Metal hydride reagents

In certain cases, metallic hydride reagents may also reduce double bonds in conjugation with C=0 bonds, as well as reducing the C=0 bonds, for example, ... 

One approach to enantioselective reduction of prochiral carbonyl compounds is to utilize chiral ligand-modified metal hydride reagents. In these reagents, the number of reactive hydride species is minimized in order to get high chemo-selectivity. Enantiofacial differentiation is due to the introduced chiral ligand. 

C. Reduction of Imines with Chiral Metal Hydride Reagents. 112... 

The most useful reagents for reducing aldehydes and ketones are the metal hydride reagents. Complex hydrides are the source of hydride ions, and the two most commonly used reagents are NaBlTj and LiAlH4. Lithium aluminium hydride is extremely reactive with water and must be used in an anhydrous solvent, e.g. dry ether. 

Acid chlorides are easy to reduce than carboxylic acids and other carboxylic acid derivatives. They are reduced conveniently all the way to 1° alcohols by metal hydride reagents (NaBH4 or LiAlH4), as well as by catalytic hydrogenation (H2/Pd—C). 

Use of more efficient solvents (tetrahydrofuran, isopropyl ether, dimethoxyethane) or more soluble metal hydride reagents (sodium borohydride, lithium tributoxy aluminum hydride, sodium bis(2-methoxyethyl) aluminum hydride) favors the alternative reduction pathway to the hydroquinone. 

The main methods of reducing ketones to alcohols are (a) use of complex metal hydrides (b) use of alkali metals in alcohols or liquid ammonia or amines 221 (c) catalytic hydrogenation 14,217 (d) Meerwein-Ponndorf reduction.169,249 The reduction of organic compounds by complex metal hydrides, first reported in 1947,174 is a widely used technique. This chapter reviews first the main metal hydride reagents, their reactivities towards various functional groups and the conditions under which they are used to reduce ketones. The reduction of ketones by hydrides is then discussed under the headings of mechanism and stereochemistry, reduction of unsaturated ketones, and stereochemistry and selectivity of reduction of steroidal ketones. Finally reductions with the mixed hydride reagent of lithium aluminum hydride and aluminum chloride, with diborane and with iridium complexes, are briefly described. 

The milder metal hydride reagents are also used in stereoselective reductions Inclusion complexes of amine-borane reagent with cyclodextrins reduce ketones to optically active alcohols, sometimes in modest enantiomeric excess [59] (equation 48). Diisobutylaluminum hydride modified by zmc broniidc-iV./V.A V -tetra-methylethylenediamine (TMEDA) reduces a,a-difluoro-(3-hydroxy ketones to give predominantly erythro-2,2-difluoro-l,3-diols [60] (equation 49). The threo isomers arc formed on reduction with aluminum isopropoxide... 

Free radicals mentioned in this chapter are not useful for organic synthesis. However, it is important to know the radical character of metal hydride reagents, since metal hydride reagents sometimes behave not only as a polar (ionic) hydride donor species, but also a single electron donor species, depending on the substrates and reaction conditions. 

Treatment of perylene (12) with LiAlH4 at room temperature induces the appearance of deep blue color. This color corresponds to the perylene anion radical formed by the SET from LiAlH4 to LUMO of perylene. ESR measurement indicates that — 80% yield of the perylene anion radical is formed [15]. Properly, formation of the anion radical depends on the kind of metal hydride reagent as shown in eq. 9.6. 

These types of SET reactions are not useful for organic synthesis however, it is important to know about the SET character of metal hydride reagents. 

This reduction is unft -selective in the reduction of a-oxy and a-amino ketones. This contrasts with syn-selectivity for metal hydride reagents and for hydrosilanes in trifluoroacetic acid. 

Numerous other metal hydride reagents have been developed to accomplish a variety of specialized reductions. The only other one that will be discussed here is di-isobutylaluminum hydride, i-Bu2A1H or DIBALH ... 

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. 

Diborane, B2H6, also reduces many carbonyl groups. In contrast to the metal hydride reagents, diborane is a relatively electrophilic reagent, as witnessed by its ability to add to carbon-carbon double bonds. 

Metal hydride reagents act as a source of H because they contain polar metal-hydrogen bonds that place a partial negative charge on hydrogen. 

NADH is a coenzyme, an organic molecule that can function only in the presence of an enzyme. The active site of the enzyme binds both the carbonyl substrate and NADH, keeping them in close proximity. NADH then donates H in much the same way as a metal hydride reagent that is, reduction consists of nucleophilic attack followed by protonation. 

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