Diborane lactones

The order of reactivities of various functional groups determined under standard conditions (using externally generated diborane, and tetrahydrofuran as solvent) is acid > alkene > ketone > nitrile > epoxide > ester > acid chloride.33 Acids, aldehydes, ketones, epoxides, nitriles, lactones and azo compounds are reduced rapidly, esters more slowly and chloral, acid chlorides and nitro compounds are inert. Double bonds undergo the hydroboration reaction,25 nitriles and azo compounds are reduced to amines, and the remaining groups to alcohols. Ketones can be reduced selectively in the presence of epoxides. Contrary to the order of reactivities given above, it has been claimed that nitriles are reduced more rapidly than ketones.223... 

The lactone ring in decinine (2) was reduced to the cyclic ether (34) with diborane generated from sodium borohydride and boron trifluoride. The Emde degradation of (34) afforded a piperidine derivative (35a). The Cyanogen bromide N-demethylation of the methyl ether (35b) followed by... 

Reduction by diborane of the sodium salt of 3/3-t-butyloxy-5,7-seco-B-norcholestan-5-on-7-oic acid gave the 5j3H lactone (339) which could be further reduced to the corresponding 5a,7-diol. Conversion into the 5a,7-dimesylate was followed by reaction with sodium sulphide to give 6-thiacholestanol butyl ether... 

The resulting acetate 116 is formulated as the tawis-isomer, too. The carboxylic group was then converted by selective reduction with diborane to the alcohol 117. The alcohol function was converted to the nitrile 119 via the tosylate 118 and displacement of the tosylate group with sodium cyanide. Methanolysis led to the methylester 120 because the acetate moiety was not cleaved under these conditions (MeOH/HCl). Hydrolysis with base yielded the deprotected lactone acid alcohol 121, which was purified by converting it into the methylester 122. 

Diborane has been used to reduce lactones to cyclic hemiacetals and, when boron trifluoride etherate was added, ethoxy compounds (24 Scheme 10) were isolated. It was later shown that yields of hemiacetals in excess of 80% were obtainable with short reaction times. ... 

Under usual conditions, lactones are reduced by lithium aluminum hydride to diols. A procedure for the reduction of 8-lactones with diborane in tetrahydrofiirane to cyclic acetals has been applied to the synthesis of several unusual oxasteroids. ... 

Reduction of y-lactones with diborane proceeds to the diol. 

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 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. 

A synthetically useful feature of 5 is its willingness to undergo monoreduction. Diborane selectively reduces the acid group of 5 to provide the monoalcohol 13. This alcohol is then converted to a methyl group, which has the chirality found in (iS)-( + )-jS-angelica lactone 15 [12,13] (Scheme 3). 

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 diborane reduction of a large array of six- and seven-membered-ring lactones belonging to the cholestane-and androstane series has been investigated under different experimental conditions. Thus, reduction of the lactone (333) under the conditions shown can lead to either a mixture of oxide (334) and diol (335) or exclusively the latter. The results which were obtained suggested the reaction mechanism shown in Scheme 14, which would account for the formation of compounds (337), (338), and (339) from (336). ... 

Oxidative hydroboration 91) of lactone 11.49 afforded a mixture of four lactarorufins (Scheme 20), in which diols 11.30 and 11.33, arising from a attack of diborane, largely predominated (more than 90%). The same type of stereoselectivity was observed for other addition reactions, i.e. epoxidation, osmylation, hydrogenation (775), (704), 43) to 2,9, 3,4- or 6,7-double bond of lactaranolides and marasmanes. Apparently, the tricyclic structures of these substrates provided enough conformational and steric bias to direct approach of reagents from the same side as the bridgehead protons H-2 and H-9. However, when the double bond was located in a different position, exceptions were observed 98). 

There has been a continuing interest in syntheses of 3-amino-2,3,6-trideoxy-hexoses such as daunosamine (9), acosamine (10), etc. In an interesting paper by Fronza et the two sugars have been synthesized from the non-carbohydrate compound (11), which was obtained in 25-30% yield from the incubation of cinnamaldehyde v th acetaldehyde in the presence of bakers yeast (Scheme 2). The crucial amino-lactone (12) was also synthesized from L-threonine. The same authors have also completed their synthesis of A-benzoyl-L-ristosamine (3-benzamido-2,3,6-trideoxy-L /6o-hexose) from 3-benzamido-2,3,6-trideoxy-L-xy/o-hexono-1,5-lactone (Vol. 13, p. 79). An alternative synthesis of methyl A-acetyl-a-L-acosaminide (13) has been described by reduction of the appropriate acetylated oxime by diborane. The thioglycoside (14) was also prepared. ... 

Peel and Sutherland [34] synthesized the lactone acid (21) starting with the formation of the epimeric diformates by a Prins reaction of norbornadiene and paraformaldehyde to give (22a). Hydrolysis and Jones oxidation of (22a) then gave the keto acid (22b) which underwent ring opening with hydrogen bromide in acetic acid to the bromo compound (23). Baeyer-Villiger oxidation of the latter and addition of sulphuric acid to the reaction mixture followed by work up with alkali afforded an overall conversion to (21) of which the p-bromo-phenacyi ester was converted by the sequence - p-phenylbenzoylation, reduction with zinc and acetic acid and diborane reduction - to the alcohol (14d), previously taken forward to the aldehyde (lb) by Corey. 

Interestingly, as also shown in Scheme 9.111, diborane (B2H6) in oxacyclopentane (THF, i.e., HsB THF) preferentially reacts with the carboxylic acid portion of the same fran5 -P-(2-carbomethoxycyclohexane)propanoic acid. Presumably this is because the bond between oxygen and boron is more easily formed and a proton can be lost to, for example, solvent. Thus, it is predicted that reduction under these circumstances preferentially leads to rran5 -3-(2-carbomethoxycyclohexane)-1-propanol, which then leads to fran5 -3-oxa-2-oxobicyclo[5.4.0]undecane, a lactone isomeric with that in the first example of the scheme. 

A further synthesis of L-rhodinose (17), as well as of D-amicetose (20), has been achieved through the deamination of L-glutamic acid (21) (Scheme 6). The 5-carboxylate (22) was converted to the chain-extended ketone (23), reduced with diborane, and the resulting C-5 epimeric lactones separated chromato-... 

Two new methods for the reduction of aldonolactones to aldoses have been developed for use in small-scale syntheses either the lactone itself was reduced with diborane in THF, or an 0-tetrahydropyranyl derivative was reduced with a 1 1 mixture of lithium aluminium hydride and aluminium chloride in ether. The yield of aldose depends on a number of factors and may be low due to the ease of reduction of the aldose to the alditol. The catalytic hydrogenation of D-glucose in the temperature range 100—170 °C and at pressures of 20—80 atmospheres has been examined the effects of pH and promoters (e.g. magnesium, barium chloride, calcium sulphate) were also examined. The rate of hydrogenation was enhanced at pH 8, and calcium sulphate was the most effective promoter at pH 6.8. 

The presence of arginine as C-terminal amino acid was checked by its conversion into N-methylornithine by action of diborane. Herbicolin A contains a lactone ring which can be opened by mild treatment with alkali. After chromic acid oxidation of herbicolin B and hydrolysis, both... 

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