Carboxylic acids with boranes

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... 

As shown in the scheme below, starting from the amino acid valine, reduction of the carboxylic acid with borane and reaction with diethyl carbonate produces the... 

This newly created species proved to be of high value due to its easy transformation into nitrogen containing molecules. The lactone amino acid does not occur naturally and was generated by reduction of the free carboxylic acid with borane tetrahydrofurane complex, followed by the spontaneous rearrangement of the... 

The key sequence in a somewhat involved stereospecihc total synthesis of a carbacephem starts by preparation of a chiral auxiliary. It is interesting to note that nitrogen is the only atom from this molecule retained in the hnal product. Constmction of this moiety starts with the formation of the carbethoxy derivative (37-2) from L(- -)-phenylglycine (37-1). Selective reduction of the free carboxyl group with borane. THF leads to the hydroxycarbamate (37-3). In a one-pot sequence, this is first cyclized to the corresponding oxazolidinone (37-4) by means of sodium hydride and then alkylated with ethyl bromoacetate (37-5). Saponification of the side chain then affords the chiral acetic acid (37-6). The carboxyl group is then activated by conversion to its acid chloride (37-7). 

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. 

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. 

The rapid reaction between carboxylic acids and borane is related to the electrophilicity of the latter. The carbonyl group of the initially formed acyloxyborane intermediate, which is essentially a mixed anhydride, is activated by the Lewis acidity of the trivalent boron atom. Addition of 1/3 equiv of the Borane-Tetrahydrofuran complex to acrylic acid in dichloromethane followed by addition of a diene at low temperature results in the formation of Diels-Alder adducts in good yield (eq 1). Further, the reaction is successful even with a catalytic amount of borane. 

Reduction of saturated carboxylic acids with the borane derivative, thexylchloro-borane, provides a direct route to aldehydes without their prior conversion to carboxylic acid derivatives. The aldehydes initially formed were isolated either as their bisulfite adducts or as their hydrazones, from which the aldehydes were regenerated. 

Yamamoto and coworkers have developed a practical Diels-Alder catalyst for aldehyde dienophiles. Treatment of a monoacylated tartaric acid with borane released ca. 2.2 equiv of H2 gas, affording a complex that has been assigned structure 7. Circrunstantial evidence for structure 7 was found in the comparable enan-tioselectivity of a catalyst in which the free carboxyl group was esterified (see below). The chiral (acyloxy)borane (CAB) complex is effective in catalyzing a number of aldehyde-based Diels-Alder reactions (Scheme 9) [56]. Reactions with... 

Acyloxy)dialkylboranes are best prepared from carboxylic acids with tri-alkylboranes.1,12-16 Other methods involve reactions of halodiorganobo-ranes with carboxylic acids17 or with acetic anhydride.18 Alternative syntheses from acetic anhydride using dialkyl(alkylthio)boranes or dialkylamino compounds have also been described.19... 

BBN has been elegantly employed for the selective hydroboration to afford the corresponding alkyl boranes, which on treatment with dianion of phenoxy acetic acid, followed by alkaline HjOj oxidation produce in good to moderate yields the corresponding carboxylic acids with two carbon homologation (Eqs. 8.2,8.3). 

In the absence of hydrogen, metallocene-based catalyst systems produce well-defined polymers which are olefin- or aluminum-terminated. Miilhaupt has polymerized propylene with a chiral metallocene and MAO under conditions where P-hydrogen elimination was the predominant chain transfer process. In a post-polymerization functionalization, the olefin endgroups of the highly isotactic polypropylene chains were converted to bromo-, epoxy-, anhydride-, ester-, amine-, carboxylic acid-, silane-, borane-, hydroxy-, thiol-terminated polymers as intermediates for the preparation of block copolymers. Using olefin-terminated atactic and isotactic polypropylene formed with MAO-activated Cp2ZrCl2 and (EBTHI)ZrCl2 Shiono has synthesized amine- and aluminum-terminated polymers." ... 

Scheme 4 outlines the synthesis of key intermediate 7 in its correct absolute stereochemical form from readily available (S)-(-)-malic acid (15). Simultaneous protection of the contiguous carboxyl and secondary hydroxyl groups in the form of an acetonide proceeds smoothly with 2,2 -dimethoxypropane and para-toluene-sulfonic acid and provides intermediate 26 as a crystalline solid in 75-85 % yield. Chemoselective reduction of the terminal carboxyl group in 26 with borane-tetrahydrofuran complex (B H3 THF) affords a primary hydroxyl group that attacks the proximal carbonyl group, upon acidification, to give a hydroxybutyrolactone. Treat-... 

Biphenylcarboxylic acid [[1,1 -Biphenyl] -2-carboxylic acid], 83 Boron tnfluonde, etherate, [Borane, tri-fluoro-, compd. with l,l -oxybis-[ethane] (11)], 10 Bromine, 108... 

Amides are derivatives of carboxylic acids, so that their coordination behavior to boranes might be similar to that of their parent compounds. B-NMR spectroscopic studies have shown that compounds 31 and 32 are monomeric species in solution, while compounds 33 and 34 with the more Lewis acidic 9-borabicyclo[3.3.1]nonyl unit form aggregates that may be dimeric, oligomeric, or polymeric. The grade of association could not be determined by mass spectrometric analyses, because in all cases only the monomer is liberated into the gas phase [65]. 

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. °... 

Triple bonds can be monohydroborated to give vinylic boranes, which can be reduced with carboxylic acids to cis alkenes or oxidized and hydrolyzed to aldehydes or ketones. Terminal alkynes give aldehydes by this method, in contrast to the mercuric or acid-catalyzed addition of water discussed at 15-4. However, terminal alkynes give vinylic boranes (and hence aldehydes) only when treated with a hindered borane such as 47, 48, or catecholborane (p. 798)," or with BHBr2—SMe2. The reaction between terminal alkynes and BH3 produces 1,1-... 

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