Rearrangement reactions in the fluorination of 3-deoxy-3-C-methyl-3- nitro-hexopyranosides (and hexo-1-thiopyranosides) of the D- and L-series by the DAST reagent

Article abstract of DOI:10.1016/S0957-4166(00)00252-4

Fluorination of diverse 3-deoxy-3-C-methyl-3-nitro-hexopyranosides and hexo-1-thiopyranosides of the D- and L-series by the DAST reagent was studied in order to establish, on this 3-branched-chain sugar domain, the influence of the stereochemical relationship of the substituents at positions 1 and 2, as well as the protection of the HO-4, on the kinds of rearrangement reaction promoted by this fluorinating agent. Three classes of pyranosidic substrate were employed: (a) 1,2-trans configured, irrespective of whether HO-4 is protected or not; (b) 4-O-protected 1,2-cis configured; and (c) 4-O- unprotected 1,2-cis configured. They were prepared starting from simple glycosides through routes involving a Baer reaction and subsequent transformations by known methodology. All the substrates of class a essayed underwent, on treatment with DAST at room or higher temperatures, a rearrangement involving a 1,2-shift to give both the anomeric 2-inverted pyranosyl fluorides (or, for the 1-thioglycosides, only the α fluoride). Substrates of class b led, through a mechanism similar to that proposed for transformations of related substrates, to ring-contracted 2,5-anhydro-1- fluoro-1-O-methyl- (or 1-deoxy-1-phenylthio-)hexitol derivatives (sometimes as 1-epimers), which are precursors of 2,5-anhydro-aldehydo-sugars. Substrates of class c led to 4,5-anhydro-1-fluoro-1-O-methylalditol derivatives in all cases, together with a ring-contracted 5-fluoro- hexofuranoside in only one case; a rationalisation for their formation is proposed. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(00)00252-4

Tetrahedron: Asymmetry 11 (2000) 2927±2946
Rearrangement reactions in the ¯uorination of 3-deoxy-3-C-
methyl-3-nitro-hexopyranosides (and hexo-1-thiopyranosides)
of the d- and l-series by the DAST reagent
Pastora Borrachero, Francisca Cabrera-Escribano,* Ana T. Carmona
and Manuel Gomez-Guillen
Â
Departamento de Quõmica Organica `Profesor Garcõa Gonzalez', Facultad de Quõmica, Universidad de Sevilla,
Â
Â
Â
Apartado de Correos No. 553, E-41071 Sevilla, Spain
Â
Received 17 May 2000; accepted 29 June 2000
Abstract
Fluorination of diverse 3-deoxy-3-C-methyl-3-nitro-hexopyranosides and hexo-1-thiopyranosides of the
d- and l-series by the DAST reagent was studied in order to establish, on this 3-branched-chain sugar
domain, the in¯uence of the stereochemical relationship of the substituents at positions 1 and 2, as well as
the protection of the HO-4, on the kinds of rearrangement reaction promoted by this ¯uorinating agent.
Three classes of pyranosidic substrate were employed: (a) 1,2-trans con®gured, irrespective of whether HO-4
is protected or not; (b) 4-O-protected 1,2-cis con®gured; and (c) 4-O-unprotected 1,2-cis con®gured. They
were prepared starting from simple glycosides through routes involving a Baer reaction and subsequent
transformations by known methodology. All the substrates of class a essayed underwent, on treatment
with DAST at room or higher temperatures, a rearrangement involving a 1,2-shift to give both the
anomeric 2-inverted pyranosyl ¯uorides (or, for the 1-thioglycosides, only the a ¯uoride). Substrates of
class b led, through a mechanism similar to that proposed for transformations of related substrates, to
ring-contracted 2,5-anhydro-1-¯uoro-1-O-methyl- (or 1-deoxy-1-phenylthio-)hexitol derivatives (some-
times as 1-epimers), which are precursors of 2,5-anhydro-aldehydo-sugars. Substrates of class c led to 4,5-
anhydro-1-¯uoro-1-O-methylalditol derivatives in all cases, together with a ring-contracted 5-¯uoro-hex-
ofuranoside in only one case; a rationalisation for their formation is proposed. # 2000 Elsevier Science
Ltd. All rights reserved.
1. Introduction
Of the known ¯uorinating agents of alcohols, diethylaminosulphur tri¯uoride (DAST) has
become considered one of the most ecient and useful under very mild conditions. Thus, it
compares favourably1 with hydrogen ¯uoride, sulphur tetra¯uoride, phenylsulphur tri¯uoride,
selenium tetra¯uoride, ¯uorophosphoranes, and others. The interest in ¯uoro sugars has
* Corresponding author. Tel: +34 95 4557150; fax: +34 95 4624960; e-mail: fcabrera@cica.es
0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00252-4

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P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
increased in the last two decades,2 5 at least in part due to the observation that the presence of a
¯uorine atom at certain positions of the sugar moiety of glycosides6 and nucleosides reinforces
the glycosidic bond, consequently enhancing the therapeutic e€ect of pharmacologically active
substrates.7,8 Fluorination with DAST occurs with inversion of con®guration (SN2 mechanism);
however, when the reaction is somewhat hindered, and an electron-rich group is at a vicinal position,
the product with retained con®guration and products showing migration of the neighbouring group
may be obtained.9,10 This kind of rearrangement requires the 1,2-trans relationship of the
hydroxyl group and the neighbouring group, and it has been proposed11,12 that it occurs through
a cyclic onium ion intermediate. In a short communication,13 we have reported on three di€erent
kinds of rearrangement reaction observed in the ¯uorination of methyl 6-deoxy-3-C-methyl-3-
nitro-a-l-hexopyranosides by DAST under mild conditions: (i) for a 4-O-protected 1,2-trans
con®gured substrate, the kind of rearrangement agreed with that cited above; (ii) when the 1,2-cis
isomer was used as substrate, another kind of rearrangementÐinvolving ring contractionÐwas
observed, similar to those found for related substrates;14 17 and (iii) ®nally, a 2,4-O-unprotected
1,2-cis substrate gave a mixture of a 5-¯uoro-hexofuranoside and a 4,5-anhydro-1-¯uoro-1-O-
methylalditol. For the third type of rearrangement, we have also suggested13 a possible bicyclic
oxonium ion as intermediate, the attack of which by the ¯uoride at C-5 or at C-2 might account
for the formation of the two products, respectively. Additional examples of the ®rst type of
rearrangement have also been encountered18 in the ¯uorination of a 2,4,6-unprotected phenyl
3-C-methyl-3-nitro-1-thio-b-d-glucopyranoside and its b-l-enantiomer by DAST at low
temperature (^35ꢀC!rt); however, the same substrates underwent no rearrangement, but only
¯uorination at C-6, if the temperature was maintained below ^20ꢀC. A more detailed study on the
in¯uence of the substrate structure and ¯uorination conditions on the stereochemical course of
the reaction and on the scope of each kind of rearrangement was undertaken, and we report here the
results found for diverse 3-deoxy-3-C-methyl-3-nitro-hexopyranosides (and hexo-1-thiopyranosides)
of the d- and l-series as substrates.
2. Results and discussion
The 3-C-methyl-3-nitro-pyranosidic substrates can be classi®ed in three groups according to
their structural characteristics: (a) substrates having the relative 1,2-trans con®guration, regardless
of whether they are 4-O-protected or unprotected; (b) 4-O-protected 1,2-cis con®gured substrates;
and (c) 4-O-unprotected 1,2-cis con®gured substrates.
We have prepared some of the substrates starting from methyl a-l-rhamnopyranoside by a
route (Scheme 1) which involves a Baer reaction with nitroethane to give 1 (class c), selective 2-O-
pivaloylation of which, followed by 4-O-methylation, a€orded 2;19 ®nally, the crystalline epimers 3
(class b) and 4 (class a) were obtained as we had previously reported,13 that is, by selective deprotection
of the O-2 position of compound 2 following the method of Van Boeckel and Van Boom.20
Scheme 1. (i) (1) Bu4N+ HO^/H2O, N2, rt; (2) IRA-120 (H+) resin

P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
2929
Another route, also involving a dialdehyde±nitroethane cyclisation, but starting from methyl a-
d-glucopyranoside, a€orded a di€erent set of substrates for our studies. From the crystalline 1:1
mixture of 5 and its diastereomer 6 obtained in this reaction,18 diverse sugar derivatives of the
d- and l-series became separately available. Benzylidenation of this mixture led to the 4,6-O-
protected derivatives 7 (class b) and 8 (class a), which could be separated by column
chromatography, thus opening access to pure 5 (a-d) (class c) and 6 (b-l) (class a) themselves by
deprotection (Scheme 2).
Scheme 2. (i) PhCH(OMe)2/TsOH (DMF); (ii) TsOH/MeOH±dioxane
Furthermore, application of the method of Hanessian and Guindon21 for preparing phenyl
1-thioglycosides to each of the pure compounds 7 and 8 led to 4:1 b:a anomeric mixtures of
branched-chain phenyl 1-thioglycosides (9+10) and (11+12), respectively, the major components
(9 and 11) being isolated as pure 2,4,6-O-unprotected 1-thioglucopyranosides by preparative
column chromatography, as we had described.18 Apart from that, each of the foregoing anomeric
mixtures (9+10) and (11+12) was treated with benzaldehyde dimethylacetal to give the respective
anomeric mixture of phenyl 4,6-O-benzylidene-1-thioglucopyranosides (13+14) and (15+16),
separation of which, in each case, was performed by preparative thin-layer chromatography;
thus, the pure b-anomers of the d-series 13 and l-series 15 (both of class a) were obtained in
higher practical yields than their respective a-anomers 14 and 16 (both of class b), although the
yield of formation was higher for the a-anomers (Scheme 3).
Lastly, treatment of the same 1:1 crystalline mixture of 5 and 6 with tert-butyl-diphenyl-
chlorosilane a€orded, after column chromatography, good yields of the 6-O-silylated-4-O-
unprotected methyl a-d-glucopyranoside 17 (class c) and its b-l-isomer (18, class a) (Scheme 4).
Fluorination of substrates belonging to the class (a 4, 6, 8, 9, 11, 13, 15 and 18) with DAST,
under conditions allowing the temperature to rise at least to the ambient, led to rearranged
pyranosyl ¯uorides 19±32 (Scheme 5); thus, the a-l-manno con®gured glycoside 4 gave rise13 to
the 1.3:1 mixture of the b-l- and a-l-gluco con®gured pyranosyl ¯uorides (19 and 20, global yield
58%). A b:a mixture (1.4:1) of the 6-¯uoro-glycosyl ¯uorides 21 and 22 (global yield 37%) was
obtained from 6, now accompanied by a non-rearranged methyl 4,6-dideoxy-4,6-di¯uoro-
pyranoside (33, 30%), but the 4,6-O-benzylidene derivative 8 a€orded only the epimeric 1.2:1 a:b
mixture 23/24 (42% from converted substrate). From each of the enantiomeric phenyl 1-thio-b-d-
and b-l-glucopyranoside derivatives 9 and 11, two rearranged a-manno-con®gured ¯uorides were
obtained, as previously described,18 the former having an additional ¯uorine atom at position 6

