P‑Chirogenic Phosphines Supported by Calix[4]arene: New Insight into Palladium-Catalyzed Asymmetric Allylic Substitution

Abstract

The first P-chirogenic mono- and diphosphine ligands supported on the upper rim of a calix[4]­arene moiety were synthesized using the ephedrine methodology. The lithiated calix[4]­arene mono- and dianions both react with the oxazaphospholidine–borane, prepared from ephedrine, to afford regio- and stereoselectively the corresponding calix[4]­arenyl aminophosphine–boranes, by cleavage of the heterocyclic ring at the P–O bond position. Subsequent reactions with HCl and then organolithium reagent and finally decomplexation with DABCO lead to the corresponding calix[4]­arenyl mono- or diphosphines. Both enantiomers of the calix[4]­arenyl phosphines were obtained either by using (+)- or (−)-ephedrine or by changing the addition order of the organolithium reagents during the synthesis. The enantiomeric excesses of the phosphines were determined either by HPLC on a chiral column of their borane complexes or by ³¹P NMR in the presence of a chiral palladium complex. The absolute configurations of the mono- and diphosphinocalix[4]­arenes were assigned by X-ray analysis of their crystalline borane complexes. The P-chirogenic calix[4]­arenyl phosphines were tested for asymmetric palladium-catalyzed allylic substitution of (<i>E</i>)-1,3-diphenylprop-2-en-1-yl acetate, by dimethyl malonate or benzylamine. When the bis-methylphenylphosphino calix[4]­arene was used, the allylic products were obtained with 82% and 79% ee, respectively. In both cases, the use of a diphosphine affords better results than using 2 equivalents of monophosphine. Despite the <i>C</i>₂ symmetry of the P-chirogenic diphosphine calix[4]­arene ligand, computer modeling of the corresponding Pd­(allyl) complex shows a clear dissymmetry of the LUMO, which is in good agreement with a complexed η¹-allyl moiety and with the regio- and enantioselectivity of the Pd-catalyzed allylations