The Domino-Knoevenagel-hetero-Diels-Alder Reaction and Related Transformations

The Domino-Knoevenagel-hetero-Diels-Alder Reaction and Related Transformations 

The development of novel materials and the search for new bioactive compounds, such as natural products and analogues, drugs, diagnostics and agrochemicals, in academic and industrial chemistry is closely connected to the efficient preparation of such compounds. Thus, the view of synthesis has altered in recent years the development of new, highly selective methods will still be an important task, but the main focus of today s chemists is on efficiency [1], Multi-step syntheses with more than 20 steps have to be avoided since they are neither economically nor ecologically justifiable. Thus, modern syntheses must deal carefully with our resources and our time, must reduce the amount of waste formed, should use catalytic transformations and finally must avoid all toxic reagents and solvents. 

In addition, synthetic methodology must be designed in a way that allows access to diversified substance libraries in an automated way [2]. Though solid-phase chemistry is now of a high standard for use in combinatorial chemistry, solution chemistry retains several advantages. 

A general way to improve synthetic efficiency, which in addition also gives access to a multitude of diversified molecules in solution, is the development of multi-component domino reactions which allow the formation of complex compounds starting from simple substrates. Domino reactions are defined as processes of two or more bond-forming reactions under identical conditions, in which the subsequent transformation takes place at the functionalities obtained in the former transformation thus, it is a time-resolved process [la,c,f,3]. The quality and importance of a domino reaction can be correlated to the number of bonds formed in such a process and the increase of complexity. Such reactions can be carried out as a single-, two- or multicomponent transformation. Thus, most of the known multicomponent transformations [4], but not all, can be defined as a subgroup of domino transformations. 

Domino reactions can be classified according to the mechanism of the single steps, which may be of the same type or of different types. The majority of the domino reactions so far developed belong to the first category and consist of two 

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