Page 999 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

There have been many studies aimed at deducing the geometry of radical sites 983
by examining the stereochemistry of radical reactions. The most direct kind of study
involves the generation of a radical at a carbon that is a stereogenic center. A planar SECTION 11.1
or rapidly inverting radical leads to racemization, whereas a rigid pyramidal structure Generation and
Characterization of Free
would lead to product of retained configuration. Some examples of reactions that have Radicals
been subjected to this kind of study are shown in Scheme 11.2. In each case racemic
product is formed, indicating that alkyl radicals do not retain the tetrahedral geometry
of their precursors.
Entry 1 is a chlorination at a stereogenic tertiary center and proceeds with
complete racemization. In Entry 2, a tertiary radical is generated by loss of C≡O,
again with complete racemization. In Entry 3, an -methylbenzyl radical is generated
by a fragmentation and the product is again racemic. Entry 4 involves a benzylic
bromination by NBS. The chirality of the reactant results from enantiospecific isotopic
labeling of ethylbenzene. The product, which is formed via an -methylbenzyl radical
intermediate, is racemic.
Cyclic molecules permit deductions about stereochemistry without the necessity
of using resolved chiral compounds. The stereochemistry of a number of reactions of
51
4-substituted cyclohexyl radicals has been investigated. In general, reactions starting
from pure cis or trans stereoisomers give mixtures of cis and trans products. This
result indicates that the radical intermediates do not retain the stereochemistry of the
precursor. Radical reactions involving t-butylcyclohexyl radicals are usually not very
stereoselective, but some show a preference for formation of the cis product. This has
been explained in terms of a torsional effect. The pyramidalization of the radical is

Scheme 11.2. Stereochemistry of Radical Reactions at Stereogenic Carbon Centers

1 a CH 3 CH 3
Cl 2
(+) ClCH 2 C CH CH 3 hv (±) ClCH 2 C CH CH 3
2
2
H CH 3 Cl CH 3
[(CH ) CO]
2 b (–) (CH ) C C CH CH 3 Δ 3 3 2 (±) (CH 3 2 C CH CH 3
) C
3 2
2
2
CH O H
CH H
3 c 3
(+) Ph C C(CH ) Ph C CH 3 + (CH ) C O
3 2
3 2
H OCl Cl
99% racemic
4 d D N-bromo- H D
succinimide
Ph C CH 3 Ph C CH 3 + Ph C CH 3
H Br Br
> 99.7% racemic
a. H. C. Brown, M. S. Kharasch, and T. H. Chao, J. Am. Chem. Soc., 62, 3435 (1940).
b. W. v. E. Doering, M. Farber, M. Sprecher, and K. B. Wiberg, J. Am. Chem. Soc., 74, 3000 (1952).
c. F. D. Greene, J. Am. Chem. Soc., 81, 2688 (1959); D. B. Denney and W. F. Beach, J. Org. Chem., 24, 108
(1959).
d. H. J. Dauben, Jr., and L. L. McCoy, J. Am. Chem. Soc., 81, 5404 (1959).
51
F. R. Jensen, L. H. Gale, and J. E. Rodgers, J. Am. Chem. Soc., 90, 5793 (1968).