Lactones From unsaturated carboxylic acids

The intramolecular cyclization of unsaturated carboxylic acids is one of the most straightforward routes to the synthesis of lactones, which leads directly to the desired products. In general, electrophilic reagents such as iodine, phenylselenium chloride, and mercuric or palladium salts promote this cyclization [26]. However, a second step is necessary to remove the reagent. Although the cyclization of unsaturated carboxylic acids promoted by a Brpnsted acid is a well-known reaction, it occurs mostly with more than stoichiometric quantities of a Brpnsted acid [27], On the other hand, it was reported that a variety of substituted y- and 5-lactones could be easily prepared from unsaturated carboxylic acids in excellent yields using trifluoromethane-sulfonic acid (TfOH) as a catalyst (Scheme 9.17) [28]. However, applications of this method, such as an asymmetric... 

The adjacent iodine and lactone groupings in 16 constitute the structural prerequisite, or retron, for the iodolactonization transform.15 It was anticipated that the action of iodine on unsaturated carboxylic acid 17 would induce iodolactonization16 to give iodo-lactone 16. The cis C20-C21 double bond in 17 provides a convenient opportunity for molecular simplification. In the synthetic direction, a Wittig reaction17 between the nonstabilized phosphorous ylide derived from 19 and aldehyde 18 could result in the formation of cis alkene 17. Enantiomerically pure (/ )-citronellic acid (20) and (+)-/ -hydroxyisobutyric acid (11) are readily available sources of chirality that could be converted in a straightforward manner into optically active building blocks 18 and 19, respectively. 

Curran s synthesis of ( )-A9(l2)-capnellene [( )-2] is detailed in Schemes 30 and 31. This synthesis commences with the preparation of racemic bicyclic vinyl lactone 147 from ( )-norbomenone [( )-145] by a well-known route.61 Thus, Baeyer-Villiger oxidation of (+)-145 provides unsaturated bicyclic lactone 146, a compound that can be converted to the isomeric fused bicyclic lactone 147 by acid-catalyzed rearrangement. Reaction of 147 with methylmagne-sium bromide/CuBr SMe2 in THF at -20 °C takes the desired course and affords unsaturated carboxylic acid 148 in nearly quantitative yield. Iodolactonization of 148 to 149, followed by base-induced elimination, then provides the methyl-substituted bicyclic vinyl lactone 150 as a single regioisomer in 66% overall yield from 147. 

The Chinese plant Amoora yunnanensis contains dammaranes 642 and 643 (746), and oleanane 644 was isolated as a triacetate from Mentha villosa (747). It is conceivable that 644 is an artifact formed by HC1 acting on the corresponding unsaturated carboxylic acid, since this type of acid-catalyzed lactone formation is well known (748). 

Iodocyclization.1 This reagent converts various unsaturated alcohols into ethers and unsaturated carboxylic acids into lactones. It is particularly useful for synthesis of 2-(l-iodomethyl)oxiranes from allylic alcohols and of 2-(l-iodomethyl)oxetanes from homoallylic alcohols. 

The following lactones were similarly prepared from the appropriate unsaturated carboxylic acids. ... 

Intramolecular cyclization is a useful method for the preparation of lactones and cyclic ethers [34], The most common examples are iodolactonization and iodoetherification, the former using a carboxylic acid derivative as the nucleophile and the latter relying on a hydroxy group. Thus, butyrolactones are available from Y, -unsaturated carboxylic acid derivatives [1,35,36], while unsaturated alcohols lead to cyclic ethers [37-40], Lactones are also available from a wide variety of nucleophiles such as carbonates [41], orthoesters [42], or carbamates [43,44], which can all be used in place of a carboxylate anion [44,45],... 

The resulting unsaturated carboxylic acid (3) was then treated with NBS in DMF. This reaction gives the bromo lactone (4) and a diastereoisomer in the ratio 94.5 5.5 and is therefore highly stereoselective. The mixture can be separated to give optically pure 4 in 64% yield from 3. Remaining steps involve reduction to... 

Oxazine derivatives are formed from unsaturated AAs. Vinylglycine, after epoxidation at the double bond, yielded methyl l,3-oxazin-2-one-4-carboxylate after treatment with sodium methoxide or p-chlorophenol (90TL2291). Similarly, some alkenes react with methyl a-methoxyhippurate and cyclization occurs with BF3-Et20 (75TL3737). In sulfuric acid butyro-lactones are formed. 

The reaction of alkenyl mercurials with alkenes forms 7r-allylpalladium intermediates by the rearrangement of Pd via the elimination of H—Pd—Cl and its reverse readdition. Further transformations such as trapping with nucleophiles or elimination form conjugated dienes[379]. The 7r-allylpalladium intermediate 418 formed from 3-butenoic acid reacts intramolecularly with carboxylic acid to yield the 7-vinyI-7-lactone 419[380]. The /3,7-unsaturated amide 421 is obtained by the reaction of 4-vinyl-2-azetidinone (420) with an organomercur-ial. Similarly homoallylic alcohols are obtained from vinylic oxetanes[381]. 

Linkers that enable the preparation of y-lactones by cleavage of hydroxy esters from insoluble supports are discussed in Section 3.5.2. Resin-bound y-lactones have been prepared by Baeyer-Villiger oxidation of cyclobutanones [39], by intramolecular addition of alkyl radicals to oximes [48], by electrophilic addition of resin-bound sele-nenyl cyanide or bromide to 3,y-unsaturated acids (Figure 9.2 [100]), and by palladium-mediated coupling of resin-bound aryl iodides with allenyl carboxylic acids (Entry 10, Table 5.7 [101]). 

B as an ester- or lactone-substituted aldehyde enolate. Such enolates undergo condensations with all kinds of aldehydes, including paraformaldehyde. An adduct E is formed initially, acy-lating itself as soon as it is heated. The reaction could proceed intramolecularly via the tetrahedral intermediate D or intermolecularly as a retro-Claisen condensation. In both cases, the result is an acyloxy-substituted ester enolate. In the example given in Figure 13.50, this is the formyloxy-substituted lactone enolate C. As in the second step of an Elcb elimination, C eliminates the sodium salt of a carboxylic acid. The a,/)-unsaturated ester (in Figure 13.50 the 0J,/3-unsaturated lactone) remains as the aldol condensation product derived from the initial ester (here, a lactone) and the added aldehyde (here, paraformaldehyde). 

In the carbonyl region, at a weak extent of conversion, photooxidation of ABS and BR led to the formation of a thin absorption band with maxima at 1697 cm-1 (a, (3-unsaturated acids) and 1683 cm-1 (a, (3-unsaturated ketone), and to the formation of a broader absorption band with a maximum at 1721 cm-1. As photooxidation proceeded, the intensity of this latter band increased and shifted to 1717 cm-1 whilst the band at 1697 cm-1 became hard to observe. The intensity of the band at 1697 cm-1 ceased to increase after 16 h of irradiation. When the exposure time was longer than 22 h, only one absorption band was observed. Its maximum shifted from 1717 to 1725 cm-1. In parallel, a shoulder was detected in the range 1775-1785 cm-1. It was shown that the absorption around 1725 cm-1 resulted from the convolution of various species saturated carboxylic acid (1717 cm - ), aliphatic ester (1735 cm-1), a, (3-unsatur-ated anhydride (1724-1782 cm-1), saturated aldehyde (1727-2720 cm-1) and saturated ketone (1725 cm-1). The maximum at 1780 cm-1 has been assigned to three types of structure a, (3-unsaturated anhydride (1724 and 1782 cm-1), perester (1789 cm-1) and 7-lactone (1775 and 1175 cm-1). 

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