C. A. Iriarte Capaccio, O. Varela / Carbohydrate Research 340 (2005) 2104–2110
2109
6.18 (dddd, 1H, J2,4 = 0.4 Hz, J4,6
=
2.7 Hz,
product (Rf = 0.33) and no starting material remaining
(Rf = 0.53). The mixture was diluted with a large excess
of CH2Cl2, washed with satd aq NaCl, dried (NaSO4),
and concentrated. The residue, which showed by 1H
NMR signals of a single product, was purified by flash
chromatography to afford 7 as a syrup (134 mg, 86%,
ee >42%); [a]D ꢁ90.8 (c 1.1, CHCl3); 1H NMR (500
MHz, CDCl3): d 7.35–7.23 (m, 5H, H-aromatic), 5.85,
5.82 (2br d, 2H, J3,4 = 10.7 Hz, H-3,4), 4.81 (d, 1H,
0
J4,6 = 1.6 Hz, H-4), 5.67 (s, 1H, H-2), 4.93 (ddd, 1H,
J6,6 = 19.1 Hz, H-6), 4.34 (ddd, 1H, H-60); 13C NMR
0
(50.3 MHz, CDCl3): d 189.0 (C-3), 148.3 (C-5), 132.8,
132.6, 129.2, 128.1 (C-aromatic), 125.9 (C-4), 88.3 (C-
2), 59.5 (C-6). Anal. Calcd for C11H10O2S: C, 64.05;
H, 4.89; S, 15.55. Found: C, 64.24; H, 4.85; S, 15.82.
Similar yields of 5 were obtained for various prepara-
tions under identical conditions starting from 1. How-
ever, variable enantiomeric excesses (ranging from 40%
to 60%) were obtained for such preparations.
0
J1,2 = 3.4 Hz, H-1), 4.35 (d, 1H, J5,5 = 16.2 Hz, H-5),
4.12 (br d, 1H, H-2), 4.06 (dd, 1H, H-50), 3.90, 3.84
(2d, 2H, J = 13.4 Hz, PhCH2S); 13C NMR (50.3 MHz,
CDCl3): d 137.9, 128.9, 128.4, 128.3 (C-aromatic),
127.1, 126.9 (C-3,4), 84.1 (C-1), 64.4 (C-2), 63.7 (C-5),
34.3 (PhCH2S). Anal. Calcd for C12H14O2S: C, 64.83;
H, 6.35; S, 14.42. Found: C, 65.14; H, 6.31; S, 14.57.
3.4.2. By iodine-promoted conversion of 4 into 5.
A
solution of 4 (148 mg, 0.48 mmol) in acetonitrile
(4 mL) was treated in the dark with iodine (27 mg,
0.11 mmol) at room temperature for 25 min. After the
usual workup for iodine reactions, the residue was sub-
jected to flash chromatography (30:1 hexane–EtOAc) to
afford the dihydropyranone 5 (73 mg, 74%) having
[a]D ꢁ433.6 (c 1.0, CHCl3), which corresponded to an
ee >94% (calculated from the 1H NMR spectra recorded
in the presence of the Yb chiral resolving agent).
1
The H NMR spectra of the crude reaction mixture
showed signals of 8 and no other diastereomers.
3.7. Diels–Alder cycloadditions of 2,3-dimethylbutadiene
to 6: synthesis of (3S,4aR,8aS)-3-benzylthio-6,7-
dimethyl-4a,5,8,8a-tetrahydro-1-H-2-benzopyran-4(3H)-
one (8) and (3S,4aS,8aR)-3-benzylthio-6,7-dimethyl-
4a,5,8,8a-tetrahydro-1-H-2-benzopyran-4(3H)-one (9)
The same reaction applied to a mixture of 3 and 4 (2.4:1
ratio, 100 mg, 0.32 mmol) afforded the enone 5 (48 mg,
72%) having [a]D ꢁ11.4 (c 1.0, CHCl3) and ee >2%.
