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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

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

Sengoku Tetsuya T Makino Koki K Iijima Ayumi A Inuzuka Toshiyasu T Yoda Hidemi H

Beilstein journal of organic chemistry 20201113

New synthetic methods for spirolactams bearing an α-methylene-γ-butyrolactone or its analogous methylene-lactam have been developed. The allylation of γ-phenylthio-functionalized γ-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 γ-hydroxyamides were cyclized under acidic conditions to affor ...[more]

PMID: 33224303

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