DoE-driven development of an organocatalytic enantioselective addition of acetaldehyde to nitrostyrenes in water

Moving from organic solvents to water is not always an easy task, especially when a lot of variables need to be screened. The development of an enantioselective enamine-catalysed Michael addition of acetaldehyde to nitroalkenes in water was developed by using a rational approach, via chemometrics-assisted ‘Design of Experiments’ (DoE) optimisation. This way it was possible to screen 9 different parameters, their interaction with each other, and the full chemical space, with minimum experiments in an efficient manner.