A -Butenolide

The term butenolide was first employed by Klobb for describing these compounds (1898BSF389). Chemical Abstracts currently has adopted the furanone system of nomenclature. Thus, A -butenolides are the 2(3//)-furanones and A ,/3-butenolides are the 2(5//)-furanones. The butenolide nomenclature still continues to be employed (76CRV625). 

Related Reagents. a,(3-Butenolide 7-Butyrolactone R)-Pantolactone p-Propiolactone 2-Trimethylsilyloxyfuran p-Vinyl-a,p-buten olide. 

Related Reagents. iV-Benzyloxycarbonyl-L-serine p-Lactone a,3-Butenolide -y-Butyrolactone Dihydro-5-(hydroxymethyl)-2(3//)-furanone p-Ethynyl-p-propiolactone 3-Propiolactone. 

Ali and Alper later developed a method for y-lactone formation under neutral conditions from allylic alcohols according to Scheme 23, involving Pd(0) and dppb. The same protocol was also applied to synthesis of a,/3-butenolides from propargylic alcohols. Other bidentate or monodentate ligands give inferior results, and this correlates well with bite angle effects on the rate of the CO insertion reaction. Also, the allylic alcohol needs to be a-alkyl substituted to facilitate ring closure, in accordance with other studies.t t This process was postulated by the authors to be of the carbopalladative type. 

Butenolides may be prepared by bhe cyclisation of 4,5-epoxyalk-2-enoates, one of the sin5)lest cases being the formation of (160) (.755 ) by treatment of (159) with HClOj in aqueous dioxane or aqueous acetone. These sinple a,3-butenolides have proved to be convenient synthons for mere ccc5)lex molecules. The starting material for these cyclisations is obtained via a Wittlg reaction of an epoxy-ketone thus (I6I X=0), when condensed with (Et0)2P(0)CH2C02Et yields a mixture of E and Z (I6I X=CHC02Et). The Z isomer forms (162) stereospecifically on hydrolysis. 

Diastereoselective aldol condensations. This furan (1) can undergo condensation with aldehydes as a butenolide to form 8-hydroxy-a,(3-unsaturated--y-lactones (2). The diastereoselectivity can be controlled by the choice of catalyst. Lewis... 

Rauter s group exploited the synthesis of sugar derived bicyclic butenolides ( e.g. 140, Fig. 44),60 which possess cytotoxic and antitumor activities. The key structural feature of such compounds consists of the presence of the a,(3-unsaturated lactone, which allows them to act as Michael acceptors for the addition of enzymes nucleophiles. 

Herstellung des /3-(trans-p-Oxy-cyclohexyl)-A fl-butenolids, by E. Hardegger, P. A. Plattner, and F. Blank, Helv. Chim. Acta, 27 (1944) 793-800. 

A pentopyranoside-fused butenolide is the key intermediate for the synthesis of the natural micotoxin patulin [226, 227]. Its synthesis involves Wittig olefination of a 3,4-di-O-protected arabinopyran-2-uloside, followed by protecting group removal and dehydration (Scheme 47). In other research, the glucopyranosid-2-uloside 190 was converted into the butenolide derivative 191 by aldol condensation with diethyl malonate and transesterification [228]. The latter was shown to be prone to autoxi-dation, leading to 192. Subsequent Michael addition with hydroxide ion, followed by decarboxylation, furnishes C-branched-chain sugar 193. 

Triethylammonium formate is another reducing agent for a, /3-unsaturated carbonyl compounds. Pd on carbon is better catalyst than Pd-phosphine complex, and citral (49) is reduced to citronellal (50) smoothly[55]. However, the trisubstituted butenolide 60 is reduced to the saturated lactone with potassium formate using Pd(OAc)2. Triethylammonium formate is not effective. Enones are also reduced with potassium formate[56]. Sodium hypophosphite (61) is used for the reduction of double bonds catalyzed by Pd on charcoal[57]. 

A novel entry to decahydrocyclopentacyclooctene derivatives via the intramolecular photocycloaddition of fused a,/3-unsaturated y-lactones has been developed (80CC1011). Irradiation of the butenolide (153) in acetone solution gave both the fused and bridged photoadducts (154) and (155) (2-3 1). The major adduct was hydrolyzed, oxidized and esterified to afford (156). Reductive cleavage of the unsaturated keto ester (156) with lithium in ammonia afforded a five-component mixture of a,/3- and /3,y-unsaturated esters. Equilibration with 0.1M sodium methoxide in methanol converted the mixture into a single a,j8-unsaturated ester (157 Scheme 34). This annelative two-carbon ring expansion method may find application in the synthesis of ophiobolin and ceroplastol sesterterpenes. 

