A. Leyva et al. / Tetrahedron 64 (2008) 2348e2358
2357
62.7, 48.0, 47.9, 17.9, 17.6, ꢀ1.4 (3C). E.A. Calcd for
Rf (20% Et2O in P.E.): 0.37. 1H NMR d: 7.44 (1H, m), 7.14
(3H, m), 6.86 (1H, d, J¼16), 6.02 (1H, dd, J¼16, 7), 4.56 (1H,
ddd, J¼11, 7, 3), 3.73 (1H, t, J¼11), 3.50 (1H, dd, J¼11, 3),
3.34 (3H, s), 3.30 (3H, s), 2.34 (3H, s), 1.34 (3H, s), 1.32 (3H,
s). HRMS (ESI) m/z 315.1591 [(MþNa)þ; calcd for
C17H24O4Na: 315.1573].
C13H26O4Si: C 56.90, H 9.55. Found: C 57.97, H 9.43.
4.1.16. (2R,3R,5S)-5-((E)-2-Bromovinyl)-2,3-dimethoxy-
2,3-dimethyl-1,4-dioxane (27)
Vinylsilane 26 (54.8 mg, 0.2 mmol) was dissolved in aceto-
nitrile (1 mL) under argon in a flask protected from light. NBS
(71.2 mg, 0.4 mmol) was added and the tube flushed again
with argon. The mixture was heated to 90 ꢁC for 1 h. Flash
chromatography (5% ether in P.E.) yielded 27 as a brown oil
(E/Z 15:1, 19.1 mg, 0.07 mmol, 34%).
4.1.19. (2R,3R,5S)-2,3-Dimethoxy-2,3-dimethyl-5-((E)-
prop-1-enyl)-1,4-dioxane (32)
Trimethylboroxine (99.0 mL, 0.71 mmol) was added to
PdCl2(dppf)$CH2Cl2 (3.87 mg, 0.005 mmol), 14 (155.6 mg,
0.47 mmol) and potassium carbonate (196.7 mg, 1.42 mmol)
in 1,4-dioxane (2 mL) under argon and heated to 110 ꢁC in
a sealed tube for 48 h. The mixture was then passed through
a pad of silica and eluted with CH2Cl2 (100 mL). Water
(100 mL) was added to the filtrate and the aqueous phase
was further extracted with ether (2ꢂ50 ml). The organic frac-
tions were combined and washed with water (2ꢂ50 mL) and
brine (50 mL), then dried (Na2SO4), filtered and concentrated
in vacuo to give 32 as a yellow oil (96.4 mg, 0.45 mmol, 95%).
Rf (10% Et2O in P.E.): 0.29. [a]2D5 ꢀ139.3 (c 1.115, CDCl3).
Rf (10% Et2O in P.E.): 0.56. [a]2D5 ꢀ107.3 (c 0.34, CDCl3).
1
IR (neat, cmꢀ1): 2782, 1630, 1142, 1117. H NMR d: 6.46
(1H, dd, J¼14, 1), 6.12 (1H, dd, J¼14, 6), 4.36 (1H, dddd,
J¼11, 6, 3, 1), 3.60 (1H, t, J¼11), 3.42 (1H, dd, J¼11, 3),
3.36 (3H, s), 3.35 (3H, s), 1.29 (3H, s), 1.27 (3H, s). 13C
NMR d: 133.1, 109.8, 99.3, 97.9, 68.2, 62.2, 48.1, 48.0,
17.7, 17.5. E.A. Calcd for C10H17BrO4: C 42.72, H 6.09, Br
28.42. Found: C 43.36, H 6.21, Br 28.36.
4.1.17. (2E,4E)-Ethyl-5-((2S,5R,6R)-5,6-dimethoxy-5,6-
dimethyl-1,4-dioxan-2-yl)penta-2,4-dienoate (29a)
1
IR (neat, cmꢀ1): 2949, 1730, 1140, 1118. H NMR d: 5.77
Ethyl acrylate (97.5 mL, 0.9 mmol), P(t-Bu)3 (60 mL of
a 1 M solution in toluene, 0.06 mmol, 10 mol %) and dicyclo-
hexylmethylamine (192.6 mL, 0.9 mmol) were added to
Pd2dba3 (27.6 mg, 0.03 mmol, 10 mol %) and 14 (196.8 mg,
0.6 mmol) in toluene (6 mL) under argon and heated to
120 ꢁC in a sealed tube for 24 h. The mixture was then passed
through a pad of silica, eluted with CH2Cl2 (600 mL) and the
solvents were removed in vacuo. The crude was purified by
column chromatography (P.E.eEt2O 4:1) to yield 29a as yel-
low oil (93 mg, 0.31 mmol, 52%).
