Dramatic effect of PSE clamping on the behaviour of d-glucal under Ferrier I conditions

Article abstract of DOI:10.1016/j.tetlet.2008.03.093

Clamped by the acid-resistant phenylsulfonylethylidene (PSE) acetal, d-glucal privileged the additive pathway over the Ferrier I rearrangement when confronted with protic nucleophiles.

Full text of DOI:10.1016/j.tetlet.2008.03.093

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3484–3488
Dramatic effect of PSE clamping on the behaviour
of D-glucal under Ferrier I conditions
a
a
a,
*
Anthony Fernandes , Maxime Dell’Olmo , Arnaud Tatiboue¨t ,
Anne Imberty b, Christian Philouze c, Patrick Rollin a,*
a Institut de Chimie Organique et Analytique, UMR6005, Universite´ d’Orle´ans, B.P. 6759, F-45067 Orle´ans, France
b CERMAV-CNRS, Universite´ Joseph Fourier, BP 53, F-38041 Grenoble, France
c DPM, UMR 5250, Universite´ Joseph Fourier, BP 53, F-38021 Grenoble, France
Received 8 February 2008; revised 17 March 2008; accepted 19 March 2008
Available online 23 March 2008
Abstract
Clamped by the acid-resistant phenylsulfonylethylidene (PSE) acetal, D-glucal privileged the additive pathway over the Ferrier I
rearrangement when confronted with protic nucleophiles.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Phenylsulfonylethylidene (PSE) acetals; Glycals; Ferrier I reaction; Glycosylation
Despite the advances of glycochemistry technologies for
the synthesis of complex oligosaccharides and the consecu-
tive development of specifically designed chemical tools, a
current need remains for original protecting groups in
carbohydrate chemistry, and more generally in multistep
organic synthesis. Cyclic acetal protecting groups are
among the most commonly used groups, for their
stability under basic conditions and their standard remov-
ability under acid-catalyzed hydrolysis.1 Phenylsulfonyl-
ethylidene (PSE) acetals have recently been introduced as
protecting groups with remarkable characteristics.2 Indeed,
those acetals show a strong reluctance to cleavage under
standard acidic hydrolysis or alcoholysis conditions
(AcOH–H2O, TFA–H2O, BF3–MeOH); in contrast, they
can easily be deprotected under basic (CsCO3–EtOH) or
strongly reductive (LiAlH4) conditions.2 In addition, they
display a remarkable stability under oxidative conditions
(DDQ)3 or in the presence of strong Lewis acids.4
Considering the stability of the PSE acetal moiety under
various acidic conditions, we turned our attention onto one
of the most classical carbohydrate transformations: the
allylic rearrangement of acylated glycals known as the
Ferrier I reaction.5 This involves the introduction under
Lewis acid conditions of a nucleophilic group at the C-1
of a glycal with simultaneous shifting of the double bond
between C-2 and C-3. Numerous efforts have been made
over decades to avoid or circumvent the Ferrier I reaction
in order to selectively favour the regioselective addition
process.6 Modifications of the protecting group array on
the glycal substrate might also greatly influence the course
of the Ferrier I reaction: because of their sensitiveness to
acidic conditions, 4,6-acetal-protected glycals—especially
benzylidene—have been scarcely studied,7 so the influence
on the reactivity of glycals of a stable PSE 4,6-O-clamping
was worth investigating.
PSE D-glucal 2 was prepared in 75% yield from commer-
cially available tri-O-acetyl-D-glucal 1 according to the
published procedure (Scheme 1).2b Three different sub-
strates were synthesized from 2. Standard O-acylations
were performed in excellent yields to produce acetate 3a
and the mixed carbonate 3b. Applying a routine O-benzyl-
ation protocol (NaH, BnBr, DMF, 0 °C) to 2 led to a
*
Corresponding authors. Tel.: +33 (0)238494854; fax: +33
(0)238417281 (A.T.).
E-mail addresses: arnaud.tatibouet@univ-orleans.fr (A. Tatiboue¨t),
patrick.rollin@univ-orleans.fr (P. Rollin).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.093

A. Fernandes et al. / Tetrahedron Letters 49 (2008) 3484–3488
3485
a- MeONa,
MeOH,
Bi(OTf)3 only afforded 6 and 7 in improved overall yields.
