Advances in Organic Synthesis

The paper presents an overview of the work conducted in our group on the synthesis of a novel class of homogeneous and immobilized Ru-complexes containing Schiff bases as O, N-bidentate ligands benefiting from a versatile, quite general and thoroughly exemplified two-step procedure. The new Ru-complexes with improved stability incorporate a variety of Schiff bases, associated with traditional inorganic and organic ligands such as chloride, phosphanes, arenes, cyclodienes, NHC etc., and different carbenes (alkylidene, vinylidene, allenylidene and indenylidene). By a proper choice of the Schiff base, useful physical and chemical properties of the derived Ru-complexes could be induced resulting in tunable catalytic activity for metathesis and related processes. A pertinent example is the latency of selected Schiff base Ru catalysts which by becoming active only under specific conditions (heat or acid activation) are ideal for industrial applications, e.g. reaction injection molding processes. The synthetic approaches that are critically discussed in this chapter have led to a diversity of Ru-complexes of which several members have risen to the rank of commercial catalysts.

The utility of ruthenium-based catalysts in the construction of furan and pyrrole derivatives is reviewed. Among others, synthetic approaches involving cycloisomerization, olefin metathesis and multicomponent reactions are discussed.

Palladium(0)-catalyzed allylation of soft nucleophiles is a powerful synthetic methodology for the construction of carbon-carbon or carbon-heteroatom bond. The possibility of controlling the regioselectivity is one of the most interesting aspects of this chemistry. In this review, the different factors that can affect the regiochemistry of the nucleophilic attack will be discussed.

This chapter highlights our studies of the nature of the true catalytic species in the Heck coupling of bromobenzene and styrene with SiO2-supported Pd particles. Approaches including kinetic test, filtration test and catalyst poisoning were used to probe the behavior and nature of the active species in combination with transmission electron microscopy and elemental analysis. We found that the catalytic activity of soluble Pd is suppressed in the presence of the supported Pd particles. Through a study of dependences of reaction rate on Pd loading and on leached Pd concentration, we demonstrated that leached soluble Pd is responsible for the catalysis irrespectively of the supported Pd particles. In terms of the growth of the supported Pd particles during the Heck reaction, we suggested that the catalysis occurs via an Ostwald ripening effect. With the aid of catalyst poisoning, we illustrated that soluble Pd clusters are inactive for the Heck reaction, soluble molecular Pd being solely active. We also discussed Pd scavenging from solution by solid-bound thiols during the Heck reaction. In addition, we proposed a ligand-free homogeneous Heck reaction mechanism with the generation of soluble molecular Pd⁰ by Pd leaching from supported Pd particles. The integrated work allowed us to suggest that the true catalytic species involve only soluble molecular Pd⁰ from the supported Pd particles by simple Pd dissolution.

Recent examples for synthesis of new polyolefins containing polar functionalities by transition metal complex catalysis have been reviewed. The contents are consisted of the following sections: 1) background, 2) radical copolymerization, 3) direct alkane activation/functionalization (post functionalization of polyolefins), 4) controlled incorporation of reactive functionalities (and the subsequent introduction of polar funtionalities under mild conditions) by coordination polymerization. In particular, we wish to introduce our recent approach for synthesis of polyolefins containing polar functionalities via copolymerization of ethylene with nonconjugated diene using nonbridged half-titanocenes.

Statins used in the treatment of dyslipidemias are top-selling drugs in the world. Economical production of statins in industrial scale is challenging, because the side chain of statins is a 3,5-dihydroxyacid derivative consisting of two asymmetric centers. The most prominent methods for the preparation of the side chain are based on biocatalysis and surveyed in this review.

Enzymes are very versatile catalysts in organic chemistry, although in many times they presented very low selectivity towards non-natural or artificial compounds. A simple strategy has recently been reported to permit greatly enhancing the enzyme selectivity. The strategy -based on the conformational changes of these enzymes during catalysis- consists in the preparation of a library of biocatalysts by using different immobilization protocols that may permit to immobilize the enzymes via different orientations, with different rigidity or generating different environments. This review examines as different enzymes such as lipases, acylases, β-galactosidases, epoxyhydrolases, phosphorylases, hydroxynitrile lyases, sulfatases, glycosyltranferases, or tyrosynases have been greatly modulated by this solid phase strategy. This methodology has permitted to obtain highly enantioselective biocatalysts in asymmetric reactions, synthesis of β-lactams antibiotics, or transglycosylation reactions.

Propargylic alcohols are valuable starting materials in organic syntheses due to their ready availability. The presence of two functional groups, an alkyne unit and an alcohol unit, provide great opportunities for further functionalization. Straightforward substitution of the hydroxyl group with nucleophiles is highly desirable due to atomefficiency and environmental concerns. Since the first report of a ruthenium-catalyzed propargylic substitution reaction in 2000, a number of propargylic substitutions using transition-metal catalysts along with Brønsted and Lewis acids have been achieved. Reactions with a variety of carbon- and heteroatom-centered nucleophiles, both intermolecular and intramolecular versions, have been reported. These reactions have been successfully applied to the syntheses of substituted furans, pyrrols, indoles, isoxazoles and natural products. Asymmetric propargylic substitution reactions have also been achieved. With the intent of recycling the Lewis acid catalyst, ionic liquid techniques have been examined in propargylic substitutions as well. In recent years, propargylic substitution reactions using a combination catalytic system, either two different transition metals or an organocatalyst and Lewis acid, have been developed. This opens a new area of cooperative catalytic reactions that generate synthetic transformations that cannot be achieved by a single catalyst. Notably, the replacement of hydroxyl groups by stereodefined halovinyl and alkynyl moieties has been recently achieved. In this chapter, a brief summary of these advances is provided.