Computational Methods of Finding Novel MCRs

This reported hetero Diels-Alder reaction [32] is catalyzed by Lewis acids and is likely to work also when performed as a 3CR instead of isolating the azomethine 

Similarly, the reaction of alkenyl boronic acids with azomethines can be found. Indeed, the corresponding 3-CR was used by Petasis [33] for the enantioselective synthesis of a-amino acids starting from amines, a-keto acids and alkenyl boronic acids. 

The formation of this novel reaction product could be shown by the experiment a posteriori, thus representing an example of a computationally described novel MCR that has subsequently been validated in the laboratory. 

However, the validity of such computer-proposed MCR reactions has always to be verified by experiment. Since such examples are scarce it cannot be judged how efficient this approach will be in suggesting useful MCRs. 

The outcome and use of this computational approach also depends on how many reactions are used and how exact the underlying reaction prototypes are. The conversion of the abundant knowledge on reaction data into such more abstract prototype reactions requires immense work and can only be automated to a limited degree. 

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