Cyclization, Michael addition azides

Taking advantage of the multifunctionalities and ready accessibility of methyl (2)-3-(dimethylamino)-2-isocyanoacrylate (Schollkopfs isocyanide) (53), Bienayme and Bouzid developed a four-component synthesis of bicyclic tetrazole 54 (Scheme 5.16) [34]. Simply stirring a methanolic solution of an aldehyde, an amine, 53, and TMSN3 afforded 54 in good to excellent yield. Trapping the nitrilium 55 by azide afforded the intermediate 56, which was subsequently cyclized to furnish the tetrazole 57. A sequence of intramolecular Michael addition followed by (3-elimina-tion of dimethylamine then provided the final product 54. The intermediate tetrazole 57 could be isolated and was found to cyclize to the bicyclic tetrazole 11 in essentially quantitative yield under the reaction conditions. 

Winnik and coworkers [11] utilized an azide functional RAFT agent to synthesize azide functional linear PNIPAM followed by a thiol-ene Michael addition reaction with propargyl acrylate, producing a-alkyne-ou-azide PNIPAM. Consequently, the cyclization reaction by CuAAC was achieved in water with CUSO4 and ascorbic acid as the catalyst (Scheme 33). Further, the solution properties showed that the cyclic PNIPAM had higher phase transition temperature due to the endless chain structure of the cycUc compared to the linear counterpart with the same molecular weight. 

In troponoid chemistry cine substitution occurs frequently. In many cases it can be explained by the intermediacy of dehydrotropolone species ( tro-polonyne ) as trapped, for example, by azides (Section II,A,3,h Scheme 34). An alternative mechanism may be a Michael-type addition followed by elimination. The intramolecular cyclizations depicted in Scheme 47 very likely proceed via Michael-type attack (73CRV293, p.351). 

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