Electrophilic component

There are two distinct groups of aldolases. Type I aldolases, found in higher plants and animals, require no metal cofactor and catalyze aldol addition via Schiff base formation between the lysiae S-amino group of the enzyme and a carbonyl group of the substrate. Class II aldolases are found primarily ia microorganisms and utilize a divalent ziac to activate the electrophilic component of the reaction. The most studied aldolases are fmctose-1,6-diphosphate (FDP) enzymes from rabbit muscle, rabbit muscle adolase (RAMA), and a Zn " -containing aldolase from E. coli. In vivo these enzymes catalyze the reversible reaction of D-glyceraldehyde-3-phosphate [591-57-1] (G-3-P) and dihydroxyacetone phosphate [57-04-5] (DHAP). 

KDPG is a member of a yet unexplored group of aldolases that utilize pymvate or phosphoenol pymvate as the nucleophile in the aldol addition. They are quite tolerant of different electrophilic components and accept a large number of uimatural aldehydes (148). The reaction itself, however, is quite specific, generating a new stereogenic center at the C-4 position. 

The Baylis-Hillman reaction is usually carried out under mild conditions (0°C or room temperature). The reaction time varies from a few minutes to even days. With the proper catalyst, good yields are possible. In the absence of an aldehyde or ketone as the electrophilic component, a dimerization of the activated alkene can take place under the influence of the catalyst, as also observed as a side reaction under the usual reaction conditions ... 

When a 1,4-quinonediazide is used as the electrophilic component, a quinoneazine is formed according to Scheme 12-50 (Huisgen and Fleischmann, 1959). 

In another application of the cyanohydrin acetonide method, cyanohydrin acetonide 64 (Fig. 2) was developed as a common precursor to both the nucleophilic and electrophilic components of a convergent coupling [30]. Orthogonal... 

Rovis and co-workers have also extended the intermolecular Stetter reaction to inclnde nitroaUcenes as the electrophilic component. Fluorinated triazolinm precatalyst 155 was effective in catalysing the reaction of a variety of heteroaromatic aldehydes 153 with nitroalkenes 154 to generate P-nitroketones in excellent yields and enantioselectivities. The authors propose that stereoelectronically induced conformational effects on the catalyst skeleton are key to the high selectivities observed with flnorinated catalyst 155 (Scheme 12.33) [69],... 

Entry 9 of Scheme 2.1 is an example of application of these conditions. Tin(II) enolates prepared in this way also show good reactivity toward ketones as the electrophilic component. 

The proline-catalyzed reaction has been extend to the reaction of propanal, butanal, and pentanal with a number of aromatic aldehydes and proceeds with high syn selectivity.197 The reaction can also be carried out under conditions in which the imine is formed in situ. Under these conditions, the conjugative stabilization of the aryl imines leads to the preference for the aryl imine to act as the electrophile. A good yield of the expected P-aminoalcohol was obtained with propanal serving as both the nucleophilic and the electrophilic component. The product was isolated as a 7-amino alcohol after reduction with NaBH4. 

As is the case for aldol addition, chiral auxiliaries and catalysts can be used to control stereoselectivity in conjugate addition reactions. Oxazolidinone chiral auxiliaries have been used in both the nucleophilic and electrophilic components under Lewis acid-catalyzed conditions. (V-Acyloxazolidinones can be converted to nucleophilic titanium enolates with TiCl3(0-/-Pr).320... 

Scheme 6.7 shows some other examples of enantioselective catalysts. Entry 1 illustrates the use of a Co(III) complex, with the chirality derived from the diamine ligand. Entry 2 is a silver-catalyzed cycloaddition involving generation of an azome-thine ylide. The ferrocenylphosphine groups provide a chiral environment by coordination of the catalytic Ag+ ion. Entries 3 and 4 show typical Lewis acid catalysts in reactions in which nitrones are the electrophilic component. 

Even mixed reagents with Lewis acids attack at the less-substituted position, indicating dominance of the nucleophilic bond making over the electrophilic component of ring opening.38... 

Methylation of the dihaptothioacyl complex 22 affords compound 23 containing a bidentate carbene ligand, which on reaction with chloride ion leads to the neutral monodentate carbene complex 24 (50,51). The chelate carbene complex 26 is generated in a novel interligand reaction from the thiocarboxamidothiocarbonyl cation 25. The thiocarbonyl carbon acts as the electrophilic component in this reaction, and 26 is further alkylated to a bidentate dicarbene species (52). 

