A New Class of Modular Phosphinite-Oxazoline Ligands: Ir-Catalyzed Enantioselective Hydrogenation of Alkenes

Abstract

Phosphinooxazolines 1 (phox ligands) have been successfully applied in many different enantioselective metal-catalyzed processes. [1] We have recently found that iridium ± phox complexes are efficient catalysts for the enantioselective hydrogenation of unfunctionalized alkenes, [2] a class of substrates that gives unsatisfactory results with other catalysts. [3] The best enantioselectivities (up to 99 % ee) have been observed for 1-alkyl-1,2-diaryl-substituted alkenes, while other alkenes such as monoaryl-1,2-dimethyl-substituted alkenes are converted with only moderate enantiomeric excesses. Here we report a new class of ligands, the phosphinite ± oxazolines 2, which induce high enantioselectivity with a much broader range of alkenes and, thus, significantly enhance the scope of Ir-catalyzed hydrogenation.Both enantiomers of the phosphinite ± oxazoline ligands 2 are readily prepared in three to four steps, starting from imidates 5 or carboxylic acids 8 and l-serine methyl ester hydrochloride (4) or the corresponding d isomer (Scheme 1). Special precautions had to be taken in the peptide coupling Scheme 1. Synthesis of compounds 2 for which R 3 Ph. a) 4,

Threonine-Derived Phosphinite-Oxazoline Ligands for the Ir-Catalyzed Enantioselective Hydrogenation

“…[7] The most promising class of ligands that we have found so far are the phosphinite-oxazolines 1. [8,9] They gave good to excellent …”

“…[7] The most promising class of ligands that we have found so far are the phosphinite-oxazolines 1. [8,9] enantioselectivities for a much wider range of substrates than the other P,N-ligands studied so far. Another advantage of this ligand system is its modular architecture allowing the introduction of many different substituents at the oxazoline ring, the backbone and the phosphine group.…”

“…In initial experiments the iridium complexes 3a and 3b were tested in the enantioselective hydrogenation of a series of olefins (Scheme 2) and the results were compared with the enantioselectivities previously obtained with the corresponding serine-derived catalyst. [8] In the hydrogenation of substrates 8, 9 and 10, the threoninederived catalysts 3a and 3b proved to be superior to the corresponding serine-derived complex [Ir(COD) (1)] (R 1 Ph, R 2 Bn, Table 1). In the hydrogenation of trans-a- [a] All reactions were performed using 0.1 mmol of alkene and 1 mL of dichloromethane at 50 bar of hydrogen pressure at rt (reaction time: 2 h).…”

“…As previously observed, [8] the ee increases with decreasing hydrogen pressure. By lowering the temperature from 23 to 0 8C, the enantioselectivity of catalyst 3a was raised from 84 to 89% ee.…”

“…[8] Tables 1 and 2). analogues and other oxazoline-based P,N-ligands. In the hydrogenation of unfunctionalized trisubstituted arylalkenes, unprecedented enantioselectivities could be obtained with these new ligands.…”