Radical reactions ring expansion

In this section, we can consider many different transformations. Unimolecular, radical, reduction, ring expansion, hydrolysis, and dechlorination reactions can all be described. The first two reactions in this list have already been addressed (Sections 6.11.2.2, 6.11.4.1, and 6.11.4.2). 

Alkoxy radicals for ring expansion can be generated from alcohols by oxidative methods such as hypohalite thermolysis/photolysis [19a] and lead tetraacetate oxidation [19b], or peroxide reduction [19c]. The recent development of the hyper-valent organoiodine reagent (diacetoxyiodo)benzene (DIB) provides another way for efficient generation of alkoxy radicals (Scheme 11) [19d]. Additional oxidative methods to prepare cyclopropyloxy radicals include reaction of tertiary cyclopropanols or their silyl ether derivatives with various reagents such as manganese(III) tris(pyridine-2-carboxylate) [Mn(pic)3] [20a], Fe(III) salts [20b], and vanadyl ace-tylacetate [20c] (Scheme 12). 

Treatment of 1-alkynylcycloalkanols 11 with reagent 4 and iodine affords (Z)-2-(l-iodo-l-organyl)methylenecycloalkanones 12 resulting from the alkoxyl radical-promoted ring-expansion reaction (Scheme 5.7) [33]. 

Baldwin et al. used a radical-mediated ring expansion of 3-stannylcyclohexanones to provide efficient routes to cis-and trans-cyclononenones. Thus, bromo ketone 109 underwent a radical reaction to generate cyclopentyl aUcoxy radical 110. Fragmentation and elimination of a stannyl radical led to cyclononenone 111, which was further elaborated to rac-phoracantholide I (Scheme 25.52), originally isolated from the metastemal secretion of the eucalypt lon-gicom Phoracantha synonyma. 

The reaction rate has also been greatly increased by the addition of a one-electron oxidant tris-(4-bromophenyl)aminium hexafluoroantimonate Ar3N SbF (Ar = / -bromophenyl)." This reagent converts the substrate to a cation radical, which undergoes ring expansion much faster." ... 

The trimethylsilyl ethers 212 of four-membered 1-alkenyl-1-cyclobutanols rearrange to the ring-expanded 0-mercuriocyclopentanones 213. These can be converted into the a-methylenecyclopentanones 214 through elimination or further expanded by one-carbon atom into cyclohexanones 215 via the Bu3SnH-mediated free radical chain reactions [116]. A similar radical intermediate is suggested to be involved in the ring expansion of a-bromomethyl-fi-keto esters [117]. (Scheme 84)... 

The kinetic data for these reactions are numerous, as shown in Table VI. Most of values were obtained by radical clock methods. The ring expansion of radical 7 has been employed as the clock in a study that provided much of the data in Table VI.74 Cyclizations of 5-hexenyl-type radicals also have been used as clocks,75-77 and other competition reactions have been used.78 Hydrogen atom abstraction from n-Bu3GeH by primary alkyl radicals containing a trimethylsilyl group in the a-, >8-, or y-position were obtained by the indirect method in competition with alkyl radical recombi-... 

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 competitive kinetics of Scheme 3.1 can also be applied to calibrate the unimolecular radical reactions provided that kn is a known rate constant. In particular the reaction of primary alkyl radicals with (Mc3Si)3SiH has been used to obtain kinetic data for some important unimolecular reactions such as the p-elimination of octanethiyl radical from 12 (Reaction 3.5) [12], the ring expansion of radical 13 (Reaction 3.6) [8] and the S-endo-trig cyclization of radical 14 (Reaction 3.7) [13]. The relative Arrhenius expressions shown below for the... 

Scheme 6.9 shows the radical clock methodology approach used for obtaining the rate constant of the ring expansion (k e)- Radical 37 was obtained by the reaction of the corresponding phenylseleno derivative with (TMS)3SiH. A relative rate constant of = 20.2 was obtained at 80 °C under first-... 

Extensive mechanistic investigation of the ring expansion 33 —> 34 was performed in order to differentiate between a ring-opening reaction to give a silyl radical 39 (path a), followed by the 6-endo cyclization, or a pentavalent silicon transition state 40 (path b). It was clearly demonstrated that the ring expansion proceeds via a pentavalent silicon transition state (Scheme 6.10) [16]. 

The cyclization of 8, s-unsaturated acyl radicals has been the research subject of several groups [27]. The propagation steps for the prototype reaction are illustrated in Scheme 7.4. The 5-exo 6-endo product ratio varies with the change of the silane concentration due to the competition of hydrogen abstraction from the silane with the ring expansion path. 

Pyrolysis of 2-substituted l,3-dibenzyl-2-methylbenzimidazoles at 200°C results in ring expansion to afford the tetrahydroquinoxalines 180 (Equation 29) <1996TL3355>. The reaction was suggested to proceed by an ionic mechanism rather than a radical one. 

Ring expansion reactions of free radicals are useful in synthesis (equation 77) and were reported independently in 1987 by the groups of Beckwith and Dowd " ... 

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