Carbonyl compounds with metal hydride reagents

The reduction of carbonyl compounds with metal hydride reagents can be viewed as nucleophilic addition of hydride to the carbonyl group. Addition of a hydride anion to an aldehyde or ketone produces an alkoxide anion, which on protonation gives the corresponding alcohol. Aldehydes give 1°-alcohols and ketone gives 2°-alcohols. 

Silicon hydrides are an interesting class of carbonyl reducing agents as they are reasonably stable under normal conditions requiring activation with a transition metal complex,fluoride ion or Lewis acid. The correct choice of reaction conditions allows highly chemo- and stereo-selective reduction of particular classes of carbonyl compounds with these convenient reagents. 

FIGURE 16.65 Alcohols can be oxidized to carbonyl compounds. This reaction is the reverse of what you have just learned— the reduction of carbonyl compounds to alcohols through reactions with metal hydride reagents. 

The state of the art of reductions with metal hydrides a decade ago was the subject of comprehensive reviews. A detailed survey of reductions of carbonyl compounds with alkali and alkaline earth metal hydrides, borane and derivatives, alane and derivatives, metal borohydrides, metal aluminohydrides, silanes, stannanes and transition metal hydrides was compiled. The properties, preparation and applications of each reagent were discussed together with methods for their determination, handling techniques... 

Section 8-6 presents two u.seful reduction processes. Carbonyl compounds such as ketones and aldehydes arc useful precursors (starting materials) for the synthesis of alcohols. Either metal-catalyzed Ht addition or reaction with the hydride reagents NaBH and LiAIH converts aldehydes to primary alcohols. The same processes convert ketones to secondary alcohols. The.se hydride reductions are the lirst of many examples that you will. see of nucleophilic additions to the electrophilic carbons of carbonyl groups. This is one of the most important clas.ses of reactions in organic chemistry. 

Nucleophilic addition reactions are mainly of technical interest in the context of further reactions at C=0 groups present in aldehydes or ketones. The electronic nature of a carbonyl group is characterized by the greater electronegativity of the oxygen atom compared to the carbon atom. Thus, the carbon atom is the preferred place of nucleophilic attack, that is, of reaction with an electron-rich reagent. Scheme 2.2.12 gives as an example the technically important cyanohydrin reaction. Other important nucleophilic additions are the reaction of carbonyl compounds with alcohols and water, bisulfite and metal hydrides. 

Nucleophilic Addition—A Two-Step Process 724 Nucleophilic Substitution—A Two-Step Process 725 LiAlH4 Reduction of RCHO and R2C = O 728 Reduction of RCOCl and RCOOR with a Metal Hydride Reagent 735 Reduction of an Amide to an Amine with LiAlH4 737 Nucleophilic Addition of R"MgX to RCHO and R2C = O 743 Reaction of R"MgX or R"Li with RCOCl and RCOOR 751 Carboxylation—Reaction of RMgX with CO2 754 1,2-Addition to an a, 3-Unsaturated Carbonyl Compound 756 1,4-Addition to an a, 3-Unsaturated Carbonyl Compound 756... 

Reagents such as LiAlH4 and KH are not effective for the synthesis of formyl complexes. LiAlH4 does react with many metal carbonyl compounds, but it can transfer more than one and usually effects the formation of metal hydride products (50). Similar results are usually found with NaBH4(50), although some neutral formyl complexes (vide infra) can be obtained under special conditions. KH will also react with some metal carbonyls. However, rates are not very rapid, and any formyl intermediates are likely to decompose faster than they form (51). 

In a bifunctional compound, if a reagent reacts with one functional group preferentially, even though the other is apparently susceptible to the reaction conditions, the reaction is said to be chemoselective. Two illustrative examples are the reduction of a carbonyl group in the presence of a cyano, nitro or alkoxycarbonyl group (Section 5.4.1, p. 519 see also Metal hydrides, Section 4.2.49, p. 445) and the acylation of an aromatic amino group in the presence of a phenolic group (Section 6.9.3, p. 984). 

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