Dynamic assembly of a zinc-templated bifunctional organocatalyst in the presence of water for the asymmetric aldol reaction

Abstract

A bifunctional organocatalytic system consisting of simple pyridine ligands containing separate catalytic functionalities was assembled using ZnCl2. This novel metal-templated catalyst furnished high yields and stereoselectivities towards the aldol reaction. The addition of controlled amounts of water turned out to be crucial to dissolve the system and achieve optimal results.

Hydrogen Bonding and Internal or External Lewis or Brønsted Acid Assisted (Thio)urea Catalysts

“…[29] Interestingly, Jimeno and Solà reported a metal-templated organocatalyst using thioureas as one of the ligands, although the thiourea scaffold was not chiral. [30] The authors assembled two monodentate pyridine ligands to a Zn salt 5 (ZnCl 2 ·P·T) containing separately a thiourea (T) and a prolinamide (P) functionality (Scheme 2). The Zn salt is generated in situ by mixing the three components in a one-pot reaction.…”

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

“…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). 27 This approach avoids the tedious preparative steps, and libraries of ligands and metal salts can be thus easily constructed and screened. In particular, we found that pyridine-based prolinamide and thiourea ligands assembled on zinc chloride to generate a highly active catalytic species, among other catalytic entities of lower activity.…”

“…We proposed that a tetrahedral geometry achieved by a ZnCl2•P3•T3 complex was responsible for the enhanced catalytic activity towards the asymmetric aldol reaction of cyclohexanone with aromatic aldehydes at -20 °C (Scheme 1). 27 It is noteworthy that complexes of the Zn(II)-prolinate [28][29][30][31][32] and Cu(II)-pyridinylamine [33][34] type have been proposed to work as single catalysts through a Lewis acid/Lewis base mechanism. Other Lewis acids have been successfully used in combination with organocatalysts too.…”

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

“…The above system was optimized on a trial-and-error basis. 24,25 In this communication, we report on the design and synthesis of a new dynamic organocatalytic system of unprecedented functional ligands based on a bipyridine scaffold (bipyPro and bipyTU, Fig. 1) for the asymmetric 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).…”