Ester with diborane

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. 

Direct reduction of a peptide bond with diborane 59 or a thioamide bond with several reductive procedures 60 is an alternative route for the production of a reduced peptide bond in a peptide. In some cases the reductive amination does not give satisfactory results. As described earlier, preparation of Boc-Pher )[CH2N]Pro-OH by reductive amination yields two diastereomers (Scheme ll). 57 In this case treatment of Boc-Phe-Pro-OBzl by diborane yielded the reduced pseudodipeptide Boc-Pher )[CH2N]Pro-OBzl without epimerization (Scheme 12). However, in some cases diborane is not entirely selective for the amide bond and can reduce ester functions when they are present. Another procedure is to prepare endothiopeptides directly from protected dipeptides 61-66 followed by their selective reduction. 60 ... 

Alternatively, the remaining sulfate ester of 70 may serve as a leaving group for a second nucleophilic displacement reaction. When this displacement is by an intramolecular nucleophile, a new ring is formed, as was first shown in the synthesis of a cyclopropane with malonate as the nucleophile [68] and of aziridines with amines as the nucleophiles [76]. The concept is further illustrated in the double displacement on (/J,/ )-stilbenediol cyclic sulfate (72) by benzamidine (73) to produce the chiral imidazoline 74 [79]. Conversion of the imidazoline (74) to (.V,.S )-stilbenediaminc 75 demonstrates an alternative route to optically active 1,2-diamines. Acylation of 75 with chloroacetyl chloride forms a bisamide, which, after reduction with diborane, is cyclized to the enantiomerically pure trans-2,3-diphenyl- 1,4-diazabicy-clo[2.2.2]octane (76) [81],... 

The solvent-free, microwave-assisted coupling of thienyl boronic acids and esters with thienyl bromides, using aluminum oxide as the solid support, served to rapidly check the reaction trends on changing times, temperature, catalyst, and base and easily optimize the experimental conditions to obtain the desired product in fair amounts. This procedure offers a novel, general, and very rapid route to the preparation of soluble thiophene oligomers. Quaterthiophene 265 was obtained in 6 min by reaction of 2-bromo-2,2 -bithiophene with bis(pinacolato)diborane(4) in 65% yield, whereas dithiophene 266 was obtained with 70% yield. The synthesis of new chiral 2,2 -bithiophenes also was reported. The detailed... 

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. 

In contrast to the usual reaction of aromatic aldehydes with cyclic ketones o-nitrobenzaldehyde condenses with 17-ketones to produce good yields of seco-acids, a reaction which has been applied to the preparation of 16-oxa-steroids. Thus, 3 -hydroxy-5a-androstan-17-one or its acetate affords the seco-steroid (153), which can be oxidised either as the free acid by ozone and alkaline hydrogen peroxide to the diacid (155) or, as its methyl ester (154), with chromium trioxide to the monomethyl ester (156). Diborane reduction of the diacid (155) or lithium aluminium hydride reduction of the dimethyl ester (157) gave the trans-diol (158), cyclised with toluene-p-sulphonic acid to 16-oxa-androstan-3)5-ol (159) or, by oxidation with Jones reagent to the lactone (152) (as 3-ketone) in quantitative yield. This lactone could also be obtained by lithium borohydride reduction of the monomethyl ester (156), whilst diborane reduction of (156) and cyclisation of the resulting (151) afforded the isomeric lactone (150). The diacid (155) reacted with acetic anhydride to afford exclusively the cis-anhydride (161) which was reduced directly with lithium aluminium hydride to the cis-lactone (160) or, as its derived dimethyl ester (162) to the cis-diol (163) which cyclised to 16-oxa-14)5-androstan-3) -ol (164). 

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.). 

Amongst saponins, those with ester functions are the source of redoubtable structural problems. They can be solved chemically, i.e. by derivatization followed by hydrolysis and identification of the fragments. Reduction reactions may be used to complement hydrolysis reactions in the fragmentation of saponins. A reagent of choice is L1AIH4 which reduces esters into diols prior protection of alcohol functions as ethers is necessary to avoid solubility problems (5). The chemoselective reduction of acids in the presence of esters by diborane is an excellent method of distinguishing these two functions in multifunctional compounds (55). 

