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We have developed a practical method to perform the reductive photocleavage of sulfonamides using thioureas as organophotocatalysts. This transformation, which tolerates a variety of substrates, occurs under mild reaction conditions in the presence of tetrabutylammonium borohydride as a reducing agent. Experimental and theoretical mechanistic investigations complete the study, shedding light on the nature of the active species involved in the photocatalytic process.

International audience; Due to their unique three-dimensional framework and intriguing electronic properties, [2.2]paracyclophanes (pCps) have been employed over the years as building blocks in materials science for the development of organic light-emitting diodes and non-linear optical systems. In addition, depending on their substitution patterns, [2.2]paracyclophanes can display planar chirality and are nowadays considered as useful scaffolds for the development of original circularly poliarized luminescence (CPL) emitters. This perspective gives an overview on the synthesis and characterization of different families of compact luminescent compounds derived from planar chiral [2.2]paracyclophanes. The chiroptical properties of these small molecules are described, with a particular focus on their ability to emit circularly polarized luminescence in solution. Some future prospects on the design and potential applications of CPL emitters derived from pCps are finally presented.

In recent years, spirocycles have been the focus of medicinal chemistry, and several drugs or drug candidates incorporating these “non-planar” chemical motifs have been developed. New advancements in this field, however, are greatly limited by the lack of innovative methods enabling the preparation of original spirocyclic cores. Here-in, an unprecedented intramolecular Buchwald-Hartwig N-arylation of bicyclic hydrazines is described. This key reaction gives access to unique spiro[indoline-2,3'-piperidine] derivatives after reductive cleavage of the nitro-gen–nitrogen bond. This approach widens the chemical space of spirocycles and may reveal useful to explore new avenues of research in drug discovery.

Targeting RNAs with small molecules is considered the next frontier for drug discovery. In this context, the development of compounds capable of binding RNA structural motifs of low complexity with high affinity and selectivity would greatly expand the number of targets of potential therapeutic value. In this study, we demonstrate that tuning the three-dimensional shape of promiscuous nucleic acid binders is a valuable strategy for the design of new selective RNA ligands. Indeed, starting from a known cyanine, the simple replacement of a phenyl ring with a [2.2]paracyclophane moiety led to a new compound able to discriminate between nucleic acids showing different structural characteristics with a marked affinity and selectivity for an octahairpin loop RNA sequence. This shape modification also affected the

This short review focuses on enantiopure planar chiral [2.2]paracyclophanes (pCps), a fascinating class of molecules that possess an unusual three-dimensional core and intriguing physicochemical properties. In the first part of the review, different synthetic strategies for preparing optically active pCps are described. Although classical resolution methods based on the synthesis and separation of diastereoisomeric products still dominate the field, recent advances involving the kinetic resolution of racemic compounds and the desymmetrization of meso derivatives open up new possibilities to access enantiopure key intermediates on synthetically useful scales. Due to their advantageous properties including high configurational and chemical stability, [2.2]paracyclophanes are increasingly employed in various research fields, ranging from stereoselective synthesis to material sciences. The applications of [2.2]paracyclophanes in asymmetric organocatalysis are described in the second part of the review. While historically enantiopure pCps have been mainly employed by organic chemists as chiral ligands in transition-metal catalysis, these compounds can also be used as efficient catalysts in metal-free reactions and may inspire the development of new transformations in the near future.

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International audience; We describe the synthesis and photophysical characterization of differently substituted planar chiral analogues of PRODAN based on a [2.2]paracyclophane scaffold. This experimental and theoretical study highlights that the (chir)optical properties of the new "phane" compounds, which incorporate an electron-withdrawing propionyl moiety and an electron-donating dimethylamino group at their para or pseudo Para positions, strongly depend on their substitution patterns. In particular, for this series of molecules, a more pronounced solvatochromism and clear chiroptical behaviors are observed when the two substituents are placed on the two rings of the pCp core in a non-"co-planar" arrangement (pseudo Para derivative). This observation may help design new pCp-based luminophores with finely tuned photophysical properties.

