Asymmetric syntheses of new polyhydroxylated quinolizidines 1: Cross-aldol reactions of 7-oxabicyclo[2.2.1]heptan-2-one and 3a,4a,7a,7b-tetrahydro[1,3]dioxolo[4,5]furo[2,3-d]isoxazole-3-carbaldehyde derivatives 2

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193

Asymmetric Syntheses of New Polyhydroxylated Quinolizidines¹):

Cross-Aldol Reactions of 7-Oxabicyclo[2.2.1]heptan-2-one and 3a,4a,7a,7b-

Tetrahydro[1,3]dioxolo[4,5]furo[2,3-d]isoxazole-3-carbaldehyde

Derivatives²)

by Christophe Schaller³) and Pierre Vogel*

Â

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

È

Dedicated to Professor Pierre Sinay on the occasion of his 62nd birthday

The cross-aldolization of ( )-(1S,4R,5R,6R)-6-endo-chloro-5-exo-(phenylseleno)-7-oxabicyclo[2.2.1]hep-

tan-2-one (( )-25) and of ()-(3aR,4aR,7aR,7bS)- (()-26) and ( )-(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahydro-

6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazole-3-carbaldehyde (( )-26) was studied for the lithium enolate

of ( )-25 and for its trimethylsilyl ether ( )-31 under Mukaiyamaꢀs conditions (Scheme 2). Protocols were

found for highly diastereoselective condensation giving the four possible aldols ()-27 (ꢁantiꢀ), ()-28 (ꢁsynꢀ),

29 (ꢁantiꢀ), and ( )-30 (ꢁsynꢀ) resulting from the exclusive exo-face reaction of the bicyclic lithium enolate of

(

)-25 and bicyclic silyl ether ( )-31. Steric factors can explain the selectivities observed. Aldols ()-27, ()-28,

29, and

(

)-30 were converted stereoselectively to ()-1,4-anhydro-3-{(S)-[(tert-butyl)dimethylsilyl-

oxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]-furo[2,3-d]isoxazol-3-yl]methyl}-3-

deoxy-2,6-di-O-(methoxymethyl)-a-d-galactopyranose (()-62), its epimer at the exocyclic position ()-70,

(

)-1,4-anhydro-3-{(S)-[(tert-butyl)dimethylsilyloxy][(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]-

dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-3-deoxy-2,6-di-O-(methoxymethyl)-a-d-galactopyranose (( )-77),

and its epimer at the exocyclic position ()-84, respectively (Schemes 3 and 5). Compounds ()-62, ( )-77,

and ()-84 were transformed to (1R,2R,3S,7R,8S,9S,9aS)-1,3,4,6,7,8,9,9a-octahydro-8-[(1R,2R)-1,2,3-trihy-

droxypropyl]-2H-quinolizine-1,2,3,7,9-pentol (21), its (1S,2S,3R,7R,8S,9S,9aR) stereoisomer ( )-22, and to its

(1S,2S,3R,7R,8S,9R,9aR) stereoisomer ()-23, respectively (Schemes 6 and 7). The polyhydroxylated quino-

lizidines ( )-22 and ()-23 adopt ꢁtrans-azadecalinꢀ structures with chair/chair conformations in which

H

C(9a) occupies an axial position anti-periplanar to the amine lone electron pair. Quinolizidines 21, ( )-22,

and ()-23 were tested for their inhibitory activities toward 25 commercially available glycohydrolases.

Compound 21 is a weak inhibitor of b-galactosidase from jack bean, of amyloglucosidase from Aspergillus niger,

and of b-glucosidase from Caldocellum saccharolyticum. Stereoisomers ( )-22 and ()-23 are weak but more

selective inhibitors of b-galactosidase from jack bean.

Introduction. ± Polyhydroxylated indolizidine (octahydroindolizine) alkaloids [2]

such as swainsonine (1) [3], castanospermine (2) [4], and lentiginosine 3 [5] have

attracted considerable interest due to their high activity as glycosidase inhibitors, and,

probably as a consequence of this, they show a wide range of biological activities [6].

This has stirred a lot of activity toward the synthesis of analogues and the study of

structure-activity relationships [2][7 ± 9]. We have shown that indolizidinepentol 4 [10]

that possesses the structure of 1 with two further OH substituents at C(5) and C(6) is,

1

)

IUPAC name for quinolizidine: 1,3,4,6,7,8,9,9a-octahydro-2H-quinolizine.

For a preliminary report, see [1].

Current address: Max-Planck-Institut für molekulare Physiologie, Otto-Hahn-Strasse 11, D-44227

Dortmund.

2

3

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like swainsonine, a potent inhibitor of a-mannosidase, but, unlike the natural alkaloid

1, it does not inhibit acidic b-galactosidases [11]. Ring-contracted analogues of

polyhydroxylated indolizine alkaloids such as alexine (5) [12] and casuarine (6) [13]

and stereoisomers [14] have also shown interesting glycohydrolase-inhibiting activities.

Ring-expanded analogues of polyhydroxyindolizidines, the polyhydroxyquinolizidines,

emerge as a new class of potential glycosidase inhibitors. The first derivatives 7 and 8

have been obtained by Ganem and co-workers [15]; 7 was also prepared by Rassu et al.

[16] and by Pearson and Hembre [17]. The latter authors have also described the

syntheses of 8 ± 10 and shown [17b] 7 to be a weak inhibitor of a-l-fucosidase from

bovine epididymis (IC₅₀ 0.36 mm). Stütz and co-workers realized the synthesis of the

castanospermine analogue 11 [18] which inhibits b-glucosidase from Aspergillus wentii

(K_i 25 mm) and b-glucosidase from almonds (K_i 250mm). Carretero et al. [19] have

prepared 12 and 13; Herczegh et al. [20] described the syntheses of isomers 14 ± 16. The

quinolizidinetriols 17 and 18 have been prepared by Carretero et al. [19], and 19 by

Pandit et al. [21]. Very interesting is the analogue 20 of a-homonojirimycin prepared by

Liu and co-workers [22] which is a potent inhibitor of a-glucosidase I from pig

kidney (IC₅₀ 0.15 mm). In a preliminary communication [1], we presented the

synthesis of (1R,2R,3S,7R,8S,9S,9aS)-1,3,4,6,7,8,9,9a-octahydro-8-[(1R,2R)-1,2,3-trihy-

droxypropyl]-2H-quinolizine-1,2,3,7,9-pentol (21), the first example of a new kind of

polyhydroxyquinolizidines bearing a polyhydroxylated side chain. We report here the

full details of our synthetic approach and its application to the preparation of

stereoisomers ( )-22 and ()-23. Our method is similar to that which we had used to

prepare analogue 24, the first example of a 7-(1,2,3-trihydroxypropyl)octahydroindo-

lizine-1,2,6,8-tetrol [23].

retro-Synthesis. ± A possible retro-synthetic analysis is to consider the quinolizi-

dines to arise from a double reductive cyclization of 5-amino-5-deoxy-dialdose

intermediates of type A (Scheme 1). The latter could be generated by reduction of the

furoisoxazoline derivatives of type B and acetal hydrolysis. Cross-aldolization of

enantiomerically pure 7-oxabicyclo[2.2.1]heptan-2-one ( )-25 with aldehydes ()-26

and ( )-26 that have been obtained enantiomerically pure [24] should enable us to

generate a number of required aldols of type D. Analogous 7-oxabicyclo[2.2.1]hepta-

none derivatives have been converted to anhydrogalacturonic esters of type C that

can be reduced to the corresponding 1,4-anhydro-galactopyranose derivatives B

[23][25][26]. Both types of starting materials, ( )-25 (PhSeCl adduct [27] to a ꢁnaked

sugar of the first generationꢀ [28]) and ()-26 or ( )-26, are derived from inexpensive

furan [24][29].

Cross-Aldol Condensations. ± The reaction of the lithium enolate derived from the

racemic ketone (Æ)-25 with racemic aldehyde (Æ)-26 led to mixtures of four aldols that

could not be separated. Addition of aldehyde ()-26 to the lithium enolate of ( )-25

generated by treatment with LiHMDS ((Me₃Si)₂NLi) under various conditions gave

mixture of ꢁantiꢀ- and ꢀsynꢀ-aldols ()-27 and ()-28 (Scheme 2, Table1). The best

yields were obtained with THF as solvent (90%) for an ꢁantiꢀ/ꢁsynꢀ-diastereoisomer

ratio of 84 :16. In the presence of an additive [30] such as DMF, DMPU, HMPT,

HMPA, or TMEDA (see Table 1), the diastereoselectivity was better, but, sometimes,

Helvetica Chimica Acta ± Vol. 83 (2000)

195

at the cost of lower yield. The best compromise was found when 10% of HMPT was

used as additive (92% yield; ꢁantiꢀ/ꢁsynꢀ-aldol ratio 88 :12). With the potassium enolate

of ( )-25 generated by treatment with (Me₃Si)₂NK, the yield of the cross-aldolization

never exceeded 30%. Attempts using phosphazene bases such as P₄-t-Bu or P₄-t-Oct

[31] were not met with success.

The reaction of the lithium enolate of ( )-25 (generated by treatment with

LiHMDS in THF) with aldehyde ( )-26 ( 788, 4 h) provided a 52 :48 mixture of ꢁantiꢀ-

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Scheme 1

Scheme 2

and ꢁsynꢀ-aldol 29 and ( )-30 in 90% yield (Scheme 2). The same low diastereose-

lectivity was observed with glyme ((MeOCH₂)₂) as the solvent instead of THF (yield

73%). In the presence of 10% of HMPTor of 10% of TMEDA (in THF, 788), 52 :48

and 58 :42 mixtures 29/( )-30, respectively, were obtained in 74% yield.

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197

Table 1. Yields and Diastereoselectivities of the Cross-Aldolizations of Aldehyde ()-26 and Ketone ( )-25

Base^a)

Solvent

Temp. [8]

Additive^b)

()-27/()-28

Yield [%]

LiHMDS

KHMDS

LiHMDS

Et₂O

THF

glyme^c)

THF

TMF

THF

78

100

78

±

62 : 38

84 : 16

85 : 15

87: 13

82 : 18

86 : 14

93 : 7

88 : 12

90 : 10

89 : 11

12

90

70

84

30

25

35

92

75

67

±

DMF (10%)

DMPU (15%)

HMPT (10%)

HMPA (10%)

TMEDA (10%)

^a) HMDS Hexamethyldisilazane. ^b) DMPU 1,3-Dimethyl-3,4,5,6-tetrahydropyrimidin-2(1H)-one; HMPA

(Me₂N)₃PO; HMPT (Me₂N)₃P; TMEDA Me₂NCH₂CH₂NMe_2.^c) MeOCH₂CH₂OMe.

Under Mukaiyamaꢀs conditions [32], the trimethylsilyl enol ether ( )-31 derived

from ( )-25 (Scheme 2) reacted with both aldehydes ()-26 and ( )-26 to give

predominantly the corresponding ꢁsynꢀ-aldols ()-28 and ( )-30, respectively (Tables 2

and 3). The best ꢁsynꢀ/ꢁantiꢀ diastereoselectivity was observed when a precooled ( 788)

solution of TiCl₄in CH₂Cl₂was added at 788 to the mixture of the enoxysilane ( )-31

and aldehyde ()-26. When SnCl₄was used instead of TiCl₄as promoter, lower yields

and diastereoselectivities were found (Table 2). With BF₃´ Et₂O, the results were even

less satisfactory.

Table 2. Yields and Diastereoselectivities of the Mukaiyama Cross-Aldolizations of ()-26 and ( )-31 in CH₂Cl₂

at 788

Lewis acid

()-27/()-28

43 : 57

24 : 76

8 : 92

13 : 87

10 : 90

5 : 95

Yield [%]

Method

a

BF₃´ Et₂O

21

24

15

53

55

65

37

)

a

TiCl₄(0.3 equiv.)

TiCl₄(1.0 equiv.)

SnCl₄(1.0 equiv.)

a

b

c

b

35 : 65

)

^a) Addition of ( )-31 to a mixture of aldehyde ()-26 and promoter in CH₂Cl₂. ^b) Addition of the promoter in

CH₂Cl₂to a mixture ()-26/( )-31. ^c) Addition of the promoter in CH₂Cl₂precooled to 788 to a mixture ()-

26/( )-31

Table 3. Yields and Diastereoselectivities of the Mukaiyama Cross-Aldolizations of ( )-26 and ( )-31 in CH₂Cl₂

at 788

Lewis acid

29/( )-30

Yield [%]

Method

c

TiCl₄(1.0 equiv.)

SnCl₄(1.0 equiv.)

5 : 95

8 : 92

12 : 88

66

43

19

)

a

b

a

b

)

^c) See Table 2.

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To determine the relative configurations of the four diastereoisomeric aldols ()-27,

()-28, 29, and ( )-30, the mixtures ()-27/()-28 on one hand and 29/( )-30 on the

other hand were converted to the corresponding mixtures of (tert-butyl)dimethylsilyl

ethers, i.e., ()-32/()-33 and 34/( )-35, respectively (Scheme 3). Treatment of these

mixtures with NaBH₄in MeOH afforded the corresponding alcohol mixtures ( )-36/

()-37 and ( )-38/( )-39. Separation by column chromatography (silica gel) gave the

pure products ( )-36, ()-37, ( )-38, and ( )-39. Deprotection of the silyl group in

( )-36, ( )-38, and ( )-39 with Bu₄NF in THF provided the corresponding diols

( )-40, ( )-41, and ( )-42. These diols were unreactive under acidic conditions and

refused to form cyclic acetonides in the presence of excess Me₂C(OMe)₂. However,

reaction of diols (Æ)-40 (obtained by aldol condensation of racemic ketone (Æ)-25 and

racemic aldehyde (Æ)-26) and ( )-41 (derived from ( )-25 and ( )-26) with (t-

Bu)₂Si(OTf)₂in the presence of 2,6-lutidine (2,6-dimethylpyridine) in CH₂Cl₂afforded

the corresponding silanaphthalene derivatives (Æ)-43 (40% yield) and ( )-44 (45%

yield), respectively (Scheme 3).

The exo relative configuration of aldols 27 ± 30 (and of their silyl ethers) was inferred from the absence of

1

coupling between vicinal protons H_endoC(3) and H C(4) [33] in the H-NMR spectra of these compounds.

The coupling constants of 4.7, 4.9, 4.7, and 4.2 Hz observed for ³J(1,2exo) and of 4.6, 3.8, 4.7, and 4.8 Hz observed

3

1

for J(2exo, 3endo) in the H-NMR spectra of ( )-36, ()-37, ( )-38, and ( )-39, respectively, confirmed the

3

endo relative configuration of OH C(2) [23][25][28]. Typical trans-diaxial coupling constants J(4,4aendo)

10.8 and 11.4 Hz were observed in the ¹H-NMR spectra of the perhydro-1,3-dioxa-2-silanaphthalene derivatives

(Æ)-43 and ( )-44, respectively, thus confirming the ꢁantiꢀ relative configuration of aldols 27 and 29. The 2D-

NOESY ¹H-NMR spectrum of ( )-44 showed cross-peaks for proton pairs H C(4) (d 4.53) and H C(8a) (d

4.66).

In general, only the 3-exo-aldols were observed in the cross-aldolizations. However,

in large-scale preparations, the condensation of ()-26 with the lithium enolate of ( )-

25 produced 5 ± 10% of a minor aldol 45 when the lithium aldolate was neutralized via

cannulation into a 1n HCl solution stirred at 08. This by-product was not seen when the

workup consisted of the addition of AcOH/MeOH to the solution of the lithium

aldolate stirred at

788. This suggested that 45 arises from the acid-induced

epimerization at C(3) of aldol ()-27. The structure of 45 was confirmed by the

following transformations (Scheme 4). Protection of the aldol 45 as (tert-butyl)dime-

thylsilyl ether gave ( )-46 (70% yield). Reduction of ketone ( )-46 with NaBH₄in

MeOH at 58 produced the endo-alcohol ()-47 (75% yield). Treatment of ()-47 with

1.2 equiv. of Bu₄NF in THF at 258 liberated the diol and induced elimination of HCl

with formation of ()-48 in 70% yield. Treatment of the latter with Me₂C(OMe)₂in

acetone in the presence of p-toluenesulfonic acid (TsOH) furnished acetonide ()-49

in 89% yield. Reduction of aldol 45 with NaBH₄in MeOH gave diol 50 (90% yield)

that was protected as acetonide ( )-51 (89% yield) on treatment with Me₂C(OMe)₂/

acetone/TsOH (258, 5 h). The 3-endo relative configuration of ( )-46, ()-47, ()-48,

and 50, the 2-endo relative configuration of ()-48 and 50, and the relative

configurations of ()-49 and ( )-51 were established by spectroscopy, thus confirming

the ꢁsynꢀ relative configuration of aldol 45 (3-epimer of ()-27).

The ¹H-NMR spectra of ( )-46, ()-47, ()-48, and 50 showed ³J(4,3exo) 6.6, 5.5, 4.5, and 5.6 Hz,

3

respectively, in accordance with the endo relative configuration at C(3) [33]. Coupling constants J(1,2exo)

Helvetica Chimica Acta ± Vol. 83 (2000)

199

Scheme 3

4.7 and 4.8 Hz were found for ()-48 and 50, confirming the endo relative configuration of OH C(2). Vicinal

coupling constants ³J(4,4a) 6.4 and 6.5Hz, ³J(4a,8a) 8.0 and 8.5 Hz, ³J(4a,5) 4.1 and 4.7 Hz, and ³J(8,8a)

1

4.5 and 4.8 Hz were observed in the H-NMR spectra of acetonides ()-49 and ( )-51, respectively. The 2D-

NOESY spectrum of ()-49 exhibited NOEs between proton pairs H C(4) (d 5.25)/H C(4a) (d 2.47) and

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Helvetica Chimica Acta ± Vol. 83 (2000)

Scheme 4

H

C(4)/H C(8a) (d 4.70). Similarly, the 2D-NOESY spectrum of ( )-51 showed cross-peaks for H C(4) (d

5.19) with H C(4a) (d 2.24) and with H C(8a) (d 4.72), in accordance with the ꢁsynꢀ relative configuration of

aldol 45.

The good ꢁantiꢀ diastereoselectivity observed for the aldol reaction of ( )-25 and

()-26 via the lithium enolate can be explained by the Zimmerman-Traxler model [34]

(Fig. 1). For steric reasons, the transition state of that condensation adopts structure 52

(lithium chelated, chair-like conformation). To minimize 1,3-diaxial steric interactions,

the isoxazolyl group occupies an equatorial position and the addition follows the like

mode between the Si face of the aldehyde (adopting a s-trans-conformation) and the Si

face of the lithium enolate as shown in Fig. 1,a with 52. The lack of diastereoselectivity

of the aldol reaction of the lithium enolate of ( )-25 with ( )-26 can be interpreted in

terms of the two possible transition structures 53a and 53c (Fig. 1,b). In 53a, which

leads to ꢁantiꢀ-aldol 29, the s-trans-conformer of aldehyde ( )-26 approaches the exo-

face of the bicyclic enolate with its concave face, thus introducing more severe steric

repulsions than in the transition structure 52, which implies the approach of the s-trans-

conformer of aldehyde ()-26 with its convex face. The steric repulsions operating in

53a make other transition states able to compete and lead to ꢁsynꢀ-aldol ( )-30

concurrently with the formation of the ꢁantiꢀ-aldol 29. Transition structure 53b, in which

the s-cis conformer of ( )-26 would approach the enolate with its convex face, also

suffers from repulsive steric interactions between the bridgehead H C(4) of the

bicyclic enolate and the tetrahydrofuran ring of the aldehyde. Transition structure 53c

in which the s-trans-conformer of ( )-26 approaches the exo-face of the enolate by its

convex face, and in which the imino moiety instead of the carbaldehyde function is

coordinated to the lithium, can explain the formation of the ꢁsynꢀ-aldol ( )-30.

The syn diastereoselectivity observed for the Mukaiyama cross-aldol condensation

of enoxysilane ( )-31 with aldehydes ()-26 and ( )-26 can be interpreted in terms of

ꢁopen transition structuresꢀ (Noyoriꢀs model [32b] 54 and 55, respectively, as shown in

Helvetica Chimica Acta ± Vol. 83 (2000)

201

Fig. 1. Possible transition states for the cross-aldolizations a) of ( )-25 and ()-26, and b) of ( )-25 and ( )-26

via the lithium enolate of ( )-25

Fig. 2). These transition structures are similar to 53c (Fig. 1,b). The Lewis acid

promoter, TiCl₄, coordinates the aldehyde moiety and, possibly, the ether function of

the tetrahydrofuran ring of ()-26 and ( )-26. The 1:1 complexes TiCl₄/aldehyde thus

obtained approach the exo-face of the bicyclic enoxysilane ( )-31 without severe steric

interactions arising from the 7-oxabicyclo[2.2.1]heptene system as shown in Fig. 2. High

exo-ꢁsynꢀ diastereoselectivity had been observed for the TiCl₄-promoted additions of

2,3-O-isopropylidene-d-glyceraldehyde to (1R)- and (1S)-7-oxabicyclo[2.2.1]heptan-2-

one-derived silyl enol ethers [35]. In these latter cases, TiCl₄also coordinates

simultaneously to the carbaldehyde and an ethereal moiety of 2,3-O-isopropylidene-d-

glyceraldehyde; the 1:1 Lewis complexes thus obtained approach the exo face of the

enoxysilane in ꢁopen transition statesꢀ in which steric repulsions are minimized.

Fig. 2. Possible transition states (Noyoriꢀs model) for the Mukaiyama cross-aldol condensations of a) ( )-31 and

()-26 (54), and b) ( )-31 and ( )-26 (55)

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Conversion of the 7-Oxabicyclo[2.2.1]heptan-2-ols into 1,4-Anhydro-galactopyr-

anose Derivatives. ± Following protocols developed earlier in our laboratory [23][25],

we converted the four 7-oxabicyclo[2.2.1]heptan-2-ol derivatives ( )-36, ()-37, ( )-

38, and ( )-39 to the corresponding 1,4-anhydro-3-{[(tert-butyl)dimethylsilyloxy]-

[3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-

3-deoxy-2,6-di-O-(methoxymethyl)-a-d-galactopyranoses ()-62, ()-70, ( )-77, and

()-84, respectively (Scheme 5).

