Butenolide

Carbonylation of alkynes is a convenient method to synthesize various carbonyl compounds. Alper et al. found that carbonylation of terminal alkynes could be carried out in aqueous media in the presence of 1 atm CO by a cobalt catalyst, affording 2-butenolide products. This reaction can also be catalyzed by a cobalt complex and a ruthenium complex to give y-keto acids (Scheme 4.8).92... 

Butenolides.1 When activated by silver trifluoroacetate, this furan is alkylated by primary alkyl iodides or ethyl a-iodoacetate to give 4-alkyl-2-butenolides (2) in 60-80% yield. 

ButenoUdes. 4-Substituted 2-butenoIides can be prepared by reaction of organolithium reagents with 4-hydroxy-2-butenolide (1), easily prepared from furfural (equation I). The reaction of 1 with 2 equivalents of RLi or ArLi in-THF at... 

The conjugate addition of aryl dithiane anions to 2-butenolide has been examined as a route to ( )-podorhizol and ( )-isopodophyllotoxone (78JOC985). The dithiane of piperonal (802) was deprotonated and reacted with 2-butenolide to give the lactone anion which was trapped in turn with 3,4,5-trimethoxybenzaldehyde to afford a mixture of the threo and erythro aldol products (803). Desulfurization of the erythro dithiane with Raney nickel gave ( )-podorhizol (804 Scheme 188). 

Photosensitized oxidation offurans.3 The endoperoxide (2) formed in photosensitized (methylene blue) oxidation of 3-substituted or 3,4-disubstituted furans in acetone at -40° rearranges at 20° to 4-hydroxy-2-butenolides in 30-97% yield. Example ... 

Bicyclobulanolides A-substituted-1-butenolides. 1 Primary and secondary Grignard reagents react with the bicyclic anhydride 1 to form bicyclobulanolides (2) in 80-100% yield. Distillation of 2 effects a retro Diels-Alder reaction to give 4-disubstituted 2-butenolides (3). 

Dehydrochlorination 4-alkylidene-2-butenolides. 2,2-Dichloro-4-alkylbutanol-ides (1), (9, 491-492), are converted into 4-alkylidene-2-butenolides (2) on didehydro-chlorination with pyridine at reflux. 

Acylation of alkenes and alkynes. Dienes and alkynes can be acylated under phase-transfer conditions by carbon monoxide and methyl iodide in the presence of -catalytic amounts of Co2(CO)s. The reaction with alkynes results in a 4-hydroxy-2-butenolide the probable mechanism is shown in equation (I). 

Acid hydrolysis of 2-alkoxyfurans easily generates a butenolide, a pathway which allows the introduction of various substituents into a butenolide ring. Protonation at the 5 position is the rule and leads via a 2-butenolide to an acrylate 3-protonation is minor and never results in a butenolide... 

The unique quality of Br/Li exchange with t-BuLi enables the synthesis of an a-hydroxy(3-furanylmethyl)-2-butenolide, whereas many other coupling method fail. ... 

Base-catalyzed reactions of the enaminones 243 with 4-hydroxy-2-butenolide give tetrahydroindole-2-acetic acids 245 (R = H) [or the methyl esters (R = Me) by in situ treatment with diazomethane], Scheme 65 (82JOC3665). 

The high reactivity of the /3-lactam ring towards cleavage by nucleophiles makes them useful synthons for the —C—C(0)—C—N moiety. A nice example is to be found in a new synthesis of 1,2-butenolides (29), as shown in Scheme 7. 

Yamazaki, T. Mizutani, K. Takeda, M. Kitazume, T. Chiral trifluoromethylated 2-butenolides for the construction of 6-deoxy-6,6,6-trifluorosugars. J. Chem. Soc., Chem. Commun. 1992, 55-57. 

Cyclic vinyl ethers such as (9) are lithiated to give acyl carbanion equivalents (10), whilst a-substituted vinyl-lithiums of type (11) react with aldehydes and ketones, ArCOR, to give substituted 2-butenolides (12). ... 

Butenolide Metabolites.- 1.2.1 Tetronic Acids. Full details have been... 

Hydroxymethyl-2-butenolide. 5-Hydroxy-2-penten-4-olide. 5-Hydroxymethyl-3-oxolen-2-one. 2,3-Dideoxy- cero-pent-2-enono-1,4-lactone... 

Dehydrochlorination of 2-(l-chloroethyl)thiophene (22) in the presence of pyridine gives 2-vinylthiophene (23) in 50-55% overall yield starting from thiophene (eq 17). Didehydrochlorina-tion of 2,2-dichloro-4-alkylbutanolides affords 4-alkylidene-2-butenolides upon reflux in pyridine (eq 18). ... 

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