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Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Parallel and modular synthesis of P-chirogenic P,O-ligands
Magnus J Johansson1, Susanne Berglund, Yinjun Hu
1Organic Chemistry, Department of Chemical and Biological Engineering, Chalmers University of Technology , 41296 Göteborg, Sweden.
Abstract:
A modular synthesis of P-chirogenic α-alkoxyphosphine ligands has been developed, allowing for the variation of two of the three groups on phosphorus. Oxidation and concomitant desymmetrization of a prochiral alkyl- or aryldimethylphosphine borane afforded α-hydroxyphosphines, which were subsequently deprotonated and alkylated in a parallel fashion. The choice of base and temperature for the alkylation step was found to be crucial for the outcome of the reaction. Selected ligands were subsequently screened in palladium catalyzed allylic substitution, affording product in good to excellent yield but moderate enantioselectivity, indicating that further optimization of the ligand structures is desirable to increase the stereoselectivity.
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