Diborane carboxylic acids

Diborane also has a useful pattern of selectivity. It reduces carboxylic acids to primary alcohols under mild conditions that leave esters unchanged.77 Nitro and cyano groups are relatively unreactive toward diborane. The rapid reaction between carboxylic acids and diborane is the result of formation of a triacyloxyborane intermediate by protonolysis of the B-H bonds. The resulting compound is essentially a mixed anhydride of the carboxylic acid and boric acid in which the carbonyl groups have enhanced reactivity toward borane or acetoxyborane. 

Although the exact mechanism is speculative, it has been found that carboxylic acids, but not esters, are reduced directly to the corresponding alcohols on reaction with benzyltriethylammonium borohydride in the presence of trichlorosilane [21]. Yields are generally in excess of 85%. The failure of the system to reduce esters suggests that diborane is not produced during the reaction [22],... 

Reduction of carboxylic acids and esters, aldehydes, and nitriles, and the hydro-boration of alkenes with diborane in non-ethereal solvents is highly effective (Table 11.8), but reduction of nitro groups or cleavage of arena-halogen bonds does not occur [1]. However, in spite of the potential advantages, very little use appears to have been made of the procedure. 

Carboxylic acids are reduced to primaiy alcohols by lithium aluminium hydride or better with diborane. Diborane does not easily... 

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],... 

Deuterioammonia, 188, 190 Deuteriobor ation, 191 Deuteriobromic acid, 214 Deuteriodiborane, 191 Deuterio-Raney nickel, 215 Deuterium gas and a surface catalyst, 199 Deuterium and tritium gas, 179 3,17/8-Diacetoxyestra-3,5-diene, 486 3,20-Diacetoxypregna-3,5,20-triene, 411 (20S)-2/3,3j3-Diacetoxy-5a-pregn-7-en-6 one-20-carboxylic acid methylester, 301 Diborane, 89, 100... 

Recently, the reduction of an N-terminal pyrrolidone carboxylic acid residue of proteins with diborane in tetrahydrofuran or tetramethyl urea was attempted with some success the N-terminal pyrrolidone carboxylic acid residue may thus be identified by its conversion to proline... 

Trimetkylsilyl esters.5 These esters are inert to diborane in THF and thus are useful for protection of carboxylic acids during hydroboration. 

Hydroboration, reduction of G=0. This complex is as efficient as BH3 THF lor hydroboration it forms diborane when dissolved in benzene. It reduces carbonyl compounds to alcohols at 0° in hexane or CH2C12. The stereoselectivity resembles that of BH3-THF. It reduces carboxylic acids to primary alcohols in 60-75% yield. 

Diborane, B H, also reduces carboxylic acids to alcohols. 

Disiamylborane has been demonstrated to be a highly selective hydroborating agent of C=C bonds in the presence of functional groups like carboxylic acids which react readily with diborane (Eq. 8). The hydroboration of 3-chloro-l -alkynes using a similar... 

Because it affords a specific route to compounds that have anti-Markovnikov, cis stereochemistry (often difficult to achieve by other means), the hydroboration reaction has assumed considerable importance in organic synthesis. Also important is the use of diborane as a reducing agent, in which it functions as an electrophile, for example, readily reducing carboxylic acids and esters BH4, in contrast, is a nucleophile and attacks electrophilic centers. 

Optically active amines. Esterification of an oxime, for example 2-hydroximino-1-phenylpropane (1), with a chiral carboxylic acid chloride, S-( + )-2-phenylbutyric acid chloride (2), gives an oximoester (3), which on reduction with diborane gives a mixture of optically active amines (4a, 4b) in which the S-enantiomcr (4a) predominates slightly. (The optical yield is about 6%.)... 

Another promising approach has been devised by Yamamoto and co-workers [8]. They found that the action of a controlled amount of diborane on a carboxylic acid leads to an (acyloxy)borane RC02BR 2 which behaves as a Lewis acid. The chiral (acyloxy)borane (CAB) complex 1 formed in situ from monoacyl tartaric acid and diborane is an excellent asymmetric catalyst (Eq. 8) for the Diels-Alder reaction of cyclopentadiene and acrylic acid (78 % ee) (Eq. 9) [8] or of cyclopentadiene and methacrolein (96 % ee) (Eq. 10) [9]. 

The reducing power of diborane has been blunted by forming its adduct with dimethyl sulfide. This adduct, Me2S BH3, is stable and commercially available and therefore more attractive as a hydride reagent than diborane itselfNevertheless, the adduct still reduces carboxylic acids to alcohols which are isolated as cyclic boroxins (2 Scheme 1). In a one-pot reaction, carboxylic acids can be reduced to boroxins and then oxidized with pyridinium chlorochromate to the required aldehyde (Scheme I)."... 

Sodium cyanoborohydride (10) produces mainly 1,4-dihydropyridines (11) in the reduction of 3,5-di-cyano- and 3,5-diethoxycarbonyl-pyridines, diborane produces more of the 1,2-isomer. With NBH, mixtures of 1,2- and 1,4-dihydro adducts are produced, the latter predominating when carried out in pyridine solution. Nicotinamide (13) in ethanol can be reduced to (8) in moderate yield at 140 C in diglyme the tetrahydropyridine (8) was isolated in admixture with the piperidine (14), presumably via dehydration of the amide. 3-Nitropyridine affords 3-nitropiperidine in moderate yield when reduced in ethanol. The carboxylic acid and halo derivatives of pyridine are generally not reactive toward NBH. 

Cyclization of the carboxylic acids (22) gave ketones (23a) which, through reaction of the dithioketals with diborane, gave rise to local anesthetic activity. ... 

Selective reductions. Brown et al.2 conducted an extensive study of reductions with diborane in THF. Most aldehydes and ketones are readily reduced unusually high stereoselectivity was realized in the case of norcamphor, which was reduced to 98% endo-norbornanol and 2% exo-norbornanol. p-Benzoquinone is reduced to hydroquinone at a moderate rate, but reduction of anthraquinone is sluggish. Carboxylic acids are reduced very rapidly indeed this group can be reduced selectively in the presence of many other substituents. Acid chlorides react much more slowly than carboxylic acids. Esters and ketones are reduced relatively slowly. Reactions with epoxides are relatively slow and complex. 

The dibenzyl ester 27 can be obtained by slowly distilling a mixture of tartaric acid and benzyl alcohol, without adding an acidic catalyst34. It is a key intermediate in the synthesis of mono-O-acylated tartaric acids 28-31 33,35 the benzyl ester groups can be selectively cleaved to the free carboxylic acid groups by catalytic hydrogenation. Such derivatives form acyloxy-boranes with diborane which are used as chiral catalysts in enantioselective Diels-Alder reactions (Section D. 1.6.1.1.1.). 

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