Substituent Effects of Ligands on Asymmetric Induction in a Prototypical Palladium-Catalyzed Allylation Reaction:  Making Both Enantiomers of a Product in High Optical Purity Using the Same Source of Chirality

Abstract

The substituent effects of the ligands 1 through 8 play a crucial role in determining the enantioselectivity in the palladium-catalyzed asymmetric allylation reaction between 1,3-diphenylprop-2-en-1-yl acetate and the sodium salt of diethyl malonate. For a given chirality of the backbone, electron-deficient and electron-rich ligands generally gave opposite enantiomers, while sterically hindered ligands had the same enantioselectivity as electron-rich ligands. In the case of flexible backbones with ligands of comparable size, a variation of the enantioselectivity with the electronic properties of the ligand is predictable. In ligands with rigid backbones, the steric effects of the substituents appear to play a more decisive role, and caution should be exercised in interpreting the role of electronic effects in such cases. Examples are provided for maximizing both the chemical yield and the enantioselectivity of the allylation reaction through the tuning of the electronic properties of the ligands. In selected cases, the major sense of the asymmetric induction could be reversed solely by changing the electronic properties of the ligands. Bisphosphinites from (R)-(+)-1,1′-bi-2-naphthol (BINOL) can be tuned to produce both (R)-and (S)-products in 80 and 87% ee, respectively. Stoichiometric reaction of complexes 10e* and 10j* with the sodium salt of diethyl malonate gave malonate adducts with enantiomeric excesses in agreement with those obtained under the catalytic conditions. Also reported are the details of an NMR study of the Pd-(η 3 -1,3-diphenylallyl)bis-diphenylphosphinite and the corresponding bis-dicyclohexylphosphinite complexes 10e* and 10j*.

Diphosphorus Ligands Containing a P‐Stereogenic Phosphane and a Chiral Phosphite or Phosphorodiamidite – Evaluation in Pd‐Catalysed Asymmetric Allylic Substitution Reactions

“…In the 31 P{ 1 H} NMR spectra, two sharp pairs of doublets, one for each diastereomer, are indicative of AX spin systems. The 2 J P,P′ values are in the range previously reported for related compounds[14d], and follow the same trends as the 4 J P,P′ values for the free ligands. The 31 P coordination chemical shifts (CCS, defined as δ complex – δ free ligand ) of the phosphane fragments are approximately +30 ppm for the complexes, as expected.…”

High Throughput Screening and Evolution of a Library of Ligands in Asymmetric H-Transfer Reduction of Acetophenone

“…with an aldehyde or a ketone [14]. The synthesis of the following ligands were carried out according to the literature procedures : L14 [15], L37 [16], L42, L45 [17], L43-L44 [18], L46 [19], L59 [20], L61, L84 [21], L65 [22], L76 [23], L77-L78 [24], L87-L88 [25], L91 [26], L92 [27], L93 [28], L94 [29], L95 [30], L100 [31], L101 [32]. Amino alcohols L68-L75 and diamine L79 were commercially available.…”

Sulfur–Sulfur‐Based Ligands Derived from D‐Sugars: Synthesis of PdII Complexes, Application in Palladium‐Catalyzed Allylic Alkylation for the Synthesis of Both Members of Enantiomer Pairs, and Structural Studies

“…Models proposed to explain the enantioselectivity observed in the Pd 0 -catalyzed allylic substitution. [37] www.eurjoc. not the absolute value, of the enantioselectivity.…”