ABSTRACT
An outstanding challenge in the Pd-catalyzed functionalization of allylamines is the control of stereochemistry. Terminal alkenes preferentially undergo Heck-type reactions, while internal alkenes may undergo a mixture of Heck and C-H activation reactions that give mixtures of stereochemical products. In the case of unprotected allylamines, the challenge in achieving C-H activation is that facile in situ formation of Pd nanoparticles leads to preferential formation of trans rather than cis-substituted products. In this study we have demonstrated the feasibility of using mono-protected amino acid (MPAA) ligands as metal protecting groups to prevent aggregation and reduction, allowing the selective synthesis of free cis-arylated allylamines. This method complements Heck-selective methods, allowing complete stereochemical control over the synthesis of cinnamylamines, an important class of amine that can serve as therapeutics directly or as advanced intermediates. To highlight the utility of the methodology, we have demonstrated rapid access to mu opioid receptor ligands.
ABSTRACT
Herein we describe a method for combining supramolecular catalysis with imininum-based organocatalysis in the Diels-Alder cycloaddition reaction. Both supramolecular host and L-proline are required for the reaction to occur, implying that encapsulation of the substrates and co-catalyst are necessary for the reaction to occur. We explore the substrate scope for a variety of E-cinnamaldehydes and dienes. Finally, we probe the supramolecular assembly processes responsible for the observed catalysis using NMR spectroscopic methods.
