Achiral Phosphine Research Articles

On the gold(I)-catalyzed enantioselective addition of indole to diphenylallene via anion-binding catalysis

Neutral dual hydrogen bond donors (HBDs) are effective catalysts that enhance the electrophilicity of substrates or the Lewis/Brønsted acidity of reagents through an anion-binding mechanism. Despite their success in various enantioselective organocatalytic reactions, their application to transition metal catalysis remains rare. Herein, we report the activation of gold(I) precatalysts by chiral ureas, leading to enantioselective hydroarylation of allenes with indoles. Experimental and computational studies support an anion-binding mechanism for gold(I) precatalyst activation. Noncovalent interactions were identified as the source of enantiodifferentiation, providing insights into the cooperativity between achiral phosphine ligands and chiral ureas.

Switchable supramolecular helices for asymmetric stereodivergent catalysis

Despite recent developments on the design of dynamic catalysts, none of them have been exploited for the in-situ control of multiple stereogenic centers in a single molecular scaffold. We report herein that it is possible to obtain in majority any amongst the four possible stereoisomers of an amino alcohol by means of a switchable asymmetric catalyst built on supramolecular helices. Hydrogen-bonded assemblies between a benzene-1,3,5-tricarboxamide (BTA) achiral phosphine ligand coordinated to copper and a chiral BTA comonomer are engaged in a copper-hydride catalyzed hydrosilylation and hydroamination cascade process. The nature of the product stereoisomer is related to the handedness of the helices and can thus be directed in a predictable way by changing the nature of the major enantiomer of the BTA comonomer present in the assemblies. The strategy allows all stereoisomers to be obtained one-pot with similar selectivities by conducting the cascade reaction in a concomitant manner, i.e. without inverting the handedness of the helices, or sequentially, i.e. by switching the handedness of the supramolecular helices between the hydrosilylation and hydroamination steps. Supramolecular helical catalysts appear as a unique and versatile platform to control the configuration of molecules or polymers embedding several stereogenic centers.

(3+2) Annulation of 4‐Acetoxy Allenoate with Aldimine Enabled by AgF‐Assisted P(III)/P(V) Catalysis

AbstractA phosphine‐catalyzed (3+2) annulation of 4‐acetoxy allenoate and aldimine with the assistance of AgF is described. The success of this reaction hinges on the metathesis between the enolate‐phosphonium zwitterion and AgF, leading to a key intermediate comprising of silver enolate and a fluorophosphorane P(V)‐moiety. The former is able to undergo a Mannich reaction with aldimine, whereas the latter initiates a cascade sequence of AcO‐elimination/aza‐addition, thus furnishing the P(III)/P(V) catalysis. By taking advantage of the silver enolate, a preliminary attempt at an asymmetric variant was conducted with the combination of an achiral phosphine catalyst and a chiral bis(oxazolinyl)pyridine ligand (PyBox), giving moderate enantioselectivity.

(3+2) Annulation of 4-Acetoxy Allenoate with Aldimine Enabled by AgF-Assisted P(III)/P(V) Catalysis.

A phosphine-catalyzed (3+2) annulation of 4-acetoxy allenoate and aldimine with the assistance of AgF is described. The success of this reaction hinges on the metathesis between the enolate-phosphonium zwitterion and AgF, leading to a key intermediate comprising of silver enolate and a fluorophosphorane P(V)-moiety. The former is able to undergo a Mannich reaction with aldimine, whereas the latter initiates a cascade sequence of AcO-elimination/aza-addition, thus furnishing the P(III)/P(V) catalysis. By taking advantage of the silver enolate, a preliminary attempt at an asymmetric variant was conducted with the combination of an achiral phosphine catalyst and a chiral bis(oxazolinyl)pyridine ligand (PyBox), giving moderate enantioselectivity.

Cinchona-Alkaloid-Derived NN Ligands and Achiral Phosphines for Iridium-Catalyzed Asymmetric Hydrogenation of Heteroaromatic and α-Chloroheteroaryl Ketones.

A concise synthesis of cinchona-alkaloid-derived NN ligands bearing alkyl substituents on chiral nitrogen atoms was described. Iridium catalysts containing new chiral NN ligands and achiral phosphines were effective for the asymmetric hydrogenation of heteroaromatic ketones, which afforded corresponding alcohols in up to 99.9% ee. The same protocol was applicable to the asymmetric hydrogenation of α-chloroheteroaryl ketones. Most importantly, the gram-scale asymmetric hydrogenation of 2-acetylthiophene and 2-acetylfuran proceeded smoothly even under 1 MPa of H2.

