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

Abstract

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.

Keywords: acetaldehyde; asymmetric organocatalysis; design of experiments; optimisation; water.