Modular chiral bidentate phosphonites: design, synthesis, and application in catalytic asymmetric hydroformylation reactions

A new class of C(2)-symmetric chiral bidentate phosphonite ligands has been synthesized in moderate to good yields from readily available starting materials. Application of these air-stable chiral phosphonites in the Rh(I)-catalyzed asymmetric hydroformylation of styrene derivatives, vinyl acetate, and allyl cyanide afforded the corresponding chiral aldehydes with high regio- and enantioselectivities under mild reaction conditions. The modular nature of the ligands allows fine-tuning of the selectivities through judicious modifications of the substituents on the ligand backbone. X-ray structural analysis of the catalyst precursor suggested that the steric hindrance caused by the protruding remote substituents of the ligands into the vicinity of the metal center might be an important factor for the enantio-control of the reaction, whereas the sense of asymmetric induction can be rationalized on the basis of a trigonal-bipyramidal transition state diagram.     

Recent applications of chiral ferrocene ligands in asymmetric catalysis

Despite the impressive progress achieved in asymmetric catalysis during the last decade, an increasing number of new catalysts, ligands, and applications are reported every year to satisfy the need to embrace a wider range of reactions and to improve the efficiency of existing processes. Because of their availability, unique stereochemical aspects, and wide variety of coordination modes and possibilities for the fine-tuning of the steric and electronic properties, ferrocene-based ligands constitute one of the most versatile ligand architectures in the current scenario of asymmetric catalysis. Over the last few years ferrocene catalysts have been successfully applied in an amazing variety of enantioselective processes. This Review documents these recent advances, with special emphasis on the most innovative asymmetric processes and the development of novel, efficient types of ferrocene ligands.     

Copper-catalyzed asymmetric conjugate addition of trialkylaluminium reagents to trisubstituted enones: construction of chiral quaternary centers

Me3Al, Et3Al, and vinylalane species undergo enantioselective conjugate addition to a wide range of 2- or 3-substituted enones (cyclopent-2-enones, cyclohex-2-enones, 3-methyl cyclohept-2-enone) in the presence of catalytic amount of copper salt (copper thiophene carboxylate, [Cu(CH3CN)4]BF4 or [CuOTf]2C6H6) and tropos-phosphoramidite-based ligand. Thus, chiral quaternary centers can be built, with up to 98% ee after rigorous optimization of experimental conditions. It was shown that the main important parameter was the order of the introduction of the reagents. Then, the generated enantioenriched aluminium enolates and the chiral conjugate adducts were functionalized and used for subsequent reactions.     

Modular phosphite-oxazoline/oxazine ligand library for asymmetric pd-catalyzed allylic substitution reactions: scope and limitations-origin of enantioselectivity

A library of phosphite-oxazoline/oxazine ligands L1-L15 a-h has been synthesized and screened in the Pd-catalyzed allylic substitution reactions of several substrate types. These series of ligands can be prepared efficiently from easily accessible hydroxyl amino acid derivatives. Their modular nature enables the substituents/configurations in the oxazoline/oxazine moiety, alkyl backbone chain and in the biaryl phosphite moiety to be easily and systematically varied. By carefully selecting the ligand components, therefore, high regio- and enantioselectivities (ee values up to 99 %) and good activities have been achieved in a broad range of mono- and disubstituted linear hindered and unhindered liner and cyclic substrates. The NMR studies on the Pd-pi-allyl intermediates provide a deeper understanding about the effect of the ligand parameters on the origin of enantioselectivity. It also indicates that the nucleophilic attack takes place predominantly at the allylic terminal carbon atom located trans to the phosphite moiety.     

Synthesis and application of chiral N-heterocyclic carbene-oxazoline ligands: iridium-catalyzed enantioselective hydrogenation

Two libraries of enantiomerically pure imidazolium salts bearing an oxazoline unit were synthesized. Deprotonation of the imidazolium salts and complexation of the resulting oxazoline-carbene ligands to iridium(I) was achieved in one step by mixing the imidazolium salts with NaOtBu and [(eta(4)-cod)IrCl](2) in THF at room temperature. The air-stable complexes were purified by flash chromatography. All complexes were analyzed by two-dimensional (2D) NMR methods and one compound from each family was characterized by X-ray structure analysis. The two libraries of iridium complexes were successfully tested in the asymmetric hydrogenation of unfunctionalized and functionalized olefins. Enantioselectivities of up to 90 % ee were obtained with trans-alpha-methylstilbene. Upon complexation of imidazolium salt 15 p with R(1) = phenyl, C-H bond activation of the phenyl ring gave rise to iridium(III) complex 17, which was fully characterized by NMR spectroscopy and X-ray structure analysis. Complex 17 proved to be catalytically inactive in the hydrogenation.     

Mixtures of chiral and achiral monodentate ligands in asymmetric Rh-catalyzed olefin hydrogenation: reversal of enantioselectivity

The recently described method of combinatorial asymmetric transition metal catalysis based on the use of mixtures of chiral monodentate P-ligands has been extended to include mixtures of chiral and achiral monodentate P-ligands, reversal of enantioselectivity in Rh-catalyzed olefin hydrogenation being possible in appropriate cases.