Lactones eight-membered

An example of a surprisingly facile and stereoselective formation of an eight-membered lactone from an acyclic precursor diene ester was observed during the total synthesis of the antitumor agent octalactin A (148) (Scheme 27) [81]. The dense substitution pattern in cyclization substrate 146 presumably imposes... 

The C(9)—C(16) subunit was synthesized from the same starting material. The chain was extended by a boron enolate addition to 2-methylpropenal (Step D-2). After introduction of a double bond by selenoxide elimination in Step E-4, a Claisen rearrangement was used to generate an eight-membered lactone ring (Step E-6). 

Ru3(CO)12 catalyzes the carbonylation of the sp carbon of allenyl alcohols, giving rise to y- and <5-lactones in good yields (Scheme 16.30) [34], The methodology was successfully applied to the syntheis of seven- and eight-membered lactones (Scheme 16.31) [35],... 

Kudoh R, Sudo A, Endo T (2009) Synthesis of eight-membered lactone having tertiary amine moiety by ring-expansion reaction of 1,3-benzoxazine and its anionic ring-opening polymerization behavior. Macromolecules 42 2327-2329... 

The methoxyketene 297, coordinated to Cr carbonyl, is formed from methoxy-carbene easily by insertion of CO under irradiation [90]. An ester is formed by the reaction of ketene with alcohol. The aminocarbene complex 298 was prepared from benzamide and converted to phenylalanine ester 300 under irradiation of sunlight in alcohol via ketene 299 [91]. The eight-membered lactone 304 was prepared in high yield by the reaction of the alkyne 301 having the OH group in a tether with Cr carbene without irradiation. The vinylcarbene 302 is formed at first and converted to the vinylketene intermediate 303 as expected. The keto lactone 304 is formed from 303 by intramolecular reaction with the OH group and hydrolysis [92],... 

The Buszek (—)-octalactin A synthesis is notable for its useage of the Corey-Nicolaou thiopyridyl ester7 protocol for saturated eight-mem-bered lactone construction. Prior to this synthesis, no eight-membered lactone ring had ever been prepared in high yield from the cyclisation of a saturated hydroxy carboxylic acid precursor. This reaction therefore broke important new ground in the arena of complex natural product synthesis. 

Exposure of 3-(tetrahydro-2-furyl)-3-trimethylsilylpropanoic acids 178 to trifluoroacetic anhydride allows intramolecular acylative ring-opening reaction to give the corresponding eight-membered lactones 180 in moderate to good yields (Scheme 46) <1999SL1757>. However, when R1 = R2 = Me, lactones 180 are not formed. The acyloxonium ion 179 is a probable intermediate in these reactions. Similarly, acids 182 afford lactones 183 (Scheme 47). 

The esterification was used in the preparation of an eight-membered lactone in the total synthesis of a new natural product, cephalosporolide D (Eq. 16) [21c]. 

Intramolecular Cp—Car couplings have been observed in the anodic oxidation of a series of 4-hy-droxy-2-vinylbiphenyls, e.g. 293), which afforded the corresponding spirodienones (c.g. 294 92% from 293). Another Cp—Car linkage resulted from the brief oxidation of the dihydrocinnamyl cinna-mate (295) with thallium tristrifluoroacetate-catalytic boron trifluoride (water-quench), when the eight-membered lactone (296) was formed. ... 

If the choice is between a seven- and an eight-membered lactone, the seven-membered ring 151 is preferred to the medium sized ring as in a recent series of experiments24 using the collidine-Br+ reagent 150. 

The lactones, the cyclic esters of hydroxy acids have been polymerised with various catalysts anionic catalysts, cationic catalysts and organometallic catalysts [28, 29, 39, 45, 54]. Five member lactone rings are unpolymerisable. Four, seven or eight member lactones are polymerisable [28, 29, 39, 45, 54]. 

The exclusive 1,2-shift nature of the contraction of six- seven- and eight-membered lactones (Scheme 10) [5] is easily appreciated to be a consequence of the enforced s-cis conformation of the lactone and recollapse of the contact ion pair before rotation about the CH2-C02 bond. Similarly the predominant 1,2-nature of several... 

Ninhydrin (858) reacts with p-cresol in the presence of zinc chloride to yield the eight-membered lactone (859). Generation of the carbene (860) from the corresponding diazopyrazole in the presence of benzene derivatives PhR (R = MeO, Me, Cl, CN, or NO2) results in mixtures of isomeric substitution products (861) and ring-expanded pyrazolo-azocines (862) electron-withdrawing substituents enhance the formation of the latter cf. p. 158). The oxadiazoloben-zodiazocinone (864) is formed by the action of phosgene on the iV-oxide (863). ... 

The formation of eight-membered rings by radical cyclization has been found to occur using a-acyl radical species. The reaction occurs at a rate that is faster remarkably even than 5-exo-trig cyclization. Hence, the eight-membered lactone 92 was formed, rather than a five-, six- or seven-membered lactone, on treatment of the bromide 91 with tributyltin hydride (4.72). 

A new concept in the ring expansion of cyclic lactones has been developed by Corey et al. involving internal translactonization. In the most spectacular example, treatment of the nine-membered lactone (115 x = 6, y = 3) with a trace of acid at ambient temperature for two hours gives the 12-membered lactone (116 jc =6, y = 3) in 97% yield. This instability of a nine-membered ring is further exemplified by a six-carbon expansion of (115 x = 6, y = 6) to the 15-membered macrolide (116 JC = 6, y = 6) in 90% yield. By contrast, eight-membered lactones (e.g. 115 JC = 5, y = 3) are converted more slowly and less cleanly into the expanded products (e.g. 116 jc = 5, y = 3) while seven-membered lactones (115 jc=4) failed to translactonize altogether. 

Unsaturated eight-membered lactones have been reported to undergo decarboxyla-tive and non-decarboxylative transannular Ireland-Claisen rearrangement reactions to give substituted vinylcyclobutanes (Scheme 12). ... 

The presence of a base or high concentrations of palladium lead to racemization. Neither the Z olefinic isomer nor the eight-membered lactone was isolated, indicating a preference for a 6-exo-trig rather than an S-endo-trig path. The trans stereochemistry of the newly created C—C bond was established by NMR. The two diastereomeric 3-lactones are epimeric at the hydroxylated carbon. ... 

Figure 5.1 Natural eight-membered lactones and related compounds.

Rao synthesized the unnatural (-b)-cephalosporolide D (ent-1) using the Yamaguchi lactonization method [58]. Cyclization of the seco-acid 41 activated by 2,4,6-trichlorobenzoyl chloride and a catalytic amount of DMAP formed eight-membered lactone 42 in 68% yield (Scheme 5.13). 

Sabitha carried out cyclization of the seco-add 43 under the Yamaguchi conditions in a manner similar to the Rao procedure to furnish the eight-membered lactone 44 in almost the same yield (70%) (Scheme 5.14) [59]. 

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