Synthesis of P‐Stereogenic Phosphoramidite and Phosphorodiamidite Ligands and Their Application in Asymmetric Catalysis

Abstract

A series of P‐stereogenic monodentate phosphoramidite (PNO2) and phosphorodiamidite (PN2O) ligands based on chiral Betti bases has been prepared by modular synthetic procedures. The chirality at the phosphorus can be controlled to a large extent by the synthetic route, leading to stereoselective access to single P‐epimers. The absolute configuration of the P‐atom was assigned by X‐ray diffraction analysis. The new ligands were evaluated in asymmetric catalysis and the influence of the exocyclic amine or alcohol moiety as well as the interplay between the P‐chirality and the stereocenters in the backbone were investigated. Enantioselectivities of up to 85 and 83 % ee were obtained in the Rh‐catalyzed hydrogenation of dimethyl itaconate and in the Pd‐catalyzed allylic amination of (rac)‐(E)‐1,3‐diphenylallyl acetate with benzylamine, respectively. In the Ni‐catalyzed hydrovinylation of styrene, ee values of up to 68 %, excellent chemoselectivities, and high activities (TOFav up to 3000 h–1) were achieved.

Bidentate Phosphine–Phosphoramidite Ligands of the BettiPhos Family for Rh‐Catalyzed Asymmetric Hydrogenation

“…The configuration of the phosphoramidite P atom was assigned by comparison of the characteristic chemical shifts in the 1 H, 13 C, and 31 P NMR spectra and the coupling constants J H,P and J C,P to the related monodentate phosphoramidite ligands, where the configuration at the phosphorus atom was conclusively determined by X‐ray crystal structure analysis …”

“…The configuration of the phosphoramidite P atom was assigned by comparison of the characteristic chemical shifts in the 1 H, 13 C, and 31 P NMR spectra and the coupling constants J H,P and J C,P to the related monodentate phosphoramidite ligands, where the configuration at the phosphorus atom was conclusively determined by X-ray crystal structure analysis. [19] The three obtained diastereomeric phosphine-phosphoramidites L10 were then evaluated in the Rh-catalyzed asymmetric hydrogenation of dimethyl itaconate 6 as a benchmark substrate. The catalysts were prepared in situ from [Rh(cod) 2 ]BF 4 and the respective ligand.…”

“…We recently reported a series of modular monodentate phosphoramidite and phosphorodiamidite ligands L8 (see Figure ) based on a chiral amino alcohol, a so‐called Betti base . In contrast to the Binol‐based ligands, this structural motif leads to a stereogenic phosphorus donor.…”

“…Examples of phosphine-phosphoramidite ligands: QuinaPhos L1, [10] IndolPhos L2, [13] L3, [14] PEAPhos L4, [15] Me-AnilaPhos L5, [16] MatPhos L6, [17] and YanPhos L7. [18] We recently reported a series of modular monodentate phosphoramidite and phosphorodiamidite ligands L8 [19] (see Figure 2) based on a chiral amino alcohol, a so-called Betti base. [20] In contrast to the Binol-based ligands, this structural motif leads to a stereogenic phosphorus donor.…”

“…Figure 2. Monodentate [19] and bidentate [21] ligands based on chiral Betti bases bearing a stereogenic P atom.…”