Acyl anion equivalents metallated, dithiane

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). 

Dithioacetals (see also dithianes and dithiolanes) alkylation of 98 as acyl anion equivalents 75 carbanions of 87,97-102 cleavage of 14-18,98,102 desulfurization of 78 metal-catalysed coupling 127 reaction with Grignard reagents 127 reductive lithiation of 89 synthesis of 12-19,97-102 Dithioacids synthesis of 40... 

In conclusion, the 1,3-dithiane unit still remains among the most valuable acyl anion equivalents, although that involving methyl methylthio sulfoxide or its diethyl analog offers the definite advantages of proceeding with metal hydride or even under phase-transfer catalysis conditions and of producing the carbonyl compound under reasonably mild conditions. 

We attributed the difficulties with this otherwise trivial RCM reaction to the close proximity of the dithiane ring to the metal center after catalyst coordination. This could allow a sulfur atom to coordinate to ruthenium, preventing catalyst turnover. A fix to this problem was not obvious as a dithiane was required as the acyl anion equivalent as determined above nevertheless, dithiomethylmethane was briefly investigated as a dithiane substitute, but this resulted in lower yields at various points in the synthesis leading up to the acrylate. Since this work was originally reported, however, more RCM catalysts have become commercially available from various chemical suppliers and those might be able to overcome the difficulties we experienced. 

In the forward direction, diene 5 was prepared by alkylation of metallated 1,3-dithiane 9 with allylic bromide 8. In this reaction, 9 plays the role of an acyl anion equivalent . We will talk about equivalencies in more detail in Chapter 6, but at this point it is worth noticing that the dithiane will eventually emerge as the C15 protected ketone. Dienophile 4 was prepared by an aldol-dehydration reaction between nitromethane and aldehyde 10, a reaction known as the Henry reaction. The Diels-Alder reaction between 4 and... 

Review. Seebach and Corey have published a general paper on the preparation and metalation of 1,3-dithianes and examples of the reaction of 2-lithio-l,3-dithianes with electrophilic reagents (alkyl halides, carbonyl compounds, acids, and oxides). The value of these sulfur-stabilized anionic reagents is that they are equivalent to acyl anions (a), in which the normal polarity of the carbonyl group is reversed (reversible umpolung). 

Lithiated dithiane 35 is another example of a formyl anion equivalent. Acylation would provide 36 and thioacetal hydrolysis would provide 29. The thioacetal hydrolysis is the FGT that establishes the equivalency. Acylation of dimsyl anion 37 (from metallation of DMSO) would afford )8-ketosulfoxide 38. Once again an oxidation is needed to establish the desired equivalency. This can be accomplished using a Pummerer rearrangement wherein oxidation occurs at carbon with reduction at sulfur. Hydrolysis of the resulting S,0-acetal would complete the required FGT. 

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