1500
S. P. Chavan, P. B. Lasonkar / Tetrahedron: Asymmetry 23 (2012) 1496–1500
bined organic layers were then washed with water, brine, dried
over anhydrous Na2SO4, filtered, and concentrated under reduced
pressure to afford a residue which was purified by flash column
chromatography using 2% EtOAc/hexane as eluent to give com-
pound 8a (0.6 g, 70%) yield. Rf (5% EtOAc/hexane) 0.5;
by flash column chromatography using (5% EtOAc/hexane) as elu-
ent to furnish the desired target molecule 1 (152 mg, 70%) as a so-
lid, melting point 56 °C (lit. 52–53 °C). Rf (10% EtOAc/hexane) 0.4;
½
a 2D5
ꢂ
¼ þ170:1 (c 1.08, CHCl3)14; IR (CHCl3, cmꢀ1): 2960, 1725,
1510, 1460, 815; 1H NMR (CDCl3 + CCl4, 200 MHz): d 0.61 (s, 3H),
1.17 (s, 3H), 1.26 (s, 3H), 1.86–1.97 (m, 1H), 2.35 (s, 3H), 2.41–
2.52 (m, 2H), 2.58-2.71 (m, 1H), 7.14–7.30 (m, 4H); 13C NMR
(CDCl3 + CCl4, 50 MHz): d 18.3, 20.8, 22.1, 25.3, 29.6, 33.7, 48.3,
53.2, 126.3, 128.9, 135.8, 141.9, 222.7; MS (EI): m/z = 216 (M+H)+.
½
a 2D5
ꢂ
¼ ꢀ29:7 (c 1.82, CHCl3); IR (CHCl3, cmꢀ1): 2956, 1515, 1454,
815, 734; 1H NMR (CDCl3 + CCl4, 200 MHz): d 1.29 (s, 3H), 1.85–
2.36 (m, 6H), 2.38 (s, 3H), 4.23–4.34 (m, 1H), 4.54 (s, 2H), 7.12–
7.38 (m, 9H); 13C NMR (CDCl3 + CCl4, 50 MHz): d 20.95, 30.20,
31.25, 38.12, 45.64, 46.82, 70.86, 80.18, 125.70(2C), 127.34,
127.53(2C), 128.27(2C), 128.78(2C), 134.69, 138.84, 148.14; MS
(EI): m/z = 303 (M+Na)+; Anal. Calcd for C20H24O: C, 85.67; H,
8.63%. Found: C, 85.85; H, 9.03%.
4.1.11. (R)-2,2,3-Trimethyl-3-p-tolylcyclopentanone 1
½
a 2D5
ꢂ
¼ ꢀ162:7 (c 1.02, CHCl3).14
Acknowledgments
4.1.7. 1-((1S,3S)-3-(Benzyloxy)-1-methylcyclopentyl)-4-methyl-
benzene 8b
We thank Dr. U. R. Kalkote for his valuable suggestions, CSIR
for a fellowship, Dr. S. Krishnaswamy for the single crystal X-ray
analysis and Mrs Kunte for HPLC analysis.
½
a 2D5
ꢂ
¼ þ18:1 (c 2.1, CHCl3); 1H NMR (CDCl3 + CCl4, 200 MHz): d
1.43 (s, 3H), 1.93–2.06 (m, 5H), 2.34 (s, 3H), 2.28–2.39(m, 1H),
4.08–4.15 (m, 1H), 4.50 (s, 2H), 7.08-7.22 (m, 4H), 7.27–7.36 (m,
5H); 13C NMR (CDCl3 + CCl4, 50 MHz): d 20.91, 31..02, 31.79,
38.34, 45.84, 46.29, 71.04, 80.36, 125.65(2C), 127.37, 127.55(2C),
128.32(2C), 128.85(2C), 134.80, 138.87, 147.74.
References
1. Dev, S.; Chetty, G. L. Tetrahedron Lett. 1964, 5, 73.
2. Benesova, V. Collect. Czech. Chem. Commun. 1976, 41, 3812.
3. For the synthesis of enantiomerically pure cuparenone, see: (a) Posner, G. H.
Tetrahedron Lett. 1984, 25, 383; (b) Taber, D. F.; Raman, K. J. Am. Chem. Soc.
1985, 107, 196; (c) Kametani, T.; Honda, T. Chem. Pharm. Bull. 1985, 33, 4821;
(d) Meyers, A. I.; Lefker, B. A. J. Org. Chem. 1986, 51, 1541; (e) Greene, A. E. J. Am.
Chem. Soc. 1987, 109, 4752; (f) Asaoka, M.; Takei, H. Tetrahedron Lett. 1988, 29,
325; (g) Takano, S.; Ogasawara, K. J. Chem. Soc., Chem. Commun. 1989, 271; (h)
Gharpure, M. M.; Rao, A. S. Synth. Commun. 1989, 19, 1813; (i) Fadel, A.; Salaun,
J. Synlett 1991, 60; (j) Fukumoto, K.; Nemoto, H. J. Org. Chem. 1992, 57, 1707; (k)
Canet, J. L.; Fadel, A. J. Org. Chem. 1992, 57, 3463; (l) Honda, T.; Tsubuki, M.
Tetrahedron: Asymmetry 1993, 4, 21; (m) Maruoka, K.; Yamamoto, H. J. Am.
Chem. Soc. 1996, 118, 2289; (n) Kosaka, T.; Shishido, K. J. Chem. Soc., Chem.
Commun. 1997, 1167; (o) Nakashima, H.; Ogasawara, K. Tetrahedron Lett. 2000,
41, 2639; (p) Satoh, T.; Ota, H. Tetrahedron: Asymmetry 2003, 14, 281; (q) Spino,
C.; Boisvert, L. J. Am. Chem. Soc. 2004, 126, 13312.
