Higher glycosamino acid precursors: C7 and C8 aminodialdoses via regio- and stereoselective [3+2] cycloaddition of vinyl trimethylsilane to C-glycosyl nitrones

TETRAHEDRON:

ASYMMETRY

Pergamon

Tetrahedron: Asymmetry 13 (2002) 2025–2038

Higher glycosamino acid precursors: C₇and C₈aminodialdoses

via regio- and stereoselective [3+2] cycloaddition of vinyl

trimethylsilane to C-glycosyl nitrones

Pastora Borrachero,^aFrancisca Cabrera-Escribano,^aM^aJesu´s Dia´nez,^bM^aDolores Estrada,^b

Manuel Go´mez-Guille´n,^a,* Amparo Lo´pez Castro,^bSimeo´n Pe´rez-Garrido^band M^aIsabel Torres^a

^aDepartamento de Qu´ımica Orga´nica ‘Profesor Garc´ıa Gonza´lez’, Facultad de Qu´ımica, Universidad de Sevilla,

Apartado de Correos No. 553, E-41071 Sevilla, Spain

^bInstituto de Ciencias de Materiales de Sevilla and Departamento de F´ısica de la Materia Condensada,

CSIC-Universidad de Sevilla, Apartado de Correos No. 1065, E-41080 Sevilla, Spain

Received 19 July 2002; accepted 5 September 2002

Abstract—Protected C₇and C₈aminodialdoses were prepared stereoselectively from readily available C₅and C₆monosaccharide

N-benzyl nitrones, by regio- and diastereoselective 1,3-dipolar cycloaddition reactions with vinyl trimethylsilane, followed by

acetyl chloride-mediated cleavage of the 5-(trimethylsilyl)isoxazolidine formed. The cycloaddition reaction took place in moderate

to good global yields (67–74%); estimation of diastereoselectivities from isolated yields showed total endo preference for the

reaction of the

conﬁgured substrate. Attack on the re face of the nitrone was predominant in all cases. The absolute conﬁguration of one of the

protected 3-(a- -galacto-pentopyranos-5-yl)isoxazolidine products was assigned by X-ray crystallographic analysis, allowing

D-galacto conﬁgured nitrone and high endo preference for the D-ribo analogue, but exo preference for the D-xylo

D

correlation of the conﬁguration at the new stereogenic centre in the corresponding aminodialdose. For non-crystalline isoxazolidi-

nes, conﬁgurations were assigned on the basis of NOESY experiments and/or chemical correlation. Combined yields of

aminodialdoses coming from isoxazolidines having identical conﬁguration at C(3) sometimes reached high values (up to 90%).

1. Introduction

obtained enantioselectively by addition of ketene silyl

acetals to C-aryl N-benzyl nitrones.⁵Simple amino

sugars have been prepared by opening of the isoxazo-

lidine ring of the cycloadducts obtained in the reaction

of C-glycosyl nitrones with conveniently substituted

oleﬁns.^6,7Complete regioselectivity and high stereo-

selectivity has been observed,⁸as expected from the

preliminary studies,^9,10in the reaction of vinyl

trimethylsilane as the dipolarophile, with various

nitrones derived from aromatic and aliphatic aldehydes

as the 1,3-dipole; the 5-(trimethylsilyl)isoxazolidine

resulting from the similar reaction of an aldehydo-tet-

rose nitrone, as treated with acetyl chloride, afforded

the corresponding 3-acetamido-2,3-dideoxy-aldehydo-

hexose derivative.¹¹To our knowledge, this methodol-

ogy has not been employed for preparing amino sugars

having a carbon chain of more than six carbon atoms,

and we planned to apply it, starting from easily avail-

Higher-carbon (C₇–C₉) amino deoxy sugars—some of

which participate as important components of natural

products—are substances of high biological interest. A

particular class of amino sugar derivatives are the gly-

cosamino acids,¹among which the sialic acids consti-

tute a very important group of biomolecules.²A review

on recent advances in the synthesis of sialic acid deriva-

tives and mimetics has been published recently.³

Diverse synthetic routes have been applied to obtain

other natural and unnatural higher-carbon amino sug-

ars. Thus, a synthesis of di-N-acetyl-legionaminic acid,

a

5,7-diamino-3,5,7,9-tetradeoxynon-2-ulosonic acid,

and eight of its stereoisomers by way of condensation

of oxalacetic acid with four 2,4-diacetamido-2,4,6-

trideoxyhexoses, has been described.⁴b-Amino acids

also having an aryl group at the b position can be

able, protected a-

D

-galacto-hexodialdo-1,5-pyranose,

-ribo-pentodialdo-1,4-furanose

and a- -xylo- and a-

D

nitrones, to the stereoselective synthesis of C₇and C₈

3-aminodialdoses, which could be considered intermedi-

* Corresponding author. Tel.: +34 95 4557151; fax: +34 95 4624960;

e-mail: mguillen@us.es

PII: S0957-4166(02)00543-8

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P. Borrachero et al. / Tetrahedron: Asymmetry 13 (2002) 2025–2038

Scheme 1. Isoxazolidine derivatives: conﬁgurational structures and yields.

ate precursors of b-amino glycuronic acids. We report

here the results of these reactions, including a study of

the endo/exo diastereoselectivity and the diastereofacial

selectivity of the [3+2] cycloaddition, necessary for

accurate determination of the absolute conﬁguration of

the new stereogenic centre created in the elongated

carbon chain of the aminodialdoses obtained.

approach of the reagents (Scheme 2), as well as a

preference for attack on the re face of the sugar nitrone,

since no other diastereomeric cycloadduct could be

isolated or detected. For the reaction of the a-D-xylo

conﬁgured nitrone 2 with 4, a mixture of four

diastereomers (6a–6d) was obtained; the major product

was 6c (33% isolated yield), followed by 6a (18%), 6b

1

(8%, as calculated from the H NMR spectrum of the

2:1 6b/6d mixture obtained after column and TL chro-

matographies), and 6d (8%, as the sum of pure fraction

yield, from TLC, and that corresponding to the mixture

2. Results

Reaction of (Z)-N-benzyl C-glycosylnitrones 1–3, eas-

with 6b, cited above). In turn, the a-D-ribo conﬁgured

ily prepared¹²from 1,2:3,4-di-O-isopropylidene-a-

D-

nitrone 3 led in the reaction with vinylsilane 4 to a

diastereomeric mixture (7a–7d), column chromatogra-

phy of which gave rise to two main fractions. The

former fraction was subjected to preparative TLC,

which afforded three products: pure 7c (16%), pure 7a

galactopyranose, and 3-O-benzyl-1,2-O-isopropyli-

dene-a- -xylo- and a- -ribofuranose, respectively, with

D

a large excess of vinyl trimethylsilane 4 in toluene at

80°C, afforded diastereomeric mixtures of the 2-benzyl-

3-(glycopyranos-5-yl or glycofuranos-4-yl)-5-(trimethyl-

silyl)isoxazolidines 5–7 regioselectively (Scheme 1). The

diastereomers could be separated by column chro-

matography, followed by TLC for certain fractions, the

global yields of pure isomers reaching 67–74%. Only

two diastereomeric compounds, 5a and 5b, were

obtained from 1; the former was the major product and

could be isolated in 54% yield as a crystalline com-

pound, X-ray diffraction analysis of which established

its (2R,3R,5S) absolute conﬁguration. The diastereomer

5b was isolated in 20% yield. In this case, the results

indicate an exclusive, or almost exclusive, endo

1

(40%), and a 4:1 diastereomeric mixture (from the H

NMR spectrum) (9%) of 7b and 7d. The latter fraction

from the column consisted of a 2:1 mixture of the same

diastereomers 7b and 7d (9%).

Opening of the isoxazolidine ring of compounds 5–7

was effected by treatment with acetyl chloride, a

method used⁶to transform other 5-(trimethylsilyl)-

isoxazolidines into 3-aminoaldehydes minimising the

b-elimination to the respective a,b-unsaturated alde-

hyde, which had been observed when ﬂuoride was used

P. Borrachero et al. / Tetrahedron: Asymmetry 13 (2002) 2025–2038

2027

Scheme 2. Reagent orientations in the cycloaddition reaction of 1–3 with 4, and conﬁgurations of the products.

as the promotor.⁸Thus, treatment of 5–7, at 0°C under

argon, with acetyl chloride and subsequent quenching

with an excess of aqueous sodium hydrogen carbonate

led to the respective 3-aminoaldehydes. However, the

corresponding a,b-unsaturated aldehyde was also iso-

lated in variable yields (even as the major product in

some cases). The reaction involves the immolation of a

stereogenic centre, and hence only two epimeric 3-

aminoaldehydes are to be expected from each set of

diastereomeric isoxazolidines 5, 6, or 7. From the crys-

talline compound 5a, the protected 6-amino-octodial-

dose 8 (21%, corresponding to 26% from converted

substrate) and its b-elimination product 9 (49% from

converted substrate) were obtained. When compound

5b was subjected to the same reaction, the products

were 9 (8% from converted substrate) and 10, the

6-epimer of 8, in 30% yield (47% from converted sub-

strate). Separate treatment of isoxazolidines 6c and 6a

under the same conditions led to the same 5-amino-

heptodialdose 11 (45%, corresponding to 71% from

converted 6c; 11%, that is 19% from converted 6a),

indicating identical 3R conﬁguration in the substrates,

and a,b-unsaturated aldehyde 12 (11%, corresponding

to 17% from converted 6c; 45% from converted 6a).

Under the same conditions, the 2:1 6b/6d mixture gave

rise to the epimer 13 (30%, corresponding to 57% from

converted substrate), and the same enone 12 (19%; 35%

from converted substrate), but none (NMR spectra) of

the other saturated epimer 11. These facts demonstrate

that 6b and 6d have the same 3S conﬁguration. The

isoxazolidines 7 showed analogous behaviour to that of

their isomers 6. Thus, in separate experiments, 7c and

7a were allowed to react with acetyl chloride under the

above conditions to afford the same aminodialdose 14

(13 and 7%, respectively)—a proof of the same 3R

conﬁguration for both substrates—and the b-elimina-

tion product 15 (36 and 38%, respectively). Conversely,

a 7b/7d mixture led to a single aminodialdose 16 (46%,

corresponding to 57% form converted substrate),

epimer of 14 (showing that both 7b and 7d have the 3S

conﬁguration) and the same enone 15 (35%; 42% from

converted substrate).

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P. Borrachero et al. / Tetrahedron: Asymmetry 13 (2002) 2025–2038

3. Discussion

isoxazolidine ring in the precursors. The ¹H NMR

spectrum of 5a in deuterochloroform or in dimethyl-

sulphoxide-d₆, at room temperature, showed the signals

of one of the diastereotopic C(4) methylene protons

and C(5)H split, indicating the existence of two con-

formers in slow equilibrium; the split signals collapsed

on heating at 120°C in dimethylsulphoxide-d₆, as

expected. The C(3)H/C(5%)H coupling constant values

observed for 5a (10.2 Hz) and 5b (8.7 Hz) enabled

deduction of the preferred (in solution) anti relationship

between these isoxazolidine and sugar protons around

the C(3)ꢀC(5%) bond. Assignment of the R conﬁguration

to C(5) of 5b was deduced from 1D NOESY experi-

ments, which showed C(5)H/C(4%)H and, to a some-

what lesser extent, C(5)H/C(5%)H contacts and absence

of contact between C(3)H and C(5)H. This supports the

assignment of the 3,5-trans relationship (see Scheme 3),

consistent with the steric hindrance that might appear

between the bulky 1,2:3,4-diprotected sugar moiety and

the trimethylsilyl group in a 3,5-cis disubstituted isoxa-

zolidine ring.

Assignment of absolute conﬁguration to C(3) and C(5)

of the diastereomeric isoxazolidines 5–7 was made

1

mainly on the basis of H NMR data, including 1D

NOESY experiments. For 5a, X-ray diffraction analysis

established its (2R,3R,5S) absolute conﬁguration, as

mentioned above. For the diastereomer 5b, the S

conﬁguration was assigned to C(3), since opening of the

isoxazolidine ring led, as explained above, to 10, the

6-epimer of 8 formed from 5a; that is, the difference in

conﬁguration of C(6) for 8 and 10 is a direct conse-

quence of the different conﬁguration at C(3) of the

The anti relationship between the isoxazolidine C(3)H

and the sugar C(4%)H, in the preferred conformation in

chloroform, was also deduced from the corresponding

coupling constant values observed (8.8–10.2 Hz) in the

¹H NMR spectra of all the diastereomeric isoxazolidi-

nes 6 obtained from the

D

-xylo conﬁgured nitrone 2.

Molecular models show that, in this conformation, a

C(5)H/C(4%)H contact is possible for the 3R,5S

conﬁgured structure 6a if the isoxazolidine ring adopts

an envelope conformation having the methylene carbon

atom out of the plane, resulting in stabilisation by

Scheme 3. NOE (1D NOESY) contacts for 5b, 6a, 6d, 7c, and

7a.

