The Synthesis of Trimethylcyclopentane-carboxylic Acids

Article abstract of DOI:10.1002/hlca.19860690525

(1RS,5SR)-2,2,5-Trimethylcyclopentane-1-carboxylic acid (17) and (1r, 2RS, 5SR)-1,2,5-trimethylcyclopentane-1-carboxylic acid (19) are the starting materials for the α-alkynone routes to (+/-)-capnellene and for similar efforts towards ptychanolide.Since 17 and 19 have, so far, been available only by a branching reaction from the same precursor, the cyanohydrin mixture 2/3, a modified synthesis for 17 and a new one for 19 was developed (Scheme 1).The common precursor 2/3 was treated with POCl3 which effected normal dehydration to 6 (47percent, major path) in competition with Me migration to 8 and 9(17percent).The minor path to 8 and 9 could be reduced to 3percent when SOCl2 was used for the dehydration of 2/3.This reaction was the basis for an improved synthesis of 17 from 1, using the steps b, e, i, r and v see Scheme 1 in an overall yield of 35percent.The POCl3 reaction was also studied with the pure cyanohydrins 2 and 3, the configurations of which were determined by an X-ray analysis of 2.Me migration did not occur from 2 but only from 3 (25percent), which has HO-C(1) and H-C(5) in a cis position.With SOCl2, 3 underwent only 5percent Me migration.The new synthesis of 19 started with 4 using the steps h,n,p and s (see Scheme 1) in an overall yield of 68percent.