Synthesis of Eupomatilone-6 and Assignment of Its Absolute Configuration

• Published in: Journal of organic chemistry Vol. 70; no. 23; pp. 9658 - 9661
• Main Authors: Gurjar, Mukund K, Karumudi, Bhargava, Ramana, C. V
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 11.11.2005; Amer Chemical Soc
• Subjects: Benzofurans - chemical synthesis; Benzofurans - chemistry; Chemistry; Chemistry, Organic; Crystallography, X-Ray; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Hydrogen Bonding; Molecular Conformation; Molecular Structure; Optical Rotation; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Stereoisomerism; PUTATIVE STRUCTURE; THIAZOLIDINETHIONES; FACILE SYNTHESIS; LACTONES; ASYMMETRIC ALDOL ADDITIONS; AQUEOUS-MEDIA; DIASTEREOSELECTIVE REDUCTION; CHIRAL SYNTHESIS; GAMMA-BUTYROLACTONES; OXAZOLIDINETHIONES; Sulfur nitrogen heterocycle; Hydroboration; Relative configuration; Natural product; Lactone; Transition metal; Organic bromine compounds; Aldehyde; Oxygen heterocycle; Zinc; Aldol condensation; Stereoselectivity; Racemic; Chiral auxiliary; Thione; Absolute configuration; Oxidation; Optical rotation; Spectrophotometry; Chemical synthesis; Diastereomer
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo0516234

The Zn-mediated Barbier reaction of the biarylaldehyde 8 with crotyl bromide followed by hydroboration and oxidation provided the γ-butyrolactones 4 and 5. The stereoselective installation of methyl group at C-3 by using LiHMDS and MeI completed the synthesis of racemic eupomatilone-6 (2) and its diastereomer 3. The spectroscopic data of 2 was in full agreement with reported spectra of natural product, thus confirming the revised relative configuration of eupomatilone-6. Similarly, an optically active (3R,4R,5S)-isomer of eupomatilone-6 (23) was prepared in which the aldol reaction with thiazolidinethione as a chiral auxiliary was employed as a key step. On the basis of the spectroscopic data and optical rotation values of 23, the absolute configuration of eupomatilone-6 was proposed.