Page 980 - Advanced Organic Chemistry Part B - Reactions & Synthesis

956 CH 3
C
CHAPTER 10 CH 3 NOH CH C N O
3
Reactions Involving + N + NHCCH 3
Carbocations, Carbenes,
and Radicals as Reactive
Intermediates
H H H H

Entries 19 and 20 are examples of lactam formation by ring expansion of cyclic
oximes.

10.3. Reactions Involving Free Radical Intermediates

The fundamental mechanisms of free radical reactions were considered in
Chapter 11 of Part A. Several mechanistic issues are crucial in development of free
radical reactions for synthetic applications. 285 Free radical reactions are usually chain
processes, and the lifetimes of the intermediate radicals are very short. To meet the
synthetic requirements of high selectivity and efficiency, all steps in a desired sequence
must be fast in comparison with competing reactions. Owing to the requirement that all
the steps be fast, only steps that are exothermic or very slightly endothermic can partic-
ipate in chain processes. Comparison between addition of a radical to a carbon-carbon
double bond and addition to a carbonyl group can illustrate this point.

.
.
C + C C C C C . C + CO C C O .
π
π
ΔH = (C C) – (C π C ) ΔH = (C C) – (C π O )
= –81 – (–64) = –17 = –81 – (–94) = +13
This comparison suggests that of these two similar reactions, only alkene additions are
likely to be a part of an efficient radical chain sequence. Radical additions to carbon-
carbon double bonds can be further enhanced by radical stabilizing groups. Addition
to a carbonyl group, in contrast, is endothermic. In fact, the reverse fragmentation
reaction is commonly observed (see Section 10.3.6) A comparison can also be made
between abstraction of hydrogen from carbon as opposed to oxygen.

.
.
C + H C C H + . C C + H O C C H + . O C
ΔH = 0 ΔH = (C—H) – (O—H) = –98 – (–109) = +11

The reaction endothermicity establishes a minimum for the activation energy; whereas
abstraction of a hydrogen atom from carbon is a feasible step in a chain process,
abstraction of a hydrogen atom from a hydroxy group is unlikely. Homolytic cleavage
of an O−H bond is likely only if the resulting oxygen radical is stabilized, such as in
phenoxy radicals formed from phenols.

. O O .

285
C. Walling, Tetrahedron, 41, 3887 (1985).