Synthesis of new chiral monodentate phosphite ligands and their use in catalytic asymmetric hydrogenation

[reaction: see text] New monodentate phosphite ligands have been developed from axially chiral biphenols, which show excellent enantioselectivity in the Rh(I)-catalyzed hydrogenation of dimethyl itaconate. The new chiral ligand system is suitable to create libraries and possesses fine-tuning capability.     

Rhodium-catalyzed asymmetric hydrogenation of olefins with PhthalaPhos, a new class of chiral supramolecular ligands

A library of 19 binol-derived chiral monophosphites that contain a phthalic acid diamide group (PhthalaPhos) has been designed and synthesized in four steps. These new ligands were screened in the rhodium-catalyzed enantioselective hydrogenation of prochiral dehydroamino esters and enamides. Several members of the library showed excellent enantioselectivity with methyl 2-acetamido acrylate (6 ligands gave >97% ee), methyl (Z)-2-acetamido cinnamate (6 ligands gave >94% ee), and N-(1-phenylvinyl)acetamide (9 ligands gave >95% ee), whilst only a few representatives afforded high enantioselectivities for challenging and industrially relevant substrates N-(3,4-dihydronaphthalen-1-yl)-acetamide (96% ee in one case) and methyl (E)-2-(acetamidomethyl)-3-phenylacrylate (99% ee in one case). In most cases, the new ligands were more active and more stereoselective than their structurally related monodentate phosphites (which are devoid of functional groups that are capable of hydrogen-bonding interactions). Control experiments and kinetic studies were carried out that allowed us to demonstrate that hydrogen-bonding interactions involving the diamide group of the PhthalaPhos ligands strongly contribute to their outstanding catalytic properties. Computational studies carried out on a rhodium precatalyst and on a conceivable intermediate in the hydrogenation catalytic cycle shed some light on the role played by hydrogen bonding, which is likely to act in a substrate-orientation effect.     

Application of P,N-sulfinyl imine ligands to iridium-catalyzed asymmetric hydrogenation of olefins

The utility of a novel class of P,N-ligands incorporating a chiral sulfinyl imine moiety is demonstrated in the iridium-catalyzed hydrogenation of both functionalized and unfunctionalized olefins, in which enantioselectivities of up to 94% are achieved. The modularity of the P,N-sulfinyl ligand class is highlighted by the facile preparation of a variety of sterically and electronically different ligands. Interesting structure-activity data for both the phosphine and sulfinamide components is provided by this expanded ligand set.     

Ir(III) complexes of diamine ligands for asymmetric ketone hydrogenation

The use of a combination of IrCl₃ with a series of ligands derived from the C2-symmetric diamine diphenylethanediamine (DPEN) forms a catalyst capable of the asymmetric hydrogenation of ketones in up to 85% ee.     

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.     

Axially chiral phosphine–oxazoline ligands in the silver(I)-catalyzed asymmetric Mannich reaction of fluorinated aldimines with trimethylsiloxyfuran

Axially chiral phosphine–oxazoline ligand L7, prepared from (S)-binol, was found to be a fairly effective chiral ligand in the silver(I)-catalyzed asymmetric Mannich reaction of fluorinated aldimines with trimethylsiloxyfuran to give the corresponding adducts in up to 99% yield, over 20:1 dr and 81% ee.     

Catalytic asymmetric hydrogenation of cyclic anhydrides using ruthenium (II) chiral phosphine complex

Optically active γ- and δ-lactones are obtained by the hydrogenation of five- and six-membered cyclic anhydrides using a Ru(II) complex with chiral phosphine ligand, DIOP, as a catalyst.     

Efficient Ru(II)-catalyzed asymmetric hydrogenation of simple ketones with C2-symmetric planar chiral metallocenyl phosphinooxazoline ligands

C₂-symmetric metallocenyl planar phosphinooxazoline ligands (2 and 3) have been applied in the Ru(II)-catalyzed asymmetric hydrogenation of simple ketones. This type of ligands enjoys the advantages of dual reaction sites as well as larger steric hindrance than their corresponding C₁-symmetric counterparts. As a result, almost quantitative conversions and excellent enantioselectivities were obtained for a series of simple ketones. Under the optimal reaction conditions, up to 99.7% ee was obtained in many cases. It was also confirmed that hydrogen rather than reaction solvent i-PrOH is at work in the hydrogenation procedure.     

New amidophosphine-phosphinites (tLANOPs) as chiral ligands for asymmetric hydrogenation reactions

The new amidophosphine-phosphinite (AMPP) ligands 4a–g (called tLANOP ligands) derived from the chiral hydroxy amide (R)- or (S)-2-hydroxy-3,3,N-trimethylbutyramide have been prepared in 48–83% yield. The crystal structures of the square planar complexes [(SP-4-3)-Pd((R)-dmphea)((S)-4a)]BF₄ and [Rh((R)-4a)(COD)]BF₄ have allowed the absolute configurations of the ligands to be assigned. In both complexes the 7-membered chelating ring of 4a has virtually the same twist-boat conformation. With this class of ligands the rhodium catalyzed asymmetric hydrogenation of 4-oxoisophorone enol acetate gave (S)-phorenol acetate in up to 71% ee. The iridium catalyzed asymmetric hydrogenation of the cyclic iminium salts 16a and 16b afforded after work-up the corresponding cyclic secondary amine (S)-17 in up to 86% ee, when bulky groups were present on the phenyl substituents on the two phosphorus atoms.     

