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SYNTHESIS, CHARACTERIZATION AND CATALYTIC ACTIVITY OF IRON, RUTHENIUM AND COBALT PORPHYRIN COMPLEXES
Full text linkThe insertion of a nitrene “RN” functionality into a C-H bond represents a valuable tool achieving a wide variety of nitrogen-containing fine chemicals, which frequently present pharmaceutical and/or biological properties. The key point to perform sustainable amination reactions are:
i) The selection of a selective, active and stable catalytic system
ii) The use of nitrene sources presenting high reactivity and atom efficiency.
The last characteristic is well exhibited by organic azides (RN3)1 which transfer a nitrene functionality to an organic skeleton by yielding eco-friendly N2 as the only stoichiometric by-product. The reaction of RN3 with organic compounds can be thermally or photochemically promoted2 but, to improve the reaction selectivity, the presence of a metal catalyst is required. Amongst the catalysts used to achieve these chemical transformations,3, 4 metal porphyrins show a good catalytic efficiency coupled with a very high chemical stability.5 In the last decade, in our research group, we have studied the efficiency of cobalt6, 7 and ruthenium8 porphyrin complexes in catalysing the amination of a wide class of substrates by using ayl azides as nitrene sources. In this research project we have in-depth investigated the behavior of these catalysts in allylic9, inter10- and intra11 benzilic aminations.
First, we have explored the catalytic activity of Ru(TPP)CO (TPP = dianion of tetraphenylporphyrin) in intermolecular benzylic amination reactions10, several benzylic substrates were reacted with different aryl azides employing the hydrocarbon as the reaction solvent and the catalytic ratio Ru(TPP)CO/azide = 4:50. It was observed that Ru(TPP)CO was also active in the amination of benzylic substrates containing an endocyclic benzylic C-H bond. The corresponding amines have been isolated in good yields.
To investigate the mechanism of the benzylic amination catalyzed by Ru(TPP)CO, a kinetic study was undertaken. The analysis of kinetics and reaction selectivities indicated the formation of an active ruthenium (VI) imido complex as a catalytic intermediate. More in-depth studies will be necessary to better clarify the reaction mechanism of the amination of benzylic C-H bonds.
Since Ru(TPP)CO has demonstrated to be a good catalyst in benzylic amination reactions we have subsequently studied the activity of this catalyst in allylic amination reactions9. Believing that an important step for the improvement of the catalytic efficiency of the reported methodology is the comprehension of the reaction mechanism, we first studied the catalyst reactivity towards the components of a model reaction, cyclohexene and azide. No catalyst modification was observed by 1H NMR when Ru(TPP)CO was suspended in cyclohexene and refluxed for a couple of hours, on the other hand, the reaction between Ru(TPP)CO and an 3,5(CF3)2C6H3N3 excess yielded the bis imido complex Ru(TPP)(NAr)2 which showed a catalytic activity similar or even better than that described for Ru(TPP)CO, his precursor.
To assess if the formation of a bis-imido complex is a general reaction, we have also studied the reactivity of Ru(TPP)CO towards other aryl azides discovering that the nature of the active intermediate strongly depends on the electronic nature of the employed azide. We discovered the formation of another bis-imido complex in the reaction of Ru(TPP)CO with 4 CF3C6H4N3 but several experimental evidences indicate also the existence of a mono-imido ruthenium (IV) intermediate. This mono-imido complex can react with another molecule of aryl azide generating the bis-imido complex, or can form the complex Ru(TPP)(ArNH2)CO by hydrogen atom abstraction reactions.
To shed some light into the Ru(TPP)CO catalysed allylic amination of cyclohexene, a kinetic study was undertaken employing two different arylazides as nitrogen source: 4 CF3C6H4N3 and 3,5-(CF3)2C6H4N3. In the first case the observed kinetics indicates the rate determine step of the reaction being the formation of the mono-imido complex that very quickly reacts with the olefin forming the allylic amine and regenerating Ru(TPP)CO. We suggest that Ru(TPP)CO is in equilibrium with the mono-amino complex for the presence of the aniline as reaction side-product. In the second case the kinetic was more complex than the previous discussed, in fact, the first order dependence was observed only for low concentrations of olefin. This behaviour indicates the coexistence of at least two mechanisms that contemporaneously occur with the prevalence of one or the other depending on the olefin concentration.
