R. Olsson et al./Carbohydrate Research 307 (1998) 13±18
17
unfavourable 4C1±1C4 equilibrium. Finally, it
remains to be seen if the combination of TiCl4 and
thiophenol-diisopropylethylamine can be devel-
oped into an ecient method for the synthesis of
thioglycosides.
(ZnMe2); EtTiCl3 (0.5 ZnEt2); Et2TiCl2 (ZnEt2);
Me3SiCꢁCTiCl3 (Me3SiCꢁCLi).
General procedure for the pyranose ring opening
reactions.ÐAlMe3 or ZnMe2 (1.0 equiv) was
added to the carbohydrate substrate (0.1 M in
hexane or CH2Cl2) at room temperature. After
30 min, the solution was cooled to 72 ꢀC and
then added by cannulation to the solution con-
taining the organotitanium reagents prepared as a
0.2 M solution in hexane or CH2Cl2 as described.
In the cases of ®ltration to remove the salt (ZnCl2),
the ®lter paper was snuggled around the ¯at end of
the cannula, and the Lewis acid solution was
instead transferred to the substrate. The tempera-
ture was then raised to the indicated value
(Table 1). The progress of the reaction was mon-
itored by TLC analysis using 1:3 E±H as eluent.
After the indicated time, the reaction mixture was
quenched by dilution with EtOAc followed by slow
addition to an aq solution of NH4Cl (2 M). After
vigorous stirring over night, the aq phase was
extracted with EtOAc (3Â30 mL) and the com-
bined organic phases were sequentially washed
with water (100 mL) and brine (2Â100 mL), dried
(MgSO4) and concentrated in vacuo. The residue
was subjected to column chromatography (1:10 E±
H) to give the products as clear oils. Spectral data
for 4, 5, 6 and 7 were as reported in the literature
[4].
3. Experimental
General.ÐColumn chromatography separations
were performed by using Merck SiO2 60A (0.035±
0.070 mm) silica gel with EtOAc±heptane (E±H)
mixtures as eluents. TLC analyses were made on
Merck SiO2 60 F254 precoated glass plates and the
spots were visualised by charring with a solution of
phosphomolybdic acid (25 g), Ce(SO4)2.4H2O
(10 g), and conc. H2SO4 (60 mL) in H2O (940 mL).
NMR spectra were recorded in CDCl3 at 21 ꢀC
[1H, 400 MHz; CHCl3 ꢂ 7.27 and 13C, 100 MHz;
CHCl3 ꢂ 77.2]. GLC analyses were performed with
a DBwax column (J&W Scienti®c) capillary col-
umn (30 m; 0.25 mm i.d., 0.25 ꢃm stationary
phase). All reactions were carried out in oven-dried
glassware equipped with rubber septa and under
Ar. The organometallic reagents were transferred
by dried, Ar-¯ushed syringes and cannulas. Hex-
ane, heptane and THF were distilled from sodium.
CH2Cl2 was distilled from CaH2 and stored over
molecular sieves. EtOAc was distilled immediately
before use. TiCl4 and Ti(OiPr)4 were purchased
from Aldrich and Janssen, respectively, distilled
and diluted with dry CH2Cl2 to give a 2.0 M stock
solution before use. ZnMe2 (2.0 M in toluene;
Merck), ZnEt2 (1.0 M in hexane; Merck), AlMe3
(2.0 M in hexane; Aldrich), ClAlEt2 (1.0 M in hexane;
Aldrich), were all used as delivered. The substrates
1,2 and 3 were prepared from commercially avail-
able l-( )- and d-(+)-arabinose as described [30].
General procedure for generation of the
organotitanium reagents [17]. MeTiCl3.ÐZnMe2
(0.313 mmol, 0.156 mL, 2.0 M in toluene) was
added dropwise along the side of the ¯ask to a
stirred solution of TiCl4 (0.625 mmol, 0.312 mL,
2.0 M in CH2Cl2) in hexane (3.0 mL) under Ar at
72 ꢀC. The resulting mixture was kept at 72 ꢀC
for 10 min, followed by 30 min at 30 ꢀC. This
resulted in a 0.2 M solution of MeTiCl3 (0.625
mmol in 1:20 CH2Cl2±hexane). It was ®nally cooled to
72 ꢀC before the addition of the benzyl glycosides.
The other titanium containing reagents were
prepared by the same procedure from 1 equiv of
TiCl4 and the reagents in parentheses: Me2TiCl2
Thiophenyl 2-deoxy-2-C-methyl-4-O-(tert-butyl-
(8).ÐTiCl4
dimethylsilyl)-a-d-arabinopyranoside
(0.256 mL, 2.0 M in CH2Cl2) was added to a cooled
( 72 ꢀC) solution of 1 (0.256 mmol) in CH2Cl2
(2 mL) and the resulting mixture was stirred for
1 h. EtN(iPr)2 (2.19 mL, 12.8 mmol) followed by
PhSH (1.57 mL, 15.3 mmol) were then added and
after stirring the resulting mixture at 72 ꢀC for
1 h, the temperature was raised to 30 ꢀC. The
progress of reaction was monitored by TLC (1:3
E±H) and when the starting material was con-
sumed (after ca. 3.5 h) the mixture was quenched
and worked-up as above. Column chromatography
(1:10!1:3 E±H) aorded 81 mg (69%) of 8;
[ꢀ]20d+68.7ꢀ (c 0.31, CHCl3); NMR (CDCl3): H,
1
ꢂ 7.27 (m, 5 H, C6H5), 4.65 (d, 1 H, J1,2 6.9 Hz, H-
0
1), 4.14 (dd, 1 H, J4,5 5.5, J5,5 12.1 Hz, H-5), 3.90
0
(dt, 1 H, J3,4 3.1, J4,5 3.1, J4,5 5.6 Hz, H-4), 3.53
(dd, 1 H, H-50), 3.45 (m, 1 H, J2,3 7.1, JOH,3 7.1 Hz,
H-3), 2.26 (d, 1 H, OH), 2.14 (m, 1 H, J2,Me 6.9 Hz,
H-2), 1.16 (d, 3 H, Me), 0.92 (s, 9 H, Me3CSi), 0.13
(2 s, each 3 H, Me2Si); 13C, ꢂ 134.9, 131.4, 128.7,
and 126.9 (PhC), 88.5 (C-1), 73.4 (C-3), 67.5 (C-4),