Hetero-Diels–Alder reaction of aromatic aldehydes catalyzed by titanium tetrachloride: computational and experimental results

Computational calculations of the hetero-Diels–Alder (HDA) reactions of benzaldehyde with 2,3-dimethyl-1,3-butadiene (DMB) catalyzed by BF3, EtAlCl2 or TiCl4 at the density functional theory (DFT) (B3LYP/6-31G(d,p)) level reveal that the reactions involve activation energy barriers of 14.59, 14.34, and 17.44 kcal mol−1, respectively. In the first two cases, reaction occurs through a concerted mechanism, whereas in the presence of TiCl4, stepwise mechanism involving zwitterionic intermediate is followed. The reaction with isoprene proceeds with complete regioselectivity leading to the expected regioisomer having O/Me in 1:4 positions. The computational results have been verified experimentally when aromatic aldehydes react with 1,3-dienes in the presence of a catalyst to give 3,6-dihydro-2H-pyran derivatives in high yields.