First Enantioselective Catalyst for the Rearrangement of Allylic Imidates to Allylic Amides

Abstract

A series of Pd(II) complexes containing chiral diamine ligands were investigated as asymmetric catalysts for the rearrangement of allylic imidates to allyl amides. The best catalysts were cations obtained by dechlorination of dichloro[(S)-2-(isoindolinylmethyl)-N-methylpyrrolidine]palladium(II) (17) with silver salts in CH2Cl2. Catalyst 18 was studied thoroughly and shown by 1H NMR and X-ray crystallography analysis to be a C 1 symmetric dimer (Figure ). A series of related catalysts 22−27 having various counterions and anionic ligands were also prepared and studied as asymmetric catalysts for the rearrangement of allylic N-(4-trifluorophenyl)benzimidate 29 to allylic benzamide 30 (eq 4). Rearrangement of 29 in CH2Cl2 (48 h at 40 °C) in the presence of 5 mol % of 18 affords (−)-30 in 69% yield and 55% ee. Enantioselection is increased to 60% when an isomerically pure sample of 18 is employed. Chemical correlation of allylic benzamide 30 with (R)-norvaline established that (−)-30 has the R absolute configuration (Scheme ). A cyclization-induced rearrangement mechanism (Scheme ) requires that in the major pathway the imidate nitrogen attacks the re face of the olefin with Pd coordinated to the si face. These studies constitute the first report of asymmetric catalysis of the rearrangement of allylic imidates to allylic amides. However, significant hurdles remain to be overcome before the enantioselective rearrangement of allylic imidates becomes a practical route to enantioenriched nitrogen compounds.

Ferrocenylimidazoline palladacycles as efficient catalysts for the aza‐Claisen rearrangement reaction of allylic imidates

“…In addition, acetyl at 1-N and two benzyl groups at C-4 and C-5 lower the electronic density of complex 1f on the imidazoline ring. Complex 1f gave noticeably higher yields of the desired products compared with catalysts 1a and 1g (entries 6 in Tables 2 and 3), which is consistent with the observation reported from Overman et al [8] Therefore, the results imply that the electronic properties of substituents in the imidazoline moiety are important factors in the catalytic properties of palladacycle dimers and strong electron-withdrawing substituents are favored for the aza-Claisen rearrangement reaction. On the other hand, the solubility of catalyst may also play a crucial role.…”

Enantioselective Organocatalysis

“…[89] This class of ligands has been utilized in other applications, such as in the asymmetric Mukaiyama-aldol reaction [90] and in the asymmetric rearrangement of allylic imidates to form allylic amides. [91] Recently, the catalyst was immobilized on a polymer support and used for the kinetic resolution of racemic mixtures of secondary alcohols. [92] Small peptide catalysts that contain modified histidine residues are efficient catalysts in enantioselective acylation reactions.…”

Comparative study on separation of diastereomers by HPLC

“…Acylation of 1 with carboxylic acid 2e was achieved with DCC [24]. Catalytic hydrogenation of compounds 3a f and hydrolysis ofdiastereomeric mixtures [(1S)-4a f; (1R)-5a f] were performed in analogous manner to established methods [23].…”