Synthesis of Densely Functionalised 5‐Halogen‐1,3‐oxazin‐2‐ones by Halogen‐Mediated Regioselective Cyclisation of N‐Cbz‐Protected Propargylic Amines: A Combined Experimental and Theoretical Study

A very efficient synthesis of 5‐halogen‐1,3‐oxazin‐2‐ones has been accomplished by the halocyclisation reaction of chiral nonracemic N‐carbobenzyloxy (N‐Cbz)‐protected propargylic amines by using I₂, Br₂ and Cl₂ as electrophile sources. The nature of the halogen influences the reaction time and yield. However, in all cases the reaction is totally regioselective taking place through a 6‐endo‐dig process regardless of the nature of the halogen and of the substituents in the starting material. To rationalise the experimental results, theoretical studies at the B3LYP/6‐311G* level have been performed.     

A Click Approach to Polymetallic Chromium(0) and Tungsten(0) Fischer‐Carbene Complexes and Their Use in the Synthesis of Functionalized Polymetallic Metal?Carbene Complexes

Alkynylamino Cr⁰ and W⁰ Fischer carbenes undergo a CuAAC reaction with a diverse range of di‐, tri‐, and tetra‐azides to produce polymetallic chromium(0) and tungsten(0) (Fischer)‐carbene complexes in good‐to‐excellent yields. This method is simple, versatile, and is suitable for the preparation of a diverse range of structures with a high level of symmetry. Moreover, the resulting polymetallic carbene complexes are suitable partners for the peripheral functionalization of the metal nuclei, whilst retaining the metal fragment. This fact has been demonstrated in a simultaneous Pauson–Khand reaction, which, in some cases, allows for the generation of four bicyclic [5,5] rings on the periphery of a tetrametallic molecule in a process that involves the formation of 12 new C? C bonds, with four simultaneous CO‐insertion processes. The electrochemistry of the polymetallic Fischer carbenes show completely independent behavior for each nucleus, as well as an anomalous observation of the reversible oxidation of the allyl substituents, which has not been reported before in this class of chemistry.     

Supramolecular Polymerization of C3‐Symmetric Organogelators: Cooperativity,Solvent, and Gelation Relationship

A systematic study of the influence of solvent and the size of C₃‐symmetric discotics on their supramolecular polymerization mechanism is presented. The cooperativity of the self‐assembly of the reported compounds is directly related to their gelation ability. The two series of C₃‐symmetric discotics investigated herein are based on benzene‐1,3,5‐tricarboxamides (BTAs) and oligo(phenylene ethynylene)‐based tricarboxamides (OPE? TAs) that are peripherally decorated with achiral ( 1 a and 2 a ) or chiral N‐(2‐aminoethyl)‐3,4,5‐trialkoxybenzamide units ( 1 b and 2 b ). The supramolecular polymerization of compounds 1 a , b and 2 a , b has been exhaustively investigated in a number of solvents and by using various techniques: variable‐temperature circular dichroism (VT‐CD) spectroscopy, concentration‐dependent ¹H NMR spectroscopy, and isothermal titration calorimetry (ITC). The supramolecular polymerization mechanism of compounds 2 is highly cooperative in solvents such as methylcyclohexane and toluene and is isodesmic in CHCl₃. Unexpectedly, chiral compound 1 b is practically CD‐silent, in contrast with previously reported BTAs. ITC measurements in CHCl₃ demonstrated that the supramolecular polymerization of BTA 1 a is isodesmic. These results confirm the strong influence of the π‐surface of the central aromatic core of the studied discotic and the branched nature of the peripheral side chains on the supramolecular polymerization. The gelation ability of these organogelators is negated in CHCl₃, in which the supramolecular polymerization mechanism is isodesmic.     

