Henning Steinhagen

Preparation of chiral phosphorus, sulfur and selenium containing 2-aryloxazolines

Abstract A series of enantiomerically pure 2-[2-(diarylphosphino)aryl]-oxazolines was prepared from commercially available or synthetic amino alcohols. For oxazoline formation three procedures were employed: ( i ) one pot condensation with a 2-halobenzoic acid, ( ii ) ZnCl 2 catalyzed condensation with a 2-halobenzonit-rile, and ( iii ) a three step sequence via a 2-halobenzamide and a tosylate or chloride. Phosphinooxazolines containing stereogenic phosphorus were prepared by either diastereoselective nucleophilic substitution of halogenide of Ar 1 Ar 2 PCl or by nucleophilic aromatic substitution with LiPAr 1 Ar 2 . In addition, sulfur and selenium analogs were prepared.

Enantioselective catalysis with complexes of asymmetric P,N-chelate ligands

Pd catalyzed asymmetric C-C and C-N bond forming substitutions at allylic compounds are an important area of current research. For a considerable time progress in this area was slow, but over the last few years dramatic improvements were achieved (ref. 1). The reaction of a chiral, racemic allylic derivative with a Pd fragment yields the complex of a symmetric allylic cation (Scheme 1). One quite obvious problem associated with this reaction is the long distance between the chiral information provided by L* and the reaction path of the nucleophile. The traditional C2-symmetric chelate diphosphines are not suited for differentiation of the diastereotopic carbon atoms of the allylic moiety; with diphosphines that gave excellent results in hydrogenations, i.e., CHIRAPHOS, BINAP etc., results were not satisfactory, particularly with cyclic allylic substrates. However, over the last few years it was demonstrated with bisoxazolines (ref. 2) and special diphosphines (ref. 3) that very high enantioselectivity is possible with a proper combination of substrate and ligand.

(η3-Phenylallyl)(phosphanyloxazoline)palladium Complexes: X-Ray Crystallographic Studies, NMR Investigations, and Ab Initio/DFT Calculations†

All possible (eta(3)-allyl)palladium complexes (1-4) of the ligand (4S)-[2-(2-diphenylphosphanyl)phenyl]-4,5-dihydro-4-(2-propyl)-oxazole (L 1) and eta(3)-allyl ligands with one to three phenyl substituents at the terminal allylic centers were synthesized and characterized by X-ray crystal structure analysis and, with respect to allylic isomers, by NMR investigations. Equilibrium geometries, electronic structures, and relative energies of isomeric complexes were computed by restricted Hartree-Fock (RHF) and density functional theory (DFT) calculations; experimentally determined isomer ratios could be reproduced. The results allowed important conclusions to be drawn regarding the mechanism of Pd-catalyzed asymmetric allylic substitutions.

Structure Determination of a Key Intermediate of the Enantioselective Pd Complex Catalyzed Allylic Substitution Reaction

The structure of a catalytic intermediate with important implications for the interpretation of the stereochemical outcome of the palladium complex catalyzed allylic substitution with phosphino-oxazoline (PHOX) ligands is determined by liquid state NMR. The complex displays a novel structure that is highly distorted compared with other palladium eta2-olefin complexes known so far. The structure has been determined from nuclear overhauser data (NOE), scalar coupling constants, and long range projection angle restraints derived from dipole dipole cross-correlated relaxation of multiple quantum coherence. The latter restraints have been implemented into a distance geometry protocol. The projection angle restraints yield a higher precision in the determination of the relative orientation of the two molecular moieties and are essential to provide an exact structural definition of the olefinic part of the catalytic intermediate with respect to the ligand.