The Intramolecular Diels-Alder Cycloaddition of N-Dienoyl Acrylimidates. An Efficient Approach for the Synthesis of Hexahydroisoquinolones and Hexahydroisoindolones

Article abstract of DOI:10.1021/jo00279a021

The intramolecular Diels-Alder reaction of aza trienes featuring the N-acyl vinyl imidate moiety in the chain linking the diene and dienophile has been investigated.The acrylimidate bases 3a-d were synthesized by O-alkylation of the corresponding acrylamides 1a-d followed by deprotonation of imidate salts 2a-d.The imidates were efficiently acylated with 3,5-dienoyl chlorides 5a,e-g in yields ranging from 73 to 87percent.The trienes 6a-g underwent cycloaddition under conditions ranging from 80 to 140 deg C, affording mixtures of cis 7a-g and trans 8a-g hexahydroisoquinolones, respectively, with a preponderance of the cis cycloadduct.The stereochemistry of the major adduct was determined from proton coupling constants and conversion of 7a to the known cis-perhydroisoquinoline 18.The cis stereochemistry is understood to originate from cyloaddition in the prefered endo conformation. 2,4-Hexadienoyl imidates 20a,d also underwent cycloaddition to afford cis hexahydroisoindolones 21a,d and 22a,d.The cycloadducts 7a,e-g were reduced with NaBH4 and NaCNBH3 to the corresponding lactams 24a,e-g.