Elimination alkoxides

The reaction of acceptor-substituted carbene complexes with alcohols to yield ethers is a valuable alternative to other etherification reactions [1152,1209-1211], This reaction generally proceeds faster than cyclopropanation [1176], As in other transformations with electrophilic carbene complexes, the reaction conditions are mild and well-suited to base- or acid-sensitive substrates [1212], As an illustrative example, Experimental Procedure 4.2.4 describes the carbene-mediated etherification of a serine derivative. This type of substrate is very difficult to etherify under basic conditions (e.g. NaH, alkyl halide [1213]), because of an intramolecular hydrogen-bond between the nitrogen-bound hydrogen and the hydroxy group. Further, upon treatment with bases serine ethers readily eliminate alkoxide to give acrylates. With the aid of electrophilic carbene complexes, however, acceptable yields of 0-alkylated serine derivatives can be obtained. 

A six-step synthesis of nonactic acid with excellent stereocontrol via sultone intermediates has been published (Scheme 26) <1998EJO2073>. The tricyclic sultone 107 was synthesized by a tandem esterification/cycloaddition with vinylsulfonyl chloride whereby only the fvo-adduct with fvo-Me was obtained <1989AGE202>. Next, the tandem elimination/alkoxide-directed 1,6-addition first led to a mixture of sulfones, but equilibration with catalytic... 

Sulfonates with a sulfur-bound C,H group can also eliminate alkoxide when treated with a strong base [82]. Phenylmethanesulfonic esters, for instance, are sufficiently base-labile to be useful protective groups for alcohols (Scheme 4.17). 

The radicals then couple, and the coupling product eliminates alkoxide ions (RO ) to yield a diketone, as shown below ... 

If a DIBALH reduction of an ester is carried out at room temperature, the ester is reduced to a primary alcohol. At low temperature, the tetrahedral carbonyl addition intermediate does not eliminate alkoxide ion, and the more reactive aldehyde is not formed until after workup, when the hydride ion has been destroyed. Thus, temperature control is critical for the selective reduction of an ester to an aldehyde. 

Like alkyls, L M-NR2 and L M-OR can (3 eliminate (Eq. 3.27) to form a ketone, aldehyde, or imine. Alcohols can therefore act as reducing agents for metal complexes, especially in the presence of a base that converts the coordinated alcohol to the alkoxide, which can then P-eliminate. Alkoxides such as MOt-Bu are stable, however, because they lack (3 hydrogens. Amide, alkoxo, and fluoro complexes of the late metals are best known, either in high oxidation states, such as in K2lrFe, where the d electrons are contracted, or in cases such as 3.32, where the 16e metal has one empty d, orbital to accept heteroatom lone-pair electrons. 

The elimination of 3-hydrogen of Pd alkoxide (17) to afford a carbonyl compound is a similar reaction. 

The slow oxidation of primary alcohols, particularly MeOH, is utilized for the oxidation of allylic or secondary alcohols with allyl methyl carbonate without forming carbonates of the alcohols to be oxidized. Allyl methyl carbonate (564) forms 7r-allylpalladium methoxide, then exchange of the methoxide with a secondary or allylic alcohol 563 present in the reaction medium takes place to form the 7r-allylpalladium alkoxide 565, which undergoes elimination of j3-hydrogen to give the ketone or aldehyde 566. The lactol 567 was oxidized selectively with diallyl carbonate to the lactone 568 without attacking the secondary alcohol in the synthesis of echinosporin[360]. 

Secondary and tertiary alkyl halides are not suitable because they react with alkox ide bases by E2 elimination rather than by 8 2 substitution Whether the alkoxide base IS primary secondary or tertiary is much less important than the nature of the alkyl halide Thus benzyl isopropyl ether is prepared m high yield from benzyl chloride a pri mary chloride that is incapable of undergoing elimination and sodium isopropoxide... 

The Williamson ether synthesis (Sec tion 16 6) An alkoxide ion displaces a halide or similar leaving group in an Sn2 reaction The alkyl halide cannot be one that is prone to elimination and so this reaction is limited to methyl and primary alkyl halides There is no limitation on the alkoxide ion that can be used... 

A cis-elimination mechanism has been postulated for this decomposition which foUows first-order kinetics (120). The rate is accelerated by addition of lithium j iZ-butoxide [4111-46-0] and other bases, and by an increase in temperature (120). Pyrolysis of j iZ-butyUithium in the presence of added alkoxide is one-half order in alkyUithium and first order in alkoxide (120). Thermal decomposition of j iZ-butyUithium at 0.18% alkoxide at 25, 40, 50, and 60°C is 0.1%, 0.6%, 2.0%, and 6.8%/d, respectively (121). 

Enols and alkoxides give chelates with elimination of alcohol. For example, in the reaction of the enol form of acetylacetone [123-54-6] all four alkoxide groups attached to zirconium can be replaced, but only two of the four attached to titanium (Fig. 3). Acetoacetic esters react similarly. 

