S. P. Chavan et al. / Tetrahedron Letters 48 (2007) 643–646
645
7. Chavan, S. P.; Dhondge, V. D.; Patil, S. S.; Subba Rao, T.
Y.; Govande, C. A. Tetrahedron: Asymmetry 1997, 8,
2517–2518.
8. Chavan, S. P.; Thakkar, M.; Kharul, R. K.; Pathak, A. B.;
Bhosekar, A. V.; Bhadbhade, M. V. Tetrahedron 2005, 61,
3873–3879.
of diastereomers) via b,c-unsaturated ester 10 using pre-
viously reported conditions in good yields.4 Since, the
stereochemistry at the newly incorporated chiral centres
in 10 and 11 was to be destroyed in the next step during
formation of the butenolide moiety, no attempt was
made to identify the diastereomers. Butenolide ring con-
struction was achieved using the protocol developed in
our group,5 according to which diol 11 was treated with
p-toluenesulfonic acid in refluxing benzene to give a 3:2
diastereomeric mixture of heritonin (2) and its C8 epi-
mer (epi-2) in 90% overall yield. Both diastereomers
were separated by repeated crystallisation.4
9. Chavan, S. P.; Thakkar, M.; Jogdand, G. F.; Kalkote,
U. R. J. Org. Chem. 2006, 71, 8986–8988.
10. (a) Ghisalberti, E. L.; Jeferies, P. R.; Stuart, A. D. Aust. J.
Chem. 1979, 32, 1627–1630; (b) Hagiwara, H.; Tomoyuki,
O.; Ono, H.; Kamat, V. P.; Hoshi, T.; Suzuki, T.; Ando,
M. J. Chem. Soc., Perkin Trans. 1 2002, 895–900.
11. Rubottom, G. M.; Gruber, J. M. J. Org. Chem. 1978, 43,
1599–1602.
12. Mancuso, A. J.; Huang, S. L.; Swern, D. J. Org. Chem.
1978, 43, 2480–2482.
13. Henry, J. R.; Weinreb, S. M. J. Org. Chem. 1993, 58, 4745.
Accordingly, on crystallisation from petroleum ether,
heritonin (2)14 was first to crystallise as white needles
(mp 115–116 °C), and from the remaining solution,
epi-heritonin (epi-2)14 was purified by crystallisation
using petroleum ether: ethyl acetate (9:1), as a white so-
lid (mp 172–173 °C). Demethylation of (2) using etha-
nethiol–aluminium chloride gave pure heritol (1)14
without any epimerisation at C8 in 80% yield. Epi-heri-
25
14. Spectral data: Compound (7): Specific rotation: ½aꢁD
ꢀ37.91 (c 1.5, CHCl3); IR (CHCl3) mmax (cmꢀ1): 3411,
1621, 1589. 1H NMR (CDCl3, 200 MHz): d 1.19 (d,
J = 7.0 Hz, 3H); 1.52–1.66 (m, 2H); 1.52 (s, 3H); 1.66 (s,
3H); 1.80–1.91 (m, 2H); 2.20 (s, 3H); 2.50–2.67 (m, 1H);
5.05 (m, 1H); 6.56–6.65 (m, 2H); 6.98 (d, J = 7.7 Hz, 1H).
13C NMR (CDCl3, 50 MHz): d 15.5 (CH3); 17.8 (CH3);
22.5 (CH3); 25.8 (CH3); 26.2 (CH2); 38.5 (CH2); 39.1
(CH); 113.6 (CH); 119.4 (CH); 120.9 (C); 124.8 (CH);
130.8 (CH); 131.2 (C); 147.0 (C); 153.7 (C). MS-ESI m/z:
218 (M)+. Anal. Calcd for C15H22O: C, 82.52; H, 10.16.
Found: C, 82.29; H, 10.35. Compound (9): Specific
tol (epi-1)14 was also synthesised similarly in 80% yield.
25
The synthetic heritol (1) showed a specific rotation ½aꢁD
ꢀ240.5 (c 0.18, CHCl3), which was opposite in sign to
25
that of naturally isolated 1 {½aꢁD +261, no solvent or
concentration were reported}.1 Assuming that the sol-
vent was CHCl3, naturally isolated (+)-heritol should
have (S,R) configuration at C10 and C8, respectively.
25
rotation: ½aꢁD ꢀ26.11 (c 1.2, CHCl3); IR (neat) mmax
(cmꢀ1): 2961 (br), 1708, 1612. 1H NMR (CDCl3,
200 MHz): d 1.27 (d, J = 7.0 Hz, 3H); 1.82–1.96 (m, 2H);
2.17 (s, 3H); 2.17–2.27 (m, 2H); 2.60–2.78 (m, 1H); 3.82 (s,
3H); 6.62–6.69 (m, 2H); 7.03 (d, J = 7.5 Hz, 1H); 8.9 (br s,
1H). 13C NMR (CDCl3, 50 MHz): d 15.9 (CH3); 22.4
(CH3); 32.3 (CH2); 33.0 (CH2); 39.4 (CH); 55.2 (CH3);
108.8 (CH); 118.6 (CH); 124.4 (C); 130.6 (CH); 144.9 (C);
157.8 (C); 179.9 (C). MS-ESI m/z: 221 (Mꢀ1)+. Anal.
