Unfavorable 1,3-diaxial

The acyclic precursor is an oc, 3-unsaturated amido aldehyde that was condensed with iV-methylhydroxylamine to generate the nitrone ( )-48, which then underwent a spontaneous cycloaddition with the alkene to afford the 5,5-ring system of the isoxazolidinyl lactam 47. The observed product arises via the ( )-nitrone transition state A [or the (Z)-nitrone equivalent] in which the position of the benzyl group ot to the nitrone effectively controls the two adjacent stereocenters while a third stereocenter is predicted from the alkene geometry. Both transition states maintain the benzyl auxiliary in an equatorial position and thus avoid the unfavorable 1,3-diaxial interaction with the nitrone methyl or oxygen found in transition state B. Semiempirical PM3 calculations confirm the extra stability, predicting exclusive formation of the observed product 47. Related cycloadducts from the intramolecular reaction of nitrones containing ester- rather than amide-tethered alkene functionality are also known (83-85). 

G=G bond approximately perpendicular to the coordination plane, with the triethylsilylmethyl group adopting an axial or pseudo-axial position about the hexenyl chelate. Gomplex 41 presumably adopts a boat-like conformation to avoid unfavorable 1,3-diaxial interaction between the triethylsilylmethyl group and one of the methoxycarbonyl groups. 

In principle, there are four possible transition states for the attack of a nucleophile on a cyclic iminium ion such as 67. Two of these, 7] and 72, are boat-like transition states and are kinetically disfavored. Of the two possible chair-like transition states, 70 and 73, the latter suffers from an unfavorable 1,3-diaxial interaction between the R group and the incoming nucleophile. Transition state 70 is therefore favored. 

The steric interference between substituents in axial positions is particularly severe when there are large groups on two carbon atoms that bear a 1,3-diaxial relationship (cis on Cl and C3, or Cl and C5), as in the two chair conformations of cis-l,3-dimethyl-cyclohexane shown here. The less stable conformation has both methyl groups in axial positions. The more stable conformation has both methyl groups in equatorial positions. Note the strongly unfavorable 1,3-diaxial interaction between the two methyl groups in the diaxial conformation. The molecule can relieve this 1,3-diaxial interference by flipping to the diequatorial conformation. Use your models to compare the diaxial and diequatorial forms of cis-1,3-dimelhylcyclohexane. 

Larger axial substituents create unfavorable 1,3-diaxial interactions, destabilizing a cyclohexane conformation. 

Diaxial interaction (Section 4.13A) A steric interaction between two axial substituents of the chair form of cyclohexane. Larger axial substituents create unfavorable 1,3-diaxial interactions, destabilizing a cyclohexane conformation. 

The observed stereoselectivity in the Evans aldol reaction can be explained by the ZImmerman-Traxler transition state model. There are eight possible transition states, four of which would lead to the anti aldol product. These, however, are disfavored due to the presence of unfavorable 1,3-diaxial interactions (not depicted below). The possible transition states leading to the syn aldol product are shown below. The preferred transition state leading to the product is transition state A, where the dipoles of the enolate oxygen and the carbonyl group are opposed, and there is the least number of unfavored steric interactions. 

Preferred formation of cis VI can be rationalized with unfavorable gauche interactions of the N methyl group with the equatorial a methyl group in the seven membered chair like transition state of the cyclization step leading to trans VI. Avoidance of the gauche interaction prevails over the unfavorable 1,3 diaxial interactions present in the cyclization transition state leading to cis VI. 

Aliphatic ketones with a stereogenic center in the a-position may also be easily epimerized by base catalysis. A mixture of epimers 4 and 5 is quantitatively transformed into 5 by sodium carbonate in methanol which releases the unfavorable 1.3-diaxial interaction suffered by 465 (for further examples see references 66 and 67). 

In contrast, a ram-decalin system with an unfavored 1,3-diaxial interaction (e.g., 2) is converted into a mixture in which the e -isomer is slightly predominant13. 

The conformational properties of dihydrothiazine oxides of types 239 and 242 have been examined by NMR spectroscopy.79,95 98,101 In the case of the (R)-oxides 239, there is a dramatic preference for the conformer 241 by contrast, the (S)-oxides 242 exist overwhelmingly as the conformer 243. These results illustrate that the conformer that possesses an axial 5-oxide is favored. The conformer 243 possesses an unfavorable 1,3-diaxial interaction between the oxide group and R1, and the conformer 241 is destabilized by an allylic interaction between R1 and R2. Evidently, these interactions are less severe than the allylic interaction between the oxide and methoxy-carbonyl groups which would be present in the conformers 244 and 240. 

The conformational properties of dihydrothiazine dioxides of type 250 have been examined by NMR spectroscopy.24 In general, N-unsubstituted derivatives, e.g., 260a-c, exist as a 1 1-3 1 mixture of the conformers 263 and 264. By contrast, N-substituted compounds, e.g. 261b and 262, favor the conformer 264. The conformer 263 is destabilized by an allylic interaction between R1 and R2, whereas the conformer 264 possesses an unfavorable 1,3-diaxial interaction between an oxide group and R1. Evidently, the latter interaction is less severe than the former when R1 and R2 are groups other than hydrogen atoms. 

A monosubstituted cyclohexane prefers an equatorial conformation 10.81a since its alternative, an axial conformation 10.81b, leads to unfavorable 1,3-diaxial inter-... 

Similar arguments can be made to explain the high degree of chirahty transfer observed with acyclic allylic alcohols (Scheme 7.18) [12]. In the preferred transition state 46a, unfavorable 1,3-diaxial interactions between the bulky dimethyl amine moiety and the R group as well as allyUc A -strain are avoided. 

The conformation of the core cholic acid scaffold is curved with three hydroxyl groups on the a surface (Figure 19). The equatorial Ba-OH group is the least hindered, while the lla-OH is less hindered than the la-OH because of unfavorable 1,3-diaxial interactions between the 7q -OH and CH2 groups. The hydroxyl groups can themselves act as hydrogen-bond donors to bind anions however, it is possible to convert all or individual hydroxyl functional groups to amine or amide moieties to further... 

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