We report herein a general, practical method based on asymmetric transfer hydrogenation (ATH) to control the planar chirality of a range of substituted [2.2]paracyclophanes (pCps). Our strategy enabled us to perform both the kinetic resolution (KR) of racemic compounds and the desymmetrization of centrosymmetric meso derivatives on synthetically useful scales. High selectivities (up to 99% ee) and good yields (up to 48% for the KRs and 74% for the desymmetrization reactions) could be observed for several poly-substituted paracyclophanes, including a series of bromine-containing molecules. The optimized processes could be run up to the gram scale without any loss in the reaction efficiencies. Because of its broad applicability, the ATH approach appears to be the method of choice to access planar chiral pCps in their enantiopure form.

International audience; In this article, we report the preparation of a series of [2.2]paracyclophane-fused coumarin systems through a simple and general procedure involving a transition-metal-catalyzed cyclization of aryl alkynoates as the key step. We also highlight the influence of the [2.2]paracyclophane (pCp) motif and its "phane" interactions on the spectroscopic properties of the newly synthesized fluorophores, which emit in the blue-green region of the visible spectrum (lambda(em), up to 560 nm) and show extremely large Stokes shifts (up to 230 nm). Finally, we demonstrate that our straightforward approach can easily be used to access optically active planar chiral 3D coumarins. Compared to previously described fluorescent paracyclophanes and other organic dyes, our compact heteroaromatic derivatives show promising chiroptical properties, both in term of circular dichroism (g(abs) similar to 8 x 10(-3)) and circularly polarized luminescence (g(lum) similar to 5 x 10(-3)), thus demonstrating a practical application of our synthetic method.

Organoaluminum derivatives are mostly appreciated for their Lewis acidity properties, but generally not considered as reagents of choice in synthetic transformations involving the creation of C–C bonds. Among these species, dimethylalkynylaluminum reagents represent a special class of compounds, with, in many cases, unique reactivity. This review summarizes the preparation and reactivity of these organometallic reagents with a focus on their synthetic potential.1 Introduction2 Preparation of Dimethylalkynylaluminum Reagents3 Reactivity of Dimethylalkynylaluminum Reagents3.1 Reactions with Csp3 Electrophiles3.2 Reactions with Csp2 Electrophiles4 Transition-Metal-Catalyzed Reactions4.1 Addition to α,β-Unsaturated Enones4.2 Coupling Reactions5 Triple Bond Reactivity6 Conclusion

Herein we wish to report a new non-enzymatic kinetic resolution of racemic 4-formyl[2.2]paracyclophane based on Noyori asymmetric transfer hydrogenations (KR-ATH). Our approach, which provides an efficient access to enantiopure (Rp)- and (Sp)-4-formyl[2.2]paracyclophane (>99% ee, 39% and 41% isolated yields, respectively), is operationally simple and can be run on the gram-scale thus confirming the practical applicability of this method.

International audience; Herein we describe the desymmetrization of a centrosymmetric pseudo-para-diformyl[2.2]paracyclophane based on Noyori asymmetric transfer hydrogenations (ATH). The reduction proceeds smoothly in the presence of commercially available ruthenium complexes to afford a monohydroxymethylated product in good yields and excellent enantioselectivities (up to 74% isolated yield and 99% ee). Our approach is operationally simple and can be run in gram-scale without any significant loss in the reaction efficiency. This desymmetrization strategy allows an easy access to an enantiopure compound bearing on each aromatic ring of the pCp core different reactive groups suitable for regioselective orthogonal postfunctionalization. T he compound [2.2]paracyclophane (pCp) and its derivatives constitute a well-known class of aromatic compounds characterized by an unusual three-dimensional framework and unique through-space interactions between their stacked aromatic subunits. 1 First discovered in the late 1940s, 2 these molecules find nowadays wide applications in material sciences for the development of through-space conjugated polymers 3 and optoelectronic devices. 4 Substituted paracyclophanes can show planar chirality due to their rigid structure which hinders the rotation of their two benzene rings. 5 This characteristic recently proved to be particularly useful for the application of pCps as chiral inductors in asymmetric catalysis and stereoselective synthesis. 1,6 Enantiopure paracyclophanes are also increasingly employed as building blocks for the development of circularly polarized light-emitting materials. 7 Over the years, optically active paracyclophanes have mostly been prepared by classical stoichiometric resolution methods and/or chromatographic separation on chiral stationary phases. 8 On the contrary, only few catalytic procedures for accessing enantioenriched pCps have been reported in the literature so far. 9 The development of new catalytic asymmetric processes allowing an efficient synthesis of planar-chiral paracyclophane derivatives is therefore highly desirable in order to expand the range of application of these molecules in different research areas. Recently, we were able to demonstrate that catalytic kinetic resolutions of racemic pCps could be employed to efficiently access valuable synthetic intermediates in their enantiopure form (Scheme 1a). 10 In order to overcome the limitation of 50% yield associated with the resolution strategy, 11 our efforts are currently directed toward the preparation of enantiopure pCp key intermediates through scalable desymmetrization reactions. The classical desymmetrization approaches involve asym-metric transformations capable of differentiating the enantio-topic functional groups of meso compounds with internal

