4.36, N 2.22, S 4.90.

(1RS,2RS,4SR,5RS,6SR,7RS)-7-endo-(Benzyloxy)-8-oxo-3,9-dioxatricyclo[4.2.1.0^2,4]non-5-endo-yl Ben-

zoate ((Æ)-40). A mixture of (Æ)-19 (2.66 g, 7.2 mmol), anh. CH₂Cl₂(150 ml), and 1,1,1-tris(acetyloxy)-1,1-

dihydro-1,2-benziodoxol-3(1H)-one (5.15 g, 12.1 mmol) was stirred at 208 for 4 h. After the addition of Et₂O

(400 ml), the soln. was washed successively with sat. aq. NaHCO₃soln. (400 ml) containing Na₂S₂O₃(19 g,

120 mmol), sat. aq. NaHCO₃soln. (400 ml), and H₂O (400 ml). The aq. phases were extracted with Et₂O

(2 Â 300 ml). The combined org. extracts were dried (MgSO₄) and evaporated: 2.62 g (100%) of (Æ)-40.

Yellowish, viscous oil, which was used as such in the next step. An anal. sample was obtained by FC (1 Â 12 cm,

CH₂Cl₂/AcOEt 95 :5): colorless solid. M.p. 119 ± 1208. UV (MeCN): 274 (1700), 229 (12500), 202 (12000). IR

(KBr): 3035, 2945, 2870, 1775, 1725, 1600, 1455, 1310, 1265, 1115, 1065, 1030, 860, 745, 720, 695. ¹H-NMR

(400 MHz, CDCl₃): 7.97, 7.55, 7.35 ± 7.17 (3m, 2 H, 1 H, 7 H, arom. H); 5.50 (dd, ³J(5,6) 6.0, ⁴J(5,2) 0.6,

H

C(5)); 5.03 (ddd, ³J(6,7) 7.6, ³J(6,5) 6.0, ⁴J(6,4) 1.6, H C(6)); 4.81, 4.65 (2d, ²J 11.8, PhCH₂O); 4.42

(br. dd, ³J(1,2) 1.7, ⁴J(1,7) 1.8,

H

C(1)); 4.34 (dd, ³J(7,6) 7.6, ³J(7,1) 1.8,

H C(7)); 3.44

(br. dd, ³J(4,2) 3.8, ⁴J(4,6) 1.6, H C(4)); 3.28 (ddd, ³J(2,4) 3.8, ³J(2,1) 1.7, ⁴J(2,5) 0.6, H C(2)).

¹³C-NMR (100.6 MHz, CDCl₃): 207.5 (s, C(8)); 165.7 (s, CO); 136.3, 129.0 (2s, arom. C); 133.4, 129.9, 128.4,

128.1, 128.0 (5d, ¹J(C,H) 160, arom. C); 78.5 (d, ¹J(C,H) 144, C(7)); 73.9 (t, ¹J(C,H) 146, PhCH₂O); 72.8

(d, ¹J(C,H) 166, C(1)); 70.2 (d, ¹J(C,H) 164, C(6)); 65.4 (d, ¹J(C,H) 153, C(5)); 51.1 (d, ¹J(C,H) 180,

C(4)); 46.6 (d, ¹J(C,H) 186, C(2)). CI-MS (NH₃): 385 (1, [M H 18] ), 367 (1, [M H] ), 279 (7, [M

Bz 18] ), 122 (10, BzOH ), 105 (100, Bz ), 91 (73, C₇H₇), 77 (28, C₆H₅). Anal. calc. for C₂₁H₁₈O₆(366.39):

C 68.84, H 4.96; found: C 68.81, H 5.03.

(1S,2S,4R,5S,6R,7S)-7-endo-(Benzyloxy)-8-oxo-3,9-dioxatricyclo[4.2.1.0^2,4]non-5-endo-yl Benzoate (( )-

40). As described for (Æ)-40, with ( )-19. White solid. M.p. 122 ± 1248. [a]_D²⁵

152, [a]

160, [a]

25

577

546

25

185, [a]

355, [a]

364 (c 1.0, CH₂Cl₂).

435

405

(1RS,2RS,3SR,4SR,5SR,6RS)-6-endo-(Benzyloxy)-2-exo,4-endo-dihydroxy-7-oxo-8-oxabicyclo[3.2.1]oct-

3-endo-yl Benzoate ((Æ)-41). A mixture of (Æ)-40 (2.62 g, 7.15 mmol), CH₂Cl₂(120 ml), and CF₃COOH

(5.5 ml, 8.2 g, 72 mmol) was stirred at 208 for 1 h. After the addition of sat. aq. NaHCO₃soln. (120 ml), the

mixture was extracted with CH₂Cl₂(6 Â 100 ml). The combined org. extracts were dried (MgSO₄) and

Helvetica Chimica Acta ± Vol. 84 (2001)

1383

evaporated: 2.69 g (96%) of (Æ)-41. Yellowish, viscous oil, which was used as such in the next step. An anal.

sample was obtained by FC (light petroleum ether/AcOEt 2 :3): white solid. M.p. 138 ± 1398. UV (MeCN): 229

(10400), 268 (1300), 274 (1350), 281 (1200). IR (KBr): 3510, 3430, 2950, 2875, 2365, 1770, 1720, 1690, 1600, 1455,

1405, 1270, 1100, 1070, 670. ¹H-NMR (400 MHz, CDCl₃): 8.07, 7.53, 7.34 (3m, 2 H, 1 H, 7 H, arom. H); 5.49

3

4

(m, ³J(3,4) 5.0, J(3,2) 2.0, J(3,1) 1.8, H C(3)); 5.00, 4.92 (2d, ²J 11.5, PhCH₂); 4.80 (br. dd, ³J(5,6)

7.4, ³J(5,4) 4.9, H C(5)); 4.55 (m, ³J(6,5) 7.4, ⁴J(6,1) 1.7, H C(6)); 4.54 (br. ddd, ³J(4,OH) 11.9,

³J(4,3) 5.0, ³J(4,5) 4.9, H C(4)); 4.17 (ddd, ³J(1,2) 2.5, ⁴J(1,3) 1.8, ⁴J(1,6) 1.7,

H C(1)); 4.10

(br. ddd, ³J(2,OH) 8.1, ³J(2,1) 2.5, ³J(2,3) 2.0, H C(2)); 3.05 (d, ³J(OH,4) 11.9, OH C(4)); 2.96

(d, ³J(OH,2) 8.1, OH C(2)). ¹³C-NMR (100.6 MHz, CDCl₃): 207.3 (s, C(7)); 165.6 (s, CO); 136.0, 128.6

(2s, arom. C); 133.5, 130.3, 128.7, 128.3, 128.0 (5d, ¹J(C,H) 160, arom. C); 80.8 (d, ¹J(C,H) 139, C(6)); 79.0

(d, ¹J(C,H) 161, C(1)); 74.7 (t, ¹J(C,H) 143, PhCH₂O); 73.4 (d, ¹J(C,H) 158, C(5)); 71.4 (d, ¹J(C,H) 158,

C(3)); 68.9 (d, ¹J(C,H) 153, C(2)); 65.8 (d, ¹J(C,H) 147, C(4)). CI-MS (NH₃): 385 (3, [M 1] ), 279 (13,

[M Bz] ), 105 (74, Bz ), 91 (100, C₇H₇), 77 (20, C₆H₅). Anal. calc. for C₂₁H₂₀O₇(384.41): C 65.61, H 5.25;

found: C 65.67, H 5.30.

(1S,2S,3R,4R,5R,6S)-6-endo-(Benzyloxy)-2-exo,4-endo-dihydroxy-7-oxo-8-oxabicyclo[3.2.1]oct-3-endo-yl

25

Benzoate (( )-41). As described for (Æ)-41, with ( )-40. White foam. [a]_D²⁵

41, [a]

42, [a]

46,

577

546

25

[a]

54, [a]

40 (c 1.1, CH₂Cl₂).

435

405

(1RS,2RS,3SR,4SR,5SR,6RS)-2-exo,4-endo-Bis(acetyloxy)-6-endo-(benzyloxy)-7-oxo-8-oxabicyclo[3.2.1]-

oct-3-endo-yl Benzoate ((Æ)-42). As described for the preparation of 26, with (Æ)-41 (2.65 g, 6.89 mmol). FC

(5 Â 18 cm, light petroleum ether/AcOEt 3 :2): 2.68 g (79% based on (Æ)-19) of (Æ)-42. White foam. UV

(MeCN): 274 (1950), 230 (15200), 201 (17200). IR (KBr): 3070, 3035, 2980, 2870, 1750, 1730, 1600, 1455, 1370,

1270, 1220, 1095, 1055, 715. ¹H-NMR (400 MHz, CDCl₃): 8.08, 7.50, 7.33, 7.18 (4m, 2 H, 1 H, 2 H, 5 H, arom. H);

5.66 (dd, ³J(4,5) 4.6, ³J(4,3) 4.6, H C(4)); 5.62 (m, ³J(3,4) 4.6, ³J(3,2) 2.1, H C(3)); 5.05 (dd, ³J(2,3)

2.1, ³J(2,1) 2.0, H C(2)); 4.86 (br. dd, ³J(5,6) 7.0, ³J(5,4) 4.6, H C(5)); 4.73, 4.69 (2d, ²J 11.5,

PhCH₂O); 4.56 (dd, ³J(6,5) 7.0, ⁴J(6,1) 1.2, H C(6)); 4.41 (m, ³J(1,2) 2.0, ³J(1,6) 1.2, H C(1)); 2.21,

1.93 (2s, 2 Ac). ¹³C-NMR (100.6 MHz, CDCl₃): 205.5 (s, C(7)); 169.7, 169.3, 165.3 (3s, CO); 136.7, 128.4 (2s,

arom. C); 133.3, 130.5, 128.1, 127.7, 127.1 (5d, ¹J(C,H) 160, arom. C); 81.1 (d, ¹J(C,H) 140, C(6)); 76.9

(d, ¹J(C,H) 163, C(1)); 73.7 (t, ¹J(C,H) 141, PhCH₂O); 72.7 (d, ¹J(C,H) 160, C(5)); 69.9 (d, ¹J(C,H) 155,

C(2)); 67.1 (d, ¹J(C,H) 159, C(3)); 66.2 (d, ¹J(C,H) 147, C(4)); 20.8, 20.5 (2q, ¹J(C,H) 130, 2 MeCO). CI-

MS (NH₃): 486 (5, [M 18] ), 469 (5, [M 1] ), 363 (3, [M Bz] ), 347 (2, [M BzO] ), 289 (3, [M BzO

AcO H] ), 247 (3, [M BzO AcO Ac 2 H] ), 180 (13), 138 (10), 105 (85, Bz ), 91 (100, C₇H₇), 77 (20,

C₆H₅). Anal. calc. for C₂₅H₂₄O₉(468.49): C 64.09, H 5.17; found: C 63.21, H 5.16.

(1S,2S,3R,4R,5R,6S)-2-exo,4-endo-Bis(acetyloxy)-6-endo-(benzyloxy)-7-oxo-8-oxabicyclo[3.2.1]oct-3-en-

do-yl Benzoate (()-42). As described for (Æ)-42, with ( )-41. Yield 72% based on ( )-19. Colorless oil. [a]_D²⁵

25

3.7, [a] 4.7, [a] 7.3, [a] 40, [a] 76 (c 1.3, CH₂Cl₂).

577

546

435

405

(1RS,2RS,5SR,6SR,7RS,8SR)-6-exo,8-endo-Bis(acetyloxy)-2-endo-(benzyloxy)-4-oxo-3,9-dioxabicyclo[3.3.1]-

non-7-endo-yl Benzoate ((Æ)-43). A dried soln. of 70% 3-chloroperbenzoic acid (3.22 g, 13.1 mmol; Fluka) was

made by dissolving mCPBA in CH₂Cl₂(200 ml) and drying with MgSO₄. After filtration, 175 ml of this soln.

were used to dissolved (Æ)-42 (2.68 g, 5.72 mmol). NaHCO₃(0.96 g, 11.4 mmol) was added and the mixture

stirred at 208 for 12 h. Then 0.5m aq. Na₂S₂O₃(50 ml) was added slowly under vigourous stirring. After 1 h,

AcOEt (400 ml) was added and the soln. washed successively with 0.5m aq. Na₂S₂O₃(150 ml), sat. aq. NaHCO₃

soln. (200 ml), and brine (200 ml). The aq. layers were extracted with AcOEt (2 Â 200 ml) and the org. extracts

dried (MgSO₄) and evaporated. The residue was purified by FC (5 cm Â 17 cm, light petroleum ether/AcOEt

3 :2): 2.3 g (83%) of (Æ)-43. Colorless oil that crystallized slowly. Washing of the crystals with Et₂O gave 1.5 g of

colorless crystals. M.p. 130 ± 1318. UV (MeCN): 281 (1100), 273 (1300), 267 (1200), 263 (1200), 230 (11900), 202

(11400). IR (KBr): 3065, 3035, 2965, 2910, 1755, 1740, 1730, 1265, 1240, 1225, 1210, 1145, 1105, 1045, 715.

