Alkoxides, 1,4-addition

As shown in Scheme 1, aliphatic phosphines such as P(n-Bu)3 catalyze the addition of alcohols (2) to methyl propiolate (3) [35]. The mechanism is believed to involve an initial addition of the phosphine to the C = C moiety to give a zwitterionic allenolate (I), which then deprotonates the alcohol, yielding a vinyl phosphonium salt (II). An alkoxide addition to give an enolate (III), followed by phosphine elimination gives the product 4 and regenerates the catalyst. Several experiments suggest that when alcohols are used in excess, the catalyst rests as the original phosphine [34]. 

A number of reagents containing oxide components are used in zeolite manufacture [19]. Silica is provided by addihon of sodium or other alkali silicate solutions, precipitated, colloidal, or fumed silica, or tetraalkylorthosihcate (alkyl = methyl, ethyl) and certain mineral silicates such as clays and kaolin. Alumina is provided as sodium aluminate, aluminum sulfate soluhon, hydrous aluminum oxides such as pseudo boehmite, aluminum nitrate, or aluminum alkoxides. Additional alkali is added as hydroxide or as halide salts, while organic amines and/or... 

Why is no addition product observed in the gas phase, in contrast to solution This is not a case of no endothermic reactions both the proton transfer reaction (6b) and the alkoxide addition reaction (6a) are exothermic pathways. When an exothermic reaction occurs in solution, the excess energy is passed to the solvent. In the gas phase, with no solvent available, the excess energy remains in the intermediate. This can result in an effective internal temperature for that intermediate of hundreds to thousands of degrees. If there is some other bond that can be broken to yield a product ion plus a neutral in a pathway that is exothermic with respect to the reactants, the intermediate will fragment by that method, and the observed product will be that fragment ion. This internal temperature is the reason for the very short lifetime of the intermediates mentioned above. 

The procedure described illustrates a new general synthetic method for the preparation of (E)-3-allyloxyacryl ic acids and their conversion to a-unsubstituted y,5-unsaturated aldehydes by subsequent Claisen rearrangement-decarboxyl at ion. Such aldehydes are traditionally prepared by Claisen rearrangements of allyl vinyl ethers. Allyl vinyl ethers are typically prepared by either mercury-catalyzed vinyl ether exchange with allylic alcohols or acid-catalyzed vinylation of allylic alcohols with acetals. The basic conditions required for alkoxide addition to the betaine to produce carboxyvinyl allyl ethers, as described in this report, nicely complements these two methods. In addition, this Claisen rearrangement is an... 

However, there is only one well-defined example of alkoxide addition. Here the formation of a coordinated alkyl nitrite occurs and the reaction may be reversed by treatment with acid (equation 23). 

The carbonylchloroiridium(III) porphyrins can be transformed into a variety of other carbonyl complexes by chloride exchange with acids or salts (path e). Concentrated sodium hydroxide in ethanol appears to destroy the carbonyl ligand in these compounds (path — d, a) in a manner similar to the alkoxide addition to RhCl(TPP) CO (path f) here, this should give a carboxylic acid RhCOOH(P) which is decarboxylated to a hydride RhH(P) according to the typical base reaction of metal carbonyls. The hydride may then be autoxidized to the hydroxide. 

An intramolecular [2+2] photocycloaddition of allyl ethers with dioxinones followed by a base-induced fragmentation leads to substituted tetrahydropyran-4-ones <1997TL5579>. A one-pot scandium triflate catalyzed diastereoselec-tive cyclization between aldehydes and (3-hydroxy dioxinones 1046 followed by alkoxide addition to the resulting bicycles 1047 leads to 3-carboxy-substituted tetrahydropyran-4-ones 1048 with high levels of diastereoselectivity as a mixture of keto/enol tautomers (Scheme 268, Table 49) <20050L1113>. 

Among the nucleophiles that add exo to coordinated dienes are aUcoxides, amines, azide, acetates, halides, and stabilized carbon enolates, such as malonates and /3-diketones. The alkoxide addition is reversible if the product is treated with HCl. With a few nucleophiles, double addition reactions are observed. Acetate will react with 1,5-cod in the presence of Pb(OAc)4 and palladium salts to give a bicyclic product from addition of two acetate groups, both exo (equation 43). 

An interesting synthesis of silyl enol ethers involves chain extension of an aldehyde. Aldehydes are converted to the silyl enol ether of a ketone upon reaction with lithium (trimethylsilyl)diazomethane and then a drrhodium catalyst. Initial reaction of lithium(trimethylsilyl)diazomethane [LTMSD, prepared in situ by reaction of butyllithium with (trimethylsilyl)diazomethane] to the aldehyde (e.g., 37) gave the alkoxide addition product. Protonation, and then capture by a transition-metal catalyst, and a 1,2-hydride migration gave the silyl enol ether, 38. 

Conventionally hydrolysis of alkoxide is performed by adding alkoxide to excess water under vigorous stirring conditions. It was observed that the uniform rate of alkoxide addition cannot be maintained due to the formation of hydrolysed product at the tip of the outlet during addition. Hence, reverse addition of water... 