International audience; In this work we report a straightforward method for the synthesis of a new class of small organic fluorophores bearing both [2.2]paracyclophane and naphthalene subunits using an intramolecular dehydrogenative Diels-Alder reaction as a key step. These compounds are characterized by a compact three-dimensional structure as well as through-space conjugated push-pull systems, and possess interesting spectroscopic characteristics that may be useful for the development of innovative chemical probes and optical sensors. Since the discovery of their parent compound in 1949, 1 mono-and polysubstituted [2.2]paracyclophane derivatives (pCp) have attracted increasing attention within the scientic community and have become the object of many studies in the last few decades. Initial investigations on the synthesis and derivatization of [2.2]paracyclophanes mainly aimed at disclosing the unusual reactivity of these molecules. 2 More recently, functionalized pCps have emerged as powerful ligands or auxiliaries in asym-metric catalysis and stereoselective synthesis. 3 Substituted paracyclophanes also found applications in material sciences as monomers for the synthesis of through-space conjugated polymers , 4 or for the production of functionalized surfaces using chemical vapor deposition (CVD) methods. 5 Due to their uncommon electronic structure, [2.2] paracyclophanes display intrinsic uorescence and can be employed to access new organic dyes. Accordingly, a wide range of pCp-based stilbene uorophores have been reported in the literature over the past few years. 6 These molecules typically present a "branched" p-extended three-dimensional structure functionalized with differently substituted para-phenylene vinylene subunits (Fig. 1a). The pCp-based stilbene uo-rophores, whose photophysical properties are generally tuned by introducing electron-donating or electron-withdrawing groups on their alkene moieties, revealed to be particularly useful in solid state application for the development of organic light-emitting diodes (OLEDs), 7 and non-linear optical materials. 8 A different approach to modulate the spectroscopic characteristics of the pCp-based uorophores consists in expanding the benzene rings of [2.2]paracyclophane to functionalized poly-condensed aromatic hydrocarbons. This should lead to more compact dyes potentially useful for the design of innovative chemical probes and biosensors. Surprisingly, this approach has only been scarcely investigated up to now. 9 In this context, our group recently became interested in the possibility to incorporate naphthalene p-conjugated frameworks (Fig. 1b) into one of the aromatic decks of pCp to tune their photophysical properties. 10 We therefore decided to focus our attention on the elaboration of pCp-based naphthalene frameworks (Fig. 1c) by an intramolecular dehydrogenative-Diels-Alder (DDA) reaction. This strategy was reported to be particularly versatile for the synthesis of tunable sol-vatochromic uorophores, 11 but has never been described on pCp. The DDA precursors 4a-h were prepared in three steps starting from differently substituted 4-formyl-[2.2] Fig. 1 (a) Structure of pCp-based stilbene fluorophores. (b) General structure of two-dimensional naphthalene systems. (c) Structure of pCp-based naphthalene fluorophores.

