Total Synthesis of (+)-Isoschizandrin Utilizing a Samarium(II) Iodide-Promoted 8-Endo Ketyl−Olefin Cyclization

• Published in: Journal of organic chemistry Vol. 68; no. 25; pp. 9533 - 9540
• Main Authors: Molander, Gary A, George, Kelly M, Monovich, Lauren G
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 12.12.2003; Amer Chemical Soc
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Alkenes - chemistry; Aza Compounds - chemistry; Boron Compounds - chemistry; Chemistry; Chemistry, Organic; Cyclization; Cyclooctanes - chemical synthesis; Cyclooctanes - chemistry; Exact sciences and technology; Iodides - chemistry; Ketones - chemistry; Lactones - chemistry; Lignans - chemical synthesis; Lignans - chemistry; Models, Chemical; Molecular Structure; Organic chemistry; Physical Sciences; Polycyclic Compounds - chemical synthesis; Preparations and properties; Samarium - chemistry; Schisandra - chemistry; Science & Technology; Stereoisomerism; DIRECTED BIARYL SYNTHESIS; RESONANCE-SPECTRA; CROSS-COUPLING REACTIONS; RADICAL-ANIONS; ASYMMETRIC-SYNTHESIS; ENANTIOSELECTIVE SYNTHESIS; KINETIC RESOLUTION; CARBONYL-COMPOUNDS; ORGANIC HALIDES; HEXAMETHYLPHOSPHORIC TRIAMIDE HMPA; Lactone; Stereochemistry; Tricyclic compound; Ketone; Total synthesis; Chemical coupling; Eight membered ring; Olefin; Cyclization; Optical resolution; Samarium II Iodides; Lignan; Aromatic compound; Chemical synthesis; Oxazaborolidine derivatives
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo0347361

The 13-step synthesis of (+)-isoschizandrin reported herein features a samarium(II) iodide-promoted 8-endo ketyl−olefin coupling to assemble the eight-membered ring present in the target concomitantly with the required functionality and stereochemistry. In constructing (+)-isoschizandrin as a single atropisomer, the synthesis utilizes a kinetic resolution of a seven-membered lactone using a CBS-oxazaborolidine.