¹H-NMR (400 MHz, CDCl₃): 8.10, 7.55, 7.43, 7.19, 7.01 (5m, 10 arom. H); 5.91 (d, ³J(2,1) 4.8, H C(2)); 5.62

3

(dd, ³J(7,8) 3.7, J(7,6) 3.3, H C(7)); 5.56 (dd, ³J(8,1) 5.9, J(8,7) 3.7, H C(8)); 5.34 (dd, ³J(6,7) 3.3,

³J(6,5) 1.8, H C(6)); 4.91, 4.53 (2d, ²J 11.3, PhCH₂O); 4.64 (d, ³J(5,6) 1.8, H C(5)); 4.63 (dd, ³J(1,8)

5.9, ³J(1,2) 4.8, H C(1)); 2.18, 1.76 (2s, Ac). ¹³C-NMR (100.6 MHz, CDCl₃): 170.0, 169.0, 165.1, 165.0 (4s,

C(4), 3 CO); 135.5, 128.7 (2s, arom. C); 133.5, 130.1, 128.4, 128.2, 128.0, 127.6 (6d, ¹J(C,H) 160, arom. C);

100.7 (d, ¹J(C,H) 174, C(2)); 72.0 (t, ¹J(C,H) 143, PhCH₂O); 70.5 (d, ¹J(C,H) 156, C(6)); 70.0

(d, ¹J(C,H) 159, C(5)); 66.7 (d, ¹J(C,H) 159, C(7)); 66.1 (d, ¹J(C,H) 148, C(8)); 65.2 (d, ¹J(C,H) 154,

C(1)); 20.7, 20.3 (2q, ¹J(C,H) 130, 2 MeCO). CI-MS (NH₃): 502 (77, [M 18] ), 485 (26, [M H] ), 363 (11,

[M BzO] ), 108 (21, BnOH ), 105 (87), 91 (100), 77 (12). Anal. calc. for C₂₅H₂₄O₁₀(484.49): C 61.97, H 5.00;

found: C 61.82, H 5.10.

1384

Helvetica Chimica Acta ± Vol. 84 (2001)

(1R,2R,5S,6S,7R,8S)-6-exo,8-endo-Bis(acetyloxy)-2-endo-(benzyloxy)-4-oxo-3,9-dioxabicyclo[3.3.1]non-

7-endo-yl Benzoate (( )-43). As described for (Æ)-43, with ()-42. White foam. Yield 84%. [a]_D²⁵

75,

25

[a]

78, [a]

89, [a]

145, [a]

169 (c 1.3, CH₂Cl₂).

577

546

435

405

Mixture of Methyl 5,7-Di-O-acetyl-4,8-anhydro-6-O-benzoyl-3-O-benzyl-2-deoxy-1-C-phenyl-dl-erythro-

ld-manno- and -dl-erythro-ld-gluco-nonuronate (45a,b). A mixture of (Æ)-43 (20 mg, 0.04 mmol), 1-phenyl-1-

[(trimethylsilyl)oxy]ethene (40 ml, 37 mg, 0.19 mmol), anh. MeNO₂(0.7 ml), and Me₃SiOSO₂CF₃(added the

latest, 100 mg) was stirred at 208 for 1 h. After the addition of anh. MeOH (0.1 ml), the mixture was stirred at

208 for 17 h. A sat. aq. NaHCO₃soln. (5 ml) was added and the mixture extracted with CH₂Cl₂(5 ml, 4 times).

The combined org. extracts were dried (MgSO₄) and evaporated. FC (1 Â 15 cm, CH₂Cl₂/Et₂O 95 :5) gave 16 mg

(63%) of (Æ)-45a/(Æ)-45b 1 :1. Colorless oil.

Mixture of Methyl 3,5-Di-O-acetyl-2,6-anhydro-4-O-benzoyl-7-O-benzyl-8,9,10-trideoxy-ld-erythro-dl-

manno-dec-9-enonate and -dl-threo-dl-manno-dec-9-enonate (46a,b). Me₃SiOSO₂CF₃(100 mg) was added to

a stirred soln. of (Æ)-43 (54 mg, 0.111 mmol) and 3-(trimethylsilyl)prop-2-ene (69 mg, 0.604 mmol) in anh.

MeCN (1.5 ml) cooled to 08. After stirring at 08 for 1 h, anh. MeOH (0.1 ml) was added and the mixture stirred

at 208 for 18 h. A sat. aq. NaHCO₃soln. (5 ml) was added and the mixture extracted with CH₂Cl₂(4 Â 5 ml). The

combined org. extracts were dried (MgSO₄) and evaporated: 58 mg of (Æ)-46a/(Æ)-46b 4.3 :1. FC (2 Â 15 cm,

light petroleum ether/CH₂Cl₂/Et₂O 40 :57:3): 8 mg (13%) of (Æ)-46a and 38 mg (63%) of (Æ)-46b.

Data for (Æ)-46a: R_f0.16. Colorless oil. UV (MeCN): 229 (21200), 209 (15900). IR (film): 3060, 3035, 2985,

2955, 1755, 1740, 1725, 1455, 1370, 1275, 1220, 1120, 1090, 1055, 715, 695. ¹H-NMR (400 MHz, CDCl₃): 7.94, 7.56,

3

7.41, 7.30 (4m, 2 H, 1 H, 2 H, 5 H, arom. H); 5.90 (dddd, ³J(9,10cis) 16.8, J(9,10trans) 10.5, J(9,8b) 8.6,

³J(9,8a) 5.9, H C(9)); 5.88 (d, ³J(5,4) 3.4, H C(5)); 5.56 (dd, ³J(3,4) 10.1, ³J(3,2) 10.0, H C(3)); 5.32

(dd, ³J(4,3) 10.1, ³J(4,5) 3.4,

H

C(4)); 5.18 (br. d, ³J(10cis,9) 16.8, H_cisC(10)); 5.17

(br. d, ³J(10trans,9) 10.5, H_transC(10)); 4.56, 4.33 (2d, ²J 10.8, PhCH₂O); 4.02 (d, ³J(2,3) 10.0, H C(2));

3.79 (s, COOMe); 3.67 (m, ³J(7,8b) 3.3,

H

C(6), H C(7)); 2.68 (m, ²J(8a,8b) 14.5, ³J(8a,9) 5.9,

H_aC(8)); 2.41 (br. ddd, ²J(8b,8a) 14.5, ³J(8b,9) 8.6, ³J(8b,7) 3.3, H_bC(8)); 2.06, 1.97 (2s, 2 Ac).

¹³C-NMR (100.6 MHz, CDCl₃): 169.8, 169.7, 167.7, 165.2 (4s, 4 CO); 137.2 (s, arom. C); 133.3, 133.1

(2d, ¹J(C,H) 161, 155, C(9), arom. C); 129.6 (d, ¹J(C,H) 160, arom. C); 129.1 (s, arom. C); 128.6, 128.5,

128.4, 127.9 (4d, ¹J(C,H) 160, arom. C); 118.5 (t, ¹J(C,H) 155, C(10)); 77.3 (d, ¹J(C,H) 138, C(7)); 76.9

(d, ¹J(C,H) 155, C(2)); 73.6 (d, ¹J(C,H) 145, C(6)); 72.6 (d, ¹J(C,H) 147, C(4)); 71.4 (t, ¹J(C,H) 145,

PhCH₂O); 67.1, 67.0 (2d, ¹J(C,H) 155, C(3), C(5)); 52.8 (q, ¹J(C,H) 148, COOMe); 33.4 (t, ¹J(C,H) 129,

C(8)); 20.8, 20.6 (2q, ¹J(C,H) 130, 2 MeCO). CI-MS (NH₃): 558 (100, [M NH₄] ). Anal. calc. for C₂₉H₃₂O₁₀

(540.61): C 64.43, H 5.98; found: C 64.42, H 6.05.

Data for (Æ)-46b: R_f0.12. Colorless solid. M.p. 116 ± 1188. UV (MeCN): 280 (1150), 272 (1400), 267 (1350),

228 (12800), 201 (11300). IR (KBr): 3070, 3035, 2980, 2955, 2920, 1760, 1740, 1725, 1640, 1455, 1370, 1275, 1235,

1120, 1095, 715. ¹H-NMR (400 MHz, CDCl₃): 7.94, 7.58, 7.44, 7.39 ± 7.26 (4m, 2 H, 1 H, 2 H, 5 H, arom. H); 5.90

(dddd, ³J(9,10cis) 17.2, ³J(9,10trans) 10.1, ³J(9,8b) 7.9, ³J(9,8a) 6.1, H C(9)); 5.69 (br. d, ³J(5,4) 3.4,

H

C(5)); 5.62 (dd, ³J(3,4) 10.1, ³J(3,2) 10.0, H C(3)); 5.28 (dd, ³J(4,3) 10.1, ³J(4,5) 3.4, H C(4)); 5.15

(br. d, ³J(10cis,9) 17.2, H_cisC(10)); 5.13 (br. d, ³J(10trans,9) 10.1, H_transC(10)); 4.80, 4.65 (2d, ²J 11.4,

PhCH₂O); 4.08 (d, ³J(2,3) 10.0, H C(2)); 3.80 (s, COOMe); 3.79 (br. d, ³J(6,7) 8.0, H C(6)); 3.70

(ddd, ³J(7,6) 8.0, ³J(7,8b) 6.8, ³J(7,8a) 3.6, H C(7)); 2.39 (m, ²J(8a,8b) 14.7, ³J(8a,9) 6.1, ³J(8a,7)

3.6, H_aC(8)); 2.16 (br. ddd, ²J(8b,8a) 14.7, ³J(8b,9) 7.9, ³J(8b,7) 6.8, H_bC(8)); 2.12, 1.99 (2s, 2 Ac).

¹³C-NMR (100.6 MHz, CDCl₃): 170.0, 169.7, 167.7, 165.4 (4s, 4 CO); 138.5, 129.0 (2s, arom. C); 133.5, 133.3

(2d, ¹J(C,H) 162, 155, C(9), arom. C); 129.6, 128.5, 128.3, 127.9, 127.6 (5d, ¹J(C,H) 160, arom. C); 118.2

(t, ¹J(C,H) 156, C(10)); 80.5 (d, ¹J(C,H) 141, C(6)); 77.6 (d, ¹J(C,H) 138, C(7)); 76.5 (d, ¹J(C,H) 151,

C(2)); 74.0 (t, ¹J(C,H) 142, PhCH₂O); 72.6 (d, ¹J(C,H) 148, C(4)); 67.5 (d, ¹J(C,H) 153, C(5)); 66.6

(d, ¹J(C,H) 156, C(3)); 52.7 (q, ¹J(C,H) 148, COOMe); 35.0 (t, ¹J(C,H) 128, C(8)); 20.7, 20.6

(2q, ¹J(C,H) 130, 2 MeCO). CI-MS (NH₃): 558 (100, [M 18] ), 540 (2, M ), 481 (6, [M Ac] ), 433 (7,

[M OBn] ), 105 (52), 91 (78), 77 (9). Anal. calc. for C₂₉H₃₂O₁₀(540.61): C 64.43, H 5.98; found: C 64.36,

H 5.91.

Mixture of Methyl 3,5-Di-O-acetyl-2,6-anhydro-4-O-benzoyl-7-O-benzyl-7-C-cyano-ld-erythro-dl-manno-

heptonate and -dl-threo-dl-manno-heptonate (47a,b). As described for 45a,b with (Æ)-43 (18 mg, 0.037 mmol)

and Me₃SiCN instead of PhCH(OSiMe₃)CH₂. FC (1 Â 16 cm, light petroleum ether/CH₂Cl₂/Et₂O 20 :76 :4):

2 mg (10%) of pure (Æ)-47a (R_f0.38) and 6 mg (Æ)-47b/(Æ)-47a 4 :1.

1

Data for (Æ)-47a: R_f0.38. Colorless oil. H-NMR (400 MHz, CDCl₃): 7.91, 7.58, 7.43, 7.36 ± 7.28 (4m, 2 H,

3

1 H, 2 H, 5 H, arom. H); 5.75 (dd, ³J(5,4) 3.3, J(5,6) 1.1, H C(5)); 5.51 (dd, ³J(3,4) 10.2, J(3,2) 10.0,

H

C(3)); 5.29 (dd, ³J(4,3) 10.2, ³J(4,5) 3.3, H C(4)); 4.84, 4.53 (2d, ²J 11.9, PhCH₂O); 4.18 (d, ³J(7,6)

Helvetica Chimica Acta ± Vol. 84 (2001)

1385

9.1,

H

C(7)); 4.14 (d, ³J(2,3) 10.0,

H

C(2)); 4.08 (dd, ³J(6,7) 9.1, ³J(6,5) 1.1,

H

C(6)); 3.78

(s, COOMe); 1.99, 1.84 (2s, 2 MeCO). CI-MS (NH₃): 543 (100, [M 18] ), 526 (2, [M H] ), 525 (1, M ),

499 (2, [M CN] ), 436 (11), 426 (4), 359 (4), 105 (35), 91 (23), 77 (10).

1

Data for (Æ)-47b: R_f0.27. Colorless oil. H-NMR (400 MHz, CDCl₃): 7.93, 7.58, 7.46 ± 7.32 (3m, 2 H, 1 H,

7 H, arom. H); 5.90 (dd, ³J(5,4) 3.3, ³J(5,6) 1.1, H C(5)); 5.67 (dd, ³J(3,4) 10.2, ³J(3,2) 10.0, H C(3));

5.30 (dd, ³J(4,3) 10.2, ³J(4,5) 3.3, H C(4)); 4.89, 4.56 (2s, ²J 11.9, PhCH₂O); 4.47 (d, ³J(7,6) 6.2,

H

C(7)); 4.08 (d, ³J(2,3) 10.0, H C(2)); 3.96 (dd, ³J(6,7) 6.2, ³J(6,5) 1.1, H C(6)); 3.79 (s, COOMe);

2.19, 1.98 (2s, 2 Ac). CI-MS (NH₃): 543 (100, [M 18] ), 499 (1, [M CN] ), 436 (10), 426 (5), 359 (4), 105

(38), 91 (21), 77 (10).

