Mumm-type rearrangement

Keywords Isocyanides, sy -chlorooximes, carboxylic acids, TEA, dichloromethane. Alcohols, room temperature, sy -a-oximinoamides, stereospecific synthesis, Passerini-type reaction, Mumm-type rearrangement... 

Isocyanides, formal divalent carbon functionalities, are ideal candidates for the development of MCRs. Their reaction with carbonyls and imines, through an a-addition process, generates a zwitterionic intermediate, which is then trapped by a nucleophile. The resulting double a-addition adduct is unstable and rapidly undergoes the Mumm rearrangement to afford the final product (Scheme 12.32). The venerable three-component Passerini reaction is the first MCR based on this type of reaction process [116]. It addresses the formation of a-acyloxycarboxamides, which constitute a class of very versatile synthons in organic chemistry. In the present context, this reaction was utilized by Schmidt and collaborators for the elaboration of intermediate 234 [117], a key fragment for the synthesis of the prolyl endopeptidase inhibitor Eurystatin A 231 (Scheme 12.33) [118]. 

The mechanism leading to adduct G presents clear analogies with that of the well established Ugi MCR, in which the isocyanide attacks the electrophilic carbon of an iminium ion for this reason, this process could be called the Ugi-Reissert reaction (Scheme 31). However, in this transformation, the adduct arises after a final hydration of the nitrilium ion, instead of undergoing the Mumm rearrangement as in the traditional Ugi reaction [188]. The novelty here lies in the use of M-acylazinium salts as a new source of reactive iminium ions for Ugi-type processes. 

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