4.1.8. (R)-3-Methyl-3-(p-tolyl)cyclopentanone 9a
To a well stirred solution of compound 8 (500 mg, 1.78 mmol)
in MeOH (10 mL), was added 10% Pd/C (20 mg). The resulting reac-
tion mixture was kept on a shaker at 60 psi under a hydrogen
atmosphere for 1 h. After the disappearance of the starting mate-
rial, the reaction mixture was filtered on Celite and the residue
was washed with MeOH (3 ꢁ 20 mL). The solvent was removed un-
der reduced pressure to afford the alcohol, which was used as such
without further purification.
To a stirred solution of alcohol (330 mg, 1.78 mmol) in dry
DMSO (10 mL) was added IBX (982 mg, 3.56 mmol) and left to stir
at room temperature for 4 h. After completion of the reaction, the
reaction mixture was diluted with water and extracted using
diethylether (3 ꢁ 20 mL). The combined organic layers were then
washed with water, brine, dried over anhydrous Na2SO4, filtered,
and concentrated under reduced pressure to afford a residue which
was purified by using flash column chromatography using (10%
EtOAc/hexane) as eluent to afford compound 9 (310 mg, 95%) as
a white solid, melting point 56–58 °C. Rf (10% EtOAc/hexane) 0.3;
4. Natarajan, A.; Garcia-Garibay, M. A. Angew. Chem., Int. Ed. 2007, 46, 6485.
5. Tsunoda, T. Tetrahedron: Asymmetry 2012, 23, 739.
6. Zhang, P.; Morken, J. P. J. Am. Chem. Soc. 2011, 133, 9716.
7. (a) Chavan, S. P.; Ethiraj, K. S. Tetrahedron Lett. 1995, 36, 2281; (b) Chavan, S. P.;
Ravindranathan, T.; Patil, S. S.; Dhondge, V.; Dantale, S. W. Tetrahedron Lett.
1996, 37, 2629; (c) Chavan, S. P.; Ravindranathan, T.; Patil, S. S. Tetrahedron
1999, 40, 4733; (d) Chavan, S. P.; Kharul, R. K.; Kale, R. R.; Khobragade, D. A.
Tetrahedron 2003, 59, 2737; (e) Chavan, S. P.; Thakkar, M.; Kharul, R. K.; Pathak,
A. B.; Bhosekar, G. V.; Bhadbhade, M. M. Tetrahedron 2005, 61, 3873; (f) Chavan,
S. P.; Dhawane, A. N.; Kalkote, U. R. Tetrahedron Lett. 2007, 48, 965.
8. Chavan, S. P.; Dhawane, A. N.; Kalkote, U. R. Synthesis 2007, 24, 3827.
9. Bertus, P. Tetrahedron Lett. 2003, 44, 3391.
10. Crystallographic data (excluding structure factors) for the structures in this
Letter have been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC 897216. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK, (fax: +044 (0) 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
11. The stereochemistry of compound 8a was confirmed by 2D NOESY
spectroscopic analysis
½
a 2D5
ꢂ
¼ þ12:3 (c 1.62, CHCl3) {lit. ½a D25
ꢂ
¼ þ13:3 (c 4.00, CHCl3)};3fIR
(CHCl3, cmꢀ1): 3019, 1720, 1614, 1246, 815,; 1H NMR (CDCl3 + CCl4,
200 MHz): d 1.39 (s, 3H), 2.21–2.29 (m, 2H), 2.35 (s, 3H), 2.35–2.37
(m, 2H), 2.46 (d, J = 17. 7 Hz, 1H), 2.65 (d, J = 17.7 Hz, 1H), 7.12–
7.22 (m, 4H); 13C NMR (CDCl3 + CCl4, 50 MHz): d 20.7, 29.3, 35.8,
36.5, 43.3, 52.1, 125.1, 129.0, 135.5, 145.3, 217.8; MS (EI):
m/z = 211 (M+Na)+.
OBn
H
4.1.9. (S)-3-Methyl-3-(p-tolyl)cyclopentanone 9b
½
a 2D5
ꢂ
¼ ꢀ10:0 (c 1.05, CHCl3)
4.1.10. (S)-2,2,3-Trimethyl-3-p-tolylcyclopentanone 1
To a stirred solution of ketone 9 (200 mg, 1.0 mmol) in dry DME
(10 mL) was added LiHMDS (371 mg, 2.2 mmol) and a catalytic
amount of HMPA (0.25 mL). This mixture was stirred for a few
minutes after which methyl iodide (0.325 mL, 5.0 mmol) in dry
DME (2 mL) was added dropwise and the reaction mixture was
stirred for 3 h. After completion, the reaction mixture was
quenched by a saturated ammonium chloride solution, extracted
with ethyl acetate (3 ꢁ 10 mL) washed with a brine solution and
the combined organic layers were dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure and purified
(1R,3S)-8a
.
12. (a) Huang-Minlon J. Am. Chem. Soc. 1946, 68, 2487; (b) Huang-Minlon J. Am.
Chem. Soc. 1949, 71, 3301.
13. Confirmed by comparing the specific rotation with the literature values. 3f
HPLC on a CHIRALCEL OD-H column was used to determine the enantiomeric
purity of (+)-9 and (ꢀ)-9 by comparison with racemic 9, which was
synthesized using the same reaction sequence using DL-malic acid.
14. The specific rotations for both enantiomers matches with the literature values;
the reported specific rotations for natural (+) and (ꢀ)-
a
-cuparenone1,2 in CHCl3
are +177.1 and ꢀ169.9, respectively.