jo0700575_si_001.pdf (84.97 kB)
Stereoselectivity in Diels−Alder Reactions of Diene-Substituted N-Alkoxycarbonyl-1,2-dihydropyridines
journal contribution
posted on 2007-04-27, 00:00 authored by Grant R. Krow, Qiuli Huang, Steven W. Szczepanski, Fredrick H. Hausheer, Patrick J. CarrollDiene substituent effects on the regiochemical and stereochemical outcomes of uncatalyzed Diels−Alder
reactions of N-alkoxycarbonyl-1,2-dihydropyridines with both styrene and methyl vinyl ketone (MVK)
were studied. Alkyl substitution on the diene in all cases examined resulted in a kinetic preference for
7-endo isomers (7-phenyl 51−96% exo and 7-acetyl 54−96% exo). For both dienophiles, the highest
stereoselectivities (≥89% endo) were observed with 5-methyl or 6-methyl substituents in the dihydropyridine. Theoretical calculations of the energies of gas phase endo and exo transition states at the RHF/3-21G(*) predict that total entropy, ΔStotal, considerations favor endo cycloadducts for both dienophiles
with DHP, while total energy considerations, ΔE⧧o, favor endo cycloadducts for styrene and exo
cycloadducts for MVK. At this level, favored endo-phenyl isomers are correctly predicted for styrene
reactions, but the calculation of 7-acetyl exo or endo isomer dominance is diene-substituent-dependent
for MVK reactions. The preference for endo addition of MVK to the parent, 5-methyl, and 6-methyl-DHPs was successfully predicted by calculations at the B3LYP/6-31G* theory level.