Purposeful regioselectivity control of the Birch reductive alkylation of biphenyl-4-carbonitrile

Birch's reductive alkylation of biphenyl-4-carbonitrile (1) provides alkylated 1,4-dihydroderivatives of various structural types: 4-alkyl-4-phenylcyclohexa-2,5-dienone, 1,4-dialkyl-4-phenylcyclohexa-2,5-dienecarbonitrile (with the same or different alkyl fragments), and 4-(1-alkylcyclohexa-2,5-dienyl)benzonitrile. Each of these products become dominant depending on the nature of long-living anionic form generated from 1, namely, the stable product of two-electrons reduction – dianion (1^2?); 1-alkyl-4-cyano-1-phenylcyclohexa-2,5-dien-4-yl anion (1-Alk₁^–), originated due to the alkylation of dianion 1^2? at the position 1 of biphenyl moiety; or 1-(4-cyanophenyl)cyclohexa-2,5-dien-1-yl anion (1-H_4’^–), being the product of dianion 1^2? protonation at position 4′ by protonating reagent (MeOH or NH₄Cl). The orientation of alkyl fragment incorporation into biphenyl-4-carbonitrile scaffold is in agreement with calculated electronic structure of the anionic species under investigation. The dominating type of their reactivity towards alkyl halides proved to be nucleophilic (S_N2 mechanism).