Aziridination of alkenes promoted by iron or ruthenium complexes

Molecules containing an aziridine functional group are a versatile class of organic synthons due to the presence of a strained three member, which can be easily involved in ring-opening reactions and the aziridine functionality often show interesting pharmaceutical and/or biological behaviours. For these reasons, the scientific community is constantly interested in developing efficient procedures to introduce an aziridine moiety into organic skeletons and the one-pot reaction of an alkene double bond with a nitrene [NR] source is a powerful synthetic strategy.Herein we describe the catalytic activity of iron or ruthenium complexes in promoting the reaction stated above by stressing the potential and limits of each synthetic protocol

SYNTHESIS, CHARACTERIZATION AND CATALYTIC ACTIVITY OF IRON, RUTHENIUM AND COBALT PORPHYRIN COMPLEXES

The insertion of a nitrene \u201cRN\u201d 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 singlet\uf0aetriplet interconversion to confer a diradical character to the \u201cArN\u201d ligand. Hence, the activation of the allylic C-H bond of cyclohexene (C6H10) occurs through a C H\u2022\u2022\u2022N adduct detected as a Transition State. The formation of the desired allylic amine follows a \u201crebound\u201d 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 \u3b1 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 1. S. Cenini, E. Gallo, A. Caselli, F. Ragaini, S. Fantauzzi and C. Piangiolino, Coord. Chem. Rev., 2006, 250, 1234-1253. 2. B. C. G. Soderberg, Curr. Org. Chem., 2000, 4, 727-764. 3. T. G. Driver, Org. Biomol. Chem., 2010, 8, 3831-3846. 4. S. Cenini, F. Ragaini, E. Gallo and A. Caselli, Curr. Org. Chem., 2011, 15, 1578-1592. 5. S. Fantauzzi, A. Caselli and E. Gallo, Dalton Trans., 2009, 5434-5443. 6. A. Caselli, E. Gallo, S. Fantauzzi, S. Morlacchi, F. Ragaini and S. Cenini, Eur. J. Inorg. Chem., 2008, 3009-3019. 7. P. Zardi, D. Intrieri, A. Caselli and E. Gallo, J. Organomet. Chem., 2012, 716, 269-274. 8. S. Fantauzzi, E. Gallo, A. Caselli, C. Piangiolino, F. Ragaini and S. Cenini, Eur. J. Org. Chem., 2007, 6053-6059. 9. D. Intrieri, A. Caselli, F. Ragaini, P. Macchi, N. Casati and E. Gallo, Eur. J. Inorg. Chem., 2012, 569-580. 10. D. Intrieri, A. Caselli, F. Ragaini, S. Cenini and E. Gallo, J. Porphyrins Phthalocyanines, 2010, 14, 732-740. 11. D. Intrieri, M. Mariani, A. Caselli, F. Ragaini and E. Gallo, Chem. Eur. J., 2012, 18, 10487-10490. 12. F. Ragaini, A. Penoni, E. Gallo, S. Tollari, C. L. Gotti, M. Lapadula, E. Mangioni and S. Cenini, Chem. Eur. J., 2003, 9, 249-259. 13. G. Manca, E. Gallo, D. Intrieri, C. Mealli; ACS, manuscript submitted 14. D. Intrieri, S. Le Gac, A. Caselli, E. Rose, B. Boitrel, E. Gallo; Chem.Commun.,manuscript submitted

Ballisistic range measurements of the drag and static and dynamic stability of a recoverable space shuttle booster vehicle

An experimental study has been conducted to determine the aerodynamic characteristics of a proposed recoverable space shuttle booster vehicle. Tests were made at Mach numbers of 0.7, 1.5, and 3.5 of two configurations, one with tail panels deflected 90 deg and one with tail panels deflected 70 deg. Both configurations were found to be highly statically stable at all Mach numbers. The dynamic behavior was erratic; the models exhibited both neutral dynamic stability and dynamic instability, and the motions experienced during free flight at the subsonic Mach number were very irregular. The flow field over the models was characterized by an extensive separated flow region which largely encompassed the tail panels. The experimental drag and static stability were not well predicted by available theoretical estimates

Porphyrin-based homogeneous catalysts for the CO 2 cycloaddition to epoxides and aziridines

