One-pot, Two-step Queuing Cascades Involving a Heck Coupling, π-Allylpalladium Trapping and Diels-Alder Reaction

Abstract

In the first part of this study, palladium catalyzed reactions of mono-substituted bicyclopropylidenes (66B E) with iodobenzene (67) in the presence of dienophiles 68a b have been performed. When this one-pot process has been utilized with methyl bicyclopropylidene carboxylate (66E), the reaction produced mainly regiodiastereomeric mixture of spiro[2.5]octenes cis/trans, trans-104E and cis/trans, cis-105E stemming from the opening of the only unsubstituted cyclopropane ring. The similar reaction involving boranate substituted bicylopropylidene 66B, however, gave as a major product spiro[2.5]octene 109a lacking the boranate group together with the mixture of diastereomers cis/trans, trans-104B. The formation of product 109a has been attributed to opening of the boranate substituted cyclopropane ring and following deboropalladation processes.In the second part, another one-pot yet two-step palladium catalyzed cascade reaction of bicyclopropylidene (66) with iodoethene (173) in the presence of a secondary amine 78 was introduced. Intermediately formed allylidenecyclopropanes (174a e) undergo immediate Diels-Alder reactions upon addition of dienophiles 68a e in the second step to give spiro[2.5]octenes (175aa ad and 175bb eb) in 29-66% yield. The same cascade reaction also carried out with other iodoalkenes including cyclic ones (191 196) and with cyclic dienophiles (122 and 189) to furnish highly substituted spirooctenes and spirocyclopropanated oligoheterocycles (176 179ab and 180 188a). In the third part, another one-pot, two-step, three-component cascade involving methylenespiropentane (81), functionalized aryl iodides 231a g and dimethyl fumarate 68d was presented. Palladium catalyzed cross-coupling of methylenespiropentane (81) with o-iodo benzylic alcohols or amines 231a g firstly generated seven membered dienes 232a g. These dienes in the second step, upon addition of dimethyl fumarate 68d underwent a Diels-Alder reaction to furnish benzoxepine and benzoazepine derivatives 234a g in 18-29% yield.