Ariel M. Sarotti

Beyond DP4: an Improved Probability for the Stereochemical Assignment of Isomeric Compounds using Quantum Chemical Calculations of NMR Shifts

The DP4 probability is one of the most sophisticated and popular approaches for the stereochemical assignment of organic molecules using GIAO NMR chemical shift calculations when only one set of experimental data is available. In order to improve the performance of the method, we have developed a modified probability (DP4+), whose main differences from the original DP4 are the inclusion of unscaled data and the use of higher levels of theory for the NMR calculation procedure. With these modifications, a significant improvement in the overall performance was achieved, providing accurate and confident results in establishing the stereochemistry of 48 challenging isomeric compounds.

Application of the Multi-standard Methodology for Calculating 1H NMR Chemical Shifts

Gauge including atomic orbitals (GIAO) (1)H NMR chemical shift calculations have been performed for 66 organic compounds at 72 different levels of theory using the multi-standard approach (MSTD) previously developed for (13)C NMR. This straightforward computational technique involves the combination of methanol and benzene as standards. The studied methodology has been shown to predict (1)H NMR chemical shifts efficiently at different levels of theory.

1,3-Dipolar cycloaddition reactions of azomethine ylides with a cellulose-derived chiral enone. A novel route for organocatalysts development.

Cellulose-derived chiral pyrrolidines were synthesized in excellent yields, regioselectivities, and stereoselectivities via a 1,3-dipolar cycloaddition reaction between levoglucosenone and azomethine ylides. An unprecedented isomerization event led to a new family of pyrrolidines with an unusual relative stereochemistry. Preliminary results showed that these compounds are promising organocatalysts for iminium ion-based asymmetric Diels-Alder reactions.

π-Stacking Effect on Levoglucosenone Derived Internal Chiral Auxiliaries. A Case of Complete Enantioselectivity Inversion on the Diels−Alder Reaction

Detailed quantum chemical calculations, experimental evidence, and NMR data rationalize the participation of pi-stacking interaction in the highly asymmetric Diels-Alder reaction using levoglucosenone derived internal chiral auxiliaries, including the appealing effect of inversion of the enantioselectivity by coordination of the substrate with Et 2AlCl.

Total Synthesis and Tentative Structural Elucidation of Cryptomoscatone E3: Interplay of Experimental and Computational Studies

A successful combination of computational chemistry and total synthesis was explored to tentatively elucidate the absolute configuration of cryptomoscatone E3, a polyketide isolated from the Brazilian tree Cryptocarya mandiocanna. Two independent synthetic approaches are discussed based on asymmetric allylation, ring closing metathesis, and aldol reactions.

GIAO C–H COSY Simulations Merged with Artificial Neural Networks Pattern Recognition Analysis. Pushing the Structural Validation a Step Forward

The structural validation problem using quantum chemistry approaches (confirm or reject a candidate structure) has been tackled with artificial neural network (ANN) mediated multidimensional pattern recognition from experimental and calculated 2D C-H COSY. In order to identify subtle errors (such as regio- or stereochemical), more than 400 ANNs have been built and trained, and the most efficient in terms of classification ability were successfully validated in challenging real examples of natural product misassignments.

Determination of the Relative Configuration of Terminal and Spiroepoxides by Computational Methods. Advantages of the Inclusion of Unscaled Data

The assignment of the relative configuration of spiroepoxides or related quaternary carbon-containing oxiranes can be troublesome and difficult to achieve. The use of GIAO NMR shift calculations can provide helpful assistance in challenging cases of structural elucidation. In this regard, the DP4 probability is one of the most popular methods to be employed when only one set of experimental data is available, though modest results were obtained when dealing with spiroepoxides. Recently, we introduced an improved probability (DP4+) that includes the use of both scaled and unscaled NMR data computed at higher levels of theory. Here, we report a comprehensive study to explore the scope and limitations of the DP4+ methodology in the stereoassignment of terminal or spiroepoxides bearing a wide variety of molecular complexity and conformational freedom. The excellent levels of correct classification achieved were interpreted on the basis of a constructive compensation of errors upon using both scaled and unscaled proton and carbon data. The advantages of the DP4+ methodology in solving two case studies that could not be unequivocally assigned by NOE experiments are also provided.

Joint Experimental, in Silico, and NMR Studies toward the Rational Design of Iminium-Based Organocatalyst Derived from Renewable Sources

An efficient organocatalyst for iminium-ion based asymmetric Diels-Alder (DA) reactions has been rationally designed. The most influential structure-activity relationships were determined experimentally, while DFT calculations and NMR studies provided further mechanistic insight. This knowledge guided an in silico screening of 62 different catalysts using an ONIOM(B3LYP/6-31G*:AM1) transition-state modeling, which showed good correlation between theory and experiment. The top-scored compound was easily synthesized from levoglucosenone, a biomass-derived chiral enone, and evaluated in the DA reaction between (E)-cinnamaldehyde and cyclopentadiene. In line with the computational finding, excellent results (up to 97% ee) were obtained. In addition, the catalyst could be easily recovered and reused with no loss in its catalytic activity.

Experimental and theoretical insights in the alkene-arene intramolecular π-stacking interaction.

Summary Chiral acrylic esters derived from biomass were developed as models to have a better insight in the aryl–vinyl π-stacking interactions. Quantum chemical calculations, NMR studies and experimental evidences demonstrated the presence of equilibriums of at least four different conformations: π-stacked and face-to-edge, each of them in an s-cis/s-trans conformation. The results show that the stabilization produced by the π–π interaction makes the π-stacked conformation predominant in solution and this stabilization is slightly affected by the electron density of the aromatic counterpart.

Fuentes alternativas de materia prima

Alternative sources of starting materials Biomass is the source of renewable carbon that will allow to achieve the future development of our society. With the prospect of the fossil resources depletion, it is necessary to find new alternative sources of energy and raw materials. Chemistry will play a key role to design new materials from biomass which will reshape our way of living and consumption.