1,3-Dithiane chemistry

For further use of dithiane chemistry in the synthesis of spongistatin, see also a)... 

Cyclodehydration of l,5-bis(acylsilanes) 4, accessible through dithiane chemistry, affords 2,6-bis(trialkylsiIyl)-4//-pyrans (Scheme 2) <00S843>. 

The most important use of 1,3-dithianes (792) stems from their ability to function as acyl anion equivalents (794 Scheme 184). Metallation of this heterocycle followed by alkylation of the anion and cleavage of the dithiane group produces a carbonyl compound. Since such aspects of dithiane chemistry have been extensively documented (69S17 75JOC231), only a few of the more current applications of these heterocycles are highlighted. We again note here that the application of heterocycles to the synthesis of carbonyl compounds has been the sole subject of an extensive review (77H(6)73l). 

The ability of sulfur to stabilize an adjacent anion will be discussed in Chapter 46, and it means that sulfur heterocycles are much easier to deprotonate than THF. The most important of these contains two sulfur atoms dithiane. Deprotonation of dithiane occurs in between the two heteroatoms, and you can see some chemistry that arises from this on p. 1234. For tire moment, we will just show you series of reactions that illustrate nicely both dithiane chemistry and the ring opening of oxygen heterocycles in the presence of BF3, This substituted derivative of dithiane is deprotonated by BuLi in the same way to give a nucleophilic organolithium that will... 

Several papers have appeared concerning new preparative pathways to cyclic keten 5S -acetals. Both the synthetic exploration of the chemistry of these keten dithioacetals and the synthetic aspects of dithian chemistry in general will not be covered in this Report (see Chap. 2, Pt I, p. 90). 

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. 

Thioacetals and thioketals have significant synthetic potential for use in organic chemistry but are often neglected because of their unpleasant odor. A polymeric reagent for the preparation of ketones via 1,3-dithianes has been reported using... 

An example where the presence of a counterion makes a difference between the gas phase and solution phase pathways involves the intriguing carbanion produced on deprotonation of 1,3-dithiane at C-2. In solution, this species, almost invariably produced by reaction of the dithiane with butyllithium, is widely used as an acyl anion equivalent in synthetic chemistry. Its importance for the present work is that this is a configurationally stable lithiated species in solution the carbanion stays sp -hybridized, and the lithium prefers the equatorial position, even to the extent of driving a terr-butyl group on the same acidic C-2 carbanion to the axial position in the lithiocarbon species. The carbanion is thought to be stabilized primarily by orbital overlap with the C-S antibonding orbitals, as opposed to more conventional polar and 7t-resonance stabilization. ... 

The lithiation of y-chloro acetal 175 with lithium and a catalytic amount of naphthalene (4%) allowed the preparation of the intermediate 176, which can be considered as a masked lithium homoenolate, and was used for the preparation of the hydroxy ketone 179 through the hydroxy acetal 177 and dithiane 178 using known chemistry (Scheme 62)" . 

In this chapter, the structures and chemistries of 1,3-dioxins, 1,3-oxathiins, and 1,3-dithiins are described, including both their fully saturated forms (1, 7, and 13) as well as their benzo analogs (6, 11, 12, and 17). The formally fully unsaturated monocyclic structures (4, 9, 10, and 16) contain only one endocyclic double bond with further unsaturation being accomodated by exocyclic double bonds (2, 3, 5, 8, 14, and 15), for example, by the introduction of a carbonyl group. Well known and intensively studied are the Meldrum s acid derivatives 18 and 19. In addition, 1,3-dioxane, 1,3-oxathiane, and 1,3-dithiane moieties can be part of spiro structures as well as hi- and tricyclic analogs. And finally, both the structures and chemistries of the corresponding sulfoxides and sulfones are also reported. 

The chemistry of the carbene l,3-dithian-2-ylidene, generated from 2-diazo-l,3-dithiane, was briefly discussed in Section 8.11.6.3.1. It reacts poorly with alkenes or alkynes if they are not highly electron deficient. However, it was found that Cso as source of C=C bonds efficiently provides the [2-1-1] cycloaddition product, which can be hydrolyzed to the Cso-cyclopropanone (Scheme 51) <2001HC0223>. 

The chemistry of l,3-dithian-2-ylidene ethyl carbene has been studied. This carbene was prepared by the reaction of the parent hydrazone with NaH (Equation 57). It reacted with nucleophiles in situ to give a variety of trapping products <1996J(P1)2773>. 

The chemistry of chiral 1,3-dithiane 1-oxides, in particular their use as chiral auxiliaries, has been reviewed <19980PP145>. Some further developments in this field are the stereoselective a-alkylation with alkyl halides <1997T13149> or a-hydrazination with di-fert-butyl azodicarboxylate (DBAD) <2000T9683>. The carbonyl group of 2-acyl-l,3-dithiane 1-oxides was also used as an electrophile (Scheme 82). Interestingly, acyclic enolates react with these substrates to give a 95 5 mixture of anti- and ry -adduct, whereas cyclic enolates produce a mixture of anti- and ry -adduct in 8 92 ratio <2000JOC6027>. 

