Organocatalysis and Beyond: Activating Reactions with Two Catalytic Species

Abstract

Since the beginning of the millennium, organocatalysis has been gaining a predominant role in asymmetric synthesis and it is, nowadays, a foundation of catalysis. Synergistic catalysis, combining two or more different catalytic cycles acting in concert, exploits the vast knowledge acquired in organocatalysis and other fields to perform reactions that would be otherwise impossible. Merging organocatalysis with photo-, metallo- and organocatalysis itself, researchers have ingeniously devised a range of activations. This feature review, focusing on selected synergistic catalytic approaches, aims to provide a flavor of the creativity and innovation in the area, showing ground-breaking examples of organocatalysts, such as proline derivatives, hydrogen bond-mediated, Cinchona alkaloids or phosphoric acids catalysts, which work cooperatively with different catalytic partners.

Green Chemistry Meets Asymmetric Organocatalysis: A Critical Overview on Catalysts Synthesis

“… [13] In fact, because of its versatility, efficiency and generality, 1 a has been extensively applied as the privileged catalyst in the nucleophilic addition or substitution of carbonyl compounds, imines, azodicarboxylates and nitrosobenzenes with a variety of electrophiles. [ 11a , 11b , 11c , 14 ] Moreover, being a natural and renewable compound, 1 a fully meets the principles of green chemistry. [15] Considering the catalytic power of natural product 1 a , chemists dedicated a lot of efforts to the development of its derivatives to improve the solubility, enhance the acidity or increase the steric hindrance of the directing group (Figure 2 ).…”

Combined Power of Organo‐ and Transition Metal Catalysis in Organic Synthesis

“…The asymmetric version of this reaction was presented in the subsequent years by Saicic and co‐workers employing pyrrolidine and chiral Pd(II) complexes as catalysts [34] . Following this, a plethora of new reactions have been discovered by merging transition‐metal catalysis with aminocatalysis [11–13,16–18] …”

“…[10] Since then, this emerging field has gained much attention among the synthetic community for achieving high regio-, chemo-, and stereoselective molecular complexities. [11][12][13][14][15][16][17][18] The combination of organocatalysis with metal catalysis can be mainly classified as "cooperative catalysis", "relay catalysis", and "sequential catalysis". [14] In cooperative catalysis, the organocatalyst and the metal catalyst independently and simultaneously activate both the substrates to drive a chemical reaction successfully.…”

“…reported a catalytic enone cycloallylation methodology by merging TM catalysis and organocatalysis [10] . Since then, this emerging field has gained much attention among the synthetic community for achieving high regio‐, chemo‐, and stereoselective molecular complexities [11–18] …”

Rapid computational evaluation of small‐molecule hydrolase mimics for preorganized H‐bond networks

“…Essentially, enzymatic transesterification has been widely explored for biodiesel production, presenting several advantages over chemical catalysts, one of the most important being mild reaction conditions 6 . As important green alternatives to biocatalysts, small organic molecules can effectively mimic functional group richness of enzymes within a much simpler molecular framework 7–20 . The interest in grafting catalytic active sites of enzymes onto organocatalytic scaffolds led to the development of new transesterification catalysts, called “spiroligozymes”, by placing the catalytic machinery of hydrolase enzymes onto modular spiro‐fused bispeptides with the help of quantum mechanical transition state (TS) calculations using the “inside‐out” approach 20 .…”