9612
J. Mulzer et al. / Tetrahedron 60 (2004) 9599–9614
water, sodium thiosulfate and brine, dried (MgSO4), and
evaporated to give the iodide (11.58 g, 100%) as a slightly
yellow oil ([a]DZK20.1 (cZ1.21, CHCl3)) which was
used for the next step without purification. Sodium
phenylsulfinate (8.15 g, 49.7 mmol) in DMF (200 mL)
was added and the mixture was stirred at 110 8C overnight,
cooled to room temperature, quenched with NaHCO3 and
extracted with ether. The ether phase was washed with
brine, dried (MgSO4) and chromatographed (hexanes/ethyl
acetate 2:1) to give sulfone 41 (9.49 g, 79%) along with the
sulfinate (1.99 g, 17%).
110.07, 128.55, 129.08, 133.36, 139.03. IR (film): nZ2952,
2869, 1462, 1109, 1086 cmK1. MS (EI, 80 eV, 40 8C):
m/zZ364, 279, 223, 209, 167, 137, 109, 95, 69, 55, 41.
Anal. Calcd for C27H42O5S: C, 67.75; H 8.84. Found: C,
67.51, H, 7.83.
2.5.3. Synthesis of 43a. The diastereomeric mixture of
sulfones 42a (1.54 g, 3.22 mmol) in methanol (35 mL) was
treated at K20 8C with di-sodiumhydrogenphosphate
(1.83 g, 12.88 mmol) and sodium amalgam (10 g, 6%) and
stirred for 3 h. Water was added and the mixture was stirred
for 30 min. The mercury was removed by decantation and
the aqueous phase was extracted with ether. The ethereal
phase was washed with brine, dried (MgSO4), and
chromatographed (hexanes/ethyl acetate 10:1) to give 43a
(910 mg, 84%) as a colorless oil. 1H NMR (CDCl3): d
[ppm]Z0.89 (t, JZ7.6 Hz, 3H), 0.95 (s, 3H), 0.97 (s,
3H),1.09–1.63 (m, 15H), 1.84 (m, 2H), 2.01 (m, 1H), 2.23
(dd, JZ9.0, 13.0 Hz, 2H) 2.47 (m, 1H), 3.07 (quint, JZ
5.6 Hz, 1H), 3.32 (s, 3H), 3.46 (s, 2H), 3.49 (s, 2H). 13C
NMR (CDCl3): d [ppm]Z9.34, 22.53, 25.64, 25.80, 30.08,
32.67, 32.98, 33.82, 35.38, 40.05, 40.25, 40.30, 47.07,
47.49, 56.35, 71.64, 72.42, 82.04, 110.55. IR (film): nZ
2934, 2854, 1462, 1111 cmK1. MS (EI, 80 eV, 40 8C): m/
zZ338, 323, 309, 265, 241, 223, 209, 181, 167, 141, 128,
73, 69, 55. [a]DZK19.3 (cZ2.01, CHCl3). Anal. Calcd for
C21H38O3: C, 74.51; H 11.31. Found: C, 74.33, H, 10.75.
Compound 41. Solid with mp 60–61 8C: 1H NMR (CDCl3):
d [ppm]Z0.89 (s, 3H), 1.20–1.44 (m, 2H), 1.55–1.74 (m,
2H), 1.88 (m, 1H), 2.02 (m, 1H), 2.07–2.25 (m, 4H), 2.49
(m, 1H), AB-part of an ABX system: dA 3.05, dB 3.17, (JZ
14, 7, 5.8 Hz, 2H), 3.41 (d, JZ11 Hz, 1H), 3.46 (d, JZ
11 Hz, 1H), 7.60 (m, 3H), 7.92 (m, 2H). 13C NMR (CDCl3):
d [ppm]Z22.40, 22.58, 30.00, 32.58, 33.91, 39.55, 40.99,
47.29, 61.26, 71.86, 72.06, 109.84, 127.86, 129.22, 133.49,
140.06. IR (film): nZ2952, 2868, 1462, 1109, 1086 cmK1
.
MS (EI, 80 eV, 40 8C): m/zZ364, 279, 223, 209, 167, 137,
109, 95, 69, 55, 41. [a]DZK30.2 (cZ2.28, CHCl3). Anal.
Calcd for C20H28O4S: C, 65.90; H 7.74. Found: C, 65.62, H,
7.51.
Sulfinate. 1H NMR (CDCl3): d [ppm]Z0.95 (s, 3H), 0.96 (s,
3H), 1.13–1.43 (m, 2H), 1.60 (m, 2H), 1.81 (m, 2H), 1.92–
2.21 (m, 4H), 2.46 (m, 1H), 3.42 (s, 2H), 3.44 (s, 2H), 3.45
(m, 1H), 3.92 (m, 1H), 7.54 (m, 3H), 7.70 (m, 2H). 13C
NMR (CDCl3): d [ppm]Z22.50, 30.04, 30.33, 32.33, 39.24,
40.15, 43.79, 46.77, 46.85, 67.31, 71.79, 72.25, 110.06,
125.24, 128.98, 131.99. IR (film): nZ2867, 1444, 1132,
1108, 944 cmK1. MS (EI, 80 eV, 40 8C): m/zZ364, 279,
239, 223, 209, 208, 167, 137, 125, 95, 81, 69, 55.
