Umpolung reagents

Direct nucleophilic acylation of nitroalkenes (164), promoted by a combination of (g) fluoride anion and thiourea catalyst (165), has been developed, using the thiazolium derivative (163) as the umpolung reagent (<20 1 dr, 74% ee).214 ... 

You have in fact met one example of each of the unnatural synthons with a2 and d1 reactivity. Such synthons are given the German name Umpolung, meaning inverse polarity because their natural reactivity is reversed, and umpolung reagents are the key to the synthesis of 1,2- and 1,4-difunc-tionalized compounds. 

This is a case of umpolung, the concept you met in Chapter 30, and dithianes are among the most important of the umpolung reagents. An example chemists wanted to make this compound (a... 

Acylsilanes are umpolung reagents that direct C-acylation of nitrones to give a-siloxyamino ketones. A TADDOL phosphite (82) engenders the reaction asymmetric. ... 

Conjugate addition to unsaturated nitro-compounds, using the reaction between 1-trimethylsilyloxycyclohex-l-ene and 2-nitropropene, under the influence of SnCl4, to give 2-acetonylcyclohexanone (i.e. the nitrocompound acts as an umpolung reagent for an acetone moiety). 

Table 8.19. Ketene Dithioacetal 385 as a Nucleophilic Umpolung Reagent...

For the addition of cyanide (a Ci-synthon) to aldehydes by hydroxynitrile lyases see Sect. 2.5.1. For the sake of simplicity, the donor representing the umpolung reagent is drawn with bold C-C bonds throughout this chapter. 

Electrolysis of disubstituted malonic acids and a-phenylthiocarboxylic acids results in decarboxylation to form ketones. This suggests that malonic and a-phenylthioacetic acids may be considered as umpolung reagents for the preparation of ketones. 

TABLE 8.1 Electrophilic and Nucleophilic Umpolung Reagents and Their Equivalents... 

An abnormal polarity carbonyl a disconnection step is shown for Compound 8.8 in Scheme 8.4. The carbonyl carbon is not nucleophilic, but an umpolung reagent will allow the carbon to behave as a nucleophile for the carbon-carbon bond forming reaction. 

The 2,3 disconnection of 1,4-difunctional molecules is also of value. The diketone in Scheme 8.10 disconnects to a pair of mutually unattractive enolate ions, but one may be replaced with an umpolung reagent. 2,3-Dibromopropene is equivalent to acetone with an electrophilic a carbon. The actual steps are shown in Equation 8.10. The initial ketone enolate was stirred at room temperature to equilibrate to the more stable more substituted enolate. The vinyl bromide intermediate was hydrolyzed to the ketone using mercury (II) acetate in formic acid [15]. 

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