A Degenerate Metal-Templated Catalytic System with Redundant Functional Groups for the Asymmetric Aldol Reaction

Abstract

A degenerate zinc-templated catalytic system containing two bipyridine ligands with redundant functional groups for either enamine or hydrogen bond formation was applied to the asymmetric aldol reaction. This concept led to both a higher probability of reaction and rate acceleration. Thus, the catalyst loading could be decreased to a remarkable 2 mol % in what we think is a general approach.

In Situ Assembly of a Metal‐Templated Catalyst for Asymmetric Aldol Reactions: From the Metal Complexes Equilibria to a Practical System

“…This ligand would render a tetracoordinate zinc complex. [22] (2) A bipyridine dihydrazide L2b developed along L3 to build a degenerate system with redundant functional groups. (3) A commercial bis(pyrinin-3-ol) L2c.…”

“…This behaviour had been observed for bipyridine L3 too. [22] Upon addition of Zn(TFA) 2 , the aldol reaction experienced a steep acceleration that led to very high conversion and stereoselectivity that can be attributed to a combination of organocatalysis-Lewis acid acceleration. [33][34] Even at 0 °C the conversion was very good and enantioselectivity could be slightly improved, from 95 to 97 % ee (Entries 2 and 3, Table 1).…”

“…This profile of reactivity and stereoselectivity is in total agreement with our previous results. [22][23][24][25] and [36]…”

“…[20][21] An auxiliary (bi)pyridine ligand with hydrogen bond donor properties was also necessary to accelerate the reaction, which prompted us to propose a tetrahedral heteromeric zinc complex with the two ligands as the real catalyst for the reaction. [22][23][24][25] The development of those catalytic systems led us to identify some geometric requirements to increase their efficiency: the presence in both bipyridine ligands of two redundant functional groups within the formation of a tetrahedral zinc complex led to a degenerate system with multiple reaction sites. The potential of this approach was demonstrated by high yields and excellent enantioselectivities with catalyst loadings as low as 2 mol % (Figure 1A).…”

Colloidal polystyrene-supported cooperative imidazolidinone/thiourea catalysts for efficient aldol reaction and substrate-selective Knoevenagel condensation in water

“…To improve cooperative behaviors, organocatalytic components need to be placed in close proximity. Several non-covalent interactions have been used for the construction of organocatalytic assemblies, [15][16][17] whereas their structures are easily disrupted by external stimuli such as temperature and pH, limiting their recovery and reuse. To overcome this limitation, one effective strategy is to immobilize organocatalytic components onto solid supports.…”