Electrophilic activation modes

Therefore, in order to obtain a 1,4-addition of an allyl residue to an enone, two activation modes can be used reactions take place either under electrophilic conditions with Lewis acid promotion, or in the presence of fluoride ions. This is important as the stereochemical outcome often depends on the activation mode selected. 

Another mode of carbon-based activation of hemiacetals relies on carbonyl-centered electrophiles 89 (Scheme 3.14). These reagents have demonstrated the highest efficiency for disaccharide synthesis among electrophilic carbon activating agents. In the event, the hemiacetal 1 is activated with electrophile 89 for in situ... 

However, it is evident that Bi(III) salts have a unique activation mode and a strong Lewis acidic behavior. In this context, Bi(III) salts are well known for being capable of activating both a-donors such as alcohols or amines and Ji-donors such as alkenes and alkynes. This fact makes Bi(III) a versatile Lewis acid for various alkylation reactions in which both alcohols and C-C multiple bonds can be utilized as an electrophilic component. 

Depending of the catalyst structure, a dual catalyst activation mode may be involved in the process. For instance, in catalyst 42 (Fig. 2.4) [62] the presence of the trans-OH group in the 4-position of the pyrroUdine ring helps to activate the electrophile and also directs its approach from the less hindered face of the -enamine (B, Fig. 2.5). The bifunctional catalyst activation behavior is also suggested for other catalysts such as Jacobsen s thiourea 41 (Fig. 2.4) [61], where binding of the nitroalkene by the thioureamoiety allows the thermodynamically favorable E enamine to attain in close proximity for a highly diastereo- and enantioselective C-C bond-formation (C, Fig. 2.5). 

Comparing the activation mode of iminium and enamine catalysis, iminium catalysis is based on a LUMO-activation mode of the electrophile whereas enamine catalysis is based on a HOMO-activation of the nucleophile. Keeping in mind the fact that enamine and iminium species are rapidly interconverted via a two-electron redox process (proton abstraction of an iminium species results in an enamine), MacMillan and co-workers reasoned that it should be possible to interrupt this equilibrium chemically by carrying out just a one-electron oxidation of an enamine. This would then generate a three-7i-electron radical cation with a singly occupied molecular orbital (SOMO) that should be activated towards catalytic transfomiatirHis (racemic or asymmetric) not possible using classical enamine or iminium activation (Scheme 80) 316). 

Electrophilic Aromatic Substitution. When activated with electrophilic reagents, such as trifluoroacetic anhydride (TFAA), diphenyl sulfoxide is converted into an acyloxysulfonium ion, which can effect electrophilic aromatic substitution. When this mode of sulfoxide activation is performed in the presence of simple aromatic substrates, such as o-xylene, the corresponding triarylsulfonium salt is formed in good yield (eq 4). The Ph2SO TFAA reagent combination reacts similarly with more complex substrates, such as indoles, affording the 3-indolylsulf-onium salts. 

A dual-activation way is invoked based on the similar widely accepted catalytic mode of activation for L-proline catalyst. In this context, the acidic tetrazole moiety activates the electrophilic imine by a hydrogen-bonding interaction, and the pyrrolidine moiety would activate the nucleophilic P-ketoester via formation of an enamine intermediate. The stereochemistry of the acidic tetrazole moiety seems to be crucial for the stereoselectivity in the final products. This... 

Diamination was first reported in 2007 by Jprgensen and coworkers with a combination of enamine and iminium-ion activation modes catalyzed by the diaryl prolinol silyl ether 3 (10 mol%) [18]. The sequential addition of succinimide as the nucleophile and diethyl azodicarboxylate as the electrophile afforded the syn-diaminated products 32 and 33 in promising overall yield (40%) with high levels of stereoselectivities (dr up to 8/2, ee 99%) (Scheme 12.14). 

Both modes benefit from the presence of the resonance-contributing heteroatom, but attack at C2 leads to an intermediate with an additional resonance form, thus indicating this position to be the preferred site of substitution. Indeed, such selectivity is generally observed. However, because C3 also is activated to electrophilic attack, mixtures of products can form, depending on conditions, substrates, and electrophiles. 

As the most represented mode of activation in organocatalysis to-date, we begin with catalysts acting as Lewis bases. Following Denmark s recommendation [11], the activation mode and catalyst itself are designated as Lewis basic, with the terms nucleophilic/electrophilic being employed to specify the properties of the reactive intermediate. 

It is believed that monofunctional imidazolidinones are optimal for iminium catalysis but without the necessary structural features to participate in bifunctional enamine catalysis (e.g., activation of electrophiles via electrostatic interaction). Conversely, proline has proved to be an enamine catalyst for which bifunctional activation is a standard mode of operation aCTOss a variety of transformation types, yet it is generally ineffective as an iminium catalyst with enals or enones. Therefore, a combination of imidazoUdinone and proline may provide a dual-catalyst system that could fully satisfy the chemoselectivify requirements for cycle-specific catalysis [136]. 

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