A True Reverse Anomeric Effect Does Exist After All: A Hydrogen Bonding Stereocontrolling Effect in 2-Iminoaldoses.

The reverse anomeric effect is usually associated with the equatorial preference of nitrogen substituents at the anomeric center. Once postulated as another anomeric effect with explanations ranging from electrostatic interactions to delocalization effects, it is now firmly considered to be essentially steric in nature. Through an extensive research on aryl imines from 2-amino-2-deoxyaldoses, spanning nearly two decades, we realized that such substances often show an anomalous anomeric behavior that cannot easily be rationalized on the basis of purely steric grounds. The apparent preference, or stabilization, of the ß-anomer takes place to an extent that not only neutralizes but also overcomes the normal anomeric effect. Calculations indicate that there is no stereoelectronic effect opposing the anomeric effect, resulting from the repulsion between electron lone pairs on the imine nitrogen and the endocyclic oxygen. Such data and compelling structural evidence unravel why the exoanomeric effect is largely inhibited. We are now confident, as witnessed by 2-iminoaldoses, that elimination of the exo-anomeric effect in the α-anomer is due to the formation of an intramolecular hydrogen bond between the anomeric hydroxyl and the iminic nitrogen, thereby accounting for a true electronic effect. In addition, discrete solvation may help justify the observed preference for the ß-anomer.

A quantitative structure-reactivity relationship in N-acetyl oxazolidines: an electrostatic interaction controls rotamer population.

The conformational population of Z and E isomers of the amide bond in N-acetyl oxazolidines is dictated by the electronic nature of the vicinal aryl ring. Experimental and theoretical data support a rationale based on a strong and stereodirecting charge-charge interaction that should be added to the arsenal of non-covalent interactions and whose influence can be more important than once thought.

Schiff bases from D-glucosamine and aliphatic ketones.

Despite the comprehensive literature and enormous versatility of chiral imines derived from aminosugars and aldehydes, the corresponding counterparts generated from ketones remain an underestimated research subject. Filling in the gap, this manuscript sheds light on the synthetic and structural aspects of such substances and updates the few antecedents reported so far.

Chiral N-acyloxazolidines: synthesis, structure, and mechanistic insights.

A series of chiral imines derived from 1-amino-1-deoxyalditols such as d-glucamine, a rather unexplored raw material from the chiral pool, have been serendipitiously transformed into a novel family of N-acetyl-1,3-oxazolidines by means of an unexpected acetylation. The structure of these substances is supported by spectroscopic and crystallographic data. The acetylates also trigger a complex dynamic transformation, in which an initially configured trans oxazolidine converts into a more stable cis-configured derivative. Both isomers can also exist as rotational conformers (E,Z) as a consequence of the restricted rotation around the N-acetyl bond. The barriers to rotation have been determined by variable-temperature experiments. Overall, this transformation most likely involves the intermediacy of a chiral iminium ion, which has been documented in the synthesis of nitrogen heterocycles, thus explaining the experimental facts.