Weaker protic or Lewis acids (entries 4 and 5) proved inef-
ficient in this reaction. In order to limit the side reactions,
the amount of acid was reduced to a catalytic level and the
nucleophile to a stoichiometric amount; under such condi-
tions the transformations proved far less effective:
BF3ꢁEt2O (entry 6) led to a complex mixture while the
other acids (entries 7 and 8) gave a moderate yield of the
expected 5, but still with some nucleophilic substitution.
With a view to circumventing the acetate problem (3a),
the study was pursued starting directly from PSE D-glucal
2. Applying with a panel of Lewis acids the conditions
described above (5 equiv MeOH, 1.1 equiv acid), we
observed a high yielding overall transformation of 2 with
an 8:1 rough ratio of the addition over the Ferrier rear-
rangement (entries 9–12). Furthermore, no side formation
of 7 was detected. When tested under catalytic conditions
with a stoichiometric amount of methanol, the reaction
was found still efficient, especially with TMSOTf (entries
13–15).
O
O
O
O
O
AcO
AcO
PS
PS
O
b- BPSE, NaH,
DMF
O
O
OH
OAc
3
2
R
75%
1
3a R = Ac, (95%)
(Ac2O pyridine)
PS = phenylsulfonyl
3b R = COOMe, (86%)
(ClCOOMe, pyridine)
3c R = Bn, (75%)
(BnBr, NaH,
Bu4NBr, DMF)
Scheme 1. Preparation of starting material.
mixture of compounds from which the O-benzyl ether 3c
could only be obtained in 30% yield.8 However, carefully
controlled alkylation conditions (ꢀ78 °C and a slow return
to room temperature, 1 equiv Bu4NBr) allowed an increase
of the yield to 75%.
In our first experiments, the acetylated glucal 3a was
chosen as a model (Table 1, entries 1-8) using standard
Lewis acid conditions and methanol as the nucleophile
(Scheme 2). Unexpected results were obtained: no rear-
ranged compound 4 was detected and a set of three com-
pounds (5–7) was isolated instead (entry 1).
It can be hypothesized that glycoside 5 is first formed,
resulting from an addition process on the enol ether 3a.
The acetyl group is then further methanolyzed to form 6
or C-substituted to afford 7 as mixtures of stereoisomers.
The addition process results in a 74% global yield. Replac-
ing BF3ꢁEt2O by other Lewis acids such as TMSOTf or
The above preliminary results converged towards the
fact that, when placed in Ferrier I conditions, either pro-
tected or unprotected PSE D-glucal mainly followed an
addition process of the alcohol. Some observations should
be emphasized: (a) a stoichiometric amount of Lewis acid
increases the reactivity, (b) the catalytic process is effective
only with the allyl alcohol 2, (c) TMSOTf is the most selec-
tive reagent for the addition process. On those grounds, we
Table 1
Methanol as a nucleophile
Entry
Glucal
Lewis acid
Methanol
5 equiv
4
5 (a/b)
6 (a/b)
7
1
2
3
4
5
3a
3a
3a
3a
3a
BF3ꢁEt2O
TMSOTf
Bi(OTf)3
CSA
1.1 equiv
—
—
—
20%
—
—
48% (7/3)
56% (8/2)
77% (8/2)
6%
21%
16%
No reaction
No reaction
ZnCl2
6
7
8
3a
3a
3a
BF3ꢁEt2O
TMSOTf
Bi(OTf)3
0.2 equiv
1.1 equiv
1.2 equiv
5 equiv
—
—
—
Complex mixture
48% (8/2)
45% (8/2)
—
—
21%
Traces
9
10
11
12
2
2
2
2
BF3ꢁEt2O
TMSOTf
Bi(OTf)3
InCl3
14%
Traces
11%
80% (8/2)
88% (8/2)
85% (8/2)
75% (8/2)
—
—
—
—
—
—
—
12%
13
14
15
16
2
2
2
2
BF3ꢁEt2O
TMSOTf
Bi(OTf)3
InCl3
0.2 equiv
1.2 equiv
21%
Traces
9%
73% (8/2)
78% (8/2)
79% (8/2)
No reaction
Lewis acid
MeOH
O
O
OMe
O
OMe
O
OMe
O
O
O
OMe
O
O
O
O
+
+
PS
PS
PS
PS
+
CH2Cl2
PS
O
O
O
O
OR
OAc
OH
OMe
2
R = H
4
5
6
7
3a R = Ac
Scheme 2. Attempted Ferrier rearrangement under standard conditions.

