First successful application of diphosphite ligands in the asymmetric hydroformylation of dihydrofurans

Good enantioselectivities and excellent regioselectivities are achieved in the Rh-catalyzed asymmetric hydroformylation of 2,5- and 2,3-dihydrofuran using diphosphite ligands; whereby the backbone of the ligand is crucial to suppressing isomerization and obtaining high ee's.     

A hybrid phosphorus ligand for highly enantioselective asymmetric hydroformylation

A new hybrid phosphorus ligand has been prepared starting from chiral NOBIN (2-amino-2'-hydroxy-1,1'-binaphthyl). Excellent enantioselectivities (up to 99% ee) have been achieved in the Rh-catalyzed asymmetric hydroformylations of styrene derivatives and vinyl acetate.     

Origin of stereoinduction by chiral aminophosphane phosphinite ligands in enantioselective catalysis: asymmetric hydroformylation

The origin of stereoinduction by chiral aminophosphane phosphinite (AMPP) ligands in asymmetric hydroformylation was investigated with a theoretical approach. The roles of the stereogenic center at the aminophosphane phosphorus atom (NP*) and of the chirality of the backbone were analyzed by considering three experimentally tested cases: 1) P-stereogenic yielding high ee, 2) P-nonstereogenic yielding low ee, and 3) P-stereogenic yielding low ee. We succeeded in reproducing the experimentally observed trends for the three studied AMPP ligands. Our results indicated that alkene insertion into the rhodium-hydride bond is the selectivity-determining step, and not alkene coordination. Additional calculations on model systems revealed that the different nonbonding weak-type interactions of styrene with the substituents of the NP* stereogenic center in an axial position is responsible for stereodifferentiation. The chirality of the AMPP backbone plays a secondary role. The rationalization of the stereochemical outcome is not straightforward, because two competitive equatorial/axial reaction paths, showing opposite asymmetric induction, must be considered. Construction of stereochemical models and evaluation of stereoinduction for novel ligand systems suggested that two prerequisites are required to improve the performance of AMPP-type ligands in asymmetric hydroformylation: 1) combination of stereorecognition and stereohindrance by substituents at the NP* atom, and 2) more rigid backbones.     

New enantioselective chiral imidazolidine ligands for Pd-catalyzed asymmetric allylic alkylation

Chiral imidazolidine ligands have been synthesized from N,N′-dialkylated cyclohexanediamine derivatives and they were found to act as effective ligands in the palladium-catalyzed asymmetric allylic substitution. The excellent levels of enantiomeric excess up to 98% were obtained in high yield.     

Highly enantioselective hydroformylation of aryl alkenes with diazaphospholane ligands

Asymmetric, rhodium-catalyzed hydroformylation of terminal and internal aryl alkenes with diazaphospholane ligands is reported. Under partially optimized reaction conditions, high enantioselectivity (>90% ee) and regioselectivities (up to 65:1 alpha:beta) are obtained for most substrates. For terminal alkenes, both enantioselectivity and regioselectivity are proportional to the carbon monoxide partial pressure, but independent of hydrogen pressure. Hydroformylation of para-substituted styrene derivatives gives the highest regioselectivity for substrates bearing electron-withdrawing substituents. A Hammett analysis produces a positive linear correlation for regioselectivity.     

Fine-tunable monodentate phosphoroamidite and aminophosphine ligands for Rh-catalyzed asymmetric hydroformylation

A biaryl-based monophosphoroamidite L1–L4a–f and aminophosphine L5–L7a–f ligand library was screened in the Rh-catalyzed asymmetric hydroformylation of several vinylarenes and heterocyclic olefins. Our results indicate that the selectivity is strongly dependent on the ligand parameters and on the substrate type. Enantioselectivities (up to 46%) were moderate in the hydroformylation of several vinylarenes S1–S5 and promising (up to 58%) for the more challenging heterocyclic olefins S6–S9.     

