Application to the Synthesis of Chiral Synthons
5.3 mmol) was treated with NaBH4 (0.100 g, 2.7 mmol) in CH2-
Cl2/MeOH (2/1) (20 mL). After the usual workup the crude
reduction mixture was treated with KOH (0.356 g, 6.4 mmol) in
MeOH (20 mL). After the usual work up column chromatography
(hexanes/ethyl acetate 8/2) afforded (2S,3R,4S)-(+)-anti,syn-3 (ee
> 99%, HPLC) (0.207 g, 19%) and (2R,3R,4S)-(-)-anti,anti-3 (ee
> 99%, HPLC) (0.262 g, 24%).
(68), 104 (100). Anal. Calcd for C16H22O2: C, 78.01; H, 9.00.
Found: C, 78.19; H, 9.15.
(f) (4R,5S,6R,E)-2,2,4,5-Tetramethyl-6-styryl-1,3-dioxane ((4R,5S,
6R)-anti,syn-27). Treatment of (2R,3S,4R)-anti,syn-3 (3.30 g, 0.016
mol) gave (4R,5S,6R)-anti,syn-27 (3.66 g, 93%): [R]D ) -51.5 (c
1
) 0.80, CHCl3); H NMR (250 MHz, CDCl3) δ 7.40-7.10 (m,
5H), 6.58 (d, 1H, J ) 16.1 Hz), 6.22 (dd, 1H, J ) 16.1, 7.2 Hz),
4.17 (quintuplet, 1H, J ) 6.5 Hz), 3.93 (t, J 7.5 Hz, 1H), 1.83 (m,
1H), 1.42 (s, 6H), 1.13 (d, J ) 6.5 Hz, 3H), 0.90 (d, 1H, J ) 6.8
Hz); 13C NMR (62.90 MHz, CDCl3) 136.7, 131.0, 128.9, 128.3,
127.4, 126.4, 100.4, 75.8, 64.8, 40.1, 24.9, 24.4, 16.6, 11.1; GC/
MS tR 20.32 min, m/z 246 (M+, 1), 188 (35), 133 (100), 104 (73).
Anal. Calcd for C16H22O2: C, 78.01; H, 9.00. Found: C, 77.81; H,
8.89.
Preparation of Acetonides. Treatment of the suitable diol (0.022
mol) with dimethoxypropane (10 mL) and acetone (100 mL) in
the presence of a catalytic amount of pyridinium p-toluenesulfonate
gave, after the usual workup, the corresponding acetonide.
(a) (4R,6R,E)-2,2,4-Trimethyl-6-styryl-1,3-dioxane ((4R,6R)-syn-
25). (2R,4R)-syn-1 (4.30 g, 0.022 mol) gave (4R,6R)-syn-25 (4.93
1
g, 95%): mp 53-55 °C; [R]D ) +41.4 (c ) 1.51, CHCl3); H
NMR (250 MHz, CDCl3) δ 7.50-7.10 (m, 5H), 6.59 (d, 1H, J )
15.9, 1.0 Hz), 6.17 (dd, 1H, J ) 15.9, 6.2 Hz), 4.53 (ddd, 1H, J )
2.5, 6.2, 11.4 Hz), 4.21 (ddq, 1H, J ) 2.5, 11.4, 6.1 Hz), 1.62 (dt,
1H, J ) 13.0, 2.6 Hz), 1.52 (s, 3H), 1.47 (s, 3H), 1.36 (m, 1H),
1.20 (d, 3H, J ) 6.1 Hz);13C NMR (62.90 MHz, CDCl3) 136.8,
130.6, 130.1, 128.5, 127.6, 126.6, 98.8, 70.1, 65.0, 38.9, 30.4, 22.2,
19.9; GC/MS tR 20.37 min, m/z 232 (M+, 1), 174 (17), 157 (28),
104 (100). Anal. Calcd for C15H20O2: C, 77.55; H, 8.68. Found:
C, 77.41; H, 8.79.