Methyl 3,5-Di-O-acetyl-2,6-anhydro-4-O-benzoyl-dl-glycero-dl-galacto-hepturonate ((Æ)-48). A soln. of

Hg(ClO₄)₂´ (H₂O)_3.4(125 mg, 0.272 mmol) in MeCN (1 ml) was added dropwise to a stirred soln. of (Æ)-57 in

MeCN (6.5 ml). After stirring at 208 for 45 min, CHCl₃(100 ml) was added, followed by Ag₂CO₃(630 mg).

After stirring at 208 for 15 min, the precipitate was filtered off (Celite) and the solvent evaporated. The residue

was taken up in CH₂Cl₂/light petroleum ether, the precipitate filtered off (Celite), and the filtrate evaporated.

The latter operation was repeated four more times, giving 48 mg (98%) of crude (Æ)-48, which was used as such

in the next step. Traces of H₂O were eliminated (if required) by azeotropic distillation with anh. toluene.

¹H-NMR (400 MHz, CDCl₃): 9.61 (s, H C(1)); 7.93, 7.58, 7.44 (3m, 2 H, 1 H, 2 H, arom. H); 5.99 (dd, ³J(3,4)

3.4, ³J(3,2) 1.5, H C(3)); 5.66 (dd, ³J(5,4) 10.1, ³J(5,6) 9.9, H C(5)); 5.36 (dd, ³J(4,5) 10.1, ³J(4,3)

3.4, H C(4)); 4.26 (d, ³J(2,3) 1.5, H C(2)); 4.20 (d, ³J(6,5) 9.9, H C(6)); 3.83 (s, COOMe); 2.07, 2.00 (2s,

2 Ac). ¹³C-NMR (100.6 MHz, CDCl₃): 195.9 (d, ¹J(C,H) 187, C(1)); 169.5, 169.3, 167.0, 165.3 (4s, 4 CO);

133.6, 129.7, 128.6 (3d, ¹J(C,H) 160, arom. C); 128.7 (s, arom. C); 80.7 (d, ¹J(C,H) 141, C(2)); 76.6

(d, ¹J(C,H) 154, C(6)); 71.7 (d, ¹J(C,H) 148, C(4)); 67.3 (d, ¹J(C,H) 156, C(3)); 66.3 (d, ¹J(C,H) 156,

C(5)); 53.0 (q, ¹J(C,H) 148, COOMe); 20.5, 20.4 (2q, ¹J(C,H) 130, 2 MeCO). CI-MS (NH₃): 426 (0.1, [M

18] ), 379 (0.2, [M CHO] ), 349 (0.6, [M AcO] ), 287 (4, [M BzO] ), 229 (6), 201 (41), 105 (100), 77

(22).

Dibenzyl Acetal of Methyl 3,5-Di-O-acetyl-2,6-anhydro-4-O-benzoyl-dl-glycero-dl-galacto-hepturonate

(51). Me₃SiOSO₂CF₃(25 ml) was added to a soln. of (Æ)-43 (100 mg, 0.21 mmol) and PhCH₂OSiMe₃(80 ml,

75 mg, 0.41 mmol) in anh. CHCl₃(3.5 ml) cooled to 108. The soln. became dark yellow. After stirring at 108

for 75 min, anh. MeOH (0.2 ml) was added and the mixture stirred at 208 for 12 h. A sat. aq. NaHCO₃soln.

(5 ml) was added to the colorless soln., the mixture extracted with CH₂Cl₂(4 Â 5 ml), the combined org. extract

dried (MgSO₄) and evaporated and the yellowish oily residue crystallized from heptane and a few drops of

AcOEt: 103 mg (82%) of pure 51. Colorless crystals. M.p. 122 ± 1238. UV (MeCN): 280 (1700), 272 (1900), 263

(2050), 229 (13800), 199 (23000). IR (KBr): 3065, 3030, 2950, 1755, 1720, 1600, 1455, 1375, 1285, 1235, 1120,

1060, 720. ¹H-NMR (400 MHz, CDCl₃): 7.92, 7.56, 7.45 ± 7.21 (3m, 2 H, 1 H, 12 H, arom. H); 5.81 (dd, ³J(3,4)

3.4, ³J(3,2) 1.1,

H

C(3)); 5.54 (dd, ³J(5,4) 10.1, ³J(5,6) 10.0,

H

C(5)); 5.28 (dd, ³J(4,5) 10.1,

³J(4,3) 3.4, H C(4)); 4.79, 4.70 (2d, ²J 11.8, PhCH₂O); 4.77 (d, ³J(1,2) 7.1, H C(1)); 4.65, 4.45 (2d, ²J

11.6, PhCH₂O); 3.93 (d, ³J(6,5) 10.0,

H

C(6)); 3.85 (dd, ³J(2,1) 7.1, ³J(2,3) 1.1,

H C(2)); 3.78

(s, COOMe); 1.97, 1.90 (2s, 2 Ac). ¹³C-NMR (100.6 MHz, CDCl₃): 169.6, 169.5, 167.4, 165.3 (4s, 4 CO);

138.0, 136.2, 129.1 (3s, arom. C); 133.4, 129.6, 129.0, 128.5, 128.4, 128.1, 127.7 (7d, ¹J(C,H) 160, arom. C); 97.5

(d, ¹J(C,H) 166, C(1)); 77.8 (d, ¹J(C,H) 141, C(2)); 76.6 (d, ¹J(C,H) 148, C(6)); 72.3 (d, ¹J(C,H) 147,

C(4)); 68.8, 68.7 (2t, ¹J(C,H) 144, 2 PhCH₂O); 67.6 (d, ¹J(C,H) 156, C(3)); 66.6 (d, ¹J(C,H) 155, C(5));

52.7 (q, ¹J(C,H) 148, COOMe); 20.6 (q, ¹J(C,H) 130, 2 MeCO). CI-MS (NH₃): 626 (54, [M 18] ), 499 (20,

[M OBn] ), 367 (9), 366 (8), 108 (17), 105 (49), 91 (100), 77 (12). Anal. calc. for C₃₃H₃₄O₁₁(606.67): C 65.33,

H 5.66; found: C 65.36, H 5.76.

O-Benzyl S-Phenyl Monothioacetal of Methyl 3,5-Di-O-acetyl-2,6-anhydro-4-O-benzoyl-dl-glycero-dl-

galacto-hepturonate (52 and 53). As described for 51, with (Æ)-43 (106 mg, 0.22 mmol) and PhSSiMe₃(200 ml,

190 mg, 1.05 mmol) instead of BnOSiMe₃. The crude oil containing 52/53 1:3.3 was crystallized from AcOEt/

pentane yielding 91 mg (68%) of 53 as colorless crystals. The mother liquor was evaporated and purified by FC

(1 Â 12 cm, light petroleum ether/CH₂Cl₂/Et₂O 57:3 :40): 18 mg (14%) of 52 as colorless oil.

Data for 52: R_f0.35. UV (MeCN): 271 (11600), 218 (20800). IR (film): 3065, 3035, 2985, 2955, 1755, 1740,

1725, 1455, 1370, 1275, 1220, 1110, 1090, 1055, 695. ¹H-NMR (400 MHz, CDCl₃): 7.89, 7.55, 7.43 ± 7.34, 7.29 (4m,

3

2 H, 3 H, 5 H, 5 H, arom. H); 5.73 (dd, ³J(3,4) 3.4, J(3,2) 1.1, H C(3)); 5.51 (dd, ³J(5,4) 10.1, J(5,6)

10.0, H C(5)); 5.12 (dd, ³J(4,5) 10.1, ³J(4,3) 3.4, H C(4)); 4.89, 4.77 (2d, ²J 11.3, PhCH₂O); 4.71

(d, ³J(1,2) 8.8, H C(1)); 3.84 (s, COOMe); 3.75 (d, ³J(6.5) 10.0, H C(6)); 3.31 (dd, ³J(2,1) 8.8, J(2,3)

3

1.1, H C(2)); 1.94, 1.84 (2s, 2 MeCO). ¹³C-NMR (100.6 MHz, CDCl₃): 169.5, 167.3, 165.3 (3s, 4 CO); 135.7,

133.3, 129.7, 129.6, 128.9, 128.8, 128.5, 128.4, 128.2 (9d, ¹J(C,H) 160, arom. C); 135.6, 130.0, 129.1 (3s,

1386

Helvetica Chimica Acta ± Vol. 84 (2001)

arom. C); 83.2 (d, ¹J(C,H) 156, C(1)); 76.7 (d, ¹J(C,H) 147, C(6)); 76.1 (d, ¹J(C,H) 144, C(2)); 72.4

(d, ¹J(C,H) 148, C(4)); 69.3 (t, ¹J(C,H) 143, PhCH₂O); 67.4 (d, ¹J(C,H) 157, C(3)); 66.7 (d, ¹J(C,H) 156,

C(5)); 52.9 (q, ¹J(C,H) 148, COOMe); 20.6, 20.5 (2q, ¹J(C,H) 130, 2 MeCO). CI-MS (NH₃): 626 (29, [M

18] ), 499 (21, [M SPh] ), 110 (8), 109 (10), 108 (9), 105 (27), 91 (100), 77 (14). Anal. calc. for C₃₂H₃₂O₁₀S

(608.71): C 63.14, H 5.31; found: C 62.93, H 5.50.

Data for 53: R_f0.30. UV (MeCN): 272 (11000), 218 (19600), 202 (22800). IR (film): 3075, 2985, 2955, 2890,

1755, 1740, 1725, 1275, 1220, 1110, 1090, 1055, 715. ¹H-NMR (400 MHz, CDCl₃): 7.94, 7.55, 7.45 ± 7.29 (3m, 2 H,

3 H, 10 H, arom. H); 6.08 (dd, ³J(3,4) 3.4, ³J(3,2) 0.8, H C(3)); 5.55 (dd, ³J(5,4) 10.2, ³J(5,6) 10.0,

H

C(5)); 5.17 (dd, ³J(4,5) 10.2, ³J(4,3) 3.4, H C(4)); 5.05, 4.79 (2d, ²J 11.9, PhCH₂O); 4.92 (d, ³J(1,2)

8.4, H C(1)); 4.00 (d, ³J(6,5) 10.0, H C(6)); 3.79 (s, COOMe); 3.76 (dd, ³J(2,1) 8.4, ³J(2,3) 0.8,

H

C(2)); 1.98, 1.96 (2s, 2 MeCO). ¹³C-NMR (100.6 MHz, CDCl₃): 169.7, 169.5, 167.5, 165.3 (4s, 4 CO);

137.0, 131.0, 129.2 (3s, arom. C); 134.0, 133.4, 129.6, 129.2, 128.5, 128.45, 128.4, 128.0, 127.9 (9d, ¹J(C,H) 160,

arom. C); 85.9 (d, ¹J(C,H) 158, C(1)); 78.5 (d, ¹J(C,H) 155, C(2)); 76.5 (d, ¹J(C,H) 147, C(6)); 72.6

(d, ¹J(C,H) 147, C(4)); 70.5 (t, ¹J(C,H) 143, PhCH₂O); 67.8 (d, ¹J(C,H) 152, C(3)); 66.5 (d, ¹J(C,H) 156,

C(5)); 52.7 (q, ¹J(C,H) 148, COOMe); 20.6 (q, ¹J(C,H) 130, 2 MeCO). CI-MS (NH₃): 626 (53, [M 18] ),

499 (23, [M PhS] ), 367 (6), 110 (8), 109 (11), 108 (13), 105 (109), 91 (100), 77 (9). Anal. calc. for C₃₂H₃₂O₁₀S

(608.71): C 63.14, H 5.31, S 5.27; found: C 62.38, H 5.44, S 5.31.

Diphenyl Dithioacetal of Benzyl 3,5-Di-O-acetyl-2,6-anhydro-4-O-benzoyl-dl-glycero-dl-galacto-hepturo-

nate (55). CF₃SO₃H (50 mg), then PhSH (50 ml, 55 mg, 0.50 mmol) were added to a soln. of (Æ)-43 (13 mg,

0.027 mmol) in anh. CH₂Cl₂(0.5 ml). After 1 h at 208, benzyl alcohol (100 mg) was added and the mixture

stirred at 208 for 17 h. After the addition of silica gel (100 mg) and evaporation, the residue was purified by FC

(1 Â 16 cm, light petroleum ether/CH₂Cl₂/Et₂O 40 :57:3): 11 mg (60%) of 55. Colorless oil. ¹H-NMR (400 MHz,

CDCl₃): 7.92, 7.56, 7.48 ± 7.28 (3m, 2 H, 3 H, 15 H, arom. H); 6.11 (dd, ³J(3,4) 3.4, ³J(3,2) 1.1, H C(3)); 5.62

(dd, ³J(5,4) 10.2, ³J(5,6) 10.1, H C(5)); 5.25, 5.19 (2d, ²J 12.1, PhCH₂O); 5.21 (dd, ³J(4,5) 10.2,

³J(4,3) 3.4, H C(4)); 4.52 (d, ³J(1,2) 9.1, H C(1)); 4.01 (d, ³J(6,5) 10.1, H C(6)); 3.66 (dd, ³J(2,1)

3

9.1, J(2,3) 1.1, H C(2)); 1.95, 1.72 (2s, 2 Ac). ¹³C-NMR (100.6 MHz, CDCl₃): 169.5, 169.4, 166.6, 165.4 (4s,

4 CO); 134.9, 133.0, 132.3, 129.0 (4s, arom. H); 134.7, 133.4, 132.9, 129.7, 129.1, 128.9, 128.7 (2Â), 128.6 (2Â),

128.5, 128.3 (12d, ¹J(C,H) 160, arom. C); 78.3 (d, ¹J(C,H) 148, C(2)); 76.8 (d, ¹J(C,H) 153, C(6)); 72.8

(d, ¹J(C,H) 147, C(4)); 67.8 (d, ¹J(C,H) 155, C(3)); 67.6 (t, ¹J(C,H) 149, PhCH₂O); 66.3 (d, ¹J(C,H) 156,

C(5)); 59.4 (d, ¹J(C,H) 154, C(1)); 20.6, 20.4 (2q, ¹J(C,H) 130, MeCO). CI-MS (NH₃): 577 (2, [M SPh] ),

457 (2), 110 (69), 109 (25), 105 (100), 91 (74), 77 (19).

