Parallel and modular synthesis of P-chirogenic P,O-ligands.

A modular synthesis of P-chirogenic α-alkoxyphosphine ligands has been developed, allowing for the variation of two of the three groups on phosphorus. Oxidation and concomitant desymmetrization of a prochiral alkyl- or aryldimethylphosphine borane afforded α-hydroxyphosphines, which were subsequently deprotonated and alkylated in a parallel fashion. The choice of base and temperature for the alkylation step was found to be crucial for the outcome of the reaction. Selected ligands were subsequently screened in palladium catalyzed allylic substitution, affording product in good to excellent yield but moderate enantioselectivity, indicating that further optimization of the ligand structures is desirable to increase the stereoselectivity.

Modular asymmetric synthesis of P-chirogenic beta-amino phosphine boranes.

A short concise route to beta-aminophosphine boranes is presented via the desymmetrization of prochiral phosphine boranes, forming P-chirogenic aldehydes that are rapidly transformed to the target compounds employing reductive amination under microwave irradiation. This sequence provides a modular route to P-chirogenic P,N ligands, and in addition, the intermediate aldehydes are versatile P-chiral building blocks for ligand design in general. An alternative pathway via the corresponding alpha-carboxyphosphines is also described. The ligands were subsequently evalutated in the asymmetric conjugate addition of diethylzinc to trans-beta-nitrostyrene.