The Passerini Reaction. III. Stereochemistry and Mechanism^1,2

Asymmetric Isocyanide‐Based MCRs

“…Since the simultaneous union of three molecules is not a very likely process, another possibility is a stepwise mechanism, with the intermediacy of a loosely bonded adduct 4 between the carbonyl compound and the carboxylic acid [2]. Since all three components are involved in rate-determining steps [12], in principle asymmetric induction may be achieved when at least one of them is chiral.…”

Three-Component Reaction between Alkyl Isocyanides, Dialkyl Acetylenedicarboxylates, and Carboxylic Acids

“…This is followed by attack of the carboxylate anion 7 on the positively charged ion 6 to form an imidoyl carboxylate 8, which undergoes rearrangement [25][26][27] under these reaction conditions to produce compound 4 (Scheme 2).…”

What do we know about multicomponent reactions? Mechanisms and trends for the Biginelli, Hantzsch, Mannich, Passerini and Ugi MCRs

“…Curiously, in 1951 a thirddegree reaction order was proposed based on kinetic data. 42 The proposition already shown in Scheme 27 fulfils this hypothesis and was found to be in accordance with much evidence. 43 Breakthrough work was later published by Floriani and coworkers 44 describing the role of TiCl 4 as a Lewis acid promoter of the Passerini reaction (Scheme 28).…”