Electrophilic dehydrating reagents

A very mild oxidation procedure that tolerates a variety of other functional groups is the oxidation of alcohols to aldehydes and ketones by the dimethyl sulfoxide (DMSO). A DMSO solution of the alcohol is treated with one of the several electrophilic dehydrating reagents. The alcohol is oxidized to the aldehyde or ketone and DMSO is reduced to dimethyl sulfide (DMS), which is a volatile liquid (b.p. 37°C). Since pure DMSO freezes at 18°C and an oxidation reaction is carried out at —50°C or lower, a co-solvent such as methylene chloride or THF (tetrahydrofuran) is needed. 

Carboxylic acid derivatives on pyridopyrimidine rings appear to undergo normal reactions with electrophilic reagents, e.g. the 6-amide (70) is dehydrated to the 6-nitrile with phosphorus oxychloride. 

Erlenmeyer was first to consider ends as hypothetical primary intermediates in a paper published in 1880 on the dehydration of glycols.1 Ketones are inert towards electrophilic reagents, in contrast to their highly reactive end tautomers. However, the equilibrium concentrations of simple ends are generally quite low. That of 2-propenol, for example, amounts to only a few parts per billion in aqueous solutions of acetone. Nevertheless, many important reactions of ketones proceed via the more reactive ends, and enolization is then generally rate-determining. Such a mechanism was put forth in 1905 by Lapworth,2 who showed that the bromination rate of acetone in aqueous acid was independent of bromine concentration and concluded that the reaction is initiated by acid-catalyzed enolization, followed by fast trapping of the end by bromine (Scheme 1). This was the first time that a mechanistic hypothesis was put forth on the basis of an observed rate law. More recent work... 

Cyclobutanone 15 is available, and also very electrophilic, so addition of the vinyl Grignard and dehydration with the rather unusual reagent iodine gave the diene 13. This diene will be used in a Diels-Alder reaction in chapter 17. 

In view of these results, attention was turned to amine 124, whose derivatives could be hoped to react with electrophiles from the opposite face. Indeed, formamide 127 gave (+)-fischerindole I (117) in 47% overall yield after treatment with ferf-butyl hypochlorite and triethylamine followed by addition of silica gel deactivated with triethylamine and subsequent exposure to the Burgess reagent. This transformation presumably takes place by generation of chloroindolenine 128, anti elimination to give 129, tautomerism to 130 and final dehydration (Scheme 30). 

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