Iridium Phosphite−Oxazoline Catalysts for the Highly Enantioselective Hydrogenation of Terminal Alkenes

Abstract

A modular library of readily available phosphite-oxazoline ligands (L1-L16a-f) has been successfully applied for the first time in the Ir-catalyzed asymmetric hydrogenation of a broad range of highly unfunctionalized 1,1,-disubstituted terminal alkenes. Enantioselectivities up to >99% and full conversions were obtained in several 1,1-disubstituted alkenes, including substrate classes that have never been asymmetrically hydrogenated before (i.e., 1,1-heteoraryl-alkyl, 1,1-diaryl, trifluoromethyl, etc.). The results indicated that these catalytic systems have high tolerance to the steric and electronic requirements of the substrate and also to the presence of a neighboring polar group. The asymmetric hydrogenations were also performed using propylene carbonate as solvent, which allowed the Ir catalyst to be reused and maintained the excellent enantioselectivities.

Unerwartete Kohlenmonoxid‐Gefahren

“…Phosphorochloridites were prepared easily in one step from the corresponding binaphthols 11. Intermediate compound ( S )‐2‐(4‐isopropyl‐4,5‐dihydrooxazol‐2‐yl)phenol,12 ligands L1 – L4 a 10 and substrates S2 ,13 S3 ,14 S4 ,15 S5 13 and S11 7c were prepared as previously reported. Substrates S6 – S10 were prepared by using the Wittig olefination procedure (for details, see the Supporting Information).…”

“…In most asymmetric transformations involving olefins as prochiral reagents (e.g., epoxidation, hydrogenation), 1,1‐disubstituted olefins are systematically challenging substrates,7 mainly due to face selectivity issues (as in the hydroboration reaction). We recently demonstrated the highest reported enantioselectivities in the iridium‐catalyzed hydrogenation of a very large range of simple 1,1‐disubstituted olefins by introducing a biaryl phosphite moiety into the ligand 7c–d. 8 Inspired by the work of Mazet and Gérard6c and the similarities of the elementary steps involved in hydroboration and hydrogenation, we studied here whether the introduction of a biaryl phosphite moiety into the ligand was also beneficial for iridium‐catalyzed hydroboration.…”

Synthesis of dihydrooxazoylarylisoxazoles by conventional and under microwave conditions

“…Some of the oxazoline compounds show ovicidal activity [27]. Oxazoline complexes are useful as catalysts for the enantioselective C-C bond formation [28,29] and enantioselective terminal alkene hydrogenation [30]. Isoxazole coupled oxazolines were reported as Ca-activated K channel openers [31] and also reported as catalysts for regioselective ring opening of propylene oxides [32].…”

Double-Asymmetric Hydrogenation Strategy for the Reduction of 1,1-Diaryl Olefins Applied to an Improved Synthesis of CuIPhEt, a C2-Symmetric N-Heterocyclic Carbenoid

“…However in a combined effort the groups of Börner, Andersson, and Diéguez showed that excellent enantioselectivities can be obtained with substrates of this type, using sterically very demanding phosphite-oxazoline ligands (Scheme 2). 21 In view of these results, we decided to screen a library of iridium complexes in the hydrogenation of diene 1 and the corresponding N -acetyl derivative.…”