Van Leusen synthesis

In tMs approach, conjugate addition of the anion from an isocyano-acetate to an a,p-unsaturated nitrocompound with evenmal loss of nitrous acid, produces 5-unsubstituted pyrrole-2-esters. The example below shows a mechanistic sequence that can be seen to parallel that in the van Leusen synthesis. The most useful route to the a,P-unsaturated nitro-compound involves the base-catalysed condensation of an aldehyde with a nitroalkane giving an a-hydroxy-nitroalkane it can alternatively be generated in situ, in the presence of the isonitrile, using diazabicycloundecane (DBU) as base on the 0-acetate of the a-hydroxy-nitroalkane (for an example see 16.16.2.1). The process works even when the unsaturated nitro unit is a component of a polycyclic aromatic compound. ... 

Oxazole syntheses employing isocyanides as starting materials are of considerable preparative value. In the van Leusen synthesis, tosylmethyl isocyanide (TosMIC) reacts with aldehydes under base catalysis, e.g. in the presence of K2CO3. The primary products are 4,5-dihydro-1,3-oxazoles 12, which are converted into oxazoles by elimination of sulfinic acid (see p 172) ... 

By analogy to the Van Leusen synthesis of oxazoles (see p 128), the carbanion formed from tosylmethylisocyanide adds to the aldimine. The addition product cyclizes to give a 4,5-dihydroaimidazole 7, which eliminates p-toluenesulfinic acid to give the imidazole 8. 

Wu B, Wen J, Zhang J, Li J, Xiang YZ, Yu XQ (2009) One-pot Van Leusen synthesis of 4,5-disubstituted oxazoles in ionic liquids. Synlett 3(137) 500-504 Wakamatsu H, Saito Y, Masubuchi M, Fujita R (2008) Synthesis of imidazolium-tagged ruthenium carbene complex remarkable activity and reusability in regard to olefin metathesis in ionic liquids. Synlett 2008 1805-1808... 

Disubstituted pyrroles are important building blocks for porphyrin synthesis (cf p. 553). With two equal 3,4-substituents, they can be straightforwardly obtained by the Piloty-Robinson synthesis [118] ofhigher flexibility are isocyanide-based methods like the Barton-Zard synthesis [119] and the Van Leusen synthesis [120]. 

The van Leusen synthesis can be rationalized by a mechanism similar to that of the Barton-Zard process in (b) and should involve intermediates 64-66. Furthermore,... 

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