2930
P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
Scheme 3. (i) PhCH(OMe)2/TsOH (DMF) and thin-layer chromatography
Scheme 4. (i) TBDPSCl/Py±DMAP and column chromatography
(25 and 27, in 60% and 58% yields, respectively) and the latter lacking it [26 (10%) and 28
(15%)]; the corresponding 4,6-O-benzylidene derivatives 13 and 15, having the expected behaviour,
gave only the respective 2-phenylthio-a-d- and a-l-mannopyranosyl ¯uorides 29 and 30 in 97 and
96% yields, respectively, from converted substrate. Finally, a derivative of 6, silylated at O-6 18,
underwent partial O-desilylation as well as the same type of rearrangement without ¯uorination
at position 4, to give only 25% of a 2.7:1 b:a mixture of l-manno-con®gured pyranosyl ¯uorides
(31 and 32).
For the class b substrates (3, 7, 14, and 16), the reaction, as carried out at room temperature or
in boiling dichloromethane, a€orded epimeric mixtures of 2,5-anhydro-1-¯uoro-1-O-methyl- (or
1-deoxy-1-phenylthio-)hexitol derivatives [(34+35) from 3 (global yield 70%) and 36 from 7 (95%
from converted substrate)] or only one of the epimers (37 from 14, 38 from 16) (Scheme 6); it is

P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
2931
Scheme 5. (i) DAST (5 mol-equiv.)/CH2Cl2, re¯ux (2 h); (ii) DAST (5 mol-equiv.)/CH2Cl2, 0ꢀC!rt (1 h). Isolated;
a
bfrom converted substrate
noteworthy that compound 36 slowly decomposed in chloroformic solution, whereas the
enantiomeric 1-phenylthio derivatives 37 and 38 were obtained in low yields (16 and 48% from
converted substrate, respectively) both facts indicate that the stability of these products is lower
than that of the respective pyranosic isomers (23+24), 29, and 30, a feature also observed14 for
related pairs of compounds.

2932
P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
Scheme 6. (i) DAST (5 mol-equiv.)/CH2Cl2; re¯ux (2 h); (ii) NMR sample in CDCl3: shaking with D2O/conc. HCl (1
drop), rt (1 week); (iii) DAST (3.5 mol-equiv.)/diglyme, rt (16 h); (iv) DAST (5 mol-equiv.)/CH2Cl2, 0ꢀC (0.5 h)!re¯ux
(1±3 h)
Of the substrates of class c (1, 5, and 17) used for ¯uorination with DAST (Scheme 7) under
conditions similar to those cited last, 1 gave rise,13 after column chromatography, to a methyl
5-deoxy-5-¯uoro-hexofuranoside (39, 46%) next to a 4,5-anhydro-1-¯uoro-1-O-methylhexitol
(40, 23%), both retaining the HO-2 free; substrate 5 a€orded a non-rearranged methyl 4,6-
Scheme 7. (i) DAST (5 mol-equiv.)/CH2Cl2, re¯ux (2 h); (ii) DAST (3.5 mol-equiv.)/diglyme, rt (2 h). aIsolated; bfrom
converted substrate

P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
2933
di¯uoro-hexopyranoside (41, 33%) next to a 4,5-anhydro-1,6-di¯uoro-1-O-methylhexitol (42,
26%) of the same kind as 40; with substrate 17, the reaction led to only one product 43 also
having an oxirane ring involving C-4 and C-5, as well as a ¯uorine atom at C-1 of the
hexitol chainÐthe poor yield (15%, corresponding to 18% from converted substrate) in this
case was attributed to extensive 6-O-deprotection, as deduced from observations during the
chromatographic control.
Structural assignment of the new products was made on the basis of analytical and spectral
1
data (MS, IR, H and 13C NMR). For the pyranosic new compounds (every novel substrateÐ3,
4, and 13±18Ðas well as a number of ¯uoro derivativesÐ19±24, 29±33 and 41), the con®gura-
tional assignments were easier than for the remaining products. Thus, the 1,2-cis a-l-glycoside 3
was easily distinguished from the 1,2-trans epimer 4 by comparing, in their 1H NMR spectra, the
ꢀ values for the H-2 [higher in compound 3 (H-2 axial) than in compound 4 (H-2 equatorial) as a
consequence of the presence of the equatorial nitro group at the neighbouring position], and the
H-1/H-2 coupling constant values (4.5 Hz for the equatorial/axial-relationship in 3 and 1.5 Hz for
the diequatorial one in 4). The b-con®guration was assigned to both the enantiomeric phenyl
1-thioglucosides 13 and 15, since they are 4,6-O-protected derivatives of b-con®gured described
compounds,18 and was con®rmed by the high value of the coupling constant J1,2 (9.9 Hz),
indicative of the trans-diaxial relationship between H-1 and H-2; the J1,2 value (6.4 Hz) for the
respective isomers 14 and 16 is consistent with the a-con®guration. Similarly, the coupling
between protons of the same kind in compounds 17 and 18 gives rise to splitting values (4.5 Hz
for 17 and 9.6 Hz for 18) that are in agreement with the a- and b-con®gurations, respectively.
With regard to the new ¯uoro pyranosic derivatives, the two components 19 and 20 of the
1
mixture obtained from 4 showed separate signals in the H and 13C NMR spectra, in which the
¯uorine couplings, particularly with H-1 (53.1 and 54.0 Hz, respectively) and H-2 (12.7 and 25.6
Hz), and with C-1 (213.0 and 232.4 Hz) and C-2 (24.0 and 23.2 Hz), agreed with well-established
antecedents22 and revealed that the ¯uorine atom is at position 1, that is, a rearrangement had
taken place; the b-con®guration was assigned to 19 and the a one to 20 on the basis of the higher
value of 3JC-3,F (11.4 Hz) for the former than for the latter (3.3 Hz), in agreement22 with the anti
and the gauche disposition of C-3 and F around the C-2/C-1 bond, respectively. This was
con®rmed by di€erential NOE experiments, which evidenced contacts between H-1 and the Me-3
protons in compound 19, but not in compound 20. In a similar manner, the presence of a ¯uorine
atom at the anomeric position was evident from the deshielding e€ect on H-1 and C-1 and the
¯uorine couplings observed in the NMR spectra of compounds 21±32; however, 33Ðobtained
together with 21 and 22 from 6Ðlacks the ¯uorine atom at that position and bears it at position 4
instead, as indicated by the high values of ꢀ for H-4 (4.96 ppm) and for C-4 (89.5 ppm), as well as
1
by the coupling constants 2J4,F (47.7 Hz) and JC-4,F (189.2 Hz), while H-1 (ꢀ 4.52 ppm) and C-1
(ꢀ 102.2 ppm) are not deshielded, the H-1/H-2 constant coupling (7.9 Hz) is compatible with a
1,2-trans-diaxial relationship, JH-1,F has a very low value (1.4 Hz) indicative of a long-range
coupling (®ve bonds), and the signal of C-1 appears as a singlet. The apparent absence of
coupling between H-4 and H-5 in 33 agrees with an axial rather than an equatorial disposition of
the ¯uorine atom, corroborated by the singlet appearance of the C-2 signal (3JC-2,F-4ꢁ0 Hz),
indicative of a gauche disposition around the C-2/C-3 bond.23 Apart from that, these three com-
pounds (21, 22, and 33) have another ¯uorine atom at the primary position 6, easily evidenced by
the ¯uorine couplings observed in the two H-6 and the C-6 signals. Assignment of b-con®guration
to 21 was made on the basis of 1D NOESY experiments, which showed enhancement of the H-1
and H-5 signals on irradiating the Me-3 singlet; hence, compound 22 must be the a-isomer.

