PREPARATION OF FATTY ACIDS AND ESTERS CONTAINING DEUTERIUM

INTRODUCTION A. Reaction sequences DEUTERIUM EXCHANGE A. Preparation of nonanal-2,2-d2 B. Preparation of tetradecanoic-2,2-d2 acid C. Preparation of perdeuterated octadecanoic acid D. Preparation of perdeuterated hexadecanoic acid MULTIPLE BOND DEUTERATION A. Reduction with Lindlar's catalyst 1. Preparation of 7-chloro-cis-3-heptene 2. Preparation of deuterated Lindlar's catalyst 3. Preparation of methyl cis-9-octadecenoate-9,10-d2 B. Reduction with Wilkinson's catalyst 1. Deuteration with tris(triphenylphosphine) chlororhodium 2. Preparation of methyl threo-12,13-dihydroxyoctadecanoate-9,10-d2 C. Deuterohydrazine reduction--preparation of methyl octadecanoate-9,10-d2 D. Hydroboration--preparation of methyl cis-9-octadecenoate-9,10-d2 E. Lithium aluminum hydride--preparation of trans-2-octen-7-ynol CHEMICAL REDUCTION A. Lithium aluminum deuteride reduction--preparation of eicosanol-l,l-d 2 B. Clemmensen reduction--Preparation of methyl octadecanoate-5,5,6,6,7,7-d 6 CHEMICAL SYNTHESIS A. Chain extension 1. With deuterated formaldehyde--preparation of 2-octynol-l,l-d2 2. Via the nitrile (a) Preparation of pentadecanenitrile-3,3-d2 (b) Preparation of pentadecanoic-3,3-d2 acid (c) Preparation of methyl cis-lO-nonadecenoate 3. With malonic ester (a) Preparation of docosanoic-3,3-d 2 acid (b) Preparation of cis-I l-eicosenoic acid (c) Preparation of cis-9,cis-12-octadecadienyl methanesulfonate B. Anodic coupling--preparation of tetradecanoic-10,10-d2 acid C. Acetylenic coupling 1. Preparation of 3-nonynol-7,7,8,8-d4 2. Preparation of 2-(9-decynyloxy)-tetrahydropyran 3. Preparation of 4-decynoic acid 4. Preparation of 10-tetradecynoic acid 5. Preparation of 2-(8-nonen-5-ynyloxy)-tetrahydropyran 6. Preparation of 11-dodecen-9-ynyl acetate D. Wittig reaction 1. Preparation of methyl cis-9-octadecenoate-14,14,15,15,17,18-d6 2. Preparation of methyl 12,15-octadecadienoates-9,10-d 2 (a) Without stereoselective control (b) With stereoselective control 3. Preparation of phosphonium salts (a) Phosphonium bromides--preparation of cis-3-hexenyltriphenylphosphonium bromide (b) Phosphonium iodides 4. Preparation of halides (a) Iodide from chloride--preparation of 1-iododecane-4,4,5,5-d4 (b) Iodide from tetrahydropyranyl ether--preparation of 1-iodononane-5,5,6,6,8,9-d6 (c) Preparation of tetrahydropyranyl ethers (d) Bromide from alcohol with PBra--preparation of l-bromononane-2,2-d 2 (e) Bromide from alcohol with triphenylphosphine dibromide (1) Preparation of l-bromo-cis-3-hexene (2) Preparation of l-bromo-cis-3-nonene-7,7,8,8-d4