Reactivity with electrophiles

Enantiomerically pure and racemic / -carbonyl sulfoximes were treated with diethylzinc to afford the corresponding ethylzinc enolates 148a-c in both racemic and optically active forms (Scheme 94).214 Despite their rather similar solution structures, these complexes exhibited markedly different solid-state structures and reactivities with electrophiles. 

Screening of over 66,000 compounds from the MLSMR by scientists at the PCMD for inhibitors of Cathepsin B resulted in the identification and characterization of an alternate substrate, SID 16952359 [29]. This study also describes issues relating to the nucleophilicity of dithiothreitol (DTT) and cysteine, reductants frequently used in HTS protocols, and the potential for reactivity with electrophilic sites of probe molecules. 

From the lack of reactivity with electrophilic reagents and from the readiness to undergo nucleophilic reactions when electron withdrawing substituents are present, may be concluded that the two carbon atoms of the heterocycle are positively polarized by the electron attracting power of the 2 and 4 nitrogen atoms. 

Whereas neutral oxazolones and the corresponding thiones are not particularly reactive with electrophiles, 2(3f/)-oxazolones (and benzoxazo-lones) give the 2-chloro derivatives on heating with phosphoryl chloride [77AHC(21)175]. With phosphorus pentachloride, though, 5-chlorination can occur (87JOU813) (Scheme 29). 

Although thiazoles structurally resemble imidazoles and oxazoles, they are less reactive with electrophiles. Calculated 7r-densities (48BSF1021) and localization energies (61CCC156) largely agree with experimental observations that positional specificities for electrophilic substitution are 5... 

Few of these species are strictly aromatic, but reactivity with electrophiles resembles that of aromatic compounds. Much of the discussion that follows will be devoted to the pyrones and thiopyrones (the fused benz-derivatives, coumarins, chromones, flavones, and isoflavones, will be covered in Part 3). 

The quinone methide carbon of 71 is also the terminal carbon of an extended enol, and therefore reacts as both a nucleophile and electrophile (Scheme 32). This carbon shows a higher relative reactivity with electrophiles compared with nucleophiles than is observed for the corresponding terminal quinone carbon of mitomycins (Scheme 30A).73 Furthermore, the addition of nucleophiles to 71 is readily reversible, but the nucleophile adduct can be trapped by reoxidation to... 

Organocopper/zinc reagents substituted by a phenylthio group at the "/-position can be prepared, and also show enhanced reactivity with electrophiles (equation II). 

The resistance of pyridine toward electrophilic substitution is well known, and this reluctance to react is enhanced in the protonated species. Incorporation of extra annular nitrogen atoms further decreases this reactivity with electrophiles each aza substituent has an electron-withdrawing effect similar to a nitro group. One estimate of the o value for an aza substituent (=N—) is 0.65, and 1.95 for the protonated species (=N + H—) [68JCS(B)1484] (see also Chapter 9, Sections 9.A-9.C). Val-... 

The carbon-silicon bond has two important effects on the adjacent alkenc. The presence of a high-energy filled CT orbital of the correct symmetry to interact with the n system produces an alkene that is more reactive with electrophiles, due to the higher-energy HOMO, and the same ff orbital stabilizes the carbocation if attack occurs at the remote end of the alkene. This lowers the transition state for electrophilic addition and makes allyl silanes much more reactive than isolated alkenes. 

Product orientation alone is insufficient for elucidation of the mechanisms of these addition reactions as the same products would be obtained by either electrophilic or nucleophilic addition. It is well knowTi that the greater electronegativity of the sp carbon in alkynes leads to lower reactivity with electrophiles and greater reactivity with nucleophiles compared with the sp carbon of alkenes. A number of nucleophilic additions to alkynes such as addition of alcohols and weak acids are known ° . 

Among organic sulfides, those derived from 1,3-dithiane occupy an important place. The interest in these reagents lies not only in their reactivity with electrophilic substrates but also in the synthetic principles which have been developed from work on these compounds. By masking the aldehyde group by the formation of a dithiane, the carbon atom may participate in nucleophilic additions or substitution reactions and after hydrolysis of the thioacetal, the carbonyl group can then be regenerated (Scheme 1). 

As with carbene complexes, metal carbynes display a range of reactivity with electrophiles and nucleophiles. Molecular orbital calculations show that even cationic Fischer carbyne complexes are polarized as M, +=C A neutral Fischer- and Schrock carbyne complexes have an even greater negative charge on Ccarbyne.93 If all reactions between carbyne complexes and other species were charge-controlled, we would predict that nucleophiles would always attack at the metal and electrophiles at Ccarbyne. As we should expect by now, the picture is more complicated in practice. 

Although 1-aza-l,3-dienes are somewhat reluctant to undergo [4+2] cycloadditions, a,3-unsaturated l drazones show increased reactivity with electrophilic dienophiles. behaving as 1-amino-l-aza-l,3-dienes. For example, the M-dimethylhydrazone derived from methacrolein gives a high yield of 3-methylbenzo[g]quinolin-5,10-dione (62) via the adduct (61) on reaction with an excess of naphtho-1,4-quinone (B. Serckx-Poncin, A.-M. Hesbain-Frisque and L. Ghosez, Tetrahedron Letters, 1982, 3261). 

Chemoselectivity is often easy to control in alkenes because the alkene is a weak functional group. It does have inherent reactivity with electrophiles such as bromine but when another functional group, whether electron-donating or electron-withdrawing, is conjugated to the alkene, the reactivity is normally dominated by the other functional group. Compounds 2-4 would normally not be described as alkenes but as benzene, an enone, and an enol ether. But they are all alkenes. You will already know many reactions that would happen with one of these compounds and not at all with another. The triene 5 has three alkenes in the same molecule and we shall want to react just one and not the others. Chemoselectivity. 

Allison, Freas and Ridge discovered in 1979 that transition metal ions in the gas phase are very reactive with alkanes. Alkanes tend to be more reactive with electrophiles than nucleophiles, so the electrophilic character of the cation may be one important factor in the success of the chemistry. 

Morales-CerfinHP, Salazar-Pereda, Mendoza-Espinosa, et al. Synthesis of Ir(III) complexes with Tp and acac hgands and their reactivity with electrophiles. Dalton Trans 2015 44 13881-13889. 

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