S. Gogoi et al. / Tetrahedron Letters 45 (2004) 5577–5579
5579
10. (a) Alcaide, B.; Almendros, P.; Aragoncillo, C.; Rodri-
guez, R. A. J. Org. Chem. 2001, 66, 5208–5216; (b) Lu, W.;
Chan, T. H. J. Org. Chem. 2000, 65, 8589–8594; (c)
Wilson, S. R.; Guazzaroni, M. E. J. Org. Chem. 1989, 54,
3087–3091.
11. The enantiomeric excess (ee) of R-(+)-7 was determined by
chiral HPLC analyses using a Daicel CHIRALCEL OD
column (250 mm · 4.6 mm, eluent: hexane–iPrOH) after
conversion to the corresponding 3,5-dinitrobenzoate.
Conversion of R-(+)-7 to the corresponding 3,5-dini-
trobenzoate was carried out bysaponification followed by
esterification.
In the next and final step, lactonization of 2 moles of 3
to give the dimeric lactone 1 was successfullyachieved
byYamaguchi’s method in 58% yield and with >95%
ee, the spectroscopic data16 of which were identical with
those of the natural product. In this step, a small
amount of the monomeric lactone 2 (30%) was formed.
No lactone formation took place at 3-OH perhaps due
to ring strain effects or steric effects.
15
In conclusion, we have completed the first total synthesis
of the macrocyclic dimeric lactone, verbalactone in a
regioselective manner in 5.2% overall yield from hex-
anal. The desired stereochemistrywas generated by
kinetic resolution of a homoallylic alcohol and a
Sharpless asymmetric dihydroxylation reaction.
12. During the Sharpless asymmetric dihydroxylation step,
diastereoisomers were formed.
+
R-(+)-7
OR
OR
OH
OAc
R-(+)-8
OH
OAc
R-(+)-10
Acknowledgements
Diastereoisomers
The diastereoisomeric ratio was determined as 85:15 by 1H
NMR (500 MHz) spectroscopic analyses of the crude
product mixture.
The authors gratefullyacknowledge the Director, Re-
gional Research Laboratory(CSIR), Jorhat, Assam,
India for providing facilities for this work. S.G. thanks
the CSIR, New Delhi for the award of a Junior Re-
search Fellowship.
13. The ee’s of R-(+)-8, 2 and 1 were determined by 1H NMR
spectroscopyin the presence of the chiral shift reagent
Eu(hfc)3.
14. (a) Aristoff, P. A.; Johnson, P. D.; Harrison, A. W. J. Am.
Chem. Soc. 1985, 107, 7967–7974; (b) Fernandes, R. A.;
Kumer, P. Tetrahedron: Asymmetry 1999, 10, 4349–
4356.
References and notes
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A.; Harvala, C. J. Nat. Prod. 2001, 64, 1093–1094.
2. Doshida, J.; Hasegawa, H.; Onuki, H.; Shimidzu, N. J.
Antibiot. 1996, 49, 1105–1109.
3. Romeyke, Y.; Keller, M.; Kluge, H.; Grabley, S.; Ham-
mann, P. Tetrahedron 1991, 47, 3335–3346.
4. (a) Bez, G.; Saikia, A. K.; Kalita, D.; Bezbarua, M. S.;
Barua, N. C. Ind. J. Chem. 1998, 37B, 325–328; (b) Kalita,
D.; Khan, A. T.; Saikia, A. K.; Barua, N. C. Synthesis
1998, 975–976; (c) Kalita, D.; Khan, A. T.; Barua, N. C.;
Bez, G. Tetrahedron 1999, 55, 5177–5184.
5. (a) Smith, J. G. Synthesis 1984, 629–656; (b) Kamal, A.;
Khanna, G. B. R.; Ramu, R. Tetrahedron: Asymmetry
2002, 13, 2039–2051; (c) Kalita, B.; Barua, N. C.;
Bezbarua, M.; Bez, G. Synlett 2001, 1411–1414; (d)
Matsubara, S.; Onishi, H.; Utimoto, K. Tetrahedron Lett.
1990, 31, 6209–6212; (e) Sassaman, M. B.; Prakash, G. K.
S.; Olah, G. A. J. Org. Chem. 1990, 55, 2016–2018.
6. (a) Sharpless, K. B.; Amberg, W.; Bennani, Y. L.;
Crispino, G.; Hartung, J.; Jeong, K.-S.; Kwong, H.-L.;
Orikawa, K.; Ang, Z.-M.; Xu, D.; Zhang, X. L. J. Org.
