Asymmetric hydrogenation with neutral substrates

The activity and enantioselectivity of chiral Ir catalysts have been tested by using 2,3,3-trimethylindolenine as a model substrate. Hydrogenation of the cyclic imine with [Ir(bdpp)Hl2 2 gives the corresponding chiral amine with 80% ce (Scheme 1.99) [350]. The stereoselectivity is somewhat better than that with acyclic substrates (see Scheme 1.94). A neutral BCPM-Ir complex with Bil3 effects asymmetric hydrogenation in 91% optical yield [354], A complex of MCCPM shows similar enantioselection [354], These complexes are not applicable to the reaction of other acyclic and six-membered cyclic imines. An MOD-DIOP-Ir complex is also usable with the aid of ( -C4H9)4NI [355], An Ir complex of BICP with phthalimide effectively... 

Asymmetric hydrogenation of Scheme 1.101 provides a general route to isoquinoline alkaloids (see Section 1.3.1.1). An imine substrate is hydrogenated with the chiral titanocene (/ )-34 to give the S product with 98% ee [346a,b,352], A neutral BCPM-Ir complex with phthalimide in toluene also shows high enantioselection [358]. The choice of a weakly polar... 

Figure 1.30 Catalytic cycle for the Ir-catalyzed asymmetric hydrogenation of imines. Dihydrogen replaces coordinated imine in A yielding molecular hydrogen complex B with a molecule of imine in the outer sphere. Then imine is pro-tonated by one of the hydrogen atoms from the H2 molecule to give neutral Ir complex C. The following hydride transfer of the hydride trans- to phosphorus gives the catalyst-product complex D. Replacement of the product with a new substrate molecule finishes the catalytic cycle recovering A.

Catalytic hydrogenation of a-keto-esters can be achieved in the presence of homogeneous neutral Rh complexes of the Wilkinson type. Asymmetric reduction occurs when chiral bis-phosphines are employed as ligands, and one of the best optical yields known for homogeneous a-keto-ester hydrogenation (76%) is observed with (20a) as a ligand and propyl pyruvate as substrate. Use of the ligand (20b) increases the lipophilicity of such rhodium catalysts, and hence their solubility in non-polar solvents. ... 

Asymmetric epoxidation of terminal alkenes with hydrogen peroxide was optimized with electron-poor chiral Pt(II) complexes bearing a pentafluorophenyl residue, as described in Section 23.3.1.6. The same catal3rtic system was made more sustainable by the employment of water as the solvent under micellar conditions. Surfactant optimization revealed the preferential use of neutral species like Triton-XIOO to solubihze both the catalyst and substrates. In several cases an increase of the asymmetric induction was observed (Scheme 23.43). The use of an aqueous phase and the strong affinity of the catalyst for the micelle allowed the recycling of the catalytic system by means of phase separation and extraction of the reaction products using an apolar solvent (hexane). The aqueous phase containing the catalyst was reused for up to three cycles with no loss of activity or selectivity. 

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