New Highly Effective Phosphite‐Phosphoramidite Ligands for Palladium‐Catalysed Asymmetric Allylic Alkylation Reactions

We have designed a new family of readily available highly‐modular phosphite‐phosphoramidite ligands for asymmetric allylic alkylation reactions. The introduction of a phosphoramidite moiety in the ligand design is highly advantageous in the product outcome. Thus, this ligand series affords high reaction rates and enantioselectivities and, at the same time, shows a broad scope for disubstituted hindered and unhindered substrate types.     

Enantioselective Addition of Diphenylphosphine to 3‐Methyl‐4‐nitro‐5‐alkenylisoxazoles

An enantioselective Michael addition reaction of diphenylphosphine to substituted alkenylisoxazoles has been developed. The reaction proceeds efficiently under mild conditions with high yields (up to 99%) and moderate to excellent enantioselectivities (up to 92%) thus providing a hitherto unavailable direct access to a library of chiral tertiary phosphine‐functionalized isoxazoles.     

Palladium‐Catalyzed Intermolecular Asymmetric Hydroamination with 4,4′‐Disubstituted BINAP and SEGPHOS

A family of tunable precatalysts [Pd((S)‐L*)(NCMe)₂](OTf)₂, where L* is 4,4′‐disubstituted BINAP or SEGPHOS, was synthesized and used for the asymmetric intermolecular hydroamination of aniline to vinylarenes with ee values of up to 85 %, and it is believed that the bulky groups on the 4,4′‐positions and the narrower dihedral angle of the biaryl moiety are responsible for the ee enhancement in these reactions.     

Highly Diastereoselective Synthesis of 2,6‐Di[1‐(2‐alkylaziridin‐1‐yl)alkyl]pyridines,Useful Ligands in Palladium‐Catalyzed Asymmetric Allylic Alkylation

C₂‐Symmetrical, enantiopure 2,6‐di[1‐(1‐aziridinyl)alkyl]pyridines (DIAZAPs) were prepared by a high‐yielding, three‐step sequence starting from 2,6‐pyridinedicarbaldehyde and (S)‐valinol or (S)‐phenylglycinol. The new compounds were tested as ligands in palladium‐catalyzed allylation of carbanions in different solvents. Almost quantitative yield and up to 99 % enantiomeric excess were obtained in the reactions of the enolates derived from malonate, phenyl‐ and benzylmalonate dimethyl esters with 1,3‐diphenyl‐2‐propenyl ethyl carbonate.     

The Role of Secondary Interactions in the Asymmetric Palladium‐Catalysed Hydrosilylation of Olefins with Monophosphane Ligands

A structure‐activity survey of monophosphane ligands used in the asymmetric palladium‐catalysed hydrosilylation reaction of olefins is presented and used to assess the role of secondary interactions on catalyst activity and selectivity.     

Palladium‐Catalyzed Asymmetric 1,4‐Addition of Diarylphosphines to Nitroalkenes for the Synthesis of Chiral P,N‐Compounds

A highly stereoselective asymmetric 1,4‐addition of diarylphosphines to nitroalkenes catalyzed by a bis(phosphine) pincer‐palladium complex has been developed for the synthesis of chiral P,N compounds with good to excellent enantioselectivities (up to 94% ee) under mild conditions.     

Modification of Chiral Monodentate Phosphine Ligands (MOP) for Palladium‐Catalyzed Asymmetric Hydrosilylation of Cyclic 1,3‐Dienes

Several MOP ligands 5 containing aryl groups at 2′ position of (R)‐2‐(diphenylphosphino)‐1,1′‐binaphthyl skeleton were prepared and used for palladium‐catalyzed asymmetric hydrosilylation of cyclic 1,3‐dienes 6 with trichlorosilane. Highest enantioselectivity was observed in the reaction of 1,3‐cyclopentadiene ( 6a ) catalyzed by a palladium complex (0.25 mol %) coordinated with (R)‐2‐(diphenylphosphino)‐2′‐(3,5‐dimethyl‐4‐methoxyphenyl)‐1,1′‐binaphthyl ( 5f ), which gave (S)‐3‐(trichlorosilyl)cyclopentene of 90% ee.     

