The Generation of Diazo Compounds in Continuous‐Flow

Abstract

Toxic, cancerogenic and explosive-these attributes are typically associated with diazo compounds. Nonetheless, diazo compounds are nowadays a highly demanded class of reagents for organic synthesis, yet the concerns with regards to safe and scalable transformations of these compounds are still exceptionally high. Lately, the research area of the continuous-flow synthesis of diazo compounds attracted significant interest and a whole variety of protocols for their "on-demand" preparation have been realized to date. This concept article focuses on the recent developments using continuous-flow technologies to access diazo compounds; thus minimizing risks and hazards when working with this particular class of compounds. In this article we discuss these concepts and highlight different pre-requisites to access and to perform downstream functionalization reaction.

Diazoacetonitrile (N2CHCN): A Long Forgotten but Valuable Reagent for Organic Synthesis

“…Continuous‐flow chemistry is an important tool to safely prepare highly reactive or explosive reagents like diazoalkanes . In this context, the Koenigs group explored the flow synthesis of diazoacetonitrile and its application in X−H functionalization reactions.…”

“…[41] Continuous-flow chemistry is an important tool to safely prepare highly reactive or explosive reagents like diazoalkanes. [42] In this context, the Koenigs group explored the flow synthesis of diazoacetonitrile and its application in XÀH functionalization reactions. Amino acetonitriles are readily prepared by NÀH functionalization and are a privileged motif in warheads of protease inhibitors.…”

An Immobilized‐Dirhodium Hollow‐Fiber Flow Reactor for Scalable and Sustainable C−H Functionalization in Continuous Flow

“…Thus,such reactive compounds are ideally not stored in large quantities on site,a nd just-in-time syntheses are preferred. [17][18][19][20][21][22][23][24][25][26][27] Thep rice of the soluble dirhodium catalysts (Rh 2 L 4 ,L= ligand) is another barrier for industrial applications.R hodium is av ery expensive noble metal and the cost for the synthesis of these ligands for the catalysts also cannot be ignored. To recycle the homogenous dirhodium catalysts, additional separation steps are required and the catalytic activities are often not maintained after recovery and recycle.…”

Electrochemical Synthesis of [1,2,3]Triazolo[1,5‐a]pyridines through Dehydrogenative Cyclization

“…[1,2,3]Triazolo[1,5‐ a ]pyridines, which exist in equilibrium with the ring‐opening diazo form in solution, have been employed as convenient precursors for carbene species in the synthesis of functionalized pyridine derivatives and several other N‐heterocycles (Scheme a) . Synthesis of [1,2,3]triazolo[1,5‐ a ]pyridines has been achieved through oxidative cyclization of hydrazones of 2‐acylpyridines employing stoichiometric chemical oxidants such as MnO 2 ,– Ag 2 O, NiO 2 , and PhI(OAc) 2 or more recently copper‐catalyzed aerobic oxidation …”