Of bicyclic lactones

In contrast to the fact that cyclic acetals can be polymerized only by cationic initiators, lactones undergo polymerization both cationically and anionically, and therefore a wide variety of initiators including coordinated catalysts can be used. In this section, the polymerization of bicyclic lactones is described, although only a limited number of papers on this subject have been published. 

Treatment of bicyclic lactones 66, derived from Diels-Alder reaction of 3-carboxy-2-pyrone under standard radical conditions using (TMSlsSiH, leads to bridged lactones 67, which can smoothly be converted to bicyclo[3.3.0]-lactones 68 (Scheme 10). For X = CHaOMe, this cascade of rearrangements took place in a 78% overall yield, providing 68 in diastereomerically pure form. Three additional steps provided a novel route toward Corey s lactone 69. 

The low yield in this reaction might be caused by a number of reasons. First, the overall reaction is only rapid for readily enolizable compounds. 1,3-Dicarbonyl compounds will therefore be a better choice as compared to acetic acid. Second, to prevent oxidation of radical 54, it is advantageous to work with excess diene and therefore speed up trapping of 54 through diene addition. Finally, lactone 55 can, as an enolizable compound itself, also be oxidized by manganese(III) acetate and form various oxidation products. Shorter reaction time and the use of understoichiometric amounts of oxidant might therefore benefit the overall result. All these factors have been taken into account in the synthesis of bicyclic /-lactone 56, which has been obtained from cyanoacetic acid and 1,3-cyclohexadiene in 78% yield within 15 min reaction time (equation 25)60,88. 

Scheme 5.41 The reaction of alkynyltungsten with epoxides synthesis of bicyclic lactones.

The iodolactonization of bicyclic lactone 143 provides a mixture of iodolactones (Equation 48) in excellent overall yield <2002JA2080>. 

Treatment of bicyclic lactone 24 with benzylamine in dioxane afforded an open chain triflate amide, which was stirred in THF in the presence of potassium carbonate to cyclizate to the spirocyclic p-lactam 25 (Scheme 9) [58]. 

The permanganate oxidation of axial and equatorial vinyl orthoesters 140 and 141 was carried out in a buffered solution (pH =10) mixed with acetonitrile. The reaction mixture was then esterified with acetic anhydride and pyridine. Both vinyl orthoesters gave an identical result >95% of acetoxy ester J46 and <5% of bicyclic lactone 147. 

Table 3. Preparation of optically active cyclic tetramer (44S) and pentamer (45S) by the oligomerization of bicyclic lactone (41) of lower optical purity , [49]...

Polymerization of Bicyclic Lactones Having a Bicyclo[2.2.2]octane Skeleton... 

The two modes of ring cleavage have been joined together in the synthesis of bicyclic lactone 27 — a precursor for certain alkaloids 19). 

In the course of model studies for the synthesis of Blapharocalyxin E, Cakir et al. reported that arylation of bicyclic lactones for the synthesis of aryl-substituted pyranoside derivatives led to highly diastereoselective arylation, only one isomer of the arylated derivative being detected and isolated (Equation (12)).39... 

On the other hand, cationic lactone polymerization may be also used to prepare cyclic oligomers of specific ring size with reasonable yield. Polymerization of bicyclic lactone, 6,8-dioxabicyclo[3.2.1]octan-7-one, generates a repeating unit containing ester and ether bonds ... 

Figure 11 Newton and Roberts synthesis of bicyclic lactone [41].

A conceptually different [4-1-2] cycloaddition catalyzed by a chiral lanthanide complex has been disclosed. The inverse electron demand Diels Alder reaction of 3-methoxycarbonyl-2-pyrone (67) and enol ethers or sulfides [135] was catalyzed by a chiral ytterbium(III) triflate-binaphthol complex in the presence of diisopropylethylamine (Scheme 51) [136]. Thermal decarboxylations of bicyclic lactones such as 68 are known to yield dienes which may undergo subsequent pericyclic reactions [137] thus, the adducts of this process are potentially useful chiral building blocks. The nature of the substituent on the 2k component was found to be crucial for the realization of high enantioselectivity. 

Exclusive trans addition is observed in reactions of bicyclic lactone radicals, in which the lactone functionality forms the /i.y-substituents43. Acetoxymercurio-, iodo-, and phenylseleno-lactones are used as precursors. The highest yields of addition products arc obtained from thermally initiated reactions of the phenylselenolactone, while the use of the mercury precursor at lower temperature leads to considerable amounts of reduced material. 

In Chapter 27 we analysed the synthesis of bicyclic lactone (6). In his vitamine B12 synthesis Eschenmoser needed to lengthen the acetic acid side chain of (6) into the propionic side chain of (7). This he accomplished by the Arndt-Eistert procedure. 

The desired synthon, acetonide 520, is prepared from carbonate 517 by treatment with acetone under acidic conditions. Alkylation of bicyclic lactone 521 with 520 affords 522 as a single isomer. Reduction of the lactone with DIBAL produces an equilibrium mixture of lactol and hydroxy aldehyde 523. Oxidation of the ally lie alcohol and decarbonylation with Wilkinson s catalyst furnishes the crucial enone intermediate 524 common to both natural products. 

This review of recent progress in [4+2] cycloaddition of 2-pyrone dienes emphasizes control of relative and absolute stereochemistry. Discussion includes the development of mild reaction conditions and electronic matching of reaction partners, allowing the isolation of bicyclic lactones with control of relative stereochemistry. Control of absolute stereochemistry in these cycloadditions features a stereo-chemical control element on one or more of the following a pyrone diene, a dienophile, or a Lewis acid promoter. Applications of this methodology to synthesizing complex organic molecules are mentioned. 

Our own experience with 3-carbomethoxy-2-pyrone has shown that it can be made to react with vinyl ethers in the presence of Lewis acid catalysts, such as montmorillonite clays, silica, or zinc salts in methylene chloride at ambient pressure and room temperature or lower to give excellent yields of bicyclic lactones 38 and 39 as single regio- and stereoisomeric products." ... 

The synthetic utility of 3-bromo-2-pyrone has been demonstrated by the conversion of bicyclic lactones 56-58 into differently functionalized A-ring fragments for a number of biologically interesting novel vitamin D analogs. ... 

Krafft and co-workers used olefin metathesis to prepare several inside-outside medium-size rings as scaffolds for natural products synthesis. Reaction of bicyclic lactone 267 with 10 mol % of 4 in refluxing dicholormethane gave the corresponding tricyclic lactone 269 in 88% yield after only two hours. 

SCHEME 5.76 Synthesis of bicyclic lactones 95 starting from a MCR. 

A novel approach to the synthesis of bicyclic lactones via an interrupted Nazarov reaction of gcm-divinyl dihydrofurans. 

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