Chem. 1992, 57, 2768–2771; (b) Pandey, R. K.; Fernandes,
R. A.; Kumer, P. Tetrahedron Lett. 2002, 43, 4425–4426.
7. (a) Denis, J.-N.; Correa, A.; Greene, A. E. J. Org. Chem.
1990, 55, 1957–1959; (b) Fleming, P. R.; Sharpless, K. B.
J. Org. Chem. 1991, 65, 2869–2875.
15. (a) Yamaguchi, M.; Inanaga, J.; Hirata, K.; Sacki, H.;
Katsuki, T. Bull. Chem. Soc. Jpn. 1979, 52, 1989–1993; (b)
Mulzer, J.; Mareski, P. A.; Buschmann, J.; Luger, P.
Synthesis 1992, 215–228.
25
D
16. Spectroscopic data: data for compound 1: ½a +6.2 (c 0.9,
25
D
CHCl3) [lit.1 ½a þ7:3 (c 0.9, CHCl3)]; 1H NMR dH
(500 MHz, CDCl3): 4.90–4.95 (2H, ddd, J ¼ 9:9, 4.7,
4.5 Hz, H-6, 12), 4.05–4.08 (2H, ddd, J ¼ 4:5, 3.8, 3.2 Hz,
H-4, 10), 3.51–3.65 (2H, br, 3-OH, 10-OH), 2.41–2.86 (4H,
d, J ¼ 3:5 Hz, H-3, 9), 2.03–2.10 (2H, ddd, J ¼ 14:5, 9.5,
3.1 Hz, H-5b, 11b), 1.96 (2H, td, J ¼ 15, 4.5 Hz, H-5a,
11a), 1.49–1.57 (4H, m, H-13, 18), 1.22–1.29 (12H, m, H-
14, 15, 16, 19, 20, 21), 0.85–0.87 (6H, t, J ¼ 7:5 Hz, H-17,
22); 13C NMR dC (125 MHz, CDCl3): 172.9 (C-2, 8), 72.5
(C-6, 12), 64.5 (C-4, 10), 39.4 (C-3, 9), 36.9 (C-5, 11), 31.5
(C-13, 18), 31.3 (C-15, 20), 24.4 (C-14, 19), 22.4 (C-16, 21),
13.9 (C-17, 22); IR mmax: 3520, 1712, 1269, 1172 cmÀ1
;
25
D
1
MS(ESI): m=z 395.2 ([M +Na]þ). Data for 2: ½a +18 (c
20
D
0.9, CHCl3) [lit.3 ½a þ36:9 (c 0.92, CH2Cl2)]; H NMR
dH (500 MHz, CDCl3): 4.62–4.68 (1H, dddd, J ¼ 10:5, 7.5,
4.8, 4.2 Hz, 5-Hax), 4.30–4.38 (1H, dddd J ¼ 5, 4.1, 3.9,
3.6 Hz, 3-Heq), 2.69–2.73 (1H, dd, J ¼ 17, 5.5 Hz, 2-Hax),
2.57–2.62 (1H, ddd, J ¼ 17, 4.2, 3 Hz, 2-Heq), 2.07–2.12
(1H, br, 3-OHax), 1.94–1.96 (1H, dddd, J ¼ 13:5, 4.5, 3.5,
2.2 Hz, 4-Heq), 1.73–1.74 (1H, ddd, J ¼ 13:5, 10.3, 4.2 Hz,
4-Hax), 1.56–1.76 (2H, m, H-6), 1.34–1.55 (2H, m, H-7),
1.31–1.34 (2H, m, H-8), 1.29–1.30 (2H, m, H-9), 0.86–0.89
(3H, t, J ¼ 7:2 Hz, H-10); 13C NMR dC (125 MHz,
CDCl3): 170.4 (C-1), 76.1 (C-5), 62.7 (C-3), 38.7 (C-2),
36 (C-4), 35.5 (C-6), 31.6 (C-8), 24.4 (C-7), 22.6 (C-9), 13.9
(C-10); IR mmax: 3200–3600 (OH), 1739 (lactone).
8. Cho, B. T.; Yang, W. K.; Choi, O. K. J. Chem. Soc.,
Perkin Trans. 1 2001, 1204–1211.
9. (a) Sing, S.; Kumar, S.; Chimni, S. S. Synlett 2002, 8,
1277–1280; (b) Mandai, T.; Oshitari, T.; Susowake, M.
Synlett 2002, 1665–1668.