3486
A. Fernandes et al. / Tetrahedron Letters 49 (2008) 3484–3488
TMSOTf (0.2 equiv.)
Nu (1.2 equiv.)
O
Nu
O
R
O
O
Nu
O
O
O
O
TMSOTf, Nu-SiR3
CH2Cl2, MS 3A
PS
+
3a
PS
PS
PS
O
8
O
O
O
CH2Cl2
OAc
OH
OH
2
H-SiEt3
11 7%
-
12 68%
13 83%
15 18%
Nu : BnOH 8a
R = BnO
PhS
79% (7/3)
78% (6/4)
Allyl-SiMe3
N3-SiMe3
PhSH
8b
14 59%
CbzNH2 8c
TMSN3 8d
Et3SiH 8e
NHCbz 67%
N3
H
degradation
degradation
Scheme 5.
Scheme 3.
stage that the hardness factor of the nucleophilic reagent
remains a prominent parameter in the behaviour of PSE
glucals under Ferrier I conditions. It is also plausible that
a rigidification of the glucal through PSE acetal clamping
exerts a dramatic effect on the reaction process; a radio-
crystallographic analysis of glucal 2 was performed in
order to detect a possible conformational anomaly. How-
ever, the X-ray picture obtained (Fig. 1)11 revealed for 2
a standard half-chair conformation, thus indicating that
the PSE-clip should have no distortional impact on the
course of the Ferrier I transformation. In other respects,
it can also be postulated that the rearrangement process
might be hampered by conformational constraints of a
2,3-enopyranoside of type 4. Therefore diol 16 was reacted
with BPSE under standard conditions2b to afford the corre-
sponding PSE acetal 17 in 86% yield (Scheme 6).
This is consistent with the results obtained notably with
the formation of 12 and 13 (Scheme 5), which indicate that
PSE acetal-clamping of a glucal does not create hindrance
to the Ferrier I rearrangement. Our attention is rather
attracted on the allyloxycarbenium transition state, in
which the sulfonyl group is likely to exert a complexation
effect on the Lewis acid, thus deviating the reaction
towards an additive pathway. Further investigation of the
atypical chemical behaviour of PSE-protected glycals is
currently under way in our laboratory.
first explored the scope of our reaction, getting simple (O,
S, N, H) nucleophiles (Nu) opposed to PSE D-glucal 2
(Scheme 3). With protic reagents, the addition performed
well with reasonable to good yields of 8a–c, whereas non-
protic reagents only led to degradations.
We then turned our attention back to protected sub-
strates 3a, and 3c reacting with protic nucleophiles; yield
optimization was ensured through combining a stoichiom-
etric amount of nucleophile and TMSOTf, associated with
˚
3 A molecular sieves (Scheme 4).
Under such conditions indeed, an even more efficient
addition process was observed. In all cases, side products
6 and 7 were either not detected or only found as traces.
Aliphatic alcohols as well as p-methoxyphenol gave the
desired compounds 5 and 9a–c in reasonable yields; on
the other hand, the O-benzylated substrate 3c allowed yield
improvement for adducts 10b–c (see Table 2).
The striking efficacy of the above process9 with protic
nucleophiles brought us to reconsider the case of aprotic
nucleophiles when confronted with the protected glucal
3a and preliminary results were found quite contradictory
(Scheme 5). Triethylsilane and allyltrimethylsilane unex-
pectedly underwent the Ferrier rearrangement to afford
unsaturated compounds 12 (with a small amount of the
adduct 11) and 13. In contrast, TMSN3 reacted preferen-
tially in the addition mode, giving a 59% yield of 14 (3:7
a/b mixture) and an 18% yield of the rearranged product
15 (1:1 a/b mixture).10 It may thus be hypothesized at this
O
OR'
O
O
TMSOTf, R'OH
O
PS
PS
O
O
MS 3Α, CH2Cl2
O
O
R
R
5, 9a-c R = Ac
3a R = Ac
3c R = Bn
10a-c R = Bn
Scheme 4.
Table 2
Glycosylation reactions on 3a and 3c (Scheme 4)
Fig. 1. ORTEP representation of PSE D-glucal 2.
