Stereoelectronic effects heterocycles

Once formed, 7 and 8 undergo a Michael reaction that gives rise to ketoenamine 9. Ring closure, to form 10, and loss of water then afforded 1,4-dihydropyridine 11. The presence of 9 and 10 could not be detected thus ring closure and dehydration were deduced to proceed faster than the Michael addition. This has the result of making the Michael addition the rate-determining step in this sequence. Conversely, if the reaction is run in the presence of a small amount of diethylamine, compounds related to 10 could be isolated. Diol 20 has been isolated in an unique case (R = CFb). Attempts to dehydrate this compound under a variety of conditions were unsuccessful. Stereoelectronic effects related to the dehydration may be the cause. In related heterocyclic ring formations, it has been determined that dehydration (20 —> 10) is about 10 times slower than diol formation (19 —> 20). Therefore, one would expect 20 to... 

Stereoelectronic effects in the formation of 5- and -6-membered heterocycles 93ACR476. 

Oxathiacyclanes, structure, reactivity, synthesis 83UK619 SOM 144. Quantum chemical nonempirical investigations of S-heterocycles 85ZC50. Stereoelectronic effects in S-heterocycles 85PS(23)169. 

The anomeric effect is an empirical, thermodynamic stereoelectronic effect that states the preference for heteroatoms to occupy the axial position in saturated six-membered heterocyclic ring systems, notably carbohydrates (Lemieux and Koto, 1974 Szarek and Horton, 1979). Features of the anomeric effect had been remarked upon many years before its advent in... 

Many of the stereoelectronic effects in the list above govern reactivity, but the next section will deal with how stereoelectronic effects affect structure—and in particular conformation. Some of the most important saturated oxygen heterocycles are the sugars. Glucose is a cyclic hemiacetal—a pentasubstituted tetrahydropyran if you like—whose major conformation in solution is shown below. About two-thirds of glucose in solution exists as this stereoisomer, but hemiacetal formation and cleavage is rapid, and this is in equilibrium with a further one-third that carries the hemiacetal hydroxyl group axial (<1% is in the open-chain form). 

We have covered a lot of ground in this chapter, and have used the huge topic of saturated heterocycles to explain a lot, not just about the reactivity and conformation of rings. Many of these explanations involved consideration of the alignment of orbitals— we called these stereoelectronic effects. The same analysis allowed us to make sense of the NMR spectra, and in particular the coupling constants, of cyclic molecules, both heterocycUc and carbocyclic. And by thinking about symmetry in these cyclic molecules we were also able to deduce the origins of symmetry-related features (such as diastereotopic protons) in the NMR spectra of acycUc compounds. 

Due to the above differences, stereoelectronic effects in O- and S-heterocycles cannot be automatically transferred to the N-heterocycles and vice versa. Differences in hybridization were shown to be important for stereoelectronic hyperconjugative interactions. ° Not only is hybridization of a donor orbital related to its absolute energy, but hybridization determines the direction in which non-bonding orbitals are projected in space. Consequently, directionality of sp" hybrids can change considerably as a function of substitution. Furthermore, hybridization controls the relative size of the two lobes of a lone pair. The front and back lobes... 

The CRC Dictionary of Natural Products comprises structures of individual chemicals of which 90% contain either carbocyclic or heterocyclic subunits [452, 453]. Therefore, not surprisingly, the formation of bonds from acyclic precursors in a regio- and stereo-controlled manner is key to the design of the synthesis of cyclic structures and is of prime importance to the architecture required for the construction of complex molecules. The rational design of the cyclization step, known as the Baldwin rules, is historically one of the most widely used in the arsenal of synthetic methods available to organic chemists [7]. Along with the widely used Baldwin rules, the most comprehensive review (1993) focuses on other important points, such as stereoelectronic effects, that are especially important in the formation of five- and six-membered rings [7]. 

C NMR spectroscopy of 1,7-dioxa- (314), l-oxa-7-thia- (315), and 1,7-dithiaspiro[5.5]undecane (316) and many of their derivatives, with special emphasis on stereoelectronic and steric effects governing the configurational and conformational properties of these compounds (484-486). This work showed that chemical-shift parameters developed for six-membered carbocyclic compounds in chair conformations (149) could be applied successfully only to sulfur and not to oxygen heterocycles (486). 

Two-electron/two-orbital h5q>erconjugative interactions of the t3q>e responsible for the anomeric effect depend on the relative orientation of bonds and lone pairs in a molecule and are also inversely proportional to the energy difference between the interacting orbitals. Spectroscopic manifestations of stereoelectronic interactions are particularly useful experimental signatures of these effects, which can be utilized for testing molecular models. Empirical observations together with theoretical interpretations in cyclohexane and six-membered heterocycles confirm the relevance of ffc uax Hax/ nx Hax (X = O or N), [Pg.210]

Three-dimensional structure and biological function of oligonucleotides is controlled by several factors. First, it is controlled by the conformation of the constituent pentofuranoses, which in turn is controlled by stereoelectronic factors, such as the anomeric and gauche effects that determine the position of pseudorotational equilibria in nucleos(t)ides. Second, it is controlled by the nature or by the configuration of one of their constituents, i.e., a heterocyclic nucleobase, a pentofuranose moiety, or C2 and C3 substituents, and finally it is controlled by the pH of the medium. 

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