Diethyl Dithioacetal of Benzyl 3,5-Di-O-acetyl-2,6-anhydro-4-O-benzoyl-dl-glycero-dl-galacto-hepturo-

nate (56). A mixture of (Æ)-43 (103 mg, 0.21 mmol), anh. CH₂Cl₂(20 ml), CF₃SO₃H (10 ml, 17 mg, 0.11 mmol),

and EtSH (0.2 ml, 170 mg, 2.70 mmol) was stirred at 208 for 4 h. Benzyl alcohol (0.11 ml, 1.06 mmol) was added

and the mixture stirred at 208 for 16 h. A sat. aq. NaHCO₃soln. (10 ml) was added, and the mixture was

extracted with CH₂Cl₂(3 Â 10 ml). The combined org. extracts were dried (MgSO₄) and evaporated. FC (1.5 Â

15 cm, light petroleum ether/AcOEt 3 :2, then light petroleum ether/CH₂Cl₂/Et₂O 40 :57:3) gave 57 mg (46%)

of 56. Colorless crystals. M.p. 149 ± 1508. UV (MeCN): 280 (1300), 272 (1600), 229 (14000), 200 (16000). IR

(KBr): 2965, 1750, 1725, 1285, 1230, 1125, 710. ¹H-NMR (400 MHz, CDCl₃): 7.92, 7.56, 7.44 ± 7.33 (3m, 2 H, 1 H,

7 H, arom. H); 5.99 (dd, ³J(3,4) 3.4, ³J(3,2) 0.9, H C(3)); 5.59 (dd, ³J(5,4) 10.1, ³J(5,6) 10.0, H C(5));

5.28 (dd, ³J(4,5) 10.1, ³J(4,3) 3.4, H C(4)); 5.20 (s, PhCH₂O); 4.14 (d, ³J(6,5) 10.0, H C(6)); 3.96

(d, ³J(1,2) 9.4, H C(1)); 3.80 (dd, ³J(2,1) 9.4, ³J(2,3) 0.9, H C(2)); 2.82 ± 2.56 (m, ³J 7.4, 2 MeCH₂S);

2.13, 1.73 (2s, 2 Ac); 1.23, 1.22 (2t, ³J 7.4, 2 MeCH₂S). ¹³C-NMR (100.6 MHz, CDCl₃): 169.6, 169.4, 166.8, 165.4

(4s, 4 CO); 134.8, 129.1 (2s, arom. C); 133.3, 129.6, 128.8, 128.6, 128.5 (5d, ¹J(C,H) 160, arom. C); 80.9

(d, ¹J(C,H) 144, C(2)); 76.7 (d, ¹J(C,H) 147, C(6)); 72.8 (d, ¹J(C,H) 147, C(4)); 68.1 (d, ¹J(C,H) 154,

C(3)); 67.6 (t, ¹J(C,H) 149, PhCH₂O); 66.4 (d, ¹J(C,H) 156, C(5)); 49.6 (d, ¹J(C,H) 152, C(1)); 26.6, 24.4

(2t, ¹J(C,H) 140, 2 MeCH₂S); 20.7, 20.4 (2q, ¹J(C,H) 130, 2 MeCO); 14.3 (q, ¹J(C,H) 128, 2 MeCH₂S). CI-

MS (NH₃): 608 (6, [M 18] ), 590 (2, M ), 529 (26, [M SEt] ), 409 (14, [M Bn Et₂S] ), 408 (12, [M

SEt OBz] ), 135 (30), 105 (82), 91 (100), 77 (15). Anal. calc. for C₂₉H₃₄O₉S₂(590.77): C 58.96, H 5.81, S 10.86;

found: C 58.88, H 5.71, S 10.81.

Diethyl Dithioacetal of Methyl 3,5-Di-O-acetyl-2,6-anhydro-4-O-benzoyl-dl-glycero-dl-galacto-hepturo-

nate ((Æ)-57). EtSH (0.4 ml, 340 mg, 5.41 mmol) then CF₃SO₃H (60 ml, 100 mg, 0.69 mmol) were added to a

stirred soln. of (Æ)-43 (0.2 g, 0.42 mmol) in anh. CH₂Cl₂(16 ml). After stirring at 208 for 25 min, anh. MeOH

(1.5 ml) was added, and stirring was continued for 16 h at 208. A sat. aq. NaHCO₃soln. (20 ml) was added, the

aq. layer extracted with CH₂Cl₂(3 Â 20 ml), the combined org. extract dried (MgSO₄) and evaporated, and the

residue submitted to FC (3 Â 13 cm, light petroleum ether/AcOEt 4 :1 (500 ml), then 3 :1): 159 mg (74%) of 57.

Helvetica Chimica Acta ± Vol. 84 (2001)

1387

White solid. M.p. 145 ± 1468. UV (MeCN): 280 (1100), 273 (1300), 228 (12300), 201 (9700). IR (KBr): 2970,

1

2930, 1755, 1725, 1455, 1375, 1290, 1235, 1125, 720. H-NMR (400 MHz, CDCl₃): 7.92, 7.57, 7.44 (3m, 2 H, 1 H,

2 H, arom. H); 6.01 (dd, ³J(3,4) 3.4, ³J(3,2) 1.0, H C(3)); 5.57 (dd, ³J(5,4) 10.1, ³J(5,6) 10.0, H C(5));

5.32 (dd, ³J(4,5) 10.1, ³J(4,3) 3.4, H C(4)); 4.10 (d, ³J(6,5) 10.0, H C(6)); 3.98 (d, ³J(1,2) 9.5, H C(1));

3

3.78 (s, COOMe); 3.77 (dd, ³J(2,1) 9.5, J(2,3) 1.0, H C(2)); 2.81 ± 2.56 (m, ³J 7.4, 2 MeCH₂S); 2.13, 1.99

(2s, 2 Ac); 1.27, 1.22 (2t, ³J 7.4, 2 MeCH₂S). ¹³C-NMR (100.6 MHz, CDCl₃): 169.7, 169.5, 167.4, 165.4 (4s,

4 CO); 133.4, 129.6, 128.5 (3d, ¹J(C,H) 160, arom. C); 129.1 (s, arom. C); 80.7 (d, ¹J(C,H) 139, C(2)); 76.8

(d, ¹J(C,H) 147, C(6)); 72.7 (d, ¹J(C,H) 147, C(4)); 68.0 (d, ¹J(C,H) 153, C(3)); 66.6 (d, ¹J(C,H) 155,

C(5)); 52.8 (q, ¹J(C,H) 148, COOMe); 49.8 (d, ¹J(C,H) 150, C(1)); 26.3, 24.3 (2t, ¹J(C,H) 140,

2 MeCH₂S); 20.8, 20.6 (2q, ¹J(C,H) 130, 2 MeCO); 14.4 (q, ¹J(C,H) 128, 2 MeCH₂S). CI-MS (NH₃): 514

(4, M ), 453 (5, [M SEt] ), 333 (24, [M OBz EtS H] ), 303 (8, [M OBz Et₂S] ), 287 (9), 271 (14),

229 (16), 135 (41), 105 (100), 77 (34). Anal. calc. for C₂₃H₃₀O₉S₂(514.67): C 53.67, H 5.89, S 12.46; found:

C 53.71, H 5.86, S 12.50.

Diethyl Dithioacetal of Methyl 3,5-Di-O-acetyl-2,6-anhydro-4-O-benzoyl-d-glycero-d-galacto-hepturonate

25

(( )-57). As described for (Æ)-57, with ( )-43. Yield 68%. White foam. [a]_D²⁵

87, [a]

89, [a]

103,

577

546

25

[a]

182, [a]

222 (c 0.9, CHCl₃).

435

405

Benzyl 3,5-Di-O-acetyl-2,6-anhydro-4-O-benzoyl-dl-glycero-dl-galacto-hepturonate (58). CdCO₃(50 mg,

0.29 mmol) was suspended in a soln. of HgCl₂(170 mg, 0.63 mmol) in acetone (0.5 ml). After stirring at 208 for

1 h, a soln. of 56 (25 mg, 0.042 mmol) in acetone (0.25 ml) was added and stirring continued for 6 h. After

filtration over a bed of CdCO₃(rinsing with acetone), the filtrate was evaporated, the viscous residue extracted

with CH₂Cl₂(4 Â 1 ml), and the combined extract washed with a KI (0.2 g) soln., Na₂S₂O₄´ H₂O (0.2 g) in H₂O

(5 ml), and then H₂O (10 ml). The aq. layers were extracted with CH₂Cl₂(2 Â 5 ml) and the org. extracts dried

(MgSO₄) and evaporated: 21 mg (100%) of 58. Yellowish foam. ¹H-NMR (400 MHz, CDCl₃): 9.62 (s, H C(1));

7.92, 7.57, 7.44 ± 7.35 (3m, 2 H, 1 H, 7 H, arom. H); 5.97 (dd, ³J(3,4) 3.4, ³J(3,2) 1.5, H C(3)); 5.67

(dd, ³J(5,4) 10.1, ³J(5,6) 10.0, H C(5)); 5.32 (dd, ³J(4,5) 10.1, ³J(4,3) 3.4, H C(4)); 5.26, 5.21 (2d, ²J

12.0, PhCH₂O); 4.24 (d, ³J(2,3) 1.5, H C(2)); 4.23 (d, ³J(6,5) 10.0, H C(6)); 2.06, 1.73 (2s, 2 Ac).

(1RS,2SR,3RS,4SR,5RS,6RS,7SR)-7-endo-(Benzyloxy)-6-exo-{[(tert-butyl)dimethylsilyl]oxy}-3-endo-

[(1RS)-1-hydroxypropyl]-4-exo-(phenylthio)-8-oxabicyclo[3.2.1]octan-2-endo-ol (61). At

788 0.7m

Me₂AlSPh in CH₂Cl₂(1.2 ml, 0.84 mmol) was added to a stirred soln. of (Æ)-13 (0.2 g, 0.56 mmol) in anh.

THF (3 ml). After stirring at 788 for 45 min, propanal (0.2 ml, 160 mg, 2.75 mmol) was added dropwise and

the mixture stirred at 788 for 12 h. The mixture was poured into cold CHCl₃

( 108) and the soln. washed

immediately with ice-cold 1n HCl (20 ml) and then with sat. aq. NaHCO₃soln. (20 ml). The aq. layers were

extracted with CHCl₃(3 Â 20 ml) and the combined org. extracts dried (MgSO₄) and evaporated. The residue 60

was taken in MeOH (10 ml) and cooled to 08. CeCl ´ 6H₂O (200 mg, 0.56 mmol), then NaBH₄(20 mg,

0.53 mmol) were added portionwise. After stirring at 08 for 10 min, AcOEt (50 ml), then sat. aq. NH₄Cl soln.

(25 ml) and H₂O (until dissolution of salts) were added. The aq. layer was extracted with AcOEt (4 Â 25 ml),

and the combined org. extract dried (MgSO₄) and evaporated. FC (2 Â 15 cm, light petroleum ether/Et₂O 3 :2)

gave 187 mg (63%) of 61. Colorless oil. UV (MeCN): 260 (6000), 210 (14500). IR (film): 3420, 2955, 2930, 2855,

1470, 1255, 1115, 1045, 840, 780, 750, 695. ¹H-NMR (400 MHz, CDCl₃): 7.53, 7.41 ± 7.23 (2m, 2 H, 8 H, arom. H);

3

4.88 (br. s, OH C(2)); 4.75, 4.57 (2d, ²J 11.4, PhCH₂O); 4.71 (dd, ³J(2,1) 7.6, J(2,3) 4.5, H C(2)); 4.30

(br. d, ³J(6,7) 4.4, H C(6)); 4.25 (br. s, H C(5)); 4.21 (dd, ³J(1,2) 7.6, ³J(1,7) 5.7, H C(1)); 4.16

(m, ³J(1,3) 3.8, H C(1')); 4.10 (dd, ³J(7,1) 5.7, ³J(7,6) 4.4, H C(7)); 3.69 (br. d, ³J(4,3) 9.9, H C(4));

3.57 (br. s, OH C(1')); 1.75 (m, ³J(2'a,3') 7.4, H_aC(2')); 1.65 (ddd, ³J(3,4) 9.9, J(3,2) 4.5, J(3,1') 3.8,

3

H

C(3)); 1.56 (m, ³J(2'b,3) 7.4, H_bC(2')); 1.03 (dd, ³J(3',2'a) 7.4, ³J(3',2'b) 7.4, H C(3')); 0.82 (s, t-

BuSi); 0.02, 0.16 (2s, Me₂Si). ¹³C-NMR (100.6 MHz, CDCl₃): 136.4, 134.3 (2s, arom. C); 133.4, 129.1, 128.8,

128.5, 128.0, 127.6 (6d, ¹J(C,H) 160, arom. C); 90.3 (d, ¹J(C,H) 151, C(7)); 89.1 (d, ¹J(C,H) 158, C(5)); 82.4

(d, ¹J(C,H) 146, C(6)); 74.2 (t, ¹J(C,H) 144, PhCH₂O); 73.1 (d, ¹J(C,H) 155, C(1)); 72.3 (d, ¹J(C,H) 146,

C(1')); 70.5 (d, ¹J(C,H) 152, C(2)); 49.0 (d, ¹J(C,H) 144, C(4)); 41.5 (d, ¹J(C,H) 128, C(3)); 28.5

(t, ¹J(C,H) 125, C(2')); 25.6 (q, ¹J(C,H) 125, Me₃CSi); 17.7 (s, Me₃CSi); 10.8 (q, ¹J(C,H) 126, C(3'));

4.9, 5.0 (2q, ¹J(C,H) 119, Me₂Si). APCI-MS (pos. mode): 531 (100, [M H] ), 513 (100, [M OH] ), 495

(50, [M H₂O OH] ), 381 (50, [M H₂O (t-Bu)SiO] ). APCI-MS (neg. mode): 529 (100, [M H] ).

