Diaxial nonbonding

This value is in excellent agreement with the calculated free energy value by the consideration of various nonbonded interactions in the epimers (69 and 70) [(2 X 1,3-diaxial Me—H interaction) — (1 x 1,3-diaxial Me—H interaction + 1 X l,2- < Me—H interaction) = (0.9 x 2) — (0.9 + 0.6) = 0.3 kcal/mole]. Hydrolysis of the enamine with dilute acetic acid gave a 3 2 mixture of cis and trans isomers of the ketone, thus confirming the assignments made to the enamine components. 

The same equatorial preference is also manifested in the 3,3-disubstituted thietane oxides66,194. Thus, the NMR spectra of 5e,f contain two Me singlets at 1.23 and 1.30 ppm and two methylene multiplets at 3.03 and 3.53 ppm (in CDC13). The large difference in the chemical shifts of the axial and equatorial a-methylene hydrogens is characteristic of an axial nonbonded electron pair on sulfur (conformation 5e equation 73). This conformational preference is corroborated by the small differences in the chemical shifts of the two methyl groups, and fits the contention that 1,3-diaxial interactions are responsible for this ultimate result. Certainly, these interactions are greater in the conformer 5f. 

Imidazole-l-sulfonate Displacements at the C-3 and C-4 Positions of Sngar Derivatives. Displacement reactions of tosylates at the C-3 position of a-D-glucopyrano-side derivatives proceed with difficulty because of a nonbonded 1,3-diaxial interaction between the aglycone and the approaching nucleophile [32], as well as complications arising from neighboring group participation [90],... 

The introduction of only one methyl group on the a-carbon atom with respect to the hydroxy group (37, R4 = Me) stabilizes the cyclic tautomer. The presence of two methyl groups (37, R4 = R5 = Me) exerts a less well expressed stabilizing effect when R1 = R3 = Me and R2 = H, but an entirely opposite effect when R1 = R2 = R3 = Me. This is presumed (89TH1) to be caused by nonbonded 2,6-diaxial (2-Me and 6-Me) interactions in the chair conformer of perhydro-l,3,4-oxadiazine 37B. 

Similarly,(31) in 6-phenyl-ll-alkyl derivatives, May s observations were confirmed. Both studies hinted of 1 la-methyl proton shielding from the 1,3-diaxial relationship with the nonbonding electrons of nitrogen in the free... 

The reaction involves nucleophilic attack by the alkene on bromine with the formation of a tertiary carbocation that probably has some bromonium ion character resulting from sharing of the nonbonding electrons on bromine with the electron-deficient C-5 carbon. This ion is attacked from the backside by bromide ion to form dibromocholesterol with the bromine atoms in the trans and diaxial configuration, the usual result when brominating a cyclohexene. 

The selectivity noted in the cyclization reaction of 29 is most readily rationalized on the basis of steric considerations. The ring fusion in product 30 must be cis. A consideration of a Dreiding model of 30 reveals that there are no serious nonbonded interactions in this molecule. However, compound 33 (the other possible bicyclic product) has one serious interaction between the methyl group on carbon 7 and one of the gem-dimethyl groups at carbon 2. Dreiding models indicate that these two methyl groups are crowded to about the same extent in 33 as are the diaxial methyl substituents in cis-1,3-dimethylcyclohexane (34). This interaction in 34 leads to an unfavorable energy term of about 3.7 kcal/mole 28> and should, therefore, favor the formation of 30 in the electrocyclization reaction. 

During this cyclodehydration, inversion of configuration occurred at CT of 751 to give the /3-D-C-nucleoside 752 rather than its a-anomer because of (i) preference of the protonated bulky heterocycle to occupy the equatorial j8 position in the (envelope) conformation (753) to gain the stabilization of the reverse anomeric effect, and (ii) destabilization of the conformation of the alternative a-anomer (754) by the nonbonded CM-l,3-diaxial interaction between the C3 hydroxyl and the bulky heterocycle (80MI8) (Scheme 195). 

The formation of trisubstituted double bonds from Cope substrates with a quaternary stereo-genic center is less selective, because nonbonding diaxial interactions arise in both ring-inversed transition states. The equatorial/axial preference of both substituents depends on the size of the substituent, and the larger one usually occupies the equatorial position, e.g., II - 12803. 

Similarly, thermal rearrangement of (R,E)-4 proceeds with 90 % ee. However, a 1 1 mixture of products 5 and 6 is obtained, since discrimination between the two chair transition states (corresponding to chair A and chair B) is unselective because of nonbonding diaxial interactions in both transition states994. ... 

The adoption of any conformation other than " Ci by 21 prior to the addition of methylhthium to the C4 carbonyl carbon should result in the axial addition of methyllithium, since the severe electrostatic and nonbonding steric interaction between the electronegative anomeric (Cl) methoxy group and the equatorially approaching methyl carbanion of methyllithium will impede the equatorial addition of methyllithium. In the case of an axial attack of methyllithium to the C4 carbonyl carbon, these severe 1,4-diaxial electrostatic and steric interactions are avoided. This rationalization is strongly supported by the finding that methyl 2, 3-di-O-methyl-6-0-triphenylmethyl-p-D-xy/o-hexopyranosid-4-ulose 22, where such 1, 4-diaxial electrostatic and nonbonded steric interactions do not exist, reacts with an ethereal solution of methyllithium at —80 °C to yield both C4 epimers (25 and 24, Fig. 1.4). 

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