Sodium borohydride reduction mechanism

Sodium borohydride and lithium aluminum hydride react with carbonyl compounds in much the same way that Grignard reagents do except that they function as hydride donors rather than as carbanion sources Figure 15 2 outlines the general mechanism for the sodium borohydride reduction of an aldehyde or ketone (R2C=0) Two points are especially important about this process... 

FIGURE 15.2 Mechanism of sodium borohydride reduction of an aldehyde or ketone. 

Dihydrocorynantheine was obtained via similar steps from normal cyanoacetic ester 319 (172). Stereoselective transformation of the alio cyanoacetic ester 315 to the normal stereoisomer 319 was achieved by utilizing a unique epimerization reaction of the corresponding quinolizidine-enamine system (174). Oxidation of alio cyanoacetic ester 315 with lead tetraacetate in acetic acid medium, followed by treatment with base, yielded the cis-disubstituted enamine 317, which slowly isomerized to the trans isomer 318. It has been proved that this reversible eipmerization process occurs at C-15. The ratio of trans/cis enamines (318/317) is about 9 1. The sodium borohydride reduction of 318 furnished the desired cyanoacetic ester derivative 319 with normal stereo arrangement. The details of the C-15 epimerization mechanism are discussed by B rczai-Beke etal. (174). 

The formation of fulvene (450) by sodium borohydride reduction of 2-formyl-4//-pyran (371) in water347 may be explained by the mechanism shown in Scheme 21. 

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... 

JA Schmidt, C Heitner. Light-induced yellowing of mechanical and ultrahigh yield pulps. Part 1. Effect of methylation, sodium borohydride reduction and ascorbic acid on chromophore formation. JWood Chem Technol 11(4) 397 18, 1991. 

Effective and selective reductions of carboxylic acids and their derivatives by eight categories of sodium borohydride reduction systems have been reviewed. The recent progress in establishing reaction mechanism and optimum conditions, as well as the reduction capacity and scope of application of the reduction systems has been discussed. i ... 

The mechanism of lithium aluminum hydride reduction of aldehydes and ketones IS analogous to that of sodium borohydride except that the reduction and hydrolysis... 

The reduction of iminium salts can be achieved by a variety of methods. Some of the methods have been studied primarily on quaternary salts of aromatic bases, but the results can be extrapolated to simple iminium salts in most cases. The reagents available for reduction of iminium salts are sodium amalgam (52), sodium hydrosulfite (5i), potassium borohydride (54,55), sodium borohydride (56,57), lithium aluminum hydride (5 ), formic acid (59-63), H, and platinum oxide (47). The scope and mechanism of reduction of nitrogen heterocycles with complex metal hydrides has been recently reviewed (5,64), and will be presented here only briefly. 

When a pyridinium salt such as (27) is treated with sodium borohydride, the final product is the tetrahydropyridine (30). The mechanism for this reaction was proposed by Katritzky (65) and experimentally verified by Anderson and Lyle (66-68). The sequence is visualized as reduction of the... 

The most plausible mechanism for the interconversion of la and Ih is shown in Scheme 2. Similar mechanism has been put forward for epimerization of a-substituted ketones under basic conditions and for the equilibration via an enolate prior to nucleophilic substitution was observed by Numazawa et al. (ref. 13). The same mechanism seems to operate in the reduction of some steroid a-haloketones (ref. 14) or tra/ty-3-chloroflavanone (ref. 15) with sodium borohydride where an inversion of configuration takes place at the a carbon parallel to the reduction of the... 

Amides can also be deacylated by partial reduction. If the reduction proceeds only to the carbinolamine stage, hydrolysis can liberate the deprotected amine. Trichloroac-etamides are readily cleaved by sodium borohydride in alcohols by this mechanism.237 Benzamides, and probably other simple amides, can be removed by careful partial reduction with diisobutylaluminum hydride (see Section 5.3.1.1).238... 

Wee, T. G., Frey, P. A. Studies on the mechanism of action of uridine diphosphate galactose 4-epimerase. Substate dependent reduction by sodium borohydride. J. Biol. Chem. 248, 33—40 (1973). 

The reaction has broad applications and a large number of secondary and especially tertiary amines was prepared in isolated yields ranging from 60% to 84% [1136]. Although the mechanism of this reaction is not clear it is likely that the key step is reduction of the acid by borane, generated in situ from sodium borohydride and the acid, to an aldehyde which reacts with the amine as described in the section on reductive amination (p. 134-136). 

Strong reducing agents like sodium borohydride and lithium aluminum hydride are capable of reducing aldehydes to primary alcohols and ketones to secondary alcohols. The general reaction is the reverse of the reactions used to form aldehydes and ketones by the oxidation of primary and secondary alcohols, respectively (to review, see the earlier section Oxidation reactions ). However, the mechanisms for reduction are different. 

Sodium borohydride is the reagent of choice for the reduction of the pyridine ring in isoquinolinium salts. It reacts so rapidly that even the carbonyl group of a 1-aroyl substituent can survive (equation 154) (63JCS2487). A 1,2-dihydro intermediate has been isolated during the cyclization of (253) to 2,3-dimethoxyberbine by sodium borohydride, which suggests that a similar mechanism to that described above is operative here (equation 155) (60JOC90). 

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