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 FeII 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.