2934
P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
Similarly, the mixture obtained in the ¯uorination of 8 proved to consist of the rearranged 4,6-O-
benzylidene glycosyl ¯uorides 23 and 24, to which the respective a- and b-con®gurations were
assigned again on the basis of the values observed for 3JC-3,F in the 13C NMR spectra (0.9 and 2.8
Hz, respectively). The enantiomeric 2-deoxy-2-phenylthio-d- and l-mannopyranosyl ¯uorides 29
and 30 showed no apparent coupling between H-1 and H-2, incompatible with an H/H trans-
diaxial relationship, and also no splitting of the C-3 signal, in agreement with a gauche disposition
of this carbon atom and the ¯uorine atom around the C-1/C-2 bond. The b- and the a-con®gura-
tions, respectively, were assigned to the anomeric rearranged glycosyl ¯uorides 31 and 32,
obtained from the methyl 6-O-tert-butyldiphenylsilyl-glycoside 18, again by application of the
same general rule (3JC-3,F values: 6.4 and ꢁ0 Hz).
As previously reported,13 the assignment of a structure of 2,5-anhydro-1-¯uoro-1-O-methyl-
alditol derivative for 34 and 35, the components of the 3:1 mixture formed in the ¯uorination of 3
(class b), was based on the quantitative formation of a unique aldehydo-sugar (44; ꢀ for CHO 9.65
ppm, J1,2 1.2 Hz) in the hydrolysis of the mixture in CDCl3 with aqueous HCl, their respective 1R
and 1S con®gurations at C-1 being tentatively assigned by considering the values of J2,F (6.8 and
10.4 Hz) and JC-2,F (30.6 and 24.9 Hz), in agreement with antecedents14 for the H-2/F-1 gauche
and anti and the F-1/ring O anti and gauche relationships observed in related compounds.
Furthermore, 34 and 35 showed all the same NOE contacts (1D NOESY), except that shown by
the latter between Me-3 and MeO-1, absent in the NOESY spectrum of the former. Spectral
patterns similar to those shown by these compounds were found for the epimeric mixture 36, and
the enantiomeric compounds 37 and 38; however, the values of the H-2/F-1 and C-2/F-1 coupling
constants for these products were not conclusive for con®gurational assignments at C-1.
One of the products obtained from each substrate (1, 5, and 17) of class c had a structure of
4,5-anhydro-1-¯uoro-1-O-methyl-alditol derivative (40, 42, and the sole product 43, respectively),
as deduced from the shielding e€ect observed over H-4 (ꢀ 3.28±3.61 ppm) and H-5 (ꢀ 3.06±3.46
ppm), as atoms bonded to an oxirane ring, and from the low value of J4,5 (2.0±2.1 Hz), indicative
of a trans relationship with respect to the ring plane. Moreover, the presence of a preferential
conformer around the C-3/C-4 bond in the chloroformic solution of 40, as has been formulated,
was established from the Me-3/H-5 contact observed in its 1D NOESY spectrum. The other
product obtained from 1 was a methyl 5-¯uoro-b-d-altrofuranoside (39), as evidenced by the
down®eld shift of the H-5 signal exerted by the ¯uorine atom at C-5, the R con®guration being
assigned to this centre on the basis of: (i) the high value of J4,5 (9.3 Hz), which shows the anti
arrangement of these protons; (ii) the value of J4,F (5.9 Hz), indicative of a gauche orientation
between H-4 and F; and (iii) the value of JC-4,F (30.1 Hz), which suggests14 the anti disposition of
the ¯uorine and the ring oxygen. In the ¯uorination of 5, the oxirane derivative 42 obtained was
accompanied by the non-rearranged 4,6-di¯uoro-glycopyranoside 41, NMR of which showed
downshifting of the signals of H-4, H-6, and H-60 (ꢀ 4.99, 4.55, and 4.52 ppm, respectively), as
well as C-4 and C-6 (ꢀ 89.9 and 80.4 ppm); the apparent lack of H-4/H-5 coupling is incompatible
with a trans-diaxial disposition of these protons, thus evidencing the inverted con®guration at C-4,
as expected.
The formation of the hexopyranosyl ¯uorides 19±32 is considered an additional case of the 1,2-
shift cited above9,10 and can be explained in terms of a classical neighbouring group e€ect involving
a cyclic onium ion intermediate, similarly to those proposed for related compounds,12,13 here
formulated as applied to the formation of (19+20) (Scheme 8). The ring contraction that occurs in
the formation of the 2,5-anhydro-1-¯uoroalditols 34±38 is explained similarly to those described
for other ring contractions undergone by hexopyranosides,14 17 application of which to the

P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
2935
formation of (34+35) being represented in Scheme 9. A possible rationalisation for the formation
of the 5-¯uorofuranoside 39 and the 4,5-anhydro-1-¯uoroalditol 40 is a ring-oxygen participation
in pushing out the leaving group from C-4 to form a cyclic oxonium ion as intermediate, which
subsequently may be opened by attack of the ¯uoride on either C-5 or C-1 (Scheme 10). The
absence of products similar to 39 when starting from 5 and 17 may be attributed, for 5, to the
presence of the free HO group at C-6, thus allowing the normal ¯uorination at the positions 4
and 6 to give 41, or the preferred opening of the cyclic oxonium ion by attack of the ¯uoride on
C-1 rather than on C-5 (having a ¯uoromethyl substituent) to give 42, whereas for 17, the bulky
group at O-6 may hinder the attack, not only on C-4 of the ®rst intermediate, but also on C-5 of
the cyclic cation, the formation of 43 apparently being the only possibility. The steric hindrance
of the ¯uoromethyl substituent at C-5 of the cyclic oxonium ion formed from 5 could
alternatively explain the diculty in attacking this position.
Scheme 8.
Scheme 9.
Scheme 10.
3. Conclusion
The foregoing results can be summarised as follows: each class of glycoside used as substrate
(a, b, c, as de®ned above) ®ts into one of the three types of rearrangement mechanism previously
cited,13 corroborating that the course of the reaction depends on the 1,2-stereochemical pattern of
the substrate and, in the case of the 1,2-cis relationship of the substituents, on whether the HO
group at C-4 is protected or not, in the terms expressed above. The new glycosyl ¯uorides 19±32
should behave as good glycosyl donors5 in the synthesis of glycosides, oligosaccharides and
nucleosides having 3-C-methyl-3-nitro-hexopyranosyl units; moreover, a good stereocontrol in
the formation of the glycosidic bond is to be expected for the 2-phenylthio derivatives 25±30 in a
route that, for analogues,10 leads to 2-deoxy-glycosidic products. The presence of a ¯uorine atom
at C-5 in compound 39 and at C-6 in some of the foregoing glycosyl ¯uorides is expected to
enhance the therapeutic activity of glycosides and nucleosides derived from them, as a

2936
P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
consequence of the reinforcing of the glycosidic bond. An aldehydo-sugar latent functionality is
present in the 2,5- (34±38) and 4,5-anhydro-1-¯uoro-1-O-methylalditols (40, 42, 43) obtained,
thus giving synthetic interest also to the last two types of rearrangement reaction described
herein.
4. Experimental
4.1. General
Hexane and ether were distilled from sodium prior to use. A commercial 40% aq. solution
of tetrabutylammonium hydroxide (Fluka) was used. TLC was performed on silica gel plates
(DC-Alufolien F254, E. Merck, or Alugram Sil G/UV254, Macherey-Nagel), and preparative TLC
on Kieselgel 60 F254 DC-Platten 105715 HR; detection of compounds was accomplished with UV
light (254 nm) and by charring with H2SO4. Silica gel 60 (E. Merck, 230±400 mesh) was used for
column chromatography. Solutions were concentrated under diminished pressure at <40ꢀC.
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 an FTIR Bomem Michelson MB-120 spectro-
1
photometer. 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 spectrometer; chemical shifts (ꢀ) are
expressed in ppm from TMS; coupling constants (J), in hertz. Assignments were con®rmed by
decoupling, homonuclear 2D COSY correlated spectra, heteronuclear 2D correlated (HETCOR)
spectra, heteronuclear 1D single quantum coherence (HSQC) spectra, di€erential NOE and 1D
NOESY experiments. EI mass spectra (70 eV) were measured with a Kratos MS-80RFA instru-
ment, with an ionising current of 100 mA, an accelerating voltage of 4 kV, and a resolution of
10 000 (10% valley de®nition). Fast-atom bombardment mass spectrometry (FABMS) was per-
formed on the same instrument; ions were produced by a beam of xenon atoms (6±7 keV) using a
matrix consisting of m-nitrobenzyl alcohol or thioglycerol and NaI as salt. HREIMS (70 eV) and
HRCIMS (150 eV) experiments were performed with a Micromass AutoSpecQ instrument with a
resolution of 10 000 (5% valley de®nition). HRFABMS was performed on a VG AutoSpec
spectrometer (Fisons Instruments) (30 keV).
4.2. Methyl 3,6-dideoxy-3-C-methyl-4-O-methyl-3-nitro-ꢁ-l-glucopyranoside 3 and methyl 3,6-
dideoxy-3-C-methyl-4-O-methyl-3-nitro-ꢁ-l-mannopyranoside 4
A magnetically stirred solution of methyl 3,6-dideoxy-4-O-methyl-3-C-methyl-3-nitro-2-O-
pivaloyl-a-l-glucopyranoside 219 (1.07 g, 3.37 mmol) in dioxane (20 mL) was treated with tetra-
butylammonium hydroxide (1.31 g, 5.05 mmol) in water (20 mL) under nitrogen. The mixture
was stirred at room temperature until TLC (30:1 dichloromethane:acetone) indicated that all
starting material had disappeared (1 h). After neutralisation with IRA-120 (H+) resin, the mixture
was concentrated. Column chromatography (60:1 dichloromethane:acetone) of the residue a€or-
ded pure 3 (0.48 g, 60%, Rf 0.45) and 4 (0.24 g, 30%, Rf 0.33). Compound 3: colourless crystals;
mp 99±101ꢀC; ‰ꢁŠ2D4=^17 (c 1.0, CH2Cl2); IR (KBr) ꢂmax 3428 (OH), 1541, and 1372 cm^1 (NO2);
1H NMR (500 MHz, CDCl3): ꢀ 4.75 (d, 1H, J1,2=4.5, H-1), 4.36 (dd, 1H, J2,OH=11.0, H-2), 3.68
(d, 1H, J4,5=9.7, H-4), 3.64 (dq, 1H, H-5), 3.43 (s, 3H, MeO-4), 3.37 (s, 3H, MeO-1), 2.37 (d, 1H,

