Metolachlor, asymmetric reductive hydrogenation

After taking up the challenge for the synthesis of (5)-metolachlor on an industrial scale, Blaser reported on the very first example of asymmetric reductive amination and succeeded to synthesize the desired (5)-enantiomer of metolachlor 77 up to 78% ee ° Blaser optimized the reaction condition where the 2-methyl-5-ethylaniline (MEA, 79) was treated with 1.2 equivalents of dry methoxyacetone (MOA, 78), 0.01 mol% Ir-xyliphos catalyst 81 in the presence of tetrabutylammonium iodide (TBAI), and a small amount of trifluoroacetic acid in cyclohexane as the solvent under 80 bar hydrogen pressure at 50 °C. Within 16 hours, almost complete conversion was reached furnishing the chiral amine 80 with 99% conversion and 78% ee. Upon chloroa-cetylization, 80 afforded the desired compound metolachlor 77 without any loss of enantioselectivity (Scheme 39.20). 

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