Chirality induction in platinum-containing polyaryleneethynylenes by exchange from achiral phosphine ligands to P-chiral phosphine ligands

This study deals with chirality induction to the main chain of platinum (Pt)-containing aryleneethynylene polymers by ligand exchange reactions. The optically inactive polymers containing –(–CC–trans-Pt(PPh3)2–CC–)– moieties in the main chain undergo ligand exchange reactions with P-chiral diphosphines, (R,R)-BenzP* and (R,R)-QuinoxP* to give optically active polymers containing –(–CC–cis-Pt(P-chiral diphosphine)–CC–)– moieties. The ligand-exchanged polymers exhibit CD signals based on the conjugated main chain, indicating chirality induction to the main chain by the P-chiral ligands. The QuinoxP*-ligated polymers emit photoluminescence likely based on the transition from the QuinoxP* moieties. Quantum mechanical calculations predict reasonable CD, UV–vis absorption and photoluminescence spectra.

Nickel-catalyzed switchable 1,3-dienylation and enantioselective allenylation of phosphine oxides

The development of general catalytic methods for the regio- and stereoselective construction of phosphoryl derivatives from identical substrates remains a formidable challenge in organic synthesis. Enabled by the newly developed BDPP-type ligands, we disclosed a nickel-catalyzed allenylation of phosphine oxides rationally and predictably, allowing the construction of versatile chiral allenylphosphoryl derivatives with high enantiopurity (up to 94% e.e.). Alternatively, using an achiral phosphine ligand dcypbz under acidic conditions, we achieved a regiochemical switch of the 1,3-dienylation to afford functionalized phosphinoyl 1,3-butadienes (up to 93% yield). The salient features of this method include switchable reactivity, broad substrate scope, readily available feedstock, single-step preparation, and high asymmetric induction.

Influence of Achiral Phosphine Ligands on a Synergistic Organo- and Palladium-Catalyzed Asymmetric Allylic Alkylation.

An unusual diastereodivergent stereoselective allylation reaction is presented. It consists of a palladium-catalyzed allylation reaction of an organocatalytically generated amino isobenzofulvene, where the diastereoselectivity is controlled by the electronic properties of a monodentate, achiral ligand on palladium. One major diastereoisomer is formed using triarylphosphines substituted with neutral or electron-donating substituents of the aryl group, while those with electron-withdrawing substituents favor the other diastereoisomer. The diastereoselectivity correlates with the Taft inductive parameter of substituents on the triarylphosphine ligand on palladium. The synergistic reaction involves both a catalytic secondary amine catalyst for the indene-aldehyde activation and the monodentate phosphine ligands on palladium, affording a highly enantioselective reaction with up to 98 % enantiomeric excess. Based on computational investigations, the role of the monodentate phosphine ligand on the diastereoselectivity is discussed.

Catalytic Asymmetric Addition and Telomerization of Butadiene with Enamine Intermediates

Herein, we report tunable asymmetric addition and telomerization of butadiene by synergistic chiral primary amine/achiral palladium catalysis. A selection of different achiral phosphine ligand in c...

Ruthenium-catalyzed hydrogenation of aromatic ketones using chiral diamine and monodentate achiral phosphine ligands

The Ru-catalyzed asymmetric hydrogenation of ketones with chiral diamine and monodentate achiral phosphine has been developed. A wide range of ketones were hydrogenated to afford the corresponding chiral secondary alcohols in good to excellent enantioselectivities (up to 98.1% ee). In addition, an appropriate mechanism for the asymmetric hydrogenation was proposed and verified by NMR spectroscopy.

A simple and efficient asymmetric hydrogenation of heteroaromatic ketones with iridium catalyst composed of chiral diamines and achiral phosphines

An efficient iridium catalyst composed of a simple and commercially available o-methoxytriphenylphosphine and 9-Amino (9-deoxy) epi-cinchonine was applied to the asymmetric hydrogenation of heteroaromatic ketones. A range of simple heteroaromatic ketones could be hydrogenated with good to excellent enantioselectivities and high activities. In particular, thiophene ketones and furyl ketones furnished 98.6% ee with up to 2.18 × 104(1/h) TOF. This catalytic system can be of practical value.

Highly activity asymmetric hydrogenation of enones catalyzed by iridium complexes with chiral diamines and achiral phosphines

A selective asymmetric hydrogenation of enones has been well established by using an iridium complex composed of cheap phosphine ligands and cinchona alkaloids derivatives as catalyst. A wide range of allylic alcohol products could be obtained in high chemoselectivities (up to 99.6%), enantioselectivities (70.1% ee) and high activities (up to 3.64 × 104(1/h) TOF). This catalytic system opens a new way of selective asymmetric hydrogenation and the method can be of practical value.

