D.A. Evans et al. / Tetrahedron 64 (2008) 4671e4699
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5.33 (ddt, J¼1.5, 17.2 Hz, 1H), 5.22 (ddt, J¼1.5, 10.3 Hz, 1H),
5.07 (d, J¼9.5 Hz, 1H), 4.63e4.56 (m, 3H), 4.44 (d, J¼11.4 Hz,
1H), 4.14 (dd, J¼5.9, 7.0 Hz, 1H), 3.87 (s, 6H), 3.72 (d,
J¼10.6 Hz, 1H), 3.66 (m, 1H), 3.23 (s, 3H), 3.19 (dd, J¼10.3,
12.8 Hz, 1H), 3.12 (s, 3H), 2.71 (d, J¼13.6 Hz, 1H), 2.64 (d,
J¼13.5 Hz, 1H), 2.57 (m, 2H), 2.15 (dd, J¼4.8, 12.8 Hz, 1H),
1.71 (s, 3H), 1.67 (m, 2H), 1.41e1.37 (m, 1H), 0.87 (s, 9H),
0.82 (d, J¼6.6 Hz, 3H), 0.69 (d, J¼7.0 Hz, 3H), 0.05 (s, 6H);
13C NMR (100.6 MHz, CDCl3) d 176.0, 169.1, 149.0, 148.9,
135.5, 132.0, 129.5, 129.1, 121.0, 118.3, 111.4, 110.8, 98.8,
76.2, 72.6, 71.6, 70.6, 65.2, 55.9, 55.8, 55.2, 47.7, 43.3, 42.8,
42.2, 39.9, 38.5, 25.9, 18.0, 17.1, 12.4, 8.6, ꢀ4.1, ꢀ4.8.
solution. After stirring at rt overnight, the mixture turned
to a clear yellow solution. The reaction was quenched with
20 mL of satd NaHCO3 (aq) and extracted with 3ꢃ30 mL of
Et2O. The combined organic layers were dried over Na2SO4,
filtered, and concentrated in vacuo. Purification by flash
chromatography (10% EtOAc/hexanes) afforded 42.1 mg
(0.070 mmol, 79%) of the title compound. [a]2D3 þ13.3 (c
1.0, CH2Cl2); IR (CH2Cl2, film) 3481, 2957, 2928, 2849,
2365, 2945, 1738, 1677, 1461, 1377, 1313, 1264, 1219,
1
1140, 1081, 1027, 933, 834, 775 cmꢀ1; H NMR (400 MHz,
CDCl3) d 5.94e5.87 (m, 1H), 5.30 (dd, J¼1.5, 17.2 Hz,
1H), 5.22 (dd, J¼1.1, 10.3 Hz, 1H), 5.08 (d, J¼9.5 Hz, 1H),
4.57 (d, J¼5.5 Hz, 2H), 4.37e4.32 (m, 1H), 3.97e3.87 (m,
1H), 3.73 (dd, J¼1.5, 10.6 Hz, 1H), 3.66 (ddd, J¼4.0,
8.9 Hz, 1H), 3.24 (s, 3H), 3.16 (s, 3H), 2.90 (q, J¼7.3 Hz,
2H), 2.67 (d, J¼2.6 Hz, 2H), 2.67e2.60 (m, 1H), 2.37 (dd,
J¼9.2, 13.9 Hz, 1H), 2.14 (dd, J¼4.4, 13.2 Hz, 1H), 1.85e
1.63 (m, 2H), 1.75 (s, 3H), 1.42e1.36 (m, 1H), 1.26 (t,
J¼7.3 Hz, 3H), 0.87 (s, 9H), 0.83 (d, J¼6.6 Hz, 3H), 0.70
(d, J¼7.0 Hz, 3H), 0.05 (s, 6H); 13C NMR (100.6 MHz,
CDCl3) d 203.9, 169.4, 135.9, 132.3, 130.7, 118.6, 99.2,
76.0, 72.0, 70.9, 65.5, 56.3, 55.7, 48.0, 45.7, 43.6, 42.5,
40.2, 38.8, 26.2, 23.1, 18.3, 17.3, 14.8, 12.7, 9.0, ꢀ3.8,
ꢀ4.4; exact mass calcd for C30H54O8SSi [MþNa]þ:
625.3206, found: 625.3205 (FAB).
