1730
A. Kamimura et al. / Tetrahedron Letters 50 (2009) 1727–1730
O
ses suggest that the radical cyclization from A2 should be irrevers-
MeO
N
MeO
ible; the 7-endo/6-exo selectivity should be determined
kinetically. Further studies on this reaction are in progress in our
laboratory and will be published elsewhere.
N
O
Br
much slower
Br
1A; 55%
than the radical
process
1B; 45%
Acknowledgment
Bu3Sn
Bu3Sn
O
MeO
We are grateful for a financial support from Grant-in-Aid
(16550041) from MEXT, Japan. We thank Prof. Murafuji and Mr.
Tao for their help for NMR measurements.
N
MeO
N
O
radical A2
radical A1
References and notes
Bu3SnH
kred
k6
1. Miller, W. H.; Alberts, D. P.; Bhatnagar, P. K.; Bondinell, W. E.; Callahan, J. F.;
Calvo, R. R.; Cousins, R. D.; Erhard, K. F.; Heerding, D. A.; Keenan, R. M.; Kwon,
C.; Manley, P. J.; Newlander, K. A.; Ross, S. T.; Samanen, J. M.; Uzinskas, I. N.;
Venslavsky, J. W.; Yuan, C. C.-K.; Haltiwanger, R. C.; Gowen, M.; Hwang, S.-M.;
James, I. E.; Lark, M. W.; Rieman, D. J.; Stroup, G. B.; Azzarano, L. M.; Salyers, K.
L.; Smith, B. R.; Ward, K. W.; Johanson, K. O.; Huffman, W. F. J. Med. Chem. 2000,
43, 22; Feuston, B. P.; Culberson, J. C.; Duggan, M. E.; Harman, G. D.; Leu, C.-T.;
Rodan, S. B. J. Med. Chem. 2002, 45, 5640.
2. Kamimura, A.; Taguchi, Y.; Omata, Y.; Hagihara, M. J. Org. Chem. 2003, 68, 4996.
3. (a) Sato, T.; Ishida, S.; Ishibashi, H.; Ikeda, M. J. Chem. Soc., Perkin Trans. 1 1991,
353; (b) Clark, A. J.; Jones, K.; McCarthy, C.; Storey, J. M. D. Tetrahedron Lett.
1991, 32, 2829; (c) Ghosh, A. K.; Ghosh, K.; Pal, S.; Chatak, U. R. J. Chem. Soc.,
Chem. Commun. 1993, 809; (d) Gibson, S. E.; Guillo, N.; Middleton, R. J.;
Thuilliez, A.; Tozer, M. J. J. Chem. Soc., Perkin Trans. 1 1997, 447; (e) Gibson, S. E.;
Guillo, N.; Tozer, M. J. Chem. Commun. 1997, 637; (f) Merritt, J. E.; Sasson, M.;
Kates, S. A.; Snider, B. B. Tetrahedron Lett. 1988, 29, 5209; (g) Ishibashi, H.;
Ishita, A.; Tamura, O. Tetrahedron Lett. 2002, 43, 473; (h) Taniguchi, T.; Ishita, A.;
Uchiyama, M.; Tamura, O.; Muraoka, O.; Tanabe, G.; Ishibashi, H. J. Org. Chem.
2005, 70, 1922.
k7
MeO
N
O
kcycl = k7 + k6
MeO
4; reduced compound
MeO
N
N
N
N
O
O
O
B
C
Bu3SnH
Bu3SnH
MeO
MeO
O
kred/kcycl = 3.0
2; 7-endo product
3; 6-exo product
4. Kamimura, A.; Taguchi, Y. Tetrahedron Lett. 2004, 45, 2335.
5. Matsuura, K.; Kuratani, T.; Gondo, T.; Kamimura, A.; Inui, M. Eur. J. Pharmacol.
2007, 563, 83.
Scheme 5.
6. Ishibashi, H.; Kobayashi, T.; Nakamura, S.; Tamura, O. J. Org. Chem. 2000, 65,
9022.
7. (a) Curran, D. P.; Guthrie, D. B.; Geib, S. J. J. Am. Chem. Soc. 2008, 130,
8437; (b) Stork, G.; Mah, R. Heterocycles 1989, 28, 723; (c) Curran, D. P.;
Tamine, J. J. Org. Chem. 1991, 56, 2746; (d) Curran, D. P.; DeMello, N. C. J.
Chem. Soc., Chem. Commun. 1993, 1314; (e) Curran, D. P.; Qi, H.; Geib, S. J.;
DeMello, N. C. J. Am. Chem. Soc. 1994, 116, 3131; (f) Curran, D. P.; Liu, H. T.
J. Chem. Soc., Perkin Trans. 1 1994, 1377; (g) Bremner, J. B.; Sengpracha, W.
Tetrahedron 2005, 61, 941.
8. Silverstein, R. M.; Bassler, G. C.; Morrill, T. C. Spectrometric Identification of
Organic Compounds, 5th ed.; John Wiley & Sons: Chichester, 1991.
9. Newcomb, M. Tetrahedron 1993, 49, 1151.
10. Compound 12 was prepared in a similar manner to the preparation of 3 except
for using CH2I2 instead of CH3I. The yield of 12 was 40%.
11. Garden, S. J.; Avila, D. V.; Beckwith, L. J.; Bowry, V. W.; Ingold, K. U.; Lusztyk, J. J.
Org. Chem. 1996, 61, 805.
12. Abeywickrema, A. N.; Beckwith, A. L. J. J. Chem. Soc., Chem. Commun. 1986, 464;
Curran, D. P.; Fairweather, N. J. Org. Chem. 2003, 68, 2972.
6-exo cyclization seems reasonable because other examples for ki-
netic studies for 7-endo cyclization at 80 °C also indicate the ki-
netic parameters in a similar range.12
In conclusion, we carefully examined the reaction profile of
7-endo selective radical cyclization using the precursor 1. The
cyclization gave three products, 7-endo adduct 2, 6-exo adduct 3
and reduced product 4. The reduction/cyclization ratio was af-
fected by the rotamer population of precursor 1. The major rot-
amer 1A gave the reduced product
4 only. The cyclization
selectivity of 1B was enhanced when less concentration of Bu3SnH
was employed. The 7-endo/6-exo selectivity was almost constant
against variations in the Bu3SnH concentration. The kinetic analy-