A Remarkable Improvement of Catalytic Performance by Electronic Substituent Effects of Chiral P-N Hybrid Ligands in Palladium-Mediated Asymmetric Allylations

Abstract

A marked advancement of reactivity and enantioselectivity in palladium-catalyzed asymmetric allylations was achieved by variations of electronic substituent effects in a new series of chiral P-N hybrid ligands 1. The first evident observation demonstrates that the introduction of electron-donating groups is effective to improve the catalytic performance in the allylic transformation.Palladium-mediated allylic substitutions have been widely employed as efficient and convenient tools for carboncarbon and carbon-heteroatom bond formation in the field of organic synthesis. 1 High levels of enantiocontrol and reactivity toward various types of allylic transformation and substrates has been one of major goals for which chiral ligands have been developed extensively. 2 Substituents on the ligands often play key roles electronically in various types of transition metal-catalyzed asymmetric reactions, 3 however there are only a few attentions regarding electronic substituent effects of ligands in terms of both enantioselectivity and reactivity on palladium-catalyzed asymmetric allylations. 4 We envisaged that the ligand system having a variety of substituent effects could realize practical levels of catalytic performance regarding various types of reactions and substrates. Herein, we wish to report a drastic improvement of enantioselectivity and catalytic activity by electronic substituent effects on a new series of chiral P-N hybrid ligands 1 in palladium-catalyzed asymmetric allylations.Variations on mixed-donor bidentate ligands were planned under considerations based on Hammett's rule. As mentioned in our preceding paper, 2g the strategy for preparing VALAP 5,6 was applicable to produce a variety of chiral ligands (Scheme 1). Thus chiral P-N hybrid ligands 1 7 consisting of imino groups with various phenyl substituents and the diphenylphosphino group were easily accessible by simply mixing (2S)-2-amino-1-(diphenylphosphinyl)-3-methylbutane 3 2g and the corresponding aldehydes.The catalytic performance of palladium-1 complexes was examined in asymmetric allylic substitutions of 4 by a soft anionic nucleophile derived from dimethyl malonate (reaction type 1) and methyl trimethylsilyl dimethylketene acetal (type 2) 2e as depicted in Scheme 2. Scheme 2

Iminophosphites as new chiral P,N-bidentate ligands

“…1 In the last years, such P,N-bidentate compounds were widely used in asymmetric metal complex catalysis and coordination chemistry. [2][3][4][5] Although they vary in molecular structure, all iminophosphines possess identical diphenylphosphine phosphorus centres. On the other hand, increasing the P-centre π-acidity of the P,N-bidentate ligand is well known to favour high chemical and optical yields in a number of catalytic reactions.…”

Origins of Enantioselectivity with Nitrogen−Sulfur Chelate Ligands in Palladium-Catalyzed Allylic Substitution

“…The development of effective chiral ligands for this process has been arduous, as the stereochemical information inherent to the chiral ligand has to be transmitted across the plane of the allyl fragment to the bond-forming/-breaking event that is responsible for enantiodiscrimination. Homobidentate C 2 -symmetric ligands have been extensively investigated and transition-state models proposed. − More recently, heterobidentate nitrogen−phosphorus chiral ligands have been reported which capitalize upon the difference in electronic character of the two donor atoms to exert a stereoelectronic bias upon intermediate π-allyl complexes . Stereoelectronically, the palladium−allyl terminus bond opposite the more powerful acceptor atom (phosphorus) will be longer and hence more susceptible to cleavage as a result of nucleophilic attack .…”

Chiral P,N-bidentate ligands in coordination chemistry and organic catalysis involving rhodium and palladium

“…Recently, a new series of phosphorus-substituted imines 123a ± f, containing substituents of different nature in the arylmethylidene fragment, have been prepared. 154 In the alkylation of dimethyl malonate with 3-pivaloyloxy-1,3-diphenylprop-1-ene {catalysed by [Pd(All)Cl] 2 . 4L}, the catalytic activity was found to be directly correlated with the enantioselectivity, on the one hand, and the electron-donating capacity of the substituent X on the other hand.…”

“…4L}, the catalytic activity was found to be directly correlated with the enantioselectivity, on the one hand, and the electron-donating capacity of the substituent X on the other hand. In the author's opinion, 154 this is due to the increase in the stability of the Pd(II) cationic complexes on passing from the ligand 123a to 123f.…”