P. Borrachero et al. / Tetrahedron: Asymmetry 13 (2002) 2025–2038

2029

Figure 1. An ORTEP view of the unit cell for 5a. On the left, the molecule A; on the right, the molecule A%.

,

Table 1. Selected bond distances (A) and torsion angles (°) for 5a

Bond lengths

Torsion angles

H2ꢀC2ꢀC1ꢀH1

Si1ꢀC8

Si2ꢀC32

O5ꢀC5

O11ꢀC29

O5ꢀC1

O11ꢀC25

C5ꢀC4

C28ꢀC29

C3ꢀC4

C28ꢀC27

C3ꢀC2

C26ꢀC27

C2ꢀC1

C26ꢀC25

O6ꢀN1

1.8884(48)

1.8907(37)

1.4347(47)

1.4193(55)

1.3970(59)

1.4031(53)

1.5198(69)

1.5104(60)

1.5331(66)

1.5380(54)

1.5100(71)

1.5083(71)

1.5117(76)

1.5080(72)

1.4630(46)

1.4674(47)

1.4779(48)

1.4582(58)

1.5347(68)

1.5256(60)

1.5145(54)

1.5209(67)

1.4491(62)

1.4526(65)

C1ꢀO5ꢀC5ꢀC4

C25ꢀO11ꢀC29ꢀC28

C5ꢀO5ꢀC1ꢀO1

C29ꢀO11ꢀC25ꢀO7

C5ꢀO5ꢀC1ꢀC2

C29ꢀO11ꢀC25ꢀC26

C3ꢀC2ꢀC1ꢀO5

C27ꢀC26ꢀC25ꢀO11

C4ꢀC3ꢀC2ꢀC1

C25ꢀC26ꢀC27ꢀC28

C6ꢀC5ꢀC4ꢀC3

C27ꢀC28ꢀC29ꢀC30

N1ꢀO6ꢀC8ꢀSi1

N2ꢀO12ꢀC32ꢀSi2

N1ꢀO6ꢀC8ꢀC7

N2ꢀO12ꢀC32ꢀC31

O6ꢀN1ꢀC6ꢀC5

O12ꢀN2ꢀC30ꢀC29

O6ꢀN1ꢀC6ꢀC7

O12ꢀN2ꢀC30ꢀC31

C18ꢀN1ꢀC6ꢀC5

C42ꢀN2ꢀC30ꢀC29

C8ꢀO6ꢀN1ꢀC6

65.96(46)

65.95(46)

86.59(45)

−23.76(60)

−24.04(61)

−74.97(53)

−74.96(53)

−0.51(59)

−0.56(58)

−51.05(54)

−51.68(53)

177.02(37)

176.76(37)

−34.91(56)

87.46(50)

H26ꢀC26ꢀC25ꢀH25

H3ꢀC3ꢀC2ꢀH2

H26ꢀC26ꢀC27ꢀH27

H3ꢀC3ꢀC4ꢀH4

H28ꢀC28ꢀC27ꢀH27

H5ꢀC5ꢀC4ꢀH4

H28ꢀC28ꢀC29ꢀH29

H6ꢀC6ꢀC5ꢀH5

H29ꢀC29ꢀC30ꢀH30

H6ꢀC6ꢀC7ꢀH7A

H6ꢀC6ꢀC7ꢀH7B

H31AꢀC31ꢀC30ꢀH30

H31BꢀC31ꢀC30ꢀH30

87.14(47)

−29.56(54)

−31.11(55)

−22.76(59)

−19.85(61)

36.63(56)

33.74(57)

−163.89(36)

−165.47(36)

−137.15(29)

−136.93(28)

−10.70(46)

−10.78(44)

−92.06(36)

−92.36(37)

29.39(40)

−35.07(56)

87.37(50)

O12ꢀN2

N1ꢀC6

N2ꢀC30

C6ꢀC7

C31ꢀC30

C7ꢀC8

C31ꢀC32

O6ꢀC8

30.22(41)

153.53(38)

152.75(37)

−11.89(42)

−12.20(42)

C12ꢀC32

C32ꢀO12ꢀN2ꢀC30

C(4%)H of compounds 7 have a gauche disposition

around the C(3)-C(4%) bond, since the corresponding

coupling constant values are in the range 2.8–3.9 Hz.

This may be explained taking into account that steric

hindrance between the sugar and the isoxazolidine moi-

eties decreases in these ribose derivatives 7 in such

conformation, in comparison with the xylose deriva-

tives 6 in the same conformation, as molecular models

show. For the diastereomer showing C(5)H/C(3%)H,

C(3)H/C(3%)H, C(3)H/C(4%)H, and C(3)H/C(5)H con-

tacts (1D NOESY), the 3R,5R structure (7c), which

might be stabilised similarly to 6a (see above), was

assigned (Scheme 3). The other product leading to the

same aminodialdose 14 must therefore have the

epimeric 3R,5S structure (7a), as was corroborated by

the lack of C(3)H/C(5)H contact. The two remaining

stacking of the phenyl rings of the N-benzyl and O-

benzyl groups. Such aromatic–aromatic interactions are

known to be involved in the stabilisation of protein

structures.¹³For the facial diastereomer 6b, the two

phenyl groups are too far from each other to interact.

Hence, the product exhibiting such C(5)H/C(4%)H con-

tact experimentally (1D NOESY) must have the struc-

ture 6a (Scheme 3). For the major product, the 3R,5R

conﬁguration was assigned (6c), since it is the 5-epimer

of 6a, as mentioned above. The structure 6d allows a

C(3)H/C(5)H contact (Scheme 3), and is assigned to the

product that experimentally showed a NOE effect

between these protons. The remaining structural possi-

bility (6b) was assigned to the other product.

Unlike the foregoing isoxazolidines, the C(3)H and

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P. Borrachero et al. / Tetrahedron: Asymmetry 13 (2002) 2025–2038

Table 2. Puckering coordinates, amplitudes and phase magnitudes, and asymmetry parameters for 5a

,

Ring

Q (A)

(°)

q (°)

DC₂

(C1)=0.086

(C25)=0.086

(O1)=0.024

(C3)=0.051

(O7)=0.051

(C28)=0.050

(O6)=0.024

(O12)=0.004

DC_s

Sequence

A pyranose

0.62(1)

0.60(1)

−48(1)

−43(1)

−97(1)

−36(1)

−94(1)

35(1)

79(1)

78(1)

(O5ꢀC5)=0.088

(O11ꢀC29)=0.079

O5ꢀC1ꢀC2ꢀC3ꢀC4ꢀC5

O11ꢀC25ꢀC26ꢀC27ꢀC28ꢀC29

O1ꢀC9ꢀO2ꢀC2ꢀC1

A% pyranose

A dioxolane

A% dioxolane

A isoxazolidine

A’ isoxazolidine

0.316(4)

0.277(5)

0.317(4)

0.285(5)

0.342(5)

0.346(4)

–

O4ꢀC4ꢀC3ꢀO3ꢀC12

O7ꢀC33ꢀO8ꢀC26ꢀC25

O9ꢀC36ꢀO10ꢀC28ꢀC27

N1ꢀC6ꢀC7ꢀC8ꢀO6

89(1)

−127(1)

N2ꢀC30ꢀC31ꢀC32ꢀO12

diastereomers 7b and 7d have the 3S conﬁguration and

differ from each other only in the conﬁguration at C(5),

as both gave rise to the same heptodialdose 16. How-

ever, accurate assignment of structure 7b or 7d to the

major or the minor component of the mixed chromato-

graphic fraction was not possible.

the bulky trimethylsilyl group and the sugar moiety

that exists in the transition state for cycloaddition from

the exo approach in comparison with the same

approach for the ribo conﬁgured nitrone 3.

Isolated yields of aminodialdoses in the ring opening of

the compounds 5–7 by reaction with acetyl chloride

were low to moderate. Despite this, the combined yields

of aminodialdose from substrates 6 and 7 having the

same conﬁguration at C(3) were higher: from 6c and 6a,

90% of 11; from (6b+6d), 57% of 13; from 7c and 7a,

20% of 14; from (7b+7d), 57% of 16 were obtained.

Thus, only from substrates 6 was the combined yield of

3.1. X-Ray structure analysis of crystalline compound 5a

The unit cell consists of two molecules of 5a in slightly

different conformations. A perspective view of the unit

cell, showing the absolute conﬁguration together with

the atomic labelling scheme, is shown in Fig. 1. Bond

lengths and torsion angles are shown in Table 1. One of

the pyranose rings (that of molecule A, on the left of

Fig. 1) shows the anomeric effect [O(5)ꢀC(5)=1.435(5)

the

D

-glycero conﬁgured aminodialdose 11 much higher

than that of the epimer 13; from the other substrates, 5

and 7, the major aminodialdose has the

conﬁguration (10 and 16).

L-glycero

,

and O(5)ꢀC(1)=1.397(6) A], while the other pyranose

ring (that of molecule A%, on the right of Fig. 1) does

not show this effect [O(11)–C(25)=1.403(5) and O(11)–

In conclusion, the diastereoselective pathway described

here for obtaining new higher-chain aminodialdoses

from readily available sugar nitrones may be considered

suitable enough for that objective, since the ﬁnal prod-

ucts are obtained as stereochemically pure compounds,

thereby overcoming the limitation of the low to moder-

ate yields achieved. Moreover, the aminodialdoses

obtained are direct precursors of higher-chain gly-

cosamino acids.

,

C(29)=1.419(6) A]. The geometry observed for the

pyranose, dioxolane, and isoxazolidine rings is shown

in Table 2; the two pyranose rings show conformations

midway between B_2,5(=−60°, q=90°) and ^OS₅(=

−30°, q=68°), instead of that explicitly corresponding

to any of these forms.¹⁴One of the two dioxolane rings

of molecule A is in a conformation intermediate

between T and E, and the other in E conformation. The

two dioxolane rings of A% show T and E conformations,

respectively. The isoxazolidine ring shows T conforma-

tion for both molecules A and A%. The dihedral angles

between the pyranose and dioxolane rings are 76.0 and

79.3° for A, and 76.8 and 78.8° for A%. The crystal

cohesion is governed by van der Waals forces. There

are two intramolecular short contacts: C5···O2=

5. Experimental

5.1. General

Hexane and ether were distilled from sodium prior to

use. TLC was performed on silica gel plates (DC-Alu-

folien F₂₅₄, E. Merck, or Alugram Sil G/UV₂₅₄, Mach-

erey–Nagel), and preparative TLC on Kieselgel 60 F₂₅₄

7739, E. Merck; detection of compounds was accom-

plished with UV light (254 nm) and by charring with

H₂SO₄. Silica gel 60 (E. Merck, 0.040–0.063 mm) was

used for column chromatography. Solutions were con-

centrated under diminished pressure at <40°. Melting

points were determined on a Gallenkamp MFB-595

apparatus and are uncorrected. A Perkin–Elmer 241

MC polarimeter was used for measurement of optical

rotations. IR spectra (neat or on a KBr disc) were

obtained on a FTIR Bomem Michelson MB-120 spec-

,

3.060(6) A, C5ꢀH5···O2=106.4(3)°, and C29···O8=

,

3.066(5) A, C29–H29···O8=106.9(3)°.

4. Conclusion

The isolated yields of each diastereomer of the isoxazo-

lidines 5–7 were used as data for an estimation of the

endo/exo cycloaddition and facial diastereoselectivities.

For the substrates 1 and 3, the re/si diastereofacial

selectivity reached ratios of 2.7:1 and ꢀ2.0:1, respec-

tively, while the endo/exo diastereoselectivity is total for

1 and ꢀ3.3:1 for 3. The xylo conﬁgured nitrone 2

showed a re/si diastereofacial selectivity of 3.0:1, but an

inverted exo/endo diastereoselectivity of ꢀ1.57:1. This

may be attributed to the lower steric hindrance between

1

trophotometer. H NMR spectra (300 and 500 MHz)

and ¹³C NMR spectra (75.4 and 125.7 MHz) were

recorded with a Bruker AMX-300 or an AMX-500

P. Borrachero et al. / Tetrahedron: Asymmetry 13 (2002) 2025–2038

2031

spectrometers; chemical shifts (l) are expressed in ppm

from TMS; coupling constants (J), in Hz. Assignments

were conﬁrmed by decoupling, homonuclear 2D COSY

correlated spectra, heteronuclear 2D correlated (HET-

COR) spectra, and 1D NOESY spectra. CI mass spec-

tra were measured with a Micromass AutoSpecQ

instrument, using methane as reagent gas and a resolu-

tion of 1000 (10% valley deﬁnition). HREIMS (70 eV)

and HRCIMS (150 eV) experiments were performed

with the same instrument, with a resolution of 10,000

(5% valley deﬁnition), or a VG AutoSpec spectrometer

(HRCIMS, 70 eV, resolution of 8,500, 10% valley

deﬁnition).

