Catalytic asymmetric hetero Diels-Alder reactions of N-sulfinyl dienophiles with chiral bis(oxazoline)copper(II) and -zinc(II) triflates

Asymmetric hetero Diels-Alder (HDA) reactions of N-sulfinyl dienophiles with bis(oxazoline)copper(II) and -zinc(II) triflates are described. The cycloaddition with cyclic and acyclic 1,3-dienes has been studied. The copper catalyst was found to be more efficient. With 10 mol-% of catalyst loading, a pronounced enhancement in turnover, diastereoselectivity (541 > 90% de), and enantioselectivity (30-98% ee) was obtained by the addition of 100 mol-% of TMSOTf. The role of the additive is unclear, but we hypothesize that it is involved in the breakdown of catalyst-sulfine aggregates assists in the release of catalyst from the HDA adducts. Mechanistic studies revealed a positive nonlinear effect with the zinc catalyst, assumed to arise from the formation of less reactive hetero-chiral complexes. The copper catalyst showed a nearly linear relationship between the enantioselectivity of the ligand tested and the HDA product formed. The relative configurations and, in one case, the absolute configuration of the HDA products were established by X-ray analysis. Finally, an enantioselective route to (3aR,6aS)-3,3a,4,6a-tetrahydrocyclopenta[d][1,3]oxazol-2-one, a precursor of the C-ring in agelastatin A, applying the asymmetric HDA reaction is described.