Methylene lactones

The reaction can be applied to allyl malonates. Alkylation of diallyl mal-onate (734) with bromoacetate and acetoxymethylation afford the mixed triester 735. Treatment of the tricster 735 with Pd catalyst affords allyl ethyl itaconate (736). In a similar way, a-methylene lactone and the lactam 737 can be prepared[462]. 

When the platinum-catalyzed hydrothiolation was performed for acetylenic alcohols, intramolecular cyclization took place to afford a-methylene lactone 25 in up to 67% yield (Eq. 7.19) [30]. 

The catalysis has made reactions of certain functionalized boronates possible. For example, a carbocupration and alkylation allowed the synthesis of boronate 5. Reaction with aldehydes gave a-methylene lactones with high stereoselectivity.53... 

The rhodium-catalyzed hydroboration has opened the way to cyclization reactions starting from dienes [92], For instance, rhodium-catalyzed hydroboration of the terminal alkenyl group of an os/Tunsaturated lactone followed by reaction with the PTOC-OMe chain transfer reagent afforded the bicyclic a-S-pyridyl lactone in 63% yield (Scheme 39). After oxidation of the sulfide with m-CPBA, thermal elimination of the sulfoxide afforded the corresponding a-methylene lactone in 65% yield. Interestingly, such bicyclic a-methylenelactones are substructures that can be found in many natural products such as mirabolide [93]. 

Methylene lactones deserve special interest due to their presence in many biologically active natural products [139]. Norton et al. have developed an... 

Applying more drastic conditions (100 bar of CO 175 °C), [Rh6(CO)i6] also catalyzes cyclocarbonylation of 2-alkynylphenols. The mechanism involves here also an 0 - H oxidative addition initial step. The a-methylene lactone is further reduced since rhodium catalyzes the water-gas-shift reaction and water is present in the medium [145]. 

Rauter and coworkers demonstrated that C-5-aIkylidene derivatives 112 of D-hexofuranurono-6,3-lactone can be obtained by Wittig olefination of the a-ketolactone 111 (Scheme 32) [160]. The related a-methylene lactone 114 was prepared in three steps from 3,6-anhydro-l,2-0-isopropylidene-a-D-j y/ )-5-hexulo-furanose 113 via Wittig reaction and aUylic oxidation. 

Meldrum s acid, like other 1,3-dicarboxyl compounds, was amenable to radical reactions at C-5. The radical reaction between Meldrum s acid benzyl alkyl ethers mediated by InCl3/Cu(OTf)2 has been reported to proceed regioselectively at the benzylic position of the ether moiety (Scheme 35) <2006AGE1949>. Radical reaction of Meldrum s acid and alkenes was carried out with 2equiv of ceric ammonium nitrate (CAN) to give the a-carboxy-lactones which were subsequently subjected to decarboxylative methylenation affording the a-methylene lactones in 35-50% yield (Scheme 35) <2006SL1523>. 

Research Focus Preparation of polymethylmethacrylate derivatives containing pendant sulfonyl or exo-methylene lactone functions. 

Methylene difluorocyclopropanes are relatively rare and their rearrangement chemistry has been reviewed recently [14]. In addition, electron deficient alkenes such as sesquiterpenoid methylene lactones may be competent substrates. Two crystal structures of compounds prepared in this way were reported recently [15,16]. Other relatively recent methods use dibromodifluoromethane, a relatively inexpensive and liquid precursor. Dolbier and co-workers described a simple zinc-mediated protocol [17], while Balcerzak and Jonczyk described a useful reproducible phase transfer catalysed procedure (Eq. 6) using bromo-form and dibromodifluoromethane [18]. The only problem here appears to be in separating cyclopropane products from alkene starting material (the authors recommend titration with bromine which is not particularly amenable for small scale use). Schlosser and co-workers have also described a mild ylide-based approach using dibromodifluoromethane [19] which reacts particularly well with highly nucleophilic alkenes such as enol ethers [20], and remarkably, with alkynes [21] to afford labile difluorocyclopropenes (Eq. 7). 

Methods for the Synthesis of a-Methylene Lactones P. A. Grieco, Synthesis, 1975, 67-82. Ruthenium Tetroxide Oxidations J. L. Courtney and K. F. Swansborough, Rev. Pure Appl. Chem., 1972, 22, 47-54. 

Anomeric radicals can be trapped by sugars having an exo-methylene group. This principle has been applied to C-2 exo-methylene lactones, opening the way to the interesting new class of carbon-linked disaccharides [113,114] (Scheme 30). 

C-Glycosidation of Pyranosyl Compounds Forming a C-Disaccharide [2-4], To a boiling solution of the methylene lactone 66 (610 mg, 1.37 mmol) in 5 mL of 1,2-dimethoxyethane under nitrogen, were added, within 30 min, a solution of tributyltin hydride (873 mg, 3.0 mmol) in 10 mL of 1,2-dimethoxyethane containing AIBN (49 mg, 0.3 mmol) and, simultaneously, a solution of the a-D-glucopyranosyl bromide 47 (1.15 g, 2.80 mmol) in 18 mL of 1,2-dimethoxyethane. After completion of the addition, the mixture was allowed to stir for 15 min at boiling temperature. The solvent was evaporated under reduced... 

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. 

This reaction has been used to prepare many a-methylene lactone derivatives.537 The above alkyne carbonylations were all catalyzed by phosphorus ligand-containing complexes. Some phosphorus-free catalysts for these reactions are also known, such as PdCl2 in presence of thiourea.538 This catalyst system also effects ring closure of 1,6-diynes (equation 131).539... 

Alkynyl(phenyl)iodonium salts can be used for the preparation of substituted alkynes by the reaction with carbon nucleophiles. The parent ethynyliodonium tetrafluoroborate 124 reacts with various enolates of /J-dicarbonyl compounds 123 to give the respective alkynylated products 125 in a high yield (Scheme 51) [109]. The anion of nitrocyclohexane can also be ethynylated under these conditions. A similar alkynylation of 2-methyl-1,3-cyclopentanedione by ethynyliodonium salt 124 was applied in the key step of the synthesis of chiral methylene lactones [110]. 

If the electrophilic end of the alkene is unsubstituted, it is particularly prone to conjugate additions. Examples include exo-methylene lactones 63, ketones 64 and vinyl ketones 65 that are often used... 

Pettus, J. A., Wing, R. M., and Sims, J. J., Marine natural products XII. Isolation of a family of multihalogenated y-methylene lactones from the red seaweed Delisea fimbriata, Tetrahedron Lett., 41, 1977. 

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