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STRATEGIES FOR THE SYNTHESIS OF LYSERGIC ACID. (+)-Lysergic acid [(+)-1] is a precursor of several substances with well-established pharmacological properties, including some drugs approved and commercialized around the world. Thus, the importance of (+)-1 as a synthetic target becomes undoubted and various strategies for the synthesis of its tetracyclic core have been reported in the literature. Therefore, in this review article we will address in chronological order the total and formal syntheses of lysergic acid (1), separating them into racemic and chiral/asymmetric syntheses. Until now, there are 24 syntheses described in the literature, namely, 11 total and 13 formal syntheses. Considering all the syntheses accomplished, 15 were planned to produce (±)-lysergic acid [(±)-1] and 9 presented routes to eventually provide (+)-lysergic acid [(+)-1]. A significant evolution regarding approaches and efficiency may be observed since the first synthesis of (±)-1 until the last asymmetric synthesis of (+)-1.

Abstract A biomimetic iodofunctionalization of aromatic and heteroaromatic compounds has been developed using NaI as a source of iodine and 30% H2O2 as a mild oxidant, as well as SeCl4 as a commercially available catalyst in water without a co-solvent. The method affords iodinated compounds in isolated yields of 37 to 99%. The catalytic system has potential for the bromination of aromatic substrates.

In this paper we gathered articles concerning insertion reactions of arynes, exclusively generated from 2-(trimethylsilyl)aryl triflates in the presence of fluoride ions, in substrates bearing nucleophilic and electrophilic portions separated by sigma bonds. Accordingly, we stand out the great importance and versatility of such transformations in the preparation of highly functionalized aromatic systems, which are hardly synthesized in just one step for other methods.

Benzofurans are important synthetic building blocks present in a high number of biologically active natural products, pursuing several medicinal properties. In this context, there is an increasing interest in developing efficient syntheses for this class of compounds. Accordingly, we present in this work our preliminary results involving the iodocyclization reaction of 2-iodo-6-alkynylanisoles, employing molecular iodine under mild conditions, leading to the formation of highly functionalized benzofurans, potential precursors of pharmaceuticals and functional materials.

Several pharmacological activities have been devoted to pyrazole containing molecules. In particular, 4-iodopyrazoles have been employed as key starting materials in cross-coupling chemistry and metal-iodine exchange reactions that focus on the synthesis of such biologically important compounds. Unfortunately, existing methods for the synthesis of 4-iodopyrazoles are not in agreement with the environmental requirements due to a series of drawbacks including the use of large excess of reagents, the generation of toxic waste and long reaction times. Recently, we developed a fast and mild reaction condition for the iodination of aromatic compounds using an I2/H2O2 system water as a nonflammable and innocuous solvent and ultrasonic irradiation as energy source. In this work, we present the application of this methodology for the iodination of pyrazoles (Scheme). Initially, a series of pyrazoles were efficiently prepared starting from 1,3-dicarbonyl compounds and hydrazines under ultrasonic irradiation. Three examples from the pyrazoles were subjected to the iodination condition shown above. Iodopyrazoles were obtained in 63-65% yields.

The cross-coupling reaction between aryl halides and terminal alkynes, catalyzed by palladium complexes and copper (I) salts, consists in an efficient synthetic tool for the formation of C-C bonds, resulting in disubstituted acetylenic compounds. Accordingly, in this work we present our preliminary results involving the selective cross-coupling reaction between 2,6-diiodoanisoles and terminal alkynes, catalyzed by Pd(PPh3)2Cl2 and CuI, in the formation of 2-iodo-alkynylanisoles (scheme 1).

Through this work we are developing our research involving the formation of arynes from 2-(trimethylsilyl)aryl triflates, under relatively mild reaction conditions. Thus, esters of amino acids are being subjected to the reaction with 2-(trimethylsilyl)aryl triflates, using cesium fluoride in acetonitrile at 80oC for 24 h, resulting in the formation of N,N-diarylamino acid derivatives, important chiral intermediates in the construction of peptides and drugs.