Hydrogenation of heteroarenes

M A K O S Z A Vicarious nucleoptiiHc substitution Synthesis of akyl substituted hetsrocydss by vicai1ous nucleophilic substitution ol hydrogen in heteroarenes, nitrodenvatives ol heleroarenes. 

Falck has recently reported dehydrogenative silylation of heteroarenes with triethylsilane (18) [97]. Coupling with the Si-H bond of triethylsilane, rather than the disilane Si-Si bond, in conjunction with the use of norbomene that presumably acts as a hydrogen acceptor, gives good yields with indoles, thiophenes, and furans, under relatively mild condition (80°C). Unlike the reaction shown in Scheme 7, silylation of indole did not require protection of the N-H group. 

Initial investigations showed that the direct hydrogenation of pyrazine carboxylic acid derivatives 14—16 was possible [15] (Fig. 13). This is one of the few examples known today for a homogeneous heteroarene hydrogenation [16]. With [Rh(NBD)Cl]2 and a variety of standard ligands, for example Chiraphos, Norphos, Duphos, Deguphos, PPm, BDPP, BINAP, BPPFOAc no reaction was observed. Similarly no reaction could be observed with Ir catalysts. The positive results are given in Tab. 6. 

M A K 0 S Z A Vicarious nucleophilic substitution Synthesis of afcyl substituted heterocydes by vicarious" nucleophilic substitution of hydrogen in heteroarenes, nitroderivatives of heteroarenes. 

Several approaches have been followed for the generation of optically active heteroarenes by homogeneous asymmetric hydrogenation. One approach involves direct asymmetric hydrogenation of the unactivated heteroarene. This approach has been most successful for heteroarenes that are polycyclic, like quinolines, isoquinolines, or quinoxa-lines (benzopyrazines). Less success has been achieved on the direct asymmetric hydrogenation of pyridines. To address this limitation, the hydrogenation of modified pyridines has been conducted. In one set of examples, pyridines and related benzo-fused heteroarenes were modified at tfie nitrogen by acylation or the installation of another auxiliary to make the pyridine more electron poor and to dock the catalyst. In a second set of examples, a chiral auxiliary was placed on the pyridine, and the product was formed diastereoselectively by an achiral catalyst. 

Asymmetric Hydrogenation of Five-Membered Ring Heteroarenes... 

Hu and Yu reported an iron/macrocyclic polyamine-catalyzed reaction of arylboronic acids with a large excess of pyrrole or pyridine at 130°C tmder air (Eqs. 26 and 27) [63], based on their previous studies on iron-mediated reactions (initial report using a stoichiometric amount of iron [64]). Pyrrole derivatives were arylated at 2-position in good yield (Eq. 26), but when pyridine was used as a substrate, the catalyst turnover was poor and 2-arylpyridine was obtained together with a small amount of 3-aryl- and 4-arylpyridine (Eq. 27). Because a catalytic amotmt of a radical scavenger did not inhibit the reaction, the authors proposed an oxoiron complex as the active species to activate the ort/io-hydrogen of the heterocycle via o-bond metathesis and also performed a DPT analysis of the mechanism. A related iron-catalyzed reaction of aryl boronic acids with heteroarenes was reported by Singh and Vishwakarma [65]. 

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