Lactone cleavage

Hall and Bischofberger177 found that, when 2,3 5,6-di-0-isopro-pylidene-D-gulono-1,4-lactone was oxidized with ruthenium(VIII) oxide and an excess of sodium periodate, it gave 2,3 5,6-di-0-isopro-pylidene-D-riho-4-hexulosono-l,4-[(R) or (S)]-lactol. Similar results were observed with 2,3 5,6-di-0-isopropylidene-D-mannono-1,4-lactone and 2,3 5,6-di-O-isopropylidene-D-allono-l,4-lactone. This oxidation presumably proceeds by way of lactone cleavage and oxidation of the free 4-hydroxyl group followed, on acidification by relac-tonization, and formation of the new lactol. 

A base-catalyzed Grob-Wharton fragmentation of a hydroxybicyclo[5.4.0]nonyl sulfone 3 yielded a cyclononenone derivative 4.193 The reaction is initiated by lactone cleavage with powdered potassium hydroxide in methanol, whereas sodium methoxide was not successful. 

Methoxide promoted lactone cleavage in a tricyclic sulfone initiated a Grob-Wharton fragmentation which gave a cycloundecadienone derivative 1 in refluxing methanol.210... 

An additional example of lactone hydrolysis includes the API lovastatin (9). In addition to lactone cleavage reactions, lactone formation can also occur as in the case of the API cephalosporin cefuroxime sodium (Fig. 4) (10). 

Synthetic Applications. (5 )-Dihydro-5-(hydroxymethyl)-2(3H)-furanone (2) was first described in 1971 as an intermediate in the synthesis of o-ribose from r-glutamic acid. Since then, this lactone and its (f )-enantiomer have found widespread use as chirons for constructing a rich variety of natural products ranging from simple pheromones to complex macrocycles and ionophore antibiotics. The chemical manipulation of these chirons often involves lactone cleavage at an early stage, - - as illustrated by the preparation of suitable intermediates for the synthesis of the Vespa orientalis pheromone (R)-S-n-hexadecanolactone (14) (eq 4), the antiviral fungal metabolite brefeldin A (15) (eq 5), and (7aa)-cp/-hemibrevetoxin B (16) (eq 6). ... 

These cyclobutanones differ only in configuration at the alkoxy-bearing position, as was shown by conversion of the two diastereomers 16 and 17 to the same product by Baeyer-Villiger oxidation/hydrogenolytic lactone cleavage. ... 

Lactone Cleavage, Analogous to esters, lactones are also efficiently cleaved with TMS-I to provide ta-iodocarboxylic acids, which may be further functionalized to afford bifunctional building blocks for organic synthesis (eq 7). Diketene reacts with TMS-I to provide a new reagent for acetoacylation. ... 

An unusual sugar lactone cleavage reaction, followed by an intramolecular rearrangement, leads to the formation of primary iodides with the same configuration. The lactone is proposed to be opened by an iodide anion, with inversion of configuration at C-5. The formation of acetoxonium ion then occurs from secondary... 

In this case the use of the Doyle dirhodium catalyst Rh2(S-MPPIM)4 (a complex containing the hgand methyl (4S)-2-oxo-3-(3-phenylpropa-noyl)-4-imidazohdine carboxylate) converted the diazoacetate (S)-97 into the ds-flised bicychc lactam (—)-98 in 70% yield together with some dimeric by-products (c. 18%). Elaboration of the piperidine ring entailed lactone cleavage with the anion of phenyl methyl sulfone followed by reduction... 

Lactone Cleavage with Auxiliaries to Force a p-H Elimination 182... 

Figure 8 Productive lactone cleavage with Bronstedt bases (A) and/or additives and final ligand exchange (B).

We therefore conclude that (a) the base (both the alkali metal and the alkoxide) plays an important role in aU lactone cleavage reactions studied so far, that (b) energy barriers are lower than those for P-hydride elimination mechanisms and for nickelalactone formation, and thus that (c) lactone formation and deprotonation in a-position to the lactone carbonyl group appear to be the most viable route from CO2 and ethylene to coordinated acrylate. 

Figure 9 The first catalytic cycle at all. The incompatibility of NaO Bu and CO2 required the separation of C02-rich lactone formation and C02-poor lactone cleavage.

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