Radical addition reaction condition effects

Although peroxide-decomposition data have to be used with great caution, it can be concluded that double bonds are consumed by radical addition reactions. One can debate whether the unsaturations are consumed by multiple radical addition reactions or via consecutive radical addition/radical transfer sequences. The latter seems most likely, considering the low tendency of alkyl radicals for addition to alkyl-substituted double bonds under these relatively mild conditions. In radical addition reactions of this kind, the stabilisation of radicals due to polar effects is negligible. Experimental studies show that the reactivity is mainly controlled by steric effects [96]. The order of reactivity MNB > DCPD ENB > HD towards radical addition reactions as found by Fujimoto and coworkers [73, 74] is in line with these considerations. 

Control of addition vs substitution by free radicals can be effected by the reaction conditions, ie, radical concentration, temperature, and phase. Using halogens as propylene reactants, high temperatures and the gas phase favor high radical concentrations and substitution reactions cold, Hquid-phase conditions favor addition reactions. 

Entry 21 involves addition to a glyoxylic hydrazone and the cis ring junction is dictated by strain effects. The primary phenylselenyl group is reductively removed under the reaction conditions. Entry 22 involves generation of a stannyloxy radical by addition of the stannyl radical at the carbonyl oxygen. Cyclization then ensues, with the cis-trans ratio being determined by the conformation of the cyclization TS. 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

The literature on liquid-phase olefin oxidation has been well reviewed (1, 2, 3, 5, 6, 8,12,14,15, 16,17, 18,19,20). Recent attention has been focused on the effects of structure and reaction conditions on the proportions of alkenyl hydroperoxy radical reaction by the abstraction and addition mechanisms at lower temperatures and conversions. The lower molecular weight cyclic and acyclic olefins have been extensively studied by Van Sickle and co-workers (17, 18, 19, 20). These studies have recently been extended to include higher molecular weight alkenes (16). 

Cyclization of either of the thiols (24) with acid provided the saturated thia-PGIi analogs (26) as a 2.7 1 mixture of the exo and endo isomers.271 Although many addition reactions of thiols to alkenes are radical reactions catalyzed by light, oxygen, or other radical initiators, conversion to (26) was not effected under photolytic conditions or with AIBN. A radical chain mechanism for selenothiolactonization has also been reported recently.275... 

Even dienes with shielded double bonds can be involved in diene synthesis. The presence of donor groups at the double bond normally prevents its involvement in conventional Diels-Alder condensations. With the cation radicals, these reactions do take place. Cyclic adducts are formed in high yields (80-90%) and under mild conditions. Polymerization that usually decreases the yield is inhibited completely in the framework of the cation radical variant (Bellville et al. 1981). The stereoselectivity of the addition, which is usually typical for diene condensation, does not change in the cation radical version and even increases. The position selectivity also increases. The regioselectivity is enhanced, as well. Bauld s group has discovered and explained these effects (Bellville Bauld 1982 Bellville et al. 1981, 1983 Bauld, Bellville, et al. 1983 Bauld Pabon 1983 Pabon Bauld 1984). 

As mentioned before, alkyl radicals and acyl radicals have a nucleophilic character therefore, radical alkylation and acylation of aromatics shows the opposite reactivity and selectivity to polar alkylation and acylation with the Friedel-Crafts reaction. Thus, alkyl radicals and acyl radicals do not react with anisole, but may react with pyridine. Eq. 5.1 shows the reaction of an alkyl radical with y-picoline (1). The nucleophilic alkyl radical reacts at the 2-position of y-picoline (1), where electron density is lower than that of the 3-position. So, 2-alkyl-4-methylpyridine (2) is obtained with complete regioselectivity. When pyridine is used instead of y-picoline, a mixture of 2-alkylpyridine and 4-alkylpyridine is obtained. Generally, radical alkylation or radical acylation onto aromatics is not a radical chain reaction, since it is just a substitution reaction of a hydrogen atom of aromatics by an alkyl radical or an acyl radical through the addition-elimination reaction. Therefore, the intermediate adduct radical (a complex) must be rearomatized to form a product and a hydrogen atom (or H+ and e ). Thus, this type of reactions proceeds effectively under oxidative conditions [1-6]. 

Prototypical radical additions were examined under manganese-mediated photolysis conditions with InCp as the Lewis acid, coupling isopropyl iodide with a variety of y-hydrazonoesters 35a-35d (Table 6) bearing varied substitution at the position a to the ester. The a-methyl, a,a-dimethyl, and a-benzyloxy substituents appeared to have little effect on reaction efficiency and selectivity, as all provided the isopropyl adducts with consistently high diastereoselectivities and excellent yields (91-98%). Surprisingly, the selectivity was only slightly... 

The tin additive is present in the liquid state under the conditions of the present experiments. It has a smaller inhibiting effect than iron on the reactivity of the phenoxy and benzyl ethers. Two explanations are plausible. Hydrogen dissolved in the tin may react with the benzyl and phenoxy radicals which are the chain propagators and remove them from the system. The rate of bond cleavage is therefore lowered. Alternatively, tin may promote radical recombination reactions. By either route the tin would be acting to inhibit propagation reactions. 

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