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M. J. Cook et al. / Tetrahedron 60 (2004) 5085–5092
dissolved in methanol (10 mL), 12 M HCl (6 drops) was
added and the mixture stirred for 1 h. The mixture was
filtered through a plug of celite and the solvents removed in
vacuo. The residue was dissolved in acetic anhydride
(10 mL), to this was added pyridine (6 mL) and DMAP
(22 mg, 0.18 mmol) and the solution was stirred for 18 h.
The solvents were removed in vacuo and the residue diluted
with CH2Cl2 (80 mL) which was washed with NaHCO3
(2£80 mL) and brine, dried (MgSO4), filtered and concen-
trated in vacuo. The residue was purified via column
chromatography (4:1 petroleum ether–ethyl acetate) to
afford a 1:1 mixture of diastereomers (88 mg, 32%
combined yield), which were separable.
115 8C (dichloromethane–40–60 petroleum ether): Rf 0.15
(2:1 40–60 petroleum ether–dichloromethane); [a]2D0¼
287.3 (c 1.58, CHCl3); IR: nmax (thin film)/cm21 1716s
(CvO), 1639m, 1450w, 1299m, 1237s, 1173w, 1087s,
1
1066s, 1022m, 953m; H NMR: (CDCl3, 400 MHz): dH
8.05 (4H, d, J¼8.5 Hz, HAr), 7.58 (2H, tq, J¼6.0 Hz, 1.5,
HAr), 7.45 (4H, t, J¼8.0 Hz, HAr), 6.72 (1H, d, J¼6.5 Hz,
H-1), 5.43–5.39 (1H, m, H-3), 5.39–5.36 (1H, m, H-4),
5.15 (1H, ddd, J¼7.5, 5.0, 1.5 Hz, H-2), 4.42 (1H, ddd,
J¼13.0, 3.0, 1.5 Hz, H-5), 4.22 (1H, dd, J¼13.0, 2.0 Hz,
H-50); 13C NMR: (CDCl3, 75 MHz): dC 165.5 (CvO), 165.4
(CvO), 148.3 (C-1), 133.4, 133.2, 129.9, 129.8, 129.7,
129.4, 128.5, and 128.4 (CAr), 97.5 (C-2), 67.6 (C-4), 64.0
(C-3), 63.9 (C-5); LRMS m/z: (CI) 283 (1%), 203 (65%,
[M2PhCO2]þ), 161 (10%), 123 (100%), 105 (95%), 81
(95%); HRMS (CI) C12H11O3 [M2(PhCO2)]þ requires:
203.0708; found: 203.0711.
(2S, 3R, 4R 5R) Methyl 30-(3,4,5-triacetoxytetrahydropyran-
2-yl)propionate (9) was isolated as a colourless solid: Rf
0.35 (1:1 ethyl acetate–petroleum ether); IR: nmax (neat)/
cm21 2925w, 2858w (C–H), 1748s (CvO); 1H NMR
(400 MHz, CDCl3): dH 5.34 (1H, dd, J¼3.5, 1.0 Hz, H-3),
5.20 (1H, td, J¼10.0, 5.5 Hz, H-5), 5.03 (1H, dd, J¼10.0,
3.5 Hz, H-4), 4.14 (1H, dd, J¼11.0, 5.5 Hz, H-6eq), 3.67
(3H, s, OMe), 3.58 (1H, ddd, J¼9.5, 4.5, 1.0 Hz, H-2), 3.23
(1H, dd, J¼11.0, 10.0 Hz, H-6ax), 2.42 (2H, m, H-20), 2.16,
2.03, and 2.00 0 (9H, 3£s, Ac), 1.91–1.83 and 1.75–1.67
(2H,0 2£m, H-3 ); 13C NMR (100 MHz, CDCl3): dC 172.6
(C-1 ), 169.9, 169.5 and 169.4 (MeCO2), 75.8 (C-2), 71.4
(C-40), 69.4 (C-3), 66.7 (C-6), 66.2 (C-5), 51.2 (OMe), 29.2
(C-2 ), 25.5 (C-30), 20.3, 20.2 and 20.1 (O2CMe); MS (CIþ)
m/z: 347 (1%, MHþ), 315 (26%, [M2OMe]þ), 273 (8%),
226 (56%), 184 (100%); HRMS (CIþ) m/z: C15H23O9
(MHþ) requires: 347.1342; found: 347.1349.
