7-Butyrolactone-a-methylene

Ethyl 3-nitroacrylate is an extremely reactive receptor in the Michael reaction. It has found use in the synthesis of the a-methylene-butyrolactone moiety3 characteristic of many sesquiterpenes, as shown... 

As early as 1950, feverfew was reported to cause contact dermatitis in at least one patient [62] and parthenolide was found to cause an allergic reaction in patients with the same condition [63]. Since then there have been many reports [64-68] of feverfew-induced allergic reactions, the condition being worst in the summer months coinciding with the flowering season of the plant. The a-methylene butyrolactone group was found to be a partial requirement for activity in contact dermatitis [69]. 

Cycloadditions to exocyclic C=C bonds have been carried out for a-methylene-butyrolactones (254) (154,155), 4-methylenepyrazol-3-ones (255) (156), 4,5-dihy-dro-5-methylene-l//-pyrazoles (256) (157), 4,5-dihydroisoxazoles (257) (158),... 

METHYLENE ACETALS Dimethyl sulf-oxide-N-Bromosuccinimide. a-METHYLENE -BUTYROLACTONES Dibenzoyl peroxide. 1,2-Dibromoethane. METHYLENE CYCLOALKENES Dichlo-roketene. 

Some examples of more elaborate radical cyclizations accompanied by I-transfer are illustrated in Scheme 3. The cyclization of alkyl radicals onto propargyl esters has been demonstrated in synthesis of a-methylene butyrolactones [17]. This procedure uses thermolysis in the presence of benzoyl peroxide in order to induce initiation, and appears to progress in the absence of a distannane reagent. Attempts to carry out the cyclization under tin hydride conditions led to uncyclized, reduced substrate. A series of more complex radical cyclizations involving both I-transfer and unimolecular H-transfer have recently been reported. In these reactions, the radical initially formed by I-abstraction underwent 5>-exo cyclization to generate a vinyl radical. This radical, in turn, abstracted H from silicon in an intramolecular... 

The a-methylene-) -butyrolactone grouping is incorporated in a large number of sesquiterpenoids, many of which have significant biological activity. A number of routes have been devised for the synthesis of this moiety but recently an important contribution from Ourisson s laboratory has demonstrated that the more accessible a-methyl-y-lactones can be converted in two steps into the a-methylene analogues.This is achieved by reaction of the lactone (263 R = H) with triphenylmethyl-lithium and quenching the resultant enolate with 1,2-dibromoethane. Dehydrobromination of the derived bromide (263 R = Br) with diazabicyclononene gives exclusively the exocyclic methylene lactone (264). This method is only suitable for c/s-y-lactones since the trans-lactone yields exclusively the endocyclic isomer. To illustrate this method Ourisson et at. have converted dihydro-6-epi-santonin (265) into (- )-frullanolide (266). More recently the same authors have developed a method which is applicable to... 

Specific examples of the synthesis of natural products containing a-methylene-butyrolactone functions are to be found in the full reports from Danishefsky s group" and from Grieco s group " on the total synthesis of ( )-vernolepin (79) and its isomer, vernomenin Grieco et al. have also reported a synthesis of ( )-desoxyvernolepin " and demonstrated the use of the selenenation method for the introduction of an a-methylene substituent with a neat total synthesis of (+)-costunolide (80) from santonin," together with a general, stereochemically-... 

Synonyms a-methylene butyrolactone Tuliposide A 4,5-dihydro-3-methylene-2(3H)-furanone 3-methylenedihydro-2(3H)-furanone dihydro-3-methylene-2(3H)-furanone Tulipaline A A... 

A number of methods describing improved syntheses of a-methylene-butyrolactones have been published. Magnesium methyl carbonate has been found to carboxylate butyrolactones (though not six-membered lactones) in high yield treatment of the acid (41) with aqueous formaldehyde and diethylamine, followed by separate treatment of the crude product with sodium acetate in acetic acid, gives the desired a-methylenebutyrolactone (42). An independently developed, complementary route involves thermal fragmentation of the salt (43), iodide ion functioning as a nucleophile for... 

Ldffler A, Pratt RD, Pucknat J, Gelbard G, Dreiding AS (1969) Preparation des a-Methylene Butyrolactones par Reaction de Reformatsky Synthese de I Acide Protolichesterinique. Chimia 23 413... 

Cheml980 Cheminat, A., Benezra, C., Farrall, M.J. and Frechet, J., Use of Polymeric Nucleotides for the Selective Binding and Removal of a-Methylene-> -Butyrolactone Allergens from Complex Mixtures, Tetrahedron Lett., 21 (1980) 617-618. 

In the presence of ZnBr2/48% Hydrobromic Acid, suitably functionalized cyclopropanes undergo ring expansion to afford cyclobutane (eq 25) and a-methylene butyrolactone products (eq 26). One-carbon ring expansion has been reported when certain trimethylsilyl dimethyl acetals are exposed to ZnBr2 with warming (eq 27). ... 

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