Calcd for C13H18O3: C, 70.24; H, 8.16. Found: C, 70.44;
Thus, (ꢀ)-heritol (1) has been synthesised enantiospeci-
fically for the first time from naturally occurring (R)-
(+)-citronellal and the absolute configuration of natural
heritol proposed to be (S,R) at C10, C8 by comparison
of the specific rotation with that of synthetic 1.
25
H, 8.33. Compound (3): mp 110 °C. Specific rotation: ½aꢁD
+26.87 (c 0.9, CHCl3); IR (CHCl3) mmax (cmꢀ1): 1670,
1607, 1570. 1H NMR (CDCl3, 200 MHz): d 1.38 (d,
J = 7.0 Hz, 3H); 1.79–1.95 (m, 1H); 2.18 (s, 3H); 2.21–2.30
(m, 1H); 2.43–2.79 (m, 2H); 2.94–3.07 (m, 1H); 3.88 (s,
3H); 6.63 (s, 1H); 7.79 (d, J = 0.8 Hz, 1H). 13C NMR
(CDCl3, 50 MHz): d 15.8 (CH3); 20.8 (CH3); 30.8 (CH2);
33.1 (CH); 35.8 (CH2); 55.3 (CH3); 107.4 (CH); 124.9 (C);
125.4 (C); 129.7 (CH); 149.2 (C); 162.1 (C); 196.8 (C). MS-
ESI m/z: 205 (M+1)+. Anal. Calcd for C13H16O2: C,
76.44; H, 7.90. Found: C, 76.11; H, 8.18. Compound (2):
Acknowledgements
We profoundly thank Takasago International Corpora-
tion, Japan for a generous gift of (R)-(+)-citronellal.
M.R.T. thanks CSIR for a fellowship. Funding from
DST, New Delhi, India to S.P.C. is gratefully
acknowledged.
25
References and notes
mp 115–116 °C. Specific rotation: ½aꢁD ꢀ312.97 (c 1.3,
CHCl3); IR (CHCl3) mmax (cmꢀ1): 3019, 1738, 1654, 1613.
1H NMR (CDCl3, 200 MHz): d 1.43 (d, J = 6.7 Hz, 3H);
1.36–1.64 (m, 1H); 2.11 (d, J = 1.6 Hz, 3H); 2.23 (s, 3H);
2.56–2.67 (m, 1H); 3.02–3.21 (m, 1H); 3.87 (s, 3H); 4.90
(ddq, J = 12.9, 4.8, 1.6 Hz, 1H); 6.84 (s, 1H); 7.40 (s, 1H).
13C NMR (CDCl3, 50 MHz): d 9.8 (CH3); 15.9 (CH3); 21.7
(CH3); 31.9 (CH); 38.6 (CH2); 55.3 (CH3); 78.1 (CH);
108.3 (CH); 115.8 (C); 120.6 (C); 125.6 (C); 129.5 (CH);
142.2 (C); 156.7 (C); 159.5 (C); 175.5 (C). Compound (epi-
1. Miles, D. H.; Lho, D.-S.; de la Cruz, A. A.; Gomez, E. D.;
Weeks, J. A.; Atwood, J. L. J. Org. Chem. 1987, 52, 2930–
2932.
2. Miles, D. H.; Maria Ly, A.; Chittawong, V. J. Nat. Prod.
1989, 52, 896–898.
3. Irie, H.; Matsumoto, R.; Nishimura, M.; Zhang, Y. Chem.
Pharm. Bull. 1990, 38, 1852–1856.
4. Zubaidha, P. K.; Chavan, S. P.; Racherla, U. S.; Ayyan-
gar, N. R. Tetrahedron 1991, 47, 5759–5768.
5. (a) Chavan, S. P.; Zubaidha, P. K.; Govande, C. A.;
Tripura Subba, R. Y. J. Chem. Soc., Chem. Commun.
1994, 9, 1101–1102; (b) Chavan, S. P.; Zubaidha, P. K.;
Ayyanger, N. R. Tetrahedron Lett. 1992, 33, 4605–4608;
(c) Chavan, S. P.; Govande, C. A. Green Chem. 2002, 4,
194–195.
25
2): mp 172–173 °C. Specific rotation: ½aꢁD +397.03 (c 1.1,
CHCl3); IR (CHCl3) mmax (cmꢀ1): 2962, 1744, 1651, 1612.
1H NMR (CDCl3, 200 MHz): d 1.41 (d, J = 7.5 Hz, 3H);
1.79–1.95 (m, 1H); 2.10 (d, J = 1.6 Hz, 3H); 2.22 (s, 3H);
2.38 (ddd, J = 12.0, 4.8, 1.5 Hz, 1H); 3.21–3.35 (m, 1H);
3.86 (s, 3H); 5.07 (ddq, J = 13.1, 4.6, 1.6 Hz, 1H); 6.64 (s,
1H); 7.37 (s, 1H). 13C NMR (CDCl3, 50 MHz): d 10.0
(CH3); 16.1 (CH3); 24.0 (CH3); 33.3 (CH); 36.5 (CH2);
55.3 (CH3); 75.4 (CH); 110.1 (CH); 116.7 (C); 120.2 (C);
6. Silveira, C. C.; Machado, A.; Braga, A. L.; Lenardao, E. J.
Tetrahedron Lett. 2004, 45, 4077–4080.