Over the past two decades, important contributions to the chemistry of thiocarbonyl ylides were made by Huisgen et al. (27). By carrying out the reaction of thiobenzophenone with diazomethane at low temperature, formation of 2,5-dihydro-l,3,4-thiadiazole (15) with subsequent elimination of N2 was established as the route to the reactive thiobenzophenone (S)-methylide (16) (17,28). In the absence of intercepting reagents, 16 undergoes electrocyclization to give 17 or head-to-head dimerization to yield 1,4-dithiane 18 (Scheme 5.3). 

See A. B. Smith, III, C. M. Adams, Accounts of Chemical Research 2004, 37,365 for an excellent tour through the authors use of the dithiane-based chemistry for the construction of complex molecules. 

A total synthesis of ( )-aromatin has utilized the lithium anion of the dithiane of (E)-2-methyl-2-butenal as a functional equivalent of the thermodynamic enolate of methyl ethyl ketone in an aprotic Michael addition (Scheme 189) (81JOC825). Reaction of the lithium anion (805) with 2-methyl-2-cyclopentenone followed by alkylation of the ketone enolate as its copper salt with allyl bromide delivered (807). Ozonolysis afforded a tricarbonyl which cyclized with alkali to the aldol product (808). Additional steps utilizing conventional chemistry converted (808) into ( )-aromatin (809). 

The chemistry of almost all of the numerous syntheses of 1,4-dioxanes, 1,4-oxathianes and 1,4-dithianes utilizes the nucleophilicity of negatively charged or neutral oxygen and... 

Several of the above approaches have proved appropriate for the preparation of alkylated derivatives whilst related but somewhat modified chemistry is required for other substituted compounds routes depicted in Scheme 24 are examples of methods for the preparation of alkoxy derivatives (47JA2449). Compounds such as 2-hydroxyketones and 2-mercap-toketones dimerize reversibly to give 2,5-dihydroxy derivatives of 1,4-dioxanes and 1,4-dithianes respectively (B-57MI22600, 66HC(21-2)104l). 

Page et al. (see [298] and references therein) have shown that generally excellent stereocontrol in organic reactions can be obtained by using DITOX (1,3-dithiane-l-oxide) derivatives as chiral auxiliaries. The one-pot stereo-controlled cycloalkanone synthesis given here outlines some aspects of the chemistry worked out for efficient acylation-alkylations steps. Of note are the use of N-acyl imidazoles under mixed base (sodium hexamethyldisilazide/n-butyllithium) conditions to yield the lithium enolates of 2-acyl-l,3-dithiane-l-oxides) and the sequential alkylation-cyclization of the latter (steps (iv) and (v)). 

Macrocyclic ligands have played an important part in the development of modern co-ordination chemistry. But what exactly is a macrocycle As far as a co-ordination chemist is concerned, the definition of Melson is probably the most useful. Melson stated that a macrocycle is a cyclic molecule with three or more potential donor atoms in a ring of at least nine atoms. Thus, ethylene oxide (6.1), 1,4-dithiane (6.2), cyclotetradecane (6.3) and cyclooctatetraene (6.4) are not commonly thought of as macrocycles (Fig. 6-1), whereas molecules such as cyclam (6.5), phthalocyanine (6.6), 1,4,7-trithiacyclononane (6.7) and dibenzo-18-crown-6 (6.8) fit the definition (Fig. 6-2). 

Eliel, E. L. Hartrriarin, A. A. Abatjoglou, A. G. Organosulfur chemistry. II. Highly stereoselective reactions of 1,3-dithianes. Contrather-modynamic formation of unstable diastereo-isorners. j. Am. Chem. Soc. 1974, 96, 1807-1816. 

The value of 1,3-dithianes in stereoselective synthesis ensures a healthy interest in their chemistry. A simple synthesis of 2-acetyl-... 

The most important S. S -acetals in organic chemistry are the six-membered ring S,S-acetals, the so-called dithianes (formulas A, C, and F in Figure 9.22). Dithianes are produced from... 

McHale, W.A. and Kutateladze, A.G. (1998) An efficient photo-SET-induced cleavage of dithiane-carbonyl adducts and its relevance to the development of photoremovable protecting groups for ketones and aldehydes. Journal of Organic Chemistry, 63, 9924—9931. 

C—C bond cleavage in dithiane-carbonyl adducts a laser flash photolysis study. Journal of Organic Chemistry, 66, 2887-2890. 

Lee, H.B. and Balasubramanian, S. (1999) Studies on a dithiane-protected benzoin photolabile safety-catch linker for solid-phase organic synthesis. Journal of Organic Chemistry, 64, 3454-3460. 

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