Unexpected Products Yield Novel MCRs

The most ancient classification considers whether a certain compound class or chemical scaffold is being formed with success under given reaction conditions -often described by the name of the chemist who discovered or made major contributions to this reactions. Between 700 and 900 such named reactions are known [1]. This classification is mostly product based, but can be connected in certain cases to specific starting materials, e.g. the nitrosamine rearrangement. 

In the context of MCRs the novelty of a reaction and the chemical backbone structures accessible from it can also be understood in terms of combining otherwise known reactions into a multicomponent assembly of starting materials that, via a domino process [23], yield a product. Although neither the individual reactions forming the MCR nor the product might be novel, in terms of creating a synthetically useful process we suggest that such MCRs should also be considered novel reactions as they create chemical innovation. 

The number of individual reactions of a given reaction type that are currently performed and analyzed in parallel combinatorial chemistry approaches is much higher than in the past. Not surprisingly we often observe that some of the expected reaction products in a compound library are not formed since, for various reasons, the corresponding starting materials may not yield the desired product under the chosen reactions conditions. In other cases unexpected reaction products may be formed. 

In one prominent example such an unexpected reaction product was observed in three research laboratories independently. During attempts to synthesize a library of Ugi-type four-component products using various isonitriles, aldehydes, acids and amines the reaction did not gave the desired Ugi-type four-component reaction product when amino pyridine-like starting materials were used as the amine component. In the case of such 2-amino pyridine-type amines the clean formation of 

Compounds of this type were considered to be interesting for pharmaceutical research and previously could only be obtained over four sequential reaction steps. 

---