P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
2937
HO-2), 1.67 (s, 3H, Me-3), and 1.34 (d, 3H, J5,6=5.9, Me-5); 13C NMR (125.7 MHz, CDCl3): ꢀ
98.5 (C-1), 95.1 (C-3), 84.8 (C-4), 72.3 (C-2), 65.6 (C-5), 61.0 (MeO-1), 55.2 (MeO-4), 17.6 (Me-5),
and 11.2 (Me-3). Anal. calcd for C9H17NO6: C, 45.95; H, 7.23; N, 5.96. Found: C, 45.81; H, 7.34;
N, 5.97. Compound 4: colourless crystals; mp 101±103ꢀC; ‰ꢁŠD24=^22 (c 1.0, CH2Cl2); IR (KBr)
1
ꢂmax 3409 (OH), 1545 and 1348 cm^1 (NO2); H NMR (500 MHz, CDCl3): ꢀ 4.67 (d, 1H,
J1,2=1.5, H-1), 4.10 (dd, 1H J2,OH=8.1, H-2), 3.94 (d, 1H, J4,5=9.7, H-4), 3.67 (dq, 1H,
J5,6=6.3, H-5), 3.62 (s, 3H, MeO-4), 3.39 (s, 3H, MeO-1), 2.43 (d, 1H, HO-2), 1.71 (s, 3H, Me-3),
and 1.41 (d, 3H, Me-5); 13C NMR (125.7 MHz, CDCl3): ꢀ 101.1 (C-1), 92.9 (C-3), 79.5 (C-4), 73.5
(C-2), 66.2 (C-5), 60.9 (MeO-4), 55.1 (MeO-1), 18.0 (Me-5), and 17.0 (Me-3). Anal. calcd for
C9H17NO6: C, 45.95; H, 7.23; N, 5.96. Found: C, 45.91; H, 7.34; N, 5.97.
4.3. Phenyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-3-nitro-1-thio-ꢃ-d-glucopyranoside 13 and
phenyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-3-nitro-1-thio-ꢁ-d-glucopyranoside 14
Benzaldehyde dimethylacetal (46 mL, 0.309 mmol) and catalytic amounts of p-toluenesulphonic
acid were added to a solution of the 4:1 mixture of phenyl 3-deoxy-3-C-methyl-3-nitro-1-thio-b-
d-glucopyranoside 9 and phenyl 3-deoxy-3-C-methyl-3-nitro-1-thio-a-d-glucopyranoside 1018
(0.065 g, 0.206 mmol) in N,N-dimethylformamide (0.5 mL). The solution was kept at room
temperature (TLC monitoring, 20:1 dichloromethane:methanol) and the methanol evolved was
from time to time evaporated under diminished pressure. It was necessary to replace the benzalde-
hyde dimethylacetal partially evaporated during the process. After neutralisation with saturated
aqueous sodium hydrogen carbonate, the reaction mixture was concentrated, the residue was
diluted with dichloromethane, and the insoluble salts were ®ltered o€. The ®ltrate was then
concentrated to a syrup, preparative TLC (3:2 hexane:ether) of which a€orded pure 13 (0.044 g,
67% from 9) and 14 (0.016 g, 98% from 10). Compound 13: ‰ꢁŠ2D4=^43.8 (c 1.0, CHCl3); HREIMS:
m/z 403.1111 (calcd for C20H21NO6S: 403.1090); 294.0945 (calcd for C20H21NO6S^SPh: 294.0978);
this product showed IR and NMR spectra identical to those of its enantiomer 15. Compound 14:
‰ꢁŠ2D2+211 (c 1.0, CHCl3); HREIMS: m/z 403.1079 (calcd for C20H21NO6S: 403.1090); 294.0985
(calcd for C20H21NO6S^SPh: 294.0978); this compound showed IR and NMR spectra identical to
those of its enantiomer 16.
4.4. Phenyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-3-nitro-1-thio-ꢃ-l-glucopyranoside 15 and
phenyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-3-nitro-1-thio-ꢁ-l-glucopyranoside 16
Benzaldehyde dimethylacetal (175 mL, 1.17 mmol) and catalytic amounts of p-toluenesulphonic
acid were added to a solution of the 4:1 mixture of phenyl 3-deoxy-3-C-methyl-3-nitro-1-thio-b-l-
glucopyranoside 11 and phenyl 3-deoxy-3-C-methyl-3-nitro-1-thio-a-l-glucopyranoside 1218
(0.245 g, 0.778 mmol) in N,N-dimethylformamide (1.5 mL). The solution was kept at room
temperature (TLC monitoring, 20:1 dichloromethane: methanol) and the methanol evolved was
from time to time evaporated under diminished pressure. It was necessary to replace the
benzaldehyde dimethylacetal partially evaporated during the process. After neutralisation with
saturated aqueous sodium hydrogen carbonate, the reaction mixture was concentrated, the
residue was diluted with dichloromethane and the insoluble salts were ®ltered o€. The ®ltrate was
then concentrated to a syrup, column chromatography (4:1 hexane:ether) of which, followed by
preparative TLC of mixed fractions, a€orded pure 15 (0.147 g, 59% from 11) and 16 (0.053 g,
85% from 12). Compound 15: syrup; Rf 0.45 (1:1 ether:hexane); ‰ꢁŠ2D3=+63 (c 1.0, CHCl3); IR

2938
P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
1
(®lm) ꢂmax 3460 (OH), 1551 and 1395 cm^1 (NO2); H NMR (300 MHz, CDCl3): ꢀ 7.57±7.34
(m, 10H, 2Ph), 5.53 (s, 1H, CH-Ph), 4.65 (d, 1H, J1,2=9.9, H-1), 4.44 (dd, 1H, J5,6=4.9,
0
J6,6 =10.5, H-6), 4.26 (d, 1H, J4,5=9.5, H-4), 4.17 (dd, 1H, J2,OH=2.6, H-2), 3.82 (dd, 1H,
0
J5,6 =10.4, H-6 ), 3.66 (ddd, 1H, H-5), 2.63 (d, 1H, HO), and 1.78 (s, 3H, Me); 13C NMR (75.6
0
MHz, CDCl3): ꢀ 136.2±125.9 (2Ph), 101.4 (CH-Ph), 92.4 (C-3), 88.0 (C-1), 80.1 (C-4), 72.3 (C-2),
68.9 (C-5), 68.7 (C-6), and 9.7 (Me); HREIMS: m/z 403.1085 (calcd for C20H21NO6S: 403.1090);
294.0953 (calcd for C20H21NO6S^SPh: 294.0978). Anal. calcd for C20H21NO6S: C, 59.54; H, 5.24;
N, 3.47. Found: C, 59.88; H, 5.24; N, 3.44. Compound 16: syrup; Rf 0.40 (1:1 ether:hexane);
‰ꢁŠ2D2=^227 (c 1.0, CHCl3); IR (®lm) ꢂmax 3468 (OH), 1545 and 1395 (NO2), and 650 cm^1 (CS);
1H NMR (300 MHz, CDCl3): ꢀ 7.52±7.35 (m, 10H, 2Ph), 5.61 (d, 1H, J1,2=6.4, H-1), 5.57 (s, 1H,
0
CH-Ph), 4.78 (brdd, 1H, J2,OH=8.6, H-2), 4.43 (dd, 1H, J5,6=5.0, J6,6 =10.5, H-6), 4.41 (d, 1H,
0
0
J4,5=9.8, H-4), 4.22 (ddd, 1H, J5,6 =9.8, H-5), 3.86 (dd, 1H, H-6 ), 2.70 (brd, 1H, HO), and 1.85
(s, 3H, Me); 13C NMR (75.6 MHz, CDCl3): ꢀ 132.1±126.0 (2Ph), 101.4 (CH-Ph), 93.0 (C-3), 91.4
(C-1), 79.7 (C-4), 72.1 (C-2), 68.7 (C-5), 62.3 (C-6), and 11.4 (Me); HREIMS: m/z 403.1073 (calcd
for C20H21NO6S: 403.1090); 294.0965 (calcd for C20H21NO6S^SPh: 294.0978). Anal. calcd for
C20H21NO6S: C, 59.54; H, 5.24; N, 3.47. Found: C, 60.02; H, 5.38; N, 3.34.
4.5. Methyl 6-O-tert-butyl-diphenylsilyl-3-deoxy-3-C-methyl-3-nitro-ꢁ-d-glucopyranoside 17 and
methyl 6-O-tert-butyl-diphenylsilyl-3-deoxy-3-C-methyl-3-nitro-ꢃ-l-glucopyranoside 18
Dry pyridine (0.4 mL) and 4-(dimethylamino)pyridine (DMAP, 0.017 g) were added to a
suspension of 1:1 mixed crystals of methyl 3-deoxy-3-C-methyl-3-nitro-a-d-glucopyranoside 5
and methyl 3-deoxy-3-C-methyl-3-nitro-b-l-glucopyranoside 618,24 (0.600 g, 2.53 mmol) in dry
dichloromethane (4 mL), and the mixture was stirred under argon. tert-Butyl-diphenyl-
chlorosilane (1.00 mL, 3.80 mmol) was added at 0ꢀC to the mixture, which was then allowed to
warm to room temperature for 48 h (TLC monitoring, 12:1 dichloromethane:methanol, or two
elutions with ether). The reaction was quenched by adding 1 M HCl until neutral pH (2 mL) and
the mixture was shaken with dichloromethane (3Â5 mL). The combined organic layers were dried
(MgSO4) and concentrated to a syrup, which was subjected to column chromatography (1:4
ether:hexane) to give, separately, 17 (0.451 g, 75%) and 18 (0.496 g, 82%). Compound 17: syrup;
Rf 0.22 (1:2 ether:hexane); ‰ꢁŠD27=+54.3 (c 1.0, CH2Cl2); IR (®lm) ꢂmax 3477 (OH), 1547 and 1391
1
(NO2), and 704 cm^1 (CSi); H NMR (500 MHz, CDCl3): ꢀ 7.7±7.4 (m, 10H, 2Ph), 4.78 (d, 1H,
0
J1,2=4.5, H-1), 4.37 (d, 1H, J4,5=9.9, H-4), 4.33 (d, 1H, H-2), 3.95 (dd, 1H, J5,6=4.7, J6,6 =11.1,
0
0
H-6), 3.92 (dd, 1H, J5,6 =4.2, H-6 ), 3.54 (m, 1H, H-5), 3.36 (s, 3H, MeO), 2.77 (br s, 1H, HO-4
or 2), 2.45 (br s, 1H, HO-2 or 4), 1.70 (s, 3H, Me-3), and 1.08 (d, 9H, CMe3); 13C NMR (125.7
MHz, CDCl3): ꢀ 135.6±127.8 (2Ph), 98.8 (C-1), 95.5 (C-3), 71.7 (C-4), 71.5 (C-2), 68.8 (C-5), 64.4
(C-6), 55.8 (MeO), 26.8 (CMe3), 19.2 (CMe3), and 11.6 (Me-3); FABMS: m/z 498 (37, [M+Na]+);
HRCIMS: m/z 476.2098 (calcd for C24H33NO7Si+H: 476.2104). Anal. calcd for C24H33NO7-
.
Si 0.5H2O: C, 59.48; H, 7.07; N, 2.89. Found: C, 59.36; H, 6.68; N, 2.75. Compound 18: colourless
crystals; mp 128±132ꢀC; Rf 0.29 (1:2 ether:hexane); ‰ꢁŠ2D7=+24.1 (c 0.8, CH2Cl2); IR (®lm) ꢂmax
3468 (OH), 1545 and 1394 (NO2), and 703 cm^1 (CSi); 1H NMR (500 MHz, CDCl3): ꢀ 7.70±7.38
(m, 10H, 2Ph), 4.41 (dd, 1H, J4,5=9.6, J4,OH=2.0, H-4), 4.24 (d, 1H, J1,2=7.9, H-1), 4.08 (d, 1H,
0
0
0
H-2), 3.95 (dd, 1H, J5,6=4.5, J6,6 =10.8, H-6), 3.92 (dd, 1H, J5,6 =5.5, H-6 ), 3.50 (s, 3H, MeO),
3.46 (ddd, 1H, H-5), 3.04 (d, 1H, HO-4), 2.39 (br s, 1H, HO-2), 1.68 (s, 3H, Me-3), and 1.06 (s,
9H, CMe3); 13C NMR (125.7 MHz, CDCl3): ꢀ 135.6±127.8 (2Ph), 101.9 (C-1), 94.3 (C-3), 73.4 (C-5),
73.3 (C-2), 73.0 (C-4), 65.0 (C-6), 57.1 (MeO), 26.8 (CMe3), 19.2 (CMe3), and 10.2 (Me-3);

