# Isocyanide Multicomponent Reactions on Solid Phase: State of the Art and Future Application
## 1 Introduction  
Multicomponent reactions (MCRs) are one-pot highly efficient transformations utilizing three or more components capable of creating highly diverse compounds. They are also atom-efficient, incorporate a substantial portion of components, and do not require any additional reagents. MCRs are ideal tools for the construction of vast arrays of biologically relevant molecules [1].  
One of the most explored and the most frequently described MCRs is the Ugi four-component reaction (U-4 CR), often named Ugi four-component condensation (U-4 CC). The U-4 CC enables the formation of a functionally complex organic molecule with a single synthetic transformation in comparison to numerous steps applied in conventional methodologies [2]. An illustrative example to generate structurally complex compounds resulted from [PERSON]'s laboratory [3]. In addition, MCRs are also attractive for automated parallel synthesis [4].  
A large number of MCRs performed in solution phase have been reported, while solid-phase applications appear less frequently. In this review, we include publications using isocyanide as one of the reaction components (so-called isocyanide-based multicomponent reactions, IMCRs). The majority of the presented syntheses utilized the Ugi reaction either as a one-step process resulting in the target products (not considering the additional step of cleavage from the resin) or as one of the steps in a several-step synthesis, which involves a transformation of the primary product. We also included Ugi four-center three-component reactions (U-4C-3 CRs) as well as nontraditional Ugi reactions, e.g., Ugi-azide four-component reactions [5; 6], or transformations unrelated to the Ugi reaction [7; 8; 9].  
To the best of our knowledge, there are only two examples of Passerini reactions leading to small molecules via a solid-phase reaction [10; 11].  
Initially employed for the formation of dipeptides, the Ugi reaction has been applied for the synthesis of complex structures [3] or natural products [12], and currently, it plays an important role for finding biologically relevant molecules [13]. Numerous research groups worldwide have contributed to this ground-breaking one-pot reaction. MCRs are very attractive due to their potential and interdisciplinary applications. MCRs are advanced tools for sustainable organic synthesis [14] due to their good compatibility with green solvents [15], high atom economy, efficiency, and mild reaction conditions. At present, the solid-phase Ugi reaction is also essential in the synthesis of macropeptides, glycopeptides, lipoproteins, and in the field of ligation and bioconjugation [16; 17]. Furthermore, IMCRs are attractive for their compatibility with DNA-encoded combinatorial synthesis [18]. In addition, chiral auxiliary has already been shown to enable direct enantio-enriched compounds [19; 20]. MCRs also have the potential to provide a basis for large-scale molecular data storage [21].  
This review is focused on the synthesis of small molecules on solid supports and demonstrates the various methodologies and strategies used in IMCRs. Herein, the presented approaches are classified according to the type of IMCRs and taking into account whether the IMCR was the only chemical transformation leading to the target products or whether it was one of several steps in the synthetic sequence. In certain sections, the reactions are classified according to the functionality bound to the solid support.