Borane carboxylic acid reduction

The reactivity of boranes is dominated by the desire to accept an electron pair into the empty p-orbital. Therefore boranes reduce electron-rich carbonyl groups fastest. In the context of carboxylic acid reduction a triacylborate 35 is formed first. Compared to, for example, ketones, esters are less electrophilic because of conjugation between the carbonyl group and the lone pair of the sp -hybridized oxygen atom. However, in the case of boron esters such as 35, the oxygen next to the boron has to share its lone pair between the carbonyl group and the empty p-orbital of the boron. This fact makes them considerably more reactive than normal esters and allows the chemoselective reduction of carboxylic acids in the presence of esters or acyl chlorides. 

The partial hydrolysis of 4a with methanolic potassium hydroxide followed by selective carboxylic acid reduction with excess borane and treatment of the resulting monoalcohol with methanesulfonyl chloride affords methyl 4-0-methanesulfonyl-2,3-0-isopropylidene-L-threonate (43). Facile displacement of the mesylate with azide followed by ester hydrolysis and catalytic reduction to an amine provides 4-amino-4-deoxy-2,3-0-isopropylidene-L-threonic acid (44). Mild acidic deprotection and ion-exchange desalting of 44 yields (2i ,3 S)-4-amino-4-deoxy-L-threonic acid (45), which has been utilized for the preparation of anthopleurine 46, the alarm pheromone of the sea anemone Anthopleura elegantissima [4] (Scheme 11). 

An indirect method ° of double-bond reduction involves hydrolysis of boranes (prepared by 15-16). Trialkylboranes can be hydrolyzed by refluxing with carboxylic acids,while monoalkylboranes RBH2 can be hydrolyzed with base. ° Triple bonds can be similarly reduced, to cis alkenes. °... 

Reduction of aromatic carboxylic acids to alcohols can be achieved by hydrides and complex hydrides, e.g. lithium aluminum hydride 968], sodium aluminum hydride [55] and sodium bis 2-methoxyethoxy)aluminum hydride [544, 969, 970], and with borane (diborane) [976] prepared from sodium borohydride and boron trifluoride etherate [971, 977] or aluminum chloride [755, 975] in diglyme. Sodium borohydride alone does not reduce free carboxylic acids. Anthranilic acid was reduced to the corresponding alcohol by electroreduction in sulfuric acid at 20-30° in 69-78% yield [979],... 

Carboxylic acids can also be converted to alkanes, indirectly,570 by reduction of the corresponding tosylhydrazides RCONHNH2 with LiAlH4 or borane.571 OS VI, 747. 

Direct reduction of aldehydes with 2,3-dimethyl-2-butylborane proceeds rapidly and gives the corresponding alcohol. Nonetheless, reduction of carboxylic acids with the same borane (Section 18-3C) proceeds slowly and gives high yields of aldehydes. Explain why the reaction of RC02H with the 2,3-dimethyl-2-butylborane produces RCHO instead of RCH2OH. 

Related to this reaction is the acid treatment of the (l-hydFoxymethylcyclohexadiene)tricarbonyliron (45), prepared via DIBAL-H reduction of ester (26) or borane reduction of the corresponding carboxylic acid, which leads to the 1-methylcyclohexadienyliron complex (46 equation 18).11 Using these methods, it is therefore possible to prepare a range of alkyl-substituted dienyl complexes having a defined substitution pattern. 

Alcohols are at a fairly low oxidation level compared to other oxygen-containing functional groups and consequently are readily prepared by reduction. Large numbers of reductive methods have been reported for the preparation of alcohols. Carboxylic acids and esters react vigorously with lithium aluminum hydride (LAH) to produce primary alcohols. Carboxylic acids, but not esters, are also reduced easily by borane, which is die only reducing agent diat reacts faster widi carboxylic acids dian widi esters or odier acid derivatives. 

Borane is a highly chemoselective reagent for the reduction of carboxylic acids in the presence of other reducible functional groups such as esters, and even ketones. 

Reduction of carboxylic acids with borane-dimethyl sulfide generally proceeds rapidly In connection with reduction experiments with p-hydroxybenzoic acid, it was found that this compound gave only low yields of p-hydroxybenzyl alcohol when treated with borane-dimethyl sulfide according to the procedure described by Knstersson et al (1980) This is in accordance with studies of the... 

Lane CF, Myatt HL, Daniels J, Hopps HB (1974) Organic synthesis using borane-methyl sulfide II Reduction of aromatic carboxylic acids in the presence of tnmethyl borate J Org Chem 39 3052-3054... 

Hemiacetals are formed from hydroxy aldehydes " or ketones which are usually first in a protected form and are deblocked prior to cyclization. Ozonolysis of cyclohexene derivative 5 and reductive workup, followed by hydrolysis of the acid chloride formed in situ and borane reduction of the carboxylic acid, leads to the six-membered hemiacetal 6. a precursor for fluo-rinated sugars that are potentially versatile as molecular probes in the elucidation of biochemical processes. ... 

Alternatively, borane in tetrahydrofuran (BH3/THI ) is a useful reagent for reducing carboxylic acids to primary iilcohols. Reaction of an acid with BH / l HF occurs rapidly at room temperature, and the proceaurc is often preferred to reduction with I iAlH4 because of its relative ease and safety. Borane reacts with carboxylic acids faster than with any other functional group, thereby allowing selective transformations such as tliat shown below on / -nitrophenylacetic acid. If the reduction of p-nitrophcnylacetic acid were done with LiAll-14, both nitro and carboxyl groups would be reduced. 

The use of hydride reagentsfor the reduction of carboxylic acids requires vigorous conditions because the carboxylatc anion, once formed, is resistant to further nucleophilic attack. An interesting exception to this is reduction with borane. A triacyloxyborane may be formed. Re.sonance involving the vacant orbitals of the boron and the lone pairs on the oxygen has the effect of making the attack of a nucleophilic hydride on the carbonyl carbon of the acid easier (see 3.21). 

Acyloxyborane as an Activating Device for Carboxylic Acids . The reduction of carboxylic acids by borane is an important procedure in organic synthesis. The remarkable reactivity of borane towards carboxylic acids over esters is characteristic of this reagent. Such selectivity is rarely seen with other hydride reagents. 

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