Synthesis of Unsymmetrical Substituted 1,4-Dihydropyridines through Thermal and Microwave Assisted [4+2] Cycloadditions of 1-Azadienes and Allenic Esters

Thermal and microwave assisted [4+2] cycloadditions of 1,4-diaryl-1-aza-1,3-butadienes with allenic
esters lead to cycloadducts, which after a 1,3-H shift afford variedly substituted unsymmetrical 2-alkyl-1,4-diaryl-3-ethoxycarbonyl-1,4-dihydropyridines in high yields. Reactions carried out under microwave
irradiation are cleaner and give higher yields with much shortened reaction times. Density functional
theory (DFT) at the B3LYP/6-31G* level has been used to calculate geometric features of the reactants,
barrier for s-trans to s-cis and reverse isomerization of azadienes (5a−d, 10a−e), dihedral angles between
N1, C2, C3, and C4 atoms of azadienes along with various indices such as chemical hardness (η), chemical
potential (μ), global electrophilicity (ω), and the difference in global electrophilicity (Δω) between the
reacting pairs and Fukui functions (f + and f -). The results revealed that s-trans is the predominant
conformation of azadienes at ambient temperature and the barrier for conversion of the s-trans rotamer
of 1-azadienes to s-cis may be the major factor influencing the chemoselectivity, i.e., [4+2] verses [2+2]
cycloaddition. The regiochemistry of the observed cycloadditions is collated with the obtained local
electrophilicity indices (Fukui functions). Transition states for the formation of both [4+2] and [2+2]
cycloadducts as located at the PM3 level indicate that the transition state for the formation of [4+2]
cycloadducts has lower energy, again supporting the earlier conclusion that preferred formation of [4+2]
cycloaaducts at higher temperature may be a consequence of barrier for s-trans to s-cis transformation of
1-azadienes.