DoE‐Driven Development of an Organocatalytic Enantioselective Addition of Acetaldehyde to Nitrostyrenes in Water

The development of an enantioselective enamine‐catalysed addition of masked acetaldehyde to nitroalkenes via a rational approach helped to move away from the use of chloroform. The presented research allows the use of water as a reaction medium, therefore improving the industrial relevance of a protocol to access very important pharmaceutical intermediates. Critical to the success is the use of chemometrics‐assisted ‘Design of Experiments’ (DoE) optimisation during the development of the presented new synthetic approach, which allows to investigate the chemical space in a rational way.