In conclusion, we have described a facile entry into a
functionalized C-aromatic taxane ring system employing an
oxonium ene cyclization reaction as the key step for the first
time. The potential of this method to construct the ABC system
of taxol is under investigation.
We are grateful to Dr M. Vairaman, IICT, Hyderabad, for
prompt help in providing HRMS data. D. K. M. and G. H. J.
thank CSIR and DST, New Delhi, India, for the award of
fellowships and financial assistance, respectively.
i
ii
iii
4
O
HO
5a
HO
enda-8
OEt
H +
O
5a
4a
O
H
H
H
7a
6a
Notes and References
+
O
OEt
O
† E-mail: pandey@ems.ncl.res.in
O
4b
1 M. C. Wani, H. L. Taylor, M. E. Wall, P. Coggon and A. T. McPhail,
J. Am. Chem. Soc., 1971, 93, 2325.
2 K. C. Nicolaou, M-W. Dai and R. K. Guy, Angew. Chem., Int. Ed. Engl.,
1994, 33, 15; A. N. Boa, P. R. Jenkins and N. J. Lawrence, Contemp.
Org. Synth., 1994, 47.
H
H
6b
7b
5b
Scheme 3 Reagents and conditions: i, SnCl4 (2.5 equiv.), 260 °C, 3 h,
CH2Cl2; ii, BunLi, THF, room temp., 7 h; iii, heat
3 I. Shiina, H. Iwadare, H. Sakoh, M. Hasegawa, Y. Tani and T.
Mukaiyama, Chem. Lett., 1998., 1 and references cited therein.
4 N. A. Petasis and M. A. Patane, Tetrahedron, 1992, 48, 5757.
5 J. J. Masters, J. T. Link, L. B. Snyder, W. B. Young and S. J.
Danishefsky, Angew. Chem., Int. Ed. Engl., 1995, 34, 1723.
6 M. H. Kress, R. Ruel, W. H. Miller and Y. Kishi, Tetrahedron Lett.,
1993, 34, 5999.
7 Y. Hirai and H. Nagaoka, Tetrahedron Lett., 1997, 38, 1969.
8 J. E. leffler and A. F. Wilson, J. Org. Chem., 1960, 25, 424.
9 H. R. Sonawane, S. G. Sudrik, M. M. Jakkam, A. Ramani and B.
Chanda, Synlett., 1996, 175. In the present work the experiment was
carried out with (±)-2 which was prepared by the Diels–Alder reaction
of 2,4-dimethylpenta-1,3-diene and acrolein catalysed by BF3·OEt2.
10 Separation of 4a and 4b via derivatisation and cyclisation is underway.
Selected data for 4: nmax(CHCl3)/cm21 3450, 2900, 1360, 1210;
dH(CDCl3, 200 MHz) 7.6–7.1 (m, 4H), 5.3 (s, 0.77H), 5.05 (s, 1H), 4.85
(d, J 10.8, 0.23H), 4.7–4.55 (m, 1H), 3.8–3.55 (m, 2H), 3.55–3.3 (m,
2H), 3.2–2.9 (m, 2H), 2.0–1.5 (m, 8H), 1.4–1.0 (m, 12H) (Calc. for
C22H34O3: C, 76.30; H, 9.82. Found: C,75.99; H, 9.43%).
11 R. W. Jackson, R. G. Higby, J. W. Gilman and K. J. Shea, Tetrahedron,
1992, 48, 7013.
Table 1 Results of Lewis acid-promoted cyclisations
Compound
Lewis acid (equiv.)
T/°C
Product Yield (%)
4
4
6
4
4
SnCl4 (2.5)
SnCl4 (1.1)
SnCl4 (1.5)
TiCl4 (1.1)
BF3·Et2O (1.1)
260
278
260
278
278
5a
6
5a
6
32
74
41
72
65
6
tandem radical macrocyclization–transannular sequence using
an appropriately functionalised A-ring unit.
Initially, the high stereoselectivity observed in the overall
cyclization process, viz. 4?5a, appeared somewhat intriguing.
However, mechanistic considerations along with an examina-
tion of the molecular models helped us greatly in increasing our
understanding. Mechanistically, in analogy with Overman’s
proposal,14 a concerted oxonium ion ene cyclization may well
be visualized in the formation of exo-5a from oxonium ion 7a,
derived from the major isomer 6a involving a favorable six-
membered transition state. The lack of the possibility of such a
transition state, due to the unfavorable geometry of the oxonium
ion 7b, from the minor isomer 6b precludes it from undergoing
an analogous type of cyclization that would lead to 5b.
In order to transform 5a into a molecule having taxane
skeleton 8 it was treated with BunLi15 at room temperature,
which furnished crystalline compound endo-816 (78%; mp 141
°C), instead of the corresponding exo-8. This observation may
possibly be explained by considering a thermal exo to endo
atropisomerization17 during the work-up stage. The structure
and stereochemical assignment of endo-8 follows from a
detailed 1H NMR decoupling experiment and selected coupling
constants. Finally, the structure was confirmed by a 2D-COSY
NMR experiment.
12 L. F.Tietze, Chem. Rev., 1996, 96, 115.
13 S. A. Hitchcock and G. Pattenden, Tetrahedron Lett., 1992, 33, 4843.
14 For an elegant application of this concept in the synthesis of
4
D -oxocene, see T. A. Blumenkopf, G. C. Look and L. E. Overman,
J. Am. Chem. Soc., 1990, 112, 4399.
15 M. E. Jung and S. J. Miller, J. Am. Chem. Soc., 1981, 103, 1984.
16 Selected data for 8: nmax(Nujol)/cm21 3273, 2950, 2800, 1254, 1021;
dH(CDCl3, 200 MHz) 7.55 (d, J 7.6, 1H), 7.2 (dt, J 6.4, 1.2, 1H); 7.1 (dt,
J 6,1.2, 1H), 7.0 (d, J 7.4, 1H), 6.6 (d, J 10.7, 1H), 6.0 (dd, J 11.7, 1H),
5.1 (s, 1H), 4.55 (br s, 1H), 2.35 (d, J 9.2, 1H), 2.1 (br s, 2H), 1.7 (br s,
1H), 1.3 (s, 3H), 1.2 (d, J 1.2, 3H), 1.05 (s, 3H ); dC(CDCl3, 50 MHz)
142.8, 135.9, 133.5, 132.1, 129.9, 126.5, 126.1, 125.6, 124.6, 120.5,
70.1, 49.9, 46.7, 32.9, 29.7, 26.1, 24.2, 22.8 (Calc. for C18H22O:
254.1670 (M+). Found: 254.1666).
17 M. Seto, K. Morihira, Y. Horiguchi and I. Kuwajima, J. Org. Chem.,
1994, 59, 3165.
Received in Cambridge, UK, 1st June 1998; 8/04084B
1774
Chem. Commun., 1998