Diarylprolinol ethers cascades

Wang elegantly demonstrated the potentiality of chiral diarylprolinol ether 54 in the synthesis of chromanes 56 via enantioselective Michael-type Friedel-Crafts alkylation/cychzation cascade synthetic sequence between 5a and a,p-unsaturated aldehydes 37a [30a]. Under optimal conditions, moderate diastereoselectivity and high enantioselectivity were obtained. Differently, phenol was found unreactive (Scheme 5.17a). The same team years later documented also the activity of a rosin-derived tertiary amine-thiourea 55 in similar process involving 1- and 2-naphthols and P,y-unsaturated a-ketoesters 25 (Scheme 5.17b) [30b]. A proposed model of the enantiodiscrimi-nating step of the reaction is also provided by the authors (58). 

Furthermore, the asymmetric PS reaction has been applied as a key step in the cascade reaction to build up chiral polycyclic compounds. In 2009, Dixon and coworkers [71] developed a chiral phosphoric acid 8f-catalyzed cyclization cascade between tryptamines and enol lactones, leading to the products in good yields and with good to excellent enantioselectivities. This was further extended to the reaction of tryptamines and ketoacids, which were more readily available than enol lactones [72]. By using diarylprolinol silyl ether as catalyst, the other cascade transformations involving Michael addition, iminium formation and PS cyclization were also efficiently realized [73]. 

SCHEME 14.16. Enantioselective synthesis of tetrahydrothiophenes through cascade processes of a,p-unsaturated aldehydes with 4-mercapto-2-butenoate and 3-mercapto a-carbonyl esters, promoted by diarylprolinol silyl ethers 17b,c. 

With a similar strategy of combined diarylprolinol silyl ether and N-heterocyclic carbene catalysts, j0rgensen and coworkers [21] examined the cascade reaction of easily accessible i-keto heteroaryl-sulfones as nucleophiles with a,P-unsaturated aldehydes (Scheme 43.11). In this cascade reaction, following the initial iminium ion-catalyzed Michael reaction of nucleophiles to a,(i-unsaturated aldehydes, the subsequent step was then promoted by carbene catalyst 57 to afford 2,4-disubstituted cyclopentenones 55 via an intramolecular benzoin condensation initiated Smiles rearrangement. The superiority of combinational use of two catalysts in the similar Michael/benzoin cascade reaction was also independently demonstrated by Enders et al. (Scheme 43.12) [22]. 

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