Fundamentals of green chemistry: efficiency in reaction design

In this tutorial review, the fundamental concepts underlying the principles of green and sustainable chemistry--atom and step economy and the E factor--are presented, within the general context of efficiency in organic synthesis. The importance of waste minimisation through the widespread application of catalysis in all its forms--homogeneous, heterogeneous, organocatalysis and biocatalysis--is discussed. These general principles are illustrated with simple practical examples, such as alcohol oxidation and carbonylation and the asymmetric reduction of ketones. The latter reaction is exemplified by a three enzyme process for the production of a key intermediate in the synthesis of the cholesterol lowering agent, atorvastatin. The immobilisation of enzymes as cross-linked enzyme aggregates (CLEAs) as a means of optimizing operational performance is presented. The use of immobilised enzymes in catalytic cascade processes is illustrated with a trienzymatic process for the conversion of benzaldehyde to (S)-mandelic acid using a combi-CLEA containing three enzymes. Finally, the transition from fossil-based chemicals manufacture to a more sustainable biomass-based production is discussed.