H-5), 3.29 (ddd, 1H, J_3,4a=1.7, J_3,4b=8.2, H-3), 2.30

(ddd, 1H, J_4a,4b=12.2, H-4a), 2.02 (ddd, 1H, H-4b),

1.43, 1.34, 1.30, 1.27 (each s, each 3H, 2CMe₂), and

0.04 (s, 9H, SiMe₃); ¹³C NMR (127.8 MHz, CDCl₃) l

129.9, 129.0, 128.5, 128.1, 127.9, 126.9 (Ph), 108.5,

108.2 (2CMe₂), 96.3 (C-1%), 71.6 (C-2%), 70.5 (C-3%), 70.5

(C-4%), 69.9 (C-5), 67.6 (C-5%), 63.0 (C-3), 63.0 (CH₂Ph),

33.8 (C-4), 26.0, 25.7, 24.8, 23.9 (2CMe₂), and −3.7

(SiMe₃); CIMS: m/z 464 (41, [M+H]⁺); 448 (27, [M−

Me]⁺); 348 (100, [M−Me₃Si–CO–CH₂]⁺). Anal. calcd for

C₂₄H₃₇NO₆Si: C, 62.20; H, 8.00; N, 3.02. Found: C,

62.59; H, 8.08; N, 3.36%.

Second eluted 5b (0.202 g, 20%); oil; R_f0.31 (6:1

hexane:ethyl acetate); [h]²_D⁵=−85 (c 1.33, CH₂Cl₂); IR

(KBr) w_max1381 (CMe₂), 1250 (_lC–H of SiCH₃), and

700 cm⁻¹(_wSi–C); ¹H NMR (300 MHz, CDCl₃) l

7.41–7.21 (m, 5H, Ph), 5.56 (d, 1H, J_1%,2%=5.0, H-1%),

4.60 (dd, 1H, J_2%,3%=2.5, J_3%,4%=7.8, H-3%), 4.42 (d, 1H,

5.2. Reaction of (Z)-N-benzyl-(1,2:3,4-di-O-isopropyli-

dene-a- -galactopyranos-6-ylidene)amine N-oxide, 1

D

with vinyl-trimethylsilane, 4: preparation of (2R,3R,5S)-

2-benzyl-3-(1,2:3,4-di-O-isopropylidene-a- -galacto-

D

pentopyranos-5-yl)-5-(trimethylsilyl)isoxazolidine, 5a

and (3S,5R)-2-benzyl-3-(1,2:3,4-di-O-isopropylidene-

J

_gem=13.9, CH^aPh), 4.31 (dd, 1H, H-2%), 4.26 (dd, 1H,

a-

D

-galacto-pentopyranos-5-yl)-5-(trimethylsilyl)-

J_4%,5%=1.9, H-4%), 3.88 (d, 1H, J_gem=13.1, CH^bPh), 3.82

(dd, 1H, J_3,5%=8.7, H-5%), 3.02 (br m, 1H, H-3), 3.51

(dd, 1H, J_4a,5=8.9, J_4b,5=9.5, H-5), 2.15 (m, 2H, 2H-4),

[1.54, 1.45 (each s, each 3H), and 1.34 (s, 6H) 2CMe₂],

and 0.02 (s, 9H, SiMe₃); NOE contacts (1D NOESY):

H-5, H-4%, H-5%; H-5%, H-5; H-3, CH₂Ph; ¹³C NMR

(75.4 MHz, CDCl₃) l 130.2 (2C of Ph), 127.8 (3C of

Ph), 126.6 (the other C of Ph), 109.2, 108.6 (2CMe₂),

96.2 (C-1%), 72.3 (C-4%), 70.8 (C-3%), 70.2 (C-2% and C-5%),

68.7 (C-5), 63.7 (C-3), 62.5 (CH₂Ph), 34.4 (C-4), 26.0,

25.9, 24.9, 24.5 (2CMe₂), and −4.0 (SiMe₃); CIMS: m/z

464 (24, [M+H]⁺); 448 (16, [M−Me]⁺); 348 (100, [M−

Me₃Si–CO–CH₂]⁺). HRCIMS: m/z 463.2397 (calcd for

isoxazolidine, 5b

To a solution of nitrone 1¹²(0.80 g, 2.20 mmol) in

toluene (31 mL), cooled in an ice bath, dipolarophile 4

(7.7 mL, 5.0 g, 50 mmol) was added under an argon

atmosphere and the mixture was heated at 80°C. Mon-

itoring of the reaction (TLC, 6:1 and 1:1 hexane:ethyl

acetate) indicated a complete conversion after 24 h. The

solution was then concentrated to give a crude residue

formed by the diastereomeric isoxazolidines 5 (0.98 g,

96%), which was subjected to column chromatography

(10:1 hexane:ethyl acetate). First eluted 5a, isolated as a

solid (0.55 g, 54%); mp 54–56°C; crystallographic anal-

ysis evidenced its (2R,3R,5S) absolute conﬁguration; R_f

0.45 (6:1 hexane:ethyl acetate); [h]²_D⁵=+3.7 (c 1.8,

CH₂Cl₂); IR (KBr) w_max1381 (CMe₂), 1252 (_lC–H of

C₂₄H₃₇NO₆Si:

463.2390),

464.2446

(calcd

for

C₂₄H₃₇NO₆Si+H: 464.2468).

5.3. Reaction of (Z)-N-benzyl-(3-O-benzyl-1,2-O-iso-

propylidene-a- -xylofuranos-5-ylidene)amine N-oxide, 2

with vinyl-trimethylsilane, 4: preparation of the 2-ben-

zyl-3-(3-O-benzyl-1,2-O-isopropylidene-a- -xylo-tetro-

1

SiCH₃), and 752 cm⁻¹(_wSi–C); H NMR (300 MHz,

D

CDCl₃) l 7.37–7.20 (m, 5H, Ph), 5.50 (d, 1H, J_1%,2%=4.9,

H-1%), 4.54 (dd, 1H, J_2%,3%=2.1, J_3%,4%=8.0, H-3%), 4.47

(dd, 1H, J_4%,5%=1.5, H-4%), 4.25 (dd, 1H, H-2%), 4.01, 3.95

(each d, each 1H, J_gem=13.1, CH₂Ph), 3.62 (dd, 1H,

J_3,5%=10.2, H-5%), 3.44 (ddd, 1H, J_3,4a=5.0, J_3,4b=7.4,

H-3), 3.44 (dd, 1H, J_4a,5=1.0, J_4b,5=11.8 for conformer

I, J_4b,5=13.1 for conformer II, H-5), 2.35 (ddd, 1H,

D

furanos-4-yl)-5-(trimethylsilyl)isoxazolidines (3R,5R)-6c,

(3R,5S)-6a, (3S,5R)-6b, and (3S,5S)-6d

To a solution of nitrone 2¹²(1.26 g, 3.30 mmol) in

toluene (46 mL), cooled in an ice bath, dipolarophile 4

(11.5 mL, 7.46 g, 74.4 mmol) was added under an

argon atmosphere and the mixture was heated at 80°C

until monitoring of the reaction (TLC, 6:1 and 1:1

hexane:ethyl acetate) indicated complete conversion (24

h). The solution was then concentrated to give a crude

residue formed by the diastereomeric isoxazolidines 6

(1.56 g, 98%), which was subjected to column chro-

matography (8:1 hexane:ethyl acetate). First eluted 6c,

isolated as an oil (0.503 g, 33%); R_f0.46 (6:1 hex-

ane:ethyl acetate); [h]²_D²=+8.4 (c 0.7, CH₂Cl₂); IR (KBr)

w_max1377 (CMe₂), 1254 (_lC–H of SiCH₃), and 735 cm⁻¹

J

_4a,4b=12.3, H-4a), 1.99 (ddd, 1H, J_4b,5=11.5 for con-

former I, J_4b,5=13.1 for conformer II, H-4b), 1.46,

1.38, 1.29, 1.27 (each s, each 3H, 2CMe₂), and 0.07 (s,

1

9H, SiMe₃); H NMR (300 MHz, DMSO-d₆) l 7.37–

7.20 (m, 5H, Ph), 5.43 (d, 1H, J_1%,2%=4.9, H-1%), 4.58

(dd, 1H, J_2%,3%=2.2, J_3%,4%=8.0, H-3%), 4.32 (dd, 1H,

J_4%,5%=1.4, H-4%), 4.30 (dd, 1H, H-2%), 3.93, 3.79 (each d,

each 1H, J_gem=13.6, CH₂Ph), 3.45 (dd, 1H, J_3,5%=9.5,

H-5%), 3.29–3.22 (m, 2H, H-3 and H-5), 2.20 (ddd, 1H,

J

_4a,4b=12.1, J_3,4a=6.3, J_4a,5:0, H-4a), 1.99 (ddd, 1H,

_4a,4b=12.4, J_4b,5=8.5 or 7.9, J_3,4b=7.9 or 8.5, H-4b),

1

1.39, 1.29, 1.26, 1.23 (each s, each 3H, 2CMe₂), and

(_wSi–C); H NMR (300 MHz, CDCl₃) l 7.31–7.21 (m,

1

0.01 (s, 9H, SiMe₃); H NMR (300 MHz, DMSO-d₆,

10H, 2Ph), 5.88 (d, 1H, J_1%,2%=3.8, H-1%), 4.55 (d, 1H,

J_2%,3%:0, H-2%), 4.54, 4.37 (each d, each 1H, J_gem=11.7,

O-CH₂Ph), 4.11 (d, 1H, J_3%,4%=3.0, H-3%), 4.01 (dd, 1H,

120°C) l 7.31–7.23 (m, 5H, Ph), 5.44 (d, 1H, J_1%,2%=4.9,

H-1%), 4.56 (dd, 1H, J_2%,3%=2.2, J_3%,4%=7.9, H-3%), 4.35

(dd, 1H, J_4%,5%=1.7, H-4%), 4.26 (dd, 1H, H-2%), 3.99, 3.86

(each d, each 1H, J_gem=13.7, CH₂Ph), 3.56 (dd, 1H,

J_3,5%=9.5, H-5%), 3.36 (dd, 1H, J_4a,5=5.9, J_4b,5=12.9,

J_3,4%=10.2, H-4%), 3.97, 3.59 (each d, each 1H, J_gem

=

13.2, N-CH₂Ph), 3.81 (dd, 1H, J_4a,5=8.4, J_4b,5=10.8,

H-5), 3.69 (ddd, 1H, J_3,4a=8.1, J_3,4b=3.8, H-3), 2.64

2032

P. Borrachero et al. / Tetrahedron: Asymmetry 13 (2002) 2025–2038

(ddd, 1H, J_4a,4b=12.5, H-4a), 2.22 (ddd, 1H, H-4b),

1.44, 1.28 (each s, each 3H, CMe₂), and 0.07 (s, 9H,

SiMe₃); NOE contacts (1D NOESY): H-3, N-CHH-Ph;

H-5, N-CH₂Ph, H-4a; ¹³C NMR (75.5 MHz, CDCl₃) l

137.6, 137.5, 129.3, 128.3, 128.1, 127.6, 127.3, 127.0

(2Ph), 111.5 (CMe₂), 104.7 (C-1%), 82.4 (C-4%), 82.1

(C-3%), 82.0 (C-2%), 71.7 (O-CH₂Ph), 66.4 (C-5), 62.7

(C-3), 58.8 (N-CH₂Ph), 35.1 (C-4), 26.5, 26.1 (CMe₂),

and −3.8 (SiMe₃); CIMS: m/z 484 (33, [M+H]⁺); 468

(37, [M−Me]⁺); 368 (100, [M−Me₃Si–CO–CH₂]⁺);

HRCIMS: m/z 483.2444 (calcd for C₂₇H₃₇NO₅Si:

483.2441).

Last eluted a 2:1 mixture (6b+6d) (0.177 g, 11.5%); oil;

R_f=0.23 (6:1 hexane:ethyl acetate); IR (KBr) w_max1379

(CMe₂), 1252 (_lC–H of SiCH₃), and 733 cm⁻¹(_wSi–C);

CIMS: m/z 484 (11, [M+H]⁺); 468 (15, [M−Me]⁺); 368

(100, [M−Me₃Si–CO–CH₂]⁺); HRCIMS: m/z 483.2436

(calcd for C₂₇H₃₇NO₅Si: 483.2441); for the major com-

1

ponent 6b: H NMR (300 MHz, CDCl₃) l 7.40–7.24

(m, 10H, 2Ph), 6.01 (d, 1H, J_1%,2%=3.9, H-1%), 4.73, 4.42

(each d, each 1H, J_gem=11.8, O-CH₂Ph), 4.63 (d, 1H,

J_2%,3%:0, H-2%), 4.26 (dd, 1H, J_3,4%=9.0, J_3%,4%=3.1, H-4%),

3.92, 3.84 (each d, each 1H, J_gem=14.0, N-CH₂Ph), 3.90

(d, 1H, H-3%), 3.46 (dd, 1H, J_4a,5=10.0, J_4b,5=8.5, H-5),

3.09 (ddd, 1H, J_3,4a=2.1, J_3,4b=6.9, H-3), 1.97 (ddd,

1H, J_4a,4b=11.8, H-4a), 1.74 (ddd, 1H, H-4b), 1.34 (s,

6H, CMe₂), and 0.006 (s, 9H, SiMe₃); ¹³C NMR (75.5

MHz, CDCl₃) l 137.9, 137.0, 130.0, 128.5, 128.2, 128.1,

127.9, 127.8 (2Ph), 111.6 (CMe₂), 105.4 (C-1%), 82.8

(C-4%)), 82.1 (C-3%), 81.2 (C-2%), 71.6 (O-CH₂Ph), 68.9

(C-5), 63.7 (C-3), 60.7 (N-CH₂Ph), 35.0 (C-4), 26.6

(CMe₂), and −3.9 (SiMe₃); the minor component had

¹H and ¹³C NMR spectra, respectively, identical to

those of 6d.