Anal. calc. for C₂₉H₄₂O₅SSi (530.87): C 65.61, H 7.97, S 6.04; found: C 65.65, H 7.94, S 5.98.

(1RS,2SR,6RS,7RS,8SR,9RS,10RS,11SR)-11-(Benzyloxy)-10-{[(tert-butyl)dimethylsilyl]oxy}-6-ethyl-4,4-

dimethyl-8-(phenylthio)-3,5,12-trioxatricyclo[7.2.1.0^2,7]dodecane (62). A mixture of 61 (12.0 mg, 22.6 mmol),

acetone (0.5 ml), 2,2-dimethoxypropane (0.5 ml), and pyridinium p-toluenesulfonate ´ H₂O (10 mg) was stirred

at 208 for 1 h. A sat. aq. NaHCO₃soln. (5 ml) was added and the mixture extracted with CHCl₃(4 Â 5 ml). The

1388

Helvetica Chimica Acta ± Vol. 84 (2001)

combined org. extracts were dried (MgSO₄) and evaporated. FC (1 Â 10 cm, light petroleum ether/Et₂O 7:3)

gave 12.2 mg (95%) of 62. Colorless oil. UV (MeCN): 260 (5100), 207 (15000). IR (film): 3065, 3030, 2985,

2955, 2930, 2880, 2855, 1475, 1465, 1380, 1255, 1225, 1105, 1050, 835, 780, 695. ¹H-NMR (400 MHz, CDCl₃): 7.47,

7.31 (2m, 2 H, 8 H, arom. H); 4.75, 4.50 (2d, ²J 12.1, PhCH₂O); 4.62 (dd, ³J(2,7) 8.2, ³J(2,1) 6.7, H C(2));

4.54 (dd, ³J(1,2) 6.7, ³J(1,11) 6.2,

H

C(1)); 4.18 (ddd, ³J(6,7) 10.0, ³J(6,15a) 8.0, ³J(6,15b) 2.8,

H

C(6)); 4.08 (dd,³J(11,1) 6.2, ³J(11,10) 4.1, H C(11)); 4.01 (br. d,³J(10,11) 4.1, H C(10)); 3.88 (br. s,

C(9)); 3.19 (br. d, ³J(8,7) 3.3, H C(8)); 2.21 (ddd, ³J(7,6) 10.0, ³J(7,2) 8.2, ³J(7,8) 3.3, H C(7));

1.81 (ddq, ²J(15b,15a) 14.8, ³J(15b,16) 7.4, ³J(15b,6) 2.8, H_bC(15)); 1.44 (ddq, ²J(15a,15b) 14.8,

³J(15a,16) 8.0, ³J(15a,16) 7.4, H_aC(15)); 1.36 (s, Me(14)); 1.20 (s, Me(13)); 0.98 (dd, ³J(16,15a) 7.4,

³J(16,15b) 7.4, Me(16)); 0.78 (s, t-BuSi); 0.06, 0.13 (2s, Me₂Si). ES-MS (pos. mode): 593 (100, [M Na] ),

571 (20, [M H] ), 513 (35, [M acetone H] ). Anal. calc. for C₃₂H₄₆O₅SSi (570.94): C 67.31, H 8.14; found:

C 67.48, H 8.17.

(1RS,5RS,6RS,7RS)-7-endo-(Benzyloxy)-6-exo-{[(tert-butyl)dimethylsilyl]oxy}-3-[(1SR)-1-hydroxypro-

pyl]-8-oxabicyclo[3.2.1]oct-3-en-2-one (64). At 788 0.5m Me₂AlSeMe in toluene (1.6 ml, 0.8 mmol) was added

to a stirred soln. of (Æ)-13 (0.2 g, 0.55 mmol) in anh. THF (2 ml). After stirring at 788 for 30 min, propanal

(0.2 ml, 160 mg, 2.75 mmol) was added dropwise. After stirring at 788 for 12 h, 100% mCPBA (275 mg,

1.6 mmol) was added. After stirring at 788 for 1 h, the mixture was allowed to warm up to 208 within ca. 3 h.

CHCl₃(20 ml) was added, and the soln. was washed successively with 1n HCl (10 ml), 0.5m aq. Na₂S₂O₃soln.

(10 ml), and sat. aq. NaHCO₃soln. (10 ml). The aq. layers were extracted with CHCl₃(3 Â 10 ml) and the

combined org. extracts dried (MgSO₄) and evaporated. FC (2 Â 13 cm, light petroleum ether/Et₂O 3 :2) gave

182 mg (79%) of 64. Colorless oil. UV (MeCN): 240 (5400), 205 (11000), 193 (15000). IR (film): 3460 (br.),

3065, 3035, 2955, 2930, 2885, 2860, 1695, 1465, 1360, 1255, 1115, 1065, 840. ¹H-NMR (400 MHz, CDCl₃): 7.35 ±

7.24 (m, 5 arom. H); 7.04 (dd, ³J(4,5) 4.9, ⁴J(4,1') 1.1, H C(4)); 4.78 (d, ³J(1,7) 7.0, H C(1)); 4.54, 4.41

4

(2d, ²J 11.2, PhCH₂O); 4.51 (br. d, ³J(5,4) 4.9, H C(5)); 4.35 (m, ³J(1',OH) 5.9, J(1',4) 1.1, H C(1'));

4.27 (br. d, ³J(7,1) 7.0, H C(7)); 4.24 (br. s, H C(6)); 2.27 (d, ³J(OH,1') 5.9, OH C(1')); 1.69 ± 1.52

(m, ³J(2',3') 7.4, 2 H C(2')); 0.90 (s, t-BuSi); 0.87 (t, ³J(3',2') 7.4, Me(3')); 0.11, 0.10 (2s, Me₂Si). ¹³C-NMR

(100.6 MHz, CDCl₃): 195.0 (s, C(2)); 141.6 (d, ¹J(C,H) 159, C(4)); 140.8 (s, C(3)); 136.8 (s, arom. C); 128.4,

128.1, 128.0 (3d, ¹J(C,H) 160, arom. C); 86.1 (d, ¹J(C,H) 153, C(7)); 83.1 (d, ¹J(C,H) 159, C(1)); 81.6

(d, ¹J(C,H) 157, C(5)); 79.4 (d, ¹J(C,H) 150, C(6)); 73.6 (t, ¹J(C,H) 142, PhCH₂O); 70.6 (d, ¹J(C,H) 143,

C(1')); 28.7 (t, ¹J(C,H) 127, C(2')); 25.7 (q, ¹J(C,H) 125, Me₃CSi); 18.1 (s, Me₃CSi); 9.6 (q, ¹J(C,H) 126,

C(3')); 4.9 (q, ¹J(C,H) 119, Me₂Si). CI-MS (NH₃): 436 (100, [M 18] ), 418 (43, M ), 401 (80, [M

OH] ), 269 (20, [M C₃H₇O Bn H] ), 264 (32), 245 (14), 207 (35), 155 (54) 108 (37), 91 (86). Anal. calc.

for C₂₃H₃₄O₅Si (418.66): C 65.98, H 8.20, Si 6.71; found: C 65.80, H 8.19, Si 6.69.

(6R)-6-{(1R,5R,6R,7R)-6-endo-(Benzyloxy)-7-exo-{[(tert-butyl)dimethylsilyl]oxy}-4-oxo-8-oxabicyclo[3.2.1]-

oct-2-en-3-yl}-1,2 :3,4-di-O-isopropylidene-a-d-galacto-pyranose (()-66). At

788, 0.5m Me₂AlSeMe in

toluene (0.7 ml, 0.35 mmol) was added dropwise to a stirred soln. of (Æ)-13 (0.1 g, 0.277 mmol) in anh. THF

(1 ml). After stirring at 788 for 1 h, a soln. of 1,2 :3,4-di-O-isopropylidene-a-d-galactohexodialdo-1,5-

pyranose (( )-65; 40 mg, 0.15 mmol) in anh. THF (0.3 ml) was added dropwise maintaining the temp. below

708. After stirring at 788 for 16 h, 100% mCPBA (135 mg, 0.78 mmol) was added. After stirring at 788 for

1 h, the mixture was allowed to warm up to 208 with in 90 min under stirring. CHCl₃(5 ml) was added, and the

soln. was immediately washed successively with ice-cold 1n HCl (5 ml), 0.5m aq. Na₂S₂O₃(5 ml), and sat. aq.

NaHCO₃soln. (5 ml). The aq. layers were extracted with CHCl₃(3 Â 5 ml) and the combined org. extracts dried

(MgSO₄) and evaporated. FC (1.5 Â 14 cm, light petroleum ether/Et₂O 1:1) gave 45 mg (27%) of ()-66.

25

Colorless foam. [a]²_D⁵ 9.6, [a] 8.8, [a] 13, [a] 187, [a] 544 (c 0.13, CH₂Cl₂). UV (MeCN):

577

546

435

405

237 (6100), 206 (12500), 195 (15000). IR (film): 3510, 2985, 2930, 2860, 1695, 1465, 1385, 1255, 1215, 1115, 1065,

1010, 840. ¹H-NMR (400 MHz, CDCl₃): 7.38 (dd, ³J(2',1') 5.1, ⁴J(2',6) 1.7, H C(2')); 7.36 ± 7.21 (m, 5 ar-

om. H); 5.57 (d, ³J(1,2) 5.0, H C(1)); 4.75 (d, ³J(5',6') 7.0, H C(5')); 4.72 (m, ³J(6,OH) 8.6, ³J(6,5) 5.2,

⁴J(6,2') 1.7,

H

C(6)); 4.57 (br. d, ³J(1',2') 5.1,

H

C(1')); 4.54, 4.38 (2d, ²J 10.9, PhCH₂O); 4.30

(br. d, ³J(6',5') 7.0, H C(6')); 4.27 (dd, ³J(5,6) 5.2, ³J(5,4) 1.7, H C(5)); 4.23 (dd, ³J(4,3) 8.0, ³J(4,5)

1.7, H C(4)); 4.20 (dd, ³J(2,1) 5.0, ³J(2,3) 2.3, H C(2)); 4.19 (br. s, H C(7')); 4.02 (dd, ³J(3,4) 8.0,

³J(3,2) 2.3, H C(3)); 3.73 (d, ³J(OH,6) 8.6, OH C(6)); 1.62, 1.46, 1.33, 1.16 (4s, 2 Me₂C); 0.92 (s, Me₃CSi);

0.12, 0.11 (2s, Me₂Si). ¹³C-NMR (100.6 MHz, CDCl₃): 194.7 (s, C(4')); 144.3 (d, ¹J(C,H) 163, C(2')); 138.1,

136.6 (2s, C(3'), arom. C); 128.7, 128.1, 128.0 (3d, ¹J(C,H) 160, arom. C); 109.0, 108.8 (2s, 2 Me₂C); 96.7

(d, ¹J(C,H) 181, C(1)); 86.5 (d, ¹J(C,H) 153, C(6')); 83.0 (d, ¹J(C,H) 160, C(5')); 81.6 (d, ¹J(C,H) 161,

C(1')); 79.8 (d, ¹J(C,H) 150, C(7')); 74.0 (t, ¹J(C,H) 142, PhCH₂O); 71.5 (d, ¹J(C,H) 151, C(4)); 70.5, 70.4,

70.2 (3d, ¹J(C,H) 150, C(6), C(3), C(2)); 65.5 (d, ¹J(C,H) 141, C(5)); 26.0, 25.7, 25.1, 23.6 (4q, ¹J(C,H) 126,

Helvetica Chimica Acta ± Vol. 84 (2001)

1389

2 Me₂C); 25.7 (q, ¹J(C,H) 125, Me₃CSi); 18.1 (s, Me₃C); 4.9 (q, ¹J(C,H) 119, Me₂Si). CI-MS (NH₃): 636

(44, [M 18] ), 619 (100, [M H] ), 601 (7, [M OH] ), 469 (12, [M H₂O (t-Bu)Me₂SiO] ), 445 (16,

[M C(CH₃)₂(t-Bu)Me₂SiO] ), 355 (80), 276 (26), 207 (15), 91 (87). Anal. calc. for C₃₂H₄₆O₁₀Si (618.79):

C 62.10, H 7.51, Si 4.54; found: C 62.18, H 7.65, Si 4.63.

