A Single Enantiomer (99 %) Directly from Continuous-Flow Asymmetric Hydrogenation

摘要

Sir John Cornforth has suggested: "It does, for example, no good to offer an elegant, difficult and expensive process to an industrial manufacturing chemist, whose ideal is something to be carried out in a disused bathtub by a one-armed man who cannot read, the product being collected continuously through the drain hole in 100% purity and yield". We now report a reaction that almost conforms to this ideal except that we replace the bath, a continuously stirred tank reactor, which cannot give 100% conversion in continuous-flow mode, by a shower, which is a plug-flow reactor so can give 100 % conversion (Figure 1). In our system, the solventless asymmetric hydrogenation of dibutyl itaconate gives a single enantiomer of dibutyl 2-methylsuccinate uncontaminated by catalyst or starting material. No further purification is required. This is a particularly difficult challenge, since it must be carried out in neat substrate and must give 100% conversion, 100% ee with no leaching of the homogeneous catalyst.