Alcohol ( )-36 was protected as the methoxymethyl ether ()-56 (86% yield) on

treatment with MeOCH₂Cl and Et₂NH in CH₂Cl₂(08, 1 h; then 258, 15 h). Oxidative

elimination of the phenylseleno group of ()-56 with m-chloroperbenzoic acid

(mCPBA) in THF/CH₂Cl₂( 788, 2 h; then 258, 4 h) [27] provided the corresponding

chloroalkene ()-57 in 95% yield. Double hydroxylation of ()-57 with Me₃NO in the

presence of a catalytical amount of OsO₄in THF/H₂O 5 :1 saturated with NaHCO₃

(258, 2 h) was, as expected for steric reasons, highly exo-face selective, leading to the

corresponding a-hydroxyketone of type E, which that was not isolated but directly

esterified with 4-bromobenzenesulfonyl chloride and Et₃N in CH₂Cl₂(08, 1 h; then 258,

12 h) giving brosylate ()-58 (88% yield based on ()-57). Baeyer-Villiger oxidation of

ketone ()-58 with mCPBA and NaHCO₃(258, 15 h) was highly regioselective [36], to

give the uronolactone ()-59 as single product (92% yield). Treatment of ()-59 with

MeOH under basic conditions led to mixtures of d-galacturonic and l-altruronic esters

()-60 and ()-61, respectively. The best yield (90%) and selectivity in favor of ()-60

(5 :1) was observed when ()-59 was methanolyzed with 25% MeOH in anhydrous

DMF containing 2 equiv. of anhydrous K₂CO₃at 08 for 30 min, then at 258 for 90 min.

Prolonged exposure of pure methyl galacturonate ()-60 to the above basic conditions

(258, 4 days) did not lead to its epimerization to ()-61, suggesting that the altruronic

derivative ()-61 arises from epimerization of the starting uronolactone ()-59 or of

the intermediate product of type F arising from the MeOH addition to ()-59. Esters

()-60 and ()-61 were readily separated by column chromatography (silica gel). They

arise most probably from the S_Ni displacement of intermediate of type F and of its 5-

epimer, respectively. Reduction of esters ()-60 and ()-61 with LiAlH₄(THF, 08)

afforded the corresponding primary alcohols, which were not isolated but directly

protected as methoxymethyl ethers ()-62 (82%) and ()-63 (82%), respectively. The

structures proposed for ()-60 to ()-63 were confirmed by their spectral data.

The exo relative configuration at C(3) of the 2,7-dioxabicyclo[2.2.1]heptane moieties in ()-60 and ()-62

was inferred from the absence of coupling constant between vicinal proton pairs H C(3) and H C(4), whereas

for ()-61 and ()-63, ³J(3,4) 4.0 and 3.6 Hz, respectively, were observed in their ¹H-NMR spectra. The 2D-

NOESY experiment with ()-60 established a cross-peak for proton pairs H C(3) (d 4.29) and H C(5) (d

2.13). The 2D-NOESY experiment with ()-63 revealed cross-peaks for proton pairs H C(5) (d 2.28) and

CH₂C(3) (d 3.98 and 3.73).

The same reaction sequence that converted ( )-36 to ()-62 and ()-63 was

applied to ()-37, ( )-38, and ( )-39 and provided the 1,4-anhydro-a-d-galactopyr-

anose derivatives ()-70, ( )-77 and ()-84, respectively, with the same ease and with

similar yields and diastereoselectivities (see ()-64 to ()-69, ( )-71 to ( )-76, and

( )-78 to ()-83, respectively). The structures of these compounds were established by

their spectral data, especially by their 1D-¹H-NMR spectra and 2D-NOESY experi-

ments (see the Exper. Part for details).

Helvetica Chimica Acta ± Vol. 83 (2000)

203

204

Helvetica Chimica Acta ± Vol. 83 (2000)

The methyl anhydrogalactopyranuronate ()-60 was obtained in 30% overall yield

in 9 steps from ketone ( )-25 and aldehyde ()-26 (Scheme 2); its 1'-epimer ()-68 was

obtained in 25% yield (9 steps) from enoxysilane ( )-31 and ()-26 (Scheme 2).

Similarly, ( )-75 was obtained in 20% overall yield (9 steps) from ( )-25 and ( )-26;

its 1'-epimer ( )-82 was obtained in 25% overall yield (9 steps) from ( )-31 and ( )-

26. In these latter procedures, mixtures of diastereoisomeric aldols, ()-27/()-28 on

one hand and 29/( )-30 on the other hand, could be used (see Scheme 3), and the

separation of diastereoisomeric products was carried out at the level of the brosylate

pairs ()-58/()-66 on one hand and ( )-73/( )-80 on the other hand.

Synthesis of Octahydro-8-(1,2,3-trihydroxypropyl)-2H-quinolizine-1,2,3,7,9-pentols. ±

The reduction of dihydroisoxazoles has been extensively studied by Jäger and co-workers

[29][37]. When we tried to reduce dihydroisoxazole ()-60, ( )-75, and ( )-82 with

LiAlH₄simultaneously with the reduction of their methyl uronate moieties, complex

mixtures of products were obtained that could not be purified. This forced us to reduce

the esters first (faster reactions than the dihydroisoxazole reductions) and to protect

the derived alcohols as the corresponding methoxymethyl ethers ()-62, ( )-77, and

()-84, respectively⁴). Their reduction with LiAlH₄in Et₂O (258, 5 days) generated the

corresponding aminodiols, the reduction of the dihydroisoxazole moieties being

accompanied by the cleavage of the silyl ether groups. In the case of ()-62, aminodiol

()-85 was obtained as a single diastereoisomer that was protected as benzyl carbamate

( )-86 (88% based on ()-62) and purified as such. The anti relative configuration of

the 1-amino-2-hydroxy moiety of ()-85 was expected [29][37] and confirmed by

conversion into ()-87, the product of condensation with glutaraldehyde in MeOH

(258) [38]. This reaction generated two further stereogenic centers, but because of the

conformational anomeric effect [39] and of steric factors, ()-87 was the major product

isolated in 65% yield (Scheme 6). The crude reaction mixture showed (¹H-NMR) the

presence of less than 8% of another diastereoisomer that was not isolated.

Scheme 6

4

)

Diastereoisomer ()-70 was not transformed further for reasons of financial shortfall.

Helvetica Chimica Acta ± Vol. 83 (2000)

205

The ¹H-NMR spectrum of ()-87 exhibited coupling constants ³J(2a,3ax) 9.7 and ³J(2a,3eq) 2.5 Hz

typical for an axial aminoacetal proton at C(2a), whereas ³J(5a,5) 2.9 and 2.4 Hz are typical for an equatorial

aminoacetal proton at C(5a). This is in agreement with the expected ꢁcis-decalinꢀ structure of

N

C(2a) C(3) C(4) C(5) C(5a) O(6) C(6a) C(10) C(10b) due to the N

C

O anomeric effect

3

[40]. Furthermore, the relatively small vicinal coupling constants J(10b,10a) 3.3 and J(6a,10a) 1.8 Hz are

consistent with axial/equatorial relationships. The dihedral angle between H C(1) and H C(10b) must be

close to 308 as given by ³J(1,10b) 6.5 Hz [41] and shown by a molecular model of ()-87. The 2D-NOESY

experiment with ()-87 revealed correlation peaks between proton pairs H C(10b) (d 3.73)/H C(5a) (d 4.69),

H

C(10b)/H C(6a) (d 4.17), and H C(6a)/H C(5a), confirming the ido-configuration of the 5-amino-5-

deoxy-1,2-O-isopropylidenehexofuranose moiety of ()-85. The observation of a strong NOE between protons

H

C(2a) (d 4.84) and H_axC(4) (d 1.72) confirmed the axial position of H C(2a) in the piperidine ring that

adopts a chair conformation as shown (Scheme 6).

Acidic hydrolysis of benzyl carbamate ( )-86 in CF₃COOH/H₂O 4 :1 at room

temperature (10 h) removed all acetal functions, generating a dialdose (mixture of

furanoses, pyranoses, anomers) that was not isolated but directly submitted to the

hydrogenolysis of the benzyl carbamate (H₂, Pd/C, H₂O), which liberated an amino-

deoxy-dialdose intermediate of type A (see Scheme 1) that was cyclized reductively

into quinolizidine 21, which could not be purified. It was fully characterized as its

octaacetate ()-88 (40% yield, based on ( )-86) obtained on treatment with Ac₂O/

pyridine and 4-(dimethylamino)pyridine (DMAP) as catalyst.

The LiAlH₄reduction of ( )-77 (Et₂O, 258, 5 d) led to a 6 :1 mixture of

diastereoisomeric aminodiols 89 and 90 that were protected and separated on

preparative scale as benzyl carbamate ()-91 (74% yield base on ( )-73) and ()-92

(minor), respectively (Scheme 7). A pure analytical sample of the major amino diol 89

Scheme 7

206

Helvetica Chimica Acta ± Vol. 83 (2000)

could be obtained by column chromatography (silica gel). It was condensed with

glutaraldehyde (MeOH, 258, 12 h) to give a major product ( )-93 isolated in 65% yield.

The structure of ( )-93 was established by its spectra including its ¹H-NMR (Table 4)

and 2D-NOESY data. Acidic hydrolysis, followed by catalytic hydrogenolysis of ()-91

provided quinolizidine ( )-22 (60% yield after purification by column chromatography

(silica gel)). The reduction of ()-84 by LiAlH₄afforded a single aminodiol 94 that was

protected as benzyl carbamate ()-95 (Scheme 7). Reaction of 94 with glutaraldehyde

1

gave ()-96 (70% yield), the structure of which was established by its H-NMR

(Table 4) and its 2D-NOESY data. Acidic hydrolysis of ()-95 followed by catalytic

hydrogenolysis liberated quinolizidine ()-23 (50% yield, after ion exchange

(Dowex)).

Table 4. ¹H-NMR Data (CDCl₃) for the 1,2a,3,5,5a,6a,6b,9a,10a,10b-Decahydro-8,8-dimethyl-4H-2,6,7,9,10-pentaoxa-

10c-azapentaleno[2,1-d]acenaphthylenes ()-87, ( )-93, and ()-96^a)

()-87

(

)-93

()-96

d [ppm] (³J(H,H) [Hz] d [ppm] (³J(H,H) [Hz] d [ppm] (³J(H,H) [Hz]

3

H

C(1) (³J(1,5'), J(1,10b))

4.21 (11.6, 6.5)

4.84 (9.7, 2.5)

4.47 (6.9, 2.3)

4.67 (10.3, 2.5)

4.65 )

4.15 (2.0)

4.55 (3.8)

5.92

3.96 (^b))

3.65 (2.3, 3.8)

4.19 (11.2, 6.0)

4.89 (10.4, 2.5)

4.68 (2.7, ^b))

4.15 (1.6)

4.46 (3.7)

5.92

4.08 (^b))

C(2a) (³J(2a,3ax), ³J(2a,3eq))

C(5a) (³J(5a,5))

C(6a) (³J(6a,10a))

C(6b) (³J(6b,9a))

C(9a)

C(10a) (³J(10a,10b), ³J(10a,6a)) 3.98 (3.3, 1.8)

C(10b) (³J(10b,1), ³J(10b,10a))

c

4.69 (2.9, 2.4)

b

4.17

)

4.48 (3.6)

5.82

3.73 (6.5, 3.3)

3.61 (6.0, 3.3)

^a) For further data, see Exper. Part. ^b) Not determined due to signal overlap or/and second-order effects.

1

Conformational Analysis of the Polyhydroxylated Quinolizidines. ± The H-NMR

spectrum of crude 21 was difficult to analyze. We thus examined the 400-MHz-

¹H-NMR spectrum of its polyacetate ()-88 (CDCl₃, 508). Coupling constants between

vicinal proton pairs and the 2D-NOESY data were consistent with two rapidly

equilibrating ꢁtrans-decalinꢀ and ꢁcis-decalinꢀ conformers 88a and 88b arising from the

inversion of the tertiary amine (Scheme 8).

NOEs were observed between proton pairs H C(9a) (d 2.95)/H_axC(4) (d 2.85), H C(9a)/H_axC(6)

(d2.65), H C(9) (d 5.07)/H C(7)(d 5.25), H C(9a)/H C(1') (d 5.51), and H_eqC(4) (d 3.01)/H_eqC(6) (d

3.35) as expected for conformer 88a. Since NOEs were also observed between proton pairs H C(9) (d 5.07)/

H

C(2') (d 5.33), H C(9)/H C(1) (d 4.98), H C(9)/H C(1'), H_axC(6)/H C(8) (d 2.65), and H C(7) (d

5.25 ppm)/H C(1'), conformer 88b is also present at equilibrium with 88a.

The ¹H-NMR spectrum of polyhydroxylated quinolizidine ( )-22 showed that this

compound existed predominantly as a trans-azadecalin with expected chair-chair

conformation in which the angular proton H C(9a) resides in an axial position anti-

1

periplanar to the lone electron pair of the N-atom. The H-NMR spectrum of ()-23

was consistent with a similar ꢁtrans-azadecalinꢀ structure in the chair-chair conforma-

tion. This is not surprising as ()-23 is the 9-epimer of ( )-22, which possesses an

equatorial instead of an axial 9-OH group.

Helvetica Chimica Acta ± Vol. 83 (2000)

207

Scheme 8

The coupling constants ³J(1,2) 3.2, ³J(2,3) 2.8, and ³J(3,4) 2.0 Hz (Table 5) of ( )-22 confirmed the axial

position for the OH groups at C(1), C(2), and C(3). The 2D-NOESY data revealed cross-peaks for proton pairs

H

C(9a) (d 2.28)/H C(8) (d 1.80), H C(9a)/H_axC(6) (d 2.31), H C(9a)/H_axC(4) (d 2.66), H C(8)/

H_axC(6), H_axC(6)/H_axC(4), H_eqC(6) (d 3.19)/H_eqC(4) (d 2.95) and H C(1) (d 4.0)/H C(9) (d 4.24).

Coupling constants ³J(1,2) 2.9, ³J(2,3) 2.9, and ³J(3,4) 1.7 Hz (Table 5) of ()-23 confirmed the axial

position of the OH groups at C(1), C(2), and C(3). The signal of H C(9) was a dd with relatively large coupling

constants ³J(8,9) 11.1 and ³J(9,9a) 9.6 Hz, a consequence of the trans-diaxial relationship of H C(8)/

H

C(9) and H C(9)/H C(9a). The coupling constants ³J(7,8) 3.2 and ³J(6,7) 3.0 and 1.4 Hz are in

agreement with the axial/equatorial and equatorial/equatorial relationships between these vicinal protons. The

2D-NOESY experiment established correlation peaks between proton pairs H C(9a) (d 2.12)/H C(8) (d

Table 5. ¹H-NMR (400 MHz) Data for the Quinolizidinepentols ( )-22 and ()-23

(

)-22 (in CD₃OD)

()-23 (in D₂O)

d [ppm] (J(H,H) [Hz])

H

C(1) (³J(1,2), ³J(1,9a))

C(2) (³J(2,3))

4.01 (3.2, 1.8)

3.84 (2.8)

3.75 (2.0, 2.2)

2.95 (12.3)

2.66

3.19 (12.2)

2.31 (2.9, 1.8)

4.24 (2.5)

1.80 (2.5, 10.2)

4.24 (^a))

3.98 (2.9, 1.6)

3.92 (2.9)

3.79 (1.7, 2.1)

2.76 (13.0)

2.48

2.79 (12.7)

2.26 (3.0, 1.4)

4.29 (3.2)

1.62 (11.1, 3.2)

4.13 (9.6)

C(3) (³J(3,4))

H_eqC(4) (²J(4ax,4eq))

H_axC(4)

H_eqC(6) (²J(6ax,6eq))

H_axC(6) (³J(6ax,7))

H

C(7) (³J(7,8))

C(8) (³J(8,9), ³J(8,1'))

C(9) (³J(9,9a))

C(9a)

C(1') (³J(1',2'))

C(2') (³J(2',3'))

C(3')

2.28

2.12

3.98 (5.3)

3.83 (6.9, 4.3)

3.63 & 3.53

4.14 (1.2)

3.93 (6.3)

3.75

^a) Not determined due to signal overlap or/and second-order effects.

208

Helvetica Chimica Acta ± Vol. 83 (2000)

1.62), H C(9a)/H_axC(6) (d 2.26), H C(9a)/H_axC(4) (d 2.48), H C(8)/H_axC(6), H_axC(6)/H_axC(4),

and H_eqC(6) (d 2.79)/H_eqC(4) (d 2.76), in agreement with the structure and conformation shown.

Glycosidase Inhibition Assays. ± The three polyhydroxylated quinolizidines 21, ( )-

22, and ()-23 have been tested for their inhibitory activities toward the following

enzymes under optimal pH and standard conditions [42]: a-l-fucosidase from bovine

epididymis and from human placenta, a-galactosidase from coffee beans, from

Aspergillus niger, and from Escherichia coli, b-galactosidase from E. coli, from bovine

liver, from Aspergillus niger, from Aspergillus orizae, and from jack beans, a-

glucosidase (maltase) from yeast and from rice, a-glucosidase (isomaltase) from

bakerꢀs yeast, amyloglucosidase from Aspergillus niger and from Rhizopus mold, b-

glucosidase from almonds and from Caldocellum saccharolyticum, a-mannosidase from

jack beans and from almonds, b-mannosidase from Helix pomatia, b-xylosidase from

Aspergillus niger, a-N-acetylgalactosaminidase from chicken liver, and b-N-acetylglu-

cosaminidase from jack beans, from bovine epididymis A, and from bovine epididymis

B. At 1 mm concentration (solution buffered just before use) of 21, b-galactosidase

from jack bean, amyloglucosidase from Aspergillus niger, and b-glucosidase from

Caldocellum saccharolyticum were inhibited by 30, 31, and 33%, respectively.

Quinolizidines ( )-22 and ()-23 were more selective inhibitors and inhibited only

b-galactosidase from jack bean by 40% and 34%, respectively.

Conclusion. ± Highly diastereoselective conditions were found for the cross-

aldolizations of ( )-(1S,4R,5R,6R)-6-endo-chloro-5-exo-(phenylseleno)-7-oxabicy-

clo[2.2.1]heptan-2-one (( )-25) and the newly obtained, enantiomerically pure

()-(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]-

isoxazole-3-carbaldehyde (()-26) and its enantiomer ( )-26. The exo,ꢁantiꢀ-aldols

()-27 and 29, and the exo,ꢁsynꢀ-aldol ( )-30 were converted in 13 steps to

(1R,2R,3S,7R,8S,9S,9aS)-8-(1,2,3-trihydroxypropyl)-2H-quinolizidine-1,2,3,7,9-pentol (21)

and its diastereoisomers ( )-22 (1S,2S,3R,7R,8S,9S,9aR) and ()-23 (1S,2S,3R,7R,

8S,9R,9aR) in 11, 9, and 9% overall yield, respectively, starting from furoisoxazole-3-

carbaldehydes ()-26 and ( )-26. These new polyhydroxylated quinolizidines are

weak, but selective glycosidase inhibitors.

We are grateful to the Swiss National Science Foundation and the Fonds Herbette (Lausanne) for financial

Â

support. We thank Prof. Volker Jäger, University of Stuttgart, for useful discussions, Miss Cecile Glanzmann,

Miss Carine Bühlmann, Mr. Maurizio Maio, Mr. Raphael Estoppey, Mr. Martial Rey, and Mr. Francisco

Â

Sepulveda for technical help, and Mr. Raynald Demange for the enzymatic assays. We thank also the European

COST D13 program for encouragement.

Experimental Part

General. See [23]. CC Column chromatography.

Enzymatic Assays. See [42b].

()-(1S,3S,4R,5R,6R)-6-endo-Chloro-3-exo-{(S)-hydroxy[(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-

dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-5-exo-(phenylseleno)-7-oxabicyclo[2.2.1]heptan-2-one

(()-27). Under Ar, 1.6m BuLi in hexane (3.66 ml, 5.8 mmol) was added slowly to anh. THF (10 ml) and

Me₃SiNHSiMe₃(1.3 ml, 6.2 mmol) in a flame-dried flask at 108, keeping the temp. at 58. After stirring at 58

for 15 min, the soln. was cooled to

788 and ( )-(1S,4R,5R,6R)-6-endo-chloro-5-exo-(phenylseleno)-7-

oxabicyclo[2.2.1]heptan-2-one (( )-25) [27] (1.42 g, 4.7 mmol) in anh. THF (15 ml) was added within 1 h. After

stirring at 788 for 15 min, a soln. of ()-(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]diox-

olo[4,5]furo-[2,3-d]isoxazole-3-carbaldehyde (()-26) [24] (1.0 g, 4.7 mmol) in anh. THF (10 ml) was added

Helvetica Chimica Acta ± Vol. 83 (2000)

209

within 1 h. After stirring at 788 for 3 h, AcOH (0.48 ml, 8.4 mmol) in MeOH (1.2 ml) was added slowly, and

the cooling bath was removed. Once at 208, the mixture was poured into a vigorously stirred mixture of sat. aq.

NaHCO₃soln. (50 ml) and CH₂Cl₂(100 ml). The aq. phase was extracted with CH₂Cl₂(50 ml, twice), the

combined org. extract dried (MgSO₄) and evaporated, and the residue purified by FC (light petroleum ether/

25

AcOEt 4 :1): 2.18 g (90%) of ()-27. M.p. 111 ± 1128. [a] 50, [a] 52, [a] 61, [a] 115,

589

577

546

435

25

[a] 150 (c 1.0, CHCl₃). UV (MeCN): 273 (1500), 207 (9300). IR (KBr): 3460, 2990, 1770, 1385, 1230,

405

1105, 1020, 900. ¹H-NMR (400 MHz, CDCl₃): 7.61 ± 7.65 (m, 2 arom. H); 7.35 ± 7.32 (m, 3 arom. H); 5.77

(d, ³J(4a'',7a'') 3.6, H C(4a'')); 5.68 (d, ³J(3a'',7b'') 6.4, H C(3a'')); 4.96 (d, ³J(7b'',3a'') 6.4, H C(7b''));

4.84 (dd, ³J(1',3) 8.3, ³J(1',OH C(1')) 2.6,

H C(1')); 4.78 ± 4.76 (m, H C(7a''), H C(4)); 4.54

(d, ³J(1,6) 5.6, H C(1)); 4.29 (ddd, ³J(6,1) 5.6, ³J(6,5) 2.8, ⁴J(6,4) 1.0, H C(6)); 3.65 (d, ³J(5,6) 2.8,

H

C(5)); 3.35 (d, ³J(HO C(1'),1') 2.6, OH C(1')); 2.78 (d, ³J(3,1') 8.3, H C(3)); 1.50 (s, Me); 1.37

(s, Me). ¹³C-NMR (100.6 MHz, CDCl₃): 204.9 (s, C(2)); 158.2 (s, C(3'')); 134.1 (s, arom. C); 133.8 (d, J 161,

2 arom. C); 129.5 (d, J 159, 2 arom. C); 128.2 (d, J 161, arom. C); 113.9 (s, C(6'')); 106.1 (d, J 184, C(4a''));

87.1 (d, J 163, C(7b'')); 86.5 (d, J 154, C(3a'')); 84.9 (d, J 168, C(7a'' or 4)); 84.6 (d, J 162, C(7a'' or 4));

83.0 (d, J 166, C(1)); 66.0 (d, J 149, C(1')); 57.0 (d, J 167, C(6)); 54.7 (d, J 138, C(3)); 50.4 (d, J 154,

C(5)); 27.8 (q, J 127, Me); 26.9 (q, J 127, Me). CI-MS (NH₃): 533 (24, [M NH₄] ), 515 (53, M ), 470 (4),

324 (40), 267 (12), 231 (48), 203 (17), 78 (100). Anal. calc. for C₂₁H₂₂ClNO₇Se (514.82): C 48.99, H 4.31, N 2.72;

found: C 49.00, H 4.41, N 2.65.

