1,721,116 research outputs found
Functionalization of phospha-thiahelicenes and application of their gold(I) complexes in enantioselective catalysis
No full textHelically chiral structures are known to display peculiar properties and applications in many fields, including asymmetric catalysis. However, both the synthesis of helical phosphorus ligands and their uses in enantioselective organometallic catalysis have been underdeveloped so far [1].
In the course of our studies on helical phosphane derivatives as potential chiral ligands in asymmetric organometallic catalysis [2], we have recently reported the synthesis of a new chiral phospha-thiahelicene based gold (I) complex, which is an excellent and selective pre-catalyst for the enantioselective cycloisomerization of N-tethered enynes [3].
On the basis of these very promising results we have effectively functionalized the phospha-thiahelicene scaffold to obtain new gold (I) complexes, which are then tested as pre-catalysts in other challenging enantioselective cycloisomerization reactions. 1. a) Y. Shen, C.-F. Chen, Chem. Rev. 2012, 112, 1463; b) P. Aillard , A. Voituriez, A. Marinetti, Dalton
Trans. 2014, 43, 15263.
2. a) S. Cauteruccio, A. Loos, A. Bossi, M. C. Blanco Jaimes, D. Dova, F. Rominger, S. Prager, A. Dreuw, E.
Licandro, A. S. K. Hashmi, Inorg. Chem. 2013, 52, 7995; b) K. Yavari, P. Aillard, Y. Zhang, F. Nuter, P.
Retailleau, A. Voituriez, A. Marinetti, Angew. Chem. Int. Ed. 2014, 53, 861.
3. P. Aillard, A. Voituriez, D. Dova, S. Cauteruccio, E. Licandro, and A. Marinetti, Chem. Eur. J. 2014, 20,
12373
Asymmetric transition metal catalysis toward screw-shaped aromatic compounds
No full textThe helix is a widespread chiral geometrical form in nature, and its elegant three-dimensional shape can be associated with different natural items (e.g., the spiral shells of molluscs and snails, the vines entwined with trees, or the left-handed helical tusk of the narwhal). Nature has also selected the homochiral topology for its biological systems at microscopic level, such as the two right-handed helices of DNA and the right-handed helical substructures (i.e., the -helices) in many proteins. Thus, helicity is a fundamental element of molecular chirality, and supramolecular interactions between helices are of outmost importance in molecular biology.1 In the chemist’s synthetic world, one remarkable example of helicity is provided by the helicenes, whose name contains both the prefix "helic-", denoting the nonplanar shape, and the suffix "-enes" indicating the presence of unsaturated system. According to the IUPAC rules, helicenes are polycyclic aromatic or heteroaromatic compounds which contain at least five ortho-fused rings that adopt a nonplanar screw-shaped skeleton due to the steric repulsive interaction between the terminal rings. Because of their nonplanarity, these molecules are chiral and, based on the helicity rule proposed by Cahn, Ingold, and Prelog,2 a left-handed helix is designed "minus" and denoted as M while a right-handed one is designed "plus" and denoted P (Figure 1). Helicenes composed by solely carbocyclic aromatic rings in their structure are defined carbohelicenes, whereas heterohelicenes contain at least one heteroaromatic ring in the screw skeleton (Figure 2).3,4 The introduction of heteroatom(s) in the helical framework significantly affects the geometric parameters and the electronic structure of the helix, providing unique functions and chiroptical response.5,6 The inherent chirality in combination with the extended -conjugated system provide helicenes with outstanding chiroptical properties, and they have been proposed in a plethora of cutting-edge applications, including nonlinear optics, circularly polarized luminescence (CPL) materials, sensors and responsive switches, asymmetric catalysis, and chiral recognition of biomolecules, among other.3,4 Therefore, the search for highly efficient and versatile stereoselective syntheses of structurally diverse helicenes is highly sought after.
Numerous synthetic methodologies for the preparation of carbo and heterohelicenes have been so far reported, and they have played a key role in the progress of the helicene chemistry. Among them, the photocyclo-dehydrogenation of cis/trans stilbene-like molecules is the most common route to helicenes,7,8 even if it often suffers from low regioselectivity in the presence of two different ortho positions in the stilbene substrate, and further oxidative cyclization processes of the formed helicene sometimes occur. Moreover, this approach usually provides racemic helicenes, whose resolution into the corresponding enantiomers is accomplished through expensive and time-consuming chiral HPLC separations.
