Luis Álvarez de Cienfuegos

Unexpected TiIII/Mn-Promoted Pinacol Coupling of Ketones

Titanocene(III) chemistry has emerged in the last decades as an indispensable tool in C-C bond-forming reactions. In this context, pinacol and related reactions allow the stereoselective synthesis of vicinal diols. In this work, we present new applications of these reactions using as starting materials aromatic ketones. Simple and smooth reaction conditions have been developed and have been applied for inter- and intramolecular processes. We also describe that although Cp(2)TiCl is usually used as a monoelectronic reducing agent, it can be also used as an efficient Lewis acid.

Mild Method for the Selective Esterification of Carboxylic Acids Based on the Garegg−Samuelsson Reaction

A mild method for the selective esterification of primary alcohols is described. The use of different phosphines, I(2), and imidazole allows the selective esterification of a wide variety of acids with excellent results. The generation of a bulky phosphonium-carboxylate salt as intermediate could justify the selectivity observed in this process. Additionally, amides also can be synthesized with use of this method.

Recent applications of Cp2TiCl in natural product synthesis

This review highlights the recent applications of titanocene(III) complexes in the field of natural product synthesis from the seminal precedents to the development of modern catalytic methods. The power of the titanocene(III)-based approaches is demonstrated by the straightforward syntheses of many natural products from readily available starting materials.

Water control over the chemoselectivity of a Ti/Ni multimetallic system: Heck- or reductive-type cyclization reactions of alkyl iodides.

A versatile Ti/Ni multimetallic protocol is described for the efficient catalysis of two different reactions, namely a Heck- and reductive-type cyclization of alkyl iodides, in the absence or presence of water, respectively. Noteworthy, the versatility of Ti(III) chemistry allows an oxidative ending step under reductive conditions to give Heck-type products, and the good H-atom transfer capabilities of Ti(III)-aqua complexes ensure reductive-type cyclizations.

Ti/Pd Bimetallic Systems for the Efficient Allylation of Carbonyl Compounds and Homocoupling Reactions

The allylation, crotylation and prenylation of aldehydes and ketones with stable and easily handled allylic carbonates is promoted by a Ti/Pd catalytic system. This Ti/Pd bimetallic system is especially convenient for the allylation of ketones, which are infrequent substrates in other related protocols, and can be carried out intramolecularly to yield five- and six-membered cyclic products with good stereoselectivities. In addition, Ti/Pd-mediated reductions and Würtz-type dimerisation reactions can be readily carried out from allyl carbonates and carboxylates.

Reduction Reactions in Green Solvents: Water, Supercritical Carbon Dioxide, and Ionic Liquids

A reduction reaction, in a general sense, is an electrochemical process in which an atom, ion, or molecule earns electrons. In organic chemistry such reduction reactions can be achieved by several methods, including the addition of hydrogen to a molecule or the removal of oxygen or other electronegative substituents. Reduction reactions have been known for a very long time, being developed almost simultaneously to modern chemistry. For example, the first catalytic hydrogenation recorded was the reduction of ethylene and acetylene to ethane in the presence of platinum black, by Von Wilde in 1874. [1] The industrial application of this reaction did not take long, and in 1901 Normann carried out the hydrogenation of fats and oils to change their melting profiles and textures. [2] From that time until now, novel methods and catalysts that make reduction reactions very broad, important, and efficacious chemical transformations have been developed. Nevertheless, and due to its industrial relevance, an extraordinary effort has to be made to develop more environmentally benign conditions. In this sense, this Review is focused on greener alternatives to conduct reduction reactions. Although this is a very wide topic, much of the effort has been focused on developed strategies to recycle and reuse catalysts and solvents, and on finding alternative media that are less contaminating than organic solvents. With respect to this point, water, supercritical CO2, and ionic liquids have emerged as fundamentally greener alternatives to organic solvents. Although the present work is focused on reduction reactions, the reader interested in knowing more about green solvents for organic synthesis will find additional

Versatile Bottom-up Approach to Stapled π-Conjugated Helical Scaffolds: Synthesis and Chiroptical Properties of Cyclic o-Phenylene Ethynylene Oligomers†

Spring loaded: the smallest members of a family of carbon nanocoils (CNCs), adopting a fixed helical structure, have been synthesized by introduction of one or two staples in o-phenylene ethynylene oligomers. The chiroptical responses of the systems having enantiopure L-tartrate-derived staples confirmed the induced helicity. Theoretical studies suggest that these CNCs are pseudoelastic.

Toward Multiple Conductance Pathways with Heterocycle-Based Oligo(phenyleneethynylene) Derivatives

In this paper, we have systematically studied how the replacement of a benzene ring by a heterocyclic compound in oligo(phenyleneethynylene) (OPE) derivatives affects the conductance of a molecular wire using the scanning tunneling microscope-based break junction technique. We describe for the first time how OPE derivatives with a central pyrimidine ring can efficiently link to the gold electrode by two pathways presenting two different conductance G values. We have demonstrated that this effect is associated with the presence of two efficient conductive pathways of different length: the conventional end-to-end configuration, and another with one of the electrodes linked directly to the central ring. This represents one of the few examples in which two defined conductive states can be set up in a single molecule without the aid of an external stimulus. Moreover, we have observed that the conductance through the full length of the heterocycle-based OPEs is basically unaffected by the presence of the heterocycle. All these results and the simplicity of the proposed molecules push forward the development of compounds with multiple conductance pathways, which would be a breakthrough in the field of molecular electronics.

Ti/Ni-mediated inter- and intramolecular conjugate addition of aryl and alkenyl halides and triflates.

In this work, we show that the unique combination of a nickel catalyst and Cp2TiCl allows the direct conjugate addition of aryl and alkenyl iodides, bromides, and to a lesser extent, chlorides and triflates to α,β-unsaturated carbonyls at room temperature, without requiring the previous formation of an organometallic nucleophile. The reaction proceeds inter- and intramolecularly with good functional group compatibility, which is key for the development of free protecting group methodologies. Carbo- and heterocycles of five- and six-membered rings are obtained in good yields. Moreover, some insights about the mechanism involved have been obtained from cyclic voltammetry, UV-vis, and HRTEM measurements.

Preparation of 2,2′-anhydronucleosides: regio- and stereoselective modifications of the base and sugar moieties

Abstract 2′-Deoxy-2′-iodonucleosides 4 – 9 , obtained from suitably protected furanoid glycals 1 and 2 with different silylated pyrimidine bases, were transformed into the corresponding 2,2′-anhydronucleosides 10 – 15 with inversion of the configuration at C-2′, by heating in DMF with n -dibutyltin oxide. Regio- and stereospecific opening at C-2′ of the 2,2′-ring in compounds 10 , 11 , and 12 with sodium azide afforded the related 2′-azido-2′-deoxynucleosides 16 , 17 and 18 , respectively. Action of sodium hydroxide on 12 caused the regioselective opening of the above-mentioned ring at C-2 with retention of the configuration at C-2′ giving 19 . Compound 19 could be transformed straightforwardly into 18 by well-established methodology. On the other hand, compound 15 could be transformed into the related 2′,3′-anhydronucleoside 23 by a regio- and stereoselective addition at N-3–C-2′ of allyl bromide concomitant with 2,2′-ring opening and inversion of the configuration at C-2′ to afford the intermediate 2′-bromo-2′-deoxynucleoside 21 , which was subsequently treated with sodium methoxide giving 23 .