Proline metal catalysis

In this reaction, L-proline reacts with a donor component to generate an enamine intermediate, which attacks the acceptor and leads to an iminium adduct. The aldol is released after hydrolysis. Since its discovery, enamine catalysis has been developed into a powerful strategy that complements enzyme and metal catalysis [6, 7]. The attractiveness of this approach is due to the following ... 

Aminocatalysis is a biomimetic strategy used by enzymes such as class I aldolases. Application of aminocatalysis in an asymmetric aldol reaction was reported in the early 1970s. Proline (19) efficiently promoted an intramolecular direct aldol reaction to afford Wieland-Miescher ketone in 93% ee [17,18]. More than 25 years later, in 2000, List, Barbas, and co-workers reported that proline (19) is also effective for intermolecular direct aldol reactions of acetone (le) and various aldehydes 3. Notably, the reaction proceeded smoothly in anhydrous DMSO at an ambient temperature to afford aldol adducts in good yield and in modest to excellent enantioselectivity (up to >99% ee, Scheme 9) [19-22]. The chemical yields and selectivity of proline catalysis are comparable to the best metallic catalysts, although high catalyst loading (30 mol %) is required. Proline (19)... 

On the other hand, polymer-supported task-specific ILs in which the imidazolium cations couple L-proline via the ionic-pair interaction have also been synthesized and applied in metal scavenging and heterogeneous catalysis. The novel materials displayed considerable ability for metal scavenging onto their surface [e.g., Cul, Pd(OAc)2, Pd and IrCh] without the aid of a non-immo-bilized ionic liquid. Moreover, attempts to use these materials in the Cul-cat-alyzed N-arylation of nitrogen-containing heterocycles revealed that these systems are characterized by a much higher activity and recycling ability than... 

Proline is a stable, nontoxic, cyclic, secondary pyrrolidine-based amino acid with an increased pK value. Thus, proline is a chiral bidentate compound that can form catalytically active metal complexes (Melchiorre et al. 2008). Bidentate means that proline has not only one tooth but also a second one to bite and react. The greatest difference to other amino acids is a Lewis-base type catalysis that facilitates iminium and enamine-based reactions. It is especially noteworthy that cross-aldol condensations of unprotected glycoladehyde and racemic glyceralde-hyde in the presence of catalytic amounts of the Zn-(proline)2 gave a mixture of pentoses and hexoses (Kofoed et al. 2004). Again, proline seems to play the decisive role. The conditions are prebiotic the reaction proceeded in water for seven days at room temperature. It is remarkable that the pentose products contained ribose (34%), lyxose (32%), arabinose (21%), and xylose (12%) and that all are stable under the conditions. Thus, the diastereomeric and enantiomeric selection observed support the idea that amino acids have been the source of chirality for prebiotic sugar synthesis. 

Figure 5.1 Reactivity modes for proline eatalysis. (a) bifunctional acid/base catalysis (b) iminium catalysis (c) metal-complexes and (d) enamine catalysis.

Dihydroquinolines are obtained via Cu- or Ag-cata-lyzed A -coupling/cyclization when using 2-alkynylbenz-aldehydes, amines, and ketones, which combines metal and enamine catalysis, as demonstrated by Wu et al. [119]. 2-Alkynylbenzaldehyde derivatives have also been used as the additional nucleophile carrier in the silver-catalyzed synthesis of naphthyridines and thienopyridines recently reported by Verma et al. [120], A variety of naphthyridines and thienopyridines were prepared via dual activation using L-proline as the organocatalyst, whereas for other... 

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