Reduction radical chain reaction

A. Studer, S. Amrein, Tin Hydride Substitutes in Reductive Radical Chain Reactions, Synthesis 2002, 835-849. 

Germanium-Hydrogen Bonds (Reductive Radical Chain Reactions)... 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

The reductive replacement of mercury using sodium borohydride is a free radical chain reaction involving a mercuric hydride intermediate.18... 

Thus, the enhancements in chlorine removal from W diads compared to EV diads and from m-W diads compared to r-W diads observed in the (n-Bu)3SnH reduction of DCP, TCH, and PVC are consistent with the free-radical chain reaction mechanism. Inductive effects produced by neighboring 7-Cl s tend to favor the reduction of W diads relative to EV diads and steric interactions resulting from different preferred conformations in each isomer favor the removal of Cl from m-W diads relative to r-W diads. 

In most other cases, however, the diene system simply becomes too unreactive to participate in radical chain reactions. Thus, the reductive decarboxylation of ester 7 by Barton-POC ester methodology20 or as the selenoester21 gives the reduced product 8, cleanly without any trace of product in which the diene system has participated in the reaction (equation 4)20-21. 

Results of a chemical activation induced by ultrasound have been reported by Nakamura et al. in the initiation of radical chain reactions with tin radicals [59]. When an aerated solution of R3SnH and an olefin is sonicated at low temperatures (0 to 10 °C), hydroxystannation of the double bond occurs and not the conventional hydrostannation achieved under silent conditions (Scheme 3.10). This point evidences the differences between radical sonochemistry and the classical free radical chemistry. The result was interpreted on the basis of the generation of tin and peroxy radicals in the region of hot cavities, which then undergo synthetic reactions in the bulk liquid phase. These findings also enable the sonochemical synthesis of alkyl hydroperoxides by aerobic reductive oxygenation of alkyl halides [60], and the aerobic catalytic conversion of alkyl halides into alcohols by trialkyltin halides [61]. 

The reduction of thiocarbonyl derivatives by EtsSiH can be described as a chain process under forced conditions (Reaction 4.50) [89,90]. Indeed, in Reaction (4.51) for example, the reduction of phenyl thiocarbonate in EtsSiD as the solvent needed 1 equiv of dibenzoyl peroxide as initiator at 110 °C, and afforded the desired product in 91 % yield, where the deuterium incorporation was only 48% [90]. Nevertheless, there are some interesting applications for these less reactive silanes in radical chain reactions. For example, this method was used as an efficient deoxygenation step (Reaction 4.52) in the synthesis of 4,4-difluoroglutamine [91]. 1,2-Diols can also be transformed into olefins using the Barton-McCombie methodology. Reaction (4.53) shows the olefination procedure of a bis-xanthate using EtsSiH [89]. 

Two examples of three-components coupling reaction are shown in Reactions (7.77) and (7.78) [27,87]. These radical chain reactions proceeded by the addition of an alkyl or vinyl radical onto carbon monoxide, generating an acyl radical intermediate, which, in turn, can further react with electron-deficient olefins to lead, after reduction, to a formal double alkylation of carbon monoxide. These three-components coupling reactions require the generation of four highly disciplined radical species, which have specific functions during the chain reaction. 

The photoinduced electron transfer (PET) initialed cyclodimerization was first studied with 9-vinylcarbazole as substrate1 and characterized mechanistically as a cation radical chain reaction.2 The overall reaction sequence3-4 consists of a) excitation of an electron acceptor (A), b) electron transfer from the alkene to the excited acceptor (A ) with formation of a radical ion pair, c) addition of the alkene radical cation to a second alkene molecule with formation of a (dimeric) cation radical, and d) reduction of this dimeric cation radical by a third alkene molecule with formation of the cyclobutanc and a new alkene cation radical. Steps c) and d) of the sequence are the chain propagation steps. The reaction sequence is shown below. 

It was previously mentioned1 that cinnoline and 3-substituted cinnolines (94) could be prepared from the condensation products (95) between an o-nitrobenzaldehyde and a nitroalkane by electrochemical reduction. The reaction has been further studied,138 and it was noticed that when the reduction was carried out stepwise, anthranils (96) were formed, especially at elevated temperatures. The final ring closure was catalyzed by traces of oxygen, whereas too much oxygen produced the cinnoline JV-oxide (97) the ring closure was believed to be a radical chain reaction where the formation of the aromatic cinnoline was part of the driving force [Eq. (76)]. 

Deoxygenation of primary and secondary alcohols.1 This deoxygenation has been effected by reduction of the thiocarbonyl esters with tributyltin hydride and AIBN as the radial initiator (11, 550). A newer, milder method uses diphenylsilane in a radical chain reaction initiated by triethylborane and air. Even secondary thiono-carbonates, particularly those derived from 4-fluorophenol, are deoxygenated at 25°. 

Finally, aryl radicals Ar, which in the presence of hypophosphoric acid (H3P02) are generated from diazonium salts and Cu(I), undergo reduction to the aromatic compounds Ar-H in a radical chain reaction (Figure 5.54). 

An intermediate reduction of aryldiazonium salts Ar-N =N to the diazo radicals Ar-N=N also occurs when aryldiazonium salts react with KI to yield aryl iodides (Figure 5.55). Therefore, aryl radicals Ar are obtained under these conditions, too. Their fate, however, differs from that of the aryl radicals, which are faced with nucleophiles in the presence of Cu(II) (cf. Figure 5.53) or H3P02 (cf. Figure 5.54) the iodination mechanism of Figure 5.55 is a radical chain reaction consisting of four propagation steps. 

One of the novel exiting developments in the field of tin-free radical chain reactions is the development of complexes of borane with NHCs as HAT reagents [6]. Borane (BH3) itself has a BDE of 106.6 kcal mol 1 which is much too high for its use in organic radical chain reactions. The group of Roberts and others have demonstrated that complexes of boranes with amines and phosphines have a reduced BDE and that they can be used in radical chain reactions [7]. However, the reduction is only moderate and too low to make these complexes generally applicable. 

---