Proton‐Assisted Hydrogen Activation on Polyhedral Cations

The treatment of [1,1‐(PR₃)₂‐3‐(Py)‐closo‐1,2‐RhSB₉H₈] (PR₃=PMe₃ ( 2 ) or PPh₃ and PMe₃ ( 3 ); Py=pyridine) with triflic acid (TfOH) affords [1,3‐μ‐(H)‐1,1‐(PR₃)₂‐3‐(Py)‐1,2‐RhSB₉H₈]⁺ (PR₃=PMe₃ ( 4 ) or PMe₃ and PPh₃ ( 5 )). These products result from the protonation of the 11‐vertex closo‐cages along the Rh(1)? B(3) edge. These unusual cationic rhodathiaboranes are stable in solution and in the solid state and they have been fully characterized by multinuclear NMR spectroscopy. In addition, compound 5 was characterized by single‐crystal X‐ray diffraction. One remarkable feature in these structures is the presence of three {Rh(PPh₃)(PMe₃)}‐to‐{ηⁿ‐SB₉H₈(Py)} (n=4 or 5) conformers in the unit cell, thus giving an uncommon case of conformational isomerism. [1,1‐(PPh₃)₂‐3‐(Py)‐closo‐1,2‐RhSB₉H₈] ( 1 ), that is, the bis‐PPh₃‐ligated analogue of compounds 2 and 3 , is also protonated by TfOH, but, in marked contrast, the resulting cation, [1,3‐μ‐(H)‐1,1‐(PPh₃)₂‐3‐(Py)‐1,2‐RhSB₉H₈]⁺ ( 6 ), is attacked by a triflate anion with the release of a PPh₃ ligand and the formation of [8,8‐(OTf)(PPh₃)‐9‐(Py)‐nido‐8,7‐RhSB₉H₉] ( 9 ). The result is an equilibrium that involves cationic species 6 , neutral OTf‐ligated compound 9 , and [HPPh₃]⁺, which is formed upon protonation of the released PPh₃ ligand. The resulting ionic system reacts readily with H₂ to give cationic species [8,8,8‐(H)(PPh₃)₂‐9‐(Py)‐nido‐8,7‐RhSB₉H₉]⁺ ( 7 ). This reactivity is markedly higher than that previously found for compound 1 and it introduces a new example of proton‐assisted H₂ activation that occurs on a polyhedral boron‐containing compound.     

Conformational Analysis of the Anti‐obesity Drug Lorcaserin in Water: How To Take Advantage of Long‐Range Residual Dipolar Couplings

The conformational state of 8‐chloro‐1‐methyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine hydrochloride (lorcaserin) in water has been determined on the basis of one‐bond and long‐range C? H residual dipolar coupling (RDC) data along with DFT computations and ³J_HH coupling‐constant analysis. According to this analysis, lorcaserin exists as a conformational equilibrium of two crown‐chair forms, of which the preferred conformation has the methyl group in an equatorial orientation.     

Controlled Click‐Assembly of Well‐Defined Hetero‐Bifunctional Cubic Silsesquioxanes and Their Application in Targeted Bioimaging

A general procedure for the assembly of hetero‐bifunctional cubic silsesquioxanes with diverse functionality and a perfectly controlled distribution of functional groups on the inorganic framework has been developed. The method is based on a two‐step sequence of mono‐ and hepta‐functionalization through the ligand‐accelerated copper(I)‐catalyzed azide–alkyne cycloaddition of a readily available octaazido cubic silsesquioxane. The stoichiometry of the reactants and the law of binomial distribution essentially determine the selectivity of the key monofunctionalization reaction when a copper catalyst with strong donor ligands is used. The methodology has been applied to the preparation of a set of bifunctional nano‐building‐blocks with orthogonal reactivity for the controlled assembly of precisely defined hybrid nanomaterials and a fluorescent multivalent probe for application in targeted cell‐imaging. The inorganic cage provides an improved photostability to the covalently attached dye as well as a convenient framework for the 3D multivalent display of the pendant epitopes. Thus, fluorescent bioprobes based on well‐defined cubic silsesquioxanes offer interesting advantages over more conventional fully organic analogues and ill‐defined hybrid nanoparticles and promise to become powerful tools for the study of cell biology and for biomedical applications.     

