4
310
G. Sabitha et al.
PAPER
1
3
C NMR (CDCl , 75 MHz): d = 138.4, 128.4, 127.5, 126.9, 98,
mL) and Et O (15 mL) and the aqueous phase was extracted with
3
2
8
9
5.6, 75.4, 73.3, 66.1, 64.2, 37.4, 36, 30.2, 29.8, 19.4, 16.3, 12.4,
.8.
Et O (3 × 20 mL). The organic layers were combined, washed once
2
with H O (15 mL), brine (20 mL), dried over anhydrous Na SO ,
2
2
4
LCMS: m/z = 359 [ M + Na]+.
and concentrated under reduced pressure. The residue was purified
by silica gel column chromatography (EtOAc–hexane, 1:19) to af-
ford pure 11 as a clear colorless liquid.
HRMS: m/z calcd for C H O Na: 359.2198; found: 359.2187.
2
0
32
4
2
5
Yield: 0.54 g (85%); [a]D +12.4 (c = 1, CHCl3).
(
1
2R,3S,4S)-3-(Benzyloxy)-2-methyl-4-[(4S,5R)-2,2,5-trimethyl-
,3-dioxan-4-yl]pentyl-4-methyl-1-benzenesulfonate (9)
A solution of 8 (1.4 g, 4.16 mmol) in anhydrous CH Cl (20 mL),
–
1
IR (neat): 3509, 2961, 1382, 1198, 1109 cm .
2
2
1
H NMR (CDCl , 300 MHz): d = 3.88 (dd, J = 2.0, 10.3 Hz, 1 H),
3
containing Et N (1.2 g, 8.33 mmol) was cooled to 0 °C and treated
with p-toluenesulfonyl chloride (0.71 g, 3.73 mmol). The reaction
mixture was stirred at r.t. for 10 h, then diluted with H O (15 mL)
and extracted with CH Cl (3 × 30 mL). The organic layer was
washed with brine (3 × 30 mL) and dried over anhydrous Na SO .
Removal of solvent under reduced pressure and purification by sil-
ica gel column chromatography (EtOAc–hexane, 1:19) afforded 9
as a viscous liquid.
3
3
.66 (dd, J = 5.1, 11.5 Hz, 1 H), 3.49 (t, J = 11.1 Hz, 1 H), 3.08 (q,
J = 7.5, 12.6 Hz, 1 H), 1.99–1.80 (m, 2 H), 1.74–1.63 (m, 1 H), 1.45
s, 3 H), 1.35 (s, 3 H), 1.02 (d, J = 6.9 Hz, 3 H), 0.99 (d, J = 6.6 Hz,
H), 0.88 (d, J = 6.7 Hz, 3 H), 0.71 (d, J = 6.7 Hz, 3 H).
2
(
3
2
2
2
4
1
3
C NMR (CDCl , 75 MHz): d = 98.2, 80.9, 75.3, 66.3, 33.8, 31.7,
3
3
0.4, 29.7, 19.4, 19.1, 18.7, 12, 11.1.
LCMS: m/z = 253 [ M + Na]+.
Yield: 1.83 g (90%).
HRMS: m/z calcd for C H O Na: 253.1779; found: 253.1775.
1
3
26
3
1
H NMR (CDCl , 300 MHz): d = 7.76 (d, J = 8.3 Hz, 2 H), 7.31–
3
(
1S,2R)-1-Isopropyl-2-[(4S,5S)-2,2,5-trimethyl-1,3-dioxan-4-
yl]propyl(methylsulfanyl)methanethioate (12)
7
.15 (m, 7 H), 4.54 (s, 2 H), 4.22 (dd, J = 5.1, 9.8 Hz, 1 H), 3.87
(
dd, J = 8.3, 9.8 Hz, 1 H), 3.75 (dd, J = 0.9, 10.1 Hz, 1 H), 3.62 (dd,
To a solution of NaH (0.1 g, 4.16 mmol) in anhydrous THF (20
mL), alcohol 11 (0.5 g, 2.17 mmol) in anhydrous THF (10 mL) was
added at 0 °C and the solution was stirred at r.t. for 30 min. Carbon
disulfide (0.5 mL, 8.7 mmol) and MeI (1 mL, 17.39 mmol) were
added at 0 °C and the mixture was stirred at r.t. for 3 h. After com-
pletion, the reaction was cooled to 0 °C and quenched by slow ad-
dition of crushed ice. The mixture was allowed to come to r.t.,
J = 4.9, 11.3 Hz, 1 H), 3.41 (t, J = 11.3 Hz, 1 H), 3.32 (dd, J = 1.8,
9
1
.8 Hz, 1 H), 2.45 (s, 3 H), 2.20–2.15 (m, 1 H), 1.86–1.76 (m, 2 H),
.30 (d, J = 6.7 Hz, 6 H), 1.05 (d, J = 6.9 Hz, 3 H), 0.83 (d,
J = 6.9 Hz, 3 H), 0.67 (d, J = 6.6 Hz, 3 H).
(
4S,5S)-4-[(1S,2S)-2-(Benzyloxy)-1,3-dimethylbutyl]-2,2,5-tri-
methyl-1,3-dioxane (10)
separated, and the aqueous layer was washed with CH Cl (2 × 30
To a stirred suspension of LAH (0.16 g, 4.21 mmol) in anhydrous
THF (10 mL) at 0 °C, was added dropwise a solution of 9 (1.78 g,
2
2
mL). The combined organic extracts were dried (Na SO ), concen-
2
4
trated under vacuum, and purified by column chromatography
3
.63 mmol) in anhydrous THF (10 mL). The reaction mixture was
(EtOAc–hexane, 1:20) to afford 12 as a liquid.
heated at reflux for 4 h, then cooled to 0 °C, diluted with Et O (20
2
mL) and quenched by dropwise addition of sat. aq Na SO (10 mL).