Ferrocene-based bidentate phosphonite ligands for rhodium(I)-catalyzed enantioselective hydroformylation

A new class of chiral modular bidentate phosphonite ligands has been synthesized in good overall yields by using cheap trans-1,2-diaminocyclohexane and ferrocene as starting materials, and applied in the Rh(I)-catalyzed asymmetric hydroformylation of vinyl acetate and styrene to afford the corresponding optically active aldehydes with good regioselectivity (up to 16.9 b/l ratio) and moderate to good enantioselectivity (up to 83% ee). The substituents on the backbone of the ligands are found to exhibit a remarkable effect on both the regio- and enantioselectivity of the catalysis.     

New 1,10-phenanthroline ligands for asymmetric catalysis: enantioselective palladium catalyzed allylic substitution

A number of new chiral C₁-symmetric 1,10-phenathrolines have been prepared and assessed in the enantioselective palladium catalyzed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethylmalonate. Enantioselectivities up to 84% were obtained.     

INDOLPhos: novel hybrid phosphine-phosphoramidite ligands for asymmetric hydrogenation and hydroformylation

Hybrid bidentate phosphine-phosphoramidite ligands are prepared in a modular 2-step sequence and their rhodium complexes display high selectivity in rhodium catalysed hydrogenation and hydroformylation reactions.     

Application of P-stereogenic aminophosphine phosphinite ligands in asymmetric hydroformylation

New chiral aminophosphine phosphinite ligands with a stereogenic center at the aminophosphine phosphorus atom were prepared based on (R,S)-ephedrine as the chiral auxiliary and backbone. Substituents at the chiral aminophosphine as well as at the phosphinite phosphorus atom were varied. These new ligands were applied to the rhodium-catalyzed asymmetric hydroformylation of vinyl arenes. The enantiomeric excess reached up to 77%. 1H and 31P NMR studies of the Rh complexes under syngas pressure reveal that [HRh(CO)2(PP)] complexes with the NP* moiety in an axial position are responsible for enantioselectivity.     

A highly enantioselective catalyst for asymmetric hydroformylation of [2.2.1]-bicyclic olefins

Rh(CO)₂(acac)/TangPhos was found to be a highly enantioselective catalyst for asymmetric hydroformylation of norbornylene under mild conditions. Application of the protocol to the desymmetrization of other [2.2.1]-bicyclic olefins gave moderate to excellent enantioselectivity (55-92% ee).     

Tetraphenol-based diphosphite ligands: synthesis, characterization, and application in the rhodium-catalyzed hydroformylation of octenes

A new class of diphosphites is described, based on a tetraphenol backbone. Ligands TP1-TP5 were synthesized and fully characterized and their application in the hydroformylation of octenes was investigated. Ligand TP3, bearing a 1-naphthoxy substituent on the phosphorus, shows the highest regioselectivity toward the linear aldehyde.     

Novel phosphine-phosphite and phosphine-phosphinite ligands for highly enantioselective asymmetric hydrogenation

Two novel phosphine-phosphite (S,R)-o-BINAPHOS and phosphine-phosphinite (S)-o-BIPNITE ligands based on ortho phenyl substituted (S)-BINOL have been synthesized. Extremely high enantioselectivity (over 99% ee in most cases) has been achieved for the Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid derivatives.     

Coordination studies on supramolecular chiral ligands and application in asymmetric hydroformylation

In this study we introduce a series of monodentate pyridine-based ligands for which the phosphorus coordination mode to rhodium can be controlled by the binding of Zn(II)-templates to the pyridyl group. A series of monodentate phosphoroamidite and phosphite ligands have been prepared and studied under hydroformylation conditions by in situ high-pressure NMR and IR techniques. These studies reveal the exclusive formation of rhodium hydride complexes in which the phosphorus atom of the ligand resides in an axial position, trans to the hydride, but only after addition of Zn(II)-template. In the absence of these templates the usual mono-coordinated rhodium hydrido complexes are formed, with the phosphorus ligated in the equatorial plane, cis to the hydride. The catalytic performance of these complexes is evaluated in asymmetric hydroformylation of unfunctionalised internal alkenes in which the supramolecular change is reflected in higher activity and selectivity.     