()-(1S,3S,4R,5R,6R)-6-endo-Chloro-3-exo-{(R)-hydroxy[(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-

dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-5-exo-(phenylseleno)-7-oxabicyclo[2.2.1]heptan-2-one

(()-28). A precooled ( 788) 0.5m TiCl₄soln. in CH₂Cl₂(2.24 ml, 1.12 mmol) was added dropwise to a soln. of

(

)-(1S,4R,5R,6R)-6-endo-chloro-5-exo-(phenylseleno)-2-(trimethylsilyloxy)-7-oxabicyclo[2.2.1]hept-2-ene (( )-

31) [43] (540 mg, 1.12 mmol) and ()-26 (240 mg, 1.12 mmol) in CH₂Cl₂(20 ml) at 788. After 1 h, the mixture

was poured into 1n HCl (40 ml), the aq. phase extracted with CH₂Cl₂(30 ml, 3 times), the combined org. extract

evaporated, and the residue purified by FC (light petroleum ether/AcOEt 4 :1): 371 mg (65%). Colorless foam.

25

[a] 27, [a] 29, [a] 32, [a] 58, [a] 73 (c 1.3, CHCl₃). UV (MeCN): 274 (2200),

589

577

546

435

405

216 (11000). IR (film): 3475, 2990, 2940, 1770, 1480, 1430, 1385, 1225, 1160, 1085, 1025, 900, 740. ¹H-NMR

3

(400 MHz, CDCl₃): 7.62 ± 7.59 (m, 2 arom. H); 7.37 ± 7.33 (m, 3 arom. H); 5.87 (d, J(4a'',7a'') 3.5, H C(4''));

5.78 (d, ³J(3a'',7b'') 7.0,

H

C(3a'')); 5.04 (s, H C(4)); 5.01 (d, ³J(7b'',3a'') 7.0,

H C(7b'')); 4.88

(d, ³J(1',3) 7.5, H C(1')); 4.78 (d, ³J(7a'',4a'') 3.5, H C(7a'')); 4.50 (dm, ³J(1,6) 5.7, H C(1)); 4.31

(ddd, ³J(6,1) 5.7, ³J(6,5) 3.0, ⁴J(6,4) 1.2, H C(6)); 3.60 (d, ³J(5,6) 3.0, H C(5)); 2.90 (br. s, OH C(1'));

2.85 (d, ³J(3,1') 7.5, H C(3)); 1.51 (s, Me); 1.38 (s, Me). ¹³C-NMR (100.6 MHz, CDCl₃): 202.3 (s, C(2)); 157.8

(s, C(3'')); 134.2 (d, J 162, 2 arom. C); 133.9 (s, arom. C); 129.5 (d, J 164, 2 arom. C); 128.3 (d, J 161, arom.

C); 114.1 (s, C(6'')); 106.0 (d, J 185, C(4a'')); 86.5 (d, J 163, C(7b'')); 86.4 (d, J 163, C(3a'')); 84.9 (d, J

158, C(7a'')); 84.3 (d, J 171, C(4)); 82.8 (d, J 172, C(1)); 65.0 (d, J 150, C(1')); 57.4 (d, J 163, C(6)); 56.0

(d, J 136, C(3)); 50.6 (d, J 153, C(5)); 27.8 (q, J 127, Me); 26.9 (q, J 127, Me). CI-MS (NH₃): 516 (3,

[M 1] ), 515 (5, M ), 514 (2), 441 (3), 338 (33), 312 (8), 191 (20), 157 (13), 71 (100). Anal. calc. for

C₂₁H₂₂ClNO₇Se (514.82): C 48.99, H 4.31, N 2.72; found: C 48.95, H 4.40, N 2.28.

(1S,3S,4R,5R,6R)-6-endo-Chloro-3-exo-{(S)-hydroxy[(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahydro-6,6-dime-

thyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-5-exo-(phenylseleno)-7-oxabicyclo[2.2.1]heptan-2-one (29).

As described for ()-27, with ( )-25 and ( )-26 [24]: 29/( )-30 1:1 (90%). This product was directly

transformed into 34.

(

)-(1S,3S,4R,5R,6R)-6-endo-Chloro-3-exo-{(R)-hydroxy[(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahydro-6,6-di-

methyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-5-exo-(phenylseleno)-7-oxabicyclo[2.2.1]heptan-2-one

25

(( )-30). As described for ()-28, with ( )-31 and ( )-26: ( )-30 (65%). Colorless foam. [a]

28, [a]

589

577

25

30, [a]

34, [a]

50, [a]

54 (c 0.5, CHCl₃). UV (MeCN): 272 (3000), 216 (13000). IR

546

435

405

(film): 3465, 3060, 2990, 2450, 1770, 1480, 1440, 1380, 1225, 1080, 1020, 900, 740. ¹H-NMR (400 MHz, CDCl₃):

7.63 ± 7.60 (m, 2 arom. H); 7.37 ± 7.33 (m, 3arom. H); 5.68 (d, ³J(3a'',7b'') 6.5,

H C(3a'')); 5.63

(d, ³J(4a'',7a'') 3.6, H C(4a'')); 5.04 (d, ³J(7b'',3a'') 6.5, H C(7b'')); 4.97 (d, ³J(1',3) 5.6, H C(1')); 4.96

(s, H C(4)); 4.78 (d, ³J(7a'',4a'') 3.6, H C(7a'')); 4.53 (dm, ³J(1,6) 5.8, H C(1)); 4.31 (ddd, ³J(6,1) 5.8,

³J(6,5) 2.9, ³J(6,4) 1.1, H C(6)); 3.62 (d, ³J(5,6) 2.9, H C(5)); 2.77 (d, ³J(3,1') 5.6, H C(3)); 2.73

(br. s, OH C(1')); 1.50 (s, Me); 1.37 (s, Me). ¹³C-NMR (100.6 MHz, CDCl₃): 202.6 (s, C(2)); 158.1 (s, C(3''));

134.3 (d, J 161, 2 arom. C); 129.6 (d, J 164, 2 arom. C); 128.4 (d, J 161, arom. C); 128.3 (s, arom. C); 113.9

(s, C(6'')); 106.2 (d, J 184, C(4a'')); 87.6 (d, J 164, C(7b'')); 86.5 (d, J 163, C(3a'')); 84.6 (d, J 162,

C(7a'')); 84.1 (d, J 168, C(4)); 82.5 (d, J 174, C(1)); 65.2 (d, J 150, C(1')); 57.3 (d, J 166, C(6)); 55.1

(d, J 135, C(3)); 50.8 (d, J 154, C(5)); 27.7 (q, J 127, Me); 26.8 (q, J 127, Me). CI-MS (NH₃): 516 (61,

210

Helvetica Chimica Acta ± Vol. 83 (2000)

[M 1] ), 515 (26, M ), 514 (36), 470 (6), 355 (60), 338 (100), 324 (83), 278 (9), 191 (18), 157 (9), 109 (18), 81

(39). Anal. calc. for C₂₁H₂₂ClNO₇Se (514.82): C 48.99, H 4.31, N 2.72; found: C 48.96, H 4.26, N 2.80.

()-(1S,3S,4R,5R,6R)-3-exo-{(S)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahy-

dro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-chloro-5-exo-(phenylseleno)-7-oxabi-

cyclo[2.2.1]heptan-2-one (()-32). At 08, 2,6-dimethylpyridine (2,6-lutidine; 1.4 ml, 12.8 mmol) and (t-

Bu)Me₂SiOSO₂CF₃(2.2 ml, 9.8 mmol) were added slowly to a soln. of ()-27 (2.20 g, 4.3 mmol) in dry CH₂Cl₂

(60 ml) at 08. The mixture was stirred at 08 for 1 h and at 258 for 5 h. After addition of CH₂Cl₂(100 ml), the

mixture was washed with sat aq. NaHCO₃soln. (50 ml, twice), the org. phase dried (MgSO₄) and evaporated,

and the residue purified by FC (light petroleum ether/AcOEt 10 :1): 2.48 g (92%) of ()-32. Colorless foam.

25

[a] 28, [a] 29, [a] 33, [a] 61, [a] 79 (c 1.1, CHCl₃). UV (MeCN): 272 (1400),

589

577

546

435

405

222 (5600). IR (film): 2930, 2850, 1775, 1250, 1230, 1100, 1025, 1000, 840, 780, 760. ¹H-NMR (400 MHz, CDCl₃):

7.62 ± 7.59 (m, 2 arom.H); 7.38 ± 7.28 (m, 3 arom. H); 5.79 (d, ³J(4a'',7a'') 3.5,

H C(4a'')); 5.51

(d, ³J(3a'',7b'') 6.0, H C(3a'')); 4.98 (d, ³J(1',3) 6.0, H C(1')); 4.86 (d, ³J(7b'',3a'') 6.0, H C(7b'')); 4.81

(s, H C(4)); 4.78 (d, ³J(7a'',4a'') 3.5, H C(7a'')); 4.40 (d, ³J(1,6) 5.6, H C(1)); 4.21 (ddd, ³J(6,1) 5.6,

³J(6,5) 3.2, ⁴J(6,4) 1.1, H C(6)); 3.49 (d, ³J(5,6) 3.2, H C(5)); 2.60 (d, ³J(3,1') 6.0, H C(3)); 1.51

(s, Me); 1.37 (s, Me); 0.87 (s, t-BuSi); 0.08 (s, MeSi); 0.05 (s, MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 201.6

(s, C(2)); 159.1 (s, C(3'')); 134.3 (d, J 161, 2 arom. C); 129.6 (d, J 159, 2 arom. C); 128.5 (d, J 161,

arom. C); 128.4 (s, arom. C); 113.4 (s, C(6'')); 106.2 (d, J 184, C(4a'')); 87.5 (d, J 163, C(7b'')); 86.8 (d, J

164, C(3a'')); 84.2 (d, J 162, C(4)); 84.1 (d, J 161, C(7a'')); 82.8 (d, J 172, C(1)); 66.5 (d, J 147, C(1')); 58.4

(d, J 134, C(3)); 57.0 (d, J 162, C(6)); 51.0 (d, J 153, C(5)); 27.7 (q, J 129, Me); 26.9 (q, J 127, Me); 25.6

(q, J 125, Me₃CSi); 18.0 (s, Me₃CSi); 4.9 (q, J 119, MeSi); 5.1 (q, J 119, MeSi). CI-MS (NH₃): 630 (1,

[M 1] ), 572 (10), 531 (1), 470 (2), 312 (4), 242 (32), 157 (17), 129 (30), 75 (100). Anal. calc. for

C₂₇H₃₆NClO₇SeSi (629.08): C 5.55, H 5.77, N 2.23; found: C 51.68, H 5.72, N 2.23.

()-(1S,3S,4R,5R,6R)-3-exo-{(R)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahy-

dro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-chloro-5-exo-(phenylseleno)-7-oxabi-

25

cyclo[2.2.1]heptan-2-one (()-33). As described for ()-32, with ()-28, ()-33 (95%). Colorless foam. [a]

589

25

22, [a] 22, [a] 26, [a] 44, [a] 54 (c 1.2, CHCl₃). UV (MeCN): 274 (3000), 215

577

546

435

405

1

(14200), 200 (18000). IR (film): 2980, 2955, 2930, 2860, 1775, 1255, 1085, 1040, 845, 780. H-NMR (400 MHz,

CDCl₃): 7.63 ± 7.60 (m, 2 arom. H); 7.35 ± 7.31 (m, 3 arom. H); 6.01 (d, ³J(4a'',7a'') 3.5, H C(4a'')); 5.76

(d, ³J(3a'',7b'') 7.4,

(d, ³J(7a'',4a'') 3.5,

H

C(3a'')); 4.97 (d, ³J(7b'',3a'') 7.4,

H C(7b'')); 4.83 (s, H C(4)); 4.79

C(7a'')); 4.77 (d, ³J(1',3) 9.4,

H

C(1')); 4.43 (d, ³J(1,6) 5.6,

H C(1)); 4.22

(ddm, ³J(6,1) 5.6, ³J(6,5) 3.3, H C(6)); 3.55 (d, ³J(5,6) 3.3, H C(5)); 2.90 (d, ³J(3,1') 9.4, H C(3));

1.53 (s, Me); 1.39 (s, Me); 0.82 (s, t-BuSi); 0.05 (s, MeSi); 0.02 (s, MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 202.0

(s, C(2)); 156.4 (s, C(3'')); 134.4 (d, J 162, 2 arom. C); 129.6 (d, J 165, 2 arom. C); 128.4 (d, J 161,

arom. C); 128.3 (s, arom. C); 114.1 (s, C(6'')); 105.9 (d, J 186, C(4a'')); 85.9 (d, J 163, C(3a'')); 85.6 (d, J

163, C(7b'')); 85.2 (d, J 165, C(7a'')); 84.5 (d, J 145, C(4)); 83.1 (d, J 167, C(1)); 65.3 (d, J 148, C(1')); 57.2

(d, J 164, C(6)); 56.8 (d, J 140, C(3)); 50.7 (d, J 153, C(5)); 27.9 (q, J 127, Me); 26.8 (q, J 125, Me); 25.6

(q, J 125, Me₃CSi); 17.9 (s, Me₃CSi); 4.8 (q, J 119, MeSi); 5.4 (q, J 119, MeSi). CI-MS (NH₃): 630 (2,

[M 1] ), 572 (6), 414 (2), 312 (5), 242 (6), 83 (100).

(1S,3S,4R,5R,6R)-3-exo-{(S)-[(tert-Butyl)dimethylsilyloxy][(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahydro-6,6-

dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-chloro-5-exo-(phenylseleno)-7-oxabicy-

clo[2.2.1]heptan-2-one (34). As described for ()-32, from mixture of 29/( )-30 1 :1: 34/( )-35 1:1. This

product was converted directly to ( )-38.

(

)-(1S,3S,4R,5R,6R)-3-exo-{(R)-[(tert-Butyl)dimethylsilyloxy][(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahydro-

6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-chloro-5-exo-(phenylseleno)-7-oxabicy-

clo[2.2.1]heptan-2-one (( )-35). As described for ()-32, with pure ( )-30: ( )-35 (93%). Colorless foam.

25

[a]

25, [a]

29, [a]

48, [a]

54 (c 0.5, CHCl₃). UV (MeCN): 272 (2600),

589

577

546

435

405

202 (13800). IR (film): 2990, 2955, 2930, 2860, 1770, 1470, 1375, 1255, 1230, 1090, 1025, 840, 740. ¹H-NMR

(400 MHz, CDCl₃): 7.61 ± 7.59 (m, 2 arom. H); 7.35 ± 7.32 (m, 3 arom. H); 5.74 (d, ³J(4a'',7a'') 3.6, H C(4a''));

5.65 (d, ³J(3a'',7b'') 6.4, H C(3a'')); 5.05 (d, ³J(7b'',3a'') 6.4, H C(7b'')); 4.87 (d, ³J(1',3) 6.9, H C(1'));

4.83 (br. s, H C(4)); 4.80 (d, ³J(7a'',4a'') 3.6, H C(7a'')); 4.45 (d, ³J(1,6) 5.6, H C(1)); 4.25 (ddd, ³J(6,1)

5.6, ³J(6,5) 2.9, ⁴J(6,4) 1.1, H C(6)); 3.60 (d, ³J(5,6) 2.9, H C(5)); 2.77 (d, ³J(3,1') 6.9, H C(3)); 1.50

(s, Me); 1.37 (s, Me); 0.84 (s, t-BuSi); 0.07 (s, MeSi); 0.04 (s, MeSi). ¹³C-NMR (100.6MHz, CDCl₃): 202.9

(s, C(2)); 158.1 (s, C(3'')); 134.0 (d, J 162, 2 arom. C); 129.6 (d, J 165, 2 arom. C); 128.4 (s, arom. C); 128.3

(d, J 161, arom. C); 113.6 (s, C(6'')); 106.2 (d, J 184, C(4a'')); 87.7 (d, J 163, C(7b'')); 86.4 (d, J 163,

C(3a'')); 84.5 (d, J 161, C(7a'')); 84.3 (d, J 161, C(4)); 82.6 (d, J 170, C(1)); 65.5 (d, J 147, C(1')); 57.2

Helvetica Chimica Acta ± Vol. 83 (2000)

211

(d, J 167, C(6)); 56.3 (d, J 135, C(3)); 51.0 (d, J 154, C(5)); 27.7 (q, J 129, Me); 26.9 (q, J 127, Me); 25.6

(q, J 125, Me₃CSi); 17.9 (s, Me₃CSi); 4.7 (q, J 119, MeSi); 5.2 (q, J 119, MeSi). CI-MS (NH₃): 630 (21,

[M 1] ), 629 (5, M ), 628 (11), 572 (6), 438 (9), 355 (48), 338 (100), 310 (14), 191 (42), 83 (83).

(

)-(1S,2R,3S,4R,5R,6R)-3-exo-{(S)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetra-

hydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]-isoxazol-3-yl]methyl}-6-endo-chloro-5-exo-(phenylseleno)-7-oxa-

bicyclo[2.2.1]heptan-2-endo-ol (( )-36). NaBH₄(150 mg, 3.95 mmol) was added portionwise to a soln. of ()-

32 (2.48 g, 3.95 mmol) in MeOH (40 ml) cooled to 58. After addition of H₂O (25 ml), the mixture was extracted

with CH₂Cl₂(4 Â 40 ml). The combined org. extract was dried (MgSO₄) and evaporated and the residue purified

25

by FC (light petroleum ether/AcOEt 9 :1): 2.27 g (91%) of ( )-36. Colorless foam. [a]

10, [a]

10,

589

577

25

[a]

11, [a]

23, [a]

31 (c 0.4, CHCl₃). UV (MeCN): 271 (2100), 216 (9700). IR (KBr): 3530,

546

435

405

2990, 2935, 2890, 1475, 1375, 1255, 1215, 1110, 840. ¹H-NMR (400 MHz, CDCl₃): 7.60 ± 7.57 (m, 2 arom. H);

7.35 ± 7.30 (m, 3 arom. H); 5.75 (d, ³J(4a'',7a'') 3.4, H C(4a'')); 5.40 (d, ³J(3a'',7b'') 6.2, H C(3a'')); 4.77

(d, ³J(7b'',3a'') 6.2, H C(7b'')); 4.76 (d, ³J(7a'',4a'') 3.4, H C(7a'')); 4.64 (d, ³J(1',3) 7.2, H C(1')); 4.47

(dd, ³J(1,6) 4.6, ³J(1,2) 4.7, H C(1)); 4.42 ± 4.35 (m, H C(2)); 4.32 (s, H C(4)); 4.25 (ddd, ³J(6,5) 4.3,

³J(6,1) 4.6, ⁴J(6,4) 1.1,

H

C(6)); 3.54 (d, ³J(5,6) 4.3,

H

C(5)); 2.70 (d, ³J(OH C(2),2) 8.3,

OH C(2)); 2.14 (dd, ³J(3,1') 7.2, ³J(3,2) 4.6, H C(3)); 1.50 (s, Me); 1.37 (s, Me); 0.88 (s, t-BuSi); 0.09

(s, MeSi); 0.08 (s, MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 159.1 (s, C(3'')); 134.3 (d, J 162, 2 arom. C); 129.4

(d, J 158, 2 arom. C); 128.2 (d, J 161, arom. C); 128.1 (s, arom. C); 113.5 (s, C(6'')); 106.1 (d, J 184,

C(4a'')); 87.3 (d, J 162, C(7b'')); 86.5 (d, J 163, C(3a'')); 86.2 (d, J 163, C(4)); 84.3 (d, J 161, C(7a'')); 78.4

(d, J 166, C(1)); 77.0 (d, J 162, C(2)); 68.3 (d, J 145, C(1')); 61.7 (d, J 160, C(6)); 56.9 (d, J 135, C(3));

52.8 (d, J 152, C(5)); 27.7 (q, J 115, Me); 26.8 (q, J 115, Me); 25.6 (q, J 120, Me₃CSi); 18.0 (s, Me₃CSi);

4.5 (q, J 118, MeSi); 5.0 (q, J 118, MeSi). CI-MS (NH₃): 574 (2), 342 (2), 314 (9), 242 (19), 158 (29), 129

(40), 78 (100). Anal. calc. for C₂₇H₃₈ClNO₇SeSi (631.08): C 51.39, H 6.07, N 2.22; found: C 50.77, H 5.85, N 2.14.

()-(1S,2R,3S,4R,5R,6R)-3-exo-{(R)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetra-

hydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-chloro-5-exo-(phenylseleno)-7-oxa-

bicyclo[2.2.1]heptan-2-endo-ol (()-37). As described for ( )-36, with ()-33: 90% of ()-37. Colorless foam.

25

[a] 40, [a] 39, [a] 46, [a] 77, [a] 90 (c 0.7, CHCl₃). UV (MeCN): 275 (2200),

589

577

546

435

405

215 (10000), 206 (10400). IR (film): 3510, 2955, 2930, 2860, 1470, 1375, 1255, 1220, 1105, 1065, 1000, 835, 760.

