Enantioselective domino reaction

Certain examples are known for asymmetric induction in domino reactions using either chiral substrates or educts with removable chiral auxiliaries. In contrast, only a few enantioselective domino reactions have been developed so far. The first example was described by us using a titanium complex of glucose diacetonide with 88% ee.[101 Quite... 

Scheme 9. Enantioselective domino reaction for the formation of hydrindanones with heterobimetallic catalysts...

Alexakis also studied the enantioselective domino reactions catalyzed by a Cu complex of phosphoramidite 28. The 1,4-addition products of this reaction can be employed in an enolate trapping with vinyl oxiran 40 with Pd(0) catalysis (Scheme 11.9) [18]. This domino process afforded the known precursor 43 in the synthesis of the anticancer agent clavularin B (44) [19]. 

Alexakis developed the enantioselective domino reaction catalyzed by a Cu complex of phosphoramidite 45 using activated allylic compounds 47 with both leaving and electron-withdrawing groups. These designed electrophiles 47 could worked well even without Pd(0) catalysis (Scheme 11.10) [20]. 

The asymmetric Friedel-Crafts (FC) reaction is one of the most powerful methods to synthesize optically active aromatic compounds and has been included in various enantioselective domino reactions. Arai [32] reported the enantioselective... 

Scheme 19.32 Enantioselective domino reaction of (yclohexa-l,2-dione with a variety of substituted p-nitrostyrenes using thiourea 25.

With the increasing interest experienced by enantioselective domino reactions as powerful tools for the direct construction of enantioenriched complex targets starting from simple and readily available precursors, many investigations have been developed in this area of research, where the organocatalysis has gained an important position [96-98]. 

A number of highly efficient asymmetric domino nitro-Michael additions of C-nucleophiles catalysed by organocatalysts were described in 2008. One of the most employed organocatalysts for these types of reactions is diphenylprolinol silyl ether. This catalyst was used by Hong et al. to develop a highly diastereo-and enantioselective domino reaction occurring between 7-oxohept-2-enoate and nitroalkenes (Scheme 1.61). ° The reaction afforded highly functionalised... 

In the last few years, several groups have developed enantioselective domino reactions catalysed by combinations of organocatalysts with palladium complexes. As an example, Murkheqee and List have reported a domino synthesis of p-all earbon quaternary amines on the basis of a highly enantioseleetive a-allqrlation of a-branched aldehydes, involving an achiral palladium catalyst and a chiral phosphoric acid. Under the catalysis of phosphoric acid, a secondary allylamine reacted with an a-branehed aldehyde to form an enammonium phosphate salt, which upon reaction with palladium catalyst afforded a cationic 7t-allyl palladium complex (Scheme 7.2). This intermediate resulted in the formation of an a-allylated iminium ion, whieh eould be reduced to the corresponding final chiral amine in high yield and exeellent enantioselectivity of 97% ee. The synthetic utility of this transformation was also demonstrated hy a formal synthesis of (+)-cuparene. 

Xiao has employed nitroolefin enol ethers 113 as starting materials for a number of enantioselective domino reactions leading to chiral chromane derivatives containing three contiguous stereocenters, one of which is quaternary (Scheme 3.35). In... 

Wang and coworkers reported the highly enantioselective domino reaction between isatin derivatives 54c and a-isothiocyanato imides 102 catalyzed by a... 

Tietze, L. R, Sommer, K. M., Zinngrebe, J., Stecker R (2005). Palladium-catalyzed enantioselective domino reaction for the efficient synthesis of vitamin E. Angewandte Chemie International Edition, 44, 257-259. 

Conventional multistep synthesis of natural products reduces the overall yield of the target molecules. In contrast, biomimetic enantioselective domino reactions, promoted by small-molecule artificial enzymes, are more useful for the practical synthesis of natural products and related compounds. The stereoselective formation of polycyclic isoprenoids by the cyclase-induced cyclization of polypren-oids is one of the most remarkable steps in biosynthesis because this reaction results in the formation of several new quaternary and tertiary stereocenters and new rings in a single step. The use of biomimetic polycyclization with artificial cyclase is the most ideal chemical method for the synthesis of these polycyclic terpenoids. In this chapter, biosynthesis of polycyclic terpenoids, biomimetic stereoselective polyene cyclization induced by artificial cyclases, and total synthesis of bioactive natural products using stereoselective polyene cyclization as a key step will be discussed. 

In spite of the explosive development of asymmetric domino processes including multicomponent reactions, domino reactions involving chiral carbohydrate derivatives still remain rare in the literature. It is particularly true with regard to carbohydrate-derived organocatalysts. This section highlights several important works dealing with stereocontrolled domino reactions of chiral carbohydrate derivatives in a first part, and a rare enantioselective domino reaction catalyzed by a chiral carbohydrate derivative in a second part. It must be noted that all the discussed domino reactions are multicomponent ones. 

Enantioselective Domino Reactions Catalyzed by Chiral Carbohydrate Derivatives... 

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