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A regio- and stereoselective one-pot C–H insertion/olefination protocol has been developed for the late stage installation of α-methylene-γ-butyrolactones into conformationally restricted cyclohexanol-derivatives. The method has been successfully applied in the total synthesis of eudesmanolide natural product frameworks, including α-cyclocostunolide.

A remarkably effective method allowing an extremely high enantioselective synthesis of the spiro-fused 2-oxindole/α-methylene-γ-butyrolactones is described. The key strategy lies in the use of indium-catalyzed asymmetric amide allylation of N-methyl isatin with functionalized allylstannanes, which can lead to the antineoplastic spirocyclic lactones in almost enantiopure forms.

An expedient access to almost enantiopure spiro compounds (III) and (V) via an unprecedented Cu-catalyzed 1,3-dipolar cycloaddition is developed.

A zinc or indium-mediated Barbier-type allylation of aldehydes with 3-bromomethyl-5H-furan-2-one in aqueous solvents was developed to provide an efficient route to α-methylene-γ-butyrolactone, which is synthetically very useful. The desired products were obtained in moderate to high yields in aqueous solvents. Excellent drs were achieved, among which the best diastereomeric ratios of products were found when water was used in the indium-mediated reaction, and THF–NH4Cl (sat, aq) (2:1) mixture in the zinc-mediated reaction. Furthermore, the allylation can be induced by chiral centers, especially those in the α-position, as a substrate-controlled reaction to obtain the enantioselective homoallylation alcohols.

In a search for inhibitors of platelet aggregation, some alpha-methylene-gamma-butyrolactones bearing 2-methylquinoline and 8-hydroxyquinoline moieties were synthesized and evaluated for antiplatelet activities against thrombin (Thr)-, arachidonic acid (AA)-, collagen (Col)-, and platelet-activating factor (PAF)-induced aggregation in washed rabbit platelets. With the exception of 2-[[2,3,4,5-tetrahydro-4-methylene-5-oxo-2-(4-phenylphenyl)-2 -furanyl]methoxy]-8-hydroxyquinoline (8f), these alpha-methylene-gamma-butyrolactones completely inhibited the platelet aggregation induced by AA and Col. The 2-methylquinoline derivatives were also active against Thr- and PAF-induced aggregation, while their 8-hydroxyquinoline counterparts were relatively inactive.

[reaction: see text] The palladium-catalyzed arylation of the alpha-methylene-gamma-butyrolactone proceeds in good yields and may be directed toward the synthesis of 3-benzylfuran-2(5H)-ones when the starting aryl iodides contain strongly electron-withdrawing groups. The combined palladium-catalyzed arylation/hydrogenation of the alpha-methylene-gamma-butyrolactone represents a new simple entry into functionalized alpha-benzyl-gamma-butyrolactones.

The reaction between dimethyl acetylenedicarboxylate and various phenols including phenol, 1-naphthol, 2-naphthol, 8-hydroxyquinoline, 1,6-dihydroxynaphthalene, cathechol, hydroquinone and resorcinol in the presence of catalytic amounts of pyridine leads to fused α-methylene-γ-butyrolactone derivatives in good yields.

The palladium-catalysed arylation/vinylation of α-methylene-γ-butyrolactone (1) proceeds in good yield, mainly to give stereodefined aryl/vinyl-substituted α-alkylidene-γ-butyrolactones 4. In addition, the palladium-catalysed arylation of α-methylene-γ-butyrolactone (1) may be directed towards the synthesis of 3-benzylfuran-2(5H)-ones 3 when the starting aryl iodides contain groups with electron-withdrawing conjugative properties. The combined palladium-catalysed coupling/hydrogenation reactions represent a new, simple route to functionalised 3-alkyl-γ-butyrolactones 5, giving prominence to the possibility of stereocontrol in the formation of the new stereocentres.

Contact allergy from handling alstroemeria (Alstroemeria) has been widely observed in horticulturalists and florists (1–5). α-methylene-γ-butyrolactone (α-MBL) has been shown to be the causative agent (6, 7). In the present study, delayed-type contact dermatitis due to alstroemeria was evaluated using the guinea pig maximization test (GMT) (8), and the intensity of allergic reactions was investigated by quantifying the contents of α-MBL in different parts of alstroemeria by high-performance liquid chromatography (HPLC) (9).

14C-labelled γ, γ-dimethyl-α-methylene-γ-butyrolactone 1 and 1-oxa-Spiro [4.5]-3-methylene-2-decanone 2 have been synthesized from acetone and cyclohexanone respectively and 14C-labelled ethyl bromomethacrylate (Reformatsky reaction). The synthesis of this last compound is also described.

The kinetics of α-methylene-γ-butyrolactone (α-MBL) homopolymerization was investigated in N,N-dimethylformamide (DMF) with azobis(isobutyronitrile) as initiator. The rate of polymerization (Rp) was expresed by Rp = k[AIBN]0.54[α-MBL]1.1 and the overall activation energy was calculated as 76.1 kJ/mol. Kinetic constants for α-MBL polymerization were obtained as follows: kp/kt1/2 = 0.161 L1/2 mol−1/2·s−1/2; 2fkd = 2.18 × 10−5 s−1. The relative reactivity ratios of α-MBL(M2) copolymerization with styrene (r1 = 0.14, r2 = 0.87) were obtained. Applying the Q–e scheme led to Q = 2.2 and e = 0.65. These Q and e values for α-MBL are higher than those for MMA

Treatment of ethyl α-(bromomethyl)acrylate with Cr(II) reagent derived from CrCl3 and LiAlH4 produces allylic chromium species which add to aldehydes efficiently to give α-methylene-γ-butyrolactones stereoselectively.

Methyl 2-siloxycyclopropanecarboxylates (1) smoothly add to dimethylmethyleneammonium trifluoromethanesulphonate, generated in situ, or to the corresponding minium chloride (4) in the presence of TiCl4, giving α-aminomethylated γ-oxoesters (6) in good yield; these can serve as precursors for α-methylene-γ-butyrolactones (7) as well as for acrylic ester derivatives (8).