β-Amino Alcohol Derived β-Hydroxy- and β-(o-Diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides: An Ester−Amide Ligand Structural Model for the Palladium-Catalyzed Allylic Alkylation Reaction

Abstract

A commercially available collection of beta-amino alcohols have been converted to their corresponding beta-hydroxy- and beta-(o-diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides 11a-f and 12a-f and have been employed in the Tsuji-Trost asymmetric alkylation reaction with 1,3-diphenylpropenyl acetate. With the exception of ligands 11b and 11f, the beta-hydroxybenzoyloxy(o-diphenylphosphino)benzamide ligands 11a-f primarily afforded the (R)-enantiomer of the product. In contrast, the bis(phosphine) ligands 12a-f consistently afforded the (S)-enantiomer. The best ligand (12c) was derived from cis-(1R,2S)-2-amino-1,2-diphenyl-1-ethanol, and when applied in the asymmetric allylic alkylation reaction, it yielded the product in an enantiomeric ratio of 97.8.22 favoring the (S)-enantiomer. A computational study was conducted on the conformation that this ligand might adopt in the palladium-catalyzed alkylation reaction as compared to that of the Trost ligand 1a.

Evaluation of phosphinoamidoester‐derived Pd catalysts in the asymmetric allylic alkylation reaction: Theoretical studies and mechanistic insights

“…The exo ‐conformation that is exhibited by this complex is probably a consequence of π‐π stacking between a phosphine phenyl ring and the allyl phenyl underneath, this has previously been suggested by Pregosin and coworkers in another phosphine‐based catalytic system 26. By applying the model presented by Hitchcock and coworkers12 (vide infra) to explain the trajectory of attack of the malonate that favors C3 as the preferred site of attack, we arrive at the correct enantiofacial selectivity that gives the ( R )‐enantiomer (Fig. 4a).…”

“…1) that furnished slightly greater enantioselectivities (up to 75% ee ). The mechanism of attack of the nucleophile on the π‐allyl Pd complexes formed with their norephedrine ligands, which was discussed in depth in a subsequent article by Mahadik et al,12 was also studied in our article, using a semiempirical computational study to support our postulate.…”

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

“…121,122 The performance of ligand L31 was rationalized by the Lloyd-Jones/Norrby model in which the nucleophilic attack is assisted through a hydrogen bond with the amido group of the ligand (see section 2.4). 122 As a further modification, β-(o-diphenylphosphino)benzoyloxy (odiphenylphosphino)benzamide (S,S)-L33 was reported, which was used in the allylic sulfonylation of rac-1,3diphenylallyl acetate with sodium p-toluenesulfinate (Scheme 39) and the allylic alkylation of the same substrate with dimethyl malonate (ee values up to 84%). 123 On the basis of a similar design, Xu and co-workers developed a trans-1,2-diaminocycloxane-derived diphosphine ligand (Fei-Phos ligand L32), which gave high enantioselectivities in the allylic alkylation of rac-1,3-diphenylallyl acetate with several malonates (ee values up to 94%; Scheme 38).…”

“…As a result the tert -leucinol-derived diphosphine L31 provided excellent ee values (up to 99%) in the allylic alkylation of rac -1,3-diphenylallyl acetate (Scheme ). , The performance of ligand L31 was rationalized by the Lloyd-Jones/Norrby model in which the nucleophilic attack is assisted through a hydrogen bond with the amido group of the ligand (see section ). As a further modification, β-( o -diphenylphosphino)­benzoyloxy ( o -diphenylphosphino)­benzamide ( S , S )- L33 was reported, which was used in the allylic sulfonylation of rac -1,3-diphenylallyl acetate with sodium p -toluenesulfinate (Scheme ) and the allylic alkylation of the same substrate with dimethyl malonate ( ee values up to 84%) …”

“…With the aim of adapting the Trost ligand to reactions with sterically demanding substrates, Hitchcock and co-workers replaced one of the amido groups by an ester group (ligand ( S )- L31 , Scheme ). , As a result, the tert -leucinol-derived diphosphine ( S )- L31 provided excellent ee values (up to 99%) in the allylic alkylation of dimethyl and diethyl malonate with 1,3-diphenylallyl acetate. Mechanistic studies confirmed that nucleophilic attack is assisted by hydrogen bonding with the amido group.…”