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Theoretical and Experimental Optimization of a New Amino Phosphite Ligand Library for Asymmetric Palladium‐Catalyzed Allylic Substitution
Author(s) -
Magre Marc,
Biosca Maria,
Norrby PerOla,
Pàmies Oscar,
Diéguez Montserrat
Publication year - 2015
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201500873
Subject(s) - enantiopure drug , allylic rearrangement , ligand (biochemistry) , chemistry , combinatorial chemistry , catalysis , palladium , substrate (aquarium) , chiral ligand , nucleophile , enantioselective synthesis , stereochemistry , substitution reaction , organic chemistry , oceanography , receptor , geology , biochemistry
A new library of modular amino phosphite ligands obtained in a few synthetic steps from enantiopure amino alcohols has been tested in asymmetric Pd‐catalyzed allylic substitution. The modular ligand design is crucial to find highly selective catalysts for each substrate type using a wide range of C‐, N‐, and O‐nucleophiles. A DFT study of the species responsible for the enantiocontrol was used to optimize the ligand structure. By selecting the ligand components, we were able to identify unprecedented catalytic systems that can create new chiral C−C, C−N, and C−O bonds in a variety of substrate types (hindered and unhindered) in high yields and enantioselectivities ( ee values up to 99 %). Further studies on the Pd‐π‐allyl intermediates provided a deep understanding of the effect of ligand structure in the origin of enantioselectivity. Potential applications of the new Pd/amino phosphite catalysts were demonstrated by the practical synthesis of a range of chiral carbocycles by simple tandem reactions, with no loss of enantioselectivity.