Mechanistic studies on Diels-Alder [4 + 2] cycloaddition reactions of α,β-substituted cyclobutenones: Role of substituents in regio- and stereoselectivity

Diels-Alder reactions of substituted cyclobutenones with 6-methoxy-1-vinyl-3,4-dihydronaphthalene and methoxy-substituted-1,3-butadiene have been studied with DFT. In the reactions of 6-methoxy-1-vinyl-3,4-dihydronaphthalene with cyclobutenone and α-bromocyclobutenone, the formation of the meta and ortho isomers have the same barriers, indicating that the two isomers might be formed in equal proportions, contrary to earlier reports. The regiochemistry of the reaction is mainly controlled by the ketone functionality at C1 on the dienophiles. In the reactions of methoxy-substituted-1,3-butadiene with cyclobutenone and α, β-substituted cyclobutenones the ortho/endo and para/endo stereo-isomeric pathways are the most favorable pathways, changing to exo selectivity when OH, Br, CH3 are placed on the β-carbon of the cyclobutenone, but still with ortho and para regioselectivity. The stereoselectivity is independent of the bulkiness of substituents. The stability of substituted cycloadducts are lower compared to unsubstituted adducts and this explains why the α-cyanoketones and α-bromoketone products readily undergo trans-methylation and angular-alkylation as electrophiles.