Divergent, generalized synthesis of unsymmetrically substituted 2,5-piperazinediones

Abstract

Disubstituted 2,5-piperazinediones (12) can be 3,6-dibrominated followed by displacement with sodium 2-mercaptopyridine to furnish sy -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 electrophilic 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

Free-Radical Reactions in the Synthesis of α-Amino Acids and Derivatives

“…With a limiting amount of that reagent the monosubstituted species 31a − c were produced and converted to the corresponding α-methoxyglycine derivatives, in overall yields ranging from 41−61% . The monobromides 31a − c have particular potential for the asymmetric synthesis of diketopiperazine derivatives. ,, …”

Beyond Breaking the Mirror Plane: The Desymmetrization of Centrosymmetric Molecules as an Efficient Strategy for Asymmetric Synthesis

“…In a diastereoselective total synthesis of the centrosymmetric alkaloid Dragmacidin B ( 27), 23 the meso configuration was introduced under substrate control (Scheme 6). Hence, substitution of the dibromide 25 (the dibromide 25 was believed to have a cis configuration 24 ) with 6-bromoindole gave the required centrosymmetric trans-substituted product as a single diastereoisomer. 23,25 Reduction of 26 gave Dragmacidin B ( 27) directly.…”

2-Mercaptopyridine - anchimerically-assisted activation of thiols, thioates and ketene thioacetals

“…BOP-Cl was recommended for condensation of dipeptides such as Aib-Aib-OMe [20]. Thus, the synthetic value of 2-mercaptopyridine for peptide synthesis rests in other applications, such as α-substitution of α-amino acids by nucleophiles, which allow selective conversion of the dibrominated piperazindione 11 into the butyrolactone 14 [22]. The meso-dibromide was transferred into the bis-N,S-acetal 12 with complete diastereoselectivity by 2 equivalents of 1 and sodium hydride.…”