Propane-1,3-dithiol, reaction with aldehydes

The stoichiometric equivalents of halofluorides have been recently applied to transform alkylene dithioacetals into gcm-difluorides.70-71 Dithioacetals such as 1,3-dithiolanes and 1,3-dithianes arc readily obtained from the corresponding carbonyl compounds by the reaction with ethane-1,2-dithiol or propane-1,3-dithiol in the presence of the complexes boron trifluoride-bis(acetic acid) or boron trifluoride-diethyl ether. Using a two-step procedure, a range of aldehydes and ketones can be converted into gem-difluorides under mild conditions. 

The acyl anion (R-C=0) is not stable as such, but when an aldehyde is converted into a 1,3-dithiane by reaction with propane-1,3-dithiol and then treated with base, it forms an acyl anion equivalent, and hence is susceptible to attack by electrophilic reagents (see Section 5.9). Two extensive compilations of formyl and acyl anion synthons together with references to their reactions... 

The reaction of aldehydes or ketones with ethane-1,2-dithiol or propane-1,3-dithiol to form 1,3-dithiolanes or 1,3-dithianes is an important reaction, as these compounds under suitable conditions are acyl anion equivalents (see Section 5.9, p. 626). These cyclic dithioacetals have been less used as protective groups, though when required are formed in high yield in the presence of boron trifluoride-etherate.138... 

Some of the problems associated with the synthesis of a-dicarbonyl starting materials have been alleviated by the use of propane-1,3-dithiol, which reacts with aldehydes to give cyclic thioacetals. With butyllithium the resulting stable dithiane anions (134) can be transformed into a-diketones or a-hydroxy ketones (Scheme 73). A further approach to such compounds is found in the reaction of a-ketonitrate esters with sodium acetate (Scheme 73), while aryl a-diketones are also available from a-ketoanils (prepared from the cyanide-ion-catalyzed transformation of aromatic aldimines) (70AHC(12)103). 

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). 

Dithians (thioketals) (48) are easily prepared by reaction of an aldehyde with propane-1,3-dithiol the dithians readily form 2-carbanions owing to the stabilising effect of the two adjacent sulfur atoms on the anion. The carbanion can subsequently be alkylated by treatment with primary or secondary alkyl halides,... 

It is possible to abstract a proton from a 2-alkylated-1,3-dithiane and perform a second alkylation reaction. If the 2-alkylated-1,3-dithiane is prepared from the aldehyde with propane-1,3-dithiol, then after alkylation and hydrolysis the sequence provides a method for converting an aldehyde into a ketone. Starting with the commercially available 1,3-dithiane, an alkyl halide or sulfonate can be converted into the homologous aldehyde. Two alkyl groups can actually be introduced successively without isolation of the intermediates and this has been applied to the synthesis of three- to seven-membered cyclic ketones. 

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