Umpolung reactions, aldehyde functionalization

Moreover, the growing group of extended umpolung reactions is attracting considerable attention. This integration of functionalized aldehyde substrates in umpolung reactions (Reynolds et al. 2004 Chow and Bode 2004), and hence their cooperative interaction to yield new, de-functionalized intermediates has already been applied in a remarkable number of stereoselective variations (Scheme 7). 

The actual umpolung reaction that allows a ketene dithioacetal to function as if it had an electrophilic carbon a to a carbonyl is achieved by conjugate addition of nucleophiles to the ketene dithioacetal, followed by hydrolysis. Both sulfide and sulfoxide ketene derivatives can be used. Conjugate addition of an ester enol-ate derived from ferf-butyl acetate (secs. 9.2, 9.4.B, 9.7.A) to the ketene dithioacetal [CH2=C(SOMe)2] gave the stable dithioacetal anion (382). Conversion of the dithioacetal to the bis(sulfoxide) enhanced the ability of that species to function as a Michael acceptor. Subsequent transformation of 382 gave the aldehyde-ester (383).370... 

The benzoin reaction dates back to 1832 when Wohler and Liebig reported that cyanide catalyzes the formation of benzoin 6 from benzaldehyde 5, a seminal example in which the normal mode of polarity of a functional group was reversed (Eq. 1) [26], This reversal of polarity, subsequently termed Umpolung [27], effectively changes an electrophilic aldehyde into a nucleophilic acyl anion equivalent. 

The metalation of vinyl ethers, the reaction of a-lithiated vinyl ethers obtained thereby with electrophiles and the subsequent hydrolysis represent a simple and efficient method for carbonyl umpolung. Thus, lithiated methyl vinyl ether 56 and ethyl vinyl ether 54, available by deprotonation with t- or n-butyllithium, readily react with aldehydes, ketones and alkyl halides. When the enol ether moiety of the adducts formed in this way is submitted to an acid hydrolysis, methyl ketones are obtained as shown in equations 72 and 73 . Thus, the lithiated ethers 56 and 54 function as an acetaldehyde d synthon 177. The reactivity of a-metalated vinyl ethers has been reviewed recently . 

Thiamine anions add to aldehydes and ketones (e.g., acetaldehyde, carbohydrates, and pyruvic acid). Pyruvic acid adducts decarboxylate with a half-life of 24 hours in water and 3.2 minutes in ethanol, since ethanol cannot stabilize the intermediate zwitterion as well as water. After acidification, acetaldehyde is split off. In the adduct between acetaldehyde and thiamine, the electrophilic carbon atom of the aldehyde undergoes an Umpolung " to a resonance-stabilized enolate carbon atom. The thiazole-bound acetaldehyde then functions as carban-ion in Michael additions under mildly basic conditions. Retro-aldo reactions are observed, when 1,3-thiazolium ions react with the carbonyl groups of carbohy-... 

The concept of umpolung has been developed on the basis of such reactions. It is defined as the change in polarity of an atom in a functional group from electrophilic to nucleophilic character and vice versa. 2-Lithio-2-alkyl-l,3-dithiane 3 behaves like an umpoled ahphatic aldehyde R-CH=0. Aldehydes as electrophiles cannot react with alkyl haUdes, but after transformation of the aldehyde to the dithiane 1 and its litbio derivative 2, alkylation proceeds according to the sequence 1 3 4 5. 

The realization that productive new pathways could be followed in the presence of reactive functional groups at the a position of aldehydes first came to light in the early part of the twenty-first century. A flurry of new reactions have since been discovered that can be classified under the general term extended umpolung. ... 

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