Methyl (7RS)-3,5-Di-O-acetyl-2,6-anhydro-4-O-benzoyl-7-C-{(1SR,2RS,3SR,4RS,5SR,6RS,7SR)-6-endo-

(benzyloxy)-7-exo-{[(tert-butyl)dimethylsilyl]oxy}-4-endo-hydroxy-2-exo-(phenylthio)-8-oxabicyclo[3.2.1]oct-

3-endo-yl}-dl-glycero-ld-manno-heptonate ((Æ)-70). At 788, 0.7m Me₂AlSPh in CH₂Cl₂(0.26 ml, 0.18 mmol)

was added dropwise to a stirred soln. of (Æ)-13 (64 mg, 0.177 mmol) in anh. THF (1 ml). After stirring at 788

for 45 min, crude (Æ)-48 (48 mg) in soln. in anh. THF (0.5 ml) was added dropwise. After stirring at 788 for

1 h, the mixture was poured into ice-cold 1n aq. HCl (10 ml) under vigourous stirring. The mixture was extracted

with CHCl₃(15 ml, then 3 Â 10 ml). The combined org. extract was washed with sat. aq. NaHCO₃soln. (10 ml),

dried (MgSO₄), and evaporated and the residue taken up in MeOH (4 ml). After cooling to 08, CeCl₃´ 6H₂O

(65 mg, 0.183 mmol), then NaBH₄(5 mg, 0.13 mmol) were added portionwise under vigourous stirring. After

15 min at 08 the mixture was poured into sat. aq. NH₄Cl soln. (10 ml), H₂O (5 ml) and AcOEt (20 ml) under

stirring. The aq. layer was extracted with AcOEt (4 Â 10 ml). The combined org. extracts were dried (MgSO₄)

and evaporated. FC (1 Â 15 cm, light petroleum ether/Et₂O/MeOH 40 :60 :1): 60 mg (56% based on (Æ)-57 of

(Æ)-70). Colorless solid. M.p. 192 ± 1948. UV (MeCN): 257 (6800), 224 (18500), 216 (19000), 198 (39500). IR

(film): 3455, 3060, 2955, 2930, 2855, 1755, 1735, 1600, 1585, 1440, 1375, 1275, 1235, 1105, 840, 715. ¹H-NMR

(400 MHz, CDCl₃): 7.95, 7.59 ± 7.28 (2m, 2 H, 13 H, arom. H); 5.98 (br. d, ³J(5,4) 3.4, H C(5)); 5.64

(dd, ³J(3,4) 10.2, ³J(3,2) 10.0, H C(3)); 5.39 (dd, ³J(4,3) 10.2, ³J(4,5) 3.4, H C(4)); 5.22 (br. s, OH);

4.76, 4.57 (2d, ²J 11.4, PhCH₂O); 4.68 (dd, ³J(4',5') 7.9, ³J(4',3') 4.4, H C(4')); 4.43 (m, ³J(7,6) 9.5,

³J(7,3') 3.8, H C(7)); 4.30 (d,³J(7',6') 4.3, H C(7')); 4.29 (s, H C(1')); 4.20 (dd, ³J(5',4') 7.9, ³J(5',6')

5.3, H C(5')); 4.08 (dd, ³J(6',5') 5.3, ³J(6',7') 4.3, H C(6')); 4.07 (br. s, OH); 4.05 (d, ³J(2,3) 10.0,

H

C(2)); 3.88 (br. d, ³J(6,7) 9.5, H C(6)); 3.80 (s, COOMe); 3.64 (d,³J(2',3') 10.7, H C(2')); 2.15, 1.98 (2s,

2 Ac); 2.00 (ddd, ³J(3',2') 10.7, ³J(3',4') 4.4, ³J(3',7) 3.8, H C(3')); 0.84 (s, t-BuSi); 0.01, 0.10 (2s, Me₂Si).

¹³C-NMR (100.6 MHz, CDCl₃): 169.9, 169.6, 167.5, 165.5 (4s, 4 CO); 136.2, 133.2, 129.2 (3s, arom. C); 134.1,

133.3, 129.7, 129.0, 128.8, 128.7, 128.5, 128.1, 127.9 (9d, ¹J(C,H) 160, arom. C); 90.2 (d, ¹J(C,H) 150, C(6'));

88.8 (d, ¹J(C,H) 158, C(1')); 82.8 (d, ¹J(C,H) 144, C(7')); 77.8 (d, ¹J(C,H) 142, C(6)); 77.3 (d, ¹J(C,H)

145, C(2)); 74.4 (t, ¹J(C,H) 144, PhCH₂O); 72.7 (d, ¹J(C,H) 149, C(4)); 72.5 (d, ¹J(C,H) 155, C(5')); 71.1

(d, ¹J(C,H) 149, C(4')); 67.9 (d, ¹J(C,H) 148, C(7)); 67.5 (d, ¹J(C,H) 157, C(5)); 67.1 (d, ¹J(C,H) 155,

C(3)); 52.8 (q, ¹J(C,H) 148, COOMe); 47.6 (d, ¹J(C,H) 143, C(2')); 37.5 (d, ¹J(C,H) 132, C(3')); 25.6

(q, ¹J(C,H) 148, Me₃CSi); 20.7, 20.6 (2q, ¹J(C,H) 130, 2 MeCO); 17.8 (s, Me₃CSi); 4.8, 4.9 (2q, ¹J(C,H)

119, Me₂Si). CI-MS (NH₃): 881 (9, [M 1] ), 676 (3, [M (t-Bu)Me₂Si Bn 2 H] ), 626 (4, [M BzOH (t-

Bu)Me₂SiOH] ), 550 (2, [M Bz (t-Bu)Me₂Si PhSH] ), 510 (3, [M AcO Bn Bz (t-Bu)Me₂Si] ),

468 (3, [M Ac AcO Bn Bz (t-Bu)Me₂Si] ), 281 (10), 207 (18), 110 (11), 108 (6), 105 (10), 91 (16), 77

(9). Anal. calc. for C₄₅H₅₆O₁₄SSi (881.17): C 61.33, H 6.42; found: C 61.41, H 6.46.

Methyl (7S)-3,5-Di-O-acetyl-2,6-anhydro-4-O-benzoyl-7-C-{(1R,2S,3R,4S,5R,6S,7R)-6-endo-(benzyloxy)-

7-exo-{[(tert-butyl)dimethylsilyl]oxy}-4-endo-hydroxy-2-exo-(phenylthio)-8-oxabicyclo[3.2.1]oct-3-endo-yl}-l-

glycero-d-manno-heptonate (( )-70). As described for (Æ)-70, from ( )-57 (source of optically active 48) and

25

(

)-13. Yield 44% based on ( )-57. White foam. [a]_D²⁵

61 (c 0.5, CH₂Cl₂).

26, [a]

28, [a]

32, [a]

51, [a]

577

546

435

405

Methyl (7RS)-3,5-Di-O-acetyl-2,6-anhydro-4-O-benzoyl-7-C-[(1RS,5RS,6RS,7RS)-6-endo-(benzyloxy)-7-

exo-{[(tert-butyl)dimethylsilyl]oxy}-4-oxo-8-oxabicyclo[3.2.1]oct-2-en-3-yl}-dl-glycero-ld-manno-heptonate

((Æ)-71). At 788, 0.5m Me₂AlSeMe in toluene (0.65 ml, 0.32 mmol) was added dropwise to a stirred soln. of

(Æ)-13 (81 mg, 0.22 mmol) in anh. THF (0.75 ml). After stirring at 788 for 90 min, a soln. of (Æ)-48 (61 mg,

0.149 mmol) in anh. THF (0.45 ml) was added dropwise. After stirring at 788 for 18 h, 100% mCPBA (112 mg,

0.65 mmol) was added. The mixture was stirred at 788 for 1 h and allowed to warm to 208 within ca. 4 h.

After dilution with cold CHCl₃( 208, 15 ml), the mixture was washed successively with ice-cold 1n aq. HCl

(10 ml), 0.5m aq. Na₂S₂O₃(10 ml), and sat. aq. NaHCO₃soln. (10 ml). The aq. layers were extracted with CHCl₃

(3 Â 10 ml). The combined org. extracts were dried (MgSO₄) and evaporated. FC (1.5 Â 12 cm, light petroleum

1

ether/Et₂O 3 :7): 77 mg (52% based on (Æ)-57) of (Æ)-71. Colorless foam. H-NMR (400 MHz, CDCl₃): 7.90,

7.57, 7.43, 7.33 (4m, 2 H, 1 H, 2 H, 5 H, arom. H); 7.13 (dd, ³J(2',1') 4.9, ⁴J(2',7) 1.1, H C(2')); 5.73

(d, ³J(5,4) 3.3, H C(5)); 5.52 (dd, ³J(3,4) 10.0, ³J(3,2) 10.0, H C(3)); 4.86 (dd, ³J(4,3) 10.0, ³J(4,5)

3.3,

H

C(4)); 4.77 (d, ³J(5',6') 7.1,

H

C(5')); 4.76 (dd, ³J(7,6) 5.3, ⁴J(7,2') 1.1,

H C(7)); 4.56

(s, PhCH₂O); 4.49 (d, ³J(1',2') 4.9, H C(1')); 4.40 (s, H C(7')); 4.27 (d, ³J(6',5') 7.1, H C(6')); 3.96

(d, ³J(2,3) 10.0, H C(2)); 3.79 (d, ³J(6,7) 5.3, H C(6)); 3.77 (s, COOMe); 2.09, 1.98 (2s, 2 Ac); 0.87 (s, t-

1390

Helvetica Chimica Acta ± Vol. 84 (2001)

BuSi); 0.09 (s, Me₂Si). ¹³C-NMR (100.6 MHz, CDCl₃): 194.9 (s, C(4')); 169.7, 169.6, 167.7, 164.8 (4s, 4 CO);

145.7 (d, ¹J(C,H) 164, C(2')); 136.8, 129.2 (2s, arom. C); 135.2 (s, C(3')); 133.3, 129.6, 128.6, 128.5, 128.4, 128.1

(6d, ¹J(C,H) 160, arom. C); 85.5 (d, ¹J(C,H) 153, C(6')); 83.0 (d, ¹J(C,H) 160, C(5')); 81.9 (d, ¹J(C,H)

163, C(1')); 78.8 (d, ¹J(C,H) 152, C(7')); 76.9, 76.7 (2d, ¹J(C,H) 145, C(2), C(6)); 73.3 (t, ¹J(C,H) 144,

PhCH₂O); 72.5 (d, ¹J(C,H) 148, C(4)); 69.1 (d, ¹J(C,H) 152, C(7)); 66.7, 66.6 (2d, ¹J(C,H) 155, C(3),

C(5)); 52.7 (q, ¹J(C,H) 148, COOMe); 25.7 (q, ¹J(C,H) 125, Me₃CSi); 20.9, 20.6 (2q, ¹J(C,H) 130,

2 MeCO); 18.0 (s, Me₃CSi); 5.0, 5.1 (2q, ¹J(C,H) 119, Me₂Si). CI-MS (NH₃): 768 (24, M ), 619 (21,

[M AcO Bn H] ), 595 (42, [M AcO TBS H] ), 505 (20), 207 (21), 105 (92), 91 (100), 77 (38).

Methyl (7RS)-3,5,7-Tri-O-acetyl-7-C-[(1SR,2RS,3SR,4RS,5SR,6SR,7RS)-2-endo-(acetyloxy)-7-endo-

(benzyloxy)-6-exo-{[(tert-butyl)dimethylsilyl]oxy}-4-exo-(phenylthio)-8-oxabicyclo[3.2.1]oct-3-endo-yl]-2,6-

anhydro-4-O-benzoyl-dl-glycero-ld-manno-heptonate ((Æ)-72). A mixture of (Æ)-70 (88 mg, 0.10 mmol),

Ac₂O (2 ml), pyridine (2 ml), and N,N-dimethylpyridin-4-amine (5 mg) was stirred at 08 for 1 h. The solvent was

evaporated at 208, 10 ¹Torr, the residue taken up in CH₂Cl₂(10 ml) and the soln. washed with 1n aq. HCl (5 ml)

and sat. aq. NaHCO₃soln. (5 ml). The aq. layers were extracted with CH₂Cl₂(4 Â 10 ml) and the combined org.

extracts dried (MgSO₄) and evaporated: 99 mg (100%) of (Æ)-72, pure enough for the next step. An anal.

sample was obtained by FC (1 Â 12 cm, light petroleum ether/Et₂O 2 :3): colorless oil that solidified slowly in the

refrigerator. UV (MeCN): 256 (6600), 197 (37000). IR (film): 3065, 2955, 2930, 2855, 1750, 1600, 1585, 1455,

1440, 1370, 1275, 1230, 1110, 1065, 1025, 840, 710. ¹H-NMR (400 MHz, CDCl₃): 7.91, 7.56, 7.42, 7.31 (4m, 2 H, 1 H,

4 H, 8 H, arom. H); 5.76 (dd, ³J(7,6) 9.5, ³J(7,3') 5.7, H C(7)); 5.58 (br. d, ³J(5,4) 3.4, H C(5)); 5.56

(dd, ³J(3,4) 10.1, ³J(3,2) 10.0, H C(3)); 5.51 (dd, ³J(2',1') 8.0, ³J(2',3') 4.4, H C(2')); 5.32 (dd, ³J(4,3)

10.1, ³J(4,5) 3.4, H C(4)); 4.45 (br. dd, ³J(1',2') 8.0, ³J(1',7') 5.4, H C(1')); 4.43, 4.40 (2d, ²J 11.0,

PhCH₂O); 4.23 (dd, ³J(6',7') 6.0, ³J(6',5') 1.8, H C(6')); 4.16 (m, ³J(5',6') 1.8, H C(5')); 4.13 (d, ³J(2,3)

10.0, H C(2)); 4.04 (br. d, ³J(6,7) 9.5, H C(6)); 3.82 (dd, ³J(7',6') 6.0, ³J(7',1') 5.4, H C(7')); 3.68

(s, COOMe); 3.23 (d, ³J(4',3') 10.2,

H

C(4')); 2.33 (ddd, ³J(3',4') 10.2, ³J(3',7) 5.7, ³J(3',2') 4.4,

H

C(3')); 2.11, 1.96, 1.95, 1.72 (4s, 4 Ac); 0.81 (s, t-BuSi); 0.00, 0.08 (2s, Me₂Si). ¹³C-NMR (100.6 MHz,

CDCl₃): 171.0, 170.5, 169.6, 169.2, 167.3, 165.4 (6s, 6 CO); 137.2, 133.0, 129.0 (3s, arom. C); 133.5, 133.1, 129.6,

129.2, 128.6, 128.5, 128.2, 127.9, 127.8 (9d, ¹J(C,H) 160, arom. C); 88.6 (d, ¹J(C,H) 148, C(7')); 87.5

(d, ¹J(C,H) 159, C(5')); 80.5 (d, ¹J(C,H) 147, C(6')); 76.5 (d, ¹J(C,H) 154, C(2)); 75.9 (d, ¹J(C,H) 145,

C(6)); 74.3 (t, ¹J(C,H) 142, PhCH₂O); 72.3 (d, ¹J(C,H) 145, C(4)); 72.1 (d, ¹J(C,H) 155, C(1')); 67.5

(d, ¹J(C,H) 149, C(7)); 66.9 (d, ¹J(C,H) 156, C(2')); 66.6, 66.4 (2d, ¹J(C,H) 155, C(3), C(5)); 52.7

(q, ¹J(C,H) 148, COOMe); 47.9 (d, ¹J(C,H) 143, C(4')); 39.2 (d, ¹J(C,H) 129, C(3')); 25.6 (q, ¹J(C,H)

125, Me₃CSi); 21.2, 20.8, 20.6, 20.5 (4q, ¹J(C,H) 130, 4 MeCO); 17.9 (s, Me₃CSi); 4.7, 5.0 (2q, ¹J(C,H)

118, Me₂Si). CI-MS (NH₃): 908 (13, [M C₄H₉ H] ), 110 (28), 105 (52), 91 (100), 77 (23). Anal. calc. for

C₄₉H₆₀O₁₆SSi (965.25): C 60.97, H 6.28; found: C 61.06, H 6.34.

