1.3- Dithianes systems

In the 1,3-dithiane system Jc h coupling constants through equatorial bonds were found (320) to be smaller than corresponding ones through axial ones, in contrast to what has been observed for 1,3-dioxane (349) and cyclohexane (350). This finding has been rationalized (317) in terms of dominant g, s-<7j,2)—h [over hyperconjugative interactions,... 

Based on indentical stretching frequencies for axial and equatorial C—D bonds (Vp jj = 2145cm ) and the absence of an isotope effect (AG° = 0 + 5 J/mol, by NMR measurments) on the conformational equilibrium in the 1,3-dithiane system 194, Anet and Kopelevich (323) concluded that the lone electron pairs on sulfur are not involved in the h(d> negative hyper-... 

Interest in the 1,3-dithiane system continues, with an improved procedure for the preparation of the parent compound (940PP377) and the preparation of new 2-substituted derivatives (94SL547). The carbanion derived from 2-trimethylsilane-l,3-dithiane is bisalkylated by chiral epoxides in the presence of... 

C=0. It is therefore susceptible to nucleophilic attack at carbon. Methods have been developed by which this polarization is effectively reversed so that the carbon atom itself becomes the nucleophilic centre. Such an inversion is known as umpolung. An example is provided by the 1,3-dithiane system. An aldehyde may be converted into a cyclic dithioacetal by reaction with propane-1,3-dithiol in the presence of an acid. The two adjacent electronegative sulphur atoms make the C—H bond of this acetal rather acidic. Treatment with butyllithium therefore affords a lithio derivative in which the carbon atom is susceptible to electrophilic attack. The 1,3-dithiane system is reconverted into a carbonyl group by acid hydrolysis in the presence of mercury(II) ions, which complex with the dithiol. The RCO group in the original aldehyde is thus equivalent to R—C=0 (Fig. 3.10). 

The commonly encountered C-2 anions derived from 1,3-dithiane and 1,3-oxathiane and their derivatives can be generated by treatment with any of a wide range of bases, but typically n-butyllithium (for 1,3-dithianes) or yec-butyllithium (sometimes necessary for 1,3-oxathianes). There are many instances where the deprotonated heterocycles have been used in synthesis, usually as acyl anion equivalents <8977643, b-95MI 608-05>. Use of 1,3-dithiane derivatives is by far the most common, and the derived anions react with with a very wide variety of electrophiles <69AG(E)639, 8977643), whether or not the dithiane system is initially substituted at C-2. For example, 2-lithio-... 

Remarkably, in contrast to the parent 1,3-oxathiane and the corresponding dithiane systems, the sulfones 1,3-oxathiane 3,3-dioxide and its 6-methyl derivative (59 R = H, Me), obtained by reaction of the 1,3-oxathianes with /-butyl hydroperoxide and molybdenyl acetylacetonate, are deprotonated, and subsequently react with a variety of electrophiles, at the 4-position (Scheme 21) <86CL1655>. 

Finally, the 1,3-dione systems prepared by Cram and Alberts deserve special note . These compounds, referred to as hexahosts are similar to the polymer-bound material illustrated as Compound 29 in Chap. 6. The synthesis is based on a methylene-bridged bis-dithiane unit. One of these may be cyclized with a polyethylene glycol, or more than one unit may be incorporated to give multiple 1,3-dione binding sites in the macrocycle. The former case is illustrated in Eq. (3.46). 

The (V-methyldihydrodithiazine 125 has also been used as an effective formyl anion equivalent for reaction with alkyl halides, aldehydes, and ketones (77JOC393). In this case there is exclusive alkylation between the two sulfur atoms, and hydrolysis to give the aldehyde products is considerably easier than for dithianes. However, attempts to achieve a second alkylation at C2 were unsuccessful, thus ruling out the use of this system as an acyl anion equivalent for synthesis of ketones. Despite this limitation, the compound has found some use in synthesis (82TL4995). 

