2250
K. Ohata, S. Terashima / Tetrahedron 65 (2009) 2244–2253
1132 cmꢀ1. MS (EIþ) m/z: 183 [(MꢀOCH3)þ]. HRMS (EIþ) m/z: calcd
for C5H11O3S2 [(MꢀOCH3)þ]: 183.0150. Found: 183.0163.
(d, J¼7.3 Hz, 2H), 3.29–3.38 (m, 7H), 4.14–4.19 (m, 1H), 4.26
(t, J¼9.5 Hz, 1H), 4.49 (t, J¼5.5 Hz, 1H), 4.68–4.76 (m, 1H), 5.70
(t, J¼7.3 Hz, 1H), 6.38 (s, 1H), 7.20–7.37 (m, 5H). 13C NMR (100 MHz,
4.8. Deconjugative asymmetric
a
-sulfenylation of (R)- and
CDCl3): d 15.4, 16.2, 26.5, 29.5, 32.7, 37.5, 53.2, 55.4, 66.5, 103.3,
(S)-4-benzyl-3-[(2E,4E)-2,4-dimethylhexa-2,4-dienoyl]oxazo-
lidin-2-one (7 and ent-7). (R)-4-Benzyl-3-[(R,E)-2-(3,3-
dimethoxypropylthio)-2,4-dimethylhexa-3,5-dienoyl]-
oxazolidin-2-one (5), its (R,Z)-isomer [(30Z)-5],
127.4, 128.9, 129.5, 129.9, 130.9, 134.2, 135.1, 139.3, 150.0, 172.5. IR
(NaCl): 1788, 1678 cmꢀ1. MS (FABꢀ) m/z: 432 [(MꢀH)ꢀ]. HRMS
(FABꢀ) m/z: calcd for C23H30NO5S [(MꢀH)ꢀ]: 432.1845. Found:
432.1868.
its (S,E)-diastereoisomer (10), (R)-4-benzyl-3-[(2E,4E)-6-(3,3-
dimethoxypropylthio)-2,4-dimethylhexa-2,4-dienoyl]oxazo-
lidin-2-one (11) and their enantiomers (ent-5, ent-[(30Z)-5],
ent-10, and ent-11)
(b) Preparation of ent-5. Compound ent-5 (870 mg, 67%) was
prepared as a colorless oil from ent-7 (900 mg, 3.01 mmol) in the
same manner as described in (a). [
a
] þ257 (c 0.5, MeOH). Three
types of by-products enantiomeric to (30Z)-5 [ent-(30Z)-5], 10 (ent-
10), and 11 (ent-11) were obtained similar to the case described in
(a). Compounds ent-(30Z)-5 (47 mg, 5%), ent-10 (101 mg, 12%), and
ent-11 (101 mg, 12%). 1H NMR, IR, and MS spectra of these samples
were identical to those described in (a). HRMS (EIþ) m/z: calcd for
C23H31NO5S (Mþ) (for ent-5, ent-(30Z)-5, and ent-10): 433.1923.
Found: 433.1881 (for ent-5), 433.1931 [for ent-(30Z)-5], 433.1902
(for ent-10). HRMS (FABꢀ) m/z: calcd for C23H30NO5S [(MꢀH)ꢀ]
(ent-11): 432.1845. Found: 432.1869 (for ent-11).
(a) Preparation of 5, (30Z)-5, 10, and 11 (Table 1, run 8). To a so-
lution of 7 (598 mg, 2.00 mmol) and HMPA (1.4 mL, 8.05 mmol) in
THF (10 mL), NaHMDS (1.0 mol/L solution in THF, 2.4 mL,
2.40 mmol) was added dropwise at ꢀ78 ꢁC, and the resulting
mixture was stirred at the same temperature for 30 min. A solution
of 6b (645 mg, 3.01 mmol) in THF (2.0 mL) was added to the re-
action mixture at the same temperature, and the resulting mixture
was allowed to slowly warm to room temperature. After quenching
the reaction by adding saturated aqueous ammonium chloride
solution (15 mL), the mixture was extracted with AcOEt (15 mLꢃ3).