Novel chiral dendritic diphosphine ligands for Rh(I)-catalyzed asymmetric hydrogenation: remarkable structural effects on catalytic properties

[reaction: see text] A series of dendritic ligands with a chiral diphosphine located at the focal point have been synthesized through coupling of pyrphos 2 with Fréchet-type polyether dendron 3. The relationship between the primary structure of the dendrimer and its catalytic properties was established in the Rh-catalyzed asymmetric hydrogenation of alpha-acetamido cinnamic acid 4. A remarkable structural effect on catalytic activity was observed.     

Ru(II)-catalyzed asymmetric cyclopropanation using chiral diphenylphosphino(oxazolinyl)quinoline ligands

Several chiral 8-diphenylphosphino-2-oxazolinylquinolines were synthesized starting from 2-cyano-8-hydroxyquinoline. These N,N,P-chelates were successfully employed in the Ru(II)-catalyzed asymmetric cyclopropanation reactions of diazo-alkenes. The catalytic system exhibited good reactivity and high thermal stability and provided high yields in the intramolecular cyclopropanation, albeit somewhat decreased enantioselectivities compared to known catalytic systems. A dramatic dependency of the enantioselectivity on the substituents of the oxazoline ring was observed.     

Ru(II) complexes of cyclohexane diamine and monodentate phosphorus ligands for asymmetric ketone hydrogenation

The incorporation of a trans-1,2-diaminocyclohexane in place of DPEN provides improvements in enantioselectivity to asymmetric ketone hydrogenation reactions using BrXuPHOS–Ru–diamine catalysts. Substrates containing halogenated aryl rings are particularly compatible with this catalyst, however, α-chlorinated ketones remain resistant to reduction under any conditions.     

Aminosulf(ox)ides as ligands for Iridium(I)-catalyzed asymmetric transfer hydrogenation

A new class of efficient catalysts was developed for the asymmetric transfer hydrogenation of unsymmetrical ketones. A series of chiral N,S-chelates (6-22) was synthesized to serve as ligands in the iridium(I)-catalyzed reduction of ketones. Both formic acid and 2-propanol proved to be suitable as hydrogen donors. Sulfoxidation of an (R)-cysteine-based aminosulfide provided a diastereomeric ligand family containing a chiral sulfur atom. The two chiral centers of these ligands showed a clear effect of chiral cooperativity. In addition, aminosulfides containing two asymmetric carbon atoms in the backbone were synthesized. Both the sulfoxide-containing beta-amino alcohols and the aminosulfides derived from 1,2-disubstituted amino alcohols gave rise to high reaction rates and moderate to excellent enantioselectivities in the reduction of various ketones. The enantioselective outcome of the reaction was favorably affected by selecting the most appropriate hydrogen donor. Enantioselectivities of up to 97% were reached in the reduction of aryl-alkyl ketones.     

Chiral sulfur-containing ligands for iridium(I)-catalyzed asymmetric transfer hydrogenation of aromatic ketones

New efficient catalyst systems, coupled with IrCl(COD)PPh₃ and chiral [SNNS]-type ligands, were employed in the asymmetric transfer hydrogenation of aromatic ketones under mild reaction conditions. The corresponding optically active alcohols were obtained in high yield and good to excellent enantioselectivities (up to 96% ee). The chiral Ir(I) complexes with the ligands of [SNNS]-type were also prepared and characterized, which showed good enantioselectivity and high activity. The reactions can be performed in air and the catalytic experiments are greatly simplified.     

Catechol-based phosphoramidites: a new class of chiral ligands for rhodium-catalyzed asymmetric hydrogenations

[reaction: see text] The synthesis and application of a new class of catechol-based phosphoramidites is described. Ees up to 99% were obtained in the rhodium-catalyzed asymmetric hydrogenation of dehydroamino acids and enamides.     

New class of chiral ligands derived from isosorbide: first application in asymmetric transfer hydrogenation

A new class of β-amino alcohol and diamine ligands was prepared from isosorbide as a chiral renewable resource. The original wedge-shaped structure of isosorbide offers an interesting chiral pocket to promote the metal-catalyzed enantioselective reduction of ketones by transfer hydrogenation.     

新的手性膦配体的合成及其在苯乙烯不对称氢酯基化中的应用

近年来,糖衍生的手性膦配体在不同的催化反应中转化率较高,对映选择性极好,三苯膦氧配体催化效果好,膦硫配体在氢甲酰化反应中也具有一定的催化活性。本文从价廉易得的甘露醇出发合成了两个手性膦配体,作了^1HNMR,^31PNMR,MS和元素分析结构表征。以苯乙     

N-carbamoyl-4-diphenylphosphino-2-diphenylphosphinomethylpyrrolidines(CAPP). Efficient new chiral ligands for asymmetric hydrogenation

A series of N-(N′-substituted carbamoyl)-4-diphenylphosphino-2-diphenylphosphinomethylpyrrolidines (CAPP) was prepared, which exhibited excellent stereoselectivity in the asymmetric hydrogenation of α-acetamidocinnamic acid derivatives and itaconic acid as chiral ligand of the rhodium(I) catalyst.