Pyrazine ring coupling

Although the heteroaryl Heck reactions of chloropyrazines with pyrrole itself were low-yielding for both mono- and bis-arylation products, better yields were obtained for N-phenylsulfonylpyrrole. Bulkier alkyl substituents on the pyrazine ring promoted the formation of C(3)-substituted pyrroles. The C(3)-substituted pyrrole 64 was the major product (62%) for the coupling of 1 and Al-phenylsulfonylpyrrole, while C(2)-substituted pyrrole 63- was a minor product (15%). 

The Pd-mediated cross-coupling reactions on the pyrazine ring of quinoxaline with organometallic reagents are more cumbersome. In one example, the Stille reaction between 2-chloroquinoxaline 87 and benzylstannane 88, attainable from the SN2 displacement of... 

Recently, Li successfully conducted the Suzuki and Stille reactions on the pyrazine ring of 3-bromoquinoxalin-2-ylamines [51]. Indolylquinoxaline 92 was obtained from the union of 3-bromoquinoxalin-2-ylamine 90 and l-phenylsulfonyl-2-tri-n-butylstannyl-l//-indole (91). A wide variety of heterocyclic stannanes bearing various functional groups underwent Stille coupling with 90 under the same conditions to give the corresponding adducts in 72-98% yields. 

The angular annelation of the pyridine and pyrazine rings in 28 have been confirmed by a large coupling constant (9 Hz), and this is believed to be attributable to oz/,4o-interaction of the protons. The same configurations on the 4-pyridone and pyrazine analogue 20 shows Vs 9 = 6Hz and Jz,3 = 1.8 Hz, respectively <2000M293>. 

As already mentioned, hydroxypyrazines exist in tautomeric equilibria with the corresponding pyrazinones which are normally the predominant species in the equilibria. Some of the reactions of hydroxypyrazines are reminiscent of those of phenols they can, for example, be coupled with diazonium salts and brominated and nitrated in either the ortho or para position to the hydroxyl group. Coupling with diazonium salts occurs in neutral or weakly alkaline solution, but if the reaction is carried out in 1 M sodium hydroxide solution, arylation of the pyrazine ring takes place. From hydroxy-pyrazine and benzenediazonium chloride 47% 2-hydroxy-3-phenyl-and 4% 2-hydroxy-3,6-diphenylpyrazine are obtained. 

The redox properties of tris(quinoxaline-2,3-dithiolato)molybdate(IV), [Mo(qdt)3]2, in the presence of protons provides a clear demonstration of the chemical versatility that is possible for a redox-active metal dithiolene center that involves a pyrazine ring linked to the dithiolene group. In an aprotic solvent, two reversible, Nernstian, waves are observed that (formally) correspond to the Mo(V)/Mo(IV) and Mo(IV)/Mo(III) couples. However, on addition of trifluoroacetic acid (Htfa), the Mo(V)/Mo(IV) couple slightly shifts to a higher potential and becomes non-Nernstian and a new three-electron, quasir-eversible, couple occurs some 900 mV less negative than the original Mo(IV)/ Mo(HI) couple. The latter is attributed to the addition of one electron and one... 

Drawn from these examples it is apparent that controlling the chemose-lectivity in inter-intermolecular Heck-Diels-Alder reactions of two different alkenes can be tedious if the alkenes show comparable reactivities. Nevertheless, the stepwise approach was realized in several other cases. In a synthesis of a derivative of cephalostatin 1 containing a central benzene instead of the pyrazine ring, Winterfeldt et al. linked two steroidal systems by a Heck coupling and subsequently performed high pressure Diels-Alder reactions of the conjugated diene with electron-deficient alkynes [34], Another example, reported by Hayashi et al., involves a selective Heck reaction of a bromoglu-cal with ethylene or acrylic acid derivatives followed by cycloadditions with maleic anhydride or N-phenylmaleimide [35]. 

The most common way to construct the pyrazine ring is the condensation of 1,2-diamines with 1,2-dicarbonyl compounds followed by the aromatization. Pritchard and co-workers developed an efficient procedure to prepare pyrazines, quinoxalines and 1,2,4-triazines by such condensations <01JCS(PI)668>. Dicarbonyl component 193, prepared by coupling amino acid 192 with (terf-butoxycarbonylmethylene)triphenylphosphine using DCC-DMAP, underwent ozonolysis to give 194. Then, 194 was treated with 1,2-ethylenediamine followed by aromatization with Pd-C to give pyrazine 195 in good yield. 

Garner and Joule next adapted the protected dithiolene strategy to target heterocyclic dithiolene complexes. This approach, first reported in 1988 by Larsen et al is illustrated in Scheme 2.25 with the formation of a cobalt quinoxalyldithiolene complex. Reaction of [CoCp(COD)] (COD = 1,5-cyclooc-tadiene) with 4-(quinoxalin-2-yl)-l,3-dithiole-2-thione (26) affords a quinox-aline dithiolene complex (27) that has been structurally characterized. This cobalt complex undergoes extensive proton-coupled electron transfer process (see Section 2.3.4). This system was further elaborated when the pyrazine ring in 4-(quinoxalin-2-yl)-l,3-dithiole-2-thione 26 was selectively... 

Fullerene-Ceo containing terthiophene 2.108 (Chart 1.21), in which a fullerene unit was attached to the central thiophene through a pyrazine ring, was prepared in 92 % yield by coupling of diketobisfiilleroid and 3, 4 -diaminoterthiophene in a mixture of o-dichlorobenzene and acetic acid [211], The bandgap of... 

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