Products
R0
Yield
a/b
5
9a
Methyl
Heptyl
Cyclohexyl
p-Methoxyphenyl
Methyl
73%
61%
55%
64%
55%
86%
96%
8/2
8/2
9/1
>95/5
7/3
BPSE, NaH
OH
O
PS
Bu4NBr
O
9b
9c
HO
O
O
THF
OEt
OEt
10a
10b
10c
16
17
Heptyl
Cyclohexyl
8/2
8/2
Scheme 6.

A. Fernandes et al. / Tetrahedron Letters 49 (2008) 3484–3488
3487
22.7, 26.2, 29.1, 29.5, 31.8 (heptyl CH2), 36.4 (C-2), 61.2 (C-8), 62.4
(C-5), 67.7 (C-9), 68.8 (C-6), 72.5 (PhCH2O), 72.8 (C-3), 83.7 (C-4),
96.9 (C-7), 97.9 (C-1), 127.6–129.2 (CH-Ar), 133.9 (CH-para-PhSO2),
138.8 (CIV-Ar), 139.9 (CIV-PhSO2). MS (IS) m/z = 519.5 [M+H]+,
542.5 [M+Na]+.
Acknowledgements
The authors would like to thank Professor D. Sinou and
Dr. P. Lhoste for helpful discussions and a generous gift of
´
´
compound 16, the CNRS and the Universite d’Orleans for
financial support.
10. 1,5-Anhydro-2,3-dideoxy-4,6-O-(2-phenylsulfonyl)ethylidene-D-erythro-
20
hex-2-enitol 12: Syrup; ½aꢃD +1 (c = 0.4, CHCl3). 1H NMR (250 MHz,
CDCl3): d = 3.25 (ddd, 1H, J5–6b = 10.3 Hz, J5–6a = 4.8 Hz, J4–5
=
8.3 Hz, H-5), 3.48 (d, 2H, J7–8 = 5.0 Hz, H-8a, H-8b), 3.53 (t, 1H,
J5–6b = J6a–6b = 10.3 Hz, H-6b), 3.92–3.95 (m, 1H, H-4), 4.06 (dd, 1H,
J5–6a = 4.8, H-6a), 4.18–4.21 (m, 2H, H-1a, H-1b), 5.11 (t,
1H, J7–8 = 5.0 Hz, H-7), 5.63 (d, 1H, J2–3 = 10.5 Hz, H-2), 5.70 (dt,
1H, J3–1 = J3–4 = 1.8 Hz, J3–2 = 10.5 Hz, H-3), 7.53–7.59 (m, 2H,
meta-H–PhSO2), 7.64–7.69 (m, 1H, para-H–PhSO2), 7.91 (d, 2H,
J = 7.3, ortho-H–PhSO2). 13C NMR (62.5 MHz, CDCl3): d = 60.1
(C-8), 66.5 (C-1), 69.2 (C-6), 69.7 (C-5), 75.0 (C-4), 97.0 (C-7), 125.3
(C-2), 127.9 (C-3), 128.4 (CH-ortho-PhSO2), 129.1 (CH-meta-PhSO2),
133.9 (CH-para-PhSO2), 139.9 (CIV-PhSO2). MS (IS) m/z = 314
[M+NH4]+, 319 [M+Na]+.
References and notes
1. (a) Haines, A. H. Adv. Carbohydr. Chem. Biochem. 1981, 39, 13–
70; (b) Gelas, J. Adv. Carbohydr. Chem. Biochem. 1981, 39, 71–
156.
´
2. (a) Chery, F.; Rollin, P.; De Lucchi, O.; Cossu, S. Tetrahedron Lett.
´
2000, 41, 2357–2360; (b) Chery, F.; Rollin, P.; De Lucchi, O.; Cossu,
S. Synthesis 2001, 286–292.
3. Cabianca, E.; Tatiboue¨t, A.; Rollin, P. Pol. J. Chem. 2005, 79, 317–
322.
3-O-Acetyl-1,5-anhydro-2-deoxy-4,6-O-(2-phenylsulfonyl)ethylidene-
20
4. Chevalier-du Roizel, B.; Cabianca, E.; Rollin, P.; Sinay, P. Tetra-
¨
D-glucitol 11: Syrup; ½aꢃD +3 (c = 1.0, CHCl3). 1H NMR (250 MHz,
hedron 2002, 58, 9579–9583.
