Hydride-Transfer Reagents

The mechanism by which all the group III complex hydrides effect reduction is believed to be quite similar. It involves hydride transfer accompanied by coordination with the metalloid atoms. Since, in general, each of the hydrogens can eventually 

LiAIH4 alcohol alcohol alcohol alcohol alcohol amine 

LiAKt-BuOljH aldehyde alcohol alcohol very slow aldehyde 

Hydride reductions of carboxylic acid derivatives such as conversion of esters to alcohols involve elimination steps in addition to hydride transfer. In the case of 

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The heterocyclic derivative successfully protects the acid from attack by Grignard or hydride-transfer reagents. The carboxylic acid group can be regenerated by acidic hydrolysis or converted to an ester by acid-catalyzed reaction with the appropriate alcohol. 

Several factors affect the reactivity of the boron and aluminum hydrides, including the metal cation present and the ligands, in addition to hydride, in the complex hydride. Some of these effects can be illustrated by considering the reactivity of ketones and aldehydes toward various hydride transfer reagents. Comparison of LiAlH4 and NaAlH4 has shown the former to be more reactive,63 which is attributed to the greater... 

Thiourea dioxide (TUDO, HN=C(NH2)S(0)0H)/Na0ff 23.23 Hydride transfer reagents... 

Pyridine is difficult to reduce (as is benzene ), but pyridinium salts, e.g. alkylpyridinium halides, are partly reduced by hydride transfer reagents such as lithium aluminium hydride (LiAlH ) and sodium borohydride (NaBH4). LiAlH, which must be used in anhydrous conditions, only gives the 1,2-dihydro derivative, but the less vigorous reductant NaBH in aqueous ethanol yields the 1,2,5,6-tetrahydro derivative (Scheme 2.30)1... 

Chemical ionization (CI) uses a reagent ion to react with the analyte molecules to form ions by either a proton or hydride transfer. Reagent ions are produced by introducing a large excess of gas, such as methane, into an El ion source. Electron collisions produce CH/ and CH,, which further react with methane to form CHs and C2H5. ... 

In an attempt to develop similar hydride transfer reagents using less active hydrides, Labinger and co-workers (88c) reacted a Nb hydride with Fe(CO)5 to give (17c), but no subsequent reduction chemistry was observed. 

This section covers the reduction of aldehydes and ketones, in complex molecules using hydride transfer reagents. Many of these are complex reagents designed specifically for particular reactions. LAH has been used for the reduction of cyclopropyl ketones199. Trialkyltin moieties in the cyclopropane ring cause diastereoselective reduction to occur (equation 51). 

Hyperforin is not reduced by sodium borohydride. Reduction with hydride-transfer reagents such as lithium aluminium hydride (LAH), RED-AL, and DIBAL-H, gave varied products in good yields. Its two dicarbonyl systems are amenable to reduction or deoxygenation upon treatment with alane reducing agents and pave the way to new and interesting modifications of the natural product.301... 

The reduction of nitriles by the nucleophilic attack of hydride transfer reagents has also been widely investigated and is a process with considerable synthetic potential. The reduction yields amine complexes, and rates are typically about ten thousand times faster than for reduction of the free ligand (Fig. 4-19). Once again, the principal effect appears to be associated with the build-up of positive charge on the ligand. 

Primary and secondary alkyl bromides, iodides, and sulfonates can be reduced to the corresponding alkanes with LiBHEt3 (superhydride) or with lithium aluminum hydride (LiAlH4, other names lithium tetrahydridoaluminate or lithium alanate). If such a reaction occurs at a stereocenter, the reaction proceeds with substantial or often even complete stereoselectivity via backside attack by the hydride transfer reagent. The reduction of alkyl chlorides to alkanes is much easier with superhydride than with LiAlH4. The same is true for sterically hindered halides and sulfonates ... 

Interestingly, the reduction shown in Figure 17.53 is highly diastereoselective. Only the tranr-configured cyclohexanol is formed, that is, the equatorial alcohol. Such a level of diastereoselectivity cannot he achieved with hydride transfer reagents (cf. Figure 10.11). 

The nucleophilic addition of a hydride to the exocyclic double bond of fulvenes, using LiBEt3H as the hydride transfer reagent, resulted in the formation of the appropriately substituted lithium cyclopentadienide intermediates, which is insoluble under the reaction conditions chosen and can be isolated for purification purposes. Two equivalents of the substituted lithium cyclopentadienide undergo a transmetallation reaction when reacted with 1 mol equivalent of titanium tetrachloride in THF under reflux to give the appropriate non-bridged substituted titanocene dichloride in overall yields of up to 77% as seen in Scheme 2. 

Hydride addition to [CpMoL2(PhC=CPh)]+ [L = P(OMe)3] at -78°C in THF with either Na[BH4] or, preferably for solubility purposes, K[HBBu3] as the hydride transfer reagent produces CpMoLj-(r]2-CPhCHPh) (172). An analogous reaction occurs with Me2SiCsCH as the alkyne ligand [Eq. (50)] (173). These colorful reactions convert the... 

Entries nos. 1 and 2 deal with a very common type of oxidant in organic chemistry, the so-called high-potential quinones (for a review, see Becker, 1974) which are normally considered to act as hydride-transfer reagents. Entry no. 1 is, however, unique in the sense that all substrates contain aromatic C—H bonds only, the strength of which precludes the operation of a hydride-transfer mechanism. Consequently, we see almost ideal electron-transfer behaviour, provided that E° (DDQH+/DDQH ) in TFA is set equal to 0.87 V. This value is entirely in line with those reported for other media (Becker, 1974). As we go to entry no. 2, where the substrate is difficult to oxidize and has at least one weak C—H bond, electron transfer is not feasible and hydride transfer takes place. The same holds for DDQ oxidation of substituted toluenes (Eberson et al., 1979). 

In this synthesis, the reactant was chosen to control stereochemistry and give an equatorial alcohol, due to an intermediate axial radical use of hydride-transfer reagents would tend to afford predominantly the axial alcohol. 

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