Palladium-catalyzed asymmetric allylic alkylation of indoles by C–N bond axially chiral phosphine ligands

The palladium-catalyzed asymmetric allylic alkylation of indoles with 1,3-diphenyl-2-propenyl acetate using P/N-type ligands such as N-aryl indole, C–N bond axially chiral aminophosphine (aS)-L4, gave the desired products 1 in good yields and with moderate to high enantioselectivities (up to 90% ee).     

New chiral phosphine–amide ligands in palladium-catalysed asymmetric allylic alkylations

Palladium-catalysed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate 8a with a dimethyl malonate–BSA–LiOAc system has been successfully carried out in the presence of new chiral phosphine–amide, such as 5, in good yields and high enantiomeric excesses of up to 85%.     

Preparation of new chiral pyrrolidinebisphosphines as highly effective ligands for catalytic asymmetric synthesis of R-(−)-pantolactone

New chiral pyrrolidinebisphosphines, MSCPM, PCPM and BCPM, were prepared. Among them, BCPM was found to be the most effective ligand for catalytic asymmetric synthesis of R-(−)-pantolactone.     

Novel carboncarbon bond formation induced by depalladation of organometallic compounds

Two internal alkynes undergo insertion at 20°C into the PdC bond of the cyclopalladated derivative of dimethylaminomethylferrocene to give new organometallic compounds. When the reaction with diphenylacetylene is performed at higher temperatures, depalladation occurs readily to give six- and seven-membered ortho-fused rings through new annulation reactions of phenyl groups, formation of one of these involving also the cleavage of a CN bond.     

N-Aryl indole-derived C–N bond axially chiral phosphine ligands: synthesis and application in palladium-catalyzed asymmetric allylic alkylation

N-Aryl indole-derived C–N bond axially chiral phosphine ligands 2a–c were obtained by DDQ oxidation of N-aryl indoline-derived phosphine oxide followed by silane reduction. Resolution of C–N bond atropisomers was achieved by chiral HPLC. The investigation of the rotation barrier for the C–N bond axial stability of phosphines and the determination of the absolute configuration of 2c are described. Finally, the ability of the chiral ligand 2c was demonstrated in a palladium-catalyzed asymmetric allylic alkylation (up to 99% ee).     

Synthesis of chelating tertiary phosphine oxides via palladium-catalysed C–P bond formation

Bis(diphenylphosphine oxides) and bis(tert-butyl(phenyl)phosphine oxides) of 1,10-phenanthroline, 2,2′-bipyridine and pyridine were synthesised in good yields via the Pd(OAc)₂/dppf mediated cross-coupling reactions between 6,6′-dichloro-2,2′-bipyridine, 2,9-dichloro-1,10-phenanthroline, or 2,6-dichloropyridine and the corresponding secondary phosphine oxides. These compounds represent potential tetradentate chelating ligands for ions of f-block elements.     

Synthesis of novel chiral oxazoline-Schiff base ligands for the catalytic asymmetric chlorination of β-keto esters

A series of novel monooxazoline-Schiff base ligands 1 has been successfully synthesized. The Cu(I)–1a complex showed excellent catalytic activities with up to 83% ee for the asymmetric α-chlorination of β-keto esters.     

Preparation of new chiral pyridine–phosphine ligands and their Pd-catalyzed asymmetric allylic alkylations

Enantiomerically pure 2-(diphenylphosphino)methyl-N-[1-(2-pyridinyl)ethyl]pyrrolidines 1 and 2 have been prepared by the stereospecific substitution of enantiomerically pure 1-(2-pyridinyl)ethyl methanesulfonate 6 with enantiomerically pure 2-(diphenylphosphino)methylpyrrolidine. Asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate 11 with dimethyl malonate sodium salt using the (S,S)-ligand 1 affords the (R)-product 12 with up to 86% e.e. in good yield.     

Efficient carboncarbon bond formation with thermally stable 1,1-dihalo-2,2,2-trifluoroethylzinc reagent

The zinc carbenoids CF₃CX₂ZnX, prepared from CF₃CX₃ and zinc powder in dimethylformamide, were found thermally stable to add to aldehyde carbonyls in excellent yields.     

α-Pinene-type chiral Schiff bases as tridentate ligands in asymmetric addition reactions

A group of tridentate Schiff bases derived from (+)-α-pinene were synthesized. The steric effects in the transition state, the importance of π-π stacking interactions as well as the electronic effects of aryl aldehydes according to Hammett constant values in the enantioselective addition of Et₂Zn to aldehydes with the use of Schiff bases as chiral ligands are described. Also, a variety of aldehydes were cyanated using a catalyst prepared in situ from titanium tetraisopropoxide and chiral Schiff bases. The influence of a conjugated double-bond in the cyanation substrates on enantioselectivity was observed. The chemical structures of the chiral Schiff base-titanium alkoxide complexes are discussed based on their ¹H and ¹³C NMR spectra. 3D models of the Zn₂-complex catalyst and Ti-complex catalyst containing α-pinane-type Schiff bases based on X-ray diffraction experiments are postulated. The models presented were consistent with the reported chirality of the addition product and observed ee.     

