Radicals, reduction alkenes

Among the electron-rich alkenes, vinylsulfides are especially amenable to cation-radical reduction an important feature is the absence of hydrogenolysis of carbon-sulfur bonds. The reduction of [(phenylthio)methylene]cyclohexane is efficient (88%), and the retention of the phenylthio group clearly contrasts with catalytic hydrogenation (Mirafzal et al. 1993). This provides versatile functionality for further synthetic operations. 

The addition of aryl radicals, generated by chemical reduction of aryldiazonium salts, onto arenes in the Gomberg-Hey reaction is well established [163]. The addition of these radicals to alkenes in the Meerwein reaction is also well known [164], Aryl o-radicals generated by electrochemical reduction of aryl halides take part in similar reactions. Good yields of the products are obtained when the intermediate phenyl radical can react in an intramolecular manner. The addition step is then fast and competes successfully with further electron transfer to form the phenyl car-banion, followed by protonation. 

In redox methods, radicals are generated and removed either by chemical or electrochemical oxidation or reduction. Initial and final radicals are often differentiated by their ability to be oxidized or reduced, as determined by substituents. In oxidative methods, radicals are removed by conversion to cations. Such oxidations are naturally suited for the additions of electrophilic radicals to alkenes (to give adduct radicals that are more susceptible to oxidation than initial radicals). Reductive methods are suited for the reverse addition of alkyl radicals to electron poor alkenes to give adducts that are more easily reduced to anions (or organometallics). 

Thus, radical generation, the formation of C-C bonds, and radical reductions are possible in reactions with alkenes and organometallic complexes with M-H bonds. 

Tris(thioalkyl)silanes may be prepared by reaction between ClsSiH and thiols in a manner similar to the preparation of alkoxysilanes and are useful reagents for radical reductions of alkyl halides or alkenes in organic chemistry (Scheme... 

In many synthetically useful radical chain reactions, hydrogen donors are used to trap adduct radicals. Absolute rate constants for the reaction of the resulting hydrogen donor radicals with alkenes have been measured by laser flash photolysis techniques and time-resolved optical absorption spectroscopy for detection of reactant and adduct radicals Addition rates to acrylonitrile and 1,3-pentadienes differ by no more than one order of magnitude, the difference being most sizable for the most nucleophilic radical (Table 8). The reaction is much slower, however, if substituents are present at the terminal diene carbon atoms. This is a general phenomenon known from addition reactions to alkenes, with rate reductions of ca lOO observed at ambient temperature for the introduction of methyl groups at the attacked alkene carbon atom . This steric retardation of the addition process either completely inhibits the chain reaction or leads to the formation of rmwanted products. 

The selectivity in addition reactions of cyclobutyl radicals to alkenes has been investigated in reactions of /1-lactam derivatives31-33. 6-Bromopenicillanic acid esters were used as precursors in reductive addition reactions with alkenes31,32 or with allylstannanes30,31. Addition to the intermediate penicillanic acid-6-yl radical occurred exclusively from the a-face of the /1-lactam ring. 

Steric factors slow the rate of intermolecular addition of radicals to non-terminal alkenes such as 1, 2 and 10-12. In the absence of a Lewis acid additive, radical additions to the cinnamate 16 or the crotonate 17 are inefficient at —78 °C because radical reduction is faster than radical addition [21, 22, 25]. The reaction is also nonselective in the absence of Lewis acid. When stoichiometric amounts of Lewis acids are added to the reaction of isopropyl radical with 16, however, both the yield and the diastereoselectivity increase significantly. Thus, Yb(OTf)3 gives a product yield of 90% in a ratio of 18a/19a of 45 1. This record P diastereoselectivity in radical addition is comparable to or better than that obtained under ionic conditions. Use of catalytic Yb(OTf)3 (10 mol%) gives only a slight reduction in selectivity. Addition to the crotonate 17 promoted by Yb(OTf)3 gives a product ratio of 18b/ 19b of 25 1. 

This began to happen in the early to mid 1980s. And, thanks to the solid foundation, synthetic radical chemistry blossomed with amazing speed. Giese s reductive additions of nucleophilic radicals to alkenes convincingly showed the synthetic community that radical additions to alkenes do not have to result in polymerization... 

However, under suitable conditions, azides react with a variety of radicals and this is the basis of several useful synthetic procedures for the formation of carbon-nitrogen bonds. For instance, synthesis of azides by radical addition of an azidyl radical to alkenes (Scheme 8.3a) and by reaction of an alkyl radical with an azidating reagent (Scheme 8.3b) will be presented. The reduction of azides leading to aminyl radicals (Scheme 8.3c) and the addition of alkyl radicals to alkyl azides (Scheme 8.3d) will also be discussed. 

Francois Morvan of the Universite de Montpellier, using the inexpensive dimethyl phosphite, optimized Tetrahedron Lett. 2008, 49, 3288) the free radical reduction of 1 to 2. Pawan K. Sharma of Kurukshetra University found Tetrahedron Lett. 2008,48, 8704) that NaBH in the presence of a catalytic amount of Rud xH O reduced monosubstituted and disubstituted alkenes, such as 3, to the corresponding alkanes. Note that benzyl ethers were stable to these conditions. 

V. T. Perchyonok and Kellie L. Tuck of Monash University found (Tetrahedron Lett. 2008, 49, 4777) that a concentrated solution of Bu NCl and HjPOj in water effected free radical reductions and cyclizations. Stephane G. Ouellet of Merck Frosst demonstrated (Tetrahedron Lett. 2008, 49, 6707) that an oxazoline such as 3 could be converted to the alcohol 4 by acylation followed by reduction. Elizabeth R. Burkhardt of BASF developed (Tetrahedron I tt. 2008, 49, 5152) a protocol for scalable reductive amination using an easily metered liquid pyridine-borane complex. Mohammad Movassaghi of MIT devised (Angew. Chem. Int Ed. 2008, 47, 8909) a strategy for conversion of an allyUc carbonate 8 by way of the ally lie diazene to the terminal alkene 9. 

Other limitations of the reaction are related to the regioselectivity of the aryl radical addition to double bond, which is mainly determined by steric and radical delocalization effects. Thus, methyl vinyl ketone gives the best results, and lower yields are observed when bulky substituents are present in the e-position of the alkene. However, the method represents complete positional selectivity because only the g-adduct radicals give reductive arylation products whereas the a-adduct radicals add to diazonium salts, because of the different nucleophilic character of the alkyl radical adduct. ... 

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