The Role of Through-Bond Stereoelectronic Effects in the Reactivity of 3-Azabicyclo[3.3.1]nonanes

Hyperconjugation/conjugation through-bond stereoelectronic effects were studied with density functional theory (DFT) in the context of 3-azabicyclo[3.3.1]nonanes to unravel puzzling differences in reactivity between a vinylogous chloride (4) and a vinylogous ester (5). These compounds—whose structures differ only by one substituent—were found to display strikingly different reactivities in hydrochloric acid by Risch and co-workers (J. Am. Chem. Soc. 1991, 113, 9411–9412). Computational analyses of substituent effects, noncovalent interactions, natural bond orbitals, isodesmic reactions, and hydration propensities lead to a model for which the role of remote, through-bond stereoelectronic effects is key to explaining 4 and 5’s diverging reactivity.

COMPUTATIONAL NMR OF NATURAL PRODUCTS

A review of the literature data on the calculation of NMR parameters in a large number of natural compounds: alkaloids, terpenes, lactones, lactams, peptides is carried out in order to study their structure, as well as various stereochemical and stereoelectronic effects

Aldol-Tishchenko Reaction of α-Oxyketones. Diastereoselective Synthesis of 1,2,3-Triol Derivatives

α-Oxyketones, easily accessible by conventional routes, can be selectively deprotonated generating an enolate intermediate, which upon treatment with paraformaldehyde undergoes an aldol-Tishchenko reaction, leading to relevant 1,2,3-triol fragments in a totally diastereoselective manner. The excellent stereocontrol in the generation of a quaternary stereocenter is attributed to stereoelectronic effects in the Evans intermediate. This methodology allows overcoming some limitations of our previously reported strategy, based on the reaction of α-lithiobenzyl ethers with esters and paraformaldehyde, broadening the scope of the obtained polyols. Synthetic applications of this process include the preparation of a new dilignol model and some functionalized oxetanes.

Challenges in Studying Steric Interactions in Highly Strained Perhalogenated Alkanes and Silanes.

The decomposition of the molecular total energy in their hyperconjugative, steric and electrostatic effects can lead to interesting interpretations about the stereoelectronic effects that govern their geometry and properties. In this work, we have studied homologous series of perfluoroalkanes, perchloroalkanes, perfluorosilanes and perchlorosilanes, and all molecules have preference for helical geometries. According to Natural Bond Orbitals (NBO) calculations, the silanes have their helical geometry stabilised by hyperconjugative interactions, as well as the perfluoroalkanes. However, it was surprisingly difficult to disclose that steric interactions are ruling the helical geometry preference in perchloroalkanes by comparing the NBO analysis and the Quantum Theory of Atoms ins Molecules (QTAIM). Although perchloroalkanes have extremely intense steric interactions between Cl lone pairs, some of them were underestimated by the NBO analysis, which showed the opposite behaviour compared with QTAIM that indicates steric effects as the leading forces to helical geometry preference.

Probing optical and magnetic properties via subtle stereoelectronic effects in mononuclear DyIII-complexes

Tapping into the secondary coordination environment of mononuclear DyIII-complexes leads to drastic changes in luminescence and magnetism. Visualization of effects induced by stereoelectronics on the opto-magnetic properties was achieved through...

Exploiting the role of stereoelectronic effects to design the antagonists of human complement C3a receptor.

The stereoelectronic effects are crucial in governing the conformational behaviour of the small molecules bearing heterocyclic ring adjacent to amides. It dictates the antagonist and agonist activity for G-protein coupled...