Nitroprolinates as Nucleophiles in Michael-type Additions and Acylations. Synthesis of Enantiomerically Enriched Fused Amino-pyrrolidino-1,2-apyrazinones and -diketopiperazines

摘要

The enantioselective formation of nitroprolinates followed by diastereoselective Michael-type addition onto a second unit of the nitro alkene is studied. The reaction occurred in a one pot-sequential process controlled by the chiral phosphoramidite.silver benzoate complex. The origin of the high diastereoselectivity is studied by DFT computational analysis where the crucial effect of the benzoic acid is justified. The employment of this strategy to the preparation of pyrazine-2-ones is also surveyed, as well as the preparation of diketopiperazines from enantiomerically enriched exo-prolinates using conventional N-acylation-amination-cyclization steps.