doi:10.1002/chem.201702841engAlegre-Requena, Juan VicenteMarqués López, María EugeniaPérez Herrera, RaquelOptimizing Accuracy and Computational Cost in Theoretical Squaramide Catalysis: the Henry ReactionART-2017-101181This study represents the first example where the accuracy of different combinations of density functional theory (DFT) methods and basis sets has been compared in squaramide catalysis. After an optimization process of the precision obtained and the computational time required in the computational calculations, highly precise results were achieved compared to the experimental outcomes while using the least amount of time as possible. Here, we have explored computationally and experimentally the mechanism of squaramide-catalyzed Henry reaction. This is a complex reaction of about 100 atoms and a great number of diverse non-covalent interactions. Moreover, this research is one of the scarce examples where the organocatalyst acts in a trifunctional manner and is the first investigation in which a trifunctional squaramide catalyst has been employed. Functional ¿B97X-D showed the best results when used with different versions of the 6-311 basis sets, leading to highly accurate calculations of the outcomes of the Henry reaction using nine aldehydes with different structural characteristics. Furthermore, in these relatively large systems, the use of a split-valence triple-zeta basis set saves a large amount of time compared to using larger basis sets that are sometimes employed in organocatalytic studies, such as the TZV and Def2TZV basis set families.2017http://zaguan.unizar.es/record/6443210.1002/chem.201702841http://zaguan.unizar.es/record/64432oai:zaguan.unizar.es:64432info:eu-repo/grantAgreement/ES/DGA/E104Chemistry - A European Journal 23, 61 (2017), 15336-15347All rights reservedhttp://www.europeana.eu/rights/rr-f/info:eu-repo/semantics/openAccess