P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
2939
FABMS: m/z 498 (100, [M+Na]+); HRCIMS: m/z 476.2086 (calcd for C24H33NO7Si+H:
476.2104). Anal. calcd for C24H33NO7Si: C, 60.61; H, 6.99; N, 2.94. Found: C, 60.37; H, 6.89; N,
2.89.
4.6. Reaction of DAST with the 3-C-methyl-3-nitro sugar derivatives 1, 3±8, and 13±18. General
procedure
DAST (660 mL, 5 mmol; or 462 mL, 3.5 mmol, as indicated in each case) was dropped into a
solution of the respective sugar derivative (1 mmol) in the solvent indicated in each case, cooled at
0ꢀC, under argon. After 15 min, the cooling bath was removed and the mixture was allowed to
warm to room temperature or heated to re¯ux, under stirring, until almost complete transformation
of the substrate (TLC monitoring, 2:1 or 1:1 ether:hexane). The mixture was poured onto
iced saturated aqueous sodium hydrogen carbonate (50 mL) and the aqueous layer was
extracted with dichloromethane (2Â25 mL). The combined organic layers were washed with
brine (25 mL), dried (MgSO4), and concentrated. Separation and puri®cation of the new
products were achieved by column chromatography or preparative TLC as indicated below
for each substrate.
(a) From methyl 3,6-dideoxy-3-C-methyl-4-O-methyl-3-nitro-a-l-mannopyranoside (4, 0.235
g); DAST: 660 mL; solvent: dry dichloromethane (10 mL); temperature: re¯ux for 2 h. After
column chromatography (1:2 dichloromethane:hexane), a 1.3:1 (by H NMR) syrupy mixture of
1
the two anomeric glycosyl ¯uorides 19 (b) and 20 (a) (global yield, 0.137 g, 58%) was obtained;
IR (®lm): 1553 and 1348 cm^1 (NO2); HRMS: m/z 218.1035 (calcd for C9H16FNO5^F: 218.1028),
191.1079 (calcd for C9H16FNO5^NO2: 191.1083).
4.6.1. 3,6-Dideoxy-3-C-methyl-2,4-di-O-methyl-3-nitro-ꢃ-l-glucopyranosyl ¯uoride 19
2
1H NMR (500 MHz, CDCl3): ꢀ 5.14 (dd, 1H, J1,2=7.2, J1,F=53.1, H-1), 3.92 (dd, 1H,
3J2,F=12.7, H-2), 3.67 (d, 1H, J4,5=9.6, H-4), 3.55 (dqd, 1H, J5,6=6.1, 4J5,F=0.5, H-5), 3.46 (d,
3H, 5JOMe,F=1.3, MeO-2), 3.35 (s, 3H, MeO-4), 1.58 (s, 3H, Me-3), and 1.40 (d, 3H, Me-5); NOE
contacts (di€erential NOE): Me-3, H-1, H-5; 13C NMR (125.7 MHz, CDCl3): ꢀ 118.7
1
3
2
(d, J1,F=213.0, C-1), 93.1 (d, J3,F=11.4, C-3), 85.1 (C-4), 82.4 (d, J2,F=24.0, C-2), 71.1
(d, 3J5,F=5.2, C-5), 60.7 (MeO-4), 60.6 (d, 4JOMe,F=2.1, MeO-2), 18.0 (Me-5), and 10.4 (Me-3).
4.6.2. 3,6-Dideoxy-3-C-methyl-2,4-di-O-methyl-3-nitro-ꢁ-l-glucopyranosyl ¯uoride 20
2
1H NMR (500 MHz, CDCl3): ꢀ 5.76 (dd, 1H, J1,2=3.2, J1,F=54.0, H-1), 4.05 (dd, 1H,
3J2,F=25.6, H-2), 3.84 (brdq, 1H, J4,5=10.2, J5,6=6.2, H-5), 3.65 (d, 1H, H-4), 3.42 (br s, 3H,
5
MeO-2), 3.36 (s, 3H, MeO-4), 1.69 (d, 3H, JMe,F=1.3, Me-3), and 1.36 (d, 3H, Me-5); NOE
contacts (di€erential NOE): Me-3, H-5; 13C NMR (125.7 MHz, CDCl3): ꢀ 103.2 (d, 1J1,F=232.4,
C-1), 93.3 (d, 3J3,F=3.3, C-3), 84.8 (C-4), 80.3 (d, 2J2,F=23.2, C-2), 68.1 (d, 3J5,F=1.4, C-5), 60.8
(MeO-4), 58.8 (MeO-2), 17.6 (Me-5), and 11.3 (d,4JMe,F=6.5, Me-3).
(b) From methyl 3-deoxy-3-C-methyl-3-nitro-b-l-glucopyranoside (6, 0.237 g); DAST: 660 mL;
solvent: dry dichloromethane (10 mL); temperature: re¯ux for 2 h. The reaction a€orded, after
column chromatography (1:4 ethyl acetate:hexane), two fractions; the ®rst one consisted of a
1
1.4:1 (by H NMR) syrupy mixture (0.089 g, 37%) of the two anomeric glycosyl ¯uorides 21 (b)
and 22 (a); IR (®lm): 3485 (OH), 1551 and 1354 (NO2), and 980 cm^1 (CF); HRCIMS: m/z
222.0781 (calcd for C8H13F2NO5^F: 222.0778), 210.0580 (calcd for C8H13F2NO5^OCH3:
210.0578); the other fraction was pure methyl glycoside 33 (0.071 g, 30%).

2940
P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
4.6.3. 3,6-Dideoxy-6-¯uoro-3-C-methyl-2-O-methyl-3-nitro-ꢃ-l-mannopyranosyl ¯uoride 21
2
1H NMR (500 MHz, CDCl3): ꢀ 5.26 (dd, 1H, J1,2=4.5, J1,F=64.2, H-1), 4.91 (d, 1H,
3
2
0
J4,5=7.0, H-4), 4.78 (dd, 1H, J2,F=9.1, H-2), 4.61 (ddd, 1H, J6,F=47.6, J5,6=2.7, J6,6 =10.7,
0
H-6), 4.51 (ddd, 1H, 2J6 ,F=46.6, J5,6 =3.7, H-6 ), 4.00 (dddd, 1H, J5,F=25.4, H-5), 3.59 (s, 3H,
MeO), and 1.70 (d, 3H, JMe,F=1.6, Me-3); NOE contacts (1D NOESY): Me-3, H-1, H-5; 13C
NMR (125.7 MHz, CDCl3): ꢀ 110.9 (d, J1,F=226.3, C-1), 94.9 (C-3), 82.4 (d, J5,F=20.1, C-5),
81.6 (d, J6,F=174.7, C-6), 81.4 (d, J2,F=25.1, C-2), 76.2 (d, J4,F=6.3, C-4), 57.5 (MeO), and
13.8 (Me-3).
3
0
0
5
1
2
1
2
3
4.6.4. 3,6-Dideoxy-6-¯uoro-3-C-methyl-2-O-methyl-3-nitro-ꢁ-l-mannopyranosyl ¯uoride 22
2
1H NMR (500 MHz, CDCl3): ꢀ 5.28 (dd, 1H, J1,2=4.6, J1,F=64.0, H-1), 4.92 (d, 1H,
3
J4,5=7.8, H-4), 4.76 (dd, 1H, J2,F=9.2, H-2), ꢁ4.61 (overlapped, H-6), ꢁ4.51 (overlapped, H-
0
5
6 ), 3.97 (m, 1H, H-5), 3.58 (s, 3H, MeO), and 1.74 (d, 3H, JMe,F=0.9, Me-3); 13C NMR (125.7
1
2
MHz, CDCl3): ꢀ 110.8 (d, J1,F=213.7, C-1), 94.0 (C-3), 82.2 (d, J5,F=22.6, C-5), 81.4
(d, J6,F=174.7, C-6), 81.3 (d, J2,F=21.4, C-2), 76.2 (d, J4,F=6.3, C-4), 57.4 (MeO), and 13.5
(Me-3).
1
2
3
4.6.5. Methyl 3,4,6-trideoxy-4,6-di¯uoro-3-C-methyl-3-nitro-ꢃ-l-galactopyranoside 33
Syrup; Rf 0.25 (1:2 ethyl acetate:hexane); ‰ꢁŠ2D3=+4.7 (c 0.75, CHCl3); IR (®lm) ꢂmax 3480 (OH),
1
1556 and 1352 (NO2), and 1058 cm^1 (CF); H NMR (500 MHz, CDCl3): ꢀ 4.96 (d, 1H,
2J4,F=47.7, H-4), 4.60 (2ddd, 2H, 2J6,F=46.1, H-6 and H-60), 4.52 (dd, 1H, J1,2=7.9, 5J1,F=1.4,
4
3
3
H-1), 4.35 (dd, 1H, J2,F=1.0, H-2), 4.00 (m, 1H, J5,F=27.2, J5,F=10.0, H-5), 3.61 (s, 3H,
4
MeO), and 1.72 (d, 3H, JMe,F=1.3, Me-3); 13C NMR (125.7 MHz, CDCl3) d 102.2 (C-1), 90.4
(d, 2J3,F=17.7, C-3), 89.5 (dd, 1J4,F=189.2, 3J4,F=4.9, C-4), 79.9 (dd, 1J6,F=170.9, 3J6,F=6.3, C-
2
2
6), 72.8 (C-2), 70.3 (dd, J5,F=25.0, J5,F=18.4, C-5), 57.4 (MeO), and 10.9 (Me-3); HRCIMS:
m/z 242.0842 (calcd for C8H13F2NO5+H: 242.0840), 210.0575 (calcd for C8H13F2NO5^OCH3:
210.0578).
(c) From methyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-3-nitro-b-l-glucopyranoside (8,18
0.326 g); DAST: 660 mL; solvent: dry dichloromethane (10 mL); temperature: re¯ux for 2 h. The
reaction a€orded, after preparative TLC (1:1 ether:hexane), unreacted starting material (0.148 g,
1
indicating 59% of conversion) and a 1.2:1 (by H NMR) syrupy mixture (0.081 g, 25%,
corresponding to 42% yield from converted substrate) of the two anomeric glycosyl ¯uorides 23
(a) and 24 (b); IR (®lm): 1561 and 1379 cm^1 (NO2).
4.6.6. 4,6-O-Benzylidene-3-deoxy-3-C-methyl-2-O-methyl-3-nitro-ꢁ-l-mannopyranosyl ¯uoride 23
1H NMR (500 MHz, CDCl3): ꢀ 7.48±7.36 (m, 5H, Ph), 5.60 (s, 1H, CH-Ph), 5.31 (dd, 1H,
J1,2=5.0, 2J1,F=65.0, H-1), 4.66 (dd, 1H, 3J2,F=12.5, H-2), 4.59 (dd, 1H, J5,6=4.2, J6,6 =9.8, H-6),
0
0
0
4.49 (d, 1H, J4,5=9.9, H-4), 3.98 (dd, 1H, J5,6 =9.8, H-6 ), 3.90 (ddd, 1H, H-5), 3.63 (d, 3H,
5
5JMeO,F=1.3, MeO), and 1.84 (d, 3H, JMe,F=0.7, Me-3); 13C NMR (125.7 MHz, CDCl3): ꢀ
1
3
136.1±126.3 (Ph), 110.1 (d, J1,F=222.5, C-1), 102.2 (CH-Ph), 91.7 (d, J3,F=0.9, C-3), 84.6 (C-
2
3
4), 83.0 (d, J2,F=23.4, C-2), 72.1 (d, J5,F=2.8, C-5), 71.1 (C-6), 57.3 (MeO), and 14.1
(d,4JMe,F=1.5, Me-3).
4.6.7. 4,6-O-Benzylidene-3-deoxy-3-C-methyl-2-O-methyl-3-nitro-ꢃ-l-mannopyranosyl ¯uoride 24
1H NMR (500 MHz, CDCl3): ꢀ 7.48±7.36 (m, 5H, Ph), 5.60 (s, 1H, CH-Ph), 5.35 (dd, 1H,
J1,2=4.3, 2J1,F=64.0, H-1), 4.70 (dd, 1H, 3J2,F=12.4, H-2), 4.59 (dd, 1H, J5,6=4.4, J6,6 =9.8, H-6),
0

