Asymmetric Addition Of Arylboronic Acids Research Articles

Pd(II)/N,N′-Disulfonyl bisimidazoline-catalyzed asymmetric arylation of isoquinoline-1,3,4-trione-derived ketimines

A palladium/chiral N,N′-disulfonyl bisimidazoline (Bim)-catalyzed asymmetric addition of arylboronic acids to isoquinoline-1,3,4-trione-derived ketimines is reported, leading to the generation of a series of functionalized isoquinoline-1,3(2H,4H)-diones bearing one quaternary carbon-amino functionality in good to excellent yields with ≥95% ee in most cases. The reaction has remarkable compatibility with both substrate scopes, providing a highly enantioselective entry to chiral heterocyclic α-tertiary amines.

Confronting the Challenge of Asymmetric Carbonyl Addition to Sterically Bulky Isatins: Upgrading Dirhodium(II)/Biphosphine Catalytic System

Catalytic asymmetric addition of arylboronic acids to ketones is a powerful transformation for directly delivering chiral tertiary alcohols. However, there is no successful example of enantioselective addition to steric bulky isatins, which contain bulky substituent at the 4-position. To confront this challenge, in this work a dirhodium/(BTFM-Garphos) system was developed that showed extremely high activity and stereoselectivity, and the reactions were usually finished within a few minutes.

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The cover picture shows that the enantioselective construction of 6‐4 carbocyclic scaffolds with ring‐junction all‐carbon stereocenters has been achieved through Pd(II)/chiral N,N’‐disulfonyl bisimidazoline (Bim) ligand‐catalyzed asymmetric reaction of yne‐allenones and arylboronic acids. In this reaction, realization of 6‐6‐4 carbocyclic skeletons with high chemo‐, regio‐ and enantio‐selectivities is a one‐step process from benzene‐linked yne‐allenones while synthesizing 6‐4 skeleton is a two‐step process, which begins with intramolecular [2 + 2] reaction of alkyl‐tethered yne‐allenones, followed by Pd catalyzed asymmetric addition of arylboronic acids to cyclic enones generated in the first step. DFT calculations have been applied to understand these reaction processes. More details are discussed in the article by Jiang et al. on page 1767—1776.image

Ru-Catalyzed Asymmetric Addition of Arylboronic Acids to Aliphatic Aldehydes via P-Chiral Monophosphorous Ligands.

Chiral alcohols are among the most widely applied in fine chemicals, pharmaceuticals and agrochemicals. Herein, the Ru-monophosphine catalyst formed in situ was found to promote an enantioselective addition of aliphatic aldehydes with arylboronic acids, delivering the chiral alcohols in excellent yields and enantioselectivities and exhibiting a broad scope of aliphatic aldehydes and arylboronic acids. The enantioselectivities are highly dependent on the monophosphorous ligands. The utility of this asymmetric synthetic method was showcased by a large-scale transformation.

Catalytic Enantioselective Construction of 6‐4 Ring‐Junction All‐Carbon Stereocenters and Mechanistic Insights

Comprehensive SummaryDeveloping reactions for the synthesis of 6‐6‐4 and 6‐4 carbocyclic scaffolds with a chiral quaternary center at the bridgehead position is highly desired, considering the existence of such skeletons in natural products with biological activities and the potential of using these molecules for downstream studies in chemical biology and medicinal chemistry. Report here is accessing these target skeletons with high chemo‐, regio‐ and enantio‐selectivities through Pd(II)/chiral N,N’‐disulfonyl bisimidazoline (Bim) ligand‐catalyzed asymmetric reaction of yne‐allenones and arylboronic acids. Realization of 6‐6‐4 skeleton with a ring‐junction all‐carbon stereocenter is a one‐step process while synthesizing 6‐4 skeleton is a two‐step process, which begins with intramolecular [2 + 2] reaction of allenes with alkynes, followed by Pd‐catalyzed asymmetric addition of arylboronic acids to cyclic enones generated in the first step. Noteworthy is that chiral Bim ligand as a C2‐symmetric N,N’‐bidentateanionic ligand, designed by us, in coordinating with Pd catalyst was first applied to catalyze asymmetric 1,4‐conjugate addition reaction with the high catalytic performance (the reaction can be carried out in air). DFT calculations have been applied to understand how these reactions take place, the origins of enantioselectivity, and relative reactivities of different substrates.

