2218
S. Chandrasekhar et al. / Tetrahedron: Asymmetry 20 (2009) 2216–2219
ꢀ92:9 (c 1.0, CHCl3), 1H NMR (300 MHz, CDCl3): d 2.64–2.4 (m, 2H),
4.48 (t, J = 7.5 Hz, 1H), 5.15–5.02 (m, 2H), 5.8–5.62 (m, 1H), 7.4–
7.23 (m, 5H); 13C NMR (75 MHz, CDCl3): d 40.5, 65.7, 118.1,
9H), 1.53 (br s, 1H), 2.15–1.8 (m, 2H), 2.57–2.41 (m, 2H), 3.76–
3.85 (m, 1H), 4.77 (br s, 1H), 5.02 (br s, 1H), 7.1–6.86 (m, 2H),
7.6–7.2 (m, 8H), 7.96 (d, J= 7.3 Hz, 2H); 13C NMR (75 MHz, CDCl3):
d 28.3, 41.1, 44.1, 68.6, 79.8, 126.4, 127.5, 128.5, 128.5, 128.5,
126.8, 128.2, 128.7, 133.6, 139.1. IR (neat):
c 2925, 2095, 1247,
700 cmꢀ1; MS-ESI: (m/z) 146.1 [Mꢀ28+H]+.
128.8, 132.8, 137.6, 145.0, 155.5, 190.4; IR (KBr): c 3361, 3264,
2921, 1673, 1179, 1010, 697 cmꢀ1; MSESI: (m/z) 396 [M+H]+;
HRMS: (m/z) calcd for C24H29NO4Na 418.1994; found 418.1983
[M+Na]+.
4.1.2. (S)-tert-Butyl 1-phenylbut-3-enylcarbamate 7
A solution of compound 6 (2.5 g, 14.4 mmol) in THF (20 mL)
was added to a suspension of LiAlH4 (0.8 g, 21.6 mmol) in THF
(3 mL) slowly at 0 °C. The reaction mixture was stirred at rt for
1 h and then the reaction was quenched with 15% NaOH (0.8 mL)
and water (2.5 mL). A solution of (Boc)2O (4.9 mL, 21.6 mmol) in
THF (5 mL) was then added and stirred for another 3 h and was fil-
tered through Celite. The filtrate was diluted with EtOAc (50 mL)
and the organic layer was washed with brine (50 mL), dried over
Na2SO4 and concentrated in vacuo to obtain the crude compound,
which was purified by column chromatography eluting with hex-
anes/EtOAc (85:15) to give 7 (3.1 g, 12.6 mmol, 90% over two steps)
4.1.5. 2-((2R,4S,6S)-4-Hydroxy-6-phenylpiperidin-2-yl)-1-
phenylethanone 2
To a solution of 3 (50 mg, 0.1 mmol) in CH2Cl2 (0.5 mL) at 0 °C
was added TFA (0.04 mL, 0.5 mmol). After 5 h, the reaction was
brought to pH 8–9 using satd NaHCO3 and the compound was ex-
tracted with CH2Cl2 (3 ꢁ 3 mL). The organic layer was dried over
Na2SO4 and concentrated in vacuo to obtain crude compound,
which was purified by column chromatography eluting with hex-
anes/EtOAc 1:1 to give pure 2 (36 mg, 0.1 mmol, 96%) as an off-
as an off-white powder: Mp: 64–66 °C. ½a D25
¼ ꢀ40:5 (c 1.0, CHCl3),
ꢂ
white powder; Mp: 148–150 °C; ½a D25
ꢂ
¼ ꢀ23:7 (c 1.25, CHCl3); 1H
1H NMR (300 MHz, CDCl3): d 1.43 (br s, 9H), 2.54 (merged t, 2H),
4.84–4.61 (m, 2H), 5.15–5.02 (m, 2H), 5.75–5.56 (m, 1H), 7.34–
7.16 (m, 5H); 13C NMR (75 MHz, CDCl3): d 28.3, 41.1, 54.0, 79.4,
118.0, 126.1, 127.0, 128.4, 133.9, 142.4, 155.1; IR (KBr): 3388,
2980, 2934, 1683, 1516, 1271, 1174, 754, 700 cmꢀ1; MSESI: (m/z)
248 [M+H]+; HRMS: (m/z) calcd for C15H21NO2Na, 270.1469; found
270.1462 [M+Na]+.