(1H, dd, J¼15, 7), 5.38 (1H, ddd, J¼15, 7, 1), 4.26 (1H,
ddd, J¼11, 7, 3), 3.58 (1H, t, J¼11), 3.36 (1H, dd, J¼11,
3), 3.26 (3H, s), 3.24 (3H, s), 1.68 (3H, dd, J¼6, 1), 1.28
(3H, s), 1.26 (3H, s). 13C NMR d: 130.4, 127.0, 99.0, 97.7,
68.7, 63.0, 47.9, 47.9, 17.9, 17.9, 17.6. E.A. Calcd for
C11H20O4: C 61.09, H 9.32. Found: C 60.66, H 8.96.
4.1.20. (2R,3R,5S)-2,3-Dimethoxy-2,3-dimethyl-5-
((3,4,5-trimethoxyphenyl)ethynyl)-1,4-dioxane (35)
Hunig’s base (543 mL, 3.12 mmol) was added to 15
¨
Rf (50% Et2O in P.E.): 0.36. [a]2D5 ꢀ91.3 (c 0.665, CDCl3).
IR (neat, cmꢀ1): 2957, 1714, 1649, 1619, 1142, 1116. 1H
NMR d: 7.20 (1H, dd, J¼15, 11), 6.43 (1H, dd, J¼15, 11),
5.94 (1H, dd, J¼15, 6), 5.89 (1H, d, J¼15), 4.50 (1H, ddd,
J¼11, 6, 3), 4.19 (2H, q, J¼7), 3.59 (1H, t, J¼11), 3.44
(1H, dd, J¼11, 3), 3.27 (3H, s), 3.25 (3H, s), 1.31 (3H, s),
1.28 (3H, s), 1.23 (3H, t, J¼7). 13C NMR d: 166.7, 143.3,
136.8, 129.8, 122.3, 99.2, 97.9, 67.7, 62.5, 60.3, 48.1, 48.0,
17.8, 17.5, 14.2.
(832 mg, 4.16 mmol), 34 (612.5 mg, 2.08 mmol), Pd(PPh3)2-
Cl2 (73.0 mg, 0.104 mmol) and CuI (19.8 mg, 0.104 mmol)
in toluene (12.5 mL) under argon, and stirred at rt for 24 h.
The mixture was then passed through a pad of silica and eluted
with ether (500 mL). Water (500 mL) was added to the filtrate
and the aqueous phase was further extracted with ether
(2ꢂ500 mL). The organic fractions were combined and
washed with water (2ꢂ500 mL) and brine (500 mL), then
dried (Na2SO4), filtered and concentrated in vacuo to
give 35 as a brown oil (556 mg, 1.52 mmol, 73%, eq./ax.
ratio 7:1).
4.1.18. (2R,3R,5S)-2,3-Dimethoxy-2,3-dimethyl-5-
(2-methylstyryl)-1,4-dioxane (30)
1
IR (neat, cmꢀ1): 2950, 2248, 1577, 1115. H NMR d: 6.66
Vinyl iodide 14 (32.8 mg, 0.10 mmol), o-tolylboronic acid
(20.39 mg, 0.15 mmol), Pd(OAc)2 (1.12 mg, 0.005 mmol), SPhos
(2-dicyclohexylphosphino-20,60-dimethoxybiphenyl, 2.63 mg,
0.0075 mmol) and K3PO4 (42.4 mg, 0.20 mmol) were dis-
solved in toluene (0.5 mL) under argon and heated at
110 ꢁC in a sealed tube for 4 h. The mixture was then passed
through a pad of silica and eluted with CH2Cl2 (50 mL). Wa-
ter (50 mL) was added to the filtrate and the aqueous phase
was further extracted with ether (2ꢂ25 mL). The organic
fractions were combined and washed with water
(2ꢂ25 mL) and brine (25 mL), then dried over Na2SO4, fil-
tered and concentrated in vacuo to give 30 as a brown oil
(22.46 mg, 0.077 mmol, 77%).
(2H, s), 4.83 (1H, dd, J¼11, 3), 3.88 (1H, t, J¼11), 3.80
(s, 3H), 3.78 (6H, s), 3.59 (1H, dd, J¼11, 3), 3.32 (3H, s),
3.26 (3H, s), 1.32 (3H, s), 1.25 (3H, s). 13C NMR d: 152.9,
139.1, 117.1, 109.2, 99.4, 97.9, 86.4, 83.1, 62.6, 60.8, 59.4,
59.1, 48.4, 48.0, 17.7, 17.5. HRMS (ESI) m/z 367.1773
[(MþH)þ; calcd for C19H27O7: 316.1757].
4.1.21. (2R,3R,5S)-5-((4-Chlorophenyl)ethynyl)-2,3-
dimethoxy-2,3-dimethyl-1,4-dioxane (37)
Hunig’s base (105 mL, 0.60 mmol) was added to 15
¨
(80 mg, 0.40 mmol), 36 (427.7 mg, 0.20 mmol), Pd(PPh3)2Cl2
(14.0 mg, 0.02 mmol) and CuI (3.8 mg, 0.02 mmol) in toluene
(1 mL) under argon, and stirred at rt for 24 h. The mixture was