Huisgen pyrrole synthesis

The strategy was based on a Huisgen pyrrole synthesis to build the B and C rings followed by a Dieckman cyclization to form ring A. The acetoxy acid (428) available in two steps from 4-hydroxy-... 

Other references related to the Huisgen pyrrole synthesis are cited in the literature. 

Mesomeric zwitterions like Munchnones, which are known as mesoionic compounds, also occur in other heterocyclic systems [276], Munchnones show the reactivity of 1,3-dipoles for instance, they react with acetylenes via the products 62 of a 1,3-dipolar cycloaddition to give pyrroles 63 after cycloreversion of 62 by loss of CO2 Huisgen pyrrole synthesis). 

Huisgen and coworkers have also described the cycloaddition behavior of the munchnones , unstable mesoionic A2-oxazolium 5-oxides with azomethine ylide character.166 Their reactions closely parallel those of the related sydnones. These mesoionic dipoles are readily prepared by cyclodehydration of N-acyl amino acids (216) with reagents such as acetic anhydride. The reaction of munchnones with alkynic dipolarophiles constitutes a pyrrole synthesis of broad scope.158-160 1,3-Dipolar cycloaddition of alkynes to the A2-oxazolium 5-oxide (217), followed by cycloreversion of carbon dioxide from the initially formed adduct (218), gives pyrrole derivative (219 Scheme 51) in good yield. Cycloaddition studies of munchnones with other dipolarophiles have resulted in practical, unique syntheses of numerous functionalized monocyclic and ring-annulated heterocycles.167-169... 

This reaction was extended by Huisgen to the reaction of proline, acetic anhydride, and dimethyl acetylenedicarboxylate to give pyrrole derivatives. In addition, a method for generating the munchnone from 1,3-oxazolium perchlorate with triethylamine at low temperatures has been developed. Moreover, an analogous pyrrole synthesis via a tran-... 

Huisgen s group488 have described a new synthesis of pyrroles (26) from oxazol-5-ones (azlactones) (25) with DMAD and MP. The pyrrole derivatives formed in situ from 2,4-dimethyl- and 4-benzyl-2-methyloxazolone with DMAD underwent nucleophilic addition to a second mole of the acetylenic ester to give the Michael adducts 27 and 28... 

Huisgen and co-workers486,490 have described a useful synthesis of N-substituted pyrroles (41) from mesoionic oxazolones (39) via the intermediates 40, which were not isolated. A variety of acetylenic esters (phenylpropiolic, propiolic, tetrolic, and DMAD) were used. The kinetics of these reactions have been studied.491 The addition of carbon... 

Ngwerume, S., W. Lewis, and J.E. Camp. 2013. Development of a gold-multifaceted catalysis approach to the synthesis of highly substituted pyrroles Mechanistic insights via Huisgen cycloaddition studies. J Org Chem 78 920-934. 

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