Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of ?-phenylthio-functionalized ?-lactams.

ABSTRACT: New synthetic methods for spirolactams bearing an ?-methylene-?-butyrolactone or its analogous methylene-lactam have been developed. The allylation of ?-phenylthio-functionalized ?-lactams with 2-(acetoxy)methyl acrylamides was accomplished by using 2.5 equivalents of NaH to give the corresponding adducts in excellent yields. The remaining phenylthio group was substituted with a hydroxy group by treatment with CuBr, and the resulting ?-hydroxyamides were cyclized under acidic conditions to afford the corresponding methylene-lactam-fused spirolactams in high yields. On the other hand, methylene-lactone-fused spirolactams could be delivered from the allyl adducts in high yields through a sequential N-Boc protection/desulfinative lactonization.

SUBMITTER: Sengoku T 

PROVIDER: S-EPMC7670114 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature