Page 1025 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

the stabilization by a phenyl substituent shifts the cyclopropyl butenyl equilibrium 1009
to favor the cyclic form.
The cyclization of the 5-hexenyl radical to cyclopentylmethyl (Entry 33) is a SECTION 11.2
Characteristics of
commonly observed reaction. The E is 6 kcal/mol. The cyclization shows a preference Reactions Involving
a
for exo cyclization to a five-membered ring over endo cyclization to a six-membered Radical Intermediates
ring, 106 even though it results in formation of a less stable primary radical. The cause
for this preference has been traced to stereoelectronic effects. In order for a bonding
interaction to occur, the radical center must interact with the * orbital of the alkene.
According to MO calculations, the preferred direction of attack is from an angle of
about 70 with respect to the plane of the double bond. 107

70°

A B
exo endo

When this stereoelectronic requirement is included with a calculation of the steric and
angle strain imposed on the TS, as determined by MM-type calculations, preferences
of the exo versus endo modes of cyclization are predicted to be as summarized in
Table 11.8.
The observed results agree with the calculated trend. Relative rates of cyclization
are in the order 5-exo > 6-endo ∼6-exo > 7-endo 108 The relationship holds only
for terminal double bonds. An additional alkyl substituent at either end of the double
bond reduces the relative reactivity by a steric effect. The underlying conformational
and stereoelectronic effects can be modified by both steric and electronic effects of
substituents. For example, a 5-methoxycarbonyl substituent promotes the 6-endo mode
of cylization by an electronic effect. 109 The reactivity of the -carbon is enhanced by
the substituent.

Table 11.8. Regioselectivity of Radical Cyclization
as a Function of Ring Size a

exo:endo Ratio
Ring size Calculated Found
5:6 10:1 50:1
6:7 >100 1 10:1
7:8 1:5.8 <1 100
a. D. C. Spellmeyer and K. N. Houk, J. Org. Chem., 52, 959 (1987).

106 A. L. J. Beckwith, C. J. Eaton, and A. K. Serelis, J. Chem. Soc., Chem. Commun., 482 (1980);
A. L. J. Beckwith, T. Lawrence, and A. K. Serelis, J. Chem. Soc., Chem. Commun., 484 (1980);
A. L. J. Beckwith, Tetrahedron, 37, 3073 (1981).
107
M. J. S. Dewar and S. Olivella, J. Am. Chem. Soc., 100, 5290 (1978); D. C. Spellmeyer and K. N. Houk,
J. Org. Chem., 52, 959 (1987).
108 A. L. J. Beckwith and C. H. Schiesser, Tetrahedron, 41, 3925 (1985).
109
E. W. Della, C. Kostakis, and P. A. Smith, Org. Lett., 1, 363 (1999).