We introduce a novel isocyanide-based multicomponent reaction, the Passerini four component reaction (P-4CR), by replacing the carboxylic acid component of a conventional Passerini three component reaction (P-3CR) with an alcohol and CO 2. Key to this approach is the use of a switchable solvent system, allowing the synthesis of a variety of a-carbonate-amides. The reaction was first investigated and optimized using butanol, isobutyraldehyde, tert-butyl isocyanide and CO 2. Parameters investigated included the effect of reactant equivalents, reactant concentration, solvent, catalyst, catalyst concentration and CO 2 pressure. Of the other parameters, the purity of the aldehyde and its tendency to oxidize was one of the most critical parameters for a successful P-4CR. After optimization, a total of twelve (12) P-4CR compounds were synthesized with conversions ranging between 16 and 82% and isolated yields between 18 and 43%. Their structures were confirmed via 1 H and 13 C NMR, FT-IR and high resolution mass spectrometry (ESI-MS). In addition, three (3) hydrolysis products of P-4CR (a-hydroxyl-amides) were successfully isolated with yields between 23 and 63% and fully characterized (1 H, 13 C NMR, FT-IR and ESI-MS) as well.Read less <