Acyloxyborohydrides

Acyloxyborohydrides [NaBH4 (02CR)n] are remarkably selective,as illustrated by the reduction of the aldehyde unit in 126, in the presence of a ketone moiety.Reduction with potassium triacetoxyborohydride (generated by dissolving potassium borohydride in acetic acid) gave 127 in 60% yield. It can also reduce 

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Unusual reducing properties can be obtained with borohydride derivatives formed in situ. A variety of reductions have been reported, including hydrogenolysis of carbonyls and alkylation of amines with sodium borohydride in carboxyHc acids such as acetic and trifluoroacetic (38), in which the acyloxyborohydride is the reducing agent. 

The applications of sodium acyloxyborohydrides, formed from sodium borohydrides in carboxylic acid media, are reviewed. ° Useful reviews of the stereoselective reduction of endocyclic C=N compounds and of the enantioselective reduction of ketones have appeared. ... 

Organocopper reagents, 207 Palladium catalysts, 230 Potassium-Graphite, 252 Raney nickel, 265 Sodium acyloxyborohydrides, 277 Sodium borohydride, 278 Sodium borohydride-Nickel chloride, 279... 

High enantioselectivities (up to 94%) are obtained in the sodium borohydride reduction of aliphatic ketones using a tartaric acid-derived boronic ester (TarB-N02) as a chiral catalyst. A mechanism (Scheme 14) involving an acyloxyborohydride intermediate has been postulated.319... 

A new chiral acyloxyborohydride has been prepared by combining sodium borohy-dride with a tartaric acid-based reagent. This reagent effects the reduction of aromatic ketones to provide the product alcohols in ees of 93-98%. Several aliphatic ketones were also reduced with moderate to excellent enantioselectivity. A mechanism has been provided with supporting calculations for the proposed active species and tran- sition state.262... 

Table 1 demonstrates that NaBH4 may be used in the presence of heterocyclic rings (entries 8-10, 13-17), esters (entries 8-10, 17), amides (entries 1, 9), conjugated double bonds (entry 7), alkynes (entry 5) and acetals (entry 4). The process can also be used to methylate an amine with formaldehyde as the carbonyl (entry 13). With certain structures, further reactions may occur subsequent to reduction (e.g. entry 6). Entry 15 illustrates a synthetically useful amine alkylation reaction which may occur in acetic acid. This remarkable reaction is attributed to self-reduction of an acyloxyborohydride to an aldehyde... 

The utility of sodium borohydride (and related metal hydrides) in carboxylic acid media in the reduction of indoles has been reviewed recently and several additional examples can be found cited in this review.There is increasing evidence to suggest that acyloxyborohydride species are the actual reducing agents that form under these conditions. ... 

The mechanism of this reduction is presumed to involve reduction of the carbonyl group to the hydroxyl group, followed by TFA-promoted solvolysis to a doubly benzylic carbocation 9, and subsequent borohydride (or acyloxyborohydride) quenching of the carbocation to give product hydrocarbon. The highly colored carbocations are visible as transient species.2... 

Reduction of nitriles. This sodium acyloxyborohydride reduces nitriles (aliphatic and aromatic) to primary amines at room temperature in high yield. The reaction appears to be sekclive —COOC2H5, —NOa, and —Cl groups are not reduced. ... 

Reduction of ketones with sodium borohydride in the presence of a carboxylic acid and 1,2 5,6-di-0-cyclohexylidene-a -D-glucofuranose gave 35-50% enantiomeric enhancement values.Another group has reported a similar reaction with the corresponding di-O-isopropylidene-glucose derivative and prochiral aromatic ketones. Optical yields of up to 64% were claimed. The chiral reagents appear to be sodium acyloxyborohydrides, which complex with the carbohydrate before reduction takes place. 

Interestingly, selective reduction of carboxylic acid moiety in an olefinic acid has been achieved by first forming the corresponding acyloxyborohydride before the addition of I2 (Scheme 9) (30). 

It may be of interest to note that this acyloxyborohydride intermediate leads to the hydroboration of the olefinic moiety in 12h in the absence of I2. The corresponding hydroxy carboxylic acid was obtained after H202/Na0H oxidation and acidification (Scheme 10) (32). 

Sodium acyloxyborohydride has been found to effect the reduction of aliphatic and aromatic nitriles to the corresponding amines any chloro, nitro, or aromatic substituents remain unaffected under the reaction conditions. Full details have appeared of the [3,3]sigmatropic rearrangement of trichloroacetamidic esters of allylic alcohols, which provides a superior method for the 1,3-transposition of amino (and hydroxy) functions (Scheme 2). 

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