The use of enol- and phenol-esters in cross-coupling reactions is a valuable protocol, as it gives an indirect way to involve readily available phenols and carbonyl compounds as the electrophilic components of cross-couplings (Equation (22)) ... 

Both heterogeneous and homogeneous CO reduction catalyst recipes often contain electrophilic components such as silica supports, metal oxides, and A1Cl3 [1,5,33,34,35,36]. 

The above examples represent Jl-heteroaromatic annulation involving the reaction of allyl anions whose double bond is a part of the heterocyclic ring system (Scheme 1). The corresponding a-oxoketene dithioacetals (1,3-electrophilic component) were generally derived from nonheterocyclic carbonyl precursors. Alternatively the Jl-heteroaromatic annulation can also be employed to a-oxoketene dithioacetals derived from heterocyclic ketones (1,3-bielectrophile) and hetero/nonheteroallyl anions (1,3-binucleophile). These reactions are described below. 

A variety of leaving groups (other than simple halide) may be associated with the electrophilic component of the reaction with these phosphorus components. These include haloepoxides (leading to (3-ketophosphoryl compounds),59 quaternary ammonium salts,60-64... 

The first group of approaches to glycosyl phosphates, wherein the carbohydrate acts as electrophilic component, entails common glycosylation methods and... 

The electron capture detector is another type of ionization detector. Specifically, it utilizes the beta emissions of a radioactive source, often nickel-63, to cause the ionization of the carrier gas molecules, thus generating electrons that constitute an electrical current. As an electrophilic component, such as a pesticide, from the separated mixture enters this detector, the electrons from the carrier gas ionization are captured, creating an alteration in the current flow in an external circuit. This alteration is the source of the electrical signal that is amplified and sent on to the recorder. A diagram of this detector is shown in Figure 12.13. The carrier gas for this detector is either pure nitrogen or a mixture of argon and methane. 

Fig. 3.2. Common catalytic groups of hydrolases involved in ester and amide bond hydrolysis (Z+ = electrophilic component polarizing the carbonyl group Y = nucleophilic group attacking the carbonyl C-atom H-B = proton donor transforming the -OR or -NR R" moiety into...

The use of the trisylhydrazone 124 of 2-butanone 123 in the coupling process provides access to products containing an ethyl-substimted olefin 126. The starting unsymmetrical hydrazone 124 undergoes deprotonation and alkylation at the terminal a-carbon leading to a single metallated olefinic product 125Li (equation 44). The electrophilic component 2,3-dibromopropene leads to 126, which can be further elaborated via subsequent reactions. 

Lithium Enolates. The control of mixed aldol additions between aldehydes and ketones that present several possible sites for enolization is a challenging problem. Such reactions are normally carried out by complete conversion of the carbonyl compound that is to serve as the nucleophile to an enolate, silyl enol ether, or imine anion. The reactive nucleophile is then allowed to react with the second reaction component. As long as the addition step is faster than proton transfer, or other mechanisms of interconversion of the nucleophilic and electrophilic components, the adduct will have the desired... 

In addition to aryl halides and inflates, aryldiazonium ions can be the source of the electrophilic component in coupling with arylboronic acids139 (entries 4 and 5 in Scheme 8.11). 

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. 

Beside the Friedel-Crafts-type alkylation of arenes, the direct functionalization of 2,4-pentanediones is of great interest in Lewis acid catalysis. Although Pd-catalyzed Tsuji-Trost type allylations of 1,3-diketones are known, direct benzylation procedures catalyzed by Lewis acids are less explored [40-43]. Based on the previously described Friedel-Crafts alkylation of arenes and heteroarenes, the Rueping group developed a Bi(OTf)3-catalyzed benzylation of 2,4-pentanediones. Alcohols such as benzyl, allyl or cinnamyl alcohols were used as the electrophilic component to yield important 2-alkylated 1,3-dicarbonyl compounds. Initially, different Bi(III) salts were screened. In contrast... 

In addition to benzyl alcohols, styrenes have also been used as the electrophilic component in this procedure. This is described in more detail in Sect. 3.2. 

Acid chloride CICOOEt PhCOCl Me2N.C0Cl One of these compounds can act only as the electrophilic component in a condensation,... 

The reaction is intra-molecular the enolate component being one end and the electrophilic component the other end of a six carbon diester ... 

Only one compound can enolise, and the diketone will act as the electrophilic component as it is more reactive than a mono ketone. We begin with a simple condensation ... 

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