¹H-NMR (400 MHz, CDCl₃): 7.61 ± 7.58 (m, 2 arom. H); 7.33 ± 7.29 (m, 3 arom. H); 5.95 (d, ³J(4a'',7a'') 3.5,

H

C(4a'')); 5.69 (d, ³J(3a'',7b'') 6.5, H C(3a'')); 4.94 (d, ³J(7b'',3a'') 6.5, H C(7b'')); 4.81 (d, ³J(7a'',4a'')

3.5, H C(7a'')); 4.52 (s, H C(4)); 4.47 (dd, ³J(1,2) 4.9, ³J(1,6) 4.9, H C(1)); 4.39 (d, ³J(1',3) 10.6,

H

C(1')); 4.23 (ddd, ³J(6,5) 5.0, ³J(6,1) 4.9, ⁴J(6,4) 1.4, H C(6)); 4.03 (br. s, H C(2)); 3.57 (d, ³J(5,6)

5.0, H C(5)); 2.88 (br. s, OH C(2)); 2.27 (dd, ³J(3,1') 10.6, ³J(3,2) 3.8, H C(3)); 1.53 (s, Me); 1.37

(s, Me); 0.81 (s, t-BuSi); 0.03 (s, MeSi); 0.03 (s, MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 157.5 (s, C(3'')); 134.3

(d, J 162, 2 arom. C); 129.4 (d, J 165, 2 arom. C); 128.6 (s, arom. C); 128.1 (d, J 161, arom. C); 114.1

(s, C(6'')); 105.9 (d, J 186, C(4a'')); 86.8 (d, J 165, C(4)); 86.5 (d, J 163, C(7b'')); 85.6 (d, J 160, C(3a''));

84.1 (d, J 153, C(7a'')); 78.7 (d, J 162, C(1)); 76.1 (d, J 161, C(2)); 69.1 (d, J 146, C(1')); 61.7 (d, J 160,

C(6)); 57.0 (d, J 137, C(3)); 51.6 (d, J 152, C(5)); 27.8 (q, J 127, Me); 26.7 (q, J 125, Me); 25.6 (q, J 125,

Me₃CSi); 17.8 (s, Me₃CSi); 4.7 (q, J 119, MeSi); 5.3 (q, J 119, MeSi). CI-MS (NH₃): 649 (100, [M

NH₄] ), 632 (72, [M 1] ), 574 (20), 457 (55), 440 (57), 389 (29), 355 (60), 314 (70), 192 (54), 129 (34), 90

(68). Anal. calc. for C₂₇H₃₈ClNO₇SeSi (631.08): C 51.39, H 6.07, N 2.22; found: C 51.41, H 5.58, N 2.33.

(

)-(1S,2R,3S,4R,5R,6R)-3-exo-{(S)-[(tert-Butyl)dimethylsilyloxy][(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahy-

dro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-chloro-5-exo-(phenylseleno)-7-oxabi-

cyclo[2.2.1]heptan-2-endo-ol (( )-38). As described for ( )-36, with 34/( )-35 1:1. FC (light petroleum ether/

25

AcOEt 9 :1) gave a first fraction containing ( )-38 (41%). Colorless foam. [a]

58, [a]

61, [a]

589

577

546

25

72, [a]

130, [a]

160 (c 0.5, CHCl₃). UV (MeCN): 272 (2500), 215 (13000), 199 (16600). IR

435

405

1

(film): 3580, 2990, 2950, 2930, 2860, 1385, 1255, 1220, 1105, 1025, 840, 780, 740. H-NMR (400 MHz, CDCl₃):

7.68 ± 7.63 (m, 2 arom. H); 7.36 ± 7.30 (m, 3 arom. H); 5.56 (d, ³J(3a'',7b'') 6.1,

H C(3a'')); 5.02

(d, ³J(4a'',7a'') 3.7, H C(4a'')); 4.85 (d, ³J(7b'',3a'') 6.1, H C(7b'')); 4.67 (d, ³J(7a'',4a'') 3.7, H C(7a''));

4.48 ± 4.46 (m, H C(1)); 4.47 (d, ³J(1',3) 10.6,

H C(1')); 4.31 ± 4.20 (m, H C(6), H C(2)); 4.18

(s, H C(4)); 3.54 (d, ³J(5,6) 4.2, H C(5)); 2.57 (d, ³J(OH C(2),2) 8.8, OH C(2)); 2.27 (dd, ³J(3,1')

10.6, ³J(3,2) 4.6, H C(3)); 1.49 (s, Me); 1.33 (s, Me); 0.88 (s, t-BuSi); 0.12 (s, MeSi); 0.01 (s, MeSi).

¹³C-NMR (100.6 MHz, CDCl₃): 158.6 (s, C(3'')); 135.6 (d, J 163, 2 arom. C); 129.3 (d, J 166, 2 arom. C);

128.3 (d, J 161, arom. C); 128.1 (s, arom. C); 113.3 (s, C(6'')); 106.0 (d, J 184, C(4a'')); 87.7 (d, J 162,

C(7b'')); 86.3 (d, J 163, C(4)); 85.7 (d, J 154, C(3a'')); 84.2 (d, J 161, C(7a'')); 79.6 (d, J 151, C(2)); 78.6

(d, J 159, C(1)); 69.9 (d, J 142, C(1')); 62.4 (d, J 162, C(6)); 55.9 (d, J 137, C(3)); 52.6 (d, J 153, C(5));

212

Helvetica Chimica Acta ± Vol. 83 (2000)

27.5 (q, J 127, Me); 26.7 (q, J 127, Me); 25.5 (q, J 125, Me₃CSi); 17.9 (s, Me₃CSi); 4.5 (q, J 118, MeSi);

5.3 (q, J 118, MeSi). CI-MS (NH₃): 574 (5), 314 (22), 279 (3), 242 (38), 184 (19), 157 (38), 129 (54), 75

(100). Anal. calc. for C₂₇H₃₈ClNO₇SeSi (631.08): C 51.39, H 6.07, N 2.22; found: C 51.44, H 6.15, N 2.29.

(

)-(1S,2R,3S,4R,5R,6R)-3-exo-{(R)-[(tert-Butyl)dimethylsilyloxy][(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahy-

dro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-chloro-5-exo-(phenylseleno)-7-oxabi-

cyclo[2.2.1]heptan-2-endo-ol (( )-39). As described for ( )-36, with pure ( )-35: ( )-39 (90%). Colorless

25

foam. [a]

43, [a]

46, [a]

53, [a]

99, [a]

123 (c 0.5, CHCl₃). UV (MeCN): 271

589

577

546

435

405

(2200), 218 (8200). IR (KBr): 3475, 2990, 2955, 2930, 2895, 2860, 1480, 1380, 1250, 1210, 1160, 1105, 1025, 840.

¹H-NMR (400 MHz, CDCl₃): 7.61 ± 7.59 (m, 2 arom. H); 7.33 ± 7.28 (m, 3 arom. H); 5.83 (d, ³J(4a'', 7a'') 3.6,

H

C(4a'')); 5.64 (d, ³J(3a'',7b'') 6.3, H C(3a'')); 4.93 (d, ³J(7b'',3a'') 6.3, H C(7b'')); 4.81 (d, ³J(7a'',4a'')

3.6, H C(7a'')); 4.55 (s, H C(4)); 4.45 ± 4.40 (m, H C(6), H C(1')); 4.31 (dd, ³J(6,5) 4.2, ³J(6,1) 3.5,

H

C(6)); 3.88 ± 3.86 (m, H C(2)); 3.58 (d, ³J(5,6) 4.2, H C(5)); 2.82 (d, ³J(OH C(2),2) 8.6, OH C(2));

2.18 (dd, ³J(3,1') 9.8, ³J(3,2) 4.8, H C(3)); 1.50 (s, Me); 1.36 (s, Me); 0.84 (s, t-BuSi); 0.05 (s, 2 MeSi).

¹³C-NMR (100.6 MHz, CDCl₃): 158.0 (s, C(3'')); 135.3 (s, arom. C); 134.4 (d, J 162, 2 arom. C); 129.4 (d, J

159, 2 arom. C); 128.2 (d, J 161, arom. C); 113.5 (s, C(6'')); 106.2 (d, J 184, C(4a'')); 87.6 (d, J 163, C(7b''));

86.4 (d, J 165, C(3a'')); 86.2 (d, J 164, C(4)); 84.2 (d, J 168, C(7a'')); 78.1 (d, J 157, C(1)); 77.0 (d, J 157,

C(2)); 69.0 (d, J 146, C(1')); 62.3 (d, J 163, C(6)); 56.4 (d, J 135, C(3)); 52.7 (d, J 152, C(5)); 27.7 (q, J

127, Me); 26.8 (q, J 127, Me); 25.7 (q, J 125, Me₃CSi); 18.0 (s, Me₃CSi); 4.5 (q, J 119, MeSi); 5.0 (q, J

119, MeSi). CI-MS (NH₃): 574 (7), 342 (3), 314 (11), 242 (27), 158 (30), 129 (45), 78 (100). Anal. calc. for

C₂₇H₃₈ClNO₇SeSi (631.08): C 51.39, H 6.07, N 2.22; found: C 51.39, H 6.13, N 2.27.

(

)-(1S,2R,3R,4R,5R,6R)-6-endo-Chloro-3-exo-{(S)-hydroxy[(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-

6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-5-exo-(phenylseleno)-7-oxabicyclo[2.2.1]heptan-2-

endo-ol (( )-40). To a soln. of ( )-36 (90 mg, 0.142 mmol) in THF (1.5 ml), 1m TBAF in THF (0.17 ml,

0.17 mmol) was added. The mixture was stirred at 258 for 2 h, then AcOEt (10 ml) was added. The mixture was

washed with brine (3 ml, 3 times), the org. phase dried (MgSO₄) and evaporated, and the residue purified by FC

25

(light petroleum ether/AcOEt 1 :2.5): 58 mg (80%) of ( )-40. Colorless solid. M.p. 162 ± 1638. [a]

10,

589

25

[a]

18, [a]

14, [a]

23, [a]

31 (c 0.1, CHCl₃). UV (MeCN): 270 (2100), 241 (3500),

577

546

435

405

209 (8200). IR (KBr): 3510, 3360, 3055, 2995, 2960, 1580, 1480, 1380, 1210, 1070, 1025, 1005. ¹H-NMR

(400 MHz, CDCl₃): 7.62 ± 7.58 (m, 2 arom. H); 7.36 ± 7.30 (m, 3 arom. H); 5.77 (d, ³J(4a'',7a'') 3.5, H C(4a''));

5.65 (d, ³J(3a'',7b'') 6.6,

H

C(3a'')); 4.93 (d, ³J(7b'',3a'') 6.6,H C(7'')); 4.78 (d, ³J(7a'',4a'') 3.5,

3

H

C(7a'')); 4.61 (dd, ³J(1',3) 7.5, J(1',OH C(1')) 7.5, H C(1')); 4.53 ± 4.48 (m, H C(2), H C(1)); 4.43

(s, H C(4)); 4.32 (ddd, ³J(6,5) 4.3, ³J(6,5) 4.2, J 1.7, H C(6)); 3.60 (d, ³J(5,6) 4.3, H C(5)); 2.88

(d, ³J(OH C(2),2) 7.9, OH C(2)); 2.51 (d, ³J(OH C(1'),1') 5.7, OH C(1')); 2.28 (dd, ³J(3,1') 7.5,

³J(3,2) 4.2, H C(3)); 1.52 (s, Me); 1.38 (s, Me). ¹³C-NMR (100.6 MHz, (D₆)acetone): 160.6 (s, C(3''));

133.5 (d, J 162, 2 arom. C); 130.7 (s, arom. C); 130.2 (d, J 160, 2 arom. C); 128.1 (d, J 161, arom. C); 113.9

(s, C(6'')); 106.9 (d, J 184, C(4a'')); 88.0 (d, J 163, C(4)); 87.7 (d, J 161, C(7b'')); 87.5 (d, J 163, C(3a''));

85.7 (d, J 161, C(7a'')); 80.1 (d, J 170, C(1)); 77.8 (d, J 161, C(2)); 68.2 (d, J 165, C(1')); 62.0 (d, J 158,

C(6)); 56.5 (d, J 138, C(3)); 52.6 (d, J 153, C(5)); 28.0 (q, J 129, Me); 27.1 (q, J 130, Me). CI-MS (NH₃):

517 (4, M ), 360 (3), 286 (5), 228 (23), 170 (25), 110 (23), 78 (100). Anal. calc. for C₂₁H₂₄ClNO₇Se (516.80):

C 48.80, H 4.68, N 2.71; found: C 48.84, H 4.76, N 2.75.

(

)-(1S,2R,3R,4R,5R,6R)-6-endo-Chloro-3-exo-{(S)-hydroxy[(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahydro-

6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-5-exo-(phenylseleno)-7-oxabicyclo[2.2.1]heptan-2-

25

endo-ol (( )-41). As described for ( )-40, with ( )-38: ( )-41 (75%). Colorless foam. [a]

50, [a]

589

577

25

53, [a]

60, [a]

108, [a]

134 (c 1.0, CHCl₃). UV (MeCN): 273 (3900), 244 (4400), 198

546

435

405

(14000). IR (film): 3515, 3390, 2990, 1580, 1380, 1210, 1065, 1005, 810. ¹H-NMR (400 MHz, CDCl₃): 7.66 ± 7.64

(m, 2 arom. H); 7.34 ± 7.31 (m, 3 arom. H); 5.68 (d, ³J(3a'',7b'') 6.3, H C(3a'')); 5.15 (d, ³J(4a'',7a'') 3.6,

H

C(4a'')); 4.92 (d, ³J(7b'',3a'') 6.3, H C(7b'')); 4.67 (d, ³J(7a'',4a'') 3.6, H C(7a'')); 4.53 (d, ³J(1',3)

10.1, H C(1')); 4.49 (dd, ³J(2,3) 4.7, ³J(2,1) 4.7, H C(2)); 4.39 (ddd, ³J(6,5) 4.2, ³J(6,1) 3.8, J 1.2,

H

C(6)); 4.30 ± 4.27 (m, H C(1)); 4.25 (s, H C(4)); 3.57 (d, ³J(5,6) 4.2, H C(5)); 3.32 (br. s, OH); 2.72

(br. s, OH); 2.24 (dd, ³J(3,1') 10.1, J(3,2) 4.7, H C(3)); 1.47 (s, Me); 1.34 (s, Me). ¹³C-NMR (100.6 MHz,

CDCl₃): 158.5 (s, C(3'')); 135.3 (d, J 162, 2 arom. C); 129.4 (d, J 165, 2 arom. C); 128.3 (d, J 161, arom. C);

128.2 (s, arom. C); 113.5 (s, C(6'')); 106.0 (d, J 185, C(4a'')); 87.6 (d, J 162, C(4)); 86.5 (d, J 155, C(7b''));

86.0 (d, J 162, C(3a'')); 84.4 (d, J 162, C(7a'')); 78.7 (d, J 151, C(1)); 78.4 (d, J 164, C(2)); 68.8 (d, J 147,

C(1')); 62.1 (d, J 160, C(6)); 54.8 (d, J 136, C(3)); 52.5 (d, J 153, C(5)); 27.6 (q, J 125, Me); 26.8 (q, J

3

125, Me). CI-MS (NH₃): 519 (4, [M 2] ), 518 (2, [M 1] ), 517 (8, M ), 360 (4), 314 (25), 259 (13), 228 (72),

Helvetica Chimica Acta ± Vol. 83 (2000)

213

192 (17), 157 (48), 111 (37), 78 (100). Anal. calc. for C₂₁H₂₄ClNO₇Se (516.80): C 48.80, H 4.68, N 2.71; found:

C 48.85, H 4.88, N 2.62.

(

)-(1S,2R,3R,4R,5R,6R)-6-endo-Chloro-3-exo-{(R)-hydroxy[(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahydro-

6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-5-exo-(phenylseleno)-7-oxabicyclo[2.2.1]heptan-2-

25

endo-ol (( )-42). As described for ( )-40, with ( )-39: ( )-42 (85%). Colorless foam. [a]

64, [a]

589

577

25

68, [a]

77, [a]

135, [a]

165 (c 1.0, CHCl₃). UV (MeCN): 270 (3100), 242 (4900), 200

546

435

405

(15000). IR (KBr): 3440, 2985, 1480, 1375, 1220, 1160, 1080, 1020. ¹H-NMR (400 MHz, CDCl₃): 7.63 ± 7.57

(m, 2 arom. H); 7.35 ± 7.30 (m, 3 arom. H); 5.75 (d, ³J(4a'',7a'') 3.5, H C(4a'')); 5.70 (d, ³J(3a'',7b'') 6.4,

H

C(3a'')); 4.97 (d, ³J(7b'',3a'') 6.4, H C(7b'')); 4.80 (d, ³J(7a'',4a'') 3.5, H C(7a'')); 4.69 (s, H C(4));

4.51 (d, ³J(1',3) 8.6, H C(1')); 4.46 (dd, ³J(6,1) 4.5, ³J(6,5) 4.2, H C(6)); 4.37 ± 4.34 (m, H C(1)); 4.13 ±

4.08 (m, H C(2)); 3.60 (d, ³J(5,6) 4.2, H C(5)); 2.87 (br. s, OH); 2.47 (br. s, OH); 2.20 (dd, ³J(3,1') 8.6,

³J(3,2) 4.8, H C(3)); 1.50 (s, Me); 1.37 (s, Me). ¹³C-NMR (100.6 MHz, CDCl₃): 158.4 (s, C(3'')); 134.3 (d, J

162, 2 arom. C); 133.4 (s, arom. C); 129.4 (d, J 162, 2 arom. C); 128.1 (d, J 161, arom. C); 113.9 (s, C(6''));

106.2 (d, J 184, C(4a'')); 87.1 (d, J 163, C(7b'')); 86.6 (d, J 163, C(3a'')); 86.1 (d, J 166, C(4)); 84.5 (d, J

168, C(7a'')); 78.2 (d, J 165, C(1 or 2)); 77.0 (d, J 162, C(1 or 2)); 67.7 (d, J 155, C(1')); 62.3 (d, J 162,

C(6)); 55.6 (d, J 135, C(3)); 52.3 (d, J 152, C(5)); 27.7 (q, J 125, Me); 26.8 (q, J 127, Me). CI-MS (NH₃):

518 (3, [M 1] ), 517 (7, M ), 464 (2), 360 (4), 314 (9), 228 (85), 158 (43), 78 (100). Anal. calc. for

C₂₁H₂₄ClNO₇Se (516.80): C 48.80, H 4.68, N 2.71; found: C 48.91, H 4.56, N 2.63.

(Æ)-(4RS,4aSR,5SR,6SR,7SR,8RS,8aSR)-2,2-Di(tert-butyl)-7-chloro-4-[(3aSR,4aSR,7aSR,7bRS)-

3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]-4a,5,6,7,8,8a-hexahydro-6-(phenyl-

seleno)-5,8-epoxy-4H-1,3,2-benzodioxasiline ((Æ)-43). Under Ar, 2,6-dimethylpyridine (0.011 ml, 0.09 mmol)

and (t-Bu)₂Si(OSO₂CF₃)₂(0.012 ml, 0.036 mmol) were added to a soln. of (Æ)-40 (15.3 mg, 0.029 mmol;

obtained as ( )-40 starting from (Æ)-25 and (Æ)-26) in anh. CH₂Cl₂(1.5 ml) at 08. After stirring at 208 for 2 h

and at 408 for 4 h, the mixture was poured into brine (2 ml) and extracted with CH₂Cl₂(8 ml, 3 times). The

combined org. extract was dried (MgSO₄) and evaporated and the residue purified by FC (light petroleum

ether/AcOEt 3 :1): 13 mg (40%) of (Æ)-43. Colorless oil. ¹H-NMR (400 MHz, CDCl₃): 7.59 ± 7.57 (m, 2 ar-

om. H); 7.34 ± 7.31 (m, 3 arom. H); 5.70 (d, ³J(4a',7a') 3.5, H C(4a')); 5.51 (d, ³J(3a',7b') 6.4, H C(3a'));

4.83 (d, ³J(7b',3a') 6.4, H C(7b')); 4.78 (dd, ³J(8a,8) 4.2, ³J(8a,4a) 3.8, H C(8a)); 4.76 (d, ³J(7a',4a')

3.5, H C(7a')); 4.49 ± 4.47 (m, H C(4), H C(8)); 4.30 (s, H C(5)); 4.15 (dd, ³J(7,6) 5.3, ³J(7,8) 3.5,

H

C(7)); 3.51 (d, ³J(6,7) 5.3, H C(6)); 2.23 (dd, ³J(4a,4) 10.8, ³J(4a,8a) 3.3, H C(4a)); 1.49 (s, Me);

1.37 (s, Me); 1.05 (s, 2 t-Bu). ¹³C-NMR (100.6 MHz, CDCl₃): 158.6 (s, C(3')); 134.0 (d, J 160, 2 arom. C); 133.9

(s, arom. C); 129.2 (d, J 162, 2 arom. C); 127.8 (d, J 159, arom. C); 113.9 (s, C(6')); 106.1 (d, J 184, C(4a'));

87.1 (d, J 165, C(5)); 86.8 (d, J 163, C(7b')); 86.5 (d, J 163, C(3a')); 84.6 (d, J 162, C(7a')); 79.4 (d, J

162, C(8)); 77.1 (d, J 165, C(8a)); 68.6 (d, J 147, C(4)); 60.4 (d, J 161, C(7)); 56.5 (d, J 136, C(4a)); 51.5

(d, J 152, C(6)); 27.7 (q, J 125, Me); 27.3 (q, J 125, Me₃CSi); 27.1 (q, J 125, Me₃CSi); 26.8 (q, J 127,

Me); 24.3 (s, Me₃CSi); 20.8 (s, Me₃CSi). CI-MS (NH₃): 658 (1, [M 1] ), 618 (11), 358 (6), 269 (14), 225 (10),

157 (20), 77 (100).

(

)-(4S,4aR,5R,6R,7R,8S,8aR)-2,2-Di(tert-butyl)-7-chloro-4-[(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahydro-6,6-

dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]-4a,5,6,7,8,8a-hexahydro-6-(phenylseleno)-5,8-epoxy-4H-1,3,2-

25

benzodioxasiline (( )-44). As described for (Æ)-43, with ( )-41: ( )-44 (45%). Colorless oil. [a]

31,

589

25

[a]

35, [a]

39, [a]

70, [a]

87 (c 0.6, CHCl₃). UV (MeCN): 272 (2300), 216 (11600),

577

546

435

405

199 (15500). IR (film): 2965, 2935, 2860, 1470, 1385, 1230, 1135, 1090, 1025, 830, 740. ¹H-NMR (400 MHz,

CDCl₃): 7.67 ± 7.65 (m, 2 arom. H); 7.34 ± 7.31 (m, 3 arom. H); 5.60 (d, ³J(3a',7b') 6.3,

H C(3a')); 5.10

(d, ³J(4a',7a') 3.7, H C(4a')); 4.90 (d, ³J(7b',3a') 6.3, H C(7b')); 4.67 (d, ³J(7a',4a') 3.7, H C(7a')); 4.66

(m, H C(8a)); 4.53 (d, ³J(4,4a) 11.4, H C(4)); 4.44 (dd, ³J(8,8a) 4.7, ³J(8,7) 4.6, H C(8)); 4.20 ± 4.16

(m, H C(7), H C(5)); 3.50 (d, ³J(6,7) 5.0, H C(6)); 2.29 (dd, ³J(4a,4) 11.4, ³J(4a,8a) 3.5, H C(4a));

1.48 (s, Me); 1.34 (s, Me); 1.04 (s, t-BuSi); 1.00 (s, t-BuSi). ¹³C-NMR (100.6 MHz, CDCl₃): 158.2 (s,C(3')); 135.5

(d, J 162, 2 arom. C); 129.3 (d, J 161, 2 arom. C); 128.2 (d, J 161, arom. C); 127.5 (s, arom. C); 113.4

(s, C(6')); 106.0 (d, J 185, C(4a')); 87.9 (d, J 163, C(7b')); 87.2 (d, J 163, C(5)); 85.7 (d, J 157, C(3a')); 84.4

(d, J 161, C(7a')); 79.5 (d, J 148, C(8)); 78.2 (d, J 150, C(8a)); 69.5 (d, J 153, C(4)); 61.1 (d, J 161,

C(7)); 55.7 (d, J 137, C(4a)); 51.8 (d, J 148, C(6)); 27.5 (q, J 127, Me); 27.2 (q, J 126, Me); 27.0 (q, J 126,

Me₃CSi); 26.8 (q, J 126, Me₃CSi); 20.8 (s, Me₃CSi); 19.9 (s, Me₃CSi). CI-MS (NH₃): 676 (11, [M NH₄] ), 658

(6, [M 1] ), 657 (2, M ), 618 (6), 484 (6), 398 (9), 338 (100), 191 (20), 126 (11).

