Iron complexes of tetramine ligands catalyse allylic hydroxyamination via a nitroso–ene mechanism

Iron complexes of tetramine ligands catalyse allylic hydroxyamination via a nitroso–ene mechanism David Porter, Belinda M.-L. Poon and Peter J. Rutledge*§ Full Research Paper Address: School of Chemistry F11, The University of Sydney, NSW 2006, Australia Email: Peter J. Rutledge* - * Corresponding author § tel: +61 2 9351 5020; fax: +61 2 9351 3329 Keywords: CH activation; hydroxyamination; iron catalysis; nitroso-ene Open Access Beilstein J. Org. Chem. 2015, 11, 2549–2556. doi:10.3762/bjoc.11.275 Received: 24 September 2015 Accepted: 24 November 2015 Published: 11 December 2015 Associate Editor: K. Itami © 2015 Porter et al; licensee Beilstein-Institut. License and terms: see end of document. Abstract Iron(II) complexes of the tetradentate amines tris(2-pyridylmethyl)amine (TPA) and N,N′-bis(2-pyridylmethyl)-N,N′dimethylethane-1,2-diamine (BPMEN) are established catalysts of C–O bond formation, oxidising hydrocarbon substrates via hydroxylation, epoxidation and dihydroxylation pathways. Herein we report the capacity of these catalysts to promote C–N bond formation, via allylic amination of alkenes. The combination of N-Boc-hydroxylamine with either FeTPA (1 mol %) or FeBPMEN (10 mol %) converts cyclohexene to the allylic hydroxylamine (tert-butyl cyclohex-2-en-1-yl(hydroxy)carbamate) in moderate yields. Spectroscopic studies and trapping experiments suggest the reaction proceeds via a nitroso–ene mechanism, with involvement of a free N-Boc-nitroso intermediate. Asymmetric induction is not observed using the chiral tetramine ligand (+)-(2R,2′R)1,1′-bis(2-pyridylmethyl)-2,2′-bipyrrolidine ((R,R′)-PDP). Introduction The selective functionalization of C–H bonds is an area of considerable current research interest [1-5]. The development of methods for catalytic C–H amination has attracted particular attention [6-11], given the significance of C–N bonds to the structures of biologically active natural products and pharmaceuticals. In this context there has been a renewed focus on the chemistry of acylnitroso species in recent times [12-15], in particular on α-hydroxyamination of carbonyl compounds via nitrosocarbonyl aldol reactions [16-21] and allylic hydroxyami- nation of alkenes via nitroso–ene reactions [22-26]. Several new developments in the related hetero-Diels–Alder reaction of acylnitroso species have also been reported recently [27-30]. These methodologies generally involve in situ generation of the acylnitroso species, achieved using a variety of oxidants including vanadium- [28], manganese- [19-21], iron- [23,24], copper- [22,31], rhenium- [26], and rhodium- [27] based reagents. 2549 Beilstein J. Org. Chem. 2015, 11, 2549–2556. The recent resurgence of interest in the nitroso–ene reaction builds on earlier work by Sharpless, Nicolas, Jørgensen and others. Sharpless reported allylic amination of 2-methyl-2hexene with N-(p-chlorophenyl)hydroxylamine using a molybdenum complex [32], a process that was made catalytic by adding excess N-phenylhydroxylamine [33]. The combination of iron(II) phthalocyanines [34,35] or iron(II)/iron(III) chloride [36-38] and N-phenylhydroxylamine effect allylic amination reactions that are believed to follow a nitroso–ene mechanism. Similar reactions have been reported using copper salts and N-phenylhydroxylamine [39] or N-Boc-hydroxylamine [40,41], presumably via oxidation of the hydroxylamine to a nitroso species which then undergoes the