Asymmetric radical carboncarbon bond forming reactions in chiral amides and imides under sulfonyl groups stereocontrol

Asymmetric radical carbon–carbon bond formation was achieved in chiral amide and imide systems under sulfonyl group stereocontrol, providing high diastereoselectivity. The stereochemistry of the products was determined and the mechanism of the stereochemical pathways is rationalized by the formation of chelates of Lewis acid metals between oxygens of acetyl, amide, and imide carbonyls, or sulfonyl groups.     

Chiral furanoside phosphite–phosphoroamidites: new ligands for asymmetric catalytic hydroformylation

We have designed a new series of phosphite–phosphoroamidites ligands 1–4 based on a furanoside backbone. These ligands were screened in the Rh-catalyzed asymmetric hydroformylation of styrene, inducing high regioselectivities with 2-phenylpropanal and moderate enantioselectivities (up to 65% e.e.). The results showed that the configuration of the stereogenic carbon atom C(3) at the ligand backbone had remarkable effects on the activity and enantioselectivity. Replacing the tert-butyl substituents with methoxy substituents at the para positions of the biphenyl moieties improved the enantioselectivities. We have also studied the solution structures of HRh(PP)(CO)₂ complexes.     

Catalytic enantioselective carboncarbon bond formation by addition of dialkylzinc reagents to cyclic 1,3-diene monoepoxides

Chiral copper complexes of 2,2′-binaphthyl-based phosphorus amidites are shown to be highly effective catalysts for the conjugate addition of dialkylzinc reagents to vinyloxiranes. The corresponding allylic alcohol reaction products (S_N2′-pathway) were obtained with moderate to high regioselectivity. Both direct- (S_N2-pathway) and conjugate-opening addition (S_N2′-pathway) seem to proceed with complete anti stereoselectivity. The enantioselectivity of these addition reactions according to a kinetic resolution protocol turned out to be high (>90% ee) with 1,3-cyclohexadiene and 1,3-cycloheptadiene monoepoxides.     

Spiro indane-based phosphine–oxazoline ligands for palladium-catalyzed asymmetric arylation of cyclic N-sulfonyl imines

Palladium complexes of indane-based phosphine–oxazoline ligands with a spirocarbon stereogenic center were examined for asymmetric addition of arylboronic acids to cyclic N-sulfonyl imines. Excellent reaction activities (up to 99% yield) and enantioselectivities (up to 99% ee) were obtained with a broad scope of substrate.

     

Design of a new class of chiral quinoline–phosphine ligands. Synthesis and application in asymmetric catalysis

The design and synthesis of a new class of chiral quinoline–phosphine ligands has been achieved. Their efficiency as asymmetric ligands in enantioselective palladium-catalyzed allylic substitution reactions and in the asymmetric copper-catalyzed addition of diethylzinc to enones was also investigated.     

Sterically congested, "roofed" β-iminodisulfides as new chiral ligands for palladium-catalyzed, asymmetric allylic alkylation

The preparation of a new class of "roofed" β-iminodisulfides from sterically congested, conformationally rigid chiral 2-thiazolidinones is described. A functional survey of palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate proved that symmetrical "roofed" β-iminodisulfides are efficient chiral ligands, showing enantioselectivity opposite that associated with chiral "roofed" β-iminothioether ligands.     

A single phosphine ligand allows palladium-catalyzed intermolecular co bond formation with secondary and primary alcohols

Forging a bond: An efficient, general palladium catalyst for C?O bond-forming reactions of secondary and primary alcohols with a range of aryl halides has been developed using the ligand 1. Heteroaryl halides, and for the first time, electron-rich aryl halides can be coupled with secondary alcohols. A diverse set of substrate combinations are possible with just a single ligand, thus obviating the need to survey multiple ligands.     

Readily available chiral phosphine–aminophosphine ligands derived from 1-phenylethylamine for Rh-catalyzed enantioselective hydrogenations

A series of new chiral phosphine–aminophosphine ligands have been prepared via a two- or three-step transformation from commercially available and inexpensive (S)-1-phenylethylamine, and successfully used in the rhodium-catalyzed asymmetric hydrogenation of various enamides, β-dehydroamino acid esters, and dimethyl itaconate. The results show that the ligand structure plays an important influence on both the reactivity and enantioselectivity. Ligand 2d bearing a N–H proton and two F-atoms on the 3,5-positions of the phenyl ring of the aminophosphino moiety was most effective for the hydrogenation of enamides and (Z)-β-aryl-β-(acylamino)acrylates, whereas ligand 1b showed the highest enantioselectivities in the hydrogenation of (Z)-β-alkyl-β-(acylamino)acrylates and dimethyl itaconate.     

Catalytic asymmetric carbon–carbon bond forming reactions catalyzed by tetrahydroisoquinoline (TIQ) N,N′-dioxide ligands

The use of TIQ-N,N′-dioxide ligands in asymmetric C–C bond forming reactions is described. In the Michael addition of cyclohexane-1,3-dione and malonates to β,γ-unsaturated α-ketoesters, excellent yields (up to 93%) and moderate to good enantioselectivities (70–89% ee) were obtained. The catalytic hetero-ene reaction of 2-methoxypropene with phenylglyoxal gave the ene product in excellent yield (95%) with moderate enantioselectivity (77% ee). The catalyst system performed well at temperatures ranging from 0 to 30 °C and relatively low catalyst loading (0.2–5 mol %) with dichloromethane being the preferred solvent for all reactions.