(1S,3R,4R,5R,6R)-6-endo-Chloro-3-endo-{(S)-hydroxy[(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-di-

methyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-5-exo-(phenylseleno)-7-oxabicyclo[2.2.1]heptan-2-one

(45). Depending on workup conditions after the aldol condensation of ()-26 via the lithium enolate of ( )-25,

214

Helvetica Chimica Acta ± Vol. 83 (2000)

45 was observed as a by-product accompanying ()-27. 45: 2nd fraction of the FC; not obtained as a pure

substance. ¹H-NMR (400 MHz, CDCl₃): 7.60 ± 7.56 (m, 2 arom. H); 7.36 ± 7.28 (m, 3 arom. H); 5.74

(d, ³J(4a'',7a'') 3.5, H C(4a'')); 5.61 (d, ³J(3a'',7b'') 6.5, H C(3a'')); 5.11 (d, ³J(4,3) 5.9, H C(4)); 4.99

(d, ³J(1',3) 6.0, H C(1')); 4.91 (d, ³J(7b'',3a'') 6.5, H C(7b'')); 4.76 (d, ³J(7a'',4a'') 3.5, H C(7a)); 4.52

(d, ³J(1,6) 5.4,

H

C(1)); 4.26 ± 4.23 (m, H C(5),

H

C(6)); 3.50 (br. s, OH); 3.28 (dd, ³J(3,1') 6.0,

³J(3,4) 5.9, H C(3)); 1.49 (s, Me); 1.36 (s, Me). ¹³C-NMR (100.6 MHz, CDCl₃): 204.7 (s, C(2)); 158.3

(s, C(3'')); 134.0 (d, J 162, 2 arom. C); 129.2 (d, J 161, 2 arom. C); 128.6 (s, arom. C); 127.9 (d, J 161,

arom. C); 113.8 (s, C(6'')); 106.0 (d, J 183, C(4a'')); 87.0 (d, J 164, C(7b'')); 86.3 (d, J 165, C(3a'')); 85.1

(d, J 161, C(4)); 84.5 (d, J 168, C(7a'')); 83.6 (d, J 169, C(1)); 63.1 (d, J 147, C(1')); 57.8 (d, J 166, C(6));

56.7 (d, J 133, C(3)); 46.0 (d, J 160, C(5)); 27.6 (q, J 126, Me); 26.7 (q, J 127, Me).

(

)-(1S,3R,4R,5R,6R)-3-endo-{(S)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahy-

dro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-chloro-5-exo-(phenylseleno)-7-oxabi-

cyclo[2.2.1]heptan-2-one (( )-46). At 08, 2,6-dimethylpyridine (0.46 ml, 4.2 mmol) and (t-Bu)Me₂SiOSO₂CF₃

(0.72 ml, 3.2 mmol) were added slowly to a soln. of crude 45 (720 mg, 1.4 mmol) in dry CH₂Cl₂(17 ml). The

mixture was stirred at 08 for 1 h and at 258 for 5 h. After addition of CH₂Cl₂(40 ml), the mixture was washed

with sat. aq. NaHCO₃soln. (30 ml, twice), the org. phase dried (MgSO₄) and evaporated, and the residue

purified by FC (light petroleum ether/AcOEt 7:1): 614 mg (70%) of ( )-46. Colorless solid. M.p. 140 ± 1418.

25

[a]

14, [a]

13, [a]

16, [a]

29, [a]

36 (c 1.0, CHCl₃). UV (MeCN): 273 (2500),

589

577

546

435

405

200 (13000). IR (KBr): 2960, 2930, 1770, 1255, 1080, 1025, 890, 840, 780. ¹H-NMR (400 MHz, CDCl₃): 7.63 ± 7.60

(m, 2 arom. H); 7.34 ± 7.27 (m, 3 arom. H); 5.75 (d, ³J(4a'',7a'') 3.6, H C(4a'')); 5.51 (d, ³J(3a'',7b'') 6.3,

H

C(3a'')); 5.01 ± 4.99 (m, H C(7b''), H C(4)); 4.91 (d, ³J(1',3) 7.5, H C(1')); 4.79 (d, ³J(7a'',4a'') 3.6,

C(7a'')); 4.50 (d, ³J(1,6) 5.8, H C(1)); 4.39 (dd, ³J(6,1) 5.8, ³J(6,5) 3.3, H C(6)); 4.06 (d, ³J(5,6) 3.3,

C(5)); 3.27 (dd, ³J(3,1') 7.5, ³J(3,4) 6.6, H C(3)); 1.48 (s, Me); 1.35 (s, Me); 0.85 (s, t-BuSi); 0.04

(s, MeSi); 0.03 (s, MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 203.0 (s, C(2)); 157.9 (s, C(3'')); 134.5 (d, J 162,

2 arom. C); 129.5 (d, J 161, 2 arom. C); 128.3 (d, J 161, arom. C); 128.1 (s, arom. C); 113.6 (s, C(6'')); 106.3

(d, J 184, C(4a'')); 87.7 (d, J 163, C(7b'')); 86.6 (d, J 163, C(3a'')); 85.2 (d, J 164, C(4)); 84.2 (d, J 161,

C(7a'')); 84.0 (d, J 170, C(1)); 65.1 (d, J 145, C(1')); 58.9 (d, J 167, C(6)); 57.7 (d, J 132, C(3)); 46.2

(d, J 153, C(5)); 27.7 (q, J 128, Me); 26.8 (q, J 127, Me); 25.8 (q, J 125, Me₃CSi); 18.0 (s, Me₃CSi); 4.7

(q, J 118, 2 MeSi). CI-MS (NH₃): 630 (0.4, [M 1] ), 572 (10), 530 (4), 470 (1), 380 (4), 312 (3), 242 (5), 129

(10), 75 (100). Anal. calc. for C₂₇H₃₆ClNO₇SeSi (629.08): C 51.55, H 5.77, N 2.23; found: C 51.63, H 5.65, N 2.24.

(

)-(1S,2R,3S,4R,5R,6R)-3-endo-{(S)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetra-

hydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-chloro-5-exo-(phenylseleno)-7-oxa-

bicyclo[2.2.1]heptan-2-endo-ol (()-47). NaBH₄(36.0 mg, 0.95 mmol) was added portionwise to a soln. of ( )-

46 (600 mg, 0.95 mmol) in MeOH (10 ml) and CH₂Cl₂(3 ml) cooled to 58. After addition of H₂O (5 ml), the

mixture was extracted with CH₂Cl₂(4 Â 15 ml), the combined org. extract dried (MgSO₄) and evaporated, and

25

the residue purified by FC (light petroleum ether/AcOEt 7:2): 450 mg (75%) of ()-47. Colorless oil. [a]

589

25

5, [a] 3, [a] 3, [a] 3; [a] 2 (c 0.8, CHCl₃). UV (MeCN): 272 (2000), 219 (8100). IR

577

546

435

405

(film): 3580, 2950, 2930, 2860, 1375, 1255, 1155, 1085, 1025, 840, 780, 740. ¹H-NMR (400 MHz, CDCl₃): 7.69 ± 7.66

(m, 2 arom. H); 7.37 ± 7.28 (m, 3 arom. H); 5.81 (d, ³J(4a'',7a'') 3.5, H C(4a'')); 5.61 (d, ³J(3a'',7b'') 6.7,

H

C(3a'')); 4.97 (d, ³J(7b'',3a'') 6.7, H C(7b'')); 4.90 (d, ³J(1',3) 10.6, H C(1')); 4.77 (d, ³J(7a'',4a'') 3.5,

C(7a'')); 4.73 (d, ³J(4,3) 5.5, H C(4)); 4.51 ± 4.45 (m, H C(6), H C(2), H C(1)); 3.89 (d, ³J(5,6) 4.5,

C(5)); 3.03 (ddd, ³J(3,1') 10.6, ³J(3,2) 5.5, ³J(3,4) 5.5,

H

C(3)); 2.80 (d, ³J(OH C(2),2) 7.6,

OH C(2)); 1.52 (s, Me); 1.37 (s, Me); 0.89 (s, t-BuSi); 0.10 (s, MeSi); 0.08 (s, MeSi). ¹³C-NMR (100.6 MHz,

CDCl₃). 158.5 (s, C(3'')); 135.4 (d, J 162, 2 arom. C); 129.2 (d, J 161, 2 arom. C); 128.4 (d, J 161, arom. C);

127.4 (s, arom. C); 113.9 (s, C(6'')); 106.0 (d, J 184, C(4a'')); 87.8 (d, J 166, C(4)); 87.2 (d, J 162, C(3a''));

86.4 (d, J 163, C(7b'')); 84.7 (d, J 161, C(7a'')); 78.9 (d, J 162, C(1)); 72.9 (d, J 152, C(2)); 65.4 (d, J 146,

C(1')); 64.3 (d, J 163, C(6)); 48.7 (d, J 137, C(3)); 45.7 (d, J 150, C(5)); 27.8 (q, J 129, Me); 26.8 (q, J

127, Me); 25.8 (q, J 125, Me₃CSi); 18.0 (s, Me₃CSi); 3.7 (q, J 119, MeSi); 4.4 (q, J 119, MeSi). CI-MS

(NH₃): 632 (1, [M 1] ), 530 (1), 416 (1), 382 (6), 314 (12), 259 (14), 129 (37), 75 (100). Anal. calc. for

C₂₇H₃₈ClNO₇SeSi (631.08): C 51.39, H 6.07, N 2.22; found: C 51.45, H 6.03, N 2.22.

()-(1R,2R,3S,4R)-3-endo-{(S)-Hydroxy[(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]di-

oxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-5-(phenylseleno)-7-oxabicyclo[2.2.1]hept-5-en-1-endo-ol (()-48).

At 258, 1m Bu₄NF in THF (0.63 ml, 0.62 mmol) was added to a soln. of ()-47 (332 mg, 0.52 mmol) in THF

(8 ml), and the mixture was stirred for 2 h. After the addition of AcOEt (30 ml), the mixture was washed with

brine (10 ml, 3 times), the org. phase dried (MgSO₄) and evaporated and the residue purified by FC (light

25

petroleum ether/AcOEt 3 :2): 150 mg (70%) of ()-48. Colorless solid. M.p. 61 ± 628. [a] 103, [a]

589

577

Helvetica Chimica Acta ± Vol. 83 (2000)

215

25

105, [a] 119, [a] 194, [a] 226 (c 1.1, CHCl₃). UV (MeCN): 253 (8800), 205 (22300). IR

546

435

405

(KBr): 3430, 2990, 2930, 1375, 1215, 1100, 1020, 900, 780, 740, 690. ¹H-NMR (400 MHz, CDCl₃): 7.59 ± 7.55

(m, 2 arom. H); 7.35 ± 7.28 (m, 3 arom. H); 6.54 (d, ³J(6,1) 1.9,

H

C(6)); 5.80 (d, ³J(3a'',7b'') 6.5,

H

C(3a'')); 5.79 (d, ³J(4a'',7a'') 3.5,

H

C(4a'')); 5.01 (ddd, ³J(1,2) 4.7, ³J(1,6) 1.9, ⁵J(1,4) 0.9,

C(1)); 4.96 (d, ³J(7b'',3a'') 6.5, H C(7b'')); 4.85 (d, ³J(4,3) 4.5, H C(4)); 4.78 (d, ³J(7a'',4a'') 3.5,

C(7a'')); 4.57 ± 4.52 (m, H C(2), H C(1')); 2.92 (br. s, OH); 2.74 (ddd, ³J(3,1') 10.6, ³J(3,2) 7.8,

³J(3,4) 4.5, H C(3)); 2.59 (br. s, OH); 1.52, 1.38 (2s, 2 Me). ¹³C-NMR (100.6 MHz, CDCl₃): 161.4 (s, C(3''));

136.1 (s, C(5)); 135.5 (d, J 155, C(6)); 133.1 (d, J 162, 2 arom. C); 129.6 (d, J 164, 2 arom. C); 128.1 (d, J

161, arom. C); 127.4 (s, arom. C); 113.8 (s, C(6'')); 105.9 (d, J 184, C(4a'')); 87.0 (d, J 165, C(3a'')); 86.3

(d, J 163, C(7b'')); 84.7 (d, J 161, C(7a'')); 83.9 (d, J 162, C(4)); 82.3 (d, J 165, C(1)); 71.1 (d, J 156,

C(2)); 65.2 (d, J 147, C(1')); 48.5 (d, J 138, C(3)); 27.7, 26.8 (2q, J 127, 2 Me). CI-MS (NH₃): 482 (2, [M

2] ), 480 (1, M ), 224 (100), 195 (12), 144 (22), 115 (97), 78 (78). Anal. calc. for C₂₁H₂₃NO₇Se (480.37): C 52.51,

H 4.83, N 2.92; found: C 52.42, H 4.72, N 2.87.

()-(4S,4aS,5R,8R,8aR)-4a,5,8,8a-Tetrahydro-2,2-dimethyl-6-(phenylseleno)-4-[(3aR,4aR,7aR,7bS)-

3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]-5,8-epoxy-4H-1,3-benzodioxine

(()-49). A mixture of ()-48 (54 mg, 0.11 mmol), (MeO)₂CMe₂(2 ml), and TsOH (15 mg) in acetone (2 ml)

was stirred at 258 for 5 h. After the addition of AcOEt (20 ml), the mixture was washed with sat. aq. NaHCO₃

soln. (7 ml) and brine (7 ml), the org. phase dried (MgSO₄) and evaporated, and the residue purified by FC

25

(light petroleum ether/AcOEt 4 :1): 51 mg (88%) of ()-49. Colorless oil. [a] 50, [a] 61, [a]

589

577

546

25

65, [a] 108, [a] 126 (c 0.1, CHCl₃). UV (MeCN): 254 (7000), 205 (15500). IR (film): 2990,

435

405

1480, 1380, 1260, 1200, 1165, 1025, 890, 740. ¹H-NMR (400 MHz, CDCl₃): 7.55 ± 7.53 (m, 2 arom. H); 7.33 ± 7.28

(m, 3 arom. H); 6.23 (d, ³J(7,8) 1.9, H C(7)); 5.85 (d, ³J(3a',7b') 6.4, H C(3a')); 5.84 (d, ³J(4a',7a') 3.5,

H

C(4a')); 5.25 (d, ³J(4,4a) 6.4,

H

C(4)); 5.22 (dd, ³J(5,4a) 4.1, ⁵J(5,8) 0.8,

H

C(5)); 5.08

C(7b')); 4.83

(ddd, ³J(8,8a) 4.5, ³J(8,7) 1.9, ⁵J(8,5) 0.8,

H

C(8)); 5.03 (d, ³J(7b',3a') 6.4,

(d, ³J(7a',4a') 3.5, H C(7a')); 4.70 (dd, ³J(8a,4a) 8.0, ³J(8a,8) 4.5, H C(8a)); 2.47 (ddd, ³J(4a,8a) 8.0,

³J(4a,4) 6.4, J(4a,5) 4.1, H C(4a)); 1.56, 1.50, 1.39, 1.29 (4s, 4 Me). ¹³C-NMR (100.6 MHz, CDCl₃): 160.2

3

(s, C(3')); 137.2 (d, J 181, C(7)); 135.5 (s, C(6)); 133.5 (d, J 161, 2 arom. C); 129.3 (d, J 163, 2 arom. C);

128.1 (s, arom. C); 127.9 (d, J 161, arom. C); 113.7 (s, C(6')); 106.2 (d, J 185, C(4a')); 97.9 (s, C(2)); 87.6

(d, J 167, C(3a')); 86.2 (d, J 163, C(7b')); 84.8 (d, J 161, C(7a')); 82.4 (d, J 166, C(5), C(8)); 69.5 (d, J

159, C(8a)); 63.2 (d, J 143, C(4)); 35.8 (d, J 137, C(4a)); 29.0, 27.8, 26.8, 21.5 (4q, J 127, 4 Me). CI-MS

(NH₃): 522 (1, [M 1] ), 306 (2), 244 (100), 195 (9), 144 (10), 115 (60), 85 (44), 83 (43). Anal. calc. for

C₂₄H₂₇NO₇Se (520.44): C 55.39, H 5.23, N 2.69; found: C 55.21, H 5.39, N 2.52.

(1S,2R,3S,4R,5R,6R)-6-endo-Chloro-3-endo-{(S)-hydroxy[(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-

dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-5-exo-(phenylseleno)-7-oxabicyclo[2.2.1]heptan-2-en-

do-ol (50). NaBH₄(10 mg, 0.95 mmol) was added portionwise to a soln. of 45 (134 mg, 0.26 mmol) in MeOH

(8 ml) cooled to 58. After the addition of H₂O (2 ml), the mixture was extracted with AcOEt (10 ml, 4 times),

the combined org. extract dried (MgSO₄) and evaporated, and the residue purified by FC (light petroleum

ether/AcOEt 2 :1): 65 mg (50%) of 50. Colorless oil. IR (film): 3450, 2990, 2940, 1480, 1380, 1265, 1225, 115, 995.

¹H-NMR (400 MHz, CDCl₃): 7.65 ± 7.63 (m, 2 arom. H); 7.33 ± 7.29 (m, 3 arom. H); 5.71 (d, ³J(4a'',7a'') 3.5,

H

C(4a'')); 5.63 (d, ³J(3a'',7b'') 6.6, H C(3a'')); 4.92 (d, ³J(1',3) 7.5, H C(1')); 4.88 (d, ³J(7b'',3a'') 6.6,

C(7b'')); 4.76 (d, ³J(4,3) 5.6, H C(4)); 4.74 (d, ³J(7a'',4a'') 3.5, H C(7a'')); 4.60 (dd, ³J(2,3) 10.1,

³J(2,1) 4.8, H C(2)); 4.49 (dd, ³J(1,6) 4.9, ³J(1,2) 4.8, H C(1)); 4.24 (dd, ³J(6,1) 4.9, ³J(6,5) 4.9,

3

H

C(6)); 4.17 (d, ³J(5,6) 4.9, H C(5)); 3.00 (br. s, 2 OH); 2.84 (ddd, ³J(3,2) 10.1, J(3,1') 8.3, J(3,4)

5.6, H C(3)); 1.59 (br. s, 2 OH); 1.50, 1.36 (2s, 2 Me). ¹³C-NMR (100.6 MHz, CDCl₃): 159.9 (s, C(3'')); 134.6

(d, J 163, 2 arom. C); 129.2 (d, J 161, 2 arom. C); 128.8 (s, arom. C); 128.0 (d, J 161, arom. C); 114.0

(s, C(6'')); 106.0 (d, J 187, C(4a'')); 87.7 (d, J 162, C(4)); 86.8 (d, J 164, C(3a'')); 86.5 (d, J 163, C(7b''));

84.7 (d, J 168, C(7a'')); 79.1 (d, J 158, C(1)); 73.3 (d, J 159, C(2)); 64.4 (d, J 143, C(1')); 62.0 (d, J 157,

C(6)); 47.3 (d, J 136, C(3)); 46.7 (d, J 153, C(5)); 27.8, 26.8 (2q, J 127, 2 Me).

(

)-(4S,4aS,5R,6R,7R,8S,8aR)-7-Chloro-2,2-dimethyl-6-(phenylseleno)-4-[(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-

tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]-4a,5,6,7,8,8a-hexahydro-5,8-epoxy-4H-1,3-ben-

zodioxine (( )-51). A mixture of 50 (50 mg, 0.1 mmol), (MeO)₂CMe₂(2 ml), and TsOH (15 mg) in acetone

(2 ml) was stirred at 258 for 5 h. After the addition of AcOEt (20 ml), the mixture was washed with sat. aq.

NaHCO₃soln. (7 ml) and brine (7 ml), the org. phase dried (MgSO₄) and evaporated, and the residue purified

25

by FC (light petroleum ether/AcOEt 4 :1): 48 mg (89%) of ( )-51. Colorless oil. [a]

9, [a]

10,

589

577

25

[a]

13, [a]

31, [a]

44 (c 1.0, CHCl₃). UV (MeCN): 272 (2300), 200 (12500). IR (film): 2990,

546

435

405

216

Helvetica Chimica Acta ± Vol. 83 (2000)

2940, 1385, 1265, 1205, 1150, 1090, 1005, 870, 740. ¹H-NMR (400 MHz, CDCl₃): 7.66 ± 7.64 (m, 2 arom. H); 7.35 ±

7.28 (m, 3 arom. H); 5.78 (d, ³J(4a',7a') 3.6,

H

C(4a')); 5.40 (d, ³J(3a',7b') 6.5,

H

C(3a')); 5.19

(d, ³J(4,4a) 6.5,

H

C(4)); 5.11 (d, ³J(5,4a) 4.7,

H

C(5)); 4.75 (d, ³J(7a',4a') 3.6,

H C(7a')); 4.72

3

5

(dd, ³J(8a,4a) 8.50, J(8a,8) 4.8, H C(8a)); 4.56 (ddd, ³J(8,8a) 4.8, ³J(8,7) 4.1, J(8,5) 0.8, H C(8));

4.50 (d, ³J(7b',3a') 6.5,

H

C(7b')); 4.07 (dd, ³J(7,6) 7.5, ³J(7,8) 4.1,

H

C(7)); 3.73 (d, ³J(6,7) 7.5,

H

C(6)); 2.24 (ddd, ³J(4a,8a) 8.5, ³J(4a,4) 6.5, ³J(4a,5) 4.7, H C(4a)); 1.52, 1.51, 1.50, 1.37 (4s, 4 Me).

