1. Josiphos-type binaphane ligands for iridium-catalyzed enantioselective hydrogenation of 1-aryl-substituted dihydroisoquinolines.
Zhao Wei, Gang Zhou, Lin Yao, Shengyong Zhang, Huifang Nie, Yupu Zhu, Xiaomu Hu, Pingan Wang, Ru Jiang. Org Lett. 2019 Nov 1; 21(21): 8641-8645. DOI: 10.1021/acs.orglett.9b03251. PMID: 31603341.
Convenient synthesis and useful application of a series of Josiphos-type binaphane ligands were described. The iridium complexes of these chiral diphosphines displayed excellent enantioselectivity and good reactivity in the asymmetric hydrogenation of challenging 1-aryl-substituted dihydroisoquinoline substrates (full conversions, up to >99%ee, 4000 TON). The use of 40% HBr (aqueous solution) as an additive dramatically improved the asymmetric induction of these catalysts. This transformation provided a highly efficient and enantioselective access to chiral 1-aryl-substituted tetrahydroisoquinolines, which were of great importance and common in natural products and biologically active molecules.
2. Studies on the 1,2-migrations in pd-catalyzed negishi couplings with josiphos ligands.
Troels Skrydstrup, Thomas M Gøgsig, Anders T Lindhardt. J Org Chem. 2009 Jan 2; 74(1): 135-43. DOI: 10.1021/jo801824e. PMID: 19032140.
We report an initial investigation with the goal of determining the factors that control the 1,2-migration in the Negishi cross-coupling, which is promoted by palladium catalyst systems generated with JosiPhos ligands. Several of the factors that were demonstrated to be important for the 1,2-migration include (1) the nucleophilicity of the organometallic reagent, which possibly influences the transmetalation step in direct competition with the intermediate beta-hydride elimination of the alkenyl Pd(II) species; (2) the structural features of the vinyl tosylates and phosphates, in which substrates possessing a bulky C1 substituent displayed highest propensity for undergoing the 1,2-migration under the coupling reaction conditions; and (3) the structure of the JosiPhos ligand, where both the sterical bulk and choice of substituents on the ferrocenyl phosphino group greatly influence the catalytic activity of the palladium complex and its capacity to facilitate the 1,2-migration.
3. P-trifluoromethyl ligands derived from josiphos in the ir-catalysed hydrogenation of 3,4-dihydroisoquinoline hydrochlorides.
A Togni, R Schwenk. Dalton Trans. 2015 Dec 7; 44(45): 19566-75. DOI: 10.1039/c5dt02019k. PMID: 26161502.
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 (SP)-configured ligand (SP)-5 yielded significantly higher enantioselectivity in hydrogenation experiments than its P-stereoisomeric counterpart (RP)-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.