In total synthesis, model studies are frequently performed on simpler systems prior to the final assault on the target molecule. In the synthesis of zaragozic acid A (1), 2-methyl-1,3-dithiane (92) was employed as a simple model for the more elaborate dithiane 67. Deprotonation of 92 with n-butyllithium under standard conditions47 and addition of the aldehyde provides a mixture of two diastereoisomers, 93 and 94 (Scheme 22), in approximately equal amounts. One of the diastereoisomers (93) lacks the TMS group,... 

To date, all saturated and unsaturated three- and larger-membered ring sulfones and sulfoxides (e.g., thiirane (3), thiirene (4), thietane (5), thiete (6), dithietane (7), thiolane (8), thiolene (9), thiane (10), thiene (11), dithiane (12), thiepane (13), thiocane (14), and their unsaturated analogues as well as isomers and closely-related systems) have been synthesized and their chemistry well-established. 

Similarly, only selected cyclic systems containing more than one sulfoxide or sulfone groups have been included and discussed here, primarily in the thietane (i.e. 1,2- and 1,3-dithietanes) and thiane (i.e. 1,2-, 1,3- and 1,4-dithianes) series. The criterion for the inclusion of these multifunctional heterocycles was their contribution to the understanding of the physical properties and chemical reactivity of cyclic sulfones and sulfoxides, and the effects of these groups on either their immediate vicinity or on the behavior of the whole molecule. 

It is noteworthy that, based on the sulfoxide- sulfenic acid rearrangement, the readily accessible 1,3-dithiolane systems (316) may be utilized (equation 116) as an efficient entry into the 1,4-dithiane series303, including the construction of carbocyclic fused systems304. The oxidation of the dithienes 318 to the corresponding sulfoxides (319 and 320) and sulfones is a simple, straightforward process. 

The same preferences have been calculated315 and observed319 in the 1,2-dithiane oxide system. Although the chair forms are also more stable than the twist or boat in 1,3-, 1,4-dithianes and 1,3,5-trithianes, the preference of the oxygen is highly variable, depending on steric and electronic interactions. 

For the 1,3-dithiane-1-oxide (R=H) case molecular dynamics simulations at the experimental temperature revealed that the R-hydroxysulfoniiun cation was considerably more stable than the more weakly adsorbed 1,3-dithiane molecule We consider that the hydroxydithiane cation may act as a proton transfer agent and this may account for the enhanced reactivity of this system. 

The molecular mechanics method has been applied to the calculation of conformational properties of the thiane, dithiane and trithiane oxide systems which are... 

A unique bis-silylation system, in which a bis(silyl)palladium intermediate is generated via recombination of two Si-Si bonds, has been developed.8,97 A bis(disilanyl)dithiane reacts with alkynes in the presence of a palladium/ isocyanide catalyst, giving five-membered ring bis-silylation products in high yield with elimination of hexamethyl-disilane (Scheme 14). The recombination, that is, bond metathesis, is so efficient that no product derived from direct insertion of acetylene into the Si-Si bonds of the bis(silyl)dithiane is formed at all. 

Ring enlargement.1 A new route to seven-membered ring systems from a cyclohexenone (1) involves a photocycloaddition of ethylene to provide the bicy-clooctanone 2. Addition of lithio-1,3-dithiane to 2 provides the adduct 3, which on reaction with HgO and HBF4 forms an unstable rearranged hydroxy aldehyde... 

The y-cthylthiosulfoxides can be converted to the corresponding carbonyl compounds by hydrolysis catalyzed by mercuric ion. In both the dithiane and alkylthiomethylsulfoxide systems, an umpolung is achieved on the basis of the carbanion-stabilizing ability of the sulfur substituents. 

Changing the sulfoxide component of the Re-catalytic system (entry 5 in Table 9) from Mc2S=0 to 8628=0 resulted in rapid oxidation to 1,2-dithiane 1-oxide in 84% yield <1997JA9309>. 

Reports on the new syntheses of six-membered ring systems with two oxygen and/or sulfur atoms in 1,2-positions are rather limited and are covered already in Section 8.10.9. Often, only one really successful synthetic path has been described or the derivatives obtained were simply by-products. Thus, a comparison of various synthetic strategies for obtaining certain dioxane/oxathiane/dithiane derivatives is not meaningful. 

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