The Gauche Effect

The importance of jj a p interactions is reflected in the C-C bond shortening and the concomitant C-C BDE increase upon progressive fluorination of one of the ethane carbons (Table 6.1).  

For X=C1, Br, I, the anti conformations are more stable. The gauche preference weakens in these systems because bonds to heavier halogens are not only good acceptors but also relatively good donors (better than 

The BLW estimate wiU range from 9.6 to 7.3kcal/mol in the staggered structures and decreases in the order Br Cl F. Out of 81 conformers considered for 3-fluoro-l,2-diX-propane, the major four conformers, accounting for more than 70% of the conformational space in the gas phase and in solution, were found to exhibit gauche relationships among the three substituents in a computational study of Freitas and coworkers.  

BLW estimates by Hiberty and coworkers suggest that for both C Hg and C Hio alkenes, hyperconjugation effects stabilize the most snbstituted prodnct by about bkcal/mol. NBO analysis of such interactions will be discussed below along with the discnssion of the role of hyperconjugative effects in conformational behavior of alkenes. 

1 Eclipsed and staggered conforntations of alkenes - stereoelectronic misnomers 

In addition to steric effects and electrostatic effects, the conformational analysis of carbohydrates requires two stereoelectronic effects to be taken into consideration the gauche effect and the anomeric effect, in its various manifestations. Both of these effects can be considered as aspects of no-bond resonance. 

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The gauche effect, anomeric effect, and related phenomena... 

Figure 3.63 illustrates the gauche effect for vicinal lone pairs and polar C—F bonds with the examples of (a) hydrazine and (b) 1,2-difluoroethane, respectively. As seen in Fig. 3.63(a), the

lone pairs are anti to one another (thus squandering their powerful donor strength on vicinal moieties with no acceptor capacity) is disfavored by 3.2 kcal mol-1 relative to the preferred = 93.9° conformer in which each nN hyperconjugates effectively with... 

Figure 3.63 Rotation-barrier profiles illustrating the gauche effect for (a) lone pairs in hydrazine and (b) polar bonds in 1,2-difluoroethane. (The angle 4> = 0°, as

The relative importance of the gauche effects associated with polar bonds and lone electron pairs is polar bond-polar bond > polar bond-lone pair > lone pair-lone pair. 

Wolfe and collaborators attempted to understand the origin of the gauche effect by using an intuitive interpretation of good quality ab initio calculations. 

T. limori, Y. Murai, Y. Wakizaka, Y. Ohtsuka, S. Ohuchi, Y. Kodama, T. Oishi, 2 - and 3 - substituted sangivamycins Conformational restriction by the Gauche effect, Chem. Pharm. Bull. 41 (1993) 775-777. 

The gauche effect — which has the same electronic origin as that of the anomeric effect—is able to stabilize a conformation that should, a priori, be disfavored by steric factors. Thus, the gauche effect prevents the trans antiperiplanar conformation of two electronegative substituents borne by two vicinal carbon atoms (Figure 3.2). ° ... 

Mono-, di-, and trifluoro derivatives of fatty acids have been prepared in regio- and stereoselective manners, in order to evaluate the gauche effect induced by fluorine atoms on the conformation of hydrocarbon chains and for enzymatic studies. 

One year after the total synthesis of (-l-)-laurencin, Crimmins disclosed total syntheses of (-l-)-prelaureatin 232 and (-f)-laurallene 233, applying a similar strategy (Scheme 43). The critical RCM reaction was undertaken with precursor 230, anticipating that the gauche effect of the C6 and C7 oxygens would accelerate the ring closure. Exposure of 230 (0.005 M in dichloromethane) to catalyst B proceeded smoothly to provide the key A -oxocene 231 in 95% yield with no detectable dimerization. 

Ab initio quantum-chemical calculations are reported at the level of second-order many-body perturbation theory aimed at the equilibrium between the all -trans (ttt) and the trans-gauche-trans (tgtl conformations of dlmethoxyethane. It is concluded that the gauche effect in dimethoxyethane and by analogy POE is mainly due to the presence of a polarizable environment and not to some intrinsic conformational preference. 

R is axial rather than equatorial, by the gauche effect (steric compression). If R is large (Bn) an (< ) disposition is preferred and 8C(3),q5) values are more downfield. 

Saul Wolfe has made important contributions on a broad range of topics in bioorganic chemistry and many aspects of theoretical organic chemistry. His special interests include the gauche effect,255 P-lactam compounds,256 and isotope effects.257... 

S. Wolfe, Acc. Chem. Res., 5, 102 (1972). The Gauche Effect. Some Stereochemical Consequences of Adjacent Electron Pairs and Polar Bonds. 

Wolfe23 defines the gauche effect as the tendency of molecules to adopt a structure maximizing the number of gauche interactions between adjacent lone pairs and/or polar bonds. Heteroatoms are assumed to be sp3 hybridized, thus having equivalent lone pairs (22). This phenomenological definition is unsatisfactory because it groups three different situations under the same title. 

The trouble is, in this conformation none of the oxygen lone pairs get the chance to donate into the C-O a orbitals. Although putting the bonds anti-periplanar to one another makes steric sense, electronically, the molecule much prefers to put the lone pairs anti-periplanar to the C-O bonds, so the bonds themselves end up gauche (synclinal) to one another. This is known as the gauche effect, but is really just another way in which the stereoelectronic effects that give rise to the anomeric effect turn up in acyclic systems. 

Electrostatic interactions have been revealed as important in influencing the "gauche effect , whereby, in 1,2-disubstituted ethanes (4.9bA), the gauche conformer (4.9bB) is populated to a larger extent than the anti conformer (4.9bC) [31, 31a] (Figure 4.9b). 

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