Synthesis of Butenolides

In the synthesis of butenolides substituted in a position adjacent to the carbonyl, the bis(dimethylamino)phosphinyloxy group has been employed for the direction of an incoming electrophile (Scheme 8). ... 

Cyclic orthoformates are useful intermediates for the synthesis of butenolides (235). Treatment of D-ribonolactone, or its 5-0-substituted derivatives, with one molar equivalent of ethyl orthoformate gave diastereoisomeric... 

Pentalenolactone E methyl ester (46), an angularly fused sesquiterpene lactone, was first isolated and characterized by Cane and Rossi [38]. One approach to the synthesis of this material is illustrated in Scheme 5. Key to the successful implementation of the plan is the synthesis of butenolide 49, the electrochemi-cally promoted cyclization of 49 to the tricyclic y-lactone 48, ring opening of the latter to convert the linearly fused system to the angularly fused six-membered ring lactone 47, and functional group elaboration leading to the natural product 46 [36,37]. 

Examples are known of hydrocoupling between methyl acrylate and ketones in both protic and aprotic solvents. Reaction in acid solution is thought to involve reduction of the protonated ketoneto a radical, which adds to acrylate. In aprotic solvents, the ketone is more difficult to reduce and electron addition occurs on methyl acrylate. Modest yields of coupling product, dimethylbutanolide, are obtained from acetone and methyl acrylate in dimethylformamide [134]. Better results are obtained by reduction of methyl acrylate and an exces of the carbonyl compound in dimethyIformamide in the presence of chlorotrimethylsilane [135]. This process is useful for the synthesis of butenolides and some examples are given in Table 3.8. 

Anodic oxidation of fiirans in acetic acid leads to the 2,5-diacetoxy-2,5-dihydro-furan 58 [185, 186]which is readily converted to 2-acetoxyfiiran, This has proved a valuable intermediate for the synthesis of butenolides [187]. Reactions in moist acetonitrile yield the 2,5-dihydro-2,5-dihydroxyfurans which can be oxidised to the maleic anhydride 59 [188], Oxidation of furan-2-carboxylic acid in methanol and sulphuric acid is a route to the ester of a-ketoglutaric acid [189]. 

Scheme 48 Synthesis of butenolides fused to pento- or hexopyranoses and thiosugar analogs from furanos-3-nloses...

The Diels-Alder cycloadduct of furan and maleic anhydride has played a key role in a new synthesis of butenolides (79S607). Treatment of the cycloadduct (24) with methanol affords a half acid ester which is reacted in turn with an excess of a Grignard reagent to produce the lactone (25) on acidic work-up. On heating this lactone at 150-180 °C, thermal fragmentation takes place to yield the 4,4-dialkylbutenolide (26) in high overall yield (Scheme 5). 

The regioselective preference for the formation of the branched product can be reversed by an increase of steric hindrance, especially at the propargylic position. Preferential formation of the linear isomer was also observed with 4-hy-droxyalkynoates, allowing the synthesis of butenolides via cyclization [37] (Eq. 26). 

Double cyclizations to butenolides and furanes. Radicals can undergo intramolecular addition to triple bonds when separated by three carbons. This strategy can be used for synthesis of butenolides (equation 1) and -substituted furanes (equation II). Cyclization of vinyl bromides." Fused and bridged ring systems can be prepared... 

Such allyloxylation reactions allow, for example, the formation of ( )-rose oxide from citronellol [161]. The synthesis of butenolides can be efficiently performed starting from )6-unsaturated acids [172] ... 

Oxidation of a 2-boronate ester is a means for the synthesis of butenolides (18.12.1). Furan-3-boronic acid and 3-tri-n-butylstannylfuran can be made by reaction of the lithiated species with tri-txo-propyl borate and tri-n-butylchlorostannane respectively. 

Directed lithiations of alkoxy furans have potential in the synthesis of butenolides, and the tetramethyldiamidophosphate moiety has been successfully used to prepare 3-substituted furans (22). Acidic cleavage of the phosphorus residue then allows access to the corresponding 2-substituted butenolide (23), and the overall process becomes equivalent to using the anion (24) (Scheme 8). 

Synthesis of butenolides by one-pot cyclization reactions of silyl enol ethers with oxalyl chloride 06SL3369. 

Recently, Ma and Shi reported a one-step procedure for the efficient synthesis of butenolides via a Pd(0)- and Ag -cocatalyzed carbopalladation-cyclization sequence of aryl/aUcenyl halides with the easily available 3-substituted allenoic acids (Scheme 38). In this reaction the presence of a catalytic amount of Ag is crucial, although its exact role is still unclear. ... 

The reactions shown in Scheme 25 are useful for the synthesis of butenolides or y-phenylthioacrylic esters/ ... 

A productive synthesis of butenolides from a-chloroketones has been published . 

SCHEME 3.48 Synthesis of butenolides via gold(in)-catalyzed Akcoupling/cycUzation sequence. 

The aldehyde component has also been replaced by diethyl formylphosphonate hydrate in the silver-catalyzed synthesis of V-PMP-protected a-aminopropargylphospho-nates [139] and by 2-oxoacetic acid [140] or glyoxylic acid [141] in copper-catalyzed microwave-assisted decarboxyla-tive three-component couplings. In addition, glyoxylic acid has been coupled with amines and alkynes in the gold-catalyzed synthesis of butenolides (see Scheme 3.48) [121]. 

This effect has been used in a clever synthesis of butenolides 5.83 (Scheme 5.25). Heck reaction of the fra -4-alkoxycrotonate 5.81 resulted in the expected inversion of alkene stereochemistry, allowing lactonization on deprotection. The alkene inversion, in an intramolecular Heck reaction, is also apparent in an approach to vitamin D compounds (Scheme 5.26). ... 

Synthesis of Butenolides/Butyroactones Using Mg/HgClx for Sulfone Cleavage. Sheng et al. have reported the synthesis of butenolides and butyroactones using the sulfone-bound resin 140 (Scheme 12.31)." ° The procedure for the synthesis of butenolides/butyroactones involved the 5-alkylation of lithiophenylsulhnate resin 79, followed by sulfonyl anion alkylation with an epoxide to yield 45. Subsequent acylation... 

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