9184
E. Thomas et al. / Tetrahedron Letters 47 (2006) 9181–9185
Takagi, K.; Wu, G. J. Am. Chem. Soc. 1989, 111, 3089–
3091; (c) Kocienski, P.; Barber, C. Pure Appl. Chem. 1990,
62, 1933–1940.
2. (a) Kasatkin, A. N.; Whitby, R. J. Tetrahedron Lett. 2000,
41, 6211–6216; (b) Kasatkin, A. N.; Whitby, R. J.
Tetrahedron Lett. 1999, 40, 9353–9357.
3. (a) Kobrich, G.; Goyert, W. Tetrahedron 1968, 24, 4327–
4342; (b) Seyferth, D.; Lambert, R. L.; Massol, M. J.
Organomet. Chem. 1975, 88, 255–286; (c) Warner, P. M.;
Chang, S. C.; Koszewski, N. J. Tetrahedron Lett. 1985, 26,
5371–5374; (d) Kitatani, K.; Hiyama, T.; Nozaki, H. J.
Am. Chem. Soc. 1975, 97, 949–951.
4. The Chemistry of the Cyclopropyl Group; Rappoport, Z.,
Ed.; Wiley: New York, 1987, parts 1 and 2, and 1995,
part 3.
5. (a) Salaun, J.; Baird, M. S. Curr. Med. Chem. 1995, 2, 511–
542; (b) Salaun, J. Top. Curr. Chem. 2000, 207, 1–67.
6. (a) Harada, T.; Hattori, K.; Katsuhira, T.; Oku, A.
Tetrahedron Lett. 1989, 30, 6035–6038; (b) Harada, T.;
Katsuhira, T.; Hattori, K.; Oku, A. J. Org. Chem. 1993,
58, 2958–2965.
7. Kakiya, H.; Inoue, R.; Shinokubo, H.; Oshima, K.
Tetrahedron 2000, 56, 2131–2137.
8. Stereochemistries of 12 and 14 were assigned by compar-
ison of NMR spectra with known compounds. (a) Schau-
mann, E.; Kirschning, A.; Narjes, F. J. Org. Chem. 1991,
56, 717–723; (b) Ishihara, T.; Ando, T.; Muranaka, T.;
Saito, K. J. Org. Chem. 1977, 42, 666–670; (c) See Ref. 6b.
9. DFT calculations were carried out with the B3LYP/6-
31G* method using Spartan04 for windows (Wavefunc-
tion Ltd.).
10. Hammerschmidt, F.; Hanninger, A.; Vollenkle, H. Chem.
Eur. J. 1997, 3, 1728–1732.
Scheme 4. Reagents and conditions: (i) nBuLi, À90 °C, 15 min; (ii)
0.5 equiv (E)-Cp2ZrCl(CH@CHR2) 5, R1 = H, À90 to À40 °C over 5 h
or R1 = Me, À90 to 20 °C over 5 h; (iii) MeOH, NaHCO3aq, 20 °C,
16 h; (iv) 180 °C, 1 h, lW, DMF; (v) 0.12 equiv or 0.5 equiv
N-phenylmaleimide, toluene, 115 °C, 4 h.
11. It is possible that addition occurs by the concerted
insertion of the carbenoid into the carbon–zirconium
bond with loss of LiBr rather than via an ‘ate’ complex.
Calculations on the structure of the carbenoid show that
both the HOMO and LUMO have their major compo-
nents on the same side as the lithium hence the stereo-
chemical result will be the same as the pathway via an ‘ate’
complex and would thus have to be taking place via the
epimer of 4.
12. We have not proved the relative stereochemistry between
the CH(hexyl)CH(OH)Ph fragment and the cyclohexyl–
cyclopropane ring fusion, which can also be viewed as the
alkene stereochemistry, but diastereoisomer 37 would only
be accessible by the attack of the electrophile anti- to the
zirconium, which is unlikely both because the cyclohexyl
ring provides an effective steric block, and because it
would then be very difficult to account for the syn
stereochemistry observed.
the inseparable dienes 34 arising from a homodienyl-1,5-
hydrogen shift (retro-ene reaction).18 Reaction of the
mixture with N-phenylmaleimide and chromatography
allowed the isolation of pure 33, together with the
Diels–Alder adduct 35 of 34.
Overall we have shown that the reaction of readily gen-
erated cyclopropyl carbenoids with alkenylzirconocenes
provides a facile convergent route to alkenylcyclo-
propanes and alkylidenecyclopropanes, important inter-
mediates in organic synthesis.19,20 In each case the
stereochemistry of the products is consistent with trans-
metallation from lithium to zirconium in the formation
of an ‘ate’ complex occurring with the inversion of the
organolithium centre.
.
13. For example, ozonolysis of alkylidene cyclopropanes is
known to be complex and not involve simple cleavage of
the double bond: Langler, R. F.; Raheja, R. K.; Schank,
K.; Beck, H. Helv. Chim. Acta 2001, 84, 1943–1951.
14. Ito, H.; Nakamura, T.; Taguchi, T.; Hanzawa, Y. Tetra-
hedron 1995, 51, 4507–4518.
15. The structures of 24–26a and b came from analysis of
NMR data and comparisons with similar literature
compounds. (a) Beruben, D.; Marek, I.; Normant, J. F.;
Platzer, N. J. Org. Chem. 1995, 60, 2488–2501; (b) Fischer,
H.; Hofmann, J. Chem. Ber. 1991, 124, 981–988; (c)
Baldwin, J. E.; Bonacorsi, S. J. Org. Chem. 1994, 59,
7401–7409; (d) Shabarov, Y. S.; Bandaev, S. G.; Volov, E.
Acknowledgements
We thank the Engineering and Physical Sciences
Research Council for supporting this work.
References and notes
1. (a) Negishi, E.; Akiyoshi, K. J. Am. Chem. Soc. 1988, 110,
646–647; (b) Negishi, E.; Akiyoshi, K.; O’Connor, B.;