Reduction using hydrides

Exceptions happen in the cases of sterically crowded substrates (R1 = i-Pr, c-C3H5)732,738 in which the hydride attack is assumed to be at hydrogen739. 

In the case of phosphonium salts substituted by an heteroaryl group, the furfuryl group is easily cleaved744 2,4-pyridindiyl bis(phosphonium) salts have been used as source of 2-pyridylphosphonio compounds745 (reaction 221). Clearly, the presence of 

Finally, heterophosphonium salts are reduced with cleavage of the phosphorus-heteroatom bond optically active aminophosphonium compounds are usefully reduced to phosphines with retention of configuration747. Methyltrineopentoxyphosphonium trifluoromethanesulphonate gave the quantitative formation of dineopentylmethyl phos-phonite, which is indicative of P—O bond cleavage748 (reaction 223) 

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The overall course of reaction depends on the relative rate constants for the various secondary radical processes. Aliphatic ketones are often photoreduced to secondary alcohols (4.121, but although there are interesting features in the stereochemistry of the reduction, the method is not a worthwhile alternative to thermal reduction using hydride reagents, except in cases where the substrate is sensitive to basic conditions. Photoaddition of methanol is promoted in the presence of titaniurnfiv) chloride, both for acyclic and cyclic (4.33) ketones the titanium involvement probably starts in the early steps of the reaction, but the detailed mechanism is not known. Addition may also be a major pathway when cyclohexene is used as hydrogen source (4.341 unlike many other simple alkenes, cydohexene does not readily give oxetanes by photocycloaddition (see p. 126). 

The reduction of (aLkylarnino)haloboranes using hydride reagents can provide a convenient route to (aLkylamino)boranes for example, LiAlH has been utilized to prepare bis (dimethyl amino)borane [23884-11-9] from chi orobis (dimethyl amino)borane [6562-41-0] (68). When this same strategy is appHed to (bis(trimethylsi1y1)amino)ch1oro((trimethylsi1y1)amino)borane [10078-93-0] the expected compound is obtained along with the formation of two... 

A few reductions using typical hydride reducing agents have been reported for azafulvaleiies. Tlius, lithium aluminium hydride reduces A-methyl-... 

The 20e complex Fe(C6Me6)2, easily synthesized in high yield by Na/Hg reduction of the dry di-cationic precursor in THF at 20 °C [28], is also very useful for functionalization. Its reaction with electrophiles RX directly gives functional cyclohexadienyl iron cations, which saves one step with respect to the route using hydride protection/deprotection [47] Scheme V ... 

By an alternative approach, the enantioselective reduction of 1,2-diketimines was achieved by using hydride reagents in the presence of stoichiometric amounts or an excess of enantiopure carboxylic acids. An... 

Soliddiquid phase-transfer catalysed reduction using lithium aluminium hydride... 

There is a rather important difference between chemical reductions using complex metal hydrides and enzymic reductions involving NADH, and this relates to stereospecificity. Thus, chemical reductions of a simple aldehyde or ketone will involve hydride addition from either face of the planar carbonyl group, and if reduction creates a new chiral centre, this will normally lead to a racemic alcohol product. Naturally, the aldehyde primary alcohol conversion does not create a chiral centre. 

Solubilities of the most frequently used hydrides and complex hydrides in most often used solvents are listed in Table 3. In choosing the solvent it is necessary to consider not only the solubility of the reactants but also the boiling points in case the reduction requires heating. 

Several reagents reduce aldehydes preferentially to ketones in mixtures of both. Very high selectivity was found in reductions using dehydrated aluminum oxide soaked with isopropyl alcohol and especially diisopropylcarbinol [755], or silica gel and tributylstamane [756]. The best selectivity was achieved with lithium trialkoxyalumimm hydrides at —78°. In the system hexanal/ cyclohexanone the ratio of primary to secondary alcohol was 87 13 at 0° and 91.5 8.5 at —78° with lithium tris(/er/-butoxy)aluminum hydride [752], and 93.6 6.4 at 0° and 99.6 0.4 at —78° with lithium tris(3-ethyl-3-pentyl-oxy)aluminum hydride [752],... 

A Although it would be possible to convert 3-bromo-4-melhylani-line (7.2) into the corresponding hydrazine, by diazotization and reduction, react it with cyclohexanone, and then subject the product hydrazone to a Fischer indolization, the bromine substituent would still remain in the indole (note two isomers would form). Of course, this substituent could be displaced reductively using tributyltin hydride and a radical initiator [AIBN, azobis(isobuty-ronitrile)], but the overall synthesis is clumsy and non-selective and there should be a simpler route. 

The ylide 140 <2000JOC8068> is stable to attempted reduction using sodium borohydride, diisobutylaluminium hydride (DIBAL-H), or lithium aluminium hydride <2000JOC6388>, but eliminates propene on heating to form the annulated parent 141. Oxidation of the latter with lead(iv) oxide and potassium carbonate forms a radical, 142, which is stable to chromatography and can be stored in air for several days. 

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