Lactones hydrogenolysis

This compound, previously prepared174 in low yield from alginic acid, has been synthesized128 from 61 by oxidation at C-2, and stereospecific reduction of the intermediate methyl 5-0-benzyl-/3-D-nrab-ino-2-hexulofuranosidurono-6,3-lactone. Hydrogenolysis of the 5-0-benzyl group yielded the title compound in a superior yield. 

A more detailed examination of the lactone hydrogenolysis method will be described later although it is worth mentioning at this stage that Shirahama has subsequently adopted this method in a related kainoid synthesis (Scheme 32).57... 

In ketones existing largely as the enol, palladium may prove effective in minimizing hydrogenolysis, Hydrogen was added slereoselectively to the least hindered side of L-ascorbic add (3) to give L-gulono-1,4-lactone (4)... 

It is important to note that the one-step conversion of 27 to 28 (Scheme 4) not only facilitates purification, but also allows differentiation of the two carbonyl groups. After hydrogenolysis of the iV-benzyl group (see 28—>29), solvolysis of the -lactone-ring in 29 with benzyl alcohol and a catalytic amount of acetic acid at 70 °C provides a 3 1 equilibrium mixture of acyclic ester 30 and starting lactone 29. Compound 30 can be obtained in pure form simply by washing the solid mixture with isopropanol the material in the filtrate can be resubjected to the solvolysis reaction. 

Lactones (cyclic esters) are usually stable toward hydrogenolysis. However, the aromatic lactones contain benzylic C—O bonds and can be hydrogenolyzed. As an example, the hydrogenolysis of an aromatic lactone was performed over Ra-Ni in THF under 4 atm H2 pressure at 50°C for 30 hours.213... 

The hydrogenolysis proceeds usually with inversion on Pd. This ability of Pd was used for stereospecific hydrogenation of a lactone during the synthesis of a phenyl kainoid on 10% Pd(OH2)/C in AcOEt at 40°C (Scheme 4.44).214... 

The lactone structure is a versatile synthetic intermediate that can be used to access a variety of 4-substituted pipecolic derivatives. Hydrogenolysis in meth-anolic HCl, followed by hydrolysis and desalting, gave 4-hydroxypipecolic... 

The described approach also allows a simple access to indole alkaloids of the vallesiachotamine type. In this process, the Cbz-protected secondary amino function in the formed cycloadducts such as ent-2-805 is deprotected by hydrogenolysis. There follows an attack at the lactone moiety to form a lactam. In this way, the indole alkaloid (-)-dihydroantirhin (2-797) was prepared [400, 401]. 

Treatment of 25 and 26, respectively, in pyridine with equimolar amounts of benzyloxycarbonyl chloride at low temperature, followed by addition of an excess of ethoxycarbonyl chloride, yielded the corresponding methyl 5-0-(benzyloxycarbonyl)-2-0-(ethoxycarbonyl)-/3-(57) and -a-D-glucofuranosidurono-6,3-lactone (58). Hydrogenolysis of the benzyloxycarbonyl group resulted in formation of methyl 2-0-(ethoxycarbonyl)-/ - (59) (70%) and -a-D-glucofuranosidurono-6,3-lactone (60) (30%), respectively, both in crystalline form. The /3-D... 

The d-lactone (Scheme 38.11) can be efficiently obtained by the telomerization of butadiene and C02. Its biphasic hydrogenation with an in-situ-prepared Rh/ mtppts catalyst yields 2-ethylidene-6-heptenoic acid (and its isomers) [136]. Note, that the catalyst is selective for the hydrogenolysis of the lactone in the presence of two olefmic double bonds this is probably due to the relatively large [P] [Rh] ratio (10 1) which is known to inhibit C = C hydrogenations with [RhCl(wtppms)3]. The mixture of heptenoic acids can further be hydrogenated on Pd/C and Mo/Rh catalysts to 2-ethylheptanol which finds several applications in lubricants, solvents, and plasticizers. This is one of the rare examples of using C02 as a Cl building block in a transition metal-catalyzed synthetic process. 

Hydrogenolysis of the benzylether of lactone 141 (H2, 10% Pd/C) quantitatively afforded (-)-wikstromol ent-3). The overall yield of ent-3 from diisopropyl malate 107 over six steps was 30% [62]. This strategy for the construction of optically-active lactone lignans provided a short and stereoselective synthesis with comparably good overall yield. 

Hydrogenation of phthalic anhydride over copper chromite afforded 82.5% yield of the lactone, phthalide, and 9.8% of o-toluic acid resulting from hydrogenolysis of a carbon-oxygen bond [1015]. Homogeneous hydrogenation of a,a-dimethylsuccinic anhydride over tris(triphenylphos-phine)rhodium chloride gave 65% of a,a-dimethyl- and 7% of )S,)S-dimethyl-butyrolactone [1016]. 

By far the most frequent reduction of esters is their conversion to alcohols. The reaction is important not only in the laboratory but also on an industrial scale where it is used mainly for hydrogenolysis of fats to fatty alcohols and glycerol. Lactones are reduced to diols. 

If, however, the catalytic hydrogenolysis of a 2,6-dibromohexonolactone was performed with no acid acceptor present, an unusual reduction took place to give a 6-bromo-2,3,6-trideoxyhexonolactone. Thus, 2 gave 6-bromo-2,3,6-tri-deoxy-D-eryfhro-hexonolactone (1) (Scheme 2) [35]. Similar reductions took place with other hexono- and pentonolactones independent of the relative stereochemistry of the C-2 and C-3 substituents [35]. A 7-bromo-2,3,7-tri-deoxyheptonolactone has also been synthesized in this way [22]. The initial step in the reactions was shown to be a reductive elimination to give an intermediate 2,3-unsaturated lactone which subsequently was saturated [35]. 

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