From this perspective, asymmetric transition metal catalysis represents one of the most straightforward and efficient strategy for the synthesis of enantioenriched molecules, and its application in the asymmetric synthesis of helicenes has attracted much attention in the last two decades.9,10,11
In particular, intra and intermolecular alkyne-based cyclization reactions promoted by transition metal-based catalysts have become a valuable alternative to photochemical processes for the synthesis of (hetero)helicenes, especially in enantioenriched form.11 On the other hand, cycloisomerizations of ortho-alkynylated biaryls and [2+2+2]-cycloadditions of triyne derivatives are versatile, atom economical and group tolerant methods for the synthesis of carbo- and heterocycles, including helicenes and their congeners. These processes involve the formation of several carbon-carbon bonds in a single step and allow enynes and related substrates to be converted into more structurally complex polycyclic products, such as (hetero)helicenes, with both high efficiency and regioselectivity. Noteworthy, the asymmetric version of these alkyne-based cyclizations have also been developed to obtain nonracemic helicenes with high stereoselectivity.
In this contribution, the most representative and recent examples of transition metal catalyzed alkyne-based cyclizations applied to the synthesis of helicenes will be described, with a special focus on the enantioselective synthesis of heterohelicenes through the intramolecular Au-catalyzed alkyne hydroarylation and the transition metal catalyzed [2+2+2]-cycloaddition of triyne derivatives, which represent the most efficient and selective approaches for the asymmetric synthesis of (hetero)helicenes thus far. The challenges and limitations still present for these procedures will be also discussed, taking into account that efforts to develop novel and improved asymmetric synthetic approaches toward (hetero)helicenes will lead to more and more important and advanced applications of these fascinating class of polycyclic aromatic compounds
From the direct C-H arylation of azoles to the synthesis of chiral helical phosphorus ligands: a journey through the eclectic world of the organometallic catalysis
No full textRegio and stereoselective synthesis using organometallic catalysts is currently one of the most active areas of research in organic chemistry. A rapid progress in the study of organometallic and coordination compounds has led to the development and successful industrial application of a number of catalytic processes based on use of these compounds as catalysts. The major advantage of organometallic catalysis is selectivity, and the ability to produce pure products in high yield.
Two different topics in the field of the transition metal complex catalyzed regio and stereoselective organic transformations will be addressed. The first topic will concern the regioselective palladium- and/or copper-mediated direct C-H arylation of π-electron-rich heteroarenes with (hetero)aryl halides. Recently, the transition metal-catalyzed direct arylation of heteroaromatic compounds has emerged as an attractive strategy for the effective construction of aryl–aryl bonds which, unlike the traditional metal-catalyzed cross-coupling strategies involving preformed organometallic reagents, enables direct elaboration of heterocyclic cores without the use of preactivated coupling partners.1 In the second issue, the study of a new class of thiahelicene-based phosphanes as potential innovative chiral ligands in asymmetric organometallic catalysis will be discussed, especially in the homogenous rhodium(I)-catalyzed hydrogenation reactions, and gold(I)-catalyzed cycloisomerizations. Although helicenes displaying phosphorus functions represent promising scaffolds for applications in enantioselective organometallic catalysis,2 to date their uses in this field is still in its infancy, especially in terms of number of compounds as well as structural diversity
Synthesis of diverse classes of thiahelicenes by transition metal-catalysed cross coupling reactions
Full text linkTetrathia[7]helicenes (7-THs) are an attractive class of polyconjugated ortho-fused heteroaromatic compounds, endowed with inherent chirality due to the helical shape of their π-conjugated system.1 Their unique structural and chiroptical properties have stimulated manifold studies in optoelectronics,2 catalysis,3 and biology.4 In our ongoing studies on the synthesis and functionalization of 7-TH systems, we have recently developed an innovative diversity-oriented synthesis of 7-THs exploiting transition metal-catalysed cross coupling reactions as key steps (Figure 1).In this communication we report the synthesis of novel classes of thiahelicenes 1ac starting from the key intermediates 2, from which we can obtain: i) helicenes 1a through Sonogashira coupling with terminal alkynes, followed by In- or Pt-catalysed intramolecular hydroarylation of alkynes 3; ii) helicenes 1b through palladium-catalysed annulation of 2 with internal alkynes; iii) helicenes 1c through Suzuki coupling with (hetero)aryl boronic esters, followed by oxidative photochemical cyclization of intermediates 4
Chiral thiophene-based biaryl systems : synthesis and characterization
No full textThe biaryl motif occupies an iconic role in chemistry, being a key structural feature of natural products, biologically active molecules, drugs, agrochemicals, and other novel optical and mechanical materials. Furthermore, the stereogenic axes provide rigid molecular frameworks for highly efficient tools in asymmetric synthesis.1 Exploiting the experience acquired in our laboratories on the synthesis of compounds based on alternating thiophene and benzene rings2, we have started the study of a simple and efficient synthetic route to prepare bis(benzoditiophenes) system 2, through Pd-catalysed cross coupling reactions, starting from bromide 1.