¹³C-NMR (100.6 MHz, CDCl₃): 157.9 (s, C(3')); 135.5 (d, J 162, 2 arom. C); 129.0 (d, J 160, 2 arom. C);

128.3 (s, arom. C); 128.0 (d, J 161, arom. C); 113.7 (s, C(6')); 106.1 (d, J 184, C(4a')); 98.6 (s, C(2)); 87.6

(d, J 163, C(5)); 86.5 (d, J 162, C(3a')); 86.3 (d, J 163, C(7b')); 84.7 (d, J 161, C(7a')); 80.5 (d, J 164,

C(8)); 69.7 (d, J 157, C(8a)); 63.3 (d, J 144, C(4)); 62.8 (d, J 159, C(7)); 45.8 (d, J 150, C(6)); 38.6 (d, J

135, C(4a)); 28.5, 27.7, 26.8, 19.8 (4q, J 127, 4-CH₃). CI-MS (NH₃): 557 (1, M ), 197 (1), 83 (100). Anal. calc.

for C₂₄H₂₈ClNO₇Se (556.90): C 51.76, H 5.07, N 2.52; found: C 51.83, H 5.16, N 2.49.

()-(1S,2R,3R,4R,5R,6R)-3-exo-{(S)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetra-

hydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-chloro-2-endo-(methoxymethyl)-5-

exo-(phenylseleno)-7-oxabicyclo[2.2.1]heptane (()-56). Under Ar, MeOCH₂Cl (3.61 ml, 47.4 mmol) was

added at 08 to a mixture of ( )-36 (1.50g, 2.37 mmol) and EtN(i-Pr)₂(8.0 ml, 47.4 mmol) in dry CH₂Cl₂(20 ml).

The mixture was stirred at 08 for 1 h, then at 258 for 20 h. After the addition of CH₂Cl₂(50 ml), the mixture was

washed successively with 1n aq. HCl (15 ml), sat. aq. NaHCO₃soln. (15 ml), and brine (15 ml), the org. phase

dried (MgSO₄) and evaporated, and the residue purified by FC (light petroleum ether/AcOEt 8 :1): 1.38 g

25

(86%) of ()-56. Colorless oil. [a] 9, [a] 8, [a] 8, [a] 9, [a] 7 (c 1.0, CHCl₃).

589

577

546

435

405

UV (MeCN): 270 (1400). IR (film): 2950, 2890, 2860, 1470, 1385, 1255, 1225, 1100, 1050, 1025, 840, 760.

¹H-NMR (400 MHz, CDCl₃): 7.62 ± 7.57 (m, 2 arom. H); 7.35 ± 7.28 (m, 3 arom. H); 5.79 (d, ³J(4a'',7a'') 3.6,

H

C(4a'')); 5.39 (d, ³J(3a'',7b'') 6.0, H C(3a'')); 4.77 (d, ³J(7a'',4a'') 3.6, H C(7a'')); 4.75 (d, ³J(7b'',3a'')

6.0, H C(7b'')); 4.71 (d, ³J(1',3) 6.7, H C(1')); 4.66 (AB, J_AB 6.6, 1 H, OCH₂O); 4.62 (AB, J_AB 6.6, 1 H,

OCH₂O); 4.56 (s,H C(4)); 4.47 (dd, ³J(1,2) 4.5, J(1,6) 4.5, H C(1)); 4.18 (dd, ³J(2,1) 4.5, J(2,3) 4.1,

3

H

C(2)); 4.12 (dd, ³J(6,5) 5.2, ³J(6,1) 4.5, H C(6)); 3.45 (d, ³J(5,6) 5.2, H C(5)); 3.40 (s, MeO); 2.25

(dd, ³J(3,1') 6.7, ³J(3,2) 4.1, H C(3)); 1.51, 1.36 (2s, 2 Me); 0.86 (s, t-BuSi); 0.05 (s, 2 MeSi). ¹³C-NMR

(100.6 MHz, CDCl₃): 159.7 (s, C(3'')); 134.2 (d, J 161, 2 arom. C); 129.4 (d, J 159, 2 arom. C); 128.8

(s, arom. C); 128.1 (d, J 161, arom. C); 113.3 (s, C(6'')); 106.2 (d, J 184, C(4a'')); 96.9 (t, J 163, OCH₂O);

87.6 (d, J 162, C(7b'')); 86.8 (d, J 164, C(3a'')); 85.6 (d, J 164, C(4)); 84.1 (d, J 162, C(7a'')); 79.8 (d, J

149, C(2)); 78.7 (d, J 163, C(1)); 68.1 (d, J 146, C(1')); 60.8 (d, J 157, C(6)); 56.4 (d, J 136, C(3)); 56.1

(q, J 142, MeO); 52.3 (d, J 152, C(5)); 27.6, 26.8 (2q, J 127, 2 Me); 25.7 (q, J 125, Me₃CSi); 18.1

(s, Me₃CSi); 4.8, 5.2 (2q, J 119, 2 MeSi). CI-MS (NH₃): 675 (9, M ), 618 (4), 520 (8), 484 (15), 368 (10),

242 (3), 78 (100). Anal. calc. for C₂₉H₄₂ClNO₈SeSi (675.15): C 51.59, H 6.27, N 2.07; found: C 51.45, H 6.38, N 1.95.

()-(1S,2R,3S,4R)-3-exo-{(S)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-

6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-chloro-2-endo-(methoxymethoxy)-7-oxabicy-

clo[2.2.1]hept-5-ene (()-(1S,4R,5S,6R)-5-exo-{(S)-[(tert-Butyl)dimethylsilyloxy]-[(3aR,4aR,7aR,7bS)-

3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-2-chloro-6-endo-(methoxy-

methoxy)-7-oxabicyclo[2.2.1]hept-2-ene, ()-57). A dried (MgSO₄) soln. of m-chloroperbenzoic acid (Fluka;

70%; 360 mg, 1.46 mmol) in dry CH₂Cl₂(10 ml) was added dropwise to a stirred soln. of ()-56 (820 mg,

1.22 mmol) in dry THF (40 ml), at 788. The mixture was stirred at 788 for 2 h, then at 258 for 14 h. The

yellow soln. was washed with sat. aq. NaHCO₃soln. (15 ml, twice), then with brine (15 ml). The org. phase was

dried (MgSO₄) and evaporated and the residue purified by FC (light petroleum ether/AcOEt 9 :1): 598 mg

25

(95%) of ()-57. Colorless oil. [a] 129, [a] 134, [a] 154, [a] 272, [a] 334 (c 1.1,

589

577

546

435

405

CHCl₃). UV (MeCN): 209 (7000). IR (film): 2950, 2930, 2860, 1595, 1385, 1250, 1150, 1100, 1030, 840, 760.

¹H-NMR (400 MHz, CDCl₃): 6.37 (d, ³J(5,4) 2.2, H C(5)); 5.87 (d, ³J(4a'',7a'') 3.6, H C(4a'')); 5.44

(d, ³J(3a'',7b'') 5.8,

(d, ³J(7b'',3a'') 5.8,

H

C(3a'')); 4.97 (d, ³J(4,5) 2.2,

H

C(4)); 4.92 (d, ³J(1',3) 6.5,

H C(1')); 4.84

C(7b'')); 4.82 (d, ³J(7a'',4a'') 3.6,

H C(7a'')); 4.70 ± 4.68 (m, H C(1)); 4.69

(AB, J_AB 6.7, 1 H, OCH₂O); 4.66 (AB, J_AB 6.7, 1 H, OCH₂O); 4.17 (dd, ³J(2,1) 4.4, ³J(2,3) 2.4,

H

C(2)); 3.39 (s, MeO); 2.02 (dd, ³J(3,1') 6.5, ³J(3,2) 2.4, H C(3)); 1.49, 1.36 (2s, 2 Me); 0.92 (s, t-BuSi);

0.11, 0.10 (2s, 2 MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 160.0 (s, C(3'')); 138.4 (s, C(6)); 130.1 (d, J 180, C(5));

113.2 (s, C(6'')); 106.3 (d, J 183, C(4a'')); 96.9 (t, J 163, OCH₂O); 87.8 (d, J 163, C(7b'')); 87.1 (d, J 164,

C(3a'')); 84.0 (d, J 162, C(7a'')); 82.3 (d, J 169, C(1)); 81.2 (d, J 166, C(4)); 76.3 (d, J 165, C(2)); 68.2

(d, J 145, C(1')); 56.0 (q, J 142, MeO); 53.2 (d, J 139, C(3)); 27.7, 26.8 (2q, J 127, 2 Me); 25.8 (q, J 125,

Me₃CSi); 18.2 (s, Me₃CSi); 4.8, 5.1 (2q, J 119, 2 MeSi). CI-MS (NH₃): 519 (1, [M 1] ), 518 (3, M ), 460

Helvetica Chimica Acta ± Vol. 83 (2000)

217

(2), 386 (10), 358 (62), 328 (5), 284 (12), 242 (45), 184 (24), 129 (100), 73 (65). Anal. calc. for C₂₃H₃₆ClNO₈Si

(518.07): C 53.32, H 7.00, N 2.70; found: C 53.19, H 7.01, N 2.63.

()-(1R,2R,4S,5R,6R)-6-exo-{(S)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahy-

dro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-5-endo-(methoxymethoxy)-3-oxo-7-oxabicy-

clo[2.2.1]hept-2-exo-yl 4-Bromobenzenesulfonate (()-58). NaHCO₃(175 mg, 2.08 mmol), 0.1m OSO₄in CCl₄

(0.1 ml) and Me₃NO ´ 2 H₂O (234 mg, 2.08 mmol) were added successively to a stirred soln. of ()-57 (540 mg,

1.04 mmol) in THF/H₂O 5 :1 (20 ml) at 258. After stirring at 258 for 2 h, the yellow soln. was poured into CH₂Cl₂

(100 ml) and 1n aq. HCl (50 ml). The org. layer was washed with 10% aq. NaHSO₃soln. (50 ml), the aq. phase

extracted with CH₂Cl₂(2 Â 50 ml), the combined org. extract dried (MgSO₄) and evaporated, and the residue

dissolved in dry CH₂Cl₂(5 ml) to which 4-bromobenzenesulfonyl chloride (405 mg, 1.56 mmol) and Et₃N

(0.2 ml, 1.25 mmol) were added at 08. The mixture was stirred at 08 for 1 h, then at 258 for 2 h and poured into

CH₂Cl₂(50 ml) and 1n aq. HCl (15 ml). The aq. layer was extracted with CH₂Cl₂(10 ml, 3 times), the combined

org. phase washed with 5% aq. Na₂CO₃soln. (30 ml) and brine (20 ml), dried (MgSO₄), and evaporated, and

the residue purified by FC (silica gel (10 g), light petroleum ether/AcOEt 6 :1): 672 mg (88%) of ()-58.

25

Colorless solid. M.p. 55 ± 56. [a] 13, [a] 14, [a] 16, [a] 41, [a] 62 (c 1.0,

589

577

546

435

405

CHCl₃). UV (MeCN): 235 (15300). IR (KBr): 2950, 1790, 1575, 1470, 1375, 1220, 1190, 1110, 1045, 995, 840.

¹H-NMR (400 MHz, CDCl₃): 7.81 (d, ³J 8.8, 2arom. H); 7.72 (d, ³J 8.8, 2 arom. H); 5.86 (d, ³J(4a'',7a'') 3.6,

H

C(4a'')); 5.51 (d, ³J(3a'',7b'') 6.1, H C(3a'')); 4.92 (d, ³J(7b'',3a'') 6.1, H C(7b'')); 4.83 (d, ³J(7a'',4a'')

3.6, H C(7a'')); 4.78 (s, H C(2)); 4.77 (d, ³J(1',6) 7.4, H C(1')); 4.64 (AB, J_AB 6.9, 1 H, OCH₂O); 4.52

(AB, J_AB 6.8, 1 H, OCH₂O); 4.47 (s, H C(1)); 4.40 (dd, ³J(4,5) 5.5, ⁵J(4,1) 1.2,

H C(4)); 4.17

(ddd, ³J(5,4) 5.5, ³J(5,6) 2.7, ⁴J(5,1) 1.2, H C(5)); 3.32 (s, MeO); 2.33 (dd, ³J(6,1') 7.4, ³J(6,5) 2.7,

H

C(6)); 1.53, 1.38 (2s, 2 Me); 0.92 (s, t-BuSi); 0.13, 0.12 (2s, 2 MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 199.4

(s, C(3)); 159.1 (s, C(3'')); 134.8 (s, arom. C); 132.7 (d, J 171, 2 arom. C); 129.6 (s, arom. C); 129.5 (d, J 176,

2 arom. C); 113.6 (s, C(6'')); 106.2 (d, J 184, C(4a'')); 97.1 (t, J 163, OCH₂O); 87.7 (d, J 163, C(7b'')); 86.7

(d, J 164, C(3a'')); 84.1 (d, J 162, C(7a'')); 81.6 (d, J 164, C(2)); 80.7 (d, J 164, C(4)); 77.0 (d, J 157,

C(1)); 76.0 (d, J 164, C(5)); 67.2 (d, J 146, C(1')); 56.4 (q, J 143, MeO); 52.9 (d, J 135, C(6)); 27.7, 26.8

(2q, J 126, 2 Me); 25.6 (q, J 120, Me₃CSi); 18.0 (s, Me₃CSi); 4.7, 5.0 (2q, J 119, MeSi). CI-MS (NH₃):

736 (11, [M 1] ), 735 (6, M ), 500 (7), 454 (7), 329 (8), 295 (10), 242 (72), 184 (21), 129 (66), 73 (100). Anal.

calc. for C₂₉H₄₀BrNO₁₂SSi (734.67): C 47.41, H 5.49, N 1.91; found: C 47.34, H 5.44, N 1.95.

()-(1R,4R,5R,6S,7R)-4-exo-{[4-(Bromophenyl)sulfonyl]oxy}-6-exo-{(S)-[(tert-butyl)dimethylsilylox-

y][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-7-

endo-(methoxymethoxy)-2,8-dioxabicyclo[3.2.1]octan-3-one ( 5-O-[(4-Bromophenyl)sulfonyl]-3-{(S)-[(tert-bu-

tyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxa-

zol-3-yl]methyl}-3-deoxy-2-O-(methoxymethyl)-b-l-altrofuranurono-6,1-lactone) (()-59). m-Chloroperbenzo-

ic acid (85%; 174 mg, 0.85 mmol) and then NaHCO₃(130 mg, 1.55 mmol) were added to a stirred soln. of ()-58

(565 mg, 0.77 mmol) in dry CH₂Cl₂(20 ml) at 08. The mixture was stirred at 08 for 5 h, then at 258 for 15 h. It was

then poured into CH₂Cl₂(50 ml) and sat. aq. NaHSO₃soln. (20 ml). The aq. layer was extracted with CH₂Cl₂

(2 Â 10 ml), the combined org. extract washed with sat. aq. NaHCO₃soln. (20 ml) and brine (20 ml), dried

(MgSO₄) and evaporated, and the residue purified by FC (light petroleum ether/AcOEt 5 :1): 532 mg of ()-59.

25

Colorless solid. M.p. 67 ± 688. [a] 18, [a] 19, [a] 22, [a] 40, [a] 50 (c 1.0,

589

577

546

435

405

CHCl₃). UV (MeCN): 235 (16100), 202 (15000). IR (KBr): 2930, 1770, 1575, 1390, 1375, 1205, 1190, 1105, 1060,

1010, 840. ¹H-NMR (400 MHz, CDCl₃): 7.83 (d, ³J 8.8, 2 arom. H); 7.73 (d, ³J 8.8, 2 arom. H); 5.82

(d, ³J(1,7) 3.5, H C(1)); 5.79 (d, ³J(4a'',7a'') 3.5, H C(4a'')); 5.56 (d, ³J(3a'',7b'') 6.7, H C(3a'')); 4.95

(d, ³J(7b'',3a'') 6.7, H C(7b'')); 4.78 (d, ³J(1',6) 5.7, H C(1')); 4.74 (d, ³J(7a'',4a'') 3.5, H C(7a'')); 4.73

(s, H C(4)); 4.64 (AB, J_AB 7.0, 1 H, OCH₂O); 4.55 (br. s, H C(5)); 4.50 (AB, J_AB 7.0, 1 H, OCH₂O); 4.19

(dd, ³J(7,6) 4.5, ³J(7,1) 3.5,

H

C(7)); 3.32 (s, MeO); 2.36 (ddd, ³J(6,1') 5.7, ³J(6,7) 4.5, ⁴J 1.9,

H

C(6)); 1.44, 1.32 (2s, 2 Me); 0.84 (s, t-BuSi); 0.06, 0.05 (2s, 2 MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 160.0

(s, C(3)); 158.0 (s, C(3'')); 134.3 (s, arom. C); 132.6 (d, J 171, 2 arom. C); 129.9 (d, J 170, 2 arom. C); 129.8

(s, arom. C); 113.9 (s, C(6'')); 106.0 (d, J 185, C(4a'')); 102.1 (d, J 185, C(1)); 97.5 (t, J 165, OCH₂O); 87.0

(d, J 162, C(7b'')); 86.9 (d, J 162, C(3a'')); 84.7 (d, J 162, C(4)); 80.2 (d, J 163, C(5)); 80.1 (d, J 159,

C(7)); 76.5 (d, J 162, C(7a'')); 67.5 (d, J 145, C(1')); 56.7 (q, J 143, MeO); 48.2 (d, J 133, C(6)); 27.8, 26.9

(2q, J 124, 2 Me); 25.6 (q, J 125, t-BuSi); 18.0 (s, Me₃CSi); 4.4, 4.8 (2q, J 118, 2 MeSi). CI-MS (NH₃):

752 (8, [M 1] ), 751 (10, M ), 694 (5), 516 (18), 458 (5), 295 (8), 242 (100), 129 (60), 75 (94). Anal. calc. for

C₂₉H₄₀BrNO₁₃SSi (750.67): C 46.40, H 5.37, N 1.87; found: C 46.38, H 5.35, N 1.93.

()-Methyl (1R,3S,4R,5S,6R)-5-exo-{(S)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-

tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-(methoxymethoxy)-2,7-dioxa-

218

Helvetica Chimica Acta ± Vol. 83 (2000)

bicyclo[2.2.1]heptan-3-exo-carboxylate (()-Methyl 1,5-Anhydro-3-{(S)-[(tert-butyl)dimethylsilyloxy][(3aR,

4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-3-deoxy-2-

O-(methoxymethyl)-a-d-galactofuranuronate; ()-60) and ()-Methyl (1R,3R,4R,5S,6R)-5-exo-{(S)-[(tert-Bu-

tyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxa-

zol-3-yl]methyl}-6-endo-(methoxymethoxy)-2,7-dioxabicyclo[2.2.1]heptan-3-endo-carboxylate (()-Methyl 1,5-

Anhydro-3-{(S)-[(tert-butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]diox-

olo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-3-deoxy-2-O-(methoxymethyl)-a-l-altrofuranuronate, ()-61). A soln. of

()-59 (0.5 g, 0.66mmol) in anh. DMF (5.6 ml) was added to a soln. of anh. K₂CO₃(184 mg, 1.33 mmol) in anh.

DMF (3.4 ml) stirred at 08. After stirring at 08 for 5 min, MeOH (2.25 ml) was added and the mixture stirred at 08

for 30 min, then at 258 for 90 min. After the addition of AcOEt (50 ml), the mixture was washed with brine (3 Â

15 ml), the aq. phase extracted with AcOEt (2 Â 10 ml), the combined org. extract dried (MgSO₄) and

evaporated, and the residue purified by FC (light petroleum ether/AcOEt 4 :1): 270 mg (75%) of ()-60 and

54 mg (15%) of ()-61.

25

Data of ()-60: Colorless oil. [a] 64, [a] 67, [a] 75, [a] 129, [a] 157 (c 0.4,

589

577

546

435

405

CHCl₃). UV (MeCN): 200 (5800). IR (film): 2950, 2850, 1760, 1735, 1470, 1375, 1250, 1220, 1155, 1095, 995, 900,

840. ¹H-NMR (400 MHz, CDCl₃): 5.87 (d, ³J(4a'',7a'') 3.6, H C(4a'')); 5.70 (d, ³J(1,6) 2.3, H C(1)); 5.55

(d, ³J(3a'',7b'') 6.0,

H

C(3a'')); 4.97 (s, H C(4)); 4.90 (d, ³J(7b'',3a'') 6.0,

H C(7b'')); 4.82

(d, ³J(7a'',4a'') 3.6, H C(7a'')); 4.76 (d, ³J(1',5) 6.6, H C(1')); 4.71 (AB, J_AB 6.8, 1 H, OCH₂O); 4.64

(AB, J_AB 6.8, 1 H, OCH₂O); 4.29 (s, H C(3)); 3.81 (dd, ³J(6,5) 3.0, ³J(6,1) 2.3,

H C(6)); 3.80

(s,COOMe); 3.43 (s, MeO); 2.13 (dd, ³J(5,1') 6.6, ³J(5,6) 3.0, H C(5)); 1.52, 1.37 (2s, 2Me); 0.92 (s, t-

BuSi); 0.12, 0.11 (2s, 2 MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 169.6 (s, COOMe); 159.0 (s, C(3'')); 113.1

(s, C(6'')); 106.0 (d, J 184, C(4a'')); 101.4 (d, J 183, C(1)); 97.0 (t, J 164, OCH₂O); 87.5 (d, J 163, C(7b''));

86.6 (d, J 164, C(3a'')); 83.9 (d, J 161, C(7a'')); 80.8 (d, J 162, C(4)); 80.7 (d, J 158, C(6)); 76.8 (d, J

155, C(3)); 67.4 (d, J 145, C(1')); 55.9 (q, J 142, MeO); 52.5 (q, J 142, COOMe); 52.4 (d, J 148, C(5));

27.5, 26.6 (2q, J 127, 2 Me); 25.5 (q, J 120, Me₃CSi); 17.9 (s, Me₃CSi); 4.9, 5.3 (2q, J 119, 2MeSi). CI-

MS (NH₃): 547 (44, [M 1] ), 546 (100, M ), 488 (18), 430 (11), 373 (11), 284 (9), 242 (17), 170 (13), 129 (33).

Anal. calc. for C₂₄H₃₉NO₁₁Si (545.65): C 52.83, H 7.20, N 2.57; found: C 52.89, H 7.15, N 2.49.

25

Data of ()-61: Colorless oil. [a] 75, [a] 76, [a] 87, [a] 150, [a] 182 (c 0.3,

589

577

546

435

405

CHCl₃). UV (MeCN): 209 (4300). IR (film): 2950, 2895, 2850, 1765, 1730, 1470, 1375, 1220, 1150, 1055, 900, 870.

