Carbonyl compounds addition reactions with alcohols

Cellobiose was prepared first by Skraup and Konig by the saponification of the octaacetate with alcoholic potassium hydroxide, and the method was improved by Pringsheim and Merkatz.3 Aqueous barium hydroxide also has been employed for the purpose, and methyl alcoholic ammonia has been used extensively for the hydrolysis of carbohydrate acetates. The method of catalytic hydrolysis with a small quantity of sodium methylate was introduced by Zemplen,i who considered the action to be due to the addition of the reagent to the ester-carbonyl groups of the sugar acetate and the decomposition of the addition compound by reaction with alcohol. The present procedure, reported by Zemplen, Gerecs, and Hadacsy, is a considerable improvement over the original method (see Note 2). 

These reversible reactions are cataly2ed by bases or acids, such as 2iac chloride and aluminum isopropoxide, or by anion-exchange resias. Ultrasonic vibrations improve the reaction rate and yield. Reaction of aromatic aldehydes or ketones with nitroparaffins yields either the nitro alcohol or the nitro olefin, depending on the catalyst. Conjugated unsaturated aldehydes or ketones and nitroparaffins (Michael addition) yield nitro-substituted carbonyl compounds rather than nitro alcohols. Condensation with keto esters gives the substituted nitro alcohols (37) keto aldehydes react preferentially at the aldehyde function. 

Adogen has been shown to be an excellent phase-transfer catalyst for the per-carbonate oxidation of alcohols to the corresponding carbonyl compounds [1]. Generally, unsaturated alcohols are oxidized more readily than the saturated alcohols. The reaction is more effective when a catalytic amount of potassium dichromate is also added to the reaction mixture [ 1 ] comparable results have been obtained by the addition of catalytic amounts of pyridinium dichromate [2], The course of the corresponding oxidation of a-substituted benzylic alcohols is controlled by the nature of the a-substituent and the organic solvent. In addition to the expected ketones, cleavage of the a-substituent can occur with the formation of benzaldehyde, benzoic acid and benzoate esters. The cleavage products predominate when acetonitrile is used as the solvent [3]. 

Wu et alP have synthesized a TSIL having 2,2,6,6-tetramethylpiper-idine-l-oxyl (TEMPO) appended to an imidazolium cation for the oxidation of alcohols to corresponding carbonyl compounds. These reactions have shown high yields similar to non-supported TEMPO, but with the additional advantage of easy separation of products. 

Zirconium and hafnium dialkylamides are highly reactive compounds. They undergo (i) protolytic substitution reactions with reagents such as alcohols, cyclopentadiene and bisftrimethylsilyOamine 63 64 (ii) insertion reactions with C02, CS2, COS, nitriles, phenyl isocyanate, methyl isothiocyanate, carbodiimides and dimethyl acetylenedicarboxylate 69-72 and (iii) addition reactions with metal carbonyls.73 These reactions are summarized with reference to Zr(NMe2)4 in Scheme 1. 

Grignard and organolithium reagents are strong nucleophiles and strong bases. Besides their additions to carbonyl compounds, they react with other acidic or electrophilic compounds. In some cases, these are useful reactions, but they are often seen as annoying side reactions where a small impurity of water or an alcohol destroys the reagent. 

The mechanisms of reactions of benzylmagnesium halides can be either homolytic or concerted. As with allylic Grignard reagents, also reversible addition reactions with benzylic Grignard reagents and carbonyl compounds have been reported. In general, yields of normal alcohols are low, and such alcohols are obtained in much better yields by use of dibenzylcadmium [66] or benzyllithium [67]. However, in 1980, it was demonstrated that, by far, the best and quickest results for the synthesis of these normal addition reaction products are obtained by applying benzylic halides in the one-step Li-Barbier reaction under ultrasonic irradiation [68,69]. 

House pointed out that 16 can disproportionate (as mentioned above) or that another mechanism may be operative in this reduction.24 Inverse addition of the hydride (a slurry of LiAlH4 is added to the carbonyl compound), short reaction times, and low reaction temperatures generally give moderate to good yields of the conjugate reduction product.24 Good yields of allylic alcohols can often be obtained from a,P-unsaturated aldehydes, however, when the reaction is done at low temperatures with strict control of the stoichiometry. 

Conjugate addition. Trialkylstannyllithium reagents prepared in ether solution undergo predominantly 1,2-addition to cyclohexenones, but solutions prepared in THF undergo conjugate addition to almost all enones, even hindered ones. The intermediate lithium enolates can be alkylated with reactive alkyl halides. These reactions are useful because secondary alkylstannanes are converted into the corresponding carbonyl compound by oxidation with Cr03-2Py. Tertiary alkylstannanes are also oxidized by CrOa-lPy, but mixtures of alcohols and products of dehydration are formed. 

An alternative method for the formation of aldehydes or ketones makes use of the complexes formed from a methyl sulfide with chlorine or A-chlorosuccinimide (NCS), in what is called the Corey-Kim oxidation. With dimethyl sulfide the salt 28 is generated and reacts with the alcohol to give the alkoxysulfonium salts and hence, on treatment with a base, the carbonyl compound. This reaction has fovmd particular application in the oxidation of 1,2-diols in which one alcohol is tertiary, to give a-hydroxy-aldehydes or ketones without rupture of the carbon-carbon bond. For example, the aldehyde 32 is formed in good yield from the diol 31 using dimethyl sulfide and NCS followed by addition of triethylamine (6.29). This transformation is thought to depend on the preferential five-membered transition... 

Mechanistically related to the Mukaiyama aldol reaction, the carbonyl ene reaction is the reaction between an alkene bearing an allylic hydrogen and a carbonyl compound, to afford homoallylic alcohols. This reaction is potentially 100% atom efficient, and should be a valuable alternative to the addition of organometallic species to carbonyl substrates. However, the carbonyl ene reaction is of limited substrate scope and works generally well in an intermolecular manner only with activated substrates, typically 1,1-disubstituted alkenes and electron-deficient aldehydes (glyoxylate esters, fluoral, a,p-unsaturated aldehydes, etc.), in the presence of Lewis acids. The first use of chiral catalyst for asymmetric carbonyl ene was presented by Mikami et al. in 1989. ° By using a catalytic amount of titanium complexes prepared in situ from a 1 1 ratio of (rPrO)2titaniumX2 (X = Cl or Br) and optically pure BINOL, the homoallylic alcohols 70a,b were obtained in... 

The Michael reaction takes place with a wide variety of a, 8-unsaturated carbonyl compounds as well as with o ,j3-unsaturated nitriles and nitro compounds. The most commonly used types of nucleophiles in Michael reactions are summarized in Table 19.1. The bases most commonly used to generate the nucleophile are metal alkoxides, pyridine, and piperidine. It is important to realize that other nucleophiles can undergo similar additions to the beta carbon of unsaturated carbonyl compounds (e.g., amines, alcohols, and water). 

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