Deadman, BJ,O'Mahony, RM,Lynch, D,Crowley, DC,Collins, SG,Maguire, AR

2016

January

Organic & Biomolecular Chemistry

Taming tosyl azide: the development of a scalable continuous diazo transfer process

Validated

Altmetric: 1 ()

CONTINUOUS-FLOW SYNTHESIS C-H INSERTION ALPHA-DIAZOCARBONYL COMPOUNDS HETERO-WOLFF REARRANGEMENT BETA-OXO SULFOXIDES ORGANIC-SYNTHESIS CARBENE INSERTION CHEMISTRY SAFE GENERATION

14

3423

3431

Heat and shock sensitive tosyl azide was generated and used on demand in a telescoped diazo transfer process. Small quantities of tosyl azide were accessed in a 'one pot' batch procedure using shelf stable, readily available reagents. For large scale diazo transfer reactions tosyl azide was generated and used in a telescoped flow process, to mitigate the risks associated with handling potentially explosive reagents on scale. The in situ formed tosyl azide was used to rapidly perform diazo transfer to a range of acceptors, including beta-ketoesters, beta-ketoamides, malonate esters and beta-ketosulfones. An effective in-line quench of sulfonyl azides was also developed, whereby a sacrificial acceptor molecule ensured complete consumption of any residual hazardous diazo transfer reagent. The telescoped diazo transfer process with in-line quenching was used to safely prepare over 21 g of an alpha-diazocarbonyl in > 98% purity without any column chromatography.

10.1039/c6ob00246c