The orbital mixing rule is successfully applied to the prediction of the π-facial selectivity in the Diels–Alder reactions of cyclopentadienes having π-systems at 5-positions, by taking into consideration the relative energies of the π-HOMO of the diene and the π and π* orbitals on the substituent. When the π orbital lies high enough to interact with the π-HOMO, the participation of the π* orbital in the mixing is negligible. The rule gives a prediction of syn
π-facial selectivity. The FMO extends and distorts inwardly to favor the reaction at the syn side of the substituent (Case A: Ψ(FMO) = π-HOMO − π + σ). On the other hand, when the π* orbital lies low enough to interact with the π-HOMO, the π* orbital plays a predominant role. The rule gives a prediction of anti
π-facial selectivity (Case B: Ψ(FMO) = π-HOMO + π* − σ). The prediction was examined by theoretical calculation of the FMO's of the model dienes 1d, e, and f (Cp–X: X = CHO, CH
NOH, and CH
CH2), and substantiated by the reactions of the corresponding pentamethylcyclopentadienes 2d, e, and f (Cp*–X: X = CHO, CH
NOH, and CH
CH2) with N-phenylmaleimide at 25 °C in CCl4 to give products with syn∶anti ratios of 0∶100, 50∶50 and 34∶66, respectively. The new modeling of the solvent effects on the π-facial selectivity in the reactions of the amphoteric diene 2e was proposed as an application of the orbital mixing rule. Enhancement of syn
π-facial selectivity is expected in a solvent which is a Lewis base. Under the conditions, the orbital mixing of Case A would be enhanced, since the hydrogen-bond formation between the solvent and the hydroxy hydrogen of 2e should raise the π and π* orbitals. The prediction was substantiated by the observation of considerable enhancement of syn
π-facial selectivity in solvents such as CF3CH2OH, pyridine, THF, MeOH, EtOH, Et3N, TMEDA and HMPA relative to CCl4, toluene and AcOH.