2.5.4. Synthesis of 1. Compound 43a (2.66 g, 7.86 mmol)
in acetone (450 mL) and water (22 mL) was treated with
p-TsOH (373 mg, 1.96 mmol) and stirred at room tempera-
ture for 20 h. The mixture was neutralized with NaHCO3
and concentrated under reduced pressure. The residue was
extracted with ether, and the ether phase was washed with
brine, dried (MgSO4), and chromatographed (hexanes/ethyl
acetate 10:1) to give 1 (1.90 g, 96%) as a colorless oil. All
analytical data were fully in agreement with those reported
above.
2.5.2. Alkylation of sulfone 41. Preparation of 42a.
Sulfone 41 (2.00 g, 5.49 mmol) in THF (8 mL) was treated
dropwise with nBuLi (1.6 M in hexane, 3.95 mL,
6.31 mmol) at K20 8C. The mixture was slowly warmed
to room temperature, then cooled to K20 8C and HMPA
(3.82 mL) was added dropwise and the mixture was stirred
at room temperature for 30 min. Then the mixture was
cooled to K30 8C and treated dropwise with bromide (S)-39
(1.29 g, 6.59 mmol) in THF (1 mL). Workup with water and
ether furnished after HPLC (hexane/iPrOH 99.2:1) 42a
(1.58 g, 60%) as a diastereomeric mixture. First diastereomer:
1H NMR (CDCl3): d [ppm]Z0.80 (t, JZ7.6 Hz, 3H), 0.90
(s, 3H), 1.01 (s, 3H),1.19–1.69 (m, 10H), 1.70–1.99 (m, 4H),
2.39 (m, 1H), 2.43 (m, 4H), 2.96 (m, 2H), 3.22 (s, 3H), AB-
system: dA 3.42, dB 3.53, (JZ11.6 Hz, 2H), 7.60 (m, 3H),
7.90 (m, 2H). 13C NMR (CDCl3): d [ppm]Z9.25, 22.36,
22.63, 24.37, 25.54, 26.54, 30.04, 32.61, 33.06, 34.18,
39.19, 40.89, 41.24, 42.60, 45.31, 56.29, 67.47, 71.70,
72.31, 81.20, 110.33, 128.45, 129.08, 133.33, 139.42.
2.5.5. Synthesis of alcohol 48. Hydroxy ester 22 (5.00 g,
17.59 mmol) in THF was treated with triphenyl phosphane
(4.73 g, 18.0 mmol), DEAD (3.13 g, 18.0 mmol) and
lithium bromide (3.34 g, 18.0 mmol) at 0 8C for 5 h. The
solvent was removed under reduced pressure and the residue
was treated with ether to crystallize the hydrazo ester and
the phosphine oxide. The mixture was filtered and the
filtrate was chromatographed (hexanes/ethyl acetate 3:1) to
give ester 46 (4.07 g, 85%) as a colorless oil, which was
reduced with DIBALH (1.6 M in toluene, 12 mL) at K30 8C
for 1 h (TP 2) to give, after aqueous workup allylic alcohol
47 (3.86 g, 92%), which was hydrogenated in ethyl acetate
(700 mL) over Rh/C (5%, 1 g) at K30 8C for 6 h under
normal pressure. The mixture was filtered and evaporated to
dryness. The residue was chromatographed (hexanes/ethyl
acetate 2:1) to give 48 (2.84 g, 74%) as a colorless solid of
1
1
Second diastereomer: H NMR (CDCl3): d [ppm]Z0.84
mp 58–59 8C. H NMR (CDCl3): d [ppm]Z0.95 (s, 3H),
(t, JZ7.6 Hz, 3H), 0.86 (s, 3H), 0.96 (s, 3H),1.21–1.50 (m,
8H), 1.53–1.74(m, 3H), 1.83–2.27 (m, 7H), 2.42 (m, 1H),
3.00 (m, 2H), AB-system: dA 3.20, dB 3.27, (JZ11.4 Hz,
2H), 3.27 (s, 3H), 3.40 (s, 2H), 7.60 (m, 3H), 7.90 (m, 2H).
13C NMR (CDCl3): d [ppm]Z9.18, 22.42, 22.55, 24.97,
25.16, 25.72, 29.35, 29.93, 32.92, 33.23, 37.40, 39.40,
40.63, 44.93, 45.40, 56.48, 66.63, 71.66, 72.05, 81.56,
0.97 (s, 3H),1.22–1.49 (m, 4H), 1.56 (s, 1H), 1.60–1.77 (m,
2H), 1.98–2.23 (m, 2H), 2.41 (m, 1H), 2.58 (m, 2H), 3.47 (s,
2H), 3.49 (s, 2H), AB-part of an ABX system: dA 3.60, dB
3.65, (JZ10, 8, 7.6 Hz, 2H). 13C NMR (CDCl3): d [ppm]Z
22.41, 22.49, 26.63, 30.11, 32.14, 33.37, 39.18, 41.14,
41.22, 45.87, 64.04, 71.28, 73.06, 109.20. IR (film): nZ
3459, 2936, 2862, 1110, 1033, 999, 977 cmK1. MS (EI,