Solvent for Base-Catalyzed Reactions. The abihty of hydroxide or alkoxide ions to remove protons is enhanced by DMSO instead of water or alcohols (91). The equiUbrium change is also accompanied by a rate increase of 10 or more (92). Thus, reactions in which proton removal is rate-determining are favorably accompHshed in DMSO. These include olefin isomerizations, elimination reactions to produce olefins, racemizations, and H—D exchange reactions. 

Besides direct hydrolysis, heterometaHic oxoalkoxides may be produced by ester elimination from a mixture of a metal alkoxide and the acetate of another metal. In addition to their use in the preparation of ceramic materials, bimetallic oxoalkoxides having the general formula (RO) MOM OM(OR) where M is Ti or Al, is a bivalent metal (such as Mn, Co, Ni, and Zn), is 3 or 4, and R is Pr or Bu, are being evaluated as catalysts for polymerization of heterocychc monomers, such as lactones, oxiranes, and epoxides. An excellent review of metal oxoalkoxides has been pubUshed (571). 

The 3-substituents in 3-nitro- and 3-phenylsulfonyl-2-isoxazolines were displaced by a variety of nucleophiles including thiolate, cyanide and azide ions, ammonia, hydride ions and alkoxides. The reaction is pictured as an addition-elimination sequence (Scheme 54) (72MI41605, 79JA1319, 78JOC2020). 

These reactions proceed by alkoxide or fluoride attack at silicon which results in C—Si bond cleavage and elimination of the leaving group from the fi carbon. These reactions are stereospecific anti eliminations. 

The pH of the solution is of overwhelming importance in determining the course of these hydrolyses. In basic solution, oxygen elimination is dominant. This is because the unprotonated nitrogen substituent is a very poor leaving group and is also more effective at facilitating the alkoxide elimination by electron donation ... 

In acidic solution, the nitrogen is protonated and becomes a better leaving group and also loses its ability to assist in the elimination of the alkoxide. Under these circumstances, nitrogen eUmination is favored ... 

Nucleophilic participation is important only for esters of alcohols that have pK <13. Specifically, phenyl and trifluoroethyl esters show nucleophilic catalysis, but methyl and 2-chloroethyl esters do not. This result reflects the fete of the tetrahedral intermediate that results fi om nucleophilic participation. For relatively acidic alcohols, the alkoxide group can be eliminated, leading to hydrolysis via nucleophilic catalysis ... 

Because of thetr electron deficient nature, fluoroolefms are often nucleophihcally attacked by alcohols and alkoxides Ethers are commonly produced by these addition and addition-elimination reactions The wide availability of alcohols and fliioroolefins has established the generality of the nucleophilic addition reactions The mechanism of the addition reaction is generally believed to proceed by attack at a vinylic carbon to produce an intermediate fluorocarbanion as the rate-determining slow step The intermediate carbanion may react with a proton source to yield the saturated addition product Alternatively, the intermediate carbanion may, by elimination of P-halogen, lead to an unsaturated ether, often an enol or vinylic ether These addition and addition-elimination reactions have been previously reviewed [1, 2] The intermediate carbanions resulting from nucleophilic attack on fluoroolefins have also been trapped in situ with carbon dioxide, carbonates, and esters of fluorinated acids [3, 4, 5] (equations 1 and 2)... 

The nucleophilic reaction of bromotrifluoroethene with alkoxides yields not only the expected addition and addition-elimination products but also a product from a bromophilic reaction of the carbanion intermediate [6] (equation 3) Similar are the reactions of sodium phenoxide with perfluorovinyl ethers in the presence of hexachloroethane or selected vicinal dibromoperfluoroalkanes The intermediate carbanion is trapped in high yield by these sources of Cl or Br, which suggests a... 

Rase-catalyzed reaction of alcohol favors addition, whereas increasing amounts of alkoxide favor addition-elimination reactions. Perfluoro-2-methyl-2-pentene and methanol form the saturated ether, whereas two equivalents of sodium methoxide form the vinylic ether [S] (equation 4). 

The nucleophilic attack of nitrogen bases leads to a variety of products as the result of addition or addition-elimination reactions The regioselectivity resembles that of attack by alcohols and alkoxides an intermediate carbanion is believed to be involved In the absence of protic reagents, the fluorocarbanion generated by the addition of sodium azide to polyfluonnated olefins can be captured by carbon dioxide or esters of fluonnated acids [J 2, 3] (equation I)... 

The reaction between an alkoxide ion and an aryl halide can be used to prepare alkyl aryl ethers only when the ar yl halide is one that reacts rapidly by the addition-elimination mechanism of nucleophilic aromatic substitution (Section 23.6). 

Together with a shift of the proton from the a-carbon to the alkoxide oxygen, the tertiary amine is eliminated from the addition product to yield the unsaturated product 3. Early examples of the Baylis-Hillman reaction posed the problem of low conversions and slow reaction kinetics, which could not be improved with the use of simple tertiary amines. The search for catalytically active substances led to more properly adjusted, often highly specific compounds, with shorter reaction times." Suitable catalysts are, for example, the nucleophilic, sterically less hindered bases diazabicyclo[2.2.2]octane (DABCO) 6, quinuclidin-3-one 7 and quinuclidin-3-ol (3-QDL) 8. The latter compound can stabilize the zwitterionic intermediate through hydrogen bonding. ... 

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