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 ac atalytic amount of iron(III) acetylacetonate [Fe(acac) 3 ], the reaction of structurally diverse ketoxime esters with trimethylsilyl azide (TMSN 3 )a fforded g-azido ketones in good to excellent yields. This unprecedented distal g-C(sp 3 )ÀHb ond azidation reaction went through as equence of reductiveg eneration of an iminyl radical, 1,5-hydrogen atom transfer (1,5-HAT) and iron-mediated redox azido transfert ot he translocated carbon radical. TMSN 3 served not only as an itrogen source to functionalise the unactivated C(sp 3 )ÀHb ond, but also as ar eductant to generate the catalytically active Fe II species in situ. Based on the same principle, an ovel b-C(sp 3 )ÀHf unctionalisation of alcohols via N-acyloxy imidates was subsequently realised, leading, after hydrolysis of the resulting ester,t ob-azido alcohols, which are important building blocks in organic and medicinal chemistry.

Functionalization of remote C(sp3)-H bonds enabled by copper-catalyzed coupling of O-acyloximes with terminal alkynes

“…In fact, the bond dissociation energy (BDE) of iminyl NH bonds (93 kcal/mol) is lower than most of the C(sp 3 )-H bond (96-105 kcal/mol), which makes the 1,5-HAT of iminyl radical to carbon radical thermodynamically unfavorable. One solution to this problem is to perform the reaction under acidic conditions 15,33,39 , which are unfortunately incompatible with the present alkynylation conditions.…”

“…In this context, redox-active acyclic 15 and cyclic 16 oxime derivatives, pioneered by Forrester and Zard, respectively, have been demonstrated to be versatile precursors of iminyl radicals under either oxidative or reductive conditions. Depending on the structure of oximes, the iminyl radicals can evolve to a carbon radical through either β-scission [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] or 1,5hydrogen atom transfer (1,5-HAT) process [33][34][35][36][37][38][39] . The resulting carbon radicals can then be trapped by radical acceptors, affording remote C(sp 3 ) functionalized alkylnitriles and ketones.…”

Iron‐Catalyzed, Iminyl Radical‐Triggered Cascade 1,5‐Hydrogen Atom Transfer/(5+2) or (5+1) Annulation: Oxime as a Five‐Atom Assembling Unit

“…Based on the aforementioned results and the previous work on iminyl radical transformations, a plausible reaction mechanism is illustrated for the cascade 1,5‐HAT/(5+2) annulation reactions (Scheme ). Single electron transfer from Fe II to the oxime results in N−O bond cleavage to generate Fe III and an iminyl radical A . The latter undergoes 1,5‐HAT to form an alkyl carbon radical B .…”

Oxime‐Derived Iminyl Radicals in Selective Processes of Hydrogen Atom Transfer and Addition to Carbon‐Carbon π‐Bonds

“…[90] Oxime esters 30 were converted to γ-azidoketones 31 using iron (II) acetylacetonate as the catalyst and TMSN 3 as the azide source (Scheme 14). [91] Presumably, the C-centered radical formed after 1,5-HAT reacts with the formed in situ Fe III N 3 to produce γazidoimine. The latter is hydrolyzed to azidoketone 31.…”