Ozonolysis of Acetonides. A solution of the suitable acetonide
(0.021 mol) in CH2Cl2-MeOH (2:1) (300 mL) was treated with
ozone. The reaction mixture was quenched with triphenylphosphine
and chromatographed on a silica gel column (hexane/ethyl acetate
8/2) to afford the corresponding carbonyl compound.
(a) (4R,6R)-2,2,6-Trimethyl-1,3-dioxane-4-carbaldehyde ((4R,6R)-
syn-7). Acetonide (4R,6R)-syn-25 (4.80 g, 0.021 mol) afforded
(4R,6R)-syn-7 (2.49 g, 75%); [R]D ) +72.5 (c ) 1.18, CHCl3); 1H
NMR (250 MHz, CDCl3) δ 9.59 (s, 1H), 4.30 (dd, 1H, J ) 12.2,
2.9 Hz), 4.05 (m, 1H), 1.74 (dt, 1H, J ) 12.8, 2.9 Hz), 1.48 (s,
6H), 1.30 (m), 1.22 (d, 1H, J ) 6.4 Hz);13C NMR (62.90 MHz,
CDCl3) 201.3, 99.1, 74.0, 64.5, 32.6, 29.8, 22.1, 19.5; GC/MS tR
(b) (4S,6R,E)-2,2,4-Trimethyl-6-styryl-1,3-dioxane ((4S,6R)-anti-
25). Treatment of (2S,4R)-anti-1 (3.50 g, 0.018 mol) gave (4S,6R)-
anti-25 (3.97 g, 94%) containing 10% of the starting diol: [R]D )
1
+71.2 (c ) 1.02, CHCl3); H NMR (250 MHz, CDCl3) δ 7.40-
-
5.97 min, m/z 143 (M+ 15, 21), 129 (23), 59 (100), 43 (92).
7.15 (m, 5H), 6.55 (d, 1H, J ) 16 Hz), 6.22 (dd, 1H, J ) 16.0, 6.3
Hz), 4.52 (dt, J ) 8.8, 6.5 Hz, 1H), 4.06 (dquintuplet, 1H, J ) 8.8,
6.5 Hz), 1.90 (ddd, J ) 12.8, 8.8, 6.5 Hz, 2H), 1.73 (ddd, J )
Anal. Calcd for C8H14O3: C, 60.74; H, 8.92. Found: C, 60.65; H,
8.86.
(b) Methyl 3,5-Dideoxy-L-threopentofuranoside) (L-28). Ac-
etonide (4S,6R)-anti-25 (3.80 g, 0.016 mol) afforded L-28 as a 3:1
mixture of two anomers (0.802 g, 38%): 1H NMR (250 MHz,
CDCl3) 4.85 (s, major anomer), 4.70 (d, J ) 4.5 Hz, minor anomer),
4.30-4.13 (m, both anomers), 3.53 (s, minor anomer), 3.38 (s,
major anomer), 2.56-2.32 (m, both anomers), 1.49 (m, both
anomers), 1.39 (d, J ) 6.1 Hz, major anomer), 1.34 (d, J ) 6.3
Hz, minor anomer); GC/MS tR 4.38 min major anomer, m/z 101
(M+ - 31, 9), 72 (48), 57 (100), 43 (42), tR 5.27 min minor anomer,
m/z 117 (M+ - 15, 3), 101 (10), 72 (42), 57 (100), 43 (47). Anal.
Calcd for C6H12O3: C, 54.53; H, 9.15. Found: C, 54.64; H, 9.27.
