Novel applications of α-diazocarbonyl compounds and enabling technologies in stereoselective synthesis

α-Diazocarbonyl compounds are widely used in organic chemistry as versatile carbene precursors which enable concise synthesis towards complex asymmetric molecules. Due to their intrinsic highly energetic nature, flow technology can be applied to ensure safer, scalable and efficient protocols. Other modern enabling tools such as Design of Experiment (DoE) and online analysis, provide great advantages to achieve faster analysis and optimisations of chemical transformations. In the first part of this work, α-diazocarbonyl compounds have been used in the enantioselective synthesis of novel trans-indolines.1 The synthesis of the diazo precursors, previously investigated in batch, was translated into a flow system and optimised following a DoE-approach. Moreover, highly Lewis acidic boranes were found to enable related α-diazocarbonyl compounds to undergo a metal-free transfer/rearrangement cascade reaction towards asymmetric benzofuran- 3H-ones.2 The focus in the final part of this work was on the development of a faster analytical method for an accelerated optimisation of stereoselective reactions. The reactions were performed in a continuous flow electrochemical reactor directly coupled to a 2D‐HPLC for immediate online analysis, which allowed a fast screening of reaction conditions using DoE.3