International audience; Mirror mirror on the wall: By taking advantage of the unique structural features of L-DNA, the first examples of left-helical enantioselective induction in the field of DNA-based asymmetric catalysis were realized. Most importantly, this approach is the only one that allows a reliable and predictable access to both enantiomers for any given reaction.

The synthesis and utility of attachable cyclopenta[b]naphthalene solvatochromic fluorophores related to Prodan are described. Two fluorophores were selected for functionalization and bioconjugation studies. The skeletons were chemically modified to include reactive functional groups and showed minimal alteration of the optical properties when compared to the parent dyes. The functionalized fluorophores were covalently attached to the carboxyl group of a fatty acid, and azido- and thiol-containing amino acids, demonstrating their potential for labeling biomolecules.

A new process for the synthesis of dimethylalkynylaluminum reagents under flow conditions is described. It involves a base-catalyzed alumination of terminal alkynes using a resin-supported organocatalyst. Final organometallic species are obtained in solution, and can further react with various aldehydes or nitrones.

Herein we wish to report a new non-enzymatic kinetic resolution of racemic 4-formyl[2.2]paracyclophane based on Noyori asymmetric transfer hydrogenations (KR-ATH). Our approach, which provides an efficient access to enantiopure (Rp)- and (Sp)-4-formyl[2.2]paracyclophane (>99% ee, 39% and 41% isolated yields, respectively), is operationally simple and can be run on the gram-scale thus confirming the practical applicability of this method.

International audience; To date, the concept of DNA-based asymmetric catalysis has been successfully applied to various synthetic transformations by way of hybrid catalysts involving either an intercalator or an integrated ligand anchored through supramolecular interactions. We report here a new anchoring strategy based on the well-known groove-binder Hoechst 33258. The interaction between calf thymus DNA (ct-DNA) and poly[d(A-T)(2)] with a series of Hoechst 33258-derived ligands was studied by UV-vis absorption spectroscopy, thermal melting analysis, fluorescence emission, CD spectroscopy, mass spectrometry, and molecular docking. The results clearly show that a groove-binding anchoring strategy can be envisioned for DNA-based asymmetric catalysis, offering additional mechanistic insight on how the intrinsic chirality of DNA can be transferred to a reaction product. Most importantly, this new anchoring strategy offers interesting compartmentalization possibilities and provides a new way to reverse the enantioselectivity outcome of a given reaction.

International audience; Polyketides are a fascinating class of natural products with highly diverse, often complex structures combined with a likewise impressive breath of strong and selective biological activities. This chapter discusses the logic of biosynthetic polyketide assembly. It focuses on the introduction of the basic mechanisms and concepts of polyketide core structure assembly using a number of well-studied representative examples, thus allowing to compare the biosynthetic versus chemical synthetic strategies to assemble such beautiful small molecules. Despite the structural diversity of polyketide natural products, there are only few different catalytic domains facilitating a small number of basic reactions common to all types of PKSs that are crucial for product biosynthesis. The structural and functional space covered by bioactive small molecules is further expanded by post-PKS functionalization reactions catalyzed by so-called tailoring enzymes. This includes reorganization of the entire PKS core but also subtle changes by group transfer reactions or oxidative transformations.

International audience; The recent development of biohybrid catalytic systems has allowed synthetic chemists to reach high levels of selectivity on a wide variety of valuable synthetic transformations. In this context, DNA-based catalysts have emerged as particularly appealing tools. Interestingly, while long RNA sequences (ribozymes) are known to catalyse specific biochemical reactions with remarkable efficiencies, RNA-based catalysts involving a catalytically active metal complex interacting in a non-covalent fashion with short sequences have never been evaluated to date. We report here our results, which have led to the first example involving a short RNA-based catalyst.

