Vinyl radicals addition reactions

The literature presents a large number of examples concerning the use of known oxazolidinones as chiral auxiliaries in many kinds of reactions. Rare is the use of A-amino derivatives of oxazolidinones, which were used to synthesise new A-acylhydrazones 207. Radical addition reactions occurred with high diastereoselectivity <00JA8329>. The use of glycolate oxazolidinones 210 proved to be efficient for the enantioselective preparation of a-alkoxy carboxylic acid derivatives . Photochemical reaction of vinyl... 

Most synthetically useful radical addition reactions pair nucleophilic radicals with electron poor alkenes. In this pairing, the most important FMO interaction is that of the SOMO of the radical with the LUMO of the alkene.36 Thus, many radicals are nucleophilic (despite being electron deficient) because they have relatively high-lying SOMOs. Several important classes of nucleophilic radicals are shown in Scheme IS. These include heteroatom-substituted radicals, vinyl, aryl and acyl radicals, and most importantly, alkyl radicals. 

Although the yield and product selectivity require further improvement, the three-component coupling reaction of azo-bis-isobutyronitrile (AIBN), phenylacetylene, and p-methoxyphenyl isonitrile proceeds to give a quinoxaline derivative (Scheme 6.9) [16]. Decomposition of AIBN gives a cyanopropyl radical, which adds to phenylacetylene to form a vinyl radical. Addition of the vinyl radical to the isoni-... 

Generally, treatment with electron-deficient olefins such as nitroethylene or vinyl sulfone is effective for radical addition reactions, since alkyl radicals derived from O-acyl esters (2) are nucleophilic and take SOMO-LUMO interaction. However, treatment of O-acyl esters ) derived from perfluoroalkyl carboxylic acids (RfC02H) generates electrophilic radicals, Rf, which react preferably with electron-rich olefins such as vinyl ether, as shown in eq. 8.16 [52]. 

As was the case with the radical addition reactions discussed in Chapter 21, the addition always occurs so as to produce the more stable radical. Because most other substituents also stabilize a radical on the carbon to which they are attached, vinyl polymers typically result from head-to-tail coupling of their monomer units. 

A diastereoselective formal addition of a 7ra i-2-(phenylthio)vmyl moiety to a-hydroxyhydrazones through a radical pathway is shown in Scheme 2.29. To overcome the lack of a viable intermolecular vinyl radical addition to C=N double bonds, not to mention a reaction proceeding with stereocontrol, this procedure employs a temporary silicon tether, which is used to hold the alkyne unit in place so that the vinyl radical addition could proceed intramolecularly. Thus, intermolecular addition of PhS" to the alkyne moiety in the chiral alkyne 161 leads to vinyl radical 163, which cyclizes in a 5-exo fashion, according to the Beckwith-Houk predictions, to give aminyl radical 164 with an a 7z-arrangement between the ether and the amino group. Radical reduction and removal of the silicon tether without prior isolation of the end product of the radical cyclization cascade, 165, yields the a-amino alcohol 162. This strategy, which could also be applied to the diastereoselective synthesis of polyhydroxylated amines (not shown), can be considered as synthetic equivalent of an acetaldehyde Mannich reaction with acyclic stereocontrol. 

Other important reactions refer to vinyl and allyl radical addition reactions on alkyl aromatic species. These substitutive addition reactions also contribute to a progressive dealkylation of the aromatic species. The reference kinetic parameters of these reactions are respectively... 

Marvel and McCain 49> have shown that ethyl cinnamate can be homopolymerized by use of typical radical-type thermal initiators, such as benzoyl peroxide or 2,2 -azobis(isobutyronitrile). Ethyl cinnamate and poly(vinyl cinnamate) can, therefore, take part in radical addition reactions. 

The majority of vinyl polymers are regioregular with a head-to-tail sequence of monomer units (0, i.e. they are isoregic (2). Some of the most notable exceptions are the polymers obtained by free-radical addition reactions of the fluoroethylenes vinyl fluoride (VF), vinylidene fluoride (VF2), and trifluoroethylene (F3E), which incorporate significant amounts of head-to-head and tail-to-tail structural defects caused by reverse monomer addition (3). 

BusSnH-mediated intramolecular arylations of various heteroarenes such as substituted pyrroles, indoles, pyridones and imidazoles have also been reported [51]. In addition, aryl bromides, chlorides and iodides have been used as substrates in electrochemically induced radical biaryl synthesis [52]. Curran introduced [4-1-1] annulations incorporating aromatic substitution reactions with vinyl radicals for the synthesis of the core structure of various camptothecin derivatives [53]. The vinyl radicals have been generated from alkynes by radical addition reactions [53, 54]. For example, aryl radical 27, generated from the corresponding iodide or bromide, was allowed to react with phenyl isonitrile to afford imidoyl radical 28, which further reacts in a 5-exo-dig process to vinyl radical 29 (Scheme 8) [53a,b]. The vinyl radical 29 then reacts in a 1,6-cyclization followed by oxidation to the tetracycle 30. There is some evidence [55] that the homolytic aromatic substitution can also occur via initial ipso attack to afford spiro radical 31, followed by opening of this cyclo-... 

During the last decade the application of radical addition reactions for solving problems in organic synthesis has grown, as documented by numerous review articles . In this survey we will deal mainly with the synthetical aspects of the radical-based addition of a molecule to alkynes, with Section IV dedicated to radical cyclizations and to the preparation of biologically active compounds. In Section II, in order to familiarize the reader with the properties of the vinyl radical, we will briefly examine the structural characteristics of vinyl radicals and make some considerations about the stereochemical outcome of their reactions. 

New fatty compounds have been synthesized in high yields using radical addition reactions. Alkyl 2-haloalkanoates have been added to the double bond of unsaturated fatty compounds to give y-lactones. 2-Haloalkanenitriles have been added as well to give 4- haloalkanenitriles. 2-Halo fatty compounds, e.g., methyl 2-bromopalmitate, have been added to alkenes, allyl alcohol, vinyl esters, and trimethylsilyl enol ethers to give interesting branched and functionalized compounds. Key features of the re-... 

Monomers which have been successfully polymerized using ATRP include styrenes, acrylates, methacrylates, and several other relatively reactive monomers such as acrylamides, vinylpyridine, and acrylonitrile, which contain groups (e.g., phenyl, carbonyl, nitrile) adjacent to the carbon radicals that stabilize the propagating chains and produce a suf cientiy large atom transfer equilibrium constant. The range of monomers polymerizable by ATRP is thus greater than that accessible by nitroxide-mediated polymerization, since it includes the entire family of methacrylates. However, acidic monomers (e.g., methacrylic acid) have not been successfully polymerized by ATRP and so also halogenated alkenes, alkyl-substimted ole ns, and vinyl esters because of then-very low intrinsic reactivity in radical polymerization and radical addition reactions (and hence, presumably, a very low ATRP equilibrium constant). 

Problem 7.6. Provide a justification for the observation that vinyl (C=C-X X=C1, Br) and allyl (C=C-C-X X = Cl,Br) halides undergo free radical addition reactions to the carbon-carbon double bond with about equal facility. 

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