Organocatalytic cascade catalysis

Several very interesting cascade processes have also been developed under phase-transfer catalysis which are initiated by a conjugate addition reaction, although the number of reports is remarkably more limited compared to other organocatalytic cascades proceeding via other different mechanisms of activation. Representative examples will be presented in the following pages. 

Another impressive example of dienamine-iminium cascade catalysis was developed during the total synthesis of a-tocopherol 59 by Liu et al. [31]. This natural product is a member of the vitamin E family and possesses remarkable biological activity. The key step in the total synthesis of this natural product involved an organocatalytic aldol/oxa-Michael cascade reaction for construction of the core... 

By merging a transition metal-catalyzed reaction with an organocatalytic cascade sequence into a cycle-specific cascade catalysis, Simmons et al. developed a new... 

The first three chapters focus on organocatalytic cascade reactions, including amines, and Brpnsted acids, and the use of organocatalytic cascade reactions in natural product synthesis and drug discovery. Subsequent chapters introduce new developments and progress in transition metal cascade catalysis. Gold- and platinum-catalyzed... 

One of the first highly enantioselective examples of multicomponent cascade reactions in orgnocatalysis was developed by Enders et al. [62] in 2006. In this report they describe an asymmetric organocatalytic triple cascade reaction for the construction of tetrasubstituted cyclohexenecarbaldehydes (93) starting from from enals (15), nitroalkenes (28), and enolizable aldehydes (94) (Scheme 10.27). In this work, they did the sequential creation of three bonds by a high enantioselective combination of enamine-iminium-enamine catalysis for a triple cascade reaction. 

The main focus in this chapter will be on combined approaches using enamine catalysis and iminium catalysis especially in one-pot cascade reactions. As discussed in the following examples, the combined use of these two activation modes has led to the development of some of the most impressive and efficient organocatalytic natural product syntheses conducted so far (301-305). 

The first organocatalytic sulfa-Michael reaction of enals was reported by j0rgensen in 2005 [68]. In this report aliphatic and aromatic aldehydes reacted with several thiols in good yields and enantioselectivities under catalysis of 28. The products must be reduced immediately due to their fast epimerization at room temperature (Scheme 33.21). In this work, j0rgensen and coworkers also developed several multicomponent cascade reactions with good to excellent results. 

The rapid development of organocatalysis impels chemists to discover new synthetic methodologies. Many important transformations that could only be realized by transition metal catalysis can now be achieved via organocatalysis. In 2010, Kim and coworkers reported a novel C-H bond functionalization reaction via a tandem 1,5-hydride transfer/ring closure sequence. Based on the iminium-enamine cascade activation of catalyst 33, the fused tetrahydroquino-Unes 35 could be synthesized from substrates 34 with good stereoselectivity. This is the first example of an organocatalytic intramolecular redox reaction (Scheme 36.10) [16]. 

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