Iron-Catalysed Remote C(sp3 )-H Azidation of O-Acyl Oximes and N-Acyloxy Imidates Enabled by 1,5-Hydrogen Atom Transfer of Iminyl and Imidate Radicals: Synthesis of γ-Azido Ketones and β-Azido Alcohols

Abstract

In the presence of a catalytic amount of iron(III) acetylacetonate [Fe(acac)₃ ], the reaction of structurally diverse ketoxime esters with trimethylsilyl azide (TMSN₃ ) afforded γ-azido ketones in good to excellent yields. This unprecedented distal γ-C(sp³ )-H bond azidation reaction went through a sequence of reductive generation of an iminyl radical, 1,5-hydrogen atom transfer (1,5-HAT) and iron-mediated redox azido transfer to the translocated carbon radical. TMSN₃ served not only as a nitrogen source to functionalise the unactivated C(sp³ )-H bond, but also as a reductant to generate the catalytically active Fe^II species in situ. Based on the same principle, a novel β-C(sp³ )-H functionalisation of alcohols via N-acyloxy imidates was subsequently realised, leading, after hydrolysis of the resulting ester, to β-azido alcohols, which are important building blocks in organic and medicinal chemistry.

Keywords: C−H activation; azide; iron catalysis; oxime; radical.