CDCl3): d = 1.63–1.75 (m, 2H, H-2), 2.08–2.17 (m, 4H, H-2, MeCO),
3.21 (dd, 1H, J5–6b = 9.5 Hz, J4–5 = 4.8 Hz, H-5), 3.39–3.57 (m, 3H,
H-1ax, H-4, H-6b), 3.47 (d, 2H, J7–8 = 4.8 Hz, H-8a, H-8b), 3.92 (dd,
5. (a) Ferrier, R. J. Top. Curr. Chem. 2001, 215, 153–175; (b) Procopio,
A.; Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Nardi, M.; Oliverio, M.;
Russo, B. Carbohydr. Res. 2007, 342, 2125–2131; (c) Rauter, A. P.;
Almeida, T.; Xavier, N. M.; Siopa, F.; Vicente, A. I.; Lucas, S. D.;
Marques, J. P.; Ribeiro, F. R.; Guisnet, M.; Ferreira, M. J. J. Mol.
Catal., A: Chem. 2007, 275, 206–213; (d) Kim, H.; Men, H.; Lee, C. J.
Am. Chem. Soc. 2004, 126, 1336–1337; (e) Hotha, S.; Tripathi, A. J.
Comb. Chem. 2005, 7, 968–976.
6. (a) Marzabadi, C. H.; Franck, R. W. Tetrahedron 2000, 56, 8345–
8417; (b) Catelani, G.; Colonna, F.; Rollin, P. Gazz. Chim. Ital. 1989,
119, 389–393; (c) Rauter, A. P.; Almeida, T.; Vicente, A. I.; Ribeiro,
V.; Bordado, J. C.; Marques, J. P.; Ribeiro, F. R.; Ferreira, M. J.;
Oliveira, C.; Guisnet, M. Eur. J. Org. Chem. 2006, 2429–2439; (d)
Sherry, B. D.; Loy, R. N.; Toste, F. D. J. Am. Chem. Soc. 2004, 126,
4510–4511; (e) Colinas, P. A.; Bravo, R. D. Org. Lett. 2003, 5, 4509–
4511; (f) Gopal Reddy, B.; Madhusudanan, K. P.; Vankar, Y. D. J.
Org. Chem. 2004, 69, 2630–2633; (g) Yadav, J. S.; Subba Reddy, B.
V.; Vijaya Bhasker, E.; Raghavendra, S.; Narsaiah, A. V. Tetrahedron
Lett. 2007, 48, 677–680.
1H, J1a–b = 12.0 Hz, J1–2 = 4.5 Hz, H-1eq), 4.04 (dd, 1H, J6a–b
=
10.5 Hz, J5–6a = 5.0 Hz, H-6a), 4.88 (ddd, 1H, J3–4 = 10.8 Hz,
J2ax–3 = 9.5 Hz, J2eq–3 = 5.4 Hz, H-3), 5.08 (t, 1H, J 7–8 = 4.8 Hz,
H-7), 7.52–7.58 (m, 2H, meta-H–PhSO2), 7.63–7.68 (m, 1H, para-H–
PhSO2) 7.91 (d, 2H, J = 7.3 Hz, ortho-H–PhSO2). 13C NMR
(62.5 MHz, CDCl3): d = 21.3 (MeCO), 31.5 (C-2), 60.1 (C-8), 66.1
(C-6), 68.5 (C-1), 70.6 (C-3), 71.4 (C-5), 80.4 (C-4), 96.9 (C-7), 128.3
(CH-ortho-PhSO2), 129.2 (CH-meta-PhSO2), 134.0 (CH-para-PhSO2),
140.1 (CIV-PhSO2), 170.5 (CO). MS (IS) m/z = 357.5 [M+H]+, 374.5
[M+NH4]+, 379.5 [M+Na]+.
(1R)-1-C-Allyl-1,5-anhydro-2,3-dideoxy-4,6-O-(2-phenylsulfonyl)-
20
ethylidene-D-erythro-hex-2-enitol 13: Syrup; ½aꢃD +6 (c 1.1, CHCl3).