4.2.13. Prop-2-enyl-2-(6-{(3E)(1R,2R,6R)-6-[(3,4-dimeth-
oxyphenyl)methoxy]-7-ethylthio-2-methoxy-1,4-dimethyl-7-
oxohept-3-enyl}(2S,4S,5S)-2-methoxy-5-methyl-4-(1,1,2,2-
tetramethyl-1-silapropoxy)perhydro-2H-pyran-2-yl)acetate
To a solution of 5.80 mg (8.20 mmol) of acid 14 in 82 mL
of CH2Cl2 were added 1.50 mL (19.7 mmol) of ethanethiol,
2.30 mL (16.40 mmol) of triethylamine, and 2.40 mg
(94.0 mmol) of BOPeCl. The resulting solution was stirred
for 10 min at 0 ꢁC and then at rt for 5 h. The reaction was
quenched with 2 mL of H2O and extracted with 3ꢃ10 mL
of CHCl3. The combined organic layers were dried over
Na2SO4, filtered, and concentrated in vacuo. Purification by
flash chromatography (10/20% EtOAc/hexanes) afforded
3.9 mg (5.17 mmol, 63%) of the title compound as a clear
oil. TLC Rf¼0.59 (30% EtOAc/hexanes); [a]2D3 þ36.4 (c 0.7,
CH2Cl2); IR (CH2Cl2, film) 2954, 2933, 2862, 1739, 1682,
1595, 1518, 1464, 1421, 1380, 1323, 1263, 1159, 1144,
4.2.15. 2-[6((3E)(1R,2R,6R)-7-Ethylthio-6-hydroxy-2-meth-
oxy-1,4-dimethyl-7-oxohept-3-enyl)(2S,4S,5S)-2-methoxy-
5-methyl-4-(1,1,2,2-tetramethyl-1-silapropoxy)perhydro-
2H-pyran-2-yl]acetic acid (15)
1
1081, 1032, 1005, 933, 837, 776 cmꢀ1; H NMR (400 MHz,
Thioester (16.1 mg, 0.066 mmol) was dissolved in 0.27 mL
of dry THF at rt under N2. Palladium tetrakistriphenylphos-
phine (3.10 mg, 2.70 mmol), 33.0 mL (0.243 mmol) of triethyl-
amine, and 9.20 mL (0.243 mmol) of formic acid were then
added to the reaction mixture. After 4 h of stirring at rt, the
volatile solvents were removed in vacuo and dried under
reduced pressure. Purification by two column flash chromatog-
raphy (column 1 to remove impurities: linear gradient 50/
80% EtOAc/hexanes; column 2 to remove residual Pd(Ph3)4
salts: 10/30% EtOAc/hexaneþ1% AcOH) afforded 9.1 mg
(0.040 mmol, 60%) of the title compound. [a]2D3 þ5.0 (c 0.4,
CH2Cl2); IR (CH2Cl2, film) 3382, 2932, 2857, 1713, 1682,
1439, 1384, 1316, 1257, 1148, 1122, 1081, 1031, 1007, 837,
CDCl3) d 6.94e6.81 (m, 3H), 5.95e5.85 (m, 1H), 5.32 (ddt,