P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
2941
0
0
4.48 (d, 1H, J4,5=9.7, H-4), 3.96 (dd, 1H, J5,6 =9.9, H-6 ), 3.88 (ddd, 1H, H-5), 3.63 (d, 3H,
5
5JMeO,F=1.3, MeO), and 1.89 (d, 3H, JMe,F=1.3, Me-3); 13C NMR (125.7 MHz, CDCl3): ꢀ
136.1±126.3 (Ph), 110.6 (d, 1J1,F=222.5, C-1), 102.2 (CH-Ph), 91.5 (d, 3J3,F=2.8, C-3), 84.5 (C-4),
82.8 (d, J2,F=26.5, C-2), 72.1 (d, J5,F=2.8, C-5), 71.1 (C-6), 57.5 (MeO), and 14.3
(d,4JMe,F=2.6, Me-3).
2
3
(d) From phenyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-3-nitro-1-thio-b-d-glucopyranoside
(13, 0.403 g); DAST: 660 mL; solvent: dry dichloromethane (10 mL); temperature: 0ꢀC (1 h) to
ambient (1 h). The reaction a€orded, after preparative TLC (1:2 ether:hexane), unreacted
starting material (0.074 g, indicating 82% of conversion) and pure compound 29 (0.324 g, 80%,
corresponding to 97% yield from converted substrate).
4.6.8. 4,6-O-Benzylidene-2,3-dideoxy-3-C-methyl-3-nitro-2-phenylthio-ꢁ-d-mannopyranosyl
¯uoride 29
Compound 29 showed physical and spectroscopic properties identical, respectively, to those of
30 [see (e), next paragraph], except for the rotatory power: ‰ꢁŠ2D5=^3.5 (c 1.1, CHCl3).
(e) From phenyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-3-nitro-1-thio-b-l-glucopyranoside
(15, 0.403 g); DAST: 660 mL; solvent: dry dichloromethane (10 mL); temperature: 0ꢀC (1 h) to
ambient (1 h). The reaction a€orded, after column chromatography (gradient 1:12 to 1:10
ether:hexane), unreacted starting material (0.048 g, indicating 88% of conversion) and pure
compound 30 (0.343 g, 85%, corresponding to 96% yield from converted substrate).
4.6.9. 4,6-O-Benzylidene-2,3-dideoxy-3-C-methyl-3-nitro-2-phenylthio-ꢁ-l-mannopyranosyl
¯uoride 30
Syrup; Rf 0.41 (1:3 ether:hexane); ‰ꢁŠ2D2=+1.3 (c 1.0, CHCl3); IR (®lm) ꢂmax 1555 and 1375
(NO2), and 1007 cm^1 (CF); 1H NMR (300 MHz, CDCl3): ꢀ 7.48±7.37 (m, 10H, 2Ph), 5.95 (d, 1H,
2
2
0
J1,F=52.3, H-1), 5.79 (s, 1H, CH-Ph), 4.59 (d, 1H, J4,5=9.7, H-4), 4.43 (dd, 1H, J6,6 =10.3,
0
3
0
J5,6=4.5, H-6), 4.09 (ddd, 1H, J5,6 =9.9, H-5), 3.93 (dd, 1H, H-6 ), 3.66 (d, 1H, J2,F=3.7, H-2),
and 2.00 (s, 3H, Me); 13C NMR (75.5 MHz, CDCl3): ꢀ 136.4±125.9 (2Ph), 108.4 (d, 1J1,F=234.8,
C-1), 101.7 (CH-Ph), 88.5 (C-3), 75.5 (C-4), 68.5 (C-6), 63.9 (C-5), 57.0 (d, 2J2,F=25.5, C-2), and
19.6 (d, JMe,F=6.2, Me); HRMS: m/z 405.1051 (calcd for C20H20FNO5S: 405.1046), 249.0925
(calcd for C20H20FNO5S^NO2^SPh^H: 249.0927). Anal. calcd for C20H20FNO5S: C, 59.25; H,
4.97; N, 3.45. Found: C, 59.32; H, 5.12; N, 3.41.
4
(f) From methyl 6-O-tert-butyldiphenylsilyl-3-deoxy-3-C-methyl-3-nitro-b-l-glucopyranoside
(18, 0.476 g); DAST: 660 mL; solvent: dry dichloromethane (10 mL); temperature: re¯ux for 2 h.
The reaction a€orded, after preparative TLC (1:1 ether:hexane), a 2.7:1 (by H NMR) syrupy
1
mixture (0.119 g, 25%) of the two anomeric glycosyl ¯uorides 31 (b) and 32 (a); IR (®lm): 3452
(OH), 1553 and 1363 (NO2), 1085 (CF), and 703 cm^1 (CSi); FABMS: m/z 500 (20, [M+Na]+);
HRFABMS: m/z 500.1879 (calcd for C24H32FNO6Si+Na: 500.1881).
4.6.10. 6-O-tert-Butyldiphenylsilyl-3-deoxy-3-C-methyl-2-O-methyl-3-nitro-ꢃ-l-mannopyranosyl
¯uoride 31
2
1H NMR (500 MHz, CDCl3): ꢀ 7.70±7.38 (m, 10H, 2Ph), 5.21 (dd, 1H, J1,2=5.4, J1,F=65.4,
3
H-1), 5.12 (d, 1H, J4,5=7.2, H-4), 4.82 (dd, 1H, J2,F=9.8, H0-2), 3.90 (dd, 1H, J5,6=3.8,
5
0
0
J6,6 =11.2, H-6), 3.84 (m, 1H, H-5), 3.79 (dd, 1H, J5,6 =2.9, H-6 ), 3.57 (d, 3H, JMeO,F=1.1,
MeO), 3.48 (br s, 1H, HO), 1.68 (d, 3H, JMe,F=0.4, Me-3), and 1.09 (s, 9H, t-Bu); 13C NMR
(125.7 MHz, CDCl3): ꢀ 135.6±127.7 (2Ph), 111.2 (d, J1,F=223.8, C-1), 93.9 (d, J3,F=6.4, C-3),
5
1
3

