2- Naphthyl isocyanide

This procedure illustrates the best way to prepare aryl isocyanides. It is quite general, having been used by Ugi and Meyr e to make the following isocyanides from the corresponding form-amides phenyl (56%), />-tolyl (66%), 2,6-dimethylphenyl (88%), mesityl (80%), o-chlorophenyl (43%), -chlorophenyl (54%), 2-chloro-6-methylphenyl (87%), -methoxyphenyl (64%), p-di-ethylaminophenyl (75%), -nitrophenyl (41%), and 2-naphthyl (50%). Aliphatic isonitriles are generally best prepared by a simpler procedure involving the action of phosphorus oxychloride on an N-alkylformamide in the presence of pyridine.7... 

On the other hand, the sp C-H bond is much less reactive, and the catalytic cleavage reaction is stdl uncommon [23,24], As a rare example, the sp C-H bond in 2,6-dimethylbenzoisocyanide takes place by RuH(naphthyl)(DMPE)2 to give 7-methylindole, though the efficiency is poor (TON = 3.5) (Scheme 14.10) [23]. In this reaction, isocyanide coordinates to the coordinatively unsaturated ruthenium(O) center, and the C-H bond cleavage reaction takes place. 

Figure 15 highlights a novel application of sp -CH activation. In this example, 7-methylindole is synthesized from an aromatic isocyanide derivative, via an intramolecular cyclization reaction. The suspected mechanism involves coordination of the ruthenium center to the C=N triple bond, followed by insertion into the benzylic C—H bond. Ru(dmpe)2(naphthyl)H (Chart 1) (dmpe = dimethylphos-phinoethane, a bidentate phosphine) is the catalytic system used (59). 

The synthesis of indoles from 2,6-xylylisocyanides involving sp C-H bond activation has been reported as early as 1986. The catalyst precursor was the ruthenium (II) complex RuH2(dmpe)2 (dmpe=l,2-dimethylphosphinoethane) and the reaction was performed at 140°C in a sealed tube in the presence of 20 mol% of the catalyst (Scheme 60) [63]. The catalytic reaction could also be carried out in the presence of RuH(2-naphthyl)(dmpe)2 but required the presence of hydrogen to complete the catalytic cycle, which is proposed in Scheme 61 [65, 66]. The catalytic preparation of indoles was only possible starting from 2,6-disubstituted isocyanides (2,6-dimethyl, 2-ethyl-6-methyl, 2,6-diethyl), whereas less substituted isocyanides only led to stoichiometric formation of indole ruthenium species [66]. 

Jones and coworkers described the formation of 7-methyl indoles from ruthenium-catalyzed C(sp )-H bond activation of 2,6-xylylisocyanide in 1986 (Eq. (7.1)) [6]. The catalytic reaction proceeded by using ruthenium(II) complex Ru(dmpe)2H2 or Ru(dmpe)2(2-naphthyl)H as catalyst (20mol%) in CgDg at high temperature (140°C). Further studies indicated that the substrate scope is restricted to 2,6-disubstituted (2,6-dimethyl, 2-ethyl-6-methyl, 2,6-diethyl) isocyanides, since less substituted isocyanides only produced stoichiometric indole N-H oxidative addition adducts with [Ru(dmpe)2]. 

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