1H NMR (250 MHz, CDCl3): d = 2.17–2.45 (m, 2H, allyl CH2), 3.32
(ddd, 1H, J5–6b = 10.1 Hz, J4–5 = 8.3 Hz, J5–6a = 4.8 Hz, H-5), 3.47–
3.60 (m, 1H, H-6b), 3.48 (d, 2H, J7–8 = 4.8 Hz, H-8a, H-8b), 3.85 (dd,
1H, J4–5 = 8.3 Hz, J1–4 = 2.0 Hz, H-4), 4.02 (dd, 1H, J6a–b = 10.3 Hz,
J5–6a = 4.8 Hz, H-6a), 4.23 (td, J1-CH ¼ J1-CH ¼ 6:3 Hz, J1–4
=
7. (a) Seeberger, P. H.; Roehrig, S.; Schell, P.; Wang, Y.; Christ, W. J.
Carbohydr. Res. 2000, 328, 61–69; (b) Geiger, J.; Barroca, N.;
Schmidt, R. R. Synlett 2004, 836–840.
2
2
2.5 Hz, H-1), 5.04–5.11 (m, 3H, H-7, @CH2), 5.63–5.87 (m, 3H,
H-2, H-3, @CH), 7.53–7.59 (m, 2H, meta-H–PhSO2), 7.63–7.69 (m,
1H, para-H–PhSO2), 7.91 (1H, d, J = 7.3 Hz, ortho-H–PhSO2). 13C
NMR (62.5 MHz, CDCl3): d = 38.3 (allyl CH2), 60.2 (C-8), 65.0
(C-5), 69.5 (C-6), 73.9 (C-1), 75.0 (C-4), 97.0 (C-7), 117.8 (@CH2),
126.1 (C-2), 128.5 (CH-ortho-PhSO2), 129.1 (CH-meta-PhSO2), 130.6
(C-3), 133.9 (CH-para-PhSO2), 134.2 (@CH), 139.9 (CIV-PhSO2). MS
(IS) m/z = 337.5 [M+H]+, 354.5 [M+NH4]+, 359.5 [M+Na]+.
3-O-Acetyl-2-deoxy-4,6-O-(2-phenylsulfonyl)ethylidene-a-D-arabino-
´
8. Strong bases readily induce ring opening of PSE acetals: Chery, F.;
Tatiboue¨t, A.; De Lucchi, O.; Rollin, P., unpublished results.
9. Representative procedure: PSE-glucal 2 or 3a (0.1 g) was dissolved in
˚
DCM (4 mL) under argon. Activated 3 A molecular sieves (0.2 g)
were added, followed by the nucleophile; the resulting slurry was then
cooled to 0 °C and stirred for 1 h. TMSOTf (1.2 equiv) was added and
the reaction allowed to warm up slowly to room temperature. At the
end of the reaction, the solution was quickly filtered over a MgSO4
pad, then diluted with EtOAc (40 mL) and washed with water
(3 ꢂ 20 mL) then brine (20 mL). The organic solution was dried over
MgSO4, evaporated under reduced pressure and purified by silica gel
chromatography (petroleum-ether–AcOEt elution).
20
hexopyranosyl azide 14a: Syrup; ½aꢃD +24 (c 1.0, CHCl3). 1H NMR
(250 MHz, CDCl3): d = 1.74 (ddd, 1H, J2ax–2eq = 13.4 Hz, J2ax–3
=
11.3 Hz,J1–2ax = 4.5 Hz, H-2ax), 2.10 (s, 3H, MeCO), 2.19 (dd, 1H,
J2eq–3 = 5.3 Hz, J1–2eq = 1.0 Hz, H-2eq), 3.43–3.57 (m, 2H, H-4,
H-6b), 3.48 (d, 2H, J7–8 = 4.8 Hz, H-8a, H-8b), 3.78 (dd, 1H, J4–5
=
10.0 Hz, J5–6 = 5.0 Hz, H-5), 4.06 (dd, 1H, J6a–b = 10.3 Hz,
J5–6a = 4.8 Hz, H-6a), 5.03–5.15 (m, 2H, H-3, H-7), 5.42 (d, 1H,
J1–2ax = 4.5 Hz, H-1), 7.52–7.58 (m, 2H, meta-H–PhSO2), 7.63–7.69
(m, 1H, para-H–PhSO2), 7.91 (d, 1H, J = 7.0 Hz, ortho-H–PhSO2).
13C (62.5 MHz, CDCl3): d = 21.2 (MeCO), 34.8 (C-2), 60.0 (C-8), 64.6
(C-5), 66.8 (C-3), 68.3 (C-6), 79.9 (C-4), 87.2 (C-1), 97.0 (C-7), 128.2
(CH-ortho-PhSO2), 129.2 (CH-meta-PhSO2), 134.0 (CH-para-PhSO2),
140.0 (CIV-PhSO2), 170.0 (CO). MS (IS) m/z = 398.5 [M+H]+, 415.5
[M+NH4]+, 420.5 [M+Na]+.
