Organocatalysis cascade reactions

Two-component cascade reactions are of paramount importance in the synthesis of cyclic products. There are a lot of examples in organocatalysis dealing with different reactants and activation modes. We wiU try to summarize the most relevant ones. First, we will describe the synthesis of different carbocycles based on the ring size. Then we will focus on cascade reactions that render acyclic compounds. 

Double Cascade Reactions Amine-based organocatalysis are often employed for these cascade reactions because they can present a dual-activation mode depending the system involved, via enamine or iminium catalysis. 

The combination of organocatalysis and metal catalysis in one pot provides high efficiency in organic synthesis [34]. Combination catalysis usually leads to a cascade reaction, in which each step is catalyzed by a certain catalyst, either an organocatalyst or a metal catalyst. The key to designing such catalysis is that both the metal catalyst and organocatalyst should tolerate each other when they catalyze different types of reactions. 

Organocatalysis have emerged recently as one of the cornerstones for the enanti-oselective synthesis of C-C or C-heteroatom bonds. Owing to the easy prediction of the stereochemical outcome of the reactions, iminium activation and specific Michael reactions is one of the most studied reaction types in organocatalysis. In the literature, we can find multiple approaches to the organocatalytic Michael reaction using different catalysts or nucleophiles, most of them with exceptional levels of stereoselectivity. Moreover, these simple additions to enals or enones have inspired multiple organocatalytic tandem and cascade reactions and, in our view, open up a new pathway for the enantioselective construction of complex scaffolds in one-pot procedures. 

In addition, the unique ability of organocatalysis to combine multiple modes of activation in cascade reactions is another great advantage, allowing for an increase in the molecular complexity that can be obtained in a limited number of operations. 

Many successful and imaginative applications of cascade reactions in stereoselective synthesis of natural products and drug-like molecules have been described in this chapter. The gigantic benefits associated with cascade reactions have secured their position in future research and development efforts. In addition to the traditional strategies, such as the metal-catalyzed cascade reactions, recent advances in organocatalysis have expanded the... 

The synthesis of structurally complex biologically active compounds usually requires multiple reaction steps, and reduction of the number of steps is important both for environmental reasons and for achieving rapid access to the desired compounds. A promising approach is the use of cascade reactions, which enable us to assemble multiple components efficiently in one pot. In this held, organocatalysis is now well recognized to be a powerful tool, and many... 

In this book, we try to give an overview of the field of organocatalysis with particular emphasis on later developments in the field. First, we will introduce the different activation modes and catalysts. Next, we show a different approach of organocatalysis not based on the different activation modes, but based on the nature of the bond formed. From C-C bond forming reactions to C-heteroatom bond formation through cascade, multicomponent reactions, we will try to give a clear of the state-of-the-art picture of this field. 

In the preceding section, we already touched upon reactions that involve more than two input substrates. MCR cascades, however, often do not require organocatalysis for activation or selectivity. The desired selectivity frequently originates from the chirality of one of the inputs, such as chiral imines, aldehydes, or amines [23]. By exploiting this feature, many distinct MCRs have been applied in the synthesis of BRMs and are currently exploited for commercial use [24]. 

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