Second eluted 6a (0.253 g, 16%); oil; R_f0.35 (6:1

hexane:ethyl acetate); [h]²_D³=+1.0 (c 0.3, CH₂Cl₂); IR

(KBr) w_max1377 (CMe₂), 1256 (_lC–H of SiCH₃), and

735 cm⁻¹(_wSi–C); ¹H NMR (300 MHz, CDCl₃) l

7.28–7.23 (m, 10H, 2Ph), 5.90 (d, 1H, J_1%,2%=3.9, H-1%),

4.59 (d, 1H, J_2%,3%:0, H-2%), 4.59, 4.39 (each d, each 1H,

J

_gem=11.6, O-CH₂Ph), 4.18 (dd, 1H, J_3,4%=9.9, J_3%,4%=

3.1, H-4%), 4.12 (d, 1H, H-3%), 3.86, 3.80 (each d, each

1H, J_gem=13.3, N-CH₂Ph), 3.70 (dd, 1H, J_3,4a:0,

J_3,4b=7.4, H-3), 3.58 (dd, 1H, J_4a,5=5.4, J_4b,5=13.5,

H-5), 2.48 (ddd, 1H, J_4a,4b=12.3, J_3,4a=0.6, H-4a), 2.08

(ddd, 1H, H-4b), 1.50, 1.30 (each s, each 3H, CMe₂),

and 0.06 (s, 9H, SiMe₃); NOE contacts (1D NOESY):

H-3, N-CH₂Ph; H-5, H-4%, H-4a; ¹³C NMR (75.5 MHz,

CDCl₃) l 137.7, 137.5, 129.4, 128.5, 128.2, 127.7, 127.5,

127.0 (2Ph), 111.6 (CMe₂), 104.9 (C-1%), 82.0, 82.0

(C-2%/C-3%), 80.2 (C-4%), 71.7 (O-CH₂Ph), 70.2 (C-5),

63.3 (N-CH₂Ph), 62.3 (C-3), 34.0 (C-4), 26.7, 26.2

(CMe₂), and −3.5 (SiMe₃); CIMS: m/z 484 (20, [M+H]⁺);

468 (28, [M−Me]⁺); 368 (100, [M−Me₃Si–CO–CH₂]⁺);

HRCIMS: m/z 483.2430 (calcd for C₂₇H₃₇NO₅Si:

483.2441).

5.4. Reaction of (Z)-N-benzyl-(3-O-benzyl-1,2-O-iso-

propylidene-a- -ribofuranos-5-ylidene)amine N-oxide, 3

D

with vinyl-trimethylsilane, 4: preparation of the 2-ben-

zyl-3-(3-O-benzyl-1,2-O-isopropylidene-a- -ribo-tetro-

D

furanos-4-yl)-5-(trimethylsilyl)isoxazolidines (3R,5R)-7c,

(3R,5S)-7a, (3S,5R)-7b, and (3S,5S)-7d

To a solution of nitrone 3¹²(0.522 g, 1.36 mmol) in

toluene (19 mL), cooled in an ice bath, dipolarophile 4

(4.76 mL, 3.08 g, 30.7 mmol) was added under an

argon atmosphere, and the mixture was heated at 80°C

for 20 h (TLC monitoring, 6:1 and 1:1 hexane:ethyl

acetate). The solution was concentrated to give a crude

residue formed by the diastereomeric isoxazolidines 7

(0.658 g, 100%), which was subjected to column chro-

matography (6:1 hexane:ethyl acetate). First eluted a

mixture of products (0.471 g), which were separated by

preparative TLC (same eluent, three runs) in three

fractions: 7c (0.103 g, 16%), 7a (0.263 g, 40%), and a

4:1 mixture (¹H NMR) of isomers (7b+7d) (0.059 g,

9%). From the column, second eluted a 2:1 mixture of

the same isomers (7b+7d) (0.058 g, ꢀ9%), and last

eluted (pure ethyl acetate as the eluent) a residual

mixture (0.094 g).

Third eluted a mixture of 6a and (6b+6d) (0.123 g,

8.0%), which was subjected to preparative TLC (6:1

hexane:ethyl acetate, two elutions), to afford three frac-

tions: that of R_f=0.65 was identiﬁed as 6a (0.025 g,

1.6%); the fraction of R_f=0.39 (0.020 g, 1.3%) was a 2:1

mixture (6b+6d), similar to the last eluted product from

the column (see below); the fraction of R_f=0.26 was

pure 6d (0.053 g, 3.5%): oil; [h]²_D⁰=−74.6 (c 1.4,

CH₂Cl₂); IR (KBr) w_max1381 (CMe₂), 1248 (_lC–H of

SiCH₃), and 739 cm⁻¹(_wSi–C); HRCIMS: m/z 483.2452

(calcd for C₂₇H₃₇NO₅Si: 483.2441); ¹H NMR (300

MHz, CDCl₃) l 7.40–7.24 (m, 10H, 2Ph), 5.97 (d, 1H,

J_1%,2%=3.9, H-1%), 4.72, 4.43 (each d, each 1H, J_gem

=

Compound 7c: oil; R_f0.42 (6:1 hexane:ethyl acetate);

[h]²_D³=+153 (c 1.52, CH₂Cl₂); IR (KBr) w_max1377

(CMe₂), 1254 (_lC–H of SiCH₃), and 735 cm⁻¹(_wSi–C);

¹H NMR (300 MHz, CDCl₃) l 7.38–7.28 (m, 10H,

2Ph), 5.69 (d, 1H, J_1%,2%=3.7, H-1%), 4.71, 4.54 (each d,

11.9, O-CH₂Ph), 4.63 (d, 1H, J_2%,3%:0, H-2%), 4.13 (dd,

1H, J_3,4%=8.8, J_3%,4%=3.4, H-4%), 3.96, 3.86 (each d, each

1H, J_gem=13.5, N-CH₂Ph), 3.84 (d, 1H, H-3%), 3.58 (dd,

1H, J_4a,5=6.1, J_4b,5=11.9, H-5), 3.35 (ddd, 1H, J_3,4a

=

7.3, J_3,4b=7.3, H-3), 2.20 (ddd, 1H, J_4a,4b=11.9, H-4a),

1.49 (overlapped m, 1H, H-4b), 1.48, 1.33 (each s, each

3H, CMe₂), and −0.002 (s, 9H, SiMe₃); NOE contacts

(1D NOESY): H-3, N-CH₂Ph, H-5, H-4a; H-5, N-

CHH–Ph, H-3, H-4a; ¹³C NMR (75.5 MHz, CDCl₃) l

138.1, 137.0, 129.6, 128.4, 128.2, 128.1, 127.9, 126.7

(2Ph), 111.5 (CMe₂), 105.2 (C-1%), 82.8 (C-4%)), 82.0

(C-3%), 81.6 (C-2%), 71.4 (O-CH₂Ph), 66.2 (C-5), 65.5

(C-3), 60.7 (N-CH₂Ph), 35.2 (C-4), 26.6, 26.3 (CMe₂),

and −3.7 (SiMe₃).

each 1H, J_gem=11.3, O-CH₂Ph), 4.55 (dd, 1H, J_2%,3%=

4.6, H-2%), 4.22 (dd, 1H, J_3%,4%=7.8, J_3,4%=3.2, H-4%), 4.06

(dd, 1H, H-3%), 4.06, 3.79 (each d, each 1H, J_gem=13.2,

N-CH₂Ph), 3.65 (dd, 1H, J_4a,5=5.3, J_4b,5=12.7, H-5),

3.35 (ddd, 1H, J_3,4a=J_3,4b=8.2, H-3), 2.30 (ddd, 1H,

J_4a,4b=12.7, H-4a), 2.14 (ddd, 1H, H-4b), 1.58, 1.36

(each s, each 3H, CMe₂), and 0.059 (s, 9H, SiMe₃);

NOE contacts (1D NOESY): H-3, H-4%, H-3%, N-CH₂-

Ph, H-5; H-5, H-3%, N-CHHPh, H-3, H-4a; ¹³C NMR

(75.5 MHz, CDCl₃) l 138.0, 137.9, 129.6, 128.1, 128.0,

P. Borrachero et al. / Tetrahedron: Asymmetry 13 (2002) 2025–2038

2033

127.9, 127.5, 126.9 (2Ph), 112.8 (CMe₂), 104.1 (C-1%),

5.5. Reaction of (2R,3R,5S)-2-benzyl-3-(1,2:3,4-di-O-

80.7 (C-4%), 78.6 (C-2%), 78.5 (C-3%), 71.8 (O-CH₂Ph),

67.1 (C-5), 66.7 (C-3), 61.9 (N-CH₂Ph), 34.9 (C-4),

26.9, 26.8 (CMe₂), and −3.7 (SiMe₃); HRCIMS: m/z

483.2437 (calcd for C₂₇H₃₆NO₅Si: 483.2441).

isopropylidene-a-D-galacto-pentopyranos-5-yl)-5-

(trimethylsilyl)isoxazolidine, 5a with acetyl chloride:

preparation of 6-(N-benzyl)acetamido-6,7-dideoxy-

1,2:3,4-di-O-isopropylidene-

D

-glycero-a- -galacto-octo-

D

dialdo-1,5-pyranose, 8 and (E)-6,7-didehydro-6,7-

Compound 7a: oil; R_f0.33 (6:1 hexane:ethyl acetate);

[h]²_D³=+101 (c 1.8, CH₂Cl₂); IR (KBr) w_max1377

(CMe₂), 1252 (_lC–H of SiCH₃), and 737 cm⁻¹(_wSi–C);

¹H NMR (300 MHz, CDCl₃) l 7.36–7.26 (m, 10H,

2Ph), 5.69 (d, 1H, J_1%,2%=3.7, H-1%), 4.77, 4.53 (each d,

dideoxy-1,2:3,4-di-O-isopropylidene-a- -galacto-

octodialdo-1,5-pyranose, 9

D

A suspension of 5a (0.19 g, 0.41 mmol) and sodium

hydrogen carbonate (0.115 g) in freshly distilled tetra-

hydrofuran (5 mL) was cooled at 0°C and treated with

acetyl chloride (0.43 mL, 0.61 mmol) under argon. The

mixture was maintained at 0°C for 3 h (TLC monitor-

ing, 6:1 and 1:1 hexane:ethyl acetate), and the reaction

was quenched by adding saturated aqueous sodium

hydrogen carbonate until neutral pH. The mixture was

extracted with ether (3×25 mL), and the combined

ethereal layers were dried (MgSO₄) and concentrated to

give a crude product, puriﬁcation of which was

achieved by column chromatography (6:11:1 gradi-

ent, hexane:ethyl acetate), to afford unreacted 5a (36

mg, indicating 81% of conversion), compound 8 (37

mg, 21%, corresponding to 26% yield from converted

substrate), and compound 9 (46 mg, 39%, correspond-

ing to ꢀ49% from converted substrate). Compound 8:

syrup; R_f0.67 (1:1 hexane:ethyl acetate); [h]²_D³=−10 (c

0.68, CH₂Cl₂); IR (KBr) w_max1717 (aldehyde CꢁO),

1653 (amide CꢁO), and 1383 cm⁻¹(CMe₂); HREIMS:

m/z 433.2091 (calcd for C₂₃H₃₁NO₇: 433.2101),

418.1849 (calcd for C₂₃H₃₁NO₇–CH₃: 418.1866); major

amide conformer (62.5%): ¹H NMR (500 MHz, CDCl₃)

l 9.39 (dd, 1H, J_CHO,7a=2.3, J_CHO,7b=2.0, CHO), 7.35–

7.14 (m, 5H, Ph), 5.48 (d, 1H, J_1,2=5.2, H-1), 4.71, 4.55

(each d, each 1H, J_gem=16.6, CH₂Ph), 4.30–4.25 (over-

each 1H, J_gem=11.4, O-CH₂Ph), 4.59 (dd, 1H, J_2%,3%

=

4.1, H-2%), 4.23 (dd, 1H, J_3%,4%=8.6, J_3,4%=2.8, H-4%),

4.15, 3.93 (each d, each 1H, J_gem=14.0, N-CH₂Ph), 4.11

(dd, 1H, H-3%), 3.48 (dd, 1H, J_4a,5=7.0, J_4b,5=11.7,

H-5), 3.17 (ddd, 1H, J_3,4a=4.2, J_3,4b=10.3, H-3), 2.33

(ddd, 1H, J_4a,4b=11.6, H-4a), 1.92 (ddd, 1H, H-4b),

1.57, 1.37 (each s, each 3H, CMe₂), and 0.02 (s, 9H,

SiMe₃); NOE contacts (1D NOESY): H-3, H-4%, H-3%,

N-CH₂-Ph; H-5, H-3%, N-CHHPh, H-4a; ¹³C NMR

(75.5 MHz, CDCl₃) l 137.5, 129.7, 128.2, 127.9, 127.8,

126.7 (2Ph), 112.8 (CMe₂), 103.7 (C-1%), 79.2 (C-4%),

78.6 (C-3%), 77.6 (C-2%), 71.9 (O-CH₂Ph), 69.5 (C-5),

63.7 (C-3), 62.2 (N-CH₂Ph), 33.6 (C-4), 26.7, 26.6

(CMe₂), and −3.9 (SiMe₃); HRCIMS: m/z 483.2429

(calcd for C₂₇H₃₆NO₅Si: 483.2441).

