Seven-membered ring lactones

On treatment with trimethyl(2-propenyl)silane and titanium(IV) chloride, chiral methyl fi-formylcarboxylates give di- and tetra-substituted y-lactones with moderate to good stereoselectivity. Participation of seven-membered ring chelates was suggested65. 

In the case of using carbon dioxide as the electrophile, seven-membered ring lactones were obtained, the reaction being exemplified with compound 405 (67% yield). On the other hand, for carbonyl compound derivatives of type 404, their cyclization under acidic conditions (85% H3PO4, toluene reflux) gave the corresponding cyclic thioethers 406 in 76-90% yield . 

The lactone concept is not restricted to the simple model biaryl synthesis presented here. It has been successfully expanded to a broad series of structurally diverse biaryl substrates (e.g., lactones with additional stereocenters and functional groups, configurationally stable lactones, seven-membered lactones, and again configurationally unstable biaryl hydroxy aldehydes ), to different activation modes in the ring-opening step (e.g., use of metallated nucleophiles, carbonyl activation by Lewis acids, (Ti -complexation, etc.), and for various strategies of stereoselection (e.g., external vs. internal asymmetric induction). ... 

Even six or seven-membered ring lactones were reported by AuCI catalyzed reactions. Pale et al. prepared y- and 6-alkylidene lactones by intramolecular cycliza-tions of co-acetylenic acids. Once again, the process was stereospecific and only Z products were obtained in the case of substituted alkynes [91]. 

Enzymatic Baeyer-Villiger oxidations have been studied for a long time some very useful applications in natural product synthesis date back more than two decades. For example, prochiral (3A, 5,S )-4-hydroxy-3,5-dimethylcyclohexanone was successfully oxidized using a CHMO from Acinetobacter sp. NCIMB 9871. In this case the seven-membered ring formed rearranges spontaneously into the thermodynamically more stable y-lactone. The rearranged lactone has been used in the synthesis of natural products such as tirandamycin or calyculin A (Fig. 25) [157-159],... 

The coordination polymerisation of lactones with a six- and seven-membered ring (5- and e-lactones respectively) occurs via ring opening at the C(0)-0 linkage to generate metal alkoxide chain terminals, following a reaction analogous to that presented by scheme (9). 

The dehydrohalogenation has also been applied to bicyclic lactones cyclopropenes can be isolated for seven-membered ring lactones but for smaller rings undergo addition of r-butanol39"41 ... 

So far, no systematic investigation of the length of the side chain in VII/116 (Scheme VII/23) has been made. There have been, however, enquieries into lactonization reactions, in which the side chain contained two [94], three [4] [83] [95] [96], and four [93] carbon atoms. In these cases, the intermediate hemiacetal ring is a five-, six-, or seven-membered ring. The yields of the lactones, generated via five- and six-membered hemiacetals, are usually high (90 % and more). If a lactonization reaction involves a seven-membered hemiacetal, the yields are distinctly lower. 

Lactones have also been reacted with trimethyl(trifluoromethyl)silane under fluoride catalysis in tetrahydrofuran however, only the silylated hemiketals could be isolated cleanly in the case of five- and six-membered ring lactones (in 70 and 75% yield, respectively). In the case of the seven-membered ring lactone, a mixture of products resulted. 

Phenylseleno-lactonization of 4-cyclooctene-l-carboxylic acid (41) gives a mixture of six- and seven-membered-ring lactones 42 A and 42B by TLC and H-NMR spectroscopy in a 3 1 ratio. After passing through a silica gel column, however, only one product, the six-membered lactone 42 A, is obtained in 94% yield 3. 

For the ring expansion step an extra carbon is needed, of course, and the 7 carbon of the lactone ring appears to be the best candidate. It not only bears a relatively labile C-O bond that upon disconnection might evolve into the carboxylate unit required for decarboxylation, but this carbon is also proximal to the a anion of the cyclohexanone portion of molecule I that is expected to appear in strong basic medium. The union of these two carbons will produce a cyclopropyl ketone whose central C-C bond might break up, prodded by the carbonyl unit, to yield a seven-membered ring system. 

In a similar manner, the diacetates from cyclic dienes were enzymatically hydrolyzed and transformed to the enantiomers of diene acids 50 [71]. The diene acids from the seven-membered ring were subsequently used in intramolecular cis- and trans-1,4-acetoxylactonizations (cf. Scheme 8-14), leading to four different isomers of enantiomerically pure lactones. 

Seven-membered ring lactones can be accessed in excellent yields by the Smia-mediated intramolecular Reformatsky reaction as well. Although several substitution patterns provide exceptional relative asymmetric induction in this process (equation 62), it is clear that high diastereoselectivity cannot be achieved for all substitution patterns in the formation of seven-membered ring lactones. ... 

Atom transfer carbonylation of 3-iodo alcohols provides a useful method for the synthesis of five-membered ring lactones (Scheme 4-49) [85]. The method is also applicable to six- and seven-membered ring lactones. 

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