COMMUNICATIONS
cyclohexane 3/7) indicated no starting material (Rf 0.5) and a major
product (Rf 0.3). The mixture was cooled to room temperature, and water
(2 mL) was added. The mixture was extracted with EtOAc (3 Â 10 mL) and
washed with water (10 mL). Combined extracts were dried (MgSO4) and
filtered, and the solvent was removed in vacuo. The residue was purified by
flash chromatography (eluent, EtOAc/cyclohexane 3/7) to afford an
inseparable mixture of the two isomers 13 and 14 as an oil (95 mg, 95%).
applied the thermal variant of this reaction to sugars under
more forcing conditions.[11]
The reaction of the thiophenyl substrate 17[12] with five
equivalents of TIBAL at 508C also gave the desired carbo-
cycle 18 in 81% yield (Scheme 6). In contrast, the Ferrier-II[13]
reaction has been applied[14] to the thiophenyl derivative 19 to
Received: July 8, 1999 [Z13694]
O
BnO
BnO
BnO
BnO
iBu3Al (5 equiv)
SPh
SPh
PhMe, 50°C, 30 min
81%
OBn
OBn
OH
[1] a) R. J. Ferrier, S. Middleton, Chem. Rev. 1993, 93, 2779 ± 2831; b) P.
SinayÈ, P. Dalko, Angew. Chem. 1999, 111, 819 ± 823; Angew. Chem. Int.
Ed. 1999, 38, 773 ± 776.
[2] S. K. Das, J.-M. Mallet, P. SinayÈ, Angew. Chem. 1997, 109, 513 ± 516;
Angew. Chem. Int. Ed. Engl. 1997, 36, 493 ± 496.
17
18
Scheme 6. Application of the TIBAL-promoted rearrangement to
thiophenyl glucoside.
a
[3] We successfully applied this methodology for the direct synthesis of
disaccharide mimetics by replacing the aglycon methoxy group with
monosaccharide substituents: A. J. Pearce, M. Sollogoub, J.-M.
Mallet, P. SinayÈ, Eur. J. Org. Chem. 1999, 2103 ± 2117.
give the hydroxy ketone 20 (i.e., with loss of the thiophenyl
moiety, Scheme 7). However, in our case the sulfur atom
stabilizes the carbenium intermediate (B, EDG SPh in
Scheme 2) to afford the cyclohexane with retention of the
thiophenyl functionality, as predicted. This example illustrates
the fundamental difference between the TIBAL-promoted
rearrangement and the Ferrier-II reaction.
Á
Á
Â
[4] D. Rouzaud, These de troisieme cycle, Universite Paris-Sud Orsay
(France), 1985.
[5] P. Pino, P. Lorenzi, J. Org. Chem. 1966, 31, 329 ± 331.
[6] Prepared according to Scheme 9 from the known (2,3,4,6-tetra-O-
acetyl-b-d-glucopyranosyl)benzene; see C. D. Hurd, R. P. Holysz, J.
Am. Chem. Soc. 1950, 72, 1732 ± 1735.
[7] Prepared according to Scheme 9 from the known (2,3,4,6-tetra-O-
acetyl-b-d-glucopyranosyl)anisol; see P. Allevi, M. Anastasia, P.
Ciuffreda, A. Fiecchi, A. Scala, J. Chem. Soc. Chem. Commun. 1987,
16, 1245 ± 1246.
[8] Prepared according to Scheme 9 from the known 2,4,6-trimethoxy-2-
(2,3,4,6-tetra-O-acetyl-b-d-glucopyranosyl)benzene; see R. A. Eade,
H.-P. Pham, Aust. J. Chem. 1979, 32, 2483 ± 2493.
O
O
OPMB
RO
BnO
RO
BnO
HgCl2
SPh
acetone, H2O
67%
PMBO
OH
19
20
Scheme 7. Application of the Ferrier-II rearrangement to a thiophenyl
glucoside.[14] PMB para-methoxybenzyl; R substituted monosacchar-
[9] Prepared by debenzoylation and subsequent benzylation of the
benzoylated compound.[11]
ide.
[10] L. A. Paquette, D. Friedrich, R. D. Rogers, J. Org. Chem. 1991, 56,
3841 ± 3849.
[11] B. Wershkun, J. Thiem, Angew. Chem. 1997, 109, 2905 ± 2906; Angew.
Chem. Int. Ed. Engl. 1997, 36, 2793 ± 2794.
Similarly, the same conditions were applied to the seleno-
phenyl glucoside 21,[15] which was converted into the cyclo-
hexane 22 (84%; Scheme 8).
[12] Prepared according to literature procedures[2] from the known phenyl
2,3,4-tri-O-benzyl-1-thio-b-d-glucopyranoside; see P. J. Pfaffli, S. Hix-
son, L. Anderson, Carbohydr. Res. 1972, 23, 195 ± 206.
[13] R. J. Ferrier, J. Chem. Soc. Perkin Trans. 1 1979, 1455 ± 1458.
[14] N. Sakairi, M. Hayashida, A. Amano, H. Kuzuhara, J. Chem. Soc.
Perkin Trans. 1 1990, 1301 ± 1313.
O
BnO
BnO
BnO
BnO
SePh
iBu3Al (5 equiv)
SePh
[15] Prepared according to literature procedures[2] from the known phenyl
2,3,4-tri-O-benzyl-1-seleno-b-d-glucopyranoside; see E. Perrin, PhD
OBn
OBn
PhMe, 50°C, 20 min
84%
OH
21
22
Â
thesis, Universite Pierre et Marie Curie Paris 6 (France), 1996.
Scheme 8. Application of the TIBAL-promoted rearrangement to
selenophenyl glucoside.
a
OAc
X
In conclusion we have demonstrated that the
TIBAL-promoted rearrangement of unsaturated
I
X
Y
Y
O
O
a-c
AcO
AcO
AcO
AcO
glycosides (5-hex-enopyranosides) into carbocycles
is generally applicable to carbohydrates, provided
the aglycon is sufficiently electron donating in
nature (O-, S-, Se-, and C-glycosides). We are
currently exploring further suitable systems known
to stabilize cations and also the wider application of
this rearrangement in non-carbohydrate systems.
OAc
Y
OAc
Y
X
X
Y
Y
O
O
d
e,f
AcO
AcO
BnO
BnO
OAc
OBn
Y
Y
5: X=Y=H
8: X=OMe, Y=H
12: X=Y=OMe
Experimental Section
TIBAL (0.9 mL, 0.9 mmol, 1m in toluene) was added to a
stirred solution of 12 (100 mg, 0.17 mmol) in anhydrous
toluene (1 mL) at room temperature under argon. The reaction
mixture was heated at 508C for 30 min, when TLC (EtOAc/
Scheme 9. Preparation of unsaturated C-aryl glucosides. Reagents: a) MeONa, MeOH;
b) I2, PPh3, DMF; c) Ac2O, pyridine; d) 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), THF,
reflux; e) MeONa, MeOH; f) BnBr, NaH, DMF.
364
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