Isomer mixture (7b+7d): oil; R_f=0.22 (6:1 hexane:ethyl

acetate); IR (KBr) w_max1377 (CMe₂), 1254 (_lC–H of

SiCH₃), and 741 cm⁻¹(_wSi–C); HRCIMS: m/z 483.2438

(calcd for C₂₇H₃₆NO₅Si: 483.2441); the NMR spectra

showed signals for two isomers in a 4:1 ratio; for the

major component: ¹H NMR (300 MHz, CDCl₃) l

7.33–7.24 (m, 10H, 2Ph), 5.83 (d, 1H, J_1%,2%=3.9, H-1%),

4.52, 4.14 (each d, each 1H, J_gem=11.4, O-CH₂Ph), 4.51

(dd, 1H, J_2%,3%=4.4, H-2%), 4.00 (dd, 1H, J_3,4%=3.9,

lapped signal, 1H, H-6), 4.51 (dd, 1H, J_2,3=2.3, J_3,4

=

J_3%,4%=8.9, H-4%), 3.92, 3.84 (each d, each 1H, J_gem

=

8.1, H-3), 4.29 (dd, 1H, J_1,2=4.8, J_2,3=2.3, H-2), 4.23

(dd, 1H, J_3,4=7.9, J_4,5=1.7, H-4), 4.60–4.50 (over-

lapped, H-5), 2.98 (ddd, 1H, J_7a,7b=17.0, J_6,7a=5.6,

13.1, N-CH₂Ph), 3.72 (dd, 1H, J_4a,5=6.4, J_4b,5=9.5,

H-5), 3.64 (dd, 1H, H-3%), 3.15 (ddd, 1H, J_3,4a=2.5,

J_3,4b=9.0, H-3), 2.33 (ddd, 1H, J_4a,4b=12.0, H-4a), 2.10

J_7a,CHO=2.5, H-7a), 2.67 (ddd, 1H, J_7a,7b=17.0, J_6,7b=

(ddd, 1H, H-4b), 1.57, 1.35 (each s, each 3H, CMe₂),

and 0.04 (s, 9H, SiMe₃); ¹³C NMR (75.5 MHz, CDCl₃)

l 137.3, 137.2, 130.0, 128.1, 128.0, 127.9, 127.8, 127.7

(2Ph), 112.5 (CMe₂), 104.3 (C-1%), 80.7 (C-4%)), 79.1

(C-3%), 76.5 (C-2%), 71.6 (O-H₂Ph), 70.4 (C-5), 63.5

(N-H₂Ph), 63.3 (C-3), 34.8 (C-4), 26.6, 26.5 (CMe₂),

5.7, J_7b,CHO=1.6, H-7b), 2.16 (s, 3H, Me–CꢁO), [1.55

(s, 3H), 1.45 (s, 6H), and 1.32 (s, 3H) 2CMe₂]; ¹³C

NMR (125.7 MHz, CDCl₃) l 200.4 (CHO), 171.7 (N-

OCH₃), 136.7, 128.9, 128.6, 127.9, 127.4, 127.3 (Ph),

109.4, 109.1 (2CMe₂), 96.7 (C-1), 71.1 (C-3), 70.9 (C-4),

70.7 (C-2), 69.0 (C-5), 54.2 (C-6), 54.2 (CH₂Ph), 44.6

(C-7), 29.7, 26.0 (each double intensity, 2CMe₂), and

1

and −3.8 (SiMe₃); for the minor component: H NMR

1

(300 MHz, CDCl₃) l 7.33–7.24 (m, 10H, 2Ph), 5.81 (d,

overlapped with the signal for the respective proton of

the major component, 1H, J_1%,2%:4.1, H-1%), 4.54, 4.12

(each d, each 1H, J_gem=11.3, O-H₂Ph), 4.51 (dd, 1H,

J_2%,3%=4.1, H-2%), 3.94 (dd, 1H, J_3,4%=3.8, J_3%,4%=8.7,

H-4%), 3.92, 3.84 (each d, each 1H, J_gem=13.1, N-H₂Ph),

3.71 (dd, 1H, J_4a,5=6.6, J_4b,5=12.2, H-5), 3.63 (dd, 1H,

H-3%), 3.26 (ddd, 1H, J_3,4a=8.3, J_3,4b=6.7, H-3), 2.44

(ddd, 1H, J_4a,4b=11.8, H-4a), 2.24 (ddd, 1H, H-4b),

1.56, 1.27 (each s, each 3H, CMe₂), and 0.06 (s, 9H,

SiMe₃); ¹³C NMR (75.5 MHz, CDCl₃) l 137.5, 137.3,

130.0, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7 (2Ph),

112.2 (CMe₂), 104.1 (C-1%), 79.9 (C-4%)), 79.4 (C-3%),

76.5 (C-2%), 71.5 (O-CH₂Ph), 67.4 (C-5), 64.9 (N-

CH₂Ph), 61.1 (C-3), 35.1 (C-4), 29.5, 26.6 (CMe₂), and

−3.7 (SiMe₃).

23.1 (Me–CO–N); minor amide conformer (37.5%): H

NMR (500 MHz, CDCl₃) l 9.33 (br s, 1H, CHO),

7.35–7.14 (m, 5H, Ph), 5.49 (d, 1H, J_1,2=5.1, H-1),

5.05, 4.06 (each d, each 1H, J_gem=15.7, CH₂Ph), 4.65

(m, 1H, H-6), 4.50 (dd, 1H, J_2,3=2.4, J_3,4=7.9, H-3),

4.29 (dd, 1H, J_1,2=4.8, J_2,3=2.3, H-2), 4.01 (dd, 1H,

J_3,4=8.0, J_4,5=1.5, H-4), 3.86 (dd, 1H, J_4,5=1.2, J_5,6=

10.2, H-5), 2.92 (dd, 1H, J_7a,7b=18.1, J_6,7a=4.1, H-7a),

2.60 (dd, 1H, J_7a,7b=18.1, J_6,7b=9.0, H-7b), 2.49 (s, 3H,

Me–CꢁO), 1.42, 1.41, 1.34, and 1.32 (each s, each 3H,

2CMe₂); ¹³C NMR (125.7 MHz, CDCl₃) l 199.3

(CHO), 172.9 (N-COCH₃), 138.5, 128.9, 128.6, 127.9,

127.4, 127.3 (Ph), 109.5, 108.7 (2CMe₂), 96.7 (C-1),

71.0 (C-3), 70.7 (C-2), 70.1 (C-4), 67.8 (C-5), 52.5 (C-6),

45.3 (CH₂Ph), 44.9 (C-7), 25.1, 24.8, 24.5, 24.3

(2CMe₂), and 21.9 (Me–CO–N). Compound 9: syrup;

2034

P. Borrachero et al. / Tetrahedron: Asymmetry 13 (2002) 2025–2038

R_f0.33 (1:1 hexane:ethyl acetate); [h]²_D⁵=−48 (c 2.0,

CH₂Cl₂); IR (KBr) w_max1684 (a,b-unsaturated HCꢁO),

1385 (CMe₂), 1090, and 1071 cm⁻¹(trans H–CꢁC–H);

CO–N); minor amide conformer (37.5%): ¹H NMR

(500 MHz, CDCl₃) l 9.10 (s, 1H, CHO), 7.32–7.10 (m,

5H, Ph), 5.51 (d, 1H, J_1,2=5.2, H-1), 5.39, 3.62 (each d,

each 1H, J_gem=16.2, CH₂Ph), 4.79 (ddd, 1H, J_5,6:10.5,

¹H NMR (300 MHz, CDCl₃) l 9.59 (d, 1H, J_CHO,7

=

7.9, CHO), 6.78 (dd, 1H, J_5,6=4.4, J_6,7=15.8, H-6),

6.38 (ddd, 1H, J_5,7=1.7, J_6,7a=15.7, J_CHO,7=7.9, H-7),

5.60 (d, 1H, J_1,2=5.0, H-1), 4.67 (dd, 1H, J_2,3=2.5,

J

_6,7a=10.5, J_6,7b=2.9, H-6), 4.63 (dd, 1H, J_2,3=2.3,

_3,4=7.8, H-3), 4.33 (dd, 1H, J_1,2=5.1, J_2,3=2.4, H-2),

J

4.11 (dd, 1H, J_3,4=7.9, J_4,5=1.7, H-4), 3.84 (d, 1H,

J_4,5:0, J_5,6=9.6, H-5), 2.59 (dd, 1H, J_7a,7b=17.7,

J_6,7a=10.6, J_7a,CHO:0, H-7a), 2.38 (dd, 1H, J_7a,7b=

J_3,4=7.8, H-3), 4.56 (dd, 1H, J_4,5=1.9, J_5,6=4.1, H-5),

4.37 (dd, 1H, J_1,2=5.0, J_2,3=2.6, H-2), 4.33 (dd,

1H,J_3,4=7.8, J_4,5=2.1, H-4), 1.52, 1.42, 1.35, and 1.33

(each s, each 3H, 2CMe₂); ¹³C NMR (75.4 MHz,

CDCl₃) l 193.1 (CHO), 151.3 (C-6), 132.6 (C-7), 109.7,

108.7 (2CMe₂), 96.2 (C-1), 72.5 (C-4), 70.7 (C-3), 70.2

(C-2), 67.5 (C-5), 25.9, 25.7, 24.6, and 24.3 (2CMe₂);

HRCIMS: m/z 285.1350 (calcd for C₁₄H₂₀O₆+H:

285.1338), 283.1175 (calcd for C₁₄H₂₀O₆-H: 283.1181),

269.1039 (calcd for C₁₄H₂₀O₆–CH₃: 269.1025).

17.8, J_6,7b=3.2, J_7b,CHO:0, H-7b), 2.35 (s, 3H, Me–

CꢁO), 1.59, 1.46, 1.34, and 1.25 (each s, each 3H,

2CMe₂); ¹³C NMR (75.4 MHz, CDCl₃) l 198.2 (CHO),

172.2 (N-COCH₃), 138.8, 128.7, 128.4, 127.5, 127.1,

126.8 (Ph), 109.7, 108.5 (2CMe₂), 96.4 (C-1), 71.1 (C-3),

70.7 (C-4), 70.1 (C-2), 66.0 (C-5), 52.0 (C-6), 44.5

(CH₂Ph), 42.7 (C-7), 29.6, 26.0, 25.9, 24.6 (2CMe₂),

1

and 22.9 (Me–CO–N). The H NMR of 10 at 120°C

(300 MHz, DMSO-d₆) showed collapsed signals: l 9.35

(s, 1H, CHO), 7.35–7.21 (m, 5H, Ph), 5.48 (d, 1H,

5.6. Reaction of (3S,5R)-2-benzyl-3-(1,2:3,4-di-O-iso-

propylidene-a-

D

-galacto-pentopyranos-5-yl)-5-(trimethyl-

J

_1,2=5.0, H-1), 4.61 (dd, 1H, J_2,3=2.4, J_3,4=8.0, H-3),

4.32 (dd, 1H, J_1,2=5.1, J_2,3=2.4, H-2), 4.27 (dd, 1H,

silyl)isoxazolidine, 5b with acetyl chloride: preparation

of 6-(N-benzyl)acetamido-6,7-dideoxy-1,2:3,4-di-

J

_3,4=7.9, J_4,5=1.8, H-4), 2.72 (ddd, 1H, J_7a,7b=17.3,

_6,7a=8.7, J_7a,CHO=2.1, H-7a), 2.60 (dd, 1H, J_7a,7b=

O-isopropylidene-

L

-glycero-a-

D

-galacto-octodialdo-

1,5-pyranose, 10 and (E)-6,7-didehydro-6,7-dideoxy-

17.3, J_6,7b=4.4, J_7b,CHO=1.6, H-7b), 2.07 (s, 3H, Me–

CꢁO), 1.49, 1.41 (each s, each 3H), and 1.31 (s, 6H),

2CMe₂. Compound 9 was identiﬁed with that obtained

from 5a (identical ¹H and ¹³C NMR spectra,

respectively).

1,2:3,4-di-O-isopropylidene-a- -galacto-octodialdo-

1,5-pyranose, 9

D

A suspension of 5b (0.094 g, 0.20 mmol) and sodium

hydrogen carbonate (0.058 g) in freshly distilled tetra-

hydrofuran (2.5 mL) was cooled at 0°C and treated

with acetyl chloride (0.21 mL, 0.30 mmol) under argon.