Palladium Catalyzed Enantioselective Hayashi-Miyaura Reaction for Pharmaceutically Important 4-Aryl-3,4-dihydrocoumarins.

The first palladium-catalyzed asymmetric addition of arylboronic acids to coumarins was successfully established, providing a straightforward asymmetric approach to achieving pharmaceutically important 4-aryl-3,4-dihydrocoumarins. This methodology features easily accessible and bench-stable ligands, a wide substrate scope, mild conditions, and accommodation of electron-withdrawing arylboronic acids.

Pd‐Catalyzed Asymmetric Addition of Arylboronic Acids to Pyrazolinone Ketimines

AbstractAn asymmetric addition of arylboronic acids to pyrazolinone ketimines is reported using palladium/chiral N,N′‐disulfonyl bisimidazoline (Bim) catalytic system, producing 25 examples of enantioenriched 4‐amino‐5‐pyrazolones bearing one quaternary carbon stereocenter with 60–91% yields and 81–98% ee. The reaction demonstrates remarkable compatibility regarding pyrazolinone ketimines and arylboronic acids, rendering an enantioselective access to chiral aza‐heterocycles bearing α‐tertiary amines.magnified image

Pd(II)/(S)-t-BuPyOx-catalyzed asymmetric addition of arylboronic acids to N-sulfonyl-arylaldimines

The asymmetric version of Pd(II)/bipyridine-catalyzed nucleophilic addition of arylboronic acids to N-sulfonyl arylaldimines was developed, and excellent asymmetric induction was achieved by the use of chiral pyridinooxazoline ligand (S)-t-BuPyOx. Moisture and oxygen-insensitive catalysis was realized under mild conditions, and 9 out of 16 examples gave 92–99% ee.

Rhodium-Catalyzed Asymmetric Addition of Arylboronic Acids to Glyoxylates: Access to Optically Active Substituted Mandelic Acid Esters

A rhodium-catalyzed enantioselective addition of glyoxylates to arylboronic acids promoted by a simple chiral sulfinamide-based olefin ligand under mild reaction conditions is described. The reaction provides access to a variety of optically active substituted mandelic acid esters in good yields with up to 83% ee. The catalytic system is also applicable to pyruvate addition. The synthetic utility of this method is highlighted by a formal synthesis of the antiplatelet drug clopidogrel.

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.

Rhodium-catalyzed asymmetric addition of arylboronic acids to 2H-chromenes leading to 3-arylchromane derivatives.

Asymmetric addition of arylboronic acids to 2H-chromenes proceeded in the presence of a hydroxorhodium/chiral diene catalyst to give 3-arylchromanes in high yields with high enantioselectivity. The reaction involves 1,4-Rh shift before protonation to release the addition product and to regenerate the hydroxorhodium species.

N-Sulfonyl Bisimidazoline Ligands and Their Applications in Pd(II)-Catalyzed Asymmetric Addition toward α-Tertiary Amines.

A new class of chiral N-sulfonyl bisimidazoline (Bim) ligands have been designed, prepared, and applied in Pd(II)-catalyzed asymmetric addition of arylboronic acids to isatin-derived N-Boc ketimines. The combination of Pd(OCOCF3)2 and N-tosyl Bim ligand shows high catalytic activity and excellent asymmetric induction, enabling asymmetric addition to offer α-tertiary amines with generally good to high yields and excellent enantioselectivity (up to 96% yield, 96% ee). This asymmetric Pd(II) catalysis can tolerate air conditions, providing a practical and operationally simple protocol toward the construction of an enantioenriched α-tertiary stereocenter.