Palladium‐Catalysed Enantioselective Conjugate Addition of Aromatic Amines to α,β‐Unsaturated N‐Imides. Effect of the Chelating Moiety

Palladium‐catalysed enantioselective additions of aromatic amines to α,β‐unsaturated N‐imides 4 – 6 are reported. The N‐substituent of the Michael acceptor appears to have an unusual modulating effect on the amine activity. The effects of introducing different substituents are examined. Overall, the yield and selectivity of the system appear to be less sensitive to environmental effects than previous systems. The importance of the counteranion is revealed.     

Chiral Phosphinopyrrolyl‐Oxazolines: A New Class of Easily Prepared,Modular P,N‐Ligands

Chiral 2‐(N‐phosphinopyrrol‐2‐2)oxazolines (PyrPHOX ligands) are readily prepared from 2‐cyanopyrrole by condensation with a chiral amino alcohol and subsequent reaction with dialkyl‐ or diaryl‐chlorophosphines. Iridium complexes of these ligands proved to be highly efficient catalysts for the enantioselective hydrogenation of olefins. With unfunctionalized arylalkenes and ethyl cinnamate enantiomeric excesses of 70–99% were obtained.     

Catalytic Asymmetric Allylation of 3‐Aryloxindoles by Merging Palladium Catalysis and Asymmetric H‐Bonding Catalysis

A catalytic asymmetric allylic alkylation reaction of 3‐aryloxindoles was accomplished via a dual catalysis merging palladium catalysis and asymmetric H‐bonding catalysis for the first time. Using this approach, allylated oxindoles bearing chiral all‐carbon quaternary centers were produced in high yields with good enantioselectivities (up to 92 % yield and 96:4 er).

     

Regio‐ and Enantioselective Catalytic Hydrophosphorylation of Vinylarenes

Regioselective and stereoselective hydrophosphorylation of vinylarenes 1 with pinacol H‐phosphonate 2 can be achieved with transition metal catalysts. The use of rhodium catalysts such as the Wilkinson complex leads to the anti‐Markovnikov adducts 3 as the only observable reaction products. In contrast, palladium catalysts give high selectivities for the Markovnikov adducts 4 . In the presence of (R,S)‐BINAPHOS as a chiral ligand, significant enantioselectivities have been obtained for the first time in hydrophosphorylation reactions.     

A New Chiral P,N‐Ligand Derived from 1‐Phenylphospholane‐2‐carboxylic Acid (Phenyl‐P‐proline) for Palladium‐Catalyzed Asymmetric Allylic Substitution Reactions

New types of P,N‐ligands, cis‐ and trans‐ 3 , containing a tetrahydroisoquinoline skeleton as an N‐donor were synthesized from (1R,2S)‐1‐phenylphospholane‐2‐carboxylic acid (phenyl‐P‐proline, 1 ). The cis isomer, cis‐ 3 , was found to act as an excellent ligand in palladium‐catalyzed asymmetric allylic substitution reactions. The reactions of 1,3‐diphenyl‐2‐propenyl acetate ( 5 ) with several nucleophiles in the presence of [Pd(π‐allyl)Cl]₂, cis‐ 3 (Pd : ligand=1 : 2), and a base afforded the desired products in high yields with high enantioselectivity. It was suggested that these ligands did not serve as P,N‐bidentate ligands but as P‐monodentate ligands in these reactions.     

Stereocontrol in Palladium‐Catalyzed Propargylic Substitutions: Kinetic Resolution to give Enantioenriched 1,5‐Enynes and Propargyl Acetates

Kinetic resolution during the catalytic allyl‐propargyl cross‐coupling with chiral starting materials can be accomplished with a chiral palladium catalyst. These reactions offer ready access to enantiomerically enriched enyne products from simple, readily available starting materials.

