The Synthesis of Trimethylcyclopentane-carboxylic Acids

(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 (47%, major path) in competition with Me migration to 8 and 9 (17%). The minor path to 8 and 9 could be reduced to 3% 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 35%. 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 form 2 but only from 3 (25%), which has HO? C(1) and H? C(5) in a cis position. With SOCl₂, 3 underwent only 5% 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 68%.