An asymmetric Mannich reaction of α-diazocarbonyl compounds and N-sulfonyl cyclic ketimines catalyzed by complexes generated from chiral and achiral phosphines with gold(i).

An unprecedented Lewis acidic gold(i)-complex generated from chiral and achiral phosphines has been developed for the Mannich reaction of α-diazocarbonyl compounds and N-sulfonyl cyclic ketimines. A series of chiral β-amino-α-diazoesters bearing a quaternary stereocenter were obtained in high yields with good enantioselectivities. In addition, the products could be converted to promising bioactive spirosuccinimide. Furthermore, operando IR, NMR and control experiments were carried out to gain insight into the mechanism.

Asymmetric Ir-catalyzed hydrogenation of 1,5-benzodiazepinones using mixtures of ligands

The catalytic hydrogenation of benzodiazepinones using metal complexes with phosphite and phosphoramidite ligands was carried out for the first time. The mixed-ligand catalytic systems containing a chiral phosphoramidite or phosphite in combination with an achiral phosphine were shown to exhibit a higher enantioselectivity compared to catalysts containing homocombinations of chiral ligands.

Palladium-catalysed α-allylation of chiral sulfinimines derived from symmetric cyclic ketones

A diastereoselective mono-allylation reaction at the α-position of symmetric cyclic ketones by using tert-butanesulfinamide as a chiral auxiliary is explored. Excellent yields and high diastereomeric ratios were achieved under palladium(0) catalysis in the presence of a readily available achiral phosphine ligand.

ChemInform Abstract: A Mixed Ligand Approach for the Asymmetric Hydrogenation of 2‐Substituted Pyridinium Salts.

AbstractThe title reaction gives 2‐substituted piperidines with full conversion and good enantioselectivity using iridium as catalyst and a mixed ligand of a chiral monodentate phosphoramidite and an achiral phosphine.

ChemInform Abstract: Palladium‐Catalyzed Diastereoselective α‐Allylation of Chiral Sulfinimines.

The first diastereoselective allylation reaction at the α-position of ketones by using tert-butanesulfinamide as a chiral auxiliary is explored. Excellent yields and high diastereomeric ratios were achieved under palladium catalysis in the presence of a readily available achiral phosphine ligand. The chiral auxiliary was removed in quantitative yield under the optimized conditions without any racemization.

A Mixed Ligand Approach for the Asymmetric Hydrogenation of 2‐Substituted Pyridinium Salts

AbstractHerein we describe a new methodology for the asymmetric hydrogenation (AH) of 2‐substituted pyridinium salts. An iridium catalyst based on a mixture of a chiral monodentate phosphoramidite and an achiral phosphine was shown to hydrogenate N‐benzyl‐2‐arylpyiridinium bromides to the corresponding N‐benzyl‐2‐arylpiperidines with full conversion and good enantioselectivity. The mechanism of the reaction under optimized conditions was investigated via kinetic measurements and isotopic labeling experiments. Our study suggests that the hydrogenation starts with a 1,4‐hydride addition and that the enantiodiscriminating step involves the reduction of an iminium intermediate.magnified image

Palladium‐Catalyzed Diastereoselective α‐Allylation of Chiral Sulfinimines

The first diastereoselective allylation reaction at the α‐position of ketones by using tert‐butanesulfinamide as a chiral auxiliary is explored. Excellent yields and high diastereomeric ratios were achieved under palladium catalysis in the presence of a readily available achiral phosphine ligand. The chiral auxiliary was removed in quantitative yield under the optimized conditions without any racemization.

Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer.

Chiral, dimeric natural products containing complex structures and interesting biological properties have inspired chemists and biologists for decades. A seven step total synthesis of the axially chiral, dimeric tetrahydroxanthone natural product rugulotrosin A is described. The synthesis employs a one-pot Suzuki coupling/dimerization to generate the requisite 2,2'-linked biaryl linkage. Highly selective point-to-axial chirality transfer was achieved using palladium catalysis with achiral phosphine ligands. Single X-ray crystal diffraction data was obtained to confirm both the atropisomeric configuration and absolute stereochemistry of rugulotrosin A. Computational studies are described to rationalize the atropselectivity observed in the key dimerization step. Comparison of the crude fungal extract with synthetic rugulotros in A and its atropisomer verified that nature generates a single atropisomer of the natural product.