The mixture was maintained at 0°C for 45 min (TLC

monitoring, 6:1 and 1:1 hexane:ethyl acetate), and the

reaction was quenched by adding saturated aqueous

sodium hydrogen carbonate until neutral pH. The mix-

ture was extracted with ether (3×15 mL), and the

combined ethereal layers were dried (MgSO₄) and con-

centrated to give a crude product (0.075 mg), puriﬁca-

tion of which was achieved by column chromatography

(6:11:1 gradient, hexane:ethyl acetate), to afford

unreacted 5b (34 mg, indicating 64% conversion), com-

pound 10 (26 mg, 30%, corresponding to 47% yield

from converted substrate), and compound 9 (3 mg,

ꢀ5%, corresponding to ꢀ8% from converted sub-

strate). Compound 10: syrup; R_f0.29 (1:1 hexane:ethyl

acetate); [h]_D²⁶=−38 (c 1.3, CH₂Cl₂); IR (KBr) w_max1734

(aldehyde CꢁO), 1653 (amide CꢁO), and 1381 cm⁻¹

(CMe₂); HRCIMS: m/z 434.2179 (calcd for

C₂₃H₃₁NO₇+H: 434.2179); major amide conformer

5.7. Reaction of (3R,5R)-2-benzyl-3-(3-O-benzyl-1,2-O-

isopropylidene-a- -xylo-tetrofuranos-4-yl)-5-(trimethyl-

D

silyl)isoxazolidine, 6c with acetyl chloride: preparation

of 5-(N-benzyl)acetamido-5,6-dideoxy-3-O-benzyl-1,2-

O-isopropylidene-

D

-glycero-a- -xylo-heptodialdo-1,4-

D

furanose, 11 and (E)-5,6-didehydro-5,6-dideoxy-3-

O-benzyl-1,2-O-isopropylidene-a- -xylo-heptodialdo-

1,4-furanose, 12

D

A suspension of 6c (0.386 g, 0.80 mmol) and sodium

hydrogen carbonate (0.223 g) in freshly distilled tetra-

hydrofuran (9.3 mL) was cooled at 0°C and treated

with acetyl chloride (0.85 mL, 1.20 mmol) under argon.

The mixture was maintained at 0°C for 4.5 h (TLC

monitoring, 6:1 and 1:1 hexane:ethyl acetate), and the

reaction was quenched by adding saturated aqueous

sodium hydrogen carbonate until neutral pH. The mix-

ture was extracted with ether (3×25 mL), and the

combined ethereal layers were dried (MgSO₄) and con-

centrated to give a crude product (0.426 g), fractiona-

tion of which was achieved by column chromatography

(6:1 hexane:ethyl acetate); ﬁrst eluted unreacted 6c

(0.139 g, indicating 64% conversion). Second eluted

compound 12 (0.027 g, 11%, corresponding to 17%

yield from converted substrate), identiﬁed (NMR spec-

tra) with the a,b-unsaturated aldehyde obtained from

6a (see next paragraph). Third eluted compound 11

(0.164 g, 45%, corresponding to 71% yield from con-

verted substrate). Last eluted a residual fraction (0.076

g) using pure ethyl acetate as the eluent. Compound 11

was an oil; R_f0.50 (1:1 hexane:ethyl acetate); [h]²_D²=−29

(c 0.53, CH₂Cl₂); IR (KBr) w_max1723 (aldehyde CꢁO),

1640 (amide CꢁO), and 1410 cm⁻¹(CMe₂); CIMS: m/z

454 (88, [M+H]⁺); 150 (75 [PhCH₂NHCOCH₃+H]⁺);

1

(62.5%): H NMR (500 MHz, CDCl₃) l 9.37 (br s, 1H,

CHO), 7.35–7.12 (m, 5H, Ph), 5.48 (d, 1H, J_1,2=5.0,

H-1), 4.68, 4.48 (each d, each 1H, J_gem=17.0, CH₂Ph),

4.62 (m, 1H, H-5), 4.57 (dd, 1H, J_2,3=2.3, J_3,4=7.9,

H-3), 4.33 (dd, 1H, J_1,2=4.9, J_2,3=2.3, H-2), 4.32 (m,

1H, H-6), 4.18 (dd, 1H, J_3,4=7.9, J_4,5=1.4, H-4), 2.89

(br m, 1H, H-7a), 2.67 (ddd, 1H, J_7a,7b=16.8, J_6,7b

=

5.2, J_7b,CHO=2.4, H-7b), 2.08 (s, 3H, Me–CꢁO), 1.51,

1.42, 1.32, and 1.28 (each s, each 3H, 2CMe₂); ¹³C

NMR (75.4 MHz, CDCl₃) l 200.4 (CHO), 173.2 (N-

COCH₃), 137.3, 128.7, 128.4, 127.5, 127.1, 126.8 (Ph),

109.4, 108.9 (2CMe₂), 96.3 (C-1), 71.0 (C-3), 70.9 (C-4),

70.4 (C-2), 67.2 (C-5), 67.2 (C-6), 52.0 (CH₂Ph), 43.6

(C-7), 25.9, 25.7, 24.9, 24.3 (2CMe₂), and 22.9 (Me–

P. Borrachero et al. / Tetrahedron: Asymmetry 13 (2002) 2025–2038

2035

107 (168, [PhCH₂NH₂]⁺); 91 [C₇H₇]⁺); 59 (100 [CH₃-

COCH₃+H]⁺); HRCIMS: m/z 454.2233 (calcd for

C₂₆H₃₁NO₆+H: 454.2230); major amide conformer

hydrogen carbonate (0.072 g) in freshly distilled tetra-

hydrofuran (3 mL) was cooled at 0°C and treated with

acetyl chloride (0.30 mL, 0.42 mmol) under argon. The

mixture was maintained at 0°C for 1 h (TLC monitoring,

6:1 and 1:1 hexane:ethyl acetate), and the reaction was

quenched by adding saturated aqueous sodium hydro-

gen carbonate until neutral pH. The mixture was

extracted with ether (4×25 mL), and the combined

ethereal layers were dried (MgSO₄) and concentrated to

give a crude product (0.100 g). Column chromatography

of 0.094 g of this crude material, successively eluting

with 3:1, 1:1, and 1:3 hexane:ethyl acetate, afforded

unreacted 6a (40 mg, indicating 57% of conversion), the

a,b-unsaturated aldehyde 12 (19 mg, ꢀ26%, corre-

sponding to 45% yield from converted substrate), and a

compound (12 mg, ꢀ11%, corresponding to ꢀ19% yield

from converted substrate) that proved to be identical

with 11 (respectively identical ¹H and ¹³C NMR spectra).

Compound 12 was an oil; R_f0.52 (3:1 hexane:ethyl

acetate); [h]_D²³=−34 (c 0.89, CH₂Cl₂); IR (KBr) w_max1620

(a,b-unsaturated HCꢁO), 1383 (CMe₂), 1092, and 1026

1

(57%): H NMR (500 MHz, CDCl₃) l 9.52 (dd, 1H,

J_CHO,6a=1.6, J_CHO,6b=2.9, CHO), 7.38–7.05 (m, 10H,

2Ph), 5.86 (d, 1H, J_1,2=3.5, H-1), 5.10 (br m, 1H, H-5),

4.66, 4.43 [or 4.59, 4.37] (each d, each 1H, J_gem=11.6 [for

both], O-CH₂Ph), 4.58 (overlapped dd, 1H, J_3,4=3.3,

J

_4,5=5.5, H-4), 4.55 (d, 1H, J_2,3:0, H-2), 4.49 (d, 1H,

_gem=17.5, one of the geminal N-CH₂Ph; the signal of

the other is overlapped), 3.90 (d, 1H, H-3), 3.00 (ddd,

1H, J_6a,6b=16.8, J_5,6a=4.6, H-6a), 2.68 (ddd, 1H, J_5,6b

=

8.1, H-6b), 2.05 (s, 3H, Me–CꢁO), 1.27, and 1.26 (each

s, each 3H, CMe₂); ¹³C NMR (125.7 MHz, CDCl₃) l

194.8 (CHO), 166.2 (N-COCH₃), 131.4, 131.2, 123.1,

122.9, 122.8, 122.7, 122.4, 122.3, 122.1, 120.5 (2Ph),

105.9 (CMe₂), 99.0 (C-1), 75.9 (C-3), 75.6 (C-2), 75.4

(C-4), 66.0 (O-CH₂Ph), 45.7 (N-CH₂Ph), 44.7 (C-5), 39.0

(C-6), 20.5, 20.3 (CMe₂), and 16.8 (Me–CO–N); minor

amide conformer (43%): ¹H NMR (500 MHz, CDCl₃) l

9.44 (br s, 1H, CHO), 7.38–7.05 (m, 10H, 2Ph), 5.85 (d,

1H, J_1,2=3.6, H-1), 4.80 (br m, 1H, H-5), 4.59, 4.37 [or

4.66, 4.43] (each d, each 1H, J_gem=11.6 [for both],

O-CH₂Ph), 4.49 (d, 1H, J_2,3:0, H-2), 4.49 (d, 1H,

1

cm⁻¹(trans H–CꢁC–H); H NMR (300 MHz, CDCl₃) l

9.57 (d, 1H, J_CHO,6=7.8, CHO), 7.54–7.24 (m, 5H, Ph),

6.75 (dd, 1H, J_5,6=15.8, J_4,5=5.1, H-5), 6.38 (ddd, 1H,

J_4,6=1.6, H-6), 6.02 (d, 1H, J_1,2=3.8, H-1), 4.89 (ddd,

J

_gem=17.5, one of the geminal N-CH₂Ph; the signal of

the other is overlapped), 4.17 (dd, 1H, J_4,5=6.8, H-4),

3.49 (d, 1H, J_3,4=3.1, H-3), 2.93 (dd, 1H, J_6a,6b=18.0,

1H, J_3,4=3.4, H-4), 4.68 (d, 1H, J_2,3=0, H-2), 4.67, 4.47

(each d, each 1H, J_gem=12.1, CH₂Ph), 4.04 (dd, 1H,

H-3), 1.50, and 1.34 (each s, each 3H, CMe₂); ¹³C NMR

(75.5 MHz, CDCl₃) l 193.0 (CHO), 150.1 (C-6), 136.9

(ipso-C of Ph), 133.4 (C-5), 128.5, 128.2, 128.0 (Ph),

112.1, (CMe₂), 105.1 (C-1), 83.7 (C-3), 83.1 (C-2), 79.4

(C-4), 72.2 (CH₂Ph), 26.8, and 26.2 (CMe₂); HRCIMS:

m/z 304.1338 (calcd for C₁₇H₂₀O₅: 304.1311), 289.1083

(calcd for C₁₇H₂₀O₅–CH₃: 289.1076).

J

_5,6a=4.2, J_CHO,6a:0, H-6a), 2.77 (ddd, 1H, J_5,6b=8.8,

_CHO,6b=1.2, H-6b), 2.20 (s, 3H, Me–CꢁO), 1.40, and

1.27 (each s, each 3H, CMe₂); ¹³C NMR (125.7 MHz,

CDCl₃) l 193.4 (CHO), 166.3 (N-COCH₃), 131.1, 130.7,

123.1, 122.8, 122.6, 122.4, 122.3, 122.1, 121.8, 121.7,

121.4, 120.5 (2Ph), 105.9 (CMe₂), 98.9 (C-1), 76.8 (C-3),

75.7 (C-2), 74.2 (C-4), 66.0 (O-CH₂Ph), 45.7 (N-CH₂Ph),

45.4 (C-5), 39.1 (C-6), 20.9, 20.8 (CMe₂), and 16.2

(Me–CO–N). The NMR spectra at 110 or 90°C in

5.9. Reaction of the 2:1 mixture of (3S,5R)- and

1

DMSO-d₆showed collapsed signals: H NMR at 110°C

(3S,5S)-2-benzyl-3-(3-O-benzyl-1,2-O-isopropylidene-a-

(300 MHz) l 9.49 (dd, 1H, J_CHO,6a=2.0, J_CHO,6b=2.0,

CHO), 7.36–7.20 (m, 10H, 2Ph), 5.80 (d, 1H, J_1,2=3.8,

H-1), 4.76 (dd, 1H, J_5,6a=5.4, J_5,6b=7.3, H-5), 4.64, 4.46

(each d, each 1H, J_gem=11.6, O-CH₂Ph), 4.63 (over-

D

-xylo-tetrofuranos-4-yl)-5-(trimethylsilyl)isoxazolidine,

6b and 6d with acetyl chloride: preparation of 5-(N-

benzyl)acetamido-5,6-dideoxy-3-O-benzyl-1,2-O-iso-

propylidene-

13 and (E)-5,6-didehydro-5,6-dideoxy-3-O-benzyl-1,2-

O-isopropylidene-a- -xylo-heptodialdo-1,4-furanose, 12

L

-glycero-a- -xylo-heptodialdo-1,4-furanose,

D

lapped, 1H,, H-4), 4.63, 4.42 (each d, each 1H, J_gem

=

16.2, N-CH₂Ph), 2.83 (ddd, 1H, J_6a,6b=16.7, J_5,6a=5.4,

H-6a), 2.68 (ddd, 1H, J_5,6b=7.7, H-6b), 2.03 (s, 3H,

Me–CꢁO), 1.30, and 1.24 (each s, each 3H, CMe₂); the

following signals are best observed at 90°C: 4.63 (d, 1H,

J_2,3:0, H-2), 3.75 (br s, 1H, H-3); ¹³C NMR at 90°C

(75.5 MHz, DMSO-d₆) l 199.9 (CHO), 170.7 (N-

COCH₃), 137.1, 127.9, 127.8, 127.4, 126.6 (Ph), 110.6

(CMe₂), 104.0 (C-1), 81.2 (C-3), 81.0 (C-4), 70.8 (C-2),

50.8 (C-5), 50.8 (O-CH₂Ph), 44.4 (N-CH₂Ph), 44.4 (C-6),

26.2, 25.9 (CMe₂), and 21.6 (Me–CO–N).

