Umpolung strategy

Umpolung is a general class of reactions in which the characteristic reactivity of a group or an atom is temporarily reversed. The concept of umpolung is helpful especially with carbonyl groups. But to understand this concept, it is important to understand the normal reactivity of the carbonyl group. For example, under normal conditions carbonyl carbon is electrophilic and the a-carbon is nucleophilic because of the resonance, as shown below  

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It is difficult to synthesize 9-[l-(2,4,6-cycloheptatrienyl)]-9-xanthydrol [347] from xanthone by a simple addition, considering the potential nucleophile, cyclohepta-trienide anion, is antiaromatic. An umpolung strategy works well in that reversed roles are given to the two reactants. 

The Classical and Umpolung Strategies in C-Aryl Glycoside Construction... 

Scheme 2. Sequence for the Umpolung Strategy -Reduction to the Group 1 (Ravidomycin) Substitution Pattern...

G3P) and D-sedoheptulose 7-P as illustrated in Scheme 5.53. In addition D-erythrose 4-phosphate can function as the ketol acceptor thus producing D-fructose-6-P and G3P (Scheme 5.53). The enzyme relies on two cofactors for activity — thiamin pyrophosphate (TPP) and Mg2+—and utilizes the nucleophilic catalysis mechanism outlined in (Scheme 5.54).83 When TPP is used as a cofactor for nucleophilic catalysis, an activated aldehyde intermediate is formed. This intermediate functions as a nucleophile, and thus TK employs a strategy that is similar to the umpolung strategy exploited in synthetic organic chemistry. 

A synthetic route for the synthesis of 2-deoxy-C-aryl glycosides using an umpolung strategy has been reported by Aidhen and co-worker (Scheme 1.7). The synthetic endeavour led to a versatile intermediate aryl ketone 1.13, which has paved the way for two important classes of C-glycosides, i.e. C-alkyl furanosides 1.14 and methyl 2-deoxy-C-aryl pyranosides 1.15. 

The most utilized Umpolung strategy is based on formyl and acyl anion equivalents derived from 2-lithio-l,3-dithiane species. These are readily generated from 1,3-dithianes (thioacetals) because the hydrogens at C(2) are relatively acidic (p f 31). In this connection it should be noted that thiols (EtSH, pi 11) are stronger acids compared to alcohols (EtOH, 16). Also, the lower ionization potential and the greater polarizability of the valence electrons of sulfur compared to oxygen make the divalent sulfur compounds more nucleophilic in Sj,2 reactions. The polarizability factor may also be responsible for the stabilization of carbanions a to sulfur. ... 

The arylthio group causes an umpolung that overrules the regiodirection of a methoxy or acetoxy group. Characteristic for an umpolung strategy, the arylthio substituent must be removed in a subsequent step, for instance by... 

NHC-Catalyzed MCRs in Heterocyclic Chemistry In 2001, Muller and coworkers developed an elegant example where chalcones could be transformed in a one-pot sequence to the corresponding pyrrole derivatives [55], stating the potential of NHC-catalyzed umpolung strategies in heterocyclic chemistry. Scheidt and coworkers... 

Radical cations, generated by single electron oxidation of enamines that are generated in situ by the reaction of aldehydes with a chiral imidazolidinone, serve as a new class of electrophiles for silyl enol ethers (Scheme 3-1and allylsilanes. This novel Umpolung strategy allows the introduction of a chiral center at the a-position of aldehydes with these silicon reagents. The chiral imidazolidinone works as an... 

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