(c) 1-((4R,6R)-2,2,6-Trimethyl-1,3-dioxan-4-yl)ethanone ((4R,6R)-
syn-8). Acetonide (4R,6R)-syn-26 (7.80 g, 0.032 mol) afforded
(4R,6R)-syn-8 (3.76 g, 69%): [R]D ) +77.8 (c ) 0.78, CHCl3);
1H NMR (250 MHz, CDCl3) 4.26 (dd, 1H, J ) 12.1, 2.6 Hz), 4.04
(ddq, 1H, J ) 11.6, 2.6, 6.4 Hz), 2.21 (s, 3H), 1.76 (dt, 1H, J )
13.0, 2.6 Hz), 1.46 (s, 6H)), 1.27 (m, 1H), 1.20 (d, 3H, J ) 6.4
Hz); 13C NMR (62.90 MHz, CDCl3) 209.2, 99.0, 75.1, 65.0, 34.3,
30.2, 25.4, 22.2, 19.6; GC/MS tR 8.88 min, m/z 157(M+ - 15, 12),
129 (50), 59 (100). Anal. Calcd for C9H16O3: C, 62.77; H, 9.36.
Found: C, 62.61; H, 9.18.
12.8, 8.8, 6.5 Hz, 2H), 1.42 (s, 6H), 1.23 (d, 1H, J ) 6.5 Hz); 13
C
NMR (62.90 MHz, CDCl3) 136.7, 131.9, 130.0, 128.6, 127.6, 126.5,
96.0, 69.5, 64.1, 42.2, 37.4, 22.2, 20.9; GC/MS tR 19.98 min, m/z
232 (M+, 1), 174 (12), 157 (14), 104 (100). Anal. Calcd for
C15H20O2: C, 77.55; H, 8.68. Found: C, 77.63; H, 8.53.
(c) (4R,6R,E)-2,2,4-Trimethyl-6-(1-phenylprop-1-en-2-yl)-1,3-
dioxane ((4R,6R)-syn-26). Treatment of (2R,4R)-syn-2 (7.60 g, 0.037
mol) gave (4R,6R)-syn-26 (8.10 g, 89%): [R]D ) -10.6 (c ) 1.04,
1
CHCl3); H NMR (250 MHz, CDCl3) δ 7.50-7.10 (m, 5H), 6.55
(br s, 1H), 4.37 (dd, 1H, J ) 11.1, 2.4 Hz), 4.07 (ddq, 1H, J )
11.1, 2.4, 6.4 Hz), 1.87 (d, J ) 1.1 Hz, 3H), 1.62 (dt, 1H, J )
13.0, 2.4 Hz), 1.53 (s, 3H), 1.47 (s, 3H), 1.41 (dt, J ) 13.0, 11.1
Hz, 1H), 1.21 (d, 3H, J ) 6.4 Hz); 13C NMR (62.90 MHz, CDCl3)
