Methylene butyrolactones, carboxylates

Methylene butyrolactone has been used as a dipolarophile to synthesize, for the first time, ethyl-l-azabicyclo[2.2.1]hept-3-yl carboxylate using Achiwa s procedure. The synthetic pathway involves rearrangement of the spiropyrrolidine lactone resulting from the [l,3]dipolar addition.430... 

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... 

Limited progress has been achieved in the enantioselective hydrogenation of a,/ -unsaturated carboxylic acid esters, amides, lactones, and ketones (Scheme 26.10). The Ru-BINAP system is efficient for the hydrogenation of 2-methy-lene-y-butyrolactone, and 2-methylene-cyclopentanone [98]. With a dicationic (S)-di-t-Bu-MeOBIPHEP-Ru complex under a high hydrogen pressure, 3-ethoxy pyr-rolidinone could be hydrogenated in isopropanol to give (R)-4-ethoxy-y-lactam in 98% ee [39]. 

The stereoselectivity of this reaction rises when more bulky nucleophiles are employed (compare entries 7, 3,1, and 5). This is most impressively demonstrated by comparison of the y-lactol reduction with its allylation leading to 205 or 206, respectively (Scheme 10). Formation of tetrahydrofuran derivative 208, dihydrofuran 209, or unsaturated a-methylen-y-butyrolactone 207 illustrate that various modes of straightforward work-up procedures provide two different five membered heterocycles 93 b-96). A second example without the geminal dialkyl substitution at C-3 of the siloxy-cyclopropane depicted in Eq. 86 making available the annulated tetrahydrofuran-3-carboxylate 210 underlines the generality of the C-C-bond forming hydroxyalkylation reaction via ester enolates. 

Acrylic monomers can be derived from biomass (53). An early synthesis of a-methylene-y-valerolactone involves two steps (54,55). The first step is the carboxylation of y-butyrolactone with methyl methoxymagnesium carbonate Stiles reagent) to produce the acid. Next, the acid is briefly treated with a mixture of aqueous formaldehyde and diethylamine, followed by a separate treatment of the crude product with sodium acetate in acetic acid. The first step requires 6-7 h and affords almost quantitative yields, whereas the second step can be accomplished in less than 30 min but with yields of only 50%. 

Alkenoic acids given in Scheme 20 are also cyclized to give good yields of lactones.f t The relative reactivity of alkenes generally follows the order disubstituted > trisubstituted > monosubstituted, probably due to a fine balance between the electron density and steric bulkiness. exo-Methylene-y-butyrolactones can similarly be synthesized from the corresponding alkenyl carboxylic acids. ... 

The reaction of potassium salts of 4-pentynoic acids—prepared from the add and KOBu-t or KH—with 1-bromo-l-alkynes affords 6-( )-alkylidene-y-butyrolactonest (Scheme 21). Lithium and sodium carboxylates have proved unsuccessful. Addition of potassium bromide, use of DMSO, and excess 4-pentynoic acid have been found to increase the yield, whereas 1-iodo-l-alkynes lead to the formation of the expected lactone along with major amounts of S-iodo- y methylene-y-butyrolactone. Tri(o-tolyl)phosphine and tri(2-furyl)phosphine can promote an effident transformation. The latter, however, has been found to give the best results. 

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