Lactones four-membered

Adam, W., Heil, M., Mosandl, T. and Saha-Moeller, C.R. (1992) Dioxetanes and a-peroxy lactones, four-membered ring cyclic peroxides, in Organic Peroxides (ed. W. Ando), John Wiley Sons, Chichester, UK, pp. 221-254. 

Heterocycles form a specific class of monomers. They do not usually undergo radical polymerization, and the kind of ionic polymerization mechanism is determined by the kind of heteroatom, substituent and ring size. Oxiranes and, aziridines are polymerized by both ionic mechanisms. With the exception of lactone, four-membered and larger heterocycles with oxygen and with substituted nitrogen can only be polymerized cationically heterocycles with unsubstituted nitrogen can also be polymerized anionically. 

Lactones whose rings are three or four membered (a lactones and p lactones) are very reactive making their isolation difficult Special methods are normally required for the laboratory synthesis of small ring lactones as well as those that contain rings larger than SIX membered... 

P-Hydroxy acids lose water, especially in the presence of an acid catalyst, to give a,P-unsaturated acids, and frequendy P,y-unsaturated acids. P-Hydroxy acids do not form lactones readily because of the difficulty of four-membered ring formation. The simplest P-lactone, P-propiolactone, can be made from ketene and formaldehyde in the presence of methyl borate but not from P-hydroxypropionic acid. P-Propiolactone [57-57-8] is a usehil intermediate for organic synthesis but caution should be exercised when handling this lactone because it is a known carcinogen. 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

Asymmetric alcoholyses catalyzed by lipases have been employed for the resolution of lactones with high enantioselectivity. The racemic P-lactone (oxetan-2-one) illustrated in Figure 6.21 was resolved by a lipase-catalyzed alcoholysis to give the corresponding (2S,3 S)-hydroxy benzyl ester and the remaining (3R,4R)-lactone [68]. Tropic acid lactone was resolved by a similar procedure [69]. These reactions are promoted by releasing the strain in the four-membered ring. 

In the case of y,6-unsaturated acids, five-membered rings (y-lactones) are predominantly formed (as shown above note that Markovnikov s rale is followed), but six-membered and even four-membered lactones have also been made by this procedure. There is a gem- dimethyl effect that favors formation of 7-11 membered ring lactones by this procedure. ... 

Several small-size (four-membered) lactones have been reported to be polymerized through lipase catalysis. The polymerization of /Tpropiolactone (/ -PL) by Pseudomonas family lipases as catalyst in bulk produced a mixture of linear... 

It will be seen that the enediolic system can theoretically be written in the isomeric 2-keto (II) or 3-keto (III) forms and these in turn are seen to be derived from the 2-keto and the 3-keto acids IV and V, respectively (compare with benzoin which reacts with iodine in an analogous fashion to L-ascorbic acid). Consequently the synthesis of L-ascorbic acid and of its analogs has consisted in devising methods for the formation of 2-keto or 3-keto hydroxy acids followed by their enolization and lactonization. Four main methods are available for the synthesis of analogs of L-ascorbic acid containing the characteristic five-membered unsaturated enediolic ring. 

Singlet oxygen reacts with electron rich or highly strained alkenes to form 1,2-dioxetanes. These four-membered ring peroxides decompose on warming to two carbonyl compounds (or moieties), usually with appearance of light emission (chemiluminescence). The macrocyclic bis-lactone in (6.17)608>, a musk fragrance, has been synthesized via such a sequence. 

Whereas lactone annulation invokes a relief of strain of the four membered ring by migration of the ring bond to an electron deficient oxygen, a similar migration to an election deficient carbon creates a cyclopentanone synthesis (Eq. 73). The release of approximately 84 kJ/mole (20 kcal/mole) provides a strong driving force. Thus, the 1,1-cyclobutanone annulation of ketones translates into a 1,1-cyclopentanone annulation. 

Configurational match/mismatch governs these reactions so that different products may be produced in high yield and selectivity when enantiomeric catalysts are apphed to the same substrate [61, 62], as illustrated by the reaction processes in Scheme 15.8 [61]. Additional examples in the steroidal field have also been reported [66]. In these cases the formation of four-membered ring y9-lactones is common. 

Polymerizations of six- and four-membered lactones initiated with aluminum porphyrins [(TPP)AlX, 1] proceed via (porphinato)aluminum alkoxide and car-boxylate as the growing species, respectively (Schemes 9 and 10) [74,75] to give polyesters with narrow MWD, although it is well known that the polymerization... 

A specific inhibitor of the major proteasomal activities is lactacystin, a compound formed by Streptomyces. Lactacystin is converted reversibly, by loss of N-acetyl-cysteine, into a P-lactone known as c/asto-lactacystin. The N-terminal amino group attacks the reactive four-membered ring of the lactone (Eq. 12-22)358/359... 

Exercise 18-46 Would you expect 3-butenoic acid to form a lactone with a five-or a four-membered ring when heated with a catalytic amount of sulfuric acid ... 

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. 

PL, unlike other lactones, undergoes polymerization with weakly nucleophilic initiators such as metal carboxylates, tertiary amines, phosphines, and a variety of other initiators [81-83]. This is primarily due to the high ring-strain in the four-membered ring. Pyridine and other tertiary amines initiate the anionic polymerization via a betaine that rapidly transforms into a pyridinium salt of acrylic acid. In order to minimize the chain transfer reactions, the polymerization is performed at a temperature between 0 and 10 °C (Scheme 9). 

---