Umpolung examples

Fermenting baker s yeast also catalyzes the 1,4-addition of a formal trifluoroethanol-d1-synthon to a,/i-unsaturated aldehydes, to give optically active l,l,l-trifluoro-2-hydroxy-5-alka-nones52. Presumably, the mechanism involves oxidation of the alcohol to the corresponding aldehyde followed by an umpolung step with thiamine pyrophosphate and Michael addition to the a,/i-unsaturated aldehyde. For example, l,l,l-trifluoro-2-hydroxy-5-hexanone (yield 26%, ee 93%) is thus obtained from trifluoroethanol and l-bnten-3-one. 

The attachment of an electron to an organic acceptor generates an umpolung anion radical that undergoes a variety of rapid unimolecular decompositions such as fragmentation, cyclization, rearrangement, etc., as well as bimolecular reactions with acids, electrophiles, electron acceptors, radicals, etc., as demonstrated by the following examples.135"137... 

As known from the Umpolung reactions, dithioacetals can be deprotonated efficiently among others [230, 306], a recent application is 122 [307] (Scheme 1.54). Even basic aluminum oxide can catalyze these isomerizations. One older example reports the isomerization of an S-propargyl phosphanesulfide to the allene [308],... 

Reactive donors can be generated ca-thodically by reductive cleavage of hahdes to carbanions or by reduction of double bonds to radical anions. Using these methods, two acceptors can be dimerized in one step by reductive Umpolung , for example, two molecules of acrylonitrile to adipodini-trile - a reaction, which normally needs two or more steps. 

Dithiane as a nucleophile, serving as a masked carbonyl equivalent. This is an example of umpolung. 

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. 

Amines are generally prepared by nucleophilic amination, which is a coupling of carbon electrophiles with a nucleophilic amination reagent, NR2, and Ni and Pd catalyzed reaction of aryl halides with arylamines (Hartwig-Buchwald amination) . Thus, the direct C—N bond formation between carbon nucleophiles and electrophilic nitrogen functionality R2N+ constitutes an example of the umpolung methodology. 

This is another example of umpolung (see 0-95) 1478 the normally electrophilic carbon of the aldehyde is made to behave as a nucleophile. The reaction can be applied to the unsubstituted dithiane (R = H) and one or two alkyl groups can be introduced, so a wide variety of aldehydes and ketones can be made starting with formaldehyde.1504 R may be primary or secondary alkyl or benzylic. Iodides give the best results. The reaction has been used to close rings.1505 A similar synthesis of aldehydes can be performed starting with ethyl ethyl-thiomethyl sulfoxide EtSOCH2SEt.1506... 

Both of these methods could be included as examples of umpolung of ir-allyl species, as the electrophilic allylpalladium has now been transformed into a nucleophilic allyl moiety. Finally, Bn can also be added to ir-allylpalladium complexes (equation 134).342... 

Re, R-0=0, CH2-C02R. These synthons have unnatural , or reversed polarity (originally called umpolung ).23 However, they are perfectly valid though their reagent equivalents are sometimes not immediately obvious. Some illustrative examples are noted below. 

At lower temperatures, a catalytic version involves the use of non-nucleophilic imines (for example tosylated imines) and the Umpolung of the ketene substrate using tertiary amines or other suitable nucleophiles, making the ketene nucleophilic ... 

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]. 

The anti-Markovnikov photochemical addition of malononitrile onto styrenes in the presence of lithium carbonate and a cyanoarene has been reported. In this case, excited 9-cyanophenanthrene (9-CP) oxidizes an olefin by PET, and the resultant radical cation adds to the malononitrile anion. The resulting radical is then reduced by 9-CP - and protonated to afford the end products [29]. This represents one of the rare examples involving the photoaddition of a carbanion to an olefin, and is explained by the PET-induced Umpolung of the latter, which thus becomes electrophilic. 

As already discussed (Section 5.2.3), a-metallated ketones were converted by IOB into a-methoxyketones, in presence of methanol. Generally, various organometallic compounds react readily with hypervalent iodine reagents undergoing an umpolung of reactivity the intermediates formed need not be isolated, since they may react in situ with a variety of nucleophiles. A simple example illustrating the point is the... 

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. 

These strategies are more difficult to realize with the reagents you have met so far but conjugate addition of a cyanide to an unsaturated carbonyl compound would be an example of the d1 + a3 strategy. We have included these to try to convince you that there is no escape from umpolung in the synthesis of a 1,4-dicarbonyl compound. If you were making this keto-ester you would have to understand two of the three strategies. 

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... 

Scheme 7. Examples for stereoselective extended umpolung reactions (Reynolds and Rovis 2005 Chow and Bode 2004 Sohn and Bode 2006 Phillips et al. 2007 Zeitler 2006 He et al. 2006a,b)...

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 ... 

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). 

Chapter 1 is devoted to exploring strategies involved in organic synthesis. It seeks to explain concepts like retrosynthetic analysis, atom economy, umpolung approach, click chemistry and asymmetric synthesis. On the basis of interesting and relevant examples, protection and deprotection of different functional groups are explained and the most probable mechanism is also mentioned for important reactions. 

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