Aspects of the Intramolecular Diels-Alder Reactions of Some 1,3,9-Trienic Amides, Amines, and Esters. An Approach to the Pentacyclic Skeleton of the Yohimboid Alkaloids

Article abstract of DOI:10.1021/jo00174a005

The intramolecular cycloadditions of a number of 1,3,9-tienes containing an amide, amine, or ester function in the chain linking the dienophile and the diene were examined, and a general preference for the formation of cis cycloadducts was observed.Thus, the aza trienes 7b-h were found to undergo intramolecular Diels-Alder reaction upon thermolysis at temperatures ranging from 25 to 275 deg C to give mixtures of the cis- and trans-hydroisoquinolines 9b-h and 10b-h, respectively, in ratios that varied from about 1.1:1 to 8:1.Thermolysis of the pentadienamide 34 produced the cis- and trans-hydroisoquinolines 35 and 36 (1.6:1).Interestingly, the aza trienes 13 and 14 in which the internal double bond is Z appear to suffer extensive isomerization, presumably via 1,5-hydrogen migration, prior to cyclization to provide isomeric trienes, which have not been isolated but have been tentatively identified as 22 and 25 since they afford corresponding mixtures of the cis- and trans-hydroisoindoles 20/21 and 23/24 as the principle cycloadducts; only small amounts of the expected cis-hydroisoquinolines 9e and 9h were obtained in these thermolyses.In order to demonstrate the feasibility of applying intramolecular Diels-Alder reactions of aza trienes to the syntheses of alkaloids containing a hydroisoquinoline ring, the trans-hydroisoquinoline 10d was converted to the yohimbine-related compounds 38 and 39 by cyclization with POCl3 followed by either catalytic hydrogenatin or hydride reduction of the intermediate iminium salt.The reactivity of the related esters 40-42 toward intramolecular <4+2> cycloaddition was also briefly examined, and it was found that only the acrylate 41 underwent cyclization at temperatures below 275 deg C.