The existence of two mechanisms was also supported by a DFT investigation.13 The theoretical study confirms that the first step of the cycle is the formation of a mono-imido complex RuIV(TPP)(NAr)(CO) which can undergo a singlettriplet interconversion to confer a diradical character to the “ArN” ligand. Hence, the activation of the allylic C-H bond of cyclohexene (C6H10) occurs through a C H•••N adduct detected as a Transition State. The formation of the desired allylic amine follows a “rebound” mechanism in which the nitrogen and carbon atoms radicals couple to yield the organic product. The release of the allylic amine restores the initial Ru(TPP)(CO) complex and allows the catalytic cycle to resume by the activation of another azide molecule. On the singlet PES, the CO ligand may be however dismissed from the mono-imido complex RuIV(TPP)(NAr)(CO)SN opening the way to an alternative catalytic cycle which also leads to allylic amine through comparable key steps. A second azide molecule occupies the freed coordination site of Ru(TPP)(NAr)SN to form the bis-imido complex Ru(TPP)(NAr)2, which is also prone to the intersystem crossing with the consequent C-H radical activation. The process continues till the azide reactant is present. The interconnected cycles have similarly high exergonic balances.
The reaction scope of the benzylic amination has been then explored studying the intramolecular amination reaction of biphenyl azides containing benzylic C-H bonds.11 This reaction allows the synthesis of N heterocyclic compounds such as dihydrophenanthridines and phenanthridines. Phenanthridines are an important class of compounds from a biological point of view. They present a significant antitumor activity and are the basis of DNA-binding. Several challenges remain to be overcome to efficiently synthesise this class of molecules, in fact, whilst many methods to access five-membered rings are known, methodologies to yield six and seven-nitrogen membered rings in few steps remain rare.
In this research project we have also studied the development of new synthetic methodologies to obtain new porphyrin frameworks and this part of my work has been developed in collaboration with Dr. Bernard Boitrel (University of Rennes, France). Some years ago we reported on the catalytic efficiency of chiral cobalt(II)-binaphthyl porphyrins in asymmetric cyclopropanations, and recorded positive data encouraging us to synthesise a structurally related chiral porphyrin.
This new porphyrin has one C2 axis within the porphyrin plane and exhibits an open space on each side for substrate access and at the same time a steric chiral bulk surrounding the N-core. The reaction of the opprhyrin with FeBr2 afforded the FeIII(OMe) complex by the initial formation of the iron (II) porphyrin complex which was oxidised by the atmospheric oxygen in the presence of CH3OH yielding the desired complex in a quantitative yield. The catalytic activity of the iron complex was initially tested in the model reaction of α methylstyrene with ethyl diazoacetate (EDA).
This new chiral iron porphyrin-based catalyst performed olefin stereoselective cyclopropanations with excellent yields (up to 99%), enantio- and diasteroselectivities (eetrans up to 87%, trans/cis ratios up to 99:1) and outstanding TON and TOF values (up to 20,000 and 120,000/h respectively).
To the best of our knowledge, the outstanding values of TON and TOF (20,000 and 120,000/h respectively) have never been reported for metallo-porphyrin catalysed cyclopropanations and the robustness of the catalyst under an inert atmosphere allowed three catalytic recycles. Finally, high cyclopropane yields were obtained without using an olefin excess in accordance with the industrial request for sustainable processes, especially when expensive olefins are involved. Studies are ongoing to expand the reaction scope, including testing the cyclopropanation of several olefins by differently substituted diazo derivatives.
