Regiodivergent Asymmetric Pyridinium Additions: Mechanistic Insight and Synthetic Applications
Thiago A. Grigolo, Joel M. Smith
Abstract
Abstract A practical protocol for the first regiodivergent asymmetric addition of aryl and alkenyl organometallic reagents to substituted N ‐alkyl pyridinium heterocycles is described. The couplings proceed with high regiochemical and stereochemical selectivities, and provide access to chiral 1,2,3‐ and 1,3,4‐trisubstituted dihydropyridine products, controlled by judicious choice of nitrogen activating agent. To this end, a correlation was found between the parameterized size of the activating group and the C2/C4 regioselectivity in the couplings. The utility of the described chemistry was demonstrated in two concise asymmetric syntheses of (+)‐ N ‐methylaspidospermidine and (−)‐paroxetine.
Topics & Concepts
PyridiniumRegioselectivityChemistryAlkylCombinatorial chemistryReagentEnantioselective synthesisArylStereochemistryComputational chemistryOrganic chemistryCatalysisAsymmetric Synthesis and CatalysisChemical synthesis and alkaloidsCatalytic C–H Functionalization Methods