Epoxidation reaction has been the subject of numerous investigations and a number of useful methodologies have been studied. The electrophilic reagents used in this epoxidation, react preferentially with electron-rich olefins. For this reason, electron-deficient olefins such us α,β-unsaturated esters react very slowly with low yields. Our group has previously reported the synthesis of enantiomerically pure α-β unsaturated diesters of TADDOL and BINOL. Optically active epoxides are highly versatile intermediates that can be converted into a wide variety of enantiomerically enriched molecules. Because of this, we decided to study the stereoselective di-epoxidation of diacrylate derivatives with C₂-symmetry. First, we studied simple substrates with the intention to extend the results to more complex molecules. Thus, several epoxidation methods were tested on α-β-unsaturated esters with the aim to improve the previously reported data. Among all the experimental conditions tested, mCPBA reagent was the best, giving the glycidic esters derivatives with very good yields and short reaction time compared with reported methods. Due to the fact that the reaction conditions were unsuccessful with the C₂-diacrylate systems, we decided to study the reactivity of these substrates applying DFT calculations. The reactivity of mCPBA, in olefins epoxidation reactions, can be rationalized by frontier orbital interactions. For this reason, we evaluated the coefficients and shape of HOMO OMs of a series of simple esters and TADDOL and BINOL derivatives. We achieved interesting results concerning the reactivity of these compounds.

Chiral organotin halides and hydrides have been widely investigated as chiral inductors for asymmetric synthesis. They have been used in a variety of reactions such as ketone reduction, alpha bromo esters reduction, radical cyclization of aldehydes, among others. Several chiral organotin hydrides are reported in literature, but to the best of our knowledge none of them have two tin hydrides moieties. So that, we were interested in the synthesis of (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-bis(diphenylmethylstannane). The synthesis of this tin hydride was achieved in six steps starting from dimethyl-(L)-tartrate. The first attempt was to apply the new chiral organotin hydride in the reduction of prochiral ketones. We faced with several disadvantages in this reaction because stoichiometric amounts of the tin hydrides were needed to reduce ketones, and despite of this, the tin hydride was unable to reduce them completely. We decided to focus on the reduction of alpha bromo esters, inspired in the work of Metzger and co-workers. Alpha bromo esters can be reduced by using an organotin halide and NaCNBH3 as a source of hydride. In this condition, the organotin halide is used in catalytic amount. We permormed the reactions with 1, 5 and 10 mol% the organotin halide and the last conditions allowed the reaction to complete.

Some N-alkyl phthalimides and saccharin derivatives are important in medicinal chemistry. These compounds can act as antipsychotic, anti-inflammatory and lipid lowering agents, among others. Furthermore, saccharin derivatives can complex with various metal ions, such as Mg²⁺, Ca²⁺, Sr²⁺, Pd²⁺, Cu²⁺. One of the most important reactions in synthetic organic chemistry is the conjugate addition of nucleophilic species to the β-carbon of α,β-unsaturated systems. This process allows the construction of carbon backbones it is very valuable from a synthetic point of view. Several attempts in the generation of β-amino derivatives have been reported and the aza-Michael addition reaction is widely recognized as one of the most important carbon-nitrogen bond–forming reaction in organic synthesis. Most of these products have special properties. For instance, the β-amino acids that can be obtained from aza-Michael additions between amines and α,β-unsaturated esters are attractive precursors in preparation of a variety of bioactive molecules and backbone of a variety of drugs. Moreover, the synthesis of β-amino esters has gained considerable attention due to the possibility of generate intermediates for the synthesis of natural products, aminoalcohols, diamines, β-lactams, β-amino acid derivatives and other molecules containing nitrogen. Thus, this reaction provides a simple and appealing route toward synthesis of N-alkyl derivatives of these compounds. In this work, we propose to study the aza-Michael reaction under microwave condition between saccharine and phtalimide with enantiomerically pure diesters of BINOL and TADDOLs derivatives. This methodology allowed us to obtain di-addition products of great synthetic interest with good yields and relatively short reaction times.

