Aldehyde reaction with NaBH

Alcohols are among the most versatile of all organic compounds. They occ. widely in nature, are important industrially, and have an unusually he chemistry. The most important methods of alcohol synthesis start with carbonyl compounds. Aldehydes, ketones, esters, and carboxylic acids are reduced by reaction with either NaBH,i or LiAIH4. Aldehydes, esters, and carboxylic acids yield primary alcohols (RCHgOH) on reduction ketones yield secondaiy alcohols (R CHOH). 

Treatment of a monosaccharide with NaBH, reduces it to a polyalcohol called an alditol. The redxiction occurs by interception of the open-chain form present in the aldehyde/ketone-hemiacctal equilibrium. Although only a small amount of the open-chain form is present at any given time, that small amount is reduced then more is produced by opening of the pyranose form and that additional amount is reduced and so on, until the entire sample has undergone reaction. 

Reformatsky-type reactions and reductions. Enolates generated from a-bromoketones by reaction with BiClj-Al in an aqueous medium condense with various aldehydes to give J-hydroxy ketones." A modification of reaction conditions (BiClj-NaBH ) and in the absence of aldehydes leads to hydrodehalogenation of the haloketones. ... 

S,S-dioxides, those authors applied spHt/pool methodology. TWo different series of compounds were prepared such as compounds 376 containing an amino acid group acylated at the nitrogen atom. According to strategy 1 shown in Scheme 90, a series of structurally diverse carboxylic acid derivatives were prepared from supported aldehyde 373 condensed with different protected amino acids in the presence of NaBH(OAc)3 to afford intermediate 374, which was then acylated affording 375. After hydrolysis of ester and reaction with bromo derivative 368 (R = H) in PTC conditions, compounds 376 were obtained. 

Section 8-6 presents two u.seful reduction processes. Carbonyl compounds such as ketones and aldehydes arc useful precursors (starting materials) for the synthesis of alcohols. Either metal-catalyzed Ht addition or reaction with the hydride reagents NaBH and LiAIH converts aldehydes to primary alcohols. The same processes convert ketones to secondary alcohols. The.se hydride reductions are the lirst of many examples that you will. see of nucleophilic additions to the electrophilic carbons of carbonyl groups. This is one of the most important clas.ses of reactions in organic chemistry. 

Another interesting application involved the formation of allylic amines 33a-e in enantiomerically pure form as published by the Jprgensen group (Scheme 5.18) [25]. This Mannich reaction was conducted between the benzothiazolesulfonyl-derived aldehydes 31a-e and the Boc-protected aldimine 23a. After the initial Mannich reaction, a subsequent reduction with NaBH was carried out to give rise to the allylic amines 33a-e in moderate yields, but high E/Z-ratios and enantioselectivity. 

Sodium borohydride has been extensively used as a reducing agent. The solid state reduction with NaBH requires longer time and use of solvents slow down the reaction. A microwave irradiation reaction has been developed for the reduction of aldehydes and ketones using alumina supported NaBH (Scheme 23). 

Acetoxymercuration of N-vinylpyrroles is a typical reaction of electrophilic addition to the N-vinyl group. Its key stage involves an attack of the mercury acetoxy cation on the double bond to generate adduct A (Scheme 2.227). The latter, upon hydrolysis, can exchange acetoxy group for the hydroxy moiety, and unstable hemi-aminal should further decompose to give free pyrrole and mercury acetaldehyde. Thus, the removal of vinyl protection can be achieved without application of sodium borohydride that is confirmed by the example of 5-phenylpyrrole-2-carbaldehyde [691], which reduces its aldehyde group under usual conditions (with NaBH ). 

The aforementioned transformation also can be performed with simple and inexpensive iV-chloro succinimide (95a). In this case either Cj-symmetric pyrrolidine 98 or prolinamide 99 in 10 mol% could be successfully used with the reaction conditions being milder than in the previous case (methylene chloride at room temperature, Scheme 4.21). The obtained chiral a-chloro aldehydes 96 are configurationally stable to pH neutral silica purification, although they can be easily transformed into a wide variety of different compounds, such as epoxides (reduction with NaBH and... 

The N-substituted aminoacids required could be prepared by microwave-assisted reductive amination of aminoacid methyl esters with aldehydes, and although in the Westman report soluble NaBH(OAc)3 was used to perform this step, other reports have shown how this transformation can be performed in using polymer-supported borohydrides (such as polymer-supported cyanoborohydride) under microwave irradiation [90]. An additional point of diversity could be inserted by use of a palladium-catalyzed reaction if suitably substituted aldehydes had been used. Again, these transformations might eventually be accomplished using supported palladium catalysts under microwave irradiation, as reported by several groups [91-93]. 

The drug candidate 1 was prepared from chiral cyclopentanol 10 as shown in Scheme 7.3. Reaction of 10 with racemic imidate 17, prepared from the corresponding racemic benzylic alcohol, in the presence of catalytic TfOH furnished a 1 1 mixture of diastereomers 18 and 19 which were only separated from one another by careful and tedious chromatography. Reduction of ester 18 with LiBH4 and subsequent Swern oxidation gave aldehyde 20 in 68% yield. Reductive animation of 20 with (R)-ethyl nipecotate L-tartrate salt 21 and NaBH(OAc)3 and subsequent saponification of the ester moiety yielded drug candidate 1. 

Treatment of a ketone or aldehyde with LiAlH or NaBH4 reduces the carbonyl group and yields an alcohol (Section 17.5). Although the exact details of carbonyl-group reduction are complex, LLAIH4 and NaBH act as if they were donors of hydride ion, H , and the key step is a nucleophilic addition reaction (Figure 19.7). Addition of water or aqueous acid after the hydride addition step protonates the tetrahedral alkoxide intermediate and gives the alcohol product. 

Allylations. Homoallylic alcohols are formed by the reaction of carbonyl compounds with allylic bromides when the latter are treated with BiCl, and a reducing agent (Zn for keto acids, and NaBH for aldehydes"). Alternatively, a Barbier-type reaction employing Mg-BiClj is more convenient. ... 

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