Dimensional Matching of Polycyclic Aromatics with Rectangular Metallacycles: Insertion Modes Determined by [C?H⋅⋅⋅π] Interactions

A family of Pd^II/Pt^II dinuclear receptors, designed to give a smooth increase in their cavity lengths (from 7.46–13.78 Å), is presented. Their inclusion complexes with a representative set of polycyclic aromatic substrates (naphthalene, carbazol, pyrene, and benzo[a]pyrene), were characterized and studied in aqueous solution and the solid state. By taking into account the dimensions of both receptors and substrates, an excellent complementarity was found between the size of the receptors and their ability to complex a given substrate. Furthermore, this dimensional matching results in specific binding modes depending on the ability of the guest to establish stabilizing [C? H???π] interactions with the host.     

Structural Diversity from the Transannular Cyclizations of Natural Germacrone and Epoxy Derivatives: A Theoretical–Experimental Study

Treatment of germacrone ( 1 ) with different electrophiles, and of its epoxy derivatives germacrone‐4,5‐epoxide ( 2 ), germacrone‐1,10‐epoxide ( 3 ) and isogermacrone‐4,5‐epoxide ( 4 ) with Brönsted/Lewis acids and Ti^III, gives rise to a great structural diversity. Thus, by using a maximum of two steps, the production of more than 40 compounds corresponding to 14 skeletons is described. Computational calculations rationalizing the structural divergence produced are also described. Finally, since some of the compounds generated are bioactive natural sesquiterpenes, the mechanisms of formation of these substances will provide new insights in their biosynthesis.     

Synthesis and Reactivity of Cationic Triruthenium Clusters Derived from 2‐Methyl‐ and 4‐Methylpyrimidines: From Conventional Cyclometalated Ligands to Novel Types of N‐Heterocyclic Carbenes

The methylation of the uncoordinated nitrogen atom of the cyclometalated triruthenium cluster complexes [Ru₃(μ‐H)(μ‐κ²N¹,C⁶‐2‐Mepyr)(CO)₁₀] ( 1 ; 2‐MepyrH=2‐methylpyrimidine) and [Ru₃(μ‐H)(μ‐κ²N¹,C⁶‐4‐Mepyr)(CO)₁₀] ( 9 ; 4‐MepyrH=4‐methylpyrimidine) gives two similar cationic complexes, [Ru₃(μ‐H)(μ‐κ²N¹,C⁶‐2,3‐Me₂pyr)(CO)₁₀]⁺( 2 ⁺) and [Ru₃(μ‐H)(μ‐κ²N¹,C⁶‐3,4‐Me₂pyr)(CO)₁₀]⁺ ( 9 ⁺), respectively, whose heterocyclic ligands belong to a novel type of N‐heterocyclic carbenes (NHCs) that have the C_carbene atom in 6‐position of a pyrimidine framework. The position of the C‐methyl group in the ligands of complexes 2 ⁺ (on C²) and 9 ⁺ (on C⁴) is of key importance for the outcome of their reactions with K[N(SiMe₃)₂], K‐selectride, and cobaltocene. Although these reagents react with 2 ⁺ to give [Ru₃(μ‐H)(μ‐κ²N¹,C⁶‐2‐CH₂‐3‐Mepyr)(CO)₁₀] ( 3 ; deprotonation of the C²‐Me group), [Ru₃(μ‐H)(μ₃‐κ³N¹,C⁵,C⁶‐4‐H‐2,3‐Me₂pyr)(CO)₉] ( 4 ; hydride addition at C⁴), and [Ru₆(μ‐H)₂{μ₆‐κ⁶N¹,N^1′,C⁵,C^5′,C⁶,C^6′‐4,4′‐bis(2,3‐Me₂pyr)}(CO)₁₈] ( 5 ; reductive dimerization at C⁴), respectively, similar reactions with 9 ⁺ have only allowed the isolation of [Ru₃(μ‐H)(μ₃‐κ²N¹,C⁶‐2‐H‐3,4‐Me₂pyr)(CO)₉] ( 11 ; hydride addition at C²). Compounds 3 and 11 also contain novel six‐membered ring NHC ligands. Theoretical studies have established that the deprotonation of 2 ⁺ and 9 ⁺ (that have ligand‐based LUMOs) are charge‐controlled processes and that both the composition of the LUMOs of these cationic complexes and the steric protection of their ligand ring atoms govern the regioselectivity of their nucleophilic addition and reduction reactions.