Extended Umpolung

Triphenylphosphine was employed as a nucleophilic catalyst for the umpolung addition of azoles (225) to the electron-deficient allenes (226 R1 = H, R2 = OEt, R3 = H, Et) to afford the addition products (227). This organocatalytic methodology has been extended to addition-cyclization reactions between electron-deficient allenes or alkynes and pyrrole-2-carboxaldehyde in the presence of a catalytic amount of tri-butylphosphine, giving the substituted indolizine-7-carboxylates (228 R2 = OEt, Me R3 = H, Et).265... 

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 original meaning of the term has been extended to the reversal of any commonly accepted reactivity pattern. For example, reaction of R-C=CX (X = halide) as a synthon for "R-C=C+ (i.e., electrophilic acetylene) is an umpolung of the normal, more common acetylide, R-C=(T (i.e., nucleophilic) reactivity. 

The phosphine-catalyzed umpolung y-addition of diphenylphosphine oxide to diphenylphosphinoyl-methylacetylene was accomplished best under MW conditions in isopropanol. The bis(phosphine oxide) was obtained in 72% yield The reaction was extended also to other model compounds, but in these cases another isomer was also formed. The unsaturation of the primary products was removed by catalytic hydrogenation (Scheme 21) ... 

Due to the unique bivalent carbene and diversity of the N-heterocyclic motif, NHCs have been demonstrated to be efficient organocatalysts for various enantioselective reactions. In addition to the traditional thioazolium and imidazolium NHCs, triazolium NHCs have become the most successful organocatalysts. Recently, NHC/Lewis acid cocatalysis and bifunctional NHCs have shown a very promising future. Beyond the classic NHC-catalysed umpolung of aldehydes, the extended umpolung of functionalised aldehydes are extremely successful. A series of NHC-catalysed reactions of ketenes have been developed for the synthesis of various enantioriched heterocycles. Esters, anhydrides, carboxylic acids and even Michael acceptors are useful alternative substrates for NHC-catalysed reactions. With increasing interest and rapid development of NHC catalysis, new structures of the catalysts, new reaction modes, and synthetic applications can be expected in the near future. 

The realization that productive new pathways could be followed in the presence of reactive functional groups at the a position of aldehydes first came to light in the early part of the twenty-first century. A flurry of new reactions have since been discovered that can be classified under the general term extended umpolung. ... 

The abiUty of enals to react as homoenolates [84] in the presence of NHC catalysts was first noted in 2004 independently by the groups of Glorius and Bode [85]. In both cases, the use of stericaUy-hindered catalyst 99 and a strong base (DBU or Bu OK) allowed a -d umpolung through the extended Breslow intermediate (101), thereby attacking an aldehyde electrophile and ultimately forming a y-lactone diastereoselectively (105, = H) (Scheme 18.18). Whereas two aldehydes can... 

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