Selected analytical data for n-heptyl 3-O-benzyl-2-deoxy-4,6-O-(2-
phenylsulfonyl)ethylidene-a-D-arabino-hexopyranoside 10b: Syrup;
20
½aꢃD +54 (c = 2.1, CHCl3). 1H NMR (400 MHz, CDCl3): d = 0.80
(3H, m, Me), 1.20 (br s, 8H, heptyl CH2), 1.45 (m, 2H, heptyl CH2),
1.62 (ddd, 1H, H-2ax), 2.13 (dd, 2H, J2a–b = 13.3 Hz, H-2eq), 3.22 (dt,
1H, Jgem = 9.6 Hz, Jvic = 4.8 Hz, H-9b), 3.33–3.56 (m, 6H, H-4, H-5,
H-6b, H-8a, H-8b, H-9a), 3.78 (ddd, 1H, J3,4 = 9.1 Hz,
J3,2eq = 5.0 Hz, J3,2ax = 11.1 Hz, H-3), 3.92 (dd, 1H, J6a,6b = 10.2 Hz,
J6a,5 = 4.7 Hz, H-6a), 4.48 and 4.62 (2d, AB system, 2H,
Jgem = 11.9 Hz, PhCH2O), 4.74 (d, 1H, J1,2ax = 3.2 Hz, H-1), 4.97
(t, 1H, J7–8 = 5.1 Hz, H-7), 7.17–7.25 (m, 5H, H–Ph), 7.40–7.42 (m,
2H, meta-H–PhSO2), 7.50–7.54 (m, 1H, para-H–PhSO2) 7.83–7.86 (d,
2H, ortho-H–PhSO2). 13C NMR (100 MHz, CDCl3): d = 14.2 (Me),
3-O-Acetyl-2-deoxy-4,6-O-(2-phenylsulfonyl)ethylidene-a-D-arabino-
20
hexopyranosyl azide 14b: Syrup; ½aꢃD ꢀ25 (c 1.1, CHCl3). 1H NMR
(250 MHz, CDCl3): d = 1.51–1.65 (m, 1H, H-2ax), 2.09 (s, 3H,
MeCO), 2.34 (ddd, 1H, J2ax–2eq = 13.0 Hz, J2eq–3 = 5.3 Hz, J1–2eq
=

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A. Fernandes et al. / Tetrahedron Letters 49 (2008) 3484–3488
2.3 Hz, H-2eq), 3.34 (dd, 1H, J5–6b = 9.8 Hz, J5–6a = 4.8 Hz, H-5),
3.47 (d, 2H, J7–8 = 4.8 Hz, H-8a, H-8b), 3.43–3.50 (m, 1H, H-4), 3.58
(t, 1H, J6a–6b = J5–6b = 10.0 Hz, H-6b), 4.07 (dd, 1H, J6a–6b
10.5 Hz, J5–6a = 4.8 Hz, H-6a), 4.78 (dd, 1H, J1–2 = 10.8 Hz,
J1–2 = 2.3 Hz, H-1), 4.90 (ddd, 1H, J3–4 = 11.3 Hz, J2–3 = 9.5 Hz,
J2–3 = 5.3 Hz, H-3) 5.09 (t, 1H, J7–8 = 4.8 Hz, H-7), 7.52–7.58 (m, 2H,
meta-H–PhSO2) 7.63–7.69 (m, 1H, para-H–PhSO2) 7.91 (d, 2H,
J = 7.3, ortho-H–PhSO2). 13C (62.5 MHz, CDCl3): d = 21.2 (MeCO),
36.1 (C-2), 60.0 (C-8), 68.1 (C-6), 68.4 (C-5), 68.9(C-3), 79.2 (C-4),
86.5 (C-1), 97.1 (C-7), 128.2 (CH-ortho-PhSO2), 129.2 (CH-meta-
PhSO2), 134.0 (CH-para-PhSO2), 140.0 (CIV-PhSO2), 170.2 (CO). MS
(IS) m/z = 398.5 [M+H]+, 415.5 [M+NH4]+, 420.5 [M+Na]+.
11. CCDC 656182 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
=