Sawamoto et al. reported in 2002 the polymerization of VAc mediated by dicaibonylcyclopentadienyliron dimer [Fe(Cp)(CO)2)]2 using iodide compounds as initiators and Al(0-i-Pr)3 or Ti(0-/-Pr)4 as an additive." However, this catalyst system was found complicated in mechanism. The metal alkoxide additives and the iodide compounds played important roles in the polymerization of VAc. Without the additive or iodide compounds, the polymerization became extremely slow or even no polymerization occurred. Additionally, the iodine-degenerative transfer process could not be excluded in this polymerization because alkyl-iodides alone could mediate degenerative transfer polymerization of VAc, as discussed in the above section.Thus, the mechanism of this polymerization system was proposed as shown in Scheme 6, but it was not verified and unclear. 

The alkoxide addition product obtained from Eq. (6) reacts with the conjugate acid obtained from Eq. (a) to yield an addition product together with the liberation of the free base [to be reutilized in Eq. (a)]. ... 

As with aldehydes, catalytic additions to ketones are more promising with less polar organometallics and some enantioselective catalytic organozinc additions to ketones have been developed [96,97]. For the synthesis of efavirenz (23), stoichiometric amounts of chiral zinc alkoxide additives proved to be highly useful. 

Although it has been proposed that this reaction is initiated by an alkoxide addition to C=N double bond followed by the loss of tosyloxy group to form a nitrene intermediate, which inserts to the of-carbon to form an alkoxy ethylenimine, more experimental evidence indicates that the Neber rearrangement involves an initial base-induced elimination of the more acidic a-proton accompanied by the loss of the tosyloxy group to give azirine... 

Ketones and aldehydes react with nucleophiles to give substituted alkoxides by acyl addition to the carbonyl to give alcohols in a two-step process (1) acyl addition and (2) hydrolysis. Nucleophilic acyl addition involves forming a new bond between the nucleophile and the acyl carbon, breaking the 7r-bond of the carbonyl with transfer of those electrons to the oxygen to give an alkoxide. Addition of an acid catalyst leads to an oxocarbe-nium ion that facilitates acyl addition. 

It is also important to note that several intermediates in this sequence have been isolated and characterized, further bolstering the mechanistic interpretation. Neber isolated an azirine of type which has been conclusively corroborated. In fact, there are many reports which do not hydrolyse the azirine to the aminoketone, but rather isolate these moieties in good yields (vide supra). Intermediates of type 13 have been isolated, after alkoxide addition to the azirine. Furthermore, the azirine was shown to be non-isomerizing under the reaction conditions," allowing predictable application of this reaction. Finally, it was shown that when two ionizable a-centers are present, deprotonation occurs at the most acidic site. ... 

It seems likely that the formal tin alkoxide addition products exist as aggregates in solution. 

Asymmetric hydrosilylation of ketones and ketoimines has been demonstrated in the absence of transition metal catalysts. Using catalytic amounts of chiral-alkoxide Lewis bases such as binaphthol (BINOL), Kagan was able to facilitate the asymmetric reduction of ketones (eq 19). This process is believed to arise from activation of the triethoxysilane by mono-alkoxide addition to give an activated pentavalent intermediate, which can undergo coordination of an aldehyde. This highly ordered hexacoordinate transition state directs reduction in an asymmetric manner, with subsequent catalyst regeneration. Brook was able to facilitate a similar tactic for asymmetric reduction by employing histidine as a bi-dentate Lewis base activator of triethoxysilane. A similar chiral lithium-alkoxide-catalyzed asymmetric reduction of imines was demonstrated by Hosomi with the di-lithio salt of BINOL and trimethoxysilane. ... 

In the above reaction one molecular proportion of sodium ethoxide is employed this is Michael s original method for conducting the reaction, which is reversible and particularly so under these conditions, and in certain circumstances may lead to apparently abnormal results. With smaller amounts of sodium alkoxide (1/5 mol or so the so-called catal3rtic method) or in the presence of secondary amines, the equilibrium is usually more on the side of the adduct, and good yields of adducts are frequently obtained. An example of the Michael addition of the latter type is to be found in the formation of ethyl propane-1 1 3 3 tetracarboxylate (II) from formaldehyde and ethyl malonate in the presence of diethylamine. Ethyl methylene-malonate (I) is formed intermediately by the simple Knoevenagel reaction and this Is followed by the Michael addition. Acid hydrolysis of (II) gives glutaric acid (III). 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

Wylation under neutral conditions. Reactions which proceed under neutral conditions are highly desirable, Allylation with allylic acetates and phosphates is carried out under basic conditions. Almost no reaction of these allylic Compounds takes place in the absence of bases. The useful allylation under neutral conditions is possible with some allylic compounds. Among them, allylic carbonates 218 are the most reactive and their reactions proceed under neutral conditions[13,14,134], In the mechanism shown, the oxidative addition of the allyl carbonates 218 is followed by decarboxylation as an irreversible process to afford the 7r-allylpalladium alkoxide 219. and the generated alkoxide is sufficiently basic to pick up a proton from active methylene compounds, yielding 220. This in situ formation of the alkoxide. which is a... 

The TT-allylpalladium complexes 241 formed from the ally carbonates 240 bearing an anion-stabilizing EWG are converted into the Pd complexes of TMM (trimethylenemethane) as reactive, dipolar intermediates 242 by intramolecular deprotonation with the alkoxide anion, and undergo [3 + 2] cycloaddition to give five-membered ring compounds 244 by Michael addition to an electron-deficient double bond and subsequent intramolecular allylation of the generated carbanion 243. This cycloaddition proceeds under neutral conditions, yielding the functionalized methylenecyclopentanes 244[148], The syn-... 

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