MaxPHOS Ligand: PH/NH Tautomerism and Rhodium‐ Catalyzed Asymmetric Hydrogenations

Abstract

MaxPHOS is an active and robust P-stereogenic ligand for asymmetric catalysis. The presence of an À NH À bridge between the two phosphine moieties allows the NH/PH tautomerism to take place. The neutral ligand, in which the NH form predominates, is an air-sensitive compound. However, protonation of MaxPHOS leads to the stable PH form of the ligand, in which the overall positive charge is distributed on both P centers. This protonation turns the MaxPHOS·HBF 4 salt 3 into an airstable compound both in the solid state and in solution.The salt 3 is also a convenient precursor for the preparation of rhodium(I) complexes by direct ligand exchange with the complexFinally, the corresponding rhodium(I)-MaxPHOS complex was tested in the asymmetric hydrogenation of a wide range of substrates. The complex proved to be a highly selective and robust system in these reactions.

P-Stereogenic bisphosphines with a hydrazine backbone: from N–N atropoisomerism to double nitrogen inversion

“…Our group has recently reported procedures for the synthesis of optically pure P-stereogenic tert-butylmethylphosphinous acid borane 1. 7 This fragment is highly versatile and has allowed access to C 1 symmetric MaxPHOS 8 and MaxPHOX 9 ligands. In this context, we addressed whether our methodology could also be amenable for the rapid and efficient synthesis of ligands with C 2 symmetry.…”

Recent Advances in the Pauson–Khand Reaction

“…[25] The P-stereogenic MaxPHOS-Rh complex (Scheme 16, top) had previously been successfully employed in asymmetric hydrogenation chemistry. [26] As shown in Scheme 16 (bottom), the reaction was higher yielding and more selective with the N-tosyl tethered enyne. Low CO pressure and low temperature tended to favor the side [2+2+2] reaction, which was only observed as a 1:1 mixture of regioisomers.…”

Structure-based design of a Cortistatin analog with improved immunoregulatory activity against inflammatory bowel disease (IBD)

“…All analogs were prepared by standard Fmoc/ t Bu solid-phase peptide synthesis (SPPS) as the wild type CST peptide. The Fmoc-protected Msa was synthetized by asymmetric hydrogenation following our previously described protocol 29 . For the NMR structural studies, the peptides were used as TFA salt and for the in vitro and in vivo studies the TFA counter ion was replaced by acetate salts using ion exchange chromatography.…”