A practical synthesis of long-chain iso-fatty acids (iso-C12-C19) and related natural products

• Published in: Beilstein journal of organic chemistry Vol. 9; no. 1; pp. 1807 - 1812
• Main Authors: Richardson, Mark B, Williams, Spencer J
• Format: Journal Article
• Language: English
• Published: Germany Beilstein-Institut 04.09.2013
• Subjects: Chemistry; chemoselective reduction; Evans’ auxiliary; Full Research Paper; Grignard addition; homologation; ionic hydrogenation; chemoselective reduction; homologation; Evans’ auxiliary; ionic hydrogenation; Grignard addition
• ISSN: 1860-5397; 1860-5397
• DOI: 10.3762/bjoc.9.210

A gram-scale synthesis of terminally-branched iso-fatty acids (iso-C12-C19) was developed commencing with methyl undec-10-enoate (methyl undecylenate) (for iso-C12-C14) or the C15 and C16 lactones pentadecanolide (for iso-C15-C17) and hexadecanolide (for iso-C18-C19). Central to the approaches outlined is the two-step construction of the terminal isopropyl group through addition of methylmagnesium bromide to the ester/lactones and selective reduction of the resulting tertiary alcohols. Thus, the C12, C17 and C18 iso-fatty acids were obtained in three steps from commercially-available starting materials, and the remaining C13-C16 and C19 iso-fatty acids were prepared by homologation or recursive dehomologations of these fatty acids or through intercepting appropriate intermediates. Highlighting the synthetic potential of the iso-fatty acids and various intermediates prepared herein, we describe the synthesis of the natural products (S)-2,15-dimethylpalmitic acid, (S)-2-hydroxy-15-methylpalmitic acid, and 2-oxo-14-methylpentadecane.