4- Hydroxy-2-butenolide, reaction with

Butenolides. The fmnal steps in a synthesis of jolkinolide E (4) involve formation of the butenolide ring by reaction of the a-hydroxy ketone 1 with the mixed anhydride of trichloroacetic acid amd a-(diethylphosphono)propionic acid (2) with catalysis by DMAP. The ester 3 undergoes an intramolecular Wittig-Horner reaction in the presence of NaH to give 4. ... 

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). 

A series of anti-inflammatory hydroxy butenolides was synthesized starting from 55. Thus heating 55 with ethyl phenyl-prop-1-ynoate 141 for 16 h at 210°C afforded 3-phenyl-4-furancarboxylic acid ethyl ester 142 (Fig. 3.42). Functionalization of the ester followed by reaction of the furan ring with singlet oxygen gave the biologically active butenolides, 143. 

An expeditious route to hydroxy butenolides, found in several natural products, also uses a 5-alkoxyoxazole-acetylene cycloaddition. Reaction of 8 with ethyl... 

The reaction of vinyloxiranes with malonate proceeds regio- and stereose-lectively. The reaction has been utilized for the introduction of a 15-hydroxy group in a steroid related to oogoniol (265)(156]. The oxirane 264 is the J-form and the attack of Pd(0) takes place from the o-side by inversion. Then the nucleophile comes from the /i-side. Thus overall reaction is sT -StM2 type, in the intramolecular reaction, the stereochemical information is transmitted to the newly formed stereogenic center. Thus the formation of the six-membered ring lactone 267 from 266 proceeded with overall retention of the stereochemistry, and was employed to control the stereochemistry of C-15 in the prostaglandin 268[157]. The method has also been employed to create the butenolide... 

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... 

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. 

If the halide and the hydroxy group are present in the same molecule, reaction (107) leads to the synthesis of lactones.484 With complex (102) as catalyst a series of butenolides were prepared in good yields from vinyl iodides (equation 110). Four- and six-membered ring lactones and a-methylene lactones were prepared. 5,486 The mechanism proposed was analogous to that of Scheme 37. This cyclization has been used in the synthesis of the natural product zearalenone.487 PdCl2 was the catalyst. 

Butenolides. 21-Hydroxy-20-keto steroids react with 1 to form cardenolides by an intramolecular Wittig reaction (equation I).2... 

For example, N-(2-hydroxyphenyl)imines 9 (R = alkyl, aryl) together with chiral zirconium catalysts generated in situ from binaphthol derived ligands were used for the asymmetric synthesis of a-amino nitriles [17], the diastereo- and/or enantioselective synthesis of homoallylic amines [18], the enantioselective synthesis of simple //-amino acid derivatives [19], the diastereo- and enantioselective preparation of a-hydroxy-//-amino acid derivatives [20] or aminoalkyl butenolides (aminoalkylation of triisopropylsilyloxyfurans, a vinylogous variant of the Mannich reaction) [21]. A good example for the potential of the general approach is the diastereo- and enantioselective synthesis of (2R,3S)-3-phenylisoserine hydrochloride (10)... 

Hydroxymethylation of ketone (155) was followed by protection of the aliphatic hydroxy group (2-methoxypropyl ether) and addition of an a-benzyloxymethylene group at C-4. Acidic workup at the last stage of the reaction sequence produced (156). Its transformation to aldehyde (157) was carried out by successive treatment with methoxypropyl ether, acetic anhydride and pyridine, hydrochloric acid and methanol, and finally chromic acid, pyridine and hydrochloric acid. Dehydration of (157) led to the formation of (158) in 20% yield. Reagents other than the mentioned produced appreciable quantities of the cis A/B isomer. The butenolide (159) was finally synthesized by oxidation and hydrogenolysis. In order to complete the synthesis of triptolide it was necessary to introduce the... 

Ried and Bodenstedt345 obtained an interesting a,)S-unsaturated butenolide, when the diazofuran (60) was warmed with water. It is possible that the a-hydroxy derivative forms first, which then dimerizes at the -position in its keto form. The reaction might proceed by a radical mechanism. 

Palladium(II) catalysts can also be applied to stereo- and regioselective syn hydroarylation and hydrovinylation of symmetrically and unsymmetrically substituted alkynes8 9. Thus, alkyl 4-hydroxy-2-alkynoates in the presence of Pd(OAc)2(PPh3)2, formic acid, and tributylamine in dimethyl formamide or acetonitrile are converted with aryl iodides in a one-pot syn hydroary-lation/cyclization reaction to give functionalized substituted butenolides. The reactions occur with high syn stereoselectivities and with good regioselectivities8. 

A convenient synthesis of the 2-aryl-5-hydroxythiophen system consists of the reaction of the corresponding butenolides with sodium hydrosulphide-hydrogen chloride, 3-Hydroxy-4-anilinomethylthiophen exists in the stable tautomeric form (25)." The allyl ether of dimethyl 3-hydroxythiophen-... 

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). 

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