D-Penicillamine derived thiazolidine ligands were prepared in a two-step synthetic sequence and used in the enantioselective alkylation of a variety of aromatic aldehydes with diethylzinc at room temperature. Excellent ee, up to >99%, and nearly complete conversions were observed. Structurally analogous L-cysteine derived thiazolidine ligands were also synthesized and tested for comparative purposes, resulting in very good, albeit slightly lower selectivities, up to 89%. The combined use of these two types of thiazolidines constitutes a very interesting strategy for synthesizing both (S) and (R) enantiomers of chiral secondary alcohols, thus leading the way to a myriad of useful optically active products with opposite absolute configurations.

Taking advantage of the opposite chirality of two privileged starting materials, l‐cysteine and d‐penicillamine, a wide range of thiazolidine‐based amino alcohols was synthesized. l‐Cysteine derivatives were more efficient chiral inductors than the d‐penicillamine ones, with ee up to 92% in the enantioselective ethylation of benzaldehyde. The scope of the best catalyst was evaluated using several aromatic, heteroaromatic, and aliphatic aldehydes, providing excellent (S)‐enantioselectivities. Given the opposite chirality of the l‐cysteine and d‐penicillamine thiazolidines, it was expected that the use of one or the other type of derivative as ligand would allow the formation of opposite configurations of the alkylated product. However, whereas the l‐cysteine thiazolidines predominantly gave the (S) form of the alkylated product, the d‐penicillamine ones led to both configurations. The significant difference in the stereochemical outcome of this reaction when catalyzed by the two types of ligands prompted us to investigate the reasons behind such results. Extensive quantum chemical calculations were performed in order to identify the transition state structures by which the enantioselective ethylation of benzaldehyde in the presence of these type of amino alcohols can proceed. An alternative path for the rate‐determining step was also explored and found decisive for the rationalization of the experimental outcomes. It was observed that the type of ligand dictates the accessible reaction paths for the formation of the chiral product, which ultimately determine the balance between the two possible configurations.

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The enantioselective Henry reaction is a very important and useful carbon–carbon bond forming reaction. The execution of this reaction requires the use of efficient chiral catalysts. In this work, in situ formed complexes of N‐substituted dihydroxypyrrolidines, chiral ligands derived from L‐tartaric acid and amines, were evaluated as catalysts in the enantioselective Henry reaction. The results showed that the nature of the N‐substituent on the ligand significantly influences the outcome of the reaction. Best results were obtained using a Cu (II) complex of (3S,4S)‐N‐benzyl‐3,4‐dihydroxypyrrolidine, in the presence of DIPEA, for the reaction of aromatic aldehydes with nitromethane, at room temperature, originating products with er up to 92:8 (R:S) and conversions up to 96%. The interaction between the pyrrolidine ligand and the copper ion, in isopropanol, was followed by UV‐vis spectrophotometry, showing a 1:1 stoichiometry and a binding constant of 4.4. The results obtained will contribute to the design and development of more efficient chiral catalysts for this type of reaction.

Molecular School (MS) is an extracurricular initiative intended to show relevant and complex concepts of chemical sciences to precollege students. The main goal is to motivate the participants to expand their awareness of chemical sciences and to acknowledge its relevance in everyday life, in order to stimulate the students to engage in chemistry undergraduate degrees. Here, we address the successful case of MS, implemented in Portugal, where recently, the universities have been facing significant difficulties in attracting new students to join chemistry-related courses. We report the first three editions of this free of cost preuniversity school, whose main subject is chemistry. All editions were held in the University of Coimbra, Portugal, and organized by PhD students of the department of chemistry of this institution. The three editions are discussed here, with particular focus on the last edition. Several participants ultimately chose chemistry BSc degrees to continue their education, which substantiates the positive outreach of this initiative. We believe MS can be replicated, adapted, and improved in other contexts and countries to increase the number of students enrolling chemistry university degrees.