Silvina C. Pellegrinet

A Multi-standard Approach for GIAO 13C NMR Calculations

The influence of the reference standard employed in the calculation of (13)C NMR chemical shifts was investigated over a large variety of known organic compounds, using different quantum chemistry methods and basis sets. After detailed analysis of the collected data, we found that methanol and benzene are excellent reference standards for computing NMR shifts of sp(3)- and sp-sp(2)-hybridized carbon atoms, respectively. This multi-standard approach (MSTD) performs better than TMS in terms of accuracy and precision and also displays much lower dependence on the level of theory employed. The use of mPW1PW91/6-31G(d)//mPW1PW91/6-31G(d) level is recommended for accurate (13)C NMR chemical shift prediction at low computational cost.

Mechanistic Insights into the BINOL-Derived Phosphoric Acid-Catalyzed Asymmetric Allylboration of Aldehydes

BINOL-derived phosphoric acids catalyze the asymmetric allylboration of aldehydes. DFT and QM/MM hybrid calculations showed that the reaction proceeds via a transition state involving both a hydrogen-bonding interaction from the catalyst hydroxyl group to the pseudoaxial oxygen of the cyclic boronate and a stabilizing interaction from the phosphoryl oxygen of the catalyst to the formyl hydrogen of the aldehyde. These interactions lower the energy of the transition structure and provide extra rigidity to the system. This mechanistic pathway is consistent with the experimentally observed enantioselectivity except in one case. We have used our models predictions to guide our own experimental work. The conflict is resolved in favor of our calculations.

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.

Theoretical study of the asymmetric conjugate alkenylation of enones catalyzed by binaphthols.

To rationalize the experimental results observed in the asymmetric conjugate addition of alkenylboronates to enones catalyzed by binaphthols and shed light into the factors controlling the rate, the selectivity, and the substituent effects of this process, a theoretical DFT study has been performed. The calculations suggest the catalytic cycle is finely balanced. Reversible exchange of methoxy ligands gives rise to the binaphthol-derived alkenylboronate, which is highly Lewis acidic and strongly coordinates to the enone carbonyl in a reversible fashion, lowering the energy barrier for the subsequent conjugate addition step. The key asymmetric step goes through a sofalike transition structure in which the boron atom is strongly bound to the carbonyl oxygen and lies in the plane of the enone moiety. A steric clash between one of the iodine atoms of the ligand and one face of the enone seems to be responsible for the facial discrimination. The alternative reaction channel in which only one methoxy ligand of the alkenylboronate is exchanged was investigated too and was computed to be disfavored. The [4 + 2] and the [4 + 3] pathways for the competitive hetero-Diels-Alder reaction were also found to be disfavored relative to the conjugate alkenylboration. In addition, the effects of substitution on the enone and the alkenylboronate have been evaluated. Calculations correctly reproduced the experimental reactivity trends and enantiomeric ratios.

Mechanistic Insights into the Catalytic Asymmetric Allylboration of Ketones: Brønsted or Lewis Acid Activation?

Binaphthol ligands promote the enantioselective addition of allylboronates to ketones. In this study, we use DFT calculations to establish the identity of the reacting chiral species. Our results show that a cyclic Lewis acid-activated boronate is the most reactive species on the basis of calculated energy barriers, and it is only this species that leads to the correct enantiomer. The stereoinduction can be rationalized in terms of the competing chairlike transition structures.

A hydrogen bond rationale for the enantioselective β-alkenylboration of enones catalyzed by O-monoacyltartaric acids

DFT calculations suggest that O-monoacyl L-tartaric acids catalyze the asymmetric conjugate alkenylboration of enones through transition structures that are stabilized by hydrogen-bonding interactions. Formation of a five-membered acyloxyborane is proposed. The hydrogen of the free carboxy group derived from the catalyst interacts with the carbonyl group of the cyclic acyloxyborane, stabilizing the transition structure and reducing the flexibility of the system. Additional stabilizing nonclassical CH···O hydrogen-bond interactions seem to determine the observed enantioselectivity.

Efficient enantiospecific entry to a highly functionalized cyclopentane building block

Abstract A simple and efficient route has been developed for the synthesis of a polyfunctionalized cyclopentane in enantiomerically pure form. D-Glucose is the source of chirality for this versatile building block and a highly diastereoselective Diels-Alder reaction with cyclopentadiene is the key step.

Enantiospecific approach to a quinane skeleton related to pentalenolactones

Abstract A novel and general approach has been delineated for the enantiomerically pure synthesis of the angularly fused tricyclic system of the pentalenolactone family of compounds. D-Glucose is used as starting material and a diasteroselective Diels-Alder reaction sets the elements for the ring junctions.

Improved Synthesis of Methyl 4,6-O-Benzylidene-3-cyano-2,3-dideoxy-α-D-erythro-hex-2-enopyranoside and Methyl 4,6-O-Benzylidene-2,3-dideoxy-3-C-formyl-α-D-erythro-hex-2-enopyranoside

Abstract Simple and efficient route to the title compounds by using diethyl aluminium cyanide in benzene for the epoxide ring opening and the electrophilic assistance of LiCIO4 during the isomerization-elimination process.

Synthetic and computational studies on the tricarboxylate core of 6,7-dideoxysqualestatin H5 involving a carbonyl ylide cycloaddition–rearrangement

Reaction of diazodiketoesters 17 and 28 with methyl glyoxylate in the presence of catalytic rhodium(II) acetate generates predominantly the 6,8-dioxabicyclo[3.2.1]octanes 29 and 30, respectively. Acid-catalysed rearrangement of the corresponding alcohol 31 favours, at equilibrium, the 2,8-dioxabicyclo[3.2.1]octane skeleton 33 of the squalestatins-zaragozic acids. Force field calculations on the position of the equilibrium gave misleading results. DFT calculations were correct in suggesting that the energy difference between 31 and 33 should be small, but did not always suggest the right major product. Calculation of the NMR spectra of the similar structures could be used to assign the isomers with a high level of confidence.