14-Membered ring lactone

The anionic Rh(I) porphyrin [Rh(OEP) induced ring-opening reactions with 4- and 5-membered ring lactones to give organometallic products with the rhodium bonded to the alkoxide carbon rather than the carbonyl carbon. 

Similar views have been expressed by Dafforn and Koshland(4), who found that the rates of formation of some 5-membered ring lactones and thiolactones, although somewhat less spaced in sulpho-lane than in water, follow the same trends in the two basically different solvents (Table II). 

No 0-allylation is observed in formation of the six-membered ring compound 79 by intramolecular allylation of the /3-keto ester 78(15,57]. Intramolecular allylation is useful for lactone fonnation. On the other hand, exclusive formation of the eight-membered ring lactone 81 from 80 may be in part derived from the preference for the nucleophile to attack the less substituted terminus of the allyl system[58]. 

The reaction of vinyloxiranes with malonate proceeds regio- and stereose-lectively. The reaction has been utilized for the introduction of a 15-hydroxy group in a steroid related to oogoniol (265)(156]. The oxirane 264 is the J-form and the attack of Pd(0) takes place from the o-side by inversion. Then the nucleophile comes from the /i-side. Thus overall reaction is sT -StM2 type, in the intramolecular reaction, the stereochemical information is transmitted to the newly formed stereogenic center. Thus the formation of the six-membered ring lactone 267 from 266 proceeded with overall retention of the stereochemistry, and was employed to control the stereochemistry of C-15 in the prostaglandin 268[157]. The method has also been employed to create the butenolide... 

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

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. ... 

Pentalenolactone E methyl ester (46), an angularly fused sesquiterpene lactone, was first isolated and characterized by Cane and Rossi [38]. One approach to the synthesis of this material is illustrated in Scheme 5. Key to the successful implementation of the plan is the synthesis of butenolide 49, the electrochemi-cally promoted cyclization of 49 to the tricyclic y-lactone 48, ring opening of the latter to convert the linearly fused system to the angularly fused six-membered ring lactone 47, and functional group elaboration leading to the natural product 46 [36,37]. 

In similar syntheses, 2,2-disubstituted vinyl derivatives (e.g., 45) were transformed to indolo- (46) and indolizinotropones (300) [Scheme 12 84H(22)791]. Five- and six-membered-ring lactones (e.g., 42b) and equiva-... 

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 . 

Common substructural motifs in polyketide natural products are six-membered ring lactones, lactols, and tetrahydropyrans. It was recognized by Wuts and co-workers that hydroformylation of readily available homoaUyhc alcohols would provide a direct and efficient entry into these ring systems. Such an approach was employed in a synthesis of Prelog-Djerassi lactone (Scheme 5.11) [13]. 

The 14-membered ring lactone 3 was methylated to give a cisjirans mixture of 4 with a 13 1 ratio in favor of the cw-isomer73. Alkylation of the dianion of the hydroxylactone 5 gave 6 with a 9 1 selectivity74, which can be interpreted in terms of a chelation-controlled conformation such as 7. 

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]. 

The molecular ion peak of five-membered ring lactones is distinct but is weaker when an alkyl substitutent is present at C4. Facile cleavage of the side chain at C4 (rules 3 and 8, Section 2.7) gives a strong peak at M -alkyl. 

If the halide and the hydroxy group are present in the same molecule, reaction (107) leads to the synthesis of lactones.484 With complex (102) as catalyst a series of butenolides were prepared in good yields from vinyl iodides (equation 110). Four- and six-membered ring lactones and a-methylene lactones were prepared. 5,486 The mechanism proposed was analogous to that of Scheme 37. This cyclization has been used in the synthesis of the natural product zearalenone.487 PdCl2 was the catalyst. 

It appears that all but one502 (eleven-membered ring) of the examples of this reaction in the literature involve the synthesis of monocyclic or tricyclic five-membered ring lactones.503-507 Sodium borohydride,508,509 sodium trimethoxyborohydride510 and sodium amalgam483 have been employed for demercuration of these substrates. 

The same reactions, carried out with potassium carbonate as base in place of a secondary amine, yield exocyclic dienes in good yield, although double-bond isomerization sometimes occurs (equation 38).93 Inclusion of tetra-zi-butylammonium chloride in the reaction mixture stops the double-bond isomerization. Thus, the reaction in equation (38) with the chloride yields only the bis(exomethylene) product in 45% yield in a slow reaction. Some N- and O-heterocyclic products, also, have been prepared by the intramolecular vinyl substitution reaction.94 A 16-membered ring lactone was made by the ring closure of a vinylic iodide group with a vinyl ketone group. The yield, based upon the reactant, was 55% but a stoichiometric amount of bis(acetonitrile)palladium dichloride was employed. The catalyst was prereduced with formic acid so that the reaction proceeded at 25 C (equation 39).95... 

Several new chiral rhodium(II) catalysts have been synthesized for evaluation as catalysts in the asymmetric oxonium ylide-[2,3]-sigmatropic rearrangements of diazocarbonyl substrates219 (see Scheme 46). The formation of 13-membered ring oxonium ylides (165) and their stereo-controlled [2,3]-sigmatropic rearrangement to 10-membered ring lactones (166) have been described.220... 

Step 3b. Selective lactonization to the six-membered ring lactone. 

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