Ring substituted lactones

Whilst all the above-mentioned examples involve the use of y,8-unsaturated esters, Bruckner [107] studied in detail the AD of the p,y-unsaturated analogues (Scheme 31). Dihydroxylation followed by Iactonization yielded ring substituted lactones such as 97. A whole host of optically active lactones and butenolides... 

Various cyclic esters have been subjected to hpase-catalyzed ring-opening polymerization. Lipase catalyzed the ring-opening polymerization of 4- to 17-membered non-substituted lactones.In 1993, it was first demonstrated that medium-size lactones, 8-valerolactone (8-VL, six-membered) and e-caprolactone (e-CL, seven-membered), were polymerized by lipases derived from Candida cylindracea, Burkholderia cepacia (lipase BC), Pseudomonas fluorescens (lipase PF), and porcine pancreas (PPL). °... 

Synthesis of Lactone Ring Substituted Analogues of AHLs. 300... 

Enantioselective Ring-Opening Polymerizations of Substituted Lactones Using Lipases... 

A clever application of this reaction has recently been carried out to achieve a high yield synthesis of arene oxides and other dihydroaromatic, as well as aromatic, compounds. Fused-ring /3-lactones, such as 1-substituted 5-bromo-7-oxabicyclo[4.2.0]oct-2-en-8-ones (32) can be readily prepared by bromolactonization of 1,4-dihydrobenzoic acids (obtainable by Birch reduction of benzoic acids) (75JOC2843). After suitable transformation of substituents, mild heating of the lactone results in decarboxylation and formation of aromatic derivatives which would often be difficult to make otherwise. An example is the synthesis of the arene oxide (33) shown (78JA352, 78JA353). 

Deprotonation of (alkylcyclopropylidenemethyl)cyclopropanes (alkyl = methyl, cyclopropyl) with BuLi and subsequent reactions with various electrophiles afforded the corresponding ring-substituted methylenecyclopropanes (equation 295)365. When the lithiated compounds are treated with C02, carboxylic acids are obtained, together with isomeric lactones. These can be regarded as formal 3+2 adducts of the methylenecyclopropanes with C02 (equation 295)366. 

Lactones and the macrocyclic lactones, like the y- and 5-lactones, are of importance since these ring systems are found widespread in nature. The simpler substituted lactones are important building blocks in the synthesis of many natural products, e.g. in the fields of antibiotics, anticancer pharmaceuticals, pheromones and prostaglandins to name but a few. 

Cobalt catalysts were used for substitution reactions of organic halides [442] and a small-ring enol lactone [Eq. (201) 443]. The cobalt salt seems to be the most effective one among a few transition metal salts involving copper, nickel, [see Eq. (130)], and iron. Without the catalyst, Grignard reagent attacked the carbonyl carbon of the enol lactone to give a mixture of a few ketonic compounds in a low yield. 

Kaneko extended the early work of Schild on tuberostemonine, demonstrating the presence of a C-ethyl group and two lactone rings (1). Edwards et al. 2) used spectroscopic methods to elaborate this picture. Bisdehydrotuberostemonine, the product of silver oxide oxidation 3,4), was shown to contain a pyrrole ring substituted as in I. The NMR-spectrum of this compound confirmed the presence of the C-ethyl group. In addition it was deduced that the second lactone ring was substituted as in II, with a possible further carbon-carbon bond at position 3. 

The ring-opening reaction of 3-substituted -lactones is promoted by cesium fluoride (Scheme 2.29) [45], which works as a base to form the S-Cs compound. -Lactones are converted into -arylthiocarboxyhc acids efficiently without elimination. 

Functionalized y-lactones are important synthetic intermediates for a number of biologically active natural products [102]. An interesting strategy based upon the AD reaction of unsatuxated esters or carbamates, combined with the spontaneous kinetic cycHzation to form five-membered ring lactones, has recently been established (Scheme 27). Thus, asymmetric dihydroxylation of p,y- and y,8-un-saturated esters 73 and 74 results in the hydroxyl-substituted lactones 75 or the side-chain functionaUzed system 76 respectively, in high optical purity. This strategy was appHed to the synthesis of numerous natural products. 

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