Initial deprotonation

The mechanism for the formations of 83, 85, and 93 can be explained as illustrated in Scheme 13. Initial deprotonation of the 1-methoxy group of 82 liberates formaldehyde and an indolyl anion 95, and then protonation of 95 affords 83. Following the reaction path a, 95 reacts with formaldehyde to produce indole-3-methanol 96. Unstable 96 collapses into 3-methyleneindolenine 97, which adds... 

The interfacial mechanism provides an acceptable explanation for the effect of the more lipophilic quaternary ammonium salts, such as tetra-n-butylammonium salts, Aliquat 336 and Adogen 464, on the majority of base-initiated nucleophilic substitution reactions which require the initial deprotonation of the substrate. Subsequent to the interfacial deprotonation of the methylene system, for example the soft quaternary ammonium cation preferentially forms a stable ion-pair with the soft carbanion, rather than with the hard hydroxide anion (Scheme 1.8). Strong evidence for the competing interface mechanism comes from the observation that, even in the absence of a catalyst, phenylacetonitrile is alkylated under two-phase conditions using concentrated sodium hydroxide [51],... 

Further information concerning the stereochemical properties of the rearrangement were evaluated by submitting rigid cyclohexane derivatives 254/255 to the reaction conditions. In 1975, House described the allylation of a cyclohexyl cyanide 248 [53]. The initial deprotonation with LDA led to a ketene imine anion 249, which was then treated with allyl bromide. Two potential paths rationalized the outcome an AT-allylation generated the intermediate ketene imines 250/251, which underwent aza-Claisen rearrangement to deliver the nitriles 252/253 alternatively, the direct C-allylation of249 produced the nitriles. 

Wittig reactions have been studied and extended by sonochemists. Starting from allylic phosphoranes, it was shown that the initial deprotonation step could be effected with an increased efficiency using butyl lithium in TH F or even in benzene (Scheme 3.23) [122]. The insoluble phosphorane disappears after 5-15 min sonication. This superposition of the two essential roles of sonication is reflected by the change in the stereoselectivity, larger proportions of the trans-diene being formed under irradiation. 

An initial deprotonation step is involved, as in Reaction (4), to generate BsHs which then reacts with an equivalent amount of the remaining B5H9 to give B9Hm. ... 

The carbamates 549 (R = OBu-f) behave similarly, though they must be lithiated with i-BuLi to avoid addition to the carbonyl group °. It is possible simply to use a lithium carbamate to protect an amino group during a lateral lithiation an initial deprotonation and carbonation generates the lithium carbamate 556, which is then deprotonated twice more by t-BuLi (Scheme 220). After electrophilic quench, acid hydrolysis of the carbamic... 

Heterocyclic carbanions stabilized by ylid formation, or by resonance that places the negative charge on a heteroatom, are specifically excluded. In addition, heterocyclic systems that do not depend on additional stabilization factors for their initial deprotonation, continued existence, or subsequent reaction with electrophilic substrates are discussed in less detail. 

Although most furazans are stable to alkali the parent compound and mono-substituted analogues are isomerized to the oximes of a-ketonitriles in a sequence which involves initial deprotonation at the 4-position (Scheme 6) <65J0C1854> 5-ethylfurazinium salts (23) react similarly to afford the N-ethyl(hydroxyimino)amide (24) via an intermediate nitrosoketenimine (25) <64JA1863>. 

In this section several azinone derivatizing reactions are collected which do not occur at an anion formed by initial deprotonation of the azinone, because they occur in neutral medium, acidic medium, or via metal-mediated processes. 

Although 1,2-diazinamines are not very nucleophilic by themselves the nucleophilicity can be increased via initial deprotonation with strong base. This strategy has been followed by Heinisch and co-workers when studying intramolecular SNAr reactions (Equations 22 and 23) <1997H(45)673, 1997AP29>. 

The mechanism for elimination in this case probably involves initial deprotonation by alkoxide, followed by loss of Cl. ... 

The most common side-reactions induced by an initial deprotonation are ... 

It has also been shown that initial deprotonation of the phenol was not necessary for optimal reactivity and that epimerisation of base sensitive compounds is not a problem... 

The widely employed Leimgruber-Batcho protocol for indole synthesis comprises two consecutive steps—the formation of enamines followed by a reductive cyclization. The formation of enamines (such as 14, Scheme 7) presumably required an initial deprotonation of the methyl ortho to the aromatic nitro-group by methoxide generated from DMF-DMA under elevated temperatures (overnight heating in DMF) [27]. The use of microwave irradiation at 180 °C allowed the reduction of the time of formation of enamines such as 14 from 22 h (at 110°C) to 4.5 h (and even to 40 min in several... 

The metalation proceeds by initial deprotonation of the amide followed by ortho-directed deprotonation at the C3 position to produce the pseudo six-membered ring organolithium species 5.36. 

Since both rings in the fused system are 7r-electron deficient, alkyl substituents with at least one a-hydrogen are open for electrophilic attack after initial deprotonation. An example is the aldol-type condensation of (702) the 5-methyl group is the more reactive (71ZC460). 

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