A practical synthesis of long-chain iso-fatty acids (iso-C(12)–C(19)) and related natural products

A gram-scale synthesis of terminally-branched iso-fatty acids (iso-C(12)–C(19)) was developed commencing with methyl undec-10-enoate (methyl undecylenate) (for iso-C(12)–C(14)) or the C(15) and C(16) lactones pentadecanolide (for iso-C(15)–C(17)) and hexadecanolide (for iso-C(18)–C(19)). 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 C(12), C(17) and C(18) iso-fatty acids were obtained in three steps from commercially-available starting materials, and the remaining C(13)–C(16) and C(19) 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.