Mikanecic acid

An efficient one-pot synthesis of mikanecic acid derivatives was accomplished from allylic phosphonates, ClC02Et, and aqueous HCHO (Eq. 12.38).100 The overall process involves a cascade sequence linking together metalation-alkoxycarbonylation, Homer-Wadsworth-Emmons,... 

Al-Badri, H., and Collignon, N., First one-pot synthesis of mikanecic acid derivatives from allylic phosphonates, via a tandem-sequence Homer-Wadsworth-Emmons and Diels-Alder reactions. Synthesis, 282, 1999. 

Little is known concerning the only necic acid containing thirteen carbon atoms which has- been isolated. Mikanecic acid was one of the hydrolysis products of mikanoidine (30), along with mikanecine. Senecioic acid was also obtained from the plant extract, but it does not appear to have been in combination with the alkaloid (28). 

In 1982, Drewes and Emslie first reported the reaction of ethyl acrylate with acetaldehyde in the presence of DABCO and successfully employed this adduct in the synthesis of integerrinecic acid (3) (Scheme 2.2). Soon after that, Hoffmann et al. developed an interesting reaction between methyl/tcrt-butyl acrylates 4 and various aldehydes rmder the catalytic influence of DABCO to provide the corresponding a-hydroxyalkyl acrylate adducts 5 and elegantly applied one of these adducts to synthesis of racemic mikanecic acid (6) (Scheme 2.3). Since then, a series of reports" have emerged and transformed the MBH reaction into a very useful and promising tool for the construction of carbon-carbon bonds in synthetic chemistry (Scheme 2.4). 

In the mid-1980s, Hoffman and co-workers described a simple synthesis of racemic mikanecic acid via in situ Diels-Alder dimerization of the diene generated from t-butyl 2-bromomethylbut-2-enoate. " The first example of a Diels-Alder reaction of a MBH adduct was the dimerization of 2-hydroxy-alkyle-nones" and the previously mentioned addition to anthracene. The appKcation of the MBH adducts as hetero dienes or precursors of dienes, and dienophiles for the Diels-Alder cycloaddition reactions was then initiated and expanded by the group of Hoffman. In a series of reports, Hofftnan and co-workers have described the in situ Diels-Alder dimerization of various dienes (157), generated via stereoselective dehydration with MsCl-DABCO-DMAP of the corresponding MBH adducts The elimination of water from MBH adducts always resulted... 

The first enantioselective synthesis of mikanecic acid, ( + )-162, a terpene dicarboxyhc add was achieved by Basavaiah et via a double stereo-differentiating asymmetric Diels Alder reaction involving the same molecule as chiral diene and chiral dienophile generated in situ. Treatment of MBH adduct with MsQ/NEts afforded the chiral dienes 161, through a Diels-Alder reaction of the in situ generated chiral l,3-butadiene-2-carboxylate 160. Hydrolysis of the diesters then afforded the desired mikanecic acid 162 (25-74% ee) in good... 

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