     

Development of a New Spiro‐BOX Ligand and Its Application in Highly Enantioselective Palladium‐Catalyzed Cyclization of 2‐Iodoanilines with Allenes

In this communication, we report the synthesis of a new chiral spiro‐bisoxazoline ligand, i.e., β‐naphthylmethyl‐substituted spiro‐BOX [(R_a,S,S)‐ L7 ] and have successfully applied it to the palladium‐catalyzed enantioselective cyclization reaction of simple allenes with o‐aminoiodobenzenes, affording highly optically active 3‐alkylideneindolines in good yields with excellent enantiomeric excesses.     

Single‐step synthesis of a radically polymerizable 1,1′‐bi‐2‐naphthol derivative for asymmetric catalysis

A new polymerizable 1,1′‐bi‐2‐naphthol derivative for polymer‐supported catalytic asymmetric synthesis is presented. The synthesis is conducted within a single reaction step, which is a major advantage over other approaches presented in the literature. The ligand‐bearing polymer is prepared through copolymerization with N‐isopropylacrylamide. Preliminary experiments on the utility in catalytic asymmetric alkylation reactions reveal the accessibility and activity of the polymer‐attached catalysts. The stereoselectivity of the reaction is found to be somewhat lower than for reactions performed in the presence of free 1,1′‐bi‐2‐naphthol, and thus requires further optimization. The enantiomeric excess of the reaction products was determined via ¹H NMR spectroscopy after chiral derivatization with (R)‐α‐methylbenzyl isocyanate. © 2015 Society of Chemical Industry     

Practical Synthesis of Chiral N,N′‐Bis(2′‐pyridinecarboxamide)‐1,2‐cyclohexane Ligands

A simple and scalable procedure for the preparation of chiral ligands 1 and 2 from trans‐1,2‐diaminocyclohexane and 2‐picolinic acid is described.     

Synthesis of Polymer‐Supported Fesulphos Ligands and their Application in Asymmetric Catalysis

The synthesis of two Fesulphos‐based chiral ligands and their immobilization on a polystyrene support is described. These supported chiral ligands act as very efficient catalysts in 1,3‐dipolar cycloaddition and allylic substitution reactions providing the products with excellent enantioselectivities (91 to >99 % ee). Filtration of the catalyst from the reaction mixtures allows simple product isolation. The polymer‐supported Cu complex of chiral ligand PS‐ 8 can be recycled without further addition of a copper salt in 1,3‐dipolar cycloaddition reactions.     

Ferrocene‐Based Chiral Phosphine‐Triazines: A New Family of Highly Efficient P,N Ligands for Asymmetric Catalysis

The presence of the additional heterocyclic nitrogen atoms in chiral P,N ligands has an important influence on the asymmetric catalysis, and a clear trend was observed in the present research that the enantioselectivity and reactivity were significantly increased by raising the number of heterocyclic nitrogen atoms in these P,N ligands. Through finely tuning the number of heterocyclic nitrogen atoms, a new family of ferrocene‐based chiral phosphine‐triazine ligands with three heterocyclic nitrogen atoms has been developed and successfully applied in Pd‐catalyzed asymmetric allylic substitution. Up to 99% ee with 99% yield of allylic alkylation products and 94% ee of allylic amination products have been obtained by the use of ligand (R_c,S_p)‐ 1f with a 4,6‐diphenoxy‐1,3,5‐triazine moiety.     

Phosphine‐Catalyzed Asymmetric [4+2] Annulation of Vinyl Ketones with Oxindole‐Derived α,β‐Unsaturated Imines: Enantioselective Syntheses of 2′,3′‐Dihydro‐1′H‐spiro[indoline‐3,4′‐pyridin]‐2‐ones

A novel asymmetric [4+2] annulation of vinyl ketones with oxindole‐derived α,β‐unsaturated imines has been developed in the presence of a multifunctional thiourea‐phosphine catalyst derived from a natural amino acid, providing the first phosphine‐catalyzed enantioselective synthesis of 2′,3′‐dihydro‐1′H‐spiro[indoline‐3,4′‐pyridin]‐2‐ones in good yields with excellent stereoselectivities under mild conditions.