Sodium borohydride carbonyl compound reduction

Varma reported a facile and rapid method for the reduction of aldehydes and ketones to the respective alcohols, using alumina-supported sodium borohydride and microwave irradiation under solvent-free conditions. Aldehydes tend to react at room temperature, while for the reduction of ketones, short microwave irradiation of 30-180 s was applied to produce the corresponding alcohols in 62-92% yield. With unsaturated carbonyl compounds, reduction at the conjugated C=C bond might occur as a side reaction under these conditions (Scheme 4.9)26. 

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... 

The tosylhydrazone is prepared from the carbonyl compound and then reduced with lithium aluminium hydride, sodium borohydride or potassium borohydride. In this way D-glucose tosylhydrazone was converted into crystalline 1-deoxyglucitol by reduction with potassium borohydride... 

The final stages of the successful drive towards amphotericin B (1) are presented in Scheme 19. Thus, compound 9 is obtained stereoselectively by sodium borohydride reduction of heptaenone 6a as previously described. The formation of the desired glycosida-tion product 81 could be achieved in dilute hexane solution in the presence of a catalytic amount PPTS. The by-product ortho ester 85 was also obtained in approximately an equimolar amount. Deacetylation of 81 at C-2, followed sequentially by oxidation and reduction leads, stereoselectively, to the desired hydroxy compound 83 via ketone 82. The configuration of each of the two hydroxylbearing stereocenters generated by reduction of carbonyls as shown in Scheme 19 (6—>9 and 82->83) were confirmed by conversion of 83 to amphotericin B derivative 5 and comparison with an... 

Reduction of carbonyl compounds can be carried out in an aqueous medium by various reducing reagents. Among these reagents, sodium borohydride is the most frequently used. The reduction of carbonyl compounds by sodium borohydride can also use phase-transfer catalysts (Eq. 8.4),10 inverse phase-transfer catalysts,11 or polyvinylpyridines12... 

Reduction of Carbonyl Compounds to Alcohols - Sodium Borohydride-... 

Scheme 6.38 Reduction of carbonyl compounds using alumina-supported sodium borohydride.

Sodium cyanoborohydride [123], sodium triacetoxyborohydride [124] or NaBH4 coupled with sulfuric acid [125] are common agents used for the reductive amination of carbonyl compounds. These reagents either generate waste or involve the use of corrosive acids. The environmentally friendlier procedures developed by Varma and coworkers have been extended to a solvent-free reductive amination protocol for carbonyl compounds using moist montmorillonite K 10 day supported sodium borohydride that is facilitated by microwave irradiation (Scheme 6.39) [126]. 

Alumina-sodium borohydride, reduction of carbonyl compounds with, 16 572-573 Alumina sols, gelation of, 23 77 Alumina-supported iodobenzene diacetate (IBD), 16 570... 

Carbonyl compounds addition to, 73 659 a-alkylation of, 73 658s reduction with alumina—sodium borohydride, 76 572-573 reduction with aluminum alkoxides, 76 572... 

Sodium borohydride is a much milder reducing agent than lithium aluminium hydride and like the latter is used for the reduction of carbonyl compounds like aldehydes and ketones. However, under normal conditions it does not readily reduce epoxides, esters, lactones, acids, nitriles or nitro groups. 

Kinetic studies established that tetra-n-butylammonium borohydride in dichloromethane was a very effective reducing agent and that, by using stoichiometric amounts of the ammonium salt under homogeneous conditions, the relative case of reduction of various classes of carbonyl compounds was the same as that recorded for the sodium salt in a hydroxylic solvent, i.e. acid chlorides aldehydes > ketones esters. However, the reactivities, ranging from rapid reduction of acid chlorides at -780 C to incomplete reduction of esters at four days at 250 C, indicated the greater selectivity of the ammonium salts, compared with sodium borohydride [9], particularly as, under these conditions, conjugated C=C double bonds are not reduced. 

Sodium dithionite is well established [ 1 ] as a powerful reducing agent under alkaline conditions. Its redox potential is close to that of sodium borohydride [2] and, in several respects, there are advantages in the use of sodium dithionite as an alternative to the metal hydrides under phase-transfer catalytic conditions, particularly in the reduction of carbonyl compounds [3],... 

Benzo[e]thieno[3,2- ]thiepin-10(5Ef)-one 388 can be smoothly reduced with sodium borohydride to the corresponding alcohol, which forms the chloro substituted compound under standard treatment with thionyl chloride (1991CPB2564). Dihydro derivatives of pyrrolo-benzothiazepine 377 have been reported starting from ketone 373 by a carbonyl reduction, bromination and amination sequence (Scheme 76, Section 5.1.1 (1998JMC3763, 2002JMC344, 2004JMC143)). 

Compound 63, the 2-formyl derivative of compound 61, undergoes a series of side-chain reactions at the carbonyl group including reduction with sodium borohydride and condensation reactions with hydroxylamine or malononitrile. The reactions afford the appropriately 2-substituted products in excellent yields <2004CHE1477>. 

Cleavage of the dithioacetal groups from the products, followed by reduction of the resultant carbonyl derivatives (46, 49, 52) with sodium borohydride leads,68 with the three compounds (45, 48, and 51), to 1,4-anhydro-L-ribitol (2,5-anhydro-D-ribitol) (47), 1,4-anhydro-L-xylitol (2,5-anhydro-D-xylitol) (50), and 1,4-anhydro-D-arabinitol (2,5-anhydro-D-lyxitol) (53), identified by comparison with their enantiomorphs, 1,4-anhydro-D-ribitol,69 1,4-anhydro-D-xylitol,70 and 1,4-anhydro-L-arabinitol. 71... 

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