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

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• 501-1193, Japan 10.3762/bjoc.16.227 Abstract 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

• -butyrolactone; spirolactams; Introduction α-Methylene-γ-butyrolactone is a pharmaceutically important motif which is found in a wide variety of bioactive molecules including natural products (Scheme 1a) [1][2][3]. For example, sesquiterpene lactones represented by parthenolide and helenalin have attracted

• reaction conditions and led to methylene-lactone-fused spirolactams 5a–h in excellent yields without exception (88–98% two-step yields). Thus, we established the bifurcated synthetic routes toward lactams spiro-fused to α-methylene-γ-butyrolactone or α-methylene-γ-butyrolactam by using 3-phenylthiolactams