Cooperative Assistance in Bifunctional Organocatalysis: Enantioselective Mannich Reactions with Aliphatic and Aromatic Imines

Abstract

Auf Grundlage von Röntgenkristallstrukturen wurden difunktionelle Thioharnstoffkatalysatoren mit aktivierender intramolekularer Wasserstoffbrücke entwickelt und in einer hoch enantioselektiven Mannich‐Reaktion von Malonaten mit aliphatischen wie auch aromatischen Iminen eingesetzt (siehe Schema; Boc=tert‐Butoxycarbonyl).

Tuning acid–base cooperativity to create next generation silica-supported organocatalysts

“…The complexity has reached the point that acid-base cooperativity can be turned on and off through external stimuli [14] in one example, and the acid component of the catalyst can be designed to be activated by a second acid component on the same catalyst in another recent example [15]. In general, the modular nature of homogeneous catalysts enables precise manipulation that can then be investigated using experiment and theory in a straightforward manner to understand the origin of the activity and selectivity.…”

Progress in (Thio)urea‐ and Squaramide‐Based Brønsted Base Catalysts with Multiple H‐Bond Donors

“…In 2012 Pihko reported purposefully designed thiourea-urea systems like C62 (Scheme 46) and demonstrated that in these systems the Hbonds established internally between each urea NH site and thiourea sulfur atom are maintained intact during catalysis. [87] C62 efficiently catalyzes the Mannich reaction of malonates with N-Boc aldimines affording products 151 in high yields for most cases and very high ee values. Analogs of C62 derived from different 1,2-diamines and 1,2-aminols were prepared and evaluated, but C62 resulted the most active and selective owing probably to an optimum structure preorganization.…”

“…Pihko, 2012, 2019. [87,88] Scheme 47. Asymmetric reaction between nitroalkanes and aromatic aldehydes catalyzed by C2-symmetric bis-thiourea BBs.…”

“…However, whether these units interact directly with the reactant(s) or just do it internally within the catalyst, tuning its conformation and electronics, remains unanswered for the majority of cases. In 2012 Pihko reported purposefully designed thiourea‐urea systems like C62 (Scheme 46) and demonstrated that in these systems the H‐bonds established internally between each urea NH site and thiourea sulfur atom are maintained intact during catalysis [87] . C62 efficiently catalyzes the Mannich reaction of malonates with N ‐Boc aldimines affording products 151 in high yields for most cases and very high ee values.…”

Remote Activation of the Nucleophilicity of Isatin

“…To our surprise, no Mannich reaction was observed even in the presence of Pihko catalysts I and III which are known to be very efficient in promoting Mannich reactions. 16 Instead, aza-Michael product 4 was formed in good yield and high enantioselectivity. During the acidic workup the imine was hydrolyzed and isatin derivative 5 was formed.…”