Endocyclic lone electron pairs

Very recently, Benn and collaborators explained the experimentally observed axial conformational preferences of 2-cyano derivatives of oxane, thiane, and selenane in terms of an attractive through-space n interaction between the nonbonded lone electron pair of the endocyclic heteroatom and the n orbital of the axial cyano group. This proposal was supported with computational (NBO) analysis (Scheme 22) (10CJC831). 

The picture is less clear when free electron pairs on other heteroatoms (O, S, etc.) are involved. There is only one clear-cut case providing evidence concerning endocyclic sulfoxides The unusually large shieldings of carbon atoms in gauche position relative to an axial oxygen atom in thiane oxides 79, 80, 82, and 83 (p. 252) (200,201) have been partially ascribed to an upfield-shifting effect of the equatorial antiperiplanar lone pair (cf. Section III-C). 

Figure 1.11 The anomeric effect interaction of the endocyclic oxygen electron lone pair with the nonbonding orbital in an axially substituted compound.

Reactions of Phosphoric Acids and Their Derivatives. - Numerous investigations of phosphate ester hydrolysis continue to be reported. The hydrolysis between 1.5 < pH < 4 of five- and six-membered cyclic phosphoramides (71) has been followed by UV and NMR spectroscopy. Small differences in hydrolysis reactivity for n = 5 and n = 6 constitutes evidence for syn lone pair catalysis. The product ratios from the hydrolysis shows that in the five-membered rings the main product is the one produced by endocyclic cleavage meanwhile, in the six- membered cyclic phosphoramide the kinetic product is the one produced by exocyclic cleavage. The syn orientation of two electron pairs on nitrogen stabilizes the transition state of water approach to the phosphoramides by ca. 3 kcal/moN when compared to the orthogonal attack. (Scheme 12). ... 

The term exoanomeric effect was introduced to describe an orientational effect of the aglycon part.31 In this case, the electron density of the lone pair of the exocyclic oxygen atom is transferred to the antibonding orbital of the endocyclic C—O bond (Figure 1.12). Essentially, this effect... 

FIGURE 1.10 The anomeric effect, (a) The n-o interaction stabilizes the a anomer. (b) The P anomer experiences unfavorable dipole-dipole interaction that is reduced in the a anomer. (c) Greater electrostatic repulsion between the lone-pair electrons of the endocyclic oxygen and the electronegative anomeric substituent in the (1 anomer. 

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