Synthesis of 1,3-Dithianes

A simple, inexpensive ionic liquid, l-methyl-3-pentylimidazolium bromide ([pmImJBr), has been used as catalyst as well as reaction medium for the 

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The reagent is prepared by the reaction of 1,3-propanedithiol (I cq.) with malondi-aldehyde bisdimethylacetal (Aldrich), in a manner similar to that used for synthesis of 1,3-dithiane. ... 

We have recently reported that [(8,8-dimethoxycamphoryl)sulfonyl]oxaziridine is a particularly effective reagent for asymmetric sulfide oxidation, especially in non-aryl sulfide substrates.11 Here we report a three-step chemical synthesis of 1,3-dithiane 1-oxide with very high ee that is based upon such an oxidation as the key step. The procedure is effective for production of multigram quantities of material of either absolute configuration. The sequence is illustrated for the preparation of 1S-(-)-1,3-dithiane 1-oxide. 

Karami, B., Taei, M., Khodabakhshi, S. and Jamshidi, M. 2012i. Synthesis of 1,3-dithiane and 1,3-dithiolane derivatives by tungstate sulfuric acid (TSA) Recyclable and green catalyst. J. Sulfur Chem. 33(l) 65-74. 

A major aspect of 1,3-dithianes is their value in synthesis and several new applications are highlighted this year. 

The synthesis of 1,3-dioxanes and congeners by transformation of a ring of the same size is not highly developed. Only a few examples of such reactions, typically transacetalizations, have been reported. An important issue of 1,3-dithiane formation, namely the stench of the 1,3-propanedithiol, has been addressed by Liu and co-workers. They found that... 

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 use in organic synthesis of carbanions stabilized by one or more adjacent thioether groups is now a well-established technique [272-275]. A landmark in this development was the work of Corey and Seebach on 1,3-dithianes [276]. They pointed out the use of the anions of 1,3-dithianes as... 

One of the most important reagent equivalents of the donor formyl synthon is 1,3-dithiane (see Chapter 1, p. 21). However the use of this reagent equivalent is not widely found for the synthesis of simple aldehydes since other methods may be economically more appropriate. An example of specific formylation by the use of 1,3-dithiane is illustrated in Expt 6.66. Disodium tetracarbonylferrate(n)... 

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

For the fast ge/w-dialkylation of 1,3-dithiane dianion, tin-lithium transmetallation at the 2-position of dithiane is a much faster process than the corresponding deprotonation. 2,2-Bis[tri(n-butyl)stannyl]dithiane (175)223 can be alkylated sequentially it was trans-metallated with n-BuLi at —78 °C, after 5 minutes treated with the first alkyl halide and after 10 more minutes the process was repeated providing dialkylated products224. This strategy has been used in the total synthesis of (—)-perhydrohistrionicotoxin, namely preparing the key compound 178 employing successively iodides 176 and 177 as electrophiles (Scheme 50)224. 

Allin, S. M. Page, P. C. B. The Development and Application of 1,3-Dithiane 1-Oxide Derivatives as Chiral Auxiliaries and Asymmetric Building Blocks for Organic Synthesis. A Reveiw, Org. Prep. Proc. Int. 1998,30,145-172. 

Argon. An Organic Syntheses procedure for the dialkylation of 1,3-dithiane with 1 -bromo-3-chloropropane, as a first step in the synthesis of cyclobutanone, specified that argon, if available, be used as the inert gas in preference lo nitrogen because of its greater density. ... 

Coupled with the fact that the proportion of trace metal contaminants detected within continuous flow reaction products is inherently low, due to reduced catalyst degradation, the use of a scavenger cartridge at the end of a reaction sequence represents a relatively long-term solution to this problem. Other examples of the use of solid-supported scavengers have been reported by Ley and co-workers [65], where in one example, two scavenger modules, comprising QuadraPure TU (126) and phosphane resin, were used in the synthesis of 1,4-disubstituted-l,2,3-triazoles [66], and by Watts and co-workers [67], where silica-supported copper sulfate was used for the removal of residual dithiol (ppb) in the synthesis of 1,3-dithiolanes and 1,3-dithianes. 

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-... 

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