Ricardo Almir Angnes

Diazenes are valuable compounds that have found broad applicability because of their optical and biological properties. We report the synthesis of alkylaryldiazenes via formal, photoredox catalyzed, deformylative C-N bond formation. The procedure employs dihydropyridines for the generation of alkyl radicals, which are then trapped by diazonium salts and reduced to the corresponding diazene. Control experiments were performed to confirm the involvement of radicals in the mechanism. The reaction can be carried out at room temperature and employs readily available reagents; the mild conditions allowed the use of highly functionalized substrates. There was no observed tautomerization of the diazene to the corresponding arylhydrazone.

Herein we report the enantioselective Heck‐Matsuda arylation of acyclic E and Z‐alkenyl aryl ethers. The reactions were carried out under mild conditions affording the enantioenriched benzyl ethers in a regioselective manner, moderate to good yields (up to 73%), and in good to excellent enantiomeric ratios (up to 97:3). The enantioselective Heck‐Matsuda arylation has shown a broad scope (25 examples), and some key Heck‐Matsuda adducts were further converted into more complex and valuable scaffolds including their synthetic application in the synthesis of (R)‐Fluoxetine, (R)‐Atomoxetine, and in the synthesis of an enantioenriched benzo[c]chromene. Finally, in silico mechanistic investigations into the reaction's enantioselectivity were performed using density functional theory. magnified image

An unprecedented deformylative halogenation of aldehydes to alkyl halides is presented. Under oxidative conditions, 1,4-dihydropyridine (DHP), derived from an aldehyde, generated a C(sp3)– radical that coupled with a halogen radical that was generated from inexpensive and atom-economical halogen sources (NaBr, NaI, or HCl), to yield an alkyl halide. Because of the mild conditions, a wide range of functional groups were tolerated, and excellent site selectivity was achieved.

Enantioselective substrate directed Heck reactions are desirable for the stereoselective synthesis of complex molecules. However, due to the coordination requirements of both chiral ligands and directing groups, such methodologies are underdeveloped. We report herein the desymmetrization of meso (1R,2S)‐cyclohex‐4‐ene‐1,2‐diol in an enantioselective and substrate directed fashion. The method provides all cis substituted highly functionalized chiral allylic alcohols in a complementary fashion to other Heck protocols.The products were obtained in high enantioselectivities (higher than 95% ee) and moderate to high yields (38–87%). The noncovalent interactions responsible for the directing effect were elucidated through computational examination of relevant minima and transition structures. magnified image

Highly diastereo‐ and enantioselective, noncovalent, substrate‐directable Heck desymmetrizations of cyclopentenyl olefins containing hydroxymethyl and carboxylate functional groups are presented. These conformationally unbiased cyclic olefins underwent effective arylations in yields of up to 97 %, diastereoselectivity up to >20:1, and enantiomeric excesses of up to 99 %. Noncovalent directing effects were shown to be prevalent in both Heck–Matsuda and oxidative Heck reactions, allowing the preferential formation of cis‐substituted aryl cyclopentenes containing two stereocenters, including quaternary stereocenters. These results further validate the internal out‐of‐coordination‐sphere ion–dipole interaction concept directing the reaction diastereoselectivity to the cis‐Heck product. This approach is complementary to existing methods using bis‐phosphine monoxide ligands to give the opposite trans‐diastereoisomer. The applicability of the method is showcased by the straightforward synthesis of a potent phosphodiesterase 4 inhibitor in a diastereo‐ and enantioselective manner. The reaction is operationally simple and has broad scope with regard to the nature of the arenediazonium salt and boronic acid employed. The mechanism and origin of stereoselectivity were investigated with control experiments and DFT calculations that fully supported the stabilizing internal out‐of‐coordination‐sphere ion–dipole interaction between the resident functional group and cationic palladium.

New computationally driven protocols for the Heck desymmetrization of 3-cyclopenten-1-ol with aryldiazonium tetrafluoroborates were developed. These new conditions furnished remarkable product selectivity originating from a resident hydroxyl group and the critical choice of the reaction solvent. Mechanistic insights gleaned from theoretical calculations of the putative transition states predicted toluene as an adequate solvent choice to attain high enantioselectivity by strengthening the noncovalent interaction of the substrate hydroxyl group and the chiral cationic palladium catalyst. Laboratory experiments validated the theoretical predictions, and by employing 2% MeOH/toluene as solvent, the Heck–Matsuda reaction provided exclusively the cis-4-arylcyclopentenols 3a–l in good to excellent yields in enantiomeric excesses up to 99%. The performance of the new PyOx ligand (S)-4-tert-butyl-2-(3,5-dichloropyridin-2-yl)-4,5-dihydrooxazole was also successfully evaluated in the Heck–Matsuda desymmetrization of 3-cyclopenten-1-ol. The synthetic potential of these highly functionalized cis-4-arylcyclopentenols is illustrated by a gold-catalyzed synthesis of cyclopenta[b]benzofuran skeletons.

The boom in visible light photoredox catalysis (VLPC) research has demonstrated that this novel synthetic approach is here to stay.

A new enantioselective Heck–Matsuda desymmetrization reaction was accomplished by using 3‐cyclopentenol to produce chiral five‐membered 4‐aryl cyclopentenol scaffolds in good yields and high ee’s, together with some 3‐aryl‐cyclopentanones as minor products. Mechanistically, the hydroxyl group of 3‐cyclopentenol acts as a directing group and is responsible for the cis‐ arrangement in the formation of the 4‐aryl‐cyclopentenols.

A comparative study of the chemical composition of essential oils of basil (Ocimum basilicum L.) grown in different localities in southern Brazil was conducted. This plant is seen as a promising source of linalool, a substance widely used in cosmetics and fragrances. The main objective of this study was to determine whether the procedures of drying plant and geographic origin of material plant (municipalities of Toledo (PR) and Jardinópolis (SC), south Brazil) provide significant changes in the chemical composition of essential oil. As a result, there were no significant differences in chemical composition of the oil from different regions, while the drying procedure has profoundly altered the chemical profile of the oil. Plant drying under sun reduced the concentration of linalool in the essential oil. These results can support future projects of essential oil production in these regions, characterized by the presence of small farms with a high incidence of family labor, which may represent a new source of income with a product with high added value.