Catalytic Synthesis of N-Heterocycles via Direct C(sp³)–H Amination Using an Air-Stable Iron(III) Species with a Redox-Active Ligand

Abstract

Coordination of FeCl3 to the redox-active pyridine–aminophenol ligand NNOH2 in the presence of base and under aerobic conditions generates FeCl2(NNOISQ) (1), featuring high-spin FeIII and an NNOISQ radical ligand. The complex has an overall S = 2 spin state, as deduced from experimental and computational data. The ligand-centered radical couples antiferromagnetically with the Fe center. Readily available, well-defined, and air-stable 1 catalyzes the challenging intramolecular direct C(sp3)–H amination of unactivated organic azides to generate a range of saturated N-heterocycles with the highest turnover number (TON) (1 mol% of 1, 12 h, TON = 62; 0.1 mol% of 1, 7 days, TON = 620) reported to date. The catalyst is easily recycled without noticeable loss of catalytic activity. A detailed kinetic study for C(sp3)–H amination of 1-azido-4-phenylbutane (S1) revealed zero order in the azide substrate and first order in both the catalyst and Boc2O. A cationic iron complex, generated from the neutral precatalyst upon reaction with Boc2O, is proposed as the catalytically active species.

Direct Comparison of C–H Bond Amination Efficacy through Manipulation of Nitrogen-Valence Centered Redox: Imido versus Iminyl

“…The presence of metal-stabilized iminyl radicals has now been observed 9,36 or implicated in H-atom abstraction reactiv-ity 12,13,21,37 and nitrene transfer catalysis 7,8,10,11,60,61 in a number of systems. 15 The supporting organic moiety on the bound nitrene can promote stabilization via heteroatom donation, akin to Fischer-type carbene ligands, 10,11 or promote reactivity by concentration of radical density on the iminyl N -atom as is the case in 6 .…”

Nitrene Radical Intermediates in Catalytic Synthesis

“…Recent studies performed by van der Vlugt, de Bruin and co‐workers focused on improving the stability of an Fe‐based catalyst and increasing the TONs of these type of reactions. Inspired by the positive effects of using redox‐active ligands observed in catalytic reactions with Pd and Rh (vide supra), an air‐ and moisture‐stable Fe III ‐based catalyst with a redox‐active NNO ligand was synthesized and used in the intramolecular C−H bond amination ring‐closure reactions of aliphatic azides to N‐heterocycles . The respective iron complex (Figure ) proved remarkably stable, and the catalyst can be efficiently recycled after the reactions.…”

Uncatalyzed Oxidative C−H Amination of 9,10‐Dihydro‐9‐Heteroanthracenes: A Mechanistic Study

“…[1] Direct (sp 3 ) CÀHa mination viam etal-nitrene intermediatesh as received increasing attentioninthe last twodecades,asnopre-functionalization of theh ydrocarbon substratesi sr equired. [2][3][4][5] Keyd evelopmentsa re theu se of activated [6][7][8] andn on-activated organic azides, [9][10][11][12][13][14][15] Haloamine-T [16,17] and( in situ generated) iminoiodanes( PhI = NR)a sn itrene precursors (Figure1). [18][19][20][21][22][23] Transitionmetalc omplexes have proven to be excellentc atalysts fort hese aminationr eactions,a nd thec ommonlya cceptedm echanism comprisest he formationo fareactive metal-nitrenei ntermediate, followed by stepwise hydrogen atom abstractiona nd radicalr ecombination or concertedi nsertion of then itrene into the CÀHb ond.…”