Construction of the Tricyclic Furanochroman Skeleton of Phomactin A via the Prins/Conia-Ene Cascade Cyclization Approach

• Published in: Journal of organic chemistry 2011-08, Vol.76 (16), p.6534-6541
• Main Authors: Huang, Shuangping, Du, Guangyan, Lee, Chi-Sing
• Format: Article
• Language: English
• Subjects: Alicyclic compounds, terpenoids, prostaglandins, steroids; Catalysis; Chemistry; Chromans - chemical synthesis; Chromans - chemistry; Cyclization; Epoxy Compounds - chemistry; Exact sciences and technology; Furans - chemical synthesis; Furans - chemistry; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Heterocyclic Compounds, 4 or More Rings - chemical synthesis; Heterocyclic Compounds, 4 or More Rings - chemistry; Molecular Structure; Naphthalenes - chemical synthesis; Naphthalenes - chemistry; Organic chemistry; Preparations and properties; Stereoisomerism; Terpenoids
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo200644t

A substrate-controlled asymmetric Prins/Conia-ene cascade cyclization has been developed with In(OTf)3 in CH3CN from 0 to 70 °C. These conditions afforded very good yields of the 1-oxadecalin product in one pot and effectively suppressed the racemization of the 1-oxadecalin product with almost no enantiomeric excess (ee) loss. This cascade cyclization has been successfully employed for the construction of the highly functionalized 1-oxadecalin unit of phomactin A with an acyclic β-keto ester and an alkynal as the substrates via a one-pot operation (66% yield, single diastereomer). The 1-oxadecalin moiety has been readily converted to the tricyclic furanochroman skeleton of phomactin A via the epoxidation/dealkoxycarbonylation protocol under very mild conditions with 52% yield in three steps.