There is a wide variety of natural and synthetic benzophenones with antibacterial activity. In previous studies,[1] we reported the synthesis of substituted diarylmethanes under Barbier conditions by Stille coupling as precursors of substituted benzophenones. Catalyzed bond formation require hours to days to complete when conventional heating is used, under inert atmosphere. Microwaves have demonstrated that the reaction rate improves significantly and allows use closed vials without inert atmosphere.[2] The Stille coupling was one of the first reactions where the assistance of microwave was applied since some organotin compound have poor reactivity and, consequently, low yield of the desired product. We present here the study of the synthesis of diarylmethanes through Stille reaction under microwave irradiation, comparing the results with and without catalytic conditions and ligands,[3] based on the optimal results applying microwaves without catalyst that have been reported for Suzuki and Sonogashira coupling.[4],[5] In most cases, reactions were completed in short time and no homocoupling product was observed. Although reaction times are slightly higher and the yields were lower than those found in catalyzed condition, the fact that in this case this difficult type of reaction (Csp3-Csp2 coupling) can be performed without catalyst, is very promising and encourages us to continue with future studies in order to find the best conditions. [1] Ocampo, R.A, Koll, L.C, Mandolesi, S.D. Ultrasonics Sonochemistry, Article in press. http://dx.doi.org/10.1016/j.ultsonch.2012.06.014 [2] a) Larhed, M. , Moberg, C., Hallberg, A. Acc. Chem. Res. 2002, 35, 717. b) Olofsson, K., Larhed, M. (Eds.: P. Lidstrum, J.P. Tierney), Blackwell, Oxford, 2004, Chap. 2 [3] a) Larhed, M., Lindeberg, G., Hallberg, A., Tetraheron Lett, 1996, 37, 8219. b) Berthault A., Berteina-Raboin, S., Finaru A., Guillaumet, G., QSAR Comb Sci, 2004, 23, 850 [4] Leadbeater, N.E., Marco, M. J. Org. Chem. 2003, 68, 5660 [5] Leadbeater, N.E., Marco, M., Tominack, B. Org. Lett. 2003, 5, 3919

Organotin compounds have shown a wide spectrum of biological effects and have been extensively studied as fungicides, bactericides, acaricides and wood preservative. A large number of papers have reported the use of organotin compounds as bacterial growth inhibitors. The biocide activity of tribenzyl- and dibenzyltin compounds has been informed, but the effect that the methoxyl group in the aromatic ring could have on the activity of the compounds has not been reported in previous literature. For that reason, we performed an in vitro qualitative assay, and evaluated the activity of benzyltri-n-butyltin (I) and 3,5-dimethoxybenzyltri-n-butyltin (II) against the growth of two bacterial strains: Staphylococcus aureus (Gram-positive) and Escherichia Coli (Gram-negative), using agar well diffusion method. In all cases Merck Art 5273 broth was employed. THF was used both as the solvent of choice for the organometallic compound (since the organotin compounds are not water soluble) and as a negative control. Different concentrations I and II were prepared and the activity was determined by measuring the diameter of the inhibition zone (in cm). The results proved not only that the Gram-positive strain is more susceptible to the inhibition growth effect of the organotin compounds evaluated, but also that 3,5-dimethoxybenzyltri-n-butyltin has higher antibacterial activity. According to this preliminary results we conclude that the presence of the methoxyl group in the aromatic ring would enhance the antibacterial activity of the organotin compound tested here.

Single-enantiomer drug candidates are important to many pharmaceutical companies, and therefore, new methods for the preparation of enantiopure compounds are critical for the development of next-generation pharmaceutical products. The use of microwave (MW) irradiation in organic synthesis has become a popular technique to develop and optimize the libraries of compounds synthesis in short reaction time compare to those obtained with the classical thermal methods in pharmaceutical and academic production. Numerous studies in the past ten years, demonstrated that microwave enhanced chemical reactions and that they are faster than conventional heating methods. In previuos studies, we reported the stereoselective radical addition of organotin hydrides to unsaturated TADDOL diesters. These reactions occurred with intramolecular cyclization under inert atmosphere, radical initiator, toluene and 75°C with high yields and stereoselectivity depending on the reactivity and steric bulk of the organotin hydride employed. Here, we decided to study a new method for the synthesis of these macrocycles through the radical addition of different triorganotin hydrides, R₃SnH (R= Me, n-Bu, Ph; Neophyl), to the same insaturated TADDOL diesters, in THF as solvent and under MW conditions. We compared these results with the previous reported method. Under MW conditions, reactions were completed in very short reaction time and neither the products of double hydrostannation nor the products of cyclopolymerization were obtained in both cases. Furthermore, we evaluated the stereoselectivity by ¹¹⁹Sn-NMR spectroscopic analysis in both methods.