New Synthetic Methodologies Directed toward Pharmacologically Active Compounds as well as Silole Based Chromophores for Analytical and Optoelectronic Applications

The development of new and efficient synthetic methodologies to prepare heterocyclic compounds has received great attention over the years due to their importance in the pharmaceuticals and fine chemicals industries. Described herein are several novel syntheses of a variety of heterocycles including siloles, azaindoles, piperideines, piperidines and tetrahydropyrans. A one-pot, two-step methodology involving Tamao’s reductive cyclization followed by Negishi cross coupling was utilized to synthesize several new series of silole-based chromophores. The property studies revealed new electropolymerized poly(thienyl-silole)s with enhanced photoefficiency for all-polymer solar cells. In addition, a new procedure is developed for the synthesis of the first dissymmetric silole tethered to amine functionality. The synthesized compounds hold great promise in the arena of biosensors and solar cell applications. Furthermore, a novel and practical two step sequence for the preparation of C2 substituted 5-azaindoles has been reported. The synthetic sequence features a [3+2] dipolar cycloaddition between nitriles and a 3,4-cyclopropanopiperidine followed by SeO2 oxidation. Finally, the annulation reaction between 2-alkoxy-1,1-cyclobutane diesters and imines or aldehydes gave access to highly functionalized piperidines and tetrahydropyrans, respectively. Both the synthesis of those donor-acceptor cyclobutanes and their subsequent annulations are catalyzed by catalytic Yb(OTf)3. Although known for more than two decades, this is the first use of 2-alkoxy-1,1-cyclobutane diesters in dipolar cycloadditions. The new reactions are done under mild conditions providing the target compounds in high yields and excellent selectivity. The divergent nature and cost effectiveness of these methods make them very suitable for combinatorial applications in the pharmaceutical industry

Silole based acetylenes as advanced π-conjugated systems for optoelectronic applications

Nonlinear optical (NLO) and electro-optical (EO) properties of π-conjugated systems have been the subject of intense interest during the past several decades. In this mini-review we focus on semiconducting materials based on alkyne π-conjugation, with particular emphasis on those examples from our laboratory of chromophores containing a silole core. Several closely related examples from the literature are also discussed

Synthesis of 5-azaindoles via a cycloaddition reaction between nitriles and donor-acceptor cyclopropanes.

A new method for the synthesis of 5-azaindole derivatives is reported. A [3+2] dipolar cycloaddition between nitriles and a 3,4-cyclopropanopiperidine followed by SeO(2) oxidation affords the target compounds in moderate to excellent yields. The divergent nature and cost effectiveness of this method makes it very suitable for combinatorial applications in the pharmaceutical industry

Ytterbium triflate catalyzed synthesis of alkoxy-substituted donor-acceptor cyclobutanes and their formal [4 + 2] cycloaddition with imines: stereoselective synthesis of piperidines.

A new synthesis of 2-alkoxy-1,1-cyclobutane diesters and their first use in dipolar cycloadditions is reported. Both the formation of the donor-acceptor cyclobutanes and their subsequent annulation with in situ formed imines are catalyzed by Yb(OTf)(3). Cyclobutanes with carbon donor groups give piperidines with high trans stereoselectivity

Polyisobutylene-paclitaxel conjugates with pendant carboxylic acids and polystyrene chains: Towards multifunctional stent coatings with slow drug release

Drug-eluting stents are used in the treatment of atherosclerosis, where the incorporation of anti-proliferative or anti-inflammatory drugs decreases the rate of restenosis, the recurrence of artery narrowing. However, these stents can suffer from limitations such as drug depletion and delamination of the drug-eluting coating from the stent surface. Described here is an approach aimed at addressing these issues. Starting from a maleic anhydride adduct of polyisobutylene (PIB) prepared from butyl rubber, ring opening using paclitaxel (PTX) or a combination of PTX and polystyrene (PS) afforded covalent conjugates of PTX and PIB or PIB-PS graft copolymers bearing pendant carboxylic acids. When coated on stainless steel, the drug release was slower than that from a control coating that ressembles a clinical formulation comprising a physical mixture of a PS-PIB-PS triblock copolymer (SIBS) and PTX. The PTX conjugates also exhibited enhanced adhesion to stainless steel and increased tensile strength in comparison with the starting rubber. Cytotoxicity assays indicated that the materials did not leach toxic levels of PTX into cell culture media. Nevertheless, they were capable of inhibiting the adhesion and proliferation of C2C12 cells on their surfaces. These properties are advantageous for the potential application of the materials as stent coatings

Formal [4 + 2] cycloaddition of alkoxy-substituted donor-acceptor cyclobutanes and aldehydes catalyzed by Yb(OTf)3.

The cycloaddition between 2-alkoxy-1,1-cyclobutane diesters and aromatic, heteroaromatic, or aliphatic aldehydes under Yb(OTf)(3) catalysis generates tetrahydropyrans in high yields with exclusive cis-stereochemistry

Rubber Functionalization by Diels–Alder Chemistry: From Cross-Linking to Multifunctional Graft Copolymer Synthesis

The functionalization of polyisobutylene-<i>co</i>-isoprene, commonly referred to as butyl rubber, was investigated with the aim of preparing multifunctional materials. First, the acid catalyzed ring-opening of epoxidized butyl rubber was investigated. Ring-opening followed by elimination resulted in the formation of different dienes depending on the reaction conditions. It was possible to cleanly isolate the <i>exo</i>-diene, which readily undergoes Diels–Alder [4 + 2] cycloaddition reactions and it was demonstrated that this chemistry could be used to prepare multifunctional graft copolymers. For example, poly­(ethylene oxide) (PEO) or polystyrene (PS) could be grafted while at the same time introducing carboxylic acid moieties along the polymer backbone, and both polymers could be simultaneously grafted to form mixed graft copolymers with tunable tensile properties. Furthermore, it was demonstrated that reaction with a dimaleimide led to efficient cross-linking of the rubber and this cross-linking could be reversed upon heating due to the thermoreversible nature of the Diels–Alder reaction. Thus, this chemistry allows for clean and facile synthesis of new rubber derivatives, opening possibilities for new rubber applications