This strategy provides a convenient approach to an interesting class of chiral atropisomeric biaryl derivatives with C2-symmetry, which are expected to have broad applications in asymmetric reactions, including the enantioselective synthesis of tetrathiahelicene derivatives
Synthesis of 4(5)-aryl-1H-imidazoles and 2,4(5)-diaryl-1H-imidazoles via highly selective palladium-catalyzed arylation reactions
No full textImidazoles aryl substituted in the 4(5)-position are central structures of many compounds which elicit important biological and pharmacological responses. Monosubstituted 4(5)-aryl-1H-imidazoles, for example, include compounds which display good in vitro antifungal activity,1 or are potent inhibitors of -glucosidase2 as well as show antiinflammatory properties.3 On the other hand, 2-alkyl-4(5)-aryl-1H-imidazoles include potent channel blockers4 and several 4(5)-aryl-5(4)-(4-fluorophenyl)-1H-imidazole derivatives are p38 mitogen-activated protein kinase inhibitor.5 As a consequence, much attention has been devoted to the development of efficient procedures for preparation of 4(5)-aryl substituted imidazole derivatives.6 Nevertheless, there are relatively few methods for the synthesis of monosubstituted 4(5)-aryl-1H-imidazoles 1 and disubstituted 2,4(5)-diaryl-1H-imidazoles 2. Moreover, these synthetic protocols suffer from being multistep synthesis, providing modest yields and / or requiring commercially unavailable and / or expensive reagents.7,8 Recently, in the course of our studies on the synthesis of arylazole derivatives,9 we became interested in the development of concise and effective novel approaches for the preparation of compounds of general formula 1 and 2 starting from cheap, commercially available starting materials. In this context, we recently developed a rapid, efficient and general protocol for the synthesis of imidazoles 1, which utilizes a Pd-catalyzed Suzuki-Miyaura type reaction between commercially available 4(5)-bromo-1H-imidazole (3) and arylboronic acids 4 under phase-transfer conditions (Scheme 1). Moreover, we succeeded in preparing several 2,4(5)-diaryl-1H-imidazole derivatives 2 by highly regioselective Pd-catalyzed and Cu-mediated direct C-2 arylation of 4(5)-aryl-1H-imidazoles 1 with aryl bromides and iodides 5 under base-free and ligandless conditions (Scheme 2).It should be noted that we had previously employed similar reaction conditions for the efficient and highly regioselective direct C-2 arylation of a large variety of heteroarenes which included 1-aryl-, 1-methyl- and 1-benzyl-1H-imidazoles, thiazole, oxazole, benzothiazole and free (NH)-imidazole, -benzimidazole and -indole.9a,c-e
In conclusion, we have found that monosubstituted 4(5)-aryl-1H-imidazoles 1 can be efficiently and selectively prepared by PdCl2(dppf)-catalyzed Suzuki-Miyaura reaction of 4(5)-bromo-1H-imidazole (3) with arylboronic acids 4 under phase-transfer conditions. We have also shown that 2,4(5)-diaryl-1H-imidazoles 2 can be obtained in modest to good yields by highly selective Pd- and Cu-mediated C-2 arylation of 4(5)-aryl-1H-imidazoles 1 with aryl iodides and bromides.