4.1.5. 3,4-O,O0-Isopropylidene D-arabinal (6g).21 Di-O-
acetyl D-arabinal (6a) (1.0 g, 5 mmol), was treated with
sodium methoxide solution (20 mg of Na/20 mL of MeOH)
and stirred for 3 h. The mixture was passed through a plug
of celite, then concentrated in vacuo and redissolved in dry
dichloromethane (30 mL), then 2,2-dimethoxypropane
(1.23 mL, 1.04 g, 10 mmol) and 2,3-dichloro-5,6-dicyano-
para-benzoquinone (114 mg, 0.5 mmol) were added and the
mixture was stirred for 12 h. The resulting dark green
solution was concentrated in vacuo and chromatographed
directly (dichloromethane) to afford 6g (562 mg, 72%) as a
colourless oil: Rf 0.3 (dichloromethane); [a]2D2¼þ52 (c 0.8,
CH2Cl2); IR: nmax (thin film)/cm21 2985w, 1456w, 1380m,
1371m, 1245m, 1215m, 1108m, 1059s, 995s, 933w; 1H
NMR: (300 MHz, CDCl3): dH 6.55 (1H, dd, J¼6.0, 1.0 Hz,
H-1), 5.12 (1H, dd, J¼6.0, 4.0 Hz, H-2), 4.49 (1H, dd,
J¼6.0, 5.0 Hz, H-3), 4.20 (1H, ddd, J¼8.0, 6.0, 5.5 Hz,
H-4), 4.03 (1H, ddd, J¼11.0, 4.0, 1.0 Hz, H-5a), 3.63 (1H,
dd, J¼11.0, 8.0 Hz, H-5b), 1.49 (3H, br. s, CH3), 1.39 (3H,
br.s, CH3); 13C NMR: (75 MHz, CDCl3): dC 147.7 (C-1),
108.9 (CCH3), 100.0 (C-2), 70.5 (C-3), 67.1 (C-4), 65.0
(C-5), 28.4 (CH3), 26.1 (CH3); LRMS m/z: (CI) 157
([MþH]þ, 3%) 149 (4%), 137 (8%), 99 (45%,
[M2(CH3)2COþH]þ), 84 (80%), 59 (100%); HRMS (CI)
C8H13O3 [Mþ1]þ requires 157.0865; found: 157.0866.
4.1.6. (2S, 5S)-Ethyl 30-(5,6-dihydro-5-(trimethyl-
acetoxy)-2H-pyran-2-yl) propionate (7b). Ethyl 3-iodo-
zincpropionate (prepared according to the general procedure
from ethyl 3-iodopropionate (483 mg, 2.12 mmol)) was
cooled to 230 8C and di-O-(trimethylacetyl) D-xylal (6b)18
(300 mg, 1.06 mmol) in dichloromethane (2 mL) was added
followed by BF3·OEt2 (301 mg, 2.12 mmol). The solution
was allowed to warm to room temperature over 12 h, then
washed with ice cold brine (2£10 mL), dried (Na2SO4) and
concentrated in vacuo. The resulting residue was subjected
to column chromatography (9:1 petroleum ether–ethyl
acetate) to afford the title compounds (213 mg,
0.752 mmol, 71%) as a 23:1 mixture of b and a
diastereomers. Only the major component b-7b could be
isolated in pure form, however, 1H NMR of the crude reaction
mixture indicated the presence of the other diastereomer.
(2S, 3S, 4S, 5R) Methyl 30-(3,4,5-triacetoxytetrahydropyran-
2-yl)propionate (10) isolated as a colourless oil: Rf 0.40 (1:1
ethyl acetate–petroleum ether); IR: nmax (neat)/cm21
2954w, 2882w (C–H), 1749s (CvO); 1H NMR
(400 MHz, CDCl3): dH 5.62 (1H, t, J¼3.0 Hz, H-4), 4.97
(1H, ddd, J¼10.5, 5.5, 3.0 Hz, H-5), 4.68 (1H, dd, J¼10.0,
3.0 Hz, H-3), 3.83 (1H, ddd, J¼10.5, 5.5, 1.0 Hz, H-6eq),
3.68 (3H, s, OMe), 3.66 (1H, td, J¼10.0, 3.0 Hz, H-2), 3.59
(1H, t, J¼10.5 Hz, H-6ax), 2.48 (1H, m, H-20), 2.42 (1H, m,
H-20), 2.16, 2.02, and 2.01 (9H, 3£s, Ac), 1.99–1,91 and
1.68–1.60 (2H0, 2£m, H-30); 13C NMR (100 MHz, CDCl3):
dC 173.1 (C-1 ), 169.4, 168.8, and 168.7 (MeCO2), 72.4
(C-2), 70.1 (C-3), 68.0 (C-4), 66.7 (C-5), 63.4 (C-6), 51.6
(OMe), 29.4 (C-20) 26.6 (C-30), 20.8, 20.7, and 20.6
(O2CMe); MS (CIþ) m/z: 347 (4%, MHþ), 315 (33%,
[M2OMe]þ), 287 (13%, [M2OAc]þ), 273 (10%), 213
(12%), 185 (40%), 167 (86%), 61 (100%); HRMS (CIþ)
m/z: C15H23O9 (MHþ) requires: 347.1342; found: 347.1342.
4.1.4. Di-O-benzoyl D-xylal (6c). Di-O-acetyl D-xylal (6a)
(1.5 g, 7.5 mmol), was treated with sodium methoxide
solution (20 mg of Na/20 mL of MeOH) and stirred for 3 h.
The mixture was passed through a plug of celite, then
concentrated in vacuo and redissolved in dichloromethane
(20 mL) to which pyridine (10 mL) and DMAP (100 mg,
0.82 mmol) were added. The solution was cooled to 0 8C,
and benzoyl chloride (5.22 mL, 6.37 g, 45 mmol) was added
slowly over 20 min. The mixture was stirred for 16 h, then
concentrated in vacuo and chromatographed directly (2:1
40–60 petroleum ether–dichloromethane) to afford 6c
(1.68 g, 69%) as a colourless crystalline solid. Mp: 113–
(2S, 5S) Ethyl 30-(5,6-dihydro-5-(trimethylacetoxy)-2H-
pyran-2-yl)-propionate b-7b, was isolated as a colourless