3-Buten-4-olides synthesis

In 1986, Keller-Schierlein, ZShner and their respective coworkers isolated ( )-differolide (135, Figure 5.14) from cultures of an actinomycete, Streptomyces aurantiogriseus Tii 3149. This compound ( )-135, whose structure was determined by X-ray diffraction studies, was reported to enhance the formation of aerial mycelium and spores of Streptomyces glaucescens. Especially noteworthy was the fact that the natural product was racemic. There are some examples of the occurrence of racemic and bioactive natural products such as magnosalicin (10) and olean (116), but they are rare. Although there was a straightforward Diels-Alder synthesis of ( )-135 by dimerization of 2-vinyl-2-buten-4-olide, this method would not afford the enantiomers of 135. 

Cerpegin (78) was isolated from Ceropegia juncea and its structure was determined using IR, UV, lH and l C NMR [215] and X-ray crystallography [216]. In a recent synthesis, 78 was obtained in five steps, beginning with a Michael reaction of phenylthioacetonitrile and 2-methoxycarbonyl-4,4-dimethyl-2-buten-4-olide [217]. 

Matsuo and co-workers have described two syntheses of cerpegin (118) (231-233). In the first synthesis, reaction of the lithium salt of phenyl-thioacetonitrile (352) with treated with 2-methoxycarbonyl-5,5-dimethyl-2-buten-4-olide (353) at -78°C and then warmed to room temperature and treated with acid afforded a stereoisomeric mixture of 354 in 93% yield. Oxidation of 354 with mefa-chloroperbenzoic acid followed by reflux in benzene gave 355. Catalytic reduction (Pd-C-HCl) and treatment with base gave 356 in 44% yield. Various methylation procedures were unsuccessful, but reaction with methyl 4-toluene sulfonate in the presence of NaH gave 118 in 81% yield (Scheme 41) (231,232). 

Hydrocarboxylation can also be used in the synthesis of heterocycles if the heterofunction is introduced at an appropriate position within the substrate. Thus, preparation of 2,4-disub-stituted 2-buten-4-olides can be achieved via stoichiometric transformation of a protected optically active propargyl alcohol without loss of optical activity30. Sequential treatment with zirconocene chloride hydride (Schwartz s reagent), carbon monoxide, and iodine gives a 55% yield of (S)-2-ethyl-4-isobutyl-2-buten-4-olide30. This reaction resembles the intramolecular hydrocarboxylation of allylic alcohols. 

The carboxylation of optically active a-lithiated-a, 3-unsaturated sulfoxides has been reported. For example, Posner and coworkers have performed a one-pot a-lithiation followed by carboxylation and esterification of the a,p-unsaturated sulfoxide (58) to give enantiomerically pure a-methoxycarbonyl-a,P-unsaturated sulfoxide (59) in 80% yield (Scheme 5.19) [52,58]. Protonation rather than methylation leads to the corresponding carboxylic acid in >95% yield. This methodology has been utilized in the synthesis of enantiomerically pure (5)-(-i-)-2-(p-tolylsulfinyl)-2-buten-4-olide (62) from the a,P-unsaturated sulfoxide (6()) via the carboxylic acid derivative (61) (Scheme 5.19) [59]. An efficient route to nonracemic 2-(p-tolylsulfinyl)-2-buten-4-olides employing carboxylation of an a-lithio-a,p-unsaturated sulfoxide has also been developed by Holton and Kim [60]. 

Bis-sulfenylation of y-butyrolactone, as well as of cyclic ketones, has been achieved with this reagent via the corresponding lithium enolates. This reaction has been utilized in an efficient synthesis of 3-substituted 2-buten-4-olides (eq 4). 

The reaction of 4-phenyl-3-buten-4-olide with benzylamine was investigated as a model for polyamide synthesis. Linear polyamides were prepared from ringopening polyaddition of 4,4 -disubstituted bis(3-buten-4-olide) in m-cresol u g aliphatic diamines. Further studies have investigated the production of hydroxy-substituted polyamides from 4,4 -disubstituted bis(4-butanoiide) and polyamide production from 2,2 -p-phenylene bis-oxazolones by similar ring opening reactions with diamines. ... 

Paleta O, Volkov A, Hetllejs J (2000) Fluorinated butanolides and butenohdes, part 5. Synthesis and nucleophilic reactions of 3-chloro-2-fluoro-2-buten-4-olide as tetronic acid analogue. Conjugate addition of hard nucleophiles and vinylic halogen displacement with soft phosphorus nucleophiles. J Fluor Chem 102 147—157... 

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