N‐Heterocyclic Carbene Iron(III) Porphyrin‐Catalyzed Intramolecular C(sp³)–H Amination of Alkyl Azides

Abstract

Metal-catalyzed intramolecular C-H amination of alkyl azides constitutes an appealing approach to alicyclic amines; challenges remain in broadening substrate scope, enhancing regioselectivity, and applying the method to natural product synthesis. Herein we report an iron(III) porphyrin bearing axial N-heterocyclic carbene ligands which catalyzes the intramolecular C(sp )-H amination of a wide variety of alkyl azides under microwave-assisted and thermal conditions, resulting in selective amination of tertiary, benzylic, allylic, secondary, and primary C-H bonds with up to 95 % yield. 14 out of 17 substrates were cyclized selectively at C4 to give pyrrolidines. The regioselectivity at C4 or C5 could be tuned by modifying the reactivity of the C5-H bond. Mechanistic studies revealed a concerted or a fast re-bound mechanism for the amination reaction. The reaction has been applied to the syntheses of tropane, nicotine, cis-octahydroindole, and leelamine derivatives.

Recent Advances in Iron‐Catalyzed C—H Bond Amination via Iron Imido Intermediate

“…Efficient iron porphyrin catalyst for C-H bond amination of alkyl azides had been lacking until Che's breakthrough reported this year. [57] Che and coworkers found that using N-heterocylcic carbene as a co-ligand and (Boc) 2 O as the product scavenger, the iron(III) porphyrin compound [Fe III (TDCPP)(IMe) 2 ]I ( Figure 7) can efficiently catalyze the conversion of aliphatic azides to pyrrolidines in good yields (Table 10). This catalytic system permits the amination of benzylic, allylic, tertiary, secondary and even primary C(sp 3 )-H bonds.…”

“…Upon treatment of the high-spin iron(III) imido complex [( Ar DP Mes )Fe(NAd)] with ClCPh 3 , Betley's group prepared the formal iron(IV) alkylimido complex [( Ar DP Mes )FeCl(NAd)] in 80% yield. Magnetic susceptibility measurement and57 Fe Mössbauer spectroscopy studies indicated its S = 2 ground spin-state that might be formed by the antiferromagnetic coupling between a high-spin (S = 5/2) iron(III) center and an iminyl radical anion[NAd] •-. Consistent with this assignment, the N K-edge X-ray absorption spectra of both [(…”

Iron porphyrin catalysed light driven C–H bond amination and alkene aziridination with organic azides

“…We next used photocatalysis of intramolecular C-H amination of alkyl azides 15,16 to form imidazolidines, 17 a versatile class of intermediates in organic synthesis. As shown in Table 3, a variety of N-containing alkyl azides underwent C-H amination to give the corresponding imidazolidines in 45-98% yield.…”

Azides and Porphyrinoids: Synthetic Approaches and Applications. Part 1—Azides, Porphyrins and Corroles

“…Recently, the same group reported the first example of the use of a cobalt(II) corrole complex in nitrene transfer reactions, more precisely in the ring-closing C-H amination of an aliphatic azide in the presence of Boc 2 O, giving the corresponding Boc-protected pyrrolidine (Scheme 58) [115]. Moreover, Che and collaborators described the synthesis of an iron(III) N-heterocyclic carbene (NHC) porphyrin complex, [Fe(III)(TDCPP)(IMe) 2 ]I (TDCPP = meso-tetrakis(2,6-dichlorophenyl)porphyrinato; IMe = 1,3-dimethylimidazol-2-ylidene), which was used to catalyze the intramolecular amination of C-H bonds with a wide range of alkyl azides in the presence of Boc 2 O and under thermal and microwave-assisted conditions [116]. A broad and atom-economical method for the preparation of cyclic sulfoximines in up to 98% yield has been established by Bolm and collaborators via intramolecular imidation reactions of azido-substituted sulfoxides as nitrene precursors (Scheme 62).…”