Three-membered ring lactone

It is very difficult to prepare three-membered ring lactones. One attempted preparation, by the epoxidation of di-f-butyl ketene, gave an unstable compound with an IR stretch at 1900 cm-1 that decomposed rapidly to the four-membered lactone shown. Do you think they made the three-membered ring ... 

The oxidation of organic substances by cyclic peroxides has been intensively studied over the last decades , from both the synthetic and mechanistic points of view. The earliest mechanistic studies have been carried out with cyclic peroxides such as phthaloyl peroxide , and more recently with a-methylene S-peroxy lactones and 1,2-dioxetanes . During the last 20 years, the dioxiranes (remarkable three-membered-ring cyclic peroxides) have acquired invaluable importance as powerful and mild oxidants, especially the epoxidation of electron-rich as well as electron-poor alkenes, heteroatom oxidation and CH insertions into alkanes (cf. the chapter by Adam and Zhao in this volume). The broad scope and general applicability of dioxiranes has rendered them as indispensable oxidizing agents in synthetic chemistry this is amply manifested by their intensive use, most prominently in the oxyfunctionalization of olefinic substrates. 

Transition metal complexes have proved very useful in both the catalytic and stoichiometric production of cyclic lactones. A series of palladium(O)-phosphine complexes have been shown to be effective for the conversion of three-membered ring systems to cyclic lactones [Eq. (45)] (114). When isopropylidenecyclopropane and [Pd(dba)2]-PPh3 (dba = dibenzylidenea-cetone)(4 1) in benzene were treated with 40 atm carbon dioxide at 126°C for 20 hr, 69% of the lactone (34) was formed. In contrast, when [Pd(diphos)2] was used as the substrate under similar conditions 48% of 35 was produced with only trace amounts of 34. None of the complexes appeared to be active for terminal alkenes such as 36 or 37. 

Barnett and Sohn (12, 13, see also 14) have discovered that the iodolactoni-zation of b,r-unsaturated carboxylic acid salts 37 yield, under kinetically controlled conditions, the Y-iodo-B-lactones 39 in preference to the more stable B-iodo-Y-lactones l. Similar results were obtained in the course of the bromolactonization reaction. Thus, here again, the formation of a four-membered ring is more facile than that of a five-membered ring. This can be rationalized on the basis of Stork s analysis, i.e. the internal opening by the carboxylate anion of the three-membered ring iodonium ion (or bromonium) 38 39 is preferred over the other mode of opening 40 41 for stereoelectronic reason. 

A formal total synthesis of (+)-aspicilin, an 18-membered ring lactone isolated from the lichen Aspicilia gibbosa, is accomplished by the FDP aldolase protocol.46 The three carbon chain extension of benzyl protected 4-hydroxy-butanal is achieved with DHAP under the influence of FDP aldolase. The acid... 

In the cyclodimerization of methylenecyclopropanes and carbon dioxide, the three-membered ring is opened to form five-membered lactones. In the presence of palladium (O)-triphenylphosphine. the 0-mcthy enc-Ucionc was obtained in 3... 

Not all substitution reactions under basic conditions occur with simple inversion. Sometimes, nucleophilic substitution at stereogenic C proceeds with retention of configuration. In such a reaction, two sequential nucleophilic substitutions have usually occurred. For example, the reaction of a-diazoniocarboxylic acids with nucleophiles such as Cl occurs with retention. In the first Sn2 substitution, the O of the carboxylate acts as a nucleophile, displacing N2 with inversion to give a three-membered ring (an a-lactone). In the second Sn2 substitution, Cl displaces O with inversion to give the product with overall retention. 

In addition to step and chain polymerizations, another mode of polymerization is of importance. This is the ring-opening polymerization of cyclic monomers such as cyclic ethers, esters (lactones), amides (lactams), and siloxanes. Examples of commercially important types are given in Table 10.1. Of those listed, only the polyalkenes are composed solely of carbon chains. Those that have enjoyed the longest history of commercial exploitation are polyethers prepared from three-membered ring cyclic ethers (epoxides), polyamides from cyclic amides (lactams), and polysiloxanes from cyclic siloxanes. 

Halolactonisation works well because bromine and iodine form three-membered ring intermediates when they attack an alkene. Sulfur (II) and selenium (II) electrophiles form even better defined intermediates of this kind and similar cyclisation reactions occur with impressive control over selectivity.27 A simple example would be the formation of the bicyclic lactone 181. As the carboxylic acid is tethered to the five-membered ring, it can cyclise only to the intermediate with S(e) on the other face 180. The mechanism is similar to that of iodolactonisation and the stereochemical points are the same. The products are useful for the generation of radicals as Bu3SnH removes a PhSe group and leaves a radical behind while oxidation and elimination leaves a new alkene (chapter 33). 

Only three macrolides have been isolated from lichens (Table VII). On the other hand, plants produce about 700 macrolides (Table VIII), but most of them are macrodiolides or macrotriolides such as tannins and alkaloids (e.g., pyrroliz-idines). Their biosynthetic pathways are quite different from polyketide macrolides. A small group of monolactone macrolides has up to 19-membered ring lactones. Some of them have a musky odor. 

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