NMR (300 MHz, CDCl3): d 1.96–1.62 (m, 4H), 2.18 (br s, 3H),
3.18–3.11 (m, 2H), 3.9–3.8 (m, 1H), 4.35–4.23 (m, 2H), 7.37–7.21
(m, 3H), 7.52–7.38 (m, 4H), 7.58 (t, J = 7.5 Hz, 1H), 7.96 (d,
J = 7.5 Hz, 2H); 13C NMR (75 MHz, CDCl3): d 38.9, 41, 45.2, 47.5,
55.5, 65.7, 127, 127.3, 128.2, 128.6, 128.8, 133.4, 137, 144.6,
199.4; IR (neat):
c 3449, 2926, 2859, 1754, 1248, 1080, 760,
695 cmꢀ1
;
MSESI: (m/z) 296 [M+H]+; HRMS: m/z calcd for
C19H22NO2 296.1650; found 296.1645 [M+H]+.
4.1.3. tert-Butyl (1S,3S)-3-hydroxyl-1-phenylhex-5-
enylcarbamate 4
Acknowledgements
To a solution of compound 7 (1.0 g, 4.0 mmol) in acetone–water
(4:1, 20 mL) were added NMO (0.82 g, 6.0 mmol) and OsO4 (50%
sol in toluene, 14 mg, 0.05 mmol) and was stirred overnight. The
solvent was evaporated in vacuo and the residue was dissolved
in THF: water (9:1, 20 mL) and NaIO4 (1.73 g, 8.0 mmol) were
added and stirred for 15 min, the reaction mixture was filtered
and the filtrate was washed with satd NaHCO3 (25 mL), brine
(25 mL), dried over Na2SO4 and concentrated in vacuo to obtain
the crude solid as an off-white powder which was pure enough
to carry out the next reaction without further purification. To a
The authors thank DST, New Delhi, for financial assistance and
CSIR, New Delhi, for research fellowship to G. S. Kiran Babu. We
are thankful to Evolva Biotech, India, for biological evaluation.
We thank Dr. J. S. Yadav for providing the synthetic sample of
(ꢀ)-diospongin A.
References
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tion was poured and the compound was extracted with ether
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der: Mp: 95–97 °C; ½a D25
ꢂ
¼ ꢀ12 (c 1.0, CHCl3); 1H NMR (300 MHz,
CDCl3): d 1.43 (br s, 9H), 1.55 (br s, 1H), 2.02–1.71 (m, 2H),
2.33–2.02 (m, 2H), 3.65–3.52 (m, 1H), 4.77 (br s, 1H), 5.18–5.03
(m, 3H), 5.84–5.65 (m, 1H), 7.35–7.16 (m, 5H); 13C NMR
(75 MHz, CDCl3): d 28.3, 42.3, 43.7, 53.6, 68.6, 79.5, 118.3, 126.3,
4. Nobuyuki, K.; Hande, S. M.; Uenishi, J. Tetrahedron 2007, 63,
9049.
127.2, 128.6, 134.2, 142.9, 155.4; IR (KBr):
c 3369, 3256, 2925,
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1676, 1367, 1174, 1015, 703 cmꢀ1; MSESI: (m/z) 292 ([M+H]+;
HRMS: m/z calcd for C17H25NO3Na 314.1732; found: 314.1736
[M+Na]+.
4.1.4. tert-Butyl (1S,3S)-3-hydroxy-7-oxo-1,7-diphenyl hept-5-
enylcarbamate 3
To a solution of 4 (0.1 g, 0.3 mmol) and 9 (0.136 g, 10 mmol) in
CH2Cl2 (1 mL) was added catalyst 10 (23 mg, 0.06 mmol) and was
stirred at rt for 1 h. The solvent was evaporated in vacuo and the
residue was purified by flash chromatography to give 3 (96 mg,
0.17 mmol, 70%) as an off-white powder: Mp: 143–146 °C;
8. Tatsuya, S.; Manabu, I.; Shigenori, K. Chem. Lett. 1990, 449.
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magnesium bromide followed by IBX oxidation. See ref: Wu, F.; Li, H.; Hong, R.;
Deng, L. Angew. Chem., Int. Ed. 2006, 45, 947.
10. Enantiomeric excess was determined by chiral HPLC with chiral column: OD-H,
250 ꢁ 4.6 mm, 5
lm; mobile phase: 30% i-propanol in hexanes; flow rate:
1 mL/min.; detection: PDA; run time: 30 min.; retention time: 6.5.
½
a 2D5
ꢂ
¼ ꢀ17 (c 0.25, CHCl3), 1H NMR (300 MHz, CDCl3): d 1.43 (s,