References
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Iron(II) bromide
No full textAlternate Names: ferrous bromide. Physical Data: d 4.63g mL−1 at 25 ◦C; bp 934 ◦C; mp 684 ◦C; yellow-brown solid. Solubility: soluble in water, methanol, ethanol, and tetrahydrofuran. Form Supplied in: commercially available either as 99.999% anhydrous solid material or with a 98% purity grade. Preparative Methods: the reaction of iron powder (10.0 g) with hydrogen bromide (45.0ml) in methanol (100.0ml) under N2 followed by the solvent evaporation yields dimethanol solvate salt, which can be converted into anhydrous FeBr2 if heated at 160 ◦C for 4 h under reduced pressure (40% yield). Note that iron(II) bromide cannot be formed by reacting metallic iron with either hydrobromidic acid or bromine due to the preferred formation of iron(III) bromide. Handling, Storage, and Precautions: handle the title compound under a laboratory fume hood while wearing personal protective equipment such as a dust mask, eye shields, gloves, and a laboratory coat. Hygroscopic. Keep the container firmly closed in a dry and well-ventilated place. Incompatible with alkali metals, such as potassium, sodium, strong oxidant agents, and strong acids. Iron(II) bromide can cause severe skin and eye damage and may cause respiratory irritation. In case of exposure to skin, immediately flush with plenty of water for at least 15 min; in case of exposure to eyes, irrigate well with water for at least 30min. Get medical assistance immediately
Recent advances in C-H bond aminations catalyzed by ruthenium porphyrin complexes
No full textThis review deals with the use of ruthenium porphyrin complexes to catalyze hydrocarbon aminations. This class of versatile porphyrin catalysts are able to activate different nitrogen sources, such as iminoiodinanes and organic azides, and promote the synthesis of a variety of aza-derivatives. Many synthetic procedures have been discussed as well as catalytic mechanisms involved in order to give an overview on the use of ruthenium porphyrins to promote nitrene transfer reactions yielding aminated derivatives
The ligand influence in stereoselective carbene transfer reactions promoted by chiral metal porphyrin catalysts
Full text linkThe use of diazo reagents of the general formula N2C(R)(R1) as carbene sources to create new C-C bonds is of broad scientific interest due to the intrinsic sustainability of this class of reagents. In the presence of a suitable catalyst, diazo reagents react with several organic substrates with excellent stereo-control and form N2 as the only by-product. In the present report the catalytic efficiency of metal porphyrins in promoting carbene transfer reactions is reviewed with emphasis on the active role of the porphyrin skeleton in stereoselectively driving the carbene moiety to the target substrate. The catalytic performances of different metal porphyrins are discussed and have been related to the structural features of the ligand with the final aim of rationalizing the strict correlation between the three-dimensional structure of the porphyrin ligand and the stereoselectivity of carbene transfer reactions
The Catalytic efficiency of Free-Base Porphyrins in promoting the N-Aryl oxazolidinones synthesis
Full text linkBetween other applications oxazolidinones are largely used as intermediates as well as chiral auxiliaries in organic synthesis1 and constitute a class of new antibacterial and antibiotics,2-7 the best pharmaceutical performances are usually observed for N-aryl oxazolidin-2-ones (NAOs), such as Linezolid,8 Tedizolid9 and Toloxatone,10 that are FDA-approved drugs. One of the most interesting methodologies for the synthesis of NAOs is the CO2 cycloaddition to aziridines in order to use this greenhouse gas as a renewable C1 synthetic building block. Recently, we have reported a ruthenium porphyrin-based catalytic procedure for synthesising N alkyl oxazolidin-2-ones11,12 and, during our efforts to extend the same procedure to the synthesis of NAOs, we discovered that this reaction was efficiently promoted by the very convenient TPPH2/TBACl catalytic system (TPPH2=tetraphenyl porphyrin; TBACl=tetrabutyl ammonium chloride). Here, we report the optimization and study scope of the synthesis of N aryl oxazolidin-2-ones, which were obtained either by reacting CO2 with purified N aryl aziridines or by applying a two-steps procedure. The latter methodology consists in the Ru(TPP)CO-catalysed synthesis of N-aryl aziridines that were converted into corresponding NAOs by the TPPH2/TBACl-catalysed cycloaddition of CO2.
1. Z. Vahideh and M. H. Majid, Current Organic Synthesis, 2018, 15, 3-20.
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4. A. Bhushan, N. J. Martucci, O. B. Usta and M. L. Yarmush, Expert Opinion on Drug Metabolism & Toxicology, 2016, 12, 475-477.
5. C. Roger, J. A. Roberts and L. Muller, Clinical Pharmacokinetics, 2018, 57, 559-575.
6. M. Nasibullah, F. Hassan, N. Ahmad, A. R. Khan and M. Rahman, Advanced Science, Engineering and Medicine, 2015, 7, 91-111.
