Recent Advances in the Application of Chiral Phosphine Ligands in Pd-Catalysed Asymmetric Allylic Alkylation

Abstract

One of the most powerful approaches for the formation of simple and complex chiral molecules is the metal-catalysed asymmetric allylic alkylation. This reaction has been broadly studied with a great variety of substrates and nucleophiles under different reaction conditions and it has promoted the synthesis of new chiral ligands to be evaluated as asymmetric inductors. Although the mechanism as well as the active species equilibria are known, the performance of the catalytic system depends on the fine tuning of factors such as type of substrate, nucleophile nature, reaction medium, catalytic precursor and type of ligand used. Particularly interesting are chiral phosphines which have proved to be effective asymmetric inductors in several such reactions. The present review covers the application of phosphine-donor ligands in Pd-catalysed asymmetric allylic alkylation in the last decade.

Multifunctional chiral aminophosphines for enantiodivergent catalysis in a palladium‐catalyzed allylic alkylation reaction

“…Classic AAA reactions proceed through a symmetrical Pd-allyl intermediate that present as "M" and "W" isomers in rapid equilibrium ( Figure 3A, left panel). 69,70 The M and W isomers interconvert readily even at temperatures below 0 71,72 ; however, the ratio can be controlled by ligands with bulky substituents, disfavoring the formation of the W isomers that position the terminal phenyl group of the allyl intermediate closer to the bulkier ligand ( Figure 3A, right panel). [73][74][75] In the case of the P,N-ligands investigated here, it is likely that the M isomer may be favored with the phosphorous center being the ligand side with bulkier substituents ( Figure 3B).…”

Synthesis of C2-Symmetric Bisphosphines and Their Application in Enantioselective Transition Metal Catalysis

“…The chiral model formed by Pd-ligand fragment is believed to be related to the P-Pd-P bite angle. [23,[55][56][57] According to all literature data, we tested all bisphosphine ligands 7-12 in the allylic alkylation of rac-1,3-diphenyl-3-acetoxyprop-1ene 13 with different nucleophiles (3 equiv) such as dimethylmalonate (DMM) and acetylacetone (Acac) in the presence of N-Obis(trimethylsilyl) acetamide (BSA) (3 equiv) and 0.1 mol % BSA activator (AcOLi or AcOK) in different solvents (dichlorometane or tetrahydrofurane) ( Table 1).…”

Spiro Indane-Based Phosphine-Oxazolines as Highly Efficient P,N Ligands for Enantioselective Pd-Catalyzed Allylic Alkylation of Indoles and Allylic Etherification

“…As a typical heterocyclic structural subunit, the indole scaffold is highly prevalent in biological compounds, pharmaceuticals, natural products and material science [1,2,3,4,5]. Notably, a variety of biologically active indole derivatives and indole-based drugs are enantiopure.…”