Iron complexes amines

The direct reductive amination (DRA) is a useful method for the synthesis of amino derivatives from carbonyl compounds, amines, and H2. Precious-metal (Ru [130-132], Rh [133-137], Ir [138-142], Pd [143]) catalyzed reactions are well known to date. The first Fe-catalyzed DRA reaction was reported by Bhanage and coworkers in 2008 (Scheme 42) [144]. Although the reaction conditions are not mild (high temperature, moderate H2 pressure), the hydrogenation of imines and/or enam-ines, which are generated by reaction of organic carbonyl compounds with amines, produces various substituted aryl and/or alkyl amines. A dihydrogen or dihydride iron complex was proposed as a reactive intermediate within the catalytic cycle. 

Fe(II)-tetrakis-N, N, N, N (2-pytidylmethyl-2-amino-ethyl)amine (Fe-TPEN) and Fe(III)-ttis [N-(2-pyridylmethyl)2-aminoethyl]amine (Fe-TPAA) are novel iron complexes containing lipophilic and neutral ligands. 

The oxidative cyclization of chiral 2-pyrrolidino-l-ethanol derivatives is shown in the reaction of 251 with trimethyl-amine iV-oxide and a substoichiometric amount of cyclohexadiene iron tricarbonyl to produce the corresponding oxazolopyrrolidine ring 252. The mechanism of this reaction is unknown. Both amine oxide and iron complex are essential for the reaction (Equation 39) <2005TL3407>. 

Iron-catalyzed carbonylations, 34 124-125 Fe(CO)5/amine catalysts, 34 124 homologation of methanol, 34 124 proposed mechanism for, 34 125 Iron complexes... 

At the same time the bond angles (C—N—C) at the N7 position vary from 112 (-fp3 as expected for an amine ligand) in the manganese complex (where repulsion is least) up to a maximum value of 120 in the iron complex with maximum repulsions. The tertiary amine nitrogen atom (N7) corresponds to a three-ribbed umbrella that has been inverted by the wind (the handle is the lone pair directed at the metal). As the a, and If levels fill, the repulsions increase, the metal-nitrogen distance increases, and the umbrella begins to flatten ... 

While sluggish under thermal conditions,274-275 the asymmetric conjugate addition of amines to alkyl crotonates is achieved at room temperature under high pressure (15 kbar).276 Thus, benzylamine can be added to the crotonate derived from 8-p-naphthyl menthol, with virtually complete diastereoselectivity. A related intramolecular 1,4-addition of an amine to a chiral enoate was used in a total synthesis of the alkaloid (-)-tylophorine.277 Additions of amines to chiral iron complexes of type (116) proceed with excellent selectivity and allow the preparation of homochiral p-lactams.l27128,l3() l32 In contrast, the addition of amine nucleophiles to chiral vinylic sulfoxides278-2811 and to chiral vinylsulfoximines281 proceeds with comparably low selectivities. 

A notable feature in all these coupling protocols is that the coupling rates of iron-phosphorus systems, of the (salen)iron complex 5, the Fe(acac)3 catalyst, and catalyst 10 with respect to the alkyl halide are rather uncommonly bromide> iodide>chloride (entries 3, 4, 9, 13), whereas the reactivity order for iron-amine catalyst systems is iodide>bromide>chloride (entries 1, 5, 6). 

All these reactions proceed most likely by initial activation of the iron(0) species by a ligand exchange with the activating additives, such as amines, benzonitrile or DMF (Fig. 7). Thus generated mononuclear iron complexes bearing a labile ligand are activated to form coordinatively unsaturated iron complexes 37A. These species reduce the polyhalo compounds to radicals 38A, which add to olefins 30 or 33. 

Iron complexes can also catalyze allylic amination [31,32]. Enders et al. have demonstrated the nucleophilic addition of various acyclic and cyclic amines to the optically active l-methoxycarbonyl-3-methyl-(T)3-allyl)-tetracarbonyliron cation 49 formed in high yield from reaction of 48 with iron carbonyls. Oxidative removal of the tetracarbonyliron group by reaction with CAN gives 50 with high optical purity and retention of the stereochemistry (Eq. (12)) [31]. The reaction proceeds well for the different amines, and has been used for the synthesis of a compound showing cytotoxic activity against diverse cell lines [31b]. 

A variety of different metal complexes have been screened as catalysts for allylic amination using phenyl hydroxylamine 108 as the nitrogen fragment donor, and it was found that iron-complexes have better redox capacity compared to molybdenum [64]. With the iron compounds, higher yields and a lower amount of hydroxylamine-derived byproducts are obtained. These byproducts constitute one of the problems in this type of allylic amination reactions in general, as their formation is difficult to suppress. The allylic amination reaction of a-methyl styrene 112 with 108 can, e.g., be catalyzed by the molybdenum dioxo complex 107, iron phthalocyanine 114, or by the combination of the iron chlorides 115 [64,65]. It appears from the results in... 

Scheme 9 that both the molybdenum and iron complexes can catalyze the allylic amination of nonfunctionalized alkenes with an ene-like transposition of the double bond, but also that the yield of the allyl amine formed, 113, is moderate to high. It is generally found that higher substituted alkenes tend to give the best yields, and un-symmetrical alkenes (trisubstituted) react with virtually complete regioselectivity, as only one isomer is detected. The byproducts are primarily azoxybenzene and aniline, which arise from condensation of nitrosobenzene with phenyl hydroxylamine and reduction of phenyl hydroxylamine, respectively. 

Azepine derivatives form a diene complex with (tricarbonyl)iron, leaving the third of the double bonds uncomplexed. If the 3-position is substituted, two different such complexes are possible and are in equilibrium, as seen in the 11 NMR spectrum. An ester group in the 1-position of the complex can be removed by hydrolysis to give an NH compound that, in contrast to the free 1 //-azcpinc, is stable (Scheme 82). The 1-position can then be derivatized in the manner usual for amines. The same (tricarbonyl)iron complex can, by virtue of the uncomplexed 2,3-double bond, serve as a dienophile with 1,2,4,5-tetrazines. The uncomplexed N-ethoxycarbonylazepine also adds the tetrazine, but to the 5,6-double bond. Thus, two isomeric adducts can be synthesized by using or not using the complex (Scheme 83). 

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