A predictive journey towards trans-thioamides/amides

Abstract

The cis-trans isomerization of (thio)amides was studied by DFT calculations to get the model for the higher preference for the cis conformation by guided predictive analyses, suggesting how to select...

Stereoretentive Formation of Cyclobutanes from Pyrrolidines: Lessons Learned from DFT Studies of the Reaction Mechanism

“…Given the experience of our group in the field of predictive chemistry, we decided to check if the methodology could be applicable to the synthesis of [2]-ladderanes , or other bicyclic structures. To tackle this objective, we envisioned adding an aliphatic chain linking the two carbons in which the biradical is located in species D-bs , i.e., studying the reaction in bicyclic 5-azabicyclo[2.1.1]­hexane, 7-azabicyclo[2.2.1]­heptane, 8-azabicyclo[3.2.1]­octane or 9-azabicyclo[4.2.1]­nonane derivatives and higher-order analogues (Figure ).…”

Photoredox catalysis leading to triazolo-quinoxalinones at room temperature: selectivity of the rate determining step

“…3ic and 3id, the energy barriers decreased to 13.5 and 12.5 kcal mol −1 , respectively. In addition, on a simple exercise of predictive chemistry, [64][65][66][67] carboxylic acid and tert-butyl ester derivatives were studied, showing barriers of 13.2 and 14.6 kcal mol −1 , respectively, and thus showing a clear trend in which the bulkier the alkyl group, the higher the activation energy. Anyway, still insufficient for the latter compound to be not active like 3af, and compared to all the systems in Table 1.…”

%VBur index and steric maps: from predictive catalysis to machine learning

“…Nevertheless, the pivotal aspect remains that calculations are conducted prior to experiments, resulting in reduced experimental needs owing to predictions derived from computations. Examples of Poater's work in predictive chemistry and predictive catalysis include the development of computational tools and methods to predict the properties, 61 reactivity, 62,63 and behaviour of chemical compounds and catalysts. 64 However, the range of uses and applications is much broader, including the development of ML algorithms to predict the reactivity of chemical compounds based on their molecular structure and properties, 64 while there are other examples using computational models to predict the performance of catalysts in chemical reactions, 57 including the rate and selectivity of the reaction.…”

“…[260][261][262][263] And thus, it could also be incorporated into workflows designed for high-throughput screening of novel catalysts using ML methodologies. 264 Even though in most of cases the %V Bur is a perfect structural tool/parameter to correlate with a series of data, experimental or computational, [265][266][267] it is also necessary to be honest in recognizing that it does not seem that the %V Bur is one of the variables with the best behaviour in terms of the reproduction of the structural and/ or steric part, 61,268,269 with preference for the Tolman electronic parameter (TEP), 270,271 and sometimes the bond distances 268 and angles can be a better choice. 61,269 And particularly, in the activation of the C-O bond of the allylic alcohol, catalysed by palladium, the multiple linear regression analysis does not use as a variable either the %V Bur or the C-O bond distance but the angle with the metal.…”

“…264 Even though in most of cases the %V Bur is a perfect structural tool/parameter to correlate with a series of data, experimental or computational, [265][266][267] it is also necessary to be honest in recognizing that it does not seem that the %V Bur is one of the variables with the best behaviour in terms of the reproduction of the structural and/ or steric part, 61,268,269 with preference for the Tolman electronic parameter (TEP), 270,271 and sometimes the bond distances 268 and angles can be a better choice. 61,269 And particularly, in the activation of the C-O bond of the allylic alcohol, catalysed by palladium, the multiple linear regression analysis does not use as a variable either the %V Bur or the C-O bond distance but the angle with the metal. 269 Actually, most of the studies base the use of steric maps, independently of the catalytic reaction under study, and based on the cleft on the metal centre, where the substrate should interact, as Gramage-Doria and coworkers have developed with non-biological catalysts that mirror enzyme principles.…”