R)-( + )-Methyloxirane, a useful chiral intermediate, has been employed in the synthesis of a variety of natural products. It is readily prepared in multi-gram quantities from ethyl L-lactate via tosylate 120b [53,54]. Reduction of the ester proceeds quantitatively with diborane over a period of 5 days to afford ( S)-( + )-propane-l,2-diol 2-tosylate (146). Cyclization with KOH gives epoxide 147 with 97% inversion of configuration. 

The side chain is constructed from ( S)-malic acid via the acetoxyester 34b (Scheme 44) [35]. Reduction of the carboxylic acid with diborane or BMS [33] affords hydroxy ester 323 in essentially quantitative yield. Hydrolysis followed by acidification gives the lactone 275 in moderate yield. Fluorination with DAST proceeds with inversion of configuration, producing the fluoro lactone 324 with > 98% ee. Treatment of this lactone with an excess of methyl-lithium under carefully controlled conditions furnishes the desired fluoro diol 325. 

The scope and mechanism of the reductions of esters and lactones to ethers with diborane has been reported in detail cf. ref. 279). Initial co-ordination of BH3 with the alkoxy-oxygen is considered to be the essential step in the reduction to alcohols. Ether formation seems to occur as an alternative pathway when the... 

The combination of crown ether and porphyrin has recently been extended by Hamilton et al. The macrotetracyclic cryptand 226 was prepared by condensation of the biphenyl-linked bis-crown ether 224 with the di-p-nitrophenyl ester porphyrin 225a, b in pyridine at 55 °C under high dilution conditions (45-54% after chromatography). Reduction to the tetra-amine 227 was effected by treating the zinc complex with diborane... 

A new application of the Schmidt rearrangement is to give unnatural aminoacids <91BMC125>. Treatment of the optically active cyclic -ketoester (266) with hydrazoic acid gives the optically active azepinone (267) which upon selective reduction with diborane furnishes the novel cyclic amino acid ester (268) (Scheme 36). 

Tetrahydrofuran treated a few min. with diborane and iodine at room temp, and the intermediate boric acid ester treated with water 4-iodobutan-l-ol. Y 90%. — Similarly Anisole phenol. 1 mole diborane cleaves 6 moles ether. Large excesses of reagents are unnecessary and should be avoided. Metal boron hydrides are comparable in reactivity to diborane. Bromine and interhalogen compounds such as iodine chloride react more vigorously but are in general less convenient. L. H. Long and G. F. Freeguard, Nature 207, 403 (1965). 

Removal of the ester group afforded the cephalosporin acid (205). 7-Amino- and 7-acylaminocephalosporin esters directly substituted at position 3 with a secondary acyclic amino group or a cyclic secondary amino group were reduced in dry solvents with diborane to yield 3-unsubstituted 3-cephems. The same 3-aminocephalosporins were reacted with an alkyl or aryl Grignard reagent to afford the corresponding 3-alkyl- or 3-aryl-3-cephem esters (U.S. Patent 4,065,618). 

Arylboronic and arylborinic acids have been produced from the hydrolysis of intermediates in the reactions of aryl-tin and aryl-lead compounds with diborane. The preparation of di[bis(trimethylsilyl)methyl]chloroborane from the reaction of bis(trimethylsilyl)methyl-lithium and boron trichloride has been published. A new reagent for O-ethylboranediylation, ethylbis-(2-isopropyl-6-methyl-4-pyrimidinyloxy)borane (3) has been synthesized and used to prepare O-ethyl-boranediyl derivatives of alcohols, phenols, alkanediols, D-mannitol, and l-arabinose. Borane-methyl sulphide reportedly reacts smoothly with primary, secondary, and tertiary alcohols and phenols to provide a general and convenient synthesis of borate esters. ... 

Diborane is also a useful reagent for reducing amides. Tertiary and secondary amides are quite easily reduced, but primary amides react only slowly. Amides require vigorous conditions for complete reduction by LiAlH4. Selective reduction of amides in the presence of such functional groups as ester and nitro are therefore best done with diborane. 

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