Exploratory Studies Aimed at a Synthesis of Vinigrol. 4. Probe of Possible Means for Direct Connection of the Side Arms and of Ring-Contraction Alternatives

• Published in: Journal of organic chemistry 2005-01, Vol.70 (2), p.514-518
• Main Authors: Paquette, Leo A, Liu, Zuosheng, Efremov, Ivan
• Format: Article
• Language: English
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Chemistry; Cyclization; Diterpenes - chemical synthesis; Diterpenes - chemistry; Drug Design; Exact sciences and technology; Lactams - chemistry; Molecular Structure; Organic chemistry; Preparations and properties; Stereoisomerism; Sulfoxides - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo048456c

Attempts have been made to gain access to the vinigrol structural framework by way of three routes. These include reductive transannular cyclization, adaptation of the Ramberg−Bäcklund rearrangement, and deployment of the lactam−sulfoxide ring contraction protocol. While the first of these options involves direct transannular C−C bond formation, the other two embody the concept of larger ring construction as a prelude to ring contraction. The initial installation of a sulfur atom involves prior thiacyclononane formation, a process believed to be potentially easier to accomplish. However, arrival at 13, 14, or 17 was not achieved. Installation of the heterocyclic ring contained in 31 proved to be equally problematic. Increased disassembly of the molecular structure as featured in dibromide 20 did allow for direct conversion to sulfone 22. This advanced building block proved not be conducive to in situ α-chlorination and extrusion of the sulfur atom.