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Palladium(0)‐Catalyzed Enantioselective Intramolecular Arylation of Enantiotopic Secondary C−H Bonds
Author(s) -
Melot Romain,
Zuccarello Marco,
Cavalli Diana,
Niggli Nadja,
Devereux Michael,
Bürgi Thomas,
Baudoin Olivier
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202014605
Subject(s) - enantioselective synthesis , chemistry , stereocenter , intramolecular force , stereochemistry , catalysis , reactivity (psychology) , palladium , steric effects , ligand (biochemistry) , amide , medicinal chemistry , combinatorial chemistry , organic chemistry , medicine , biochemistry , alternative medicine , receptor , pathology
The enantioselective functionalization of nonactivated enantiotopic secondary C−H bonds is one of the greatest challenges in transition‐metal‐catalyzed C−H activation proceeding by an inner‐sphere mechanism. Such reactions have remained elusive within the realm of Pd 0 catalysis. Reported here is the unique reactivity profile of the IBiox ligand family in the Pd 0 ‐catalyzed intramolecular arylation of such nonactivated secondary C−H bonds. Chiral C 2 ‐symmetric IBiox ligands led to high enantioselectivities for a broad range of valuable indane products containing a tertiary stereocenter, as well as the arylation of secondary C−H bonds adjacent to amides. Depending on the amide substituents and upon control of reaction time, indanes containing labile tertiary stereocenters were also obtained with high enantioselectivities. Analysis of the steric maps of the IBiox ligands indicated that the level of enantioselectivity correlates with the difference between the two most occupied and the two less occupied space quadrants, and provided a blueprint for the design of even more efficient ligands.