Axial configuration

The rate-determining step in the formation of the x-lithio ethers is the formation of a carbon radical as a precursor to the anion. The intermediate radical in the tetrahydropyranyl system is expected to be nonplanar, to be capable of rapid equilibration between the quasiequatorial and quasiaxial epimers, and to exist largely or entirely in the axial configuration at — 78 °C. However, treatment of the a-phenylthio ether 4 with LDMAN at higher temperature in the presence of A, A, lV, ./V -tetramethylethylenediamine leads to the more stable equatorial epimer of the lithio ether 5 and, after addition to benzaldehyde, the axial- and equatorial-substituted products were obtained in a ratio of 13 87. 

Leahy demonstrated that unsaturation at the 5-position of a 4-cyano-l,3-dioxane can lead to a reversal in selectivity [12] (Eq. 6). Alkylation of cyanohydrin acetonide 19 with benzyl bromide generated a 9 1 mixture of 20 and 21, with the flufz-isomer 20 predominating, in 57% overall yield. An alkylithium intermediate in which overlap with the methylidene tt orbital favors the axial configuration could account for this anomalous selectivity. 

A single enzyme, inositol monophosphatase, leads to loss of the remaining phosphate and the regeneration of free inositol. This enzyme exhibits similar affinities for all five of the equatorial inositol monophosphate hydroxyls. Inositol 2-phosphate, which is not produced in this degra-dative pathway, is a poor substrate, a property that is probably attributable to its axial configuration. The enzyme is inhibited by Li+ in an uncompetitive manner i.e. the degree of inhibition is a function of substrate concentration. The putative link between the ability of Li+ to interfere with phosphoinositide turnover and its therapeutic efficacy in the treatment of bipolar disorders is discussed in Box 20-1 and Chapter 55. It should be noted that unlike most other tissues, brain can synthesize inositol de novo by the action of inositol monophosphate synthase, which cyclizes glucose 6-phosphate to form I(3)P. The enzyme has been localized immunohistochemically to the brain vasculature. 

Cotton effect for deuterium a and /i positions of chair cyclohexanone. And application of those data to conformationally mobile systems led to the interesting stereochemical conclusion that deuterium prefers the more sterically crowded axial configuration in 3-deuteriocyclohexanone55,69. 

In the synthesis of 29 [78], axially chiral precursor was obtained via biaryl coupling between benzodithiophenes with chiral oxazoline [derived from (S)-valinol] as an auxiliary, e.g. Stille cross-coupling of 25 and 26 provided bis(benzodithio-phene) 27 in 68% yield with 49% de (Fig. 15.10). Although the diastereomers were not separable by silica gel column chromatography, crystallization of diastereomers from hexane-ethyl acetate gave crystals with an S-axial configuration. 

Figure 13. (a)-(d). Chair conformation (upper), approximate Ae (middle), and octant projection diagrams (lower) for a and 0-methylcyclohexanones. The Ae values are from refs 6-8, 1 and 12. (e)-(h). (3R)-Methylcyclohexanone with CH3 in an axial configuration (e) (15,3R)-4(a)-methyladamantan-2-one (f) and octant diagrams for back octants (g) and front octants (h). 

The NaBH4 and NaBD4 reductions of thiohemiaminals carried out in ethanol by MacLean etal. (56) correspond only in part to the results obtained in methanol. Using 6,6 -dihydroxythiobinupharidine (54) and 6-hydroxythiobinupharidine (53) for the reduction, they concluded that at C-6 the reduction follows only one steric mode, introducing deuterium in an axial configuration (95% incorporation). This observation corresponds to results described earlier by LaLonde. However, the reduction at C-6 in ethanol as opposed to methanol follows two steric modes, introducing 60% of the deuterium in an axial fashion and 40% equatorially (95% incorporation of deuterium). Furthermore, the differences in the course of the reduction were also shown as a more rapid reduction at C-6 as compared with C-6 and 95% incorporation of deuterium in comparison with 70%... 

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