Anomeric interactions

In cyclic systems such as 1, the dominant conformation is the one with the maximum anomeric effect. In the case of 1, only conformation lA provides the preferred antiperiplanar geometry for both oxygens. Antiperiplanar relationships are indicated by including lone pairs in the oxygen orbitals. Other effects, such as torsional strain and nonbonded repulsion, contribute to the conformational equilibrium, of course. Normally, a value of about 1.5 kcal/mol is assigned to the stabilization due to an optimum anomeric interaction in an acetal. 

A comparison of 190 with 1,3-dioxane 177 shows that the anomeric interactions in 177 are much stronger than in 190. Moreover, the balance of the computed hyper-conjugative interactions successfully accounts for the relative C—Ha and C—Hgq... 

Studies of n4 compounds possessing three P-C bonds are presented below. In addition to a diazaphospho1e oxide,174 the internal molecular motions of triphenylphosphine oxide have been analysed,173 and the anomeric interaction of a diphenylphosphinoyl-1,3-dithiane estimated.174 The structures of two sulphides have been examined,... 

In comparison with previous plots of this section, the no-crco anomeric interaction of Fig. 3.65 can be seen to be a rather typical example of hyperconjugative donor-acceptor interactions. Consequently, there seems to be no valid reason to invoke a special effect for the conformational preferences of sugars, obscuring their essential conformity with a unified donor-acceptor picture of ethane-like rotation barriers. 

The role of steric effects is unclear but the anomeric effect could also contribute to an increase in electron density at nitrogen. X-ray data for the two TV-acyloxy-TV-alkoxyamides, a urea and a carbamate outlined above show clear evidence, both from bond lengths and conformations, of an anomeric interaction RO-N bonds are short when compared to alkoxyamines. This interaction is responsible for SN1, SN2, homolytic and rearrangement reactions of /V-acyloxy-TV-alkoxyamides (vide infra) and has also been supported computationally. Acyloxylation of the hydroxamic esters results in both pyramidalisation as well as anomeric donation from the... 

These results clearly indicate that barriers to all isomerisation processes are at least less than about 8kcalmol 1. In /V-benzyloxy-7V-chlorobenzamide 44 the amide isomerisation was not observable but the anomeric overlap resulted in diastereotopic benzylic hydrogens, which at coalescence afforded a barrier for rotation about the N-OBn bond of around 10.3 kcalmol-1.32 Like its /V-chloro analogue, the amide isomerisation barrier in 43 is too low to be observed by 3H NMR and even though there is definitive X-ray and theoretical evidence for anomeric effects in /V-acyloxy-/Y-alkoxyamidcs, the barrier to isomerisation about the N-OBn bond must be lower than 10.3 kcalmol-1. The n0-CN ci anomeric interaction in 44 is predicted to be stronger than the n0-CN OAc interaction in 43 on purturbation arguments.32... 

The physical and spectroscopic properties of /V-acyloxy-A-alkoxyamides confirm pyramidality at nitrogen and the disconnection of the nitrogen lone pair from the amide carbonyl. The presence of an acyloxyl and an alkoxyl group at nitrogen also results in an anomeric interaction between the oxygens, which is facilitated by the sp3-hybridised nitrogen. Experimental observations, including X-ray analysis are fully supported by results from computational chemistry. 

C—N—C bond angles. Theory predicts22-25 an opening of these angles as a result of an anomeric interaction. Thus conformationally dependent correction terms for 8° were derived according to ... 

Anderson and Sepp (68JOC3272) equilibrated some cis/trans isomeric 2-OR-4-Me-, 2-OR-6-Me-, and 2-OR-6-CH20H-oxanes and discussed their equilibria in terms of anomeric interactions. The corresponding conformational equilibria were assumed to be strongly one sided [e.g., the 2,4-isomers cis isomer 2-eq-4-axy, trans isomer 2-ax-A-eq)]. 

B. The Anomeric Interaction in A/-Heteroatom-substituted Hydroxamic Esters... 

By definition, a generalized anomeric effect is observed at carbon of an XCY system when a molecule preferentially adopts a conformation that optimizes a secondary, stabilizing electronic interaction involving overlap between the lone pair on one heteroatom with the a orbital of the bond between the central carbon atom and the second heteroatom . Figure 5a illustrates that in XNY systems, as with anomeric carbon centres, two anomeric interactions are possible and involve either an ny-CT x ° nx-o NY overlap where nx and ny represent the p-type lone pairs on X and Y and NX and NY represent the N—X and N—Y a orbitals. In either case, the result is a net stabilization of the lone pair of electrons (Figure 5b). Except where the nitrogen is symmetrically substituted, one of these interactions will be strongest. 

Anomeric interactions are also affected by the sizes of the interacting orbitals and will be best where the Y has orbitals of similar size to N. Thns, in an ONCl system, the similarity in size of orbitals on N and O and lower energy of the N—Cl a orbital favours the no-anomeric effect over the alternative nci-[Pg.844]

FIGURE 5. (a) Anomeric interactions in bisheteroatom-substituted amides (b) lone-pair stabilization through an ny NX anomeric interaction... 

Anomeric effects in ONCl systems are Uo-Oj a even though oxygen is more electronegative than chlorine N and O orbitals are similar in size and chlorine is a 3p element, thus favouring overlap between the p-type lone pair on O with the low-energy N-Cl <7 orbital. In XNY systems, occupation by Uy leads to transfer of electron density to the X substituent and the substantially higher electron affinity of chlorine will also favour this anomeric interaction rather than an Uci-cTno overlap. 

These results indicate that barriers to all isomerization processes in A-acyloxy-A-alkoxyamides are likely to be less than about 8 kcalmol. Like that for its A-chloro analogue, the amide isomerization barrier in 100 is too low to be observed by H NMR. While there is dehnihve X-ray and theoretical evidence for anomeric effects in A-acyloxy-A-alkoxyamides, in the case of 100 the barrier to isomerization about the A-OBn bond must be lower than 10.3 kcalmol, the barrier in the corresponding A-chlorohydroxamic ester (Section in.B.2). The no-Oj Q anomeric interaction in A-chloroadducts is predicted to be stronger than the uo-Oj oAcyi interaction on perturbation arguments . 

Shtamburg and coworkers have reported that A,A -dialkoxy-A,A -dicarboalkoxyhydra-zines (219) have lower barriers to amide isomerization and weaker anomeric interactions . They measured a barrier to amide isomerization of only 9.8 kcalmoD. Furthermore, benzylic methylenes in A-benzyloxy systems were isochronous down to at least —90°C. These results are in line with observations for the A,A -diacyl-A,A -dialkoxyhydrazines since, in the carboalkoxy systems, the nitrogen lone pairs are lowered in energy by the additional electron demand, thereby reducing both amide conjugation and anomeric overlap. 

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