Synthesis Of β-Halo-pyrrolidinones Through A Tandem Sequence Of5Endo Halolactamization And C-H Oxidative Functionalization

Pyrrolidones and relative derivatives exhibit a wide range of interestingbiological activities, especially in the area of anti-cancer and anti-tumor therapy.Besides, these compounds could be regarded as the important synthetic intermediatesfor the synthesis of some natural products. Because of their unique structure, excellentbioactivities and the essential role in the total synthesis of natural product, more andmore research groups have focused on the synthesis of pyrrolidones. According toliteratures, we found that until now most of the strategies to synthesize thepyrrolidones are metal-catalyzed synthesis and ammoniation of the correspondinglactone. Therefor, developing a green, efficient and mild method to synthesize thepyrrolidones is necessary.According to the results of Literature survey and previous achievement, we foundsome halo-unsaturated amides could be further transformed to the correspondingpyrrolidones in the presence of iodine-donating reagent. In this paper, we usedβ-halo-β, γ-unsaturated amide as starting material to react withtBuOCl/I2(or NIS) inthe commercial acetonitrile at room temperature. During the reaction, the substratescould be converted to5-hydroxylpyrrol-2(5H)-ones via iodonium ion, followed by5-endo cyclization and elimination of hydrogen iodide. And through experiments, weknew that β-halo moiety is very important for the substrate, and the (Z)-unsaturatedamides are favored to the successful reaction. In a word, our method can realize thesynthesis of a series of β halo-pyrrolidinones through a tandem sequence of5endohalolactamization and C-H oxidative functionalization.In our paper, we synthesized a series of4-halo-5-hydroxylpyrrol-2(5H)-ones andwe also attempted to explore the applications of products we have obtained. At last,the structures of pyrrolidinones that were derived from experiments have beenconfirmed by1H-NMR,13C-NMR, HRMS or elemental analysis. At the same time,we did some studies about the mechanism and provided the possible mechanisticpathway of the reaction.