A novel base-mediated intramolecular hydroamination to build fused heteroaryl pyrazinones

A Review of the Synthetic Strategies toward Dihydropyrrolo[1,2-a]Pyrazinones

“…in a dimethylformamide (DMF)/tetrahydrofuran(THF) mixture at 100 °C, in the presence of a stoichiometric benzoquinone oxidant, gave a 1:1 mixture of the two isomeric [2,3c] and [3,2-c] fused pyrrolopyridinone derivatives 17 and 18, apparently as the result of cyclization involving the 2-position of the pyrrole followed by rearrangement [48]. Remarkably, when the Pd(OAc)2 method was applied to the N-cinnamyl derivative 15 (R 1 = Ph), the dihydro derivative 19 was obtained in modest yield and different oxidants failed to afford the corresponding pyrrolo[1,2-a]pyrazine 16b [49] (Scheme 4). The palladium-catalyzed cyclization of N-allyl pyrrole-2-carboxamide 15 (R 1 = H) leads to different products depending on the catalyst.…”

Diversity-Oriented Approach to Pyrrole-Imidazole Alkaloid Frameworks

“…Interestingly, we found that both reactions proceeded equally or more efficiently in the absence of the Pd-catalyst, indicating that the reaction is simply base-mediated. 24 Of particular note is the relative efficiency of the base-induced formation of 16 , which is presumably a result of the buttressing effect of the Tr-moiety. 25 …”

“…Interestingly, we found that both reactions proceeded equally or more efficiently in the absence of the Pdcatalyst, indicating that the reaction is simply basemediated. 24 Of particular note is the relative efficiency of the base-induced formation of 16, which is presumably a result of the buttressing effect of the Tr-moiety. 25 Given our success with the cyclization of substrates via the pyrrole nitrogen (Scheme 1), we decided to introduce substituents on this nitrogen to prevent cyclization via this manifold to establish whether cyclization would occur via C-H insertion at the pyrrole C4 atom (net hydroarylation).…”

“…Similarly, it was found that the Tr-protected amide 12 participated in the cyclization with Pd-catalysis providing the corresponding pyrazinone 16 (∼80%, Scheme ). Interestingly, we found that both reactions proceeded equally or more efficiently in the absence of the Pd-catalyst, indicating that the reaction is simply base-mediated . Of particular note is the relative efficiency of the base-induced formation of 16 , which is presumably a result of the buttressing effect of the Tr-moiety …”