Diels-Alder Reaction of Levoglucosenone with a Protected cis-Cyclohexadienediol: Structural and Electronic Basis behind the Unexpected Stereoselectivity

摘要

abstract_textpRecently, we found that the Diels-Alder reaction between levoglucosenone and the acetonide of (1S,2R)-3-methylcyclohexa-3,5-diene-1,2-diol occurs through the most hindered face of the diene. This unexpected facial selectivity has no precedent for di-O-isopropylidene-protected dienes, and the reasons behind it remain unclear. Here, we expand on our earlier findings, computationally assessing the structural and electronic factors responsible for this unforeseen stereoselectivity. The B3LYP/6-31+G(d,p) results identify the three main adducts (-endo-ortho:-endo-meta:-exo-ortho), giving a product ratio (63:9:28) that is in line with the experimental value (64:16:10). The -endo attack allows to maximize the electrostatic attraction between the reactants, giving rise to dipolar C-OH-C interactions with the isopropylidene group at the transition state. The endo/exo preference can be rationalized through electrostatic repulsion and steric hindrance between the isopropylidene and methylene fragments. Finally, the non-classical C=OH-C hydrogen bonding stabilizes the ortho transition structures, making them more polar and asynchronous./p/abstract_text