7. K. Michalska, I. Karpiuk, M. Król and S. Tyski, Bioorg. Med. Chem., 2013, 21, 577-591.
8. A. Zahedi Bialvaei, M. Rahbar, M. Yousefi, M. Asgharzadeh and H. Samadi Kafil, J. Antimicrob. Chemother., 2017, 72, 354-364.
9. D. McBride, T. Krekel, K. Hsueh and M. J. Durkin, Expert Opinion on Drug Metabolism & Toxicology, 2017, 13, 331-337.
10. F. Moureau, J. Wouters, D. P. Vercauteren, S. Collin, G. Evrard, F. Durant, F. Ducrey, J. J. Koenig and F. X. Jarreau, European Journal of Medicinal Chemistry, 1992, 27, 939-948.
11. D. Carminati, E. Gallo, C. Damiano, A. Caselli and D. Intrieri, Eur. J. Inorg. Chem., 2018, 2018, 5258-5262.
12. D. Intrieri, C. Damiano, P. Sonzini and E. Gallo, J. Porphyrins Phthalocyanines, 2019, 23, 305-328
DFT mechanistic proposal of the ruthenium porphyrin-catalyzed allylic amination by organic azides
No full textA DFT-based theoretical analysis describes the allylic amination of cyclohexene by 3,5(CF3)2phenylazide
catalyzed by [Ru](CO) ([Ru]= Ru(TPP), TPP = dianion of tetraphenylporphyrin). The activation of an azide molecule (RN3) at the free ruthenium coordination site allows the formation of a monoimido complex [Ru](NR)(CO) with the eco-friendly dismissal of a N2 molecule. The monoimido complex can undergo a singlet→triplet interconversion to confer a diradical character to the RN ligand. Hence, the activation of the allylic C−H bond of cyclohexene (C6H10) occurs through a C−H···N interaction over the transition state. The formation of the desired allylic amine follows a “rebound” mechanism in which the nitrogen and carbon atom radicals couple to yield the organic product. The release of the allylic amine restores the initial [Ru](CO) complex and allows the catalytic cycle to resume by the activation of another azide molecule. On the singlet PES, the CO ligand may however be eliminated from the monoimido complex [Ru](NR)(CO)S, opening the way to an alternative catalytic cycle which also leads to allylic amine through comparable key steps. A second azide molecule occupies the vacant coordination site of [Ru](NR)S to form the bis-imido complex Ru(TPP)(NR)2, which is also prone to the intersystem crossing with the consequent C−H radical activation. The process continues until the azide reactant is present. The interconnected cycles have similarly high exergonic balances. Important electronic aspects are highlighted, also concerning the formation of experimentally observed byproducts
Co(porphyrin)-catalysed amination of 1,2-dihydronaphthalene derivatives by aryl azides
No full textCo(porphyrin) complexes promote an unusual reactivity of dihydronaphthalene towards several aryl azides. The reaction affords the benzylic amine of tetrahydronaphthalene instead yielding the amine of dihydronaphthalene as it normally happens in the presence of Ru(porphyrin)CO catalysts. The amination process occurs with the concomitant reduction of the dihydronaphthalene double bond probably due to the high reactivity of the endocyclic CC bond coupled with the good hydrogen donor capability of dihydronaphthalene. Two mechanisms for this reaction are proposed
[Ru(TPP)CO]-Catalysed Intramolecular Benzylic C-H Bond Amination, Affording Phenanthridine and Dihydrophenanthridine Derivatives
No full textShedding light on azides: [Ru(TPP)CO] (TPP=tetraphenyl porphyrin dianion), white light and O 2 were found to be a suitable catalyst combination to perform the annulation of several biaryl azides (see scheme). The high chemoselectivity of the process allows the synthesis of phenanthridines and dihydrophenanthridines in good yield and purity
Cyclopropanation Reactions Mediated by Group 9 Metal Porphyrin Complexes
No full textThe one pot reaction of diazocompounds with olefins represents a useful strategy to synthesise cyclopropanes, which are important both for their employment as organic starting materials and their intrinsic pharmaceutical properties. Herein we describe the catalytic activity of group 9 metal porphyrin complexes to cyclopropanate olefins that present different electronic behaviour. All the most important porphyrin-based methodologies have been reviewed stressing the stereocontrol of the reactions achieved in each case. Moreover, mechanism investigations have provided data that can help greatly to elaborate more efficient catalytic systems in the future
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