138.4, 137.9, 129.2, 128.1, 126.5, 125.6, 98.9, 74.5, 65.3, 37.8,
30.5, 22.4, 20.1, 14.2; GC/MS tR 21.58 min, m/z 246 (M+, 5), 188
(36), 171 (30), 118 (100). Anal. Calcd for C16H22O2: C, 78.01; H,
9.00. Found: C, 78.14; H, 9.12.
(d) (4R,6S,E)-2,2,4-Trimethyl-6-(1-phenylprop-1-en-2-yl)-1,3-
dioxane ((4R,6S)-anti-26). Treatment of (2R,4S)-anti-2 (6.30 g,
0.030 mol) gave (4R,6S)-anti-26 (6.77 g, 90%): [R]D ) -13.8 (c
1
) 0.73, CHCl3); H NMR (250 MHz, CDCl3) δ 7.40-7.10 (m,
(d) 1-((4S,6R)-2,2,6-Trimethyl-1,3-dioxan-4-yl)ethanone ((4S,6R)-
anti-8). Acetonide (4R,6S)-anti-26 (6.50 g, 0.026 mol) afforded
(4S,6R)-anti-8 (2.95 g, 65%): [R]D ) -61.8 (c ) 1.10, CHCl3);
1H NMR (250 MHz, CDCl3) 4.23 (t, J ) 7.6 Hz, 1H), 3.96
(dquintuplet, 1H, J ) 9.9, 6.2 Hz), 2.22 (s, 3H), 2.01 (ddd, J )
13.0, 7.6, 6.2, 1H), 1.71 (ddd, J ) 13.0, 9.9, 7.6, 1H), 1.40 (s,
6H), 1.21 (d, 1H, J ) 6.2 Hz); 13C NMR (62.90 MHz, CDCl3)
209.0, 100.6, 73.2, 62.8, 34.5, 26.2, 24.5, 21.8; GC/MS tR 7.09
5H), 6.52 (br s, 1H, CHdC), 4.37 (dd, J ) 9.2, 6.5 Hz, 1H), 4.03
(dquintuplet, 1H, J ) 9.2, 6.5 Hz), 1.94 (ddd, J ) 13.0, 9.2, 6.5,
1H), 1.87 (d, J ) 1.1 Hz, 3H), 1.69 (ddd, J ) 13.0, 9.2, 6.5, 1H),
1.44 (s, 3H), 1.43 (s, 3H), 1.24 (d, 1H, J ) 6.5 Hz); 13C NMR
(62.90 MHz, CDCl3) 138.3, 138.0, 129.2, 128.2, 126.5, 125.1,
100.6, 71.7, 63.3, 38.7, 31.8, 25.3, 22.8, 14.3; GC/MS tR 21.21
min, m/z 246 (M+, 2), 188 (35), 118 (100). Anal. Calcd for
C16H22O2: C, 78.01; H, 9.00. Found: C, 77.86; H, 8.78.
(e) (4S,5S,6R,E)-2,2,4,5-Tetramethyl-6-styryl-1,3-dioxane ((4S,5S,
6R)-anti,anti-27). Treatment of (2S,3S,4R)-anti,anti-3 (3.30 g, 0.016
mol) gave (4S,5S,6R)-anti,anti-27 (3.58 g, 91%): [R]D ) -23.1
(c ) 1.04, CHCl3); 1H NMR (250 MHz, CDCl3) δ 7.50-7.10 (m,
5H), 6.59 (d, 1H, J ) 15.9 Hz), 6.11 (dd, 1H, J ) 15.9, 7.5 Hz),
4.06 (dd, 1H, J ) 10.0, 7.5 Hz), 3.68 (dq, 1H, J ) 10.0, 6.1 Hz),
1.52 (s, 3H), 1.45 (s, 3H), 1.34 (m, 1H), 1.21 (d, 3H, J ) 6.1 Hz),
0.81 (d, J ) 6.5 Hz, 3H); 13C NMR (62.90 MHz, CDCl3) 136.9,
133.3, 128.8, 128.6, 127.9, 126.8, 98.3, 76.9, 70.9, 41.0, 30.4, 20.1,
20.0, 12.8; GC/MS tR 20.44 min, m/z 246 (M+, 5), 188 (51), 171
-
min, m/z 157 (M+ 15, 8), 129 (58), 59 (100). Anal. Calcd for
C9H16O3: C, 62.77; H, 9.36. Found: C, 62.96; H, 9.49.
(e) (4S,5S,6S)-2,2,5,6-Tetramethyl-1,3-dioxane-4-carbaldehyde
((4S,5S,6S)-anti,anti-9). Acetonide (4S,5S,6R)-anti,anti-27 (3.30 g,
0.013 mol) afforded (4S,5S,6S)-anti,anti-9 (1.54 g, 67%): [R]D )
1
-136.8 (c ) 0.70, CHCl3); H NMR (250 MHz, CDCl3) δ 9.51
(d, J ) 2 Hz), 3.82 (dd, 1H, J ) 11.0, 2 Hz), 3.66 (dq, 1H, J )
10.0, 5.8 Hz), 1.53-1.39 (m + 2s, 7H), 1.21 (d, 3H, J ) 5.8 Hz),
0.88 (d, J ) 6.5 Hz, 3H); 13C NMR (62.90 MHz, CDCl3) 200.3,
98.4, 78.9, 70.3, 35.3, 29.9, 19.8, 19.7, 11.7; GC/MS tR 8.24 min,
J. Org. Chem, Vol. 71, No. 14, 2006 5237