Reactivity umpolung

Stetter expanded Umpolung reactivity to include the addition of acyl anion equivalents to a,P-unsaturated acceptors to afford 1,4-dicarbonyls Eq. 5a [57-60]. Utilizing cyanide or thiazolylidene carbenes as catalysts, Stetter showed that a variety of aromatic and aliphatic aldehydes act as competent nucleophilic coupling partners with a wide range of a,p-unsaturated ketones, esters, and nitriles [61]. The ability to bring two different electrophilic partners... 

Fn and co-workers describe Umpolung reactivity of Michael acceptors catalyzed by triazolinylidene carbenes (Eq. 33) [168], Nncleophilic addition followed by tantomerization renders the [3 position of the Michael acceptor nncleophilic, which snbseqnently nndergoes alkylation. Compatible leaving gronps inclnde Br, Cl, and OTs. a,P-unsatnrated esters, nitriles, and amides all provide good to excellent yields of cyclized products. 

In the same way, disconnection of a 1,4-diketone requires either an acyl anion equivalent reacting with a normal /3-carbonyl electrophile or a normal o -carbonyl nucleophile reacting with an abnormal cr-carbonyl electrophile. These abnormal or reversed-polarity reagents are said to have umpolung reactivity. 

In addition to the stabilized carbanions, electron-rich aromatic compounds, for example indole derivatives have emerged as new Michael donors [25], In these reactions, aromatic sp2-C-H transformation is involved. These reactions are described in detail in Section 111.1.3.1.3. A highly enantioselective intramolecular Stetter reaction, in which umpolung reactivity of a formyl group was accomplished using a chiral triazolium salt, has also been reported by Rovis [26]. 

Overall the reaction achieves an anti-Michael addition across the double bond of 42, an umpolung reactivity pattern also observed in some unsaturated amides (see below).31... 

Umpolung reactivity is also evident in the addition of an organolithium to a vinyl carbamate 56.34 The product 57 can be quenched with electrophiles at low temperature, but rearranges to 58 by a [l,2]-acyl transfer on warming. 

In Chapter 30, you came across the idea of umpolung, the inversion of the usual reactivity pattern of a molecule. You may have already noticed that radicals often have an umpolung reactivity pattern. Alkyl halides are electrophiles in polar reactions yet they generate nucleophilic radicals that react with electrophilic alkenes. 

Interestingly, deprotection (hydrolysis) of the heterocyclic auxiliary exposes a synthetically useful carbonyl group. This is possible in our system since the auxiliary is bonded to the carbonyl group by a carbon atom rather than a heteroatom. Such hydrolyses are well established for 1,3-dithiane derivatives as a result of their ubiquity as synthons for umpolung reactivity of the carbonyl group (Fig. I).5... 

The dithiane anion 1.9 also reacts with acyl halides, ketones and aldehydes to give the corresponding dioxygenated compounds. Schemes 1.4 and 1.5 show the reaction of dithiane anions 1.11 and 1.12 with ketones. The most common example of umpolung reactivity of a carbonyl group is the benzoin condensation (Scheme 1.6). 

The use of iV-heterocyclic carbene (NHC) as organocatalysts is well-documented [47]. However, it is their ability to render aldehydes as nucleophilic, thus setting up an umpolung reactivity, which is their greatest asset to organocatalysis. This nuclephilic... 

Abstract The discovery and development of new A-heterocyclic carbene-catalyzed reaction is described. Based on inspiration from nature, we have taken thiazolium-based approaches to umpolung reactivity and invented a suite of related reactions involving acyl anions, homoenolate, and enolate nucleophiles all generated under catalytic conditions. 

Masked lithium homoenolates of type XII are of interest in synthetic organic chemistry and can be considered as three-carbon homologating reagents with umpolung reactivity [122]. The lithiation of the jS-chloro orthoester 147 with lithium in the presence of a catalytic amount of DTBB, under Barbier-reaction conditions, and using carbonyl compounds as electrophiles, followed by acidic hydrolysis, led to lactones 149 as reaction products, the masked lithium homoenolate 148 bang proposed as a reaction intermediate (Scheme 2.20) [123]. 

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