Stereoretentive Regio‐ and Enantioselective Allylation of Isoxazolinones by a Planar Chiral Palladacycle Catalyst

Abstract

The catalytic allylic substitution is one of the most important tools in asymmetric synthesis to form CÀ C bonds in an enantioselective way. While high efficiency was previously accomplished in terms of enantio-and regiocontrol using different catalyst types, a strong general limitation is a very pronounced preference for the formation of allylic substitution products with (E)-configured C=C double bonds. Herein, we report that with a planar chiral palladacycle catalyst a diastereospecific reaction outcome is achieved using isoxazolinones and allylic imidates as substrates, thus maintaining the C=C double bond geometry of the allylic substrates in the highly enantioenriched products. DFT calculations show that the reactions proceed via an S N 2 mechanism and not via π-allyl Pd complexes. Crucial for the high control is the stabilization of the allylic fragment in the S N 2 transition state by π-interactions with the phenyl substituents of the pentaphenylferrocenyl catalyst core.

Planar Chiral Ferrocendiyl and Ruthenocendiyl Bisimidazoline Bispalladacycles Featuring Pyridin‐2‐olates and Ketophenolates as Potentially Hemilabile Ligands in Asymmetric 1,4‐Additions

“…Due to the electronegativity difference, the oxygen anion in pyridonate should be the harder Lewis base compared to the pyridine nitrogen. This behavior is in line with other ferrocene derived imidazoline palladacycles reported by our research group [4,6a,j,7e] …”

Use of the N–O Bonds in N-Mesyloxyamides and N-Mesyloxyimides To Gain Access to 5-Alkoxy-3,4-dialkyloxazol-2-ones and 3-Hetero-Substituted Succinimides: A Combined Experimental and Theoretical Study

“…The alternative assumption that the product is isoxazolone 13b could also not be proven experimentally as the isolated material was reluctant for a nucleophile/ethoxy exchange under various conditions. 14 In order to gain clarity, the reaction mechanism was investigated by computational methods. To minimize computing time and reduce conformational complexity, DFT calculations were carried out with the -methyl-substituted N-mesyloxyamide 9a.…”

Enantioselective construction of quaternary stereocenters via organocatalytic arylation of isoxazolin-5-ones with o-quinone diimides

“…Peters described in 2015 the enantioselective alkylation of isoxazol-5-ones with vinyl ketones 14 and later two methods of C4-allylation using iridium or palladium catalysis (Scheme 1b). 15 Recently, the group of Li and Li have achieved an organocatalytic addition of isoxazolinones to alkynyl iminoesters providing chiral tetrasubstituted α-amino allenoates. 16…”