Methyl (7S)-3,5,7-Tri-O-acetyl-7-C-[(1R,2S,3R,4S,5R,6R,7S)-2-endo-(acetyloxy)-7-endo-(benzyloxy)-6-

exo-{[(tert-butyl)dimethylsilyl]oxy}-4-exo-(phenylthio)-8-oxabicyclo[3.2.1]oct-3-endo-yl]-2,6-anhydro-4-O-

benzoyl-l-glycero-d-manno-heptonate (( )-72). As described for (Æ)-72, from ( )-70. Colorless oil. [a]_D²⁵

25

1.7, [a]

2.0, [a]

1.5, [a] 0.3, [a] 2.1 (c 0.9, CH₂Cl₂).

577

546

435

405

Methyl (7RS)-3,5,7-Tri-O-acetyl-7-C-[(1SR,2RS,3SR,4RS,5SR,7RS)-2-endo-(acetyloxy)-7-endo-(benzyl-

oxy)-6-oxo-4-exo-(phenylthio)-8-oxabicyclo[3.2.1]oct-3-endo-yl]-2,6-anhydro-4-O-benzoyl-dl-glycero-ld-

manno-heptonate ((Æ)-73). A mixture of (Æ)-72 (99 mg, 0.102 mmol), MeCN (7 ml), and 40% aq. HF soln.

(0.35 ml) was stirred at 08 for 15 min, then at 208 for 2 h. A sat. aq. NaHCO₃soln. (10 ml) was added and the

mixture extracted with AcOEt (30 ml, then 4 Â 5 ml). The combined org. extracts were dried (MgSO₄) and

evaporated giving 87 mg of yellowish foamy alcohol that was taken up in anh. CH₂Cl₂(3.5 ml) containing 1,1,1-

tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3(1H)-one (64 mg, 0.15 mmol). After stirring at 208 for 45 min,

AcOEt (15 ml) was added. The soln. was washed with sat. aq. NaHCO₃soln. containing Na₂S₂O₃(240 mg,

10 ml), then with H₂O (10 ml). The aq. layers were extracted with AcOEt (4 Â 10 ml). The combined org.

extracts were dried (MgSO₄) and evaporated: 89 mg (quant.) of (Æ)-73. Yellowish foam, which was used as such

in the next step. An anal. sample was obtained by FC (1 Â 12 cm, light petroleum ether/Et₂O 15 :35): colorless

oil that solidified in the refrigerator. UV (MeCN): 217 (18000), 201 (21500). IR (film): 3065, 2955, 2875, 1755,

1750, 1730, 1600, 1585, 1455, 1440, 1370, 1270, 1225, 1115, 1025, 960, 715. ¹H-NMR (400 MHz, CDCl₃): 7.91, 7.56,

7.43, 7.33 (4m, 2 H, 1 H, 4 H, 8 H, arom. H); 5.77 (dd, ³J(7,6) 9.5, ³J(7,3') 4.6, H C(7)); 5.64 (dd, ³J(2',1')

3

7.6, J(2',3') 3.5, H C(2')); 5.58 (dd, ³J(3,4) 10.1, J(3,2) 10.0, H C(3)); 5.54 (dd, ³J(5,4) 3.4, J(5,6)

1.0, H C(5)); 5.32 (dd, ³J(4,3) 10.1, ³J(4,5) 3.4, H C(4)); 4.72 (ddd, ³J(1',2') 7.6, ³J(1',7') 6.3, ⁴J(1',5')

1.9, H C(1')); 4.63, 4.57 (2d, ²J 11.6, PhCH₂O); 4.38 (m, ⁴J(5',1') 1.9, ⁴J(5',7') 1.4, H C(5')); 4.26

(dd, ³J(7',1') 6.3, ⁴J(7',5') 1.4, H C(7')); 4.11 (d, ³J(2,3) 10.0, H C(2)); 3.96 (dd, ³J(6,7) 9.5, ³J(6,5)

Helvetica Chimica Acta ± Vol. 84 (2001)

1391

1.0, H C(6)); 3.73 (s, COOMe); 3.48 (br. d, ³J(4',3') 10.9, H C(4')); 2.52 (ddd, ³J(3',4') 10.9, ³J(3',7) 4.6,

³J(3',2') 3.5, H C(3')); 2.11, 1.98, 1.92, 1.83 (4s, 4 Ac). ¹³C-NMR (100.6 MHz, CDCl₃): 209.6 (s, C(6')); 170.8,

170.4, 169.6, 169.1, 167.2, 165.4 (6s, 6 CO); 136.3, 132.5, 128.9 (3s, arom. C); 133.5, 132.1, 129.6, 129.3, 128.6,

128.4, 128.3, 127.7 (8d, ¹J(C,H) 160, arom. C); 81.8, 81.7 (2d, ¹J(C,H) 147, 157, C(5'), C(7')); 76.7

(d, ¹J(C,H) 150, C(2)); 75.5 (d, ¹J(C,H) 140, C(6)); 74.3 (d, ¹J(C,H) 162, C(1')); 73.9 (t, ¹J(C,H) 143,

PhCH₂O); 72.2 (d, ¹J(C,H) 148, C(4)); 67.0 (d, ¹J(C,H) 152, C(7)); 66.5 (d, ¹J(C,H) 155, C(3)); 66.2

(d, ¹J(C,H) 155, C(5)); 66.1 (d, ¹J(C,H) 155, C(2')); 52.8 (q, ¹J(C,H) 148, COOMe); 44.4 (d, ¹J(C,H)

145, C(4')); 39.2 (d, ¹J(C,H) 131, C(3')); 21.0, 20.7, 20.6 (3q, ¹J(C,H) 130, 4 MeCO). CI-MS (NH₃): 866 (1,

[M 18] ), 849 (2, [M H] ), 789 (0.5, [M AcO] ), 731 (0.5, [M 2AcO H] ), 619 (2, [M BnO

BzOH] ), 531 (5), 109 (13), 105 (67), 91 (100), 77 (20). Anal. calc. for C₄₃H₄₄O₁₆S (848.94). C 60.84, H 5.22;

found: C 60.88, H 5.29.

Methyl (7S)-3,5,7-Tri-O-acetyl-7-C-[(1R,2S,3R,4S,5R,7S)-2-endo-(acetyloxy)-7-endo-(benzyloxy)-6-oxo-

4-exo-(phenylthio)-8-oxabicyclo[3.2.1]oct-3-endo-yl]-2,6-anhydro-4-O-benzoyl-l-glycero-d-manno-heptonate

25

(( )-73). As described for (Æ)-73, with ( )-72. Colorless oil. [a]_D²⁵

19, [a]

24, [a]

577

546

435

25

31, [a]

28 (c 0.6, CH₂Cl₂).

405

Methyl (7RS)-3,5,7-Tri-O-acetyl-7-C-[(1SR,4SR,5SR,6RS,7SR,8RS)-6-endo-(acetyloxy)-4-endo-(benzyloxy)-

2-oxo-8-exo-(phenylsulfonyl)-3,9-dioxabicyclo[3.3.1]non-7-endo-yl]-2,6-anhydro-4-O-benzoyl-dl-glycero-ld-

manno-heptonate ((Æ)-74). A mixture of (Æ)-73 (89 mg, 0.105 mmol), NaHCO₃(10 mg), 90% mCPBA (74 mg,

0.39 mg), and anh. CHCl₃(4 ml) was stirred at 208 for 16 h. AcOEt (25 ml) was added and the soln. washed with

0.5m aq. Na₂S₂O₃(15 ml), then with sat. aq. NaHCO₃soln. (15 ml). The aq. layers were extracted with AcOEt

(4 Â 15 ml) and the combined org. extracts dried (MgSO₄) and evaporated; 90 mg (96%) of (Æ)-74. Yellowish

foam, which was used in the next step. An anal. sample was obtained by FC (1 Â 12 cm, light petroleum ether/

AcOEt 4 :5): colorless foam. UV (MeCN): 271 (6600), 264 (7000), 217 (32000), 196 (63000). IR (film): 2955,

2920, 1755, 1450, 1375, 1270, 1225, 1110. ¹H-NMR (400 MHz, CDCl₃): 8.00, 7.92, 7.70, 7.65 ± 7.54, 7.44 ± 7.28 (5m,

2 H, 2 H, 1 H, 3 H, 7 H, arom. H); 6.03 (dd, ³J(7,6) 9.3, ³J(7,7') 2.2, H C(7)); 6.02 (dd, ³J(6',5') 7.1,

³J(6',7') 2.2, H C(6')); 5.63 (dd, ³J(3,4) 10.1, ³J(3,2) 10.0, H C(3)); 5.62 (d, ³J(4',5') 3.7, H C(4')); 5.44

(br. d, ³J(5,4) 3.4, H C(5)); 5.32 (dd, ³J(4,3) 10.1, ³J(4,5) 3.4, H C(4)); 5.05 (m, ⁴J(1',5') 1.1, H C(1'));

4.89, 4.69 (2d, ²J 11.7, PhCH₂O); 4.23 (ddd, ³J(5',6') 7.1, ³J(5',4') 3.7, ⁴J(5',1') 1.1, H C(5')); 4.18

(d, ³J(2,3) 10.0, H C(2)); 4.03 (br. d, ³J(6,7) 9.3, H C(6)); 3.81 (s, COOMe); 3.74 (br. d, ³J(8',7') 10.6,

H

C(8')); 2.93 (ddd, ³J(7',8') 10.6, ³J(7',6') 2.2, ³J(7',7) 2.2, H C(7')); 2.15, 1.99, 1.95, 1.85 (4s, 4 Ac).

¹³C-NMR (100.6 MHz, CDCl₃): 170.2, 169.5, 169.0, 168.9, 167.6, 167.0, 165.4 (7s, 6 CO, C(2')); 136.9, 135.0,

129.0 (3s, arom. C); 134.4, 133.4, 129.7, 129.5, 129.4, 128.7, 128.6, 128.5, 128.2 (9d, ¹J(C,H) 160, arom. C); 100.6

(d, ¹J(C,H) 177, C(4')); 76.7 (d, ¹J(C,H) 150, C(2)); 75.4 (d, ¹J(C,H) 144, C(6)); 72.1 (d, ¹J(C,H) 146,

C(4)); 71.8 (t, ¹J(C,H) 144, PhCH₂O); 70.2 (d, ¹J(C,H) 154, C(5')); 69.9 (d, ¹J(C,H) 153, C(1')); 68.2

(d, ¹J(C,H) 152, C(7)); 66.3 (d, ¹J(C,H) 155, C(5)); 66.2 (d, ¹J(C,H) 155, C(3)); 63.7 (d, ¹J(C,H) 154,

C(6')); 62.2 (d, ¹J(C,H) 144, C(8')); 52.9 (q, ¹J(C,H) 148, COOMe); 34.4 (d, ¹J(C,H) 132, C(7')); 21.1, 20.6

(2q, ¹J(C,H) 130, 4 MeCO). CI-MS (NH₃): 914 (2, [M 18] ), 896 (1, M ), 717 (1, [M AcO Bz H] ),

577 (1, [M AcO Bz PhSO₂ 2 H] ), 471 (2), 122 (11), 108 (14), 105 (67), 91 (100), 77 (34). Anal. calc. for

C₄₃H₄₄O₁₉S (896.94): C 57.59, H 4.94, S 3.57; found: C 57.47, H 4.88, S 3.49.

Methyl (7S)-3,5,7-Tri-O-acetyl-7-C-[(1R,4R,5R,6S,7R,8S)-6-endo-(acetyloxy)-4-endo-(benzyloxy)-2-oxo-

8-exo-(phenylsulfonyl)-3,9-dioxabicyclo[3.3.1]non-7-endo-yl]-2,6-anhydro-4-O-benzoyl-l-glycero-d-manno-

25

heptonate (( )-74). As described for (Æ)-74, with ( )-73. White foam. [a]_D²⁵

62, [a]

66, [a]

74,

577

546

25

[a]

122, [a]

144 (c 0.3, CH₂Cl₂).

