Conformations, anti equilibration

The large sulfur atom is a preferred reaction site in synthetic intermediates to introduce chirality into a carbon compound. Thermal equilibrations of chiral sulfoxides are slow, and parbanions with lithium or sodium as counterions on a chiral carbon atom adjacent to a sulfoxide group maintain their chirality. The benzylic proton of chiral sulfoxides is removed stereoselectively by strong bases. The largest groups prefer the anti conformation, e.g. phenyl and oxygen in the first example, phenyl and rert-butyl in the second. Deprotonation occurs at the methylene group on the least hindered site adjacent to the unshared electron pair of the sulfur atom (R.R. Fraser, 1972 F. Montanari, 1975). 

Reaction of the epoxy alcohol with LiBr forms the halohydrin salt that equilibrates to the equatorial-Br conformer, which then undergoes ring contraction via an /-parallel displacement of Br (Step A). Proton transfer (Step B), although proceeding at a slower rate, leads to another anti-parallel Br displacement (Step C), forming the minor product FI. 

The full mechanism provides a plethora of routes to the observed products, and by adjustment of the positions at which hydrogen atoms are added, and the relative rates of the steps, it should be possible to account for every conceivable blend. To facilitate discussion of how the nature of the metal and the state of its surface determines the choice of elementary steps, the complete scheme has been factorised into three parts. In mechanism 1, the sequence is simply II V 1-butene. In mechanism 2, species I and III can equilibrate via II, and lead respectively through rv or VIII to 1-butene -I- -2-butene, and through Vin or IX to 1-butene -I- Z-2-butene. The existence of species VIII and IX is not however an absolute requirement to account for the products. Provided the constraint that favours the anti- conformation is relaxed somewhat in the adsorbed state, and the structures I and ni (and their counterparts) are of comparable stability, the occurrence of Z/E ratios of about unity can be explained. Indeed on the very simple-minded assumption that they are equally probable, and that the two ways of adding the second hydrogen atom are also equally balanced, we should obtain the three isomers in the ratio 50 25 25, which is not so far from the observed with several metals (e.g. Sc, V, Ir). The Z/ ratio is said to be fixed by the relative stabilities IV and Vll, equilibrating via V but equilibration of I and III via II will have the same effect. 

Ultrasonic absorption measurements have clearly indicated that adenosine 3, 5 -phosphate exists in aqueous or 7M-urea solutions (pH 8.0) as a rapidly equilibrating mixture of syn and anti conformers about the iV-glycosidic bond. ... 

It is self-evident that the transition state hypotheses discussed above are exclusively relevant to kinetically controlled aldol additions. Although this type of reaction control is the rule when preformed enolates are used, one should be aware that the reversibility of aldol additions cannot be excluded a priori and in any instance. In aldol reactions of preformed enolates, reversibility becomes noticeable in equilibration of syn aldolates with anti aldolates rather than in an overall low yield as found in the traditional aldol reaction. Considering the chair conformations of the syn and the anti aldolates, the former seem to be thermodynamically less stable, because of the axial position of the a-substituent R. This situation is avoided in the anti adduct (Eq. 

Michael addition to the unsaturated aldehyde in 321 provided the anti-aldehyde 320 at —40°, which equilibrated to 322 at room temperature. Only this material can populate a conformation without any 1,3-diaxial interaction with one sulfur atom... 

This diastereoselectivity may be explained by a rapid equilibration of the ( )- and (Z)-aUylchromium(III) intermediates 5 and 6, which are preferentially a-bound to chromium at the primary allyl position. The (E)-aUylchromimn species is more highly favored and is thought to add to the aldehyde via a Zimmerman-Traxler transition state 7, in which both the y-substituent of the allylic system and the aldehyde substituent prefer equatorial positions (thus. Scheme 12.5). An exception to this remarkable anti-selectivity is observed in the reaction of y-monosubstimted allylic halides with very bulky aldehydes, for example, t-BuCHO, which may force the transition state to adopt a twist-boat rather than a chair conformation, thus, favoring the. syw-product. 

---