Umpolung reactions

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],... 

This is reminiscent of the Umpolung reactions of organic chemistry. As the group CO—CH2OH is transferred from a donor molecule (R —CO—CH2OH) to the aldehyde (R—CHO), the corresponding enzymes are classified among transferases. The use of transketolase will be considered in this Section. 

Three approaches leading to 8 were considered (Figure 3.6.9) Following the biosynthetic pathway directly, polymer-supported thiamine 9 was constructed (path A) and could lead via crossed acyloin couplings to the target structure. Polymer-supported hydrazones 10 were reported to add directly to aldehydes in a non-catalyzed Umpolung reaction (path B) with results reported in due course. Finally, phosphine ylides 11 were investigated as polymer-supported acyl anion equivalents (path C). 

Abstract. N-Heterocyclic carbenes (NHC) have become an important class of organocatalysts and class of ligands for transition-metal catalysis. In organocat-alyzed umpolung reactions, thiazolium salt-derived NHC have been used successfully for decades. Even so, during recent years there has been an increased interest in NHC-catalyzed transformations and many new reactions have been developed. This article focuses on the use of NHC in the conjugate umpolung of ,f>-unsaturated aldehydes. 

Thiazolium and triazolium salt-derived NHC, in particular, are well known catalysts for benzoin- and Stetter-type umpolung reactions. In the course of these reactions, the NHC catalyst adds to the electrophilic aldehyde, resulting in the formation of a nucleophilic enamine species. Subsequently, this enamine can react with a series of different electrophiles such as aldehydes (benzoin condensation) or a, )-unsaturalcd substrates (Stetter reaction) (Scheme 4). 

As many natural products contain y-butyrolactone fragments (Seitz and Reiser 2005) the scope of this conjugate umpolung reaction was investigated in detail. 

Not only can this umpolung reaction be used to form 5-membered y-butyrolactones, but 4-membered p-lactones can be formed also. Interestingly, this change does not rely on a change of catalyst, but rather the reaction conditions are crucial for the reaction outcome. Using the same substrates and the same catalyst, but changing the base, the solvent and the reaction temperature allowed a change of the outcome of this reaction. Under optimized reaction conditions, P-lactones 18 formed with... 

Chan A, Scheldt KA (2005) Conversion of a,fS-unsaturated aldehydes into saturated esters an umpolung reaction catalyzed by nucleophilic carbenes. Org Lett 7 905-908... 

Schrader W, Handayani PP, Burstein C, Glorius F (2007) Investigating organo-catalytic reactions mass spectrometric studies of a conjugate umpolung reaction. Chem Comm 2007 716-718... 

Triazolylidene carbenes show great versatility as they not only catalyze classical umpolung reactions, but have also been shown to be successful catalysts for enantioselective extended umpolung reactions (for details, please see the following sections). 

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)...

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). 

In general, all extended umpolung reactions deal with aldehyde substrates that bear somehow reducible side chains prone to subsequent interaction at the stage of the common so-called Breslow intermediate (Zeitler 2005). Their subsequent participation leads—depending on the... 

The first step of this unprecedented umpolung reaction is identical to the standard MBH mechanism. Only the tautomerization event differentiates between a- (enolate) and -functionalization (homoenolate). 

For several tautomeric systems ketones/enols, imines/enamin and others) a distinct reversal of the stability order is observed when going from the neutral compounds to the radical cations, the first use of which in a new preparative a-Umpolung reaction has been documented for keto/enol systems. The present review provides a critical evaluation of the chemistry of enol radical cations in solution with a special emphasis on the Umpolung reaction and the intermediates thereof. Other enol type of radical cations are discussed with respect to their potential to provide a-carbonyl radical and a-carbonyl cation intermediates. Hence, this article does not constitute a comprehensive summary on all enol type of radical cation reactions. All potentials in this review are referenced versus SCE, unless noted otherwise. Potentials measured against the ferrocene/ferrocenium couple were converted to SCE by adding 0.334 V. 

Hence, for a rational design of the a-Umpolung reaction some questions have to be answered ... 

In summary, these data support the proposed overall mechanistic scheme for the a-Umpolung reaction (Scheme 8), which invokes rapid deprotonation of the enol radical cations 86Should the other mechanisms (Scheme 3, mech. 4 and 5) be valid for the a-Umpolung reaction of 86 one would expect the yields to go up with less electron rich enols, since both the benzyl radical ArCH -C(OH)(OMe)CH3 and the a-hydroxy radical ArCH(OMe)-C-(OH)CH3 should be readily oxidized even for a p-chloroaryl system. In competition experiments... 

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

In the following section, the chemistry of other enol type of radical cations will be analyzed with respect to the a-Umpolung reaction. Thus, emphasis was given to reactions of masked enol radical cations that provide a-carbonyl radical and/or a-carbonyl cation intermediates. 

Other a-Umpolung reactions of ketones via oxidative reactions of silyl enol ethers can be accomplished by using MCPBA as oxidant following the Rubot-tom method [213], Pb OAc)4 [214], OSO4 [215], Ni(II)complex/oxygen [216] and iodosobenzene with BF3 [217] or Mn(III) [218] but certainly radical... 

Enol ether radical cations undergo a variety of reactions, e.g. carbon-carbon bond formation [206,230-235], isomerization [236,237], oxygenation [238-241], cycloaddition [242-245], and they play an important role in the damage to DNA by ionizing radiation [246,247]. According to ESR studies most of the spin density resides at the -carbon (89% for EtO" = CH-CH2 [248]) [234,249,250]. The focus of the present brief section, however, will be conremed with their role as potential intermediates in a formal a-Umpolung reaction of ketones. 

Halogen-metal exchange reactions are umpolung reactions that transform C-electrophiles into C-nucleophiles. 

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... 

N-Heterocyclic carbenes catalyzed umpolung reactions via homoenolates 07Y1009. 

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