Mechanistic studies on Diels-Alder [4þ2] cycloaddition reactions ofa,b-substituted cyclobutenones: Role of substituents in regio- andstereoselectivity

Abstract

Diels-Alder reactions of substituted cyclobutenones with 6-methoxy-1-vinyl-3,4-dihydronaphthaleneand methoxy-substituted-1,3-butadiene have been studied with DFT. In the reactions of 6-methoxy-1-vinyl-3,4-dihydronaphthalene with cyclobutenone anda-bromocyclobutenone, the formation of themetaandorthoisomers have the same barriers, indicating that the two isomers might be formed in equalproportions, contrary to earlier reports. The regiochemistry of the reaction is mainly controlled by theketone functionality at C1 on the dienophiles. In the reactions of methoxy-substituted-1,3-butadienewith cyclobutenone anda,b-substituted cyclobutenones theortho/endoandpara/endostereo-isomericpathways are the most favorable pathways, changing toexoselectivity when OH, Br, CH3are placedon theb-carbon of the cyclobutenone, but still withorthoandpararegioselectivity. The stereoselectivityis independent of the bulkiness of substituents. The stability of substituted cycloadducts are lowercompared to unsubstituted adducts and this explains why thea-cyanoketones anda-bromoketoneproducts readily undergotrans-methylation and angular-alkylation as electrophiles.