868
K. Nakai et al.
LETTER
(6) (a) Brown, F. K.; Raimondi, L.; Wu, Y.-D.; Houk, K. N.
8.8%
2.7%
H
Tetrahedron Lett. 1992, 33, 4405. (b) Raimondi, L.; Wu,
Y.-D.; Brown, F. K.; Houk, K. N. Tetrahedron Lett. 1992,
33, 4409.
H
H
Me
5
4.3%
H
6
4
OSEM
A-ring
H
8
(7) Takahashi, T.; Nakazawa, M.; Sakamoto, Y.; Houk, K. N.
Tetrahedron Lett. 1993, 34, 4075.
(8) Lee, G. A. Synthesis 1982, 508.
3
OTBS
H
9
N
O
(9) Majumdar, S.; Bhattacharjya, A.; Patra, A. Tetrahedron Lett.
1997, 38, 8581.
H
4.1%
(10) The structure of 7 was determined based on 1H NMR and
DEPT spectra.
Figure 2 NOE observation of 22.
(11) The b-elimination of the 5-acetoxy group in 13 disabled
further transformation.
(12) (a) Nicolaou, K. C.; Yang, Z.; Sorensen, E. J.; Nakada, M. J.
Chem. Soc., Chem. Commun. 1993, 1024. (b) Di Grandi, M.
J.; Jung, D. K.; Krol, W. J.; Danishefsky, S. J. J. Org. Chem.
1993, 58, 4989.
In summary, we have demonstrated the [3+2] cycloaddi-
tion for the formation of the paclitaxel C ring in an ad-
vanced intermediate containing the A ring moiety. It is
found that the stereoelectronic effect from the 1,2-cyclic
carbonate controls the reaction pathway, favoring the de-
sired [3+2] cycloaddition rather than cationic cyclization.
Further study on the formation of the B ring toward the
synthesis of paclitaxel is underway in our laboratory.
(13) The aldehyde 15 was prepared as follows: (i) LDA, ethyl 3-
methyl-2-butenoate; 2,4-O-benzylidene-2,4-dihydroxy-
butanal, 50% d.s., cf. ref.3b; (ii) LiAlH4; (iii) TBSCl; (iv)
SEMCl; (v) TBAF; (vi) TPAP, NMO.
(14) The stereochemistry was determined by the 1H NMR
coupling constants (J2,3 = J3,4 = 10 Hz) after acetonide
formation for 2,4-diol from 17.
References
(15) Spectral data of 22: IR (neat): 2957, 1798, 1726, 1463, 1362,
1250, 1150, 1070, 837 cm–1. 1H NMR (400 MHz, CDCl3):
d = 0.02 (s, 9 H), 0.12 (s, 3 H), 0.15 (s, 3 H), 0.89 (s, 9 H),
0.86–0.97 (m, 2 H), 1.03 (s, 3 H), 1.11 (s, 3 H), 1.20 (s, 9 H),
1.33 (s, 3 H), 1.72 (s, 3 H), 2.00–2.17 (m, 2 H), 2.31–2.52
(m, 2 H), 2.43 (dd, 1 H, J = 1.93, 15.00 Hz), 2.69 (dd, 1 H,
J = 2.90, 15.00 Hz), 2.87 (d, 1 H, J = 10.60 Hz), 3.55 (dt, 1
H, J = 6.28, 10.10 Hz), 3.60 (d, 1 H, J = 7.25 Hz), 3.74 (dt,
1 H, J = 6.28, 10.10 Hz), 3.77 (d, 1 H, J = 10.60 Hz), 4.15
(d, 1 H, J = 7.25 Hz), 4.32 (s, 1 H), 4.53–4.60 (m, 1 H), 4.56
(d, 1 H, J = 12.60 Hz), 4.60 (d, 1 H, J = 12.60 Hz), 4.70 (d,
1 H, J = 6.77 Hz), 4.81 (d, 1 H, J = 6.77 Hz). 13C NMR (99.6
MHz, CDCl3): d = –4.5 (CH3), –4.3 (CH3), –1.3 (CH3), 17.7
(CH3), 18.2 (C), 18.3 (CH2), 19.5 (CH3), 24.0 (CH2), 25.8
(CH3), 25.9 (CH3), 27.27 (CH3), 27.35 (CH3), 29.4 (CH2),
29.6 (CH2), 38.9 (C), 43.0 (C), 43.7 (CH), 56.0 (C), 61.1
(CH2), 66.7 (CH2), 68.6 (CH), 78.0 (CH), 80.9 (CH2), 81.4
(CH), 88.7 (C), 96.5 (CH2), 126.4 (C), 136.5 (C), 154.8 (C),
160.0 (C), 178.6 (C). ESI-TOF: m/z = 724.4 [M + H]+.
(1) For a recent review, see: (a) Kingston, D. G. I. Chem.
Commun. 2001, 867. (b) Kingston, D. G. I.; Jagtap, P. G.;
Yuan, H.; Samala, L. In Progress in the Chemistry of
Organic Natural Products, Vol. 84; Herz, W.; Falk, H.;
Kirby, G. W., Eds.; Springer: Wien, New York, 2002, 53.
(2) (a) Takahashi, T.; Iwamoto, H.; Nagashima, K.; Okabe, T.;
Doi, T. Angew. Chem., Int. Ed. Engl. 1997, 36, 1319.
(b) Miyamoto, S.; Doi, T.; Takahashi, T. Synlett 2002, 97.
(3) (a) Takahashi, T.; Iwamoto, H. Tetrahedron Lett. 1997, 38,
2483. (b) Takahashi, T.; Hirose, Y.; Iwamoto, H.; Doi, T. J.
Org. Chem. 1998, 63, 5742.
(4) (a) Nakai, K.; Kamoshita, M.; Doi, T.; Yamada, H.;
Takahashi, T. Tetrahedron Lett. 2001, 42, 7855. (b) Nakai,
K.; Miyamoto, S.; Sasuga, D.; Doi, T.; Takahashi, T.
Tetrahedron Lett. 2001, 42, 7859. (c) Fuse, S.; Hanochi, M.;
Doi, T.; Takahashi, T. Tetrahedron Lett. 2004, 45, 1961.
(5) (a) Alcaraz, L.; Harnett, J. J.; Mioskowski, C.; Le Gall, T.;
Shin, D.-S.; Falck, J. R. J. Org. Chem. 1995, 60, 7209.
(b) Nivlet, A.; Dechoux, L.; Martel, J.-P.; Proess, G.;
Manner, D.; Alcaraz, L.; Harnett, J. J.; Le Gall, T.;
Mioskowski, C. Eur. J. Org. Chem. 1999, 3241.
Synlett 2005, No. 5, 866–868 © Thieme Stuttgart · New York