An approach to the synthesis of [2]benzopyrano[3,4‐c]pyrroles; alternative dopaminergic molecules

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Benzyloxy‐substituted [2]benzopyrano[3,4‐c]pyrroles have been prepared by thermolysis of suitably substituted benzocyclobutenes, via an intramolecular Diels‐Alder reaction of the quinodimethane intermediate with an aldehyde function. Upon thermolysis of 3,4‐bis(benzyloxy)‐7‐[[(methoxycarbonyl)(2‐oxoethyl) amino]methyl]bicyclo‐[4.2.0]octa‐l,3,5‐triene (12), in refluxing bromobenzene,tras‐7,8‐bis(benzyloxy)‐2‐(methoxy‐carbonyl)‐l,2,3,3a,5,9b‐hexahydro[2]benzopyrano[3,4‐c]pyrrole (13) was isolated. Upon thermolysis of N‐alkyl‐N‐(2‐oxoethyl)bicyclo[4.2.0]octa‐l,3,5‐triene‐7‐carboxamides (such as 19, 29a‐d and 33a,b) in bromobenzene,trans/cismixtures of N‐substituted‐3,3a,5,9b,tetrahydro‐2H‐[2]‐benzopyrano‐[3,4‐c]pyrrol‐1‐ones were obtained in yields of 70 to 85%. In this way, 20, 21, 30a‐d, 31a‐d, 34a,b and 35a,b have been obtained. As starting materials, suitably substituted benzocyclo‐butenecarboxylic acids were used (7, 46 and 54). These compounds were converted into the acid chlorides and condensed with substituted 2‐(hydroxyethyl)amines to afford the N‐alkyl‐N‐(2‐hydroxyethyl)benzobicyclo[4.2.0]octa‐l,3,5‐triene‐7‐carboxamides 27, 28a‐d and 32a,b, which were then oxidized to the required N‐(2‐oxoethyl) derivatives by means of DMSO‐oxalyl chloride complex. Reduction of the tetrahydro‐2H‐[2]benzopyrano[3,4‐c]pyrrol‐1‐ones 20, 21, 30b, 30c and 35b with borane‐dimethyl sulfide complex or with LiAlH4‐AlCl3complex gave the hexahydro[2]benzo‐pyrano[3,4‐c]pyrroles 22, 23, 36, 37 and 38. Subsequently, these compounds were converted into catecholamines 24, 25, 39, 40 and 41 by catalytic reduction.