Asymmetric Cleavage of Racemic 1,3‐Oxazolidines – A New Dynamic Process in Homogeneous Rh(I)‐Catalyzed Hydrogenation

Abstract

The mechanism of the homogeneously catalyzed hydrogenation of 1,3-oxazolidines with a Rh(I) diphosphane catalyst affording tertiary hydroxyethyl-substituted amines was investigated with the help of D 2 labelling experiments. It was found that the reaction proceeds via prochiral intermediates with, preferentially, an iminium cation being in equilibrium with the 1,3-oxazolidine. This observation opened up the opportunity to run the reaction stereoselectively by employment of a racemic 1,3-oxazolidine and a chiral catalyst. By means of high-throughput screening considering 144 catalysts a cationic Rh(NOR-PHOS)-complex was identified as the most efficient catalyst, which afforded after optimization of solvent, temperature and H 2 pressure the corresponding chiral hydroxyethylamine in 95% yield and 80% ee.

High‐Throughput Experimentation and Ligand Libraries

“…After some mechanistic studies showing that the reduction of N,O-acetals proceeds via a prochiral iminium cation, Börner et al aimed at finding an enantioselective catalyst for this transformation by preparing a library of 144 catalysts [17]. Pre-catalysts were generated in situ by mixing one ligand out of a library of 48 members with either [Rh(COD) 2 ]BF 4 , [Rh(COD) 2 ]OTf, or [Rh(COD)Cl] 2 .…”

Direct Reductive Amination versus Hydrogenation of Intermediates –A Comparison

“…Hence evaluation of efficient selective and enantioselective catalysts for DRA seems to be a separate task. Obviously in some cases first isolation of intermediates, e.g., imines, enamines or even sometimes N,O-acetals [15] and subsequent hydrogenation is preferred over DRA. On the other hand, the DRA approach presents the only possibility to produce amines in those cases when intermediates are not stable as has been proven in the reductive amination of a-keto acids.…”

Iminium cations as intermediates in the hydrodenitrogenation of alkylamines over sulfided NiMo/γ-Al2O3

“…Addition of H 2 S or an amine molecule to the iminium cation can take place and, after ammonia or amine elimination and hydrogenation, a thiol or a dialkylamine can be formed. Iminium cations are well known as intermediates in organic radical reactions [27,28]. On a heterogeneous catalyst, they can be formed when the surface contains reductionoxidation centers as well as protons, as is the case for metal sulfides where the metal ions may undergo redox reactions and the H atoms of surface SH groups may act as protons.…”