2-Chloropyrazine Subject

The vinyl triflate of Komfeld s ketone has been subjected to Heck reactions with methyl acrylate, methyl methacrylate, and methyl 3-(Af-rerf-butoxycarbonyl-lV-methyl)amino-2-methylenepropionate leading to a formal synthesis of lysergic acid [259]. A similar Heck reaction between l-(phenylsulfonyl)indol-5-yl triflate and dehydroalanine methyl ester was described by this research group [260]. Chloropyrazines undergo Heck couplings with both indole and 1-tosylindole, and these reactions are discussed in the pyrazine Chapter [261], Rajeswaran and Srinivasan described an interesting arylation of bromomethyl indole 229 with arenes [262]. Subsequent desulfurization and hydrolysis furnishes 2-arylmethylindoles 230. Bis-indole 231 was also prepared in this study. 

To synthesize pyrazinecarboxylic esters and pyrazinecarboxamides, chloropyrazines were subjected to Pd-catalyzed carbonylation reactions in either alcohols or dialkylamines [44, 45]. 2-Chloro-3,6-dimethylpyrazine (23) was smoothly carbonylated in methanol containing a catalytic amount of Pd(dba)2 and Ph3P to give 2-methoxycarbonyl-3,6-dimethylpyrazine (70). Somewhat lower yields were observed in the preparation of pyrazinecarboxylic diesters under the same conditions. 

Substituted chloropyrazines including a dichloro derivative were also the subject of P-C couplings using Pd(dppf)Cl2 as the catalyst and DBU as the base to afford monophosphinoyl and diphosphinoyl products (Schemes 40-1 and 40-2)." A dithiophosphinoylpyrazine was also prepared via the diphosphine intermediate (Scheme 40-3)." ... 

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