The synthesis and photophysical properties of a series of naphthalene-containing solvatochromic fluorophores are described within. These novel fluorophores are prepared using a microwave-assisted dehydrogenative Diels-Alder reaction of styrene, followed by a palladium-catalyzed cross coupling reaction to install an electron donating amine group. The new fluorophores are structurally related to Prodan. Photophysical properties of the new fluorophores were studied and intriguing solvatochromic behavior was observed. For most of these fluorophores, high quantum yields (60-99%) were observed in methylene chloride in addition to large Stokes shifts (95-226 nm) in this same solvent. As the solvent polarity increased, so did the observed Stokes shift with one derivative displaying a Stokes shift of ~300 nm in ethanol. All fluorophore emission maxima, and nearly all absorption maxima were significantly red-shifted when compared to Prodan. Shifting the absorption and emission maxima of a fluorophore into the visible region increases its utility in biological applications. Moreover, the cyclopentane portion of the fluorophore structure provides an attachment point for biomolecules that will minimize disruptions of the photophysical properties.

(Pentamethylcyclopentadienyl)iridium di- I chloride dimer {[IrCp*Cl2]2}-catalyzed hydroalkoxylation of bis-homopropargylic alcohols provides an efficient access to dioxabicyclo[2.2.1]ketals. The cycloisomerizations proceed under mild conditions, with low catalytic loadings and short reaction times. This new protocol involving an Ir(III) catalyst also promoted the cycloisomerization of nitrogen-tethered 1,6-enynes to give azabicyclo[4.1.0]heptenes, enhancing the synthetic potential of our method.

The gold(I)-catalyzed cycloisomerization of β-allenylhydrazones provides an efficient access to multisubstituted N-aminopyrroles, which are obtained in good to excellent yields. This new intramolecular cyclization method can be applied either to alkyl- or aryl-substituted allenes. The reaction proceeds under mild conditions with short reaction times through a selective intramolecular 1,2-alkyl or -aryl migration extending the general scope of the reaction.

Recognition and sensing of various biologically relevant species using boronic acid-based chemosensors have become increasingly popular over the last few years. Herein, we describe a new convenient method for monitoring boronic acid-diol interactions in aqueous media based on (19)F NMR spectroscopy with fluorinated boronic acid probes.

The challenge in DNA-based asymmetric catalysis is to perform a reaction in the vicinity of the helix by incorporating a small-molecule catalyst anchored to the DNA in a covalent, dative, or non-covalent yet stable fashion in order to ensure high levels of enantio-discrimination. Here, we report the first generation of a DNA-based catalyst bound to a cellulose matrix. The chiral biomaterial is commercially available, trivial to use, fully recyclable and produces high levels of enantioselectivity in various Cu(II)-catalyzed asymmetric reactions including Friedel–Crafts alkylations and Michael additions. A single-pass, continuous-flow process is also reported affording fast conversions and high enantioselectivities at low catalyst loadings thus offering a new benchmark in the field of DNA-based asymmetric catalysis.

publisher: Elsevier articletitle: Recent developments in alkyne borylations journaltitle: Tetrahedron articlelink: http://dx.doi.org/10.1016/j.tet.2014.06.026 content_type: article copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

International audience; Within the past few decades, organoboron derivatives have become essential intermediates in organic and medicinal chemistry. As a matter of fact, while boronic acids have found wide applications as saccharide sensors1, 2 and 3 self-organizing systems,4, 5, 6 and 7 and medicine,8, 9 and 10 the unique reactivity of the C–B bond has profoundly affected the way organic chemists foresee the construction of carbon–carbon bonds. The contribution of organoboron chemistry to organic chemistry was recognized with two Nobel Prizes awarded in 1979 to Herbert C. Brown and in 2010 to Akira Suzuki who both instigated the development of new synthetic tools for the introduction of boron atoms into organic molecules. Of particular interest are vinylboron species due to their importance in a wide range of applications in natural product total synthesis.11 The stereocontrol of the new carbon–carbon bond is also of high significance. Whereas uncatalyzed and catalyzed processes have already been reviewed in the past,12, 13 and 14 the present report covers mostly recent developments published in the past ten years in the field of metal-free direct and transition metal-catalyzed synthesis of mono-, bis- and metallo-boronate compounds starting from alkynes.13 The mechanistic features and the stereochemical outcome (E/Z nomenclature) will be discussed as well.

