The Role of Achiral Pyrazolidinone Templates in Enantioselective Diels−Alder Reactions: Scope, Limitations, and Conformational Insights

We have evaluated the role of achiral pyrazolidinone templates in conjunction with chiral Lewis
acids in room temperature, enantioselective Diels−Alder cycloadditions. The role of the fluxional N(1)
substituent was examined, with the bulky 1-naphthylmethyl group providing enantioselectivities up to 99%
ee, while templates with smaller fluxional groups gave lower selectivities. High selectivities were also
observed in reactions of 7d with chiral Lewis acids derived from relatively small chiral ligands, suggesting
the pyrazolidinone templates are capable of relaying stereochemical information from the ligand to the
reaction center. Lewis acids capable of adapting square planar geometries, such as Cu(OTf)2, Cu(ClO4)2,
and Pd(ClO4)2, were found to be particularly effective at providing high selectivities. Additionally, substitution
at the C-5 position of the pyrazolidinone templates has been shown to be critical for optimal selectivity.
Reactions of the optimal pyrazolidinone appended with a number of common dienophiles and various dienes
demonstrate the utility of this achiral template. Furthermore, catalytic loadings could be lowered to 2.5 mol
% with essentially no loss in selectivity. π−π interactions were evaluated as a means to explain the unusually
high selectivity observed at room temperature. Finally, non-C2-symmetric ligands were employed as a test
to determine if chiral relay was operative.