1. Imidazole-1-sulfonyl azide-based diazo-transfer reaction for the preparation of azido solid supports for solid-phase synthesis
Vida Castro, Juan B Blanco-Canosa, Hortensia Rodriguez, Fernando Albericio ACS Comb Sci. 2013 Jul 8;15(7):331-4.doi: 10.1021/co4000437.Epub 2013 Jun 6.
An efficient, standard, mild, and copper-free imidazole-1-sulfonyl azide hydrochloride-based diazo-transfer method was implemented in a set of four resins that cover a broad range of hydrophobicity. The imidazole-1-sulfonyl azide hydrochloride is easily prepared/commercially available, stable upon storage at 4 °C, and proved to be a suitable alternative to triflyl azide for diazo-transfer reactions in amine functionalized resins. We have successfully applied the azido resins for the conjugation of a TFA-labile Wang-type linker using Click Chemistry.
2. Taming tosyl azide: the development of a scalable continuous diazo transfer process
Benjamin J Deadman, Rosella M O'Mahony, Denis Lynch, Daniel C Crowley, Stuart G Collins, Anita R Maguire Org Biomol Chem. 2016 Apr 7;14(13):3423-31.doi: 10.1039/c6ob00246c.Epub 2016 Mar 9.
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 β-ketoesters, β-ketoamides, malonate esters and β-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 α-diazocarbonyl in >98% purity without any column chromatography.
3. A 'sulfonyl-azide-free' (SAFE) aqueous-phase diazo transfer reaction for parallel and diversity-oriented synthesis
Dmitry Dar'in, Grigory Kantin, Mikhail Krasavin Chem Commun (Camb). 2019 May 8;55(36):5239-5242.doi: 10.1039/c9cc02042j.Epub 2019 Apr 15.
Diazo transfer reactions are notoriously associated with the use of potentially explosive sulfonyl azides. The first 'sulfonyl-azide-free' (SAFE) protocol for producing diazo compounds from their active-methylene precursors via the Regitz diazo transfer reaction was developed and has displayed a remarkable substrate scope. It can be applied to generating arrays of diazo compounds for further evolution via combinatorial chemistry and a range of scaffold-generating transformations.