2942
P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
2
83.0 (C-5), 81.6 (d, J2,F=25.6, C-2), 77.4 (C-4), 63.1 (C-6), 57.2 (MeO), 26.7 (CMe3), 19.1
(CMe3), and 12.6 (Me-3).
4.6.11. 6-O-tert-Butyldiphenylsilyl-3-deoxy-3-C-methyl-2-O-methyl-3-nitro-ꢁ-l-mannopyranosyl
¯uoride 32
2
1H NMR (500 MHz, CDCl3): ꢀ 7.70±7.38 (m, 10H, 2Ph), 5.26 (dd, 1H, J1,2=5.2, J1,F=64.0,
3
H-1), 5.09 (d, 1H, J4,5=7.9, H-4), 4.80 (dd, 1H, J2,F=7.6, H0-2), 3.93 (dd, 1H, J5,6=3.7,
5
0
0
J6,6 =11.3, H-6), 3.84 (m, 1H, H-5), 3.81 (dd, 1H, J5,6 =2.8, H-6 ), 3.60 (d, 3H, JMeO,F=1.3,
MeO), 3.37 (br s, 1H, HO), 1.73 (d, 3H, JMe,F=0.9, Me-3), and 1.09 (s, 9H, t-Bu); 13C NMR
5
1
(125.7 MHz, CDCl3): ꢀ 135.6±127.7 (2Ph), 110.8 (d, J1,F=218.7, C-1), 93.5 (C-3), 82.4 (C-5),
81.2 (d, 2J2,F=29.7, C-2), 77.4 (C-4), 63.0 (C-6), 57.3 (MeO), 26.7 (CMe3), 19.1 (CMe3), and 12.7
(Me-3).
(g) From methyl 3,6-dideoxy-3-C-methyl-4-O-methyl-3-nitro-a-l-glucopyranoside (3, 0.235 g);
DAST: 660 mL; solvent: dry dichloromethane (10 mL); temperature: re¯ux for 2 h. After column
1
chromatography (1:1 dichloromethane:hexane), a 3:1 mixture of 34 and 35 (by H NMR) was
obtained as a syrup (global yield, 0.166 g, 70%) IR (®lm): 1545 and 1345 cm^1 (NO2); HRMS: m/z
218.1025 (calcd for C9H16FNO5^F: 218.1028), 206.0839 (calcd for C9H16FNO5^OCH3:
206.0828), 191.1082 (calcd for C9H16FNO5^NO2: 191.1083).
4.6.12. (1R)-2,5-Anhydro-3,6-dideoxy-1-¯uoro-3-C-methyl-1,4-di-O-methyl-3-nitro-l-mannitol 34
2
1H NMR (500 MHz, CDCl3): ꢀ 5.20 (dd, 1H, J1,2=5.9, J1,F=64.3, H-1), 4.65 (dd, 1H,
3J2,F=6.8, H-2), 4.21 (d, 1H, J4,5=7.7, H-4), 3.92 (dq, 1H, J5,6=6.3, H-5), 3.58 (d, 3H,
5
4JOMe,F=1.4, MeO-1), 3.37 (s, 3H, MeO-4), 1.71 (d, 3H, JMe,F=1.4, Me-3), and 1.42 (d, 3H,
Me-6); NOE contacts (1D NOESY): Me-6, H-4, H-2; Me-3, H-5, H-1; MeO-4, H-1; 13C NMR
(125.7 MHz, CDCl3): ꢀ 110.5 (d, 1J1,F=218.7, C-1), 93.1 (C-3), 92.2 (C-4), 81.3 (d, 2J2,F=30.6, C-2),
77.7 (C-5), 58.9 (MeO-4), 57.2 (MeO-1), 19.3 (C-6), and 12.4 (d, 4JMe,F=2.2, Me-3).
4.6.13. (1S)-2,5-Anhydro-3,6-dideoxy-1-¯uoro-3-C-methyl-1,4-di-O-methyl-3-nitro-l-mannitol 35
2
1H NMR (500 MHz, CDCl3): ꢀ 5.14 (dd, 1H, J1,2=6.3, J1,F=64.4, H-1), 4.62 (dd, 1H,
3J2,F=10.4, H-2), 4.22 (d, 1H, J4,5=7.6, H-4), 3.93 (dq, 1H, J5,6=6.2, H-5), 3.53 (d, 3H,
4JOMe,F=1.2, MeO-1), 3.36 (s, 3H, MeO-4), 1.63 (s, 3H, Me-3), and 1.43 (d, 3H, Me-6); NOE
contacts (1D NOESY): Me-6, H-4, H-2; Me-3, H-5, H-1, MeO-1; MeO-4, H-1; 13C NMR (125.7
1
3
MHz, CDCl3): ꢀ 110.8 (d, J1,F=222.7, C-1), 93.0 (d, J3,F=6.1, C-3), 92.2 (C-4), 81.6
(d, 2J2,F=24.9, C-2), 77.8 (C-5), 58.9 (MeO-4), 57.0 (MeO-1), 19.4 (C-6), and 12.1 (Me-3).
A few drops of D2O and one drop of concentrated hydrochloric acid were added to the same
solution of the 3:1 mixture of 34 and 35 in CDCl3 used for NMR spectroscopy. After a week at
1
room temperature, the H NMR spectrum of this reaction mixture showed the quantitative
transformation into 2,5-anhydro-3,6-dideoxy-4-O-methyl-3-C-methyl-3-nitro-aldehydo-l-mannose
44: 1H NMR (300 MHz, CDCl3): ꢀ 9.65 (dd, 1H, J1,2=1.2, CHO), 5.00 (m, 1H, H-2), 4.16 (d, 1H,
J4,5=6.2, H-4), 4.11 (ddq, 1H, J5,Me-6=6.2, 5J2,5=0.5, H-5), 3.46 (s, 3H, MeO), 1.65 (s, 3H, Me-3),
and 1.41 (d, 3H, Me-6); 13C NMR (75.8 MHz, CDCl3): ꢀ 198.4 (C-1), 93.1 (C-3), 92.8 (C-4), 85.3
(C-2), 79.3 (C-5), 59.1 (MeO), 19.1 (C-6), and 11.5 (Me-3).
(h) From methyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-3-nitro-a-d-glucopyranoside (718,
0.325 g); DAST: 470 mL; solvent: dry diglyme (7.9 mL); temperature: ambient (16 h). The
reaction a€orded, after preparative TLC (two elutions with 1:2 ether:hexane), unreacted starting
material (0.247 g, indicating 24% of conversion) and a 2.5:1 (by 1H NMR) mixture of epimers 36

P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
2943
(0.074 g, 23%, corresponding to 95% yield from converted substrate). Syrup; Rf 0.54 (1:2
ether:hexane); IR (®lm) ꢂmax 1548 and 1379 (NO2), and 1028 cm^1 (CF); HRMS: m/z 327.1124
(calcd for C15H18FNO6: 327.1118).
4.6.14. (1R and 1S)-2,5-Anhydro-4,6-O-benzylidene-3-deoxy-1-¯uoro-3-C-methyl-1-O-methyl-3-
nitro-d-mannitol 36
Major isomer: 1H NMR (500 MHz, CDCl3): ꢀ 7.50±7.36 (m, 5H, Ph), 5.61 (s, 1H, CH-Ph), 5.37
2
3
2
0
(dd, 1H, J1,F=64.1, J1,2=4.3, H-1), 4.72 (dd, 1H, J2,F=12.4, H-2), 4.60 (dd, 1H, J6,6 =9.5,
0
0
J5,6=4.2, H-6), 4.49 (d, 1H, J4,5=9.7, H-4), 3.98 (dd, J5,6 =9.7, H-6 ), 3.91 (ddd, 1H, H-5), 3.64
4
(d, 3H, JMeO,F=1.3, MeO), and 1.90 (d, 3H, JMe,F=1.4, Me-3); 13C NMR (125.7 MHz,
5
1
CDCl3): ꢀ 132.3±126.1 (Ph), 111.0 (d, J1,F=219.6, C-1), 110.1 (CH-Ph), 94.2 (C-3), 83.0 (C-4),
81.1 (d, 2J2,F=28.8, C-2), 65.5 (C-5), 61.5 (C-6), 57.4 (MeO), and 13.7 (d, JMe,F=10.5, Me-3).
4
1
Minor isomer: H NMR (500 MHz, CDCl3): ꢀ 7.50±7.36 (m, 5H, Ph), 5.62 (s, 1H, CH-Ph),
2
3
5.33 (dd, 1H, J1,F=65.0, J1,2=5.0, H-1), 04.67 (dd, 1H, J2,F=12.6, H-2), 4.50 (d, 1H, J4,5=9.9,
2
4
0
H-4), 3.99 (dd, J6,6 =9.8, J5,6 =9.8, H-6 ), 3.63 (d, 3H, JMeO,F=1.2, MeO), and 1.59 (s, 3H,
0
Me-3).
(i) From phenyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-3-nitro-1-thio-a-d-glucopyranoside
(14, 0.403 g); DAST: 660 mL; solvent: dry dichloromethane (10 mL); temperature: 0ꢀC (0.5 h) to
re¯ux (3 h). The reaction a€orded, after preparative TLC (1:1.5 ether:hexane), unreacted starting
material (0.169 g, indicating 58% of conversion), compound 37 (0.038 g, 9.5%, corresponding to
16% yield from converted substrate), and a more polar product (Rf ꢁ0) which was not studied.
4.6.15. (1R or 1S)-2,5-Anhydro-4,6-O-benzylidene-1,3-dideoxy-1-¯uoro-3-C-methyl-3-nitro-1-
phenylthio-d-mannitol 37
Compound 37 showed physical and spectroscopic properties identical, respectively, to those of
38 [see (j), next paragraph], except for the rotatory power: ‰ꢁŠ2D6=^92.3 (c 0.65, acetone).
(j) From phenyl 4,6-O-benzylidene-3-deoxy-3-C-methyl-3-nitro-1-thio-a-l-glucopyranoside
(16, 0.403 g); DAST: 660 mL; solvent: dry dichloromethane (10 mL); temperature: 0ꢀC (0.5 h) to
re¯ux (1 h). The reaction a€orded, after preparative TLC (1:1.5 ether:hexane), unreacted starting
material (0.118 g, indicative of 71% of conversion), compound 38 (0.139 g, 34%, corresponding to
48% yield from converted substrate), and a more polar product (0.118 g, Rf ꢁ0) which was not studied.
4.6.16. (1R or 1S)-2,5-Anhydro-4,6-O-benzylidene-1,3-dideoxy-1-¯uoro-3-C-methyl-3-nitro-1-
phenylthio-l-mannitol 38
Syrup; Rf 0.54 (1:1 ether:hexane); ‰ꢁŠD23=+84.5 (c 0.84, acetone); IR (®lm) ꢂmax 1557 and 1391
1
(NO2), and 1107 cm^1 (CF); H NMR (500 MHz, CD3COCD3): ꢀ 7.58±7.33 (m, 10H, 2Ph), 5.76
2
(s, 1H, CH-Ph), 5.75 (dd, 1H, J1,F=50.9, J1,2=8.2, H-1), 4.48 0(d, 1H, J4,5=9.2, H-4), 4.39 (dd,
2
3
0
1H, J6,6 =9.1, J5,6=4.0, H-6), 4.00±3.95 (m, 2H, H-5 and H-6 ), 3.91 (dd, 1H, J2,F=21, H-2),
and 1.87 (s, 3H, Me); 13C NMR (125.7 MHz, CD3COCD3): ꢀ 134.0±127.1 (2Ph), 110.2
1
3
(d, J1,F=212.4, C-1), 102.4 (CH-Ph), 92.5 (d, J3,F=7.6, C-3), 81.8 (C-4), 69.0 (C-6), 66.3
4
2
(d, J5,F=5.0, C-5), 59.6 (d, J2,F=25.1, C-2), and 12.8 (Me); HRMS: m/z 405.1046 (calcd for
C20H20FNO5S: 405.1046).
(k) From methyl 3,6-dideoxy-3-C-methyl-3-nitro-a-l-glucopyranoside (119, 0.221 g); DAST:
660 mL; solvent: dry dichloromethane (10 mL); temperature: re¯ux for 2 h. After column
chromatography (1:3 ether:hexane), the pure products 39 (0.102 g, 46%) and 40 (0.051 g, 23%)
were obtained.

