Catalysis umpolung

Keywords Benzoin Carbene NHC Nucleophihc Catalysis Organocatalysis Redox Stetter Transesterification Umpolung... 

Redistribution of electron density in CT complexes results in a modification of the chemical properties of coordinated arenes, and this effect is widely used in organometallic catalysis [2]. To demonstrate the relationship between charge transfer in arene complexes and their reactivity, we focus our attention on carbon-hydrogen bond activation, nucleophilic/ electrophilic umpolung, and the donor/acceptor properties of arenes in a wide variety of organometallic reactions. 

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. 

Fischer C, Smith SW, Powell DA, Fu GC (2006) Umpolung of Michael acceptors catalyzed by N-heterocyclic carbenes. J Am Chem Soc 128 1472-4173 Glorius F (2007) (ed) N-Heterocyclic carbenes in transition metal catalysis. (Topics in Organometalic Chemistry, vol 28) Springer, Berlin Heidelberg... 

Within the field of nucleophilic carbene catalysis, with the exception of umpolung-directed transformations (see below), one of the most important classes in terms of applications already realized are transesterifications (Scheme 5 Grasa et al. 2003 Nyce et al. 2002 Singh et al. 2004) and related reactions (Dove et al. 2006). 

The second major class of non-umpolung nucleophilic carbene catalysis comprises reactions by initial NHC-activation of various silicon compounds. Their proposed common pathway is thought to lead to a hypervalent silicon complex4 and thus provide carbene-catalyzed activation of the corresponding nucleophiles such as TMSCN, TMSCF3 etc. (Kano et al. 2006 Song et al. 2005 2006). It is not only certain carbon-silicon bonds that can be effectively activated, but a comparable activation of Si-O bonds, e.g. of trimethylsily enol ethers etc., allows for mild, NHC-promoted Mukaiyama aldol reactions (Scheme 6 Song et al. 2007). 

G3P) and D-sedoheptulose 7-P as illustrated in Scheme 5.53. In addition D-erythrose 4-phosphate can function as the ketol acceptor thus producing D-fructose-6-P and G3P (Scheme 5.53). The enzyme relies on two cofactors for activity — thiamin pyrophosphate (TPP) and Mg2+—and utilizes the nucleophilic catalysis mechanism outlined in (Scheme 5.54).83 When TPP is used as a cofactor for nucleophilic catalysis, an activated aldehyde intermediate is formed. This intermediate functions as a nucleophile, and thus TK employs a strategy that is similar to the umpolung strategy exploited in synthetic organic chemistry. 

When addressing the synthesis of a 7,4-di-heterosubstitued portion of a target structure, one should consider a braod range of synthetic methods. While a stoichiometric umpolung is not the first choice, one should remember the advantage of in situ umpolung tactics. In the context of 7,4-difunctionalized skeletons, the most attractive variant is provided by the Stetter reaction [62] (Scheme 2.41), which emulates nature s thiamine catalysis (cf. p. 17). 

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. 

NHC-catalyzed reactions are unique in organic synthesis, and very useful for the construction of carbon-carbon bonds. Great success has been made for the NHC-catalyzed benzoin condensation, Stetter reactions, and a -d Umpolung reactions in the past decades. NHC catalysis has also hnd application in many other reactions, such as umpolung of Michael acceptors, Morita-Baylis-Hilman reaction, Michael additions, redox reaction, and reactions of ketenes. With the rapid development of NHC catalysis, more reactions will surely be found, and the wide applications in organic synthesis could be expected. 

In 2006, Tamaru and coworkers have reported that vinyloxirane 118 is capable of undergoing amphiphilic allylation of aldehydes 117 where, under Pd(0) catalysis, the allylic ether moiety serves as an allyl cation and reacts with aldehydes in the a-position, giving 6-hydroxy-4-hexenals 119 in good yields (Scheme 12.57). In the second step, the allyl alcohol moiety in turn serves as an allyl anion under umpolung catalysis with Pd(0)-EtjB and furnishes 2-vinylcyclobutanols 120 in good to modest yields [138]. 

The reactivity of activated C-C double bonds with NHC has been reviewed more specifically. This report details the umpolung reaction involving Michael acceptors, the use of carbenes in Morita-Baylis-Hillman as well as in various cycloadditions. The catalysis of alkyne cycloaddition with nitrile oxide is also covered. 

Keywords Asymmetric methodology Biomimetic Catalysis Lewis base Umpolung... 

Through the presumed intermediacy of Breslow intermediates, several other reactions have been developed featuring an inversion of reactivity for the aldehyde or umpolung [7, 8]. Other reactions in which the NHC plays the role of a nucle-ophihc or basic catalyst have also been reported recently. Although each type of catalysis is conceptually distinct, some generaUties can be drawn from their common use of NHC catalysts. 

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]. 

SCHEME 28.10. Catalysis mechanism of the ThDP-dependent enzyme involving an umpolung enabling the C—C bond formation, an example of a BAL-catalyzed reaction. 

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