D

A suspension of the 2:1 mixture 6b/6d (0.087 g, 0.18

mmol) and sodium hydrogen carbonate (0.050 g) in

freshly distilled tetrahydrofuran (2 mL) was cooled at

0°C and treated with acetyl chloride (0.21 mL, 0.30

mmol) under argon. The mixture was maintained at 0°C

for 3 h (TLC monitoring, 6:1 and 1:1 hexane:ethyl

acetate), and the reaction was quenched by adding

saturated aqueous sodium hydrogen carbonate until

neutral pH. The mixture was extracted with ether (3×20

mL), and the combined ethereal layers were dried

(MgSO₄) and concentrated to give a crude product

(0.080 g). A major part of this (0.072 g) was subjected

to column chromatography (3:1 and 1:1 hexane:ethyl

acetate, successively); ﬁrst eluted a 4:1 mixture of unre-

acted starting material (0.046 g, indicating 53% of

conversion) and the a,b-unsaturated aldehyde 12 (19%,

corresponding to 35% yield from converted substrate);

second eluted a unique 5-acetamido compound 13 (22

mg, 30%, corresponding to 57% yield from converted

5.8. Reaction of (3R,5R)-2-benzyl-3-(3-O-benzyl-1,2-O-

isopropylidene-a- -xylo-tetrofuranos-4-yl)-5-(trimethyl-

D

silyl)isoxazolidine, 6a with acetyl chloride: preparation

of 5-(N-benzyl)acetamido-5,6-dideoxy-3-O-benzyl-1,2-

O-isopropylidene-

D

-glycero-a- -xylo-heptodialdo-

D

1,4-furanose, 11 and (E)-5,6-didehydro-5,6-dideoxy-

3-O-benzyl-1,2-O-isopropylidene-a- -xylo-heptodialdo-

1,4-furanose, 12

D

A suspension of 6a (0.127 g, 0.26 mmol) and sodium

2036

P. Borrachero et al. / Tetrahedron: Asymmetry 13 (2002) 2025–2038

substrate), different from 11 described in the above two

paragraphs; 13 was an oil; R_f0.32 (1:1 hexane:ethyl

acetate); [h]_D²⁰=−35 (c 0.85, CH₂Cl₂); IR (KBr) w_max

1723 (aldehyde CꢁO), 1642 (amide CꢁO), and 1412

cm⁻¹(CMe₂); HRCIMS: m/z 454.2219 (calcd for

C₂₆H₃₁NO₆+H: 454.2230); major amide conformer

hydrogen carbonate (0.028 g) in freshly distilled tetra-

hydrofuran (1.2 mL) was cooled at 0°C and treated

with acetyl chloride (0.11 mL, 0.16 mmol) under argon.

The mixture was maintained at 0°C for 2 h (TLC

monitoring, 6:1 and 1:1 hexane:ethyl acetate), and the

reaction was quenched by adding saturated aqueous

sodium hydrogen carbonate until neutral pH. The mix-

ture was extracted with ether (3×10 mL), and the

combined ethereal layers were dried (MgSO₄) and con-

centrated to give a crude product (0.028 g), puriﬁcation

of which was achieved by preparative TLC (1:1 hex-

ane:ethyl acetate) to afford three fractions; that of R_f

0.69 was the a,b-unsaturated aldehyde 15 (0.011 g,

36%) identical with that obtained from 7a (see below);

a second fraction (0.010 g, R_f0.51) showed no sugar

1

(56%): H NMR (300 MHz, CDCl₃) l 9.24 (dd, 1H,

J_CHO,6a:J_CHO,6b:2.5, CHO), 7.34–7.13 (m, 10H, 2Ph),

5.92 (d, 1H, J_1,2=3.8, H-1), 5.00, 4.03 (each d, each 1H,

J

_gem=16.2, O-CH₂Ph), 4.7–4.6 (overlapped m, 1H, H-

5), 4.7–4.6 (overlapped m, 1H, H-4), 4.62 (overlapped

d, 1H, J_2,3:0, H-2), 4.62, 4.30 (each d, each 1H,

J

_gem=11.6, N-CH₂Ph), 3.79 (d, 1H, J_3,4=2.8, H-3), 2.74

(ddd, 1H, J_6a,6b=16.3, J_5,6a=7.1, H-6a), 2.21 (ddd, 1H,

J

_5,6b=4.7, H-6b), 2.10 (s, 3H, Me–CꢁO), 1.42, and 1.31

(each s, each 3H, CMe₂); ¹³C NMR (75.5 MHz, CDCl₃)

l 199.6 (CHO), 172.0 (N-COCH₃), 137.0, 136.6, 128.6,

128.5, 128.4, 128.3, 128.2, 128.1, 127.8, 127.5, 127.0,

126.9 (2Ph), 111.8 (CMe₂), 104.6 (C-1), 81.5 (C-4), 80.9

(C-3), 78.6 (C-2), 70.9 (O-CH₂Ph), 50.8 (C-5), 44.2

(N-CH₂Ph), 44.0 (C-6), 29.5, 26.6 (CMe₂), and 23.0

proton signal in its H NMR spectrum, and the third

1

fraction was 14 (0.006 g, 13%); HRCIMS: m/z 454.2238

(calcd for C₂₆H₃₁NO₆+H: 454.2230); major amide con-

1

former (68%): H NMR (300 MHz, CDCl₃) l 9.50 (br

s, 1H, J_CHO,6a:J_CHO,6b:0, CHO), 7.43–7.11 (m, 10H,

2Ph), 5.65 (d, 1H, J_1,2=3.7, H-1), 5.36 (m, 1H, H-5),

4.77, 4.53 (each d, each 1H, J_gem=11.5, O-CH₂Ph),

4.52, 4.06 (each d, each 1H, J_gem=16.8, N-CH₂Ph), 4.49

1

(Me–CO–N); minor amide conformer (44%): H NMR

(300 MHz, CDCl₃) l 9.01 (br s, 1H, CHO), 7.34–7.13

(m, 10H, 2Ph), 5.90 (d, 1H, J_1,2=3.7, H-1), 5.00, 4.03

(each d, each 1H, J_gem=16.2, O-CH₂Ph), 4.90 (ddd, 1H,

J_5,6a:J_4,5:10.3, J_5,6b=2.9, H-5), 4.71, 4.32 (each d,

each 1H, J_gem=12.1, N-CH₂Ph), 4.66 (d, 1H, J_2,3:0,

H-2), 4.11 (dd, 1H, J_3,4=3.1, H-4), 3.70 (d, 1H, H-3),

2.48 (ddd, 1H, J_6a,6b=17.7, J_CHO,6a=1.1, H-6a), 2.41 (s,

3H, Me–CꢁO), 1.66 (dd, 1H, H-6b), 1.39, and 1.32

(each s, each 3H, CMe₂); ¹³C NMR (75.5 MHz, CDCl₃)

l 197.6 (CHO), 173.0 (N-COCH₃), 138.4, 136.0, 128.6,

128.5, 128.4, 128.3, 128.2, 128.1, 127.8, 127.5, 127.0,

126.7 (2Ph), 111.6 (CMe₂), 104.5 (C-1), 81.6 (C-2), 79.8

(C-3), 78.0 (C-4), 71.0 (O-CH₂Ph), 52.0 (N-CH₂Ph),

50.8 (C-5), 42.4 (C-6), 26.2, 26.0 (CMe₂), and 22.1

(Me–CO–N). The NMR spectra at 90°C in DMSO-d₆

(dd, 1H, J_2,3=4.1, H-2), 4.13 (dd, 1H, J_3,4=8.9, J_4,5

6.3, H-4), 3.29 (dd, 1H, H-3), 2.57 (dd, 1H, J_6a,6b=17.0,

_5,6a=4.9, H-6a), 2.48 (ddd, 1H, J_5,6b=8.0, J_6b,CHO

=

J

=

2.3, H-6b), 2.03 (s, 3H, Me–CꢁO), and 1.26 (s, 6H,

CMe₂); ¹³C NMR (75.5 MHz, CDCl₃) l 199.9 (CHO),

172.6 (N-COCH₃), 137.5, 137.4, 129.7, 128.8, 128.4,

128.3, 127.3, 127.1, 127.0, 126.8, 126.7, 125.9 (2Ph),

113.1 (CMe₂), 103.9 (C-1), 80.3 (C-3), 77.9 (C-4), 76.2

(C-2), 72.2 (O-CH₂Ph), 50.5 (C-5), 49.4 (N-CH₂Ph),

43.8 (C-6), 31.9 (Me–CO–N), 26.6, and 26.4 (CMe₂);

1

minor amide conformer (32%): H NMR (300 MHz,

CDCl₃) l 9.14 (s, 1H, J_CHO,6a:J_CHO,6b:0, CHO),

7.43–7.11 (m, 10H, 2Ph), 5.72 (d, 1H, J_1,2=3.5, H-1),

4.81, 4.57 (each d, each 1H, J_gem=11.6, O-CH₂Ph), 4.62

(m, 1H, H-5), 4.52, 4.06 (each d, each 1H, J_gem=16.8,

N-CH₂Ph), 4.51 (overlapped, 1H, H-2), 4.15 (dd, 1H,

1

showed collapsed signals: H NMR (300 MHz) l 9.34

(dd, 1H, J_CHO,6a=1.6, J_CHO,6b=2.1, CHO), 7.34–7.24

(m, 10H, 2Ph), 5.85 (d, 1H, J_1,2=3.8, H-1), 4.80 (dd,

J

_3,4=9.5, J_4,5=3.1, H-4), 3.41 (dd, 1H, J_2,3=4.2, H-3),

1H, J_5,6a:J_4,5=9.6, J_5,6b=3.9, H-5), 4.74 (d, 1H, J_2,3

:

2.74 (dd, 1H, J_6a,6b=18.2, J_5,6a=9.7, H-6a), 2.32 (m,

1H, H-6b), 1.93 (s, 3H, Me–CꢁO), 1.37, and 1.29 (each

s, each 3H, CMe₂); ¹³C NMR (75.5 MHz, CDCl₃) l

198.8 (CHO), 169.8 (N-COCH₃), 138.7, 138.2, 129.1,

128.7, 128.6, 128.5, 128.4, 128.2, 127.9, 125.9 (2Ph),

113.4 (CMe₂), 104.3 (C-1), 80.6 (C-4), 78.8 (C-3), 76.7

(C-2), 72.1 (O-CH₂Ph), 52.8 (C-5), 49.4 (N-CH₂Ph),

43.5 (C-6), 32.8 (Me–CO–N), 26.7, and 26.5 (CMe₂).

0, H-2), 4.67, 4.45 (each d, each 1H, J_gem=11.7, O-

CH₂Ph), 4.57, 4.35 (each d, each 1H, J_gem=16.0,

N-CH₂Ph), 4.25 (m, 1H, H-4), 3.89 (d, 1H, J_3,4=3.2,

H-3), 2.71 (overlapped with the water signal, 1H, H-

6a), 2.68 (ddd, 1H, J_6a,6b=16.8, H-6b), 2.08 (s, 3H,

Me–CꢁO), 1.32, and 1.27 (each s, each 3H, CMe₂); ¹³C

NMR (75.5 MHz, CDCl₃) l 184.5 (CHO), 172.5 (N-

COCH₃), 142.6, 142.4, 133.3, 132.9, 132.8, 132.2 (2Ph),

125.0 (CMe₂), 109.1 (C-1), 86.2 (C-2), 85.4 (C-3), 82.8

(C-4), 75.6 (O-CH₂Ph), 55.5 (N-CH₂Ph), 55.5 (C-5),

47.2 (C-6), 30.9, 30.6 (CMe₂), and 26.5 (Me–CO–N).