Functionalized naphthalenes have applications in a variety of research fields ranging from the synthesis of natural or biologically active molecules to the preparation of new organic dyes. Although numerous strategies have been reported to access naphthalene scaffolds, many procedures still present limitations in terms of incorporating functionality, which in turn narrows the range of available substrates. The development of versatile methods for direct access to substituted naphthalenes is therefore highly desirable. The Diels-Alder (DA) cycloaddition reaction is a powerful and attractive method for the formation of saturated and unsaturated ring systems from readily available starting materials. A new microwave-assisted intramolecular dehydrogenative DA reaction of styrenyl derivatives described herein generates a variety of functionalized cyclopenta[b]naphthalenes that could not be prepared using existing synthetic methods. When compared to conventional heating, microwave irradiation accelerates reaction rates, enhances yields, and limits the formation of undesired byproducts. The utility of this protocol is further demonstrated by the conversion of a DA cycloadduct into a novel solvatochromic fluorescent dye via a Buchwald-Hartwig palladium-catalyzed cross-coupling reaction. Fluorescence spectroscopy, as an informative and sensitive analytical technique, plays a key role in research fields including environmental science, medicine, pharmacology, and cellular biology. Access to a variety of new organic fluorophores provided by the microwave-assisted dehydrogenative DA reaction allows for further advancement in these fields.

Structurally diverse aniline derivatives or analogous benzylamines and benzamides are subjected to ring-closing metathesis according to conditions A).

Under microwave irradiation, a range of alkenynylbenzenes undergo an intramolecular cyclization reaction to give cyclopenta-fused naphthalenes.

International audience; Novel regioselective ring closing ene-yne metathesis provided an efficient access to different substituted 1-benzazepine scaffolds. The reported synthetic approach could also be used as a powerful tool for the selective formation of a highly functionalizable 2-benzazepine core. This synthetic protocol was even proved to be an efficient way to obtain a functionalizable benzazocine derivative. By modifying the structure of the starting materials, the optimized cyclization finally proved to be a suitable technique to obtain five-and six-membered lactams, enhancing the synthetic application of our method. Five-and six-membered lactams were efficiently prepared by ring-closing metathesis involving the loss of ethylene moiety and affording highly functionalizable compounds showing both electron-withdrawing substituents and electron-donor groups.

Functionalized naphthalenes are valuable building blocks in many important areas. A microwave-assisted, intramolecular dehydrogenative Diels–Alder reaction of styrenyl derivatives to provide cyclopenta[b]naphthalene substructures not previously accessible using existing synthetic methods is described. The synthetic utility of these uniquely functionalized naphthalenes was demonstrated by a single-step conversion of one of these cycloadducts to a fluorophore bearing a structural resemblance to Prodan.

A novel Ir-catalyst for the straightforward cycloisomerization of different functionalized 1,6-enynes is found.

The gold(I)-catalyzed cycloisomerization of β-allenylhydrazones provides an efficient access to multisubstituted N-aminopyrroles, which are obtained in good to excellent yields. This new intramolecular cyclization method can be applied either to alkyl- or aryl-substituted allenes. The reaction proceeds under mild conditions with short reaction times through a selective intramolecular 1,2-alkyl or -aryl migration extending the general scope of the reaction.

International audience; The multistep synthesis of original antennas incorporating substituted [2.2]paracyclophane (pCp) moieties in the π-conjugated skeleton is described. These antennas, functionalized with an electron donor alkoxy fragment (A1) or with a fused coumarin derivative (A2), are incorporated in a triazacyclonane macrocyclic ligand L1 or L2, respectively, for the design of Eu(III), Yb(III), and Gd(III) complexes. A combined photophysical/theoretical study reveals that A1 presents a charge transfer character via through-space paracyclophane conjugation, whereas A2 presents only local excited states centered on the coumarin–paracyclophane moiety, strongly favoring triplet state population via intersystem crossing. The resulting complexes EuL1 and YbL2 are fully emissive in red and near-infrared, respectively, whereas the GdL2 complex acts as a photosensitizer for the generation of singlet oxygen.