Alkoxides. Bases or Nucleophiles

Alkoxides, RO, have dual reactivity, and can act as bases or nucleophiles. 

Many factors influence the chemical behavior of an alkoxide, including leaving group, metal ion, solvent and temperature. Electrophile geometry can also promote one type of alkoxide behavior over another. 

Examine space-filling models of ethyl bromide and 2-methyl-2-propyl bromide. Given that Sn2 reactions require backside attack, which of these is more likely to react with EtO in an Sn2 fashion What will the product be What E2 products would be obtained from each alkyl bromide  

The molecule below has four stereoisomeric forms exoO exoCH2Br, exoO endoCH2Br, and so on. Examine electrostatic potential maps of the four ions and identify the most nucleophilic (electron-rich) atom in each. Examine the electron-acceptor orbital (the lowest-unoccuped molecular orbital or LUMO) in each and identify electrophilic sites that are in close proximity to the nucleophilic. Which isomers can undergo an intramolecular E2 reaction Draw the expected 8 2 and E2 products. Which isomers should not readily undergo intramolecular reactions Why are these inert  

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Reactions of /)-benzoquinone and its derivatives with alkoxide ions (RO R = H, Me, Et, i-Pr, PhCH2) in MeCN also result in formation of the corresponding semiquinone radical anions accompanied by the formation of RO-substituted p-benzoquinones, which are the oxidized products of p-benzoquinones [360], Detailed product and kinetic analyses of the reactions indicate that RO-adduct anion of /)-benzoquinone is an actual electron donor and that RO is acting as a very strong base or nucleophile rather than a one-electron reductant in an aprotic solvent, such as MeCN [360], Similarly, the reaction of C o with methoxide anion (MeO ) in benzonitrile (PhCN) results in the disproportionation of Cgo to yield both C(,o and the methoxy adduct [360]. Spectroscopic and kinetic studies also indicate that a methoxy adduct anion of Ceo is a real electron donor and that MeO is acting as a very strong base or nucleophile rather than an electron donor in PhCN [360],... 

Because of the role of precursor structure on film processing behavior (consolidation, densification, crystallization behavior), the reaction pathways are typically biased through the use of the catalyst, which is simply an acid or a base. This steers the reaction toward an electrophilic or nucleophilic attack of the M—OR bond.1,63 Hydrolysis sensitivity of singly or multiply hydrolyzed silicon alkoxides is also influenced by the catalyst, which contributes to the observed variations in oligomer length and structure. Figure 2.3b illustrates... 

Generally, alkoxides are problematic nucleophiles because of their basic character. In metal-catalyzed allylic substitutions, superior results were obtained with Zn-alkoxides (achiral Ir-catalysts) [66] and Cu-alkoxides (achiral Rh-catalyst with chiral substrates) [67]. Shu and Hartwig developed aUyUc substitutions with alkoxides using Ir/phosphoramidite catalysts [68] these authors used catalysts obtained from [Ir(COD)Cl]2 and LI or L3 without explicit base activation [procedure (a) in Section 9.2.4.2) (Scheme 9.34). 

The mechanism of the thermal ROP of (Cl2PN)3 has been proposed to involve a cationic mechanism (see Scheme 8.2 in Section 8.1.2.2). The unique reaction sequence involving ROP followed by nucleophilic substitution with oxygen- or nitrogen-based nucleophiles (generally alkoxides, aryloxides or primary amines) permits a diverse range of polyorganophosphazenes to be... 

Williamson ether synthesis preparation of ether The sodium or potassium alkoxides are strong bases and nucleophiles. Alkoxides (RO ) can react with primary alkyl halides to produce symmetrical or unsymmetrical ethers. This is known as Williamson ether synthesis. The reaction is limited to primary alkyl halides. Higher alkyl halides tend to react via elimination. For example, sodium ethoxide reacts with ethyl iodide to produce diethyl... 

Compounds with a high HOMO and LUMO (Figure 5.5c) tend to be stable to selfreaction but are chemically reactive as Lewis bases and nucleophiles. The higher the HOMO, the more reactive. Carbanions, with HOMO near a, are the most powerful bases and nucleophiles, followed by amides and alkoxides. The neutral nitrogen (amines, heteroaromatics) and oxygen bases (water, alcohols, ethers, and carbonyls) will only react with relatively strong Lewis acids. Extensive tabulations of gas-phase basicities or proton affinities (i.e., —AG° of protonation) exist [109, 110]. These will be discussed in subsequent chapters. 

Commonly used metal salts and palladium precursors include Pd(OAc)2, Pd (acac)2 (acac = acetylacetonato) and Pd2(dba)3 or Pd(dba)2 (dba = dibenzylide-neacetone). If a Pd(II) salt is used as pre-catalyst, reduction by base or by excess phosphine ligand is required. The exact nature of the reducing agent is somewhat contended, but it is often assumed that the phosphine takes up this role, for which evidence has been reported [26]. A typical catalytic system consists of a palladium source and an aryl- or alkylphosphine (typically PPh3), in at least 2 eq., as ligand. The addition of bases, typically amines and alkoxides, is often found to be beneficial for activity, which is also reflected in the patent literature [27-29]. The bases are thought to facilitate in the attack of the nucleophile in the rate-determining step and, in the case of the amines, in the reduction of Pd(II) to Pd(0). 

