Alcohols proton source

The term Birch reduction was originally applied to the reduction of aromatic compounds by alkali metals and an alcohol in ammonia. In recent years many chemists have used the term to include all metal-ammonia reductions, whether an alcoholic proton source is present or not. The author prefers to use the term Birch reduction to designate any reduction carried out in ammonia with a metal and a proton donor as or more acidic than an alcohol, since Birch customarily used such a proton donor in his extensive pioneering work. The term metal-ammonia reduction is best reserved for reductions in which ammonia is the only proton donor present. This distinction in terminology emphasizes the importance of the acidity of the proton donor in the reduction process. 

In a detailed kinetic study, Flowers showed that the rate of ketone reduction is directly related to the pof the alcohol proton source used in the reaction and that the proton source must be sufficiently acidic to protonate the ketyl radical anion intermediate 3.11 Interestingly, when H20 is used as a proton... 

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)... 

Organolithium compounds are sometimes prepared in hydrocarbon solvents such as pentane and hexane, but nonnally diethyl ether is used. It is especially important that the solvent be anhydrous. Even trace amounts of water or alcohols react with lithium to form insoluble lithium hydroxide or lithium alkoxides that coat the surface of the metal and prevent it from reacting with the alkyl halide. Furthennore, organolithium reagents are strong bases and react rapidly with even weak proton sources to fonn hydrocarbons. We shall discuss this property of organolithium reagents in Section 14.5. 

The mechanism of the oxidation reaction, resulting from treatment of an alcohol with dicyclohexylcarbodiimide and methyl sulfoxide in the presence of a proton source, was elucidated by isotope experiments (24). These confirmed that the reaction proceeded by formation of a... 

As we carefully analyze the first step of this mechanism, we see that the reducing agent (LAH) is simply functioning as a source of H. The mechanism of this first step is the same whether we use LAH or NaBH4. Then, in the second step, a proton source is used to generate the alcohol. 

Homoenolate Protonation The p-protonation of homoenolates has been observed by Scheidt and co-workers, resulting in a redox transformation of enals to afford saturated esters 48. This process is catalysed by the NHC derived from imidazolium salt 46 and utilises phenol as a proton source [14]. A range of primary and secondary alcohols, and phenol itself, are competent nucleophiles with which to trap the acylazolium intermediate 47 generated by protonation (Scheme 12.8). 

Dissolving-Metal Reduction of Aromatic Compounds and Alkynes. Dissolving-metal systems constitute the most general method for partial reduction of aromatic rings. The reaction is called the Birch reduction,214 and the usual reducing medium is lithium or sodium in liquid ammonia. An alcohol is usually added to serve as a proton source. The reaction occurs by two successive electron transfer/proto-nation steps. 

The spirocompounds 34 (M = Ti or Zr) have been prepared . Studies of the thermolysis of pentacoordinate 1,2-oxasiletanides 35, potential intermediates in both the Peterson reaction and the homo-Brook rearrangement of p-hydroxyalkylsilanes with bases, in the presence of a proton source afforded the olefin, RCH=C(CF3)2 and/or the alcohol, (CF3)2CHOH <99CL1139>. 

Trialkyl phosphites readily undergo conjugate addition with a,(3-unsaturated carbonyl compounds in the presence of a proton source, such as a protic solvent.359 The use of a protic solvent, such as an alcohol, obviates the difficulties found in the performance of the simple Abramov-type reaction with a,(3-unsaturated carbonyl compounds.189198 In alcohol medium, an ether is generated as a by-product in the dealkylation process (Equation 3.22). 

An enantioenriched propargylic phosphate was converted to a racemic allene under the foregoing reaction conditions (Eq. 9.152) [124]. It is proposed that the racemization pathway involves equilibration of the allenyl enantiomers via a propargylic intermediate (Scheme 9.37). Both the allenylpalladium precursor and the allenylsamarium reagent could racemize by this pathway. When a chiral alcohol was used as the proton source, the reaction gave rise to enantiomerically enriched allenes (Table 9.61) A samarium alcohol complex is thought to direct the protonolysis (Scheme 9.38). 

At the outset of our studies of the reactivity of I and II, it was necessary to investigate claims that tertiary henzamides were inappropriate substrates for the Birch reduction. It had been reported that reduction of A,A-dimethylbenzamide with sodium in NH3 in the presence of tert-butyl alcohol gave benzaldehyde and a benzaldehyde-ammonia adduct. We formd that the competition between reduction of the amide group and the aromatic ring was strongly dependent on reaction variables, such as the alkali metal (type and quantity), the availability of a proton source more acidic than NH3, and reaction temperature. Reduction with potassium in NH3-THF solution at —78 °C in the presence of 1 equiv. of tert-butyl alcohol gave the cyclohexa-1,4-diene 2 in 92% isolated yield (Scheme 3). At the other extreme, reduction with lithium in NH3-THF at —33 °C in the absence of tert-butyl alcohol gave benzaldehyde and benzyl alcohol as major reaction products. ... 

Dihydroaromatics find diverse applications. The main way to prepare them is through Birch reduction of aromatic compounds (Birch 1944, Wooster and Godfrey 1937, Hueckel and Bretschneider 1939). Aromatic compounds are hydrogenated in diethyl ether or liquid ammonia, with alkali metals as reductants and alcohols as proton sources. 

In the example shown overleaf where hydride attacks the epoxide function, the product is an alcohol, the reaction being completed by supplying a proton source, usually water. 

Reduction of benzenoid hydrocarbons with solvated electrons generated by the solution of an alkali metal in liquid ammonia, the Birch reaction [34], involves homogeneous electron addition to the lowest unoccupied 7t-molecular orbital. Protonation of the radical-anion leads to a radical intermediate, which accepts a further electron. Protonation of the delocalised carbanion then occurs at the point of highest charge density and a non-conjugated cyclohexadiene 6 is formed by reduction of the benzene ring. An alcohol is usually added to the reaction mixture and acts as a proton source. The non-conjugated cyclohexadiene is stable in the presence of... 

In 1991, Inanaga achieved Sml2-mediated intermolecular cross-coupling between C=0 (ketones or aldehydes) and C=N by using 0-benzyl formaldoxime as a C=N component7 The reaction requires HMPA as a co-solvent and a suitable proton source such as /-butyl alcohol or ethylene glycol. A cross-coupling reaction between ketones and... 

Unsaturated hydrocarbons (alkenes, dienes) react with carbon monoxide and a proton source (H20, alcohols, amines, acids) under strong acidic conditions to form carboxylic acids or carboxylic acid derivatives. Since a carbocationic mechanism is operative, not only alkenes but also other compounds that can serve as the carbocation source (alcohols, saturated hydrocarbons) can be carboxylated. Metal catalysts can also effect the carboxylation of alkenes, dienes, alkynes, and alcohols. 

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