Synthesis of prostaglandins by conjugate addition and alkylation of a directed enolate ion. 4,5-Allenyl prostaglandins

• Published in: Journal of organic chemistry Vol. 55; no. 20; pp. 5528 - 5531
• Main Author: Patterson, John W
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.09.1990
• Subjects: 551000 - Physiological Systems; ACETIC ACID; ADSORBENTS; ALCOHOLS; Alicyclic compounds, terpenoids, prostaglandins, steroids; ALKALI METAL COMPOUNDS; ALKENES; ALKYLATION; ANIONS; BASIC BIOLOGICAL SCIENCES; BROMIDES; BROMINE COMPOUNDS; CARBANIONS; CARBOXYLIC ACIDS; CHARGED PARTICLES; CHEMICAL PREPARATION; CHEMICAL REACTIONS; Chemistry; CHROMATOGRAPHY; COPPER COMPOUNDS; COPPER HALIDES; COPPER IODIDES; DECOMPOSITION; ENOLS; ETHERS; Exact sciences and technology; HALIDES; HALOGEN COMPOUNDS; HYDROCARBONS; HYDROLYSIS; HYDROXY COMPOUNDS; INFRARED SPECTRA; IODIDES; IODINE COMPOUNDS; IONS; ISOMERS; LIQUID COLUMN CHROMATOGRAPHY; LITHIUM BROMIDES; LITHIUM COMPOUNDS; LITHIUM HALIDES; LYSIS; MONOCARBOXYLIC ACIDS; NMR SPECTRA; ORGANIC ACIDS; Organic chemistry; ORGANIC COMPOUNDS; ORGANIC OXYGEN COMPOUNDS; ORGANIC SILICON COMPOUNDS; OXIDATION; Preparations and properties; PROSTAGLANDINS; RACEMATES; SEPARATION PROCESSES; SILICA GEL; SOLVOLYSIS; SPECTRA; SYNTHESIS; THIN-LAYER CHROMATOGRAPHY; TRANSITION ELEMENT COMPOUNDS; Prostaglandin; Aliphatic compound; Epimer; Ketol; Secondary alcohol; Allenic compound; Allylic compound; Monocyclic compound
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo00307a028

Over the previous two decades many elegant syntheses of prostaglandins, which in more sophisticated forms, allow the stereospecific introduction of the various asymmetric carbons have been accomplished. However, among these approaches the cuprate addition/enolate alkylation of suitable cyclopentenone {sup 2} stands out because of brevity and convergence. The recent reports by Noyori{sup 3} and Corey{sup 4} and their colleagues have reduced to practice the conversion of 4-alkoxycyclopentenones to prostaglandin E{sub 2} (PGE{sub 2}) by conjugate addition of an organocopper derivative of the lower side chain followed by alkylation of the resulting carbanion with methyl 7-halohept-2-enoate. The subject of this paper is application of the Tardella tin enolate alkylation developed by Noyori to the synthesis of 4, 5-allenic prostaglandins, a pharmacologically important class of compounds. The authors results demonstrate that the tandem alkylation of an enone precursor with a cuprate reagent followed by alkylation of the corresponding tin enolate with bromide reagent is a viable synthetic method for 4,5-didehydro-PGE{sub 2}. Because the optically active forms of 1 and the vinyl iodide precursor of the PGE{sub 2} lower side chain have been employed to produce a single enantiomer of PGE{sub 2}, the extension of the methodology described here to the synthesis of single enantiomers of 4a awaits only the preparation of the separate enantiomers of allene 14.