25
2
4
Yield: 0.62 g (90%); [a]D +8.3 (c = 1, CHCl3).
The solid material was filtered and washed thoroughly with hot
EtOAc several times. The combined organic layers were dried over
anhydrous Na SO , the solvent was removed under vacuum, and the
–
1
IR (neat): 2965, 1563, 1382, 1227, 1047 cm .
1H NMR (CDCl
, 500 MHz): d = 5.84 (dd, J = 2.8, 12.5 Hz, 1 H),
2
4
3
residue was purified by silica gel column chromatography (EtOAc–
hexane, 1:24) to afford 10 as a viscous liquid.
3.62 (dd, J = 4.8, 11.5 Hz, 1 H), 3.47–3.39 (m, 2 H), 2.55 (s, 3 H),
2.11–2.03 (m, 2 H), 1.83–1.76 (m, 1 H), 1.27 (d, J = 4.8 Hz, 6 H),
1.0 (d, J = 6.7 Hz, 3 H), 0.95 (d, J = 6.7 Hz, 3 H), 0.92 (d,
J = 6.7 Hz, 3 H), 0.71 (d, J = 6.7 Hz, 3 H).
2
5
Yield: 1.05 g (91%); [a]D +36.6 (c = 1, CHCl3).
–
1
IR (neat): 2963, 1459, 1380, 1196, 1064 cm .
1
3
C NMR (CDCl , 75 MHz): d = 215.9, 98.2, 87.3, 72.9, 66, 35.9,
3
1
H NMR (CDCl , 300 MHz): d = 7.31–7.24 (m, 5 H), 4.60 (ABq,
3
30.3, 30.1, 29.5, 20.4, 18.8, 18.6, 15.4, 12.3, 9.2.
J = 11.7, 18.1 Hz, 2 H), 3.85 (d, J = 10.3 Hz, 1 H), 3.63 (dd, J = 1.5,
LCMS: m/z = 343 [ M + Na]+.
9
1
.8 Hz, 1 H), 3.44 (t, J = 11.3 Hz, 1 H), 3.27 (dd, J = 1.5, 9.8 Hz,
H), 1.95–1.72 (m, 3 H), 1.33 (d, J = 2.8 Hz, 6 H), 1.06 (d,
HRMS: m/z calcd for C15H O S Na: 343.1377; found: 343.1366.
28 3 2
J = 6.9 Hz, 3 H), 0.89 (d, J = 6.7 Hz, 3 H), 0.82 (d, J = 6.9 Hz, 3 H),
0
.70 (d, J = 6.6 Hz, 3 H).
(4S,5S)-4-[(1S)-1,3-Dimethylbutyl]-2,2,5-trimethyl-1,3-dioxane
(13)
A solution of 12 (0.57 g, 1.78 mmol), tributyltin hydride (0.8 mL,
1
3
C NMR (CDCl , 75 MHz): d = 139.6, 128.2, 127.1, 126.8, 97.9,
3
8
9
3.5, 74.8, 73.5, 66.3, 37, 30.3, 30.1, 29.9, 21.2, 19.5, 14.7, 12.4,
.5.
2
.85 mmol) and AIBN (0.029 g, 0.17 mmol) in anhydrous toluene
(15 mL) was heated to reflux for 30 min. The mixture was cooled,
LCMS: m/z = 343 [ M + Na]+.
concentrated under vacuum, and purified by column chromatogra-
phy (EtOAc–hexane, 1:33) to afford 13 as a colorless liquid.
HRMS: m/z calcd for C H O Na: 343.2249; found: 343.2246.
2
0
32
3
2
5
Yield: 0.32 g (84%); [a]D +8.6 (c = 1, CHCl3).
(
3S,4S)-2-Methyl-4-[(4S,5S)-2,2,5-trimethyl-1,3-dioxan-4-
–
1
IR (neat): 2959, 1380, 1197, 1063 cm .
1H NMR (CDCl
, 300 MHz): d = 3.64 (dd, J = 5.2, 11.3 Hz, 1 H),
yl]pentan-3-ol (11)
To freshly distilled ammonia (20 mL) in a 50-mL two-necked
round-bottom flask fitted with a cold finger condenser, was added
lithium metal (0.13 g, 18.6 mmol) in portions at –33 °C, and the re-
sulting gray-colored suspension was stirred for 15 min. To this mix-
ture was added a solution of 10 (0.9 g, 2.81 mmol) in anhydrous
THF (10 mL) over a period of 10 min. The reaction mixture was
stirred for a further 30 min at –33 °C, then quenched by the addition
of solid ammonium chloride (3 g) and the ammonia was then al-
3
3.42 (t, J = 11.3 Hz, 1 H), 3.33 (dd, J = 2.2, 10.5 Hz, 1 H), 1.87–
1.46 (m, 2 H), 1.43–1.11 (m, 3 H), 1.37 (s, 3 H), 1.32 (s, 3 H), 0.96–
0.81 (m, 9 H), 0.71 (d, J = 6.7 Hz, 3 H).
13
C NMR (CDCl , 75 MHz): d = 98, 76.9, 66.4, 42.9, 30.8, 30.5,
3
2
9.6, 24.9, 22.9, 22.6, 19, 12.7, 12.3.
LCMS: m/z = 237 [ M + Na]+.
lowed to evaporate. The residue was partitioned between H O (15
HRMS: m/z calcd for C H O Na: 237.1877; found: 237.1871.
2
13 26
2
Synthesis 2010, No. 24, 4307–4311 © Thieme Stuttgart · New York