Alcohols from Reduction of Carbonyl Compounds

Aldehydes are easily reduced give primary alcohols, and ketones are reduced to give secondary alcohols. 

Literally dozens of reagents arc used in the laboratory to reduce aldehydes and ketones, depending on the circumstances, but sodium borohydride, NaRLLp is usually chosen because of its safety and ease of handling. Sodium borohydride 

Lithium aluminum hydride, LiAlH4, is another reducing agent often used for reduction of aldehydes and ketones. A grayish powder that is soluble in ether and tetrahydrofuran, LiAlH4 is much more reactive than NaBH4 but also moie dangerous. It reacts violently with water and decomposes explosively when healed above 120 C. 

Weil defer a detailed discussion of the mechanisms of these reductions until Chapter 19. For the moment, weil simply note that they involve the addition of a nucleophilic hydride ion ( H ) to the positively polarized, electrophilic carbon atom of the carbonyl group. The initial product is an alkoxide ion, which is protonated by addition of H30 in a second step to yield the alcohol product. 

In living organisms, aldehyde and ketone reductions arc carried out by either of the coenzymes NADH (reduced nicotinamide adenine dinucleotide) or NADPH (reduced nicotinamide adenine dinucleotide phosphate). Although 

An aldehyde A primary alcohol A ketone A secondary alcohol 

One of the most general methods for preparing alcohols is by reduction of a carbonyl compound. As we saw in Section 10.10, an organic reduction a reaction that adds hydrogen to a molecule  

All kinds of carbonyl compounds can be reduced, including aldehydes, ketones, carboxylic acids, and esters. 

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Alcohols from Reduction of Carbonyl Compounds 609 Problem 17.6 i Predict the products of the following reactions ... 

C=X bonds The stereochemistry of the reduction of carbonyl compounds has been intensely studied with regard to synthetic and mechanistic aspects. The reduction of 1,2-diphenyl-l-propanone at a Hg cathode in aqueous EtOH and pH 8 affords the erythro alcohol as the major diastereomer (erythro threo = 5 to 1.4 1) [332]. This selectivity is in accord with a protonation of the intermediate anion, formed in an ECE sequence, from the least hindered side (Fig. 61). 

Allylic acetates are usually prepared by esterification from allylic alcohols. However, the corresponding alcohols are often only accessible by the fairly expensive hydride reduction of carbonyl compounds. Consequently, direct allylic functionalization of easily available olefins has been intensively investigated. Most of these reactions involve peroxides or a variety of metal salts.However, serious drawbacks of these reactions, (e.g. toxicity of some metals, stoichiometric reaction conditions, or nongenerality) may be responsible for their infrequent use for the construction of allylic alcohols or acetates. 

Reduction of carbonyl compounds with metal hydrides or boranes a. primary alcohols from aldehydes, acids, acid halides, and esters... 

Addition of hydrosilane to alkenes, dienes and alkynes is called hydrosilylation, or hydrosilation, and is a commercially important process for the production of many organosilicon compounds. As related reactions, silylformylation of alkynes is treated in Section 7.1.2, and the reduction of carbonyl compounds to alcohols by hydrosilylation is treated in Section 10.2. Compared with other hydrometallations discussed so far, hydrosilylation is sluggish and proceeds satisfactorily only in the presence of catalysts [214], Chloroplatinic acid is the most active catalyst and the hydrosilylation of alkenes catalysed by E PtCU is operated commercially [215]. Colloidal Pt is said to be an active catalytic species. Even the internal alkenes 558 can be hydrosilylated in the presence of a Pt catalyst with concomitant isomerization of the double bond from an internal to a terminal position to give terminal silylalkanes 559. The oxidative addition of hydrosilane to form R Si—Pt—H 560 is the first step of the hydrosilylation, and insertion of alkenes to the Pt—H bond gives 561, and the alkylsilane 562 is obtained by reductive elimination. 

The reaction differs from the Ritter reaction by the two types of electrophilic activation of the reagents and by the two types of rearrangement of nitrilium 285 and carboxonium ions 288 (equation 94). Besides, this interaction proceeds at an oxidation level of two, while the Ritter reaction occurs at an oxidation level of one17. While it may be shown that A-acyliminium ions 365 can be obtained from a carbonyl compound and a nitrile via the Ritter reaction, then it is only the second step b) in a three-step process where the first step (a) is the reduction of carbonyl compound 364 to alcohol 366 and the third step (c) is an oxidative dehydrogenation of amide 369 obtained3 (equation 105). 

A variety of other electron transfer reagents have been employed in reactions which appear to be mechanistically similar to the more common metal-NH3 or metal-alcohol systems. These include K-graphite, Zn-KOH-DMSO and both Li and AP amalgams. The amalgams from Zn, Mg, Ni, Cu, Sn and Pb have been found not to be effective in the reduction of cyclohexanone in aqueous THF. Also, several low-valent metal cations have been employed in the reduction of carbonyl compounds to alcohols. Among these reagents are low-valence salts of Ti, " Ce and Sm. ... 

C. Alcohols from reduction of o ,)6-unsaturated carbonyl compounds References... 

C. Alcohols From Reduction of a. -Unsaturated Carbonyl Compounds... 

Systematics are also available for the 8 0-values of the compounds in queshon [56[ carboxyl and carbonyl functions in isotopic equilibrium with the surrounding water are, due to equilibrium isotope effects, enriched in 0 relative to this water by 19 and by 25 to 28%o, respectively. From here, the 8 0-values of natural alcohols, mostly descendants of carbonyl compounds, will have (maximally) similar 8 0-values, provided the precursors have attained isotopic equilibrium with water and their reduction has not been faster than their equilibration. Alcohols from addihon of water to C=C double bonds or from exchange of halogen functions by OH groups, typical for synthetic alcohols, will have 8 0-values close to or even below that of the water, due to kinetic isotope effects. The few available results [246, 289, 290] seem to confirm this expectation. The 8 0-values of natural (and also synthetic) esters and lactones can be, especially in the carbonyl group, extremely high (up to 50%o), probably as a consequence of an intramolecular kinetic isotope effect on the activation of the carboxyl function. 

Selective preparation of unsaturated alcohols from corresponding unsaturated carbonyl compounds is a difficult task to achieve with heterogeneous catalysis. Thermodynamically preferred reduction of double C=C bond can be restricted only with difficulties. Industrial relevance of unsaturated alcohols [1,2] in conjunction with economically expensive methods based on chemical reduction of unsaturated carbonyl compounds calls for the development of new catalysts for highly selective preparation of unsaturated alcohols. 

The Meerwein-Ponndorf-Verley reduction of carbonyl compounds and the Oppenauer oxidation of alcohols, together denoted as MPVO reactions, are considered to be highly selective reactions. For instance, C=C double bonds are not attacked. In MPV reductions a secondary alcohol is the reductant whereas in Oppenauer oxidations a ketone is the oxidant. It is generally accepted that MPVO reactions proceed via a complex in which both the carbonyl and the alcohol are coordinated to a Lewis acid metal ion after which a hydride transfer from the alcohol to the carbonyl group occurs (Fig. 1) [1]. Usually, metal ec-alkoxides are used as homogeneous catalysts in reductions and metal t-butoxides in oxidations [1]. 

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