Enantioselective Organocascade Catalysis

Electrophilic a-amination reactions were also included in organocascade sequences. Jorgensen developed a formation of hydro) - and amino-esters in combination by aminocatalysis using diaiylprolinol silyl ether and a redox reaction followed by acyl transfer to the corresponding esters using NHC catalysis. This useful method did not require an inert atmosphere or anhydrous conditions to form the corresponding products in excellent enantioselectivities and high yield. 

A closely related synthesis of tricyclic oxazines and oxazolidines was reported shortly afterward by Ye s group when the internal nucleophile is a hydroxyl function from a benzyhc alcohol or a phenol, respectively [18]. Enamides have also been proposed by Wang and collaborators [19] as functionalized pronucleophiles in a similar organocascade with unsaturated aldehydes promoted by diphenyl prolinol silyl ether in the presence of phenylacetic acid to give cychc hemiaminals. Recently, we proposed the first example of activation of 7V-tosyl-l,3-ketoamides under thiourea-based bifimctional catalysis for an enantioselective domino Michael/spirolactamiza-tion sequence leading to chiral scaffolds of high synthetic interest [20]. 

Reports depicting organocascades involving more than one Diels-Alder reaction are scarce. However, under imidazolidinone catalysis, achiral dendralenes and enals as dienophiles are able to undergo a double Diels-Alder cascade with high efficiency and enantioselectivities (Scheme 7.30) [48]. 

---