A New Class of Modular P,N-Ligand Library for Asymmetric Pd-Catalyzed Allylic Substitution Reactions: A Study of the Key Pd-π-Allyl Intermediates

• Published in: Chemistry : a European journal Vol. 16; no. 2; pp. 620 - 638
• Main Authors: Mazuela, Javier, Paptchikhine, Alexander, Tolstoy, Päivi, Pàmies, Oscar, Diéguez, Montserrat, Andersson, Pher G.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 11.01.2010; WILEY‐VCH Verlag; Wiley
• Subjects: Allyl Compounds - chemistry; Allylic substitution; Asymmetric catalysis; Backbone; Catalysis; Chemistry; Chemistry, Multidisciplinary; Combinatorial Chemistry Techniques; Derivatives; Kemi; Libraries; Ligand design; Ligands; Modular; Molecular Structure; N,P ligands; NATURAL SCIENCES; NATURVETENSKAP; P ligands; Palladium; Palladium - chemistry; Physical Sciences; Science & Technology; Stereoisomerism; Substitution reactions; Substrates; COORDINATION CHEMISTRY; N,P ligands; PHOSPHORUS-CONTAINING OXAZOLINE; VERSATILE LIGANDS; asymmetric catalysis; PHOSPHORAMIDITE LIGAND; PHOSPHITE-OXAZOLINE LIGANDS; AMINATION; ligand design; palladium; ALKYLATION REACTIONS; ENANTIOSELECTIVE ALLYLATION; allylic substitution; METAL-COMPLEXES; DIPHOSPHITE LIGANDS
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.200901842

A new class of modular P,N‐ligand library has been synthesized and screened in the Pd‐catalyzed allylic substitution reactions of several substrate types. These series of ligands can be prepared efficiently from easily accessible hydroxyl–oxazole/thiazole derivatives. Their modular nature enables the bridge length, the substituents at the heterocyclic ring and in the alkyl backbone chain, the configuration of the ligand backbone, and the substituents/configurations in the biaryl phosphite moiety to be easily and systematically varied. By carefully selecting the ligand components, therefore, high regio‐ and enantioselectivities (ee values up to 96 %) and good activities are achieved in a broad range of mono‐, di‐, and trisubstituted linear hindered and unhindered substrates and cyclic substrates. The NMR spectroscopic and DFT studies on the Pd–π‐allyl intermediates provide a deeper understanding of the effect of ligand parameters on the origin of enantioselectivity. Substrate substitutions: We describe the synthesis and application of a library of phosphite–oxazole/thiazole ligands in the Pd‐catalyzed allylic substitution reactions of several substrate types (see scheme). High regio‐ and enantioselectivities and good activities have been achieved.