Umpolung table

Although the estimated oxidation potentials of the a-carbonyl radicals 90 are lower than those of the corresponding enols 86, a strong oxidant is needed to prevent radical type of reactions. According to the rates calculated on the basis of the Marcus theory [188], one-electron oxidation of the radicals can only compete with other radical processes when the electron transfer step is strongly exergonic. Thus, for radicals 90a and 90b the one-electron oxidant TTA" is too weak an oxidant, as reflected by both the yields of the a-Umpolung (Table 14) and the slow electron transfer rates (Table 13). 

We (and in parallel Bode et al.) were pleased to find that the IMes-catalyzed conjugate umpolung of a,(j-unsaluralcd aldehydes has a broad scope (Burstein and Glorius 2004 Burstein et al. 2006 Schrader et al. 2007 Sohn et al. 2004 He and Bode 2005 Sohn and Bode 2005) (For related applications of NHC in organocatalysis, see Chow and Bode 2004 Reynolds et al. 2004 Chan and Scheidt 2005 Reynolds and Ro-vis 2005 Zeitler 2006 Nair et al. 2006a,b He et al. 2006 Fischer et al. 2006 Chiang et al. 2007 Philips et al. 2007 Maki et al. 2007). Under optimized conditions, a 1 1 mixture of cinnamaldehyde and the ben-zaldehyde derivative in THF was treated with IMes (prepared in situ from IMes HCl and an excess of KOtBu) and stirred at ambient temperature for 16 h (Table 1). A variety of differently substituted aromatic... 

Umpolung of Ketones via Enol Radical Cations Table 7. Irreversible oxidation potentials of enolates [89,151]... 

For example, addition of 2 equivalents of a nonnucleophilic base, 2,6-di-tert-butylpyridine, to the reaction system almost totally suppressed the reaction (Table 9). This proposes that acid catalyzed enolization is important for the a-Umpolung. In support of mechanism 1 the yields of the a-methoxylated products increased with decreasing oxidation strength of the oxidant (Table 10), since endergonic oxidation of the ketone 70 is slowed down (Fig. 2). On the other hand, in the presence of stronger aminium salts the ketone tautomer is oxidized which however does not lead to deprotonation in the benzylic position... 

Table 14. Yields of the a-Umpolung reaction of various arylacetones 91a-d with different oxidants ...

Most organometallic acceptors are positively charged complexes which show highly increased reduction potentials as compared to the isoelectronic neutral complexes. Several examples of such cationic organometallic acceptors (obtained by umpolung ) and their isoelectronic neutral counterparts which act as donors are summarized in Table 7. 

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

B.V. A R(C=0)CH2CH2CH2+ Equivalent. In this umpolung equivalent, the potentially positive center is even further removed from the carbonyl (see 342 in Table 8.18). This umpolung equivalent is best achieved by reaction of a nucleophile with a vinylogous ketene dithioacetal such as 395.376 initial reaction of... 

B.vi. An R(C=0)CH2CH2CH2CH2" Equivalent. The final umpolung equivalent in Table 8.18 is 343, where the reactive center is separated from the carbonyl by three carbons. This umpolung equivalent is... 

Table 1 Umpolung of 7i-allyl-, 7i-propargyl-, and allenylpalladium by reduction...

Table 2 Umpolung ofn-allyl-, 71-propargyl-, and allenylpalladium by transmetallation with organometallics...

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

The ThDP-dependent enzyme from Serratia marcescens (PigD), is an interesting carboligase since it has the ability to catalyze umpolung, Stetter type 1,4-additions to a,p-unsaturated ketones using pyruvate as donor substrate (Table 10.7) [51]. Aliphatic, aromatic as wdl as heterocydic a,p-unsaturated ketones selectively furnish the 1,4-adducts in the presence of pyruvate with PigD catalysis. Pyruvate is the preferred donor substrate, but 2-oxobutanoate can also be employed depending on the acceptor [51]. 

Recently, Maruoka and coworkers have also developed an asymmetric inverse electron demand 1,3-dipolar cycloaddition of C,A -cyclic azomethine imines with fort-butyl vinyl ether catalyzed by a newly developed axially chiral dicarboxylic acid having diarylmethyl groups at the 3,3 -positions (Scheme 7.7) [18]. Based on this finding, the concept of the inverse electron demand umpolung 1,3-dipolar cycloaddition was introduced as a strategy for switching the regioselectivity of the cycloaddition from that of the titanium BINOLate-catalyzed normal electron demand 1,3-dipolar cycloaddition with enals (Table 7.3) by... 

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