Rh-Catalyzed Asymmetric Addition of Aryl-boronic Acids to α,β-Unsaturated Ketimines

Key words rhodium catalysis - site-selectivity - boronic acids - ketimines - addition

Ligand-Controlled Rhodium-Catalyzed Site-Selective Asymmetric Addition of Arylboronic Acids to α,β-Unsaturated Cyclic N-Sulfonyl Ketimines.

A site-selective rhodium-catalyzed asymmetric 1,4-/1,2-addition of arylboronic acids to challenging α,β-unsaturated cyclic ketimines was realized through a ligand-controlled strategy. By employing different chiral olefin ligands, a ligand-controlled switch in the reaction regioselectivity was attained for the first time. The reactions allow the synthesis of highly valuable α,α-disubstituted chiral allylic amines and enantioenriched 1,4-adducts. Further product transformation provided easy access to various quaternary carbon-containing chiral amines and amino acid derivatives bearing multifunctional groups.

Modified Amino Acid‐Derived Phosphine‐Imine Ligands for Palladium‐Catalyzed Asymmetric Arylation of Cyclic N‐Sulfonyl Imines

AbstractA series of chiral phosphine‐imine ligands were synthesized starting with α‐amino acids and examined for palladium‐catalyzed asymmetric addition of arylboronic acids to cyclic N‐sulfonyl imines. High catalytic activities (up to 99% yield) and high enantioselectivities (up to 98% ee) were achieved for cyclic N‐sulfonyl aldimines and ketimines with five and six‐membered ring structures.magnified image

Ni(ii)-catalyzed asymmetric addition of arylboronic acids to cyclic imines.

A Ni(ii)-catalyzed asymmetric addition of arylboronic acids to cyclic aldimines and ketimines is reported. Our tropos phosphine-oxazoline biphenyl ligand is crucial for the high catalytic activity, which coordinates to Ni(ii) to form a complex with a single axial configuration. The desired chiral amine products could be prepared with excellent yields (up to 99%) and enantioselectivities (up to 99.8%) under mild reaction conditions.

ChemInform Abstract: Pd(II)‐Catalyzed Asymmetric Addition of Arylboronic Acids to Isatin‐Derived Ketimines.

AbstractThe method tolerates functionalized isatin‐derived ketimines as well as various aryl and hetaryl boronic acids, and provides 2‐oxindoles with a chiral α‐tertiary amino group in often very high yields and with very high enantiomeric purity.

Pd(II)-Catalyzed Asymmetric Addition of Arylboronic Acids to Isatin-Derived Ketimines.

A Pd(II)/Pyrox-catalyzed enantioselecitve addition of arylboronic acids to 3-ketimino oxindoles was developed, providing chiral 3-amino-2-oxindoles with a quaternary stereocenter in high yields and with good enantioselectivities. A variety of functionalized 3-ketimino oxindoles can be used, and the method tolerates some variation in arylboronic acid scope. This asymmetric arylation provides an alternative efficient catalytic method for the preparation of chiral 3-aryl-3-amino-2-oxindoles, which also represents the first example of a Pd(II)-catalyzed addition of arylborons to exocyclic ketimines.

ChemInform Abstract: Synthesis of a Class of Chiral‐Bridged Phosphoramidite Ligands and Their Applications in the First Iridium‐Catalyzed Asymmetric Addition of Arylboronic Acids to Isatins.

A series of novel chiral phosphoramidite ligands based on chiral-bridged biphenyl backbones have been prepared conveniently and characterized. The ligands complexed with [IrCodCl]2 provided the first iridium catalyst system for the asymmetric addition of arylboronic acids to N-protected isatins with high efficiency. When performed in THF/H2O at 80 °C with 2 equiv of the arylboronic acids, the transformations acquired good to excellent results (up to 98% yield and 95% ee).

ChemInform Abstract: Chiral Metal Nanoparticle Systems as Heterogeneous Catalysts Beyond Homogeneous Metal Complex Catalysts for Asymmetric Addition of Arylboronic Acids to α,β‐Unsaturated Carbonyl Compounds.

AbstractA secondary amide‐substituted, chiral diene‐modified Rh/Ag nanoparticles system is developed as novel heterogeneous system and employed for asymmetric C—C bond‐forming reactions.