Benzylamines, oxidative coupling with

Madsen and co-workers have reported an important extension to the amine alkylation chemistry, in which oxidation takes place to give the amide product [13]. A ruthenium NHC complex is formed in situ by the reaction of [RuCl Ccod)] with a phosphine and an imidazolium salt in the presence of base. Rather than returning the borrowed hydrogen, the catalyst expels two equivalents of H. For example, alcohol 31 and benzylamine 27 undergo an oxidative coupling to give amide 32 in good isolated yield (Scheme 11.7). 

The catalytic oxidative system H/oxidant has also been applied for the synthesis of the following heterocyclic systems 2-imidazolines 134 by the oxidative coupling of benzaldehydes with ethylenediamines [113], benzimidazoles 135 by a similar oxidative coupling reaction of phenylenediamines with aromatic or aliphatic aldehydes [109] and oxazole derivatives 136 by the oxidative coupling of p-ketoesters with benzylamines (Scheme 4.70) [114]. 

In this domino process, benzylamine was reacted with 2-halobenzamides through UUman-type coupling to yield the N-arylated intermediate 144 (Scheme 9.26). Then, a copper-catalyzed aerobic oxidation of 144 afforded the intermediate 145, which underwent an intramolecular nucleophilic addition of the amide to provide 146. Under the used reaction conditions, the intermediate 146 was oxidized to provide the desired products 147 in excellent yield. This protocol was also utilized by Fu et al. [80] by employing easily available a-amino adds instead of benzylamines to synthesize similar analogs. Very recently, the same method was applied for the synthesis of pyrimido[4,5-b]carbazoles by Nagarajan et al. [81]. 

Almost at the same time, Nguyen and coworkers reported the multicomponent oxidative coupling of amines 94 with thioamides 96 catalyzed by elemental sulfur [64]. The reactions were carried out under solvent-free and harsh conditions (130°C) to afford the final thioamides 97 in good to excellent yields (62-95%). The proposed mechanism of this reaction is shown in Scheme 11.16. First, the oxidation of benzylamine 94 with sulfur affords the corresponding imine 95. Next, the oxidation of imine 95 with sulfur affords the corresponding thioamide 96 that undergoes franithioamidation to afford the final products 97. 

Step. The kinetics and mechanism of QDC oxidation of some benzaldehydes, benzylamines, and para- and mefa-substituted phenols by QDC have been reported. In the case of substituted benzaldehydes and phenols, the reaction is retarded by electron-withdrawing substituents and enhanced by electron-releasing substituents. The oxidative coupling reaction of anilines with QDC in acidic medium gave the... 

Lledos, Urriolabeitia, and coworkers have used M06(MeOH) calculations to model the oxidative coupling of benzylamines with 2-butyne at [Ru(Cl)2 (/j-cymene)] 2 (Figure 1.35) [85]. The presence of protic N-H bonds in benzy-lamine promotes the formation of H-bonded ion pairs upon OAc dissociation, and these proved more reactive than non-ion-paired species where OAc was modeled as fully dissociated in solution. Thus, after OAc/amine substitution at Ru(OAc)2( -cymene) to give l OAc, an outer-sphere C-H activation is computed via a transition state at 24.6 kcal mol , 2.5 kcal mol below a more conventional intramolecular process. Although this external deprotonation caimot strictly... 

Figure 1.35 (a) Ru-catalyzed oxidative coupling of benzylamines with 2-butyne to form isoquinolones (b) transition state for C-H activation via external deprotonation with key distances (A) and (c) key stationary points on the free energy profile (kcal mol energies quoted relative to the reactants at 0.0 kcal mol ). Double arrows indicate several steps are involved, with the energy of the highest transition state between the two minima indicated in square brackets [85],... 

Many arylations are assisted by functional groups that promote ortho-metallation. Thus, for example, acetanihdes react with arylsilanes at the ortho position via pal-ladacycles 78 and 79 to form derivatives 80 (Scheme 11.27) [84]. Mechanistically, this transformation is similar to a cross-coupling reaction, in which the oxidative addition step is replaced by the ortho-metallation, although in this case the Pd(0) intermediate must be oxidized in situ to generate the reactive Pd(ll) species. Unsubstituted benzylamines and N-methylbenzylamine are ortho-arylated with Pd(OAc)2 in the presence of trifluoroacetic acid (TFA) and silver acetate [85], and a mechanism which differs from the usual Pd(0)/Pd(II) catalytic cycle was suggested for this. Ortho-alkylation was also observed in the palladium-catalyzed... 

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