Intermolecular Radical Reactions

Initiation of radical reactions with uv radiation is widely used in industrial processes (85). In contrast to high energy radiation processes where the energy of the radiation alone is sufficient to initiate reactions, initiation by uv irradiation usually requires the presence of a photoinitiator, ie, a chemical compound or compounds that generate initiating radicals when subjected to uv radiation. There are two types of photoinitiator systems those that produce initiator radicals by intermolecular hydrogen abstraction and those that produce initiator radicals by photocleavage (86—91). 

Scheme 3.2. General scheme for an intermolecular domino radical reaction.

The first example of an intermolecular radical addihon/intermolecular trapping domino reactions of an acyclic system in a stereocontrolled fashion to build stereo-genic centers at the a- and 3-carbons was described by Sibi and coworkers [59]. Enantioselective addition of in-sitw-prepared alkyl radical to crotonate or cinnamate,... 

In a combination of photochemical cyclization and a radical reaction Yoshimatsu et al synthesized 2-azabicyclo[33.0locta-3,7-diene 169 from the trienal hydrazone 166.1891 The domino process was initiated by irradiation of 166 at 400-500 nm in benzene. The transformation may include an intermolecular [2+2]-cyclization, followed by ring opening to give... 

Investigations conducted by the same group using laser flash photolysis techniques elucidated details of the PET-reductive activation of selenosilanes and the application of this chemistry to a bimolecular group-transfer radical reaction and intermolecular radical chain-transfer addition [59], Based on this new concept, a catalytic procedure utilizing PhSeSiRs for radical reactions such as cycliza-tion, intermolecular addition and tandem anellation was designed (Scheme 39) [60],... 

The biperoxy radical produced by the ceric ion oxidation of 2,5-di-methylhexane-2,5-dihydroperoxide decays rapidly with first-order kinetics [k = ioio.e exp( -11,500 1000)/RT sec.1 = 180 sec."1 at 30°C. (30)]. After the first-order decay has run to completion, there is a residual radical concentration (—4% of the initial hydroperoxide concentration) which decays much more slowly by a second-order process. The residual second-order reaction cannot be eliminated or changed even by repeated recrystallization of the dihydroperoxide. This suggests that a small fraction of the biperoxy radicals react intermolecularly rather than by an intramolecular process and thus produce monoperoxy radicals. The bimolecular decay constant for this residual species of peroxy radical is similar to that found for the structurally similar radical from 1,1,3,3-tetra-methylbutyl hydroperoxide. Photolysis of the dihydroperoxide gave radicals with second-order decay kinetics which are presumed to be 2,5-hydroperoxyhexyl-5-peroxy radicals. 

Intennoleciilar Reactions. The intermolecular version of free radical reactions of sugar-derived radicals consists mainly of addition onto suitably activated olefins, such as acrylonitrile, generally used in excess. This approach has been explored by Giese [102]. The stereochemical course of the reaction is dictated by steric effects of the vicinal substituents, as seen from the reaction of radical 71 where equatorial attack is favored over the axial with acrylonitrile (Scheme 28). Only equatorial attack is observed using... 

The rate of this reaction (which is the main decay of tertiary alkoxyl radicals) is also strongly enhanced in water as compared to the gas phase and organic solvents. If different substituents can be cleaved off, it is the more highly-substituted one (weaker C-C bond) that is broken preferentially (Riichardt 1987). Thus in the case of secondary alkoxyl radicals, substitution in p-position also decides the ratio of 1,2-H-shift and -fragmentation (Schuchmann and von Sonntag 1982). Because of the fast 1,2-H-shift and p-fragmentation reactions in water, intermolecular H-abstraction reactions of alkoxyl radicals [reaction (61)] are usually inefficient, but intramolecular H-abstraction may occur quite readily if an H atom is in a favorable distance (e.g., six-membered transition state). 

The electronic nature of a nitrogen centered radical, dictated by reaction conditions and/or the radical precursor employed, is crucial to the mode of reaction, to the ability to undergo efficient intramolecular cyclizations or intermolecular additions, and to the products isolated from the radical reaction. The types of radicals discussed in this review include neutral aminyl radicals, protonated aminyl radicals (aminium cation radicals), metal complexed aminyl radicals, and amidyl radicals. Sulfonamidyl and urethanyl radicals are known (71S1 78T3241), but they are not within the scope of this chapter. 

Intra- and intermolecular hydrogen transfer processes are important in a wide variety of chemical processes, ranging from free radical reactions (which make up the foundation of radiation chemistry) and tautomeriza-tion in the ground and excited states (a fundamental photochemical process) to bulk and surface diffusion (critical for heterogeneous catalytic processes). The exchange reaction H2 + H has always been the preeminent model for testing basic concepts of chemical dynamics theory because it is amenable to carrying out exact three-dimensional fully quantum mechanical calculations. This reaction is now studied in low-temperature solids as well. 

Intermolecular free radical reactions. Giese notes the diastereoselectivity of reactions of acrylonitrile with cyclic 5- and 6-membered ring radicals can be controlled by adjacent substituents. Thus an axial 3-substituent can favor axial attack, whereas an equatorial 3-substituent favors equatorial attack in the case of 6-membered cyclic radicals. Glucosyl radicals, regardless of the precursor, yield a-substi-tuted products (88 12). 

As a combined reaction of (3-cleavage of a cyclopropylcarbinyl radical and intermolecular addition, treatment of vinylcyclopropane (266) and activated alkyne in the presence of PhSSPh and AIBN forms a cyclopentene skeleton (267), through the initial addition of a thiyl radical to the vinyl group, P-cleavage of the cyclopropylcarbinyl radical, addition of the carbon-centered radical to the alkyne, ring closure of a vinyl radical via 5-exo-trig manner, and finally subsequent P-elimination of the thiyl radical, as shown in eq. 3.107 [272-276]. Here, PhSSPh acts as a catalyst, since the thiyl radical is regenerated. Aliphatic disulfides such as... 

Hydantocidin, which bears a spiro skeleton, is a natural product and a herbicide. Eq. 3.113 shows the typical preparation method of spiro-diketone (277) from the reaction of a-diazoketone (276) with Rh2(OAc)4 via a carbenoide species. However, this spiro skeleton can be also constructed by radical reactions. Treatment of (3-keto ester (278) with Mn(OAc)3 in the presence of electron-rich olefin generates spiro-cyclic thioketal (279) through the formation of a (3-keto ester radical, intermolecular radical addition to... 

B. Giese, The Stereoselectivity of Intermolecular Free Radical Reactions, Angew. Chem. Int. Ed. Engl. 1989, 28, 969-980. 

It is as efficient as Bu3SnH for initiation of intermolecular or intramolecular radical reactions with alkenes.3... 

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