In our opinion these simple and convenient synthetic procedures will enable rapid access to a variety of pharmacologically significant imidazole derivatives
Non photochemical route to functionalized thiophene-based [7]helicenes
Full text linkHelicenes are an intriguing class of ortho-annulated polycyclic aromatic or heteroaromatic compounds endowed with inherent chirality owing to the helical shape of their -conjugated system. These curved organic molecules provide unique opportunities for applications in manifold fields, including materials sciences, chiroptical devices, and asymmetric synthesis.1 Among helicenes, thiahelicenes are emerging as one of the most popular class of heterohelicenes thanks to their unique characteristics combining the electronic properties of oligothiophenes, with the chiroptical properties of helical shape molecules.2 For several years, we have been interested in the study of the synthesis and functionalization of thiahelicenes, such as tetrathiahelicene (7-TH) derivatives (Figure), that are configurationally stable and potentially very interesting for applications in optoelectronics,3 catalysis,4 and biology.5 Recently, we have developed a versatile non-photochemical procedure to prepare functionalized thiahelicenes, including a novel class of 7,8-diaryl substituted 7-TH compounds. This strategy involves the synthesis of chiral heterobiaryl derivatives as key intermediates, whose configurational stability have been elucidated in order to design an asymmetric version for the synthesis of enantioenriched thiahelicenes
New synthesis of benzo[1,2-b:4,5-b′]dithiophene (BDT)
Full text linkThiophene-containing polycondensed aromatic compounds are important source of functional organic materials for different applications. Within this class of molecules, benzo[1,2-b:4,5-b′]dithiophene (BDT, figure 1) is recognized as one of the most successful building blocks in the synthesis of highly efficient photovoltaic and semiconducting materials.1 In fact the rigid and planar conjugated structure of BDT makes it attractive for achieving highly tunable molecular energy levels and optical band gaps as well as high hole mobilities. In recent years, benzannulation and thieannulation approaches, involving several steps, have been applied to the synthesis of BDT and of -extended thienoacenes,2 but the search of alternative easy access to this class of heterocycles is always a valuable synthetic target.
We present here a new two-step synthesis of BDT, starting from 3-thiophene carbaldehyde as unique thiophene precursor.
Although the second step of the synthesis needs to be optimized, this new methodology is certainly competitive to the classical approach3 which involves four steps, more expensive reagents and gives a comparable overall yield.
In addition, the use of different hetero/aromatic aldehydes in the reaction with intermediate 2 gives access to a series of thiophene benzocondensed heterocycles
Tetrathiahelicenes: eclectic chiral tools in chemistry and biology
No full textHelicenes, as part of the larger family of helical shaped small molecules, are not only original, aesthetically fascinating, intriguing, flexible chiral systems, but have nowadays reached a high degree of appeal within the scientific community thanks to the association of synthetic challenge to manifold applications that they provide, ranging from nanosciences, chemosensing, material science, asymmetric catalysis and molecular recognition. Among helicenes, tetrathiahelicenes are emerging as the most popular systems, thanks to the remarkable improvements reached in their preparation, and thanks to their unique magnetic, conductive, and optical properties. Other recent interesting applications are emerging in catalysis1 and biology. Such a versatility and eclectic behaviour is closely related to the possibility of obtaining a structural variety still maintaining the defining property of the helical structure.
Over the years, our research group has contributed in a significative manner to the development of efficient methods for the synthesis of the helical scaffold of tetrathiahelicenes and its functionalization with the most diverse functional groups. This research has allowed the access to a class of novel variously substituted tetrathiahelicenes. Among them, we have recently developped chiral helicene-based phosphine and phosphine oxide ligands for application in organic and organometallic catalysis, and some interesting results have already been obtained
Metal-mediated reactions for the heteroaryl-heteroaryl bond formation: non photochemical synthesis of thiahelicenes
No full textTetrathia[7]helicenes (7-TH), are chiral helical-shaped polyaromatic systems containing four thiophene and three benzene rings. They exhibit peculiar electronic and chiroptical properties suitable for applications in optoelectronics [1], biology [2], and catalysis [3]. For these reasons they are emerging as one of the most popular class of chiral helical-shaped molecules. We are deeply involved in the development of these molecules, with a particular focus on innovative synthesis of the helical scaffold through metal-mediated cross-coupling reactions.
In this presentation, our recent studies on the synthesis of 7-TH derivatives using cross-coupling reactions at different stages of the synthetic sequence will be illustrated. The most recent results are reported in the scheme below
- …