nitroso–ene reaction. Stemming from our interest in iron-catalysed hydrocarbon oxidation using systems inspired by the non-heme iron-dependent enzyme family [42-47], we have investigated the capacity of iron complexes of simple tetramine ligands to promote the reaction between an alkene and N-Boc-hydroxylamine. Herein we report that iron complexes of tris(2-pyridylmethyl)amine (TPA, 1) [48,49], N,N′-bis(2-pyridylmethyl)-N,N′-dimethylethane-1,2diamine (BPMEN, 2) [48,50] and (+)-(2R,2′R)-1,1′-bis(2pyridylmethyl)-2,2′-bipyrrolidine ((R,R′)-PDP, 3) [51] (Figure 1) catalyse the allylic amination of cyclohexene. Mechanistic investigations suggest the reaction proceeds via nitroso–ene reaction of the oxidised hydroxylamine and the alkene. Results and Discussion Synthesis of metal complexes The tetramine ligands TPA (1), BPMEN (2) and (R,R′)-PDP (3) were synthesised following literature procedures [48,50,51], then combined with iron(II) triflate as previously reported to generate the complexes [Fe(TPA)(CH3CN)2](OTf)2 (FeTPA, 4) [52], [Fe(BPMEN)(OTf)2] (FeBPMEN, 5) [48] and [Fe(R,R′PDP)(OTf)2] (Fe(R,R′)-PDP, 6) [51]. Allylic amination reactions As an extension of our previously reported iron-catalysed allylic oxidation of cyclohexene (7) [45-47], we wished to explore potential C–N bond formation at this position using iron catalysis. Combining cyclohexene (7, in excess) with N-Bochydroxylamine (8) as the nitrogen source and the iron complex FeTPA (4) or FeBPMEN (5) afforded a mixture of products: the allylic hydroxylamine 9 alongside the Fenton oxidation products alcohol 10 and ketone 11 [53], and a small amount of tertbutyl carbamate (12, Scheme 1). Initial reactions under an argon or air atmosphere returned product mixtures in the ratios shown in Table 1. Scheme 1: Allylic hydroxyamination of cyclohexene (7) using iron catalysts 4 and 5; i. 4 or 5 (10 mol %), BocNHOH (8), CH3CN, rt, 18 h; for yields see Table 1. Under an argon atmosphere, the allylic hydroxylamine 9 was produced in ~10% yield with either ligand; performing the reaction open to air lifted the yield of the allylic hydroxyamination product 9 as high as 40%, but also substantially increased yields of 10 and 11 (Table 1). Control experiments using just the metal salt or each of the ligands on their own returned trace quantities of product 9 and varying levels of Fenton-type pathways (Table S3, Supporting Information File 1), confirming that FeTPA (4) and FeBPMEN (5) are active agents in promoting allylic hydroxyamination of cyclohexene. The effect of catalyst loading was screened under an air atmosphere, since initial results indicated that better yields of 9 are obtained under air than argon. Thus cyclohexene (0.7 mL, 7 mmol, 100 equiv) was added to a solution of catalyst 4 or 5 (1–20 mol %) and BocNHOH (70 μmol, 1 equiv) in CH3CN (Table S4, Supporting Information File 1). Lowering the catalyst loading of FeTPA from 10 to 5 mol % led to a small Figure 1: TPA (1), BPMEN (2) and (R,R′)-PDP (3) ligands. 2550 Beilstein J. Org. Chem. 2015, 11, 2549–2556. Table 1: Catalytic allylic amination of cyclohexene (Scheme 1). Reaction conditions: catalyst 4 or 5 (7 μmol) and cyclohexene (0.7 mL, 7 mmol) were dissolved in CH3CN (total volume 10 mL) and stirred at room temperature under air or argon atmosphere while BocNHOH (8, 70 μmol) was added, then stirring was continued overnight (18 h). Entrya Catalyst mol % Atmosphere 9b,c 10b,c 11b,c 12b,c 1 2 3 4 4 4 5 5 10 10 10 10 argon air argon air 10 27 9 40 5 54 6 32 2 36 2 14 (...truncated)