The organic extracts were combined, washed with brine (15 mL),
dried over anhydrous Na2SO4, filtered, and then concentrated in
vacuo. Flash column chromatography (hexane/AcOEt¼4:1) of the
residue gave a mixture of 5, (30Z)-5, and 10 (780 mg, 90%) and
a pure sample of 11 (70 mg, 8%), both as an oil. The mixture of 5,
(30Z)-5, and 10 was further separated by HPLC [Daicel Chiralpak AD-
4.9. (R,E)-Benzyl 2-(3,3-dimethoxypropylthio)-2,4-
dimethylhexa-3,5-dienoate (15) and its enantiomer (ent-15)
(a) Preparation of 15. To benzyl alcohol (8.8 mL, 85.0 mmol),
Ti(OiPr)4 (1.3 mL, 4.40 mmol) was added and the resulting mixture
was stirred at room temperature for 5 h under a reduced pressure
(0.5–1.0 mmHg). The mixture was added to 5 (893 mg, 2.06 mmol),
and the whole mixture was stirred at 70 ꢁC for 16 h. After cooling,
the mixture was diluted with CH2Cl2 (30 mL) and the reaction was
quenched by adding 1 mol/L HCl (10 mL). The insoluble materials,
which appeared were removed by filtration through a pad of Celite
and washed with CH2Cl2. The filtrates were combined, diluted with
H2O (10 mL), and extracted with CH2Cl2 (25 mLꢃ3). The organic
extracts were combined, washed with brine (25 mL), dried over
anhydrous Na2SO4, filtered, and then concentrated in vacuo. Flash
column chromatography (hexane/AcOEt¼10:1) of the residue gave
H,
f
2.0 cmꢃ25 cm: hexane/2-propanol/EtOH¼93:4:3, flow rate
10 mL/min, HPLC analysis; Daicel Chiralpak AD-H,
f
0.46 cmꢃ25 cm,
hexane/2-propanol¼95:5, flow rate 1.0 mL/min; tR 10.4 min ((30Z)-
5), 14.7 min (5), 25.1 min (10)] to give pure samples of 5, (30Z)-
5, and 10, all as an oil.
Compound 5 (641 mg, 74%). [
(400 MHz, CDCl3):
a
] ꢀ253 (c 0.5, MeOH). 1H NMR
d
1.72 (d, J¼1.2 Hz, 3H), 1.82–1.89 (m, 2H),1.95 (s,
3H), 2.62 (t, J¼7.3 Hz, 2H), 2.72 (dd, J¼13, 10 Hz, 1H), 3.318 (s, 3H),
3.324 (s, 3H), 3.27–3.38 (m,1H), 4.09–4.14 (m, 2H), 4.48 (t, J¼5.5 Hz,
1H), 4.65–4.71 (m, 1H), 5.01 (d, J¼11 Hz, 1H), 5.14 (d, J¼17 Hz, 1H),
5.72 (s, 1H), 6.36 (dd, J¼17, 11 Hz, 1H), 7.22–7.36 (m, 5H). 13C NMR
15 (619 mg, 82%) as a colorless oil. [
a
] þ4.4 (c 0.5, MeOH). 1H NMR
(400 MHz, CDCl3):
d
1.66 (s, 3H), 1.70 (d, J¼1.2 Hz, 3H), 1.73–1.79
(m, 2H), 2.50–2.65 (m, 2H), 3.28 (s, 6H), 4.36 (t, J¼5.5 Hz, 1H), 5.03
(d, J¼11 Hz, 1H), 5.15–5.23 (m, 3H), 6.34 (dd, J¼17, 11 Hz, 1H), 7.30–
7.38 (m, 5H). IR (NaCl): 1726 cmꢀ1. MS (EIþ) m/z: 364 (Mþ). HRMS
(EIþ) m/z: calcd for C20H28O4S (Mþ): 364.1708. Found: 364.1710.
(b) Preparation of ent-15. Compound ent-15 (590 mg, 81%) was
prepared as a colorless oil from ent-5 (870 mg, 2.01 mmol) in the
(100 MHz, CDCl3): d 12.6, 24.4, 25.7, 31.9, 38.0, 52.9, 53.3, 55.0, 57.4,
66.2, 103.3, 112.7, 127.4, 129.0, 129.4, 133.7, 133.9, 135.4, 140.9, 150.9,
173.1. IR (NaCl): 1790, 1680 cmꢀ1. MS (EIþ) m/z: 433 (Mþ). HRMS
(EIþ) m/z: calcd for C23H31NO5S (Mþ): 433.1923. Found: 433.1941.
