Iron-Catalyzed Direct Olefin Diazidation via Peroxyester Activation Promoted by Nitrogen-Based Ligands

Abstract

We herein report an iron-catalyzed direct diazidation method via activation of bench-stable peroxyesters promoted by nitrogen-based ligands. This method is effective for a broad range of olefins and -heterocycles, including those that are difficult substrates for the existing olefin diamination and diazidation methods. Notably, nearly a stoichiometric amount of oxidant and TMSN are sufficient for high-yielding diazidation for most substrates. Preliminary mechanistic studies elucidated the similarities and differences between this method and the benziodoxole-based olefin diazidation method previously developed by us. This method effectively addresses the limitations of the existing olefin diazidation methods. Most notably, previously problematic nonproductive oxidant decomposition can be minimized. Furthermore, X-ray crystallographic studies suggest that an iron-azide-ligand complex can be generated in situ from an iron acetate precatalyst and that it may facilitate peroxyester activation and the rate-determining C-N bond formation during diazidation of unstrained olefins.

Enantioselective Synthesis of Oseltamivir Phosphate (Tamiflu) via the Iron-Catalyzed Stereoselective Olefin Diazidation

“…In the subsequent rate-determining C—N 3 bond forming step, the bulky iron(III) azide species derived from 39 may oxidize 42a or 42b through direct azido-ligand transfer from the iron center. 5,7 Considering the significant unfavorable 1,3-diaxial interactions that may build up in 42b (between the iron-azide complex and the CO 2 Et or NO 2 group) along the reaction trajectory, it is less likely that this oxidation occurs with 42b from either the α or β face.…”

“…Recently, we disclosed a second iron- catalyzed olefin diazidation method via ligand-promoted activation of bench-stable peroxyesters. 7 In this method, nearly a stoichiometric amount of commercially available tert -butyl perbenzoate 20 and TMSN 3 are sufficient for high-yielding diazidation of a wide variety of olefins and N-heterocycles (Scheme 4b). 7 These and other concurrent olefin diazidation methods 8 add useful tools in the repertoire of synthetic chemists.…”

Transition Metal Catalyzed Azidation Reactions

“…In 2018, the same authors investigated a diazidation process using the alkenes 47 and exploiting peroxide agents for the generation of the azido radical to yield products 48 (Scheme 47) [106]. The activation of peroxide by Fe(II) precatalyst may be facilitated by the formation of an iron-azido-ligand complex I-47 generated in situ, which speeds up the rate-determining C-N 3 bond formation.…”

Practical and stereoselective electrocatalytic 1,2-diamination of alkenes

“…Unfortunately, these methods are not without drawbacks. First, the use of stoichiometric amounts of transition metal reagents (e.g., osmium or cobalt) 3,7 , chemical oxidants (e.g., iodine (III) reagents or organic peroxides) 5,6,10,11 , or azide reagents 8–14 raises cost, environmental, and safety issues, especially for large-scale applications 19,20 . Second, they are often limited in substrate scope, sometimes requiring special amination reagents (e.g., diaziridinone and its analogs 4,15,16 , or azido-iodine compounds 9 ).…”