Hydrides metal hydride reagents

Metal Amalgams and Hydrides. Metal hydrides and amalgams are sometimes the preferred method of reducing various functional groups in the laboratory, especially when the necessary equipment for catalytic hydrogenations is unavailable. However, these reagents are usually too expensive to make their use on a large commercial scale feasible. 

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 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... 

Although of relatively weak acidity, amines will react with either carbanionic metal alkyls or hydridic metal hydrides to form amides with the elimination of alkane or hydrogen, respectively. The easiest and most exploited method for the synthesis of lithium and magnesium amides is to treat lithium alkyls or Grignard reagents (normally commercially available) with the corresponding amine (equations 25,47 264 and 2749). 

The reagents used in this procedure were obtained from the following sources lithium aluminum hydride, Alfa Inorganics, Inc. thionyl chloride, Matheson Coleman and Bell sodium hydride, Metal Hydrides, Inc. The nitrogen was prepurified. 

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. 

Co I Mechanism 20.4 Reduction of RCOCI and RCOOR with a Metal Hydride Reagent... 

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