Azomethine ylids intramolecular

The cyclodehydration of 2-substituted-A/-acylthiazolidine-4-carboxylic acids yields bicyclic munchnones. This mesoionic ring system acts as a cyclic azomethine ylid and can undergo 1,3-dipolar cycloaddition reactions with dipolarophiles. A range of chiral pyrrolo[l,2-c]thiazoles have been prepared by this method both intermolecularly and intramolecularly. 

Due to the presence of these resonance forms in azomethine ylids, reaction with alkenes often leads to mixtures of regioisomeric cycloadducts. Resonance stabilizing substituents are usually employed to enhance the regioselectivity. Intramolecular reactions usually favor only one mode of addition. An example of an intermolecular reaction is taken from Williams synthesis of spirotryprostatin B,372 in which 5,6-diphenylmor-pholin-2-one (473) reacted with the aldehyde shown to give a mixture of ( )- and (Z)-azomethine ylids (474). This product was generated in situ with oxindole 475, and [3-i-2]-cycloaddition product 476 was obtained in 82% yield. 

Intramolecular versions of the reaction are not only possible but are quite useful. One illustration is Pandey s treatment of bis(trimethylsilylamine) 477 with AgF to generate azomethine ylid 478. 23 in the presence of the conjugated ester unit, cycloaddition gave a 61% yield of the azatricyclo product 479. 

The quaternization of a j8-carboline, followed by the generation of an azomethine ylid, enables cycloaddition of diethyl acetylenedicarboxylate to yield the fused pyrrole product (357) (Scheme 115) <89TL3423>. Similar systems, namely the pyrrolo[2,l-a]isoquinolines, have been formed by an intramolecular electrophilic substitution on the 2-aryl ring of a suitably substituted pyrrole (358) (Equation (104)) <93JCS(Pi)276i>. 

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