Compound (30Z)-5 (51 mg, 6%). 1H NMR (400 MHz, CDCl3):
d 1.83
(d, J¼1.2 Hz, 3H), 1.83–1.90 (m, 2H), 1.96 (s, 3H), 2.65–2.74 (m, 3H),
3.318 (s, 3H), 3.324 (s, 3H), 3.29–3.37 (m, 1H), 4.04 (q, J¼7.9 Hz, 1H),
4.09 (dd, J¼8.6, 2.4 Hz, 1H), 4.48 (t, J¼6.1 Hz, 1H), 4.59–4.63 (m, 1H),
5.11 (d, J¼11 Hz, 1H), 5.22 (d, J¼17 Hz, 1H), 5.60 (s, 1H), 6.62 (dd,
J¼17, 11 Hz, 1H), 7.22–7.36 (m, 5H). 13C NMR (100 MHz, CDCl3):
same manner as described in (a). [
a
] ꢀ4.3 (c 0.5, MeOH). 1H NMR,
IR, and MS spectra of this sample were identical to those described
in (a). HRMS (EIþ) m/z: calcd for C20H28O4S (Mþ): 364.1708. Found:
364.1737.
d
19.7, 24.8, 26.2, 32.0, 38.0, 53.0, 53.3, 54.8, 57.6, 66.4, 103.4, 115.7,
4.10. (R,E)-Benzyl 2,4-dimethyl-2-(3-oxopropylthio)-
hexa-3,5-dienoate (16) and its enantiomer (ent-16)
127.3, 128.9, 129.5, 131.4, 132.4, 133.2, 135.5, 151.1, 173.9. IR (NaCl):
1790, 1680 cmꢀ1. MS (EIþ) m/z: 433 (Mþ). HRMS (EIþ) m/z: calcd for
C23H31NO5S (Mþ): 433.1923. Found: 433.1901.
(a) Preparation of 16. To a solution of 15 (805 mg, 2.21 mmol) in
THF (9.0 mL), 6% HCl (7.0 mL) was added at room temperature, and
the resulting mixture was stirred at the same temperature for 6 h.
After quenching the reaction by adding saturated aqueous sodium
hydrogen carbonate solution (20 mL) under cooling in an ice bath,
the mixture was extracted with AcOEt (15 mLꢃ3). The organic ex-
tracts were combined, washed with brine (15 mL), dried over an-
hydrous Na2SO4, filtered, and then concentrated in vacuo. Flash
column chromatography (hexane/AcOEt¼6:1) of the residue gave
Compound 10 (77 mg, 9%). 1H NMR (400 MHz, CDCl3):
d 1.71 (d,
J¼1.2 Hz, 3H), 1.84 (s, 3H), 1.84–1.91 (m, 2H), 2.59–2.70 (m, 3H),
3.313 (s, 3H), 3.318 (s, 3H), 3.34 (dd, J¼13, 3.1 Hz, 1H), 4.06–4.14 (m,
2H), 4.47 (t, J¼5.5 Hz, 1H), 4.65–4.70 (m, 1H), 5.01 (d, J¼11 Hz, 1H),
5.13 (d, J¼18 Hz, 1H), 5.77 (s, 1H), 6.36 (dd, J¼18, 11 Hz, 1H), 7.24–
7.37 (m, 5H). 13C NMR (100 MHz, CDCl3):
d 12.6, 24.3, 25.2, 32.0,
37.6, 53.1, 53.2, 53.7, 57.4, 66.0, 103.3, 112.5, 127.3, 129.0, 129.4,
133.2, 134.3, 135.6, 141.0, 150.8, 172.3. IR (NaCl): 1790, 1676 cmꢀ1
.
MS (EIþ) m/z: 433 (Mþ). HRMS (EIþ) m/z: calcd for C23H31NO5S
16 (667 mg, 95%) as a colorless oil. [
a
] þ27.5 (c 0.4, CHCl3). 1H NMR
(Mþ): 433.1923. Found: 433.1902.
(400 MHz, CDCl3):
d
1.66 (s, 3H), 1.72 (d, J¼1.2 Hz, 3H), 2.56
Compound 11. 1H NMR (400 MHz, CDCl3):
d
1.86–1.96 (m, 5H),
(t, J¼7.3 Hz, 2H), 2.76–2.86 (m, 2H), 5.05 (d, J¼11 Hz, 1H), 5.20
(d, J¼17 Hz, 1H), 5.20 (q, J¼12 Hz, 2H), 5.74 (s, 1H), 6.34 (dd, J¼17,
2.05 (s, 3H), 2.55 (t, J¼7.3 Hz, 2H), 2.84 (dd, J¼13, 9.2 Hz, 1H), 3.27