P-Trifluoromethyl ligands derived from Josiphos in the Ir-catalysed hydrogenation of 3,4-dihydroisoquinoline hydrochloridesElectronic supplementary information (ESI) available: Description of general experimental procedures, NMR spectra of new compounds, and HPLC chromatograms. CCDC 1000084 and 1000085. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5dt02019k

• Main Authors: Schwenk, R, Togni, A
• Format: Journal Article
• Language: English
• Published: 10.11.2015
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c5dt02019k

The synthesis of mono P-trifluoromethyl and therefore P-stereogenic Xyliphos-derived ligands 5 and their application in the Ir-catalyzed enantioselective hydrogenation of 1-substituted 3,4-dihydroisoquinolinium species (DHIQ) are reported. The ligands were prepared following previous procedures involving the reaction of a bistrifluoromethylphosphine with lithiated ( R )-Ugi amine 1 . Chloroiridium( i ) cyclooctadiene precatalysts containing these new partially electron-poor ligands 9 were found to be poorly active in the hydrogenation of free 1-phenyl-3,4-dihydroisoquinoline 12a . However, the corresponding hydrochloride 12a ·HCl was smoothly reduced at 55-60 °C and 100 bar hydrogen pressure. The ( S P )-configured ligand ( S P )- 5 yielded significantly higher enantioselectivity in hydrogenation experiments than its P-stereoisomeric counterpart ( R P )- 5 . These new ligands were subsequently applied in the hydrogenation of a series of different 1-substituted 3,4-DHIQ chlorides 12a-l ·HCl. Good to excellent enantioselectivity was observed for substrates bearing relatively large substituents in position 1, reaching 96% ee for 1-Ph-DHIQ chloride 12a ·HCl without the help of any additives. Furthermore, an interesting counter ion effect was found with chloride being the best and hexafluorophosphate being very detrimental to enantioselectivity. Ferrocenyl phosphines containing a stereogenic P-CF 3 group show improved selectivities in the Ir-catalysed hydrogenation of dihydroisoquinolinium derivatives.