Page 993 - Advanced Organic Chemistry Part B - Reactions & Synthesis

969

SECTION 10.3
Reactions Involving Free
Radical Intermediates
2.24 Å
2.26 Å

6-endo boat
6-endo chair

2.19 Å

2.19 Å

5-exo boat
5-exo chair

• R 1 R 1 R 1
2
3 • + R
R R 3 •
2
R R 2 R 3
6-endo pathway 5-exo pathway

reactant chair TS boat TS chair TS boat TS
2
1
3
R =H, R =H, R =H, 9.1 11.6 6.4 8.1
2
3
1
R =Me, R =H, R =H, 9.6 12.2 7.0 8.7
1
3
2
R =H, R =Me, R =H, 8.4 10.7 9.1 10.3
3
2
1
R =H, R =H, R =Me, 9.8 12.5 6.5 8.1
Fig. 10.14. Relative energies of 5-exo and 6-endo transition structures. Insert shows the
effect of methyl substituents. Reproduced from J. Am. Chem. Soc., 125, 4271 (2003),
by permission of the American Chemical Society.
This reaction has subsequently been used in a number of other cases. 324 The five-
membered rings are usually fused in a cis manner, minimizing strain. When cyclization
is followed by hydrogen abstraction, the hydrogen atom is normally delivered from the
less hindered side of the molecule. The following example illustrates these generaliza-
tions. The initial tetrahydrofuran ring closure gives the cis-fused ring. The subsequent
hydrogen abstraction is from the less hindered axial direction. 325

324 X. J. Salom-Roig, F. Denes, and P. Renaud, Synthesis, 1903 (2004).
325
M. J. Begley, H. Bhandal, J. H. Hutchinson, and G. Pattenden, Tetrahedron Lett., 28, 1317 (1987).