Butane-gauche effects

Empirically, y-gauche effects are extremely useful in stereochemical analysis. For example, the cis- and trans-fusion of six-membered rings can be easily differentiated, since, in contrast to the trans-isomer of bicyclo[4.4.0]decane, there are gauche-butane fragments in the m-isomer (emphasized bonds) causing upheld signal shifts of the carbons involved (numbers refer to I3C chemical shifts in ppm)49-52. 

The y-gauche effect involving only C-H bonds has been recently investigated by means of a modified version of the INDO finite perturbation theory of 13C chemical shifts, using butane as a model. (41) While the expected geometrical dependence on the methyl chemical... 

Figure 2.1 Preferred conformations of butane and 1,2-difluoroethane, illustrating the gauche effect. In the gauche conformation each C-F a orbital can overlap with a C-H a orbital on the vicinal carbon, corresponding to no-bond resonance as shown. Such no-bond resonance would be disfavoured if the C-F bonds were trans, since it would remove electron density from an electronegative element. The effect is strong enough in this case to overcome the electrostatic repulsion between the two C-F dipoles, which favours the trans form.

For butane and most compounds of the form YCH2CH2X, antiperiplanar conformers are the most stable ones. The long alkyl chains of fatty acids are usually also all-anti or all-trans conformers in molecular assemblies (Fig. 1.2.3). If the substituents are, however, electronegative atoms, in particular oxygen, the synclinal (= gauche) form usually dominates. Important gauche effects (= the tendency to adopt conformations with the maximum number of gauche interactions between adjacent electron pairs and/or polar bonds) are found in peroxides. 

A basic tenet of organic conformational analysis is that the lessons learned from the extensively studied hydrocarbon systems will carry over more or less unperturbed to systems with heteroatoms. The conformational analysis of methyl ethyl ether should not be too different from that of n-butane. However, in certain cases, when multiple heteroatoms are superimposed on a hydrocarbon framework in close proximity, a number of novel "effects" arise, which often stabilize otherwise unstable conformations. These effects, such as the anomeric effect and the gauche effect, all have similar origins that can be easily understood using the bonding models of Chapter 1. Let s start by analyzing bond length effects. 

The decalin (bicyclo[4.4.0]decane) ring system provides another important system for study of conformational effects in cyclohexane rings. Equilibration of the cis and trans isomers reveals that the trans isomer is favored by about 2.8 kcal/mol. Note that this represents a change in configuration, not conformation. The energy difference can be analyzed by noting that the cis isomer has three more gauche butane interactions that are... 

Examine space-filling models for the two conformers and identify any likely unfavorable nonbonded interactions. Based on steric effects, which conformer would you anticipate would be the more stable Compare energies of anti-1,2-ethanediol and gauche-1,2-ethanediol to see if you are correct. Is this the same ordering of conformer energies as seen for n-butane (see Chapter 5, Problem 3)7... 

Muller et al. focused on polybead molecules in the united atom approximation as a test system these are chains formed by spherical methylene beads connected by rigid bonds of length 1.53 A. The angle between successive bonds of a chain is also fixed at 112°. The torsion angles around the chain backbone are restricted to three rotational isomeric states, the trans (t) and gauche states (g+ and g ). The three-fold torsional potential energy function introduced [142] in a study of butane was used to calculate the RIS correlation matrix. Second order interactions , reflected in the so-called pentane effect, which almost excludes the consecutive combination of g+g- states (and vice-versa) are taken into account. In analogy to the polyethylene molecule, a standard RIS-model [143] was used to account for the pentane effect. 

The hemiacetal thiol 75 (Fig. 13) gave on acid cyclization an equilibrium mixture of cis and trans monothioacetals 76 and 77 in a 1 1 ratio (63). If a value of 1.7 kcal/mol is accepted for the steric effects in 76 (two gauche forms of SCl XCHg = 0.8 kcal/mol and one gauche form of butane= 0.9 kcal/mol), the anomeric effect for the ether oxygen in 76 must also be equal to 1.7. 

The first precise evaluation of the anomeric effect was realized by Descotes and co-workers in 1968 (22). These authors have studied the acid catalyzed isomerization of the cis and trans bicyclic acetals 6 and 6 and found that, at equilibrium, the mixture contains 57% ci s and 43% trans at 80°C. The cis isomer is therefore more stable than the trans by 0.17 kcal/mol. The cis isomer 5 has one (stabilizing) anomeric effect whereas the trans isomer 6 has none. Steric interactions in cis acetal 5 were estimated tobel.65 kcal/mol (one gauche form of ri-butane, 0.85 kcal/mol and an OR group axial to cyclohexane, 0.8 kcal/mol). By subtracting an entropy factor (0.42 kcal/ mol at 80°C) caused by the fact that the cis acetal S exists as a mixture of two conformations (cis decalin system), they arrived at a value of 1.4 kcal/mol for the anomeric effect. 

This last study is quite interesting because it permits an evaluation of the anomeric effect for the nitrogen atom. Conformer 91 with the axial N-methyl group should be less stable than conformer 92 by approximately 1.3 kcal/mol on the basis of steric effects (one gauche form of n-butane, =0.9 kcal/mol and one gauche form of CHj — N - CHj-0, =0.4 kcal/mol). The second anomeric effect caused by the equatorial orientation of the nitrogen electron pair in 91 must compensate for the steric effect. An approximate value of 1.3 kcal/mol must therefore be taken for that electronic effect, a value close to that estimated for the oxygen atom of the acetal function. 

Recently, Crabb, Turner, and Newton (68) have observed that perhydropyrido-[1.3]oxazine exists as a =9 1 mixture of the trans and the cis forms 97 and 98. The cis form 98 has two anomeric effects (-2.8 kcal/mol), two gauche forms of butane (1.8 kcal/mol) and one gauche form of -propyl ether (0.4 kcal/mol) whereas the trans form 97 has only one anomeric effect (-1.4 kcal/ mol). On that basis, the trans form 97 should be more stable than the cis form 98 by about 0.8 kcal/mol, in agreement with the experimental result. Katritzky and co-workers (69) have also shown that 1-oxa-3,5-diaza and 1,3-dioxa-5-aza cyclohexane derivatives exist respectively in the conformations 99 and 100. With an alkyl group in the axial orientation, both conformations gain two anomeric effects. 

A requirement for an a/m-orientation of the hydridic p-C—H and C—metal bonds as in [10] is indicated by the reaction of threo-3-deuterio-2-(trimethylstannyl)butane with triphenylcarbenium tetrafluoroborate in methylene chloride at 24° which yields a mixture of 3-deuterio-l -butene, /ra v-2-deuterio-2-butene, and undeuteriated c/.v-2-butene as the major product (Hannon and Traylor, 1981). Comparison of the product distributions for the protio- and deuterio-stannanes yields primary and secondary isotope effects of 3.7 and 1.1 respectively. These reactions appear to avoid the complications of adduct formation between the triarylcarbenium salt and the hydride donor, but the preferential formation of the cw-2-butenes is not fully explained. The requirement for the anti-orientation is also shown by the relatively low hydride-donating properties of tris[(triphenylstannyl)methyl-methane (Ducharme et ai, 1984a) which adopts a C3-conformation with the P-C—H gauche to all three C—Sn bonds. In contrast, 1,3,5-triphenyl-2,4,6-trithia-1,3,5-tristannyladamantane, in which anti-orientations with respect to the bridgehead C—H bond are locked, shows high reactivity (Ducharme et al., 1984b). 

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