SIMON T. R. MÜLLER¹, AURÉLIEN MURAT², PAUL HELLIER², THOMAS WIRTH¹*
*Corresponding author
1. School of Chemistry, Cardiff University, Park Place, Main Building, Cardiff CF10 3AT, United Kingdom
2. Institut de Recherche Pierre Fabre, 81603 Gaillac, France

Abstract

Through the use of flow chemistry in multistep processes, dangerous but synthetically useful diazo reagents can be made accessible for large scale applications. The generation, isolation and use of diazo compounds can be performed continuously, therefore never accumulating large quantities of highly energetic material. The use of inline analytics via infrared spectroscopy is key in developing these processes.

INTRODUCTION

Synthetic chemists thrive to develop and use the most efficient ways to assemble complex molecules. For this purpose, some functional groups stand out in their ability to be used flexibly and selectively for target synthesis. One of the most versatile functional groups is the diazo group, a highly reactive carbene precursor. Their reactivity stems from the formation of metal carbenes using catalysis which undergo a broad range of reactions under high chemo-, regio-, and stereocontrol. Examples include stereoselective cyclopropanation (1), C-H insertion(2) and ring expansion reactions (3). Diazo compounds have been used in the synthesis of natural products such as (+)-Salvileucalin B (4), (+)-Lithospermic Acid (5), and (-)-Serotobenine (6). Although diazo reagents are well studied academically, they are rarely used ind ... ...