Divergent, Generalized Synthesis of Unsymmetrically Substituted 2,5-Piperasinediones

Article abstract of DOI:10.1021/ja00297a034

N,N'-Disubstituted 2,5-piperazinediones (12) can be 3,6-dibrominated followed by displacement with sodium 2-mercaptopyridine to furnish syn-1,4-disubstituted 3,6-bis(2'-thiopyridyl)-2,5-piperazinediones (8) in high yield.Precomplexation of these sulfides with silver(I) triflate followed by addition of trimethylsilyl enol ethers leads to chemoselective C-C bond formation, furnishing the homologated piperazinediones 10.The remaining sulfide functionality of 10 is relatively inert to a second substitution.These electrophylic 2,5-piperazinediones provide access to relatively inaccessible, unsymmetrical 2,5-piperazinediones and provide advantages over the corresponding well-known enolate anion approach.Substrates that contain N-p-methoxybenzyl residues can be deprotected to the lipophobic N,N'-unsubstituted 2,5-piperazinediones with aqueous ceric ammonium nitrate.The diastereoselectivity observed in the coupling reactions is discussed in the context of a single crystal X-ray structure determination of 20.