C₁‐Symmetric Atropisomeric NHC Palladium(II) Complexes: Synthesis, Resolution and Characterization

Abstract

Series of chiral palladium(II) allyl and cinnamyl complexes bearing a C 1 -symmetric N-heterocyclic carbenes were synthesized from achiral precursors. The chirality of theses complexes results from the formation of the carbene-palladium bond which restricts the rotation of dissymmetric N-aryl substituents of the NHC and thus creates an axis of chirality. Chiral HPLC at preparative scale enabled the resolution of racemic complexes and provided a straightforward access to complexes with excellent enantiopurities (> 99.5% ee). Enantiopure complexes were studied by crystal X-ray diffraction and electronic circular dichroism (ECD). Their configuration stabilities were investigated both experimentally and theoretically through the determination of the rotational barrier values. These complexes were tested for the intramolecular α-arylation of amides, with a moderate chiral induction (up to 54% ee).

Transition metal complexes bearing atropisomeric saturated NHC ligands

“…With copper(I) and silver(I), complexes 5a and 6a , configuration stabilities should be significantly reduced and even if the observation of enantiomers by chiral HPLC analysis was expected, the isolation of enantiopure complexes by cHPLC in a preparative scale might be troublesome. Theoretical calculations suggested that the more favorable rotation would take place on the metal side as it was concluded from our previous studies 22,23 …”

“…With an unsubstituted backbone, unsaturated (complexes 1) or saturated (complexes 2), enantiomers could not be observed by cHPLC analyses suggesting low rotational barriers values. 23 This statement was confirmed by theoretical calculations, which allowed to quantify enantiomerization barriers with a reasonable level of confidence in addition to predict on which side the most favorable rotation will take place.…”

“…Theoretical calculations suggested that the more favorable rotation would take place on the metal side as it was concluded from our previous studies. 22,23…”

“…Complexes 4a and 4c were tested in asymmetric catalysis for the intramolecular α-arylation of amide 13, which represents a benchmark substrate to evaluate the efficiency of palladium complexes bearing monodentate chiral NHC ligand. [27][28][29][30] Using the reaction conditions that have been optimized for palladium complexes 3 bearing C 1 -symmetric NHC ligands, 23 a substantial decrease in reaction yields compared with complex 3a was observed (63%-69% vs. 91%) suggesting a lower catalytic activity of palladium complexes bearing a saturated NHC 4 (Scheme 3). However, complexes 4a and 3a gave oxindole 14 with identical optical purities (46%-47% ee) indicating that the nature of the NHC backbone does not influence the ability of palladium complexes to induce enantioselectivity.…”

“…Recently, we have disclosed a new design of metal-NHC complexes containing an axis of chirality. 22,23 As depicted in Figure 1C, the concept is [This article is part of the Special Issue: Chirality in France. See the first articles for this special issue previously published in Volumes 33:9, 33:10, 33:11, and 33:12.…”