¹H-NMR (400 MHz, CDCl₃): 5.84 (d, ³J(4a'',7a'') 3.5, H C(4a'')); 5.59 (d, ³J(1,6) 2.0, H C(1)); 5.50

(d, ³J(3a'',7b'') 5.9, H C(3a'')); 4.90 (d, ³J(3,4) 4.0, H C(3)); 4.85 (d, ³J(7b'',3a'') 5.9, H C(7b'')); 4.80

(d, ³J(7a'',4a'') 3.5, H C(7a'')); 4.70 (d, ³J(1',5) 7.2, H C(1')); 4.69 (AB, J_AB 6.9, 1 H, OCH₂O); 4.64

(AB, J_AB 6.9, 1 H, OCH₂O); 4.46 (d, ³J(4,3) 4.0, H C(4)); 3.77 (s, COOMe); 3.75 (dd, ³J(6,5) 2.9,

³J(6,1) 2.0, H C(6)); 3.42 (s, MeO); 2.03 (dd, ³J(5,1') 7.2, ³J(5,6) 2.9, H C(5)); 1.48; 1.34 (2s, 2 Me);

0.88 (s, t-BuSi); 0.06, 0.05 (2s, 2 MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 168.5 (s, COOMe); 159.3 (s, C(3''));

113.2 (s, C(6'')); 106.3 (d, J 184, C(4a'')); 102.6 (d, J 183, C(1)); 97.0 (t, J 163, OCH₂O); 87.9 (d, J 162,

C(7b'')); 86.5 (d, J 164, C(3a'')); 83.9 (d, J 161, C(7a'')); 81.3 (d, J 161, C(6)); 79.3 (d, J 163, C(4)); 77.6

(d, J 157, C(3)); 67.6 (d, J 146, C(1')); 55.9 (q, J 142, MeO); 52.2 (q, J 148, COOMe); 48.7 (d, J 136,

C(5)); 27.6 (q, J 127, Me); 26.8 (q, J 125, Me); 25.6 (q, J 120, Me₃CSi); 18.0 (s, Me₃CSi);

4.8,

5.3

(2q, J 119, 2 MeSi). CI-MS (NH₃): 546 (2, [M 1] ), 530 (11), 488 (55), 373 (17), 284 (7), 242 (19), 184 (10),

129 (22), 73 (100). Anal. calc. for C₂₄H₃₉NO₁₁Si (545.65): C 52.83, H 7.20, N 2.57; found: C 52.84, H 7.20, N 2.51.

()-1,4-Anhydro-3-{(S)-[(tert-butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-dime-

thyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-3-deoxy-2,6-bis-O-(methoxymethyl)-a-d-galactopyranose

(()-62). At 08 1m LiAlH₄in Et₂O (0.46 ml, 0.46 mmol) was added dropwise to a stirred soln. of ()-60 (250 mg,

0.46 mmol) in anh. THF (10 ml). After stirring at 08 for 10 min, a few drops of MeOH were added, and the

mixture was poured into 1n aq. HCl (3 ml) and extracted with AcOEt (3 Â 5 ml). The combined org. extract was

washed with sat. aq. NaHCO₃soln. (8 ml), dried (MgSO₄); and evaporated and the residue dissolved in anh.

CH₂Cl₂(5 ml) and cooled to 08. (i-Pr)₂NEt (1.55 ml, 9.2 mmol) and MeOCH₂Cl (0.7 ml, 9.2 mmol) were added

successively, and the mixture was stirred at 08 for 1 h, then at 258 for 15 h. The soln. was poured into 1n aq. HCl

(10 ml) and extracted with CH₂Cl₂(15 ml, 3 times), the combined org. extract dried (MgSO₄) and evaporated,

25

and the residue purified by FC (light petroleum ether/AcOEt 4 :1): 212 g (82%) of (4)-62. Colorless oil. [a]

589

25

54, [a] 57, [a] 64, [a] 110, [a] 134 (c 0.7, CHCl₃). UV (MeCN): 210 (3600). IR

577

546

435

405

(film): 2930, 2890, 2860, 1475, 1375, 1220, 1150, 840. ¹H-NMR (400 MHz, CDCl₃): 5.86 (d, ³J(4a'',7a'') 3.6,

H

C(4a'')); 5.55 (d, ³J(3a'',7b'') 6.0, H C(3a'')); 5.47 (d, ³J(1,2) 2.4, H C(1)); 4.89 (d, ³J(7b'',3a'') 6.0,

C(7b'')); 4.82 (d, ³J(7a'',4a'') 3.6, H C(7a'')); 4.72 (d, ³J(1',3) 7.0, H C(1')); 4.71 (AB, J_AB 6.8, 1 H,

OCH₂O); 4.64 ± 4.60 (m, 4 H,OCH₂O; H C(4)); 3.93 (dd, ³J(5,6B) 8.0, ³J(5,6A) 5.2, H C(5)); 3.81

Helvetica Chimica Acta ± Vol. 83 (2000)

219

(dd, ³J(2,3) 2.8, ³J(2,1) 2.4, H C(2)); 3.46 (dd, ²J(6A,6B) 10.3, ³J(6,5A) 5.2, H_AC(6)); 3.41 ± 3.39

(m, H_BC(6)); 3.40 (s,MeO); 3.35 (s, MeO); 2.05 (dd, ³J(3,1') 7.0, ³J(3,2) 2.8, H C(3)); 1.51, 1.36 (2s,

2 Me); 0.91 (s, t-BuSi); 0.11, 0.09 (2s, 2 MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 159.5 (s, C(3'')); 113.3 (s, C(6''));

106.2 (d, J 183, C(4a'')); 100.5 (d, J 182, C(1)); 97.0 (t, J 163, OCH₂O); 96.8 (t, J 163, OCH₂O); 87.6

(d, J 162, C(7b'')); 86.9 (d, J 164, C(3a'')); 84.1 (d, J 161, C(7a'')); 81.1 (d, J 156, C(2)); 78.8 (d, J 163,

C(4)); 78.0 (d, J(C,H) 162, C(5)); 68.0 (t, J 144, C(6)); 67.8 (d, J 145, C(1')); 55.9, 55.3 (2q, J 142,

2 MeO); 52.8 (d, J 136, C(3)); 27.7 (q, J 127, Me); 26.8 (q, J 125, Me); 25.7 (q, J 125, Me₃CSi); 18.3

(s, Me₃CSi); 4.8, 5.1 (2q, J 119, 2 MeSi). CI-MS (NH₃): 563 (3, [M 1] ), 562 (6, M ), 530 (32), 504

(65), 373 (87), 328 (9), 284 (48), 242 (23), 184 (15), 129 (34), 73 (100). Anal. calc. for C₂₅H₄₃NO₁₁Si (561.70):

C 53.46, H 7.72, N 2.49; found: C 53.59, H 7.74, N 2.48.

()-1,4-Anhydro-3-{(S)-[(tert-butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-dime-

thyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-3-deoxy-2,6-bis-O-(methoxymethyl)-a-d-altropyranose

25

(()-63). As described for ()-62, with ()-61: ()-63 (82%). Colorless foam. [a] 63, [a] 65,

589

577

25

[a] 74, [a] 127, [a] 156 (c 0.4, CHCl₃). UV (MeCN): 210 (4600). IR (film): 2935, 2890,

546

435

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2860, 1470, 1385, 1375, 1250, 1155, 1090, 1040, 840, 780, 740. ¹H-NMR (400 MHz, CDCl₃): 5.87 (d, ³J(4a'',7a'')

3.7, H C(4a'')); 5.57 (d, ³J(3a'',7b'') 6.0, H C(3a'')); 5.50 (d, ³J(1,2) 2.4, H C(1)); 4.86 (d, ³J(7b'',3a'')

6.0, H C(7b'')); 4.82 (d, ³J(7a'',4a'') 3.7, H C(7a'')); 4.70 (AB, J_AB 6.8, 1 H, OCH₂O); 4.68 (d, ³J(1',3) 8.1,

H

C(1')); 4.63 ± 4.60 (m, 4 H, H C(4), OCH₂O); 4.10 (ddd, ³J(5,6A) 10.4, ³J(5,6B) 7.4, ³J(5,4) 3.6,

C(5)); 3.98 (dd, ³J(6A,5) 10.4, ²J(6A,6B) 6.6, H_AC(6)); 3.76 ± 3.70 (m, H C(2), H_BC(6)); 3.39, 3.36

(2s, 2 MeO); 2.28 (dd, ³J(3,1') 8.1, ³J(3,2) 2.6, H C(3)); 1.50, 1.37 (2s, 2 Me); 0.91 (s, t-BuSi); 0.11, 0.09 (2s,

2 MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 159.6 (s, C(3'')); 113.2 (s, C(6'')); 106.3 (d, J 183, C(4a'')); 101.5

(d, J 182, C(1)); 96.9 (t, J 163, OCH₂O); 96.8 (t, J 162, OCH₂O); 87.9 (d, J 162, C(7b'')); 86.6 (d, J 164,

C(3a'')); 84.0 (d, J 161, C(7a'')); 81.6 (d, J 151, C(2)); 80.1 (d, J 161, C(4)); 76.3 (d, J 155, C(5)); 68.0

(d, J 145, C(1')); 66.1 (t, J 143, C(6)); 55.9, 55.4 (2q, J 142, 2 MeO); 47.2 (d, J 136, C(3)); 27.7 (q, J 125,

Me); 26.8 (q, J 124, Me); 25.7 (q, J 119, Me₃CSi); 18.1 (s, Me₃CSi); 4.7, 5.1 (2q, J 119, 2 MeSi). CI-MS

(NH₃): 563 (4, [M 1] ), 562 (6, M ), 530 (11), 504 (36), 428 (10), 373 (37), 284 (26), 242 (18), 149 (48), 75

(100). Anal. calc. for C₂₅H₄₃NO₁₁Si (561.70): C 53.46, H 7.72, N 2.49; found: C 53.47, H 7.80, N 2.54.

()-(1S,2R,3R,4R,5R,6R)-3-exo-{(R)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetra-

hydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-(methoxymethyl)-5-exo-(phenylsele-

no)-7-oxabicyclo[2.2.1]heptane (()-64). As described for ()-56, with ()-37: ()-64 (90%). Colorless oil.

25

[a] 50, [a] 51, [a] 58, [a] 94, [a] 110 (c 1.0, CHCl₃). UV (MeCN): 270 (2500),

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577

546

435

405

1

196 (14800). IR (film): 2990, 2960, 2860, 1470, 1375, 1225, 1155, 1055, 835, 755. H-NMR (400 MHz, CDCl₃):

7.61 ± 7.58 (m, 2 arom. H); 7.31 ± 7.29 (m, 3 arom. H); 5.89 (d, ³J(4a'',7a'') 3.5,

H C(4a'')); 5.74

(d, ³J(3a'',7b'') 7.1, H C(3a'')); 4.91 (d, ³J(7b'',3a'') 7.1, H C(7b'')); 4.69 (d, ³J(7a'',4a'') 3.5, H C(7a''));

4.58 (AB, J_AB 6.5, 1 H, OCH₂O); 4.55 ± 4.53 (m, H C(4), H C(1)); 4.50 (AB, J_AB 6.5, 1 H, OCH₂O); 4.41

(d, ³J(1',3) 10.0, H C(1')); 4.17 (ddd, ³J(6,5) 5.0, ³J(6,1) 4.8, ⁴J(6,2) 1.2, H C(6)); 4.00 (dd, ³J(2,1)

3.3, ³J(2,3) 4.3, H C(2)); 3.53 (d, ³J(5,6) 5.0, H C(5)); 3.36 (s, MeO); 2.51 (dd, ³J(3,1') 10.0, ³J(3,2)

4.3, H C(3)); 1.52, 1.38 (2s, 2 Me); 0.83 (s, t-Bu); 0.04, 0.03 (2s, 2MeSi). ¹³C-NMR (100.6 MHz, CDCl₃):

157.9 (s, C(3'')); 134.4 (d, J 162, 2 arom. C); 129.3 (d, J 161, 2 arom. C); 128.6 (s, arom. C); 128.0 (d, J 161,

arom. C); 113.8 (s, C(6'')); 105.8 (d, J 185, C(4a'')); 96.8 (t, J 163, OCH₂O); 86.5 (d, J 163, C(3a'')); 85.8

(d, J 162, C(7b'')); 85.7 (d, J 162, C(4)); 84.9 (d, J 161, C(7a'')); 80.2 (d, J 146, C(2)); 78.9 (d, J 163,

C(1)); 69.3 (d, J 146, C(1')); 61.2 (d, J 161, C(6)); 56.5 (q, J 142, MeO); 54.4 (d, J 139, C(3)); 52.0 (d, J

152, C(5)); 27.8 (q, J 127, Me); 26.8 (q, J 128, Me); 25.6 (q, J 125, Me₃CSi); 17.9 (s, Me₃CSi); 4.8, 5.3

(2q, J 119, 2 MeSi). CI-MS (NH₃): 676 (2, [M 1] ), 675 (1, M ), 662 (9), 617 (28), 530 (15), 328 (18), 242

(17), 129 (31), 73 (100). Anal. calc. for C₂₉H₄₂ClNO₈SeSi (675.15): C 51.59, H 6.27, N 2.07; found: C 51.62,

H 6.22, N 2.05.

()-(1S,2R,3S,4R)-3-exo-{(R)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-

6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-chloro-2-endo-(methoxymethoxy)-7-oxabicy-

clo[2.2.1]hept-5-ene (()-65; for systematic numbering, see ()-57). As described for ()-57, with ()-64: ()-65

25

(90%). Colorless foam. [a] 63, [a] 66, [a] 76, [a] 128, [a] 153 (c 0.9, CHCl₃).

589

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UV (MeCN): 208 (7300). IR (film): 2950, 2935, 1595, 1470, 1370, 1050, 880, 840. ¹H-NMR (400 MHz, CDCl₃):

6.35 (d, ³J(5,4) 2.2, H C(5)); 5.80 (d, ³J(4a'',7a'') 3.5, H C(4a'')); 5.71 (d, ³J(3a'',7b'') 6.8, H C(3a''));

4.90 (d, ³J(7b'',3a'') 6.8, H C(7b'')); 4.89 (dd, ³J(4,5) 2.2, ⁵J(4,1) 1.0, H C(4)); 4.74 (d, ³J(1,2) 4.2,

H

C(1)); 4.70 (d, ³J(7a'',4a'') 3.5, H C(7a'')); 4.54 (AB, J_AB 6.5, 1 H, OCH₂O); 4.52 (d, ³J(1',3) 10.4,

C(1')); 4.51 (AB, J_AB 6.5, 1 H, OCH₂O); 4.04 (dd, ³J(2,1) 4.2, ³J(2,3) 2.5, H C(2)); 3.35 (s, MeO); 2.23

(dd, ³J(3,1') 10.4, ³J(3,2) 2.5, H C(3)); 1.49, 1.34 (2s, 2 Me); 0.90 (s, t-BuSi); 0.09, 0.00 (2s, 2 MeSi).

220

Helvetica Chimica Acta ± Vol. 83 (2000)

¹³C-NMR (100.6 MHz, CDCl₃): 158.9 (s, C(3'')); 137.7 (s, C(6)); 130.3 (d, J 180, C(5)); 113.8 (s, C(6'')); 105.8

(d, J 184, C(4a'')); 96.5 (t, J 163, OCH₂O); 86.4 (d, J 164, C(3a'')); 85.9 (d, J 163, C(7b'')); 84.5 (d, J

161, C(7a'')); 82.6 (d, J 168, C(1)); 81.0 (d, J 167, C(4)); 77.1 (d, J 150, C(2)); 69.4 (d, J 146, C(1')); 56.1

(q, J 142, MeO); 51.9 (d, J 141, C(3)); 27.8 (q, J 125, Me); 26.8 (q, J 126, Me); 25.6 (q, J 125, Me₃CSi);

18.0 (s, Me₃CSi); 4.8, 5.4 (2q, J 119, 2 MeSi). CI-MS (NH₃): 519 (2, [M 1] ), 518 (2, M ), 460 (4), 386

(11), 358 (66), 242 (21), 185 (30), 129 (39), 83 (100). Anal. calc. for C₂₃H₃₆ClNO₈Si (518.07): C 53.32, H 7.00,

N 2.70; found: C 53.35, H 7.13, N 2.70.

()-(1R,2R,4S,5R,6R)-6-exo-{(R)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahy-

dro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-5-endo-(methoxymethoxy)-3-oxo-7-oxabicy-

clo[2.2.1]hept-2-exo-yl 4-Bromobenzenesulfonate (()-66). As described for ()-58, with ()-65: ()-66 (88%).

25

Colorless foam. [a] 4, [a] 4, [a] 4, [a] 11, [a] 18 (c 1.2, CHCl₃). UV (MeCN):

589

577

546

435

405

234 (19600). IR (film): 2960, 2860, 1790, 1575, 1475, 1375, 1190, 1095, 1045, 840, 780. ¹H-NMR (400 MHz,

CDCl₃): 7.85 (d, ³J 8.8, 2 arom. H); 7.74 (d, ³J 8.8, 2 arom. H); 5.75 (d, ³J(4a'',7a'') 3.5, H C(4a'')); 5.73

(d, ³J(3a'',7b'') 6.6,

H

C(3a'')); 4.95 (d, ³J(7b'',3a'') 6.6,

H C(7b'')); 4.91 (s, H C(2)); 4.76

(d, ³J(7a'',4a'') 3.5, H C(7a'')); 4.53 (d, ³J(1',6) 10.4, H C(1')); 4.48 (AB, J_AB 6.8, 1 H, OCH₂O); 4.45

(m, H C(4), H C(1)); 4.44 (AB, J_AB 6.8, 1 H, OCH₂O); 3.90 (ddd, ³J(5,4) 5.3, J(5,6) 2.8, J(5,1) 1.1,

3

H

C(5)); 3.28 (s, MeO); 2.53 (dd, ³J(6,1') 10.4, ³J(6,5) 2.8, H C(6)); 1.55, 1.38 (2s, 2 Me); 0.93 (s, t-BuSi);

0.15, 0.04 (2s, 2 MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 200.0 (s, C(3)); 158.0 (s, C(3'')); 134.7 (s, arom. C); 132.7

(d, J 171, 2 arom. C); 129.6 (d, J 170, 2 arom. C); 129.5 (s, arom. C); 114.0 (s, C(6'')); 105.9 (d, J 184,

C(4a'')); 96.9 (t, J 164, OCH₂O); 86.5 (d, J 163, C(7b'')); 86.0 (d, J 169, C(3a'')); 84.3 (d, J 158, C(7a''));

81.3 (d, J 155, C(2)); 81.1 (d, J 165, C(1)); 77.0 (d, J 162, C(4)); 76.5 (d, J 162, C(5)); 67.7 (d, J 147,

C(1')); 56.4 (q, J 143, MeO); 51.5 (d, J 138, C(6)); 27.8 (q, J 129, Me); 26.7 (q, J 130, Me); 25.5 (q, J

120, Me₃CSi); 17.9 (s, Me₃CSi); 4.8, 5.4 (2q, J 119, 2 MeSi). CI-MS (NH₃): 753 (57, [M NH₄] ), 548

(100), 517 (31), 401 (5), 280 (4), 233 (10). Anal. calc. for C₂₉H₄₀BrNO₁₂SSi (734.67): C 47.41, H 5.49, N 1.91;

found: C 47.45, H 5.58, N 2.03.

()-(1R,4R,5R,6S,7R)-4-exo-{[4-(Bromophenyl)sulfonyl]oxy}-6-exo-{(R)-[(tert-butyl)dimethylsilyl-

oxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-

7-endo-(methoxymethoxy)-2,8-dioxabicyclo[3.2.1]octan-3-one (()-67). As described for ()-59, with ()-66:

25

()-67 (92%). Colorless solid. M.p. 66 ± 678. [a] 53, [a] 55, [a] 63, [a] 107, [a]

589

577

546

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405

128 (c 1.0, CHCl₃). UV (MeCN): 234 (17300), 202 (15800). IR (KBr): 2930, 1770, 1575, 1470, 1370, 1190,

1060. ¹H-NMR (400 MHz, CDCl₃): 7.86 (d, ³J 8.8, 2 arom. H); 7.71 (d, ³J 8.8, 2 arom. H); 5.85

(d, ³J(4a'',7a'') 3.5, H C(4a'')); 5.82 (d, ³J(1,7) 3.4, H C(1)); 5.71 (d, ³J(3a'',7b'') 6.7, H C(3a'')); 4.98

(d, ³J(7b'',3a'') 6.7, H C(7b'')); 4.88 (dd, ³J(5,4) 0.9, ³J(5,6) 1.9, H C(5)); 4.83 (d, ³J(4,5) 0.9, H C(4));

4.77 (d, ³J(7a'',4a'') 3.5, H C(7a'')); 4.68 (d, ³J(1',6) 7.5, H C(1')); 4.59 (AB, J_AB 7.0, 1 H, OCH₂O); 4.56

(AB, J_AB 7.0, 1 H, OCH₂O); 3.90 (dd, ³J(7,6) 4.9, ³J(7,1) 3.6, H C(7)); 3.36 (s, MeO); 2.41 (ddd, ³J(6,1')

7.5, ³J(6,7) 5.0, ³J(6,5) 1.9, H C(6)); 1.54, 1.39 (2s, 2 Me); 0.93 (s, t-BuSi); 0.16, 0.04 (2s, 2 MeSi). ¹³C-NMR

(100.6 MHz, CDCl₃): 160.1 (s, C(3)); 158.1 (s, C(3'')); 134.7 (s, arom. C); 132.5 (d, J 171, 2 arom. C); 129.8

(d, J 170, 2 arom. C); 129.6 (s, arom. C); 114.1 (s, C(6'')); 106.1 (d, J 185, C(4a'')); 101.4 (d, J 192, C(1));

97.3 (t, J 164, OCH₂O); 86.8 (d, J 163, C(7b'')); 85.8 (d, J 164, C(3a'')); 84.4 (d, J 168, C(7a'')); 81.2

(d, J 145, C(7)); 79.0 (d, J 152, C(5)); 76.5 (d, J 159, C(4)); 67.9 (d, J 146, C(1')); 56.6 (q, J 142, MeO);

47.8 (d, J 136, C(6)); 27.8, 26.8 (2q, J 126, 2 Me); 25.5 (q, J 130, Me₃CSi); 17.9 (s, Me₃CSi); 4.7, 5.3

(2q, J 119, 2 MeSi). CI-MS (NH₃): 769 (46, [M NH₄] ), 689 (12), 548 (100), 417 (5), 296 (3), 219 (5), 180

(31). Anal. calc. for C₂₉H₄₀BrNO₁₃SSi (750.67): C 46.40, H 5.37, N 1.87; found: C 46.32, H 5.43, N 1.78.

()-Methyl (1R,3S,4R,5S,6R)-5-exo-{(R)-[(tert-Butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-

tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-(methoxymethoxy)-2,7-dioxa-

bicyclo[2.2.1]heptan-3-exo-carboxylate (()-68) and ()-Methyl (1R,3R,4R,5S,6R)-5-exo-{(R)-[(tert-Butyldi-

methylsilyloxy][(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-

3-yl]methyl}-6-endo-(methoxymethoxy)-2,7-dioxabicyclo[2.2.1]heptane-3-endo-carboxylate (()-69). As de-

scribed for ()-60 and ()-61, with ()-67: ()-68/()-69 4.5 :1 (80%).

