Steric interactions 1,3-diaxial

Diaxial interaction (Section 4.8) The strain energy caused by a steric interaction between axial groups three carbon atoms apart in chair cyclohexane. 

The stereoselectivity is enhanced if there is an alkyl substituent at C(l). The factors operating in this case are similar to those described for 4-r-butylcyclohexanone. The tnms-decalone framework is conformationally rigid. Axial attack from the lower face leads directly to the chair conformation of the product. The 1-alkyl group enhances this stereoselectivity because a steric interaction with the solvated enolate oxygen distorts the enolate to favor the axial attack.57 The placement of an axial methyl group at C(10) in a 2(l)-decalone enolate introduces a 1,3-diaxial interaction with the approaching electrophile. The preferred alkylation product results from approach on the opposite side of the enolate. 

In contrast to 21, the diol epoxide derivative of the 8,9-dihydrodiol of DMBA was relatively stable. Although only the anti isomer was isolated and identified from epoxidation of the 8,9-dihydrodiol with m-chloroperbenzoic acid (84), it is likely that the syn isomer may also be formed in this reaction. The 8,9-dihydrodiol exists predominantly in the diaxial conformation as a consequence of steric interaction between the 8-hydroxyl and 7-methyl groups (88). 

Chemical shifts for monohydroxy-steroids may be used additively to predict those for diols, except in cases where the two functional groups are in a 1,2-relationship or in certain 1,3-relationships. Steric interactions of hydroxy-groups in 1,2-gauche or 1,3-diaxial relationships are thought to explain some of the observed deviations from additivity, which closely resemble those asociated with... 

Interestingly, Allingham et al. (66) have analyzed a series of N-alkyl 5-nitrotetrahydro 1,3-oxazines and concluded that there is a preference for the N-alkyl axial conformer U)l when the alkyl substituent is methyl, ethyl or propyl and a preference for the N-alkyl equatorial conformer 102 when the substituent is isopropyl, cyclohexyl or t-butyl. Thus, J01 is still preferred despite the 1,3-diaxial steric interaction between the nitro group and a primary N-alkyl group. Finally, Katritzky et al (70) have proposed the conformation 103 as the major one for compounds 104 and 105,... 

Values of 4.0 and 3.0 kcal/mol were used for the steric interactions of a methyl group 1,3-diaxial to methyl (or methylene) and to oxygen respectively (24). 

These results can be readily interpreted if the rate-determining step of these reactions is the formation of the tetrahedral intermediates 241 and 245. Indeed, there is a direct relationship between the relative ease of formation of these two intermediates (which depends upon their respective steric hindrance) and that of the acetamidoalcohol products 243 and 247 (R=H or CHj). In intermediate 241, when R=CH3, there is a strong 1,3-diaxial steric interaction between the N-CH3 group and the axial phenyl group. Such-steric interaction does not exist when R=H. Consequently, the formation of acetamidoalcohol 243 (via 241) should occur with ease only when R=H. This conclusion agrees with the experimental results. In the case of intermediate 245, when R=CH3, there is no 1,3-diaxial steric interaction caused by the N-methyl group. On that basis, intermediate 245 (R CHg) should be readily formed. However in this intermediate, there is a strong 1,3-diaxial steric... 

It has been postulated that methyl group relaxation times reflect energy differences between preferred conformations and the transition state for rotation. (32) Decreasing the number of diaxial 1,3-steric interactions lowers the energy of the preferred conformation but increases the energy of activation for the rotational process. Rotation rates are decreased but the efficiency of the relaxation process is enhanced, i.e. 71, is decreased. In Fig. 3 are shown the Tx data for a related series of steroids of interest to us. As can be seen, loss of 1,3-diaxial interactions does markedly reduce methyl Tx values. This is particularly evident for the change to an a/B-cis ring fusion as in compound [11]. 

In general -substituent effects are small, but a marked exception exists when the substituent and the carbon in question have a syn-diaxial relation. While the steric interactions suggest a shielding of the carbon, in fact an appreciable deshielding is found. Thus, the C-l9 methyls in the 2/7- and 4/ hydroxy-5cc-cholestanes are 2-5 and 2-4 ppm to high frequency of the value in 5 cc-cholestane itself. This type of evidence has also been advanced against the operation of the steric polarization mechanism. 

Noyori et al. proposed that the reaction would be initiated by complexation of the Lewis acidic lithium cation to the ketone oxygen atom then hydride transfer occurs from aluminum to the carbonyl carbon by way of a six-membered chairlike transition state3 (Scheme 4.3c). Between the two competing six-membered chairlike transition states A and B, transition state B is disfavored, due to the substantial n/it-type electronic repulsion between the axially oriented binaph-thoxyl oxygen and the unsaturated phenyl or alkenyl moiety. Although there is a 1,3-diaxial steric interaction between the Al-0 and C-R bonds in transition state... 

In most cases, steric effects control the axial-equatorial equilibrium and favor the equatorial position of the substituents. Indeed, an axial substituent experiences gauche interactions with C-3 and C-5, while the equatorial substituent is trans to C-3 and C-5 and thus relieves the strain of these gauche, interactions. Furthermore, the two axial hydrogens on C-3 and C-5 experience steric interactions with the hydrogen atom (LXXXa) or the substituent (LXXXb) occupying the C-1 axial position. These diaxial 1 /3 interactions are larger with a substituent than with H. 

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. 

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