Reductive elimination reactions, involving radicals

Recently An et al. disclosed a palladium(II)-catalyzed bis(peroxidation)/cycli-zation method for the synthesis of 3-(peroxymethyl)-3-peroxyoxindoles 209 from N - ar y 1 aery I a m i d e s 208 (Fig. 52) [235]. Using 5 mol% of Pd(OAc)2 in the presence of terf-butyl hydroperoxide, 46-96% of products 209 were obtained. The reactions were proposed to involve a Pd-catalyzed radical bis(peroxidation) of the acrylic unit [236] followed by a two-electron directed cyclometalation/reductive elimination reaction of intermediate bis(peroxide) 208A. 

As regards to the reaction mechanisms involved in this type of reactions, the principle of microscopic reversibility suggests that reductive elimination reactions should show the same variety of mechanisms than oxidative additions (Fig. 1.4). Furthermore, it implies that the intermediates and transition states involved in these two reactions should be the same. Hence, reductive eliminations can occur through a concerted mechanism, a mechanism, a radical mechanism or an ionic mechanism. All these mechanisms have been previously described in the section devoted to oxidative addition (Fig. 1.4) and thus, they will be not described again herein. 

Under hypoxic conditions, cellular enzymes reduce the benzotriazine di-N-oxide [(reaction (68) P450 reductase Cahill and White 1990 and NADPH may be involved Walton et al. 1992 Wang et al. 1993]. Upon microsomal reduction of tirapazamine the radical formed in reaction (68) has been identified by EPR (Lloyd et al. 1991). Using the pulse radiolysis technique, it has been shown that this radical has a pKd of 6 (Laderoute et al. 1988), and it is the protonated form that undergoes the DNA damaging reaction (Wardman et al. 2003). The rate constants of the bimolecular decay of the radical [reaction (70)] has been found to be 2.7 x 107 dm3 mol-1 s 1. The reaction with its anion is somewhat faster (8.0 x 108 dm3 mol-1 s 1), while the deprotonated radicals do not react with one another at an appreciable rate. From another set of pulse radiolysis data, a first-order process has been extracted (k = 112 s 1) that has been attributed to the water elimination reaction (72), and the tirapazamine action on DNA [reaction (74)] has been considered to be due to the resulting radical (Anderson et al. 2003). 

We are here concerned with various organometallic reactions for which there is evidence that organic free radicals are implicated in the reaction pathway. Many of these arc formally two-electron oxidative additions or their retrogressions, the reductive eliminations (Section V,A). We shall focus attention on systems in which transition metal Group VIII complexes are involved. 

The reduction of aryl iodides to arenes by KHFe(CO)4 under mild conditions was performed215. This reaction involves an ET from HFe(CO)4" ions to the aryl iodide. The resulting aryl radicals either abstract hydrogen atom or combine with the HFe(CO)4 radical species to form ArHFe(CO)4 which yields ArH by reductive elimination. 

More recently Sternberg (8) has studied the dissolution of coal by reductive alkylation, which Involves a variety of reactions, Including free radical and elimination reactions. 

In the absence of the activating second carbonyl functionality, it is necessary to use more ingenious methods to produce the same net effect. These procedures more often than not involve radical reactions. Among them is the thermolysis of tert-butyl esters of peroxyacids 437, which are readily synthesized in a standard esterification of tert-butyl hydroperoxide with an acid chloride. Decarboxylation proceeds via an initial homolytic cleavage of the 0-0 bond, elimination of CO2, and reduction of the incipient alkyl radical by an added hydrogen atom donor such as 438 (Scheme 2.143). Examples showing the exceptional synthetic importance of this decarboxylation procedure will be presented later. 

In a stereocontrolled route to thromboxane B2, Corey and coworkers used the Eschenmoser rearrangement for the preparation of lactone (91 Scheme 14). The product of the 3,3-sigmatropic shift, amide (90), is directly iodolactonized, thus avoiding often troublesome amide hydrolysis conditions. Another application involving a carbohydrate derivative was demonstrated by Fraser-Reid and coworkers (Scheme 15). Reductive elimination of benzylidene (92), followed by in situ alkylation, Wittig reaction, DIBAL-H reduction and rearrangement, led to amide (94), which was transformed into the corresponding pyranoside diquinane by double radical cyclization. 

The anions of nitroalkanes (nitronates) can be used as precursors in a connective and regiospecific synthesis of tetrasubstituted alkenes. They are easily formed on reaction with LiOMe and undergo oxidative dimerization in the presence of bromine. The resultant 1,2-dinitroalkanes (Scheme 37) participate in a reductive elimination involving an rc1 radical chain mechanism when irradiated in the presence of Na2S, PhSNa or the lithium nitronate derived from 2-nitropropane. 

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