Stereocontrolled Total Syntheses of Isodomoic Acids G and H via a Unified Strategy

• Published in: Journal of organic chemistry 2011-01, Vol.76 (1), p.201-215
• Main Authors: Denmark, Scott E, Liu, Jack Hung-Chang, Muhuhi, Joseck M
• Format: Article
• Language: English
• Subjects: Alkenes - chemistry; Chemistry; Cross-Linking Reagents; Cyclization; Exact sciences and technology; Heptanoic Acids - chemical synthesis; Heptanoic Acids - chemistry; Heptanoic Acids - classification; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Molecular Structure; Organic chemistry; Preparations and properties; Silicon - chemistry; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo101790z

Marine neuroexcitatory compounds isodomoic acids G and H were efficiently synthesized from a common intermediate using a silicon-based cross-coupling reaction. Dividing each target compound into the core fragment and the side-chain fragment enabled the synthesis to be convergent. The trans-2,3-disubstituted pyrrolidine core fragment was accessed through a diastereoselective rhodium-catalyzed carbonylative silylcarbocyclization reaction of a vinylglycine-derived 1,6-enyne. A stereochemically divergent desilylative iodination reaction was developed to convert the cyclization product to both E- and Z-alkenyl iodides, which would eventually lead to isodomoic acid G and isodomoic acid H, respectively. The late-stage alkenyl−alkenyl silicon-based cross-coupling reaction uniting the core alkenyl iodides and the side-chain alkenylsilanol was achieved under mild conditions. Finally, two mild deprotections afforded the target molecules.