Phosphoramidite ligands for the enantioselective iridium-catalyzed asymmetric hydroboration of meso-bicyclic hydrazines

Twenty phosphoramidites or phosphite ligands have been screened in the iridium-catalyzed hydroboration of a meso-bicyclic hydrazine. Enantiomeric excesses of up to 67% could be obtained with moderate to good yields. Although bidentate ligands are believed to be more efficient in transition metal-catalyzed asymmetric hydroboration, this study shows that monodentate ligands have to be investigated for further development of this type of reaction.     

New chiral aminophosphine carboxyphosphinite ligands (AMPCP). Synthesis and application in asymmetric hydrogenation and hydroformylation

The synthesis of the first three aminophosphine-carboxyphosphinite diphosphanes derived directly from α-amino acids is presented. These ligands were applied in the asymmetric hydrogenation of dihydro-2,4-dimethyl-2,3-furandione giving the corresponding pantolactone with up to 42% ee. They were also involved, in association with platinum, in the asymmetric hydroformylation of styrene giving the branched aldehyde with low ee (<5%).     

Highlights of the Rh-catalysed asymmetric hydroformylation of alkenes using phosphorus donor ligands

Rhodium is currently the metal of choice to achieve high enantioselectivities in the hydroformylation of a relatively high variety of alkene substrates. The elucidation of the different steps of the catalytic cycle and the characterisation of the resting state, together with the discovery of several types of ligands that are able to provide high enantioselectivities, have made the rhodium-catalysed hydroformylation a synthetically useful tool. For years, ligands containing phosphite moieties such as diphosphites and phosphine–phosphites were considered the most successful ligands to achieve high enantioselectivies in this process. In fact, the phosphite–phosphine BINAPHOS 43 and its derivatives are even today the most successful ligands in terms of selectivity and scope. Recently however, diphosphine derivatives were shown to provide high levels of selectivity. It can consequently be concluded that the key to achieve high enantioselectivities is not the type the phosphorus function involved in the coordination to the metal, but the particular spatial arrangement of the coordinated ligand.     

C1-symmetric carbohydrate diphosphite ligands for asymmetric Pd-allylic alkylation reactions. Study of the key Pd-allyl intermediates

A series of C(1)-symmetrical 1,3-diphosphite ligands with a furanoside backbone have been applied in the Pd-catalysed asymmetric allylic alkylation of mono- and disubstituted linear substrates. These diphosphite ligands were designed by selective modification of the successful diphosphite ligand L1a with the 6-deoxy-1,2-O-isopropylidene-glucofuranose backbone in order to study the effect of the ligand structure on the catalytic performance. The effect of the solvent, the substrate/metal ratio and ligand/metal ratio were also investigated. The results in the Pd-allylic alkylation of rac-1,3-diphenyl-3-acetoxyprop-1-ene showed that the ligand structure and the reaction conditions had a considerable effect on enantioselectivity and on the kinetics of the reaction producing the kinetic resolution of the substrate. The alkylated product 2 was therefore obtained in 95% ee at 53% conversion and the enantiopure substrate 1 was recovered in 99.9% ee. Furthermore, the effect of the ligand structure and solvent were also observed in the Pd-allylic alkylation of monosubstituted 1-phenyl-3-acetoxyprop-1-ene. The use of a pro-chiral nucleophile was also explored in this reaction leading to excellent regioselectivities but moderate enantioselectivities. Finally, in order to determine how the ligand structure affected the chiral pocket of the Pd-π-allyl intermediates, the complexes [Pd(η(3)-C(15)H(13))(L)]PF(6), where L = L1a, L5-L8a, were synthesised and characterised by NMR spectroscopy.