Salt effects on the conformational behavior of 5-substituted 1,3-dioxanes

Abstract

Since their introduction by E. L. Eliel nearly four decades ago, derivatives of 1,3-dioxane have proved useful in conformational analysis. Examples are discussed, where 5-polar substituents permit the evaluation of fundamental phenomena such as attractive and repulsive gauche effects, electrostatic interactions, and stereoelectronic effects. By the same token, 2-substituted 1,3-dioxanes, 1,3-dithianes, and 1,3-oxathianes are useful frameworks for the study of the anomeric effect and the associated structural and spectroscopic manifestations, such as the so-called Perlin effects. In view of the varied and essential involvement of metal ions and inorganic salts in biological processes, 5-substituted 1,3-dioxanes are presently being examined in the presence of Li + , Na + , K + , Ag + , Mg 2+ , Ca 2+ , Ba 2+ , and other cations, with the aim to increase the understanding of biomolecular properties in vivo. 1,3-DIOXANES AS MODEL SYSTEMS IN CONFORMATIONAL ANALYSISInterestingly, H. Sachse's proposal of a strain-free, chair-shaped cyclohexane [1a] was published in 1890, the same year A. Baeyer advanced the idea that cyclohexane was planar (and thus strained) [1b]. Baeyer's model was favored during several decades, owing to the fact that rapid-ring inversion prevented isolation of the axial and equatorial isomers that should originate in monosubstituted cyclohexane derivatives (Scheme 1).

Tuning Selectivity of Anionic Cyclizations: Competition between 5-Exo and 6-Endo-Dig Closures of Hydrazides ofo-Acetylenyl Benzoic Acids and Based-Catalyzed Fragmentation/Recyclization of the Initial 5-Exo-Dig Products

“…Taking into account our long-standing interest in hyperconjugative stereoelectronic effects, we analyzed delocalizing hyperconjugative interactions in the key anionic species using Natural Bond Orbital (NBO) analysis. Similar interactions which involve σ bonds manifest themselves in numerous stereoelectronic effects controlling organic structure and reactivity. , In particular, hyperconjugation influences conformational equilibria, , modifies reactivity, determines selectivity, and is enhanced dramatically in excited, radical, and ionic species . In the following part, we will show that observed stereoselectivity stems from an interesting interplay of hyperconjugative effects which are developed to a different extent at the different stages of the cyclization process…”

A Dioxane Template for Highly Selective Epoxy Alcohol Cyclizations

“…19 A plausible explanation for the enhanced selectivity, therefore, is the tendency for 1,3-dioxane rings to even more readily adopt such a twist conformation. 20 As reported by Eliel over 40 years ago, 1,3-dioxanes often adopt more puckered conformations due to the presence of shortened endocyclic C–O bond lengths that in turn distort the ring bond angles. 18c,d This was further corroborated by Rychnovski in 1993, who demonstrated through various means that substitution at the 4- or 6-positions orients the ring into the twist conformation to minimize steric interaction with C2 substituents that are augmented by the short C–O bond distances.…”

Homoanomeric Effects in Six-Membered Heterocycles

“…10,49 This choice of heteroatoms allowed us to scan a variety of donor lone pairs of different hybridizations, energies, spatial orientations, and sizessthe factors which are crucial for stereoelectronic interactions. To understand the cooperativity of homonoanomeric effects, we have extended our analysis to 1,3-diheterocyclohexanes which were also a subject of several recent theoretical 7,50-53 and experimental 52,[54][55][56][57][58] studies. Finally, cyclohexane was used as a useful reference point.…”