Herein, we report the synthesis of chiral phosphabarrelene-pyridine ligands. Their synthesis benefit from modified reaction conditions to overcome the low yields normally associated with the [4+2] cycloaddition reaction of phosphinines with hexafluoro-2-butyne, which is a key to install the P-stereocenter in the phosphabarrelene. Their potential as chelating ligands in asymmetric catalysis was assessed in the Rh- and Ir-catalyzed hydrogenation of cyclic beta-enamides and beta-dehydroamino acid derivatives. The catalytic system containing a tert-butyl substituent at the ortho position of the phosphabarrelene moiety successfully hydrogenates a range of cyclic beta-enamides (ee's between 92% to 94%) and beta-dehydroamino acid derivatives (ee's between 93% to 95%). Moreover, the reactions can be carried out in the environmentally friendly 1,2-propylene carbonate as solvent with no loss of enantioselectivity. Mechanistic studies with the Rh/P,N catalytic systems agree with the Landis-Halpern mechanism and explain the influence of the substituent at the phosphabarrelene on enantioselectivity. Finally, the hydrogenation reactions can be carried out at large scale maintaining high enantioselectivities. +image

Since its early stages, ligands incorporating P-stereogenic phosphine/aminophosphine donor groups have shown significant potential in metal-catalyzed asymmetric hydrogenation. Despite the initial promise, their synthesis presented challenges that led to a period of reduced attention from the scientific community. However, recent advancements in the development of more straightforward methodologies for introducing chirality to the phosphine moiety have given rise to new P-stereogenic phosphine/aminophosphine-containing ligands for this process. This chapter summarizes the progress made in this field from the end of 2010 to the present.

The front cover picture is an artistic rendering illustrating the inside of the pressure reactor during an Ir-catalyzed asymmetric hydrogenation of benzofused exocyclic olefins. The schematic orange ball represents the new simple Ir/phosphine-triazole catalytic system which, surpassing previous limitations, hydrogenate in high enantioselectivities (ee's up to 99%) a wide range of exocyclic olefins bearing benzofused five- and six-membered ring pattern. Details can be found in the Research Article by Montserrat Diéguez and co-workers (M. Biosca, P. de la Cruz-Sánchez, D. Tarr, P. Llanes, E. A. Karlsson, J. Margalef, O. Pàmies, M. À. Pericàs, M. Diéguez, Adv. Synth. Catal. 2023, 365, 167–177; DOI: 10.1002/adsc.202200870).

Pd-catalyzed asymmetric allylic substitution (AAS) is a highly effective method for producing chiral molecules with alkene-substituted frameworks which can be further derivatized. However, its stereochemical outcome is affected by the steric requirements of the substrate and only a narrow set of nucleophiles yield excellent enantioselectivities. In this regard, phosphite-oxazolines have emerged as strong candidates to be privileged ligands for this process, providing results that surpass most of the previously published studies. They have provided high enantiocontrol when used in the Pd-AAS of several hindered and unhindered substrates, using a wide range of C-, O-, and N-nucleophiles. In this concept, we review and discuss the current progress made in the design of tailor-made phosphite-oxazoline ligand libraries for the Pd-AAS of a broad range of substrates and nucleophiles and its application in the construction of chiral complex molecules.

The Front Cover illustrates the designed biaryl phosphite-oxazoline ligand libraries by our group for the asymmetric Pd-catalyzed allylic substitution through the years, highlighting the best family of ligands discovered, along with a diverse array of products that can be obtained through this method. Some of these products can be further modified to create chiral bi- and tricyclic complex molecules, adding to the versatility of this approach. More information can be found in the Concept by M. Biosca et al.

Herein, we report a chiral phosphine-triazole ligand for the Ir-catalyzed asymmetric hydrogenation of exocyclic benzofused alkenes. Overcoming previous limitations, the catalytic system is able to successfully hydrogenate exocyclic olefins bearing a benzofused five- and six-membered ring motif (ee's between 92 to 99%). The catalyst tolerates well the presence of several substituents and substitution patterns at both aromatic rings. The absence of a competing isomerization process together with the perfect fit of the olefins in the catalyst chiral pocket are key to surpass the previous limitations in the hydrogenation of both 5- and 6-membered ring benzofused exocyclic olefins.