Deciphering the roles of multiple additives in organocatalyzed Michael additions

Abstract

The synergistic effects of multiple additives (water and acetic acid) on the asymmetric Michael addition of acetone to nitrostyrene catalyzed by primary amine-thioureas (PAT) were precisely determined. Acetic acid facilitates hydrolysis of the imine intermediates, thus leading to catalytic behavior, and minimizes the formation of the double addition side product. In contrast, water slows down the reaction but minimizes catalyst deactivation, eventually leading to higher final yields.

Water in asymmetric organocatalytic systems: a global perspective

“…In the research developed by Tsogoeva et al, water and acetic acid were essential components for an effective promotion of the asymmetric Michael addition of acetone to nitrostyrene (Scheme 17). 49,50 Before this finding, the Michael addition of ketones was considered a challenging reaction. Asymmetric hydrosilylation (in practice, a hydrogenation of dehydro-β-aminoacids) was achieved by Sun and co-workers using a chiral sulfoxide catalyst, which was able to activate trichlorosilane.…”

A copper-templated, bifunctional organocatalyst: a strongly cooperative dynamic system for the aldol reaction

“…[11][12] The following recent example also shows the potential of metal-bound organocatalytic ligands: Mirkin et al have demonstrated how Pt complexes bearing amino-squaramide P,S-ligands can be allosterically regulated by HCl in the nonasymmetric Michael addition of nitroethane to nitrostyrene. 19 In the context of our program aimed at understanding and developing water-tolerant organocatalysts [20][21][22][23][24] and dynamic systems able to recognize organic molecules in aqueous environment, [25][26] we have recently developed a metaltemplated, dynamic approach wherein ligands and metal salts were simply mixed together to generate efficient organocatalytic asymmetric systems. Catalysis was carried out solely through the ligands, which upon binding to the metal center generate a new bifunctional, efficient catalyst in the asymmetric aldol reaction (Scheme 1).…”

An efficient dynamic asymmetric catalytic system within a zinc-templated network

“…We recently approached this issue through a simple methodology combining our developments in dynamic systems [12][13][14][15][16][17][18][19] and organocatalysis. [20][21][22][23] In our approach, the rapidly exchanging metalÀpyridine ligand bonds furnished the catalytic network. The dynamic system thus generated contained sufficient amounts of a catalytically (kinetically) competent self-assembled species leading to high reaction rate acceleration and subsequent high enantioselectivity in the direct aldol reaction.…”

“…was crucial to ensure the activity of the catalytic system, as we have always encountered during the development of organocatalytic Michael and aldol reactions. [20][21][22][23][24][25][26][27] Moreover, our methodology involves the catalyst pre-formation in solution for 1 hour at room temperature before the reaction temperature is set and substrates are added. Otherwise, an induction period is observed before the catalytic activity can be detected (see ESI ‡ for details).…”