Deprotonation electrophilic

Florio and coworkers have also reported the use of oxazolinyl groups as anion-stabilizing substituents. Lithiation/electrophile trapping of oxazolinylepoxide 202 provided access to acyloxiranes 205 [72], while deprotonation/electrophile trapping of oxazolinylepoxide 206 with nitrones gave access to enantiopure a-epoxy- 3-amino acids 208 (Scheme 5.48) [73],... 

Hodgson and coworkers have demonstrated that the use of diamine ligands in combination with s-BuLi allows the direct deprotonation/electrophile trapping of... 

Seebach and coworkers examined the deprotonation/electrophile trapping of phe-nylthioaziridine carboxylates 236 (Scheme 5.58). These thioesters were found to be more stable than their oxy-ester congeners when lithiated treatment of 236 with LDA at -78 °C, followed by trapping with Mel at -100 °C, stereoselectively afforded aziridine 237 [83]. 

Direct deprotonation/electrophile trapping of simple aziridines is also possible. Treatment of a range of N-Bus-protected terminal aziridines 265 with LTMP in the presence ofMe3SiCl in THF at-78 °C stereospecifically gave trans-a, 3-aziridinylsi-lanes 266 (Scheme 5.67) [96]. By increasing the reaction temperature (to 0 °C) it was also possible to a-silylate a (3-disubstituted aziridine one should note that attempted silylation of the analogous epoxide did not provide any of the desired product [81],... 

Hodgson, D. M. Norsikian, S. L. M. First direct deprotonation-electrophile trapping of simple epoxides synthesis of a,/f-epoxysilanes from terminal epoxides. Org. Lett. 2001, 3, 461—463. 

An attractive flexibility in using anomeric phenyl sulfones is that a stereodivergent synthesis of C-glycosides is available by alkylation before the reductive desulfonylation event. Thus, a one-pot four-step sequence of sulfone deprotonation-electrophile quenching-reductive lithiation-methanol quenching on sulfone 14 provides stereoselectively P-C-glycosides 19 as shown with aldehyde 16 (Fig. 

Since hydrazone anion chemistry is complementary to more conventional deprotonation-electrophilic substitutions effected with carbonyl derivatives such as ketones and aldehydes, and since hydrazone chemistry involves two additional synthetic operations, the use of hydrazones has to have some additional advantages. Compensating for the additional synthetic effort required to prepare and hydrolyze the... 

Polyphosphazenes with ferrocenyl substituents 35 have also been synthesized via the functionalization of poly-(methylphenylphosphazene) and related polymers by means of a deprotonation-electrophilic addition strategy (e.g., see Equation (10)). This versatile reaction sequence has yielded materials with, for example, degrees of substitution of 45% and 36% for polymers 35 (R = H and Me), respectively. The molecular weights of the polymers were M = Z.O x 10 and 1.5 x 10 for 35 (R = H and Me), respectively (with PDI values of 1.4-2.0). The glass transition temperatures increased in comparison with the unsubstituted polymer (Tg = 37°G) for 35 with values of 92 °C (R = H) and 87 °G (R = Me). 

Table 2 o-Deprotonation/electrophile quenching of halobenzene-CrfCOlj... 

Electrophilic substitution at the 4-position of pyrylium salts can be achieved using benzotriazole (Bt) -mediated methodology. Pyrylium salts are readily converted into the 4W-(benzotriazol-l-yl)pyrans. Subsequent deprotonation, electrophilic trapping of the Bt-stabilised anion and cleavage of benzotriazole affords the 4-substituted pyrylium (Scheme 6) <97JOC8198>. 

The first example of enantioselective deprotonation-electrophile trapping of a meso-epoxide is shown in Eq. (31) [37,74]. This reaction was favoured by both the stabihsation of the lithiated epoxide by the adjacent phenyl group, and the use of TMSCl as an internal electrophile. 

Very recently, deprotonation-electrophile trapping of simple meso-epoxides was applied to medium-sized meso-cycloalkene oxides [77]. When cyclooctene oxide 62 is treated with s-BuLi in the presence of a diamine at -90°C, the Hthiated epoxide is stable enough to be trapped with a wide range of electrophiles, allowing the creation of carbon-heteroatom or carbon-carbon bonds [Eq. (33)]. The deprotonation is a symmetry-breaking step, and enantioselective deprotonation was successfully achieved in the presence of (-)-sparteine, leading to a range of enantio enriched functionalised epoxides 115 (in up to 86% ee). 

Scheme 5.4 Enantioselective deprotonation-electrophilic quenching of aryldi-methylphosphine boranes.

Another variation of the Madelung synthesis involves use of an O-alkyl or O-silyl imidate as the C2 electrophile. The mechanistic advantage of this modification stems from avoiding competing N-deprotonation, which presumably reduces the electrophilicity of the amide group under the classical conditions. Examples of this approach to date appear to have been limited to reactants with a EW substituent at the o-alkyl group[15,16]. 

Retrosynthetic path b in Scheme 3.1 corresponds to reversal of the electrophilic and nucleophilic components with respect to the Madelung synthesis and identifies o-acyl-iV-alkylanilines as potential indole precursors. The known examples require an aryl or EW group on the iV-alkyl substituent and these substituents are presumably required to facilitate deprotonation in the condensation. The preparation of these starting materials usually involves iV-alkyla-tion of an o-acylaniline. Table 3.3 gives some examples of this synthesis. 

Hydrogen exchange, in thiazole, especially deuteration, has been quantitatively investigated (379,380), but the mechanism of the reaction carried out at acidic or neutral pH corresponds to a protonation-deprotonation process (380), different from electrophilic substitution and is discussed in section I.3.E. 

We can extend the general principles of electrophilic addition to acid catalyzed hydration In the first step of the mechanism shown m Figure 6 9 proton transfer to 2 methylpropene forms tert butyl cation This is followed m step 2 by reaction of the car bocation with a molecule of water acting as a nucleophile The aUcyloxomum ion formed m this step is simply the conjugate acid of tert butyl alcohol Deprotonation of the alkyl oxonium ion m step 3 yields the alcohol and regenerates the acid catalyst... 

Alkyl groups attached to pyridopyrimidines adjacent to a nitrogen are activated , i.e. they are readily deprotonated and react with electrophilic reagents as their anions, or resonance stabilized equivalents, e.g. (64). This ready deprotonation, of course, leads to facile exchange of the alkyl protons for deuterium (Sections 2.15.2.2.1, 2.15.4.2), but, in... 

The dianions derived from furan- and thiophene-carboxylic acids by deprotonation with LDA have been reacted with various electrophiles (Scheme 64). The oxygen dianions reacted efficiently with aldehydes and ketones but not so efficiently with alkyl halides or epoxides. The sulfur dianions reacted with allyl bromide, a reaction which failed in the case of the dianions derived from furancarboxylic acids, and are therefore judged to be the softer nucleophiles (81JCS(Pl)1125,80TL505l). 

Dioxins aromaticity, 3, 945 deprotonation, 3, 972 electronic energy levels, 3, 946 electrophilic reactions, 3, 965 half-wave potential, 3, 968... 

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