Ketones hydride reduction with

In many cases also the reduction agent itself influences the result of the reduction, especially if it is bulky and the environment of the function to be reduced is crowded. A more detailed discussion of stereochemistry of reduction with hydrides is found in the section on ketones (p. 114). 

The domain of hydrides and complex hydrides is reduction of carbonyl functions (in aldehydes, ketones, acids and acid derivatives). With the exception of boranes, which add across carbon-carbon multiple bonds and afford, after hydrolysis, hydrogenated products, isolated carbon-carbon double bonds resist reduction with hydrides and complex hydrides. However, a conjugated double bond may be reduced by some hydrides, as well as a triple bond to the double bond (p. 44). Reductions of other functions vary with the hydride reagents. Examples of applications of hydrides are shown in Procedures 14-24 (pp. 207-210). 

A convenient method for the specific introduction of 2H or 3h (or both) into a molecule is by ketone reduction with labeled metal hydride. Beale and MacMillan (10) have utilized this method for the preparation of GAs labeled at the 1, 2 or 3 positions from GA3 or GA7 (Figure 12). One point of interest is the lithium borohydride reduction of the enone formed by manganese dioxide oxidation of GA3 or GA7. When the reaction is carried out in anhydrous tetrahydrofuran it proceeds in two steps. Initially the lithium enolate is formed which incorporates a proton at carbon-2 from the acid used in the work-up, forming the 3 ketone. This ketone is reduced to the 3 -alcohol by the borohydride which is decomposed more slowly than is the lithium enolate. Thus it is possible to introduce two different labels in a single reaction. 

REDUCTION OF ALDEHYDE AND KETONE ARYLSULFONYLHYDRAZONES WITH HYDRIDE REAGENTS... 

The novel enol sulphonates (331) have been prepared from the 3-oxo-steroids with the appropriate sulphonic anhydride in dimethylformamide. They are stable to aqueous acids and bases, but attacked at sulphur by methoxide ion, regenerating the ketone. Reduction with lithium aluminium hydride afforded mainly the 3)8-alcohol, and no olefin (see p. 400 for rearrangement). 

As with monocyclic ketones, bicyclic ketones show excellent diastereoselectivity upon reduction with hydride reagents. A typical example is the selectivity observed in the reduction of bicyclo[2.2.1]heptan-2-one (315, norbornanone) and 7,7-dimethylbicyclo[2.2.1]heptan-2-one (317). The exo face (path a in 315a) is... 

Sodium cyanoborohydride reduces aldehydes and ketones less rapidly than sodium borohydride, but it reduces iminium ions rapidly. To take advantage of this selectivity, reductive aminations are carried out at mildly acidic pH, where the imines are protonated. Iminium ions are also more reactive than imines toward reduction with hydride. 

A reinvestigation of ketone reduction with lithium aluminum hydride and d-camphor (Portoghese, 1962) refutes an earlier claim (Bothner-By, 1951) that this system produces asymmetric reduction. Addition of 0.2 mole of d-camphor to 0.2 mole of LiAlH and subsequent addition of either 2-butanone or methyl tert-butyl ketone yielded, after hydrolysis, inactive alcohol. Portoghese speculates that A1H4, rather than Al(OR)H3 , may be the primary reducing agent. 

Reduction of aldehydes (RCHO) and ketones (RCOR) with hydride ions (H ) Oxidation levels can be used to leads to alcohols. Primary alcohols (RCH2OH) are formed from reduction of assess if a reaction involves aldehydes, and secondary alcohols (R2CHOH) from reduction of ketones. The reduction (Section 4.5) hydride ion can be derived from a number of reagents. 

Reduction Carbonyl groups in carbohydrates are reduced by the same methods used for aldehydes and ketones reduction with sodium borohydride or lithium aluminum hydride or by catalytic hydrogenation. 

Reduction to alcohols (Section 15 2) Aide hydes are reduced to primary alcohols and ketones are reduced to secondary alcohols by a variety of reducing agents Catalytic hydrogenation over a metal catalyst and reduction with sodium borohydride or lithium aluminum hydride are general methods... 

Hydride reduction (with L1AIH4 or NaBH4) of each of the following ketones has been... 

The milder metal hydnde reagents are also used in stereoselective reductions Inclusion complexes of amine-borane reagent with cyclodexnins reduce ketones to opucally active alcohols, sometimes in modest enantiomeric excess [59] (equation 48). Diisobutylaluminum hydride modified by zmc bromide-MMA. A -tetra-methylethylenediamme (TMEDA) reduces a,a-difluoro-[i-hydroxy ketones to give predominantly erythro-2,2-difluoro-l,3-diols [60] (equation 49). The three isomers are formed on reduction with aluminum isopropoxide... 

Hydride reduction (with LiAlH4 or NaBH4) of each of the following ketones has been reported in the chemical literature and gives a mixture of two diastereomeric alcohols in each case. Give the structures or build molecular models of both alcohol products for each ketone. 

The chemical reduction of enamines by hydride again depends upon the prior generation of an imonium salt (111,225). Thus an equivalent of acid, such as perchloric acid, must be added to the enamine in reductions with lithium aluminum hydride. Studies of the steric course (537) of lithium aluminum hydride reductions of imonium salts indicate less stereoselectivity in comparison with the analogous carbonyl compounds, where an equatorial alcohol usually predominates in the reduction products of six-membered ring ketones. 

The reduction of carbonyl compounds by reaction with hydride reagents (H -) and the Grignard addition by reaction with organomagnesium halides (R - +MgBr) are examples of nucleophilic carbonyl addition reactions. What analogous product do you think might result from reaction of cyanide ion with a ketone ... 

---