5.11. Reaction of (3R,5S)-2-benzyl-3-(3-O-benzyl-1,2-

O-isopropylidene-a- -ribo-tetrofuranos-4-yl)-5-(trimethyl-

D

silyl)isoxazolidine 7a with acetyl chloride: preparation

of 5-(N-benzyl)acetamido-5,6-dideoxy-3-O-benzyl-1,2-

5.10. Reaction of (3R,5R)-2-benzyl-3-(3-O-benzyl-1,2-

O-isopropylidene-

D

-glycero-a- -ribo-heptodialdo-1,4-

D

O-isopropylidene-a-

D

-ribo-tetrofuranos-4-yl)-5-(trimethyl-

furanose, 14 and (E)-5,6-didehydro-5,6-dideoxy-3-

silyl)isoxazolidine, 7c with acetyl chloride: preparation

O-benzyl-1,2-O-isopropylidene-a- -ribo-heptodialdo-

1,4-furanose, 15

D

of 5-(N-benzyl)acetamido-5,6-dideoxy-3-O-benzyl-1,2-

O-isopropylidene-

D

-glycero-a- -ribo-heptodialdo-1,4-

D

furanose, 14 and (E)-5,6-didehydro-5,6-dideoxy-3-

A suspension of 7a (0.171 g, 0.354 mmol) and sodium

hydrogen carbonate (0.099 g) in freshly distilled tetra-

hydrofuran (4.2 mL) was cooled at 0°C and treated

with acetyl chloride (0.38 mL, 0.54 mmol) under argon.

The mixture was maintained at 0°C for 2 h (TLC

O-benzyl-1,2-O-isopropylidene-a- -ribo-heptodialdo-

1,4-furanose, 15

D

A suspension of 7c (0.048 g, 0.10 mmol) and sodium

P. Borrachero et al. / Tetrahedron: Asymmetry 13 (2002) 2025–2038

2037

CH₂Cl₂); IR (KBr) w_max1723 (aldehyde CꢁO), 1642

(amide CꢁO), and 1410 cm⁻¹(CMe₂); HRCIMS: m/z

454.2230 (calcd for C₂₆H₃₁NO₆+H: 454.2230); ﬁrst

amide conformer (51%): ¹H NMR (300 MHz, CDCl₃) l

9.49 (br s, 1H, J_CHO,6a:J_CHO,6b:0, CHO), 7.52–7.10

(m, 10H, 2Ph), 5.46 (d, 1H, J_1,2=3.6, H-1), 4.97, 4.30

(each d, each 1H, J_gem=15.8, O-CH₂Ph), 4.70, 4.40

(each d, each 1H, J_gem=10.9, N-CH₂Ph), 4.69 (over-

lapped m, 1H, H-5), 4.46 (dd, 1H, J_2,3=3.9, H-2), 4.27

(overlapped, 1H, H-4), 3.59 (dd, 1H, J_3,4=8.3, H-3),

2.94 (dd, 1H, J_6a,6b=17.7, J_5,6a=6.1, H-6a), 2.65 (dd,

1H, J_5,6b=6.5, H-6b), 2.10 (s, 3H, Me–CꢁO), 1.51, and

1.47 (each s, each 3H, CMe₂); ¹³C NMR (75.5 MHz,

CDCl₃) l 199.1 (CHO), 171.0 (N-COCH₃), 138.5,

136.5, 128.3, 128.2, 127.9, 127.2, 126.6 (2Ph), 113.0

(CMe₂), 103.4 (C-1), 79.4 (C-3), 78.8 (C-4), 77.0 (C-2),

71.8 (O-CH₂Ph), 51.3 (C-5), 45.5 (N-CH₂Ph), 44.0

(C-6), 21.9 (Me–CO–N), and 20.9 (CMe₂); second

amide conformer (49%): ¹H NMR (300 MHz, CDCl₃) l

9.22 (s, 1H, J_CHO,6a:J_CHO,6b:0, CHO), 7.52–7.10 (m,

10H, 2Ph), 5.61 (d, 1H, J_1,2=3.7, H-1), 5.05 (m, 1H,

H-5), 4.97, 4.30 (each d, each 1H, J_gem=15.8, O-

CH₂Ph), 4.69, 4.40 (each d, each 1H, J_gem=11.3, N-

monitoring, 6:1 and 1:1 hexane:ethyl acetate), and the

reaction was quenched by adding saturated aqueous

sodium hydrogen carbonate until neutral pH. The mix-

ture was extracted with ether (3×15 mL), and the

combined ethereal layers were dried (MgSO₄) and con-

centrated to give a crude product (0.120 g), puriﬁcation

of which was achieved by column chromatography (3:1

hexane:ethyl acetate). First eluted the a,b-unsaturated

aldehyde 15 (0.041 g, 38%); oil, R_f0.38 (3:1 hex-

ane:ethyl acetate); [h]²_D⁰=+54.5 (c 0.4, CH₂Cl₂); IR

(KBr) w_max1690 (a,b-unsaturated HCꢁO), 1381 (CMe₂),

1

1092, and 1022 cm⁻¹(trans H–CꢁC–H); H NMR (300

MHz, CDCl₃) l 9.47 (d, 1H, J_CHO,6=7.8, CHO), 7.36–

7.34 (m, 5H, Ph), 6.68 (dd, 1H, J_5,6=15.8, J_4,5=4.5,

H-5), 6.35 (ddd, 1H, J_4,6=1.6, H-6), 5.80 (d, 1H, J_1,2

=

3.7, H-1), 4.79, 4.55 (each d, each 1H, J_gem=12.0,

CH₂Ph), 4.71 (dddd, 1H, J_3,4=3.4, J_2,4=0.5, H-4), 4.63

(ddd, 1H, J_2,3=4.2, H-2), 3.56 (dd, 1H, H-3), 1.62, and

1.38 (each s, each 3H, CMe₂); ¹³C NMR (75.5 MHz,

CDCl₃) l 192.9 (CHO), 151.7 (C-5), 136.8 (ipso-C of

Ph), 132.0 (C-6), 128.4, 128.2, 128.1 (Ph), 113.3,

(CMe₂), 103.9 (C-1), 81.8 (C-3), 77.2 (C-2), 76.6 (C-4),

72.5 (CH₂Ph), 26.6, and 26.3 (CMe₂); HRCIMS: m/z

304.1297 (calcd for C₁₇H₂₀O₅: 304.1311), 289.1077

(calcd for C₁₇H₂₀O₅–CH₃: 289.1076).

CH₂Ph), 4.58 (dd, 1H,

J_2,3=3.9, H-2), 4.05

(overlapped, 1H, H-4), 3.56 (dd, 1H, J_3,4=8.3, H-3),

2.89 (dd, 1H, J_6a,6b=18.3, J_5,6a=8.3, H-6a), 2.64 (dd,

1H, J_5,6b=4.4, H-6b), 2.34 (s, 3H, Me–CꢁO), 1.33, and

1.30 (each s, each 3H, CMe₂); ¹³C NMR (75.5 MHz,

CDCl₃) l 198.1 (CHO), 171.0 (N-COCH₃), 137.3,

137.0, 128.6, 128.4, 128.3, 128.2, 127.1, 126.2 (2Ph),

112.9 (CMe₂), 103.4 (C-1), 79.4 (C-3), 78.1 (C-4), 76.7

(C-2), 71.8 (O-CH₂Ph), 52.5 (C-5), 45.5 (N-CH₂Ph),

44.4 (C-6), 22.4 (Me–CO–N), and 14.0 (CMe₂). The

Second eluted was a mixture which was resolved by

preparative TLC (1:1 hexane:ethyl acetate) in three

fractions; that of R_f0.43 (0.022 g) and that of R_f:0

1

(0.024 g) showed no sugar proton signal in their H

NMR spectra; the second fraction (R_f0.13) was the

amino sugar 14 (0.011 g, 7%); oil, identical (¹H NMR)

with that obtained from 7c.

NMR spectra at 80°C in DMSO-d₆showed collapsed

1

signals: H NMR (300 MHz) l 9.43 (s, 1H, J_CHO,6a

:

5.12. Reaction of the mixture of (3S,5R)- and (3S,5S)-

J_CHO,6b:0, CHO), 7.35–7.18 (m, 10H, 2Ph), 5.60 (d,

1H, J_1,2=3.6, H-1), 4.70 (dd, 1H, J_2,3=4.1, H-2), 4.61,

4.44 (each d, each 1H, J_gem=11.3, O-CH₂Ph), 4.53

(overlapped m, 1H, H-5), 4.53 (br s, 1H, N-CH₂Ph),

4.03 (m, 1H, H-4), 3.71 (dd, 1H, J_3,4=8.6, H-3), 3.00

(overlapped with the water signal, 1H, H-6a), 2.80

(ddd, 1H, J_6a,6b=17.3, J_5,6b=5.7, H-6b), 2.07 (s, 3H,

Me–CꢁO), 1.36, and 1.28 (each s, each 3H, CMe₂); ¹³C

NMR (75.5 MHz, CDCl₃) l 205.7 (CHO), 176.2 (N-

COCH₃), 144.1, 143.4, 133.5, 133.3, 133.0, 132.9, 131.9,

131.4 (2Ph), 117.2 (CMe₂), 108.4 (C-1), 83.8 (C-3), 82.6

(C-4), 81.5 (C-2), 75.7 (O-CH₂Ph), 54.2 (C-5), 49.1

(N-CH₂Ph), 44.5 (C-6), 35.2 (Me–CO–N), 31.5 and

30.7 (CMe₂).

2-benzyl-3-(3-O-benzyl-1,2-O-isopropylidene-a- -ribo-

D

tetrofuranos-4-yl)-5-(trimethylsilyl)isoxazolidine (7b+7d)

with acetyl chloride: preparation of 5-(N-benzyl)-

acetamido-5,6-dideoxy-3-O-benzyl-1,2-O-isopropylidene-

L

-glycero-a-

5,6-didehydro-5,6-dideoxy-3-O-benzyl-1,2-O-isopropylide

ne-a- -ribo-heptodialdo-1,4-furanose 15

D

-ribo-heptodialdo-1,4-furanose 16 and (E)-

D

A suspension of the mixture of 7b and 7d (0.095 g,

0.200 mmol) and sodium hydrogen carbonate (0.055 g)

in freshly distilled tetrahydrofuran (2.4 mL) was cooled

at 0°C and treated with acetyl chloride (0.22 mL, 0.31

mmol) under argon. The mixture was maintained at

0°C for 2 h (TLC monitoring, 6:1 and 1:1 hexane:ethyl

acetate), and the reaction was quenched by adding

saturated aqueous sodium hydrogen carbonate until

neutral pH. The mixture was extracted with ether (3×15

mL), and the combined ethereal layers were dried

(MgSO₄) and concentrated to give a crude product

(0.082 g), puriﬁcation of which was achieved by column

chromatography (3:1 and 1:1 hexane:ethyl acetate).

First eluted unreacted (7b+7d) (0.018 g, indicating 81%

of conversion). Second eluted the a,b-unsaturated alde-

hyde 15 (0.021 g, ꢀ35%, corresponding to 42% yield

from converted substrate). Last eluted 16 (0.042 g, 46%,

corresponding to 57% from converted substrate); oil, R_f

0.36 (1:1 hexane:ethyl acetate); [h]²_D²=+33 (c 0.4,

5.13. Crystallographic analysis of compound 5a^†

Single crystals of the compound were in the form of

colourless prisms with well shaped faces. The crystal

^†Crystallographic data (excluding structure factors) for this structure

have been deposited with the Cambridge Crystallographic Data Cen-

tre as supplementary publication number CCDC 185112. Copies of

the data can be obtained, free of charge, on application to CCDC, 12

Union Road, Cambridge CB2 1EZ, UK [fax: +44(0)-1223-336033 or

e-mail: deposit@ccdc.cam.ac.uk].

2038

P. Borrachero et al. / Tetrahedron: Asymmetry 13 (2002) 2025–2038

used had approximate dimensions 0.32×0.32×0.60 mm

and belonged to the triclinic system with systematic

absences consistent with the space group P1. Unit-cell

parameters and crystal orientation matrix, determined

on a CAD4 Enraf–Nonius four-circle automated,

graphite-monochromated, diffractometer from the

least-squares treatment of the setting angles of 25 inde-

pendent reﬂections within the range 3<q<13°, were

tigacio´n, Ministerio de Ciencia y Tecnolog´ıa of Spain

(grant No. BQU2000-1155), and the Direccio´n General

de Universidades e Investigacio´n, Consejer´ıa de Educa-

cio´n y Ciencia of Andalusia (FQM 142), for ﬁnancial

support.

,

a=5.823(2), b=12.793(1), and c=18.891(1) A, h=

References

3

,

103.11(1), i=98.83(1), k=103.13(2)°, V=1303.2(5) A ,

D

_calcd=1.182 g cm⁻³for Z=1, F(000)=500 and the

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,

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w=1/[|²(F_o)+(0.111.2P)²+0.0741P] where P=(F_o+

2

2F_c)/3 for 577 variables, (D/|)_max=0.009 and S=1.04.

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−3

,

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We are grateful to the Direccio´n General de Ensen˜anza

Superior, Ministerio de Educacio´n y Cultura of Spain

(grant No. PB98-1126), the Direccio´n General de Inves-

Article Doi

Higher glycosamino acid precursors: C7 and C8 aminodialdoses via regio- and stereoselective [3+2] cycloaddition of vinyl trimethylsilane to C-glycosyl nitrones

DOI: 10.1016/S0957-4166(02)00543-8

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