1,3-Dithiane solvent effects

The conformational preference of the monosulfoxides of 1,2-, 1,3- and 1,4-dithianes (179-181) were determined by NMR experiments which included variable-temperature studies, double irradiation, solvent effects and the influence of lanthanide shift reagents167. For 179 and 181, the axial conformers were the dominant species in CD3OD, but for 180, the equatorial conformer was in excess. 

Thus, Juaristi et al. (SI) observed that whereas the solvent effects at room temperature for 2-carbomethoxy-l,3-dithiane (S3) agree with the anticipated trend, low-temperature AG° measurements show an opposite relationship, that is, the amount of axial species 53a (Scheme 19) increases with increasing... 

In the course of our studies on the anomeric effect in the C—S—C—P system we also become interested in the influence of solvent on the pertinent conformational equilibria in the hope that solvent effects could shed light on the origin of the observed anomeric effect. As models for our study 2-diphenylthiophosphinoyl-l,3-dithianes 55 and 56 were chosen (54). Confor-... 

It must be stressed that AG° values for 57 and 58 in the same solvent (e.g., MeOH or EtOH 95%) can differ by more than 1.5kJ/moI. Such differences seem to arise from different solvent effects on the two equilibria under scrutiny (despite the very similar structure of 57 and 58). This point of view is strongly supported by the fact that the relevant AH° and AS° values for 57 and 58 are also different. They are 5.19 0.23 kJ/mol and 10.6 + 0.7 J/mol/K for 57 and 5.71 0.12 kJ/mol and 13.8 0.4 J/mol/K for 58, respectively, in 6 4 (v/v) benzene-methanol solution (54). We also observed analogous differences between the equilibria in other derivatives of 1,3-dithianes (54, 98). Support for the hypothesis presented above comes from the work of Tschierske et al. (38), who showed that AG° values for dioxanes 59 and 60 (Scheme 21) differ... 

Quantitative data for the conformational equilibrium of 1,3-dithiane S-oxide (31) were also collected by Khan et al. [12] G 2K = -0.63 kcal mol , in CHCIF ) and by Juaristi et al. [64] (AG, - -0.64 kcal mol ). The lack of a solvent effect appears to indicate that dipole-dipole interactions do not control the (31-ax) (31-eq) equilibrium (Scheme 3.42). 

Finally, Seebach has used the cyclic urea (69), DMPU, as a co-solvent in double lithiations, oxirane ring-opening, Wittig reactions, Michael additions of lithiated dithianes to cycloalkenones, and the selective generation of enolates." The interesting point here is that DMPU exhibits the same solvent effect as the carcinogen HMPA and might therefore be a safe substitute. 

Suda and coworkers described the anodic oxidation of 2-silyl-l,3-dithianes which have two sulfur atoms on the carbon adjacent to silicon [42], In this case, however, the C Si bond is not cleaved, but the C-S bonds are cleaved to give the corresponding acylsilanes (Scheme 12). Although the detailed mechanism has not been clarified as yet, the difference in the anode material seems to be responsible for the different pathway of the reaction. In fact, a platinum plate anode is used in this reaction, although a carbon anode is usually used for the oxidative cleavage of the C-Si bond. In the anodic oxidation of 2-silyl-l,3-dithianes the use of a carbon anode results in a significant decrease in the yield of acylsilanes. The effects of the nature of the solvent and the supporting electrolyte may also be important for the fate of the initially formed cation radical intermediate. Since various 2-alkyl-2-silyl-l,3-dithianes can be readily synthesized, this reaction provides a convenient route to acylsilanes. 

The decrease of the anomeric effect in polar solvents was also supported by quantum mechanics calculations.13 Nevertheless further studies on the anomeric effect demonstrated the limitations of the electrostatic model. In particular, Juaristi et al.14 demonstrated that, at low temperature, the dependence of conformational equilibria of 2-carbomethoxy-l,3-dithiane upon solvent shows an opposite trend to the stronger anomeric effect in less polar media observed at 25 °C (Table 4). 

A large number of workers have examined the effects of temperature, solvent and reaction times on the ratio of the products of 1,4-addition versus 1,2-addition of dithiane and other a-thioalkyl carb-anions.34 Their results show that in general 1,2-addition is kinetically favored and therefore predominates at low temperatures and in less polar solvents,34 34 5 whereas 1,4-addition is thermodynamically favored... 

Apaydin et al. (97JMS(T)113) also calculated the conformational equilibria of some 5-substituted 1,3-dithianes by the PM3 method in the gas phase and in solution, displaying a resonable agreement with available experimental data. The chair conformation of the six-membered ring was confirmed the equatorial position of the substituents in position 5 (alkyl, OMe, SMe) are the most stable in all media and the effect of the solvent on the equilibrium is only minor. 

Fuchs et al. (129). They suggested that when the molecular dipoles of the axial and equatorial conformers are of similar magnitude, the more polar double bond-no bond structure, resulting from hyperconjugative interactions in the axial conformer, 54a (see Scheme 20), will be stabilized in the more polar solvent. This hypothesis would support the importance of the hyperconjugative origin of the anomeric effect. The appearance of a large proportion of the axial conformers of 2-(arylseleno)-l,3-dithianes 37 (Scheme 13), even in... 

A reversed dependence of the axial preference on solvent polarity, which is sometimes regarded as a proof for the reverse anomeric effect, is discussed together with our results on phosphonio-l,3-dithianes in Section II.I. 

In fact, however, more polar solvents may enhance axial preferences without the intervention of a reverse anomeric effect, as was shown by Lemieux (27), Fuchs et al. (129), Zefirov and Fedorovskaya (171), and Giralt et al. (172). In the course of our studies on the conformation of 2-phosphonio-l,3-dithianes 85 we also found (173) that the axial preference may increase with increasing solvent polarity, as expected based on the concept of the reverse anomeric effect. However, 2-phosphonio-l,3-dithianes 85 do not exhibit the reverse but the generalized anomeric effect (see Section V.A). Since the axial... 

Early workers reacted the ketone with an excess of the thiol in the presence of an acid catalyst such as zinc chloride , hydrogen chloride or />-toluenesulphonic acid to prepare dithioacetals. The results were erratic and the yields often disappointing. The use of boron trifluoride etherate has led to consistently better results . This method is particularly effective when the thiol is used for the solvent of the ketone as the boron trifluoride etherate is added. Ethanedithiol and propanedithiol are usually the thiols of choice forming 1,3-dithiolanes and 1,3-dithianes respectively. For example, the 1,3-dithiolane of cholestane-3-one (equation 1) can be prepared in high yield by this method . Occasionally the choice... 

The 1,2-adducts (32) of 2-litho-l,3-dithians and cyclohex-2-enone can be isomerized to the more stable 1,4-adducts (33) by conversion into the potassium alkoxides (but not the less dissociated sodium or lithium salts).Direct formation of enone 1,4-adducts occurs when HMPA-THF is used as the solvent, and enolate trapping can be effected when the initial enone 1,4-adduct is treated with methyl iodide.The allylic anion derived from (34) undergoes cr-1,4-addition to cyclohexenone in the presence of Cul (Scheme 2). In the absence of the copper salt, both y-1,4- and cr-1,4-addition occur, with the former predominating. In contrast, allylation of (34) in the presence of Cul occurs primarily at the y-position, while cr-allylation is observed otherwise.The lithio-anion of 2-(yff-styryl)-... 

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