Typical bases such as sodium hydroxide or an alkoxide ion cannot be used to form enolates for alkylation because at equilibrium a large quantity of the hydroxide or alkoxide base is still present. These strongly nucleophilic bases give side reactions with the alkyl halide or tosylate. Problem 22-4 shows an example of these side reactions. Lithium diisopropylamide (LDA) avoids these side reactions. Because it is a much stronger base, LDA converts the ketone entirely to its enolate. All the LDA is consumed in forming the enolate, leaving the enolate to react without interference from the LDA. Also, LDA is a very bulky base and thus a poor nucleophile, so it generally does not react with the alkyl halide or tosylate. 

In most of this chapter, we used enolates as our nucleophiles and worked under equilibrating conditions with alkoxide bases. There was alkoxide base present throughout the reaction, so the enolate didn t get used up deprotonating the product or, if it did, it could be re-deprotonated by the... 

While the major use for palladium catalysis is to make carbon-carbon bonds, which are difficult to make using conventional reactions, the success of this approach has recently led to its application to forming carbon-heteroatom bonds as well. The Overall result is a nucleophilic substitution at a vinylic or aromatic centre, which would not normally be possible. A range of aromatic amines can be prepared direcdy from the corresponding bromides, iodides, or triflates and the required amine in the presence of palladium(O) and a strong alkoxide base. Similarly, lithium thiolates couple with vinylic triflates to give vinyl sulfides provided lithium chloride is present. 

AUyhc carbonates also undergo oxidative addition, cleavage of the allyl bond, and loss of CO2 can occur to give a species formulated as the allyl Pd-alkoxide (equation 48). In the presence of a snitably acidic carbon acid (pATalS or lower), the carbanion is generated and nucleophile addition can occur. The overall process requires only a catalytic amount of Pd no base or other stoichiometric reagents is necessary. ... 

Controlled addition of a suitable proton donor or electrophile (reductions) or nucleophile (oxidations) is often useful in determining a reaction mechanism. The strength of a proton donor may vary from perchloric acid through acetic acid and a phenol to an alcohol C acids, such as malonic ester, or N acids, such as urea, may also be used. Used as bases may be pyridine, carboxylate ions, alkoxides, or salts of malonic ester. Sometimes it is of interest to determine whether it is the basic or the nucleophilic properties of the compound that are important. The use of two bases with approximately the same pK values but widely differing in nucleophilicity, such as pyridine and a 2,6-dialkylpyridine, might answer the question. 

The aim of this section is to show how cyclic precursors can serve as an appropriate starting material for the construction of open-chained or monocyclic intermediates with defined regio- and/or stereo-specifity. The nucleofuge usually is halide or sulfonate and the electrofuge an alkoxide, generated from an alcohol by base or from a keto group by attack of a nucleophile. 

In the first step the base (usually an alkoxide, LDA, or NaH) deprotonates the a-proton of the ester to generate an ester enolate that will serve as the nucleophile in the reaction. Next, the enolate attacks the carbonyl group of the other ester (or acyl halide or anhydride) to form a tetrahedral intermediate, which breaks down in the third step by ejecting a leaving group (alkoxide or halide). Since it is adjacent to two carbonyls, the a-proton in the product p-keto ester is more acidic than in the precursor ester. Linder the basic reaction conditions this proton is removed to give rise to a resonance stabilized anion, which is much less reactive than the ester enolate generated in the first step. Therefore, the p-keto ester product does not react further. 

The chemistry involved in the formation of mesoporous silica thin films is qualitatively well understood. However, specific reaction mechanisms of the individual steps are still debated. In addition, owing to the complexity of the sol-gel reaction pathways and cooperative self-assembly, full kinetic models have not been developed. From the time of mixing, hydrolysis reactions, condensation reactions, protonation and deprotonation, dynamic exchange with solution nucleophiles, complexation with solution ions and surfactants, and self-assembly, all occur in parallel and are discussed here. Although the sol-gel reactions involved may be acid or base catalyzed, mesoporous silica film formation is carried out under acidic conditions, as silica species are metastable and the relative rates of hydrolysis and condensation reactions lead to interconnected structures as opposed to the stable sols produced at higher pH. Silicon alkoxides are the primary silica source (tetramethyl orthosilicate, tetraethyl orthosilicate, tetrapropyl orthosilicate, etc.) and are abbreviated TMOS, TEOS, and TPOS, respectively. Starting from the alkoxide, Si(OR)4, in ROH and H2O solution, some of the general reactions are ... 

FIGURE 8.11 When a Lewis base reacts with an alkyl halide, either substitution or elimination can occur. Substitution (Sn2) occurs when the nucleophile attacks carbon to displace bromide. Elimination occurs when the Lewis base abstracts a proton from the p carbon. The alkyl halide shown is isopropyl bromide. The carbon atom that bears the leaving group is somewhat sterically hindered, and elimination (E2) predominates over substitution with alkoxide bases. 

The release and obtention of esters by transesterification is another classical procedure to detach esterified compounds using, in this case, an alcohol or an alkoxide as the nucleophile. Care must be taken that water is excluded otherwise the acid will be obtain as a by-product [4]. Typical cleavage conditions involved the use of the desired alcohol in the presence of a non-nucleophilic base such as a tertiary amine (if primary or secondary amines are used, there is the risk of obtaining also the amide) [12] or the alkoxide dissolved in the corresponding alcohol or... 

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