1,3-Diaxial interactions table

The interaction of a pair of cw-l,3-diaxial substituents (1,3-diaxial interaction Table 2.2)... 

The conformational energies of monosubstituted oxanes studied to date are collected in Table I. In position 2, polar substituents (except NR2) prefer the axial position other substituents prefer the equatorial orientation, which is generally the case for groups in positions 3 and 4. Destabilizing 1,3-diaxial interactions cause the equatorial geometry to be usually favored in the 2-position, the anomeric effect stabilizes the axial conformation. A large purine moiety in position 2 of oxane, for example, prefers the equatorial position because the 1,3-diaxial interactions overcome the anomeric effect (75TL1553). 

Eliel et al. (82JA3635) examined the conformational equilibria of a number of disubstituted oxanes (Table III) by low-temperature C NMR spectroscopy (830MR94) and estimated the AG° values of 3-Me and 2-C=CH substituents (see Table I). The concentration of the axial 2-Me and 4-Me conformers, however, was so small and difficult to detect by NMR spectroscopy that they were forced to employ the use of counterpoised di-2-C=CH and ds-2-CH = CH2 groups to generate equilibria that were sufficiently balanced to measure accurately (AG° values in Table I). Eliel et al. (82JA3635) also discussed the conformational energies in terms of 1,3-diaxial interactions and the anomeric effect. 

Several 8a-substituted cw-octahydroquinazolin-2(l//)-ones 346C clearly prefer the N l)-in chair-chair conformation [71JCS(C)1812], as confirmed by the small values of the two /H.4,H-4a coupling constants (2-4 Hz). Similar small values were found for both yH-4,H-3 couplings of 4a-methyl-ds-octahydroquinazolin-2(l//)-one. This can be explained by either an N 1)-in or an N(2)-out conformation [N(3)-H equatorial], but the latter (347C) appears to be more probable because the 1,3-diaxial Me,NH interactions are less severe than Me,CH2 interactions (Table IV). 

Other examples of the formation of six-membered rings by means of an intramolecular alkylation of an ester enolate are given in Table 7. Entry 6, i.e., stereoselective transformation of the epoxy ester into the cyclohexane derivative, should be discussed briefly as a representative for the other cases. The probable reason for the unexpectedly high selectivity i.e., the nonappearance of the diastereomer 8, can be demonstrated by the two transition-state-like conformations 9 and 10. 9 displays a very severe 1,3-diaxial interaction in comparison to 10, thus, formation of the diastereomer 7 from conformation 10 is highly favored113. 

Strategy Draw the two chair conformations of each molecule, and look for gauche and 1,3-diaxial interactions. Use Table 4.1 to estimate the values of the interactions. Calculate the total strain the conformation with the smaller value for strain energy is more stable. 

Strategy To solve this problem (1) Find the energy cost of a 1,3-diaxial interaction by using Table 4.1. (2) Convert this energy difference into a percent by using Figure 4.12. 

We are now in a position to interpret the reactions of steroid amines, particularly with respect to the dominant retention of configuration in substitution and the considerable or exclusive elimination of axial amino groups. Shoppee has pointed out [3] that the ratio, elimination/substitution, for a series of axial amines follows the order expected on the basis of steric hindrance to the formation of the axial alcohol. In simple mono- and bi-cyclic systems, as well as in acycUc amines, the proportion of olefinic products is far lower (often ca. 30% than for many steroids. This agrees with the concept that very high yields of olefins result from steric frustration of cis substitution. A semi-quantitative correlation of olefin yield with the number and nature of the sy -diaxial interactions at the reaction centre is even possible (Table 27). 

How can you account for the fact (Table 4.2) that an axial tert-butyl substituent has much larger 1,3-diaxial interactions than isopropyl, but isopropyl is fairly similar to ethyl and methyl Use molecular models to help with your answer. 

Ireland s deprotonation model is widely used to rationalize the stereochemistry with various ethyl ketones and bases. " In the absence of additives that solvate the lithium cation such as HMPA, proton transfer occurs via a chair-hke closed transition state. Under these conditions, the (Z)-enolate is disfavored because of the 1,3-diaxial interaction between the Me and the i-Pr group on nitrogen. As the steric requirement of the R group increases, so does the A strain between the R and Me groups in forming the double bond, thus destabilizing the ( )-(0)- relative to the (Z)-(0)-enolate (Table 6.2). 

In monosubstituted cyclohexanes, the substituent prefers to be equatorial to an extent that is greater the larger the substituent. The substituent experiences destabilizing 1,3-diaxial interactions when axial, and so by ring inversion assumes the equatorial position (see Chapter 1). This inversion is an equilibrium process and the equilibrium ratios, of course, can be expressed as a free energy difference in the present context they are known as A values1 and these are collected in Table 6.2. 

Table 1.2 displays the tautomeric composition of pentoses and hexoses in aqueous solution as well as 1-deoxy fructose 1.20, and fructofuranose-l,6-diphosphate 1.21. The predominance of pyranoses is observed. The galactofuranoses 1.22 are relatively more stable than the glucofuranoses 1.23, perhaps due to the trans arrangement of the hydroxyl at C-3 and the side chain in the former. We also see that there are ten times as many jS- as there are a-pyranoses in the fructose solutions. At this point we are jumping ahead to Chapter 2, which is devoted to problems of conformation. We can draw /To-fructopyranose as confonnation 1.24 where only one unfavorable interaction takes place between H-3 and OH-5. The exchange of substituents at C-2 leads to an eminently unfavorable conformation which shifts to 1.25, the lesser of two evils, but where strong 1,3-diaxial interactions remain. 

In all cases, allyl-9-BBN provides the best diastereoselectivity. The high 1,3-asymmetric induction (96 4) produced in allyl-9-BBN addition to (36 R = Ph entry 1, Table 9) is consistent with a proposed cyclic chair transition state shown in Figure 11a. Diastereofacial selectivity is reversed in methallyl-9-BBN addition to (36 R = Ph entry 3, Table 9). As a result of additional 1,3-diaxial interactions invol-... 

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