435

405

Diethyl Dithioacetal of Methyl 3-O-Acetyl-2,6-anhydro-4,5-dideoxy-5-C-(phenylsulfonyl)-4-C-{[methyl

(7RS)-3,5,7-tri-O-acetyl-2,6-anhydro-4-O-benzoyl-dl-glycero-ld-manno-heptonate]-7-C-yl}-dl-glycero-ld-ga-

lacto-hepturonate ((Æ)-75. EtSH (0.1 ml, 1.35 mmol) and CF₃SO₃H (15 ml) were added successively to a stirred

soln. of crude (Æ)-74 (90 mg, 0.10 mmol) in anh. CH₂Cl₂(5 ml). After stirring at 208 for 15 min, a soln. of

diazomethane in Et₂O was added until persistence of the yellow color. A drop of AcOH was added, then a sat.

aq. NaHCO₃soln. (15 ml). The mixture was extracted with AcOEt (25 ml, then 4 Â 15 ml). The combined org.

extracts were dried (MgSO₄) and evaporated. FC (1 Â 15 cm, light petroleum ether/AcOEt 1:1) gave 57 mg

(61% based on (Æ)-70) of (Æ)-75. Colorless foam. UV (MeCN): 272 (3200), 265 (3300), 260 (3400), 222

(15000), 202 (30500). IR (film): 2955, 2930, 1750, 1450, 1375, 1270, 1225, 1150, 1110, 1065, 1020. ¹H-NMR

(400 MHz, CDCl₃): 8.03, 7.89, 7.70, 7.56, 7.41 (5m, 2 H, 2 H, 3 H, 1 H, 2 H, arom. H); 5.86 (dd, ³J(3,4) 3.3,

³J(3,2) 1.1, H C(3)); 5.51 (dd, ³J(3',4') 10.0, ³J(3',2') 9.9, H C(3')); 5.38 (br. d, ³J(5',4') 3.5, H C(5'));

5.34 (dd, ³J(4',3') 10.0, ³J(4',5') 3.5, H C(4')); 5.19 (br. s, H C(6)); 4.97 (dd, ³J(7',6') 9.5, ³J(7',4) 3.2,

H

C(7')); 4.33 (br. d, ³J(6',7') 9.5, H C(6')); 4.23 (m, ³J(5,4) 6.5, H C(5)); 4.22 (d, ³J(2',3') 9.9,

1392

Helvetica Chimica Acta ± Vol. 84 (2001)

H

C(2')); 3.85, 3.78 (2s, 2 COOMe); 3.82 (d, ³J(1,2) 8.8, H C(1)); 3.67 (dd, ³J(2,1) 8.8, ³J(2,3) 1.1,

C(2)); 2.97 (ddd, ³J(4,5) 6.5, ³J(4,3) 3.3, ³J(4,7') 3.2,

H

C(4)); 2.77 ± 2.58 (m, 4 H, ³J 7.4,

2 MeCH₂S); 1.99, 1.99, 1.95, 1.92 (4s, 4 Ac); 1.27, 1.22 (2t, ³J 7.4, 2 MeCH₂S). ¹H-NMR (400 MHz, C₆D₆):

8.18, 7.20, 7.04 (3m, 4 H, 2 H, 4 H, arom. H); 6.30 (br. d, ³J(3,4) 3.1, H C(3)); 5.94 (dd, ³J(3',4') 10.2,

³J(3',2') 10.0, H C(3')); 5.86 (dd, ³J(5',4') 3.4, J(5',6') 0.7, H C(5')); 5.55 (dd, ³J(4',3') 10.2, J(4',5')

3.4, H C(4')); 5.46 (br. s, H C(6)); 5.42 (dd, ³J(7',6') 9.5, ³J(7',4) 3.0, H C(7')); 4.71 (dd, ³J(6',7') 9.5,

³J(6',5') 0.7, H C(6')); 4.65 (br. d, ³J(5,4) 6.7, H C(5)); 4.07 (s, H C(1), H C(2)); 3.93 (d, ³J(2',3') 10.0,

3

H

C(2')); 3.43 (ddd, ³J(4,5) 6.7, J(4,3) 3.1, J(4,7') 3.0, H C(4)); 3.34, 3.20 (2s, 2 COOMe); 2.79 ± 2.55

(m, ³J 7.4, 2 MeCH₂S); 1.72, 1.71, 1.68, 1.62 (4s, 4 Ac); 1.19, 1.14 (2t, ³J 7.4, 2 MeCH₂S). ¹³C-NMR

(100.6 MHz, CDCl₃): 170.6, 170.1, 170.0, 169.7, 169.0, 167.2, 165.2 (7s, 7 CO); 136.5, 128.9 (2s, arom. C);

134.3, 133.4, 130.1, 129.6, 129.5, 128.5 (6d, ¹J(C,H) 160, arom. C); 77.8 (d, ¹J(C,H) 147, C(2)); 76.2

(d, ¹J(C,H) 151, C(2')); 74.3 (d, ¹J(C,H) 144, C(6')); 71.9 (d, ¹J(C,H) 149, C(4')); 69.9 (d, ¹J(C,H) 147,

C(6)); 68.9 (d, ¹J(C,H) 151, C(7')); 66.5 (d, ¹J(C,H) 157, C(3')); 65.9 (d, ¹J(C,H) 156, C(5')); 64.8

(d, ¹J(C,H) 157, C(3)); 59.7 (d, ¹J(C,H) 139, C(5)); 52.8 (q, ¹J(C,H) 148, 2 COOMe); 52.0 (d, ¹J(C,H)

151, C(1)); 37.3 (d, ¹J(C,H) 131, C(4)); 25.2, 24.1 (2t, ¹J(C,H) 139, 2 MeCH₂S); 21.4, 20.7, 20.6, 20.5

(4q, ¹J(C,H) 130, 4 MeCO); 14.6, 14.3 (2q, ¹J(C,H) 128, 2 MeCH₂S). CI-MS (NH₃): 944 (0.5, [M 18] ),

926 (0.4, M ), 865 (1, [M SEt] ), 849 (1, [M Ph] ), 745 (13, [M Ph Bz H] ), 663 (9, [M PhSO₂

BzOH] ), 603 (6, [M PhSO₂BzOH AcOH] ), 559 (5), 135 (14), 105 (100), 77 (31).

Diethyl Dithioacetal of Methyl 3-O-Acetyl-2,6-anhydro-4,5-dideoxy-4-C-{[methyl (7S)-3,5,7-tri-O-acetyl-

2,6-anhydro-4-O-benzoyl-l-glycero-d-manno-heptonate]-7-C-yl}-5-C-(phenylsulfonyl)-l-glycero-d-galacto-

hepturonate (( )-75). As described for (Æ)-75, with ( )-74. Yield 48% based on ( )-70. White foam. [a]_D²⁵

25

39, [a]

40, [a]

49, [a]

81, [a]

95 (c 0.7, CH₂Cl₂).

577

546

435

405

Methyl 3-O-Acetyl-2,6-anhydro-4,5-dideoxy-4-C-{[methyl (7RS)-3,5,7-tri-O-acetyl-2,6-anhydro-4-O-ben-

zoyl-dl-glycero-ld-manno-heptonate]-7-C-yl}-5-C-(phenylsulfonyl)-dl-glycero-ld-galacto-hepturonate ((Æ)-

76). A mixture of (Æ)-75 (32 mg, 0.035 mmol), anh. MeCN (2.3 ml), and Hg(ClO₄)₂´ H₂O (35 mg, 0.076 mmol)

was stirred at 208 for 30 min. CHCl₃(25 ml) and Ag₂CO₃(140 mg, 0.51 mmol) were added and the mixture

stirred at 208 for 15 min. The precipitate was filtered off (Celite) and the solvent evaporated. The residue was

taken up in CHCl₃/light petroleum ether 1:1 (1 ml). The precipitate was filtered off and the solvent evaporated.

The latter operation was repeated 3 times giving 27 mg (94%) of crude (Æ)-76. Colorless foam, which was used

directly in the next step. ¹H-NMR (400 MHz, CDCl₃): 9.56 (s, H C(1)); 8.19, 7.23, 7.04 (3m, 4 H, 2 H, 4 H, arom.

H); 6.09 (dd, ³J(3,4) 3.0, ³J(3,2) 2.8, H C(3)); 5.93 (dd, ³J(3',4') 10.2, ³J(3',2') 10.0, H C(3')); 5.83

(br. d, ³J(5',4') 3.1, H C(5')); 5.57 (dd, ³J(4',3') 10.2, ³J(4',5') 3.1, H C(4')); 5.53 (br. s, H C(6)); 5.39

(dd, ³J(7',6') 9.5, ³J(7',4) 2.8, H C(7')); 4.53 (br. d, ³J(5,4) 7.1, H C(5)); 4.52 (br. d, ³J(6',7') 9.5,

H

C(6')); 3.81 (d, ³J(2',3') 10.0, H C(2')); 3.78 (d, ³J(2,3) 2.8, H C(2)); 3.35, 3.09 (2s, 2 COOMe); 3.33

3

(ddd, ³J(4,5) 7.1, ³J(4,3) 3.0, J(4,7') 2.8, H C(4)); 1.70, 1.64, 1.46 (3s, 3 H, 6 H, 3 H, 4 Ac).

Methyl (7RS)-5-O-Acetyl-2,6-anhydro-7-C-[(1RS,5RS,6RS,7RS)-6-endo-(benzyloxy)-7-exo-{[(tert-bu-

tyl)dimethylsilyl]oxy}-4-oxo-8-oxabicyclo[3.2.1]oct-2-en-3-yl]-3,4-dideoxy-4-C-{[methyl (7RS)-3,5,7-tri-O-ace-

tyl-2,6-anhydro-4-O-benzoyl-dl-glycero-ld-manno-heptonate]-7-C-yl}-3-C-(phenylsulfonyl)-dl-glycero-ld-

gluco-heptonate ((Æ)-77). At 788, 0.5m Me₂AlSeMe in toluene (0.25 ml) was added dropwise to a stirred soln.

of (Æ)-13 (36 mg, 0.10 mmol) in anh. THF (1 ml). After stirring at 788 for 45 min, a soln. of (Æ)-76 (27 mg,

0.033 mmol) in anh. THF (0.5 ml) was added dropwise. After stirring at 788 for 2 h, 100% mCPBA (27 mg,

0.156 mmol) was added and the mixture stirred at 788 for 45 min. The mixture was allowed to warm up to

208 within 15 min. CHCl₃(10 ml) was added and the soln. washed successively with 1n HCl (10 ml), 0.5m aq.

Na₂S₂O₃(10 ml), and sat. aq. NaHCO₃soln. (10 ml). The aq. layers were extracted with CHCl₃(4 Â 10 ml) and

the combined org. extracts dried (MgSO₄) and evaporated. FC (1 Â 14 cm, light petroleum ether/AcOEt 1 :1)

gave 22 mg (53% based on (Æ)-75) of (Æ)-77 as colorless foam and 26 mg (72%) of (Æ)-13. (Æ)-77: UV

(MeCN): 219 (21000), 197 (39500). IR (KBr): 3480 (br.), 2955, 2930, 2860, 1755, 1695, 1450, 1370, 1270, 1230,

1150, 1110, 1065. ¹H-NMR (400 MHz, 558, C₆D₆): 8.18, 8.07, 7.74, 7.44, 7.22, 7.11 (6m, 2 H, 2 H, 3 H, 2 H, 3 H, 3 H,

arom. H); 7.28 (dd, ³J(2'',1'') 5.2, ⁴J(2'',7) 2.0, H C(2'')); 6.11 (dd, ³J(3',4') 10.1, ³J(3',2') 10.0, H C(3'));

5.82 (d, ³J(5',4') 3.1, H C(5')); 5.69 (dd, ³J(4',3') 10.1, ³J(4',5') 3.1, H C(4')); 5.25 (d, ³J(5,4) 4.7,

H

C(5)); 5.24 (dd, ³J(7',4) 9.0, ³J(7',6') 8.6,

H

C(7')); 5.17 (br. d, ³J(3,4) 3.7,

H C(3)); 4.86

(m, ³J(7,6) 3.5, ⁴J(7,2'') 2.0, H C(7)); 4.79 (d, ³J(2',3') 10.0, H C(2')); 4.78 (br. s, H C(2)); 4.76 (br. s,

H

C(7'')); 4.74 (d, ³J(5'',6'') 7.0, H C(5'')); 4.58 (d, ³J(6',7') 8.6, H C(6')); 4.50 (br. d, ³J(1'',2'') 5.2,

C(1'')); 4.47, 4.25 (2d, ²J 10.5, PhCH₂O); 4.40 (d, ³J(6,7) 3.5, H C(6)); 4.29 (br. d, ³J(6'',5'') 7.0,

C(6'')); 4.04 (br. s, OH C(7)); 3.54, 3.24 (2s, 2 COOMe); 2.76 (ddd, ³J(4,7') 9.0, ³J(4,5) 4.7, ³J(4,3) 3.7,

C(4)); 1.87, 1.78, 1.76, 1.74 (4s, 4 Ac); 1.02 (s, t-BuSi); 0.21, 0.18 (2s, Me₂Si). ¹³C-NMR (100.6 MHz, 558,

Article Doi

Stereoselective synthesis of 8-oxabicyclo[3.2.1]octane-2,3,4,6,7-pentols and total asymmetric synthesis of 2,6-anhydrohepturonic acid derivatives and of β-C-manno-pyranosides suitable for the construction of (1 → 3)-C,C-linked trisaccharides

DOI: 10.1002/1522-2675(20010613)84:6<1363::AID-HLCA1363>3.0.CO;2-M

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Full text of DOI:10.1002/1522-2675(20010613)84:6<1363::AID-HLCA1363>3.0.CO;2-M

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