25

Data of ()-68: Colorless foam. [a] 63, [a] 66, [a] 74, [a] 125, [a] 151 (c

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405

1

0.3, CHCl₃). UV (MeCN): 210 (3400). IR (film): 2960, 2860, 1765, 1735, 1260, 1160, 1055, 880, 840. H-NMR

(400 MHz, CDCl₃): 5.79 (d, ³J(4a'',7a'') 3.4,

H C(4a'')); 5.77 ± 5.75 (m,H C(1), H C(3a'')); 4.97

(s, H C(4)); 4.94 (d, ³J(7b'',3a'') 6.9, H C(7b'')); 4.70 (d, ³J(7a'',4a'') 3.4, H C(7a'')); 4.58 (AB, J_AB 6.7,

1 H, OCH₂O); 4.55 (AB, J_AB 6.7, 1 H, OCH₂O); 4.43 (d, ³J(1',5) 10.4, H C(1')); 4.35 (s, H C(3)); 3.79 (s,

COOMe); 3.60 (dd, ³J(6,5) 3.0, J(6,1) 2.4, H C(6)); 3.38 (s, MeO); 2.40 (dd, ³J(5,1') 10.4, J(5,6) 3.0,

3

H

C(5)); 1.53, 1.38 (2s, 2 Me); 0.93 (s, t-BuSi); 0.13, 0.03 (2s, 2 MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 170.0

Helvetica Chimica Acta ± Vol. 83 (2000)

221

(s, COOMe); 157.8 (s, C(3'')); 114.1 (s, C(6'')); 105.6 (d, J 188, C(4a'')); 102.0 (d, J 192, C(1)); 96.8 (t, J

163, OCH₂O); 86.3 (d, J 162, C(3a'')); 85.5 (d, J 163, C(7b'')); 84.7 (d, J 161, C(7a'')); 81.3 (d, J 148,

C(6)); 80.7 (d, J 168, C(4)); 77.2 (d, J 165, C(3)); 68.5 (d, J 147, C(1')); 56.0 (q, J 142, MeO); 52.5 (q, J

148, COOMe); 51.5 (d, J 140, C(5)); 27.9 (q, J 127, Me); 26.8 (q, J 126, Me); 25.6 (q, J 125, Me₃CSi); 18.0

(s, Me₃CSi); 4.7, 5.3 (2q, J 119, 2 MeSi). CI-MS (NH₃): 547 (41, M 1] ), 546 (88, M ), 545 (34), 514

(25), 488 (31), 373 (80), 328 (12), 284 (25), 242 (8), 73 (100). Anal. calc. for C₂₄H₃₉NO₁₁Si (545.65): C 52.38,

H7.20, N 2.57; found: C 51.77, H 7.20, N 2.51.

25

Data of ()- 69: Colorless oil. [a] 89, [a] 91, [a] 104, [a] 177, [a] 213 (c

589

577

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0.4, CHCl₃). UV (MeCN): 209 (4600). IR (film): 3060, 2960, 2860, 1765, 1735, 1265, 1225, 1100, 1055, 880, 840,

740. ¹H-NMR (400 MHz, CDCl₃): 5.79 (d, ³J(4a'',7a'') 3.5, H C(4a'')); 5.70 (d, ³J(3a'',7b'') 7.1, H C(3a''));

5.66 (d, ³J(1,6) 2.2, H C(1)); 4.95 (d, ³J(4,3) 4.1, H C(4)); 4.92 (d, ³J(7b'',3a'') 7.1, H C(7b'')); 4.68

(d, ³J(7a'',4a'') 3.5, H C(7a'')); 4.61 (AB, J_AB 6.8, 1 H, OCH₂O); 4.58 (AB, J_AB 6.8, 1 H, OCH₂O); 4.52

(d, ³J(3,4) 4.1, H C(3)); 4.50 (d, ³J(1',5) 9.3, H C(1')); 3.81 (s, COOMe); 3.63 (dd, ³J(6,5) 3.3, ³J(6,1)

2.2, H C(6)); 3.44 (s, MeO); 2.24 (dd, ³J(5,1') 9.3, ³J(5,6) 3.3, H C(5)); 1.51, 1.38 (2s, 2 Me); 0.94 (s, t-

BuSi); 0.14, 0.03 (2s, 2 MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 168.5 (s, COOMe); 158.0 (s, C(3'')); 113.8

(s, C(6'')); 105.6 (d, J 185, C(4a'')); 102.8 (d, J 183, C(1)); 96.6 (t, J 163, OCH₂O); 86.4 (d, J 163, C(3a''));

85.8 (d, J 163, C(7b'')); 85.0 (d, J 154, C(7a'')); 81.7 (d, J 152, C(6)); 79.4 (d, J 152, C(3 or 4)); 77.7

(d, J 154, C(4 or 3)); 68.6 (d, J 147, C(1')); 55.8 (q, J 143, MeO); 52.2 (q, J 148, COOMe); 47.8 (d, J

139, C(5)); 27.8, 26.9 (2q, J 127, 2 Me); 25.5 (q, J 125, Me₃CSi); 18.0 (s, Me₃CSi); 4.8, 5.4 (2q, J 119,

2 MeSi). CI-MS (NH₃): 564 (74, [M NH₄] ), 563 (14), 546 (11, M ), 514 (3), 488 (9), 373 (7), 284 (2), 108

(100), 79 (75). Anal. calc. for C₂₄H₃₉NO₁₁Si (545.65): C 52.38, H 7.20, N 2.57; found: C 52.65, H 7.15, N 2.53.

()-1,4-Anhydro-3-{(R)-[(tert-butyl)dimethylsilyloxy]-[(3aR,4aR,7aR,7bS)-3a,4a,7a,7b-tetrahydro-6,6-

dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-3-deoxy-2,6-bis-O-(methoxymethyl)-a-d-galactopyr-

25

anose (()-70). As described for ()-62, with ()-68, ()-70 (75%). Colorless oil. [a] 73, [a] 75,

589

577

25

[a] 86, [a] 147, [a] 175 (c 0.4, CHCl₃). UV (MeCN): 211 (4100). IR (film): 2960, 2935,

546

435

405

2890, 1475, 1375, 1225, 1155, 1055, 940, 880, 840. ¹H-NMR (400 MHz, CDCl₃): 5.81 (d, ³J(4a'',7a'') 3.4,

H

C(4a'')); 5.76 (d, ³J(3a'',7b'') 7.0, H C(3a'')); 5.54 (d, ³J(1,2) 2.3, H C(1)); 4.93 (d, ³J(7b'',3a'') 7.0,

C(7b'')); 4.70 (d, ³J(7a'',4a'') 3.4, H C(7a'')); 4.63 (s, H C(4)); 4.62 (s, OCH₂O); 4.57 (AB, J_AB 6.6, 1 H,

OCH₂O); 4.55 (AB, J_AB 6.6, 1 H, OCH₂O); 4.45 (d, ³J(1',3) 10.4, H C(1')); 3.99 (dd, ³J(5,6A) 7.8,

³J(5,6B) 5.6, H C(5)); 3.61 (dd, ³J(2,3) 2.8, J(2,1) 2.3, H C(2)); 3.46 (dd, ²J(6B,6A) 10.0, ³J(6B,5)

3

5.6, H_BC(6)); 3.42 (dd, ²J(6A,6B) 10.0, ³J(6A,5) 7.8, H_AC(6)); 3.37, 3.36 (2s, 2 MeO); 2.33 (dd, ³J(3,1')

10.4, ³J(3,2) 2.8, H C(3)); 1.53, 1.38 (2s, 2 Me); 0.92 (s, t-BuSi); 0.13, 0.04 (2s, 2 MeSi). ¹³C-NMR

(100.6 MHz, CDCl₃): 158.0 (s, C(3'')); 114.0 (s, C(6'')); 105.6 (d, J 184, C(4a'')); 100.9 (d, J 181, C(1)); 96.6

(t, J 167, OCH₂O); 96.5 (t, J 160, OCH₂O); 86.4 (d, J 163, C(3a'')); 85.6 (d, J 163, C(7b'')); 84.7 (d, J

167, C(7a'')); 81.4 (d, J 151, C(2)); 78.5 (d, J 166, C(4)); 77.6 (d, J 156, C(5)); 68.7 (d, J 146, C(1')); 67.7

(t, J 135, C(6)); 55.8, 55.2 (2q, J 142, 2 MeO); 51.5 (d, J 139, C(3)); 27.9, 26.8 (2q, J 127, 2 Me); 25.6

(q, J 125, Me₃CSi); 18.0 (s, Me₃CSi); 4.8, 5.3 (2q, J 119, 2 MeSi). CI-MS (NH₃): 563 (22, [M 1] ), 562

(41, M ), 530 (15), 504 (21), 428 (12), 373 (71), 328 (14), 284 (61), 242 (9), 129 (33), 73 (100). Anal. calc. for

C₂₅H₄₃NO₁₁Si (561.70): C 53.46, H 7.72, N 2.49; found: C 53.52, H 7.60, N 2.41.

(

)-(1S,2R,3R,4R,5R,6R)-3-exo-{(S)-[(tert-Butyl)dimethylsilyloxy][(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahy-

dro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-endo-chloro-2-endo-(methoxymethyl)-5-exo-

(phenylseleno)-7-oxabicyclo[2.2.1]heptane (( )-71). As described for ()-56, with ( )-38: ( )-71 (97%).

25

Colorless oil. [a]

62, [a]

65, [a]

75, [a]

134, [a]

165 (c 1.0, CHCl₃). UV

589

577

546

435

405

(MeCN): 272 (2100), 215 (11200). IR (film): 2955, 2930, 2860, 1470, 1385, 1375, 1255, 1220, 1155, 1105, 1050,

1015, 840, 780, 740. ¹H-NMR (400 MHz, CDCl₃): 7.68 ± 7.64 (m, 2 arom. H); 7.34 ± 7.30 (m, 3 arom. H); 5.55

(d, ³J(3a'',7b'') 6.1, H C(3a'')); 5.09 (d, ³J(4a'',7a'') 3.6, H C(4a'')); 4.83 (d, ³J(7b'',3a'') 6.1, H C(7b''));

4.71 (AB, J_AB 6.6, 1 H, OCH₂O); 4.67 (d, ³J(7a'',4a'') 3.6, H C(7a'')); 4.60 (AB, J_AB 6.6, 1 H, OCH₂O);

4.50 (dd, ³J(1,6) 4.6, ³J(1,2) 4.6, H C(1)); 4.46 (d, ³J(1',3) 10.6, H C(1')); 4.23 (s, H C(4)); 4.17 ± 4.14

(m, H C(2), H C(6)); 3.47 (d, ³J(5,6) 5.2, H C(5)); 3.41 (s, MeO); 2.41 (dd, ³J(3,1') 10.6, ³J(3,2) 3.7,

H

C(3)); 1.48, 1.33 (2s, 2 Me); 0.87 (s, t-BuSi); 0.09, 0.01 (2s, 2MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 158.8

(s, C(3'')); 135.6 (d, J 163, 2 arom. C); 129.2 (d, J 166, 2 arom. C); 128.2 (d, J 161, arom. C); 128.2

(s, arom. C); 113.3 (s, C(6'')); 106.0 (d, J 185, C(4a'')); 96.6 (t, J 163, OCH₂O); 87.5 (d, J 163, C(7b'')); 86.6

(d, J 163, C(4)); 85.8 (d, J 164, C(3a'')); 84.2 (d, J 161, C(7a'')); 81.4 (d, J 148, C(2)); 79.3 (d, J 161,

C(1)); 69.3 (d, J 151, C(1')); 61.4 (d, J 159, C(6)); 56.3 (q, J 142, MeO); 54.8 (d, J 138, C(3)); 51.7 (d, J

153, C(5)); 27.5, 26.7 (2q, J 127, 2 Me); 25.7 (q, J 125, Me₃CSi); 18.0 (s, Me₃CSi); 4.6, 4.7 (2q, J 120,

2 MeSi). CI-MS (NH₃): 676 (6, [M 1] ), 675 (3, M ), 644 (5), 618 (10), 531 (12), 582 (3), 358 (7), 328 (14),

222

Helvetica Chimica Acta ± Vol. 83 (2000)

242 (30), 129 (41), 73 (100). Anal. calc. for C₂₉H₄₂ClNO₈SeSi (675.15): C 51.59, H 6.27, N 2.07; found: C 51.49,

H 6.38, N 1.98.

(

)-(1S,2R,3S,4R)-3-exo-{(S)-[(tert-Butyl)dimethylsilyloxy][(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahydro-6,6-

dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-6-chloro-2-endo-(methoxymethoxy)-7-oxabicy-

clo[2.2.1]hept-5-ene (( )-72; for systematic numbering, see ()-57). As described for ()-57, with ( )-71, ( )-72

25

(86%). Colorless foam. [a]

76, [a]

83, [a]

94, [a]

159, [a]

191 (c 0.7, CHCl₃).

589

577

546

435

405

1

UV (MeCN): 208 (7100). IR (film): 3020, 2990, 2950, 2860, 1590, 1470, 1370, 1250, 1150, 1115, 840. H-NMR

(400 MHz, CDCl₃): 6.33 (d, ³J(5,4) 2.2,

H

C(5)); 5.85 (d, ³J(4a'',7a'') 3.6,

H C(4a'')); 5.60

(d, ³J(3a'',7b'') 5.9, H C(3a'')); 4.90 (d, ³J(7b'',3a'') 5.9, H C(7b'')); 4.86 (d, ³J(7a'',4a'') 3.6, H C(7a''));

4.77 (AB, J_AB 6.6, 1 H, OCH₂O); 4.75 (d, ³J(1,2) 4.4, H C(1)); 4.58 (AB, J_AB 6.6, 1 H, OCH₂O); 4.53

(d, ³J(1',3) 10.8, H C(1')); 4.52 ± 4.51 (m, H C(4)); 4.23 (dd, ³J(2,1) 4.4, ³J(2,3) 2.2, H C(2)); 3.41

(s, MeO); 2.13 (dd, ³J(3,1') 10.8, J(3,2) 2.2, H C(3)); 1.51, 1.37 (2s, 2 Me); 0.90 (s, t-BuSi); 0.14, 0.04 (2s,

3

2 MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 159.1 (s, C(3'')); 138.0 (s, C(6)); 129.9 (d, J 181, C(5)); 113.6

(s, C(6'')); 106.3 (d, J 184, C(4a'')); 96.1 (t, J 163, OCH₂O); 87.5 (d, J 161, C(7b'')); 85.9 (d, J 164,

C(3a'')); 84.1 (d, J 162, C(7a'')); 82.8 (d, J 168, C(1)); 82.2 (d, J 166, C(4)); 77.5 (d, J 157, C(2)); 69.5

(d, J 145, C(1')); 55.9 (q, J 136, MeO); 51.9 (d, J 140, C(3)); 27.7, 26.8 (2q, J 127, 2 Me); 25.7 (q, J 125,

Me₃CSi); 18.0 (s, Me₃CSi); 4.6, 4.8 (2q, J 120, 2 MeSi). CI-MS (NH₃): 518 (1, M ), 460 (1), 386 (4), 358

(100), 328 (3), 284 (19), 242 (32), 184 (13), 129 (81), 73 (57). Anal. calc. for C₂₃H₃₆ClNO₈Si (518.07): C 53.32,

H 7.00, N 2.70; found: C 53.22, H 7.06, N 2.57.

(

)-(1R,2R,4S,5R,6R)-6-exo-{(S)-[(tert-Butyl)dimethylsilyloxy][(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahydro-

6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-5-endo-(methoxymethoxy)-3-oxo-7-oxabicy-

clo[2.2.1]hept-2-exo-yl 4-Bromobenzenesulfonate (( )-73). As described for ()-58, with ( )-72: ( )-73 (85%).

25

Colorless solid. M.p. 57 ± 588. [a]

97, [a]

103, [a]

117, [a]

198, [a]

235 (c 0.8,

589

577

546

435

405

CHCl₃). UV (MeCN): 234 (12700), 199 (22000). IR (KBr): 2955, 2895, 2850, 1790, 1575, 1470, 1380, 1225, 1190,

1115, 995. ¹H-NMR (400 MHz, CDCl₃): 7.82 (d, ³J 8.8, 2 arom. H); 7.71 (d, ³J 8.8, 2 arom. H); 6.13

(d, ³J(4a'',7a'') 3.6, H C(4a'')); 5.63 (d, ³J(3a'',7b'') 6.0, H C(3a'')); 4.96 (d, ³J(7b'',3a'') 6.0, H C(7b''));

4.93 (d, ³J(7a'',4a'') 3.6, H C(7a'')); 4.70 (AB, J_AB 6.8, 1 H, OCH₂O); 4.56 (d, ³J(1',6) 11.2, H C(1')); 4.52

(br. s, H C(1)); 4.48 (AB, J_AB 6.8, 1 H, OCH₂O); 4.45 (m, H C(4), H C(2)); 4.09 (ddd, ³J(5,4) 5.6,

³J(5,6) 2.4 ⁴J(5,1) 1.2, H C(5)); 3.31 (s, MeO); 2.44 (dd, ³J(6,1') 11.2, ³J(6,5) 2.4, H C(6)); 1.55, 1.40

(2s, 2 Me); 0.88 (s, t-BuSi); 0.13, 0.03 (2s, 2 MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 199.9 (s, C(3)); 158.4

(s, C(3'')); 134.5 (s, arom. C); 132.6 (d, J 171, 2 arom. C); 129.6 (d, J 170, 2 arom. C); 129.6 (s, arom. C);

113.5 (s, C(6'')); 106.7 (d, J 187, C(4a'')); 96.2 (t, J 164, OCH₂O); 88.2 (d, J 162, C(7'')); 85.4 (d, J 164,

C(3a'')); 84.0 (d, J 162, C(7a'')); 82.1 (d, J 166, C(1)); 81.0 (d, J 165, C(2)); 76.7 (d, J 155, C(5)); 76.4

(d, J 167, C(4)); 68.1 (d, J 152, C(1')); 56.2 (q, J 143, MeO); 52.0 (d, J 138, C(6)); 27.7 (q, J 127, Me);

26.8 (q, J 127, Me); 25.6 (q, J 125, Me₃CSi); 17.9 (s, Me₃CSi);

4.6,

5.0 (2q, J 120, 2 MeSi). CI-MS

(NH₃): 735 (2, M ), 678 (8), 620 (1), 531 (3), 454 (8), 328 (11), 242 (27), 184 (20), 129 (48), 75 (100). Anal. calc.

for C₂₉H₄₀BrNO₁₂SSi (734.67): C 47.41, H 5.49, N 1.91; found: C 47.37, H 5.61, N 1.99.

(

)-(1R,4R,5R,6S,7R)-4-exo-{[4-(Bromophenyl)sulfonyl]oxy}-6-exo-{(S)-[(tert-butyl)dimethylsilyloxy]-

[(3aS,4aS,7aS,7bR)-3a,4a,7a,7b-tetrahydro-6,6-dimethyl[1,3]dioxolo[4,5]furo[2,3-d]isoxazol-3-yl]methyl}-7-endo-

(methoxymethoxy)-2,8-dioxabicyclo[3.2.1]octan-3-one (( )-74). As described for ()-59, with ( )-73;( )-74

25

(93%). Colorless solid. M.p. 68 ± 708. [a]

44, [a]

46, [a]

52, [a]

90, [a]

109 (c

589

577

546

435

405

0.7, CHCl₃). UV (MeCN): 235 (12300). IR (KBr): 2955, 2935, 2860, 1770, 1575, 1470, 1375, 1190, 1110, 1060,

1015, 840, 780. ¹H-NMR (400 MHz, CDCl₃): 7.80 (d, ³J 8.8, 2 arom. H); 7.69 (d, ³J 8.8, 2 arom. H); 6.22

(d, ³J(4a'',7a'') 3.6, H C(4a'')); 5.86 (d, ³J(1,7) 3.7, H C(1)); 5.57 (d, ³J(3a'',7b'') 5.7, H C(3a'')); 5.03

(s, H C(4)); 4.95 (d, ³J(7b'',3a'') 5.7, H C(7b'')); 4.95 (d, ³J(7a'',4a'') 3.6, H C(7a'')); 4.72 (AB, J_AB 7.1,

1 H, OCH₂O); 4.58 (AB, J_AB 7.1, 1 H, OCH₂O); 4.56 (d, ³J(1',6) 10.7, H C(1')); 4.39 (br. s, H C(5)); 4.02

(dd, ³J(7,6) 3.8, ³J(7,1) 3.7,

H

C(7)); 3.39 (s, MeO); 2.45 (ddd, ³J(6,1') 10.7, ³J(6,7) 3.8, ⁴J 1.6,

H

C(6)); 1.55, 1.40 (2s, 2 Me); 0.89 (s, t-BuSi); 0.13, 0.03 (2s, 2 MeSi). ¹³C-NMR (100.6 MHz, CDCl₃): 160.2

(s, C(3)); 158.5 (s, C(3'')); 134.9 (s, arom. C); 132.4 (d, J 171, 2 arom. C); 129.7 (d, J 170, 2 arom. C); 129.6

(s, arom. C); 113.5 (s, C(6'')); 106.9 (d, J 187, C(4a'')); 101.9 (d, J 191, C(1)); 97.2 (t, J 164, OCH₂O); 89.0

(d, J 162, C(7b'')); 85.1 (d, J 164, C(3a'')); 83.7 (d, J 168, C(7a'')); 82.0 (d, J 162, C(7)); 79.8 (d, J 162,

C(5)); 75.6 (d, J 155, C(4)); 68.8 (d, J 146, C(1')); 56.7 (q, J 143, MeO); 48.0 (d, J 136, C(6)); 27.6, 26.8

(2q, J 127, 2 Me); 25.5 (q, J 125, Me₃CSi); 17.9 (s, Me₃CSi);

4.5,

5.1 (2q, J 122, 2 MeSi). CI-MS

(NH₃): 752 (5, [M 1] ), 751 (3, M ), 694 (3), 516 (6), 463 (2), 373 (2), 242 (21), 129 (20), 83 (100). Anal. calc.

for C₂₉H₄₀BrNO₁₃SSi (750.67): C 46.40, H 5.37; found: C 46.35, H 5.48.

Article Doi

Asymmetric syntheses of new polyhydroxylated quinolizidines 1: Cross-aldol reactions of 7-oxabicyclo[2.2.1]heptan-2-one and 3a,4a,7a,7b-tetrahydro[1,3]dioxolo[4,5]furo[2,3-d]isoxazole-3-carbaldehyde derivatives 2

DOI: 10.1002/(SICI)1522-2675(20000119)83:1<193::AID-HLCA193>3.0.CO;2-I

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Full text of DOI:10.1002/(SICI)1522-2675(20000119)83:1<193::AID-HLCA193>3.0.CO;2-I

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