Many examples of natural furans are recorded as having been prepared from five-membered heterocycles such as 2(5H)-furanones (butenolides), which are reduced to furans with diisobutylaluminum hydride. The facile elimination of selenoxides derived from a-phenylseleneyl-y-lactones with formation of endocyclic a,/3-unsaturated butenolides is reported (75JOC542) as a useful route to 2,4- and 2,3,4-substituted furans via their corresponding butenolides. The mixture of dihydrofurans obtained from the tosylhydrazone of tetrahydro-2-furanone (Scheme 88) was oxidized to furans by 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (66CJC1083). 

Methoxy-2-furylcarbinols (367) were converted into a 3 1 mixture of 4-ylidene-butenolides (369) and 4-oxo-2-enoic acid methyl esters (370) by zinc chloride catalysis. The carbonium ion (368) is the key intermediate, the stability of which made the conversion very fast, providing high yields (Scheme 99) (80T3071). 

OLyfi-Butenolides.1 Reaction of (E)-y-hydroxy-a, (3-unsaturated esters with thiophenol results in cyclization to 3-phenylthiobutyrolactones, which can be converted into 3-phenylthiobutenolides or butenolides. 

Few examples exist for the conjugate addition of ester enolates to a,(3-unsaturated esters typically the incipient enolate undergoes decomposition and secondary reactions. The first examples, described by Schlessinger,144 are the addition of /-butyl lithioacetate and /-butyl a-lithio-a-(methylthio)propionate to butenolide (176 Scheme 69). Similarly, Normant reported that cyclopropanes are obtained from a-ha-loesters (177) and ethyl acrylate or acrylonitrile.145... 

Alkenes from 1,2-diols (7, 385-386). An efficient synthesis of (S)-(—)-y-methoxymethyl-a, /J-butenolide (3) from (+)-5-0-methyl-D-ribonolactone (1) involves conversion to the cyclic orthoformate 2 followed by pyrolysis to give 3 in 66.5% overall yield.1 In this case, the Corey-Winter reaction and the Hanessian route (8,192) were... 

The [2 + 2]-photocycloaddition chemistry of a,(3-unsaturated lactones has been widely explored. The factors governing regio- and simple diastereoselectivity are similar to what has been discussed in enone photochemistry (substrate class Al, Section 6.2). The HT product is the predominant product in the reaction with electron-rich alkenes [84]. A stereogenic center in the y-position of ot,P-unsaturated y-lactones (butenolides) can serve as a valuable control element to achieve facial diastereoselectivity [85, 86]. The selectivity is most pronounced if the lactone is substituted in the a- and/or P-position. The readily available chiral 2(5H)-furanones 79 and 82 have been successfully employed in natural product total syntheses (Scheme 6.30). In both cases, the intermediate photocycloaddition product with 1,2-dichloroethylene was reductively converted into a cyclobutene. In the first reaction sequence, the two-step procedure resulted diastereoselectively (d.r. = 88/12) in product 80, which was separated from the minor diastereoisomer (9%). Direct excitation (Hg lamp, quartz) in acetonitrile solution was superior to sensitized irradiation (Hg lamp, Pyrex) in acetone, the former providing the photocycloaddition products in 89% yield, the latter in only 45%. Cyclobutene 80 was further converted into the monoterpenoid pheromone (+)-lineatin (81) [87]. In the second reaction... 

The crossed intramolecular [2 + 2]-photocycloaddition of allenes to a, 3-unsat-urated y-lactones has been extensively studied by Hiemstra et al. in an approach to racemic solanoedepin A (87). The sensitized irradiation of butenolide 85 in a 9 1 mixture of benzene and acetone, for example, led selectively to the strained photocycloadduct 86 (Scheme 6.31) [89]. The facial diastereoselectivity is determined by the stereogenic center, to which the allene is attached. The carbon atom in exposition to the carbonyl carbon atom is attacked from its re face, forming a bond to the tertiary allene carbon atom, while the P-carbon atom is being connected to the internal allene carbon atom by a si face attack. The method allows facial diaster-eocontrol over three contiguous stereogenic centers in the bicyclo[2.1.1]heptane part of the natural product. 

Butenolides,1 Addition of the Schwartz reagent to a protected propargylic alcohol (2) followed by carbonylation provides an acyl zirconocene complex (3). This is not isolated but treated in situ with iodine to provide an intermediate (a) that cyclizes to a 3,5-disubstituted butenolide (4). Optically active substrates undergo this sequence with no loss of optical purity. 

Butenolides and furanes.6 The [2 4- 2] cycloadducts (3) of alkynes with keten-iminium salts (2), readily formed from 1 (11,560-561), undergo Baeyer-Villiger oxidation to give A ,0-butenolides 4 exclusively. The products are readily reduced to furanes (5) by DIBAH. 

When a,/3-epoxydiazomethylketones are irradiated in benzene, they rearrange to butenolides, whereas in a large excess of methanol they are converted to y-hydroxy-a,(l-unsaturated esters, via epoxyketenes (Eq. 345). ... 

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