Azomethine spirooxindole synthesis

The group of Gong and coworkers explored a biomimetic 1,3-dipolar cycloaddition between a-ketoester 79 and benzylamine derivatives 80 with electron-deficient olefins 81a,b to devise a straightforward route to proline derivatives 82 in high yields and enantioselectivities [49]. The proposed biomimetic three-component 1,3-dipolar cycloaddition proceeds as illustrated in Scheme 2.22a. The azomethine ylide B is formed, via a transamination from ketimine ester A, which is in turn prepared from a-ketoesters 79 and benzyl-amine derivatives 80 then, the 1,3-dipolar cycloaddition with electron-poor olefins 81a takes place. For this purpose, the bisphosphoric acid 83 was found to be the catalyst of choice to promote such transformation (Scheme 2.22b). Replacing dimethyl maleate (previously used as deficient olefins) by methyleneindolinones, the same approach could be extended to spirooxindoles synthesis in high yields and... 

Williams has reported a MCR in the synthesis of spirotryprostatin B 50, a spirooxindole-substituted diketo-piperazine with a prenylsubstituent at C-18 (Scheme 6.7). In the key step, diphenylmorphoUnone 66 reacts with isovaleraldehyde 67 to form azomethine ylide 69, which is attacked by the oxindole 68 to build the latter 70 in a [3+2]-dipolar cycloaddition [24]. 

Cycloadditions have emerged as one of the most used approaches for the formation of cyclic compounds by organocatalysis [8a]. Based on the previous knowledge, [3-1-2] cycloadditions can serve as an excellent platform for the synthesis of spirocyclic compounds. For example, alkylideneindolones act as activated alkenes that react with azomethine ylides to afford pyrrolidine derivatives. Recently, several research groups have used this approach to synthesize spirooxindoles and related... 

Scheme 42.45 Phosphoric acid-catalyzed enantioselective synthesis of spirooxindoles by enantioselective domino 1,3-dipolar cycloaddition of in situ formed azomethine ylides and methylene-indolinones.

The spirocyclic oxindole core structure was constructed by an asymmetric 1,3-dipolar cycloaddition in the total synthesis of (—)-spirotryprostatin B. A reaction of oxazi-none 137 with aldehyde 138 and oxindole 139 resulted in spirooxindole 141 via the chiral azomethine yhde 140, simultaneously creating three bonds and four stereogenic centers in one step (Scheme 16.20). ... 

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