Presented by Dr. Tobias Sandmeier, Rovis Group
4:00pm - 5:00pm
Saturated N-heterocycles, especially piperidines and pyrrolidines, have emerged as privileged structures in medicinal chemistry and are prominent motifs in agrochemical agents. In contrast to their aromatic counterparts, saturated heterocycles are often chiral. While this increased molecular complexity opens new opportunities for the development of highly selective biologically active compounds it also poses a major synthetic challenge. Enantiomers can have distinctly different pharmacological activities. Therefore, efficient enantioselective synthetic routes for the preparation saturated N-heterocycles are highly desirable.
The Carreira group has a long-standing interest in the development of new enantioselective reactions, especially in the field of iridium-catalyzed allylic substitution. Throughout this talk two novel approaches for the stereoselective synthesis of piperidines and pyrrolidines will be presented. First, we have developed a protocol for the iridium-catalyzed enantiospecific cyclocondensation of enantioentriched amino alcohols and aldehydes to furnish 3,4-disubstituted piperidines. Due to the modularity of the approach, the mild reaction conditions, and the broad functional group tolerance a diverse set of piperidine products could be accessed efficiently. In addition, we have established conditions for the chemo- and enantioselective intramolecular N– and O-alkylation of oximes. Iridium-catalyzed kinetic resolution of hydroxy oximes furnishes cyclic nitrones, oxime ethers and enantioenriched allylic alcohols. Key features of this reaction are its compatibility with E/Z-isomeric mixtures of oximes and chemodivergent N– vs O-alkylation depending on the reaction conditions. The utility of these methods was demonstrated with the asymmetric synthesis of quinuclidine scaffolds as well as the formal syntheses of (–)-roxifiban, a glycoprotein GP IIb‐IIIa receptor antagonist and the marine natural product (+)-halichlorine.
Friday, January 15, 2021 at 4:00pm EST
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