3.7.1. Et2OÆBF3-promoted cycloaddition. A solution of
3.5. (2S)-2-Benzylthio-2H-pyran-3(6H)-one (6)
6 (129 mg, 0.59 mmol, ee >42%) in dry toluene
(1.2 mL) was cooled to ꢁ18 ꢁC and Et2OÆBF3 (74 lL,
0.50 mmol) was added under argon. The vial was sealed
and the mixture was stirred at ꢁ18 ꢁC for 15 min, then
2,3-dimethylbutadiene (113 lL, 1.00 mmol) dissolved
in anhydrous toluene (0.5 mL) was slowly injected into
the solution. When the addition was finished, the mix-
ture was stirred at ꢁ18 ꢁC for 15 min. The reaction mix-
ture was diluted with ethyl ether, washed with satd aq
NaHCO3, dried (MgSO4), and concentrated. The 1H
NMR spectrum of the crude reaction mixture showed
only traces of other products (a diastereomeric ratio
for 8 >50:1). The mixture was subjected to flash chroma-
tography (60:1 hexane–EtOAc) to afford cycloadduct 8
(132 mg, 75%, ee >42%) as a white amorphous solid;
[a]D ꢁ152.4 (c 1.0, CHCl3); 1H NMR (500 MHz,
CDCl3): d 7.34–7.22 (m, 5H, H-aromatic), 5.07 (s, 1H,
Dihydropyranone 6 was prepared following the proce-
dure described for 5 in the previous item. Thus, reaction
of 1 (200 mg, 0.77 mmol) with x-toluenethiol (100 lL,
0.85 mmol) afforded 6 (108 mg, 63%) as an amorphous
yellowish solid. The ee of 6 was established as indicated
for 5. Compound 6 (ee >42%) had [a]D ꢁ179.7 (c 1.2,
1
CHCl3); H NMR (500 MHz, CDCl3): d 7.36–7.24 (m,
5H, H-aromatic), 7.04 (ddd, 1H, J4,5 = 10.5 Hz,
0
J5,6 = 1.8 Hz, J5,6 = 4.0 Hz, H-5), 6.12 (dddd, 1H,
0
J2,4 = 0.5 Hz, J4,6 = 2.7 Hz, J4,6 = 1.6 Hz, H-4), 5.29
0
(br s, 1H, H-2), 4.72 (ddd, 1H, J6,6 = 18.8 Hz, H-6),
4.24 (ddd, 1H, H-60), 3.92, 3.83 (2d, 2H, J = 13.3 Hz,
PhCH2S); 13C NMR (50.3 MHz, CDCl3): d 190.0 (C-
3), 148.0 (C-5), 137.0, 129.0, 128.6, 127.4 (C-aromatic),
125.8 (C-4), 83.4 (C-2), 59.0 (C-6), 34.8 (PhCH2S). Anal.
Calcd for C12H12O2S: C, 65.43; H, 5.49; S, 14.56.
Found: C, 65.67; H, 5.51; S, 14.43.
0
H-3), 4.53 (dd, 1H, J1,1 = 11.6 Hz, J1,8a = 2.3 Hz, H-
1), 3.90, 3.81 (2d, 2H, J = 13.3 Hz, PhCH2S), 3.59 (dd,
1H, J1 ,8a = 1.7 Hz, H-10), 3.09 (dd, 1H, J4a,5 = 6.5 Hz,
0
0
0
3.6. S-Benzyl 3,4-dideoxy-1-thio-a-L-glycero-pent-3-eno-
pyranoside (7)
J4a,8a = 5.3 Hz, H-4a), 2.53 (d, 1H, J5,5 = 17.6 Hz,
H-5), 2.35 (m, 1H, H-8a), 2.21 (br dd, 1H,
0
J8a,8 = 11.7 Hz, J8,8 = 17.3 Hz, H-8), 1.96 (br d, 1H,
To a solution of 6 (155 mg, 0.70 mmol, ee >42%) in dry
MeOH (14 mL) was added cerium(III) chloride heptahy-
drate (96 mg, 0.26 mmol).16 The solution was stirred for
5 min at room temperature and then cooled to 0 ꢁC.
Sodium borohydride (29 mg, 0.77 mmol) was added
and the stirring was maintained for 15 min, when TLC
(2:1 hexane–EtOAc) showed formation of a more polar
H-50), 1.83 (br dd, 1H, H-80), 1.62, 1.56 (2 br s, 6H, 2
CH3); 13C NMR (125 MHz, CDCl3):
d
203.7
(C-4), 137.1, 129.1, 128.6, 127.4 (C-aromatic), 123.5,
122.9 (C-6,7), 85.9 (C-3), 64.4 (C-1), 44.4 (C-4a), 36.6
(C-8a), 35.3, 31.4, 28.8 (C-5,8, PhCH2S), 19.1, 18.7
(2CH3). Anal. Calcd for C18H22O2S: C, 71.49; H, 7.33;
S, 10.60. Found: C, 71.63; H, 7.27; S, 10.76.