Time Economy in Total Synthesis

It is often said that is money. This is certainly true in a multistep synthesis when a high-valued product or set of products is needed urgently. Fulfilling this need requires the sensible balancing of atom economy, step economy, and redox with the time taken to make the product. In this age of flu-based pandemics, the need for rapid provision of effective therapeutic agents makes the importance of economy particularly clear. In this Perspective, the importance of time in total synthesis is described, as well as the general considerations underlining the timely production of desired molecules. As case studies, the syntheses of Tamiflu, Corey lactone, and ibuprofen are discussed, with emphasis on comparing classical and contemporary approaches to a rapid total synthesis. By using modern tactics such as one-pot reaction procedures and versatile synthetic methodologies such as organocatalyst mediated domino reactions coupled with strict-control technologies such as flow chemistry, Tamiflu and Corey lactone can now be synthesized within 60 and 152 min, respectively, using one vessel via a batch system. Tamiflu and ibuprofen can be prepared via flow system, and their total residence times are 11.5 and 3 min, respectively.