Highly enantioselective Michael additions of α-cyanoacetate with chalcones catalyzed by bifunctional cinchona-derived thiourea organocatalyst

Organocatalysis in Enantioselective α‐Functionalization of 2‐Cyanoacetates

“…Of these, bifunctional thiourea OC-33 proved to be the best organocatalyst. [32] Although the syn/anti diastereoselectivity was only moderate (63/37), both Michael adducts were obtained with acceptable enantioselectivity levels (ca. 88% ee) when the reaction was performed in toluene at room temperature and in the presence of 10 mol% of the organocatalyst.…”

Asymmetric catalysis with bifunctional cinchona alkaloid-based urea and thiourea organocatalysts

“…Chen and co-workers later studied the addition of a-cyanoacetate to chalcones. 38 Again catalyst 19 proved optimal and the reactions proceeded with high enantioselectivity but low diastereoselectivity (ca. 2 : 1 syn : anti in most cases).…”

Cinchona‐Catalyzed Nucleophilic Conjugate Addition to Electron‐Deficient CC Double Bonds

“…By employing this methodology, enantioenriched (R)-rolipram (86) was concisely prepared from the reaction of nitromethane and a,b-unsaturated N-acylpyrrole 85 (Scheme 9. 30 Soon afterward, a broad spectrum of Michael donors and Michael acceptors were successfully employed in the thiourea-catalyzed Michael addition [24][25][26][27]. Selected examples are outlined in Schemes 9.31-9.…”

“…In contrast to the results obtained with thiourea catalysts, the natural quinidine catalyst afforded only the racemic product (Scheme 9.31). The cyano acetates 91 were also examined as nucleophilic partners by Chen and coworkers [25,26]. In the presence of the cinchona-based thiourea catalyst 81a and 81b (10 mol%), ethyl cyanoacetate 91 reacted with various chalcones 92 to afford the Michael adducts 93 in high yields (80-95%) and with high to excellent enantioselectivities for both syn/anti-diastereomers (83-95% ee) (Scheme 9.32) [26], while the reaction of the a-substituted cyanoacetate (94) with methyl vinyl ketone (MVK) gave only modest enantioselectivity (up to 62% ee) [25].…”