The direct insertion of carbon dioxide (CO2) into three-membered rings, such as epoxides and aziridines, represents a relevant strategy to obtain cyclic carbonates and oxazolidinones, which are two useful classes of fine chemicals. The synthesis of these compounds can be efficiently catalyzed by a combination of metal porphyrin complexes and various co-catalysts in homogeneous systems. The catalytic efficiency of these systems is discussed herein by taking into account both the characteristics of the metals and the nature of the co-catalysts, either when used as two-component systems or when combined in bifunctional catalysts. Moreover, mechanistic proposals of the CO2 cycloaddition processes are reported to provide a rationale of catalytic cycles in order to pave the way for designing more active and efficient catalytic procedures

Ruthenium Porphyrin Catalyzed Synthesis of Oxazolidin-2-ones by Cycloaddition of CO2 to Aziridines

The reaction between N-substituted-2-arylaziridines and CO2 is efficiently promoted by ruthenium(VI) imidoporphyrin complexes and yields a mixture of 5-aryl (A) and 4-aryl (B) substituted oxazolidin-2-ones with a regioisomeric A/B ratio up to 99:1. Several oxazolidin-2-one molecules were synthesized at 100 \ub0C and 0.6 MPa of carbon dioxide by using the low catalytic loading of 1 mol-%. The formation of a deactivated compound, deriving from the ruthenium catalyst, suggested a possible catalytic role of imido nitrogen atoms

Iron and Ruthenium Glycoporphyrins: Active Catalysts for the Synthesis of Cyclopropanes and Aziridines

In view of the relevance of cyclopropanes and aziridines as synthetic building blocks as well as active parts in biological and pharmaceutical compounds, the development of sustainable synthetic procedures for obtaining these products continues to be a significant challenge. Herein, we report the synthesis of iron and ruthenium glycoporphyrins and their catalytic activity in promoting cyclopropanations and aziridinations by using diazo compounds and aryl azides as carbene and nitrene precursors, respectively. The number and location of carbohydrate units on the porphyrin skeleton modulated the shape- and diastereoselectivity of the reactions. Interestingly, while iron(III) glycoporphyrins showed good performances in alkene cyclopropanations, ruthenium(II) complexes performed better in aziridination reactions. Although none of the reported complexes induced enantiocontrol, probably due to the long distance between the chiral carbohydrate and the active metal center, excellent trans-diastereoselectivities were observed by using iron-glycoporphyrins as cyclopropanation promoters

Synthesis in mesoreactors: Ru(porphyrin)CO-catalyzed aziridination of olefins under continuous flow conditions

The Ru(porphyrin)CO-catalyzed addition of aryl azides to styrenes to afford N-aryl aziridines was successfully performed for the first time in mesoreactors under continuous flow conditions

Catalytic Applications of Pyridine-Containing Macrocyclic Complexes

The introduction of a pyridine moiety into the skeleton of a polyazamacrocyclic ligand affects both the thermodynamic properties and the coordination kinetics of the resulting metal complexes. These features have attracted great interest from the scientific community in recent years. The field of application of pyridine-containing macrocyclic ligands ranges from biology to supramolecular chemistry, encompassing MRI, molecular recognition, materials and catalysis. In this microreview we provide a perspective of the catalytic applications of metal complexes of pyridine-containing macrocycles, including an account of investigations from the authors' laboratories dealing with stereoselective C\u2013C and C\u2013O bond-forming reactions. The increased conformational rigidity imposed by the pyridine ring allowed for the isolation and characterisation of metal complexes in high oxidation states and the study of their relevance in oxidation reactions. On the other hand, the very different conformations accessible upon the metal coordination and the easily tuneable synthesis of the macrocyclic ligands have been exploited in stereoselective synthesis

Site-fidelity and movement patterns of bottlenose dolphins (<i>Tursiops truncatus</i>) in central Argentina: essential information for effective conservation

The effectiveness of conservation measures such as marine protected areas (MPAs) for the conservation of cetaceans is determined by how well their home range or critical habitat is covered. The present study seeks to provide information on the site-fidelity and movement patterns of individual bottlenose dolphins (Tursiops truncatus) in central Argentina. Between 2007 and 2013, photo-identification data of bottlenose dolphins were collected in four study sites some 90-200km apart from each other along the central Argentinean coast. Results show long-term site-fidelity (over 5years) in one of the study areas. Re-sighting rates further suggest the existence of different sub-populations of bottlenose dolphins, but also confirm some connectivity (with movements over 200-290km) and thus potential for gene flow within the region. Considering the population declines of bottlenose dolphins in Argentina, information on site-fidelity and movement patterns will be of value to improve the effectiveness of existing MPAs for the conservation of the species as well as prioritizing areas for increased research

The ligand influence in stereoselective carbene transfer reactions promoted by chiral metal porphyrin catalysts

The 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