Imines radical coupling

Aldehydes and ketones are useM building blocks in organic synthesis. The direct a-C-H substitutions of carbonyl compounds are well known. However, selective P-C(sp )-H functionalization remains rare. The MacMillan group introduced Site activation model by dual aminocatalysis and photocatalysis, opening up a practical synthetic route to P-substituted aldehydes and ketones (Scheme 3.25). With this novel strategy, radical-radical coupling of enaminyl radical with electron-poor cyanobenzene radical anion can elegantly produce P-aiylated aldehydes and ketones [74]. A recombination of enaminyl radical with imine anion radical was also developed [75]. In the presence of Michael acceptors, radical addition of enaminyl radical to electron-deficient alkenes affords P-alkylated aldehydes [76]. 

One other, perhaps even more dramatic and common example concerns compounds like 2 and 4 hydroxy- and amino-pyridines. These compounds exhibit tautomeric behaviour and tend to exist in solution as the corresponding pyridone and imine. This reduces the familiar pyridine-like properties of the ring system, accentuating the effects of these substituents (in terms of induced chemical shifts) and at the same time, radically increasing the expected couplings 2 -3 couplings. 

The mechanism will vary in precise detail according to the metal. In the case of ruthenium complexes, it is quite common to observe a conproportionation and the formation of a ruthenium(iv) intermediate. In other cases, the unavailability of the metal oxidation states precludes reaction. For example, cobalt(m) complexes of cyclam cannot be oxidised to imine species because although a cobalt(ii)/cobalt(m) couple is possible, the cobalt(n) oxidation state is not accessible under oxidative conditions. In the case of metal ions which can undergo two oxidation state changes, alternative mechanisms which do not involve radical species have been suggested. 

Many reports on tributyltin hydride-mediated intramolecular aryl-aryl coupling reactions have appeared in the literature in the 1990s [27, 121], One of the latest articles, in which many references on previous work have been included, focuses on the preparation of aporphines (Scheme 23) [122], Due to steric repulsion, an undesired 5-endo cyclization of the aryl radical on the imine nitrogen atom occurs only when more bulky substituents R are present in the benzyldihydroisoquinoline 64. With R = H, the cyclization to 65 proceeds in high yields. 

For several tautomeric systems ketones/enols, imines/enamin and others) a distinct reversal of the stability order is observed when going from the neutral compounds to the radical cations, the first use of which in a new preparative a-Umpolung reaction has been documented for keto/enol systems. The present review provides a critical evaluation of the chemistry of enol radical cations in solution with a special emphasis on the Umpolung reaction and the intermediates thereof. Other enol type of radical cations are discussed with respect to their potential to provide a-carbonyl radical and a-carbonyl cation intermediates. Hence, this article does not constitute a comprehensive summary on all enol type of radical cation reactions. All potentials in this review are referenced versus SCE, unless noted otherwise. Potentials measured against the ferrocene/ferrocenium couple were converted to SCE by adding 0.334 V. 

In imine reductions rapid equilibration of dimeric dianions and the precursor radical anions leads to the thermodynamically more stable isomer [257]. In the reductive coupling of salicylideneanilines, however, rate-determining C-C bond formation is preceded by intramolecular H-bridging [258]. 

According to the proposed mechanism for this novel photoaddition reaction, other substrates capable of forming radicals upon CdS photoinduced one-electron oxidation or reduction should undergo similar C-C coupling. Replacing the 1,2-diazene by the trisubstituted imine 17 indeed affords the new homoallylamines 18a-g in isolated yields of 30-75 % (Figure 28) [210]. 

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