Radical: rearrangements

Scheme 12.6 gives some examples of reactions in which free-radical rearrangements have been observed. 

The radical rearrangement reaction, serving as a timing device, has been called a free radical clock 2 It provides a means of evaluating the rate constant for reactions of this radical with other substrates. The example shows how the radical-chromium(II) rate constant can be determined. A number of other instances have been summarized.13... 

Hodgson, D.M. Galano, J.M. (2005) Enantioselective Access to Isoquinuclidines by Tropen-one Desymmetrization and HomoaHylic Radical Rearrangement Synthesis of (-F)-Ibogamine. Organic Letters, 1, 2221-2224. 

Finally, we note the informative work of Garcia-Garibay and co-workers, who have extensively studied QMT in hydrogen transfer reactions in the excited triplet states of ort/zo-alkylarylketones, for example, 6 —> 7, which are electronically similar to radical rearrangements. 

The fragmentation of alkoxyl radicals is especially favorable because the formation of a carbonyl bond makes such reactions exothermic. Rearrangements of radicals frequently occur by a series of addition-fragmentation steps. The following two reactions involve radical rearrangements that proceed through addition-elimination sequences. 

Cyclic 0,y-unsaturated ketones undergo a photochemical rearrangement thought to involve a-cleavage and radical rearrangement. The products of these cyclic ketones are j8,y-unsaturated ketones possessing exocyclic olefinic linkages,<41,4a)... 

Scheme 3.4. Walton s and McCarroll s classification of unimolecular free-radical rearrangements.

An excellent review by Walton and McCarroll has recapitulated the various processes which can be featured during a radical cascade [2]. Moreover, these authors have elaborated a compilation of classes of unimolecular free-radical rearrangements, as illustrated in Scheme 3.4. 

In the case of 13-LOXs, the active site is again penetrated by the substrate using its methyl end first, whereas with 9-LOXs, the substrate is forced into an inverse orientation, favoring penetration with its carboxy group first. Consequently, a radical rearrangement at either [+2] or [-2], respectively, may be facilitated in both cases by the same mechanism within the active site. 

Charge density-NMR chemical shift correlation in organic ions, 11, 125 Charge distribution and charge separation in radical rearrangement reactions, 38, 111 Chemically induced dynamic nuclear spin polarization and its applications, 10, 53 Chemiluminesance of organic compounds, 18, 187 Chiral clusters in the gas phase, 39, 147... 

Radical rearrangement reactions, charge distribution and charge separation in, 38, 111... 

Methyl 2,3-butadienoate can undergo 1,3-dipolar cycloaddition with nitrones leading to the formation of 528, which would undergo homolytic cleavage of the N-O bond followed by radical rearrangement and coupling to afford benzazepinone 531 [239]. 

In the gas phase, this decarbonylation reaction is very efficient. Radical rearrangements, which are also possible if the change leads to a more stable product ... 

It has been shown" that isomerization of the exocyclic allylic system of the five-membered ring D of kaurenols depends on the orientation of the C(15) hydroxyl group. The total synthesis of methyl atis-16-en-19-oate, a tetracyclic diterpenoid possessing a bicyclo[2.2.2]octane skeleton, has been accomplished" using a homoallyl-homoallyl radical rearrangement process of methyl 12-hydroxykaur-16-en-19-oate monothioimid-azolide (280) as the pivotal step. Two plausible mechanisms have been presented" ... 

The kinetic data for the reaction of primary alkyl radicals (RCH2 ) with a variety of silanes are numerous and were obtained by applying the free-radical clock methodology. The term free-radical clock or timing device is used to describe a unimolecular radical reaction in a competitive study [2-4]. Three types of unimolecular reactions are used as clocks for the determination of rate constants for this class of reactions. The neophyl radical rearrangement (Reaction 3.1) has been used for the majority of the kinetic data, but the ring expansion rearrangement (Reaction 3.2) and the cyclization of 5-hexenyl radical (Reaction 3.3) have also been employed. 

The concept of this method is illustrated in Scheme 3.1, where the clock reaction (U R ) is the unimolecular radical rearrangement with a known rate constant ( r)- The rate constant for the H atom abstraction from RsSiH by a primary alkyl radical U can be obtained, provided that conditions are found in which the unrearranged radical U is partitioned between the two reaction channels, i.e., the reaction with RsSiH and the rearrangement to R. At the end of the reaction, the yields of unrearranged (UH) and rearranged (RH) products can be determined by GC or NMR analysis. Under pseudo-first-order conditions of silane concentration, the following relation holds UH/RH = (A H/A r)[R3SiH]. A number of reviews describe the radical clock approach in detail [3,4]. 

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