2944
P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
4.6.17. Methyl 3,5,6-trideoxy-5-¯uoro-3-C-methyl-3-nitro-ꢃ-d-altrofuranoside 39
Syrup; Rf 0.4 (3:1 ether:hexane); ‰ꢁŠ2D2=^104 (c 1.2, CH2Cl2); IR (®lm) ꢂmax 3540 (OH), 1549,
1
5
and 1352 cm^1 (NO2); H NMR (500 MHz, CDCl3): ꢀ 4.99 (dd, 1H, J1,2=5.2, J1,F=2.9, H-1),
4.89 (dd, 1H, J2,OH=9.7, H-2), 4.62 (ddq, 1H, J4,5=9.3, J5,6=6.1, J5,F=47.4, H-5), 4.48 (dd, 1H,
3J4,F=5.9, H-4), 3.47 (s, 3H, MeO), 2.73 (d, 1H, HO), 1.76 (d, 3H, 5JMe,F=1.65, Me-3), 1.45 (dd,
3H, 3J6,F 25.2, Me-6); NOE contacts (1D NOESY): Me-3, H-5; 13C NMR (125.7 MHz, CDCl3): ꢀ
1
2
101.7 (C-1), 94.4 (C-3), 87.9 (d, J5,F=168.9, C-5), 84.3 (d, J4,F=30.1, C-4), 78.2 (C-2), 56.1
2
4
(MeO), 18.3 (d, JMe,F=21.2, C-6), and 13.2 (d, JMe,F=3.8, Me-3); FABMS: m/z 246 (100,
[M+Na]+); HRMS: m/z 192.0671 (calcd for C8H14FNO5^OCH3: 192.0672).
4.6.18. (1R or 1S)-4,5-Anhydro-3,6-dideoxy-1-¯uoro-3-C-methyl-1-O-methyl-3-nitro-l-galactitol
40
Syrup; Rf 0.6 (3:1 ether:hexane); ‰ꢁŠD22=^28.4 (c 0.90, CH2Cl2); IR (®lm) ꢂmax 3532 (OH), 1547,
1
2
and 1350 cm^1 (NO2); H NMR (500 MHz, CDCl3): ꢀ 5.31 (dd, 1H, J1,2=4.1, J1,F=64.7, H-1),
3
4
4.38 (dd, 1H, J2,F=9.0, H-2), 3.61 (d, 3H, JMeO,F=1.4 Hz, MeO), 3.28 (dd, 1H, J4,5=2.1,
5J4,F=3.3, H-4), 3.06 (dq, 1H, J5,6=5.2, H-5), 2.76 (br s, 1H, HO), 1.42 (d, 3H, 5JMe,F=1.0, Me-3),
and 1.32 (d, 3H, Me-6); NOE contacts (1D NOESY): Me-3, H-5; 13C NMR (125.7 MHz,
1
3
2
CDCl3): ꢀ 110.1 (d, J1,F=221.4, C-1), 90.9 (d, J3,F=3.0, C-3), 75.2 (d, J2,F=27.8, C-2), 58.7
(d, 4J4,F=2.0, C-4), 57.4 (MeO), 51.4 (C-5), 16.7 (C-6), and 12.9 (d, 4JMe,F=1.0, Me-3); FABMS
m/z 246 (100, [M+Na]+); HRMS: m/z 192.0674 (calcd for C8H14FNO5^OCH3: 192.0672).
(l) From methyl 3-deoxy-3-C-methyl-3-nitro-a-d-glucopyranoside (5, 0.236 g); DAST: 660 mL;
solvent: dry dichloromethane (10 mL); temperature: re¯ux for 2 h. After column chromatography
(1:3 ether:hexane), the pure products 41 (0.080 g, 33%) and 42 (0.062 g, 26%) were obtained.
4.6.19. Methyl 3,4,6-trideoxy-4,6-di¯uoro-3-C-methyl-3-nitro-ꢁ-d-galactopyranoside 41
Syrup; Rf 0.26 (1:1 ether:hexane); ‰ꢁŠ1D9=+92.4 (c 1.0, CHCl3); IR (®lm) ꢂmax 3460 (OH), 1555
1
2
and 1358 (NO2), and 1064 cm^1 (CF); H NMR (500 MHz, CDCl3): ꢀ 4.99 (d, 1H, J4,F=47.8,
2
J4,5=0, H-4), 4.91 (d, 1H, J1,2=4.5, H-1), 4.73 (d, 1H, H-2), 4.55 (ddd, 1H, J6,F=46.1,
0
2
4
0
0
0
0
J6,6 =9.5, J5,6=6.4, H-6), 4.52 (dddd, 1H, J6 ,F=46.4, J6 ,F=1.3, J5,6 =6.3, H-6 ), 4.13 (dddd,
3
1H, J5,F=29.0, J5,F=11.4, H-5), 3.42 (s, 3H, MeO), and 1.75 (d, 3H, JMe,F=1.3, Me-3); 13C
3
4
2
1
NMR (125.7 MHz, CDCl3): d 99.0 (C-1), 90.2 (d, J3,F=17.3, C-3), 89.9 (dd, J4,F=187.5,
3J4,F=5.4, C-4), 80.4 (dd, J6,F=170.8, J6,F=6.4, C-6), 66.1 (C-2), 65.8 (d, J5,F=24.8,
2J5,F=18.1, C-5), 56.4 (MeO), and 17.7 (Me-3); HRCIMS: m/z 242.0840 (calcd for
C8H13F2NO5+H: 242.0840), 210.0582 (calcd for C8H13F2NO5^OCH3: 210.0578).
1
3
2
4.6.20. (1R
galactitol 42
or
1S)-4,5-Anhydro-3,6-dideoxy-1,6-di¯uoro-3-C-methyl-1-O-methyl-3-nitro-d-
Syrup; Rf 0.31 (1:1 ether:hexane); ‰ꢁŠD25=^19.0 (c 0.85, acetone); IR (®lm) ꢂmax 3515 (OH), 1553
and 1355 (NO2), 1220 (oxirane), and 1093 cm^1 (CF); H NMR (500 MHz, CD3COCD3): ꢀ 5.35
1
2
0
(dd, 1H, J1,2=5.0, J1,F=64.2, H-1), 5.27 (s, HO), 4.74 (ddd, 1H, J5,6=2.0, J6,6 =11.2,
J6,F=47.8, H-6), 4.41 (dd, 1H, J2,F=11.2, H-2), 4.36 (ddd, 1H, J5,6 =5.7, J6 ,F=47.2, H-60),
2
3
2
0
0
4
4
3.57 (d, 3H, JMeO,F=1.5, MeO), 3.55 (dd, 1H, J4,5=2.0, J4,F=3.5, H-4), 3.46 (dddd, 1H,
5
3J5,F=13.7, H-5), and 1.52 (d, 3H, JMe,F=0.7, Me-3); 13C NMR (125.7 MHz, CD3COCD3, at
^25ꢀC): ꢀ 112.2 (d, 1J1,F=226.3, C-1), 92.3 (C-3), 83.1 (d, 1J6,F=176.0, C-6), 75.1 (d, 2J2,F=27.7,
C-2), 57.4 (MeO), 55.1 (dd, 3J4,F=8.8, 4J4,F=5.0, C-4), 53.1 (d, 2J5,F=22.6, C-5), and 12.6 (Me-3);
CIMS: m/z 242 (10, [M+1]+); HRCIMS: m/z 242.0841 (calcd for C8H13F2NO5+H: 242.0840).

P. Borrachero et al. / Tetrahedron: Asymmetry 11 (2000) 2927±2946
2945
(m) From methyl 6-O-tert-butyldiphenylsilyl-3-deoxy-3-C-methyl-3-nitro-a-d-glucopyranoside
(17, 0.475 g); DAST: 462 mL; solvent: diglyme (7.6 mL); temperature: ambient for 2 h. After
quenching the reaction by adding methanol (20 mL), the general workup was followed. Column
chromatography (1:4 ether:hexane) a€orded unreacted starting material (0.076 g, indicative of
85% of conversion) and pure product 43 (0.076 g, 15%, corresponding to 18% yield from
converted substrate).
4.6.21. (1R or 1S)-4,5-Anhydro-6-O-tert-butyldiphenylsilyl-3-deoxy-1-¯uoro-3-C-methyl-1-O-
methyl-3-nitro-d-galactitol 43
Syrup; Rf 0.35 (1:1 ether:hexane); ‰ꢁŠD21=+17.4 (c 0.86, acetone); IR (®lm) ꢂmax 3436 (OH), 1545
and 1386 (NO2), 973 (CF), 820 (oxirane), and 703 cm^1 (CSi); 1H NMR (500 MHz, CD3COCD3):
2
3
ꢀ 7.70±7.43 (m, 10H, 2Ph), 5.35 (dd, 1H, J1,2=4.9, J1,F=64.2, H-1), 4.46 (m, 1H, J2,F=5.7,
0
0
H-2), 3.93 (dd, 1H, J5,6=2.7, J6,6 =12.0, H-6), 3.76 (dd, 1H, J5,6 =4.4, H-6 ), 3.61 (dd, 1H,
0
5
J4,5=2.0, J4,F=1.8, H-4), 3.57 (s, 3H, MeO), 3.32 (ddd, 1H, H-5), 1.52 (s, 3H, Me-3), and 1.03
1
(s, 9H, t-Bu); 13C NMR (125.7 MHz, CD3COCD3): ꢀ 136.5±128.5 (2Ph), 112.6 (d, J1,F=226.3,
2
C-1), 93.0 (C-3), 75.9 (d, J2,F=25.1, C-2), 63.9 (C-6), 57.7 (C-4), 55.8 (C-5), 56.1 (MeO), 27.1
(CMe3), 19.8 (CMe3), and 13.6 (Me-3); FABMS: m/z 500 (45, [M+Na]+); HRCIMS m/z 478.2036
(calcd for C24H32FNO6Si+H: 478.2061).
Acknowledgements
We are grateful to the Direccion General de Ensenanza Superior, Ministerio de Educacion y
Cultura of Spain (Grant No. PB96-1326) and the Direccion General de Universidades e Investigacion,
Consejerõa de Educacion y Ciencia of Andalusia, for ®nancial support.
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