K. Krohn, Stephan Cludius-Brandt
Aug 1, 2010
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Synthesis
Abstract
Aldehydes and ketones were converted into the cone- sponding homologous carboxylic acids in two steps by treatment with 2-(trimethylsilyl)-1,3-dithiane l-oxide. A modified Peterson olefination ofthe carbonyl compounds gave ketene thioacetal sulf- oxides that were readily cleaved in acidic acetonitrile to give the re- quired carboxylic acids. One-carbon homologation reactions of aldehydes, ke- tones, or carboxylic acids are important transformations in organic synthesis, and many different strategies for these transformations have been developed in recent decades.l This one-carbon transfer does not follow mainstream eno- late chemistry,z and in many cases umpolung reagents are used.3 Aldehyde-to-acid homologation is possible by the addition of an appropriate dithio-substituted nucleophile and subsequent hydrolysis. Indeed, an increase in oxida- tion state to the corresponding acid was observed during our work on the acid-catalyzed reanangement reactions of a-hydroxy-1,3-dithianes and cr-hydroxy-1,3-dithiane l- oxides (Scheme l).an The intermediate ketene dithioace- tals, such as A, are assumed to act as intermediates.ab De- pending on the hydrolysis conditions, an ester,s thioester,6 or carboxylic acidT can be isolated. Similarly, methyl (methylsulfanyl)methyl sulfoxide can be used in the trans- formation of substituted benzaldehydes into the corre- sponding phenylacetic acids.atse However, the synthesis of this reagent required a somewhat tedious multistep pro- cedure, and its action is restricted to the transformation of aromatic aldehvdes.ab We therefore looked for a more general and more easily obtainable reagent, and preferably one that is available commercially. After some experimentation, we found that 2-(trimethylsilyl)-1,3-dithiane ideally fulfilled our re- quirements because it is commercially available and it can be oxidized nearly quantitatively in one step by sodium metaperiodate or tert-btfiyl hydroperoxide to give the cor- responding l-oxide. The oxide reagent can also be readily prepared by addition of lithiated 1,3-dithiane to trimethyl- silyl chloridee and subsequent oxidation by sodium meta- periodate.rO Oxidation is not required for the addition reaction ofthe dithiane with carbonyl compounds, but it is needed to facilitate the subsequent cleavage of the dithio- acetals to give carboxylic compounds.s ln addition, the re- quired elimination step to give the intermediate ketene acetal (see Scheme l) is facilitated when a modified Peterson olefination procedure is used. We now wish to report on this method, which permits the synthesis of the homologous aromatic or aliphatic carbox- ylic acids from the corresponding aldehydes or ketones in a simple two-step process. The general route for the homologation of the carbonyl compound I involves the formation of an intermediate ketene acetal(2) and its subsequent hydrolysis to the acid 3 (Scheme 2).