J¼1.5, 17.2 Hz, 1H), 5.22 (ddt, J¼1.5, 10.3 Hz, 1H), 5.02
(d, J¼8.8 Hz, 1H), 4.65 (d, J¼11.0 Hz, 1H), 4.57 (d,
J¼5.1 Hz, 2H), 4.38 (d, J¼11.0 Hz, 1H), 4.08 (t, J¼6.6 Hz,
1H), 3.88 (s, 3H), 3.87 (s, 3H), 3.88e3.83 (m, 1H), 3.72
(dd, J¼1.8, 10.6 Hz, 1H), 3.66 (ddd, J¼4.8, 9.5 Hz, 1H),
2.88 (q, J¼7.3 Hz, 2H), 2.70 (d, J¼13.5 Hz, 1H), 2.63
(d, J¼13.2 Hz, 1H), 2.49 (d, J¼7.0 Hz, 1H), 2.15 (dd,
J¼4.8, 12.8 Hz, 1H), 1.69 (d, J¼1.1 Hz, 3H), 1.69e1.59 (m,
2H), 1.42e1.35 (m, 1H), 1.26 (t, J¼7.3 Hz, 3H), 0.88 (s,
9H), 0.81 (d, J¼6.6 Hz, 3H), 0.67 (d, J¼7.3 Hz, 3H), 0.05
(s, 6H); 13C NMR (100.6 MHz, CDCl3) d 203.4, 169.1,
148.9, 148.8, 135.6, 134.7, 132.0, 129.6, 129.5, 129.4,
120.9, 118.3, 111.5, 110.8, 98.8, 83.2, 73.1, 71.5, 70.6,
65.2, 55.9, 55.8, 55.2, 47.7, 44.1, 43.4, 42.2, 39.9, 38.5,
25.9, 22.4, 18.0, 17.2, 14.6, 12.3, 8.7, ꢀ4.1, ꢀ4.7; exact
mass calcd for C39H64O10SSi [MþNa]þ: 775.3862, found:
775.3887 (ES).
776, 724 cmꢀ1 1H NMR (400 MHz, CDCl3) d 5.10 (d,
;
J¼9.5 Hz, 1H), 4.35 (dd, J¼4.0, 9.2 Hz, 1H), 3.91 (m, 2H),
3.67 (ddd, J¼4.4, 9.9 Hz, 1H), 3.26 (s, 3H), 3.18 (s, 3H),
2.91 (q, J¼7.7 Hz, 2H), 2.84 (d, J¼15.0 Hz, 1H), 2.66 (m,
1H), 2.61 (d, J¼15.4 Hz, 1H), 2.38 (dd, J¼9.2, 14.3 Hz,
1H), 2.09 (dd, J¼4.8, 12.8 Hz, 1H), 1.78 (m, 1H), 1.75 (d,
J¼1.1 Hz, 3H), 1.65 (dd, J¼6.2, 16.1 Hz, 1H), 1.52 (m, 1H),
1.27 (t, J¼7.32 Hz, 3H), 0.87 (s, 9H), 0.86 (d, J¼6.6 Hz,
3H), 0.79 (d, J¼7.3 Hz, 3H), 0.06 (s, 3H), 0.05 (s, 3H); 13C
NMR (100.6 MHz, CDCl3) d 203.9, 171.7, 136.3, 130.0,
99.2, 77.7, 76.0, 73.1, 70.3, 55.7, 48.6, 45.6, 43.2, 42.3,
40.2, 38.6, 26.0, 23.1, 18.2, 17.3, 14.8, 12.6, 9.4, ꢀ3.9,
ꢀ4.6; exact mass calcd for C27H50O8SSi [MþNa]þ:
585.2893, found: 585.2899 (ES).
4.2.14. Prop-2-enyl-2-[6-((3E)(1R,2R,6R)-7-ethylthio-6-
hydroxyl-2-methoxy-1,4-dimethyl-7-oxohept-3-enyl)-
(2S,4S,5S)-2-methoxy-5-methyl-4-(1,1,2,2-tetramethyl-
1-silapropoxy)perhydro-2H-pyran-2-yl]acetate
Thioester (66.5 mg, 0.088 mmol) was dissolved in 8.1 mL
of CH2Cl2 and 0.9 mL of MeOH at rt. Addition of 40.0 mg
(0.176 mmol) of DDQ to the reaction produced a clear green