Schmidt rearrangement double

Although the Schmidt reaction is formally analogous to the Beckmann rearrangement, it is less versatile in the 20-keto steroid series since only 1,4-addition to the double bond has been observed with the important A -derivatives. 

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]. 

While catalyst 22/23 has been known to be valuable in other C-C bond-forming strategies, for example, 1,3-dipolar cycloaddition [149], hetero-Diels-Alder reaction [150], Friedel-Crafts-type alkylation [151], double-Michael reaction [152], [2,3]-Wittig rearrangement [153], and Claisen-Schmidt condensation [154], only references are given here. 

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