Preparation of deuterated methyl 6,9,12‐octadecatrienoates and methyl 6,9,12,15‐octadecatetraenoates

Abstract

AbstractMethyl 6,9,12‐octadecatrienoate‐15,15,16,16‐d4 was obtained by Wittig coupling between 6,6,7,7‐tetradeutero‐3‐nonenyltriphenylphosphonium iodide, 8, and the aldehyde ester, methyl 9‐oxo‐6‐nonenoate. Methyl 6‐oxohexanoate, obtained by ozonolysis of cyclohexene, was coupled in a Wittig reaction with [2‐(1,3‐dioxan‐2‐yl)ethyl]triphenylphosphonium bromide to give methyl 8‐dioxanyl‐6‐octenoate. This compound was transacetalized to methyl 9,9‐dimethoxy‐6‐nonenoate, which was then hydrolyzed to the aldehyde ester. For the preparation of compound 8, the tetrahydropyranyl ether of 2‐pentynol was deuterated with deuterium gas and tris‐(triphenylphosphine)chlororhodium. The tetradeuterated tetrahydropyranyl ether was converted to the bromide with triphenylphosphine dibromide, and the bromide was coupled with 3‐butynol by means of lithium amide in liquid ammonia to give 3‐nonynol‐6,6,7,7‐d4. Hydrogenation over Lindlar's catalyst converted the deuterated alkynol to 3‐nonenol‐6,6,7,7‐d4. This deuterated alkenol was converted to the bromide with triphenylphosphine dibromide, then to the iodide with sodium iodide in acetone, and finally to 8 with triphenylphosphine in acetonitrile. Methyl 6,9,12,15‐octadecatetraenoate‐12,13,15,16‐d4 was obtained by Wittig coupling between methyl 9‐oxo‐6‐nonenoate and 3,4,6,7‐tetradeutero‐3,6‐nonadienyltriphenylphosphonium iodide, 15. For the preparation of compound 15, the bromide obtained from the reaction of 2‐pentynol with triphenylphosphine dibromide was coupled with 3‐butynol with lithium amide in liquid ammonia. The resulting 3,6‐nonadiynol was deuterated with deuterium gas in the presence of P‐2 nickel, and the resultant deuterated nonadienol was converted to 15 through the bromide and iodide. The final products were separated from isomers formed during the synthetic sequences by silver resin chromatography.