Aldehydes bimolecular reduction

Addition of a masked Grignard reagent to an aldehyde or ketone From aromatic aldehydes and carbanions Bimolecular reduction of aldehydes or ketones... 

Symmetrical 1,2-glycols, known as pinacols, are prepared by bimolecular reduction of aldehydes or ketones. 

Bimolecular Reduction of Aldehydes and Ketones to 1,2-Diols 21O-Hydrogen-coupling... 

Bimolecular Reduction of Aldehydes or Ketones to Alkenes De-oxygen-coupling... 

Thiophenecarbaldehydes add smoothly to a,f3-unsaturated ketones and nitriles under cyanide ion catalysis to form y-diketones (366) and y-ketonitriles (367) respectively (76CB534). The 2,5-dicarbaldehyde gives the bis-adduct (368). The aldehydes undergo normal reduction to the hydroxymethylthiophenes by sodium borohydride. However, electrochemical reduction of the 2,5-dialdehyde on a mercury electrode at pH 1-3 gives the bimolecular reduction product (369) as a mixture of meso- and ( )-forms in the ratio 7 3. Reduction with zinc and acetic acid gives only the meso -form of (369) (75CR(C)(280)165>. 

This one-pot procedure for titanium-induced reactions is also applicable to the synthesis of crowded products 5 to completely chemo- and regioselective "zipper-type" polycyclizations,7 to bimolecular reductions of alkynes,5 and to conventional McMurry reactions of aldehydes or ketones.5 Some representative examples are compiled in the Table. 

Indium chloride is known to have little water sensitivity and this has led to the discovery of a novel multicomponent synthesis of monocyclic 1,4-diazepines from aldehyde, amine, and a,p-xmsaturated ketone [89]. The initial step was the bimolecular reductive coupling of the aldimine formed in situ leading to the formation of N, N -diphenyl-l,2-diaryl-l,2-diamino ethane, which underwent aza-Michael addition to the a,p-xmsaturated ketone. The product 129 (Scheme 26) was isolated by simple recrystallization and obtained in very good yield witir excellent diastereose-lectivity favoring the trans-isomer. In the dimerization of tire radical Zn anion of aldimine, the repulsion of the lone pair on nitrogen and steric hindrance between the aryl groups seemed to have contributed toward frans-selectivity. 

The reaction rate of Co3+ with benzaldehyde was measured in independent experiments from the consumption of Co3+ in the absence of oxygen. The rate constant of this bimolecular reaction was found to coincide with k. Thus, in this process the limiting step of initiation is the reduction of Co3+ by aldehydes, and the complete cycle of initiation reactions includes the reactions [50,51] ... 

The reduction is bimolecular and thus the rate is dependent on concentration. Running the reaction neat provides the fastest rates. Usually an excess of Alpine-Borane is used to insure that the reaction does not become excessively slow at the end of the reduction. The excess organoborane may be destroyed by addition of an aldehyde such as Acetaldehyde. The resulting alkoxy-9-BBN may be treated with Ethanolamine to liberate the alcohol and precipitate the majority of the 9-BBN. Any remaining borane impurities may be removed by oxidation with basic Hydrogen Peroxide. 

Kinetic studies of the Midland reduction confirmed that the reduction of aldehydes is a bimolecular process and the changes in ketone structure have a marked influence on the rate of the reaction (e.g., the presence of an EWG in the para position of aryl ketones increases the rate compared to an EDG in the same position). However, when the carbonyl compound is sterically hindered, the rate becomes independent of the ketone concentration and the structure of the substrate. The mechanism with sterically unhindered substrates involves a cyclic boatlike transition structure (similar to what occurs in the Meerwein-Ponndorf-Verley reduction). The favored transition structure has the larger substituent (Rl) in the equatorial position, and this model correctly predicts the absolute stereochemistry of the product. 

The reactions may be run on a large scale but is advisable to cool the reaction to 0 "C or 25 "C since the reduction may become exothermic. Usually an excess of organoborane is used since the bimolecular process becomes very slow towards the end of the reduction. Excess organoborane is destroyed by the addition of a low-boiling aldehyde such as acetaldehyde. This helps prevent contamination of the desired product with isopinocampheol. The borane component may be removed by precipitation as an ethanolamine complex or by an oxidative workup using hydrogen peroxide and base. Alternatively, these two steps may be combined, with the majority of the borane removed with ethanolamine and any remaining boron components removed by oxidation. 

The Clemmensen reduction of aldehydes and ketones to methyl or methylene groups takes place by heating with zinc and hydrochloric acid. A non-miscible solvent can be used and serves to keep the concentration in the aqueous phase low, and thus prevent bimolecular condensations at the metal surface. The choice of acid is confined to the hydrogen halides, which appear to be the only strong acids whose anions are not reduced with zinc amalgam. The Clemmensen reduction employs rather vigorous conditions and is not suitable for the reduction of polyfunctional molecules, such as 1,3- or 1,4-diketones, or of sensitive compounds. However, it is effective for simple compounds that are stable to acid (7.38). A modification under milder conditions uses zinc dust and HCl dissolved in diethyl ether (ethereal HCl). Other methods for converting C=0 to CH2 are described in Schemes 7.87 and 7.105. 

The synthesis of the non-symmetric ligands is based on the Bimolecular Aromatic Mannich reaction. Non-symmetric ligands can be obtained via two different routes. The first route comprises a sequential Mannich reaction on a phenol using two different secondary amines. An alternative route is a Mannich reaction using a secondary amine and a substituted salicylaldehyde followed by either condensation of the aldehyde functionality with a primary amine and subsequent reduction or reductive amination with a secondary amine. 

The mechanism of Gutknecht pyrazine synthesis has been studied and is well understood. Reduction of the a-oximino ketone affords an a-amino ketone. If the reduction is carried out under acidic conditions, the a-amino ketone may be isolated as an acid salt. These acid addition salts are entirely stable. In these salts the ketone carbonyl may be hydrated, and this is particularly true for a-amino aldehydes. However, as soon as the free base of the amine is generated, either from the salt or during reduction of the oxime if this is carried out under neutral or basic conditions, rapid bimolecular imine formation occurs, which is then followed by rapid intramolecular formation of a second imine to afford a dihydropyrazine. Oxidation to the pyrazine may occur spontaneously upon exposure to air, particularly in the presence of transition metals, and it is this facile aerobic oxidation that doubtless accounts for the isolation of pyrazines by early workers in the field. 

Similar to the reduction of aldehydes, reduction of ketones with Alpine-Borane also involves two competing reaction pathways, a bimolecular -hydride elimination process (cyclic mechanism) affording optically active product [6], and a dehydroboration-reduction sequence yielding racemic product [2] (Scheme 26.1). 

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